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  • drug2448: Placebo
  • Placebo (459) Hydroxychloroquine (102) Standard of Care (41) Azithromycin (38) Tocilizumab (36) Remdesivir (34) Placebo oral tablet (33) Questionnaire (32) Convalescent Plasma (28) Standard of care (27) No intervention (24) Favipiravir (23) Ivermectin (23) Convalescent plasma (21) Placebos (17) Enoxaparin (16) Methylprednisolone (15) Nitazoxanide (15) Survey (15) Colchicine (14) Vitamin C (14) placebo (14) Dexamethasone (12) Hydroxychloroquine Sulfate (12) Questionnaire Administration (12) Blood sample (11) Vitamin D (11) Anakinra (10) Control (10) Ruxolitinib (10) Saline (10) Usual Care (10) blood sample (10) no intervention (10) Camostat Mesilate (9) Losartan (9) Questionnaires (9) Standard care (9) questionnaire (9) Baricitinib (8) Blood sampling (8) Lopinavir/ritonavir (8) Zinc (8) survey (8) Gam-COVID-Vac (7) Nasopharyngeal swab (7) Quality-of-Life Assessment (7) Standard treatment (7) Chloroquine (6) Clazakizumab (6) DAS181 (6) LY3819253 (6) Lung ultrasound (6) Oseltamivir (6) Prone position (6) Rivaroxaban (6) Saliva collection (6) Sarilumab (6) Vitamin D3 (6) convalescent plasma (6) Aspirin (5) Best Practice (5) COVID-19 (5) COVID-19 Convalescent Plasma (5) COVID-19 convalescent plasma (5) Camostat (5) Cholecalciferol (5) Data collection (5) Doxycycline (5) Hydroxychloroquine (HCQ) (5) Lopinavir / Ritonavir (5) Nafamostat Mesilate (5) Online Survey (5) Online questionnaire (5) Online survey (5) Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector) (5) Standard Medical Treatment (5) Standard of Care (SOC) (5) UC-MSCs (5) blood sampling (5) hydroxychloroquine (5) questionnaire assesment (5) Acalabrutinib (4) Ad26.COV2.S (4) Ascorbic Acid (4) BCG Vaccine (4) BCG vaccine (4) BNT162b2 (4) Best Supportive Care (4) Biospecimen Collection (4) CELLECTRA® 2000 (4) Colchicine Tablets (4) HCQ (4) Heparin (4) Interferon Beta-1A (4) Interview (4) Lopinavir/Ritonavir (4) Mavrilimumab (4) Melatonin (4) Nitric Oxide (4) Normal Saline (4) Normal saline (4) Observation (4) Observational (4) Opaganib (4) Oxygen (4) Placebo Administration (4) Povidone-Iodine (4) Prednisone (4) Prone positioning (4) REGN10933+REGN10987 combination therapy (4) RLS-0071 (4) SARS-CoV-2 (4) SARS-CoV-2 convalescent plasma (4) Sargramostim (4) Standard Care (4) Survey Administration (4) Telemedicine (4) Telerehabilitation (4) anti-SARS-CoV-2 convalescent plasma (4) standard care (4) 0.9% saline (3) 3D Telemedicine (3) ACE inhibitor (3) AG0302-COVID19 (3) AZD1222 (3) AZD7442 (3) Abatacept (3) Allocetra-OTS (3) Anti-SARS-CoV2 Serology (3) Apremilast (3) BCG-Denmark (3) BNT162b1 (3) Blood draw (3) Blood samples (3) COVID-19 RT-PCR (3) COViage (3) Chloroquine or Hydroxychloroquine (3) Chloroquine phosphate (3) Clinical assessment (3) Clinical data (3) Clopidogrel (3) Control group (3) Cyclosporine (3) DWRX2003 (3) EIDD-2801 (3) Echocardiography (3) Famotidine (3) Hydrocortisone (3) INO-4800 (3) Ibrutinib (3) Inactivated SARS-CoV-2 Vaccine (Vero cell) (3) Interferon Beta-1B (3) Interferon beta-1a (3) Interferon beta-1b (3) Lenzilumab (3) Leronlimab (700mg) (3) Mesenchymal Stromal Cells (3) Mesenchymal stromal cells (3) Methotrexate (3) Naltrexone (3) Niclosamide (3) Nitric Oxide Gas (3) No Intervention (3) PLACEBO (3) Phase 2 (3) Placebo (Normal saline solution) (3) Placebo oral capsule (3) Plasma (3) Povidone-Iodine Nasal Spray and Gargle (3) Probiotic (3) Prone Positioning (3) Prospective study with two measurement points investigating the impact of viral mitigation protocols on mental health (3) RT-PCR (3) Ravulizumab (3) Remestemcel-L (3) Ribavirin (3) Saline Placebo (3) Selinexor (3) Serological test (3) SnPP Protoporphyrin plus Sunlight exposure (3) Standard of care (SOC) (3) Supportive Care (3) Suspension of heat killed (autoclaved) Mycobacterium w (3) TY027 (3) Telmisartan (3) Tofacitinib (3) Usual care (3) VPM1002 (3) Vitamin Super B-Complex (3) Yoga (3) blood donation SMS (3) exhaled breath sampling (3) hzVSF-v13 (3) mRNA-1273 (3) observational (3) self-administered questionnaire (3) serology (3) standard of care (3) standard therapy (3) 0.9% Saline (2) 100 mg/mL Virazole (2) 2D Telemedicine (2) 300 mg of omega3-FA (2) 50 mg/mL Virazole (2) AG0301-COVID19 (2) ARB (2) AVIGAN 200 MG Film Tablets (2) Abidol hydrochloride (2) Acebilustat (2) Aeonose (2) Aerobic Exercise Training (2) Alteplase 50 MG [Activase] (2) Ampion (2) Angiotensin 1-7 (2) Angiotensin converting enzyme inhibitor (2) Angiotensin-(1-7) (2) Apixaban 2.5 MG (2) Assessment of behavioral response to emotional stimulation (2) Assessment of work-related stress (2) Atorvastatin (2) Attention Placebo (2) Ayurveda (2) Azithromycin Tablets (2) Bacille Calmette-Guérin (BCG) (2) Baricitinib Oral Tablet (2) Bemiparin (2) Bevacizumab Injection (2) Bicalutamide 150 Mg Oral Tablet (2) Biological data (2) Biological sample collection (2) Blood collection on admission and longitudinally (2) Blood collection on their first consultation and 10 to 14 days later (2) Blood test (2) Blood tests (2) Breath Biopsy face masks with removable filters and fitted PVA strip (2) Brequinar (2) Bucillamine (2) COVID Convalescent Plasma (2) COVID-19 Serology (2) COVID-19 Therapeutic Biologics - Spike-GM-CSF Protein Lactated Ringer's Injection (2) COVID-19 exposure (2) COVID-19 pandemic (2) COVID-19 patients (2) COVID-19 survey (2) CT-P59 (2) CT-Scan (2) CVnCoV Vaccine (2) CYT107 (2) Camostat Mesylate (2) Canakinumab (2) Cannabidiol (2) Cardiac and electrodermal recordings (2) Carrimycin (2) ChAdOx1 nCoV-19 (2) Chloroquine Sulfate (2) Chloroquine or hydroxychloroquine (2) Ciclesonide (2) Clinical Examination (2) Convalescent COVID 19 Plasma (2) Convalescent Plasma (CP) (2) Convalescent Plasma (anti-SARS-CoV-2 plasma) (2) Convalescent Plasma Transfusion (2) Conventional treatment (2) Corticosteroid (2) Crizanlizumab (2) Daclatasvir (2) Data Collection (2) Data record (2) Deferoxamine (2) Defibrotide (2) Dexamethasone injection (2) Diagnostic Laboratory Biomarker Analysis (2) Diagnostic test (2) Disulfiram (2) Dornase Alfa Inhalation Solution [Pulmozyme] (2) Double-Trunk Mask (2) Duvelisib (2) EC-18 (2) ECG (2) EDP1815 (2) EXO 1 inhalation (2) EXO 2 inhalation (2) Early-Dexamethasone (2) Ebselen (2) Eculizumab (2) Electronic Health Record Review (2) Electronic questionnaire (2) Enoxaparin 40 Mg/0.4 mL Injectable Solution (2) Exercise (2) Exercise & Nutrition (2) Exercise training (2) Exposure (2) Expressive writing (2) Famotidine 20 MG (2) Favipiravir Placebo (2) Fisetin (2) Flow cytometric analysis (2) Fluoxetine (2) Fluvoxamine (2) Follow up (2) Fostamatinib (2) Guduchi Ghan Vati (2) HB-adMSCs (2) HFNC (2) High dosage Inactivated SARS-CoV-2 Vaccine on a 0- and 28-day schedule (2) Human Amniotic Fluid (2) Human biological samples (2) Human immunoglobulin (2) Hydroxychloroquine + azithromycin (2) Hydroxychloroquine - Weekly Dosing (2) Hydroxychloroquine 200 Mg Oral Tablet (2) Hydroxychloroquine Sulfate 200 MG (2) Hydroxychloroquine Sulfate 200 MG [Plaquenil] (2) Hydroxychloroquine Sulfate Loading Dose (2) Hydroxychloroquine Sulfate Regular dose (2) Hydroxychloroquine Sulfate Tablets (2) Hydroxychloroquine and Azithromycin (2) Hyperbaric oxygen (2) ICU treatment (2) IMU-838 (2) IVIG (2) Icosapent ethyl (2) Infliximab (2) Interleukin-7 (2) Intramuscular injection (2) Iodine Complex (2) Ion Mobility Spectrometry (IMS) (2) Ivermectin Oral Product (2) Ivermectin Pill (2) Ivermectin and Doxycycline (2) KB109 + Self Supportive Care (SSC) (2) Ketogenic diet (2) L-ascorbic acid (2) LY3832479 (2) Leflunomide (2) Lopinavir-Ritonavir (2) Low Dose Radiation Therapy (2) Low Dose Radiotherapy (2) Low dosage Inactivated SARS-CoV-2 Vaccine on a 0- and 28-day schedule (2) Low molecular weight heparin (2) M5049 (2) MSC (2) MW33 injection (2) MW33 injection placebo (2) MagPro X100 Stimulator, B70 Fluid-Cooled Coil (2) Matching Placebo (2) Meditation (1 x 20-minute guided audio training) (2) Medium dosage Inactivated SARS-CoV-2 Vaccine on a 0- and 28-day schedule (2) Meplazumab for Injection (2) Metformin (2) Methylprednisolone Sodium Succinate (2) Mindfulness (2) Mindfulness Based Intervention (2) Molnupiravir (2) N-Acetyl cysteine (2) N-acetylcysteine (2) NORS (Nitric Oxide Releasing Solution) (2) Nasal swab (2) Nasopharyngeal swabs (2) Niclosamide Oral Tablet (2) Nigella Sativa / Black Cumin (2) Nitrogen gas (2) Observational study (2) Olokizumab 64 mg (2) Online Questionnaire (2) Ophthalmologic exam (2) PLX-PAD (2) PUL-042 Inhalation Solution (2) Patient-Reported Online Questionnaire on Olfactory & Taste Disturbances (2) Peginterferon Lambda-1A (2) Pentoxifylline (2) Peripheral blood draw (2) Phase 1 (2) Physiotherapy (2) Pirfenidone (2) Placebo (NaCl 0.9%) (Group 2D) (2) Placebo Comparator (2) Placebo inhalation (2) Placebo on a 0- and 28-day schedule (2) Poly-ICLC (Hiltonol®) (2) Practice details (2) Pulmonary Rehabilitation (2) Pulmozyme (2) RECOP unit patient (2) RLF-100 (aviptadil) (2) RTB101 (2) Radiation therapy (2) Remdesivir placebo (2) Routine care for COVID-19 patients (2) Ruxolitinib Oral Tablet (2) SAB-185 (2) SARS-CoV-2 PCR (2) SARS-CoV-2 diagnostic rapid test (2) SARS-CoV-2 rS/Matrix-M1 Adjuvant (2) SARS-Cov2 testing (2) SCTA01 (2) SOC (2) SOC + Placebo (2) Saline solution (2) Saliva sample collection (2) Sample collection (2) Self Supportive Care (SSC) Alone (2) Semi-directive interview (2) Seraph 100 (2) Serology test for COVID-19 (2) Serum testing (2) Sevoflurane (2) Silmitasertib (2) Siltuximab (2) Simple cognitive task intervention (2) Simvastatin (2) Single Dose of Hydroxychloroquine (2) Sirolimus (2) SivoMixx (200 billion) (2) Spirometry (2) Standard Therapy (2) Standard of Care (SoC) (2) Standard of Care Treatment (2) Standard of care treatment (2) Stellate Ganglion Block (2) TD-0903 (2) Taking blood samples (capillary and venous), saliva sampling and nasopharyngeal sampling. (2) Therapeutic Plasma Exchange (2) Therapeutic anticoagulation (2) Throat swab (2) Thymalfasin (2) Tocilizumab (TCZ) (2) Tocilizumab Injection (2) Tofacitinib 10 mg (2) Tranexamic acid (2) Two doses of low dosage inactivated SARS-CoV-2 vaccine at the schedule of day 0,28 (2) Two doses of medium dosage inactivated SARS-CoV-2 vaccine at the schedule of day 0,28 (2) Two doses of placebo at the schedule of day 0,28 (2) Unfractionated heparin (2) Volatile Organic Compounds analysis (2) basic treatment (2) blood draw (2) blood samples (2) blood test (2) conjunctival swab (2) human monoclonal antibody DZIF-10c (Group 1A-2D) (2) lung ultrasound (2) nasopharyngeal swab (2) online survey (2) other (2) oxygen therapy (2) pregnant women with laboratory-confirmed 2019-n-CoV (2) retrospective analysis (2) unfractionated Heparin (2) venous ultrasound (2) vv-ECMO + cytokine adsorption (Cytosorb adsorber) (2) vv-ECMO only (no cytokine adsorption) (2) "Calm" is a mindfulness meditation mobile app (1) "Sham"-block with Placebo (Isotone NaCl) (1) "Vernonia amygdalina" (1) (Standard of Care) SoC (1) - Synthetic anti-malarial drugs (1) 0.075% Cetylpyridinium Chloride (1) 0.12% Chlorhexidine Gluconate (1) 0.12% Chlorhexidine Gluconate Mouth Rinse (1) 0.12% Chlorhexidine oral/nasal rinse (1) 0.5% Povidone Iodine (1) 0.5% Povidone/Iodine oral/nasal rinse (1) 0.9% (w/v) saline (1) 0.9% Normal Saline (1) 0.9% Sodium-chloride (1) 0.9% sodium chloride (normal saline) (1) 0.9%NaCl (1) 0.9%sodium chloride (1) 1% Hydrogen Peroxide (1) 1% w/v Povidone-iodide (1) 1. Characterize the immune response after infection with SARS-CoV-2 (1) 1.5-2% w/v Hydrogen Peroxide (1) 10% Povidone-iodine nasal decolonization swab plus 0.12% CHG oral rinse (1) 150 ppm Nitric Oxide delivered through LungFit Delivery System (1) 18F-αvβ6-BP (1) 1: ILT101 (1) 1: Naproxen (1) 1: Prone positioning (1) 1: Usual practice (1) 1: discontinuation of RAS blocker therapy (1) 2 post-mortem transcutaneous lung biopsies (1 anterior ; 1 posterior) using anatomical landmarks (1) 20 Mg Prednisone for 14 days (1) 2019-nCoV IgG/IgM Rapid Test Cassette (1) 2019-nCoV PCR (1) 21% Ethanol plus essential oils (1) 24 hour Holter ECG (1) 25-OH cholecalciferol (1) 2: No instruction regarding positioning (1) 2: Placebo Comparator (1) 2: Standard of care (1) 2: Usual practice + SYMBICORT RAPIHALER (1) 2: continuation of RAS blocker therapy (1) 35 ml blood, 5 tubes LITHIUM HEPARINATE at each time (cured Patients) (1) 35 ml blood, 5 tubes LITHIUM HEPARINATE at each time (hospitalized Patients ) (1) 38 questions questionnaire (1) 38-questions questionnaire (1) 40-Steps-test (1) 40ml blood sample (1) 4Plants/Azythromycin (1) 5-ALA-Phosphate + SFC (5-ALA + SFC) (1) 6 minute walk test (1) 80 ppm Nitric Oxide delivered through LungFit Delivery System (1) A $10 Survey Incentive (1) A $20 Survey Incentive (1) A short video intervention (1) A vignette intervention (1) AAZ Covid-19 rapid test (1) ABBV-47D11 (1) ABPM (1) ABX464 (1) ACE Inhibitors and Calcium Channel Blockers (1) ACE inhibitor, angiotensin receptor blocker (1) ACEI (1) ACEI/ARB (1) ACEIs (1) ACP Decisions Video Program (1) ACT-20-CM (1) ACT-20-MSC (1) ADAM Sensor (1) ADM03820 (1) AI model (1) AK119 (1) ALLOGENEIC AND EXPANDED ADIPOSE TISSUE-DERIVED MESENCHYMAL STEM CELLS (1) AMA Acknowledgement Drug Pricing (1) AMY-101 (1) AN69-Oxiris (1) AN69-Standard (1) ANNE One (1) APL-9 (1) APPS (1) ARBIDOL 100 MG KAPSUL (1) ARBOX (1) ARBs and/or ACE inhibitors (1) ARCT-021 Dose 1 (1) ARCT-021 Dose 2 (1) ARCT-021 Dose 3 (1) ARCT-021 Dose 4 (1) ARCT-021 Dose Regimen 1 (1) ARCT-021 Dose Regimen 2 (1) ARCT-021 single dose priming (1) ARCT-021 two higher dose priming (1) ARCT-021 two lower dose priming (1) ARDSNet (1) ARFC mask (1) ART Therapy (1) AS03-adjuvanted SCB-2019 vaccine (1) ASC09/ritonavir group (1) ASC09F+Oseltamivir (1) AT-001 (1) AT-100 (1) AT-527 (1) ATAFENOVIR 200 MG KAPSUL (1) ATI-450 (1) ATYR1923 1 mg/kg (1) ATYR1923 3 mg/kg (1) AV-COVID-19 (1) AVICOD 200 MG Film Tablet (1) AVIGAN (1) AVIGAN 200 mg FT (1) AVIGAN 200 mg Film Tablets (1) AVM0703 (1) AWARD advice (1) AWARD plus COVID-specific advice (1) AZD1656 (1) AZVUDINE (1) AZVUDINE placebo (1) Abdominal ultrasound (1) Abidol Hydrochloride combined with Interferon atomization (1) Abivertinib (1) Acacia Senegal (1) Acalabrutinib Treatment A (1) Acalabrutinib Treatment B (1) Acalabrutinib Treatment C (1) Acalabrutinib Treatment D (1) Accuchek Inform II platform (1) Accuracy of CAD4TB and Afinion CRP assay for pulmonary TB (1) Acetyl L-Carnitine (1) Acetylsalicylic acid (1) Acknowledgement Racial Injustice AMA (1) Active COVID-19 disease (1) Active Comparator (1) Active PBMT/sMF (1) Active control:Healthy Living (1) Activity (1) Ad5-nCoV (1) AdCLD-CoV19 (1) AdCOVID (1) Additional and minimal collection of products of the human body carried out during a sample for standard of care (1) Additional biological samples (1) Adenosine (1) Adenovirus Type-5 Vectored COVID-19 Vaccine (1) AdimrSC-2f (1) Adipose tissue (1) Administration of Equine immunoglobulin anti SARS-CoV-2 (1) Admission to ICU for COVID-19 (1) Adsorbed COVID-19 (inactivated) Vaccine (1) Aerobic Exercises (1) Aerobic training (1) Aerolized Hydroxychloroquine Sulfate (1) Aerosol Box (1) Aerosol-reducing Mask (1) Aerosolized 13 cis retinoic acid (1) Aerosolized 13 cis retinoic acid plus Inhalation Inhaled testosterone (1) Aerosolized 13 cis retinoic acid plus Inhalation administration by nebulization captopril 25mg (1) Aerosolized All trans retinoic acid (1) Aerosolized All-Trans Retinoic acid plus oral Tamoxifen (1) Aerosolized Isotretinoin plus Tamoxifen (1) African American Sender Acknowledgement (1) African American Sender in Informational Videos. (1) After COVID-19 Pandemic (1) AirFLO2 (1) AirGo Respiratory Monitor (1) Airwave Oscillometry (1) Airway pressure release ventilation (1) Alexa Amazon (1) Alisporivir (1) AlloStim (1) Allogeneic NK transfer (1) Allogeneic and expanded adipose tissue-derived mesenchymal stromal cells (1) Allogenic pooled olfactory mucosa-derived mesenchymal stem cells (1) Almitrine (1) Alpha-interferon alpha, abidol, ribavirin, Buzhong Yiqi plus and minus formula, Huhuang Detoxicity Paste, Baimu Qingre Jiedu Paste, fumigation/inhalation of vitamin C (1) Alpha-interferon, abidol, ribavirin, Buzhong Yiqi plus and minus formula, Huhuang Detoxicity Paste, Baimu Qingre Jiedu Paste and 5% glucose (1) Alpha-interferon, abidol, ribavirin, Buzhong Yiqi plus and minus formula, Huhuang Detoxicity Paste, Baimu Qingre Jiedu Paste and high-dose vitamin C treatment (1) Alteplase (1) Alvelestat (1) Ambrisentan (1) Amiodarone (1) Amlodipine (1) Amoxicillin-clavulanate (1) An auto-questionnaire comprising three psychometric scales (1) Anakinra +/- Ruxolitinib (stages 2b/3) (1) Anakinra 100Mg/0.67Ml Inj Syringe (1) Anakinra 149 MG/ML Prefilled Syringe [Kineret] (1) Anakinra Prefilled Syringe (1) Anakinra alone (stages 2b/3) (1) Anakinra and Ruxolitinib (Advanced stage 3) (1) Anakinra and Ruxolitinib (overcome stage 3) (1) Anakinra plus oSOC (1) Analogs, Prostaglandin E1 (1) Analysis of cytokine response, innate and adaptive immune response, complement activation, and serum neurofilaments as a marker of neurological damage. (1) Anger message (1) Angiography scanner (1) Angiotensin II (1) Angiotensin II Receptor Blockers (1) Angiotensin Receptor Blockers (1) Angiotensin receptor blocker (1) Angiotensin-Converting Enzyme Inhibitors (ACE-I) and Angiotensin II Receptor Blockers (ARB) (1) Anluohuaxian (1) Anti SARS-CoV 2 Convalescent Plasma in critical COVID-19 patients (1) Anti SARS-CoV 2 Convalescent Plasma in severe COVID-19 patients (1) Anti- SARS-CoV-2 Plasma (1) Anti-COVID-19 human immunoglobulin (1) Anti-SARS-CoV-2 Human Convalescent Plasma (1) Anti-SARS-CoV-2 IgT seropositivity (1) Anti-SARS-CoV-2 convalescent plasma (1) Anti-SARS-CoV-2 equine immunoglobulin fragments (INOSARS) (1) Anti-SARS-CoV-2 immunoglobulin (1) Anti-SARS-CoV2 serological controls and serum neutralization (1) Anti-Sars-CoV-2 Convalescent Plasma (1) Anti-coronavirus antibodies (immunoglobulins) obtained with DFPP form convalescent patients (1) Anti-coronavirus antibodies (immunoglobulins)obtained with DFPP from convalescent patients (1) Antibiotic (1) Antibiotics (1) Antibody Test (1) Antibody test (SARS-CoV2) (1) Antibody testing (1) Antibody titration (1) Antibody-Rich Plasma from COVID-19 recovered patients (1) Anticoagulant Therapy (1) Anticoagulation Agents (Edoxaban and/or high dose LMWH) (1) Antihypertensive Agents (1) Antioxidation Therapy (1) Antithrombin III (1) Antithrombotic Therapy (anticoagulant and/or antiplatelet) before admission for Covid19 (1) Antiviral Agents (1) Antroquinonol (1) Anxiety Reduction Training (1) Apilimod Dimesylate Capsule (1) Apixaban (1) Apixaban 5MG (1) Apo-Hydroxychloroquine (1) Appendectomy (1) Apple Watch Series 5 (1) Aprepitant injectable emulsion (1) Aprotinin (1) Arbidol (1) Arbidol Hydrochloride Granules (1) Argatroban (1) Artemesia annua (1) ArtemiC (1) Artemisia Annua Leaf (1) Artemisinin / Artesunate (1) Arterial Blood Gas test (ABG) (1) Arterial blood gas (1) Artesunate (1) Artesunate-amodiaquine (1) Ascorbic Acid and Zinc Gluconate (1) Ashmolean Website (1) Aspirin 100mg (1) Aspirin 75mg (1) Aspirin 81 mg (1) Assembled mask (1) Assessing antibody responses, neutralizing capacity and memory B-cell function (1) Assessing impact of COVID19 (1) Assessment of Dietary Changes in Adults in the Quarantine (1) Assessment of cardiovascular diseases and cardiovascular risk factors (1) Assessment of coagulopathy, Platelets activation and Platelets-Neutrophils interplay (1) Assessment of lung mechanics and heart-lung interactions (1) Assessment of postnatal depression using the the Edinburgh questionnaire between 4 and 6 weeks after delivery (1) Assessment of ventilator-associated pneumonia criteria (1) Assigned Strategies: Active Choice (1) Assigned Strategies: Enhanced Active Choice (1) Assigned Strategies: Opt-in (1) Association of diltiazem and niclosamide (1) AstroStem-V (1) Asunercept (1) Asynchronies detection (1) Atazanavir (1) Atazanavir and Dexamethasone (1) Atorvastatin 20 Mg Oral Tablet (1) Atorvastatin 20mg (1) Atorvastatin 40mg (1) Atovaquone/Azithromycin (1) Attention control (1) Audio-Visual Triage System (AVT) (1) Auditory Evoked Potentials (AEP) (1) Auricular neuromodulation (1) Auricular percutaneous neurostimulation (1) Auscul-X (1) Auto-questionnaires (patients co infected HIV Sras-CoV-2) (1) Autologous Adipose MSC's (1) Autologous Non-Hematopoietic Peripheral Blood Stem Cells (NHPBSC) (1) Automated oxygen administration - FreeO2 (1) Autophagy inhibitor (GNS651) (1) Auxora (1) Avdoralimab (1) Aviptadil 67μg (1) Aviptadil by intravenous infusion + standard of care (1) Awake Prone Positioning (1) Awake Proning (1) Awake prone positioning (1) Awake proning (1) Ayurvedic Kadha (1) Azinc (1) Azithromycin (Azithro) (1) Azithromycin / Ivermectin / Ribaroxaban / Paracetamol (1) Azithromycin / Ribaroxaban / Paracetamol (1) Azithromycin 250 MG (1) Azithromycin 250 MG Oral Capsule (1) Azithromycin 500 milligram (mg) oral Tablet (1) Azithromycin 500Mg Oral Tablet (1) Azithromycin Capsule (1) Azithromycin and hydroxychloroquine (1) Azithromycin with amoxicillin/clavulanate (1) Açaí palm berry extract - natural product (1) BACMUNE (MV130) (1) BAT (1) BAT + Calcifediol (1) BAT2020 (1) BBV152 (1) BBV152A - Phase I (1) BBV152A - Phase II (1) BBV152B - Phase I (1) BBV152B - Phase II (1) BBV152C - Phase I (1) BCG (1) BCG GROUP (1) BCG vaccine (Freeze-dried) (1) BCG-10 vaccine (1) BDB-001 Injection (1) BGB DXP593 (1) BGB-DXP593 (1) BI 764198 (1) BIO 300 Oral Suspension (1) BIO101 (1) BIOMARKERS IN THE LONG TERM IMPACT OF CORONAVIRUS INFECTION IN THE CARDIORRESPIRATORY SYSTEM (1) BIOVITALS (1) BLD-2660 (1) BM-Allo.MSC (1) BM-MSCs (1) BMS-986253 (1) BNT162a1 (1) BNT162b3 (1) BNT162c2 (1) BRII-196 (1) BRII-198 (1) BTL-TML-COVID (1) BVA-100 (1) Background questionnaire (1) Bactek-R (1) Bacterial species isolated (1) Bamlanivimab (1) Bardoxolone methyl (1) Bariatric procedures (1) Baricitinib (janus kinase inhibitor) (1) Baricitinib 4 MG Oral Tablet (1) Baricitinib or Anakinra (1) Base therapy (1) Baseline and during hospitalization blood samples (1) Baseline blood sample (1) Baseline message (1) Basic Body Awareness Therapy (1) Beck Depression Inventory (BDI) (1) Bedside lung ultrasound (1) Behavioral Activation SSI (1) Behavioral: OCAT (1) Behavioral: OCAT-sham (1) Behaviour Change Technique Intervention to Improve Quality of Life (1) Bemiparin sodium (1) Bempegaldesleukin (1) Berberine (1) Bereavement Virtual Support Group (1) Best Available Therapy (1) Best Message + Augmented Message or Implementation Strategy (1) Best Message Alone (1) Best Standard of Care (1) Best Standard of Care + CARDIO (1) Best available care (1) Best available treatment (1) Best standard of care (1) Best supportive care" which includes antivirals /antibiotics/ hydroxychloroquine; oxygen therapy (1) Bevacizumab (1) Bicalutamide 150 mg (1) BioMedomics COVID-19 IgM-IgG Rapid Test (1) Bioarginina® (1) Biobehavioral Tele-rehabilitation Sessions (1) Biocollection (1) Biological (1) Biological Sample Collection (1) Biological collection (patients co infected HIV Sras-CoV-2) (1) Biological collection with nasopharyngeal samples, saliva, blood, stool and urine (1) Biological sample and clinical data collection (1) Biological samples specific to research (1) Biological sampling (1) Biological test (1) Biological/Vaccine: Angiotensin peptide (1-7) derived plasma (1) Biological/Vaccine: Recombinant new coronavirus vaccine (CHO cell) low-dose group (1) Biological/Vaccine: Recombinant new coronavirus vaccine (CHO cells) high-dose group (1) Biological/Vaccine: Recombinant new coronavirus vaccine (CHO cells) placebo group (1) Biological: COVID-19 convalescent plasma (1) Biological: mRNA-1273: 100 mcg (1) Biological: mRNA-1273: 50 mcg (1) Biological: oral polio vaccine (1) Biomarker (TropT, Myoglobin, CK, CK-MB, LDH, D-dimer, CRP, PCT) (1) Biomarkers expression (1) Biosensor (1) Biosensors (1) Biospecimen collection (1) Bivalirudin Injection (1) Blink and Masseter Inhibitory Reflex (1) Blood D-dimer assay (1) Blood Sample (1) Blood analysis (1) Blood and derivatives. (1) Blood collection (1) Blood collection at Day 8, Day 16, Day 24, Month 6 and Month 12 after first symptoms from SARS-CoV-2 infection (1) Blood donation from convalescent donor (1) Blood for anti-drug antibody (ADA) (1) Blood for pharmacokinetic samples (1) Blood for research purposes (1) Blood group determination (1) Blood plasma (1) Blood sample and data record (1) Blood sample collection (1) Blood sample for serological test (1) Blood sample for serology to measure past infection with SARS-CoV-2 (1) Blood sample for whole genome sequencing (1) Blood samples (collection of 5 mL of blood in a dry tube) (1) Blood samples collection (1) Blood sampling (venesection) (1) Blood test for IgG antibodies against SARS-CoV-2 (1) Blood tests sputum, nasal lavage and brushing (1) Bloodwork (1) Bolus placebo (1) Bolus vitamin D3 (1) Bone Marrow Harvest (1) Bone Marrow Mesenchymal Stem Cell Derived Extracellular Vesicles Infusion Treatment (1) Bone conduction headphones (1) Botulinum Neurotoxin (1) Bovine Lactoferrin (1) Bovine Lipid Extract Surfactant (1) Brain MRI (1) Brain MRI scan (1) Brainstem Responses Assessment Sedation Score (BRASS) (1) Brazilian Green Propolis Extract (EPP-AF) (1) Breath Biopsy (1) Breath Biopsy Analysis (1) Breath Test & Cheek Swab (1) Breath biopsy sampling using the ReCIVA Breath Sampler (1) Breath sample (1) Breath test (1) Breathing exercise, intensive spirometry use, supported cough, progressive mobilisation and ambulation (1) Brexanolone (1) Bridge therapy (1) Brief Behavioral Activation with Mental Imagery (1) Brief Interpersonal Telepsychotherapy (1) Brief Psychiatric Rating Scale (1) Brief Skills for Safer Living (1) Brief cognitive behavioral therapy (1) Brief educational video (1) Brief informational infographic (1) Bromhexine 8 MG (1) Bromhexine Hydrochloride (1) Bromhexine Hydrochloride Tablets (1) Bromhexine Oral Tablet and/or hydroxychloroquine tablet (1) Bromhexine and Spironolactone (1) Broncho-Vaxom® (1) Bronchoalveolar Lavage (BAL) (1) Budesonide (1) Budesonide Nasal (1) Budesonide dry powder inhaler (1) Burnout (1) Butterfly (1) Butterfly iQ (1) C-reactive protein (1) C21 (1) C2Rx (1) C3+ Holter Monitor (1) CAD4COVID+WBC and COVID-19 RDT for SARS-CoV-2 infection (1) CAG length <22 (1) CAG length >=22 (1) CAP-1002 (1) CAP-1002 Allogeneic Cardiosphere-Derived Cells (1) CAStem (1) CBD Isolate (1) CCP (1) CD24Fc (1) CERC-002 (1) CHAMindWell (1) CHEST CT SCAN (1) CHLORPROMAZINE (CPZ) (1) CHX0.12+CPC0.05 oral rinse (PerioAidActive Control) (1) CIG Axial (1) CIG Tilted (1) CK0802 (1) CLBS119 (1) CLIA of IgG and IgM against SARS-Cov-2 (1) CM4620-IE (Injectable Emulsion) (1) CNM-ZnAg (1) CNS magnetic resonance imaging (MRI) imaging (1) COM-COVID anonimous survey (1) COMPASS (1) CONTROL GROUP (1) CONVALESCENT PLASMA (1) COPAN swabbing and blood sample collection (1) COR-101 (1) CORVax (1) COSH Self-help smoking cessation booklet (1) COVI-AMG (1) COVI-GUARD (1) COVI-VAC (1) COVICU (1) COVID 19 Convalescent Plasma (1) COVID 19 Diagnostic Test (1) COVID 19 Self-Questionnaire (1) COVID 19 diagnostic test by PCR (1) COVID 19 impact (1) COVID 19 serology (1) COVID WHELD (1) COVID Watch (1) COVID positive via testing (1) COVID visitation restrictions (1) COVID-19 Androgen Sensitivity Test (CoVAST) (1) COVID-19 Antibody testing (1) COVID-19 Antigen/Antibody Rapid Testing, mobile device image capture and telemedicine support (1) COVID-19 Breastfeeding Support (1) COVID-19 Convalescent Plasma (CCP) (1) COVID-19 Convalscent Plasma (1) COVID-19 Diagnostic and Assessment Tests (1) COVID-19 FACILITY (1) COVID-19 IgG / IgM rapid test (whole blood, serum, plasma) (1) COVID-19 IgG/IgM Rapid Test Cassette test (Healgen Scientific, Houston, Texas, USA) (1) COVID-19 PCR (1) COVID-19 PCR Swab (1) COVID-19 PCR and Serology (1) COVID-19 PCR and serology testing (1) COVID-19 Pandemic (1) COVID-19 Pneumonia (1) COVID-19 Specific T Cell derived exosomes (CSTC-Exo) (1) COVID-19 Swab (1) COVID-19 and Intensive Care (1) COVID-19 antibodies testing (1) COVID-19 antibody point of care test kit (1) COVID-19 barrier box (1) COVID-19 convalescent hyperimmune plasma (1) COVID-19 convalescent plasma (CCP) plus standard of care (SOC) (1) COVID-19 convalescent plasma treatment (1) COVID-19 diagnostic PCR (1) COVID-19 diagnostic test (1) COVID-19 e-package: Psychological wellbeing for healthcare workers (1) COVID-19 experience surveys (1) COVID-19 infection (1) COVID-19 infection status (1) COVID-19 positive via testing (1) COVID-19 related health warning leaflet (1) COVID-19 standard care (1) COVID-19 swap test PCR (1) COVID-19 test (1) COVID-19 test, polymerase chain reaction for SARS-CoV-2 (1) COVID-19 testing (1) COVID-19 treatment (1) COVID-19 treatments (1) COVID-19+ observational (1) COVID-HIGIV (1) COVID-VIRO® test (1) COVID-surgRES questionaire (1) COVID19 (1) COVID19 convalescent plasma infusion (1) COVID19 immunization testing (1) COVID19 vaccine (1) COVIDSeq Test (1) COVSurf Drug Delivery System (1) CPAP (1) CPAP treatment (1) CPI-006 (1) CRI management (1) CSL324 (1) CSL760 (1) CT of the chest (1) CT score (1) CT-P59/Placebo (1) CT-V (1) CT-imaging (1) CT-scan (1) CT-scan with minimal invasive autopsy (1) CTUS examination (1) CUROSURF® (poractant alfa) (1) CVnCoV (1) CVnCoV 12 μg (1) CVnCoV 12μg (1) CVnCoV 6 μg (1) CYNK-001 (1) CYP-001 (1) Calcium Channel Blockers (1) Calm Meditation App (1) Cambridge Validated Viral Detection Method (1) CanSwab (1) Canakinumab 150 MG/ML [Ilaris] (1) Canakinumab Injection 300mg (1) Canakinumab Injection 600mg (1) Candesartan (1) Canine odor detection of Volatile Organic Compounds (1) Cannabidiol, pharmaceutically produced with < 5 ppm THC (1) Cannabis, Medical (1) Capillary Collection & Testing (1) Capillary and salivary sampling (1) Capnography (1) Caption AI (1) Cardiac CT (1) Cardiac MRI (1) Cardiac Magnetic resonance imaging (1) Cardiac surgery (1) Cardiopulmonary resuscitation (1) Cardiorespiratory Exercise (1) Cardiovascular Magnetic Resonance (CMR) Imaging (1) Caring Contacts (1) Carotid Artery Reactivity Testing (1) Carrageenan nasal and throat spray (1) Cartography of air contamination, environment contamination and biological fluid by Sars-Cov2 during visceral surgery in COVID19 patients. (1) Case fatality rate (1) Cash transfer (1) Ceftaroline (1) Ceftriaxone (1) Cell therapy protocol 1 (1) Cell therapy protocol 2 (1) Cellular response (1) Cenicriviroc (1) Cenicriviroc (CVC) (1) Centricyte 1000 (1) Centrum Adult (under 50) multivitamin (1) Cerebral compliance and hemodynamics monitoring (1) Cerebrospinal fluid sampling, meningeal and brain parenchyma biopsies (1) Certified cloth face mask plus preventive information (1) ChAdOx1 nCoV-19 (Abs 260) (1) ChAdOx1 nCoV-19 (Abs 260) + 2.2x10^10vp (qPCR) boost (1) ChAdOx1 nCoV-19 (qPCR) (1) ChAdOx1 nCoV-19 0.5mL boost (1) ChAdOx1 nCoV-19 0.5mL prime plus boost (1) ChAdOx1 nCoV-19 full boost (1) ChAdOx1 nCoV-19 half boost (1) ChAdOx1 nCoV-19 single dose + paracetamol (1) ChAdOx1 nCoV-19 two dose + paracetamol (1) Change in knowledge, motivation, skills, resources (1) Change in preference to surgery under COVID-19 pandemic. (1) Chat-based instant messaging support (1) Chat-based support (1) Chemotherapy (1) Chest MRI (1) Chest computed tomography (CT) (1) Chest physiotherapy post-covid19 (1) Chest physiotherapy using a non-invasive oscillating device (1) Chinese Herbal Medicine (1) Chinese medicine treatment (1) Chiropractic care (1) Chiropractic care (more than one visit) (1) Chiropractic care (one visit) (1) Chloroquine Diphosphate (1) Chloroquine Phosphate Tablets (1) Chloroquine diphosphate (1) Chlorpromazine (1) Choice of Assignment: Active Choice (1) Choice of Assignment: Enhanced Active Choice (1) Choice of Assignment: Opt-in (1) Choices and judgements (1) ChulaCov19 mRNA vaccine (1) Ciclesonide Inhalation Aerosol (1) Ciclesonide Metered Dose Inhaler [Alvesco] (1) Clarithromycin (1) Clarithromycin 500mg (1) Clazakizumab 12.5 mg (1) Clazakizumab 25 mg (1) Clevudine (1) Clinical Observation (1) Clinical Trial Matching (1) Clinical diagnosis of COVID-19 by a health care professional (1) Clinical examination (1) Clinical interview (1) Clinical, functional and radiological lung involvement evolution (1) Clinical, laboratory and imaging characteristics of pneumonia (1) Cliniporator (1) CloSYS mouthwash (1) Clofazimine (1) Clopidogrel 75mg (1) Closed face shield with Surgical face mask use (1) Closed-loop control of oxygen supplementation by O2matic (1) Cloth Face Mask (1) Clungene rapid test cassette (1) Co-mestring (co-coping) (1) Cod liver oil (1) Cognitive Behavioral Brief-Telepsychotherapy (1) Cognitive Behavioural Group Therapy for Perinatal Anxiety (1) Cognitive and behavioral intervention. (1) Cognitive behavior therapy (CBT), specifically using the Facing Your Fears (FYF) curriculum (1) Cognitive testing (1) Cognitive training (1) Cohort (1) Colchicine 0.5 MG (1) Colchicine 1 MG Oral Tablet (1) Colchicine Pill (1) Colchicine plus symptomatic treatment (paracetamol) (1) Colgate Peroxyl mouthwash (1) Colgate Total mouthwash (1) Colgate periogard mouthwash (1) Collagen-Polyvinylpyrrolidone (1) Collection of Biological Samples (1) Collection of blood samples in order to create a biocollection (1) Collection of blood, salivary and nasopharyngeal samples. (1) Collection of breath sample (1) Collection of odour samples (1) Collection of samples (1) Collection of tears and saliva. (1) Colonoscopy (1) Colorectal resections (1) Combination (1) Combination of oral polio vaccine and NA-831 (1) Combined ART/hydroxychloroquine (1) Combined use of a respiratory broad panel multiplex PCR and procalcitonin (1) Communication (1) Communication type (1) Community interest message (1) Community popular opinion leader (POL) based intervention (1) Community-based, mobile van testing (1) Community-driven messages to promote COVID-19 testing (1) Comparable Placebo (1) Comparable Placebo of Oral Polio Vaccine and Placebo of drug (1) Comparable Placebo of drug (1) Comparative Observational Cohort Study (1) Comparator (1) Compassion focused intervention (1) Complement dosage (1) Complete blood picture, bone marrow aspiration cytology (1) Complete thrombophilic profile testing by multiplex PCR (1) Completion of post telemedicine encounter survey (1) Completion of pre-pandemic survey (1) Completion of survey after peak of pandemic (1) Complex diagnostic panel (1) Comprehensive treatment (1) Computed Tomography (CT) (1) Computer task questionnaires (1) Conestat alfa (1) Confinement and Communication During the COVID-19 Pandemic (1) Conjunctival swab and nasopharyngeal swab (1) Connected devices measurements (1) Connor-Davidson Resilience Scale 10 items (CD-RISC 10) (1) Contain COVID Anxiety SSI (1) Continuation of ACEi/ARB (1) Continuation of ARB/ACEI (1) Continuous Positive Airway Pressure (1) Continuous positive airway pressure (CPAP) treatment (1) Continuous renal replacement therapy (1) Continuous vital sign monitoring - Isansys Patient Status Engine (1) Contrast-enhanced CMR (1) Control (albumin 5%) (1) Control Blend (1) Control Group (1) Control Group (pharmacotherapy and/or psychotherapy, n=10) (1) Control Period (1) Control Test (1) Control arm (1) Control message (1) Control patients (1) Control swab (1) ConvP (1) Convalescent Immune Plasma (1) Convalescent Plasma 1 Unit (1) Convalescent Plasma 2 Units (1) Convalescent Plasma Infusion (1) Convalescent Plasma as Therapy for Covid-19 patients (1) Convalescent Plasma from COVID-19 donors (1) Convalescent Plasma of patients with COVID-19 (1) Convalescent SARS COVID-19 plasma (1) Convalescent Serum (1) Convalescent anti-SARS-CoV-2 MBT Plasma (1) Convalescent anti-SARS-CoV-2 MBT plasma (1) Convalescent anti-SARS-CoV-2 plasma (1) Convalescent plasma (CP) (1) Convalescent plasma transfusion (1) Convalesscent Plasma (1) Conventional N95 respirator (1) Conventional Oxygen Therapy (1) Conventional medicines (Oxygen therapy, alfa interferon via aerosol inhalation, and lopinavir/ritonavir) (1) Conventional medicines (Oxygen therapy, alfa interferon via aerosol inhalation, and lopinavir/ritonavir) and Traditional Chinese Medicines (TCMs) granules (1) Conventional oxygen therapy (1) Conventional physical therapy (1) Conventional therapy first (1) Coping strategies video (1) Cordio App (1) Core Warming (1) Corn oil (placebo) (1) Coromec Registry with ECL-19 (1) CoronaCideTM COVID-19 IgM/IgG Rapid Test and Premier Biotech COVID-19 IgM/IgG Rapid Test (1) CoronaVac (1) Coronavirus Anxiety Scale , COVID-19 Phobia Scale (1) Coronavirus Disease 2019 (1) Corticosteroid injection (1) Corticosteroid with or without colchicine (1) Corticosteroids and Derivatives (1) Cospherunate/Azythromycine (1) Cospherunate/Phytomedicine/Azythromycien (1) Cost-Benefit Frame (1) CovX (1) Covax-19™ (1) Covid ICU containment measures (1) Covid-19 + patients (1) Covid-19 Antibody testing (IgG and IgM) (1) Covid-19 PCR , IGM (1) Covid-19 Rapid Test Kit (RAPG-COV-019) (1) Covid-19 Standard of Care (1) Covid-19 presto test (1) Covid-19 swab PCR test (1) Covid19 (1) Covid19 RT-PCR (1) Covidfree@home (1) Covigenix VAX-001 (1) Covigenix VAX-001 placebo (1) Crest Pro-Health Multi-Protection mouthwash (1) Crisis intervention therapy (1) Crisis management coaching (1) Cross Sectional study using scientifically validated psychometric Scales (1) Cross-sectional observational study (1) Cross-sectional study examining the impact of information sources to obtain information about COVID-19 on depression and anxiety symptoms (1) Cross-sectional study investigating the association of NPIs with mental health (1) Cross-sectional survey (1) Curently used therapy for COVID-19 non-critical patients (1) Current care per UCLA treating physicians (1) Customized questionnaire (1) Cyclosporin A (1) CytoSorb (1) CytoSorb 300 mL device (1) CytoSorb-Therapy (1) Cytokine Adsorption (1) Cytokines dosage (1) Cytokines measurement (1) D-beta-hydroxybutyrate-(R)-1,3 butanediol monoester (1) D-dimer,CBC.ESR,CRP, (1) DAS181 COVID-19 (1) DAS181 OL (1) DASS-21 instrument (depression and anxiety) (1) DB-001 (1) DFV890 (1) DIG Axial (1) DIG Tilted (1) DUR-928 (1) DWJ1248 (1) Daclatasvir 60 mg (1) Daily Coping Toolkit (1) Daily Monitoring (1) Daily Vitamin D3 (1) Daily placebo (1) Dalcetrapib (1) Danoprevir+Ritonavir (1) Dapagliflozin (1) Dapagliflozin 10 MG (1) Darunavir and Cobicistat (1) Darunavir/Cobicistat (1) Data Collection: Clinical Care Assessments (1) Data collection and clinical testing of subjects (1) Data collection and rhinopharyngeal swab (1) Data collection from blood draw (1) Data collection from lumbar puncture (1) Data collection from medical files (1) Data collection up to 1 year (1) Data monitoring for 48h within the first 12 hours of admission for COVID-19 (1) Data registry (1) Data research, database analysis (1) Ddrops® products, 50,000 IU, Oral (1) Decidual Stromal Cells (DSC) (1) Decitabine (1) Deep Breathing training (1) Deep Venous Disease Diagnostic (1) Defibrotide 25 mg/kg 24 hours continuous infusion for 15 days (1) Defibrotide Injection (1) Degarelix (1) DeltaRex-G (1) Dental pulp mesenchymal stem cells (1) Depression, Anxiety and Stress Scale (1) Descartes 30 (1) Description of groups caracteristics (1) Desferal 500 MG Injection (1) Desidustat (1) Detection of anti-COVID-19 antibody level (1) Determination of physical activity, quality of life, stress levels of isolated people at home with the danger of coronavirus. (1) Device used to record voice for screening (1) Dexamethasone (high dose) (1) Dexamethasone 2 MG/ML (1) Dexamethasone and Hydroxychloroquine (1) Dexcom G6 (1) Dexmedetomidine Injectable Product (1) DiaBetter Together (1) DiaNose (1) Diabetes type 2 (1) Diagnosis of SARS-Cov2 by RT-PCR and : IgG, Ig M serologies in the amniotoc fluid, the blood cord and the placenta (1) Diagnostic Test: serology test for COVID-19 (1) Diagnostic examination for venous thromboembolism (1) Diagnostic test Covid-19 (1) Diagnostic test for SARS-Cov2 for patients and health staff (1) Diagnostic test for detection of SARS-CoV-2 (1) Dialectical Behavioral Therapy (DBT) Skills (1) Dialyzable Leukocyte Extract (1) Diet tracking and survey (1) Dietary Supplement containing resistant starch (1) Dietary counselling on Food Groups according to IYC Feeding practices, WHO (1) Dietary supplementation in patients with covid disease admitted to hospital (1) Differences in triage (1) Differential Leucocyte Count (CLDC) device and algorithm (1) Difficulties lived by disabled children's parents in the period of COVID-19 pandemic (1) Diffusing capacity of carbon monoxide (1) DigiVis visual acuity app (1) Digital Health Online Platform (1) Digital cardiac Counseling (1) Digital oximeter monitoring (1) Digital problem solving tool (1) Diphenhydramine (1) Dipyridamole (1) Dipyridamole 100 Milligram(mg) (1) Dipyridamole ER 200mg/ Aspirin 25mg orally/enterally AND Standard of care (1) Direct Antigen Tests for COVID-19 (1) Direct laryngoscopy (1) Discontinuation of ACEi/ARB (1) Discontinuation of ARB/ACEI (1) Discussion Board for Social Support +Basic Feedback (1) Discussion Board for Social Support+Personalized Feedback (1) Disease-modifying antirheumatic drugs (DMARDs) (1) Distilled water (1) Dociparastat sodium (1) Doctella telehealth monitoring (1) Doctor Spot (1) Doctorgram Patient Kit (1) Doppler Echo (1) Dornase Alfa (1) Dornase Alfa Inhalation Solution (1) Dose Finding Phase (MTD) (1) Dose of Tinzaparin or Dalteparin (1) Dose of tinzaparin or dalteparin (1) Double-Blind NT-I7 (1) Double-Blind Placebo (1) Doxycyclin (1) Doxycycline Hcl (1) Drug COVID19-0001-USR (1) Drug Isotretinoin (13 cis retinoic acid ) capsules+standard treatment (1) Drug: GS-5734 - 1.00 mg/kg (1) Drug: GS-5734 - 2.00 mg/kg (1) Drug: Isotretinoin plus Tamoxifen (1) Drug: Isotretinoin(Aerosolized 13 cis retinoic acid) (1) Drug: Isotretinoin(Aerosolized 13 cis retinoic acid) plus Aerosolized Itraconazole (1) Drug: NA-831 (1) Drug: NA-831 - 0.10 mg/kg (1) Drug: NA-831 - 0.20 mg/kg (1) Drug: Standard treatment Standard treatment (1) Drugs and supportive care (1) Drugs: NA-831 (0.10 mg/kg) plus GS-5734 (1.00 mg/kg) (1) Drugs: NA-831 (0.20 mg/kg) plus GS-5734 (2.00 mg/kg) (1) DuACT (1) Duplex ultrasound and Computed Tomography Angiography (1) During COVID-19 Pandemic (1) Dutasteride (1) Duty Frame (1) Dysphagia Handicap Index (DHI) (1) ECCO2R (1) ECG from handheld device (1) ECG-Holter (1) ECMO Implantation (1) EEG (1) EG-HPCP-03a (1) EG-HPCP-03a Placebo (1) EIT-Group (1) ELISA (1) ELISA and Rapid test to detect antibodies against COVID-19 (1) ELISPOT (1) ELMO PROJECT AT COVID-19: PROOF OF CONCEPT AND USABILITY (1) ELMO PROJECT AT COVID-19: STUDY IN HUMANS (1) EMDR (1) ENT exam (1) EP (1) EPDS (Edinburgh Postnatal Depression Scale) (1) EPIC risk score display (1) EQ001 (1) EQ001 Placebo (1) ESOGER (1) EUROIMMUN assay (1) EXTRA-CVD Virtual Care (1) EarSats Pulse Oximeter Probe (1) Early rehabilitation (1) EasyCov POC (1) Eating habits (1) Echo-Doppler (1) Economic benefit message (1) Economic freedom message (1) Edinburgh Postnatal Depression Scale (EDPS) (1) Edoxaban Tablets (1) Education (1) Education sessions (1) Educational meetings and visual prompts (1) Eicosapentaenoic acid gastro-resistant capsules (1) Ejaculated semen sample (1) Elective Cancer Surgery (1) Electric pad for human external pain therapy (1) Electrical Impedance Tomography (EIT) (1) Electrical Impedance tomography (1) Electro impedance tomography (1) Electrocardiogram (ECG) (1) Electrocardiogram, telemetry, echocardiogram, laboratory values (1) Electrocardiogram, transthoracic echocardiography and clinico-biological parameters in routine care (1) Electroencephalogram with EKG lead (1) Electronic Survey questionnaire (1) Electronic survey (1) Elisa-test for IgM and IgG to SARS-CoV-2 (1) Eltrombopag (1) Emapalumab (1) Embarrassment message (1) Emergency Laparotomy (1) Emergency Ventilator Splitter (1) Emergency surgery (1) Emotion Regulation Training via Telehealth (1) Emotional Freedom Technique (1) Emotional Support Plan (1) Emphasis of Academic Researchers Involvement (1) Emphasis of Government Involvement (1) Emtricitabine/Tenofovir Alafenamide 200 MG-25 MG Oral Tablet (1) Emtricitabine/tenofovir (1) Emtricitabine/tenofovir disoproxil (1) Endoscopic intervention (1) Endoscopic management according to standard of care (1) Endoscopic procedure (1) Endothelial damage and angiogenic biomarkers (1) Endotracheal intubation (1) Enduring Happiness and Continued Self-Enhancement (ENHANCE) for COVID-19 (1) Enhanced hygiene measures (1) Enoxaparin 1 mg/kg (1) Enoxaparin 40Mg/0.4Ml Inj Syringe 0.4Ml (1) Enoxaparin Higher Dose (1) Enoxaparin Prefilled Syringe [Lovenox] (1) Enoxaparin Prophylactic Dose (1) Enoxaparin sodium (1) Enoxaparin/Lovenox Intermediate Dose (1) Enriched Survey Feedback (1) Ensifentrine Dose 1 (1) Entrée: Behavioral skills (1) Entrée: Cognitive skills (1) Entrée: Interpersonal skills (1) Environmental exposure and clinical features (1) Enzalutamide (1) Enzalutamide Pill (1) EpiVacCorona (EpiVacCorona vaccine based on peptide antigens for the prevention of COVID-19) (1) Equipment with smartwatch throughout hospital stay on the general ward (1) Eritoran (1) Escin (1) Essential Oil Blend (1) Essential oils (1) Estradiol patch (1) Estrogen Therapy (1) Ethanol with Asprin (1) Etoposide (1) Evaluate HACOR score effectivity in this patients (1) Evaluation of changes in the diagnostic-therapeutic pathway for patients affected by pancreatic cancer (1) Evaluation of clinical, instrumental and laboratory diagnostics tests (1) Evaluation of the epidemiological characteristics of coronavirus infection (SARS-CoV-2) (1) Ex vivo expanded Wharton's Jelly Mesenchymal Stem Cells (1) Examinations for the research: (1) Examine the impact of COVID-19 during pregnancy (1) Exebacase (1) Exercise Group (1) Exercise booklet (1) Exercise brochure (1) Exercise capacity (1) Exercise physiology (1) Exercise program (1) Exercise test ECG (1) Exercise training group (1) Experience of pandemic (1) Experiences in Close Relationship Scale questionnaire (ECR-S) (1) Experimental Group (1) Experimental drug (1) Experimental: Questionnaire without precaution information (1) Experts consensus (1) Expiratory training device (1) Exposure (not intervention) - SARS-CoV-2 infection (1) Exposure to the Dutch measures due to the Covid-19 pandemic. (1) Exposure to the SARS-CoV-2 (1) Exposure to the SARS-CoV-2 and its consequences (1) Exposure: Covid-19 infection (1) Expression of receptors and activating proteases (1) Extended sampling and procedures (1) External evacuation device (EED) (1) Extra blood sample (1) Extracorporeal blood purification using the oXiris® (AN69ST) hemofilter (1) Extracorporeal left hemicolectomy anastomosis (1) Extracorporeal membrane oxygenation (1) Extraoral vacuum aspirator (EVA) (1) Extravascular Lung Water Index (1) Eye Movement Desensitisation and Reprocessing Recent traumatic Event Protocol (1) F-652 (1) FAVICOVIR 200 mg Film Tablet (1) FAVIR 200 MG FT (1) FAVIRA 200 MG Film Tablet (1) FFP (1) FFP2 (1) FMD (1) FNC dummy tablet+Standard of Care (1) FNC+Standard of Care (1) FOY-305 (1) FSD201 (1) FT516 (1) FX06 (1) Face Mask + Soap (1) Face mask (1) Face mask awareness (1) Face mask sampling (1) Facebook Ads on the importance of staying safe during the Thanksgiving holiday (1) Facial fractures reduction or osteosynthesis (1) Facial mask (1) Family Nurture Intervention (FNI) (1) FamilyChildCare (provisional name of app) (1) Farmalarm (1) Fast dissolving film (1) Favipiravir (3200 mg + 1200 mg) (1) Favipiravir (3200 mg + 1200 mg) combined with Azithromycin (1) Favipiravir (3200 mg + 1200 mg) combined with Hydroxychloroquine (1) Favipiravir (3600 mg + 1600 mg) (1) Favipiravir + Currently used therapy (1) Favipiravir + Standard of Care (1) Favipiravir Combined With Tocilizumab (1) Favipiravir and Hydroxychloroquine (1) Favipiravir plus Nitazoxanide (1) Feeling Good Digital App (1) Fenofibrate (1) Fiberoptic Bronchoscopy (FOB) (1) Fibreoptic Endoscopic Evaluation of Swallowing (FEES) (1) Fibrin generation markers assays (1) File Scanning (1) File scanning (1) FilmArray PCR on respiratory samples (1) FilmArray Pneumonia (1) Filtration Test (1) Fingerstick (1) Fingolimod 0.5 mg (1) Fit test (1) Five-days oseltamivir (1) Fixed site standard of care testing (1) Fixed-Dose Combination of Pertuzumab and Trastuzumab for Subcutaneous Administration (PH FDC SC) (1) Fixed-duration Hydrocortisone (1) Fixed-duration higher dose Hydrocortisone (1) Flow controlled ventilation (Evone-ventilator) (1) Flow cytometry (1) Flu shot (1) Flucelvax (1) Fluvirin (1) Fluzone High Dose (1) FoTv (1) Focused/Targeted Message (1) Folic Acid (1) Follow up calls (1) Follow-up at 14 days (1) Follow-up of patients with COVID-19 (1) Follow-up phone call (1) Follow-up visit (1) Fondapariniux (1) Fondaparinux (1) Freestyle Libre 14 day CGM system (1) Full Spectrum CBD Oil (1) Functional MRI (1) Fuzheng Huayu Tablet (1) Fuzheng Huayu tablet (1) GAD-7 (7-item Generalized Anxiety Disorder) (1) GAD-7 (General Anxiety Disorder) scale (1) GAD-7 General anxiety disorder scale (1) GAMUNEX-C (1) GC4419 (1) GC5131 (1) GENETIC (1) GLS-1027 (1) GLS-1200 (1) GLS-5310 (1) GNS561 (1) GO2 PEEP MOUTHPIECE (1) GPs reports of potential patient safety incidents, non-COVID-19 related (1) GRAd-COV2 (1) GX-19 (1) Galidesivir (1) Gam-COVID-Vac Lyo (1) Gamification (1) Ganovo+ritonavir+/-Interferon nebulization (1) Garadacimab, Factor XIIa Antagonist Monoclonal Antibody (1) Gargle/Mouthwash (1) Gas exchange measurement (1) Gas exchanges at different PEEP (1) Gastrointestinal endoscopy (1) General Communication Message (1) General Public cohort (1) General health education (1) Generalized Anxiety Disorder-7 (GAD 7) (1) Generalized Anxiety Disorder-7 (GAD-7) (1) Gimsilumab (1) Global Longitudinal Strain (1) Glucose tablets (1) Glycaemic levels (1) Glycine (1) Graded exercise test (1) Grocery store gift cards (1) Group 1 (1) Group 1: Rivaroxaban 20mg/d followed by enoxaparin/unfractionated heparin when needed (1) Group 2: control group with enoxaparin 40mg/d (1) Group A (AG0302-COVID19) (1) Group A (Placebo) (1) Group A HCQ (1) Group A: oropharygeal spray and immunostimulant (1) Group B (AG0302-COVID19) (1) Group B (Placebo) (1) Group B Control (1) Group B: Placebo oropharyngeal spray + Active principle immunostimulant (1) Group C:Active principle oropharyngeal spray + Placebo taken PO (1) Group D:Placebo oropharyngeal spray + Placebo taken PO (1) Group1 (1) Growth Hormone (1) Growth Mindset SSI (1) Guided online support program (1) Guilt message (1) HADS (1) HADS questionnaire (1) HB-adMSC (1) HCFWO (1) HCQ & AZ (1) HCQ & AZ vs HCQ+SIR (1) HCQ+AZT (1) HFB30132A (1) HFNO (1) HIT-exercise (1) HLX70 (1) HLX71 (1) HOME-CoV rule implementation (1) HOPE intervention (1) Health Care Worker Survey (1) Health Enhancement Program (1) Health Questionnaire (1) Health supplements (1) Health warning leaflet (1) Health-related quality of life (1) Healthy Minds Program Foundations Training (1) Healthy lifestyle advise (1) Helmet CPAP (1) Helmet Continuous Positive Airway Pressure (CPAP) (1) Helmet non-invasive ventilation (1) Hemodynamics changes at different PEEP (1) Hemopurifier (1) Heparin - Prophylactic dosage (1) Heparin - Therapeutic dosage (1) Heparin Infusion (1) Heparin SC (1) Heparin sodium (1) Hepatitis A vaccine (1) Hesperidin and Diosmin mixture (1) Heterologous stimuli (1) Hidroxicloroquina (1) High Dose of KBP-COVID-19 (1) High Flow Nasal Oxygen (HFNO) (1) High Flow Nasal Therapy (1) High Intensity Interval Training group (1) High PEEP with end inspiratory pause (1) High PEEP without end inspiratory pause (1) High dosage Inactivated SARS-CoV-2 Vaccine on a 0- and 14-day schedule (1) High dose Interferon-beta 1a (1) High dose radiation 100 cGy (1) High flow nasal cannula (1) High flow nasal cannula HFNC (1) High intensity interval training (1) High volume evacuation (HVE) (1) High-Concentration Essential Oil (1) High-Titer Anti-SARS-CoV-2 (COVID 19) Convalescent Plasma (1) High-Titer COVID-19 Convalescent Plasma (HT-CCP) (1) High-dose Recombinant COVID-19 vaccine (Sf9 cells) (18-59 years) & Three dose regimen (1) High-dose Recombinant COVID-19 vaccine (Sf9 cells) (18-59 years) & Two dose regimen (1) High-dose Recombinant COVID-19 vaccine (Sf9 cells) (60-85 years) & Three dose regimen (1) High-dose Recombinant COVID-19 vaccine (Sf9 cells) (60-85 years) & Two dose regimen (1) High-dose placebo (18-59 years) & Three dose regimen (1) High-dose placebo (18-59 years) & Two dose regimen (1) High-dose placebo (60-85 years) & Three dose regimen (1) High-dose placebo (60-85 years) & Two dose regimen (1) High-flow nasal cannula treatment (1) High-titer Convalescent COVID-19 Plasma (CCP1) (1) Home Pulse Oximetry Monitoring (1) Home Sleep Apnea Testing or In-hospital Polysomnography (1) Home exercise (1) Home exercise program (1) Home sample collection of concerning mole with physician supervision (1) Home-based exercise (1) Home-based exercise training (1) Home-use Test and Follow-up Questionnaire (1) Honey (1) Hormones (1) Hospital admission (1) Hospital anxiety and depression scale (1) Hospital: DD-CA (1) Hospital: Usual Care (UC) (1) Hospitalized Patients for COVID-19 Infection (1) Huaier Granule (1) Human Biological samples (1) Human Coach first, then Virtual Assistant (1) Human Ezrin Peptide 1 (HEP1) (1) Human milk donors (1) Human umbilical cord derived CD362 enriched MSCs (1) Human umbilical cord mesenchymal stem cells + best supportive care (1) Humoral and cellular immunity (1) Hydrogen Oxygen Generator with Nebulizer (1) Hydrogen Peroxide (1) Hydrogen-Oxygen Generator with Nebulizer, AMS-H-03 (1) Hydroxychloroquin with Azithromycin (1) Hydroxychloroquine (placebo) (1) Hydroxychloroquine + Azithromycin (1) Hydroxychloroquine + Metabolic cofactor supplementation (1) Hydroxychloroquine + Sorbitol (1) Hydroxychloroquine + azithromycin + / - tocilizumab (1) Hydroxychloroquine + lopinavir/ritonavir (1) Hydroxychloroquine + placebo (1) Hydroxychloroquine , Sofosbuvir, daclatasvir (1) Hydroxychloroquine - Daily Dosing (1) Hydroxychloroquine - Daily dosing (1) Hydroxychloroquine Only Product in Oral Dose Form (1) Hydroxychloroquine Oral Product (1) Hydroxychloroquine Pill (1) Hydroxychloroquine Pre-Exposure Prophylaxis (1) Hydroxychloroquine SAR321068 (1) Hydroxychloroquine Sulfate (HCQ) (1) Hydroxychloroquine Sulfate + Azithromycin (1) Hydroxychloroquine Sulfate + Azythromycin (1) Hydroxychloroquine Sulfate 200 milligram (mg) Tab (1) Hydroxychloroquine Sulfate 400 mg twice a day (1) Hydroxychloroquine Sulfate 600 mg once a day (1) Hydroxychloroquine Sulfate 600 mg twice a day (1) Hydroxychloroquine Sulfate Tablets plus Lopinavir/ Ritonavir Oral Tablets (1) Hydroxychloroquine and azithromycin treatment (1) Hydroxychloroquine and azithromycin treatment arm. (1) Hydroxychloroquine as post exposure prophylaxis (1) Hydroxychloroquine combined with Azithromycin (1) Hydroxychloroquine in combination of Azithromycin (1) Hydroxychloroquine plus Nitazoxanide (1) Hydroxychloroquine plus standard preventive measures (1) Hydroxychloroquine sulfate (1) Hydroxychloroquine sulfate &Azithromycin (1) Hydroxychloroquine, Azithromycin (1) Hydroxychloroquine, Clindamycin (1) Hydroxychloroquine, Clindamycin, Primaquine - high dose. (1) Hydroxychloroquine, Clindamycin, Primaquine - low dose. (1) Hydroxychloroquine, Doxycycline (1) Hydroxychloroquine, lopinavir/ritonavir or azithromycin and placebo (standard therapy) (1) Hydroxychloroquine/Azithromycine (1) Hydroxychloroquine/Chloroquine (1) Hydroxycloroquine and Azythromycine (1) Hyperbaric Chamber (1) Hyperbaric Oxygen (1) Hyperbaric Oxygen Therapy (1) Hyperbaric Oxygen Therapy (HBOT) (1) Hyperbaric oxygen therapy (1) Hyperbaric oxygen treatment (HBOT) i.e. inhalation of pressurized oxygen delivered by a hyperbaric chamber (drug/device) (1) Hyperimmune immunoglobulin to SARS-CoV-2 (hIVIG) (1) Hyperimmune plasma (1) Hyperpolarized Xe129 (1) Hyperpolarized Xenon-129 MRI of the lungs (1) Hypertension (1) Hypothermia (1) Hypothermia Via Cooling Machine- Arctic Sun 5000 (1) IC14 (1) IC14, a monoclonal antibody against CD14 (1) ICU Recovery + Physical Therapy (1) ID NOW vs. Accula (1) IER-R (posttraumatic stress) (1) IIBR-100 high-dose (prime) (1) IIBR-100 low-dose (prime-boost) (1) IIBR-100 medium dose (prime) (1) IIBR-100, low dose (prime) (1) IIEF-5 questionnaire (1) IL-12 plasmid (1) IMM-101 (1) IN01 vaccine (1) INB03 (1) INC424 / Ruxolitinib (1) INM005 (1) INOpulse (1) IP-10 in CDS protocol (1) IPSS questionnaire (1) ISIS 721744 (1) IV Deployment Of cSVF In Sterile Normal Saline IV Solution (1) IV Dexamethasone (1) IVERMECTIN (IVER P®) arm will receive IVM 600 µg / kg once daily plus standard care. CONTROL arm will receive standard care. (1) Ibudilast (1) Ibuprofen (1) Icatibant (1) Icosapent ethyl (IPE) (1) Identification by PCR of the SARS-COV-2 virus in samples taken from the fetus (1) Identification of genetic variants (1) IgG (1) IgG SARS CoV 2 antibodies (1) IgG SARS CoV2 (1) IgG antibodies immunoassay (1) IgG test (1) IgIV (1) IgM and IgG antibodies assay (1) IgM and IgG diagnostic kits to SARS-CoV-2 (1) Iloprost (1) Imaging (1) Imaging by thoracic scanner (1) Imaging of the lungs (1) Imatinib (1) Imatinib Mesylate (1) Imatinib tablets (1) Immediate vs. delayed provision of antibody test results (1) Immune response study (1) Immunfluorescence (1) ImmunoFormulation (1) Immunofree tablets and Reginmune capsule (1) Immunoglobulin (1) Immunoglobulin of cured patients (1) Immunoglubulins (1) Immunological profiling (1) Immunosuppressive (1) Immunosuppressive Agents (1) Impact Event Score (1) Impact of COVID-19 questionnaire (1) Impact of Event Scale-Revised (1) Impact of respiratory isolation on quality of life (1) In-person instruction (1) In-person postoperative visit (1) Inactivated SARS CoV 2 vaccine (Vero cell). Wuhan (1) Inactivated SARS-CoV-2 vaccine (Vero cell) (1) Inactivated convalescent plasma (1) Increasing Willingness and Uptake of COVID-19 Testing and Vaccination (1) Individualised Ayurveda (1) Individualized-Chinese herbal medicine (1) Indomethacin (1) Infectious Disease and Cardiology Clinical Consultations (1) Inflammatory cytokines and chemokines profiles of patients with dexmedetomidine administration (1) Information (1) Informational videos and social media campaigns encouraging cancer screening. (1) Informed consent (1) Infrared Energy and Dietary Supplement (1) Infusion IV of Mesenchymal Stem cells (1) Infusion placebo (1) Inhaled Hypertonic ibuprofen (1) Inhaled ILOPROST (1) Inhaled Supplemental Oxygen (1) Inhaled budesonide (1) Inhaled nitric oxide (iNO) (1) Inhaled nitric oxide gas (1) Inhaled sedation (1) Injection and infusion of LV-SMENP-DC vaccine and antigen-specific CTLs (1) Innova Lateral Flow Device (1) Inspiratory training device (1) Instrumental Activities of Daily Living Shaping (1) Insulin (1) Insulin film (1) Insulin regimen (1) Interferon alfa (1) Interferon-Alpha2B (1) Interferon-Beta (1) Interferon-ß-1a (1) Interferon-β 1a (1) Interferon-β1a (1) Interleukin 6 (IL6) Antagonist (1) Interleukin 6 (IL6) Antagonist and corticosteroids (1) Interleukin assessment in semen (1) Interleukin-1 receptor antagonist (1) Interleukin-6 Gene-174C detection (1) Intermediate dose thromboprophylaxis (1) Intermittent prone positioning instructions (1) Internet Cognitive Behavioral Therapy plus CHAMindWell (1) Internet-based Cognitive Behavioral Therapy (1) Internet-based guided self-help based on CBT principles (1) Internet-based self-help (1) Internet-based self-help after 3 weeks (1) Internet-delivered cognitive behavior therapy (ICBT) for dysfunctional worry related to the Covid-19 pandemic (1) Interpersonal Psychotherapy (1) Intervention (1) Intervention App (1) Intervention for COVID-19 preventive protocols (1) Intervention for TECC Model (1) Intervention group CoronaCope (1) Intervention group_rehabilitation program (1) Intervention program (1) Intervention training: (1) Intervention, TBN (1) Interview by psychologists (1) Intracorporeal left hemicolectomy anastomosis (1) Intramuscular Vaccine (1) Intramuscular vaccine (1) Intranasal heparin sodium (porcine) (1) Intraosseous access (1) Intravenous Immune Globulin (1) Intravenous Immunoglobulin (1) Intravenous Infusions of Stem Cells (1) Intravenous access (1) Intravenous drug (1) Intravenous saline injection (Placebo) (1) Intravenous sedation (1) Intubation Box (1) Invasive mechanical ventilation (1) Invasive mechanical ventilation using the Unisabana-Herons Ventilator during 24 hours (1) Investigation of smell and taste disorders (1) Investigation of the prevalence of test positivity (1) Investigational Product - ViraCide (1) Iota carrageenan nasal spray and Ivermectin oral drops (used as buccal drops) (1) Iota-Carrageenan (1) Isoflurane Inhalant Product (1) Isoprinosine (1) Isoquercetin (1) Isoquercetin (IQC-950AN) (1) Isotonic saline (1) Isotonic saline 0.9% (1) Isotretinoin Only Product in Oral Dose Form (1) Isotretinoin(Aerosolized 13 cis retinoic acid) +standard treatment (1) Itolizumab IV infusion (1) Ivermectin (IVM) (1) Ivermectin + Doxycycline (1) Ivermectin + Doxycycline + Placebo (1) Ivermectin + Placebo (1) Ivermectin 3mg Tab (1) Ivermectin 5 MG/ML oral solution, Aspirin 250 mg tablets (1) Ivermectin 5 MG/ML oral solution, Dexamethasone 4-mg injection, Enoxaparin injection. Inpatient treatment with mechanical ventilation in ICU. (1) Ivermectin 5 mg/mL oral solution, Dexamethasone 4-mg injection, Aspirin 250 mg tablets (1) Ivermectin 6 MG Oral Tablet (2 tablets) (1) Ivermectin Injectable Solution (1) Ivermectin Tablets (1) Ivermectin and Doxycyline (1) Ivermectin nasal (1) Ivermectin oral (1) Ivermectin plus Nitazoxanide (1) JS016 (anti-SARS-CoV-2 monoclonal antibody) (1) Janus Kinase Inhibitor (ruxolitinib) (1) KELEA Excellerated Water (1) KIR phenotype evaluation (1) Kaletra and beta interferon (1) Kamada Anti-SARS-CoV-2 (1) Kaplan Meier analysis (1) Ketamine (1) Ketogenic diet with phytoextracts (1) Ketotifen 1 MG (1) Kevzara sc (1) Knowledge, Attitude, Practice, Awareness, Preference (1) Kukaa Salama: mHealth intervention (1) Kundalini Yoga and Anxiety Reduction Training (1) L-Citrulline (1) L-citrulline (1) LAMP (1) LAU-7b (1) LB1148 (1) LEAF-4L6715 (1) LMWH (1) LSALT peptide (1) LY3127804 (1) LYMPHOCYTE MONOCYTE RATIO (1) LYT-100 (1) Lab workup (on admission and regularly during follow up). (1) Laboratory Analyses (1) Laboratory test positive for SARS-CoV-2 virus (1) Laboratory tests (1) Lactobaciltus rhamnosus GG (1) Lactobaciltus rhamnosus GG Placebo (1) Lactoferrin (1) Lactoferrin (Apolactoferrin) (1) Lambda 180 mcg S.C (1) Lanadelumab (1) Late dexamethazone (1) Late-Dexamethasone (1) Lateral Position (left and right lateral decubitus) (1) Learning running subcuticular sutures on the Gamified Educational Network (1) Lenalidomide as a 5 mg capsule PO daily, days 1, 3, and 5. (1) Let It Out (LIO)-C (1) Leukapheresis (1) Levamisole (1) Levamisole Pill + Budesonide+Formoterol inhaler (1) Levamisole and Isoprinosine (1) Levamisole and isoprinosine (1) Levilimab (1) Lianhua Qingwen (1) Liberase Enzyme (Roche) (1) Licensed seasonal influenza vaccine (1) Licorice extract (1) Lidocaine 2% (1) Life2000® Ventilator (1) LifeSignals Biosensor 1AX* (1) Lifelight® Data Collect Blood Pressure Group (1) Lifelight® Data Collect Oxygen Saturation Group (1) Lifestyle change promotion program (1) Lift (1) Limbix Spark (1) Linagliptin (1) Linagliptin 5 MG (1) Linagliptin tablet (1) Liquid Alpha1-Proteinase Inhibitor (Human) (1) Listerine Mouthwash Product (1) Liu-Wei-Di-Huang formula (1) Liver function tests (1) Liver function tests ,serum ferritin and PCR for COVID-19 . (1) Liver injury (1) Liver, lung, heart and kidney biopsy (1) Local standard of care (1) Lock-down and social distancing (1) Longeveron Mesenchymal Stem Cells (LMSCs) (1) Lopinavir (1) Lopinavir / ritonavir tablets combined with Xiyanping injection (1) Lopinavir / ritonavir, alpha-interferon nebulization,Abidor Hydrochloride (1) Lopinavir 200 MG / Ritonavir 50 MG [Kaletra] (1) Lopinavir 200Mg/Ritonavir 50Mg FT Reference (1) Lopinavir 200Mg/Ritonavir 50Mg FT Test (1) Lopinavir 200Mg/Ritonavir 50Mg Tab (1) Lopinavir and ritonavir (1) Lopinavir-Ritonavir Drug Combination (1) Lopinavir/ Ritonavir (1) Lopinavir/ Ritonavir Oral Tablet (1) Lopinavir/ Ritonavir Placebo (1) Lopinavir/Ritonavir + hydoxychloroquine (1) Lopinavir/Ritonavir 200 MG-50 MG Oral Tablet (1) Lopinavir/Ritonavir 400 mg/100 mg (1) Lopinavir/ritonavir treatment (1) Losartan 50 mg and Spironolactone 25 mg pillules oral use (1) Losmapimod oral tablet (1) Lovenox 40 MG in 0.4 mL Prefilled Syringe (1) Low Dose (10 mg) Control (1) Low Dose Radiation Therapy (LD-RT) (1) Low Dose of KBP-COVID-19 (1) Low Molecular Weight Heparin (1) Low PEEP - FiO2 high (1) Low PEEP - FiO2 low (1) Low dosage Inactivated SARS-CoV-2 Vaccine on a 0- and 14-day schedule (1) Low dose Interferon-beta 1a (1) Low dose Low molecular weight heparin or Placebo (1) Low dose Radiotherapy (1) Low dose prednisolone (1) Low dose radiation 35 cGy (1) Low dose radiation therapy (1) Low dose whole lung radiotherapy for older patients with COVID-19 pneumonitis (1) Low flow ECMO driving by CVVH machine (1) Low or upper respiratory tract sample (1) Low-Concentration Essential Oil (1) Low-Intensity Psychosocial Interventions through Telemental health (1) Low-dose Chest CT (1) Low-dose Recombinant COVID-19 vaccine (Sf9 cells) (18-59 years) & Three dose regimen (1) Low-dose Recombinant COVID-19 vaccine (Sf9 cells) (18-59 years) & Two dose regimen (1) Low-dose Recombinant COVID-19 vaccine (Sf9 cells) (60-85 years) & Three dose regimen (1) Low-dose Recombinant COVID-19 vaccine (Sf9 cells) (60-85 years) & Two dose regimen (1) Low-dose placebo (18-59 years) & Three dose regimen (1) Low-dose placebo (18-59 years) & Two dose regimen (1) Low-dose placebo (60-85 years) & Three dose regimen (1) Low-dose placebo (60-85 years) & Two dose regimen (1) Low-dose radiotherapy (1) Lower-dose prophylactic anticoagulation (1) Lucinactant (1) Lung CT (1) Lung CT scan analysis in COVID-19 patients (1) Lung Function Test (1) Lung Function tests (1) Lung Low Dose Radiation (1) Lung Ultrasound (1) Lung impedance technique (1) Lung ultrasound use in patients hospitalized with COVID (1) LungFit™ (1) MAGEC Spine Rod (1) MANAGEMENT OF COVID-19 (1) MAS825 (1) MCC IMS (1) MCN (Methylene blue, vitamin C, N-acetyl cysteine) (1) MF59 adjuvanted SARS-CoV-2 Sclamp vaccine 15mcg (1) MF59 adjuvanted SARS-CoV-2 Sclamp vaccine 45mcg (1) MF59 adjuvanted SARS-CoV-2 Sclamp vaccine 5mcg (1) MFS (1) MK-5475 (1) MLS Laser (1) MMR vaccine (1) MPT0B640 (1) MR or M-M-R II ® vaccine (1) MR-Pro-ADM (1) MRG-001 (1) MRI (1) MRI (heart, brain, lungs, liver) (1) MRI scans (1) MRx-4DP0004 (1) MSC Treatment (1) MSCT (1) MSCs (1) MSCs-derived exosomes (1) MSTT1041A (1) MSTT1041A-matched Placebo (1) MVA-SARS-2-S vaccinations (days 0 & 28) (1) MVC-COV1901 (1) Machine Learning/AI Algorithm (1) Machine learning model (1) Macrolide administered for 3-5 days (1) Macrolide administered for up to 14 days (1) Magnetic Resonance Imaging (1) Magnetic Resonance Spectroscopy (MRS). (1) Maintenance or reduction of immunosuppression (1) MakAir (1) Male Sexual Health Questionnaire (MSHQ) (1) Maltodextrin (1) Mannitol (1) Manremyc (1) Maraviroc (1) Maraviroc + Currently used therapy (1) Maraviroc 300 mg (1) Maraviroc+Favipiravir+CT (1) Marker Therapeutics D2000 Cartridge (D2000) for use with the Spectra Optia® Apheresis System (Optia SPD Protocol) (1) Masimo, LidCO (1) Masitinib (1) Mask with Mask Adhesive/Arm 1 (1) Mask without Mask Adhesive / Arm 2 (1) Masked Saline Placebo (1) Maslach Burnout Inventory (MBI) (1) Massive parallel sequencing of host genome (1) Matched Placebo (1) Matched Placebo Hydroxychloroquine (1) Matched placebo (1) Matching placebo (1) Maternal attachment, Edinburgh depression scoring and postpartum anxiety scale scores (1) Maternal stress (1) Maximal effort test (1) Measles-Mumps-Rubella Vaccine (1) Mechanical Trombectomy (1) Mechanical ventilation with the automated BVM compressor (1) Media Intervention (1) Medical Mask (1) Medical Music (1) Medical Ozone procedure (1) Medical Record Review (1) Medical Record Review - Inpatient Treatment (1) Medication Review (1) Meditation Therapy (1) Meditation and Anxiety Reduction Training (1) Meditation app usage (1) Medium dosage Inactivated SARS-CoV-2 Vaccine on a 0- and 14-day schedule (1) Medium dose prednisolone (1) Mefloquine (1) Mefloquine + azithromycin + / - tocilizumab (1) MejoraCare (1) Melatonin 2mg (1) Melatonin intravenous (1) Melphalan (1) MenACWY (1) MenACWY boost (1) MenACWY prime & saline placebo boost + paracetamol (1) MenACWY single dose + paracetamol (1) MenACWY vaccine (1) MenCare+/Bandebereho fathers'/couples' group education (1) Mental Health questionnaire (1) Mental imagery (1) Merimepodib (1) Mesenchymal Stem Cell (1) Mesenchymal Stem Cells derived from Wharton Jelly of Umbilical cords (1) Mesenchymal Stromal Cells infusion (1) Mesenchymal Stromal Stem Cells - KI-MSC-PL-205 (1) Mesenchymal cells (1) Mesenchymal stem cell (1) Mesenchymal stem cell therapy (1) Mesenchymal stem cells (1) Mesenchymal stromal cell-based therapy (1) Message directing subjects to information on COVID-19 vaccine safety and efficacy (1) Messaging (1) MetaNeb® System (1) Metformin Glycinate (1) Methotrexate-LDE phase 1 (1) Methotrexate-LDE phase 2 (1) MethylPREDNISolone 80 Mg/mL Injectable Suspension (1) Methylene Blue (1) Methylene Blue 5 MG/ML (1) Methylene-Blue Photodisinfection (1) Methylprednisolone Injectable Product (1) Methylprednisolone Injection (1) Methylprednisolone, Placebo (1) Microcannula Harvest Adipose Derived tissue stromal vascular fraction (tSVF) (1) Microcrystalline Cellulose, NF (1) Micronized and ultra-micronized Palmitoylethanolamide (mPEA and umPEA, 300mg + 600mg) oral suspension (1) Microscopy of defined brain regions on autopsy specimens (1) MindRhythm Harmony (1) Mindfullness based cognitive program (1) Mindfulness + Compassion Intervention (MC) (1) Mindfulness Alone (MO) Intervention (1) Mindfulness Based Cognitive Therapy for Resilience During COVID-19 plus CHAMindWell (1) Mindfulness Rounds (1) Mindfulness based intervention (1) Mindfulness intervention (1) Mindfulness program (1) Mindfulness session(s) (1) Mindfulness training (1) Mindfulness training (MT) Connect (1) Mindfulness-Based Cognitive Therapy (1) Minimal Attention Control Intervention (1) MinnRAP Peer Support Program (1) Mixture 3,6% H2 in N2 (96.4%) (1) Mobile Mental Health App - 1 (1) Mobile Mental Health App - 10 (1) Mobile Mental Health App - 2 (1) Mobile Mental Health App - 3 (1) Mobile Mental Health App - 4 (1) Mobile Mental Health App - 5 (1) Mobile Mental Health App - 6 (1) Mobile Mental Health App - 7 (1) Mobile Mental Health App - 8 (1) Mobile Mental Health App - 9 (1) Model Building (1) Model validation (1) Moderate Intensity Aerobic Exercises (1) Modified Bai He Gu Jin Tang (1) Modified CariesCare International management (1) Modified Rankin score (1) Molgramostim nebuliser solution (1) Monalizumab (1) Monitoring Visit - Baseline (1) Monitoring Visit - Week 4 (1) Monitoring Visit - Week 8 (1) Monitoring for aggravation (1) Monitoring physiological data with the Hexoskin smart shirt (1) Montelukast 10mg (1) Montmorrillonite (1) Motivational social support from nurse (1) Motivational social support from nurse with additional support from significant other (1) Motivational telephone intervention (1) Moxibustion plus Cupping (1) Moxifloxacin or Levofloxacin (1) Mucodentol (1) MultiStem (1) Multicapillary column coupled ion mobility spectrometry (1) Multifrequency Bioimpedance Spectroscopy (1) Multiple Doses of Anti-SARS-CoV-2 convalescent plasma (1) Muscle Relaxation Therapy (1) Muscle ultrasound (1) MuscleSound Ultrasound (1) Museum virtual guided tours (1) Music Therapy (1) N terminal pro B type natriuretic peptide (NTproBNP), D-Dimer, and serum Tropinin - I (1) N-803 (1) N-95 Respirator (1) N-acetyl cysteine (1) N95 respirator (1) NA (no intervention) (1) NA-831 (1) NA-831 and Atazanavir (1) NA-831and Dexamethasone (1) NAD+ (1) NBT-NM108 (1) NETosis markers (1) NG Biotech (1) NG test (1) NGM621 (1) NHANES smell and taste tests (1) NIO® (Intraosseous access) (1) NIVOLUMAB (1) NK Cells (1) NK cells,IL15-NK cells,NKG2D CAR-NK cells,ACE2 CAR-NK cells,NKG2D-ACE2 CAR-NK cells (1) NK-1R antagonist (1) NO intervention planned due to the observational study design - only a diagnostic testing (1) NO intervention planned due to the observational study design only a diagnostic testing (1) NO-Immunosuppressive (1) NOX66 (1) NP-120 (Ifenprodil) (1) NRICM101 (1) NT-I7 (1) NaCl (1) NaCl 0.9% (1) NaCl Solution (1) Nafamostat Mesylate (1) Nanomix eLab® COVID-19 Rapid Antigen Panel (non-interventional) (1) Narrative Writing (1) Nasal Brushing (1) Nasal Dexamethasone (1) Nasal Irrigation (1) Nasal Spray (1) Nasal Swab (1) Nasal lavage (1) NasoVAX (1) Nasopharyngeal (NP) swab (1) Nasopharyngeal Swab (1) Nasopharyngeal and throat/oropharyngeal swabs analyses by RT-PCR and ddPCR (1) Nasopharyngeal swab and main laboratory (1) Nasopharyngeal, oropharyngeal, or saliva swab (1) Natural Honey (1) Natural Killer Cells infusion (1) Nebulised heparin (1) Nebulised unfractionated heparin (UFH) (1) Nebulized Furosemide (1) Nebulized Platelet Lysate (1) Nebulized Saline (1) Nebulized Sterile Saline (1) Nebulized administration of RLF-100 or Placebo (1) Negative COVID Test Result - Hypothetical Scenario (1) Neonatal resuscitation with PPE for the prevention of SARS-Cov-2 infection (1) Neonatal resuscitation without PPE for the prevention of SARS-Cov-2 infection (1) NestaCell® (1) Neural network diagnosis algorithm (1) Neurocognitive assessment (1) Neuromuscular Blocking Agents (1) Neuromuscular Electrical Stimulation (1) Neuromuscular evaluation (1) Neutral writing control (1) Neutralizing antibodies (1) New QIAstat-Dx fully automatic multiple PCR detection platform (1) New screening strategy (1) Newsfeed function (1) Next generation Sequencing (NGS) analysis (1) Niclosamide suspension (1) Nicotinamide riboside (1) Nicotine 7 mg/ 24h Transdermal Patch - 24 Hour (1) Nicotine patch (1) Nigella sativa (1) Nil intervention (1) Nintedanib (1) Nintedanib 150 MG (1) Nintedanib 150 MG [Ofev] (1) Nitazoxanide 500 MG (1) Nitazoxanide 500Mg Oral Tablet (1) Nitazoxanide Tablets (1) Nitazoxanide and atazanavir/ritonavir (1) Nitazoxanide with ivermectin (1) Nitric Oxide 0.5 % / Nitrogen 99.5 % Gas for Inhalation (1) Nitric Oxide delivered via LungFit™ system (1) Nitric Oxide lozenges, 30 mg (1) Nitric Oxide-Continuous and Sessions (1) Nitric Oxide-Releasing Drug (1) Nitric Oxide-Sessions (1) Nivolumab (1) Nivolumab Injection (1) No Messaging (1) No Personal protective equipment (PPE) (1) No Racial Inequality Highlighting (1) No intervention (survey study for medical doctors). (1) No intervention - exposure is to COVID-19 (1) No intervention - quality of life measure (1) No intervention / Compare the difference in respiratory rate between H0 and H12 of the initiation of morphine between the control and interventional groups (1) No intervention / Evaluation of the ferritin and glycosylated ferritin by standard approved serological tests (1) No intervention on patients (1) No intervention, observational (1) No intervention, this is an observational study that uses validated questionnaires and qualitative interviews.. (1) No interventions (1) No interventions planned (1) No interverntion (1) No research related technology based social interactions (1) No special intervention (1) Non Intervention (1) Non applicable (1) Non interventional study (1) Non invasive visual acuity testing (1) Non-ACEI/ARB (1) Non-Interventional (1) Non-Mindfulness intervention (1) Non-contact ECG (1) Non-contact MCE system (1) Non-convalescent Plasma (control plasma) (1) Non-convalescent fresh frozen plasma (Standard plasma) (1) Non-enhanced CT scan of the chest (1) Non-hospitalization procedures (1) Non-interventional (1) Non-interventional study (1) Non-invasive cardiac imaging (1) Non-invasive red LLLT treatment to chest of patient. (1) Non-invasive ventilatory support (1) None - NA (1) Noninvasive ventilation treatment (1) Normal Saline 0.9% (1) Normal Saline Infusion + standard of care (1) Normal Saline intranasal (1) Normal saline 0.9% (1) Normal saline solution (NSS), Placebo - Phase 1 (1) Normal saline solution (NSS), Placebo - Phase 2 (1) Normal saline solution (NSS), Placebo, Day 189 - Phase 2 (1) Normal saline solution (NSS), Placebo, Day 21 - Phase 1 (1) Normal saline solution (NSS), Placebo, Day 21 - Phase 2 (1) Not bravery message (1) Novaferon (1) Novel laser inferometry test for CORONA virus (1) NuSepin® 0.1 mg (1) NuSepin® 0.2 mg (1) Nudge (1) Nursing care to reduce anxiety, fear and loneliness (1) Nutrition (1) Nutrition Consult and Protein Supplementation (1) Nutrition support (1) Nutritional assessment (1) Nutritional support system (NSS) (1) Nuvastatic (1) NİCaS (1) OCTAPLAS (1) OLO-1 Medical Molecular Sieve Oxygen Generator (1) OP-101 (1) Obesity (1) Observation for study group (1) Observation of behavior and COVID-19 infection will be conducted. (1) Observation of different courses of SARS-CoV-2 infection in different phases (acute vs. post-acute) and settings (1) Observation of patients with known, suspected, or at risk for COVID-19 infection (1) Observation only (1) Observational (registry) (1) Observational Study (1) Observational cohort study on the natural history of hospitalized SARS-COV-2 patients. (1) Observational measurement of biometric data. No change to health care provided. (1) Observational only (1) Observational study only (1) Obtainment of nasopharyngeal, oropharyngeal, buccal, nasal and saliva samples (1) Obvio-19 app (1) Occupational health workers (1) Octagam (1) Octagam 10% (1) Odd/Even birth year intervention groups (1) Olfaction testing (1) Olfactometry (1) Olfactory retraining (1) Omega 3/Nigella Sativa Oil (1) Omega 3/Nigella Sativa Oil/Anise seed capsule (1) Omega 3/Nigella Sativa Oil/Deglycyrrhizinated Licorice (1) Omega 3/Nigella Sativa Oil/Indian Costus (1) Omega 3/Nigella Sativa Oil/Quinine pills (1) Omega-3 Fatty Acid Supplement (1) Omegaven® (1) Omeprazole 20mg (1) Omnibiotic AAD (1) On-Line Survey (1) One COVID-19 vaccine candidate (TMV-083) administration - High dose (1) Online Intervention Grief COVID-19 (1) Online Intervention Mental Health COVID-19 (1) Online Questionnaires (1) Online Survey about Dietary and Lifestyle Habits (1) Online bibliotherapy programme (1) Online cognitive behavioral therapy (CBT) (1) Online instruction (1) Online questionnaire and interviews (1) Online support Group (1) Only Standard Treatment (1) Ophtamesone (1) Opt-in Recruitment Email (1) Opt-out Recruitment Email (1) Optical Coherence Tomography (OCT) (1) Optical coherence tomography angiography (1) Optimized Management of Covid-19 Positive Kidney Transplant Recipients: Single Center Experience from the Middle East (1) Optional blood completion (1) Optional questionnaire completion (1) Oral (1) Oral 25-Hydroxyvitamin D3 (1) Oral administration of Colchicine plus Herbal Phenolic Monoterpene Fractions (1) Oral fluid swab (1) Oral supplement enriched in antioxidants (1) Oral-B Mouth Sore mouthwash (1) Oropharyngeal Swab (1) Orthopaedic Surgical Procedures (1) Oseltamivir 75mg (1) Other (1) Others(No intervention) (1) Otilimab (1) Outpatient MRI (1) Ovotransferrin (1) Oxaloacetate Medical Food/Dietary Supplement (1) Oxidative Stress ELISA Kit (1) Oxygen Hood (1) Oxygen Therapy (1) Oxygen gas (1) Oxygen supply (1) Oxygen-ozone therapy, probiotic supplementation and Standard of care (1) Oxytocin (1) Ozanimod (1) Ozone auto-hemotherapy (1) Ozonized oil (HOO (1) P2Et (Caesalpinia spinosa extract) (1) PCL COV05 - COVID 19 Ag Rapid FIA test (Rapid Antigen Test) (1) PCR (1) PCR Value (1) PCR for COVID-19 (1) PCR, lung ultrasound (1) PD-1 blocking antibody+standard treatment (1) PEEP trial (1) PEP flute (1) PET-CT of 18F-FDG (1) PF-06650833 (1) PF-07304814 (1) PH94B (1) PHQ-9 (9-item Patient Health Questionnaire) (1) PHQ-9 (Patient Health Questionnaire) Depression Scale (1) PHQ-9 Depression Scale (1) PHR160 Spray (1) PLACEBO GROUP (1) PLN-74809 (1) POOL LAMP (1) POOL RT-PCR (1) PRAYER (1) PRO-SERO-COV (1) PROTECTIVE VENTILATION (1) PSC-04 (1) PSG (1) PSQI (1) PSS (Perceived Stress Scale) (1) PT-PCR test for SARS-CoV-2 (1) PT-Pal (1) PT-X and IMT (1) PTC299 (1) PTSD (1) PWV (1) Pacebo: Calcium citrate (1) Pacritinib (1) Pamrevlumab (1) Pandemic control measures (1) Paracetamol (1) Paraclinical examination (1) Part 1 - TL-895 (1) Part 2 - Placebo (1) Part 2 - TL-895 (1) Partially HLA-matched SARS-CoVSTs (1) Participate in a massive musical event (1) Passed infection of SARS-CoV-2 (1) Passive Microwave Radiometry (1) Patch, Nicotine (1) Patch, Placebo (1) Pathogen-specific aAPC (1) Patient Characteristics (1) Patient Education (1) Patient Health Questionnaire (PHQ-9) (1) Patient Health Questionnaire-9 (PHQ-9) (1) Patient Status Engine (1) Patient management suffering of coronavirus infection (1) Patient sampling (1) Patient with SAR-CoV-2 infection (1) Patient-centred advice on Telephone Consultation in TB Patients: (1) Patients admitted in Intensive Care Units (1) Patients admitted to Intensive Care Unit with SARS-CoV2 (1) Patients received standard of care treatment during hospitalization (1) Patients with the treatment agains COVID19 (1) Pectin (1) Peer Mentor Delivery (1) Peer Resilience Champion (1) Peginterferon Lambda-1a (1) Peginterferon beta-1a (1) Peginterferon lambda alfa-1a subcutaneous injection (1) Pegylated Interferon-α2b (1) Pegylated interferon lambda (1) Pembrolizumab (MK-3475) (1) Pemziviptadil (PB1046) (1) Percutaneous Coronary Revascularization for STEMI (1) Performance of the test antigenic and test RT-PCR (1) Performing of lung ultrasound (1) Performing routine care (clinical and paraclinical tests) (1) Peripheral Blood (1) Peripheral blood sampling (1) Peripheral venous ultrasound (1) Personal Exercise Intervention (1) Personal Protective Testing Booth (1) Personal behaviours (1) Personal freedom message (1) Personal protective equipment (1) Personal protective equipment (PPE) (1) Personal protective equipment from biological hazard (1) Personalized ambulatory training (1) Personalized health education (1) Phage Therapy (1) Philips Lumify Ultrasound System (1) Phlebotomy (1) Phone call (1) Phone call interview (1) Phone interviews (1) Phone-call screening and management by a medical student/general practitioner tandem (1) Phsyiotherapy (1) Physical Exercises (1) Physical Therapy (1) Physical Therapy Exercise (1) Physical and Cognitive Activity (1) Physical examination (1) Physical exercise (1) Physical exercise training (1) Physiological saline solution (1) Physiological serum (1) Physiology (1) Piclidenoson (1) Pilot a rapid SARS-CoV-2 testing strategy (1) Pioglitazone (1) Pioglitazone 30 mg (1) Pioglitazone 45 mg (1) Piperacillin-tazobactam (1) Piperacillin/tazobactam (1) Placebo (0.9% normal saline) (1) Placebo (1 tablet daily during 60 days) + Personal Protective Equipment (PPE) (1) Placebo (Methylcellulose) capsule (1) Placebo (PB0) (1) Placebo (PBO) (1) Placebo (Plasma-Lyte 148) (1) Placebo (carrier control) (1) Placebo (human albumin 1%) (1) Placebo (potato starch and magnesium stearate) (1) Placebo (saline) (1) Placebo (sodium chloride bufus, solvent for the preparation of dosage forms for injection 0.9%) (1) Placebo (two doses), priming (1) Placebo - Phase I (1) Placebo - Starch Powder Soft gels (1) Placebo 0.10 mg + 1.00 mg/kg (1) Placebo 0.20 mg + 2.00 mg/kg (1) Placebo 0.9% NaCl solution (1) Placebo 250 cc 24 hours continuous infusion for 15 days (1) Placebo Atazanavir (1) Placebo Atrovastatin (1) Placebo Control (1) Placebo Daclatasvir 60 mg (1) Placebo EC-18 (1) Placebo Group (1) Placebo Hydroxychloroquine (1) Placebo Nitazoxanide (1) Placebo Oil (1) Placebo PBMT/sMF (1) Placebo Ribavirin (1) Placebo Saline (1) Placebo Sofusbuvir + Daclatasvir 60 mg (1) Placebo Starch (1) Placebo Subcutaneous Solution (1) Placebo Tablet (1) Placebo Vaccine (1) Placebo booster (1) Placebo capsules (1) Placebo comparator: DW-NI (1) Placebo comparator: DW-NS (1) Placebo control (non-behavioral infographic) (1) Placebo control + best supportive care (1) Placebo for "Deficiency of Qi and Yang" (1) Placebo for "Deficiency of Qi and Yin" (1) Placebo for ABBV-47D11 (1) Placebo for Azithromycin (1) Placebo for Hydroxychloroquine (1) Placebo intravenous (1) Placebo mouthwash (water) (1) Placebo multiple (1) Placebo nebuliser solution (1) Placebo of FX06 (1) Placebo of Hydroxychloroquine (1) Placebo of LPV/r Tablets (1) Placebo of NICOTINE Transdermal patch (1) Placebo of excipient(s) will be administered (1) Placebo on a 0- and 14-day schedule (1) Placebo oral (1) Placebo oral capsule; From August 2020 'no additional treatment' (1) Placebo pMDI (1) Placebo patch (1) Placebo plus standard preventive measures (1) Placebo single (1) Placebo solution (1) Placebo to Match RDV (1) Placebo videos (1) Placebo- 0.10 mg/kg (1) Placebo- 0.20 mg/kg (1) Placebo- 1.00 mg/kg (1) Placebo- 2.00 mg/kg (1) Placebo-LDE phase 2 (1) Placebo/Aluminum Adjuvant of Inactivated SARS-CoV-2 vaccine (1) Placebo/Control (1) Placebo: Emtricitabine/tenofovir disoproxil Placebo (1) Placebo: Hydroxychloroquine (1) Placebo; 0.9% saline (1) Placenta-Derived MMSCs; Cryopreserved Placenta-Derived Multipotent Mesenchymal Stromal Cells (1) Plant Polyphenol (1) Plaquenil 200Mg Tablet (1) Plasma Donation (1) Plasma IgG levels (1) Plasma exchange (1) Plasma exchange and convalescent plasma (1) Plasma expansion with Ringer's Acetate (1) Plasma from COVID-19 convalescent patient (1) Plasma from a volunteer donor (1) Platelet count, platelet, mean platelet volume and platelet distribution Width in COVID-19 (1) Pleth variability index (1) Plethysmography & DLCO (1) Plitidepsin 1.5 mg/day (1) Plitidepsin 2.0 mg/day (1) Plitidepsin 2.5 mg/day (1) Pneumococcal vaccine (1) Point-of-Care Ultrasonography (POCUS) (1) Point-of-care test for SARS-CoV-2 (1) Polymorphism of the HSD3B1 (1) Polyoxidonium (1) Positive COVID Test Result - Hypothetical Scenario (1) Positive feedback (1) Post COVID-19 Functional Satus Scale (1) Post Traumatic Stress Disorder questionnaire (PTSD-8) (1) Post-intensive Care unit syndrome (1) Postpartum women under investigation for Coronavirus or diagnosed with COVID-19 (1) Postural Positioning (1) Povidine iodine nasal swabs (1) Povidone-Iodine 0.4% NI (1) Povidone-Iodine 0.5% (1) Povidone-Iodine 0.5% NI (1) Povidone-Iodine 0.5% NS (1) Povidone-Iodine 0.6% NI (1) Povidone-Iodine 0.6% NS (1) Povidone-Iodine 2% (1) Povidone-Iodine Solution 1.25% w/w [0.125% available iodine] USP (1) Povidone-iodine (1) Prasugrel (1) Prasugrel Hydrochloride 10 MG Oral Tablet (1) Prazosin (1) Prediction Market (1) Predictive factors for clinical response in patients with COVID-19. (1) Predictors adverse evolution (1) Predictors of health care provide (1) Prednisolone 5 mg (1) Prednisone tablet (1) Pregnant women under investigation for Coronavirus or diagnosed with COVID-19 (1) Premier Biotech COVID-19 IgG/IgM Rapid test Cassette (1) Presence of specific anti-SARS-CoV-2 antibodies (1) PreserVision AREDS formulation gel tabs (1) Preservative-free saline (1) Prevalence of COVID-19 (1) Preventive information (1) Previfenon® (1) Primary care (1) Primary care professionals reports of potential patient safety incidents, non-COVID-19 related (1) Primary exposure is hypoxia (no intervention) (1) PrimePro (1) Pro BNP , Vitamin D (1) Probiorinse (1) Probiotics (1) Probiotics (2 strains 10x10^9 UFC) (1) Problem-solving and relationship improvement intervention. (1) Produce prescription program (1) Progesterone 100 MG (1) Prognostic score (1) Progressive cycling exercise test to exhaustion (1) Progressive muscle relaxation (1) Project ECHO (1) Prolastin (1) Prolectin-M; a (1-6)-alpha-D-Mannopyranose class (1) Prolonged Exposure Therapy (1) Prolonged Proned Positioning (1) Prone (1) Prone Position (PP) (1) Prone Positioning (PP) (1) Prone decubitus (1) Prone position ventilation (1) Prone positioning (PP) (1) Prophylactic/Intermediate Dose Enoxaparin (1) Propofol (1) Propranolol Hydrochloride (1) Proprietary extract of Nerium oleander (1) Prosocial acts (1) Prospective Chart Review (1) Prospective oberservational registry (1) Prospective observation (1) Prospective study across two time-points examining the impact of viral mitigation protocols on mental health (1) Prospective study with two measurement points investigating the impact of viral mitigation protocols on parental burnout (1) Protocolised mechanical ventilation strategy (1) Prototype swab (1) Proxalutamide (1) Psychiatric counseling (1) Psycho-Social Questionnaire (1) Psycho-education (1) Psychoeducation (1) Psychoeducational intervention (1) Psychological and Behaviour Change Support (1) Psychological stress and adaptation at work score (PSAS) (1) Psychological treatment (1) Public Health England Gold Standard (1) Public space exposure (1) Pulmonary Function Tests (PFT) (1) Pulmonary Physiotherapy Techniques (1) Pulmonary Vascular Permeability Index (1) Pulmonary and Motor Rehabilitation (1) Pulmonary function testing (1) Pulmonary function tests (1) Pulmonary tele-rehabilitation (1) Pulmonary ultrasound (1) Pulmozyme/ Recombinant human deoxyribonuclease (rh-DNase) (1) Pulse Oximeter (1) Pulse oximetry (1) Pyridostigmine Bromide (1) Pyronaridine-Artesunate (1) Pyronaridine-artesunate (1) Q-NRG Metobolic Cart Device (1) Q16 testing (1) QUANTIFERON (1) QazCovid-in® - COVID-19 inactivated vaccine (1) QuadraMune(TM) (1) Qualitative interviews (in 40 patients : 20 with COVID-19 and 20 without COVID-19) (1) Quality of Life (1) Quality of life assessment (1) Quality of life promotion (1) Quantitative IgG Test (1) Quantitative analysis of SARS-CoV-2 antibodies (1) Quantitative analysis of anti-SARS-CoV-2-antibodies (1) Quantitative and qualitative assessments of mental health (1) Quantra System (1) Quasistatic pressure-volume curve (1) Quercetin (1) Quercetin Phytosome (1) Quercetin Prophylaxis (1) Quercetin Treatment (1) Querying the INSEE database (1) Questionaire (1) Questionnaire : Preparedness for Caregiving Scale (1) Questionnaire and interview (1) Questionnaire by phone call (1) Questionnaire collection (1) Questionnaire completion (1) Questionnaire for evaluation of confinement on deviant sexual fantasies (1) Questionnaire forms (1) Questionnaire including validated tools such as Patient Health Questionnaire (PHQ-9), the 7-item Generalised Anxiety Disorder (GAD- 7), the 7-item insomnia severity index (1) Questionnaire with precaution information (1) Questionnaire, phone call (1) Questionnaire, same tools as before, with inclusion of PCL5 questionnaire too. (1) Questionnaire-based observational study (1) Questionnaires for specific phobia (1) Questionnaires on psychological quality of life (1) Questionnaires, spirometry (1) Questionnary (1) Quetiapine (1) Quidel Sofia SARS Antigen FIA (1) Quinquina-Stevia/Azythromycin (1) RAAS inhibitor [continued standard of care] (1) RAPA-501-Allo off-the-shelf Therapy of COVID-19 (1) RAPID-3 (1) RBA-2 (1) RBT-9 (90 mg) (1) RD-X19 (1) RDV (1) RECHARGE (1) REGN10933 + REGN10987 (1) REGN10933+REGN10987 (1) RESP301, a Nitric Oxide generating solution (1) REmotely Monitored, Mhealth (REMM) supported High Intensity Interval Training (HIIT) (1) RIA-device (Remote Investigation and Assessment) (1) RPH-104 80 mg (1) RT PCR SARS-CoV-2 (1) RT-PCR Covid-19 (1) RT-PCR SARS-Cov2 (1) RT-PCR and antibody testing (1) RT-qPCR test (1) RUTI® vaccine (1) Racial Inequality Highlighted (1) Racial/Ethnic Frame (1) Radiological Detection (1) Radiotherapy (1) Raman analysis of saliva, characterization of the Raman database and building of the classification model (1) Ramelteon 8mg (1) Ramipril 2.5 MG Oral Capsule (1) Random Donor Plasma (1) Randomized booster (1) Rapamycin (1) Rapid Antigen Test (1) Rapid Diagnostic Test vs PCR (1) Rapid Onsite COVID-19 Detection (1) Rapid Pathogen Detection (1) Rapid detection test (1) Rapid molecular test (1) Rarefaction (1) Rayaldee 30Mcg Extended-Release (ER) Capsule (1) Razuprotafib (1) Razuprotafib Subcutaneous Solution (1) Reading a Book (1) Recombinant Bacterial ACE2 receptors -like enzyme of B38-CAP (rbACE2) (1) Recombinant Bacterial ACE2 receptors -like enzyme of B38-CAP (rbACE2) plus Aerosolized 13 cis retinoic acid (1) Recombinant Human Interferon α2b Spray (1) Recombinant Interferon Alfa-2b (1) Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector) -placebo (1) Recombinant human angiotensin-converting enzyme 2 (rhACE2) (1) Recombinant human interferon α1β (1) Recombinant human plasma gelsolin (Rhu-pGSN) (1) Recombinant new coronavirus vaccine (CHO cell) group (1) Recombinant new coronavirus vaccine (CHO cells) placebo group (1) Recombinant novel coronavirus vaccine (Adenovirus type 5 vector) (1) Recombinase aided amplification (RAA) assay (1) Reference: Favipiravir 200 mg (Avigan) (1) Referral card (1) Regadenoson (1) Registery Data Collection (1) Regular Inpatient Medical Care (1) Rehabilitation (1) Rehabilitation by Concentric exercises (1) Rehabilitation by Eccentric exercises (1) Rehabilitation exercise protocol (1) Rehabilitation-focused program (1) Reinforcement learning message delivery (1) Relation between frailty and clinical outcomes in elderly patients with COVID-19. (1) Remain COVID Free SSI (1) Remdesivir (RDV) (1) Remdesivir-HU (1) Remimazolam (1) Remote Automated Monitoring System (1) Remote Cognitive Behavioral Therapy for Insomnia (1) Remote Ischemic Conditioning (1) Remote Problem Management Plus (1) Remote consultation (1) Remote controlled exercise (1) Remote pulmonary rehabilitation (1) Removal of dead space filter (1) Renin-angiotensin system inhibitors (1) Repeat SARS-CoV-2 IgG antibodies at 45-65 days (1) Reporting of anosmia, ageusia and other clinical symptoms (1) ResCure™ (1) Resilience Program (1) Respiratory Exercise Training (1) Respiratory Mechanics (1) Respiratory Training (1) Respiratory and psychological rehabilitation (1) Respiratory infections (1) Respiratory mechanics measurement (1) Respiratory monitoring (1) Respiratory muscles ultrasound (1) Respiratory physiotherapy (1) Respiratory rehabilitation (1) Respiratory rehabilitation program (RR). (1) Respiratory symptoms, symptoms of anxiety and depression, and post-traumatic stress screening (1) Respiratory tele-rehabilitation program (TRR). (1) Resting 12 lead ECG (1) Resveratrol (1) Resveratrol Placebo (1) Retrospective case-control analysis (1) Retrospective data collection (1) Reverse transcription polymerase chain reaction (1) Reverse-transcription polymerase chain reaction (RT-PCR) (1) Review of medical patient file (1) Reward Re-Training (1) RhACE2 APN01 (1) Rhea Health Tone® (1) Ringer solution (1) Ringer's lactate (1) Rintatolimod (1) Risankizumab (1) Risk factors (1) Ritonavir (1) Ritonavir+Oseltamivir (1) Ritonavir/lopinavir (1) Rivaroxaban 10 MG (1) Rivaroxaban 2.5 MG (1) RoActemra iv (1) RoActemra sc (1) Robot Assisted Percutaneous Cardiovascular Intervention (1) Robotic therapy (1) Rosuvastatin (1) Routine care (no SARS-CoVSTs) (1) Routine standard of care (1) Rt PCR (1) Ruconest (1) Ruxolitinib 5 MG (1) Ruxolitinib administration (1) Ruxolitinib plus simvastatin (1) SAMBA II (Diagnostic for the Real World) (1) SAR443122 (1) SARILUMAB (1) SARS-CoV 2 RNA PCR Semen (1) SARS-CoV 2 RNA PCR Urine (1) SARS-CoV-2 Ab (1) SARS-CoV-2 Antibody Analysis (1) SARS-CoV-2 IgG (1) SARS-CoV-2 IgG Antibody Testing Kit (1) SARS-CoV-2 S1/S2 IgG (1) SARS-CoV-2 Specific T Cells (1) SARS-CoV-2 and/or MIS-C Exposure (1) SARS-CoV-2 antibody based IVIG therapy (1) SARS-CoV-2 antibody immunoassays (1) SARS-CoV-2 antibody test (1) SARS-CoV-2 antibody testing (1) SARS-CoV-2 convalescent plasma treatment (1) SARS-CoV-2 inactivated vaccine (1) SARS-CoV-2 non-immune Plasma (1) SARS-CoV-2 plasma (1) SARS-CoV-2 questionnaire survey (1) SARS-CoV-2 rS - Phase 1 (1) SARS-CoV-2 rS/Matrix M1-Adjuvant (1) SARS-CoV-2 rS/Matrix-M Adjuvant - Day 189 - Phase 2 (1) SARS-CoV-2 rS/Matrix-M Adjuvant - Phase 1 (1) SARS-CoV-2 rS/Matrix-M Adjuvant, Day 0 - Phase 1 (1) SARS-CoV-2 rS/Matrix-M Adjuvant, Day 0 - Phase 2 (1) SARS-CoV-2 rS/Matrix-M Adjuvant, Days 0 and 21 - Phase 2 (1) SARS-CoV-2 rapid diagnostic test (COVID-PRESTO® IgM/IgG, AAZ, Boulogne-Billancourt, France) (1) SARS-CoV-2 research in nasopharyngeal swab, sperm and serologics (1) SARS-CoV-2 serological assessment (IgG) (1) SARS-CoV-2 serology (1) SARS-CoV-2 testing on the Eppendorf Thermal Cycler PCR system using self-collected saliva as the specimen (1) SARS-CoV-2 vaccine (inactivated) (1) SARS-CoV-2 vaccine formulation 1 with adjuvant 1 (1) SARS-CoV-2 vaccine formulation 1 with adjuvant 2 (1) SARS-CoV-2 vaccine formulation 2 with adjuvant 1 (1) SARS-CoV-2 vaccine formulation 2 with adjuvant 2 (1) SARS-CoV-2 vaccine formulation 2 without adjuvant (1) SARS-CoV-2 viral composition (1) SARS-CoV-2-test (1) SARS-CoV2 Autoantibody detection (1) SARS-CoV2 Infection (1) SARS-CoV2 nasal swab (1) SARS-CoV2 serum antibody testing (1) SARS-Cov-2 infection (1) SARSCoV2 Convalescent Plasma (1) SBI-101 (1) SCB-2019 (1) SCB-2019 with AS03 adjuvant (1) SCB-2019 with CpG 1018 adjuvant plus Alum adjuvant (1) SCD (1) SCH Intervention (1) SECRET questionnaire (1) SELF-BREATHE (1) SF12, EQ-5D-5L and work status standardized quantitative assessments (1) SHG (1) SHINGRIX (Zoster Vaccine REcombinant, Adjuvanted) (1) SIR1-365 (1) SLEDD with a L-MOD (1) SMS message support (1) SMS-based support (1) SNDX-6352 (1) SNG001 (1) SNO (1) SOC + IFX-1 (1) SOC + Intravenous Famotidine (1) SOC plus 15mg/kg EB05 IV (1) SOC plus Placebo IV (1) SPEQ (Specific Psychotic Experiences Questionnaire) - Paranoia and Grandiosity Subscales (1) SPIN-CHAT Program (1) SSE educational intervention (1) STC-19 score (1) STI-5656 (1) STP + COVID-19 Convalescent Plasma (CP) (1) STP + Standard Plasma (SP) (1) Saline Control (1) Saline Nasal Irrigation (1) Saline containing 1% Human serum albumin(solution without UC-MSCs) (1) Saline nasal and throat spray (1) Saline oral/nasal rinse (1) Saline with Baby Shampoo Nasal Irrigation (1) Saline-sodium citrate (SSC) buffer (1) Saliva Assay (1) Saliva and NPS test (1) Saliva based assay: crude RNA extraction (1) Saliva sample (1) Saliva specimen (1) Saliva test kit (1) Saliva-based testing (1) Sample (1) Sample Collection/Performance Evaluation (A) (1) Sample Collection/Performance Evaluation (B) (1) Sampler skills (1) Sampling (1) Sampling (EDTA blood, pharyngeal and nose swabs, bronchoalveolar lavage ,urine) (1) Sampling of SARS-CoV-2 RNA from nasopharyngeal swab specimen or saliva collected via Salivette Cortisol (1) Sampling of tissue (1) Sampling salivary (1) Sarilumab 200 MG/1.14 ML Subcutaneous Solution [KEVZARA] (1) Sarilumab 400 MG/2.28 ML Subcutaneous Solution [KEVZARA] (1) Sarilumab Prefilled Syringe (1) Sarilumab SAR153191 (1) Sars-Cov-2 serology (1) Sars-Cov2 serology (1) Satisfaction evaluation (1) Savicell's ImmunoBiopsy™ (1) Scanning Chest X-rays and performing AI algorithms on images (1) Schirmer Test I (1) Screening test for covid ( RT PCR and CT Chest) (1) Secukinumab 150 MG/ML Subcutaneous Solution [COSENTYX] (1) Self Study (1) Self measurement with pulse oximeter (1) Self-Compassion for Chronic Pain Virtual Group Treatment Program (1) Self-Help Therapy (1) Self-acupressure (1) Self-administered questionnaires (1) Self-collected, home-based testing (1) Self-focused acts (1) Self-guided exercises (1) Self-help booklet (1) Self-interest message (1) Self-management booklet (SWitCh: Stay well during COVID-19) (1) Self-prone position recommendation (1) Self-questionnary (1) Semen Qualitative Analysis (1) Semi-structured telephone questionnaire (1) Sending thorax ct video images via smartphone applications (1) Senicapoc (1) Sensbiosys (1) SensiumVitals wearable sensor (1) Sequencing (1) Seraph®-100 Microbind® Affinity Blood Filter (1) Serelogy testing, RT PCR (1) Serial seroconversion measurements in hospital employees during the COVID-19 pandemic (1) Serologic SARS-CoV-2 screening (1) Serologic assays for antibodies to SARS-CoV-2 (1) Serologic immunoassays to SARS-CoV-2 antibodies (1) Serologic testing (1) Serological Assay or IgG for SARS-CoV-2 (1) Serological analyses to be lead on a pre-existing biobank (1) Serological screening for IgG and IgM antibodies against COVID-19 (1) Serological test and phone interview (1) Serological test for COVID-19. (1) Serological testing (1) Serological tests will be applied on patients blood sampling (1) Serology (1) Serology SARS-CoV2 (1) Serology Test (1) Serology for Covid-19 (1) Serology test follow-up (1) Seroprevalence of SARS-CoV-2 infection in patients with HIV infection (1) Serum SARs COV 2 IGg screening in health care workers (1) Serum protein level analysis (1) Serum test (1) Serum tube collection (1) Serum zinc, vitamin d vitamin b12 levels . (1) Severe Acute Respiratory Syndrome CoronaVirus 2 detection (1) Sevoflurane inhalant product (1) Sham (1) Sham Device Treatment (1) Sham intervention (1) Sham irradiation (1) Shanshamani Vati Plus (1) Shared Decision Making (1) Shock-dependent hydrocortisone (1) Sildenafil (1) Sildenafil citrate tablets (1) Silymarin (1) Simha Kriya (1) Simple chest tomography (1) Simulation Intervention (1) Simulation of Repurposed Drugs for COVID-19 (1) Single fraction whole lung radiotherapy (1) Single high dose vitamin D (1) Single passive leg movement (1) Sirolimus 1 MG/ML (1) Sirukumab (1) Sitagliptin (1) Six Minute Walk Test (6MWT) (1) Six-minute walk test (6MWT) (1) Six-month ARV dispensing (1) Skin biopsy (1) Slef questionnaires fulfilment (1) Smartphone-based voice and self-reported symptom collection (1) Social Distancing Advertisements (1) Social media & news consumption (1) Socialization (1) Sodium Bicarbonate (1) Sodium Bicarbonate 150Meq/L/D5W Inj (1) Sodium Chloride 9mg/mL (1) Sodium Nitrite (1) Sodium bicarbonate (1) Sodium chloride (1) Sofosbuvir (1) Sofosbuvir 400 MG plus Daclatasvir 200mg (1) Sofosbuvir and Ledipasvir (1) Sofosbuvir ledipsavir (1) Sofosbuvir plus Ledipasvir (1) Sofosbuvir/Daclatasvir (1) Sofosbuvir/daclatasvir (1) Software Messaging (1) Sofusbuvir + Daclastavir 60 mg (1) Soluble Urokinase Plasminogen Activator Receptor (1) Solution-Focused Support Program (1) Sonclot Coagulation and platelet function Analyzer SCP1, Sienco, USA (1) Sonoclot (1) Soterix taVNS model 0125-LTE Stimulator - Active-Active Group (1) Soterix taVNS model 0125-LTE Stimulator - Sham-Active Group (1) Spartan COVID-19 System (1) Spartan COVID-19 Test (1) Spartan COVID-19 v2 System (1) Spartan Cube Point-of Care Covid-19 test (1) Specific anti-SARS-CoV-2 antibodies (1) Specimen Collection (1) Speed of Processing Training (1) Sphenopalatine Ganglion Block with Local Anesthetic (1) Sphenopalatine Ganglion Block with Placebo (Isotone NaCl) (1) Spironolactone 100mg (1) Sputum analysis (1) St. George's Respiratory Questionnaire (SGRQ) (1) Staff Wellbeing Centres (1) Stakeholder of TIP-OA Program (1) Standar medical treatmen (1) Standar of care (1) Standard (specific) therapy for COVID-19 (1) Standard 12-lead ECG, NT-proBNP, echocardiography (1) Standard COVID-19 care (1) Standard COVID-19 therapies (1) Standard Care Plus Monitoring (1) Standard Care Therapy (1) Standard Donor Plasma (1) Standard Mask (1) Standard Of Care (SOC) (1) Standard Of Care (SOC) + Placebo (1) Standard Oxygen Delivery System (1) Standard Plasma (FFP) (1) Standard Public Health measures (1) Standard Therapy Protocol (STP) (1) Standard Treatment (1) Standard Ventilation Strategy (1) Standard administration of oxygen flow (1) Standard care delivered in the isolation hospitals. (1) Standard care therapy (1) Standard charity resources (1) Standard interface (1) Standard medical care (1) Standard of Care (Intravenous access) (1) Standard of Care (SOC) + ANG-3777 (1) Standard of Care (SOC) and Colchicine+Rosuvastatin (1) Standard of Care thromboprophylaxis (1) Standard of care (Paracetamol) (1) Standard of care (SOC) plus placebo (1) Standard of care for SARS-CoV-2 infection (1) Standard of care management (1) Standard of care therapies (1) Standard of care therapy (1) Standard of care. (1) Standard oxygen therapy (1) Standard screening strategy (1) Standard supportive care (1) Standard therapeutic protocol (1) Standard therapy (1) Standard therapy for COVID-19 according to the stablished hospital protocols. (1) Standard therapy recommended by the Ministry of Health of the Russian Federation and Dalargin inhalation (1) Standard therapy recommended by the Ministry of Health of the Russian Federation and Dalargin intramuscular injection (1) Standard therapy recommended by the Ministry of Health of the Russian Federation and Dalargin intramuscular injection combined with Dalargin inhalation (1) Standard therapy recommended by the Ministry of Health of the Russian Federation. (1) Standard treatment according to the Clinical protocols (1) Standard treatment for COVID-19 (1) Standard-of-care (1) Standard-of-care treatment (1) Standard-titer Convalescent COVID-19 plasma (CCP2) (1) Standardised questionnaires (1) Standardized crisis management and coping protocol plan toward Coronavirus disease 2019 (COVID-19) (1) Standards of Care (1) State-trait anxiety inventory scale (1) Statins (Cardiovascular Agents) (1) Stem Cell Educator-Treated Mononuclear Cells Apheresis (1) Stem Cell Product (1) Sterile Normal Saline for Intravenous Use (1) Sterile Water for Injection (1) Sterile normal saline (0.9%) (1) Stimulation test with arginine infusion in order to verify the possible existence of damage to the beta cell function induced by COVID-19 infection (1) Stool collection (1) Stool collection or fecal swab (1) Stools (1) Storage of operating waste (1) Stress and emotion management (1) Study A (1) Study Arm (1) Study B (1) Study C (1) Study D (1) Study Group (1) Study of immune-mediated mechanisms in patients tested positive for SARS-CoV-2 (1) Subacute rehabilitation (1) Sublingual Methylene blue (1) Sudarshan Kriya Yoga (SKY) (1) Sulfonatoporphyrin(TPPS) plus Sunlight exposure. (1) Sulfur hexafluoride lipid-type A microspheres (1) Sulodexide (1) Supine Positioning (1) Supine position (1) Support treatment (1) Supportive Therapy (1) Supportive Therapy SSI (1) Supportive tratment (1) Surfactant (1) Surfactant assessment (1) Surge capacity (1) Surgery (1) Surgery: Dynamic Hip Screw, hemiarthroplasty, hip replacement, intramedullary nail (1) Surgical Mask (1) Surgical face mask use only (1) Surgical facial mask (1) Surgical procedures performed under general anesthesia (1) Survey Group (1) Survey administration (1) Survey and Questionnaire (1) Survey to assess Post traumatic stress and anxiety at inclusion and 6 months later (1) Surveys (1) Susceptibility to infection (1) Suspension or Maintenance of Angiotensin Receptor Blockers and Angiotensin-converting Enzyme Inhibitors (1) Swab (1) Swallowing evaluation with the EAT-10 and the volume-viscosity swallowing test (V-VST) (1) Symptom Survey (1) Symptom and Exposure Surveys (1) Symptomatic drugs (1) Symptomatic treatment (paracetamol or best symptomatic treatment based on doctor recommendations) (1) Symptomatology, Treatment. daily Activities and Anxiety for Cardiovascular patients Survey (STRATA) (1) Symptoms entered into the CovidX application (1) Symptoms questionnare (1) Synthetic neutralising antibodies (1) Systemic indirect endovenous ozone therapy (1) T memory cells and NK cells (1) T-Detect™ SARS-CoV-2 Assay (1) T-cell receptor (TCR) repertoire (1) T3 solution for injection (1) T89 (1) T89 capsule (1) TAK-671 (1) TAK-671 Placebo (1) TAK-919 (1) TAK-981 (1) TAPE-Software (1) TAVR or SAVR (1) TCC-COVID mHealth solution (1) TCM prescriptions (1) TD139 (1) TDR (1) TEM-tPA (1) TJ003234 (1) TLRs activation measurement (1) TM5614 (1) TNKase (1) TOF protocol (1) TRV027 (1) TXA127 (1) Tacrolimus (1) Tafenoquine Oral Tablet (1) Taking biological samples (1) Tap water (1) Taste and olfactory function evaluation (1) Tear Collection (1) Tears swab (1) Technology based social interactions (1) Tele-Pulmonary rehabilitation (1) Tele-Yoga Therapy (1) Tele-delivered psychological intervention (1) Tele-interventions related to diabetes management and mental well-being (1) Tele-medicine platform (1) Tele-yoga therapy (1) Teleconsultation either by phone or by computer consultation (1) Telehealth (1) Telehealth coaching sessions (1) Telehealth monitoring (1) Telehealth phone calls (1) Telemedicine to remote outpatient visit in bariatric patient (1) Telemedicine visit (1) Telephone follow-up (1) Telephone interview (1) Telephone survey (1) Telephonic interview during the Italian lockdown. (1) Telephonic medical visit (1) Telepsychoeducation (1) Telepsychoeducation with personalized videos (1) Telepsychoeducation without personalized videos (1) Telerehabilitation-Based (1) Telesimulation (1) Telmisartan 40Mg Oral Tablet (1) Telmisartan 40mg (1) Telmisartan arm will receive 80 mg Telmisartan twice daily plus standard care. (1) Temporarily holding the RAAS inhibitor [intervention] (1) Ten-days oseltamivir (1) Tenecteplase (1) Tenofovir/ Emtricitabine ( 300 mg / 200 mg daily during 60 days) + Personal Protective Equipment (PPE) (1) Test Group: experimental - UVC Therapy applied (1) Test PCR (1) Test for SARS-CoV-2 (1) Test: Favipiravir 200 mg (LOQULAR) (1) TestNPass (1) Tested for SARS-CoV-2 (regardless of the result) (1) Testing Sensitivity for SARS-CoV-2 Virus in Symptomatic Individuals (1) Testing for SARS-CoV-2 (1) Testing of SARS-CoV-2 antibodies (1) Testing procedure for Binding antibodies (1) Tetrandrine (1) Text material for psychoeducation and audio for relaxation techniques (1) Thalidomide (1) The POP02 study is collecting bodily fluid samples (i.e., whole blood, effluent samples) of children prescribed the following drugs of interest per standard of care: (1) The PREPARE program (1) The Vie Scope laryngoscope (1) The control group will not receive hydroxychloroquine (1) The demographic, clinical, laboratory, and instrumental data (1) The psychosocial effects of COVID-19 pandemic on dental professionals (1) The standard Macintosh laryngoscope (1) The standard of care (1) The standard therapy (1) The study does not required (1) The use of the MentalPlus® digital game for assessment and rehabilitation of cognitive function after remission of the symptoms of COVID-19 (1) The usual treatment (1) Therapeutic Anticoagulation (1) Therapeutic Exercise and Education (1) Therapeutic Plasma Exchange (TPE) (1) Therapeutic Plasma exchange (1) Therapeutic plasma exchange (1) Therapeutic plasma exchange (TPE) (1) Therapist Guided E-Therapy (1) Therapy Intervention (1) There is no intervention (1) There is no intervention in this study (1) Thermography (1) Thiazide or Thiazide-like diuretics (1) This is an online survey with no intervention. (1) Thoracic CT Scan (1) Thorax CT (1) Thoraxic computed tomography (1) Three doses of high-dose recombinant SARS-CoV-2 vaccine (CHO Cell) at the schedule of day 0, 14, 28 (1) Three doses of high-dose recombinant SARS-CoV-2 vaccine (Sf9 Cell) at the schedule of day 0, 14, 28 (1) Three doses of middle-dose recombinant SARS-CoV-2 vaccine (CHO Cell) at the schedule of day 0, 14, 28 (1) Three doses of placebo at the schedule of day 0, 14, 28 #High-dose group# (1) Three doses of placebo at the schedule of day 0, 14, 28 #middle-dose group# (1) Three doses of placebo at the schedule of day 0, 14, 28(high-dose group) (1) Threshold IMT device (1) Throat swab sample for measuring current infection with SARS-CoV-2 (1) Thrombin Generation Assay (TGA) (1) Thrombin generation test assay (1) Thrombomodulin Modified Thrombin Generation Assay (TGA-TM) (1) Thromboprophylaxis (1) Thymosin+standard treatment (1) Thyroidectomy (1) Ticagrelor (1) Tice® BCG (for intravesical use) BCG LIVE strain of the BCG (Merck) vaccine (1) Tigerase® and best available care (1) Tinzaparin or unfractionated heparin (1) Tirofiban Injection (1) Tissue plasminogen activator (1) Titanium blood test (1) To assess for development of IgG antibodies against SARS-CoV2 (1) Tociliuzumab (1) Tocilizumab +/- ruxolitinib (stages 2b/3) (1) Tocilizumab 180 MG/ML (1) Tocilizumab 20 MG/ML Intravenous Solution [ACTEMRA] (1) Tocilizumab 20 MG/ML Intravenous Solution [ACTEMRA]_#1 (1) Tocilizumab 20 MG/ML Intravenous Solution [ACTEMRA]_#1 (2 doses) (1) Tocilizumab Injection [Actemra] (1) Tocilizumab Prefilled Syringe (1) Tocilizumab and Ruxolitinib (Advanced stage 3) (1) Tomeka® (1) Toraymyxin PMX-20R (PMX Cartridge) (1) Toremifene (1) Tracheal intubation and cardiopulmonary resuscitation (1) Tracheostomy (1) Tracheostomy with aerosol box in COVID-19 positive patients (1) Tracheotomy (1) Tradipitant (1) Traditional Chinese Medicine Prescription (1) Traditional Proning Arm (1) Traditional antirheumatic drugs (1) Training clinicians in basic critical care and the management of severe COVID-19 cases (1) Training for Awareness, Resilience, and Action (TARA) (1) Training load (1) Training of youth, community health assistants and community health workers. (1) Training session adressing information and health literacy (1) Training video on anxiety, fear and loneliness in the COVID-19 environment. (1) Tramadol (1) Tranexamic acid tablets (1) Trans Sodium Crocetinate (1) Transcendental Meditation (1) Transcutaneous Auricular Vagus Nerve Stimulation (1) Transfer Package from CI Therapy (1) Transfusion of COVID-19 convalescent plasma (1) Transfusion of SARS-CoV-2 Convalescent Plasma. (1) Transfusion of standard Plasma. (1) Transitional Online Peer Support Group (n=20) (1) Transparent mask (1) Transplant patient (1) Transpulmonary pressure measurements (1) Transpulmonary thermodilution (1) Transthoracic echocardiogram (TTE) (1) Trauma Informed Psychotherapy (1) Trauma Informed Yoga (1) Trauma-informed yoga video recording (1) Travelan OTC (1) Treamid (1) Treatment and prophylaxis (1) Treatment as usual (1) Treatment as usual vitamin D (1) Treatment for COVID-19 (1) Treatment group (1) Treatment group: will receive a combination of Nitazoxanide, Ribavirin and Ivermectin for a duration of seven days : (1) Treatment with Dexmedetomidine (1) TriCor® 145mg tablets (1) Triazavirin (Riamilovir) (1) Trier Social Stress Test (1) Trimodulin (1) Trust in science message (1) Tuberculin test (1) Two COVID-19 vaccine candidate (TMV-083) administrations - High dose (1) Two COVID-19 vaccine candidate (TMV-083) administrations - Low dose (1) Two dose ChAdOx1 nCoV-19/Covishield 0.25mL & 0.5mL (1) Two dose ChAdOx1 nCoV-19/Covishield 0.5mL (1) Two dose MenACWY vaccine (1) Two dose MenACWY vaccine min. 4 weeks apart (1) Two doses of commercial scale inactivated SARS-CoV-2 vaccine at the schedule of day 0,14 (1) Two doses of high dosage inactivated SARS-CoV-2 vaccine at the emergency vaccination schedule (1) Two doses of high dosage inactivated SARS-CoV-2 vaccine at the routine vaccination schedule (1) Two doses of high dosage inactivated SARS-CoV-2 vaccine at the schedule of day 0,28 (1) Two doses of high-dose recombinant SARS-CoV-2 vaccine (CHO Cell) at the schedule of day 0, 14 (1) Two doses of high-dose recombinant SARS-CoV-2 vaccine (Sf9 Cell) at the schedule of day 0, 28 (1) Two doses of medium dosage inactivated SARS-CoV-2 vaccine at the emergency vaccination schedule (1) Two doses of medium dosage inactivated SARS-CoV-2 vaccine at the routine vaccination schedule (1) Two doses of middle-dose recombinant SARS-CoV-2 vaccine (CHO Cell) at the schedule of day 0, 14 (1) Two doses of middle-dose recombinant SARS-CoV-2 vaccine (Sf9 Cell) at the schedule of day 0, 28 (1) Two doses of pilot scale inactivated SARS-CoV-2 vaccine at the schedule of day 0,14 (1) Two doses of pilot scale inactivated SARS-CoV-2 vaccine at the schedule of day 0,14 in elderly (1) Two doses of placebo at the emergency vaccination schedule (1) Two doses of placebo at the routine vaccination schedule (1) Two doses of placebo at the schedule of day 0, 14 #High-dose group# (1) Two doses of placebo at the schedule of day 0, 14 #middle-dose group# (1) Two doses of placebo at the schedule of day 0, 28(high-dose group) (1) Two doses of placebo at the schedule of day 0, 28(middle-dose group) (1) Tympanic Temperature (1) Typical surgical covered mask (1) UB-612 (1) UCMSCs (1) ULTRAPROTECTIVE VENTILATION (1) UNI911 INHALATION (1) UNIKINON (Chloroquine phosphate) 200mg tablets (1) UTTR1147A (1) UTTR1147A-matched Placebo (1) UV Light Treatment (1) Ulinastatin (1) Ultra Brief Online Mindfulness-based Intervention (1) Ultra-Low-dose radiotherapy (1) Ultrasonography (1) Ultrasound lung imaging as part of FAST+ evaluation (1) Ultrasound of the lower limbs (1) Umbilical Cord Lining Stem Cells (ULSC) (1) Umbilical Cord Mesenchymal Stem Cells (1) Umbilical Cord Mesenchymal Stem Cells + Heparin along with best supportive care. (1) Umbilical cord Wharton's jelly-derived human (1) Umbilical cord derived mesenchymal stem cells (1) Umifenovir (1) Unavailable COVID Test Result - Hypothetical Scenario (1) Unfractionated Heparin IV (1) Unfractionated heparin SC (1) Unfractionated heparin nebulized (1) Unified Protocol for COVID-19 Parenting Stress (UP-COVID) (1) Uniform random message delivery (1) Unsupervised physical activities (1) Use of Facetime with child and parents during induction (1) Use of mobile application (1) Use of social media during COVID-19 (1) Use of the pinpointIQ solution (physIQ, Inc.) (1) Use of virus (Covid-19) genome sequence report to inform infection prevention control procedures (1) Usual Care Only (1) Usual antibiotic treatment (1) Usual care positioning with no instructions (1) V-SARS (1) V/Q SPECT-CT (1) V/Q Vest (1) V590 (1) V591 (1) VC (1) VCPM (1) VESTA respirator (1) VIB7734 (1) VIR-7831 (1) VITROS Anti-SARS-CoV-2 IgG test (1) VLA2001 (1) VR for psychoeducation and relaxation (1) VXA-CoV2-1 (1) Vacciantion status in health care workers (1) Vaccinated with polio vaccine (IPV) (1) Vaccine Therapy (1) Vaccine coverage assessment (1) Vaginal fluid Covid-19 PCR test (1) Validation of the LAMP assays (1) Validation of the NGS method (1) Validation of the POCT Antigen tests (1) Valproate (1) Valsartan (Diovan) (1) Vascular surgery (1) Vehicle + Heparin along with best supportive care (1) Vehicle Control (1) Venepuncture (1) Venous Draw & Testing (1) Venous blood was collected for biochemistry testing (1) Venous blood was collected for biochemistry testing. (1) VentaProst (inhaled epoprostenol delivered via a dedicated delivery system) (1) Verapamil (1) Veru-111 (1) VibroLUNG (1) Video Chat + Basic Feedback (1) Video Chat +Personalized Feedback (1) Video Dance classes (1) Video about safety and effectiveness of adult seasonal flu vaccination (1) Video based aerobic exercise (1) Video based exercise (1) Video-Based (1) Video-Based intervention (1) Videofluoroscopic Swallowing Study (VFSS) (1) Videofluoroscopy (1) Vie Scope laryngoscopy (1) Vielight RX Plus (1) Views and experiences of health care professionals working in intensive care units during the COVID-19 pandemic (1) Viral Specific T-cells (VSTs) (1) Virtual Assistant first, then Human Coach (1) Virtual Care and Remote Automated Monitoring (1) Virtual Care at Home (1) Virtual Family-Based Treatment (1) Virtual Group Exercise (1) Virtual Group Intervention (1) Virtual Peer Support Platform (1) Virtual Reality (1) Virtual reality therapy first (1) Virtual-Care Cognitive Behavioural Therapy (1) Viruxal Oral and Nasal Spray (1) Vit D (1) VitalConnect Vital Sign Patch (1) VitalTalk communication skills training (1) Vitamin B12 (1) Vitamin C tablets (1) Vitamin D 1000 IU (1) Vitamin D supplementation (1) Vitamin D3 (cholecalciferol) (1) Vitamin D3 or Placebo (1) Vitamin E (1) Vitamins (1) Vitamins and Minerals (1) Viusid and Asbrip (1) VivaDiag™ COVID-19 lgM/IgG Rapid Test (1) Voice Symptom Scale (VoiSS) (1) Volunteer of TIP-OA Program (1) WEB embolization (1) WFI 5% glucose (1) WFI water nebulization (1) WHO recommendations (waiting condition) (1) WHOQOL-BREF (1) WHOQOL-BREF survey (1) WJ-MSCs (1) Walk Test (1) Water Without an Elevated Level of KELEA (1) Wearable Medical Device (Empatica E4) (1) Wearing surgical face mask sprayed with hypertonic saline (1) Web Based Questionnaire (1) Web Based Survey (1) Web application users (1) Web-based REDCap survey (1) Web-based psychosocial peer-to-peer support (1) WebEx Physical Activity Program (1) Weck-cel Swab Collection (1) Weekly Assessment (1) Weight Counseling (1) Wharton's jelly derived Mesenchymal stem cells. (1) White Sender in Acknowledgement (1) White Sender in Informational Videos (1) Whole Exome Sequencing (1) Whole Genome Analysis (1) Whole exome sequencing (1) Withings ScanWatch (1) Woebot Substance Use Disorder (1) WofB (1) Written Information (1) Written Summary of Rounds (1) XAV-19 (1) XC221 (1) XC7 100 mg single (1) XC7 200 mg multiple (1) XC7 200 mg single (1) XCEL-UMC-BETA (1) Xiang-Sha-Liu-Jun formula (1) Xiyanping injection (1) Yin Hu Qing Wen Granula(low does) (1) YinHu QingWen Decoction (1) YinHu QingWen Decoction(low dose) (1) Yinhu Qingwen Granula (1) Yoga group (1) Yu-Ping-Feng formula (1) Zanubrutinib (1) Zaritt Burden Interview (1) Zavegepant (BHV-3500) (1) Zilucoplan® (1) Zinc (Placebo) (1) Zinc (zinc gluconate) (1) Zinc (zinc gluconate) & Vitamin D (cholecalciferol) (1) Zinc Citrate (1) Zinc Gluconate (1) Zinc Picolinate (1) Zinc Picolinate Placebo (1) Zinc Sulfate (1) Zinc Sulfate 220 MG (1) Zinc gluconate (1) Zithromax Oral Product (1) Zofin (1) ZofinTM (OrganicellTM Flow) (1) Zotatifin (1) [18F]FP-R01-MG-F2 (1) [68Ga]Ga-DOTA-(RGD)2 PET/CT (1) [TIMP-2]*[IGFBP-7] (1) a specifically designed self-administered questionnaire (1) a survey (1) acetylsalicylic acid (1) actigraphy (1) acute kidney injury (1) additional blood tubes (1) aerosol box (1) aerosolized DNase (1) after-each-case room disinfection (1) agenT-797 (1) airway management during sedation or general anesthesia (1) all treatment about COVID-2019 (1) allogeneic human dental pulp stem cells (BSH BTC & Utooth BTC) (1) allogeneic mesenchymal stem cell (1) alpha one antitrypsin inhalation (1) alpha1-proteinase inhibitor (1) alveolar recruitment (1) amoxicillin/clavulanate (1) anti-SARS-CoV-2 IgY (1) anti-SARS-CoV-2 human convalescent plasma (1) anti-SARS-CoV-2 plasma (1) antidiabetic treatment (1) appendectomy (1) assessment of the sequelae after hospitalization for Sars-COV-2 (1) attendance by ambulance crew (1) autologous adipose-derived stem cells (1) autopsy (1) avdoralimab (1) azithromycin (1) azoximer bromide (1) bacTRL-Spike (1) bamlanivimab (1) bidirectional oxygenation mouthpiece (1) biochemical analysis (1) biological assays in particular on the lipid metabolism (1) biological sample (1) biological samples collection (1) biological samples day of delivery (1) biological samples, questionnaires and interviews (1) biopsies of subcutaneous adipose tissue (1) blood collection via fingerprick (1) blood sample for seroepidemiological investigation (1) blood sampling for biobank (1) blood test for SARS-COV2 serology (1) blood tests (1) bovhyaluronidase azoxymer (1) brief mindfulness based intervention (1) bromelain (1) canakinumab (1) captopril 25mg (1) cardiac magnetic resonance (1) cardiovascular and respiratory systems monitoring (1) care as usual (1) care modalities (1) carotid-femoral pulse-wave velocity (1) cellulose-containing placebo capsules (1) cenicriviroc (1) chest radiography (1) chest x-ray (1) chlorine dioxide (1) chlorine dioxide 3000 ppm (1) chloroquine (1) cholecalciferol 200,000 IU (1) cholecalciferol 50,000 IU (1) clinical features and laboratory values (1) collection of biological samples (1) collection of mucosal lining fluid (1) collection of swabs (1) community health worker support (1) comparison of sample collection methods (1) complication (1) congenital malformation (1) conjunctival RT PCR (1) consultation (1) control (1) control group (1) convalescent plasma application to SARS-CoV-2 infected patients (1) convalescent plasma from recovered COVID 19 donor (1) conventional management of patients (1) conventional oxygen (1) corticosteroid nasal irrigation (1) covid-19 positive pregnant women (1) cries 13 questionnaire (1) current IPAC-UHN PPE (1) daily room disinfection (1) daily syndromic surveillance (1) dapansutrile capsules (1) data record (1) decisions of limitations and stop processing (1) demographic and clinical data obtained from hospital's electronic medical record. (1) diagnostic (1) diagnostic tests for COVID-19 infection (1) dialysis (1) double gloves (1) draw blood (1) duplex sonography (1) e-Psychotherapy (1) e-ink screen (1) eHealth (1) eHealth +counselling contacts (1) echocardiogram 2D (1) eculizumab (1) electrolytes (1) ensoETM device (1) evaluation of skin microvascular flow and reactivity (1) exchange blood transfusion from normal donor (1) exercise brochure (1) exercise capacity (1) exercise group (1) exercise training (1) exposure (1) faecal sample collector (1) favipiravir (1) favorable outcome (1) feces samples (COVI-BIOME ancillary study) (1) fingertip tests for POC assays (1) fostamatinib (1) fsfi survey (1) further processing of health data (1) gammaCore® (Vagus nerve stimulation) (1) gammaCore® Sapphire (non-invasive vagus nerve stimulator) (1) geko T3 (1) glenzocimab (1) global survey (1) glucose control and sensor usage (1) hAd5-S-Fusion+N-ETSD vaccine (1) heat therapy (1) high flow nasal cannula (HFNC) (1) high flow nasal cannula device (1) high-titer anti-Sars-CoV-2 plasma (1) home care monitoring (1) home spirometry (1) hormones (1) hospital bedroom booking (1) hospitalisation, necessity of ICU, mortality rate, lung involvement (1) hospitalization for premature birth (1) hospitalized children with Covid19 (1) host genotype (1) host immune factors (1) human cord tissue mesenchymal stromal cells (1) hydrocortisone (1) hydroxychloroquine + azithromycin (1) hydroxychloroquine in combination with camostat mesylate (1) hydroxychloroquine placebo (1) hydroxychloroquine sulfate 200 MG (1) hyper immunoglobulins containing anti-Corona VS2 immunoglobulin (1) hyperbaric oxygen therapy (HBOT) (1) hyperimmune plasma (1) hypoxia : 14.3 and 12.7% FIO2, hypercapnia 7% CO2, inspiratory mechanical constraint (1) iAMP test (1) iNO (inhaled nitric oxide) delivered via the INOpulse Delivery System (1) identify SARS-CoV-2 infection by serology (1) imPulse™ Una e-stethoscope (1) imaging, blood tests (1) immune plasma (1) impliminting Online Distance Learning (1) in-hospital mortality rate (1) indirect calorimetry (1) inhalable hydroxychloroquine (HCQ) (1) inhaled hydroxychloroquine (1) inhaled type I interferon (1) inspiratory muscle traiing (1) insurance navigation (1) integrated clinical evaluation (1) intensive care unit admission ratio (1) interleuken 6 level measurment (1) intermediate dose Enoxaparin/ unfractionated heparin (1) intradermal injection of BCG Vaccine (1) intramuscular accine (1) intravenous immunoglobulin therapy (1) it is a survey (1) iv Tocillizumab (TCZ) (1) laboratory biomarkers (1) labs (1) lactoferrin, green tea extract (1) lanadelumab (1) laparoscopic or open appendicectomy (1) lay telephone coaching (1) less-frequency hemodialysis (1) life questionnaires (1) liposomal lactoferrin (1) lopinavir/ritonavir (1) lopinavir/ritonavir group (1) lopinavir/ritonavir tablets or Arbidol or chloroquine phosphate (1) low-molecular-weight heparin (1) lung mechanics at different PEEP (1) lung ultrasound (LUS) (1) mHealth Assessments (1) mMRC (Modified Medical Research Council) Dyspnea Scale (1) mRNA in urine test (1) management strategy of outpatient with mild to moderate SARS-CoV-2 pneumonia (1) maslach burnout inventory questionnair (1) mavrilimumab (1) measurement of circulating sFlt1 concentration (1) mechanical ventilation (1) mechanical ventilator settings and position (1) melatonin (1) mesenchymal stem cells (1) metenkefalin + tridecactide (1) metformin glycinate (1) methylprednisolone therapy (1) microcirculation recording (1) miniprobe Alveoflex (1) mobile internet survey on self-test (1) modification of the planned therapeutic management (1) modified IPAC-UHN PPE (1) molecular testing for virus RNA using RT-PCR (1) mometasone furoate nasal spray (1) monthly serologic IgM/G test (1) morning Yoga-based breathing support (1) mortality (1) mouthrinse with bêta-cyclodextrin and citrox (1) mouthrinse without bêta-cyclodextrin and citrox (1) multipeptide cocktail (1) muscle ultrasound (1) n/a - samples collected along routine care samples only (1) nCapp, a cell phone-based auto-diagnosis system (1) nangibotide (1) nasal pharyngeal (NP) swab samples (1) nasopharyngeal Covid 19 RT-PCR (1) nasopharyngeal and throat swab (1) nebulised recombinant tissue-Plasminogen Activator (rt-PA) (1) newborns from covid 19 positive mothers (1) no intervention-mechanistic study (1) no intervention. observational cohort study (1) no interventional study (1) non (1) non applicable (1) non interventional study (1) non-RAS blocking antihypertensives (1) non-contact magnetically-controlled capsule endoscopy (1) non-interventional (1) none - observational (1) none, this study is observational (1) noninvasive ventilation (1) normal saline (1) nosocomial infection/hospital acquired infection (1) not applicable (observational study) (1) not required (1) nutritional intervention (1) oSOC (1) observation (1) observation of covid 19 pneumonia (1) olfactory and gustatory tests (1) olfactory device (1) online KKH Sports Singapore Program with Usual Care (1) online mindfulness group (1) online questionnaires (1) oral co-trimoxazole (1) oral polio vaccine + information (1) oropharyngeal and intestinal microbiota (1) oropharyngeal swabs (1) oxygen treatment (1) oxyhydrogen (1) pathogen reduced SARS-CoV-2 convalescent plasma (1) patients COVID 19 (1) patients receiving nasal high flow (1) performance evaluation study of RealDetect RT-PCR Kit for COVID-19 detection (1) peripheral blood draw (1) personal protective Measures (1) phone call (1) photobiomodulation and photodynamic therapy (1) physical activity program (1) physiological effects of awake prone position in COVID 19 patients (1) placebo (hartmann plus albumine) (1) placebo capsules (1) placebo for clazakizumab (1) placebo rinse (1) plasma from convalescent patients with COVID-19 (1) plasma hyperimmune (1) plasma therapy using convalescent plasma with antibody against SARS-CoV-2 (1) poractant alfa (1) power breathe (1) prayer (1) pre-operative screening (1) pre_dinner Yoga-based breathing support (1) pre_lunch Yoga-based breathing support (1) predict admission of covid-19 patients to ICU and death with routine and quickly avalaible clinical, biological and radiological variables? (1) prone position (1) proper diet (1) prophylactic heparin (1) prophylactic lactoferrin daily (1) psycho-education video (1) psychological and sociological interviews (1) psychological assessment (1) pulmonary anomalies 4 months after documented COVID-19 pneumonia (1) pulmonary rehabilitation (1) pulmonary ultrasound (1) pulse oximeter (1) qRT-PCR and serology (1) quality of life questionnaires (1) quality of live assessment (1) quesionnair (1) questionaire to husband and wife (1) questionnair about Emerging Legal and Ehical Disputes Over Patient Confidentiality (1) questionnaire and optional interview (1) questionnaire filling (1) quetionnary (1) rNAPc2 (1) rapid salivary test (1) rapid serological test (1) realtime PCR (1) recombinant human interferon Alpha-1b (1) recovered covid 19 patients plasma (1) rectal swab (1) regular care (1) research specific blood sample (1) respiratory function rehabilitation training (1) retrospective metagenomics on clinical samples collected during hospitalization (1) revised HOME-CoV score (1) rhDNase I (1) rhTPO (1) risk factors (1) saint george respiratory questionnaire (1) saliva collection (1) saliva sample (1) samling of oropharynx and nasopharynx (1) sample of blood and saliva (1) self-administered structured questionnaire (1) self-care tools (1) semaglutide (1) semen analysis (1) serological test (1) serology test (1) serum NGAL and cystatin c (1) serum chemistry analysis (1) serum inflammatory biomarkers (1) service of questionnaire (1) severe covid-19 pneumonia with ET (1) severity of lung involvement with COVID-19. (1) smell household Items (1) sodium chloride 0.9% (1) sofosbuvir (1) specific exercise rehabilitation treatment (1) spirometry (1) spirometry, thoracic CT, CPET, 6 minute walking test, SF-36 questionnaire (1) standard concomitant therapy (1) standard medical treatment (1) standard operating procedures (1) standard procedure (1) standard prophylactic dose Enoxaparin/ unfractionated heparin (1) standard protocol (1) standard treatment (1) standard western medicine treatment (1) standardized Lung Ultrasound (LUS) examination (1) stem cells (1) stress and anxiety questionnaire (1) supportive and symptomatic treatment (1) survey work (1) surveys and questionnaires (1) suspected of COVID-19 infection (1) sweat samples (COVIDOG ancillary study) (1) teleconsultation (1) telehealth applications (1) telemedicine (1) telephone consult (1) test (1) thalidomide (1) therapeutic plasmaexchnage (1) theraputic heparin (1) this study is non- interventional (1) thoracic CT-scan (1) thoracic computed tomography scan (1) thoracic lung ultrasound (1) thromboprofylaxis protocol (1) thromboprophylaxis with low-molecular-weight heparin or fondaparinux (1) thymosin alpha 1 (1) topical steroids and cyclosporin-A (1) traditional communication tools (1) transparent sheet (1) treated with hyperimmune plasma (1) turkish physicians (1) unfractionated heparin (1) urinary NGAL, TIMP-2, IGFBP7, IL-6, viral load and metabolomic (1) users (1) vaccine (1) vaccine BCG (1) vadadustat (1) venipuncture in peripheral vein (1) ventilatory support with oxygen therapy (1) viral sequence (1) virgin coconut oil (VCO) (1) visual analogue scale (1) vitamin D (1) vitamin d (1) vv-ECMO (1) washed microbiota transplantation (1) web based survey (1) zinc (1) zinc acetate (1) zinc gluconate and ascorbic acid (1) ıt will be compared pain, sleep, fatigue, physical activity level and quality of life and questioning exercise habits before and after the covid-19 outbreak in patients with Behçet and FMF. (1) γ-Globulin (1) Оxygen therapy (1)

    Placebo

    Developed by Shray Alag, The Harker School
    Sections: Correlations, Clinical Trials, and HPO

    Correlations computed by analyzing all clinical trials.

    Navigate: Clinical Trials and HPO


    Correlated Drug Terms (768)


    Name (Synonyms) Correlation
    drug2153 Nitazoxanide Wiki 0.13
    drug1750 LY3819253 Wiki 0.11
    drug1472 Hydroxychloroquine Wiki 0.11
    Name (Synonyms) Correlation
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    drug2786 Remestemcel-L Wiki 0.05
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    drug2333 PF-06650833 Wiki 0.05
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    drug234 Anti-SARS-CoV-2 equine immunoglobulin fragments (INOSARS) Wiki 0.05
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    drug1804 Lopinavir Wiki 0.05
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    drug2752 Rayaldee 30Mcg Extended-Release (ER) Capsule Wiki 0.05
    drug1556 INM005 Wiki 0.05
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    drug2620 Prone position ventilation Wiki 0.05
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    drug3637 Zavegepant (BHV-3500) Wiki 0.05
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    drug592 COVID-19 IgG / IgM rapid test (whole blood, serum, plasma) Wiki 0.05
    drug31 1: Usual practice Wiki 0.05
    drug526 Budesonide Wiki 0.05
    drug4006 semen analysis Wiki 0.05
    drug533 C21 Wiki 0.05
    drug409 Bempegaldesleukin Wiki 0.05
    drug3204 Support treatment Wiki 0.05
    drug1894 MSC Treatment Wiki 0.05
    drug155 AdCOVID Wiki 0.05
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    drug3014 Serological analyses to be lead on a pre-existing biobank Wiki 0.05
    drug3912 not applicable (observational study) Wiki 0.05
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    drug2476 Placebo Group Wiki 0.05
    drug1710 Ivermectin 3mg Tab Wiki 0.05
    drug116 AV-COVID-19 Wiki 0.05
    drug1357 Group 2: control group with enoxaparin 40mg/d Wiki 0.05
    drug3511 V591 Wiki 0.05
    drug1879 MF59 adjuvanted SARS-CoV-2 Sclamp vaccine 45mcg Wiki 0.05
    drug1429 High-Titer Anti-SARS-CoV-2 (COVID 19) Convalescent Plasma Wiki 0.05
    drug3270 Taste and olfactory function evaluation Wiki 0.05
    drug2633 Prospective study with two measurement points investigating the impact of viral mitigation protocols on parental burnout Wiki 0.05
    drug3809 hydrocortisone Wiki 0.05
    drug3477 Ulinastatin Wiki 0.05
    drug171 Aerosol-reducing Mask Wiki 0.05
    drug2164 Nitric Oxide-Continuous and Sessions Wiki 0.05
    drug1554 INB03 Wiki 0.05
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    drug1647 Interleukin 6 (IL6) Antagonist Wiki 0.05
    drug2802 Respiratory Mechanics Wiki 0.05
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    drug1977 Mesenchymal cells Wiki 0.05
    drug3678 anti-SARS-CoV-2 plasma Wiki 0.05
    drug3564 Virtual Reality Wiki 0.05
    drug2125 Nebulized administration of RLF-100 or Placebo Wiki 0.05
    drug1387 HLX70 Wiki 0.05
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    drug564 COR-101 Wiki 0.05
    drug1764 Late dexamethazone Wiki 0.05
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    drug3263 TXA127 Wiki 0.05
    drug2565 Povidone-Iodine 0.4% NI Wiki 0.05
    drug3230 Symptom Survey Wiki 0.05
    drug1778 Levilimab Wiki 0.05
    drug156 Additional and minimal collection of products of the human body carried out during a sample for standard of care Wiki 0.05
    drug2364 Paracetamol Wiki 0.05
    drug3057 Single high dose vitamin D Wiki 0.05
    drug3122 Standard Of Care (SOC) Wiki 0.05
    drug2954 Saliva specimen Wiki 0.05
    drug2149 Nil intervention Wiki 0.05
    drug3653 Zotatifin Wiki 0.05
    drug346 BACMUNE (MV130) Wiki 0.05
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    drug1267 Favipiravir + Currently used therapy Wiki 0.05
    drug3714 captopril 25mg Wiki 0.05
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    drug1558 INOpulse Wiki 0.05
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    drug1095 EIT-Group Wiki 0.05
    drug2593 Previfenon® Wiki 0.05
    drug356 BCG Wiki 0.05
    drug1269 Favipiravir Combined With Tocilizumab Wiki 0.05
    drug660 CVnCoV Wiki 0.05
    drug3737 conjunctival RT PCR Wiki 0.05
    drug3869 melatonin Wiki 0.05
    drug3190 Study Arm Wiki 0.05
    drug3198 Sudarshan Kriya Yoga (SKY) Wiki 0.05
    drug4010 serum NGAL and cystatin c Wiki 0.05
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    drug1382 HCQ+AZT Wiki 0.05
    drug1769 Lenalidomide as a 5 mg capsule PO daily, days 1, 3, and 5. Wiki 0.05
    drug373 BM-MSCs Wiki 0.05
    drug97 ARCT-021 Dose 4 Wiki 0.05
    drug3782 feces samples (COVI-BIOME ancillary study) Wiki 0.05
    drug3201 Sulodexide Wiki 0.05
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    drug647 CSL324 Wiki 0.05
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    drug1881 MFS Wiki 0.05
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    drug1492 Hydroxychloroquine Sulfate Wiki 0.01
    drug1166 Enoxaparin Wiki 0.01

    Correlated MeSH Terms (165)


    Name (Synonyms) Correlation
    D018352 Coronavirus Infections NIH 0.38
    D045169 Severe Acute Respiratory Syndrome NIH 0.31
    D007239 Infection NIH 0.21
    Name (Synonyms) Correlation
    D012128 Respiratory Distress Syndrome, Adult NIH 0.18
    D055371 Acute Lung Injury NIH 0.18
    D003141 Communicable Diseases NIH 0.17
    D011014 Pneumonia NIH 0.17
    D012127 Respiratory Distress Syndrome, Newborn NIH 0.17
    D013577 Syndrome NIH 0.14
    D055370 Lung Injury NIH 0.10
    D000077062 Burnout, Psychological NIH 0.09
    D012141 Respiratory Tract Infections NIH 0.08
    D011658 Pulmonary Fibrosis NIH 0.07
    D009164 Mycobacterium Infections NIH 0.07
    D000755 Anemia, Sickle Cell NIH 0.07
    D000690 Amyotrophic Lateral Sclerosis NIH 0.07
    D016472 Motor Neuron Disease NIH 0.07
    D058345 Asymptomatic Infections NIH 0.07
    D000370 Ageusia NIH 0.07
    D011024 Pneumonia, Viral NIH 0.06
    D007249 Inflammation NIH 0.06
    D014947 Wounds and Injuries NIH 0.06
    D018450 Disease Progression NIH 0.06
    D012140 Respiratory Tract Diseases NIH 0.06
    D014777 Virus Diseases NIH 0.05
    D001987 Bronchiectasis NIH 0.05
    D001321 Autistic Disorder NIH 0.05
    D008231 Lymphopenia NIH 0.05
    D008171 Lung Diseases, NIH 0.05
    D019973 Alcohol-Related Disorders NIH 0.05
    D000544 Alzheimer Disease NIH 0.05
    D000532 Altitude Sickness NIH 0.05
    D008569 Memory Disorders NIH 0.05
    D000067877 Autism Spectrum Disorder NIH 0.05
    D009877 Endophthalmitis NIH 0.05
    D000071074 Neonatal Sepsis NIH 0.05
    D000070627 Chronic Traumatic Encephalopathy NIH 0.05
    D002481 Cellulitis NIH 0.05
    D006948 Hyperkinesis NIH 0.05
    D058070 Asymptomatic Diseases NIH 0.05
    D011470 Prostatic Hyperplasia NIH 0.05
    D002532 Intracranial Aneurysm NIH 0.05
    D015817 Eye Infections NIH 0.05
    D054517 Orbital Cellulitis NIH 0.05
    D000783 Aneurysm, NIH 0.05
    D050197 Atherosclerosis NIH 0.05
    D000741 Anemia, Aplastic NIH 0.05
    D015004 Yellow Fever NIH 0.05
    D006965 Hyperplasia NIH 0.05
    D010265 Paraproteinemias NIH 0.05
    D011552 Pseudomonas Infections NIH 0.05
    D018184 Paramyxoviridae Infections NIH 0.05
    D001469 Barotrauma NIH 0.05
    D011645 Puerperal Infection NIH 0.05
    D056660 Hereditary Autoinflammatory Diseases NIH 0.05
    D008998 Monoclonal Gammopathy of Undetermined Significance NIH 0.05
    D066087 Perinatal Death NIH 0.05
    D005879 Tourette Syndrome NIH 0.05
    D004646 Emphysema NIH 0.05
    D000275 Adjustment Disorders NIH 0.05
    D017093 Liver Failure NIH 0.05
    D008218 Lymphocytosis NIH 0.05
    D010505 Familial Mediterranean Fever NIH 0.05
    D002006 Brucellosis NIH 0.05
    D003424 Crohn Disease NIH 0.05
    D016739 Behavior, Addictive NIH 0.05
    D008258 Waldenstrom Macroglobulinemia NIH 0.05
    D007010 Hyponatremia NIH 0.05
    D019896 Alpha 1-Antitrypsin Deficiency NIH 0.05
    D063130 Maternal Death NIH 0.05
    D000071257 Emergence Delirium NIH 0.05
    D012120 Respiration Disorders NIH 0.04
    D000073397 Occupational Stress NIH 0.04
    D007676 Kidney Failure, Chronic NIH 0.04
    D003333 Coronaviridae Infections NIH 0.04
    D014115 Toxemia NIH 0.04
    D016638 Critical Illness NIH 0.04
    D005355 Fibrosis NIH 0.04
    D002318 Cardiovascular Diseases NIH 0.04
    D029424 Pulmonary Disease, Chronic Obstructive NIH 0.04
    D001008 Anxiety Disorders NIH 0.04
    D017563 Lung Diseases, Interstitial NIH 0.04
    D013927 Thrombosis NIH 0.04
    D000860 Hypoxia NIH 0.04
    D008173 Lung Diseases, Obstructive NIH 0.04
    D030341 Nidovirales Infections NIH 0.03
    D005356 Fibromyalgia NIH 0.03
    D005334 Fever NIH 0.03
    D007945 Leukemia, Lymphoid NIH 0.03
    D012598 Scoliosi NIH 0.03
    D000505 Alopecia NIH 0.03
    D000070642 Brain Injuries, Traumatic NIH 0.03
    D018805 Sepsis NIH 0.03
    D012640 Seizures NIH 0.03
    D009190 Myelodysplastic Syndromes NIH 0.03
    D002659 Child Development Disorders, Pervasive NIH 0.03
    D020522 Lymphoma, Mantle-Cell NIH 0.03
    D016470 Bacteremia NIH 0.03
    D003231 Conjunctivitis NIH 0.03
    D001528 Behcet Syndrome NIH 0.03
    D000068376 Compassion Fatigue NIH 0.03
    D000067073 Psychological Trauma NIH 0.03
    D012327 RNA Virus Infections NIH 0.03
    D006526 Hepatitis C NIH 0.03
    D000428 Alcohol Drinking NIH 0.03
    D044882 Glucose Metabolism Disorders NIH 0.03
    D001714 Bipolar Disorder NIH 0.03
    D000857 Olfaction Disorders NIH 0.03
    D059350 Chronic Pain NIH 0.03
    D058186 Acute Kidney Injury NIH 0.03
    D004417 Dyspnea NIH 0.03
    D014808 Vitamin D Deficiency NIH 0.03
    D011251 Pregnancy Complications, Infectious NIH 0.03
    D007319 Sleep Initiation and Maintenance Disorders NIH 0.03
    D008659 Metabolic Diseases NIH 0.03
    D001249 Asthma NIH 0.03
    D001289 Attention Deficit Disorder with Hyperactivity NIH 0.03
    D045888 Ganglion Cysts NIH 0.03
    D000257 Adenoviridae Infections NIH 0.03
    D015451 Leukemia, Lymphocytic, Chronic, B-Cell NIH 0.03
    D003550 Cystic Fibrosis NIH 0.03
    D053120 Respiratory Aspiration NIH 0.03
    D013315 Stress, Psychological NIH 0.03
    D019966 Substance-Related Disorders NIH 0.02
    D007938 Leukemia, NIH 0.02
    D003643 Death, NIH 0.02
    D003327 Coronary Disease NIH 0.02
    D003324 Coronary Artery Disease NIH 0.02
    D016769 Embolism and Thrombosis NIH 0.02
    D003863 Depression, NIH 0.02
    D007154 Immune System Diseases NIH 0.02
    D001930 Brain Injuries, NIH 0.02
    D001927 Brain Diseases NIH 0.02
    D003693 Delirium NIH 0.02
    D009102 Multiple Organ Failure NIH 0.02
    D001327 Autoimmune Diseases NIH 0.02
    D007674 Kidney Diseases NIH 0.02
    D007153 Immunologic Deficiency Syndromes NIH 0.02
    D010300 Parkinsonian NIH 0.02
    D008223 Lymphoma, NIH 0.02
    D004194 Disease NIH 0.02
    D040921 Stress Disorders, Traumatic NIH 0.02
    D003920 Diabetes Mellitus, NIH 0.02
    D009103 Multiple Sclerosis NIH 0.02
    D011665 Pulmonary Valve Insufficiency NIH 0.02
    D006331 Heart Diseases NIH 0.02
    D003289 Convalescence NIH 0.02
    D015212 Inflammatory Bowel Diseases NIH 0.02
    D013313 Stress Disorders, Post-Traumatic NIH 0.02
    D009369 Neoplasms, NIH 0.02
    D006333 Heart Failure NIH 0.02
    D054556 Venous Thromboembolism NIH 0.02
    D060825 Cognitive Dysfunction NIH 0.02
    D007251 Influenza, Human NIH 0.01
    D020246 Venous Thrombosis NIH 0.01
    D001172 Arthritis, Rheumatoid NIH 0.01
    D003924 Diabetes Mellitus, Type 2 NIH 0.01
    D020521 Stroke NIH 0.01
    D001168 Arthritis NIH 0.01
    D011655 Pulmonary Embolism NIH 0.01
    D004617 Embolism NIH 0.01
    D006973 Hypertension NIH 0.01
    D013923 Thromboembolism NIH 0.01
    D003866 Depressive Disorder NIH 0.01
    D004630 Emergencies NIH 0.01

    Correlated HPO Terms (72)


    Name (Synonyms) Correlation
    HP:0002090 Pneumonia HPO 0.17
    HP:0011947 Respiratory tract infection HPO 0.08
    HP:0002206 Pulmonary fibrosis HPO 0.07
    Name (Synonyms) Correlation
    HP:0006802 Abnormal anterior horn cell morphology HPO 0.07
    HP:0000224 Hypogeusia HPO 0.07
    HP:0007354 Amyotrophic lateral sclerosis HPO 0.07
    HP:0002110 Bronchiectasis HPO 0.05
    HP:0001888 Lymphopenia HPO 0.05
    HP:0002088 Abnormal lung morphology HPO 0.05
    HP:0003811 Neonatal death HPO 0.05
    HP:0002487 Hyperkinetic movements HPO 0.05
    HP:0002354 Memory impairment HPO 0.05
    HP:0002617 Vascular dilatation HPO 0.05
    HP:0008711 Benign prostatic hyperplasia HPO 0.05
    HP:0100827 Lymphocytosis HPO 0.05
    HP:0012133 Erythroid hypoplasia HPO 0.05
    HP:0002863 Myelodysplasia HPO 0.05
    HP:0002902 Hyponatremia HPO 0.05
    HP:0004944 Dilatation of the cerebral artery HPO 0.05
    HP:0002511 Alzheimer disease HPO 0.05
    HP:0040187 Neonatal sepsis HPO 0.05
    HP:0100658 Cellulitis HPO 0.05
    HP:0100280 Crohn's disease HPO 0.05
    HP:0002621 Atherosclerosis HPO 0.05
    HP:0001399 Hepatic failure HPO 0.05
    HP:0030858 Addictive behavior HPO 0.05
    HP:0005508 Monoclonal immunoglobulin M proteinemia HPO 0.05
    HP:0001626 Abnormality of the cardiovascular system HPO 0.04
    HP:0006510 Chronic pulmonary obstruction HPO 0.04
    HP:0006515 Interstitial pneumonitis HPO 0.04
    HP:0006536 Pulmonary obstruction HPO 0.04
    HP:0012418 Hypoxemia HPO 0.04
    HP:0100806 Sepsis HPO 0.03
    HP:0000717 Autism HPO 0.03
    HP:0001945 Fever HPO 0.03
    HP:0005526 Lymphoid leukemia HPO 0.03
    HP:0005550 Chronic lymphatic leukemia HPO 0.03
    HP:0100754 Mania HPO 0.03
    HP:0002293 Alopecia of scalp HPO 0.03
    HP:0000509 Conjunctivitis HPO 0.03
    HP:0000458 Anosmia HPO 0.03
    HP:0012532 Chronic pain HPO 0.03
    HP:0001919 Acute kidney injury HPO 0.03
    HP:0100512 Low levels of vitamin D HPO 0.03
    HP:0002098 Respiratory distress HPO 0.03
    HP:0001250 Seizure HPO 0.03
    HP:0002099 Asthma HPO 0.03
    HP:0007018 Attention deficit hyperactivity disorder HPO 0.03
    HP:0000729 Autistic behavior HPO 0.03
    HP:0100785 Insomnia HPO 0.03
    HP:0001677 Coronary artery atherosclerosis HPO 0.02
    HP:0000077 Abnormality of the kidney HPO 0.02
    HP:0002960 Autoimmunity HPO 0.02
    HP:0002665 Lymphoma HPO 0.02
    HP:0001298 Encephalopathy HPO 0.02
    HP:0002721 Immunodeficiency HPO 0.02
    HP:0000819 Diabetes mellitus HPO 0.02
    HP:0002037 Inflammation of the large intestine HPO 0.02
    HP:0010444 Pulmonary insufficiency HPO 0.02
    HP:0002664 Neoplasm HPO 0.02
    HP:0001635 Congestive heart failure HPO 0.02
    HP:0001268 Mental deterioration HPO 0.02
    HP:0001370 Rheumatoid arthritis HPO 0.01
    HP:0001909 Leukemia HPO 0.01
    HP:0002625 Deep venous thrombosis HPO 0.01
    HP:0005978 Type II diabetes mellitus HPO 0.01
    HP:0001297 Stroke HPO 0.01
    HP:0001369 Arthritis HPO 0.01
    HP:0002204 Pulmonary embolism HPO 0.01
    HP:0000822 Hypertension HPO 0.01
    HP:0001907 Thromboembolism HPO 0.01
    HP:0000716 Depressivity HPO 0.01

    Clinical Trials

    Navigate: Correlations   HPO

    There are 459 clinical trials


    1 A Phase III Randomized Placebo-Controlled Study to Examine the Efficacy and Safety of DAS181 for the Treatment of Lower Respiratory Tract Parainfluenza Infection in Immunocompromised Subjects

    This study will seek to enroll immunocompromised patients with Lower Tract parainfluenza infection. It also contains a sub-study to enroll patients with severe COVID-19.

    NCT03808922
    Conditions
    1. Lower Respiratory Tract Infection
    2. Parainfluenza
    3. Immunocompromised
    4. COVID-19
    Interventions
    1. Drug: DAS181
    2. Drug: Placebo
    3. Drug: DAS181 COVID-19
    4. Drug: DAS181 OL
    MeSH:Infection Communicable Diseases Respiratory Tract Infections Paramyxoviridae Infections
    HPO:Respiratory tract infection

    Primary Outcomes

    Description: Removal of all oxygen support (with stable SpO2)

    Measure: Percent of subjects who Return to Room Air (RTRA) (main study)

    Time: by Day 28

    Measure: Percent of subjects with improved COVID-19 Clinical Status Scale (sub-study)

    Time: Day 14

    Secondary Outcomes

    Measure: All-cause mortality rate (main study)

    Time: at Day 28

    Measure: Percent of subjects who Return to Room Air (RTRA) (main study)

    Time: by Day 21

    Measure: Time (in days) to RTRA (main study)

    Time: Days 10, 14, 21, 28

    Measure: Percent of subjects who achieve clinical stability (main study)

    Time: by Day 28

    Measure: Percent of subjects discharged (without mortality and hospice) (main study)

    Time: by Days 14, 21, 28 and 35

    Measure: Time (in days) to first hospital discharge (without hospice) (main study)

    Time: through Day 35

    Measure: Total number of inpatient days (main study)

    Time: up to Day 35

    Measure: Baseline SAD-RV infection-related mortality rate (main study)

    Time: at Day 28

    Measure: Baseline SAD-RV infection-related mortality rate (main study)

    Time: at Day 35

    Measure: All-cause mortality rate (main study)

    Time: at Day 35

    Measure: Change in pulmonary function (FEV1% predicted) (main study)

    Time: Day 1, Day 7, Day 14, Day 28

    Measure: Time to improved COVID19 clinical status (Sub-study)

    Time: Day 5, Day 10, Day 21, Day 28

    Measure: Time to RTRA

    Time: Day 10, Day 14, Day 21, Day 28

    Measure: Time to Clinical stability

    Time: Day 14, Day 21, Day 28

    Measure: Time to SARS-CoV-2 RNA in the respiratory specimens being undetectable

    Time: Day 5, Day 10, Day 14, Day 21, Day 28

    Measure: Time to Clinical deterioration

    Time: Day 5, Day 10, Day 14, Day 21, Day 28

    Measure: Time to Discharge from hospital (without readmission before Day 28).

    Time: Day 14, Day 21, Day 28

    Measure: Time to Death (all causes)

    Time: Day 14, Day 21, Day 28
    2 Prevention of Maternal and Neonatal Death/Infections With a Single Oral Dose of Azithromycin in Women in Labor (in Low- and Middle-income Countries): a Randomized Controlled Trial

    Maternal and neonatal infections are among the most frequent causes of maternal and neonatal deaths, and current antibiotic strategies have not been effective in preventing many of these deaths. Recently, a randomized clinical trial conducted in a single site in The Gambia showed that treatment with oral dose of 2 g azithromycin vs. placebo for all women in labor reduced selected maternal and neonatal infections. However, it is unknown if this therapy reduces maternal and neonatal sepsis and mortality. The A-PLUS trial includes two primary hypotheses, a maternal hypothesis and a neonatal hypothesis. First, a single, prophylactic intrapartum oral dose of 2 g azithromycin given to women in labor will reduce maternal death or sepsis. Second, a single, prophylactic intrapartum oral dose of 2 g azithromycin given to women in labor will reduce intrapartum/neonatal death or sepsis.

    NCT03871491
    Conditions
    1. Maternal Death
    2. Maternal Infections Affecting Fetus or Newborn
    3. Neonatal SEPSIS
    4. Maternal Sepsis During Labor
    5. Neonatal Death
    6. Postpartum Sepsis
    Interventions
    1. Drug: Azithromycin
    2. Drug: Placebo
    MeSH:Infection Sepsis Toxemia Neonatal Sepsis Pregnancy Complications, Infectious Puerperal Infection Perinatal Death Maternal Death Death
    HPO:Neonatal death Neonatal sepsis Sepsis

    Primary Outcomes

    Description: Incidence of maternal death or sepsis within 6 weeks (42 days) post-delivery in intervention vs. placebo group.

    Measure: Maternal: Incidence of maternal death or sepsis within 6 weeks (42 days) post-delivery in intervention vs. placebo group.

    Time: within 6 weeks (42 days)

    Description: Incidence of intrapartum/neonatal death or sepsis within 4 weeks (28 days) post-delivery in intervention vs. placebo group

    Measure: Neonatal: Incidence of intrapartum/neonatal death or sepsis within 4 weeks (28 days) post-delivery in intervention vs. placebo group

    Time: 4 weeks (28 days) post-delivery

    Secondary Outcomes

    Description: Fever (>100.4°F/38°C) in addition to one or more of the following: fetal tachycardia ≥160 bpm, maternal tachycardia >100 bpm, tender uterus between contractions, or purulent/foul smelling discharge from uterus prior to delivery.

    Measure: Incidence of chorioamnionitis

    Time: prior to delivery

    Description: Fever (>100.4°F/38°C) in addition to one or more of maternal tachycardia >100 bpm, tender uterine fundus, or purulent/foul smelling discharge from uterus after delivery.

    Measure: Incidence of endometritis

    Time: within 42 days post-delivery

    Description: Wound infection (Purulent infection of a perineal or Cesarean wound with or without fever. In the absence of purulence, requires presence of fever >100.4°F/38°C and at least one of the following signs of local infection: pain or tenderness, swelling, heat, or redness around the incision/laceration); Abdominopelvic abscess (Evidence of pus in the abdomen or pelvis noted during open surgery, interventional aspiration or imaging); Pneumonia (Fever >100.4°F/38°C and clinical symptoms suggestive of lung infection including cough and/or tachypnea >24 breaths/min or radiological confirmation); Pyelonephritis (Fever >100.4°F/38°C and one or more of the following: urinalysis/dip suggestive of infection, costovertebral angle tenderness, or confirmatory urine culture); Mastitis/breast abscess or infection (Fever >100.4°F/38°C and one or more of the following: breast pain, swelling, warmth, redness, or purulent drainage).

    Measure: Incidence of other infections

    Time: within 42 days post-delivery

    Description: Use of subsequent maternal antibiotic therapy after randomization to 42 days postpartum for any reason.

    Measure: Incidence of use of subsequent maternal antibiotic therapy

    Time: after randomization to 42 days post-delivery

    Description: Time from drug administration until initial discharge after delivery (time may vary by site).

    Measure: Maternal initial hospital length of stay

    Time: within 42 days post-delivery

    Description: Maternal readmissions within 42 days of delivery

    Measure: Incidence of maternal readmissions

    Time: within 42 days post-delivery

    Description: Maternal admission to special care units

    Measure: Incidence of maternal admission to special care units

    Time: within 42 days post-delivery

    Description: Maternal unscheduled visit for care

    Measure: Incidence of maternal unscheduled visit for care

    Time: within 42 days post-delivery

    Description: Maternal GI symptoms including nausea, vomiting, and diarrhea and other reported side effects.

    Measure: Incidence of maternal GI symptoms

    Time: within 42 days post-delivery

    Description: Maternal death due to sepsis using the Global Network algorithm for cause of death

    Measure: Incidence of maternal death due to sepsis

    Time: within 42 days post-delivery

    Description: Incidence of other neonatal infections.

    Measure: Incidence of other neonatal infections (e.g. eye infection, skin infection)

    Time: within 42 days post-delivery

    Description: Neonatal initial hospital length of stay, defined as time of delivery until initial discharge (time may vary by site).

    Measure: Neonatal initial hospital length of stay

    Time: within 28 days of delivery

    Description: Neonatal readmissions within 42 days of delivery

    Measure: Incidence of neonatal readmissions

    Time: within 42 days of delivery

    Description: Neonatal admission to special care units

    Measure: Incidence of neonatal admission to special care units

    Time: within 28 days of delivery

    Description: Neonatal unscheduled visit for care

    Measure: Incidence of neonatal unscheduled visit for care

    Time: within 42 days post-delivery

    Description: Neonatal death due to sepsis using the Global Network algorithm for causes of death

    Measure: Incidence of neonatal death due to sepsis

    Time: within 28 days of delivery

    Description: Pyloric stenosis within 42 days of delivery, defined as clinical suspicion based on severe vomiting leading to death, surgical intervention (pyloromyotomy) as verified from medical records, or radiological confirmation.

    Measure: Incidence of pyloric stenosis within 42 days of delivery

    Time: within 42 days of delivery
    3 A Phase 1b Double-blind, Placebo-controlled, Dose-ranging Study to Evaluate the Safety, Pharmacokinetics, and Anti-viral Effects of Galidesivir Administered Via Intravenous Infusion to Subjects With Yellow Fever or COVID-19

    This is a placebo-controlled, randomized, double-blind study to evaluate the pharmacokinetics, safety and antiviral activity of galidesivir in subjects with yellow fever (YF) or COVID-19.

    NCT03891420
    Conditions
    1. COVID-19
    2. Yellow Fever
    Interventions
    1. Drug: Galidesivir
    2. Drug: Placebo
    MeSH:Yellow Fever Fever
    HPO:Fever

    Primary Outcomes

    Measure: number of subjects with treatment emergent adverse events and serious adverse events

    Time: absolute number through the end of the study, approximately 56 days

    Measure: number of subjects with change in laboratory parameters

    Time: absolute number and change from baseline through the end of the study, approximately 56 days

    Measure: exposure of galidesivir as measured by plasma concentrations

    Time: 24 hours post dose on Day 1 through 12 hours post dose on Day 7

    Secondary Outcomes

    Measure: yellow fever virus (YFV) titer (Group A)

    Time: change in YFV titer from baseline through Day 21

    Measure: antiviral effect on SARS-CoV-2 in the respiratory tract - COVID-19 (Group B)

    Time: change in SARS-CoV-2 from baseline through Day 21

    Measure: changes in clinical status using 8-point ordinal scale in COVID-19 (Group B)

    Time: through Day 21

    Measure: changes from baseline and time to improvement using NEWS in COVID-19 (Group B)

    Time: through Day21

    Measure: mortality

    Time: mortality at Day 56
    4 Clinical Study of Human Umbilical Cord Mesenchymal Stem Cells in the Treatment of Severe COVID-19

    The novel coronavirus pneumonia is a kind of new emerging respiratory infectious disease, characterized by fever, dry cough, and chest tightness, and caused by the infection of the 2019 novel coronavirus (2019-nCoV). In severe cases, there will be rapid respiratory system failure. The novel coronavirus pneumonia is extremely contagious and the disease progresses rapidly. It has become a urgent and serious public health event that threatens human life and health globally. Among them, severe pneumonia caused by novel coronavirus is characterized by extensive acute inflammation of the lungs and the patient is critically ill. At present, there is no effective treatment in clinical practice.Most of them should receive supportive care to help relieve symptoms. For severe cases, treatment should include care to support vital organ functions. This clinical trial is to inspect the safety and efficiency of Human Umbilical Cord Mesenchymal Stem Cells (UC-MSCs) therapy for severe pneumonia patients infected with 2019-nCoV.

    NCT04273646
    Conditions
    1. 2019 Novel Coronavirus Pneumonia
    2. COVID-19
    Interventions
    1. Biological: UC-MSCs
    2. Drug: Placebo
    MeSH:Coronavirus Infections Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Evaluation of Pneumonia Improvement

    Measure: Pneumonia severity index

    Time: From Baseline (0W) to 12 week after treatment

    Description: Evaluation of Pneumonia Improvement

    Measure: Oxygenation index (PaO2/FiO2)

    Time: From Baseline (0W) to 12 week after treatment

    Secondary Outcomes

    Description: Incidence of acute and chronic treatment-related adverse events in patients with novel coronavirus severe pneumonia receiving UC-MSCs infusion as assessed.

    Measure: Side effects in the UC-MSCs treatment group

    Time: From Baseline (0W) to 96 week after treatment

    Description: Marker for efficacy of treatment

    Measure: 28-days survival

    Time: Day 28

    Description: Markers of organ function(Score each criterion on a scale of 0 to 4, and the higher the score, the worse the prognosis.)

    Measure: Sequential organ failure assessment

    Time: Day 28

    Description: Markers of Infection

    Measure: C-reactive protein

    Time: From Baseline (0W) to 12 week after treatment

    Description: Markers of Infection

    Measure: Procalcitonin

    Time: From Baseline (0W) to 12 week after treatment

    Description: Marker of Immunological function

    Measure: Lymphocyte count

    Time: From Baseline (0W) to 12 week after treatment

    Description: Marker of Immunological function

    Measure: CD3+, CD4+ and CD8+ T celll count

    Time: From Baseline (0W) to 12 week after treatment

    Description: Marker of Immunological function

    Measure: CD4+/CD8+ratio

    Time: From Baseline (0W) to 12 week after treatment
    5 The Efficacy of Treating Pulmonary Fibrosis and Pulmonary Function Injury in COVID-19 With the Fuzheng Huayu Tablets: a Multicenter Randomized Controlled Trial

    According to previous studies, viral pneumonia can develop into pulmonary fibrosis, which can affect patients'lung function and even life health.This study aims to observe the efficacy and safety of Fuzheng Huayu Tablets in the treatment of pulmonary fibrosis after COVID-19.

    NCT04279197
    Conditions
    1. Pulmonary Fibrosis Due to COVID-19
    Interventions
    1. Drug: Fuzheng Huayu Tablet
    2. Drug: Vitamin C tablets
    3. Other: Placebo
    4. Other: respiratory function rehabilitation training
    MeSH:Pulmonary Fibrosis Fibrosis
    HPO:Pulmonary fibrosis

    Primary Outcomes

    Description: Evaluation of pulmonary fibrosis Improvement. pulmonary fibrosis judged by HRCT score.HRCT images are divided into four grades according to the score, and a reduction of one grade is an improvement.

    Measure: The improvement proportion of pulmonary fibrosis

    Time: Week 24

    Secondary Outcomes

    Description: Evaluation of Lung Function Improvement

    Measure: Blood oxygen saturation

    Time: Week 24

    Description: Discomfort symptoms include dyspnea, cough, exhausted, fatigue, insomnia, sweating, poor appetite, diarrhea, etc., which are common manifestations of patients with COVID-19

    Measure: Clinical symptom score

    Time: Week 24

    Description: This scale can reflect the quality of life of patients to some extent.

    Measure: Quality of Life-BREF (QOL-BREF)

    Time: Week 24

    Description: This scale can reflect the quality of life of patients to some extent.

    Measure: Patient Health Questionnaire-9(PHQ-9)

    Time: Week 24

    Description: This scale can reflect the quality of life of patients to some extent.

    Measure: Generalized anxiety disorder-7(GAD-7)

    Time: Week 24

    Description: Evaluation of Lung Function Improvement

    Measure: The 6-minute walk distance

    Time: Week 24
    6 A Multicenter, Adaptive, Randomized Blinded Controlled Trial of the Safety and Efficacy of Investigational Therapeutics for the Treatment of COVID-19 in Hospitalized Adults

    This study is an adaptive, randomized, double-blind, placebo-controlled trial to evaluate the safety and efficacy of novel therapeutic agents in hospitalized adults diagnosed with COVID-19. The study is a multicenter trial that will be conducted in up to approximately 100 sites globally. The study will compare different investigational therapeutic agents to a control arm. There will be interim monitoring to introduce new arms and allow early stopping for futility, efficacy, or safety. If one therapy proves to be efficacious, then this treatment may become the control arm for comparison(s) with new experimental treatment(s). Any such change would be accompanied by an updated sample size. Because background standards of supportive care may evolve/improve over time as more is learned about successful management of COVID-19, comparisons of safety and efficacy will be based on data from concurrently randomized subjects. An independent Data and Safety Monitoring Board (DSMB) will actively monitor interim data to make recommendations about early study closure or changes to study arms. To evaluate the clinical efficacy, as assessed by time to recovery, of different investigational therapeutics as compared to the control arm.

    NCT04280705
    Conditions
    1. COVID-19
    Interventions
    1. Other: Placebo
    2. Drug: Remdesivir

    Primary Outcomes

    Description: Day of recovery is defined as the first day on which the subject satisfies one of the following three categories from the ordinal scale: 1) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Not hospitalized, no limitations on activities.

    Measure: Time to Recovery

    Time: Day 1 through Day 29

    Secondary Outcomes

    Description: Blood to evaluate ALT was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.

    Measure: Change From Baseline in Alanine Transaminase (ALT)

    Time: Days 1, 3, 5, 8, 11, 15 and 29

    Description: Blood to evaluate AST was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.

    Measure: Change From Baseline in Aspartate Transaminase (AST)

    Time: Days 1, 3, 5, 8, 11, 15 and 29

    Description: Blood to evaluate serum creatinine was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.

    Measure: Change From Baseline in Creatinine

    Time: Days 1, 3, 5, 8, 11, 15 and 29

    Description: Blood to evaluate serum glucose was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.

    Measure: Change From Baseline in Glucose

    Time: Days 1, 3, 5, 8, 11, 15 and 29

    Description: Blood to evaluate hemoglobin was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.

    Measure: Change From Baseline in Hemoglobin

    Time: Days 1, 3, 5, 8, 11, 15 and 29

    Description: Blood to evaluate platelets was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.

    Measure: Change From Baseline in Platelets

    Time: Days 1, 3, 5, 8, 11, 15 and 29

    Description: Blood to evaluate PT was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.

    Measure: Change From Baseline in Prothrombin Time (PT)

    Time: Days 1, 3, 5, 8, 11, 15 and 29

    Description: Blood to evaluate total bilirubin was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.

    Measure: Change From Baseline in Total Bilirubin

    Time: Days 1, 3, 5, 8, 11, 15 and 29

    Description: Blood to evaluate WBC was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.

    Measure: Change From Baseline in White Blood Cell Count (WBC)

    Time: Days 1, 3, 5, 8, 11, 15 and 29

    Description: Blood to evaluate neutrophils was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.

    Measure: Change From Baseline in Neutrophils

    Time: Days 1, 3, 5, 8, 11, 15 and 29

    Description: Blood to evaluate lymphocytes was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.

    Measure: Change From Baseline in Lymphocytes

    Time: Days 1, 3, 5, 8, 11, 15 and 29

    Description: Blood to evaluate monocytes was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.

    Measure: Change From Baseline in Monocytes

    Time: Days 1, 3, 5, 8, 11, 15 and 29

    Description: Blood to evaluate basophils was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.

    Measure: Change From Baseline in Basophils

    Time: Days 1, 3, 5, 8, 11, 15 and 29

    Description: Blood to evaluate eosinophils was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.

    Measure: Change From Baseline in Eosinophils

    Time: Days 1, 3, 5, 8, 11, 15 and 29

    Description: The NEW score has demonstrated an ability to discriminate patients at risk of poor outcomes. This score is based on 7 clinical parameters (respiration rate, oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate, level of consciousness). The NEW Score is being used as an efficacy measure. The minimum score is 0, representing the better outcome, and the maximum value is 19, representing the worse outcome.

    Measure: Change in National Early Warning Score (NEWS) From Baseline

    Time: Days 1, 3, 5, 8, 11, 15, 22, and 29

    Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.

    Measure: Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 1

    Time: Day 1

    Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.

    Measure: Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 3

    Time: Day 3

    Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.

    Measure: Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 5

    Time: Day 5

    Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.

    Measure: Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 8

    Time: Day 8

    Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.

    Measure: Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 11

    Time: Day 11

    Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.

    Measure: Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 15

    Time: Day 15

    Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.

    Measure: Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 22

    Time: Day 22

    Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.

    Measure: Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 29

    Time: Day 29

    Description: Grade 3 AEs are defined as events that interrupt usual activities of daily living, or significantly affects clinical status, or may require intensive therapeutic intervention. Severe events are usually incapacitating. Grade 4 AEs are defined as events that are potentially life threatening.

    Measure: Percentage of Participants Reporting Grade 3 and 4 Clinical and/or Laboratory Adverse Events (AEs)

    Time: Day 1 through Day 29

    Description: An SAE is defined as an AE or suspected adverse reaction is considered serious if, in the view of either the investigator or the sponsor, it results in death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect.

    Measure: Percentage of Participants Reporting Serious Adverse Events (SAEs)

    Time: Day 1 through Day 29

    Description: Participants may have been discontinued from investigational therapeutics due to discharge or death. The halting or slowing of the infusion for any reason was collected, as was missed doses in the series of 10 doses.

    Measure: Percentage of Participants Discontinued or Temporarily Suspended From Investigational Therapeutics

    Time: Day 1 through Day 10

    Description: Duration of hospitalization was determined two ways. The first includes imputations for participants who died. The second method is restricted to participants who did not die.

    Measure: Duration of Hospitalization

    Time: Day 1 through Day 29

    Description: Duration of new non-invasive ventilation or high flow oxygen use was measured in days among participants who were not on non-invasive ventilation or high-flow oxygen use at baseline, determined two ways. The first includes imputations for participants who died. The second method is restricted to participants who did not die

    Measure: Duration of New Non-invasive Ventilation or High Flow Oxygen Use

    Time: Day 1 through Day 29

    Description: Duration of new oxygen use was measured in days among participants who were not on oxygen at baseline, determined two ways. The first includes imputations for participants who died. The second method is restricted to participants who did not die .

    Measure: Duration of New Oxygen Use

    Time: Day 1 through Day 29

    Description: Duration of new ventilator or ECMO use was measured in days among participants who were not on a ventilator or ECMO at baseline, determined two ways. The first includes imputations for participants who died. The second method is restricted to participants who did not die

    Measure: Duration of New Ventilator or Extracorporeal Membrane Oxygenation (ECMO) Use

    Time: Day 1 through Day 29

    Description: New non-invasive ventilation or high-flow oxygen use was determined as the percentage of subject not on non-invasive ventilation or high-flow oxygen at baseline.

    Measure: Percentage of Participants Requiring New Non-invasive Ventilation or High-flow Oxygen Use

    Time: Day 1 through Day 29

    Description: The percentage of participants requiring new oxygen use was determined as the percentage of participants not requiring oxygen at baseline

    Measure: Percentage of Participants Requiring New Oxygen Use

    Time: Day 1 through Day 29

    Description: The percentage of participants requiring new ventilator or ECMO use was determined as the percentage not on a ventilator or ECMO at baseline

    Measure: Percentage of Participants Requiring New Ventilator or Extracorporeal Membrane Oxygenation (ECMO) Use

    Time: Day 1 through Day 29

    Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities. A positive change indicates a worsening and a negative change is an improvement.

    Measure: Mean Change in the Ordinal Scale

    Time: Day 1, 3, 5, 8, 11, 15, 22, and 29

    Description: The mortality rate was determined as the proportion of participants who died by study Day 15.

    Measure: 14-day Participant Mortality

    Time: Day 1 through Day 15

    Description: The mortality rate was determined as the proportion of participants who died by study Day 29.

    Measure: 29-day Participant Mortality

    Time: Day 1 through Day 29

    Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities. Time to improvement by at least one category was determined for each participant

    Measure: Time to an Improvement by at Least One Category Using an Ordinal Scale

    Time: Day 1 through Day 29

    Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities. Time to improvement by at least two categories was determined for each participant

    Measure: Time to an Improvement of at Least Two Categories Using an Ordinal Scale

    Time: Day 1 through Day 29

    Description: The NEW score has demonstrated an ability to discriminate patients at risk of poor outcomes. This score is based on 7 clinical parameters (respiration rate, oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate, level of consciousness). The NEW Score is being used as an efficacy measure. The minimum score is 0, representing the better outcome, and the maximum value is 19, representing the worse outcome. The time to discharge or a NEWS of less than or equal to 2 was determined for each participant.

    Measure: Time to Discharge or to a NEWS of 2 or Less and Maintained for 24 Hours, Whichever Occurs First

    Time: Day 1 through Day 29
    7 Human Umbilical Cord Mesenchymal Stem Cells Treatment for Pneumonia Patients Infected by 2019 Novel Coronavirus

    The 2019 novel coronavirus pneumonia outbroken in Wuhan, China, which spread quickly to 26 countries worldwide and presented a serious threat to public health. It is mainly characterized by fever, dry cough, shortness of breath and breathing difficulties. Some patients may develop into rapid and deadly respiratory system injury with overwhelming inflammation in the lung. Currently, there is no effective treatment in clinical practice. The present clinical trial is to explore the safety and efficacy of Human Umbilical Cord Mesenchymal Stem Cells (UC-MSCs) therapy for novel coronavirus pneumonia patients.

    NCT04293692
    Conditions
    1. COVID-19
    Interventions
    1. Biological: UC-MSCs
    2. Other: Placebo
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Evaluation of Pneumonia change

    Measure: Size of lesion area by chest imaging

    Time: At baseline, Day 1, Week 1, Week 2, Week 4, Week 8

    Description: Evaluation of Pneumonia change

    Measure: Blood oxygen saturation

    Time: At baseline, Day 1, Week 1, Week 2, Week 4, Week 8

    Secondary Outcomes

    Description: Marker for efficacy of treatment

    Measure: Rate of mortality within 28-days

    Time: At baseline, Day 1, Week 1, Week 2, Week 4, Week 8

    Description: 0-4 score, the higher the score is, the poor of the prognosis will be.

    Measure: Sequential organ failure assessment

    Time: At baseline, Day 1, Week 1, Week 2, Week 4, Week 8

    Description: Number of participants with treatment-related adverse events

    Measure: Side effects in the UC-MSCs treatment group

    Time: At baseline, Day 1, Week 1, Week 2, Week 4, Week 8

    Description: Markers of the heart function

    Measure: Electrocardiogram, the changes of ST-T interval mostly

    Time: At baseline, Day 1, Week 1, Week 2, Week 4, Week 8

    Description: Markers of infection

    Measure: Concentration of C-reactive protein C-reactive protein, immunoglobulin

    Time: At baseline, Day 1, Week 1, Week 2, Week 4, Week 8

    Description: Marker of Immunology and inflammation

    Measure: CD4+ and CD8+ T cells count

    Time: At baseline, Day 1, Week 1, Week 2, Week 4, Week 8

    Description: Marker of Immunology and inflammation

    Measure: Concentration of the blood cytokine (IL-1β, IL-6, IL-8,IL-10,TNF-α)

    Time: At baseline, Day 1, Week 1, Week 2, Week 4, Week 8

    Description: Markers of the heart function

    Measure: Concentration of the myocardial enzymes

    Time: At baseline, Day 1, Week 1, Week 2, Week 4, Week 8
    8 A Phase IIb Randomized Placebo-Controlled Study to Examine the Efficacy and Safety of DAS181 for the Treatment of Severe Influenza Infection

    This is a Phase IIb study consisting of two cohorts to evaluate efficacy, safety and pharmacokinetics of DAS181 in IFV infection. An approximate total of 280 subjects will be enrolled into this study.

    NCT04298060
    Conditions
    1. Influenza Infection
    2. SAD-RV Infection and COVID-19
    Interventions
    1. Drug: DAS181
    2. Drug: Placebo
    MeSH:Infection Communicable Diseases Influenza, Human

    Primary Outcomes

    Description: Percent of subjects who have returned to room air

    Measure: Percent of subjects who have returned to room air

    Time: 7 days

    Description: Percent change of subjects return to baseline oxygen requirement by Day 7 compared to Day 1

    Measure: Percent change of subjects return to baseline oxygen requirement

    Time: 7 days
    9 Chloroquine/ Hydroxychloroquine Prevention of Coronavirus Disease (COVID-19) in the Healthcare Setting; a Randomised, Placebo-controlled Prophylaxis Study (COPCOV)

    The study is a double-blind, randomised, placebo-controlled trial that will be conducted in healthcare settings and other facilities directly involved in COVID-19 case management. We will recruit healthcare workers and other staff working in a facility where there are cases of either proven, or suspected, COVID-19, who can be followed reliably for 5 months. 40,000 participants will be recruited and we predict an average of 400-800 participants per site in 50-100 sites. The participant will be randomised to receive either chloroquine or placebo (1:1 randomisation), or to hydroxychloroquine or placebo (1:1 randomisation). A loading dose of 10mg base/kg (four 155mg tablets for a 60kg subject), followed by 155 mg daily (250mg chloroquine phosphate salt/ 200mg hydroxychloroquine sulphate) will be taken for 3 months. If the participant is diagnosed with COVID-19, they will take continue to take the study medication until: - 90 days after enrolment (i.e., completion of kit) - hospitalised due to COVID-19 disease (i.e., not for quarantine purposes) in which case they will stop, or - advised to stop by their healthcare professional for other reasons Episodes of symptomatic respiratory illness, including symptomatic COVID-19, and clinical outcomes will be recorded in the Case Record Form during the follow-up period.

    NCT04303507
    Conditions
    1. COVID19
    2. Coronavirus
    3. Acute Respiratory Illnesses
    Interventions
    1. Drug: Chloroquine or Hydroxychloroquine
    2. Drug: Placebo
    MeSH:Coronavirus Infections

    Primary Outcomes

    Description: Number of symptomatic COVID-19 infections will be compared between the chloroquine or hydroxychloroquine and placebo groups

    Measure: Number of symptomatic COVID-19 infections

    Time: Approximately 90 days

    Secondary Outcomes

    Description: Symptoms severity of COVID-19 will be compared between the two groups using a respiratory severity score.

    Measure: Symptoms severity of COVID-19

    Time: Approximately 90 days

    Description: Number of asymptomatic cases of COVID-19 will be determined by comparing serology in all participants at time of enrolment and at the end of follow up.

    Measure: Number of asymptomatic cases of COVID-19

    Time: Approximately 90 days

    Description: Number of symptomatic acute respiratory illnesses will be compared between the chloroquine or hydroxychloroquine and placebo groups.

    Measure: Number of symptomatic acute respiratory illnesses

    Time: Approximately 90 days

    Description: Severity of symptomatic acute respiratory illnesses will be compared between the chloroquine or hydroxychloroquine and placebo groups.

    Measure: Severity of symptomatic acute respiratory illnesses

    Time: Approximately 90 days

    Other Outcomes

    Description: Genetic loci and levels of biochemical components will be correlated with frequency of COVID-19, Acute Respiratory Infection and disease severity.

    Measure: Genetic loci and levels of biochemical components will be correlated with frequency of COVID-19, ARI and disease severity.

    Time: Approximately 90 days

    Description: Number of days lost to work in relation to the treatment arm

    Measure: Assess the impact of chloroquine or hydroxychloroquine prophylaxis on number of days lost to work during the pandemic.

    Time: Approximately 90 days

    Description: The trial will collect data on monetary costs associated with the use of healthcare resources and determine the effects between treatment groups.

    Measure: Assess the impact of chloroquine or hydroxychloroquine prophylaxis on healthcare costs

    Time: Approximately 90 days

    Description: The trial will collect data on health-related quality of life using the quality of life questionnaire (EQ-5D-3L) to determine the effects between treatment groups.

    Measure: Assess the impact of chloroquine or hydroxychloroquine prophylaxis on quality of life measures using the quality of life questionnaire (EQ-5D-3L)

    Time: Approximately 90 days
    10 Post-exposure Prophylaxis or Preemptive Therapy for SARS-Coronavirus-2: A Pragmatic Randomized Clinical Trial

    Study Objective: 1. To test if post-exposure prophylaxis with hydroxychloroquine can prevent symptomatic COVID-19 disease after known exposure to the SARS-CoV-2 coronavirus. 2. To test if early preemptive hydroxychloroquine therapy can prevent disease progression in persons with known symptomatic COVID-19 disease, decreasing hospitalizations and symptom severity.

    NCT04308668
    Conditions
    1. Corona Virus Infection
    2. Acute Respiratory Distress Syndrome
    3. SARS-CoV Infection
    4. Coronavirus
    5. Coronavirus Infections
    Interventions
    1. Drug: Hydroxychloroquine
    2. Other: Placebo
    MeSH:Infection Communicable Diseases Coronavirus Infections Severe Acute Respiratory Syndrome Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury

    Primary Outcomes

    Description: Number of participants at 14 days post enrollment with active COVID19 disease.

    Measure: Incidence of COVID19 Disease among those who are asymptomatic at baseline

    Time: 14 days

    Description: Repeated Measure mixed regression model of change in: Visual Analog Scale 0-10 score of rating overall symptom severity (0 = no symptoms; 10 = most severe)

    Measure: Overall change in disease severity over 14 days among those who are symptomatic at baseline

    Time: 14 days

    Secondary Outcomes

    Description: Outcome reported as the number of participants in each arm who require hospitalization for COVID19-related disease.

    Measure: Incidence of Hospitalization

    Time: 14 days

    Description: Outcome reported as the number of participants in each arm who expire due to COVID-19-related disease.

    Measure: Incidence of Death

    Time: 90 days

    Description: Outcome reported as the number of participants in each arm who have confirmed SARS-CoV-2 infection.

    Measure: Incidence of Confirmed SARS-CoV-2 Detection

    Time: 14 days

    Description: Outcome reported as the number of participants in each arm who self-report symptoms compatible with COVID19 infection.

    Measure: Incidence of Symptoms Compatible with COVID19 (possible disease)

    Time: 90 days

    Description: Outcome reported as the number of participants in each arm who discontinue or withdraw medication use for any reason.

    Measure: Incidence of All-Cause Study Medicine Discontinuation or Withdrawal

    Time: 14 days

    Description: Visual Analog Scale 0-10 score of rating overall symptom severity (0 = no symptoms; 10 = most severe)

    Measure: Overall symptom severity at 5 and 14 days

    Time: 5 and 14 days

    Description: Participants will self-report disease severity status as one of the following 3 options; no COVID19 illness (score of 1), COVID19 illness with no hospitalization (score of 2), or COVID19 illness with hospitalization or death (score of 3). Increased scale score indicates greater disease severity. Outcome is reported as the percent of participants who fall into each category per arm.

    Measure: Ordinal Scale of COVID19 Disease Severity at 14 days among those who are symptomatic at trial entry

    Time: 14 days
    11 Randomized Controlled Trial of Losartan for Patients With COVID-19 Not Requiring Hospitalization

    This is a multi-center, double-blinded study of COVID-19 infected patients randomized 1:1 to daily losartan or placebo for 10 days or treatment failure (hospital admission).

    NCT04311177
    Conditions
    1. Corona Virus Infection
    2. Acute Respiratory Distress Syndrome
    3. SARS-CoV Infection
    Interventions
    1. Drug: Losartan
    2. Other: Placebo
    MeSH:Infection Communicable Diseases Coronavirus Infections Severe Acute Respiratory Syndrome Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury

    Primary Outcomes

    Description: Outcome reported as the number of participants per arm admitted to inpatient hospital care due to COVID-19-related disease within 15 days of randomization. Currently, there is a pre-planned pooled analysis with a national trial network under development.

    Measure: Hospital Admission

    Time: 15 days

    Secondary Outcomes

    Description: The PROMIS Dyspnea (shortness of breath) item banks and pools assess self-reported shortness of breath in general, intensity, frequency and duration on a 0-10 scale, with 0 being no symptoms and 10 being the most severe. Finally, the patient answers the question "I've been short of breath" using a 0-4 scale, 0 being none and the most severe. There is no validated, unified single score and each item is evaluated individually.

    Measure: Change in PROMIS Dyspnea scale

    Time: 10 days

    Description: The SF-12 is a self-reported validated outcome measure assessing the impact of health on an individual's everyday life. Patients fill out a 12 question survey which is then scored by a clinician or researcher. Physical score is computed using the scores of twelve questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health. The 33-item Severity bank assesses the severity of difficulty breathing during various specific activities (the same 33 activities assessed in Dyspnea Functional Limitations). Each activity is rated in terms of degree of dyspnea (0 = no shortness of breath, 1 = mildly short of breath, 2 = moderately short of breath, 3 = severely short of breath) while engaging in the activity over the past 7 days. Total scores range from 0 to 99 with higher scores reflecting greater levels of dyspnea during daily activity.

    Measure: Change in SF-12 Physical Composite Score

    Time: 10 days

    Description: The SF-12 is a self-reported validated outcome measure assessing the impact of health on an individual's everyday life. Patients fill out a 12 question survey which is then scored by a clinician or researcher. Mental composite score is computed using the scores of twelve questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health.

    Measure: Change in SF-12 Mental Composite Score

    Time: 10 days

    Description: Participants will report their maximum daily oral temperature to the study team. Outcome is reported as the mean maximum daily body temperature (in degrees Celsius) over 10 days.

    Measure: Daily Maximum Temperature

    Time: 10 days

    Description: Outcome is reported as the mean number of emergency department and clinic presentations combined per participant in each arm.

    Measure: Emergency Department/Clinic Presentations

    Time: 28 days

    Description: Outcome reported as the number of participants in each arm who fall into each of 7 categories. Lower scores indicate greater condition severity. The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen; 6) Not hospitalized, limitation on activities; 7) Not hospitalized, no limitations on activities.

    Measure: Disease Severity Rating Day 7

    Time: 7 days

    Description: Outcome reported as the number of participants in each arm who fall into each of 7 categories. Lower scores indicate greater condition severity. The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen; 6) Not hospitalized, limitation on activities; 7) Not hospitalized, no limitations on activities.

    Measure: Disease Severity Rating Day 15

    Time: 15 days

    Description: Outcome reported as the number of participants in each arm who fall into each of 7 categories. Lower scores indicate greater condition severity. The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen; 6) Not hospitalized, limitation on activities; 7) Not hospitalized, no limitations on activities.

    Measure: Disease Severity Rating Day 28

    Time: 28 days

    Description: Participants will collect oropharyngeal swabs every third day for the duration of study participation. Viral load is measured as number of viral genetic copies per mL.

    Measure: Viral Load by Oropharyngeal Swab Day 9

    Time: 9 days

    Description: Participants will collect oropharyngeal swabs every third day for the duration of study participation. Viral load is measured as number of viral genetic copies per mL.

    Measure: Viral Load by Oropharyngeal Swab Day 15

    Time: 15 days

    Description: Outcome reported as the mean number of days participants in each arm did not require ventilator use.

    Measure: Ventilator-Free Days

    Time: 28 days

    Description: Outcome reported as the mean number of days participants in each arm did not require therapeutic oxygen use.

    Measure: Therapeutic Oxygen-Free Days

    Time: 28 days

    Description: Outcome reported as the percent of participants in each arm who require hospital admission by day 15 following randomization.

    Measure: Need for Hospital Admission at 15 Days

    Time: 15 days

    Description: Outcome reported as the percent of participants in each arm who require oxygen therapy by day 15 following randomization.

    Measure: Need for Oxygen Therapy at 15 Days

    Time: 15 days
    12 Randomized Controlled Trial of Losartan for Patients With COVID-19 Requiring Hospitalization

    This is a multi-center, double-blinded study of COVID-19 infected patients requiring inpatient hospital admission randomized 1:1 to daily Losartan or placebo for 7 days or hospital discharge.

    NCT04312009
    Conditions
    1. Corona Virus Infection
    2. Acute Respiratory Distress Syndr
    3. Acute Respiratory Distress Syndrome
    4. SARS-CoV Infection
    Interventions
    1. Drug: Losartan
    2. Other: Placebo
    MeSH:Infection Communicable Diseases Coronavirus Infections Severe Acute Respiratory Syndrome Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury

    Primary Outcomes

    Description: Outcome calculated from the partial pressure of oxygen or peripheral saturation of oxygen by pulse oximetry divided by the fraction of inspired oxygen (PaO2 or SaO2 : FiO2 ratio). PaO2 is preferentially used if available. A correction is applied for endotracheal intubation and/or positive end-expiratory pressure. Patients discharged prior to day 7 will have a home pulse oximeter send home for measurement of the day 7 value, and will be adjusted for home O2 use, if applicable. Patients who died will be applied a penalty with a P/F ratio of 0.

    Measure: Difference in Estimated (PEEP adjusted) P/F Ratio at 7 days

    Time: 7 days

    Secondary Outcomes

    Description: Outcome reported as the mean number of daily hypotensive episodes (MAP < 65 mmHg) prompting intervention (indicated by a fluid bolus >=500 mL) per participant in each arm.

    Measure: Daily Hypotensive Episodes

    Time: 10 days

    Description: Outcome reported as the number of participants in each arm requiring the use of vasopressors for hypotension.

    Measure: Hypotension Requiring Vasopressors

    Time: 10 days

    Description: Outcome reported as the number of participants in each arm who experience acute kidney injury as defined by the Kidney Disease Improving Global Outcomes (KDIGO) guidelines: Increase in serum creatinine by 0.3mg/dL or more within 48 hours OR Increase in serum creatinine to 1.5 times baseline or more within the last 7 days OR Urine output less than 0.5 mL/kg/h for 6 hours.

    Measure: Acute Kidney Injury

    Time: 10 days

    Description: The SOFA assessment is used to track a person's risk status during stay in the Intensive Care Unit (ICU). The score is based on six different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal, and neurological systems. Each organ system is assigned a point value from 0 (normal) to 4 (high degree of dysfunction/failure). Total score is calculated by entering patient data into a SOFA calculator, a widely-available software. Total scores range from 0-24, with higher scores indicating greater chance of mortality.

    Measure: Sequential Organ Failure Assessment (SOFA) Total Score

    Time: 10 days

    Description: Oxygen saturation (percent) is measured by pulse oximeter. Fraction of inspired oxygen (FiO2) (unitless) is the volumetric fraction of oxygen to other gases in respiratory support. The F/S ratio is unitless.

    Measure: Oxygen Saturation / Fractional Inhaled Oxygen (F/S)

    Time: 10 days

    Description: Outcome reported as the number of participants who have expired at 28 days post enrollment.

    Measure: 28-Day Mortality

    Time: 28 days

    Description: Outcome reported as the number of participants who have expired at 90 days post enrollment.

    Measure: 90-Day Mortality

    Time: 90 days

    Description: Outcome reported as the number of participants in each arm who require admission to the Intensive Care Unit (ICU).

    Measure: ICU Admission

    Time: 10 days

    Description: Outcome reported as the mean number of days participants in each arm did not require mechanical ventilation during an in-patient hospital admission.

    Measure: Number of Ventilator-Free Days

    Time: 10 days

    Description: Outcome reported as the mean number of days participants in each arm did not require therapeutic oxygen usage during an in-patient hospital admission.

    Measure: Number of Therapeutic Oxygen-Free Days

    Time: 10 days

    Description: Outcome reported as the mean number of days participants in each arm did not require vasopressor usage during an in-patient hospital admission.

    Measure: Number of Vasopressor-Free Days

    Time: 10 days

    Description: Outcome reported as the mean length of stay (in days) in the Intensive Care Unit (ICU) for participants in each arm.

    Measure: Length of ICU Stay

    Time: 10 days

    Description: Outcome reported as the mean length of in-patient hospital stay (in days) for participants in each arm.

    Measure: Length of Hospital Stay

    Time: 10 days

    Description: Outcome reported as the number of participants requiring BiPAP OR high flow nasal cannula OR mechanical ventilation OR extracorporeal membranous oxygenation (ECMO) utilization during in-patient hospital care in each arm.

    Measure: Incidence of Respiratory Failure

    Time: 10 days

    Description: The PROMIS Dyspnea (shortness of breath) item banks and pools assess self-reported shortness of breath in general, intensity, frequency and duration on a 0-10 scale, with 0 being no symptoms and 10 being the most severe. Finally, the patient answers the question "I've been short of breath" using a 0-4 scale, 0 being none and the most severe. There is no validated, unified single score and each item is evaluated individually.

    Measure: Change in PROMIS Dyspnea scale

    Time: 10 days

    Description: The SF-12 is a self-reported validated outcome measure assessing the impact of health on an individual's everyday life. Patients fill out a 12 question survey which is then scored by a clinician or researcher. Physical score is computed using the scores of twelve questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health.

    Measure: Change in SF-12 Physical Composite Score

    Time: 10 days

    Description: The SF-12 is a self-reported validated outcome measure assessing the impact of health on an individual's everyday life. Patients fill out a 12 question survey which is then scored by a clinician or researcher. Mental composite score is computed using the scores of twelve questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health.

    Measure: Change in SF-12 Mental Composite Score

    Time: 10 days

    Description: Outcome reported as the number of participants in each arm who fall into each of 7 categories. Lower scores indicate greater condition severity. The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen; 6) Not hospitalized, limitation on activities; 7) Not hospitalized, no limitations on activities.

    Measure: Disease Severity Rating

    Time: 10 days

    Description: Nasopharyngeal swabs will be collected every third day for the duration of study participation. Viral load is measured as number of viral genetic copies per mL.

    Measure: Viral Load by Nasopharyngeal Swab Day 9

    Time: 9 days

    Description: Nasopharyngeal swabs will be collected every third day for the duration of study participation. Viral load is measured as number of viral genetic copies per mL.

    Measure: Viral Load by Nasopharyngeal Swab Day 15

    Time: 15 days

    Description: Blood will be collected every third day for viral load assessment for the duration of study participation. Viral load is measured as number of viral genetic copies per mL.

    Measure: Viral Load by Blood Day 9

    Time: 9 days

    Description: Blood will be collected every third day for viral load assessment for the duration of study participation. Viral load is measured as number of viral genetic copies per mL.

    Measure: Viral Load by Blood Day 15

    Time: 15 days
    13 A Phase 2 Multiple Dose Study to Evaluate the Efficacy and Safety of PUL-042 Inhalation Solution in Reducing the Severity of COVID-19 in Adults Positive for SARS-CoV-2 Infection

    Adults who have tested positive for SARS-CoV-2 infection and who do not require supplemental oxygen will receive PUL-042 Inhalation Solution or placebo 3 times over a one week period in addition to their normal care. Subjects will be be followed and assessed for their clinical status over 28 days to see if PUL-042 Inhalation Solution improves the clinical outcome

    NCT04312997
    Conditions
    1. COVID-19
    Interventions
    1. Drug: PUL-042 Inhalation Solution
    2. Drug: Placebo
    MeSH:Infection Respiratory Aspiration

    Primary Outcomes

    Description: To determine the efficacy of PUL-042 Inhalation Solution in decreasing the severity of COVID-19 in subjects: 1) who have documented SARS-CoV-2 infection and, 2) who do not require supplemental oxygen (Ordinal Scale for Clinical Improvement 3 or less) at the time of enrollment. The primary endpoint is the difference in the proportion of patients with clinically meaningful worsening of COVID-19 within 28 days from the start of experimental therapy, as indicated by an increase of at least 2 points on the Ordinal Scale for Clinical Improvement. The Ordinal Scale for Clinical Improvement is a nine point scale (0-8) with 0 being no clinical or virological evidence of infection and 8 being death.

    Measure: Severity of COVID-19

    Time: 28 days

    Secondary Outcomes

    Description: SARS-Co-V-2 positivity up to 28 days from the start of experimental therapy

    Measure: SARS-CoV-2 infection

    Time: 28 days

    Description: To determine the difference in the proportion of COVID-19 patients with clinically meaningful worsening of COVID-19 within 14 days from the start of experimental therapy, as indicated by an increase of at least 2 points on the Ordinal Scale for Clinical Improvement. The Ordinal Scale for Clinical Improvement is a nine point scale (0-8) with 0 being no clinical or virological evidence of infection and 8 being death.

    Measure: Severity of COVID-19 over 14 days

    Time: 14 days

    Description: To assess the progression of COVID-19 severity during the study as measured by the SARS-CoV-2 Symptom Score. The SARS-CoV-2 Symptom Score measures 3 elements on a 0-3 scale (cough, shortness of breath or difficulty breathing, and muscle aches or fatigue) ranging from 0 for none to 3 for severe. The fourth element is fever and it is rated on a 0-4 scale with 0 being no fever and 4 being life-threatening.

    Measure: Severity of COVID-19 symptoms

    Time: 28 days

    Description: The requirement for ICU admission within 28 days from the start of the experimental therapy.

    Measure: ICU admission

    Time: 28 days

    Description: The requirement for mechanical ventilation within 28 days from the start of the experimental therapy.

    Measure: Mechanical Ventilation

    Time: 28 days

    Description: All cause mortality at 28 days from the start of experimental therapy

    Measure: Mortality

    Time: 28 days
    14 A Phase 2 Multiple Dose Study to Evaluate the Efficacy and Safety of PUL-042 Inhalation Solution in Reducing the Infection Rate and Progression to COVID-19 in Adults Exposed to SARS-CoV-2

    Subjects who have documented exposure to SARS-CoV-2 (COVID-19) will receive 4 doses of PUL-042 Inhalation Solution or 4 doses of a placebo solution by inhalation over 10 days. Subjects will be followed for the incidence and severity of COVID-19 over 28 days. Subjects will be tested for infection with SARS-CoV-2 at the beginning, middle and end of the study.

    NCT04313023
    Conditions
    1. COVID-19
    Interventions
    1. Drug: PUL-042 Inhalation Solution
    2. Drug: Placebo
    MeSH:Infection Disease Progression

    Primary Outcomes

    Description: To determine the efficacy of PUL-042 Inhalation Solution in the prevention of viral infection with SARS-CoV-2 and progression to COVID-19 in subjects: 1) who have repeated exposure to individuals with SARS-CoV-2 infection and, 2) are asymptomatic at enrollment. The primary endpoint is the severity of COVID-19 as measured by the maximum difference from the baseline value in the Ordinal Scale for Symptom Improvement within 28 days from the start of experimental therapy.

    Measure: Severity of COVID-19

    Time: 28 days

    Secondary Outcomes

    Description: Positive test for SARS-CoV-2 infection 28 days from the start of experimental therapy in subjects who test negative for SARS-CoV-2 at the pre-treatment visit

    Measure: Incidence of SARS-CoV-2 infection

    Time: 28 days

    Description: Positive test for SARS-CoV-2 infection 14 days from the start of experimental therapy in subjects who test negative for SARS-CoV-2 at the pre-treatment visit

    Measure: Incidence of SARS-CoV-2 infection

    Time: 14 days

    Description: The severity of COVID-19 as measured by the maximum difference from the baseline value in the Ordinal Scale for Symptom Improvement within 14 days from the start of experimental therapy.

    Measure: Severity of COVID-19

    Time: 14 days

    Description: The requirement for ICU admission within 28 days from the start of experimental therapy.

    Measure: ICU admission

    Time: 28 days

    Description: The requirement for mechanical ventilation within 28 days from the start of experimental therapy.

    Measure: Mechanical ventilation

    Time: 28 days

    Description: All cause mortality at 28 days from the start of experimental therapy.

    Measure: Mortality

    Time: 28 days
    15 An Adaptive Phase 2/3, Randomized, Double-Blind, Placebo-Controlled Study Assessing Efficacy and Safety of Sarilumab for Hospitalized Patients With COVID-19

    Phase 2: The primary objective of the study is to evaluate the clinical efficacy of sarilumab relative to the control arm in adult patients hospitalized with COVID-19 regardless of disease severity strata. Phase 3 Cohort 1: The primary objective of the study is to evaluate the clinical efficacy of sarilumab relative to the control arm in adult patients hospitalized with critical COVID-19 receiving mechanical ventilation at baseline. Phase 3 Cohort 2: The primary objective of the study is to evaluate the clinical efficacy of sarilumab relative to the control arm in adult patients hospitalized with COVID-19 receiving mechanical ventilation at baseline.

    NCT04315298
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Sarilumab
    2. Drug: Placebo

    Primary Outcomes

    Description: Phase 2

    Measure: Percent change in C-reactive protein (CRP) levels in patients with serum IL-6 level greater than the upper limit of normal

    Time: Day 4

    Description: Phase 3 Cohort 1 7-point Ordinal Scale: Death; Hospitalized, requiring invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); Hospitalized, requiring non-invasive ventilation or high flow oxygen devices; Hospitalized, requiring supplemental oxygen; Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care Not hospitalized

    Measure: Proportion of patients with at least 1-point improvement in clinical status using the 7-point ordinal scale in patients with critical COVID-19 receiving mechanical ventilation at baseline

    Time: Up to day 22

    Description: Phase 3 Cohort 2

    Measure: Proportion of patients with at least 1-point improvement in clinical status using the 7-point ordinal scale in patients with COVID-19 receiving mechanical ventilation at baseline

    Time: Up to day 22

    Secondary Outcomes

    Description: Phase 2

    Measure: Time to improvement (2 points) in clinical status assessment on the 7-point ordinal scale in severe or critical patients with serum IL-6 levels greater than the upper limit of normal

    Time: Up to day 29

    Description: Phase 2

    Measure: Time to improvement (2 points) in clinical status assessment on the 7-point ordinal scale reporting in severe or critical patients with all IL-6 levels

    Time: Up to day 29

    Description: Phase 2 Resolution of fever defined as postbaseline body temperature <37.2°C (oral), or <37.6°C (rectal or tympanic) or <36.8°C (temporal or axillary) Documented fever defined as ≥38°C (oral), ≥38.4°C (rectal or tympanic), or ≥37.6°C (temporal or axillary)

    Measure: Time to resolution of fever for at least 48 hours without antipyretics in patients with documented fever

    Time: Up to day 29

    Description: Phase 2 Defined as postbaseline body temperature <37.2°C (oral), or <37.6°C (rectal or tympanic) or <36.8°C (temporal or axillary)

    Measure: Time to resolution of fever for at least 48 hours without antipyretics by clinical severity

    Time: Up to day 29

    Description: Phase 2 Defined as postbaseline body temperature <37.2°C (oral), or <37.6°C (rectal or tympanic) or <36.8°C (temporal or axillary)

    Measure: Time to resolution of fever for at least 48 hours without antipyretics by baseline IL-6 levels

    Time: Up to day 29

    Description: Phase 2 Improvement in oxygenation defined as increase in SpO2/FiO2 of 50 or greater compared to the nadir SpO2/FiO2

    Measure: Time to improvement in oxygenation for at least 48 hours

    Time: Up to day 29

    Description: Phase 2 Defined as increase in SpO2/FiO2 of 50 or greater compared to the nadir SpO2/FiO2

    Measure: Time to improvement in oxygenation for at least 48 hours by clinical severity

    Time: Up to day 29

    Description: Phase 2 Defined as increase in SpO2/FiO2 of 50 or greater compared to the nadir SpO2/FiO2

    Measure: Time to improvement in oxygenation for at least 48 hours by baseline IL-6 levels

    Time: Up to day 29

    Description: Phase 2 Resolution of fever defined as postbaseline body temperature <37.2°C (oral), or <37.6°C (rectal or tympanic) or <36.8°C (temporal or axillary) Improvement in oxygenation defined as increase in SpO2/FiO2 of 50 or greater compared to the nadir SpO2/FiO2

    Measure: Time to resolution of fever and improvement in oxygenation for at least 48 hours

    Time: Up to day 29

    Description: Phase 2

    Measure: Mean change in the 7-point ordinal scale

    Time: Up to day 29

    Description: Phase 2

    Measure: Percentage of patients in each clinical status category using the 7-point ordinal scale

    Time: Up to day 29

    Description: Phase 2 NEWS2 consists of: Physiological Parameters: Respiration rate (per minute), SpO2 Scale 1 (%), SpO2 Scale 2 (%), Use of Air or oxygen, Systolic blood pressure (mmHg), Pulse (per minute), Consciousness, Temperature (°C)

    Measure: Time to discharge or to a National Early Warning Score 2 (NEWS2) of ≤2 and maintained for 24 hours

    Time: Up to day 29

    Description: Phase 2

    Measure: Change from baseline in NEWS2 scoring system

    Time: Up to day 29

    Description: Phase 2 Defined as ≥38°C (oral), ≥38.4°C (rectal or tympanic) or ≥37.6°C (temporal or axillary)

    Measure: Number of days with fever

    Time: Up to day 29

    Description: Phase 2

    Measure: Proportion of patients alive, off oxygen

    Time: At day 29

    Description: Phase 2

    Measure: Number of days of resting respiratory rate >24 breaths/min

    Time: Up to day 29

    Description: Phase 2

    Measure: Number of days with hypoxemia

    Time: Up to day 29

    Description: Phase 2

    Measure: Number of days of supplemental oxygen use

    Time: Up to day 29

    Description: Phase 2

    Measure: Time to saturation ≥94% on room air

    Time: Up to day 29

    Description: Phase 2

    Measure: Number of ventilator free days in the first 28 days

    Time: Baseline to day 29

    Description: Phase 2

    Measure: Number of patients requiring initiation of mechanical ventilation

    Time: Up to day 29

    Description: Phase 2

    Measure: Number of patients requiring non-invasive ventilation

    Time: Up to day 29

    Description: Phase 2

    Measure: Number of patients requiring the use of high flow nasal cannula

    Time: Up to day 29

    Description: Phase 2

    Measure: Number of patients admitted into an intensive care unit (ICU)

    Time: Up to day 29

    Description: Phase 2

    Measure: Number of days of hospitalization among survivors

    Time: Up to day 29

    Description: Phase 2

    Measure: Number of deaths due to any cause

    Time: Up to day 60

    Description: Phase 3

    Measure: Proportion of patients with at least 1-point improvement in clinical status using the 7-point ordinal scale

    Time: Up to day 22

    Description: Phase 3 Defined as discharged, or alive without supplemental oxygen use or at pre-COVID oxygen use

    Measure: Proportion of patients who recover

    Time: Up to day 22

    Description: Phase 3

    Measure: Proportion of deaths

    Time: Through day 29

    Description: Phase 3

    Measure: Proportion of patients alive not receiving mechanical ventilation

    Time: At day 22

    Description: Phase 3

    Measure: Proportion of patients alive not requiring extracorporeal membrane oxygenation (ECMO)

    Time: At day 22

    Description: Phase 3

    Measure: Proportion of patients with a 2-point improvement in clinical status on the 7-point ordinal scale

    Time: Up to day 22

    Description: Phase 3

    Measure: Time to at least 1-point improvement in clinical status assessment on the 7-point ordinal scale

    Time: Up to day 29

    Description: Phase 3

    Measure: Time to at least 2-point improvement in clinical status assessment on the 7-point ordinal scale

    Time: Up to day 29

    Description: Phase 3

    Measure: Proportion of patients receiving mechanical ventilation

    Time: Up to day 22

    Description: Phase 3

    Measure: Proportion of patients receiving ECMO

    Time: Up to day 22

    Description: Phase 3

    Measure: Proportion of patients discharged and alive

    Time: At day 22

    Description: Phase 3 Defined as discharged or alive without supplemental oxygen use or at pre-COVID oxygen use

    Measure: Time to recovery

    Time: Up to day 29

    Description: Phase 3

    Measure: Proportion of deaths

    Time: Through day 60

    Description: Phase 3

    Measure: Time to death due to any cause

    Time: Through day 60

    Description: Phase 3

    Measure: Number of ventilator free days

    Time: Up to day 29

    Description: Phase 3

    Measure: Number of days of hospitalization among survivors

    Time: Up to day 29

    Description: Phase 2 and Phase 3

    Measure: Proportion of patients with serious adverse events

    Time: Up to Day 29

    Description: Phase 2 and Phase 3

    Measure: Proportion of patients with Grade 4 neutropenia (ANC <500/mm3)

    Time: Up to day 29

    Description: Phase 2 and Phase 3

    Measure: Proportion of patients with severe or life-threatening bacterial, invasive fungal, or opportunistic infection

    Time: Up to day 29

    Description: Phase 2 and Phase 3

    Measure: Proportion of patients with severe or life-threatening bacterial, invasive fungal, or opportunistic infection in patients with Grade 4 neutropenia (ANC <500/mm3)

    Time: Up to day 29

    Description: Phase 2 and Phase 3

    Measure: Proportion of patients with hypersensitivity reactions

    Time: Up to day 29

    Description: Phase 2 and Phase 3

    Measure: Proportion of patients with infusion reactions

    Time: Up to day 29

    Description: Phase 2 and Phase 3

    Measure: Proportion of patients with gastrointestinal perforation

    Time: Up to day 29

    Description: Phase 2 and Phase 3

    Measure: White blood cell count

    Time: Up to day 29 if still hospitalized

    Description: Phase 2 and Phase 3

    Measure: Hemoglobin levels

    Time: Up to day 29 if still hospitalized

    Description: Phase 2 and Phase 3

    Measure: Platelet count

    Time: Up to day 29 if still hospitalized

    Description: Phase 2 and Phase 3

    Measure: Creatinine levels

    Time: Up to day 29 if still hospitalized

    Description: Phase 2 and Phase 3

    Measure: Total bilirubin level

    Time: Up to day 29 if still hospitalized

    Description: Phase 2 and Phase 3

    Measure: Alanine aminotransferase (ALT) level

    Time: Up to day 29 if still hospitalized

    Description: Phase 2 and Phase 3

    Measure: Aspartate aminotransferase (AST) level

    Time: Up to day 29 if still hospitalized
    16 Exploratory Clinical Study to Assess the Efficacy of NestaCell® Mesenchymal Stem Cell to Treat Patients With Severe COVID-19 Pneumonia

    This is phase II study to assess the efficacy of NestaCell® (mesenchymal stem cell) to treat severe COVID-19 pneumonia.

    NCT04315987
    Conditions
    1. COVID-19 Pneumonia
    Interventions
    1. Biological: NestaCell®
    2. Biological: Placebo
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Ordinal scale (WHO ordinal scale that measures illness severity over time)

    Measure: Change in Clinical Condition

    Time: 10 days

    Secondary Outcomes

    Description: Evaluation of Pneumonia change

    Measure: Rate of mortality within 10-days

    Time: 10 days

    Description: Evaluation of Pneumonia change

    Measure: Change of Clinical symptoms - respiratory rate

    Time: 10 days

    Description: oxygen saturation

    Measure: Hypoxia

    Time: 10 days

    Description: oxygen saturation

    Measure: PaO2 / FiO2 ratio

    Time: 10 days

    Description: Marker of Immunological function

    Measure: CD4+ and CD8+ T cell count

    Time: Days 1, 2, 4, 6 and 8.

    Description: PaO2 / FiO2 ratio

    Measure: Changes of blood oxygen

    Time: 10 days

    Description: Number of participants with treatment-related adverse events

    Measure: Side effects in the treatment group

    Time: 10 days

    Description: Complete blood count, ALT, AST, GGT, CK, CKmB and creatinine

    Measure: Complete blood count, cardiac, hepatic and renal profiles;

    Time: Days 1, 2, 4, 6 and 8.
    17 A Randomized, Double-blind, Placebo-controlled, Multi-site, Phase III Study to Evaluate the Safety and Efficacy of CD24Fc in COVID-19 Treatment

    The study is designed as a randomized, placebo-controlled, double blind, multicenter, Phase III trial to compare two COVID-19 treatment regimens in hospitalized adult subjects who are diagnosed with severe and critical COVID 19. Arm A: CD24Fc/Best Available Treatment; Arm B: placebo/ Best Available Treatment. CD24Fc will be administered as single dose of 480 mg via IV infusion on Day 1. Total of 270 subjects will be enrolled and randomized in 1:1 ratio to receive CD24Fc or placebo. All subjects will be treated with the best available treatment. The follow up period is 28 days.

    NCT04317040
    Conditions
    1. Covid19
    Interventions
    1. Drug: CD24Fc
    2. Drug: Placebo

    Primary Outcomes

    Description: Time to improve in clinical status: the time (days) required from the start of treatment to the improvement of clinical status "severe" to "moderate/mild"; or improvement from "scale 2, 3, or 4" to "scale 5 or higher" based on NIAID ordinal scales.

    Measure: Improvement of COVID-19 disease status

    Time: 29 days

    Secondary Outcomes

    Description: Proportion of patients who died or had respiratory failure, defined as the need for mechanical ventilation, ECMO, non-invasive ventilation, or high flow oxygen devices, at Day 29

    Measure: Proportion of patients who died or had respiratory failure.

    Time: 29 days

    Description: Time for disease progression from NIAID scale 3 or 4 to need to be on invasive mechanical ventilation, or ESMO, or death, or from NIAID scale 2 to death.

    Measure: Disease progression of COVID-19

    Time: 29 days

    Description: All cause of death

    Measure: All cause of death

    Time: 15 days and 29 days

    Description: Proportion of clinical relapse, as defined by rate of return to oxygen support for more than 1 day within 29 days from randomization after initial recovery

    Measure: Proportion of clinical relapse

    Time: 29 days

    Description: Conversion rate of clinical status on days 8 (proportion of subjects who changed from NIAID ordinal "scale 3 or 4" to "scale 5 or higher")

    Measure: Conversion rate of clinical status at Day 8

    Time: 8 days

    Description: Conversion rate of clinical status on days 15 (proportion of subjects who changed from NIAID ordinal "scale 3 or 4" to "scale 5 or higher")

    Measure: Conversion rate of clinical status at Day 15

    Time: 15 days

    Description: The discharge time, calculated after the randomization.

    Measure: Hospital discharge time

    Time: 29 days

    Description: Duration of mechanical ventilation (IMV, NIV) (days)

    Measure: Duration of mechanical ventilation

    Time: 29 days

    Description: Duration of pressors (days)

    Measure: Duration of pressors

    Time: 29 days

    Description: Duration of extracorporeal membrane oxygenation (days)

    Measure: Duration of ECMO

    Time: 29 days

    Description: Duration of oxygen therapy (oxygen inhalation by high flow nasal cannula or mask) (days)

    Measure: Duration of high flow oxygen therapy

    Time: 29 days

    Description: Changes of absolute lymphocyte count in peripheral blood

    Measure: Absolute lymphocyte count

    Time: 29 days

    Description: The changes of plasma concentration of D-dimers

    Measure: Change of D-dimers

    Time: 15 and 29 days
    18 A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Safety and Efficacy of Tocilizumab in Patients With Severe COVID-19 Pneumonia

    This study will evaluate the efficacy, safety, pharmacodynamics, and pharmacokinetics of tocilizumab (TCZ) compared with a matching placebo in combination with standard of care (SOC) in hospitalized patients with severe COVID-19 pneumonia.

    NCT04320615
    Conditions
    1. COVID-19 Pneumonia
    Interventions
    1. Drug: Tocilizumab (TCZ)
    2. Drug: Placebo
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Measure: Clinical Status Assessed Using a 7-Category Ordinal Scale

    Time: Day 28

    Secondary Outcomes

    Measure: Time to Clinical Improvement (TTCI), Defined as a National Early Warning Score 2 (NEWS2) of Time: Up to 60 days

    Measure: Time to Improvement of at Least 2 Categories Relative to Baseline on a 7-Category Ordinal Scale of Clinical Status

    Time: Up to 60 days

    Measure: Incidence of Mechanical Ventilation

    Time: Up to 60 days

    Measure: Ventilator-Free Days to Day 28

    Time: Up to Day 28

    Measure: Incidence of Intensive Care Unit (ICU) Stay

    Time: Up to 60 days

    Measure: Duration of ICU Stay

    Time: Up to 60 days

    Measure: Time to Clinical Failure

    Time: From first dose to time of death, mechanical ventilation, ICU admission, or study withdrawal (whichever occurs first, for up to 60 days). If already in ICU on ventilation, failure = a one-category worsening on the ordinal scale, withdrawal, or death

    Measure: Mortality Rate

    Time: Days 7, 14, 21, 28, and 60

    Measure: Time to Hospital Discharge

    Time: Up to 60 days

    Measure: Time to Recovery

    Time: Up to 60 days

    Measure: Duration of Time on Supplemental Oxygen

    Time: Up to 60 days

    Measure: Percentage of Participants with Adverse Events

    Time: Up to 60 days

    Measure: COVID-19 (SARS-CoV-2) Viral Load Over Time

    Time: Up to 60 days

    Measure: Time to Reverse-Transcriptase Polymerase Chain Reaction (RT-PCR) Virus Negativity

    Time: Up to 60 days

    Measure: Proportion of Participants with Post-Treatment Infection

    Time: Up to 60 days

    Measure: Serum Concentration of IL-6

    Time: Up to 60 days

    Measure: Serum Concentration of sIL-6R

    Time: Up to 60 days

    Measure: Serum Concentration of Ferritin

    Time: Up to 60 days

    Measure: Serum Concentration of C-Reactive Protein (CRP)

    Time: Up to 60 days

    Measure: Serum Concentration of TCZ

    Time: Up to 60 days
    19 Hydroxychloroquine Versus Placebo in Patients Presenting COVID-19 Infection and at Risk of Secondary Complication: a Prospective, Multicentre, Randomised, Double-blind Study

    A new human coronavirus responsible for pneumonia, SARS-CoV-2, emerged in China in December 2019 and has spread rapidly. COVID-19, the disease caused by this virus, has a very polymorphous clinical presentation, which ranges from upper respiratory tract infections to acute respiratory distress syndrome. It may appear serious straightaway or may evolve in two stages, with a worsening 7 to 10 days after the first clinical signs, potentially linked to a cytokine storm and accompanied by a high risk of thrombosis. The global mortality rate of COVID-19 is between 3% and 4%, with severe forms being more frequent among older patients. Management is symptomatic as no antiviral treatment has demonstrated any clinical benefit in this condition. Hydroxychloroquine is a derivative of chloroquine commonly used in some autoimmune diseases, such as systemic lupus erythematosus. It is active in vitro in cellular models of infection by many viruses such as HIV, hepatitis C or SARS-CoV. However, its interest in viral infections in humans has not been demonstrated. Very recently, a preliminary uncontrolled study evaluated the effect of hydroxychloroquine on viral shedding in subjects with COVID-19. Among 20 patients treated with hydroxychloroquine at a dose of 600 mg per day, the percentage of patients with detectable SARS-CoV-2 RNA in the nasopharynx decreased from 100% at inclusion (start of treatment) to 43% six days later. In comparison, 15 of 16 untreated patients had a positive RT-PCR six days after inclusion. Furthermore, hydroxychloroquine has immunomodulating and anti-inflammatory properties, which could theoretically prevent or limit secondary worsening. The research hypothesis is that treatment with hydroxychloroquine improves prognosis and reduces the risk of death or use for invasive ventilation in patients with COVID-19.

    NCT04325893
    Conditions
    1. Coronavirus
    Interventions
    1. Drug: Hydroxychloroquine
    2. Drug: Placebo
    MeSH:Coronavirus Infections

    Primary Outcomes

    Measure: Number of death from any cause, or the need for intubation and mechanical ventilation during the 14 days following inclusion and start of treatment.

    Time: Day 14

    Secondary Outcomes

    Measure: Number of death from any cause, or the need for intubation and mechanical ventilation during the 28 days following inclusion and start of treatment.

    Time: Day 28

    Description: WHO Ordinal Scale for Clinical Improvement ranges from 0 to 8, higher score meaning poorer outcome

    Measure: Clinical evolution on the WHO Ordinal Scale for Clinical Improvement for COVID-19 between day 0 and day 14

    Time: Day 14

    Description: WHO Ordinal Scale for Clinical Improvement ranges from 0 to 8, higher score meaning poorer outcome

    Measure: Clinical evolution on the WHO Ordinal Scale for Clinical Improvement for COVID-19 between day 0 and day 28.

    Time: Day 28

    Measure: Number of all-cause mortality at day 14

    Time: Day 14

    Measure: Number of all-cause mortality at day 28

    Time: Day 28

    Measure: Rate of positive SARS-CoV-2 RT-PCR on nasopharyngeal samples at day 5

    Time: Day 5

    Measure: Rate of positive SARS-CoV-2 RT-PCR on nasopharyngeal samples at day 10

    Time: Day 10

    Measure: The rate of venous thromboembolic events at day 28, documented and confirmed by an adjudication committee.

    Time: Day 28

    Measure: Number of all-cause mortality at day 28 in patients aged 75 and older

    Time: day 28

    Measure: Clinical evolution on the WHO OSCI scale for COVID-19 between day 0 and day 28 for patients aged 75 or older

    Time: day 28

    Measure: Rate of severe adverse events at day 28

    Time: day 28

    Measure: Number of all-cause mortality at day 14 in patients aged 75 and older

    Time: day 14
    20 ODYSSEY: A Randomized, Double-blind, Placebo-controlled Study to Investigate the Efficacy of Tradipitant in Treating Inflammatory Lung Injury and Improving Clinical Outcomes Associated With Severe or Critical COVID-19 Infection

    This is a randomized, double-blind placebo-controlled trial to investigate the efficacy and safety of tradipitant 85 mg orally given twice daily to treat inflammatory lung injury associated with severe or critical COVID-19 infection. On evaluation for enrollment, participant will need to meet all inclusion and exclusion criteria. If participant consents, they will be randomized 1:1 to treatment with either tradipitant 85 mg PO BID or placebo in addition to standard of care for COVID-19 infection as per the protocol at the treating hospital. NEWS 2 will be assessed at screening and daily following randomization. Inflammatory lab markers as detailed should be collected once per day in the morning, preferably at the same time every morning. All enrolled participants will have whole blood collected for whole genome sequencing.

    NCT04326426
    Conditions
    1. Coronavirus Infection
    Interventions
    1. Drug: Tradipitant
    2. Drug: Placebo
    MeSH:Infection Communicable Diseases Coronavirus Infections Severe Acute Respiratory Syndrome

    Primary Outcomes

    Measure: Time to improvement on a 7-point ordinal scale as compared to baseline

    Time: 14 days or discharge

    Secondary Outcomes

    Measure: Treatment and prevention of inflammatory lung injury as measured by change in baseline of interleukin-6 (IL-6)

    Time: 14 days or discharge

    Measure: Rate of Decline of COVID-19 viral load assessed by RT-PCR from nasopharyngeal samples

    Time: 14 days or discharge

    Measure: In-hospital mortality

    Time: 14 days or discharge

    Measure: Mean change in NEWS2 score from baseline

    Time: 14 days or discharge

    Measure: Understand the effect of genetics for treatment response through whole genome sequence of the participant and the COVID-19 virus

    Time: 14 days or discharge

    Measure: Reduction from baseline of NRS for cough

    Time: 14 days or discharge

    Measure: Reduction from baseline of NRS for nausea

    Time: 14 days or discharge

    Measure: Time to normalization of fever for at least 48 hours

    Time: 14 days or discharge

    Measure: Time to improvement in oxygenation for at least 48 hours

    Time: 14 days or discharge
    21 An Adaptive Phase 3, Randomized, Double-blind, Placebo-controlled Study Assessing Efficacy and Safety of Sarilumab for Hospitalized Patients With COVID19

    Primary Objective: To evaluate the clinical efficacy of sarilumab relative to the control arm in adult patients hospitalized with severe or critical COVID-19 Secondary Objectives: - Evaluate the 28-day survival rate - Evaluate the clinical efficacy of sarilumab compared to the control arm by clinical severity - Evaluate changes in the National Early Warning Score 2 (NEWS2) - Evaluate the duration of predefined symptoms and signs (if applicable) - Evaluate the duration of supplemental oxygen dependency (if applicable) - Evaluate the incidence of new mechanical ventilation use during the study - Evaluate the duration of new mechanical ventilation use during the Study - Evaluate the proportion of patients requiring rescue medication during the 28-day period - Evaluate need for admission into intensive care unit (ICU) - Evaluate duration of hospitalization (days) - The secondary safety objectives of the study are to evaluate the safety of sarilumab through hospitalization (up to day 29 if patient is still hospitalized) compared to the control arm as assessed by incidence of: - Serious adverse events (SAEs) - Major or opportunistic bacterial or fungal infections in patients with grade 4 neutropenia - Grade ≥2 infusion related reactions - Grade ≥2 hypersensitivity reactions - Increase in alanine transaminase (ALT) ≥3X upper limit of normal (ULN) (for patients with normal baseline) or >3X ULN AND at least 2-fold increase from baseline value (for patients with abnormal baseline) - Major or opportunistic bacterial or fungal infections

    NCT04327388
    Conditions
    1. Corona Virus Infection
    Interventions
    1. Drug: Sarilumab SAR153191
    2. Drug: Placebo
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome

    Primary Outcomes

    Description: The ordinal scale is an assessment of the clinical status. Score ranges 1-7. Lower score is worse.

    Measure: Time to improvement of 2 points in clinical status assessment from baseline using the 7-point ordinal scale

    Time: Baseline to Day 29

    Secondary Outcomes

    Measure: Percent of patients alive at Day 29

    Time: Day 29

    Description: The ordinal scale is an assessment of the clinical status. Score ranges 1-7. Lower score is worse.

    Measure: Proportion of patients with one point improvement from baseline in clinical status assessment at days 4, 7, 15, 21, 29 using the 7-point ordinal scale

    Time: Baseline to Days 4, 7, 15, 21, 29

    Description: The ordinal scale is an assessment of the clinical status. Score ranges 1-7. Lower score is worse.

    Measure: Mean change in the 7-point ordinal scale from baseline to Days 4, 7, 15, 21, and 29 (or until discharge)

    Time: Baseline to Days 4, 7, 15, 21, 29 (or until discharge)

    Description: Defined as body temperature (≤36.6°C [axilla], or ≤37.2 °C [oral], or ≤37.8°C [rectal or tympanic]) for at least 48 hours without antipyretics or until discharge, whichever is sooner.

    Measure: Time to resolution of fever

    Time: Baseline to Day 29

    Description: Resolution of both fever and improvement in oxygenation. Resolution of fever is defined as body temperature (≤36.6°C [axilla], or ≤37.2 °C [oral], or ≤37.8°C [rectal or tympanic]) for at least 48 hours without antipyretics or until discharge, whichever is sooner. Improvement in oxygenation is defined as SpO2/FiO2 of 50 or greater compared to the nadir SpO2/FiO2 for at least 48 hours, or until discharge, whichever is sooner.

    Measure: Time to resolution of fever and improvement in oxygenation

    Time: Baseline to Day 29

    Description: Fever is defined as >37.4°C (axilla), or >38.0 °C (oral), or >38.4°C (rectal or tympanic) based on maximum value observed during a 24-hour period.

    Measure: Days with fever

    Time: Baseline to Day 29

    Description: The National Early Warning Score (NEWS2) is used to standardize the assessment of acute-illness severity, track the clinical condition of patients, and to alert clinical teams to patient deterioration. Score ranges from 0-20. A higher score is worse.

    Measure: Time to change in NEWS2 from baseline

    Time: Baseline to Day 29

    Description: The NEWS2 is used to standardize the assessment of acute-illness severity, track the clinical condition of patients, and to alert clinical teams to patient deterioration. Score ranges from 0-20. A higher score is worse.

    Measure: Time to NEWS2 of <2 and maintained for 24 hours

    Time: Baseline to Day 29

    Description: The NEWS2 is used to standardize the assessment of acute-illness severity, track the clinical condition of patients, and to alert clinical teams to patient deterioration. Score ranges from 0-20. A higher score is worse.

    Measure: Mean change from baseline to days 4, 7, 15, 21, and 29 in NEWS2

    Time: Baseline to days 4, 7, 15, 21, and 29

    Description: SpO2/FiO2 of 50 or greater compared to the nadir for at least 48 hours, or until discharge, whichever is sooner. SpO2 is oxygen saturation and FiO2 is the fraction of inspired oxygen.

    Measure: Time-to-improvement in oxygenation

    Time: Baseline to Day 29

    Description: Supplemental oxygen is defined as oxygen administration by nasal cannula, simple face mask, or other similar oxygen delivery device.

    Measure: Alive off supplemental oxygen at day 29

    Time: Day 29

    Description: Hypoxemia is defined as SpO2 <93% on room air, or requiring supplemental oxygen, or mechanical ventilatory support.

    Measure: Days of hypoxemia

    Time: Baseline to Day 29

    Description: Supplemental oxygen is defined as oxygen administration by nasal cannula, simple face mask, or other similar oxygen delivery device.

    Measure: Days of supplemental oxygen use

    Time: Baseline to Day 29

    Measure: Days of resting respiratory rate >24 breaths/min

    Time: Baseline to Day 29

    Measure: Time to saturation ≥94% on room air

    Time: Baseline to Day 29

    Measure: Ventilator free days in the first 28 days (to day 29)

    Time: Baseline to Day 29

    Description: For those not requiring these interventions at baseline.

    Measure: The number of patients with Initiation of mechanical ventilation, non-invasive ventilation, or use of high flow nasal cannula

    Time: Baseline to Day 60

    Measure: Proportion of patients requiring rescue medication during the 28-day period

    Time: Baseline to Day 28

    Description: For patients are not in ICU at baseline

    Measure: The number of patients transferred to the ICU or the need to transfer to the ICU (if the ICU is not available)

    Time: Baseline to Day 60

    Measure: Days of hospitalization among survivors

    Time: Baseline to Day 60

    Measure: Incidence of serious adverse events

    Time: Baseline to Day 60

    Measure: The incidence of major or opportunistic bacterial or fungal infections

    Time: Baseline to Day 60

    Measure: The incidence of major or opportunistic bacterial or fungal infections in patients with grade 4 neutropenia

    Time: Baseline to Day 60

    Measure: The incidence of hypersensitivity reactions, infusion reactions, gastrointestinal perforation

    Time: Baseline to Day 60

    Measure: The number of patients with clinically significant laboratory abnormalities

    Time: Baseline to Day 60
    22 Reducing Health Care Workers Absenteeism in COVID-19 Pandemic by Enhanced Trained Immune Responses Through Bacillus Calmette-Guérin Vaccination, a Randomized Controlled Trial.

    Rationale: Covid-19 spreads rapidly throughout the world. A large epidemic in the Netherlands would seriously challenge the available hospital capacity, and this would be augmented by absenteeism of healthcare workers (HCW). Strategies to prevent absenteeism of HCW are, therefore, desperately needed to safeguard continuous patient care. Bacille Calmette-Guérin (BCG) is a vaccine against tuberculosis, with protective non-specific effects against other respiratory tract infections in in vitro and in vivo studies, and reported significant reductions in morbidity and mortality. The hypothesis is that BCG vaccination can reduce HCW absenteeism during the epidemic phase of Covid-19. Objective: Primary objective: To reduce absenteeism among HCW with direct patient contacts during the epidemic phase of Covid-19. Secondary objective: To reduce hospital admission, ICU admission or death in HCW with direct patient contacts during the epidemic phase of Covid-19. Study design: A placebo-controlled adaptive multi-centre randomized controlled trial. Study population: HCW with direct patient contacts among which nurses and physicians working at emergency rooms and wards where Covid-19-infected patients are treated. Intervention: Participants will be randomized between intracutaneous administration of BCG vaccine or placebo in a 1:1 ratio. Main study parameters/endpoints: Primary endpoint: number of days of (unplanned) absenteeism for any reason. Secondary endpoints include the number of days of (unplanned) absenteeism because of documented Covid-19 infection, and the cumulative incidence of hospital admission, Intensive Care Admission, and death. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Based on previous experience and randomized controlled trials in adult and elderly individuals, the risks of BCG vaccination are considered low. The objective of this trial is to evaluate the beneficial effects of BCG vaccination through a lower work absenteeism rate of HCW and/or a mitigated clinical course of Covid-19 infection. The primary endpoint and the adaptive design with frequent interim analyses facilitate maximum efficiency of the trial, so that results can inform policy making during the ongoing epidemic.

    NCT04328441
    Conditions
    1. COVID-19
    Interventions
    1. Drug: BCG Vaccine
    2. Drug: Placebo

    Primary Outcomes

    Description: Number of days of unplanned absenteeism for any reason

    Measure: Health Care Workers absenteeism

    Time: Maximum of 365 days

    Secondary Outcomes

    Measure: the cumulative incidence of documented COVID-19

    Time: Maximum of 365 days

    Measure: the cumulative incidence of Hospital Admission due to documented COVID-19

    Time: Maximum of 365 days

    Measure: the number of days of unplanned absenteeism, because of documented COVID-19

    Time: Maximum of 365 days

    Measure: the cumulative incidence of self-reported acute respiratory symptoms or fever

    Time: Maximum of 365 days

    Measure: the cumulative incidence of death due to documented COVID-19

    Time: Maximum of 365 days

    Measure: the cumulative incidence of Intensive Care Admission due to documented COVID-19

    Time: Maximum of 365 days

    Description: Exploratory

    Measure: the number of days of absenteeism, because of imposed quarantine as a result of exposure to COVID-19

    Time: Maximum of 365 days

    Description: Exploratory

    Measure: the number of days of absenteeism, because of imposed quarantine as a result of having acute respiratory symptoms, fever or documented COVID-19

    Time: Maximum of 365 days

    Description: Exploratory

    Measure: the number of days of unplanned absenteeism because of self-reported acute respiratory symptoms

    Time: Maximum of 365 days

    Description: Exploratory

    Measure: the number of days of self-reported fever (≥38 gr C)

    Time: Maximum of 365 days

    Description: Exploratory

    Measure: the cumulative incidence of self-reported fever (≥38 gr C)

    Time: Maximum of 365 days

    Description: Exploratory

    Measure: the number of days of self-reported acute respiratory symptoms

    Time: Maximum of 365 days

    Description: Exploratory

    Measure: the cumulative incidence of self-reported acute respiratory symptoms

    Time: Maximum of 365 days

    Description: Exploratory

    Measure: the cumulative incidence of death for any reason

    Time: Maximum of 365 days

    Description: Exploratory

    Measure: the cumulative incidence of Intensive Care Admission for any reason

    Time: Maximum of 365 days

    Description: Exploratory

    Measure: the cumulative incidence of Hospital Admission for any reason

    Time: Maximum of 365 days

    Description: Exploratory

    Measure: the cumulative incidence and magnitude of plasma/serum antibodies (IgA,M,G) and SARS-CoV-2-specific antibodies at 12 weeks after vaccination and at the end of the study period

    Time: Maximum of 365 days

    Description: Exploratory

    Measure: the cumulative incidence and magnitude of plasma/serum antibodies (IgA,M,G) and SARS-CoV-2-specific antibodies at 12 weeks after vaccination and at the end of the study period

    Time: 3-6 months after inclusion
    23 Pre-exposure Prophylaxis for SARS-Coronavirus-2: A Pragmatic Randomized Clinical Trial

    Objective: To determine if pre-exposure prophylaxis with hydroxychloroquine is effective for the prevention of COVID-19 disease.

    NCT04328467
    Conditions
    1. COVID-19
    2. Corona Virus Infection
    3. ARDS
    4. Acute Respiratory Distress Syndrome
    Interventions
    1. Drug: Hydroxychloroquine
    2. Other: Placebo
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury

    Primary Outcomes

    Description: Outcome reported as the percent of participants in each arm who are COVID-19-free at the end of study treatment.

    Measure: COVID-19-free survival

    Time: up to 12 weeks

    Secondary Outcomes

    Description: Outcome reported as the percent of participants in each arm who have a confirmed SARS-CoV-2 infection during study treatment.

    Measure: Incidence of confirmed SARS-CoV-2 detection

    Time: up to 12 weeks

    Description: Outcome reported as the percent of participants in each arm who report COVID-19-related symptoms during study treatment.

    Measure: Incidence of possible COVID-19 symptoms

    Time: up to 12 weeks

    Description: Outcome reported as the percent of participants in each arm who discontinue study medication use for any reason during treatment.

    Measure: Incidence of all-cause study medicine discontinuation

    Time: up to 12 weeks

    Description: Participants will self-report COVID-19 status on an ordinal scale as follows: No illness (score=1), Illness with outpatient observation (score=2), Hospitalization (or post-hospital discharge) (score=3), or Hospitalization with ICU stay or death (score=4). Possible scores range from 1-4 with higher scores indicating greater disease severity.

    Measure: Ordinal Scale of COVID-19 Disease maximum severity if COVID-19 diagnosed at study end

    Time: up to 12 weeks

    Description: Outcome reported as the percent of participants in each arm who are hospitalized or expire due to COVID-19 during study treatment.

    Measure: Incidence of Hospitalization for COVID-19 or death

    Time: up to 12 weeks

    Description: Outcome reported as the percent of participants in each arm who experience medication-related side effects during study treatment.

    Measure: Incidence of study medication-related side effects

    Time: up to 12 weeks
    24 A Phase 2 Randomized, Single-Blind Study of a Single Dose of Peginterferon Lambda-1a (Lambda) Compared With Placebo in Outpatients With Mild COVID-19

    To evaluate the efficacy of a single dose of subcutaneous injections of 180 ug of Peginterferon Lambda-1a, compared with placebo in reducing the duration of viral shedding of SARS-CoV-2 virus in patients with uncomplicated COVID-19 disease.

    NCT04331899
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Peginterferon Lambda-1a
    2. Other: Placebo

    Primary Outcomes

    Description: Time to first of two consecutive negative respiratory secretions obtained by oropharyngeal and/or anterior nare swabs for SARS-CoV-2 by qRT-PCR.

    Measure: Duration of Viral shedding of SARS-CoV-2 by qRT-PCR

    Time: 28 days

    Secondary Outcomes

    Description: Sars-CoV-2 RNA level in oropharyngeal and/or anterior nare swabs collected daily.

    Measure: Sars-CoV-2 viral load

    Time: 28 days

    Description: Area under the curve of SARSCoV-2 viral load in oropharyngeal and/or anterior nare swabs collected daily.

    Measure: Area under the curve of SARS-COV-2 viral load

    Time: 28 days

    Description: Time to alleviation of all symptoms (fever, chills, cough, nasal congestion, muscle pains), defined as the time from initiation of treatment until all symptoms are rated as absent or mild in symptomatic patients.

    Measure: Time to alleviation of all symptoms Time to alleviation of all symptoms

    Time: 28 days

    Measure: Number of participants requiring emergency department visits or hospitalizations within 28 days of initiation of treatment

    Time: 28 days
    25 Outcomes Related to COVID-19 Treated With Hydroxychloroquine Among In-patients With Symptomatic Disease

    ORCHID is a multicenter, blinded, placebo-controlled, randomized clinical trial evaluating hydroxychloroquine for the treatment of adults hospitalized with COVID-19. Patients, treating clinicians, and study personnel will all be blinded to study group assignment.

    NCT04332991
    Conditions
    1. Coronavirus
    2. Acute Respiratory Infection
    3. SARS-CoV Infection
    Interventions
    1. Drug: Hydroxychloroquine
    2. Drug: Placebo
    MeSH:Infection Communicable Diseases Respiratory Tract Infections Coronavirus Infections Severe Acute Respiratory Syndrome
    HPO:Respiratory tract infection

    Primary Outcomes

    Description: We will determine the COVID Ordinal Scale for all patients on study day 15 COVID Ordinal Scale defined as: Death Hospitalized on invasive mechanical ventilation or ECMO ( extracorporeal membrane oxygenation) Hospitalized on non-invasive ventilation or high flow nasal cannula Hospitalized on supplemental oxygen Hospitalized not on supplemental oxygen Not hospitalized with limitation in activity (continued symptoms) Not hospitalized without limitation in activity (no symptoms)

    Measure: COVID Ordinal Outcomes Scale on Day 15

    Time: assessed on study day 15

    Secondary Outcomes

    Description: Vital status of the patient on day 15 will be determined using any of the following methods: medical record review, phone calls to patient or proxy

    Measure: all-location, all-cause mortality assessed on day 15

    Time: assessed on study day 15

    Description: Vital status of the patient at day 28 will be determined using any of the following methods: medical record review, phone calls to patient or proxy

    Measure: all-location, all-cause mortality assessed on day 29

    Time: assessed on study day 29

    Description: We will determine the COVID Ordinal Scale for all patients on study day 3

    Measure: COVID Ordinal Outcomes Scale on Study Day 3

    Time: assessed on study day 3

    Description: We will determine the COVID Ordinal Scale on study day 8

    Measure: COVID Ordinal Outcomes Scale on Study Day 8

    Time: assessed on study day 8

    Description: We will determine the COVID Ordinal Scale on study day 29

    Measure: COVID Ordinal Outcomes Scale on Study Day 29

    Time: assessed on study day 29

    Description: We will determine the number of patients who are either dead or on ECMO ( extracorporeal membrane oxygenation) between enrollment and day 28

    Measure: Number of patients dead or with receipt of ECMO between enrollment and Day 28

    Time: Enrollment to Day 28

    Description: The number of calendar days between randomization and 28 days later that the patient is alive and without the use of oxygen therapy. Patients who die prior to day 28 are assigned zero oxygen free days.

    Measure: Oxygen-free days through Day 28

    Time: 28 days after randomization

    Description: Ventilator-free days is defined to be 28 days minus the duration of mechanical ventilation through day 28. Participants who do not survive to day 28 are assigned zero ventilator-free days.

    Measure: Ventilator-free days through Day 28

    Time: 28 days after randomization

    Description: The number of calendar days between randomization and 28 days later that the patient is alive and without the use of vasopressor therapy. Patients who die prior to day 28 are assigned zero vasopressor free days.

    Measure: Vasopressor-free days through Day 28

    Time: 28 days after randomization

    Description: The number of days spent out of the ICU to day 28.

    Measure: ICU-free days to Day 28

    Time: 28 days after randomization

    Description: Defined as 28 days minus the number of days from randomization to discharge home.If a patient has not been discharged home prior to day 28 or dies prior to day 28, hospital free days will be zero.

    Measure: Hospital-free days to Day 28

    Time: 28 days after randomization

    Other Outcomes

    Description: We will determine the number of patients that experience seizure between randomization and day 28

    Measure: Number of patients with seizures to day 28

    Time: 28 days after randomization

    Description: We will determine the number of patients that experience ventricular arrhythmia between randomization and day 28

    Measure: Number of patients with atrial or ventricular arrhythmia to day 28

    Time: 28 days after randomization

    Description: We will determine the number of patients that experience cardiac arrest between randomization and day 28

    Measure: Number of patients with cardiac arrest to day 28

    Time: 28 days after randomization

    Description: We will determine the number of patients that experience elevation in aspartate aminotransferase or alanine aminotransferase to twice the local upper limit of normal between randomization and day 28

    Measure: Number of patients with elevation in aspartate aminotransferase or alanine aminotransferase to twice the local upper limit of normal to day 28

    Time: 28 days after randomization

    Description: We will determine the number of patients that experience acute pancreatitis between randomization and day 28

    Measure: Number of patients with acute pancreatitis arrest to day 28

    Time: 28 days after randomization

    Description: We will determine the number of patients that experience acute kidney injury between randomization and day 28

    Measure: Number of patients with acute kidney injury to day28

    Time: 28 days after randomization

    Description: We will determine the number of patients that experience renal replacement therapy between randomization and day 28

    Measure: Number of patients with receipt of renal replacement therapy to day 28

    Time: 28 days after randomization

    Description: We will determine the number of patients that experience symptomatic hypoglycemia between randomization and day 28

    Measure: Number of patients with symptomatic hypoglycemia to day 28

    Time: 28 days after randomization

    Description: We will determine the number of patients that experience neutropenia, lymphopenia, anemia, or thrombocytopenia between randomization and day 28

    Measure: Number of patients with neutropenia, lymphopenia, anemia, or thrombocytopenia to day 28

    Time: 28 days after randomization

    Description: We will determine the number of patients that experience severe dermatologic reaction between randomization and day 28

    Measure: Number of patients with severe dermatologic reaction to day 28

    Time: 28 days after randomization

    Description: Time to recovery, defined as time to reaching level 5, 6, or 7 on the COVID Outcomes Scale, which is the time to the earlier of final liberation from supplemental oxygen or hospital discharge

    Measure: Time to recovery, defined as time to reaching level 5, 6, or 7 on the COVID Outcomes Scale, which is the time to the earlier of final liberation from supplemental oxygen or hospital discharge

    Time: 28 days after randomization
    26 Piclidenoson for Treatment of COVID-19 - A Randomized, Double-Blind, Placebo-Controlled Trial

    Patients with documented moderate COVID-19 infection will be randomized 1:1 to receive piclidenoson 2 mg Q12H orally with standard supportive care (SSC - intervention arm) or placebo orally with SSC (control arm) for up to 28 days.

    NCT04333472
    Conditions
    1. COVID-19
    2. Coronavirus Infection
    Interventions
    1. Drug: Piclidenoson
    2. Drug: Placebo
    MeSH:Coronavirus Infections Severe Acute Severe Acute Respiratory Syndrome

    Primary Outcomes

    Description: Proportion of subjects alive and free of respiratory failure (defined as need for non-invasive or invasive mechanical ventilation, high-flow oxygen, or extracorporeal membrane oxygenation) at Day 29

    Measure: Proportion of subjects alive and free of respiratory failure

    Time: 29 days

    Description: Proportion of subjects alive and discharged to home without need for supplemental oxygen at Day 29

    Measure: Proportion of subjects discharged home alive

    Time: 29 days

    Description: Proportion of patients experiencing AEs

    Measure: Treatment-emergent adverse events (AEs)

    Time: 29 days

    Secondary Outcomes

    Description: • Clinical status at Day 29 on NIAID 8-point ordinal scale (NIH 2020): Not hospitalized, no limitations Not hospitalized, with limitations Hospitalized, no active medical problems Hospitalized, not on oxygen Hospitalized, on oxygen Hospitalized, on high-flow oxygen or noninvasive mechanical ventilation Hospitalized, on mechanical ventilation or ECMO Death

    Measure: Clinical status

    Time: 29 days

    Description: Time (days) to improvement of 2 points on 7-point ordinal clinical scale

    Measure: Time to improvement

    Time: 29 days

    Description: Proportion of patients who require mechanical ventilation

    Measure: Incidence of mechanical ventilation

    Time: 29 days

    Description: Ventilator-free days to Day 29

    Measure: Ventilator-free days

    Time: 29 days

    Description: Proportion of patients who require ICU admission

    Measure: Incidence of Intensive Care Unit (ICU) admission

    Time: 29 days

    Description: Duration (days) of ICU stay

    Measure: Duration of ICU stay

    Time: 29 days

    Description: Time (days) to hospital discharge

    Measure: Time to hospital discharge

    Time: 29 days

    Description: Duration (days) of need for supplemental oxygen

    Measure: Duration of need for supplemental oxygen

    Time: 29 days

    Description: Time (days) to virus negativity by RT-PCR, defined as absence of SARS CoV 2 on 2 consecutive days of sampling

    Measure: Time to virus negativity

    Time: 29 days

    Description: SARS-CoV-2 viral load (number of copies) by quantitative RT-PCR

    Measure: SARS-CoV-2 viral load

    Time: 29 days

    Description: Proportion of patients experiencing AEs leading to early discontinuation of trial treatment

    Measure: AEs leading to withdrawal

    Time: 29 days

    Description: Proportion of patients experiencing SAEs

    Measure: Treatment-emergent serious AEs (SAEs)

    Time: 29 days

    Description: Proportion of patients experiencing treatment-emergent changes in clinical laboratory parameters or ECGs

    Measure: Treatment-emergent abnormalities in clinical laboratory parameters or electrocardiograms (ECGs)

    Time: 29 days

    Description: Proportion of patients who meet study safety-related stopping rules

    Measure: Incidence of meeting safety-related stopping rules

    Time: 29 days

    Description: Plasma concentrations over time of piclidenoson

    Measure: Pharmacokinetics of piclidenoson in this patient population

    Time: 5 days

    Description: Change from baseline in serum concentrations of cytokines

    Measure: Serum cytokine levels

    Time: 29 days
    27 A Phase 1b, Randomized, Double-blinded, Placebo-controlled Study of Hydroxychloroquine in Outpatient Adults With COVID-19

    Primary Objective: To assess the effect of hydroxychloroquine versus placebo on nasopharyngeal SARS-CoV-2 viral load in outpatient adults with COVID-19 Secondary Objectives: - To assess the effect of hydroxychloroquine versus placebo on clinical signs and symptoms and progression of disease in outpatient adults with COVID-19 - To assess the safety and tolerability of hydroxychloroquine in outpatient adults with COVID-19

    NCT04333654
    Conditions
    1. Coronavirus Infection
    Interventions
    1. Drug: Hydroxychloroquine SAR321068
    2. Drug: Placebo
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome

    Primary Outcomes

    Description: Viral load assessed by PCR from a nasopharyngeal swab

    Measure: Change from baseline to Day 3 in nasopharyngeal SARS-CoV-2 viral load (if quantitative PCR is available)

    Time: Baseline to Day 3

    Description: Viral load assessed by PCR from a nasopharyngeal swab - 2. Viral load assessed by PCR from a nasopharyngeal swab

    Measure: Number of participants by PCR result status (positive or negative) (if quantitative PCR is not available)

    Time: Baseline to Day 3

    Secondary Outcomes

    Description: Viral load assessed by PCR from a nasopharyngeal swab

    Measure: Change from baseline to Day 5 in nasopharyngeal SARS-CoV-2 viral load

    Time: Baseline to Day 5

    Description: Viral load assessed by PCR from a nasopharyngeal swab

    Measure: Number of participants by PCR result status (positive or negative)

    Time: Baseline to end of study (Day14)

    Description: COVID-19 symptoms (feverishness, sore throat, cough, shortness of breath, myalgias) will be scored by the participant on a 4-point scale ( 0 =none; 1 = mild; 2 = moderate; 3 = severe)

    Measure: Number of participants with COVID-19 symptoms by severity

    Time: Baseline to end of study (Day14)

    Description: COVID-19 symptoms (feverishness, sore throat, cough, shortness of breath, myalgias) will be scored by the participant on a 4-point scale ( 0 =none; 1 = mild; 2 = moderate; 3 = severe). Resolution of a symptom is defined as when a symptom previously scored ≥ 1 on the scale is scored as 0

    Measure: Time to resolution of COVID-19 Symptoms

    Time: Baseline to end of study (Day14)

    Description: Resolution of fever defined as the first day of 2 consecutive daily temperatures < 37.7 C

    Measure: Time to resolution of fever

    Time: Baseline to end of study (Day14)

    Description: Resolution of fever defined as the first day of 2 consecutive daily temperatures < 37.7 C

    Measure: Percentage of participants with resolution of fever

    Time: Baseline to end of study (Day14)

    Measure: Percentage of participants hospitalized

    Time: Baseline to end of study (Day14)

    Measure: Number of participants with Adverse Events

    Time: Baseline to end of study (Day14)
    28 An International, Multi-site, Bayesian Platform Adaptive, Randomized, Placebo-controlled Trial Assessing the Effectiveness of Candidate Agents in Mitigating COVID-19 Disease in Healthcare Workers

    The objective of CROWN CORONATION is the prevention of symptomatic COVID-19 by using combinations of approved and safe repurposed interventions, with complementary mechanisms of action.

    NCT04333732
    Conditions
    1. COVID 19
    Interventions
    1. Drug: MR or M-M-R II ® vaccine
    2. Drug: Placebo

    Primary Outcomes

    Description: To determine the incidence of the trial intervention(s) in preventing laboratory test-confirmed, symptomatic COVID19 (i.e. any of the following: cough, shortness of breath or difficulty breathing, fever, chills, muscle pain, sore throat, new loss of taste or smell, nausea, vomiting, or diarrhea), in healthcare workers with repeated exposures to SARS-CoV-2 by day 60 after enrollment.

    Measure: Symptomatic COVID-19

    Time: 60 days

    Secondary Outcomes

    Description: Severity of COVID-19 will be graded on a simplified version of the ordinal World Health Organization COVID-19 severity scale (WHO COVID-19 severity scale).

    Measure: Severity of COVID-19 over the study period

    Time: 60 days

    Description: SARS-CoV-2 infection (by serology) over up to 5 months of follow-up

    Measure: Effectiveness of preventing/reducing SARS-CoV-2 infection

    Time: 5 months
    29 A Randomised, Double-blind, Placebo Controlled Study of Eicosapentaenoic Acid (EPA-FFA) Gastro-resistant Capsules to Treat Hospitalised Subjects With Confirmed SARS-CoV-2

    This is an double-blind, randomized, placebo controlled phase III study in hospitalized subjects with confirmed SARS-CoV-2.

    NCT04335032
    Conditions
    1. SARS-CoV-2
    Interventions
    1. Drug: Eicosapentaenoic acid gastro-resistant capsules
    2. Drug: Placebo

    Primary Outcomes

    Description: Time to treatment failure during the 28-day treatment period. Treatment failure is defined as additional or alternative treatment required, or intubation and invasive ventilation, or transfer to intensive care unit, or death.

    Measure: Evaluation of EPA-FFA efficacy compared to placebo

    Time: 28 days

    Secondary Outcomes

    Description: To determine whether EPA-FFA gastro-resistant capsules decreases the time to and amount of clinical improvement as determined by the WHO 9-point ordinal scale during the study.

    Measure: Time to and amount of clinical improvement

    Time: 28 days

    Description: To determine whether EPA-FFA gastro-resistant capsules increases the number of subjects alive and discharged home without supplemental oxygen therapy.

    Measure: Change in recovery and survival rate

    Time: 28 days

    Description: To determine whether EPA-FFA gastro-resistant capsules decreases CRP and IL-6 during the study.

    Measure: Reduction of CRP and IL-6

    Time: 28 days

    Description: To determine whether EPA-FFA gastro-resistant capsules increases IFN-γ during the study

    Measure: Increase in IFN-γ

    Time: 28 days

    Description: To determine whether EPA-FFA gastro-resistant capsules decreases other proinflammatory chemokines and cytokines.

    Measure: Reduction in proinflammatory chemokines and cytokines.

    Time: 28 days

    Other Outcomes

    Description: To evaluate the safety of EPA-FFA gastro-resistant capsules in the treatment of COVID-19 (SARS-CoV-2) by assessing subjects clinical lab parameters and vital signs, and the number and proportion of subjects with AEs.

    Measure: Safety - Vitals, AEs and Clinical lab parameters

    Time: throughout the study, about 3 months
    30 CORON-ACT - a Multicenter, Double-blind, Randomized Controlled Phase II Trial on the Efficacy and Safety of Tocilizumab in the Treatment of Coronavirus Induced Disease (COVID-19)

    The mortality rate of the disease caused by the corona virus induced disease (COVID-19) has been estimated to be 3.7% (WHO), which is more than 10-fold higher than the mortality of influenza. Patients with certain risk factors seem to die by an overwhelming reaction of the immune system to the virus, causing a cytokine storm with features of Cytokine-Release Syndrome (CRS) and Macrophage Activation Syndrome (MAS) and resulting in Acute Respiratory Distress Syndrome (ARDS). Several pro-inflammatory cytokines are elevated in the plasma of patients and features of MAS in COVID-19, include elevated levels of ferritin, d-dimer, and low platelets. There is increasing data that cytokine-targeted biological therapies can improve outcomes in CRS or MAS and even in sepsis. Tocilizumab (TCZ), an anti-IL-6R biological therapy, has been approved for the treatment of CRS and is used in patients with MAS. Based on these data, it is hypothesized that TCZ can reduce mortality in patients with severe COVID-19 prone to CRS and ARDS. The overall purpose of this study is to evaluate whether treatment with TCZ reduces the severity and mortality in patients with COVID-19.

    NCT04335071
    Conditions
    1. SARS-CoV-2 Infection
    Interventions
    1. Drug: Tocilizumab (TCZ)
    2. Drug: Placebo
    MeSH:Coronavirus Infections

    Primary Outcomes

    Measure: Number of patients with ICU admission

    Time: 7 days after randomisation

    Measure: Number of patients with intubation

    Time: 14 days after randomisation

    Measure: Number of patients with death

    Time: 28 days after randomisation

    Secondary Outcomes

    Description: Assessed by the 8-point WHO scale

    Measure: Illness severity

    Time: At days 2, 7, 14, 28 after randomisation

    Description: Clinical improvement is defined as a ≥ 2-point improvement in the 8-point WHO scale

    Measure: Number of patients with clinical improvement

    Time: At days 2, 7, 14, 28 after randomisation

    Description: Clinical improvement is defined as a ≥ 2-point improvement in the 8-point WHO scale

    Measure: Time to clinical improvement (days)

    Time: Up to day 28 after randomisation

    Measure: Duration of hospitalization (days)

    Time: Up to day 28 after randomisation

    Measure: Time to ICU admission (days)

    Time: Up to day 28 after randomisation

    Measure: Duration of ICU stay

    Time: Up to day 28 after randomisation

    Measure: Time to intubation

    Time: Up to day 28 after randomisation

    Measure: Duration of mechanical ventilation (days)

    Time: Up to day 28 after randomisation

    Other Outcomes

    Measure: Number of deaths

    Time: Within 28 days after randomisation

    Measure: Number of patients with ICU admission

    Time: Within 28 days after randomisation

    Measure: Number of patients with intubation

    Time: Within 28 days after randomisation

    Description: Events of special interest are defined as secondary infections, acute kidney failure, hepatic, and cardiac failure

    Measure: Number of patients with events of special interest

    Time: Within 28 days after randomisation

    Measure: Number of patients with SAEs considered by the investigator to be at least probably related to the IMP

    Time: Within 28 days after randomisation
    31 A Multi-center, Randomized, Double-blind, Placebo-controlled, Phase III Clinical Study Evaluating the Efficacy and Safety of Favipiravir in the Treatment of Patients With COVID-19-Moderate Type

    This study evaluates treatment with Favipiravir combined with supportive care for adult patients with COVID-19-moderate type.

    NCT04336904
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Favipiravir
    2. Other: Placebo

    Primary Outcomes

    Description: The duration from start of treatment (Favipiravir or placebo) to normalization of pyrexia, respiratory rate and SPO2 and relief of cough (where there are relevant abnormal symptoms at enrolment) that is maintained for at least 72 hours.

    Measure: Time from randomization to clinical recovery

    Time: 90 days

    Secondary Outcomes

    Description: 1. Time from randomization to negativity in RT-PCR nucleic acid test for 2019-nCov within 28 days of randomization;

    Measure: Time from randomization to negativity in RT-PCR nucleic acid test

    Time: 28 days

    Description: Incidence of deterioration/aggravation of pneumonia (defined as SPO2≤93% or PaO2/FiO2 ≤300 mmHg or distressed RR≥30/min without oxygen inhalation and requiring oxygen therapy or more advanced breath support) within 28 days of randomization;

    Measure: Incidence of deterioration/aggravation of pneumonia

    Time: 28 days

    Description: Time from randomization to resolution of pyrexia (defined the same as for the primary efficacy variable; applicable to subjects with pyrexia at enrolment) within 28 days of randomization;

    Measure: Time from randomization to resolution of pyrexia

    Time: 28 days

    Description: Time from randomization to relief of cough (defined the same as for the primary efficacy variable; applicable to subjects with cough at enrolment) within 28 days of randomization; It is recommended that the severity of cough be graded as per NCI-CTCAE v5.0: Mild: Requires non-prescription treatment; Moderate: Requires medication treatment; limits instrumental activities of daily living; Severe: Limits self-care activities of daily living

    Measure: Time from randomization to relief of cough

    Time: 28 days

    Description: Time from randomization to relief of dyspnoea (defined as subject-perceived improvement or resolution of dyspnoea; applicable to subjects with dyspnoea at enrolment) within 28 days of randomization;

    Measure: Time from randomization to relief of dyspnoea

    Time: 28 days

    Description: 6. Rate of auxiliary oxygen therapy or non-invasive ventilation within 28 days of randomization

    Measure: Rate of auxiliary oxygen therapy

    Time: 28 days

    Description: ICU admission rate within 28 days of randomization

    Measure: ICU admission rate

    Time: 28 days

    Description: All-cause mortality within 28 days of randomization

    Measure: Mortality

    Time: 28 days
    32 Efficacy and Safety of Nintedanib Ethanesulfonate Soft Capsule in the Treatment of Pulmonary Fibrosis in Patients With Moderate to Severe COVID-9(COVID 19) : a Single-center, Randomized, Placebo-controlled Study

    This center intends to conduct a single-center, randomized, placebo-controlled study to evaluate the effectiveness and safety of Nintedanib ethanesulfonate soft capsule in the treatment of pulmonary fibrosis in patients with moderate to severe COVID-19.

    NCT04338802
    Conditions
    1. COVID-19
    2. Nintedanib
    3. Safety
    4. Effect of Drugs
    Interventions
    1. Drug: Nintedanib 150 MG
    2. Other: Placebo
    MeSH:Pulmonary Fibrosis
    HPO:Pulmonary fibrosis

    Primary Outcomes

    Description: Changes in forced vital capacity (FVC) after treatment compared to baseline.

    Measure: Changes in forced vital capacity (FVC)

    Time: 8 weeks

    Secondary Outcomes

    Description: Changes incarbon monoxide dispersion (DLco%) after treatment compared to baseline.

    Measure: Changes in carbon monoxide dispersion (DLco%)

    Time: 8 weeks

    Description: Changes in the six-minute walk test (6MWT) after treatment compared to baseline.

    Measure: Changes in the six-minute walk test (6MWT)

    Time: 8 weeks

    Description: Changes in High resolution CT score after treatment compared to baseline.The minimum and maximum values are 0 and 25 , and higher scores mean a worse outcome. As for the score, it is the expected value and will be determined according to the actual result

    Measure: Changes in High resolution CT score

    Time: 8 weeks
    33 Evaluation of the Efficacy and Safety of Camostat Mesilate + Hydroxychloroquine Combination Therapy in Hospitalized Patients With Moderate COVID-19 Infection

    Evaluation of the efficacy and safety of hydroxychloroquine - camostat combination therapy in hospitalized patients with moderate COVID-19 infection, CLOCC-Trial Primary Objectives: The primary objective of this study is to demonstrate, that a combination therapy of hydroxychloroquine and camostat (Foipan®) is superior to hydroxychloroquine + placebo in participants with moderate COVID-19.

    NCT04338906
    Conditions
    1. COVID
    Interventions
    1. Drug: Camostat Mesilate
    2. Drug: Placebo
    3. Drug: Hydroxychloroquine

    Primary Outcomes

    Measure: Not hospitalized

    Time: day 14 from baseline

    Secondary Outcomes

    Measure: Time to improvement of 2 categories from admission on a 7-point ordinal scale

    Time: day 14

    Measure: Proportion of participants in each group with normalization of fever

    Time: day 7 and day 14

    Measure: Proportion of participants in each group with oxygen saturation > 94% on room air for >24h

    Time: day 7 and day 14

    Measure: Time to fever normalization (if febrile at baseline)

    Time: within 14 days

    Measure: Time to first negative SARS-CoV-2 PCR in NP swap (if pos. at baseline)

    Time: within 14 days

    Measure: Time to first negative SARS-CoV-2 PCR in lower respiratory tract specimens (sputum, bronchoalveolar lavage, tracheal aspirate) (if positive at baseline)

    Time: within 14 days

    Measure: Duration of oxygen therapy

    Time: within 28 days

    Measure: Proportion of participants in each group with need for mechanical ventilation

    Time: within 28 days

    Measure: Duration of hospitalization

    Time: within 28 days

    Measure: All cause mortality

    Time: day 28
    34 Clinical Research of Human Mesenchymal Stem Cells in the Treatment of COVID-19 Pneumonia

    The COVID-19 pneumonia has grown to be a global public health emergency since patients were first detected in Wuhan, China, in December 2019, which spread quickly to worldwide and presented a serious threat to public health. It is mainly characterized by fever, dry cough, shortness of breath and breathing difficulties. Some patients may develop into rapid and deadly respiratory system injury with overwhelming inflammation in the lung. Currently, no specific drugs or vaccines are available to cure the patients with COVID-19 pneumonia. Hence, there is a large unmet need for a safe and effective treatment for COVID-19 pneumonia patients, especially the critically ill cases. The significant clinical outcome and well tolerance was observed by the adoptive transfer of allogenic MSCs. We proposed that the adoptive transfer therapy of MSCs might be an ideal choice to be used. We expect to provide new options for the treatment of critically ill COVID-19 pneumonia patients and contribute to improving the quality of life of critically ill patients.

    NCT04339660
    Conditions
    1. COVID-19
    Interventions
    1. Biological: UC-MSCs
    2. Other: Placebo
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Improvement and recovery time of inflammatory and immune factors

    Measure: The immune function (TNF-α 、IL-1β、IL-6、TGF-β、IL-8、PCT、CRP)

    Time: Observe the immune function of the participants within 4 weeks

    Description: Evaluation of Pneumonia change

    Measure: Blood oxygen saturation

    Time: Monitor blood oxygen saturation of the participants within 4 weeks

    Secondary Outcomes

    Description: Marker for efficacy of treatment

    Measure: Rate of mortality within 28-days

    Time: At baseline, Day 1, Day 2, Day 7, Week 2, Week 3, Week 4

    Description: Evaluation of Pneumonia change

    Measure: Size of lesion area by chest imaging

    Time: At baseline, Day 1, Day 2, Day 7, Week 2, Week 3, Week 4

    Description: Marker of Immunology and inflammation

    Measure: CD4+ and CD8+ T cells count

    Time: At baseline, Day 1, Day 2, Day 7, Week 2, Week 3, Week 4

    Description: Degree of infection

    Measure: Peripheral blood count recovery time

    Time: At baseline, Day 1, Day 2, Day 7, Week 2, Week 3, Week 4

    Description: Indirect response to lung function

    Measure: Duration of respiratory symptoms (fever, dry cough, difficulty breathing, etc.)

    Time: At baseline, Day 1, Day 2, Day 7, Week 2, Week 3, Week 4

    Description: Clearance time of COVID-19 in participant

    Measure: COVID-19 nucleic acid negative time

    Time: At baseline, Day 1, Day 2, Day 7, Week 2, Week 3, Week 4
    35 Azithromycin Added to Hydrochloroquine in Patients Admitted to Intensive Care Due to Coronavirus Disease 2019 (COVID-19)- Randomised Controlled Trial

    Trial design: Prospective, multi-centre, randomised, pragmatic, double blind trial Methods: Participants: Adult (>18 years) within 24 hours of admission to intensive care unit with proven or suspected COVID-19 infection, whether or not mechanically ventilated. Exclusion criteria: symptoms of febrile disease for ≥1 week, treatment limitations in place or moribund patients, allergy or intolerance of any study treatment, incl. long QT syndromes, participation in another outcome-based interventional trial within last 30 days, patients taking Hydrochloroquine for other indication than COVID-19, pregnancy. Interventions: Patients will be randomised in 1:1:1 ratio to receive Hydrochloroquine 800mg orally in two doses followed by 400mg daily in two doses and Azithromycin 500 mg orally in one dose followed by 250 mg in one dose for a total of 5 days (HC-A group) or Hydrochloroquine+ placebo (HC group) or placebo + placebo (C-group) in addition to best standard of care, which may evolve during the trial period but will not differ between groups. Objective: To test the hypothesis that early administration of combination therapy slows disease progression and improves mechanical-ventilation free survival. Outcomes: Primary outcome: Composite percentage of patients alive and not on end-of-life pathway who are free of mechanical ventilation at day 14. Secondary outcomes: Composite percentage of patients alive and not on end-of-life pathway who are free of mechanical ventilation at day 14 in the subgroup of patients without the need of mechanical ventilation at baseline. ICU-LOS D28 and D 90 mortality (in hospital) Tertiary (exploratory) outcomes: Viral load at D7 of study enrolment (No of viral RNA copies/ml of blood), proportion of patients alive and rtPCR negative from nasal swab at D14, Difference of FiO2 requirement and respiratory system compliance between day 0 and 7. Randomization: In 1:1:1 ratio and stratified according to study centre and patients age (cut-off 70 years) Blinding (masking): Patients, treating clinicians, outcome assessors and data analyst will be blinded to study treatment allocation. Unblinded study pharmacist or research nurse will prepare investigational products.

    NCT04339816
    Conditions
    1. COVID-19
    2. Respiratory Failure
    Interventions
    1. Drug: Azithromycin
    2. Drug: Hydroxychloroquine
    3. Drug: Placebo
    MeSH:Respiratory Insufficiency

    Primary Outcomes

    Description: Composite percentage of patients alive and not on end-of-life pathway who are free of mechanical ventilation at day 14.

    Measure: Proportion of alive patients free off mechanical ventilation

    Time: 14 days after enrolment

    Secondary Outcomes

    Description: Composite percentage of patients alive and not on end-of-life pathway who are free of mechanical ventilation at day 14 in the subgroup of patients without the need of mechanical ventilation at baseline.

    Measure: Proportion of patients who avoided the need of mechanical ventilation

    Time: 14 days

    Description: Length of stay in intensive care unit

    Measure: ICU LOS

    Time: 28 days

    Description: Proportion of patients who died by day 28

    Measure: Mortality28

    Time: 28 days

    Description: Proportion of patients who died by day 90

    Measure: Mortality90

    Time: 90 days
    36 Hydroxychloroquine for the Treatment of Mild COVID-19 Disease

    The current outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) is a global health emergency with a case fatality rate so far approximately 4% and a growing number of confirmed cases (>57.000) in Germany. There is no data available on the efficacy of antiviral agents for the treatment of COVID-19. In-vitro data show that hydroxychloroquine can inhibit SARS-CoV-2 [1] replication and anecdotal reports from Chinese COVID-19 patients [2, 3] suggest that chloroquine is a good candidate for treatment. No data have been published and reported evidence is based on non-controlled use of hydroxychloroquine. The aim of this placebo-controlled trial is to assess the effect of hydroxychloroquine on duration of symptoms in mild COVID-19 patients and time of virus shedding as an important tool to reduce the risk of further community transmissions. This data will inform practice for the design of larger trials on clinical efficacy of hydroxychloroquine in the treatment and post- and preexposure prophylaxis of COVID-19 and as a tool for reduction of community transmission.

    NCT04340544
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Hydroxychloroquine
    2. Drug: Placebo

    Primary Outcomes

    Measure: Difference in time to resolution of clinical signs and symptoms of mild COVID-19 treated with hydroxychloroquine or placebo as assessed by daily self-assessment

    Time: 28±2 days

    Secondary Outcomes

    Measure: Difference between hydroxychloroquine- and placebotreated patients on an ordinal outcome scale until Day 28 (death, admission to intensive care, hospitalization, continuing disease, recovered)

    Time: 28±2 days

    Measure: All-cause mortality within 28 days

    Time: 28±2 days

    Other Outcomes

    Measure: Proportion of patients with negative COVID-19 PCR test at day 14 in per protocol population as per throat swab

    Time: 28±2 days

    Measure: Change in COVID-19 virus load from baseline to day 14

    Time: 28±2 days
    37 A Phase 2/3, Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study to Evaluate the Safety and Efficacy of TJ003234 in Subjects With Severe Coronavirus Disease 2019 (COVID-19)

    This is a randomized, double-blind, placebo-controlled, multi-center trial to evaluate the safety and efficacy of TJ003234 administered as an intravenous (IV) infusion in subjects with severe COVID-19 under supportive care, and to assess the effect of TJ003234 on the levels of cytokines.

    NCT04341116
    Conditions
    1. Coronavirus Disease 2019 COVID-19
    Interventions
    1. Drug: TJ003234
    2. Drug: Placebo
    MeSH:Coronavirus Infections

    Primary Outcomes

    Measure: Proportion (%) of subjects recovered

    Time: Day 1 through Day 14

    Secondary Outcomes

    Measure: Proportion (%) of subjects recovered on Day 30

    Time: Day 1 through Day 30

    Measure: All-cause mortality rate by Day 30

    Time: Day 1 through Day 30

    Measure: Time to recovery among subjects alive by Day 30

    Time: Day 1 through Day 30

    Measure: Length of hospitalization

    Time: Day 1 through Day 30

    Measure: Incidence of treatment-emergent Adverse events by Day 30

    Time: Day 1 through Day 30
    38 A Randomized, Double-blind, Placebo-controlled Phase II Clinical Trial to Evaluate the Safety and Immunogenicity of the Recombinant Novel Coronavirus Vaccine (Adenovirus Vector) in Healthy Adults Aged Above 18 Years

    This is a phase II, randomised, double-blinded and placebo-controlled clinical trial in healthy adults above 18 years of age. This clinical trial is designed to evaluate the immunogenicity and safety of Ad5-nCoV which encodes for a full-length spike (S) protein of SARS-CoV-2.

    NCT04341389
    Conditions
    1. COVID-19
    Interventions
    1. Biological: Recombinant novel coronavirus vaccine (Adenovirus type 5 vector)
    2. Other: Placebo
    MeSH:Adenoviridae Infections

    Primary Outcomes

    Measure: Occurrence of adverse reactions

    Time: 0-14 days post vaccination

    Measure: Anti SARS-CoV-2 S IgG antibody response(ELISA)

    Time: 28 days post vaccination

    Measure: Neutralizing antibody response to SARS-CoV-2

    Time: 28 days post vaccination

    Secondary Outcomes

    Measure: Occurrence of adverse events

    Time: 0-28 days post vaccination

    Measure: Occurrence of serious adverse reaction

    Time: 0-6 months post vaccination

    Measure: Anti SARS-CoV-2 S IgG antibody response(ELISA)

    Time: 0, 14 days and 6 months post vaccination

    Measure: Neutralizing antibody response to SARS-CoV-2

    Time: 0 and 6 months post vaccination

    Measure: Neutralizing antibody response to Ad5-vector

    Time: 0, 28 days and 6 months post vaccination

    Measure: IFN-γ ELISpot responses to SARS-CoV-2 spike protein

    Time: 0 and 28 days post vaccination
    39 Sirolimus Treatment in Hospitalized Patients With COVID-19 Pneumonia (The SCOPE Trial)

    The main objective of our study is to determine if treatment with sirolimus can improve clinical outcomes in hospitalized patients with COVID-19. The investigators will employ a randomized, double blind, placebo-controlled study design. 30 subjects will be randomized in a 2:1 fashion to receive sirolimus or placebo. Sirolimus will be given as a 6mg oral loading dose on day 1 followed by 2mg daily for a maximum treatment duration of 14 days or until hospital discharge, whichever happens sooner. Chart reviews will be conducted daily to determine changes in clinical status, concomitant medications and laboratory parameters. Study specific biomarkers will be measured at baseline and then at days 3, 7 and 14.

    NCT04341675
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Sirolimus
    2. Drug: Placebo
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Death or progression to respiratory failure requiring advanced support measures, either due to inadequate ventilation (non-invasive or invasive mechanical ventilation) or inadequate oxygenation (CPAP* or high flow supplemental oxygen at rates ≥ 15 liters/minute), in patients given sirolimus compared to the placebo group. * CPAP use for known obstructive sleep apnea will not be considered as disease progression.

    Measure: Proportion of patients who are alive and free from advanced respiratory support measures at day 28.

    Time: 28 days

    Secondary Outcomes

    Description: Progression to a higher level of care, e.g. ICU

    Measure: Proportion of patients who require escalation in care

    Time: 14 days

    Description: Change over time in study-specific biomarkers (LDH, Ferritin, D-dimer, lymphocyte count)

    Measure: Change over time in study-specific biomarkers (LDH, Ferritin, D-dimer, lymphocyte count)

    Time: 14 days

    Description: Survival to hospital discharge

    Measure: Proportion of patients surviving to hospital discharge

    Time: days

    Description: Incidence and type of adverse events

    Measure: Drug safety profile

    Time: 14 days

    Description: Number of days spent on advanced respiratory support measures

    Measure: Duration of advanced respiratory support

    Time: days

    Description: Length of hospitalization (in patients who survive to discharge)

    Measure: Duration of hospital stay

    Time: days

    Description: Number of days between study initiation and death (in the subset of patients who die during the hospitalization)

    Measure: Time from treatment initiation to death

    Time: days

    Description: Time (in days) to resolution of fever

    Measure: Time to resolution of fever

    Time: 14 days

    Description: Patients needing off-label treatments such as Anti-IL-6 inhibitors at the discretion of primary clinicians

    Measure: Proportion of patients who require initiation of off-label therapies

    Time: 14 days
    40 Randomized Controlled Trial of Hydroxychloroquine Versus Placebo for the Treatment of Adult Patients With Acute Coronavirus Disease 2019 - COVID-19

    The current outbreak of COVID-19 caused by SARS-CoV-2 is a global health emergency with a case fatality rate so far approximately 4% and a growing number of confirmed cases (>9500) in Germany. There is no data available on the efficacy of antiviral agents for the treatment of COVID-19. In vitro data show that hydroxychloroquine can inhibit SARS-CoV-2 replication and anecdotal reports from COVID-19 patients in China and France suggest that chloroquine or hydroxychloroquine is a good candidate for treatment. In the French study a favourable effect was seen when hydroxychloroquine was used together with azithromycin in a small series of COVID-19 patients. However, so far all published evidence is based on non-controlled use of hydroxychloroquine. We propose to conduct a placebo-controlled trial in COVID-19 patients with mild to moderate disease in Germany to assess virological efficacy, tolerability and safety of hydroxychloroquine in the treatment of COVID-19. The objective of this trial is to identify an effect of hydroxychloroquine on viral clearance in vivo. This data will inform practice for the design of larger trials on clinical efficacy of hydroxychloroquine in the treatment and post-exposure prophylaxis of COVID-19.

    NCT04342221
    Conditions
    1. COVID-19, Hydroxychloroquine Sulfate
    Interventions
    1. Drug: Hydroxychloroquine Sulfate
    2. Drug: Placebo

    Primary Outcomes

    Description: Viral clearance defined as time to sustained SARS-CoV-2-specific RNA copy number ≤100, measured by real time reverse-transcription polymerase chain reaction RT-PCR in throat swabs.

    Measure: Effect of HCQ on in vivo viral clearance

    Time: 6 months

    Other Outcomes

    Measure: In-hospital mortality

    Time: 60 days

    Measure: All-cause mortality

    Time: 60 days

    Measure: Proportion requiring non-invasive or invasive ventilation

    Time: 6 months

    Measure: Proportion admitted to ICU

    Time: 6 months

    Measure: Duration of hospitalization

    Time: 6 months

    Measure: Reduction in viral RNA load in upper respiratory tract specimen as assessed by area under viral load curve

    Time: 6 months

    Measure: Reduction in viral RNA load in upper respiratory tract specimen defined as decline of RNA load by 2 log-levels or to below detection level

    Time: 6 months
    41 A Double-blind, Placebo-controlled Clinical Trial of Fluvoxamine for Symptomatic Individuals With COVID-19 Infection

    The purpose of this research study is to determine if a drug called fluvoxamine can be used early in the course of the COVID-19 infection to prevent more serious complications like shortness of breath. Fluvoxamine is an anti-depressant drug approved by the FDA for the treatment of obsessive-compulsive disorder. The use of fluvoxamine for the treatment of COVID-19 is considered investigational, which means the US Food and Drug Administration has not approved it for this use. This study is fully-remote, which means that there is no face-to-face contact; study materials including study drug will be shipped to participants' houses. Only residents of Missouri and Illinois may participate.

    NCT04342663
    Conditions
    1. COVID 19
    2. Coronavirus
    Interventions
    1. Drug: Fluvoxamine
    2. Drug: Placebo
    MeSH:Infecti Infection Coronavirus Infections

    Primary Outcomes

    Description: Clinical worsening is defined meeting both of the following: (1) presence of dyspnea and/or hospitalization for shortness of breath or pneumonia, plus (2) decrease in O2 saturation (<92%) on room air and/or supplemental oxygen requirement in order to keep O2 saturation >92%.

    Measure: Time to clinical worsening

    Time: RCT (approximately 15 days)

    Secondary Outcomes

    Description: (1) moderate severity of illness as defined by O2 saturation <92% but no supplemental oxygen requirement; (2) O2 saturation plus supplemental oxygen requirement; (3) O2 saturation <92% plus hospitalization (related to dyspnea/hypoxia); (4) the above, plus ventilator support requirement; (5) the above, plus ventilator support for at least 3 days; (6) death.

    Measure: clinical deterioration on a Likert-type scale (1-6)

    Time: RCT (approximately 15 days)

    Description: (1) requiring supplemental oxygen; (2) requiring hospitalization; (3) requiring ventilator support.

    Measure: clinical deterioration measured by number of days

    Time: RCT (approximately 15 days)

    Description: Outcomes will be collected daily, with symptomatic data collected approximately twice daily. The most severe symptom at baseline will be the focus.

    Measure: Symptomatic severity on a likert scale (0-10 where 0= none and 10=very severe)

    Time: RCT (approximately 15 days)
    42 A Randomized, Double-blind, Placebo-controlled, Clinical Trial of LY3127804 in Patients Who Are Hospitalized With Pneumonia and Presumed or Confirmed COVID-19

    A randomized, double-blind, placebo-controlled, clinical trial of LY3127804 in participants who are hospitalized with pneumonia and presumed or confirmed COVID-19. The study may last up to 9 weeks and include daily visits up to day 28, and follow-up visits by phone.

    NCT04342897
    Conditions
    1. COVID-19
    2. Pneumonia
    Interventions
    1. Drug: LY3127804
    2. Drug: Placebo
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Number of days on which a participant breathes without assistance

    Measure: Number of Ventilator Free Days

    Time: Day 1 to Day 28

    Secondary Outcomes

    Description: The scale is an assessment of clinical status. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities

    Measure: Number of Participants Reporting Each Severity Rating on the National Institute of Allergy and Infectious Diseases (NIAID) Ordinal Assessment

    Time: Day 1 to Day 28

    Description: Survival without Respiratory Failure

    Measure: Percentage of Participants who are Alive and Respiratory Failure Free

    Time: Day 1 to Day 28

    Description: Mortality

    Measure: Mortality

    Time: Day 1 to Day 28

    Description: Days of Hospitalization

    Measure: Length of Hospitalization

    Time: Day 1 to Day 28

    Description: Number of Participants with any Serious Adverse Event (SAE)

    Measure: Number of Participants with any Serious Adverse Event (SAE)

    Time: Day 1 to Day 28

    Description: Number of Participants with any Treatment Emergent Adverse Event (TEAE)

    Measure: Number of Participants with any Treatment Emergent Adverse Event (TEAE)

    Time: Day 1 to Day 28
    43 A Randomized, Double-Blind, Placebo Controlled Trial to Evaluate the Efficacy and Safety of Nitazoxanide (NTZ) for Post-Exposure Prophylaxis of COVID-19 and Other Viral Respiratory Illnesses in Elderly Residents of Long-Term Care Facilities (LTCF)

    Trial to evaluate the efficacy and safety of NTZ for post-exposure prophylaxis of COVID-19 and other VRIs in elderly LTCF residents.

    NCT04343248
    Conditions
    1. COVID-19
    2. Viral Respiratory Illnesses
    Interventions
    1. Drug: Nitazoxanide
    2. Drug: Placebo
    3. Dietary Supplement: Vitamin Super B-Complex

    Primary Outcomes

    Description: The proportion of subjects with symptomatic laboratory-confirmed COVID-19 identified after start of treatment and before the end of the 6-week treatment period.

    Measure: Symptomatic laboratory-confirmed COVID-19

    Time: up to 6 weeks

    Description: The proportion of subjects with symptomatic laboratory-confirmed VRI identified after the start of treatment and before the end of the 6-week treatment period.

    Measure: Symptomatic laboratory-confirmed VRI

    Time: up to 6 weeks
    44 Pyridostigmine in Patients With Severe Acute Respiratory Syndrome Secondary to SARS-CoV-2 Infection

    We will evaluate low-dose pyridostigmine as add-on therapy to best medical care in patients with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and its related Coronavirus Disease 2019 (COVID-19) who require hospitalization. Our hypothesis is that, in comparison to the placebo, pyridostigmine will reduce in at least 10% a composite outcome [death; mechanical ventilation; >2 point-increase in the SOFA score) by day 28. We will also evaluate interleukin (IL)-6 kinetics during the first 14 days of in-hospital stay. It is estimated that 25-33% of patients hospitalized for COVID-19 are admitted to intensive care units (ICU) for severe hypoxemia. The reported mortality in those with severe disease ranges between 38% and 49%. So far, there is no pharmacological therapeutic (or else) strategy known to reduce morbidity and mortality in these patients. Mortality in COVID-19 appears to be mediated not necessarily by the direct effect of the infection, but by the disproportionate inflammatory response of the host. Pyridostigmine is an old drug that, by inhibiting acetylcholine-esterase, the enzymatic machinery that degrades acetylcholine (ACh), results in increased ACh bioavailability. ACh, in turn, ligates to nicotinic-alpha7 receptors in macrophages and T cells, resulting in reduced overactivation of these immune cells. In experimental murine sepsis, this family of drugs has resulted in reduced inflammation and mortality. Human evidence is scarce for severe inflammatory conditions. However, recent evidence from our group and others indicates that pyridostigmine has an immunomodulatory effect in people living with HIV, resulting in elevation of CD4+ T cell counts, decreased immune activation, and reduction in inflammatory mediators. Altogether, this suggests that ACh-esterase inhibitors may act as immunomodulators during viral infections, potentially reducing the inflammatory cascade (the so-called "cytokine storm") observed in critically ill COVID-19 patients. At the proposed dose (60mg/d), the rate of minor adverse events is less than 5% with no reported serious adverse effects. From that perspective, we consider that pyridostigmine can function as an immuno-modulator and reduce morbidity and mortality in COVID-19-stricken patients, with the added value of a safe pharmacological profile. Moreover, as an old drug, re-purposing it for a novel indication may be a simpler, more efficient approach than developing a novel one from the ground up.

    NCT04343963
    Conditions
    1. COVID-19
    2. SARS-CoV-2
    Interventions
    1. Drug: Pyridostigmine Bromide
    2. Drug: Placebo
    MeSH:Infection

    Primary Outcomes

    Description: Composite of death, Need for mechanical ventilation, or an increase of 2 or more points in the SOFA score

    Measure: Critical condition or death

    Time: 28 days

    Description: Kinetics of circulating IL-6

    Measure: IL-6

    Time: 14 days in-hospital, hospital discharge, or death
    45 A Randomized Placebo-controlled Safety and Dose-finding Study for the Use of the IL-6 Inhibitor Clazakizumab in Patients With Life-threatening COVID-19 Infection

    In this study invetigators propose to administer clazakizumab to patients with life-threatening COVID-19 infection manifest by pulmonary failure and a clinical picture consistent with a cytokine storm syndrome. This is a single-center randomized, double-blind, placebo-controlled trial in which 80 patients will be enrolled and randomly assigned in a 1:1:1 ratio to three study arms and received clazakizumab at a dose of 12.5 mg, 25 mg or placebo. Based on interim analysis, the remaining 10 subjects at NYU will be randomly assigned to a 1:1 ratio to two arms that will receive clazakizumab at a dose of 25 mg or placebo. The NYU site will serve as the central data management site for other centers who undertake this protocol. Other sites will enroll patients based on the two arm 1:1 randomization. 60 patients at outside sites are expected to enroll.

    NCT04343989
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Clazakizumab 25 mg
    2. Drug: Clazakizumab 12.5 mg
    3. Other: Placebo
    MeSH:Infection

    Primary Outcomes

    Measure: Cumulative incidence of serious adverse events associated with clazakizumab or placebo

    Time: 60 days

    Secondary Outcomes

    Measure: Cumulative incidence of intubation

    Time: 14 days

    Measure: Time to extubation

    Time: 14 days

    Measure: Length of ICU stay

    Time: 14 days

    Measure: Number of patients who present a decrease in C-reactive protein

    Time: 14 days

    Description: Number of patients who remain alive at time point.

    Measure: Patient Survival

    Time: 28 days

    Description: Number of patients who remain alive at end of study.

    Measure: Patient Survival

    Time: 60 days
    46 SAFEty Study of Early Infusion of Vitamin C for Treatment of Novel Coronavirus Acute Lung Injury (SAFE EVICT CORONA-ALI)

    This study will the safety of a 96-hour intravenous vitamin C infusion protocol (50 mg/kg every 6 hours) in patients with hypoxemia and suspected COVID-19.

    NCT04344184
    Conditions
    1. COVID-19
    2. Lung Injury, Acute
    3. Kidney Injury
    Interventions
    1. Drug: L-ascorbic acid
    2. Other: Placebo
    MeSH:Lung Injury Acute Lung Injury Respiratory Distress Syndrome, Adult Wounds and Injuries

    Primary Outcomes

    Description: COVID disease status will be measured by the 9-point (from 0 to 8) World Health Organization (WHO) ordinal scale for disease improvement at 28 days.

    Measure: Change in COVID disease status

    Time: Baseline to 28, 60 and 90 days

    Secondary Outcomes

    Description: Change in serum oxalate levels

    Measure: Renal safety biomarkers - serum oxalate

    Time: On days 5,7 and 14

    Description: Microscopic analysis of urine for presence of oxalate stones

    Measure: Renal safety biomarkers - urine oxalate stones

    Time: On days 5,7 and 14

    Description: 24-hour urine oxalate levels

    Measure: Renal safety biomarkers - 24-hour urine oxalate levels

    Time: On days 5,7 and 14

    Description: Renal-failure free days, with AKI defined by the KDIGO criteria

    Measure: Acute Kidney Injury-free days

    Time: On day 28, 90

    Description: Mortality by all causes

    Measure: Number of deaths

    Time: On day 28, 60 and 90 days

    Description: Difference in plasma ferritin levels in ng/mL, compared to baseline levels

    Measure: Change in plasma ferritin levels

    Time: Days 1-7 compared with baseline

    Description: Difference in D-dimer levels in mcg/mL, compared to baseline levels

    Measure: Change in plasma D-dimer levels

    Time: Days 1-7 compared with baseline

    Description: Difference in lactate dehydrogenase (LDH) levels in units/L, compared to baseline levels

    Measure: Change in serum lactate dehydrogenase (LDH) levels

    Time: Days 1-7 compared with baseline

    Description: Difference in plasma IL-6 levels in pg/mL, compared to baseline levels

    Measure: Change in plasma IL-6 levels

    Time: Days 1-7 compared with baseline

    Description: Respiratory failure defined as resource utilization requiring at least 1 of the following: Endotracheal intubation and mechanical ventilation, Oxygen delivered by high-flow nasal cannula (heated, humidified, oxygen delivered via reinforced nasal cannula at flow rates >20L/min with fraction of delivered oxygen ≥0.5), noninvasive positive pressure ventilation, extracorporeal membrane oxygenation

    Measure: Proportion of patients alive and free of respiratory failure

    Time: At 28-days

    Description: Percentage of patients alive and not requiring invasive mechanical ventilation

    Measure: Proportion of patients alive and free of invasive mechanical ventilation

    Time: At 28-days
    47 A Randomized Double Blind, Placebo-Controlled Study of Auxora for the Treatment of Severe COVID-19 Pneumonia (CARDEA)

    Part 1 of this trial enrolled 30 patients to receive Auxora (formerly CM4620) in a 2:1 randomized, open label trial of patients with severe and critical COVID-19 pneumonia. Part 2 will consist of a randomized, double blind, placebo-controlled (RCT) study that will evaluate efficacy, safety, and the pharmacokinetic profile of Auxora in patients with severe COVID-19 pneumonia. Four hundred patients will be randomized 1:1 to receive Auxora or matching placebo. Patients with an estimated PaO2/FiO2 of 75-200 will be stratified to ensure balanced randomization between the Auxora and placebo arms. The number of patients with an imputed PaO2/FiO2 >200 randomized into the study will be capped at 80. Subgroup analyses will be performed to explore how time to recovery is influenced by baseline variables and to evaluate the treatment effect at different levels of each of these variables. The dose of Auxora will be 2.0 mg/kg (1.25 mL/kg) administered at 0 hour, and then 1.6 mg/kg (1 mL/kg) at 24 hours and 1.6 mg/kg (1 mL/kg) at 48 hours from the SFISD. The dose of placebo will be 1.25 mL/kg administered at 0 hour and then 1 mL/kg at 24 hours and 1 mL/kg at 48 hours from the SFISD. Remdesivir, corticosteroids and convalescent plasma will be allowed. The infusion of Auxora will start within 12 hours from the time the patient or LAR provides informed consent.

    NCT04345614
    Conditions
    1. Pneumonia
    Interventions
    1. Drug: Auxora
    2. Drug: Placebo
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Defined as the number of days hospitalized but not requiring supplemental oxygen or ongoing medical care, or; discharged and requiring supplemental oxygen, or; discharged, not requiring supplemental oxygen.

    Measure: Number of days from the Start of the First Infusion of Study Drug (SFISD) to recovery

    Time: From start of first infusion of study drug to day 30

    Secondary Outcomes

    Measure: Proportion of patients requiring invasive mechanical ventilation or dying

    Time: from start of start of first infusion of study drug and up to day 30

    Measure: Proportion of patients requiring invasive mechanical ventilation

    Time: from start of start of first infusion of study drug and up to day 30

    Description: The ordinal scale is an assessment of the clinical status in a given day. The scale is as follows: 1. Death 2. Hospitalized, requiring invasive mechanical ventilation or ECMO 3. Hospitalized, requiring non-invasive ventilation or high flow supplemental oxygen 4. Hospitalized, requiring low flow supplemental oxygen 5. Hospitalized, not requiring supplemental oxygen, but requiring ongoing medical care 6. Hospitalized, not requiring supplemental oxygen or ongoing medical care 7. discharged, requiring supplemental oxygen 8. Discharged, not requiring supplemental oxygen

    Measure: Differences in outcomes as measured by an 8-point ordinal scale

    Time: from randomization through Days 12 and 30

    Measure: Proportion of patients who have died at day 30 (mortality)

    Time: Day 30

    Measure: Number of days in the hospital

    Time: from admission into the hospital until discharge from the hospital

    Measure: Number of days in the Intensive Care Unit (ICU)

    Time: from admission into ICU until discharge from ICU

    Measure: Incidence of treatment emergent adverse events (TEAE) and serious adverse events (SAE)

    Time: from randomization and through day 30

    Description: Concentration measured using a validated assay

    Measure: CM4620-IE serum concentration

    Time: enrollment through 72 hours
    48 Safety and Efficacy of Intravenous Infusion of Bone Marrow-Derived Mesenchymal Stem Cells in Severe Patients With Coronavirus Disease 2019 (COVID-19): A Phase 1/2 Randomized Controlled Trial

    Coronavirus Disease 2019 (COVID-19) is spreading worldwide and has become a public health emergency of major international concern. Currently, no specific drugs or vaccines are available. For severe cases, it was found that aberrant pathogenic T cells and inflammatory monocytes are rapidly activated and then producing a large number of cytokines and inducing an inflammatory storm.Mesenchymal stem cells (MSCs) have been shown to possess a comprehensive powerful immunomodulatory function. This study aims to investigate the safety and efficacy of intravenous infusion of mesenchymal stem cells in severe patients with COVID-19.

    NCT04346368
    Conditions
    1. Coronavirus Disease 2019 (COVID-19)
    Interventions
    1. Biological: BM-MSCs
    2. Biological: Placebo
    MeSH:Coronavirus Infections

    Primary Outcomes

    Description: Evaluation of pneumonia improvement

    Measure: Changes of oxygenation index (PaO2/FiO2)

    Time: At baseline, 6 hour, Day 1, Day 3,Week 1, Week 2, Week 4, Month 6.

    Description: Proportion of participants with treatment-related adverse events

    Measure: Side effects in the BM-MSCs treatment group

    Time: Baseline through 6 months

    Secondary Outcomes

    Description: Improvement of clinical symptoms including duration of fever, respiratory destress, pneumonia, cough, sneezing, diarrhea.

    Measure: Clinical outcome

    Time: At baseline, 6 hour, Day 1, Day 3,Week 1, Week 2, Week 4, Month 6.

    Description: days of the patients in hospital

    Measure: Hospital stay

    Time: Baseline through 6 months

    Description: Evaluation of pneumonia improvement

    Measure: CT Scan

    Time: At baseline, 6 hour, Day 1, Day 3,Week 1, Week 2, Week 4, Month 6.

    Description: (deep sputum / pharyngeal swab / nasal swab / anal swab / tear fluid / stomach fluid / feces / blood or alveolar lavage fluid)

    Measure: Changes in viral load

    Time: At baseline, 6 hour, Day 1, Day 3,Week 1, Week 2, Week 4, Month 6.

    Description: Immunological status

    Measure: Changes of CD4+, CD8+ cells count and concentration of cytokines

    Time: At baseline, 6 hour, Day 1, Day 3,Week 1, Week 2, Week 4, Month 6.

    Description: Marker for efficacy

    Measure: Rate of mortality within 28-days

    Time: From baseline to day 28

    Description: Markers of Infection

    Measure: Changes of C-reactive protein

    Time: At baseline, 6 hour, Day 1, Day 3,Week 1, Week 2, Week 4, Month 6.
    49 BHV3500-203: Double-Blind, Randomized, Placebo Controlled, Safety and Efficacy Trial of Zavegepant* (BHV-3500) Intranasal (IN) for Hospitalized Patients With COVID-19 Requiring Supplemental Oxygen

    The purpose of this study is to determine if a CGRP receptor antagonist may potentially blunt the severe inflammatory response at the alveolar level, delaying or reversing the path towards oxygen desaturation, ARDS, requirement for supplemental oxygenation, artificial ventilation or death in patients with COVID-19 on supplemental oxygen. * BHV-3500, formerly "vazegepant", is now referred to as "zavegepant" (za ve' je pant). The World Health Organization (WHO) International Nonproprietary Names (INN) Expert Committee revised the name to "zavegepant" which was accepted by the United States Adopted Names (USAN ) Council for use in the U.S. and is pending formal adoption by the INN for international use.

    NCT04346615
    Conditions
    1. COVID-19 Infection
    Interventions
    1. Drug: Zavegepant (BHV-3500)
    2. Drug: Placebo

    Primary Outcomes

    Description: a. Efficacy will be measured by the difference between groups in the meah 6-point severity rating at Day 15. The severity ratings are: Death Hospitalized, on invasive mechanical ventilation or ECMO Hospitalized, on non-invasive ventilation or high flow oxygen devices Hospitalized, requiring supplemental oxygen Hospitalized, not requiring supplemental oxygen Not hospitalized

    Measure: To compare the efficacy of zavegepant (BHV-3500) to placebo in subjects hospitalized with COVID-19 infection requiring supplemental oxygen, using a six-point rating scale at Day 15. .

    Time: Baseline to Day 15

    Secondary Outcomes

    Measure: Proportion of subjects who have a 6-point severity rating of 5 or 6, are alive, and do not use supplemental oxygen as a procedure at Day 29.

    Time: Baseline to Day 29

    Measure: Proportion of subjects who have a 6-point severity rating of 2 or 3, or use any ventilation or high-flow nasal cannula as procedures, on any day through Day 29.

    Time: Baseline to Day 29

    Measure: Proportion of subjects admitted into an ICU on any day through Day 29 from AE eCRFs.

    Time: Baseline to Day 29

    Measure: Proportion of subjects who have a 6-point severity rating of 3, 4, 5, or 6, are alive, and do not use invasive mechanical ventilation as a procedure at Day 15. The analogous definition is applied to Day 29.

    Time: Baseline at Day 15 and at Day 29

    Measure: Proportion of subjects who have a 6-point severity rating of 4, 5 or 6, or use a low- or high-flow nasal, are alive, and do not use any ventilation at Day 15. The analogous definition is applied to Day 29.

    Time: Baseline at Day 15 and at Day 29

    Measure: Difference between treatment groups in the mean 6-point severity rating at Day 29

    Time: Baseline to Day 29

    Measure: Number of days from baseline to the first day through Day 29 with any 6-point severity rating greater than baseline.

    Time: Baseline to Day 29

    Measure: Number of days from baseline to the first of any 2 consecutive days through Day 29 with all SpO2/FiO2 ratios > 400 on both days.

    Time: Baseline to Day 29

    Measure: Number of days from baseline to the first day through Day 29 with ≥ 1-point decrease in any NEWS2 score from baseline.

    Time: Baseline to Day 29

    Measure: Number of days from baseline to the first day through Day 29 with all NEWS2 scores < 2 on that day.

    Time: Baseline to Day 29

    Measure: Mean change from baseline in NEWS2 score at Days 15 and 29 for subjects who are alive at these time points

    Time: Baseline at Day 15 and at Day 29.

    Measure: Proportion of subjects who have a 6-point severity rating of 5 or 6, are alive, and do not use supplemental oxygen as a procedure at Day 15.

    Time: Baseline to Day 15

    Measure: Proportion of subjects who are discharged from the hospital, have a 6-point severity rating of 6 on any day after discharge, and use supplemental oxygen on any day after discharge.

    Time: Baseline to Day 60

    Measure: Mean number of days with respiratory rate > 24 breaths/minute through Day 29 for subjects who are alive at Day 29 and do not use invasive mechanical ventilation.

    Time: Baseline to Day 29

    Measure: Mean number of days with supplemental oxygen use through Day 29 for subjects who are alive at Day 29. A day in which any 6-point severity rating is 2, 3, or 4, or supplemental oxygen is used as a procedure counts.

    Time: Baseline to Day 29

    Measure: Number of days from baseline to the first day through Day 29 on which any SpO2 ≥ 90%, any 6-point severity rating is 5 or 6, and no supplemental oxygen is used as a procedure.

    Time: Baseline to Day 29

    Measure: Mean number of ventilator-free days through Day 29 for subjects who are alive at Day 29.

    Time: Baseline to Day 29

    Measure: Mean SOFA total scores at ICU admission and Day 29 (if still in ICU), from SOFA and AE eCRFs.

    Time: Baseline to Day 29

    Measure: Mean number of days of hospitalization through Day 29 for subjects who are alive on Day 29. All days on study on or before hospitalization discharge are days of hospitalization, from 6-point severity rating scale eCRFs

    Time: Baseline to Day 29

    Measure: Number of days from baseline to the first of any 2 consecutive days through Day 29 in which all temperatures show lack of fever on both days and no antipyretics are used on either day.

    Time: Baseline to Day 29

    Measure: Number of subjects with deaths, SAEs, severe AEs, and Grade 3 or 4 laboratory test abnormalities at any time on study.

    Time: Screening to Day 60

    Measure: Number and percentage of subjects with severe or life-threatening bacterial, invasive fungal, or opportunistic infections at any time through Day 29 from AE/SAE eCRFs.

    Time: Baseline to Day 29

    Measure: Number and percentage of subjects with intranasal administration reactions at any time through Day 29 from AE/SAE eCRFs.

    Time: Baseline to Day 29

    Measure: Proportion of subjects with ≥ 50% reduction in eGFR from baseline at any time on study from laboratory test eCRFs.

    Time: Baseline to Day 60
    50 A Phase 2 Randomized, Double Blinded, Placebo Controlled Study of Oral Favipiravir Compared to Standard Supportive Care in Subjects With Mild or Asymptomatic COVID-19

    The objective of this study is to evaluate the efficacy of oral favipiravir plus standard of care treatment (SOC) compared with placebo plus SOC in reducing the duration of shedding of SARS-CoV2 virus in patients with mild or asymptomatic COVID-19.

    NCT04346628
    Conditions
    1. Sars-CoV2
    2. COVID-19
    Interventions
    1. Drug: Favipiravir
    2. Drug: Placebo
    3. Other: Standard of care treatment

    Primary Outcomes

    Description: Time in days from randomization to the first two negative results of nasal and/or oropharyngeal swab.

    Measure: Time until cessation of oral shedding of SARS-CoV-2 virus

    Time: Up to 28 days

    Secondary Outcomes

    Description: Viral load (nucleic acid) will be assessed by RT-PCR over time.

    Measure: Sars-CoV-2 viral load

    Time: Up to 28 days

    Description: Clinical worsening will be determined by clinician assessment.

    Measure: Count of participants with clinical worsening of COVID-19 disease

    Time: Up to 28 days

    Measure: Count of participants with development of SARS-CoV-2 antibodies

    Time: Up to 28 days

    Measure: Time until cessation of symptoms

    Time: Up to 28 days

    Description: This outcome will be assessed in patient who are asymptomatic of COVID-19 infection at the time of enrollment

    Measure: Count of participant with absence of development of any symptoms

    Time: Up to 28 days

    Description: Cmax is a pharmacokinetic parameter that measures the maximum concentration of drug in plasma.

    Measure: Cmax of favipiravir

    Time: Days 1 and 10 (samples taken 30 minutes prior to and 1 hour following favipiravir administration)

    Description: Cmin is a pharmacokinetic parameter that measures the minimum concentration of drug in plasma.

    Measure: Cmin of favipiravir

    Time: Days 1 and 10 (samples taken 30 minutes prior to and 1 hour following favipiravir administration)
    51 Use and Dosage of Hydroxychloroquine and Chloroquine to Convert Real Time Polymerase Chain Reaction (RT-PCR) Positive Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Coronavirus Infectious Disease 2019 (COVID-19) Patients to RT- PCR-Negative as a Means to Reduce Hospitalization Rate

    To create a protocol for treatment of Pakistani patients with SARS-CoV-2 infection with an intent to reduce burden on institutional healthcare services by determining efficacy of different quinone drug dosing regimens in controlling SARS-CoV-2 infection for asymptomatic patients.

    NCT04346667
    Conditions
    1. SARS-CoV-2
    2. Coronavirus Infection
    3. Asymptomatic Condition
    4. COVID-19
    Interventions
    1. Drug: Hydroxychloroquine Sulfate Regular dose
    2. Drug: Hydroxychloroquine Sulfate Loading Dose
    3. Drug: Chloroquine
    4. Drug: Placebo
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Asymptomatic Diseases

    Primary Outcomes

    Description: Percentage of patients who become RT-PCR negative with two RT-PCR tests performed at day 6 and day 7

    Measure: RT-PCR negative status

    Time: 6-7 days

    Secondary Outcomes

    Description: Time to progression to next stage of SARS-CoV-2 disease severity index

    Measure: Progression of symptoms

    Time: 7 days

    Description: Time to onset of fever (temperature greater than 100 degree F), cough, or shortness of breath (respiratory rate >22 per minute).

    Measure: Development of Symptoms

    Time: 7 days

    Description: Drug related adverse events as determined by data safety and monitoring board (DSMB)

    Measure: Adverse events

    Time: 7 days
    52 A Clinical Trial to Evaluate the Safety and Efficacy of Mycobacterium W in Critically Ill Patients Suffering From COVID 19 Infection

    The trial is randomized, blinded, two arms, active comparator controlled, clinical trial to evaluate the safety and efficacy of Mycobacterium w in combination with standard care as per hospital practice versus standard care alone in critically ill adult patients suffering from COVID-19 infection.

    NCT04347174
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Suspension of heat killed (autoclaved) Mycobacterium w
    2. Drug: Placebo
    MeSH:Mycobacterium Infections Critical Illness

    Primary Outcomes

    Description: To study the effect of Mw on recovery of organ function as assessed by Ordinal scale

    Measure: 7-category ordinal scale that ranges from 1 (not hospitalized with resumption of normal activities) to 7 (death)

    Time: Change in Ordinal scale from baseline to day 3, day 7, day 14, day 21 and day 28 and day of transfer from ICU, if discharged earlier than 28 days post-randomization.

    Description: 28 day mortality

    Measure: 28 day mortality

    Time: Till day 28, post-randomization or death or discharge, whichever is earlier.

    Secondary Outcomes

    Description: Any AE / SAE or event of clinical significance observed during the study.

    Measure: Incidence of AE / SAE or event of clinical significance

    Time: Till day 28

    Description: Percent of subjects with SARS-CoV-2 detectable in nasal or oropharyngeal (OP) sample.

    Measure: SARS-CoV-2 detectable in nasal or oropharyngeal (OP) sample

    Time: At days 3, 7, 14, 21, and 28

    Description: ICU length of stay

    Measure: ICU length of stay

    Time: Till day 28

    Description: Duration of mechanical ventilation

    Measure: Duration of mechanical ventilation

    Time: Till day 28

    Description: Duration of hospitalization

    Measure: Duration of hospitalization

    Time: Till day 28

    Description: Percentage of subjects having clinical improvement defined as two-point improvement on a seven category ordinal scale.

    Measure: Clinical improvement

    Time: From baseline to day 14 & Day 28

    Description: Time (in days) from treatment initiation to death.

    Measure: Time (in days) from treatment initiation to death

    Time: Till day 28

    Description: To study the effect of Mw on recovery of organ function as assessed by Sequential Organ Failure Assessment (SOFA) which is based on six different scores, one for each of the respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems each scored from 0 to 4 with an increasing score reflecting worsening organ dysfunction

    Measure: Sequential Organ Failure Assessment (SOFA) scores

    Time: Change in SOFA score from baseline to day 3, day 7, day 14, day 21 and day 28 and day of transfer from ICU, if discharged earlier than 28 days post-randomization.
    53 A Single Blind, Randomized, Placebo-controlled, Multi-center Phase 2 Study to Evaluate the Safety and Efficacy of Clevudine in Patients Diagnosed With Moderate COVID-19

    The purpose of this clinical trial is to assess the safety and efficacy of Clevudine 120 mg versus placebo once daily administration with standard of care therapy for 14 days (maximum up to 21 days) in patients with moderate COVID-19.

    NCT04347915
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Clevudine
    2. Drug: Placebo

    Primary Outcomes

    Description: The primary efficacy endpoint for this clinical trial is the rate of patients with negative SARS-Coronavirus-2 (SARS-CoV-2) in a two-day continuous Real-Time-RT-PCR test from baseline to before the 15th day.

    Measure: The rate of subjects tested as negative SARS-Coronavirus-2 (SARS-CoV-2)

    Time: within 15days

    Secondary Outcomes

    Measure: The rate of subjects tested as negative SARS-Coronavirus-2 (SARS-CoV-2) in consecutive two days of Real-Time RT-PCR tests

    Time: Day 4, 8, 11, 15, 22, 29(or EOT) day comparing the baseline

    Measure: The rate of subjects indicated by the improvement of lung invasive

    Time: within Day 29 (or EOT)

    Measure: The change of viral load

    Time: Day 4, 8, 11, 15, 22, and 29(or EOT) comparing the baseline
    54 Proof of Concept, Multicentre, Parallel, Randomized, Double-blind Clinical Trial to Assess the Safety and Efficacy of Nitazoxanide 600 mg Compared to Placebo in the Treatment of Hospitalized Patients With COVID-19 in Moderate Condition.

    This is a proof of concept study to evaluate the efficacy of nitazoxanide (600 mg BID) to treat hospitalized patients with moderate COVID-19.

    NCT04348409
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Nitazoxanide Tablets
    2. Drug: Placebo

    Primary Outcomes

    Description: PCR will be done to evaluate the change in viral load

    Measure: Viral load

    Time: day 1, 4, 7, 14 and 21

    Secondary Outcomes

    Description: Time to wean off oxygen supplementation

    Measure: Evolution of acute respiratory syndrome

    Time: 21 days

    Description: WHO Ordinal Scale for Clinical Improvement that measures illness severity over time (0=uninfected; ambulatory, no limitation of activities=1; ambulatory, limitation of activities=2, hospitalized no oxygen therapy=3; hospitalized oxygen by mask or nasal prongs=4; hospitalized non invasive ventilation or high-flow oxygen=5; hospitalized intubation or mechanical ventilation=6; hospitalized ventilation + additional organ support=7; death=8)

    Measure: Change in Clinical Condition

    Time: 21 days

    Description: Time to be discharged from hospital

    Measure: Hospital discharge

    Time: 21 days

    Description: Evaluation of change in acute respiratory syndrome

    Measure: Rate of mortality within 21-days

    Time: 21 days

    Description: Evaluation of change in acute respiratory syndrome

    Measure: Need of mechanical ventilation

    Time: 21 days
    55 Triiodothyronine for the Treatment of Critically Ill Patients With COVID-19 Infection (Thy-Support)

    This study is a phase II, parallel, prospective, randomized, double-blind, placebo controlled trial. The present study will aim to address the efficacy and safety of acute administration of triiodothyronine on ICU patients diagnosed with pulmonary infection due to COVID-19 and require mechanical respiratory support or ECMO.

    NCT04348513
    Conditions
    1. Pulmonary Infection
    2. Covid-19
    Interventions
    1. Drug: T3 solution for injection
    2. Drug: Placebo
    MeSH:Infection Communicable Diseases

    Primary Outcomes

    Description: The primary objective of the study is to determine whether the administration of intravenous triiodothyronine in ICU patients diagnosed with pulmonary infection due to COVID-19 facilitates weaning from cardiorespiratory support compared to placebo. Successful weaning is defined as no requirement for ventilatory support after extubation (mechanical support) or support from ECMO for 48 hours. The primary objective will be measured as percentage of patients successfully weaned after 30 days of follow-up.

    Measure: Assessment of weaning from cardiorespiratory support

    Time: 30 days

    Secondary Outcomes

    Description: Hemodynamic status will be assessed by continuous blood pressure measurements (systolic BP in mmHg)

    Measure: Assessment of hemodynamic status

    Time: 30 days

    Description: Hemodynamic status will be assessed by continuous blood pressure measurements (diastolic BP in mmHg)

    Measure: Assessment of hemodynamic status

    Time: 30 days

    Description: Hemodynamic status will be assessed by continuous blood pressure measurements (mean BP in mmHg)

    Measure: Assessment of hemodynamic status

    Time: 30 days

    Description: Hemodynamic status will be assessed by the number of participants with use of inotropic and vasoactive drugs

    Measure: Assessment of hemodynamic status

    Time: 30 days

    Description: Pulmonary function will be assessed by arterial measurement of blood gases (arterial partial pressure of oxygen in mmHg)

    Measure: Assessment of pulmonary function

    Time: 30 days

    Description: Pulmonary function will be assessed by arterial measurement of blood gases (arterial partial pressure of carbon dioxide in mmHg)

    Measure: Assessment of pulmonary function

    Time: 30 days

    Description: Pulmonary function will be assessed by arterial measurement of lactate levels (in mmol/L)

    Measure: Assessment of pulmonary function

    Time: 30 days

    Description: Hepatic function will be assessed by laboratory measurements in blood. Changes in aspartate aminotransferase (AST in IU/L) will be measured.

    Measure: Assessment of hepatic function

    Time: 30 days

    Description: Hepatic function will be assessed by laboratory measurements in blood. Changes in alanine aminotransferase (ALT in IU/L) will be measured.

    Measure: Assessment of hepatic function

    Time: 30 days

    Description: Hepatic function will be assessed by laboratory measurements in blood. Changes in gamma-glutamyl transpeptidase (γ-GT in IU/L) will be measured.

    Measure: Assessment of hepatic function

    Time: 30 days

    Description: Hepatic function will be assessed by laboratory measurements in blood. Changes in bilirubin in mg/dL will be measured.

    Measure: Assessment of hepatic function

    Time: 30 days

    Description: Hepatic function will be assessed by laboratory measurements in blood. Changes in fibrinogen in mg/dL will be measured.

    Measure: Assessment of hepatic function

    Time: 30 days

    Description: Hepatic function will be assessed by laboratory measurements in blood. Changes in d-dimers in ng/ml will be measured.

    Measure: Assessment of hepatic function

    Time: 30 days

    Description: Urine volume during 24 hours (in ml) will be recorded.

    Measure: Assessment of renal function

    Time: 30 days

    Description: Changes in urea (in mg/dL) will be recorded.

    Measure: Assessment of renal function

    Time: 30 days

    Description: Changes in uric acid (in mg/dL) will be recorded.

    Measure: Assessment of renal function

    Time: 30 days

    Description: Changes in creatinine (in mg/dL) will be recorded.

    Measure: Assessment of renal function

    Time: 30 days

    Description: Echocardiographic assessment of cardiac left ventricular ejection fraction (LVEF, %)

    Measure: Assessment of cardiac function

    Time: 30 days

    Description: Measurements of cardiac troponin I (in μg/L) will be used to assess myocardial injury

    Measure: Assessment of cardiac injury

    Time: 30 days

    Description: COVID-19 infection will be assessed by inflammatory indices in blood (white blood cells in number per μL)

    Measure: Assessment of the course of COVID-19 infection

    Time: 30 days

    Description: COVID-19 infection will be assessed by inflammatory indices in blood (CRP in mg/L)

    Measure: Assessment of the course of COVID-19 infection

    Time: 30 days

    Description: COVID-19 infection will be assessed by inflammatory indices in blood (erythrocyte sedimentation rate in mm/hr)

    Measure: Assessment of the course of COVID-19 infection

    Time: 30 days

    Description: COVID-19 infection will be assessed by temperature monitoring (in degrees Celsius)

    Measure: Assessment of the course of COVID-19 infection

    Time: 30 days

    Description: COVID-19 infection will be assessed by time needed (in days) for the patient to become negative in COVID-19

    Measure: Assessment of the course of COVID-19 infection

    Time: 30 days

    Description: Number of participants with major (death, cardiac Arrest, electromechanical dissociation, pulmonary embolism, new myocardial infarction, stroke, pulmonary edema, cardiogenic shock and hypotension, septic shock, pulmonary embolism, serious bleeding) events be recorded during the follow up period

    Measure: Assessment of clinical outcome and safety

    Time: 30 days

    Description: Number of participants with minor (myocarditis, Venous Thromboembolism, left Ventricular mural thrombus, renal failure, hepatic failure, stress ulcers, minor bleeding, paroxysmal supraventricular tachycardia and atrial fibrillation, rhythm disturbances) events will be recorded during the follow up period

    Measure: Assessment of clinical outcome and safety

    Time: 30 days
    56 A Phase 2 Randomized Single-Blind Study to Evaluate the Activity and Safety of Low Dose Oral Selinexor (KPT-330) in Patients With Severe COVID-19 Infection

    The main purpose of this study is to evaluate the activity of low dose oral selinexor (KPT-330) and to evaluate the clinical recovery, the viral load, length of hospitalization and the rate of morbidity and mortality in participants with severe COVID-19 compared to placebo.

    NCT04349098
    Conditions
    1. Coronavirus Infection
    Interventions
    1. Drug: Selinexor
    2. Other: Placebo
    MeSH:Infection Communicable Diseases Coronavirus Infections Severe Acute Respiratory Syndrome

    Primary Outcomes

    Measure: Percentage of Participants with at Least a 2 Point Improvement in the Ordinal Scale

    Time: Baseline to Day 14

    Secondary Outcomes

    Measure: Time to Clinical Improvement (TTCI)

    Time: Up to Day 28

    Measure: Overall Death Rate

    Time: Day 14, Day 28

    Measure: Rate of Mechanical Ventilation

    Time: Up to Day 28

    Measure: Time to Mechanical Ventilation

    Time: Up to Day 28

    Measure: Overall Survival

    Time: Up to Day 28

    Measure: Time to Improvement (2 points) in Clinical Measures Using the Ordinal Scale

    Time: Baseline, Day 28

    Measure: Time to Intensive Care Unit (ICU) Admission

    Time: Up to Day 28

    Measure: Rate of Intensive Care Unit (ICU) Admission

    Time: Up to Day 28

    Measure: Length of Stay in Hospital

    Time: Up to Day 28

    Measure: Percentage of Participants Discharged from Hospital

    Time: Up to Day 28

    Measure: Length of Stay in Intensive Care Unit (ICU)

    Time: Up to Day 28

    Measure: Duration of Oxygen Supplementation

    Time: Up to Day 28

    Measure: Duration of Mechanical Ventilation

    Time: Up to Day 28

    Measure: Time to Clinical Improvement in Participants ≤ 70 Years Old

    Time: Up to Day 28

    Measure: Time to Clinical Improvement in Participants > 70 Years Old

    Time: Up to Day 28

    Measure: Time to Clinical Improvement in Participants with Pre-existing Diseases

    Time: Up to Day 28

    Measure: Change in Oxygenation Index

    Time: Up to Day 28

    Measure: Time to Improvement of One Point Using WHO Ordinal Scale Improvement

    Time: Up to Day 28

    Measure: Percentage of Participants Experiencing WHO Ordinal Scale Improvement of >1 point

    Time: Up to Day 28

    Measure: Change from Baseline in C-reactive protein (CRP) Levels

    Time: Up to Day 28

    Measure: Change from Baseline in Ferritin Levels

    Time: Up to Day 28

    Measure: Change from Baseline in Lactate Dehydrogenase (LDH) Levels

    Time: Up to Day 28

    Measure: Changes from Baseline in Blood Plasma Cytokines Levels

    Time: Up to Day 28

    Measure: Number of Participants with Adverse Events (AE)

    Time: From start of study drug administration up to Day 28
    57 Value of Early Treatment With Polyvalent Immunoglobulin in the Management of Acute Respiratory Distress Syndrome Associated With SARS-CoV-2 Infections

    As of 30/03/2020, 715600 people have been infected with COVID-19 worldwide and 35500 people died, essentially due to respiratory distress syndrome (ARDS) complicated in 25% of the with acute renal failure. No specific pharmacological treatment is available yet. The lung lesions are related to both the viral infection and to an intense inflammatory reaction. Because of it's action, as an immunomodulatory agent that can attenuate the inflammatory reaction and also strengthen the antiviral response, it is proposed to evaluate the effectiveness and safety of intravenous immunoglobulin administration (IGIV) in patients developing ARDS post-SARS-CoV2. IGIV modulates immunity, and this effect results in a decrease of pro-inflammatory activity, key factor in the ARDS related to the COVID-19. It should be noted that IGIV is part of the treatments in various diseases such as autoimmune and inflammatory diffuse interstitial lung diseases. In addition, they have been beneficial in the post-influenza ARDS but also have been in 3 cases of post-SARS-CoV2 ARDS. IGIV is a treatment option because it is well tolerated, especially concerning the kidney. These elements encourage a placebo-controlled trial testing the benefit of IGIV in ARDS post-SARS-CoV2.

    NCT04350580
    Conditions
    1. Acute Respiratory Distress Syndrome
    2. COVID-19
    Interventions
    1. Drug: Human immunoglobulin
    2. Drug: Placebo
    MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

    Primary Outcomes

    Description: Sum of the days the patient did not receive VM, but if death occurs before D28, the score is zero

    Measure: Ventilator-free days

    Time: 28 days

    Secondary Outcomes

    Description: Vital status at 28 and 90 days

    Measure: Mortality

    Time: 28 and 90 days

    Description: Used to determine the extent of a person's organ function or rate of failure, from 0 to 24, with severity increasing the higher the score

    Measure: Sequential Organ Failure Assessment Score

    Time: Days 1, 3, 7, 14, 21 and 28

    Description: Ratio of arterial oxygen partial pressure (PaO2 in mmHg) to fractional inspired oxygen (FiO2 expressed as a fraction, not a percentage)

    Measure: P/F ratio

    Time: Days 1, 3, 7, 14, 21 and 28

    Description: Measure of lung compliance

    Measure: Lung compliance

    Time: Days 1, 3, 7, 14, 21 and 28

    Description: Severity scoring of lung oedema on the chest radiograph

    Measure: Radiological score

    Time: Days 1, 3, 7, 14, 21 and 28

    Description: Concentration in mg/L

    Measure: Biological efficacy endpoints - C-reactive protein

    Time: Days 1, 3, 7, 14, 21 and 28

    Description: Concentration in microgram/L

    Measure: Biological efficacy endpoints - Procalcitonin

    Time: Days 1, 3, 7, 14, 21 and 28

    Description: Number of CD4 HLA-DR+ and CD38+, CD8 lymphocytes

    Measure: Immunological profile

    Time: Up to 28 days

    Description: Use of corticosteroids, antiretroviral, chloroquine

    Measure: Number of patients using other treatments for COVID-19 related ARDS

    Time: Up to 28 days

    Description: Diagnosis of deep vein thrombosis or pulmonary embolism through imaging exam (eg ultrasound and CT scan)

    Measure: Occurrence of deep vein thrombosis or pulmonary embolism

    Time: 28 days

    Description: Total time of mechanical ventilation, weaning and use of neuromuscular blockade

    Measure: Total duration of mechanical ventilation, ventilatory weaning and curarisation

    Time: 28 days

    Description: Divided in 3 stages, with higher severity of kidney injury in higher stages

    Measure: Kidney Disease: Improving Global Outcomes (KDIGO) score and need for dialysis

    Time: 28 days

    Description: Kidney failure, hypersensitivity with cutaneous or hemodynamic manifestations, aseptic meningitis, hemolytic anemia, leuko-neutropenia, transfusion related acute lung injury (TRALI)

    Measure: Occurrence of adverse event related to immunoglobulins

    Time: 28 days

    Description: Medical research council sum score on awakening

    Measure: Occurrence of critical illness neuromyopathy

    Time: Up to 28 days

    Description: Radiological and clinical context associated with a bacteriological sampling in culture of tracheal secretions, bronchiolar-alveolar lavage or a protected distal sampling

    Measure: Occurrence of ventilator-acquired pneumonia

    Time: Up to 28 days
    58 An International, Multicenter, Randomized, Double-blind, Placebo-controlled, Phase III Study Evaluating the Efficacy and Safety of Dapagliflozin in Respiratory Failure in Patients With COVID-19

    This is an international, multicenter, parallel-group, randomized, double-blind, placebo controlled, study in hospitalized adult patients with COVID-19 in the US and other countries with high prevalence of COVID-19. The study is evaluating the effect of dapagliflozin 10 mg versus placebo, given once daily for 30 days in addition to background local standard of care therapy, in reducing disease progression, complications, and all-cause mortality.

    NCT04350593
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Dapagliflozin 10 MG
    2. Drug: Placebo
    MeSH:Respiratory Insufficiency

    Primary Outcomes

    Description: Respiratory decompensation (e.g., invasive or non-invasive mechanical ventilation) New or worsening congestive HF Requirement for vasopressor therapy and/or inotropic or mechanical circulatory support Ventricular tachycardia or fibrillation lasting at least 30 seconds and/or associated with hemodynamic instability or pulseless electrical activity, or resuscitated cardiac arrest Initiation of renal replacement therapy

    Measure: Time to first occurrence of either death from any cause or new/worsened organ dysfunction through 30 days of follow up, defined as at least one of the following:

    Time: Randomization through Day 30

    Secondary Outcomes

    Description: Time to death from any cause Time to new/worsened organ dysfunction (as defined in the primary outcome measure) Clinical status at Day 30 for patients still hospitalized and without any worsening organ dysfunction (using points 3 to 5 of a 7-point ordinal scale) Time to hospital discharge

    Measure: Hierarchical composite outcome measures including time to death from any cause, time to new/worsened organ dysfunction, clinical status at day 30 and time to hospital discharge

    Time: Randomization through Day 30

    Description: Time to hospital discharge

    Measure: Time to hospital discharge

    Time: Randomization through Day 30

    Description: Total number of days alive, out of hospital, and/or free from mechanical ventilation

    Measure: Total number of days alive, out of hospital, and/or free from mechanical ventilation

    Time: Randomization through Day 30

    Description: Total number of days alive, not in the ICU, and free from mechanical ventilation (as defined in the primary outcome measure)

    Measure: Total number of days alive, not in the ICU, and free from mechanical ventilation (as defined in the primary outcome measure)

    Time: Randomization through Day 30

    Description: Time to death from any cause

    Measure: Time to death from any cause

    Time: Randomization through Day 30

    Description: Time to new/worsened organ dysfunction

    Measure: Time to new/worsened organ dysfunction

    Time: Randomization through Day 30

    Description: Time to acute kidney injury (defined as doubling of s-Creatinine compared to baseline)

    Measure: Time to acute kidney injury (defined as doubling of s-Creatinine compared to baseline)

    Time: Randomization through Day 30
    59 A Phase 1, Double-blind, Randomized, Placebo-controlled, Sponsor-open, SAD and MAD Study in Healthy Subjects to Evaluate the Safety, Tolerability, and PK of Inhaled TD-0903, a Potential Treatment for ALI Associated With COVID-19

    This is a phase 1 study in healthy subjects to evaluate the safety, tolerability and pharmacokinetics of single (Part A and B) and multiple (Part B) doses of inhaled TD-0903.

    NCT04350736
    Conditions
    1. Acute Lung Injury (ALI) Associated With COVID-19
    2. Inflammatory Lung Conditions Associated With COVID-19
    Interventions
    1. Drug: TD-0903
    2. Drug: Placebo
    MeSH:Lung Injury Acute Lung Injury Respiratory Distress Syndrome, Adult

    Primary Outcomes

    Description: Number and severity of treatment emergent adverse events

    Measure: Safety and Tolerability of SAD of TD-0903: Adverse Events

    Time: Day 1 to Day 8

    Description: Number and severity of treatment emergent adverse events

    Measure: Safety and Tolerability of MAD of TD-0903: Adverse Events

    Time: Day 1 to Day 14

    Secondary Outcomes

    Description: Multiple PK variables of TD-0903 will be assessed during SAD and may include, but are not limited to: Area under the plasma concentration-time curve (AUC)

    Measure: Pharmacokinetics (PK) of TD-0903 when given as a Single Ascending Dose (SAD): AUC

    Time: Day 1 through Day 4

    Description: Multiple PK variables of TD-0903 will be assessed during SAD and may include, but are not limited to: Maximum observed concentration (Cmax)

    Measure: Pharmacokinetics (PK) of TD-0903 when given as a Single Ascending Dose (SAD): Cmax

    Time: Day 1 through Day 4

    Description: Multiple PK variables of TD-0903 will be assessed during SAD and may include, but are not limited to: Time to reach maximum observed concentration (Tmax)

    Measure: Pharmacokinetics (PK) of TD-0903 when given as a Single Ascending Dose (SAD): Tmax

    Time: Day 1 through Day 4

    Description: Multiple PK variables of TD-0903 will be assessed during MAD and may include, but are not limited to: Area under the plasma concentration-time curve (AUC)

    Measure: Pharmacokinetics (PK) of TD-0903 when given as a Multiple Ascending Dose (MAD): AUC

    Time: Day 1 through Day 9

    Description: Multiple PK variables of TD-0903 will be assessed during MAD and may include, but are not limited to: Maximum observed concentration (Cmax)

    Measure: Pharmacokinetics (PK) of TD-0903 when given as a Multiple Ascending Dose (MAD): Cmax

    Time: Day 1 through Day 9

    Description: Multiple PK variables of TD-0903 will be assessed during MAD and may include, but are not limited to: Time to reach maximum observed concentration (Tmax)

    Measure: Pharmacokinetics (PK) of TD-0903 when given as a Multiple Ascending Dose (MAD): Tmax

    Time: Day 1 through Day 9
    60 Use and Dosage of Hydroxychloroquine and Chloroquine to Convert Symptomatic RT-PCR Positive Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Coronavirus Infectious Disease 2019 (COVID-19) Patients to RT- PCR-Negative as a Means to Reduce Hospitalization Rate

    To treat Pakistani patients with non-life threatening symptomatic SARS-CoV-2 infection with an intent to reduce burden on institutional healthcare services by determining efficacy of different chloroquine and hydroxychloroquine dosing regimens in controlling SARS-CoV-2 infection.

    NCT04351191
    Conditions
    1. Sars-CoV2
    2. Symptomatic Condition
    3. Covid-19
    Interventions
    1. Drug: Hydroxychloroquine Sulfate Regular dose
    2. Drug: Hydroxychloroquine Sulfate Loading Dose
    3. Drug: Chloroquine
    4. Drug: Placebo

    Primary Outcomes

    Description: Percentage of patients who become RT-PCR negative with two RT-PCR tests performed at day 6 and day 7

    Measure: RT-PCR result

    Time: 6th and 7th day

    Secondary Outcomes

    Description: Time to progression to next stage of SARS-CoV-2 disease severity index

    Measure: Progression of symptoms

    Time: 7 days

    Description: Death

    Measure: Mortality

    Time: 30 days
    61 A Multi-Center, Adaptive, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy and Safety of Gimsilumab in Subjects With Lung Injury or Acute Respiratory Distress Syndrome Secondary to COVID-19 (BREATHE)

    Study KIN-1901-2001 is a multi-center, adaptive, randomized, double-blind, placebo-controlled study to assess the efficacy and safety of gimsilumab in subjects with lung injury or acute respiratory distress syndrome (ARDS) secondary to COVID-19.

    NCT04351243
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Gimsilumab
    2. Drug: Placebo
    MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Lung Injury

    Primary Outcomes

    Measure: Incidence of mortality

    Time: Day 43

    Secondary Outcomes

    Measure: Incidence of subjects who are alive and not on mechanical ventilation

    Time: Day 29

    Description: Subjects who die will be assigned "0" ventilator-free days

    Measure: Number of ventilator-free days

    Time: Baseline to Day 29

    Measure: Time to hospital discharge

    Time: Baseline to Day 43
    62 Randomized Controlled Trial of Hydroxychloroquine Versus Placebo in Early Ambulatory Diagnosis and Treatment of Elderly COVID19 Patients

    Patients over equal or older than 65 yearswill be treated with a hydroxychloroquine versus placebo reduced loading dose of 600mg on the first day followed with 400mg/day divided in 2x200mg for 6 more days resulting in a total duration of therapy of 7 days. Measurement of Hydroxychloroquine-levels will be performed on day 7, . A follow-up by video or telephone conference will be performed to observe drug intake and collect adverse events during treatment phase on a daily base on working days and once during the weekend (i.e. 6 out of 7 days). After treatment phase follow-up by telephone calls will be done on day 10, 30, 60 (+/- 2 days).

    NCT04351516
    Conditions
    1. SARS-CoV 2
    2. COVID-19
    Interventions
    1. Drug: Hydroxychloroquine
    2. Other: Placebo

    Primary Outcomes

    Measure: ● Rate of hospitalization or death at day 7 after study inclusion

    Time: 7 days
    63 RAndomized Clinical Trial in COvid19 Patients to Assess the Efficacy of the Transmembrane Protease Serine 2 (TMPRSS2) Inhibitor NAfamostat (RACONA Study)

    RACONA is a prospective trial that will test the hypothesis that nafamostat can lower lung function deterioration and need for intensive care admission in COVID-19 patients. Design: Adult hospitalized COVID-19 patients will be randomized in a prospective double-blind randomized placebo-controlled study to test the clinical efficacy of nafamostat mesylate (administered intravenously) on top of best standard of care. Primary outcome measures: the time-to-clinical improvement, defined as the time from randomization to an improvement of two points (from the status at randomization) on a seven category ordinal scale or live discharge from the hospital, whichever comes first.

    NCT04352400
    Conditions
    1. COVID19
    Interventions
    1. Drug: Nafamostat Mesilate
    2. Drug: Placebo

    Primary Outcomes

    Description: Time-to-clinical improvement (time from randomization to an improvement of two points (from the status at randomization) on a 7 category ordinal scale or live discharge from the hospital, whichever came first.

    Measure: Time-to-clinical improvement

    Time: day 1 until day 28

    Secondary Outcomes

    Description: Rate of patients showing improvement of 2 points in 7 category ordinal scale (with 7 points the worst)(PubMed ID: 32187464)

    Measure: Responders

    Time: day 1 until day 28

    Description: Proportion of patients who will progress to critical illness/death

    Measure: Critical or dead patients

    Time: day 1 until day 28

    Description: Change in pO2/FiO2 ratio over time

    Measure: pO2/FiO2 ratio

    Time: day 1 until day 28

    Description: Change Sequential organ failure assessment score (SOFA score) over time. The Score ranges from 0 to 24 (with 24 the worst)(PubMed ID: 11594901)

    Measure: SOFA score over time

    Time: day 1 until day 28

    Description: Duration of hospitalization in survivors (days)

    Measure: Hospitalization

    Time: day 1 until day 28

    Description: Number of patients who require ventilation

    Measure: Mechanical ventilation

    Time: day 1 until day 28

    Description: Duration of ventilation (days)

    Measure: Mechanical ventilation duration

    Time: day 1 until day 28

    Description: Proportion of patients who develop arrhythmia, or myocardial infarction, or other cardiovascular disease not present at the baseline

    Measure: Cardiovascular disease

    Time: day 1 until day 28
    64 A Randomized Phase 2/3 Trial of Hydroxychloroquine In Covid-19 Kinetics

    To test if the medication Hydroxychloroquine will decrease the amount of virus(as measured by PCR) , 7 days after initiation of therapy compared to control patients receiving placebo. The study design is a randomized (5 days of medication v. 5 days of placebo) clinical trial initiated immediately after diagnosis in ambulatory health care workers at University of South Alabama Health, or in ambulatory USA patients. At 7 days after enrollment another nasopharyngeal swab will be taken to measure if the virus is still present. At 10 weeks we will measure immunity from Covid-19 using a single blood sample. It is a phase 2/3 clinical trial.

    NCT04353271
    Conditions
    1. Covid 19
    2. Corona Virus Infection
    Interventions
    1. Drug: Hydroxychloroquine
    2. Other: Placebo
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome

    Primary Outcomes

    Description: Nasopharyngeal swab PCR measurement of viral load expressed as the % of negative PCR swabs

    Measure: Percentage of virus free subjects

    Time: 7 days after initiation of trial

    Description: Participants will self-report disease severity status as one of the following 5 options; no COVID19 illness (score of 1), COVID19 illness with no hospitalization (score of 2), or COVID19 illness with hospitalization (score of 3), or Covid 19 with care requiring hospitalization (score of 4), or Covid 19 with death (Score of 5) .

    Measure: Disease severity

    Time: 6 days

    Secondary Outcomes

    Description: Number of subjects in each arm who are hospitalized for Covid 19 infection

    Measure: Incidence of hospitalization

    Time: 14 days

    Description: Number of subjects in each arm who die secondary to Covid-19 infection

    Measure: Incidence of Death

    Time: 70 Days (10 weeks)

    Description: Number of subjects in each arm who have confirmed Covid-19 infection

    Measure: Incidence of confirmed SARS-CoV-2 Detection

    Time: 14 days

    Description: Number of subjects in each arm who discontinue or withdraw medication use for any reason

    Measure: Incidence of all-cause study medication discontinuation or withdrawal

    Time: 14 days

    Description: Blood tests to determine level of immunity in each subject

    Measure: Immunity to Covid-19

    Time: 70 days (10 weeks)
    65 The Effect of Camostat Mesylate on COVID-19 Infection in Ambulatory Patients: An Investigator-Initiated Randomized, Placebo-Controlled, Phase IIa Trial

    The rationale of the present clinical trial is that an orally available drug given to outpatients that could reduce the viral burden in the upper respiratory tract could forestall complications of SARS-CoV-2 infection and reduce transmission from one infected individual to another.

    NCT04353284
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Camostat Mesilate
    2. Other: Placebo

    Primary Outcomes

    Description: To determine whether camostat mesylate reduces SARS-COV-2 viral load in early COVID-19 disease, change from day 0 to day 4 in respiratory (oropharyngeal swab RT-PCR) log10 viral load will be assessed.

    Measure: Change in SARS-COV-2 viral load

    Time: 5 days

    Secondary Outcomes

    Description: To determine whether camostat mesylate reduces SARS-COV-2 viral load in early COVID-19 disease, change from day 0 to day 2 in respiratory (oropharyngeal swab RT-PCR) log10 viral load will be assessed.

    Measure: Change in SARS-COV-2 viral load

    Time: 3 days

    Description: To determine whether camostat mesylate reduces SARS-COV-2 viral load in early COVID-19 disease, change from day 0 to day 6 in respiratory (oropharyngeal swab RT-PCR) log10 viral load will be assessed.

    Measure: Change in SARS-COV-2 viral load

    Time: 7 days

    Description: Change in risk for a positive COVID-19 test at day 6 after enrollment (day 0) will be assessed by analyzing the proportion of positive cases in each study arm.

    Measure: Change in positive COVID-19 status

    Time: 7 days

    Description: Change in risk for a positive COVID-19 test at day 13 after enrollment (day 0) will be assessed by analyzing the proportion of positive cases in each study arm.

    Measure: Change in positive COVID-19 status

    Time: 14 days

    Description: Change in risk for a positive COVID-19 test at day 27 after enrollment (day 0) will be assessed by analyzing the proportion of positive cases in each study arm.

    Measure: Change in positive COVID-19 status

    Time: 28 days

    Description: Change of COVID-19 symptom severity from day 0 to day 6 will be assessed with the COVID-19 daily self score tool. Adapted from the FLU-PRO instrument, it consists of 39 items that are answered daily. Items 1-33 are Likert scale questions (rated 0-4) where 0 = not at all and 4 = very much. These items are summed to score the severity of symptoms- where a total score of 132 would indicate the greatest severity of symptoms and a score of 0 would indicate no severity of symptoms. Items 34-38 are also Likert scale questions (rated 0-4) that measure the frequency of specific daily symptoms where 0 = 0 times and 4 = 4 times or more. These items are summed to score the frequency of symptoms- where the highest score for the frequency of symptoms (20) indicates the greatest burden of symptom frequency. The last question (39) asks patients for their highest temperature in Fahrenheit.

    Measure: Change in COVID-19 symptom severity

    Time: 7 days

    Description: Change of COVID-19 symptom severity from day 0 to day 14 will be assessed with the COVID-19 daily self score tool. Adapted from the FLU-PRO instrument, it consists of 39 items that are answered daily. Items 1-33 are Likert scale questions (rated 0-4) where 0 = not at all and 4 = very much. These items are summed to score the severity of symptoms- where a total score of 132 would indicate the greatest severity of symptoms and a score of 0 would indicate no severity of symptoms. Items 34-38 are also Likert scale questions (rated 0-4) that measure the frequency of specific daily symptoms where 0 = 0 times and 4 = 4 times or more. These items are summed to score the frequency of symptoms- where the highest score for the frequency of symptoms (20) indicates the greatest burden of symptom frequency. The last question (39) asks patients for their highest temperature in Fahrenheit.

    Measure: Change in COVID-19 symptom severity

    Time: 14 days

    Description: Change of COVID-19 symptom score from day 0 to day 6 will be assessed with the COVID-19 daily self score tool. Adapted from the FLU-PRO instrument, it consists of 39 items that are answered daily. Items 1-33 are Likert scale questions (rated 0-4) where 0 = not at all and 4 = very much. These items are summed to score the severity of symptoms- where a total score of 132 would indicate the greatest severity of symptoms and a score of 0 would indicate no severity of symptoms. Items 34-38 are also Likert scale questions (rated 0-4) that measure the frequency of specific daily symptoms where 0 = 0 times and 4 = 4 times or more. These items are summed to score the frequency of symptoms- where the highest score for the frequency of symptoms (20) indicates the greatest burden of symptom frequency. The last question (39) asks patients for their highest temperature in Fahrenheit.

    Measure: Change in COVID-19 symptom frequency

    Time: 7 days

    Description: Change of COVID-19 symptom score from day 0 to day 14 will be assessed with the COVID-19 daily self score tool. Adapted from the FLU-PRO instrument, it consists of 39 items that are answered daily. Items 1-33 are Likert scale questions (rated 0-4) where 0 = not at all and 4 = very much. These items are summed to score the severity of symptoms- where a total score of 132 would indicate the greatest severity of symptoms and a score of 0 would indicate no severity of symptoms. Items 34-38 are also Likert scale questions (rated 0-4) that measure the frequency of specific daily symptoms where 0 = 0 times and 4 = 4 times or more. These items are summed to score the frequency of symptoms- where the highest score for the frequency of symptoms (20) indicates the greatest burden of symptom frequency. The last question (39) asks patients for their highest temperature in Fahrenheit.

    Measure: Change in COVID-19 symptom frequency

    Time: 14 days

    Description: Change of COVID-19 symptom score from baseline to day 6 will be assessed with the COVID-19 daily self score tool. Adapted from the FLU-PRO instrument, it consists of 39 items that are answered daily. Items 1-33 are Likert scale questions (rated 0-4) where 0 = not at all and 4 = very much. These items are summed to score the severity of symptoms- where a total score of 132 would indicate the greatest severity of symptoms and a score of 0 would indicate no severity of symptoms. Items 34-38 are also Likert scale questions (rated 0-4) that measure the frequency of specific daily symptoms where 0 = 0 times and 4 = 4 times or more. These items are summed to score the frequency of symptoms- where the highest score for the frequency of symptoms (20) indicates the greatest burden of symptom frequency. The last question (39) asks patients for their highest temperature in Fahrenheit.

    Measure: Change in body temperature

    Time: 7 days

    Description: Change of COVID-19 symptom score from baseline to day 14 will be assessed with the COVID-19 daily self score tool. Adapted from the FLU-PRO instrument, it consists of 39 items that are answered daily. Items 1-33 are Likert scale questions (rated 0-4) where 0 = not at all and 4 = very much. These items are summed to score the severity of symptoms- where a total score of 132 would indicate the greatest severity of symptoms and a score of 0 would indicate no severity of symptoms. Items 34-38 are also Likert scale questions (rated 0-4) that measure the frequency of specific daily symptoms where 0 = 0 times and 4 = 4 times or more. These items are summed to score the frequency of symptoms- where the highest score for the frequency of symptoms (20) indicates the greatest burden of symptom frequency. The last question (39) asks patients for their highest temperature in Fahrenheit.

    Measure: Change in body temperature

    Time: 14 days
    66 A Randomized, Double-blind, Two Arm, Placebo Controlled Clinical Trial to Evaluate the Efficacy and Safety of Mycobacterium w in Preventing COVID-19 in Subjects at Risk of Getting Infected With COVID-19.

    This clinical trial is a randomized, blinded, two arms, placebo controlled, clinical trial to evaluate the safety and efficacy of Mycobacterium w in combination with standard care as per hospital practice to prevent COVID 19 in subjects at risk of getting infected with COVID 19.

    NCT04353518
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Suspension of heat killed (autoclaved) Mycobacterium w
    2. Other: Placebo
    MeSH:Mycobacterium Infections

    Primary Outcomes

    Description: To compare proportion of subjects acquiring COVID-19 infection between two arms over the time till 8 weeks from administration of 1st dose

    Measure: Number of subject acquiring COVID-19 infection

    Time: From first dosing to week 1, week 2, week 4, week 8 or at any time during the study till 8 week post first dosing..

    Secondary Outcomes

    Description: Any AE / SAE observed during the study.

    Measure: Incidence of Adverse Event and Serious Adverse Event (safety and tolerability)

    Time: Till 8 weeks

    Description: Whether administration of Mw prevents development of Upper Respiratory Tract Infection (URTI) symptoms in close contacts of COVID-19 patients.

    Measure: Number of subject developing Upper Respiratory Tract Infection (URTI) symptoms

    Time: From first dosing to week 1, week 2, week 4, week 8 or at any time during the study till 8 week post first dosing.

    Description: Whether administration of Mw prevents development of severe COVID-19 infection.

    Measure: Number of subject developing severe COVID-19 infection based on ordinal scale

    Time: From first dosing to week 1, week 2, week 4, week 8 or at any time during the study till 8 week post first dosing
    67 DAS181 for COVID-19: A Phase II Multicenter, Randomized, Placebo-Controlled, Double-Blind Study

    It is a multicenter, randomized, placebo-controlled, double-blind study. The study population is defined as subjects diagnosed with lower respiratory tract COVID-19 who require supplemental oxygen ≥2 LPM at the time of randomization.

    NCT04354389
    Conditions
    1. COVID-19
    Interventions
    1. Drug: DAS181
    2. Drug: Placebo
    3. Drug: DAS181

    Primary Outcomes

    Measure: Percent of subjects return to room air (RTRA)

    Time: Day 14

    Secondary Outcomes

    Description: Percent of subjects who reach level 1 of COVID-19 Clinical Classification (discharged or return to normal activity)

    Measure: Percent of subjects who have recovered

    Time: Day 5, 10, 14, 21, 28

    Description: time to Improved COVID-19 Clinical Classification 1 to 6 (where higher score means worse outcome)

    Measure: Improved COVID-19 Clinical Classification

    Time: Day 28

    Description: Percent of subjects RTRA

    Measure: Return To Room Air (RTRA)

    Time: Day 10, 21, 28

    Measure: Percent of subjects who achieve clinical stability

    Time: Day 28

    Description: Time to

    Measure: SARS-CoV-2 RNA undetectable

    Time: Day 28

    Description: Time to

    Measure: Clinical Deterioration

    Time: Day 28

    Description: Percent of subjects discharge

    Measure: Percent of subjects discharged

    Time: Day 14, 21, 28

    Description: Time to

    Measure: Death (all cause)

    Time: Day 28
    68 Efficacy of Intravenous Almitrine in Reducing the Need for Mechanical Ventilation in Patients With Hypoxemic Acute Respiratory Failure Due to Covid-19-related Pneumonia: a Randomized Controlled Double-blind Study From the Skip-icu Consortium

    The COVID-19 outbreak is associated with a surge in ICU bed requirement and substantial mortality (estimated between 0.5% and 3.6%). Admission in the intensive care unit (ICU) and need for mechanical ventilation is reportedly associated with an estimated hospital mortality of more than 30%. Furthermore, the surge in ICU bed requirement is a worldwide-shared issue, leading to sub-optimal ICU management. In acute respiratory failure due to COVID-19-related pneumonia, vasoplegia with vascular enlargement inside the lung lesions and dilation of small vessels seen on chest CT scan largely account for severe hypoxemia whose physiological response is hyperventilation leading to hypocapnia. Almitrine, initially described to reduce intrapulmonary shunt by enhancement of hypoxic pulmonary vasoconstriction in combination with inhaled nitric oxide (iNO), redistributes pulmonary blood flow from shunt areas to lung units with normal ventilation/perfusion (VA/Q) ratio. Low dose of intravenous almitrine (2 µg.kg-1.min-1) alone also improves oxygenation (without combination with iNO) by selective pulmonary vasoconstriction of precapillary pulmonary arteries perfusing lung areas exposed to a hypoxic challenge with a slight increase in mean arterial pulmonary. Therefore, our hypothesis is that 5 days of low dose of almitrine therapy may improve the ventilation-perfusion (VA/Q) ratio at a relatively early stage of this specific lung disease and limit respiratory worsening and subsequent need for mechanical ventilation.

    NCT04357457
    Conditions
    1. Covid 19
    2. Hypoxemic Respiratory Failure
    Interventions
    1. Drug: Almitrine
    2. Drug: Placebo
    MeSH:Pneumonia Respiratory Insufficiency
    HPO:Pneumonia

    Primary Outcomes

    Description: Endotracheal intubation within 7 days after randomization Death will be considered as a failure (endotracheal intubation).

    Measure: Rate of endotracheal intubation

    Time: 7 days

    Secondary Outcomes

    Measure: 28-day mortality

    Time: 28 days

    Measure: In-hospital mortality

    Time: 28-day

    Measure: Number of ventilator-free days

    Time: 28 days

    Measure: Number of days in the ICU

    Time: 28 days

    Measure: Number of days in the hospital

    Time: 28 days

    Description: safety assessment: discontinuation rate of the treatment for arterial lactate more than 4 mmol/L, ALT/AST levels greater than 3 times the upper limit, and diagnosis of pulmonary arterial hypertension or acute cor pulmonale documented by echocardiography.

    Measure: Discontinuation rate of the treatment

    Time: 28 days
    69 Use of a Medical Device, Viruxal Oral and Nasal Spray, for Treating the Symptoms of COVID-19 Via Application to the Naso- and Oropharyngeal Mucosa

    Viruxal Oral and Nasal Spray is a Class I CE marked medical device manufactured by Kerecis hf (the "Device"). A double blind clinical trial will be conducted to evaluate the Device against placebo in COVID-19 positive, symptomatic patients in Iceland. Immediate access to COVID-19 patients is available through a well-organized COVID-19 outpatient follow-up clinic. Up to 128 patients with mild to moderate symptoms of COVID-19 will be recruited (so called "higher end of the low risk group"). These patients will be positive for COVID-19, be symptomatic with upper respiratory symptoms, but without involvement of the entire respiratory system. The patients will be randomized to receive treatment with the Study Device or to receive placebo. 64 patients will be randomized into the Study Device group and 64 patients into the Control group. Patients will administer Study Device or Control for 14 days and will have their symptoms recorded until no further symptoms are reported, up to a maximum of 28 days follow-up.

    NCT04357990
    Conditions
    1. COVID-19
    Interventions
    1. Device: Viruxal Oral and Nasal Spray
    2. Other: Placebo

    Primary Outcomes

    Description: The number of days until participants report no symptoms, which they attribute to COVID-19, will be compared between groups. Symptoms include: Fever (38.0°C or higher), chills, dry cough, cough with rise, shortness of breath (rest), shortness of breath (Exercise), dyspnoea, sore throat, runny nose, headache, myalgia/bone pain, anorexia, nausea, vomiting, loss of smell, osteoporosis, abdominal pain, diarrhea, weakness.

    Measure: Number of days until complete resolution of symptoms per group

    Time: 28 days

    Description: The number of participants admitted to hospital due to deterioration of their condition due to COVID-19 will be compared between groups.

    Measure: Number of hospital admissions per group

    Time: 28 days

    Secondary Outcomes

    Description: The number of days until participants report a reduction in symptoms, which they attribute to COVID-19, will be compared between groups. Symptoms include: Fever (38.0°C or higher), chills, dry cough, cough with rise, shortness of breath (rest), shortness of breath (Exercise), dyspnoea, sore throat, runny nose, headache, myalgia/bone pain, anorexia, nausea, vomiting, loss of smell, osteoporosis, abdominal pain, diarrhea, weakness.

    Measure: Number of days until a reduction in symptoms per group

    Time: 28 days

    Description: The number of adverse events reported will be compared between groups.

    Measure: Number of adverse events per group

    Time: 28 days
    70 A Multi-center, Randomized, Double-blinded, Placebo-controlled Study to Evaluate the Safety and Efficacy of Hydroxychloroquine Monotherapy and in Combination With Azithromycin in Patients With Moderate and Severe COVID-19 Disease

    Two recent studies have suggested that in patients with Covid19, treatment with hydroxychloroquine may shorten the duration of symptoms and improve viral clearance, an effect that appears most pronounce when combined with azithromycin. Hydroxychloroquine treatment may inhibit viral nucleic acid-mediated activation of various innate immune pathways, as well as blockade of lysosomal functions in cell types relevant for viral entry and antigen presentation. The purpose of the study is to determine if oral hydroxychloroquine monotherapy, or in combination with azithromycin results in clinical benefit in patients hospitalized with COVID19 pneumonia.

    NCT04358081
    Conditions
    1. Covid-19
    Interventions
    1. Drug: HCQ
    2. Drug: HCQ+AZT
    3. Drug: Placebo

    Primary Outcomes

    Description: To demonstrate in patients receiving standard of care that the percentage who achieve clinical response with hydroxychloroquine or hydroxychloroquine and azithromycin is superior to placebo at Day 15

    Measure: Percentage of participants who achieve clinical response

    Time: 15 days

    Secondary Outcomes

    Description: To demonstrate in patients receiving standard of care that the percentage with viral clearance at Day 15 with hydroxychloroquine or hydroxychloroquine and azithromycin is superior to placebo

    Measure: Percentage of Participants with Viral Clearance

    Time: 15 Days

    Description: To assess in patients receiving standard of care the safety of hydroxychloroquine or hydroxychloroquine and azithromycin compared to placebo

    Measure: Number of participants receiving hydroxychloroquine or hydroxychloroquine and azithromycin with adverse events of hydroxychloroquin or hydroxychloroquine and azithromycin compared to placebo

    Time: 40 days
    71 A Phase 2 Randomized, Double-Blind, Placebo-Controlled, Proof-Of-Concept Study To Evaluate Efficacy And Safety Of Recombinant Human Plasma Gelsolin (Rhu-pGSN) Added To Standard Of Care In Subjects With Severe Covid-19 Pneumonia

    Study Objectives: Primary - To assess the efficacy (survival without organ failure on Day 14) of three doses of rhu-pGSN administered intravenously (IV) plus standard of care (SOC) to hospitalized subjects with a primary diagnosis of COVID-19 pneumonia and a severity score of 4, 5 or 6 on the World Health Organization (WHO) 9-point severity scale - To evaluate the safety and tolerability of three IV doses of rhu-pGSN administered to hospitalized subjects with a primary diagnosis of COVID-19 pneumonia and a severity score of 4, 5, or 6 on the WHO 9-point severity scale Secondary - To further assess the efficacy of IV administered rhu-pGSN - To assess changes in WHO 9-point severity score for SOC with or without rhu-pGSN - To evaluate the effect of administered rhu-pGSN on survival rates - To assess the relationship of pGSN levels (and other biomarkers) at baseline with clinical outcomes - [OPTIONAL] To follow the pharmacokinetics (PK) of administered rhu-pGSN Immunogenicity • To investigate the development of antibodies against rhu-pGSN post-treatment

    NCT04358406
    Conditions
    1. Sars-CoV2
    Interventions
    1. Drug: Recombinant human plasma gelsolin (Rhu-pGSN)
    2. Other: Placebo
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Proportion of subjects alive not on vasopressors, mechanical ventilator, and dialysis

    Measure: Efficacy: Proportion of subjects alive not on vasopressors, mechanical ventilator, and dialysis

    Time: Day 14

    Description: Proportion of subjects with SAEs as judged by the investigator

    Measure: Safety and Tolerability: Proportion of subjects with serious adverse events (SAEs)

    Time: Continuous through Day 28

    Secondary Outcomes

    Description: Daily change in the 9-point Severity Score (ordinal scale) proposed by a special WHO committee for COVID-19 pneumonia where a score of 8 indicates death and 0 is no clinical or virological evidence of COVID-19 infection

    Measure: Efficacy: Daily change in the WHO 9-point severity score

    Time: Daily through at least Day 14

    Description: All cause mortality rate using Kaplan-Meier survival analysis

    Measure: Efficacy: All cause mortality rate at Days 28 and 90

    Time: At Days 28 and 90

    Description: Proportion of subjects alive without the ongoing use of vasopressors, ongoing intubation/mechanical ventilation, ongoing residence in an intensive care unit, new ongoing need for dialysis/renal replacement therapy

    Measure: Efficacy: Proportion of subjects alive without the ongoing use of vasopressors, ongoing intubation/mechanical ventilation, ongoing residence in an intensive care unit (ICU), new ongoing need for dialysis/renal replacement therapy

    Time: Days 7, 28, 60, and 90

    Description: Proportion of subjects discharged to home or immediate prior residence

    Measure: Efficacy: Proportion of subjects discharged to home or immediate prior residence

    Time: Continuous through Day 28

    Description: LOS of surviving subjects in the hospital and in ICU

    Measure: Efficacy: Length of stay (LOS) of surviving subjects in the hospital and in ICU

    Time: Continuous through day 28

    Description: Proportion of subjects readmitted to the hospital

    Measure: Efficacy: Proportion of subjects readmitted to the hospital

    Time: Up to 90 days

    Description: Proportion of subjects with adverse events (AEs) graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0

    Measure: Safety and Tolerability: Proportion of subjects with adverse events (AEs)

    Time: Continuous through Day 28

    Description: Proportion of subjects with new or worsening clinically significant laboratory abnormalities

    Measure: Safety and Tolerability: Proportion of subjects with new or worsening clinically significant laboratory abnormalities

    Time: Continuous through Day 28

    Description: Proportion of subjects with rhu-pGSN antibodies

    Measure: Immunogenicity: Proportion of subjects with rhu-pGSN antibodies

    Time: Days 1, 28, and 90

    Description: Blood samples for dose #1 will be collected within 15 minutes predose, and at 1 (±15 min), 2 (±15 min), 6 (±30 min), and 12 (±30 min) hours after end of administration (but prior to Dose #2); for Dose #3 within 15 minutes predose, and at 1 (±15 min), 2 (±15 min), 6 (±30 min), 12 (±30 min) and 24 (±30 min) hours after the end of administration (participants refusing these blood samplings can enter and remain in the trial).

    Measure: Pharmacokinetics: Maximum concentration (C max) of added rhu-pGSN

    Time: Continuous through day 3

    Description: Blood samples for dose #1 will be collected within 15 minutes predose, and at 1 (±15 min), 2 (±15 min), 6 (±30 min), and 12 (±30 min) hours after end of administration (but prior to Dose #2); for Dose #3 within 15 minutes predose, and at 1 (±15 min), 2 (±15 min), 6 (±30 min), 12 (±30 min) and 24 (±30 min) hours after the end of administration (participants refusing these blood samplings can enter and remain in the trial).

    Measure: Pharmacokinetics: Time to maximum concentration (T max) of added rhu-pGSN

    Time: Continuous through day 3

    Description: Blood samples for dose #1 will be collected within 15 minutes predose, and at 1 (±15 min), 2 (±15 min), 6 (±30 min), and 12 (±30 min) hours after end of administration (but prior to Dose #2); for Dose #3 within 15 minutes predose, and at 1 (±15 min), 2 (±15 min), 6 (±30 min), 12 (±30 min) and 24 (±30 min) hours after the end of administration (participants refusing these blood samplings can enter and remain in the trial)

    Measure: Pharmacokinetics: Half-life (T 1/2) of added rhu-pGSN

    Time: Continuous through day 3

    Description: Blood samples for dose #1 will be collected within 15 minutes predose, and at 1 (±15 min), 2 (±15 min), 6 (±30 min), and 12 (±30 min) hours after end of administration (but prior to Dose #2); for Dose #3 within 15 minutes predose, and at 1 (±15 min), 2 (±15 min), 6 (±30 min), 12 (±30 min) and 24 (±30 min) hours after the end of administration (participants refusing these blood samplings can enter and remain in the trial)

    Measure: Pharmacokinetics: Area under the curve from time 0 to 8 hours (AUC 0-8) of added rhu-pGSN

    Time: Continuous through day 3

    Description: Blood samples for dose #1 will be collected within 15 minutes predose, and at 1 (±15 min), 2 (±15 min), 6 (±30 min), and 12 (±30 min) hours after end of administration (but prior to Dose #2); for Dose #3 within 15 minutes predose, and at 1 (±15 min), 2 (±15 min), 6 (±30 min), 12 (±30 min) and 24 (±30 min) hours after the end of administration (participants refusing these blood samplings can enter and remain in the trial)

    Measure: Pharmacokinetics: Area under the curve from time 0 to infinity (AUC 0-inf) of added rhu-pGSN

    Time: Continuous through day 3
    72 A Randomized, Double-blind, Two Arm, Controlled Clinical Trial to Compare the Efficacy and Safety of Mycobacterium w (Mw) Administered Along With Standard of Care Versus Placebo Administered Along With Standard of Care, in Adult, COVID 19 Positive Patients Hospitalized But Not Critically Ill.

    This is a randomized, double blind, two arms, placebo controlled, clinical trial to study to evaluate the the safety and efficacy of Mycobacterium w in combination with standard of care versus placebo with standard of care for preventing the progression of COVID-19 disease and for reduction in transfer to ICU in COVID-19 infected patients admitted to the hospital.

    NCT04358809
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Suspension of heat killed (autoclaved) Mycobacterium w
    2. Other: Placebo
    MeSH:Mycobacterium Infections Critical Illness

    Primary Outcomes

    Description: To compare the difference in proportion of patients with increased disease severity

    Measure: Number of patients with increased disease severity

    Time: From baseline to Day 3, Day 7, Day 14, Day 21, Day 28 or at any time during the study till 28 days post first dosing.

    Secondary Outcomes

    Description: To evaluate safety of Mw in COVID-19 patients admitted to hospital

    Measure: Incidence of adverse events and serious adverse events (Safety)

    Time: Till day 28

    Description: To compare the proportion of patients discharged from hospital

    Measure: Number of COVID-19 patients discharged from hospital

    Time: From baseline to Day 3, Day 7, Day 14, Day 21, Day 28 or at any time during the study till 28 days post first dosing.

    Description: To compare the proportion of patients transfer to ICU

    Measure: Number of COVID-19 patients transfer to ICU

    Time: From baseline to Day 3, Day 7, Day 14, Day 21, Day 28 or at any time during the study till 28 days post first dosing.

    Description: To compare the proportion of patients with reduction in disease severity by 1 ordinal scale

    Measure: Number of COVID-19 patients with reduction in disease severity by 1 ordinal scale

    Time: From baseline to Day 3, Day 7, Day 14, Day 21, Day 28 or at any time during the study till 28 days post first dosing.

    Description: To compare the proportion of symptom free patients

    Measure: Number of of symptom free patients

    Time: From baseline to Day 3, Day 7, Day 14, Day 21, Day 28 or at any time during the study till 28 days post first dosing.
    73 Comparative Efficacy of Various Doses of Hydroxychloroquine in Pre-Exposure Prophylaxis for COVID 19 in Healthcare Personnel

    Hydroxychloroquine has been approved by FDA as one of the treatment options for COVID 19.Healthcare personnel are amongst those at highest risk to contract the disease. Several health authorities are now recommending the use of hydroxychloroquine as pre-exposure prophylaxis is in health care personnel. Several studies are on going in this context. However there is a controversy regarding the dosage regimen. This drug has a half life of 22.4 days. In this study we will be comparing three different doses of Hydroxychloroquine and additionally have a control group in order to determine the efficacy of hydroxychloroquine as pre- exposure prophylaxis in healthcare personnel in various doses.

    NCT04359537
    Conditions
    1. COVID 19
    Interventions
    1. Drug: Hydroxychloroquine Sulfate 200 MG
    2. Other: Placebo

    Primary Outcomes

    Description: Outcome reported as the percentage of participants in each arm who are COVID-19-free at the end of study treatment

    Measure: COVID-19-free survival in experimental arms compared to placebo

    Time: 12 weeks

    Secondary Outcomes

    Description: Outcome reported as the percent of participants in each arm who have a confirmed SARS-CoV-2 infection during study treatment.

    Measure: Incidence of confirmed SARS-COV-2 detection

    Time: 12 weeks

    Description: Outcome reported as the percent of participants in each arm who report COVID-19-related symptoms during study treatment

    Measure: Incidence of possible COVID-19 symptoms

    Time: 12 weeks

    Description: Outcome reported as the percent of participants in each arm who discontinue study medication use for any reason during treatment.

    Measure: Incidence of all-cause study medicine discontinuation

    Time: 12 weeks

    Description: Participants will self-report COVID-19 status on an ordinal scale as follows: No illness (score=1), Illness with outpatient observation (score=2), Hospitalization (or post-hospital discharge) (score=3), Hospitalization with ICU stay (score 4),Death from COVID 19(score=5) Possible scores range from 1-5 with higher scores indicating greater disease severity.

    Measure: Ordinal Scale of COVID-19 Disease maximum severity if COVID-19 diagnosed at study end

    Time: 12 weeks

    Description: Outcome reported as the percent of participants in each arm who are hospitalized or expire due to COVID-19 during study treatment.

    Measure: Incidence of Hospitalization for COVID-19 or death

    Time: 12 weeks

    Description: Outcome reported as the percent of participants experiencing any possible adverse events from Hydroxychloroquine

    Measure: Incidence of study medication-related adverse events

    Time: 12 weeks
    74 A Randomized, Double-Blind, Placebo Controlled Trial to Evaluate the Efficacy and Safety of Nitazoxanide (NTZ) for Pre- and Post Exposure Prophylaxis of COVID-19 and Other Viral Respiratory Illnesses (VRI) in Healthcare Workers and Others at Increased Risk of SARS-CoV-2 Infection

    Trial to Evaluate the Efficacy and Safety of Nitazoxanide (NTZ) for Pre- and Post Exposure Prophylaxis of COVID-19 and Other Viral Respiratory Illnesses (VRI) in Healthcare Workers and Others at Increased Risk of SARS-CoV-2 Infection

    NCT04359680
    Conditions
    1. COVID-19
    2. Viral Respiratory Illnesses
    Interventions
    1. Drug: Nitazoxanide
    2. Drug: Placebo
    3. Dietary Supplement: Vitamin Super B-Complex
    MeSH:Infection

    Primary Outcomes

    Measure: The proportion of subjects with symptomatic laboratory-confirmed COVID-19 identified after start of treatment and before the end of the 6-week treatment period.

    Time: Up to 6 weeks

    Measure: The proportion of subjects with symptomatic laboratory-confirmed VRI identified after the start of treatment and before the end of the 6-week treatment period.

    Time: Up to 6 weeks
    75 Inhaled Aviptadil for the Treatment of Moderate and Severe COVID-19

    Brief Summary: SARS-CoV-2 virus infection is known to cause Lung Injury that begins as dyspnea and exercise intolerance, but may rapidly progress to Critical COVID-19 with Respiratory Failure and the need for noninvasive or mechanical ventilation. Mortality rates as high as 80% have been reported among those who require mechanical ventilation, despite best available intensive care. Patients with moderate and severe COVID-19 by FDA definition who have not developed respiratory failure be treated with nebulized RLF-100 (aviptadil, a synthetic version of Vasoactive Intestinal Polypeptide (VIP)) 100 μg 3x daily plus Standard of Care vs. placebo + Standard of Care using an FDA 501(k) cleared mesh nebulizer. The primary outcome will be progression to in severity of COVID-19 (i.e. moderate progressing to to severe or critical OR severe progressing to critical) over 28 days. Secondary outcomes will include blood oxygenation as measured by pulse oximetry, dyspnea, exercise tolerance, and levels of TNFα IL-6 and other cytokines.

    NCT04360096
    Conditions
    1. SARS-CoV 2
    2. COVID
    3. ARDS
    4. ALI
    5. Acute Lung Injury/Acute Respiratory Distress Syndrome (ARDS)
    6. Dyspnea
    Interventions
    1. Drug: RLF-100 (aviptadil)
    2. Drug: Placebo
    3. Device: Nebulized administration of RLF-100 or Placebo
    MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Sy Respiratory Distress Syndrome, Adult Acute Lung Injury Dyspnea Lung Injury
    HPO:Dyspnea Respiratory distress

    Primary Outcomes

    Description: Progression to ARDS is defined as the need for mechanical ventilation

    Measure: Progression to ARDS

    Time: 28 days

    Secondary Outcomes

    Description: Blood PO2 as measured by pulse oximetry

    Measure: Blood oxygenation

    Time: 28 days

    Description: 0 = no shortness of breath at all 0.5 = very, very slight shortness of breath = very mild shortness of breath = mild shortness of breath = moderate shortness of breath or breathing difficulty = somewhat severe shortness of breath = strong or hard breathing 7 = severe shortness of breath or very hard breathing 8 9 = extremely severe shortness of breath 10 = shortness of breath so severe you need to stop the exercise or activity

    Measure: RDP Dsypnea Scale

    Time: 28 days

    Description: Distance walked in six minutes

    Measure: Distance walked in six minutes

    Time: 28 days
    76 Randomized, Double-Blind, Placebo-Controlled Pilot Clinical Trial of the Safety and Efficacy of Telmisartan for the Mitigation of Pulmonary and Cardiac Complications in COVID-19 Patients

    This study will enroll 40 symptomatic outpatients tested positive for Coronavirus 2019 (COVID-19). Patients to be randomized 1:1 to Telmisartan (40 mg) vs placebo to be administered orally once daily x 21 days. Daily, the study patients will be asked to keep a record of the severity of their fever, dyspnea and fatigue and take their blood pressure (BP) and temperature. Study visits to occur on day 1 (entry), day 4, day 10 and day 21. Oro-pharyngeal swabs, and approximately 25 cc of blood will be collected at each study visit for safety labs and for the evaluation of the renin-angiotensin system (RAS) system and for various blood biomarkers of inflammation, coagulation and fibrosis.

    NCT04360551
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Telmisartan 40mg
    2. Drug: Placebo

    Primary Outcomes

    Description: Based on a modified World Health Organization (WHO) COVID-19 7-point ordinal scale

    Measure: Maximum clinical severity of disease

    Time: Over the 21 day period of study

    Secondary Outcomes

    Description: Number of adverse events grade 2 and above utilizing the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0, November 2014

    Measure: Incidence of treatment emergent adverse events

    Time: Through study completion at day 21 of study

    Description: Angiotensin I (AngI), AngII, Ang1-9 and Ang1-7

    Measure: Renin angiotensin system peptides

    Time: At each study time point (day 4, day 10, day 21)

    Description: plasma biomarkers of organ function/coagulation, inflammation, leukocyte chemotaxis, tissue remodeling/fibrosis and immune exhaustion by Luminex multiplexing assays such as TNF-alpha, IL-6, CK-MB, Troponin I, Fractalkine, MCP-1, PD-1, TIMP-1

    Measure: Plasma biomarkers

    Time: At each study time point (day 4, day 10, day 21)
    77 Double-blind Randomized Controlled Clinical Trial of Low-dose Lenalidomide in the Treatment of COVID-19 Disease

    Double-blind randomized controlled clinical trial (RCT) of low-dose lenalidomide in the treatment of elderly patients (> 60 years of age) with mild to moderate clinical signs of COVID-19 disease from the Hospital Universitario of Getafe. The study will include patients of both sexes (> 60 years of age) with mild to moderate clinical presentation of COVID-19 (ROX index > 10). Subjects will be randomly assigned to the experimental arm with lenalidomide (5 mg/24h, day 1, 3 and 5) or to the controlled arm. Other concomitant medication for the treatment of COVID-19 will be also considered.

    NCT04361643
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Lenalidomide as a 5 mg capsule PO daily, days 1, 3, and 5.
    2. Drug: Placebo

    Primary Outcomes

    Description: Days to clinical recovery or days until discharge

    Measure: Clinical improvement

    Time: 30 days

    Description: o Improvement of the neutrophil-to-lymphocyte ratio (NLR)

    Measure: Immune-inflammatory improvement

    Time: 30 days

    Secondary Outcomes

    Description: All-cause mortality at 30 days after enrollment

    Measure: Mortality

    Time: 30 days
    78 Double Blind, Placebo-controlled, Phase II Trial to Evaluate Safety and Efficacy of Allogenic Mesenchymal Stromal Cells MSV_allo for Treatment of Acute Respiratory Failure in Patients With COVID-19 Pneumonia (COVID_MSV)

    Novel coronavirus COVID-19 has become a health emergency around the world. Since first patients were detected in Wuhan China, in December 2019, COVID-19 has spread quickly worldwide, being a severe threat to public health. Fever, dry cough, shortness of breath and breathing distress are the main characteristics of COVID-19 infection. Some patients develop overwhelming lung inflammation and acute respiratory failure, for which there is no specific therapy. Therefore, safe and effective treatment for COVID-19 pneumonia is utterly necessary, mainly in critical cases. Mesenchymal stem cells (MSCs) have been widely used in the immune-mediated inflammatory diseases. MSCs can regulate both innate and adaptive immunity by suppressing the proliferation, differentiation and activation of different cells. These immunomodulatory properties of MSCs support performance of the phase I/II, placebo- controlled, randomized MSCs for treatment of severe COVID-19 pneumonia.

    NCT04361942
    Conditions
    1. COVID-19 Pneumonia
    Interventions
    1. Biological: Mesenchymal Stromal Cells
    2. Other: Placebo
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Index of therapy success to preserve Intensive Care Hospitalization space

    Measure: Proportion of patients who have achieved withdrawal of invasive mechanical ventilation

    Time: 0-7 days

    Description: To measure global success

    Measure: Rate of mortality

    Time: 28 days

    Secondary Outcomes

    Description: Index based in the 4 most relevant symptoms and signs: fever, shortness of bread, %Hemoglobin Saturation and PaO2 / FiO2

    Measure: Proportion of patients who have achieved clinical response

    Time: 0-7days

    Description: Evaluation of pneumonia changes

    Measure: Proportion of patients who have achieved radiological responses

    Time: 0-28 days

    Other Outcomes

    Description: Haemogram and cell subpopulations

    Measure: Blood white cell counts and their subpopulations.

    Time: 0-180 days

    Description: Lymphocyte profiles, CD3, CD19, CD16+CD56, CD4/CD8, Tregs

    Measure: Cellular markers of inflammation

    Time: 0-180 days

    Description: IL-10, IL-6, IP-10, TNF-alpha

    Measure: Cytokines and chemokines in peripheral blood

    Time: 0-180 days
    79 Performance Evaluation of BCG Vaccination in Healthcare Personnel to Reduce the Severity of SARS-COV-2 Infection in Medellín, Colombia, 2020

    Until the first half of April, Colombia has more than 2,800 infected cases and a hundred deaths as a result of COVID-19, with Antioquia being the third department with the highest number of cases. Official records indicate that, in Colombia, the first case was diagnosed on March 6, 2020, corresponding to a patient from Italy. However, in conversations with several infectologists and intensivists from Medellín, it was agreed that clinical cases similar to the clinical presentation that is now recognized as COVID-19 had arisen since the end of 2019 when it was still unknown to everyone. The previous suggests that the virus was already circulating in the country since before March 6, 2020. But at that moment, there were no tools to make a clinical identification, nor to diagnose it from the laboratory's point of view. Considering as real the hypothesis that the infection has been circulating in the country since before the first official diagnosis, the question arises: Why does not the country still has the same healthcare and humanitarian chaos that countries such as Italy and Spain are suffering at this time? To answer this question may be that there are differences in vaccination rates with BCG (Bacille Calmette-Guérin or tuberculosis vaccine), which is significantly higher in Latin America compared to those in Europe. This finding could explain to some extent the situation in the country, since previous studies have shown the influence that this vaccine can have on the immune response against various other pathogens, including viruses. Among the population at risk of infection, health-care workers due to their permanent contact with patients are the population group with the highest risk of contracting SARS-Cov-2 and developing COVID-19 in any of its clinical manifestations, and currently there are no vaccines or proven preventive interventions available to protect them. For this reason, this research study aims to demonstrate whether the centennial vaccine against tuberculosis (BCG), a bacterial disease, can activate the human immune system in a broad way, allowing it to better combat the coronavirus that causes COVID-19 and, perhaps, prevents the complications that lead the patient to the intensive care unit and death. In the future, and if these results are as expected, they may be the basis for undertaking a population vaccination campaign that improves clinical outcomes in the general population.

    NCT04362124
    Conditions
    1. COVID-19
    Interventions
    1. Biological: vaccine BCG
    2. Other: Placebo
    MeSH:Infection

    Primary Outcomes

    Description: Incidence of COVID-19 cases confirmed or probable in the study population

    Measure: Primary outcome

    Time: From date of randomization to 360 day of the study

    Secondary Outcomes

    Description: Incidence of severe or critical infection in COVID-19 cases

    Measure: Secondary outcome

    Time: From date to diagnosis to 1 month after

    Description: Lethality of the infection in both groups

    Measure: Secondary outcome

    Time: From date to diagnosis to 1 month after

    Description: Assess the safety (frequency, seriousness, and severity of adverse events) of BCG vaccination

    Measure: Secondary outcome

    Time: From date of randomization to 7 day of the study

    Description: Prevalence of SARS-Cov-2 infection

    Measure: Secondary outcome

    Time: At baseline evaluation
    80 Phase 3 Randomized, Double-blind, Placebo-controlled Multi-center Study to Assess the Efficacy and Safety of Ruxolitinib in Patients With COVID-19 Associated Cytokine Storm (RUXCOVID)

    This is a randomized, double-blind, placebo-controlled, 29-day, multicenter study to assess the efficacy and safety of ruxolitinib + standard-of-care (SoC) therapy, compared with placebo + SoC therapy, in patients aged ≥12 years with COVID-19 pneumonia.

    NCT04362137
    Conditions
    1. Cytokine Storm (Covid-19)
    Interventions
    1. Drug: Ruxolitinib
    2. Drug: Placebo

    Primary Outcomes

    Description: Efficacy is measured by a composite endpoint of proportion of patients who die, develop respiratory failure [require mechanical ventilation], or require intensive care unit [ICU] care for the treatment of COVID-19.

    Measure: Proportion of patients who die, develop respiratory failure [require mechanical ventilation] or require intensive care unit (ICU) care

    Time: 29 days

    Secondary Outcomes

    Description: Clinical status is measured with the 9-point ordinal scale. The scoring is - Uninfected patients have a score 0 (no clinical or virological evidence of infection). - Ambulatory patients (not in hospital or in hospital and ready for discharge) can have a score 1 (no limitation of activities) or 2 (limitation of activities). - Hospitalized patients with mild disease can have score 3 (no oxygen therapy defined as SpO2 ≥ 94% on room air) or 4 (oxygen by mask or nasal prongs). - Hospitalized patients with severe disease can have score 5 (non-invasive ventilation or high-flow oxygen), 6 (intubation and mechanical ventilation) or 7 (ventilation + additional organ support - pressors, RRT (renal replacement therapy), ECMO (extracorporeal membrane oxygenation)). - Patients who die have a score 8.

    Measure: Clinical status

    Time: Day 15, Day 29

    Description: Percentage of patients with at least two points improvement in clinical status on the 9-point ordinal scale.

    Measure: Percentage of patients with at least two-point improvement from baseline in clinical status

    Time: Baseline, Day 15, Day 29

    Description: Percentage of patients with at least one point improvement in clinical status on the 9-point ordinal scale.

    Measure: Percentage of patients with at least one-point improvement from baseline in clinical status

    Time: Baseline, Day 15, Day 29

    Description: Percentage of patients with at least one point deterioration in clinical status on the 9-point ordinal scale.

    Measure: Percentage of patients with at least one-point deterioration from baseline in clinical status

    Time: Baseline, Day 15, Day 29

    Description: Time to improvement from baseline category to one less severe category of the 9-point ordinal scale.

    Measure: Time to improvement in clinical status

    Time: 29 days

    Description: Mean change from baseline in the 9-point ordinal scale.

    Measure: Mean change from baseline in the clinical status

    Time: Baseline, Day 15, Day 29

    Description: Mortality rate at Day 15 and at Day 29

    Measure: Mortality rate

    Time: Day 15, Day 29

    Description: Proportion of patients requiring mechanical ventilation

    Measure: Proportion of patients requiring mechanical ventilation

    Time: 29 days

    Description: Duration of hospitalization

    Measure: Duration of hospitalization

    Time: 29 days

    Description: The time to discharge or to a National Early Warning Score 2 (NEWS2) of ≤2 and maintained for 24 hours whichever comes first. The NEWS2 is based on a simple aggregate scoring system in which a score is allocated to physiological measurements, already recorded in routine practice presentation or when a patient is being monitored in hospital. The score ranges from 0 (best) to 23 (worst).

    Measure: Time to discharge or to a NEWS2 score of ≤2

    Time: 29 days

    Description: The National Early Warning Score 2 (NEWS2) is based on a simple aggregate scoring system in which a score is allocated to physiological measurements, already recorded in routine practice presentation or when a patient is being monitored in hospital. The score ranges from 0 (best) to 23 (worst).

    Measure: Change from baseline in NEWS2 score

    Time: Baseline, Days 3, 5, 8, 11, 15, and 29

    Description: Change from baseline in peripheral oxygen saturation / fraction of inspired oxygen ratio (SpO2/FiO2 ratio)

    Measure: Change from baseline in SpO2/FiO2 ratio.

    Time: Baseline, Day 15, Day 29

    Description: No oxygen therapy is required if oxygen saturation is ≥ 94% on room air.

    Measure: Proportion of patients with no oxygen therapy

    Time: Day 15, Day 29
    81 Passive Immunity Trial for Our Nation (PassItOn)

    The purpose of this study is to test the safety and efficacy of convalescent donor plasma to treat COVID-19 in hospitalized adults in a randomized, placebo-controlled setting. The effect of convalescent plasma will be compared to placebo on clinical outcomes, measured using the COVID-19 7-point Ordinal Clinical Progression Outcomes Scale at Day 15, among adults with COVID-19 requiring hospitalization.

    NCT04362176
    Conditions
    1. COVID-19
    2. Coronavirus
    3. SARS-CoV-2
    Interventions
    1. Biological: pathogen reduced SARS-CoV-2 convalescent plasma
    2. Biological: Placebo
    MeSH:Coronavirus Infections

    Primary Outcomes

    Description: Not hospitalized with resumption of normal activities. Not hospitalized, but unable to resume normal activities. Hospitalized, not on supplemental oxygen. Hospitalized, on supplemental oxygen. Hospitalized, on nasal high-flow oxygen therapy, noninvasive mechanical ventilation, or both Hospitalized, on ECMO, invasive mechanical ventilation, or both. Death

    Measure: COVID-19 7-point Ordinal Clinical Progression Outcomes Scale

    Time: Study Day 15

    Secondary Outcomes

    Description: All-location, all-cause 14-day mortality

    Measure: All-location, all-cause 14-day mortality

    Time: Baseline to Study Day 14 (assessed on Study Day 15)

    Description: All-location, all-cause 28-day mortality

    Measure: All-location, all-cause 28-day mortality

    Time: Baseline to Study Day 28 (assessed on Study Day 29)

    Description: Number of participants that survived to Day 28

    Measure: Survival through 28 days

    Time: Baseline to Day 28 (assessed on Study Day 29)

    Description: Number days from admission to discharge thru Day 28

    Measure: Time to hospital discharge through 28 days

    Time: Admission to discharge (assessed on Study Day 29)

    Description: Not hospitalized with resumption of normal activities. Not hospitalized, but unable to resume normal activities. Hospitalized, not on supplemental oxygen. Hospitalized, on supplemental oxygen. Hospitalized, on nasal high-flow oxygen therapy, noninvasive mechanical ventilation, or both Hospitalized, on ECMO, invasive mechanical ventilation, or both. Death

    Measure: COVID-19 7-point Ordinal Clinical Progression Outcomes Scale on Study Day 3

    Time: Baseline to Study Day 3

    Description: Not hospitalized with resumption of normal activities. Not hospitalized, but unable to resume normal activities. Hospitalized, not on supplemental oxygen. Hospitalized, on supplemental oxygen. Hospitalized, on nasal high-flow oxygen therapy, noninvasive mechanical ventilation, or both Hospitalized, on ECMO, invasive mechanical ventilation, or both. Death

    Measure: COVID-19 7-point Ordinal Clinical Progression Outcomes Scale on Study Day 8

    Time: Study Day 8

    Description: Not hospitalized with resumption of normal activities. Not hospitalized, but unable to resume normal activities. Hospitalized, not on supplemental oxygen. Hospitalized, on supplemental oxygen. Hospitalized, on nasal high-flow oxygen therapy, noninvasive mechanical ventilation, or both Hospitalized, on ECMO, invasive mechanical ventilation, or both. Death

    Measure: COVID-19 7-point Ordinal Clinical Progression Outcomes Scale on Study Day 29

    Time: Study Day 29

    Description: Number of days without use of oxygen

    Measure: Oxygen-free days through Day 28

    Time: Baseline to Day 28

    Description: Number of days without use of a ventilator

    Measure: Ventilator-free days through Day 28

    Time: Baseline to Day 28

    Description: Number of days without use of vasopressors

    Measure: Vasopressor-free days through Day 28

    Time: Baseline to Day 28

    Description: Number of days outside of ICU

    Measure: ICU-free days through Day 28

    Time: Baseline to Day 28

    Description: Number of days outside of the hospital

    Measure: Hospital-free days through Day 28

    Time: Baseline to Day 28

    Other Outcomes

    Description: Number of participants with Acute kidney injury

    Measure: Acute kidney injury

    Time: Baseline to Day 28

    Description: Number of participants requiring renal replacement therapy

    Measure: Renal replacement therapy

    Time: Baseline to Day 28

    Description: Number of participants with documented venous thromboembolic disease (DVT or PE)

    Measure: Documented venous thromboembolic disease (DVT or PE)

    Time: Baseline to Day 28

    Description: Number of Participants with myocardial infarction or ischemic stroke

    Measure: Documented cardiovascular event (myocardial infarction or ischemic stroke)

    Time: Baseline to Day 28

    Description: Number of participants with transfusion reaction (fever/rash)

    Measure: Transfusion reaction

    Time: Baseline to Day 28

    Description: Number of participants with transfusion related acute lung injury (TRALI)

    Measure: Transfusion related acute lung injury (TRALI)

    Time: Baseline to Day 28

    Description: Number of participants with transfusion associated circulatory overload (TACO)

    Measure: Transfusion associated circulatory overload (TACO)

    Time: Baseline to Day 28

    Description: Number of participants with transfusion related infection

    Measure: Transfusion related infection

    Time: Baseline to Day 28
    82 A Randomized, Placebo-Controlled, Double-Blind, Efficacy and Safety Study of Allogeneic HB-adMSCs for the Treatment of COVID-19

    Hope Biosciences is conducting a research study of an investigational product called allogeneic adipose-derived mesenchymal stem cells (abbreviated as HB-adMSCs) as treatment for patients suspected to have COVID-19. The study purpose is to evaluate the safety and efficacy of four IV infusions of either placebo or HB-adMSCs in subjects with COVID-19.

    NCT04362189
    Conditions
    1. COVID-19
    Interventions
    1. Drug: HB-adMSC
    2. Drug: Placebo

    Primary Outcomes

    Description: change from baseline in interleukin-6

    Measure: Interleukin-6

    Time: screening, day 0, 7, 10

    Description: Change from baseline in C Reactive protein

    Measure: C Reactive protein

    Time: screening, day 0, 7, 10

    Description: change from baseline oxygenation (%)

    Measure: Oxygenation

    Time: screening, day 0, 7, 10

    Description: change from baseline in TNF alpha

    Measure: TNF alpha

    Time: screening, day 0, 7, 10

    Description: change from baseline level of IL-10 in the blood (pg/mL)

    Measure: IL-10

    Time: screening, day 0, 7. 10

    Description: Time to return to room air

    Measure: Return to room air (RTRA)

    Time: Day 0, 3, 7, 10, 28

    Secondary Outcomes

    Description: Monitoring for changes in qt interval

    Measure: EKG qt interval

    Time: screening, day 0, 3, 7, 10

    Description: change from baseline in leukocyte differential

    Measure: Leukocyte differential

    Time: screening, day 0, 7, 10

    Description: clinical lab evaluation of level of glucose in the blood (mg/dL)

    Measure: Glucose

    Time: screening, day 0, 7, 10

    Description: clinical lab evaluation of level of calcium in the blood (mg/dL)

    Measure: Calcium

    Time: screening, day 0, 7, 10

    Description: clinical lab evaluation of level of albumin in the blood (g/dL)

    Measure: Albumin

    Time: screening, day 0, 7, 10

    Description: clinical lab evaluation of level of total protein in the blood (g/dL)

    Measure: Total protein

    Time: screening, day 0, 7, 10

    Description: clinical lab evaluation of level of sodium in the blood (mol/L)

    Measure: Sodium

    Time: screening, day 0, 7, 10

    Description: clinical lab evaluation of level of total carbon dioxide in the blood (mmol/L)

    Measure: Total carbon dioxide

    Time: screening, day 0, 7, 10

    Description: clinical lab evaluation of level of potassium in the blood (mmol/L)

    Measure: Potassium

    Time: screening, day 0, 7, 10

    Description: clinical lab evaluation of level of chloride in the blood (mmol/L)

    Measure: Chloride

    Time: screening, day 0, 7, 10

    Description: clinical lab evaluation of level of BUN in the blood (mg/dL)

    Measure: BUN

    Time: screening, day 0, 7, 10

    Description: clinical lab evaluation of level of creatinine in the blood (mg/dL)

    Measure: Creatinine

    Time: screening, day 0, 7, 10

    Description: clinical lab evaluation of level of alkaline phosphatase in the blood (IU/L)

    Measure: Alkaline phosphatase

    Time: screening, day 0, 7, 10

    Description: clinical lab evaluation of level of alanine aminotransferase in the blood (IU/L)

    Measure: Alanine aminotransferase

    Time: screening, day 0, 7, 10

    Description: clinical lab evaluation of level of total bilirubin in the blood (mg/dL)

    Measure: Total bilirubin

    Time: screening, day 0, 7, 10

    Description: clinical lab evaluation of level of white blood cells in the blood (x10^3/uL)

    Measure: White blood cells

    Time: screening, day 0, 7, 10

    Description: clinical lab evaluation of level of red blood cells in the blood (x10^6/uL)

    Measure: Red blood cells

    Time: screening, day 0, 7, 10

    Description: clinical lab evaluation of level of hemoglobin in the blood (g/dL)

    Measure: Hemoglobin

    Time: screening, day 0, 7, 10

    Description: clinical lab evaluation of level of hematocrit in the blood (%)

    Measure: Hematocrit

    Time: screening, day 0, 7, 10

    Description: clinical lab evaluation of level of mean corpuscular volume in the blood (fL)

    Measure: Mean corpuscular volume

    Time: screening, day 0, 7, 10

    Description: clinical lab evaluation of level of mean corpuscular hemoglobin in the blood (pg)

    Measure: Mean corpuscular hemoglobin

    Time: screening, day 0, 7, 10

    Description: clinical lab evaluation of level of mean corpuscular hemoglobin concentration in the blood (g/dL)

    Measure: Mean corpuscular hemoglobin concentration

    Time: screening, day 0, 7, 10

    Description: clinical lab evaluation of level of red cell distribution width in the blood (%)

    Measure: Red cell distribution width

    Time: screening, day 0, 7, 10

    Description: clinical lab evaluation of level of neutrophils in the blood (%)

    Measure: Neutrophils

    Time: screening, day 0, 7, 10

    Description: clinical lab evaluation of level of lymphocytes in the blood (%)

    Measure: Lymphs

    Time: screening, day 0, 7, 10

    Description: clinical lab evaluation of level of monocytes in the blood (%)

    Measure: Monocytes

    Time: screening, day 0, 7, 10

    Description: clinical lab evaluation of level of eosinophils in the blood (%)

    Measure: Eosinophils

    Time: screening, day 0, 7, 10

    Description: clinical lab evaluation of level of basophils in the blood (%)

    Measure: Basophils

    Time: screening, day 0, 7, 10

    Description: clinical lab evaluation of level of absolute neutrophils in the blood (x10^3/uL)

    Measure: Absolute neutrophils

    Time: screening, day 0, 7, 10

    Description: clinical lab evaluation of level of absolute lymphocytes in the blood (x10^3/uL)

    Measure: Absolute lymphs

    Time: screening, day 0, 7, 10

    Description: clinical lab evaluation of level of absolute monocytes in the blood (x10^3/uL)

    Measure: Absolute monocytes

    Time: screening, day 0, 7, 10

    Description: clinical lab evaluation of level of absolute eosinophils in the blood (x10^3/uL)

    Measure: Absolute eosinophils

    Time: screening, day 0, 7, 10

    Description: clinical lab evaluation of level of absolute basophils in the blood (x10^3/uL)

    Measure: Absolute basophils

    Time: screening, day 0, 7, 10

    Description: clinical lab evaluation of level of immature granulocytes in the blood (x10^3/uL)

    Measure: Immature granulocytes

    Time: screening, day 0, 7, 10

    Description: clinical lab evaluation of level of platelets in the blood (x10^3/uL)

    Measure: Platelets

    Time: screening, day 0, 7, 10

    Description: clinical lab evaluation of time for blood to coagulate (seconds)

    Measure: Prothrombin time

    Time: screening, day 0, 7, 10

    Description: clinical lab evaluation of international normalized ratio of blood coagulation (no unit)

    Measure: INR

    Time: screening, day 0, 7, 10

    Description: clinical lab evaluation of percentage of cells CD3- and CD54+ (%)

    Measure: NK cell surface antigen (CD3-CD54+)

    Time: screening, day 0, 7, 10

    Description: clinical lab evaluation of ratio of CD4+ cells to CD8+ cells (no unit)

    Measure: CD4+/CD8+ ratio

    Time: screening, day 0, 7, 10

    Description: clinical lab evaluation of level of myoglobin in the blood (ng/mL)

    Measure: Myoglobin

    Time: screening, day 0, 7, 10

    Description: clinical lab evaluation of level of myoglobin in the blood (ng/mL)

    Measure: Troponin

    Time: screening, day 0, 7, 10

    Description: clinical lab evaluation of level of creatinine kinase in the blood (U/L)

    Measure: Creatinine kinase MB

    Time: screening, day 0, 7, 10

    Description: clinical lab evaluation of level of serum ferritin in the blood (ng/mL)

    Measure: Serum ferritin

    Time: screening, day 0, 7, 10

    Description: incidence of adverse events

    Measure: Adverse events

    Time: screening through day 28

    Description: change from baseline in ordinal scale score; scale of 1-7; a score of 1 indicates death and 7 indicates subject is not hospitalized and has no limitations on activities.

    Measure: 7-point ordinal scale

    Time: screening, day 0, 3, 7, 10, 28

    Description: change from baseline in D-dimer

    Measure: D-dimer

    Time: screening, day 0, 7, 10

    Description: change from baseline chest x-ray result

    Measure: Chest X-ray

    Time: Day 0, Day 28

    Description: change from baseline CT scan result

    Measure: CT scan

    Time: Day 0, Day 28

    Description: time to achieve negative PCR test results

    Measure: PCR test for SARS-CoV-2

    Time: day 0, 3, 7, 10
    83 Phase 3 Multicenter, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy and Safety of Canakinumab on Cytokine Release Syndrome in Patients With COVID-19-induced Pneumonia (CAN-COVID)

    This is a multicenter, randomized, double-blind, placebo-controlled study to assess the efficacy and safety of canakinumab plus standard-of-care (SOC) compared with placebo plus SOC in patients with COVID-19-induced pneumonia and cytokine release syndrome (CRS).

    NCT04362813
    Conditions
    1. Pneumonia and Cytokine Release Syndrome (Covid-19)
    Interventions
    1. Drug: Canakinumab
    2. Drug: Placebo
    MeSH:Pneumonia Syndrome
    HPO:Pneumonia

    Primary Outcomes

    Description: Clinical response is defined as survival without ever requiring invasive mechanical ventilation from Day 3 to Day 29 (both inclusive). A patient will be defined as a non-responder if the worst clinical status at any time from Day 3 to Day 29 is score 6, 7 or 8 on a 9-point ordinal scale ranging from 0 up to 8. Scores 6, 7 and 8 in the 9-point ordinal scale are defined as follows: Hospitalized patients with severe disease have score 6 if they need intubation and mechanical ventilation and score 7 if they need ventilation + additional organ support (pressors, renal replacement therapy, extracorporeal membrane oxygenation). Patients who die have score 8.

    Measure: Number of patients with clinical response

    Time: Day 3 to Day 29

    Secondary Outcomes

    Description: COVID-19-related death during the 4-week period after study treatment.

    Measure: COVID-19-related death rate during the 4-week period after study treatment

    Time: 4 weeks

    Description: Clinical chemistry measurement in a blood sample.

    Measure: Ratio to baseline in the C-reactive protein (CRP)

    Time: Baseline, Day 29

    Description: Clinical chemistry measurement in a blood sample.

    Measure: Ratio to baseline in the serum ferritin

    Time: Baseline, Day 29

    Description: Clinical chemistry measurement in a blood sample.

    Measure: Ratio to baseline in the D-dimer

    Time: Baseline, Day 29

    Description: Safety will be monitored from the canakinumab or placebo dose (Day 1) up to 126 days post-dose (Day 127).

    Measure: Number of participants with Adverse Event (AE), serious adverse events (SAE), clinically significant changes in laboratory measures, and vital signs

    Time: 127 days
    84 A Pilot, Multiple Dose Study to Evaluate the Efficacy and Safety of MRx-4DP0004 in Hospitalised Patients With Symptoms of COVID-19 (SARS-CoV-2 Infection)

    This is a randomised, double-blind, placebo controlled study to evaluate the efficacy and safety of MRx-4DP0004 in patients with COVID-19. 90 hospitalised patients will be enrolled and randomised (2:1) to receive MRx-4DP0004 or placebo for up to 14 days. MRx-4DP0004 is an immunomodulating Live Biotherapeutic Product (LBP) which is expected to prevent or reduce the hyperinflammatory response to SARS-CoV-2 infection without impairing viral clearance.

    NCT04363372
    Conditions
    1. COVID-19
    Interventions
    1. Drug: MRx-4DP0004
    2. Drug: Placebo

    Primary Outcomes

    Description: Clinical status score will be measured using the WHO Ordinal Scale for Clinical Improvement where patients are scored on a scale of 0-8 with 0 being uninfected and 8 being dead

    Measure: Change in mean clinical status score in each treatment arm

    Time: Baseline to Day 42

    Secondary Outcomes

    Description: Safety and tolerability will be determined according to clinically relevant reported adverse events

    Measure: Number of adverse events in each treatment arm

    Time: Baseline to Day 42

    Description: Point changes in clinical status score will be measured using the WHO Ordinal Scale for Clinical Improvement

    Measure: Number of patients with an improvement in clinical status score in each treatment arm

    Time: Day 1 to Day 42

    Description: Point changes in clinical status score will be measured using the WHO Ordinal Scale for Clinical Improvement

    Measure: Number of patients with a deterioration in clinical status score in each treatment arm

    Time: Day 1 to Day 42

    Description: Oxygen saturation will be measured as per local standard procedures

    Measure: Number of patients with at least 95% oxygen saturation on room air in each treatment arm

    Time: Day 1 to Day 14

    Description: Oxygen saturation will be recorded daily during hospitalisation to determine the mean time for each arm to reach at least 95% saturation

    Measure: Time to patients with at least 95% oxygen saturation on room air in each treatment arm

    Time: Day 1 to Day 14

    Description: The NEWS 2 is based on aggregate scoring of physiological measurements including respiration rate, oxygen saturation, systolic blood pressure, pulse rate, level of consciousness and temperature

    Measure: Number of patients with an improvement in the National Early Warning Score (NEWS) 2 in each treatment arm

    Time: Day 1 to Day 14

    Description: The NEWS 2 is based on aggregate scoring of physiological measurements including respiration rate, oxygen saturation, systolic blood pressure, pulse rate, level of consciousness and temperature

    Measure: Number of patients with an deterioration in the National Early Warning Score (NEWS) 2 in each treatment arm

    Time: Day 1 to Day 14

    Description: Details of required respiratory support will be recorded throughout hospitalisation

    Measure: Number of patients requiring Continuous Positive Airway Pressure in each treatment arm

    Time: Day 1 to Day 14

    Description: Details of required respiratory support will be recorded throughout the treatment period

    Measure: Number of patients requiring Intermittent Positive Pressure Ventilation in each treatment arm

    Time: Day 1 to Day 14

    Description: Details of required respiratory support will be recorded throughout the treatment period

    Measure: Time to patients requiring Continuous Positive Airway Pressure in each treatment arm

    Time: Day 1 to Day 14

    Description: Details of required respiratory support will be recorded throughout the treatment period

    Measure: Time to patients requiring Intermittent Positive Pressure Ventilation in each treatment arm

    Time: Day 1 to Day 14

    Description: Length of hospital stay will be compared

    Measure: Time to discharge in each treatment arm

    Time: Day 1 to Day 42

    Description: All cause mortality will be compared

    Measure: Number of deaths in each treatment arm

    Time: Day 1 to Day 42
    85 Hydroxychloroquine as Primary Prophylaxis for COVID-19 in Healthcare Workers (HCQPreP)

    This a double-blind, randomized, placebo-controlled clinical trial to determine if primary prophylaxis with hydroxychloroquine in healthcare workers reduces symptomatic COVID-19 infection. Healthcare workers will be randomized at a 1:1 allocation between intervention and placebo arms and followed for 12 weeks. This study will enroll up to 1,700 participates in Lafayette, Louisiana. The primary outcome will number of symptomatic COVID-19 infections. Secondary endpoints included number of days healthcare workers are absent from work and rate of severe infection.

    NCT04363450
    Conditions
    1. COVID-19
    2. Corona Virus Infection
    3. Wuhan Coronavirus
    4. Prophylaxis
    5. Healthcare Worker
    6. Sars-CoV2
    7. Hydroxychloroquine
    Interventions
    1. Drug: Hydroxychloroquine
    2. Drug: Placebo
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome

    Primary Outcomes

    Description: Number of participants who develop symptoms of COVID-19 in the setting of a positive COVID-19 assay

    Measure: Incidence of symptomatic COVID-19 infection in healthcare workers

    Time: 12 weeks

    Secondary Outcomes

    Description: Number of days healthcare workers are absent from work due to symptomatic COVID-19 infection

    Measure: Absenteeism from work due to COVID-19

    Time: 12 weeks

    Description: Rate of severe COVID-19 infection in healthcare works (hypoxia in setting of chest imaging >50% lung involvement, respiratory failure, end organ damage or shock)

    Measure: Severity of COVID-19 infection

    Time: 12 weeks
    86 A Randomized Placebo-controlled Safety and Dose-finding Study for the Use of the IL-6 Inhibitor Clazakizumab in Patients With Life-threatening COVID-19 Infection

    In this study Investigators propose to administer clazakizumab to patients with life-threatening COVID-19 infection manifest by pulmonary failure and a clinical picture consistent with a cytokine storm syndrome. This is a single-center randomized, double-blind, placebo-controlled trial in which 30 patients will be enrolled and randomly assigned in a 1:1 ratio to two study arms that will receive clazakizumab at a dose of 25 mg or placebo.

    NCT04363502
    Conditions
    1. Covid19
    Interventions
    1. Drug: Clazakizumab
    2. Drug: Placebo
    MeSH:Infection

    Primary Outcomes

    Description: Serum CRP (measured in mg/dl) will be evaluated at baseline and on days 1 and 2 following clazakizumab or placebo administration to assess response

    Measure: Change in C-reactive protein (CRP) level

    Time: Up to 3 days
    87 A Randomized-Control Pilot Study to Assess Hydroxychloroquine in Patients Infected With SARS-CoV-2 (COVID-19)

    This is a prospective, randomized, double-blinded, placebo-controlled, pilot study to assess the preliminary efficacy and safety of hydroxychloroquine for the treatment of patients with lower respiratory tract SARS-CoV-2 infection.

    NCT04363866
    Conditions
    1. COVID-19
    2. SARS-CoV-2
    Interventions
    1. Drug: Hydroxychloroquine
    2. Drug: Placebo

    Primary Outcomes

    Description: A 6-point ordinal scale ranging from "Death" to "Not hospitalized with full resumption of normal activities" is used to evaluate differences in the clinical status between participants that receive placebo vs hydroxychloroquine

    Measure: Clinical Status at Day 5 Assessed by a 6-Point Ordinal Scale

    Time: Day 5

    Secondary Outcomes

    Description: Assess differences in SARS-CoV-2 viral shedding between participants that receive placebo vs hydroxychloroquine

    Measure: Number of Participants with Detectable SARS-CoV-2 Virus from Day 0 to Day 28 and at Day 5

    Time: Day 0 to Day 28 and at Day 5

    Description: Assess by incidence of Grade 3, Grade 4, and Serious Adverse Events (AEs)

    Measure: Toxicity of Study Drug Assessed by Incidence of Adverse Events

    Time: Day 0 to Day 28

    Other Outcomes

    Description: Assess length of hospitalization

    Measure: Duration of Initial Hospitalization

    Time: Day 0 to Day 28

    Description: Assess number of deaths during study follow-up

    Measure: Mortality During Follow-Up

    Time: Day 0 to Day 28

    Description: Assess number of deaths in the hospital during initial hospitalization

    Measure: Mortality During Initial Hospitalization

    Time: Day 0 to Day 28

    Description: Assessing utilization of hospital resources

    Measure: Incidence of New Hospital Resource Utilization

    Time: Day 0 to Day 28

    Description: Assessing duration of hospital resource utilization

    Measure: Duration of Hospital Resource Utilization

    Time: Day 0 to Day 28

    Description: Provide preliminary characterization of differences in inflammatory response between participants that receive placebo vs hydroxychloroquine

    Measure: Changes in Cytokine Profile

    Time: Day 0 to Day 28
    88 Study of Immunomodulation Using Naltrexone and Ketamine for COVID-19

    Ideal new treatments for Novel Coronavirus-19 (COVID-19) would help halt the progression disease in patients with mild disease prior to the need for artificial respiration (ventilators), and also provide a rescue treatment for patients with severe disease, while also being affordable and available in quantities sufficient to treat large numbers of infected people. Low doses of Naltrexone, a drug approved for treating alcoholism and opiate addiction, as well as Ketamine, a drug approved as an anesthetic, may be able to interrupt the inflammation that causes the worst COVID-19 symptoms and prove an effective new treatment. This study will investigate their effectiveness in a randomized, blinded trial versus standard treatment plus placebo.

    NCT04365985
    Conditions
    1. COVID-19
    2. Acute Respiratory Distress Syndrome
    3. Severe Acute Respiratory Syndrome (SARS)
    4. Coronavirus Infections
    Interventions
    1. Drug: Naltrexone
    2. Drug: Ketamine
    3. Other: Placebo
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

    Primary Outcomes

    Description: Count of participants initially presenting with mild/moderate disease who progress to requiring advanced oxygenation (high flow nasal canula, non-rebreather, continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), or intubation)

    Measure: Progression of oxygenation needs

    Time: up to 1 month

    Secondary Outcomes

    Description: Count of participants who develop or experience worsened renal failure as defined by RIFLE criteria, a 5-point scale where the categories are labeled: Risk-Injury-Failure-Loss-End stage renal disease, with Risk being the least severe and End stage renal disease being the most severe. The criteria for determination of stage are factors of serum creatinine and urine output. Numbers of participants worsening one or more RIFLE stages will be reported.

    Measure: Renal failure

    Time: up to 1 month

    Description: Count of participants who develop or experience worsened liver failure as defined by serum transaminases five times normal limits

    Measure: Liver failure

    Time: up to 1 month

    Description: Count of participants who develop cytokine storm as measured by elevated markers of inflammation (elevated D-dimer, hypofibrinogenemia, hyperferritinemia), evidence of acute respiratory distress syndrome (ARDS) measured by imaging findings and mechanical ventilator requirements, and/or continuous fever (≥ 38.1 ° Celsius unremitting)

    Measure: Cytokine Storm

    Time: up to 1 month

    Description: Count of participants who die from COVID-19

    Measure: Mortality

    Time: up to 1 month post hospital discharge

    Description: Length of hospital stay in days

    Measure: Length of hospital stay

    Time: up to 1 month

    Description: Count of patients admitted to the ICU at any time during index hospitalization

    Measure: Intensive Care Unit (ICU) admission

    Time: up to 1 month

    Description: Length of ICU stay in days

    Measure: Intensive Care Unit (ICU) duration

    Time: up to 1 month

    Description: Count of participants requiring intubation

    Measure: Intubation

    Time: up to 1 month

    Description: Length of intubation, measured in days

    Measure: Intubation duration

    Time: up to 1 month

    Description: Time measured in days from hospital admission to determination patient is stable for discharge

    Measure: Time until recovery

    Time: up to 1 month
    89 A Randomized, Double-Blind, Placebo-Controlled, Phase 1/2 Study Evaluating AVM0703 in Patients With COVID-19

    This is a randomized, double-blind, placebo-controlled, single-ascending dose study of AVM0703 administered as a single intravenous (IV) infusion to patients with COVID-19. The study is designed to evaluate the safety, tolerability, and pharmacokinetics of single-ascending dosing of AVM0703 in patients with COVID-19.

    NCT04366115
    Conditions
    1. Covid19
    2. Acute Respiratory Distress Syndrome
    Interventions
    1. Drug: AVM0703
    2. Drug: Placebo
    3. Drug: hydrocortisone
    MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury

    Primary Outcomes

    Description: The primary endpoint of the Phase 1 portion of the study is to evaluate the safety of AVM0703 in subjects with severe or life-threatening COVID-19 infection, and to identify the RP2D.

    Measure: Dose-Limiting Toxicities

    Time: 0-12 months

    Description: The primary endpoint of the Phase 1/2 portion of the study is to evaluate the efficacy of AVM0703 in subjects with severe or life-threatening COVID-19 infection.

    Measure: 28 day all-cause mortality will be a primary end point for Phase 1 and 2

    Time: 0-12 months
    90 A Phase 2/3 Study to Assess the Safety and Efficacy of MultiStem® Therapy in Subjects With Acute Respiratory Distress Syndrome (ARDS) Due to Coronavirus Disease (COVID-19)

    Multicenter investigation featuring an open-label lead-in followed by a double blinded, randomized, placebo-controlled Phase 2/3 part to evaluate the safety and efficacy of MultiStem therapy in subjects with moderate to severe Acute Respiratory Distress Syndrome (ARDS) due to COVID-19.

    NCT04367077
    Conditions
    1. ARDS
    Interventions
    1. Biological: MultiStem
    2. Biological: Placebo

    Primary Outcomes

    Measure: Ventilator-Free Days

    Time: Day 0 through Day 28.

    Measure: Safety and Tolerability as measured by the incidence of treatment-emergent adverse events as assessed by CTCAE v5.0.

    Time: Day 28

    Secondary Outcomes

    Measure: All-cause mortality

    Time: Day 60

    Measure: Ranked hierarchical composite outcome of alive and ventilator-free

    Time: Day 28

    Measure: Ventilator-free days

    Time: Day 0 through Day 60
    91 A PHASE 1/2/3, PLACEBO-CONTROLLED, RANDOMIZED, OBSERVER-BLIND, DOSE-FINDING STUDY TO EVALUATE THE SAFETY, TOLERABILITY, IMMUNOGENICITY, AND EFFICACY OF SARS-COV-2 RNA VACCINE CANDIDATES AGAINST COVID-19 IN HEALTHY INDIVIDUALS

    This is a Phase 1/2/3, randomized, placebo-controlled, observer-blind, dose-finding, vaccine candidate-selection, and efficacy study in healthy individuals. The study consists of 2 parts: Phase 1: to identify preferred vaccine candidate(s) and dose level(s); Phase 2/3: an expanded cohort and efficacy part. The study will evaluate the safety, tolerability, and immunogenicity of 2 different SARS CoV 2 RNA vaccine candidates against COVID 19 and the efficacy of 1 candidate: - As a 2-dose (separated by 21 days) schedule; - At various different dose levels in Phase 1; - In 3 age groups (Phase 1: 18 to 55 years of age, 65 to 85 years of age; Phase 2/3: ≥12 years of age [stratified as 12-15, 16-55 or >55 years of age]). The candidate selected for evaluation in Phase 2/3 is BNT162b2 (mid-dose).

    NCT04368728
    Conditions
    1. SARS-CoV-2 Infection
    2. COVID-19
    Interventions
    1. Biological: BNT162b1
    2. Biological: BNT162b2
    3. Other: Placebo

    Primary Outcomes

    Description: Pain at the injection site, redness, and swelling as self-reported on electronic diaries.

    Measure: Percentage of participants in Phase 1 reporting local reactions

    Time: For 7 days after dose 1 and dose 2

    Description: Fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain as self-reported on electronic diaries.

    Measure: Percentage of participants in Phase 1 reporting systemic events

    Time: For 7 days after dose 1 and dose 2

    Description: As elicited by investigational site staff

    Measure: Percentage of participants in Phase 1 reporting adverse events

    Time: From dose 1 through 1 month after the last dose

    Description: As elicited by investigational site staff

    Measure: Percentage of participants in Phase 1 reporting serious adverse events

    Time: From dose 1 through 6 months after the last dose

    Description: As measured at the central laboratory

    Measure: Percentage of Phase 1 participants with abnormal hematology and chemistry laboratory values

    Time: 1 day after dose 1

    Description: As measured at the central laboratory

    Measure: Percentage of Phase 1 participants with abnormal hematology and chemistry laboratory values

    Time: 7 days after dose 1

    Description: As measured at the central laboratory

    Measure: Percentage of Phase 1 participants with abnormal hematology and chemistry laboratory values

    Time: 7 days after dose 2

    Description: As measured at the central laboratory

    Measure: Percentage of Phase 1 participants with grading shifts in hematology and chemistry laboratory assessments

    Time: Between baseline and 1 day after dose 1

    Description: As measured at the central laboratory

    Measure: Percentage of Phase 1 participants with grading shifts in hematology and chemistry laboratory assessments

    Time: Between baseline and 7 days after dose 1

    Description: As measured at the central laboratory

    Measure: Percentage of Phase 1 participants with grading shifts in hematology and chemistry laboratory assessments

    Time: Between before dose 2 and 7 days after dose 2

    Description: Pain at the injection site, redness, and swelling as self-reported on electronic diaries.

    Measure: In the first 360 participants randomized into Phase 2/3, percentage of participants reporting local reactions

    Time: For 7 days after dose 1 and dose 2

    Description: Fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain as self-reported on electronic diaries.

    Measure: In the first 360 participants randomized into Phase 2/3, percentage of participants reporting systemic events

    Time: For 7 days after dose 1 and dose 2

    Description: As elicited by investigational site staff

    Measure: In the first 360 participants randomized into Phase 2/3, percentage of participants reporting adverse events

    Time: From dose 1 through 1 month after the last dose

    Description: As elicited by investigational site staff

    Measure: In the first 360 participants randomized into Phase 2/3, percentage of participants reporting serious adverse events

    Time: From dose 1 through 6 months after the last dose

    Description: Pain at the injection site, redness, and swelling as self-reported on electronic diaries.

    Measure: In a subset of at least 6000 participants randomized in Phase 2/3, percentage of participants reporting local reactions

    Time: For 7 days after dose 1 and dose 2

    Description: Fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain as self-reported on electronic diaries.

    Measure: In a subset of at least 6000 participants randomized in Phase 2/3, percentage of participants reporting systemic events

    Time: For 7 days after dose 1 and dose 2

    Description: As elicited by investigational site staff

    Measure: Percentage of participants in Phase 2/3 reporting adverse events

    Time: From dose 1 through 1 month after the last dose

    Description: As elicited by investigational site staff

    Measure: Percentage of participants in Phase 2/3 reporting serious adverse events

    Time: From dose 1 through 6 months after the last dose

    Description: Per 1000 person-years of follow-up

    Measure: Confirmed COVID-19 in Phase 2/3 participants without evidence of infection before vaccination

    Time: From 7 days after the second dose of study intervention to the end of the study, up to 2 years

    Description: Per 1000 person-years of follow-up

    Measure: Confirmed COVID-19 in Phase 2/3 participants with and without evidence of infection before vaccination

    Time: From 7 days after the second dose of study intervention to the end of the study, up to 2 years

    Description: As elicited by investigational site staff

    Measure: Percentage of participants 12-15 years of age in Phase 3 reporting adverse events

    Time: From dose 1 through 1 month after the last dose

    Description: As elicited by investigational site staff

    Measure: Percentage of participants 12-15 years of age in Phase 3 reporting adverse events

    Time: From dose 1 through 6 months after the last dose

    Description: Pain at the injection site, redness, and swelling as self-reported on electronic diaries.

    Measure: In participants 12-15 years of age randomized in Phase 3, percentage of participants reporting local reactions

    Time: For 7 days after dose 1 and dose 2

    Description: Fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain as self-reported on electronic diaries.

    Measure: In participants 12-15 years of age randomized in Phase 3, percentage of participants reporting systemic events

    Time: For 7 days after dose 1 and dose 2

    Secondary Outcomes

    Description: As measured at the central laboratory

    Measure: In Phase 1 participants, SARS-CoV-2 serum neutralizing antibody levels, expressed as GMTs

    Time: Through 2 years after the final dose

    Description: As measured at the central laboratory

    Measure: In Phase 1 participants, GMFR in SARS-CoV-2 serum neutralizing titers from before vaccination to each subsequent time point

    Time: Through 2 years after the final dose

    Description: As measured at the central laboratory

    Measure: Proportion of participants in Phase 1 achieving a greater than or equal to 4-fold rise from before vaccination in SARS-CoV-2 serum neutralizing antibody levels

    Time: Through 2 years after the final dose

    Description: As measured at the central laboratory

    Measure: In Phase 1 participants, SARS-CoV-2 anti-S1 binding antibody levels and anti-RBD binding antibody levels, expressed as GMCs

    Time: Through 2 years after the final dose

    Description: As measured at the central laboratory

    Measure: Proportion of participants in Phase 1 achieving a greater than or equal to 4-fold rise from before vaccination in SARS-CoV-2 anti-S1 binding antibody levels and anti-RBD binding antibody levels

    Time: Through 2 years after the final dose

    Description: As measured at the central laboratory

    Measure: In Phase 1 participants, GMFR in SARS-CoV-2 anti-S1 binding antibody levels and anti-RBD binding antibody levels from before vaccination to each subsequent time point

    Time: Through 2 years after the final dose

    Description: As measured at the central laboratory

    Measure: In Phase 1 participants, GMR of the geometric mean of SARS-CoV-2 serum neutralizing titers to the geometric mean of SARS CoV 2 (anti-S1 and anti-RBD) binding antibody levels

    Time: Through 2 years after the final dose

    Description: Per 1000 person-years of follow-up

    Measure: Confirmed COVID-19 in Phase 2/3 participants without evidence of infection before vaccination

    Time: From 14 days after the second dose of study intervention to the end of the study, up to 2 years

    Description: Per 1000 person-years of follow-up

    Measure: Confirmed COVID-19 in Phase 2/3 participants with and without evidence of infection before vaccination

    Time: From 14 days after the second dose of study intervention to the end of the study, up to 2 years

    Description: Per 1000 person-years of follow-up

    Measure: Confirmed severe COVID-19 in Phase 2/3 participants without evidence of infection before vaccination

    Time: From 7 days after the second dose of study intervention to the end of the study, up to 2 years

    Description: Per 1000 person-years of follow-up

    Measure: Confirmed severe COVID-19 in Phase 2/3 participants without evidence of infection before vaccination

    Time: From 14 days after the second dose of study intervention to the end of the study, up to 2 years

    Description: Per 1000 person-years of follow-up

    Measure: Confirmed severe COVID-19 in Phase 2/3 participants with and without evidence of infection before vaccination

    Time: From 7 days after the second dose of study intervention to the end of the study, up to 2 years

    Description: Per 1000 person-years of follow-up

    Measure: Confirmed severe COVID-19 in Phase 2/3 participants with and without evidence of infection before vaccination

    Time: From 14 days after the second dose of study intervention to the end of the study, up to 2 years

    Description: Per 1000 person-years of follow-up

    Measure: Confirmed COVID-19 (according to the CDC-defined symptoms) in Phase 2/3 participants without evidence of infection before vaccination

    Time: From 7 days after the second dose of study intervention to the end of the study, up to 2 years

    Description: Per 1000 person-years of follow-up

    Measure: Confirmed COVID-19 (according to the CDC-defined symptoms) in Phase 2/3 participants without evidence of infection before vaccination

    Time: From 14 days after the second dose of study intervention to the end of the study, up to 2 years

    Description: Per 1000 person-years of follow-up

    Measure: Confirmed COVID-19 (according to the CDC-defined symptoms) in Phase 2/3 participants with and without evidence of infection before vaccination

    Time: From 7 days after the second dose of study intervention to the end of the study, up to 2 years

    Description: Per 1000 person-years of follow-up

    Measure: Confirmed COVID-19 (according to the CDC-defined symptoms) in Phase 2/3 participants with and without evidence of infection before vaccination

    Time: From 14 days after the second dose of study intervention to the end of the study, up to 2 years

    Description: As measured at the central laboratory

    Measure: GMR of SARS CoV 2 neutralizing titers in the 2 age groups (12-15 years of age to 16-25 years of age)

    Time: 1 month after the second dose
    92 A Single-blinded, Randomized, Placebo Controlled Phase II Trial of Prophylactic Treatment With Oral Azithromycin Versus Placebo in Cancer Patients Undergoing Antineoplastic Treatment During the Corona Virus Disease 19 (COVID-19) Pandemic

    Prophylactic treatment in cancer patients undergoing antineoplastic therapy during the COVID-19 pandemic.

    NCT04369365
    Conditions
    1. COVID
    Interventions
    1. Drug: Azithromycin 500 milligram (mg) oral Tablet
    2. Drug: Placebo
    MeSH:Virus Diseases Coronavirus Infections

    Primary Outcomes

    Description: assessed by positive polymerase chain reaction (PCR) from routine nasal swabs (performed every 28 days)

    Measure: Cumulative number of severe acute respiratory syndrome corona virus 2 (SARS-COV-2) infections

    Time: 12 weeks after initiation of therapy

    Secondary Outcomes

    Description: defined as combined endpoint of hospitalization rate or death

    Measure: Number of severe COVID-19 cases

    Time: 12 weeks after initiation of therapy

    Description: grading as outlined by the world health organization (WHO)

    Measure: Severity of COVID-19 cases

    Time: 12 weeks after initiation of therapy

    Description: significant clinical and laboratory abnormalities according to CTCAE criteria

    Measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

    Time: 12 weeks after initiation of therapy

    Description: other than COVID-19

    Measure: Number of viral and bacterial infections

    Time: 12 weeks after initiation of therapy

    Description: Development of azithromycin-resistant bacterial strains as assessed by nasal swabs test

    Measure: Number of participants with azithromycin-resistant bacterial strains in nasal swabs test

    Time: 12 weeks after initiation of therapy
    93 COVID-19: BCG As Therapeutic Vaccine, Transmission Limitation, and Immunoglobulin Enhancement

    To date, there is no vaccine or treatment with proven efficiency against COVID-19, and the transmissibility of the SARS-CoV-2 virus can be inferred by its identification in the oro-nasopharynx. The bacillus Calmette Guérin (BCG) has the potential for cross-protection against viral infections. This study evaluates the impact of previous (priming effect, from the titer of anti-BCG interferon-gamma) or current BCG exposure (boost with intradermal vaccine) on 1) clinical evolution of COVID-19; 2) elimination of SARS-CoV-2 at different times and disease phenotypes; and 3) seroconversion rate and titration (anti-SARS-CoV-2 IgA, IgM, and IgG).

    NCT04369794
    Conditions
    1. COVID-19
    2. Therapeutic Vaccine
    3. BCG
    4. SARS-CoV 2
    5. Transmission
    Interventions
    1. Biological: BCG
    2. Biological: Placebo

    Primary Outcomes

    Description: Classified as mild, moderate and severe

    Measure: Clinical evolution of COVID-19

    Time: 45 days of symptoms onset or diagnosis

    Description: Virus detection by PCR

    Measure: SARS-CoV-2 elimination

    Time: 7 days of symptoms onset or diagnosis

    Description: Titration of anti SARS-CoV-2 IgA, IgM and IgG

    Measure: Seroconversion rate and titration

    Time: 7 days of symptoms onset or diagnosis

    Secondary Outcomes

    Description: Classified according to type and severity

    Measure: Local and systemic adverse events to BCG vaccination

    Time: 3 months

    Other Outcomes

    Description: Virus detection by PCR

    Measure: SARS-CoV-2 elimination

    Time: 21 days of symptoms onset or diagnosis

    Description: Titration of anti SARS-CoV-2 IgA, IgM and IgG

    Measure: Seroconversion rate

    Time: 21 days of symptoms onset or diagnosis

    Description: Virus detection by PCR

    Measure: SARS-CoV-2 elimination

    Time: 45 days of symptoms onset or diagnosis

    Description: Titration of anti SARS-CoV-2 IgA, IgM and IgG

    Measure: Seroconversion rate and titration

    Time: 45 days of symptoms onset or diagnosis
    94 A Multicenter, Double-Blind, Randomized, Placebo-Controlled Trial of INB03 in the Treatment of Participants With Pulmonary Complications From Coronavirus Disease (COVID-19)

    The purpose of this study is to determine whether XPro1595 can prevent the progression of respiratory complications in COVID19 patients.

    NCT04370236
    Conditions
    1. COVID-19
    Interventions
    1. Drug: INB03
    2. Drug: Placebo

    Primary Outcomes

    Description: Disease progression is defined by the development of need for mechanical ventilation or death. Mechanical ventilation includes CPAP, BIPAP or mechanical ventilation requiring intubation.

    Measure: Proportion of participants with disease progression from randomization to 28 days post-randomization

    Time: 28 days

    Secondary Outcomes

    Measure: Proportion of participants with all-cause mortality

    Time: 28 days

    Measure: Proportion of participants who transfer to ICU level care by Day 28 (ICU level care is defined as a hospital setting where patient to nurse ratio is < 4);

    Time: 28 days

    Measure: Proportion of participants with a new onset of neurologic disease (requiring medical intervention), including stroke by Day 28;

    Time: 28 days

    Measure: Proportion of participants with evidence of new CHF or new MI requiring medical intervention by Day 28;

    Time: 28 days

    Measure: Proportion of participants with a new onset embolus or thrombus by Day 28;

    Time: 28 days

    Measure: Proportion of participants who develop a need for renal replacement therapy (defined as need for any type of dialysis including intermittent or continuous peritoneal or hemodialysis) by Day 28;

    Time: 28 days

    Measure: Proportion of participants with an increase in the WHO Ordinal Scale of Clinical Improvement score at any time during the study;

    Time: 28 days

    Measure: Length of hospital stay defined as the number of days in hospital from time of randomization to time of discharge or death, whichever occurs first;

    Time: 28 days

    Measure: Change from baseline in inflammation markers over time.

    Time: 28 days

    Other Outcomes

    Measure: Incidence of adverse events and serious adverse events not due to underlying disease

    Time: 28 days

    Measure: Incidence of abnormal findings in clinical safety laboratory parameters, vital signs, and ECGs.

    Time: 28 days
    95 A Double-blind, Randomized Study Versus Placebo of Avdoralimab (IPH5401), an Anti-C5aR Antibody, in Patients With COVID-19 Severe Pneumonia

    The primary objective of this trial is to improve the proportion of COVID-19 patients with severe pneumonia who no longer need to be hospitalized, and to reduce the need for and duration of mechanical ventilation in patients with COVID-19 pneumonia complicated by acute respiratory distress syndrome (ARDS).

    NCT04371367
    Conditions
    1. COVID
    Interventions
    1. Biological: avdoralimab
    2. Other: Placebo
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: improvement of WHO ordinal scale

    Measure: Clinical improvement using WHO ordinal scale

    Time: day 28

    Description: Number of days without mechanical ventilation at Day 28 for COVID-19 related Acute Respiratory Distress Syndrome (ARDS) Patients hospitalized in ICU

    Measure: Number of ventilator-free days at Day 28 (VFD28)

    Time: day 28

    Secondary Outcomes

    Measure: Number of participants with treatment-related adverse events

    Time: day 28
    96 Mesenchymal Stromal Cells for the Treatment of Moderate to Severe COVID-19 Acute Respiratory Distress Syndrome

    The mortality rate in SARS-CoV-2-related severe ARDS is high despite treatment with antivirals, glucocorticoids, immunoglobulins, and ventilation. Preclinical and clinical evidence indicate that MSCs migrate to the lung and respond to the pro-inflammatory lung environment by releasing anti-inflammatory factors reducing the proliferation of pro-inflammatory cytokines while modulating regulatory T cells and macrophages to promote resolution of inflammation. Therefore, MSCs may have the potential to increase survival in management of COVID-19 induced ARDS. The primary objective of this phase 3 trial is to evaluate the efficacy and safety of the addition of the mesenchymal stromal cell (MSC) remestemcel-L plus standard of care compared to placebo plus standard of care in patients with acute respiratory distress syndrome (ARDS) due to SARS-CoV-2. The secondary objective is to assess the impact of MSCs on inflammatory biomarkers.

    NCT04371393
    Conditions
    1. Mesenchymal Stromal Cells
    2. Remestemcel-L
    3. Acute Respiratory Distress Syndrome
    4. COVID
    Interventions
    1. Biological: Remestemcel-L
    2. Drug: Placebo
    MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

    Primary Outcomes

    Description: Number of all-cause mortality within 30 days of randomization.

    Measure: Number of all-cause mortality

    Time: 30 days

    Secondary Outcomes

    Description: Number of days alive off mechanical ventilatory support calculated as the number of days, within the 60 days window, that patients were alive and free of mechanical ventilatory support.

    Measure: Number of days alive off mechanical ventilatory support

    Time: 60 days

    Description: Safety analyses will be assessed by adverse event rates calculated as the ratio of the total number of events over 30 days divided by total patient-time at risk for the specific event from randomization.

    Measure: Number of adverse events

    Time: 30 days

    Measure: Number of participants alive at day 7

    Time: 7 days

    Measure: Number of participants alive at day 14

    Time: 14 days

    Measure: Number of participants alive at day 60

    Time: 60 days

    Measure: Number of participants alive at day 90

    Time: 90 days

    Measure: Number of participants alive at 12 Months

    Time: 12 Months

    Description: The number and percent of patients with resolution and/or improvement of ARDS at day 7

    Measure: Number of participants with resolution and/or improvement of ARDS

    Time: 7 days

    Description: The number and percent of patients with resolution and/or improvement of ARDS at day 14

    Measure: Number of participants with resolution and/or improvement of ARDS

    Time: 14 days

    Description: The number and percent of patients with resolution and/or improvement of ARDS at day 21

    Measure: Number of participants with resolution and/or improvement of ARDS

    Time: 21 days

    Description: The number and percent of patients with resolution and/or improvement of ARDS at day 30

    Measure: Number of participants with resolution and/or improvement of ARDS

    Time: 30 days

    Description: severity of ARDS according to Berlin Criteria at days 7 post-randomization Change from baseline of the severity of ARDS according to Berlin Criteria at days 7, 14, 21 and 30 post-randomization will be compared between treatment groups using a Cochran-Mantel-Haenszel test stratified by baseline severity.

    Measure: Severity of ARDS

    Time: baseline and 7 days

    Description: severity of ARDS according to Berlin Criteria at days 14 post-randomization Change from baseline of the severity of ARDS according to Berlin Criteria at days 7, 14, 21 and 30 post-randomization will be compared between treatment groups using a Cochran-Mantel-Haenszel test stratified by baseline severity.

    Measure: Severity of ARDS

    Time: baseline and 14 days

    Description: severity of ARDS according to Berlin Criteria at days 21 post-randomization Change from baseline of the severity of ARDS according to Berlin Criteria at days 7, 14, 21 and 30 post-randomization will be compared between treatment groups using a Cochran-Mantel-Haenszel test stratified by baseline severity.

    Measure: Severity of ARDS

    Time: baseline and 21 days

    Description: severity of ARDS according to Berlin Criteria at days 30 post-randomization Change from baseline of the severity of ARDS according to Berlin Criteria at days 7, 14, 21 and 30 post-randomization will be compared between treatment groups using a Cochran-Mantel-Haenszel test stratified by baseline severity.

    Measure: Severity of ARDS

    Time: baseline and 30 days

    Description: Hospital length of stay

    Measure: Length of stay

    Time: 12 months

    Description: number of readmission

    Measure: Readmissions

    Time: 12 months

    Measure: Length of Stay in Intensive Care Unit

    Time: 12 months

    Description: Change from baseline in Clinical Improvement Scale at day 7. Clinical Improvement Scale full scale from 1 to 7, with higher score indicating more clinical improvement.

    Measure: Clinical Improvement Scale

    Time: 7 days

    Description: Change from baseline in Clinical Improvement Scale at day 14. Full scale from 1 to 7, with higher score indicating more clinical improvement.

    Measure: Clinical Improvement Scale

    Time: 14 days

    Description: Change from baseline in Clinical Improvement Scale at day 21. Clinical Improvement Scale full scale from 1 to 7, with higher score indicating more clinical improvement.

    Measure: Clinical Improvement Scale

    Time: 21 days

    Description: Change from baseline in Clinical Improvement Scale at day 30. Clinical Improvement Scale full scale from 1 to 7, with higher score indicating more clinical improvement.

    Measure: Clinical Improvement Scale

    Time: 30 days

    Description: Changes from baseline in plasma hs-CRP concentration at days 7

    Measure: Change in plasma hs-CRP concentration

    Time: baseline and 7 days

    Description: Changes from baseline in plasma hs-CRP concentration at days 14

    Measure: Change in plasma hs-CRP concentration

    Time: baseline and 14 days

    Description: Changes from baseline in plasma hs-CRP concentration at days 21

    Measure: Change in plasma hs-CRP concentration

    Time: baseline and 21 days

    Description: Changes from baseline in serum hs-CRP concentration at days 30

    Measure: Change in serum hs-CRP concentration

    Time: baseline and 30 days

    Description: Changes from baseline in IL-6 inflammatory marker level at 7 days

    Measure: Change in IL-6 inflammatory marker level

    Time: baseline and 7 days

    Description: Changes from baseline in IL-6 inflammatory marker level at 14 days

    Measure: Change in IL-6 inflammatory marker level

    Time: baseline and 14 days

    Description: Changes from baseline in IL-6 inflammatory marker level at 21 days

    Measure: Change in IL-6 inflammatory marker level

    Time: baseline and 21 days

    Description: Changes from baseline in IL-6 inflammatory marker level at 30 days

    Measure: Change in IL-6 inflammatory marker level

    Time: baseline and 30 days

    Description: Changes from baseline in IL-6 inflammatory marker level at 7 days

    Measure: Change in IL-8 inflammatory marker level

    Time: baseline and 7 days

    Description: Changes from baseline in IL-6 inflammatory marker level at 21 days

    Measure: Change in IL-8 inflammatory marker level

    Time: baseline and 21 days

    Description: Changes from baseline in IL-6 inflammatory marker level at 14 days

    Measure: Change in IL-8 inflammatory marker level

    Time: baseline and 14 days

    Description: Changes from baseline in IL-6 inflammatory marker level at 30 days

    Measure: Change in IL-8 inflammatory marker level

    Time: baseline and 30 days

    Description: Changes from baseline in TNF-alpha inflammatory marker level at 7 days

    Measure: Change in TNF-alpha inflammatory marker level

    Time: baseline and 7 days

    Description: Changes from baseline in TNF-alpha inflammatory marker level at 14 days

    Measure: Change in TNF-alpha inflammatory marker level

    Time: baseline and 14 days

    Description: Changes from baseline in TNF-alpha inflammatory marker level at 21 days

    Measure: Change in TNF-alpha inflammatory marker level

    Time: baseline and 21 days

    Description: Changes from baseline in TNF-alpha inflammatory marker level at 30 days

    Measure: Change in TNF-alpha inflammatory marker level

    Time: baseline and 30 days

    Description: including the presence of emphysema, COPD, asthma, pulmonary fibrosis, other pulmonary disease, and the need for respiratory support will be reported by randomization

    Measure: Pulmonary symptoms

    Time: 6 months

    Description: including the presence of emphysema, COPD, asthma, pulmonary fibrosis, other pulmonary disease, and the need for respiratory support will be reported by randomization

    Measure: Pulmonary symptoms

    Time: 12 months
    97 A Randomized, Double-Blinded, Placebo-Controlled Trial Evaluating the Virological Efficacy, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Sirolimus Adjuvant Therapy in Patients With Coronavirus Disease (COVID-19)

    This is a double-blinded, two-arm, randomized, placebo controlled study comparing the virological efficacy of add-on sirolimus with standard care to placebo and standard care. Virological efficacy is defined as the change from baseline to day 7 in SARS-CoV-2 viral burden measured by quantitative real-time polymerase chain reaction.

    NCT04371640
    Conditions
    1. SARS-CoV-2
    2. Covid-19
    Interventions
    1. Drug: Sirolimus 1 MG/ML
    2. Drug: Placebo

    Primary Outcomes

    Description: SARS-CoV-2 viral burden will be quantified for both arms using a qRT-PCR

    Measure: Change in SARS-CoV-2 viral burden from baseline to day 7 of treatment

    Time: Baseline, and days 1, 2, 3, 4, 5, 6, & 7 post-dose for all patients

    Secondary Outcomes

    Description: SARS-CoV-2 viral burden will be quantified for both arms using a qRT-PCR

    Measure: Change in SARS-CoV-2 viral burden at days 1-6

    Time: Days 1, 2, 3, 4, 5, and 6 post-dose for all patients

    Description: Safety and tolerability of sirolimus in patients with COVID-19

    Measure: Rate of treatment emergent adverse events

    Time: Days 1, 2, 3, 4, 5, and 6 post-dose for all patients
    98 Doxycycline Versus Placebo in COVID-19 + Patients Without Hospitalization Criteria: Prospective, Multicenter, Randomized, Double-blind Study

    The aim of the study is to compare a treatment with doxycycline vs a placebo as soon as the patient is confirmed COVID-19 + and before the onset of oxygen dependence with the aim of reducing or even abolishing the cytokine explosion and thus the evolution towards a serious form of the disease which can lead to death. Three criteria support the rational use of tetrcycline in COVI-19 (1) The coronaviruses is known to bind to metalloproteases (MMPs) of the host, in particular to ensure viral survival. Tetracyclines are known to chelate zinc from MMPs. Their chelating activity may help inhibit COVID19 infection by limiting its ability to replicate in the host. (2) Tetracyclines may also be able to inhibit the replication of positive-polarity single-stranded RNA viruses, such as COVID19 (demonstrated on the dengue virus). (3) In addition, tetracyclines are modulators of innate immunity (anti-inflammatory activity), a property used in the treatment of inflammatory skin diseases for many years. These modulating effects are noted on several targets of innate immunity: They can decrease the expression of NFKB, the release of inflammatory cytokines such as TNF-α, IL-1β and IL-6, inhibit granulomas inflammatory and free radical release. Tetracyclines could therefore participate in limiting the cytokine release induced by COVID19. Their lipophilic nature and their strong pulmonary penetration could allow them to inhibit viral replication.

    NCT04371952
    Conditions
    1. COVID19
    Interventions
    1. Drug: Doxycycline
    2. Drug: Placebo

    Primary Outcomes

    Description: Percentage of patients with clinical worsening (SaO2 ≤ 93%) after at least 48 hours of treatment

    Measure: Percentage of Patients with Clinical Respiratory Aggravation

    Time: after at least 48 hours of treatment

    Description: Percentage of patients hospitalized after at least 48 hours of experimental treatment

    Measure: Percentage of patients hospitalized

    Time: after at least 48 hours of experimental treatment

    Description: Percentage of patients requiring ventilatory assistance

    Measure: Percentage of patients requiring ventilatory assistance

    Time: Day 0 to Day 28

    Secondary Outcomes

    Description: Number of positive SARS-CoV-2 PCR tests on D-1 / D0 and D7 (+/- 2 days)

    Measure: Positive SARS-CoV-2 PCR Test

    Time: Day -1 or day 0 AND Day 7

    Description: Duration of symptoms (fever, painful symptoms: headache, sore throat, dyspnea)

    Measure: Duration of symptoms

    Time: Day 0 to Day 28

    Description: Total duration of hospitalization

    Measure: Duration of hospitalization

    Time: From day 0 until to the end of hospitalization or date of death for any cause, whichever came first, assessed up to 3 months after Day0

    Description: Duration of hospitalization in intensive care or reanimation

    Measure: Hospitalization intensive care or reanimation

    Time: From day 0 until to the end of hospitalization or date of death for any cause, whichever came first, assessed up to 3 months after Day0

    Description: Duration of mechanical ventilatory assistance

    Measure: Duration of mechanical ventilatory assistance

    Time: to the end of mechanical ventilatory assistance if any, assessed up to 3 months after Day0

    Description: Percentage of deaths related to SARS-CoV-2 infection

    Measure: Percentage of deaths related to SARS-CoV-2

    Time: Day 28, or end of hospitalization if any (assessed up to 3 months after Day0)

    Description: Number of AE / SAE in both arms

    Measure: AE / SAE in both arms

    Time: Day 28, or end of hospitalization if any (assessed up to 3 months after Day0)
    99 A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of Tocilizumab in Hospitalized Patients With COVID-19 Pneumonia

    This study (EMPACTA) will a) evaluate the efficacy and safety of tocilizumab (TCZ) compared with a placebo in combination with standard of care (SOC) in hospitalized participants with COVID-19 pneumonia, and b) include an optional substudy to explore the long-term sequelae of resolved COVID-19 pneumonia.

    NCT04372186
    Conditions
    1. COVID-19 Pneumonia
    Interventions
    1. Drug: Placebo
    2. Drug: Tocilizumab
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Measure: Cumulative Proportion of Participants Requiring Mechanical Ventilation by Day 28

    Time: Up to Day 28

    Secondary Outcomes

    Measure: Time to Improvement of at Least 2 Categories Relative to Baseline on a 7-Category Ordinal Scale of Clinical Status

    Time: Up to Day 28

    Measure: Time to Clinical Failure, Defined as the Time to Death, Mechanical Ventilation, ICU Admission, or Withdrawal (whichever occurs first)

    Time: Up to Day 28

    Measure: Mortality Rate by Day 28

    Time: Up to Day 28

    Measure: Time to Hospital Discharge or "Ready for Discharge" (as evidenced by normal body temperature and respiratory rate, and stable oxygen saturation on ambient air or >/= 2 liters (L) supplemental oxygen)

    Time: Up to Day 28

    Measure: Percentage of Participants with Adverse Events

    Time: Up to Day 60

    Measure: Percentage of Participants with any Post-Treatment Bacterial and/or Fungal Infection

    Time: Up to Day 60

    Measure: Incidence of Post-Treatment Acute Kidney injury (defined by 50% increase of creatinine from baseline)

    Time: Up to Day 60
    100 A Pilot Study of Duvelisib to Combat COVID-19

    The exceedingly high mortality rates of severe and critical COVID-19 warrant the identification and evaluation of novel therapies that could potentially mitigate the advanced disease manifestations. Based on preclinical data from this institution and others, the investigators hypothesize that PI3K inhibition with duvelisib could potentially quell aberrant hyperactivtation of the innate immune system, preferentially polarize macrophages, reduce pulmonary inflammation, and limit viral persistence, thereby improving patient outcomes.

    NCT04372602
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Duvelisib
    2. Procedure: Peripheral blood draw
    3. Drug: Placebo

    Primary Outcomes

    Measure: Overall survival

    Time: Through 28 days

    Secondary Outcomes

    Measure: Length of hospital stay

    Time: Through completion of follow-up (estimated to be 7 months)

    Measure: Length of ICU stay

    Time: Through completion of follow-up (estimated to be 7 months)

    Description: -For those on a ventilator at the time of randomization

    Measure: Duration of ventilator use

    Time: Through completion of follow-up (estimated to be 7 months)

    Measure: Duration of vasopressors use

    Time: Through completion of follow-up (estimated to be 7 months)

    Measure: Duration on renal replacement therapy

    Time: Through completion of follow-up (estimated to be 7 months)

    Description: -Defined as increase in viral load of >0.5 log on two consecutive days, or >1 log increase in one day, not in keeping with any baseline trend of rising viral loads during the pre-treatment viral testing

    Measure: Viral kinetics as measured by virologic failure

    Time: Through completion of follow-up (estimated to be 7 months)

    Measure: Number of adverse events as measured by CTCAE v. 5.0

    Time: Through completion of follow-up (estimated to be 7 months)
    101 Trial of Early Therapies During Non-hospitalized Outpatient Window (TREAT NOW) for COVID-19

    Blinded, multicenter, placebo-controlled, randomized clinical trial evaluating lopinavir/ritonavir vs placebo in early outpatient treatment of adults with COVID-19

    NCT04372628
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Lopinavir/Ritonavir 400 mg/100 mg
    2. Other: Placebo

    Primary Outcomes

    Description: Death Hospitalized on mechanical ventilation or extracorporeal membrane oxygenator (ECMO) Hospitalized on supplemental oxygen Hospitalized not on supplemental oxygen Not hospitalized with symptoms and limitation in activity Not hospitalized with symptoms but with no limitation in activity Not hospitalized without symptoms nor limitation in activity symptoms at the milder end of the scale for this outpatient trial

    Measure: Modified COVID Ordinal Outcomes Scale: Study Day 15

    Time: Day 15

    Secondary Outcomes

    Description: Death Hospitalized on mechanical ventilation or ECMO Hospitalized on supplemental oxygen Hospitalized not on supplemental oxygen Not hospitalized with symptoms and limitation in activity Not hospitalized with symptoms but with no limitation in activity Not hospitalized without symptoms nor limitation in activity

    Measure: Modified COVID Ordinal Outcome Scale: Study Day 8

    Time: Day 8

    Description: Death Hospitalized on mechanical ventilation or ECMO Hospitalized on supplemental oxygen Hospitalized not on supplemental oxygen Not hospitalized with symptoms and limitation in activity Not hospitalized with symptoms but with no limitation in activity Not hospitalized without symptoms nor limitation in activity Ordinal Scale

    Measure: Modified COVID Ordinal Outcome Scale: Study Day 29

    Time: Day 29

    Description: Proportion hospitalized

    Measure: Proportion of patients hospitalized: Day 1 to 29

    Time: Day 1 to Day 29

    Description: Number of days from enrollment to hospitalization

    Measure: Time to hospitalization Day 1 to Day 29

    Time: Day 1 to Day 29

    Description: Number of days from enrollment to resolution of COVID-19 symptoms

    Measure: Time to symptom resolution: Day 1 to Day 29

    Time: Day 1 to Day 29

    Description: Survival status

    Measure: All-cause, all-location mortality: Day 1 to Day 29

    Time: Day 1 to Day 29

    Description: Number of Days without oxygen

    Measure: Oxygen-free days: Day 1 to Day 29

    Time: Day 1 to Day 29

    Description: Number of days without fever

    Measure: Fever-free days: Day 1 to Day 29

    Time: Day 1 to Day 29

    Description: Number of days without ventilator use

    Measure: Ventilator-free days: Day 1 to Day 29

    Time: Day 1 to Day 29

    Description: Number of days outside the ICU

    Measure: ICU-free days: Day 1 to Day 29

    Time: Day 1 to Day 29

    Description: Number of days outside the hospital

    Measure: Hospital-free days: Day 1 to Day 29

    Time: Day 1 to Day 29
    102 RCT in Asymptomatic Volunteers With COVID-19 Comparing Azithromycin and Hydroxychloroquine vs. Hydroxychloroquine Alone vs Standard of Care Without Antibiotics

    The coronavirus disease-2019 (COVID-19) is spreading throughout the United States. While there are no known therapies to treat those who have become sick, there have been some reports that a medication currently used to treat rheumatoid arthritis, lupus, and malaria (Hydroxychloroquine sulfate, also known as Plaquenil) may help to lessen the chance or severity of illness, especially if combined with a medicine that treats other kinds of infections (Azithromycin, also known as Zithromax or Zmax or Zpak). There are some people who test positive for the virus but who are otherwise not ill. Current standard of care is to advise these people to self-monitor but no treatment is offered. It is not known how many of these individuals will remain symptom free, and how many will become sick or how severe those symptoms will be. This study will randomize those people who do not have symptoms into one of three treatment plans 1) Hydroxycholoquine and Azithromycin, or 2) no active medication (placebo). All participants will be followed for 2 months. The study will determine if there is any benefit to those who are asymptomatic to taking taking Hydroxychloroquine sulfate in combination with Azithromycin, or if there is no benefit from taking these medications.

    NCT04374552
    Conditions
    1. SARS-CoV-2 Infection
    Interventions
    1. Drug: Hydroxychloroquine sulfate &Azithromycin
    2. Drug: Placebo

    Primary Outcomes

    Description: Change in SARS-CoV-2 viral from baseline to day 6

    Measure: The primary outcome is the rate of decline in viral load over the 10 days after randomization

    Time: 10 days
    103 IbrutiNib in SARS CoV-2 Induced Pulmonary Injury and Respiratory Failure (iNSPIRE)

    Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Lung failure is the main cause of death related to COVID-19 infection. The main objective of this study is to evaluate if Ibrutinib is safe and can reduce respiratory failure in participants with COVID-19 infection. Ibrutinib is an investigational drug being developed for the treatment of COVID-19. Participants are assigned 1 of 2 groups, called treatment arms. Each group receives a different treatment. There is a 1 in 2 chance that participants will be assigned to placebo. Around 46 adult participants with a diagnosis of COVID-19 will be enrolled at multiple sites in Unites States. Participants will receive oral doses of Ibrutinib or placebo capsules once daily for 4 weeks along with standard care. There may be higher treatment burden for participants in this trial compared to their standard of care. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects.

    NCT04375397
    Conditions
    1. CoronaVirus Induced Disease-2019 (COVID-19)
    Interventions
    1. Drug: Ibrutinib
    2. Drug: Placebo
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Respiratory Insufficiency Lung Injury

    Primary Outcomes

    Description: Respiratory failure is defined by clinical diagnosis of respiratory failure and initiation of 1 of the following therapies: Endotracheal intubation and mechanical ventilation OR Extracorporeal membrane oxygenation OR high-flow nasal cannula oxygen delivery OR non-invasive positive pressure ventilation OR clinical diagnosis of respiratory failure with initiation of none of these measures only when clinical decision-making driven is driven solely by resource limitation.

    Measure: Percentage of Participants Alive and Without Respiratory Failure

    Time: Day 28

    Secondary Outcomes

    Description: WHO-8 is an 8 point ordinal scale for clinical improvement with scores ranging from 0 (uninfected) through 8 (Death).

    Measure: Change in the World Health Organization (WHO)-8 Point Ordinal Scale From Baseline

    Time: Day 14

    Description: Time on supplemental oxygen imputed to the maximum number of days on study drug (28) for all points following the death of a participant.

    Measure: Median Reduction in Days Spent on Supplemental Oxygen

    Time: Up to Day 28

    Description: Percentage of participants with mortality from any cause.

    Measure: All-Cause Mortality

    Time: Up to Day 28

    Description: Respiratory failure is defined by clinical diagnosis of respiratory failure and initiation of 1 of the following therapies: Endotracheal intubation and mechanical ventilation OR Extracorporeal membrane oxygenation OR high-flow nasal cannula oxygen delivery OR non-invasive positive pressure ventilation OR clinical diagnosis of respiratory failure with initiation of none of these measures only when clinical decision-making driven is driven solely by resource limitation.

    Measure: Percentage of Participants Experiencing Respiratory Failure or Death

    Time: Up to Day 28

    Description: Percentage of participants alive and not requiring mechanical ventilation.

    Measure: Mechanical Ventilation-Free Survival

    Time: Up to Day 56

    Description: Defined as number of days from the first day of using mechanical ventilation to the last day of using mechanical ventilation.

    Measure: Days on Mechanical Ventilation

    Time: Up to Day 56

    Description: The duration of hospitalization is defined as the time in days from the first day of hospitalized to the date of discharge or death.

    Measure: Duration of hospitalization

    Time: Up to Day 56

    Description: Time to discharge is defined as the time in days from the first day of hospitalized to the date of discharge.

    Measure: Time to Discharge

    Time: Up to Day 56

    Description: PaO2:FiO2 ratio is an index of respiratory distress.

    Measure: Partial Pressure of Oxygen in Arterial Blood (PaO2) to Fraction of Inspired Oxygen (FiO2) Ratio

    Time: Up to Day 56

    Description: Oxygenation Index is a parameter of pulmonary function of participants.

    Measure: Oxygenation Index

    Time: Up to Day 56

    Description: An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent adverse events (TEAEs) are defined as any event that began or worsened in severity on or after the first dose of study drug.

    Measure: Number of Participants With Adverse Events

    Time: Up to Day 56

    Description: Laboratory abnormalities will be analyzed according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

    Measure: Number of Participants With Abnormal Laboratory Findings

    Time: Up to Day 56
    104 A Randomized, Double-blind, Placebo-controlled, Study Evaluating the Efficacy and Safety of Otilimab IV in Patients With Severe Pulmonary COVID-19 Related Disease

    OSCAR (Otilimab in Severe COVID-19 Related Disease) is a multi-center, double-blind, randomized, placebo-controlled trial to assess the efficacy and safety of otilimab for the treatment of severe pulmonary COVID-19 related disease. Otilimab is a human monoclonal anti-granulocyte macrophage colony stimulating factor (GM-CSF) antibody that has not previously been tested in participants with severe pulmonary COVID-19 related disease. The aim of this study is to evaluate the benefit-risk of a single infusion of otilimab in the treatment of participants with severe COVID-19 related pulmonary disease. The study population will consist of hospitalized participants with new onset hypoxia requiring significant oxygen support or requiring early invasive mechanical ventilation (less than or equal to [<=] 48 hours before dosing). Participants will be randomized to receive a single intravenous (IV) infusion of otilimab or placebo, in addition to standard of care.

    NCT04376684
    Conditions
    1. Severe Acute Respiratory Syndrome
    Interventions
    1. Biological: Otilimab
    2. Biological: Placebo
    3. Drug: Standard of care
    MeSH:Severe Acute Respiratory Syndrome Coronavirus Infections

    Primary Outcomes

    Description: Participants are alive and free of respiratory failure if they are in category 1, 2, 3 or 4 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale is as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized, limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, high-flow oxygen (≥15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death.

    Measure: Proportion of participants alive and free of respiratory failure at Day 28

    Time: Day 28

    Secondary Outcomes

    Description: Number of deaths due to all causes will be assessed.

    Measure: Number of deaths due to all causes at Day 60

    Time: Day 60

    Description: Time to death due to all causes will be assessed.

    Measure: Time to number of deaths due to all causes up to Day 60

    Time: Up to Day 60

    Description: Participants alive and free of respiratory failure if they are in category 1, 2, 3 or 4 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale is as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized, limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, high-flow oxygen (≥15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death.

    Measure: Proportion of participants alive and free of respiratory failure at Days 7, 14, 42 and 60

    Time: Days 7, 14, 42, and 60

    Description: Time will be recorded from dosing to recovery from respiratory failure. Participants are in respiratory failure if they are in category 5 or above from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale is as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized, limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, high-flow oxygen (≥15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death.

    Measure: Time to recovery from respiratory failure

    Time: Up to Day 28

    Description: Participants are independent of supplementary oxygen if they are in category 1, 2 or 3 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale is as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized, limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, high-flow oxygen (≥15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death.

    Measure: Proportion of participants alive and independent of supplementary oxygen at Days 7, 14, 28, 42, and 60

    Time: Days 7, 14, 28, 42, and 60

    Description: Participants are independent of supplementary oxygen if they are in category 1, 2 or 3 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale is as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized, limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, high-flow oxygen (≥15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death.

    Measure: Time to last dependence on supplementary oxygen

    Time: Up to Day 28

    Description: For participants not in ICU at time of dosing, the proportion of participants admitted to the ICU prior to Day 28.

    Measure: Proportion of participants admitted to Intensive Care Unit (ICU)

    Time: Up to Day 28

    Description: Defined as the time from dosing to when the participant is discharged from the ICU.

    Measure: Time to final ICU discharge

    Time: Up to Day 28

    Description: Time from dosing to when a participant is discharged from the hospital.

    Measure: Time to final hospital discharge

    Time: Up to Day 28

    Description: AEs and SAEs will be collected.

    Measure: Number of participants with Adverse events (AEs) and Serious adverse events (SAEs)

    Time: Up to Day 60
    105 A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Assess the Efficacy and Safety of Ruxolitinib in Participants With COVID-19-Associated ARDS Who Require Mechanical Ventilation (RUXCOVID-DEVENT)

    The purpose of this study is to evaluate the efficacy and safety of ruxolitinib in the treatment of participants with COVID-19-associated Acute Respiratory Distress Syndrome (ARDS) who require mechanical ventilation.

    NCT04377620
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Placebo
    2. Drug: Ruxolitinib

    Primary Outcomes

    Description: To evaluate the 28-day mortality rate of ruxolitinib 5 mg BID + SoC therapy and ruxolitinib 15 mg BID + SoC compared with placebo + SoC therapy, in participants with COVID-19-associated ARDS who require mechanical ventilation.

    Measure: Proportion of participants who have died due to any cause

    Time: Up to Day 29

    Secondary Outcomes

    Description: Number of days participant did not require mechanical ventilation

    Measure: Number of Ventilator free days

    Time: Day 29

    Description: Number of days participant is out of the ICU

    Measure: Number of ICU free days

    Time: Day 29

    Description: Number of days participant did not receive supplemental oxygen

    Measure: Oxygen free days

    Time: Day 29

    Description: Number of days without use of vasopressor therapy

    Measure: Vasopressor free days

    Time: Day 29

    Description: Number of days Partcipant is out of the hospital

    Measure: Hospital free days

    Time: Day 29

    Description: Clinical status of participant at Day 15 and 29 based on participant state. The scale ranges from 0-8 with 0 being no clinical or virological evidence of infection and 8 being dead

    Measure: Improvement in the COVID-19 ordinal scale

    Time: Day 15 and 29

    Description: SOFA score is a scoring system to determine the extent of a person's organ function or rate of failure. The score is based on 6 different scores, 1 each for the respiratory, cardiovascular, hepatic, coagulation, renal, and neurological systems.

    Measure: Change in SOFA Score

    Time: from baseline to Days 3, 5, 8, 11, 15, and 29

    Description: Adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug/treatment.

    Measure: Number of treatment-related adverse events

    Time: Day 29
    106 A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety and Efficacy of Ciclesonide Metered-Dose Inhaler in Non-hospitalized Patients 12 Years of Age and Older With Symptomatic COVID-19 Infection

    The purpose of this study is to assess the safety and efficacy of Alvesco (ciclesonide) Inhalation Aerosol in non hospitalized patients with symptomatic COVID-19 infection in a multicenter, randomized, double-blind, placebo controlled study

    NCT04377711
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Ciclesonide
    2. Drug: Placebo

    Primary Outcomes

    Measure: Percentage of patients hospital admission or death by day 30

    Time: Day 30

    Secondary Outcomes

    Measure: All-cause mortality by day 30

    Time: Day 30

    Measure: COVID-19-related mortality by day 30

    Time: Day 30

    Measure: Percentage of patients with subsequent emergency department visit or hospital admission for reasons attributable to COVID 19 by day 30

    Time: Day 30

    Measure: Time to hospital admission or death

    Time: Day 30

    Measure: Time to alleviation of COVID-19-related symptoms of cough, dyspnea, chills, and feeling feverish, defined as symptom-free for a continuous period of more than 24 hours (ie, > 3 AM/PM assessments)

    Time: Day 30

    Measure: Change from baseline in oxygen saturation levels

    Time: Day 30

    Measure: Change from baseline in COVID-19 viral load in nasopharyngel sample nasal secretions at day 30

    Time: Day 30

    Measure: Safety will be assessed based on adverse events.

    Time: Day 60
    107 A Prospective, Multi-Center, Randomized, Placebo-Controlled, Double-Blinded Study to Evaluate the Efficacy, Safety and Tolerability of IMU-838 as Addition to Investigator's Choice of Standard of Care Therapy, in Patients With Coronavirus Disease 19

    At present there is no approved drug treatment for Covid-19. In this study we plan to investigate if an experimental drug called IMU-838 (vidofludimus calcium) can improve your symptoms, prevent worsening that would initiate further treatments such as ventilation, and can lower your virus number if given in addition to your doctor's choice of standard therapy. We will also test if IMU-838 has any side effects and measure the level of IMU 838 in your blood. Experimental drug means that it is not yet authorized for marketing in your country. To date approximately 600 individuals have received IMU-838 (or a drug similar to IMU-838 that contains the same active substance as IMU-838) in research studies.

    NCT04379271
    Conditions
    1. COVID-19
    Interventions
    1. Drug: IMU-838
    2. Other: Placebo
    MeSH:Coronavirus Infections

    Primary Outcomes

    Description: Clinical

    Measure: Proportion of patients without any need* for INV until end-of-study (EoS)

    Time: Throughout the Study (Day 0 to Day 28)

    Secondary Outcomes

    Description: Key Secondary

    Measure: Duration of ICU treatment until EoS

    Time: Throughout the Study (Day 0 to Day 28 )

    Description: Key Secondary

    Measure: 28-day all-cause mortality

    Time: Throughout the Study (Day 0 to Day 28 )

    Description: Efficacy: defined as the time from first dose of investigational medicinal product (IMP) to an improvement of at least 2 points on the WHO 9 category ordinal scale , or live discharge from hospital without oxygen supplementation, whichever comes first

    Measure: Time to clinical improvement

    Time: Throughout the Study (Day 0 to Day 28 )

    Description: Efficacy: Duration of hospitalization (for US sites only: or treatment in special outpatient setting in lieu of hospitalization due to resource restraints)

    Measure: Duration of hospitalization

    Time: Throughout the Study (Day 0 to Day 28 )

    Description: Efficacy

    Measure: Proportion of patients both for all patients and surviving patients free of renal-replacement therapy (RRT)* until EoS

    Time: Throughout the Study (Day 0 to Day 28 )

    Description: Efficacy

    Measure: Proportion of patients both for all patients and surviving patients free from extracorporeal membrane oxygenation (ECMO)* until EoS

    Time: Throughout the Study (Day 0 to Day 28 )

    Description: Efficacy

    Measure: Proportion of patients free of INV until Days 6 and 14*

    Time: Throughout the Study (Day 0 to Day 28 )

    Description: Efficacy

    Measure: Proportion of patients free of RRT until Days 6 and 14*

    Time: Day 0 to Days 6 and 14

    Description: Efficacy

    Measure: Proportion of patients free ECMO until Days 6 and 14*

    Time: Day 0 to Days 6 and 14

    Description: Efficacy

    Measure: Proportion of patients with improvement of at least 2 points (from randomization) on the 9-category WHO ordinal scale1 on Days 6, 14, and 28

    Time: on Days 6, 14, and 28

    Description: Efficacy

    Measure: Proportion of patients with auxiliary oxygen therapy (including all types of oxygen therapy) on Days 6, 14, and 28

    Time: on Days 6, 14, and 28

    Description: Efficacy

    Measure: Proportion of patients with clinical recovery: Axillary temperature ≤36.6 ℃, or oral temperature ≤37.2 ℃, or rectal or tympanic temperature ≤37.8 ℃;

    Time: Throughout the Study (Day 0 to Day 28 )

    Description: Efficacy

    Measure: Proportion of patients with clinical recovery: Respiratory frequency ≤24 times/min without oxygen inhalation; and

    Time: Throughout the Study (Day 0 to Day 28 )

    Description: Efficacy

    Measure: Proportion of patients with clinical recovery: Oxygen saturation ≥98% without oxygen inhalation

    Time: Throughout the Study (Day 0 to Day 28 )

    Description: Efficacy

    Measure: Proportion of patients with clinical improvement, defined as the time from first dose of IMP to an improvement of at least 2 points on the WHO 9 category ordinal scale, or live discharge from hospital without oxygen supplementation, whichever comes first

    Time: Throughout the Study (Day 0 to Day 28 )

    Description: Efficacy

    Measure: Clinical patient status on the 9-category WHO ordinal scale1 on Days 6, 14, and 28

    Time: on Days 6, 14, and 28

    Description: Efficacy

    Measure: Duration of INV

    Time: Throughout the Study (Day 0 to Day 28 )

    Description: Efficacy

    Measure: Duration of ECMO

    Time: Throughout the Study (Day 0 to Day 28)

    Description: Efficacy

    Measure: Duration of RRT

    Time: Throughout the Study (Day 0 to Day 28)

    Description: Efficacy

    Measure: Duration of auxiliary oxygen therapy (including all types of oxygen therapy)

    Time: Throughout the Study (Day 0 to Day 28)

    Description: Efficacy

    Measure: Duration of hospitalization for survivors

    Time: Throughout the Study (Day 0 to Day 28)

    Description: Efficacy

    Measure: The rate of ICU* admission on Days 6, 14, and 28

    Time: on Days 6, 14, and 28

    Description: Efficacy

    Measure: Hospital-free days

    Time: Throughout the Study (Day 0 to Day 28)

    Description: Efficacy

    Measure: Time from IMP treatment initiation to death

    Time: Throughout the Study (Day 0 to Day 28)

    Description: Efficacy

    Measure: Time to first prescription of INV

    Time: Throughout the Study (Day 0 to Day 28)

    Description: Efficacy

    Measure: Time to first prescription of RRT

    Time: Throughout the Study (Day 0 to Day 28)

    Description: Efficacy

    Measure: Time to first prescription of ECMO

    Time: Throughout the Study (Day 0 to Day 28)

    Description: Efficacy

    Measure: Time to first prescription of INV, RRT, and ECMO

    Time: Throughout the Study (Day 0 to Day 28)

    Description: Efficacy

    Measure: Time to ICU admission

    Time: Throughout the Study (Day 0 to Day 28)

    Description: Efficacy

    Measure: Cumulative dose of vasoactive therapies and days with vasoactive therapies (daily until Day 14)

    Time: Day 0 to day 14

    Description: Efficacy

    Measure: Time to clinical recovery

    Time: Throughout the Study (Day 0 to Day 28)

    Description: Pharmacokinetics

    Measure: Morning trough plasma levels of IMU-838 on Days 0, 1, 2, 3, 6, 14, and 28

    Time: on Days 0, 1, 2, 3, 6, 14, and 28

    Description: Pharmacokinetics

    Measure: Correlation of trough levels (quartiles) to selected clinical outcomes (Clinical improvement accoding to WHO criteria)

    Time: on Days 0, 1, 2, 3, 6, 14, and 28

    Description: Safety

    Measure: Adverse events (AEs) and serious AEs

    Time: Throughout the Study (Day 0 to Day 28)

    Description: Safety Height in centimeters will be recorded without shoes. Changes in vital signs judged by the investigator as clinically significant will be reported as an AE.

    Measure: Vital signs: height

    Time: only at Screening

    Description: Safety Weight in kilograms will be recorded without shoes. Changes in vital signs judged by the investigator as clinically significant will be reported as an AE.

    Measure: Vital signs: weight

    Time: Throughout the Study (Day 0 to Day 28)

    Description: Safety Body temperature can be measured axillary, oral, rectal or tympanic, but should be always measured by the same method for a patient. Changes in vital signs judged by the investigator as clinically significant will be reported as an AE.

    Measure: Vital signs: body temperature (ºC)

    Time: Throughout the Study (Day 0 to Day 28)

    Description: Safety Pulse must be measured with the patient in a seated position (if possible), after at least 5 minutes at rest. Changes in vital signs judged by the investigator as clinically significant will be reported as an AE.

    Measure: Vital signs: pulse rates,

    Time: Throughout the Study (Day 0 to Day 28)

    Description: Safety Blood pressure (systolic and diastolic) must be measured with the patient in a seated position (if possible), after at least 5 minutes at rest. Changes in vital signs judged by the investigator as clinically significant will be reported as an AE.

    Measure: Vital signs: systolic and diastolic blood pressures

    Time: Throughout the Study (Day 0 to Day 28)

    Description: Safety

    Measure: Clinical laboratory parameters: blood chemistry

    Time: Throughout the Study (Day 0 to Day 28)

    Description: Safety

    Measure: Clinical laboratory parameters: hematology

    Time: Throughout the Study (Day 0 to Day 28)

    Description: Safety

    Measure: Clinical laboratory parameters: urinalysis

    Time: Throughout the Study (Day 0 to Day 28)

    Description: Safety

    Measure: 12-lead electrocardiogram: heart rate

    Time: Day 0 to Day 6 and Day 28

    Description: Safety

    Measure: 12-lead electrocardiogram: PQ-interval

    Time: Day 0 to Day 6 and Day 28

    Description: Safety

    Measure: 12-lead electrocardiogram: QRS-interval

    Time: Day 0 to Day 6 and Day 28

    Description: Safety

    Measure: 12-lead electrocardiogram: QT interval

    Time: Day 0 to Day 6 and Day 28

    Description: Safety

    Measure: 12-lead electrocardiogram: the heart rate-corrected QTc interval (according to Bazett's formula)

    Time: Day 0 to Day 6 and Day 28

    Description: Safety

    Measure: Temperature

    Time: Throughout the Study (Day 0 to Day 28)

    Description: Disease markers

    Measure: D-dimer

    Time: Throughout the Study (Day 0 to Day 28)

    Description: Disease markers

    Measure: Lactate dehydrogenase (LDH)

    Time: Throughout the Study (Day 0 to Day 28)

    Description: Disease markers

    Measure: C-reactive protein

    Time: Throughout the Study (Day 0 to Day 28)

    Description: Disease markers

    Measure: Troponin I

    Time: Throughout the Study (Day 0 to Day 28)

    Description: Disease markers

    Measure: Procalcitonin

    Time: Throughout the Study (Day 0 to Day 28)

    Description: Disease markers

    Measure: Correlation of disease markers to selected clinical outcomes (Clinical improvement accoding to WHO criteria)

    Time: Throughout the Study (Day 0 to Day 28)

    Description: Virologic markers

    Measure: Severe Acute Respiratory Syndrome Coronavirus Virus (SARS-CoV-2) mean viral load - log10 copies in spontaneous sputum and nasopharyngeal swab samples: Decrease of SARS-CoV-2 viral load

    Time: Throughout the Study (Day 0 to Day 28)

    Description: Virologic markers

    Measure: Severe Acute Respiratory Syndrome Coronavirus Virus (SARS-CoV-2) mean viral load - log10 copies in spontaneous sputum and nasopharyngeal swab samples: Time course of SARS-CoV-2 viral load

    Time: Throughout the Study (Day 0 to Day 28)

    Description: Virologic markers

    Measure: Qualitative virologic clearance in spontaneous sputum and nasopharyngeal swab samples (= 2 consecutive negative SARS-CoV-2 reverse transcriptase polymerase chain reaction tests at least 24 hours apart)

    Time: Throughout the Study (Day 0 to Day 28)

    Description: Virologic markers

    Measure: Rate of conversion to a negative SARS-CoV-2 (qualitative) test on Days 6, 14 and 28

    Time: on Days 6, 14 and 28

    Description: Virologic markers

    Measure: Time to conversion to a negative SARS-CoV-2 (qualitative) test

    Time: Throughout the Study (Day 0 to Day 28)

    Description: Biomarkers

    Measure: Interleukin (IL)-17

    Time: Day 0, 6, 14 and Day 28

    Description: Biomarkers

    Measure: Interleukin (IL)-1ß

    Time: Day 0, 6, 14 and Day 28

    Description: Biomarkers

    Measure: Interleukin (IL)-6

    Time: Day 0, 6, 14 and 28

    Description: Biomarkers

    Measure: interferon gamma (IFNγ)

    Time: Day 0, 6, 14 and 28

    Description: Biomarkers

    Measure: tumor necrosis factor alpha

    Time: Day 0, 6, 14 and 28

    Description: Serologic markers

    Measure: Immunoglobulin (Ig)A and IgG antibodies against SARS-CoV-2: • Time to appearance of IgA and/or IgG antibodies

    Time: Day 0, 6, 14 and 28

    Description: Serologic markers

    Measure: Immunoglobulin (Ig)A and IgG antibodies against SARS-CoV-2: • Proportion of patients with IgA and/or IgG antibodies on Days 6, 14, and 28

    Time: Day 0, 6, 14 and 28
    108 Single-center, Phase II, Randomized Double-blind, Placebo-controlled Study of Hydroxychloroquine Compared to Placebo as Treatment for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection

    This study is being done to see if hydroxychloroquine is an effective treatment for COVID-19.

    NCT04379492
    Conditions
    1. COVID-19
    2. COVID19
    3. Sars-CoV2
    4. SARS-Cov-2
    Interventions
    1. Drug: Hydroxychloroquine
    2. Other: Placebo

    Primary Outcomes

    Description: Clinical improvement is defined as a composite endpoint of a two-point clinical improvement on the Ordinal Scale for Clinical Improvement (OSCI). The OSCI is an ordinal scale of 9 severity levels (from 0 to 8) for COVID-19

    Measure: Clinical improvement on the Ordinal Scale for Clinical Improvement (OSCI)

    Time: 14 days

    Description: Clinical improvement is defined as no mechanical ventilation for respiratory failure attributed to SARS-CoV-2 within 14 days of randomization.

    Measure: Number of participants requiring mechanical ventilation for respiratory failure

    Time: 14 days
    109 An International, Multicenter, Randomized, Double-blind, Adaptive Placebo-controlled Study of the Efficacy and Safety of a Single Administration of Olokizumab and RPH-104 With Standard Therapy in Patients With Severe SARS-CoV-2 Infection (COVID-19)

    The primary objective of the study is to evaluate the efficacy and safety of a single dose of RPH-104 (80 mg) or OKZ (64 mg) compared to placebo in addition to standard therapy in patients with severe SARS-CoV-2 infection (COVID-19) at Day 15 of the study

    NCT04380519
    Conditions
    1. COVID-19
    Interventions
    1. Biological: RPH-104 80 mg
    2. Drug: Olokizumab 64 mg
    3. Drug: Placebo
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome

    Primary Outcomes

    Description: Proportion of patients, responded to the study therapy, in each of the treatment groups. The patient can be considered as the therapy responder, in case tocilizumab or sarilumab were not administered and there is an improvement of a clinical status at least by 1 point on a 6-points COVID-19 scale, where 1 point means most favorable outcome, 6 points means most undesirable outcome.

    Measure: Proportion of patients, responded to the study therapy, in each of the treatment groups

    Time: Day 15

    Secondary Outcomes

    Description: Changes of patients' clinical status on a 6 points ordinal scale over time

    Measure: Changes of patients' clinical status on a 6 points ordinal scale over time

    Time: from Day 2 until Day 15, Day 29

    Description: Mortality rate over the follow-up period

    Measure: Mortality rate over the follow-up period

    Time: from Day 1 until Day 29

    Description: Improvement of the patient's clinical status by at least 2 points on a 6-point ordinal scale in the absence of tocilizumab or sarilumab administration.

    Measure: Improvement of the patient's clinical status by at least 2 points on a 6-point ordinal scale in the absence of tocilizumab or sarilumab administration.

    Time: on screening and then from Day 1 until Day 29

    Description: Proportion of patients received tocilizumab or sarilumab due to COVID-19

    Measure: Proportion of patients received tocilizumab or sarilumab due to COVID-19

    Time: from Day 1 until the Day 29

    Other Outcomes

    Description: Proportion of patients having National Early Warning Score 2 (NEWS2) of ≤ 4 maintained for 2 consecutive days

    Measure: Proportion of patients having National Early Warning Score 2 of ≤ 4 maintained for 2 consecutive days

    Time: from day 3 until day 15

    Description: Time to a NEWS2 of ≤ 2 maintained for two consecutive days

    Measure: Time to a NEWS2 of ≤ 2 maintained for two consecutive days

    Time: from day 1 until day 15

    Description: Changes from baseline of cytokine storm surrogate markers: white blood counts, lymphocyte counts, neutrophils counts, CRP, ferritin (if applicable), D-dimer (if applicable)

    Measure: Changes from baseline of cytokine storm surrogate markers: white blood counts, lymphocyte counts, neutrophils counts, C-Reactive protein (CRP), ferritin (if applicable), D-dimer (if applicable)

    Time: Day 2, Day 3, Day5, Day 7, Day 15

    Description: Mortality during an ICU stay, on days 7, 15, 29 of the study

    Measure: Mortality during an ICU stay, on days 7, 15, 29 of the study

    Time: On Day 7, Day 15, Day 29

    Description: Time to increase of oxygen saturation SpO2 ≥ 94% n the absence of oxygen support maintained for two consecutive days

    Measure: Time to increase of oxygen saturation SpO2 ≥ 94% n the absence of oxygen support maintained for two consecutive days

    Time: from Day 2 until Day 15

    Description: Changes of oxygenation index PaO2/FiO2 from baseline (if applicable) during hospitalization period

    Measure: Changes of oxygenation index PaO2/FiO2 from baseline (if applicable) during hospitalization period

    Time: On Day 1 and from Day 2 until Day 15

    Description: Duration of ICU stay measured in days

    Measure: Duration of ICU stay measured in days

    Time: from Day 2 until Day 15

    Description: Changes from baseline (if applicable) in severity of ARDS according to WHO criteria

    Measure: Changes from baseline (if applicable) in severity of Acute Respiratory Distress Syndrome (ARDS) according to World Health Organization (WHO) criteria

    Time: from Day 1 until Day 15

    Description: Duration of mechanical ventilation and EMO (if applicable) measured in days

    Measure: Duration of mechanical ventilation and Extracorporeal Membrane Oxygenation (EMO) (if applicable) measured in days

    Time: from Day 2 until Day 15

    Description: Duration of oxygen support (if applicable) measured in days

    Measure: Duration of oxygen support (if applicable) measured in days

    Time: from Day 1 until Day 15

    Description: Proportion of patients having National Early Warning Score 2 of ≤ 2 maintained for 2 consecutive days

    Measure: Proportion of patients having National Early Warning Score 2 of ≤ 2 maintained for 2 consecutive days

    Time: from day 3 until day 15

    Description: Time to a NEWS2 of ≤ 4 maintained for two consecutive days

    Measure: Time to a NEWS2 of ≤ 4 maintained for two consecutive days

    Time: from day 1 until day 15

    Description: Time to improvement in severity of ARDS according to WHO criteria in one category changing from baseline (if applicable)

    Measure: Time to improvement in severity of ARDS according to WHO criteria in one category changing from baseline (if applicable)

    Time: On Day 1 and from Day 2 until Day 15

    Description: Time to fever resolution i.e. setting of axillary body temperature <38 °C without antipyretics when measured for 2 consecutive days (if applicable)

    Measure: Time to fever resolution i.e. setting of axillary body temperature <38 °C without antipyretics when measured for 2 consecutive days (if applicable)

    Time: from day 1 until day 15

    Description: Time to improvement of clinical status by 1 point on a 6-points COVID-19 scale

    Measure: Time to improvement of clinical status by 1 point on a 6-points COVID-19 scale

    Time: from day 1 until day 29

    Description: Time to improvement of clinical status by 2 points on a 6-points COVID-19 scale

    Measure: Time to improvement of clinical status by 2 points on a 6-points COVID-19 scale

    Time: from day 1 until day 29

    Description: Proportion of patients with the deterioration of clinical status by 1 point on a 6-points COVID-19 scale during the study

    Measure: Proportion of patients with the deterioration of clinical status by 1 point on a 6-points COVID-19 scale during the study

    Time: from Day 1 until Day 29

    Description: Proportion of patients with the deterioration of clinical status by 1 point on a 6-points COVID-19 scale during the study, excluding the patients moved to the category 6, if applicable

    Measure: Proportion of patients with the deterioration of clinical status by 1 point on a 6-points COVID-19 scale during the study, excluding the patients moved to the category 6, if applicable

    Time: from Day 1 until Day 29

    Description: Time to the deterioration of clinical status by 1 point on a 6-points COVID-19 scale during the study (if applicable)

    Measure: Time to the deterioration of clinical status by 1 point on a 6-points COVID-19 scale during the study (if applicable)

    Time: from Day 1 until Day 29
    110 Phase 2, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Sirukumab in Confirmed Severe or Critical COVID-19 Disease

    The purpose of this study is to evaluate the clinical response of sirukumab (administered as a single intravenous dose) plus standard of care (SOC) compared to placebo plus SOC in COVID-19.

    NCT04380961
    Conditions
    1. Severe or Critical Confirmed Coronavirus Disease (COVID)-19
    Interventions
    1. Drug: Sirukumab
    2. Drug: Placebo
    3. Other: Standard of Care (SOC)
    MeSH:Coronavirus Infections

    Primary Outcomes

    Description: Time to improvement is defined as an improvement of at least 2 categories relative to baseline on the 6-point ordinal clinical recovery scale. The 6-point ordinal clinical recovery scale provides 6 mutually exclusive conditions ordered from best to worst, and the score reflects the participant's worst situation on the day assessed. The ordinal clinical recovery scale categories are : not hospitalized (category 1); Hospitalization; not requiring supplemental oxygen (category 2); hospitalized, requiring low flow supplemental oxygen (category 3); hospitalized, on non-invasive pressure ventilation or high flow oxygen devices (category 4); hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO (category 5); death (category 6).

    Measure: Time to Improvement of at Least 2 Categories Relative to Baseline on the 6-Point Ordinal Clinical Recovery Scale

    Time: Up to Day 28

    Secondary Outcomes

    Description: Percentage of participants with an improvement of at Least 2 categories relative to baseline on the 6-point ordinal clinical recovery scale on Day 28 will be reported.

    Measure: Percentage of Participants with an Improvement of at Least 2 Categories Relative to Baseline on the 6-Point Ordinal Clinical Recovery Scale on Day 28

    Time: Day 28

    Description: Percentage of participants with all-cause mortality will be reported.

    Measure: Percentage of Participants with All-cause Mortality

    Time: Up to Day 28

    Description: A SAE is any adverse event (AE) that results in: death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect and is a suspected transmission of any infectious agent via a medicinal product, is medically important.

    Measure: Percentage of Participants with Serious Adverse Events (SAEs)

    Time: Up to Day 28

    Description: An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product.

    Measure: Percentage of Participants with Related Adverse Events

    Time: Up to Day 28

    Description: Percentage of participants with severe or life-threatening, bacterial, invasive fungal, viral or opportunistic infections (other than severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) will be reported.

    Measure: Percentage of Participants with Severe or Life Threatening Bacterial, Invasive Fungal, Viral or Opportunistic Infections

    Time: Up to Day 28

    Description: Percentage of participants with grade 3 (severe) or 4 (life-threatening) neutropenia will be reported.

    Measure: Percentage of Participants with Grade 3 and 4 Neutropenia

    Time: Up to Day 28

    Description: Percentage of participants with grade 3 (severe) or 4 (life-threatening) lymphocytopenia will be reported.

    Measure: Percentage of Participants with Grade 3 and 4 Lymphocytopenia

    Time: Up to Day 28

    Description: Percentage of participants with increased ALT >=3 times ULN combined with increased bilirubin >2 times ULN (up to Day 28) will be reported.

    Measure: Percentage of Participants with Increased Alanine Aminotransferase (ALT) Greater than or equal to 3 Times Upper Limit of Normal (ULN) Combined with Increased Bilirubin > 2 Times ULN

    Time: Up to Day 28

    Description: Time to improvement of at least 1 category relative to baseline on the 6-point ordinal clinical recovery scale will be reported.

    Measure: Time to Improvement of at least 1 Category Relative to Baseline on the 6-Point Ordinal Clinical Recovery Scale

    Time: Up to Day 28

    Description: Percentage of participants with an improvement of at Least 1 category relative to baseline on the 6-point ordinal clinical recovery scale on Day 28 will be reported.

    Measure: Percentage of Participants with an Improvement of at Least 1 Category Relative to Baseline on the 6-Point Ordinal Clinical Recovery Scale on Day 28

    Time: Day 28

    Description: Time from study intervention to end of oxygen supplementation is defined as achieving category 1 or 2 on the 6-point ordinal clinical recovery scale.

    Measure: Time from Study Intervention to end of Oxygen Supplementation

    Time: Up to Day 28

    Description: Time from study intervention to hospital discharge among the surviving participants will be reported.

    Measure: Time from Study Intervention to Hospital Discharge Among the Surviving Participants

    Time: Up to Day 28

    Description: Total length of hospitalization (days from admission to hospital discharge) among the surviving participants will be reported.

    Measure: Total Length of Hospitalization

    Time: Up to Day 28

    Description: Number of Ventilation free Days will be reported.

    Measure: Number of Ventilation Free Days

    Time: Up to Day 28

    Description: Participant's clinical status at Day 7, 14, 21, 28 will be assessed by 6-point ordinal clinical recovery scale.

    Measure: Participant's Clinical Status at Day 7, 14, 21, 28 as Assessed by 6-Point Ordinal Clinical Recovery Scale

    Time: Day 7, 14, 21, 28

    Description: Total time on invasive mechanical ventilation will be reported.

    Measure: Total Time on Invasive Mechanical Ventilation

    Time: Up to Day 28

    Description: Percentage of participants with a worsening of at least 1 category on the 6-point ordinal clinical recovery scale over time (between Day 5 and Day 28) will be reported.

    Measure: Percentage of Participants with a Worse Category Relative to Baseline on the 6-Point Ordinal Clinical Recovery Scale over Time

    Time: From Day 5 up to Day 28

    Description: Percentage participants on ECMO over time will be reported.

    Measure: Percentage of Participants on Extracorporeal Membrane Oxygenation (ECMO) Over Time

    Time: Up to Day 28

    Description: Total time on ECMO will be reported.

    Measure: Total Time on ECMO

    Time: Up to Day 28

    Description: Percentage of alive participants at Day 28, Week 8 and Week 16 will be reported.

    Measure: Percentage of Alive Participants at Day 28, Week 8 and Week 16

    Time: Day 28, Week 8 and Week 16

    Description: Percentage of alive participants that required readmission (if previously discharged) at Week 8 and Week 16 will be reported.

    Measure: Percentage of Alive Participants that Required Readmission at Week 8 and Week 16

    Time: Week 8 and Week 16

    Description: A SAE is any adverse event (AE) that results in: death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect and is a suspected transmission of any infectious agent via a medicinal product, is medically important.

    Measure: Percentage of Participants with Serious Adverse Events (SAEs)

    Time: Up to Week 16
    111 A Randomized Placebo-Controlled Safety and Dose-Finding Study for the Use of the IL-6 Inhibitor Clazakizumab in Patients With Life-threatening COVID-19 Infection

    In this study, the investigators propose to administer clazakizumab to patients with life-threatening Coronavirus Disease 2019 (COVID-19) infection manifest by pulmonary failure and a clinical picture consistent with a cytokine storm syndrome. This is a single-center randomized, double-blind, placebo-controlled trial in which 30 patients will be enrolled and randomly assigned in a 1:1 ratio to two study arms and receive clazakizumab at a dose of 25 mg or placebo.

    NCT04381052
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Clazakizumab
    2. Other: Placebo
    MeSH:Infection

    Primary Outcomes

    Measure: Cumulative incidence of serious adverse events associated with clazakizumab or placebo

    Time: 60 days

    Secondary Outcomes

    Measure: Cumulative Incidence of Intubation

    Time: 14 days

    Measure: Time to Extubation

    Time: 14 days

    Measure: Length of Intensive Care Unit (ICU) stay

    Time: 14 days

    Measure: Number of Patients who Present a Decrease in C-reactive protein (CRP)

    Time: 14 days

    Measure: Number of Patients with Acute Kidney Injury (AKI)

    Time: 14 days

    Measure: Number of Patients with a Need for Renal Replacement Therapy (RRT)

    Time: 14 days

    Measure: Duration of Renal Replacement Therapy (RRT)

    Time: 60 days

    Description: Number of participants alive at day 28.

    Measure: Patient Survival

    Time: 28 days

    Description: Number of participants alive at day 60, end of study.

    Measure: Patient Survival

    Time: 60 days

    Measure: Number of Patients with Hemodialysis

    Time: 60 days

    Measure: Number of Patients with Continuous Renal Replacement Therapies (CRRT)

    Time: 60 days

    Measure: Number of Patients with Peritoneal Dialysis

    Time: 60 days
    112 A Multi-centre, Adaptive, Randomized, Double-blind, Placebo-controlled Comparative Clinical Study of the Safety and Efficacy of Polyoxidonium®, Lyophilizate for Solution for Injections and Topical Application, 6 mg (NPO Petrovax Pharm LLC, Russia) in Patients With Coronavirus Disease (COVID-19).

    The purpose of this study is to demonstrate the superiority of Polyoxidonium®, lyophilizate for solution for injections and topical application, 6 mg over placebo in hospitalized patients with coronavirus disease (COVID-19). This is a multicentre prospective, randomized, double-blind, placebo-controlled, parallel-group phase IIb\IIIa clinical trial.

    NCT04381377
    Conditions
    1. Infections, Coronavirus
    Interventions
    1. Drug: azoximer bromide
    2. Other: Placebo
    MeSH:Coronavirus Infections

    Primary Outcomes

    Description: The primary efficacy outcome will be defined based on the blinded analysis of data of the first 100 patients in the 1st part of the study. There is uncertainty about the clinical course and potential different trajectories according to baseline disease severity, so the day of the primary endpoint may be modified based on a blinded evaluation of the primary efficacy outcome in various days.

    Measure: Clinical status of the patient (according to 7-point ordinal scale)

    Time: Day 15

    Secondary Outcomes

    Description: Time to improvement by one category from admission on the ordinal scale. Clinical status of the patient. Average change in the ordinal scale from baseline.

    Measure: Clinical status of the patient (according to 7-point ordinal scale)

    Time: Clinical status of the patient and the average change in the ordinal scale from baseline, both on days 3, 5, 8, 11, 29.

    Description: The time to discharge or to a NEWS of ≤ 2 and maintained for 24 hours, whichever occurs first. Change in NEWS from baseline.

    Measure: NEWS

    Time: Change in NEWS from baseline on days 3, 5, 8, 11, 15, 29.

    Description: Oxygenation free days. Incidence and duration of new oxygen use.

    Measure: Oxygenation

    Time: Oxygenation free days in the first 28 days (to day 29). Incidence and duration of new oxygen use during the study.

    Description: Ventilator free days. Incidence and duration of new mechanical ventilation use.

    Measure: Mechanical Ventilation

    Time: Ventilator free days in the first 28 days (to day 29). Incidence and duration of new mechanical ventilation use during the trial.

    Measure: Mortality

    Time: 28-day mortality
    113 A Phase II Randomized Double-Blind Placebo-Controlled Clinical Trial Of Hydroxychloroquine For Prophylaxis Against Covid-19 In Patients Receiving Radiotherapy (COVID)

    The researchers are doing this study to find out whether the study drug hydroxychloroquine can prevent infection with the COVID-19 virus, compared with placebo, in people who are receiving radiation therapy for their cancer. The placebo used in this study is a tablet that looks the same as the study drug and is taken in the same way, but it does not contain any active ingredients.

    NCT04381988
    Conditions
    1. COVID-19
    2. Cancer
    Interventions
    1. Drug: Hydroxychloroquine
    2. Other: Placebo
    3. Radiation: Radiation therapy

    Primary Outcomes

    Description: Any patients who are enrolled and subsequently test positive for SARS-CoV-2 by RT-PCR (outside RT-PCR test results allowed) at any point during the 9 weeks following enrollment will be an event that is considered in the 9-week SARS-CoV-2 infection rate primary endpoint.

    Measure: cumulative incidence of SARS-CoV-2 infection

    Time: within 9 weeks from randomization

    Secondary Outcomes

    Description: Patients who are positive for SARS-CoV-2 (as defined above) who develop a new oxygen requirement attributable to COVID-19, tachypnea (RR > 20), or those who require hospitalization due to COVID-19 will be considered to have severe COVID-19.

    Measure: cumulative incidence of severe COVID-19 or death

    Time: within 12 weeks of randomization
    114 A Phase II, Controlled Clinical Study Designed to Evaluate the Effect of ArtemiC in Patients Diagnosed With COVID-19

    Agent Name and Study Duration ArtemiC is a medical spray comprised of Artemisinin (6 mg/ml), Curcumin (20 mg/ml), Frankincense (=Boswellia) (15 mg/ml) and vitamin C (60 mg/ml) in micellar formulation for spray administration. Patients will receive up to 6 mg Artemisinin, 20 mg Curcumin, 15 mg Frankincense and 60 mg vitamin C given daily as an add-on therapy (in addition to standard care) in two divided doses, on Days 1 and 2. Patients will be randomized in a manner of 2:1 for study drug (ArteminC) and Standard of Care to Placebo and Standard of Care. Patient follow-up will last 2 weeks. During this time, patients will be monitored for adverse events. Additional time will be required for follow up (until hospital discharge) in order to check side effects and study drug efficacy. Placebo, composed of the same solvent but without active ingredients, will be given in the placebo group as add-on therapy, 2 times a day, on Days 1 and 2. Overall rationale A preparation of ArtemiC, comprising Artemisinin, Curcumin, Boswellia, and Vitamin C in a nanoparticular formulation, is proposed as a treatment for the disease associated with the novel corona virus SARS-CoV-2. It is readily available in light of its status as a food supplement. This initiative is presented under the urgent circumstances of the fulminant pandemic caused by this lethal disease, which is known as COVID-19 and has spread across the globe causing death and disrupting the normal function of modern society. The grounds for the proposal are rooted in existing knowledge on the components and pharmacological features of this formulation and their relevance to the current understanding of the disease process being addressed. Leading among these considerations are well established immuno-modulatory activities of the active ingredients as established in vitro and in vivo and published over the years. These activities as apparent, for example, in diminishing activity of TNF alpha and IL-6 levels are acknowledged to be relevant to the pathophysiology processes involved in the progressive form of COVID-19. The active agents have in addition prominent anti-oxidant, anti-inflammatory as well as anti-aggregant and anti-microbial activities. Based on these activities and observations in animal models, together with clinical experience of the separate ingredients and in various combinations in other contexts it is proposed to evaluate their effect in the context of COVID-19. Study Purpose This study is designed to evaluate the safety and efficacy of ArtemiC on patients diagnosed with COVID-19. Methodology 50 adult patients who suffer from COVID-19 infection studied in parallel groups treated with active agent or placebo as add on to standard care. Safety will be assessed through collection and analysis of adverse events, blood and urine laboratory assessments and vital signs.

    NCT04382040
    Conditions
    1. COVID-19
    2. Corona Virus Infection
    3. SARS-CoV 2
    4. Coronavirus
    5. Coronavirus Infection
    Interventions
    1. Drug: ArtemiC
    2. Drug: Placebo
    MeSH:Infection Com Communicable Diseases Coronavirus Infections Severe Acute Respiratory Syndrome

    Primary Outcomes

    Description: patient will be assessed using a scoring table for changes in clinical signs

    Measure: Time to clinical improvement, defined as a national Early Warning Score 2 (NEWS2) of Time: 24 hours

    Description: Adverse events caused by the study drug will be assessed

    Measure: Percentage of participants with definite or probable drug related adverse events

    Time: 14 days

    Secondary Outcomes

    Measure: Time to negative COVID-19 PCR

    Time: 14 days

    Measure: Proportion of participants with normalization of fever and oxygen saturation through day 14 since onset of symptoms

    Time: 14 days

    Measure: COVID-19 related survival

    Time: 14 days

    Measure: Incidence and duration of mechanical ventilation

    Time: 14 days

    Measure: Incidence of Intensive Care Init (ICU) stay

    Time: 14 days

    Measure: Duration of ICU stay

    Time: 14 days

    Measure: Duration of time on supplemental oxygen

    Time: 14 days
    115 A Phase 2, Randomized, Double Blind, Placebo-Controlled Study of Zanubrutinib Treatment in Patients Hospitalized for COVID-19 Infection and Pulmonary Distress

    The primary objective of this study is to evaluate if the addition of zanubrutinib to supportive care increases the respiratory failure-free survival rate at Day 28 in participants hospitalized for Corona Virus Disease 2019 (COVID-19) and pulmonary distress.

    NCT04382586
    Conditions
    1. COVID-19 Pulmonary Complications
    2. COVID-19
    Interventions
    1. Drug: Zanubrutinib
    2. Drug: Supportive Care
    3. Drug: Placebo
    MeSH:Infection

    Primary Outcomes

    Description: Respiratory failure-free survival rate 28 is defined as the proportion of patients who have not had respiratory failure nor died <= 28 days from randomization.

    Measure: Respiratory failure-free survival rate at day 28

    Time: 28 Days

    Secondary Outcomes

    Measure: Median reduction in days spent on supplemental oxygen

    Time: Up to 28 Days

    Measure: All-cause mortality

    Time: Up to 28 Days

    Measure: Proportion of participants experiencing respiratory failure or death

    Time: Up to 28 Days

    Measure: Mechanical ventilation-free survival

    Time: Up to 28 Days

    Measure: Days on mechanical ventilation

    Time: Up to 28 Days

    Measure: Duration of hospitalization

    Time: Up to 28 Days

    Measure: Time to discharge

    Time: Up to 28 Days

    Measure: PaO2:FiO2 and/or oxygenation index

    Time: Up to 28 Days

    Description: This scale evaluates the safety and efficacy of investigational therapeutic agents in combination with care for the treatment of hospitalized participants suffering from COVID-19 infections on a scale of scores from 0 to 8, with higher scores indicating higher level of severity of the disease. (0 = No clinical or virological evidence of disease, and 8 = Death)

    Measure: Change from Baseline to Day 14 in WHO - 8 Point Ordinal Scale

    Time: Up to 28 Days
    116 A Prospective, Randomized, Open-label, Interventional Study to Investigate the Efficacy of Complement C5 Inhibition With Zilucoplan® in Improving Oxygenation and short-and Long-term Outcome of COVID-19 Patients With Acute Hypoxic Respiratory Failure

    The study is a randomized controlled, open-label trial comparing subcutaneous Zilucoplan® with standard of care to standard of care alone. In the active group, Zilucoplan® will be administered subcutaneously once daily for 14 days or till discharge from the hospital, whichever comes first. The hypothesis of the proposed intervention is that Zilucoplan® (complement C5 inhibitor) has profound effects on inhibiting acute lung injury post COVID-19, and can promote lung repair mechanisms, that lead to a 25% improvement in lung oxygenation parameters. This hypothesis is based on experiments performed in mice showing that C5a blockade can prevent mortality and prevent ARDS in mice with post-viral acute lung injury. Eligible patients include patients with confirmed COVID-19 infection suffering from hypoxic respiratory failure defined as O2 saturation below 93% on minimal 2l/min O2 therapy and/or ratio PaO2/FiO2 below 350.

    NCT04382755
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Zilucoplan®
    2. Drug: Placebo
    MeSH:Respiratory Insufficiency

    Primary Outcomes

    Description: defined by Pa02/FiO2 ratio while breathing room air, P(Aa)O2 gradient and a/A pO2 ratio

    Measure: Mean change in oxygenation

    Time: at predose, day 6 and day 15 (or at discharge, whichever comes first)

    Description: defined by Pa02/FiO2 ratio while breathing room air, P(Aa)O2 gradient and a/A pO2 ratio

    Measure: Median change in oxygenation

    Time: at predose, day 6 and day 15 (or at discharge, whichever comes first)

    Secondary Outcomes

    Measure: number of AE's (Adverse Events)

    Time: during hospital admission (up to 28 days)

    Measure: number of SAE's (Serious Adverse Events)

    Time: during hospital admission (up to 28 days)]

    Description: 6-point ordinal scale defined as Death Hospitalized, on invasive mechanical ventilation or ECMO; Hospitalized, on non-invasive ventilation Hospitalized, requiring supplemental oxygen Hospitalized, not requiring supplemental oxygen Not hospitalized

    Measure: mean change in 6-point ordinal scale change

    Time: between day 1 and respectively day 6, day 15 (or discharge, whichever comes first) and day 28 (by phone call).

    Description: defined as independence from supplemental oxygen

    Measure: Time since randomization until improvement in oxygenation

    Time: during hospital admission (up to 28 days)

    Description: defined as SpO2 < 93% breathing room air or the dependence on supplemental oxygen

    Measure: Number of days with hypoxia

    Time: during hospital admission (up to 28 days)

    Measure: Number of days of supplemental oxygen use

    Time: during hospital admission (up to 28 days)

    Measure: Time to absence of fever (defined as 37.1°C or more) for more than 48h without antipyretic

    Time: during hospital admission (up to 28 days)

    Description: defined as 37.1°C or more

    Measure: Number of days with fever

    Time: during hospital admission (up to 28 days)

    Measure: Mean change in CRP levels between day 1 and day 6

    Time: day 1, day 6

    Measure: Mean change in CRP levels between day 1 and day 15 (or discharge whichever comes first)

    Time: day 1, day 15

    Measure: Mean change in ferritin levels between day 1 and day 6

    Time: day 1, day 6

    Measure: Mean change in ferritin levels between day 1 and day 15 (or discharge, whichever comes first)

    Time: day 1, day 15

    Measure: Incidence of AE's

    Time: during hospital admission (up to 28 days)

    Measure: Incidence of SAE's

    Time: at 10-20 weeks follow-up

    Measure: Incidence of SUSAR's (Suspected Unexpected Serious Adverse Reaction)

    Time: during hospital admission (up to 28 days)

    Measure: Incidence of SAR's (Serious Adverse Reaction)

    Time: during hospital admission (up to 28 days)

    Measure: Duration of hospital stay

    Time: during hospital admission (up to 28 days)

    Measure: Duration of hospital stay in survivors

    Time: during hospital admission (up to 28 days)

    Description: SOFA score: 0 (best) - 24 (worse)

    Measure: Mean change of SOFA score between day 1 and day 6 (or on discharge, whichever is first)

    Time: day 1, day 6 or on discharge, whichever is first

    Description: SOFA score: 0 (best) - 24 (worse)

    Measure: Mean change of SOFA score between day 1 and day 15 or on discharge, whichever is first)

    Time: day 1, day 15 or on discharge, whichever is first

    Description: 6-point ordinal scale: Death Hospitalized, on invasive mechanical ventilation or ECMO; Hospitalized, on non-invasive ventilation or high flow oxygen devices; Hospitalized, requiring supplemental oxygen Hospitalized, not requiring supplemental oxygen Not hospitalized

    Measure: Percentage of patients reporting each severity rating on a 6-point ordinal scale at randomization, day 6 and 15 (or discharge, whichever comes first) and day 28 (phone call)

    Time: day 1, day 6, day 15 (or discharge, whichever comes first)

    Description: 6-point ordinal scale: Death Hospitalized, on invasive mechanical ventilation or ECMO; Hospitalized, on non-invasive ventilation or high flow oxygen devices; Hospitalized, requiring supplemental oxygen Hospitalized, not requiring supplemental oxygen Not hospitalized

    Measure: 6-point Ordinal Scale at 6 and 15 days (or discharge whichever comes first) and day 28 (phone call), in relation to serum D-dimers and complement C5a levels at randomization

    Time: day 1, day 6, day 15 (or discharge, whichever comes first)

    Measure: Incidence of nosocomial bacterial or invasive fungal infection for 28 days (phone call) after enrolment in trial

    Time: day 28

    Measure: Time since randomization until first use of high-flow oxygen devices in non-ventilated patients

    Time: during hospital admission (up to 28 days)

    Measure: Time since randomization until first use of non-invasive mechanical ventilation in non-ventilated patients

    Time: during hospital admission (up to 28 days)

    Measure: Time since randomization until first use of invasive mechanical ventilation in non-ventilated patients

    Time: during hospital admission (up to 28 days)

    Measure: Number of ventilator-free days

    Time: day 1, day 28 or discharge whichever comes first

    Measure: Duration of invasive and non-invasive mechanical ventilation in ventilated patients

    Time: during hospital admission (up to 28 days)

    Measure: Duration of ICU stay in patients that enrolled in trial on invasive or non-invasive mechanical ventilation for less than 24h prior to or after randomization

    Time: during hospital admission (up to 28 days)

    Description: criteria-defined ARDS criteria-defined ARDS according to the adapted Berlin criteria as follow: within 1 week of a known Clinical insult or new or worsening respiratory symptoms bilateral infiltrates not supposed to be of cardiac origin or fluid overload PaO2/FiO2 < 300 mmHg

    Measure: Time since randomization to progression to ARDS (Acute Respiratory Distress Syndrome)

    Time: during hospital admission (up to 28 days)

    Measure: Time to progression to ARDS in ventilated patients according to D-dimers at randomization

    Time: during hospital admission (up to 28 days)

    Measure: Time to progression to ARDS in ventilated patients according to complement C5a at randomization

    Time: during hospital admission (up to 28 days)

    Measure: All-cause mortality rate (excluding group that entered during ventilation)

    Time: at day 28

    Measure: All-cause mortality rate (including group that entered during ventilation)

    Time: at day 28

    Measure: Percentage of patients in clinical status on 6-point Ordinal Scale

    Time: at 12-22 weeks follow-up

    Measure: Incidence of lung function abnormalities at follow up

    Time: at 12-22 weeks follow-up

    Measure: Incidence of lung fibrosis on chest CT scan at follow up

    Time: at 12-22 weeks follow-up

    Measure: All cause mortality for the entire study population

    Time: at follow up 12-22 weeks
    117 Randomized, Double-blind, Placebo-controlled Clinical Trial of Convalescent Plasma for the Treatment of COVID-19 Pneumonia With Severity Criteria

    A multicenter randomized, double-blind, placebo-controlled clinical trial of Convalescent SARS COVID-19 plasma versus Placebo to evaluate the effect between arms on an ordinal score of six mutually exclusive categories of clinical status at day 30 after study initiation.

    NCT04383535
    Conditions
    1. SARS Virus
    2. SARS-CoV-2
    3. COVID-19
    Interventions
    1. Other: Convalescent SARS COVID-19 plasma
    2. Other: Placebo
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Ordinal outcome with six mutually exclusive categories to describe the patient's clinical status during follow-up. The six categories are: (1) death; (2) in intensive care; (3) hospitalised but requiring supplemental oxygen; (4) hospitalised and not requiring supplemental oxygen; (5) discharged but unable to resume normal activities; or (6) discharged with full resumption of normal activities.

    Measure: Clinical status during follow-up at 30th day

    Time: 30th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)

    Secondary Outcomes

    Description: Ordinal outcome with six mutually exclusive categories to describe the patient's clinical status during follow-up. The six categories are: (1) death; (2) in intensive care; (3) hospitalised but requiring supplemental oxygen; (4) hospitalised and not requiring supplemental oxygen; (5) discharged but unable to resume normal activities; or (6) discharged with full resumption of normal activities.

    Measure: Clinical status during follow-up at 7th day

    Time: 7th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)

    Description: Ordinal outcome with six mutually exclusive categories to describe the patient's clinical status during follow-up. The six categories are: (1) death; (2) in intensive care; (3) hospitalised but requiring supplemental oxygen; (4) hospitalised and not requiring supplemental oxygen; (5) discharged but unable to resume normal activities; or (6) discharged with full resumption of normal activities.

    Measure: Clinical status during follow-up at 14th day

    Time: 14th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)

    Description: Hospital discharge or intrahospital death

    Measure: Time until hospital discharge (days).

    Time: Whenever the patient is discharge from the hospital or die without discharge, through study completion, an average of 14 days from admission

    Description: ICU discharge or ICU death

    Measure: Time until discharge from ICU (days)

    Time: Whenever the patient is discharge from ICU or die in ICU, through study completion, an average of 10 days from admission

    Description: Death and time to death

    Measure: Time to death

    Time: In a 30 days follow up period

    Description: Time until complete functional recovery (according to basal status).

    Measure: Time until complete functional recovery

    Time: Whenever the patient returns to basal functional status until 1 month from discharge

    Description: Percentage of participants with adverse events / serious adverse events

    Measure: Percentage of participants with adverse events / serious adverse events

    Time: In a 30 days follow up period

    Description: Percentage of patients with negative SARS-CoV-3 PCR

    Measure: Percentage of patients with negative SARS-CoV-3 PCR at Day 14th

    Time: 14th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)

    Description: D Dimer plasma concentration

    Measure: D Dimer plasma concentration at Day 14th

    Time: 14th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)

    Description: Ferritin plasma concentration

    Measure: Ferritin plasma concentration at Day 13th

    Time: 13th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)

    Description: Plasma concentration of neutralizing antibodies

    Measure: Plasma concentration of neutralizing antibodies at Day 2nd

    Time: 2nd Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)

    Description: Plasma concentration of neutralizing antibodies

    Measure: Plasma concentration of neutralizing antibodies at Day 7th

    Time: 7th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)

    Description: Post-transfusion adverse reactions between study groups

    Measure: Post-transfusion adverse reactions

    Time: In a 30 days follow up period
    118 A Phase I/II Randomized, Double Blinded, Placebo Trial to Evaluate the Safety and Potential Efficacy of Intravenous Infusion of Zofin for the Treatment of Moderate to SARS Related to COVID-19 Infection vs Placebo

    The purpose of this research study is to evaluate the safety and potential efficacy of Intravenous Infusion of Zofin for treatment of moderate to severe Acute Respiratory Syndrome (SARS) related to COVID-19 infection vs Placebo.

    NCT04384445
    Conditions
    1. Corona Virus Infection
    2. COVID-19
    3. SARS
    4. Acute Respiratory Distress Syndrome
    Interventions
    1. Biological: Zofin
    2. Other: Placebo
    MeSH:Infection Coronavirus Infections Severe Acute Respiratory Syndrome Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury

    Primary Outcomes

    Description: Safety will be defined by the incidence of any infusion associated adverse events as assessed by treating physician

    Measure: Incidence of any infusion associated adverse events

    Time: 60 Days

    Description: Safety will be defined by the incidence of severe adverse events as assessed by treating physician

    Measure: Incidence of Severe Adverse Events

    Time: 60 Days

    Secondary Outcomes

    Description: Measured at day 60 or at hospital discharge, whichever comes first.

    Measure: All Cause Mortality

    Time: 60 Days

    Description: Number of participants that are alive at 60 days post first infusion follow up

    Measure: Survival Rate

    Time: 60 Days

    Description: Measure IL-6, TNF-alpha from serum of blood samples

    Measure: Cytokine Levels

    Time: Day 0, Day 4, Day 8, Day14, Day 21, Day 28

    Description: D-dimer from serum of blood samples methodology using blood samples or nose / throat swab

    Measure: D-dimer Levels

    Time: Day 0, Day 4, Day 8, Day14, Day 21, Day 28

    Description: CRP from serum of blood samples

    Measure: C-reactive protein Levels

    Time: Day 0, Day 4, Day 8, Day14, Day 21, Day 28

    Description: Viral load by real time RT methodology using blood samples or nose / throat swab

    Measure: Quantification of the COVID-19

    Time: Day 0, Day 4, Day 8

    Description: Improved organ failure within 30 days, including cardiovascular system, coagulation system, liver, kidney and other extra-pulmonary organs using Sequential Organ Failure Assessment (SOFA) score.

    Measure: Improved Organ Failure

    Time: Day 30

    Description: Chest imaging changes for 30 days compare to placebo: 1) Ground-glass opacity, - 2) Local patchy shadowing, 3) Bilateral patchy shadowing, and 4) Interstitial abnormalities.

    Measure: Chest Imaging Changes

    Time: Day o, Day 30
    119 A Randomised Double-blind Placebo-controlled Trial to Determine the Safety and Efficacy of Inhaled SNG001 (IFN-β1a for Nebulisation) for the Treatment of Patients With Confirmed SARS-CoV-2 Infection

    SNG001 is an inhaled drug that contains a antiviral protein called interferon beta (IFN-β). IFN-β in produced in the lungs during viral lung infections. It has been shown that older people and people with some chronic diseases have an IFN-β deficiency. Many viruses inhibit IFN-β as part of their strategy to evade the immune system. Addition of IFN-β in vitro protects lung cells from viral infection. IFN-β protects cells against the MERS and SARS coronaviruses (close relatives of SARS-CoV-2, the virus that causes COVID-19). SNG001 is an inhaled formulation of interferon beta-1a it is currently in Phase II clinical trials for COPD patients. Synairgen has conducted randomised placebo controlled clinical trials of SNG001 involving >200 asthma and COPD patients. These trials have shown that SNG001 has: - been well tolerated during virus infections - enhanced antiviral activity in the lungs (measured in sputum and blood samples) - provided significant lung function benefit over placebo in asthma in two Phase II trials. Synairgen believes SNG001 could help prevent worsening or accelerate recovery of severe lower respiratory tract illness in COVID-19 patients. Patients who are in hospital or non-hospitalised but are a high risk groups (e.g. elderly or diabetics) will be invited to take part in the trial. The patient would receive either SNG001 or placebo once daily for 14 days. The severity of the patients condition would be recorded on a scale developed by the World Health Organisation and the patient would be asked questions about their breathlessness, cough and sputum every day, as well as assess their general medical condition and safety. The study will start as a Pilot phase where 100 patients will be randomised in the hospital setting and a 120 patients randomised in the home setting. Once each of the Pilot phases are complete, a Pivotal phase will be conducted. It is estimated that the size of each of the Pivotal phases (hospital and home) will be around 100 to 300 patients per arm. The actual number will be determined after the data review at the end of each of the Pilot phases. If SNG001 proves to be beneficial it would be a major breakthrough for the treatment of COVID-19.

    NCT04385095
    Conditions
    1. SARS-CoV-2
    Interventions
    1. Drug: SNG001
    2. Drug: Placebo
    MeSH:Infection

    Primary Outcomes

    Description: Change in condition measured using the Ordinal Scale for Clinical Improvement during the dosing period - minimum of 0 (patient is well) to a maximum of 8 (death)

    Measure: Ordinal Scale for Clinical Improvement

    Time: Day 1 to Days 15 and 28

    Secondary Outcomes

    Description: Progression to pneumonia as diagnosed by chest x-ray, if no pneumonia is present at time of enrolment

    Measure: Progression to pneumonia (hospital setting only)

    Time: Day 2 to Day 28

    Description: Evolution of pneumonia, as diagnosed by chest x-ray, if pneumonia is present at time of enrolment

    Measure: Progression to pneumonia (hospital setting only)

    Time: Day 1 to Day 28

    Description: Time to clinical improvement

    Measure: Time to clinical improvement (hospital setting only)

    Time: Time to hospital discharge OR Time to NEWS2 of ≤ 2 maintained for 24 hours

    Description: NEWS2 assessment of acute-illness severity on a scale of 0 ( being well) up to 24 (requiring emergency response)

    Measure: National Early Warning Score 2 (NEWS2) assessment of acute-illness severity (hospital setting only)

    Time: Day 1 to Day 28

    Description: Changes in daily breathlessness, cough and sputum scale (BCSS) on a scale of 0 (no symptoms) up to 4 (severe symptoms)

    Measure: Changes in daily breathlessness, cough and sputum scale (BCSS)

    Time: Day 1 to Day 28

    Description: Looking at blood pressure measured in mmHg

    Measure: Safety and tolerability - blood pressure II. Viral load

    Time: Day 1 to Day 28

    Description: Looking at heart rate measured in beats per minute

    Measure: Safety and tolerability - heart rate II. Viral load

    Time: Day 1 to Day 28

    Description: Looking at temperature measured in degrees Celsius

    Measure: Safety and tolerability - temperature II. Viral load

    Time: Day 1 to Day 28

    Description: Looking at respiratory rate measure in breaths per minute

    Measure: Safety and tolerability - respiratory rate II. Viral load

    Time: Day 1 to Day 28

    Description: Looking at oxygen levels measured in a %

    Measure: Safety and tolerability - oxygen saturation II. Viral load

    Time: Day 1 to Day 28

    Description: Looking at adverse events (numbers and terms)

    Measure: Safety and tolerability - adverse events II. Viral load

    Time: Day 1 to Day 28

    Description: Looking at concomitant medications given during treatment

    Measure: Safety and tolerability - concomitant medications II. Viral load

    Time: Day 1 to Day 28

    Description: Temperature ≤37.8 °C AND COVID-19 symptoms (breathing, cough, sputum, muscle aches, headache, fatigue, sore throat, loss or change to sense of smell and taste, rhinorrhoea and anorexia) all rated as absent or mild

    Measure: Time to clinical improvement (home setting only)

    Time: Day 1 to Day 28

    Description: Time to improvement of COVID-19 symptoms (fever, breathing, cough, sputum, muscle aches, headache, fatigue, sore throat, loss or change to sense of smell and/or taste, rhinorrhoea and anorexia)

    Measure: Time to improvement of COVID-19 symptoms (home setting only).

    Time: Day 1 to Day 28

    Description: Time to self-reported recover

    Measure: Time to self-reported recovery (home setting only)

    Time: Day 2 to Day 16

    Description: Self-reported daily rating of overall feeling of wellness

    Measure: Self-reported daily rating of overall feeling of wellness (home setting only).

    Time: Day 1 to Day 28

    Description: Quality of life measured using EQ-5D-5L

    Measure: Quality of life measured using EQ-5D-5L (home setting only).

    Time: Day 1 to Day 28

    Description: Time to virus clearance and viral load

    Measure: Virus clearance/load (if samples are available)

    Time: Day 1 to Day 28

    Description: Blood and sputum biomarkers

    Measure: Blood and sputum biomarkers (if samples are available).

    Time: Day 1 to Day 28

    Description: Contact with health services

    Measure: Contact with health services (home setting only

    Time: Day 1 to Day 28

    Description: Consumption of antibiotics

    Measure: Consumption of antibiotics (home setting only

    Time: Day 1 to Day 28
    120 A Phase III, Double-blind, Randomized, Placebo-controlled Multicentre Clinical Trial to Assess the Efficacy and Safety of VPM1002 in Reducing Healthcare Professionals' Absenteeism in the SARS-CoV-2 Pandemic by Modulating the Immune System

    The aim of this study is to investigate whether vaccination of healthcare professionals with VPM1002 could reduce the number of days absent from work due to respiratory disease (with or without documented SARS-CoV-2 infection). VPM1002 is a vaccine that is a further development of the old Bacillus Calmette-Guérin (BCG) vaccine, which has been used successfully as a vaccine against tuberculosis for about 100 years, especially in developing countries. VPM1002 has been shown in various clinical studies to be significantly safer than the BCG vaccine. VPM1002 strengthens the body's immune defence and vaccination with BCG reduces the frequency of respiratory diseases. It is therefore assumed that a VPM1002 vaccination could also provide (partial) protection against COVID-19 disease caused by the new corona virus "SARS-CoV 2". A total of 1200 health care professionals (doctors, nurses and paramedical staff) with high expected exposure to SARSCoV-2 infected patients will receive a single dose of either VPM1002 or Placebo. All subjects will be requested to enter data regarding absenteeism, adverse events / serious adverse events, hospitalizations, intensive care unit admissions into an online questionnaire.

    NCT04387409
    Conditions
    1. Infection, Respiratory Tract
    Interventions
    1. Biological: VPM1002
    2. Biological: Placebo
    MeSH:Respiratory Tract Infections
    HPO:Respiratory tract infection

    Primary Outcomes

    Measure: Number of days absent from work due to respiratory disease (with or without documented SARS-CoV-2 infection)

    Time: From day 0 to day 240

    Secondary Outcomes

    Measure: Cumulative incidence of documented SARS-CoV-2 infection

    Time: From day 0 to day 240

    Measure: Number of days absent from work due to documented SARS-CoV-2 infection

    Time: From day 0 to day 240

    Measure: Number of days absent from work due to exposure to person with documented SARS-CoV-2 infection

    Time: From day 0 to day 240

    Measure: Number of days absent from work due to symptoms of respiratory disease, documented SARS-CoV-2 infection, or fever (≥ 38 °C)

    Time: From day 0 to day 240

    Measure: Number of days of self-reported fever (≥ 38 °C)

    Time: From day 0 to day 240

    Measure: Number of days of self-reported acute respiratory symptoms

    Time: From day 0 to day 240

    Measure: Cumulative incidence of self-reported acute respiratory symptoms

    Time: From day 0 to day 240

    Measure: Cumulative incidence of death for any reason

    Time: From day 0 to day 240

    Measure: Cumulative incidence of death due to documented SARS-CoV-2 infection

    Time: From day 0 to day 240

    Measure: Cumulative incidence of ICU admission for any reason

    Time: From day 0 to day 240

    Measure: Cumulative incidence of ICU admission due to documented SARS-CoV-2 infection

    Time: From day 0 to day 240

    Measure: Cumulative incidence of hospital admission for any reason

    Time: From day 0 to day 240

    Measure: Cumulative incidence of hospital admission due to documented SARS-CoV-2 infection

    Time: From day 0 to day 240
    121 A Randomized, Double-Blind, Placebo-Controlled, Multicenter, Parallel-Group Phase II Study to Evaluate the Efficacy and Safety of Intramuscular Injections of PLX PAD for the Treatment of Severe COVID-19

    This clinical trial will examine if a new treatment of Mesenchymal-like Adherent stromal Cells (called PLX-PAD) can help patients intubated and mechanically ventilated due to COVID-19 to recover more quickly with less complications.

    NCT04389450
    Conditions
    1. COVID
    2. ARDS
    Interventions
    1. Biological: PLX-PAD
    2. Biological: Placebo

    Primary Outcomes

    Measure: Number of ventilator free days

    Time: 28 days

    Secondary Outcomes

    Measure: All-cause mortality

    Time: 28 days

    Measure: Duration of mechanical ventilation

    Time: 8 weeks
    122 A Phase 2/3 Study to Evaluate the Safety and Efficacy of Dociparstat Sodium for the Treatment of Severe COVID-19 in Adults at High Risk of Respiratory Failure

    A randomized, double-blind, placebo-controlled Phase 2/3 study to evaluate the safety and efficacy of DSTAT in patients with Acute Lung Injury (ALI) due to COVID-19. This study is designed to determine if DSTAT can accelerate recovery and prevent progression to mechanical ventilation in patients severely affected by COVID-19.

    NCT04389840
    Conditions
    1. COVID-19
    2. Acute Lung Injury
    3. SARS-CoV-2
    Interventions
    1. Drug: Dociparastat sodium
    2. Drug: Placebo
    MeSH:Respiratory Insufficiency Lung Injury Acute Lung Injury Respiratory Distress Syndrome, Adult

    Primary Outcomes

    Description: Alive and free of invasive mechanical ventilation

    Measure: Proportion of participants who are alive and free of invasive mechanical ventilation

    Time: Through Day 28

    Secondary Outcomes

    Description: Time to all-cause mortality

    Measure: All-cause mortality

    Time: Through Day 28
    123 Pilot Study to Evaluate the Potential of Ivermectin to Reduce COVID-19 Transmission

    SAINT is a double-blind, randomized controlled trial with two parallel groups that evaluates the efficacy of ivermectin in reducing nasal viral carriage at seven days after treatment in SARS-CoV-2 infected patients who are at low risk of progression to severe disease. The trial is currently planned at a single center in Navarra.

    NCT04390022
    Conditions
    1. Covid-19
    2. Coronavirus Infection
    3. SARS-CoV-2 Infection
    Interventions
    1. Drug: Ivermectin
    2. Drug: Placebo
    MeSH:Infection Communicable Diseases Coronavirus Infections Severe Acute Respiratory Syndrome

    Primary Outcomes

    Description: Proportion of patients with a positive SARS-CoV-2 PCR from a nasopharyngeal swab at day 7 post-treatment. PCRs were performed using two target genes (E and N).

    Measure: Proportion of Patients With a Positive SARS-CoV-2 PCR

    Time: 7 days post-treatment

    Secondary Outcomes

    Description: Quantitative and semi-quantitative PCR in nasopharyngeal swab. PCRs were performed using two target genes (E and N).

    Measure: Median Viral Load

    Time: Baseline and on days 4, 7, 14 and 21

    Description: Proportion of patients with fever and cough

    Measure: Fever and Cough Progression

    Time: Days 4, 7, 14 and 21

    Description: Proportion of participants with positive IgG at day 21

    Measure: Seroconversion at Day 21

    Time: Up to and including day 21

    Description: Proportion of drug-related adverse events

    Measure: Proportion of Drug-related Adverse Events

    Time: 7 days post treatment

    Description: Levels in median fluorescence intensity (MFI) of IgG, IgM and IgA against the receptor-binding domain of the spike glycoprotein of SARS-CoV-2 in plasma, measured by a Luminex assay. [Results not yet available]

    Measure: Levels of IgG, IgM and IgA

    Time: Up to and including day 28

    Description: Frequency (% over total PBMC) of innate immune cells (myeloid and plasmacytoid dendritic cells, NK cell, classical, intermediate and pro-inflammatory macrophages) measured in cryopreserved PBMC by flow cytometry. [Results not yet available]

    Measure: Frequency of Innate Immune Cells

    Time: Up to and including day 7

    Description: Frequency of CD4+ T and CD8+ T cells (% over total CD4+T and CD8+ T) expressing any functional marker upon in vitro stimulation of PBMC with SARS-CoV-2 peptides, measured by flow cytometry. [Results not yet available]

    Measure: Frequency SARS-CoV-2-specific CD4+ T and and CD8+ T Cells

    Time: Up to and including day 7

    Description: Concentration (all in pg/mL) of epidermal growth factor (EGF), fibroblast growth factor (FGF), granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), tumour necrosis factor (TNF), interferon (IFN)-α, IFN-γ, interleukin (IL)-1RA, IL-1β, IL-2, IL-2R, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12(p40/p70), IL-13, IL-15, IL-17, IFN-γ induced protein (IP-10), monocyte chemoattractant protein (MCP-1), monokine induced by IFN-γ (MIG), macrophage inflammatory protein (MIP)-1α, MIP-1β in plasma measured by a Luminex assay using a commercially available kit (Cytokine Human Magnetic 30-Plex Panel from ThermoFisher). [Results not yet available]

    Measure: Results From Cytokine Human Magnetic 30-Plex Panel

    Time: Up to and including day 28
    124 A Prospective, Double-blind, Randomized, Parallel, Placebo-controlled Pilot Clinical Trial for the Evaluation of the Efficacy and Safety of Two Doses of WJ-MSC in Patients With Acute Respiratory Distress Syndrome Secondary to Infection by COVID-19

    Randomized, double-blind, parallel, two-arms clinical trial to assess the efficacy and safety of 2 infusions of Wharton-Jelly mesenchymal stromal cells (day 1 and day 3, endovenously at 1E6cells/Kg per dose) in patients with moderate acute respiratory distress syndrome (ARDS) secondary to SARS-CoV-2 infection. Follow-up will be established on days 3, 5, 7, 14, 21, and 28. Long term follow-up will be performed at 3, 6 and 12 months.

    NCT04390139
    Conditions
    1. COVID-19
    2. SARS-CoV 2
    3. Adult Respiratory Distress Syndrome
    Interventions
    1. Drug: XCEL-UMC-BETA
    2. Other: Placebo
    MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

    Primary Outcomes

    Description: Number of patients who died, by treatment group

    Measure: All-cause mortality at day 28

    Time: Day 28

    Secondary Outcomes

    Description: Number of patients with treatment-emergent adverse events, by treatment group

    Measure: Safety of WJ-MSC

    Time: Day 28

    Description: Number of patients who, after the start of treatment, required rescue medication, by treatment group

    Measure: Need for treatment with rescue medication

    Time: Day 28

    Description: Number of days that the patient requires invasive mechanical ventilation from the start of treatment to day +28, by treatment group

    Measure: Need and duration of mechanical ventilation

    Time: Day 28

    Description: Days after treatment in which the patient remains alive and free of invasive mechanical ventilation, per treatment group.

    Measure: Ventilator free days

    Time: Day 28

    Description: Variation of the oxygenation index (PaO2 / FiO2) with respect to the baseline value, by treatment group.

    Measure: Evolution of PaO2 / FiO2 ratio

    Time: Day 28

    Description: Variation of the score of the Sequential Organ Failure Assessment (SOFA) Index with respect to the baseline value, by treatment group.

    Measure: Evolution of the SOFA index

    Time: Day 28

    Description: Variation of Acute Physiology and Chronic Health disease Classification System II (APACHE II) score, by treatment group.

    Measure: Evolution of the APACHE II score

    Time: Day 28

    Description: Days of stay in the ICU from the day of admission until discharge to day 28, or date of death if earlier, by treatment group.

    Measure: Duration of hospitalization

    Time: Day 28

    Description: Variation in the count and percentage of leukocytes and neutrophils, by treatment group.

    Measure: Evolution of markers of immune response (leucocyte count, neutrophils)

    Time: Day 28

    Description: Feasibility will be evaluated by the time elapsed from the request of the treatment by the hospital center until the delivery date

    Measure: Feasibility of WJ-MSC administration

    Time: Day 28

    Description: Feasibility will be evaluated by the number of patients treated within 2 days of the request for treatment.

    Measure: Feasibility of WJ-MSC administration

    Time: Day 28

    Description: Variation in the values of the biomarker, by treatment group.

    Measure: Evolution of disease biomarker: polymerase chain reaction (RT-PCR)

    Time: Day 28

    Description: Variation in the values of the biomarker, by treatment group.

    Measure: Evolution of disease biomarker: lactate dehydrogenase (LDH)

    Time: Day 28

    Description: Variation in the values of the biomarker, by treatment group.

    Measure: Evolution of disease biomarker: D-dimer

    Time: Day 28

    Description: Variation in the values of the biomarker, by treatment group.

    Measure: Evolution of disease biomarker: Ferritin

    Time: Day 28

    Other Outcomes

    Description: Blood sample analysis

    Measure: Analysis of subpopulations of lymphocytes and immunoglobulins

    Time: Day 28

    Description: In vitro response will be assessed using commercial viral antigens (Miltenyi Biotech)

    Measure: Evaluation of the in vitro response of the receptor lymphocytes

    Time: Day 28

    Description: Reactivity will be assessed using ELISPOT

    Measure: Study of reactivity against SARS-CoV-2 peptides

    Time: Day 28

    Description: Blood sample analysis

    Measure: Immunophenotypic study of memory cells in response to SARS-CoV-2 peptides

    Time: Day 28

    Description: Blood sample analysis for the patient's genomic sequencing

    Measure: Genetic variability of patient's genotype in response to treatment

    Time: Day 28

    Description: Genomic sequencing of the SARS-CoV-2 in a nasopharyngeal sample

    Measure: Genetic variability of the SARS-CoV-2 genotype in response to treatment

    Time: Day 28
    125 A Phase 2 Study to Evaluate LB1148 for the Treatment of Pulmonary Dysfunction Associated With COVID-19 Pneumonia

    This is a Phase 2, proof of concept, randomized, placebo-controlled, multicenter study to evaluate the ability of LB1148 to attenuate pulmonary dysfunction associated with COVID-19 pneumonia. The primary objective of this study is to determine if enteral administration of LB1148 will effect disease progression in hospitalized patients with moderate to severe COVID-19 via measurement of the proportion of subjects alive and free of respiratory failure at Day 28.

    NCT04390217
    Conditions
    1. COVID-19
    2. Coronavirus Disease 2019
    3. Covid19
    4. COVID-19 Pneumonia
    Interventions
    1. Drug: LB1148
    2. Drug: Placebo
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: The proportion of subjects alive and free of respiratory failure at Day 28.

    Measure: Effect of LB1148 on disease progression via measurement of the proportion of patients who are alive and free of respiratory failure.

    Time: 28 Days

    Secondary Outcomes

    Description: Number and proportion of patients with improved clinical status as assessed by a 9-point ordinal scale of disease severity at fixed timepoints (Days 3, 5, 7, 8, 10, 14, 28)

    Measure: Clinical status at fixed time points

    Time: Measured at 3, 5, 7, 8, 10, 14 and 28 Days

    Description: Length of hospital stay (live discharge)

    Measure: Duration of hospital stay

    Time: 28 Days

    Description: Number and proportion of patients requiring admission to the intensive care unit

    Measure: Measurement of the number and proportion of patients requiring admission to the intensive care unit (ICU) during hospitalization

    Time: 28 Days

    Description: Length of ICU stay

    Measure: Duration of ICU stay

    Time: 28 Days

    Description: Number and proportion of patients requiring invasive mechanical ventilation

    Measure: Invasive mechanical ventilation requirements

    Time: 28 Days

    Description: Length of time patients require invasive mechanical ventilation

    Measure: Duration of invasive mechanical ventilation

    Time: 28 Days

    Description: The number and proportion of patients deceased at Day 28

    Measure: All-cause 28-day mortality

    Time: 28 Days

    Description: The incidence and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs)

    Measure: Safety and tolerability of LB1148

    Time: 28 Days
    126 Efficacy and Safety of Hydroxychloroquine and Ivermectin in Hospitalized no Critical Patients Secondary to COVID-19 Infection: Randomized Controlled Trial

    Background: In December 2019, patients with pneumonia secondary to a new subtype of Coronavirus (COVID-19) were identified in China. In a few weeks the virus spread and cases started practically all over the world. In February 2020, the WHO declared a pandemic. Severe symptoms have been found in patients mainly with comorbidities and over 50 years of age. At this time there is no proven therapeutic alternative. In vitro studies and observational experiences showed that antimalarial drugs (Chloroquine and hydroxychloroquine) had antiviral activity and increased viral clearance. Ivermectin, on the other hand, has been shown in vitro to reduce viral replication and in an observational cohort, greater viral clearance with promising clinical results. So far there is no standard of treatment and clinical trials are needed to find effective treatment alternatives. Objective: To evaluate the safety and efficacy of treatment with hydroxychloroquine and ivermectin for serious COVID-19 infections in no critical hospitalized patients. Material and methods: Randomized controlled trial of patients diagnosed with respiratory infection by COVID-19, who present criteria for hospitalization. Randomization will be performed to receive hydroxychloroquine at a dose of 400 mg every 12 hours for one day and then 200 mg every 12 hours, to complete a 5-day treatment schedule. Group 2: Ivermectin 12 mg every 24 hours for one day (less than 80 kg) or Ivermectin 18 mg every 24 hours for one day (greater than 80 kg) + placebo until the fifth day. Group 3: Placebo. Prior to randomization, the risk of cardiovascular complications determined by corrected QT interval, related to hydroxychloroquine intake will be assessed. If the patient is at high risk, the allocation will be to ivermectin only or to placebo in an independent randomization, if the risk is low, any of the three groups could be assigned. Outcomes: The primary outcome will be discharge from hospital for improvement. The safety outcomes will be requirement of mechanical intubation, septic shock or death. Viral clearance will also be evaluated by means of PCR, which will be taken on the 5th day after admission, day 14 and 21.

    NCT04391127
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Hydroxychloroquine
    2. Drug: Ivermectin
    3. Drug: Placebo
    MeSH:Infection

    Primary Outcomes

    Description: Days from admission as a suspected case of COVID with hospitalization criteria until discharge

    Measure: Mean days of hospital stay

    Time: Three months

    Description: Respiratory deterioration defined by respiratory rate > 25 per minute, requirement of high oxygen supply (FiO2 > 80% ) to maintain oxygen saturation > 90 %, invasive mechanical ventilation or dead.

    Measure: Rate of Respiratory deterioration, requirement of invasive mechanical ventilation or dead

    Time: Three months

    Description: Daily delta of oxygenation index during the hospitalization

    Measure: Mean of oxygenation index delta

    Time: Three months

    Secondary Outcomes

    Description: Mean time to viral negativization of RT-qPCR SARS-CoV-2. Pre Specified time: 5, 14, 21 and 28 days after the first positive PCR.

    Measure: Mean time to viral PCR negativization

    Time: 5, 14, 21 and 28 days after the first positive PCR
    127 Phase 2, Randomized, Double-Blind, Placebo-Controlled Study of the Effect of Anti-CD14 Treatment in Patients With SARS-CoV-2 (COVID-19)

    This is a multicenter, randomized, double-blind, placebo-controlled phase 2 study of IC14, an antibody to CD14, in reducing the severity of respiratory disease in hospitalized COVID-19 patients.

    NCT04391309
    Conditions
    1. SARS-CoV2
    Interventions
    1. Biological: IC14
    2. Other: Placebo

    Primary Outcomes

    Description: Days alive and free of any episodes of acute respiratory failure through Day 22 defined by need for high-flow nasal cannula, noninvasive positive-pressure ventilation, endotracheal intubation and mechanical ventilation, and extracorporeal membrane oxygenation

    Measure: Acute respiratory failure

    Time: Day 1-22

    Secondary Outcomes

    Description: Defined as time to the first day that a subject is in categories 6, 7, or 8 on the Eight-Point Ordinal Scale. The Eight-Point Ordinal Scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high-flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen-requiring ongoing medical care (COVID-19-related or otherwise); 6) Hospitalized, not requiring supplemental oxygen-no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.

    Measure: Time to clinical improvement

    Time: Day 1-29

    Description: Proportion of patients alive and free of any episode of acute respiratory failure through Days 8, 15, 22, and 29

    Measure: Acute respiratory failure

    Time: Days 1-8, 1-15, 1-22, 1-29

    Description: Proportion of patients alive and free of invasive mechanical ventilation through Days 8, 15, 22, and 29

    Measure: Invasive mechanical ventilation

    Time: Days 1-8, 1-15, 1-22, 1-29

    Description: Days alive and free of acute respiratory failure through Days 15 and 29

    Measure: Acute respiratory failure

    Time: Days 1-15 and 1-29

    Description: Days alive and free of invasive mechanical ventilation through Days 15, 22, and 29

    Measure: Invasive mechanical ventilation

    Time: Days 1-15, 1-22, 1-29

    Description: Days alive and hospitalized through Day 29

    Measure: Hospitalization

    Time: Days 1-29

    Description: Change in Sequential Organ Failure Assessment (SOFA) score (range 0 [best] to 24 [worst]) from baseline to Day 8, Day 15, and Day 22

    Measure: Sequential Organ Failure Assessment

    Time: Days 1-8, 1-15, 1-22

    Description: Worst SOFA score from baseline to Day 22

    Measure: Sequential Organ Failure Assessment

    Time: Days 1-22

    Description: Proportion of patients alive and discharged from the hospital at Days 15 and 29.

    Measure: Hospitalization

    Time: Days 1-15, 1-29

    Description: Mean change in the eight-point ordinal scale (1 [worst] to 8 [best]) through Day 29

    Measure: Ordinal Scale

    Time: Days 1-29

    Description: Time to improvement in one category from baseline using an eight-point ordinal scale (1 [worst] to 8 [best]) through Day 29.

    Measure: Time to clinical improvement

    Time: Days 1-29

    Description: Time to improvement in two categories from baseline using an eight-point ordinal scale (1 [worst] to 8 [best]) through Day 29.

    Measure: Time to clinical improvment

    Time: Days 1-29

    Description: Time to recovery through Day 29. Day of recovery is defined as the first day on which the subject satisfies one of categories 6-8 from the ordinal scale.

    Measure: Time to recovery

    Time: Days 1-29

    Description: Change in C-reactive protein in blood on Days 4 and 8 compared to baseline (from normal < 10 mg/L [normal] to >10 mg/L [worse])

    Measure: Change in C-reactive protein

    Time: Day 4 compared to baseline; Day 8 compared to baseline

    Description: Cumulative incidence of Grade 3 and 4 clinical and/or laboratory adverse events

    Measure: Adverse events

    Time: Days 1-60

    Description: Cumulative incidence of serious adverse events

    Measure: Serious adverse events

    Time: Days 1-60
    128 A Randomized, Double-Blind, Placebo-Controlled, First-in-Human Study Designed to Evaluate the Safety, Tolerability, and Pharmacokinetics of EIDD-2801 Following Oral Administration to Healthy Volunteers

    This is a First In Human study designed to assess the safety, tolerability and pharmacokinetics of EIDD-2801 in healthy human volunteers.

    NCT04392219
    Conditions
    1. Coronavirus
    Interventions
    1. Drug: EIDD-2801
    2. Drug: Placebo
    MeSH:Coronavirus Infections

    Primary Outcomes

    Description: Number and severity of treatment emergent adverse events

    Measure: Safety and Tolerability of Single Ascending Dose (SAD) of EIDD-2801 (Part 1): Adverse Events

    Time: From screening through study completion, up to 15 days

    Description: Number and severity of treatment emergent adverse events

    Measure: Safety and Tolerability of Multiple Ascending Dose (MAD) of EIDD-2801 (Part 3): Adverse Events

    Time: From screening through study completion, up to 20 days

    Description: Multiple pharmacokinetic variables of EIDD-2801 will be assessed and may include, but are not limited to: Maximum observed concentration Cmax

    Measure: Pharmacokinetics (PK) of EIDD-2801 when given as Single Doses (Part 2): Maximum observed concentration Cmax

    Time: Day 1 through Day 18

    Secondary Outcomes

    Description: Multiple PK variables of EIDD-2801 will be assessed and may include, but are not limited to: Maximum observed concentration Cmax

    Measure: Pharmacokinetics (PK) of EIDD-2801 when given as Single Ascending Dose (SAD) (Part 1): Maximum observed concentration Cmax

    Time: Day 1 up to Day 4

    Description: Multiple PK variables of EIDD-2801 will be assessed and may include, but are not limited to: Maximum observed concentration Cmax

    Measure: Pharmacokinetics (PK) of EIDD-2801 when given as Multiple Ascending Dose (MAD) (Part 3): Maximum observed concentration Cmax

    Time: Day 1 up to Day 14

    Description: Number and severity of treatment emergent adverse events

    Measure: Safety and Tolerability of Single Doses of EIDD-2801 (Part 2): Adverse Events

    Time: From screening through study completion, up to 30 days
    129 A Phase 2/3, Randomized, Double Blind, Placebo-controlled Study to Evaluate the Efficacy and the Safety of ABX464 in Treating Inflammation and Preventing COVID-19 Associated Acute Respiratory Failure in Patients Aged ≥ 65 and Patients Aged ≥18 With at Least One Additional Risk Factor Who Are Infected With SARS-CoV-2.

    A phase 2/3, randomized, double blind, placebo-controlled study to evaluate the efficacy and the safety of ABX464 in treating inflammation and preventing acute respiratory failure in patients aged ≥65 and patients aged ≥18 with at least one additional risk factor who are infected with SARS-CoV-2 (the MiR-AGE study).

    NCT04393038
    Conditions
    1. COVID-19
    Interventions
    1. Drug: ABX464
    2. Drug: Placebo
    MeSH:Respiratory Insufficiency Inflammation

    Primary Outcomes

    Measure: Rate of patients with no invasive or non-invasive mechanical ventilation (IMV and NIV, respectively), but excluding simple nasal/mask oxygen supplementation, and who are alive

    Time: at the end of the 28-day treatment period

    Secondary Outcomes

    Measure: Rate of patients hospitalized

    Time: 28-day treatment period

    Description: 7-point ordinal scale is defined as Not hospitalized, no limitations on activities; Not hospitalized, limitation on activities; Hospitalized, not requiring supplemental oxygen; Hospitalized, requiring supplemental oxygen; Hospitalized, on non-invasive ventilation or high flow oxygen devices; Hospitalized, on invasive mechanical ventilation or ECMO; Death

    Measure: Percentage of patients reporting each severity rating on a 7-point ordinal scale

    Time: 28-day treatment period

    Measure: Change from enrolment in inflammatory markers in plasma and in immune phenotype and assessment of cell-activation markers in PBMCs

    Time: at each study visit during the 28-day treatment period

    Measure: Rate of patients requiring oxygen supplementation

    Time: 28-day treatment period

    Measure: Time to hospitalization

    Time: 28-day treatment period

    Measure: Time to assisted ventilation and oxygen supplementation

    Time: 28-day treatment period

    Measure: Change from baseline in microRNA-124 levels

    Time: at each study visit during the 28-day treatment period

    Measure: Change from baseline in CRP, Troponin I & T and D-dimer

    Time: at each study visit during the 28-day treatment period

    Description: Nasopharyngeal sample and/or in blood

    Measure: SARS-CoV-2 viral load

    Time: at each study visit during the 28-day treatment period

    Measure: Number and rates of participants with Treatment Emergent Adverse Event

    Time: 28-day treatment period
    130 A Multi-Center, Randomized, Double-Blind, Placebo Controlled Study of the Safety and Efficacy of Ulinastatin for the Treatment of COVID-19 in Hospitalized Patients

    The primary objective of this study is to evaluate the safety and efficacy of intravenous (IV) infusion of ulinastatin compared to placebo with respect to time to recovery, disease severity, need for ventilator support, and mortality in patients with COVID 19.

    NCT04393311
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Ulinastatin
    2. Drug: Placebo

    Primary Outcomes

    Description: Time to recovery, defined as attaining a score of 6, 7, or 8 on the COVID-19 disease severity scale, an 8 point ordinal scale used in the NIH Adaptive COVID-19 Treatment Trial (ACTT; NCT04280705). = Death; = Hospitalized and on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); = Hospitalized and on non-invasive ventilation or high-flow oxygen devices; = Hospitalized and requiring supplemental oxygen; = Hospitalized and not requiring supplemental oxygen but requiring ongoing medical care (COVID-19-related or otherwise); = Hospitalized and not requiring supplemental oxygen and no longer requiring ongoing medical care; = Not hospitalized, limitation on activities and/or requiring home oxygen; = Not hospitalized, no limitation on activities

    Measure: Time to recovery

    Time: Up to 29 days

    Secondary Outcomes

    Description: COVID-19 disease severity scale (range; 1-8, higher scores correspond to better health state).

    Measure: COVID-19 disease severity scale score on Day 8

    Time: Day 8

    Description: COVID-19 disease severity scale (range; 1-8, higher scores correspond to better health state).

    Measure: COVID-19 disease severity scale score on Day 15

    Time: Day 15

    Description: COVID-19 disease severity scale (range; 1-8, higher scores correspond to better health state).

    Measure: COVID-19 disease severity scale score on Day 22

    Time: Day 22

    Description: COVID-19 disease severity scale (range; 1-8, higher scores correspond to better health state).

    Measure: COVID-19 disease severity scale score on Day 29

    Time: Day 29

    Measure: Incidence of mortality at Day 29

    Time: 29 days

    Measure: Incidence of in-hospital mortality

    Time: Up to 29 days

    Measure: Number of days alive and not on mechanical ventilator or ECMO in the 28 days following first dose

    Time: Up to 29 days

    Measure: Number of patients with resolution of symptoms defined as score of 8 on the 8-point ordinal scale at Day 29

    Time: Day 29

    Measure: Number of patients alive and free of respiratory failure defined as score of 4, 5, 6, 7, or 8 on the 8-point ordinal scale at Day 29

    Time: Day 29

    Description: For patients requiring mechanical ventilation.

    Measure: Duration of mechanical ventilation

    Time: Up to 29 days

    Description: For patients requiring mechanical ECMO.

    Measure: Duration of ECMO

    Time: Up to 29 days

    Description: For patients requiring non-invasive ventilation

    Measure: Duration of noninvasive ventilation

    Time: Up to 29 days

    Description: For patients admitted to ICU

    Measure: Duration of ICU stay

    Time: Up to 29 days

    Measure: Duration of hospital stay

    Time: Up to 29 days

    Measure: Change in oxygen saturation

    Time: Between screening and 24 hours after last dose (up to 6 days)
    131 Trial of Silymarin in Adults With COVID-19 Pneumonia

    A randomized placebo controlled trial to assess the clinical outcome in COVID-19 Pneumonia following administration of Silymarin owing to its role as a p38 MAPK pathway inhibitor and its antiviral, anti-inflammatory and anti-oxidant effects

    NCT04394208
    Conditions
    1. COVID-19
    2. Viral Pneumonia Human Coronavirus
    Interventions
    1. Drug: Silymarin
    2. Drug: Placebo
    MeSH:Pneumonia, Viral Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Defined as the time from randomization to an improvement of two points (from the status of randomization) on seven category ordinal scale or live discharge from the hospital, whichever comes first.

    Measure: Time to clinical improvement

    Time: 7-28 days

    Secondary Outcomes

    Description: Clinical status as assessed with the seven-category ordinal scale on days 7 and 14

    Measure: Clinical outcome

    Time: 7-14 days

    Description: Time in days patient was intubated

    Measure: Duration of Mechanical Ventilation

    Time: Randomization till hospital discharge or death whichever came first, assessed up to 28 days

    Description: Total days of hospitalization

    Measure: Hospitalization

    Time: Randomization till hospital discharge or death whichever came first, assessed up to 28 days

    Description: number of days patient remained with positive RT-PCR SARS-CoV-2 swab

    Measure: Virologic Response

    Time: Randomization till discharge, up to 28 days

    Description: Any adverse events whether related to medication or not

    Measure: Adverse events

    Time: Randomization till hospital discharge, up to 28 days
    132 Aerosol Combination Therapy of All-trans Retinoic Acid and Isotretinoin as A Novel Treatment for Inducing Neutralizing Antibodies in COVID -19 Infected Patients Better Than Vaccine : An Innovative Treatment

    Aerosol Combination therapy of All-trans retinoic acid and Isotretinoin as A novel Treatment for Inducing Neutralizing Antibodies in COVID -19 Infected Patients better than vaccine : An innovative Treatment Mahmoud ELkazzaz(1),Tamer Haydara(2), Mohamed Abdelaal(3), Ahmed M. Kabel(4), Abedelaziz Elsayed(5) ,Yousry Abo-amer(6) ,Hesham Attia(7) 1. Department of chemistry and biochemistry, Faculty of Science, Damietta University,Egypt. 2. Department of Internal Medicine,Faculty of Medicine, Kafrelsheikh University, Egypt 3. Department of Cardiothoracic Surgery,Faculty of Medicine, Kafrelsheikh University, Egypt 4. Department of Clinical Pharmacy, Faculty of Medicine , Tanta University,Egypt. 5. Department of Pharmaceutical Biotechnology, Faculty of Pharmacy,Tanta University,Egypt. 6. Hepatology,Gastroenterology and Infectious Diseases Department, Mahala Hepatology Teaching Hospital,Egypt 7. Department of Immunology and Parasitology, Faculty of Science, Cairo University, Egypt. - Study Chair ((( Dr.Tamer Hydara))), Department of Internal Medicine,Faculty of Medicine, Kafrelsheikh University, Egypt Contact: Dr.Tamer Hydara-Tel: 00201142233340 Mail: tamerhydara@yahoo.com - Principal Investigator ((( Mahmoud Elkazzaz))), Faculty of Science, Damietta University,GOEIC,Egypt Contact:Tel: 00201090302015 Mail: mahmoudramadan2051@yahoo.com - Study coordinator ((Prof/Dr Mohamed Abdelaal)), Department of Cardiothoracic Surgery,Faculty of Medicine, Kafrelsheikh University, Egypt Contact:Tel: 00201001422577 Mail: Malaal2@hotmail.com Abstract The pandemic of COVID-19 which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) has infected over 20,000,000 people causing over 700,000 deaths .It has no currently approved treatments. In this clinical study we confirm that combination of isotretinoin and All trans retinoic acid can be used in the treatment of SARS-COV-2 better than vaccine according to the findings of previous studies and researches. Retenoic acid can induce neutralizing antibodies in case of corona virus (COVID-19) by restoring inhebited and exhausted T cells via inhebiting both CD13 and Angiotensin-converting enzyme-2 (ACE2). CD13 amyloid receptor which abundantly overexpressed on cell surface of lymphocyte, Dentritic cell, Macrophage, granulocytes and monocytes and is ubiquitous in respiratory tract epithelial cells, smooth muscle cells, fibroblasts, epithelial cells in the kidneys and small intestine, activated endothelial cells, and platelets In addition inhibing of Angiotensin-converting enzyme-2 (ACE2) , Angiotensin T1 protein and Angiotensin II-mediated intracellular calcium release pathway which is responsible for COVID-19 cell fusion and entry.ACE2-expressing cells are prone to SARS-CoV-2 infection as ACE2 receptor facilitates cellular viral entry and replication. A study demonestrated that patients with hypertension and diabetes mellitus may be at higher risk of SARS-CoV-2 infection, as these patients are often treated with ACE inhibitors (ACEIs) or angiotensin II type-I receptor blockers (ARBs), which have been previously suggested to increase ACE2 expression.Butisotretinoin was found to be the strongest down-regulator of ACE 2 receptors.and this will give hope for diabetic patients or patients with hypertension infected with COVID-19.Therefore we suggest that Retinoic Acid will help in inhabiting factors which may enhance antibody dependent enhancement (ADE), A phenomenon caused by covid-19 which expected to lead to failure of vaccination specially in case of corona virus (covid-19) as a hyper mutatated COVID-19 antigens can lead to (ADE) phenomenon in which IgG antibodies facilitate viral entry and fusion with infected cell through uptake of the virus-IgG complex via the Fc receptors and later viral fusion with antigen presenting cells like Dentric cells, macrophages and B cells via FcR , through the neonatal FcR instead of antibodies induced viral agglutination and this is known as antibody dependent enhancement (ADE)(2) ADE can hamper vaccine development, as a vaccine may cause the production of antibodies which, via ADE, worsen the disease the vaccine is designed to protect against. ADE in COVID-19 infection can be caused by high mutation rate of the gene that encodes spike (S) protein. In this clinical study we suggest that Hyper mutated spike protein ,lymphopenia, and impaired dentreic cells all these factors can help in and lead to delayed antibodies response and appearing after a period of covid -19 symptoms onset and this may be responsible for antibody dependent enhancement (ADE) Keywords: COVID 2019 , Retinoic acid, Lymphopenia ,T Cells, Dentric cells , ADE, Vaccine

    NCT04396067
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Aerosolized 13 cis retinoic acid
    2. Drug: Aerosolized All trans retinoic acid
    3. Other: Placebo

    Primary Outcomes

    Description: Proportion of lung injury score decreased or increased after treatment

    Measure: lung injury score

    Time: at 7 days

    Secondary Outcomes

    Description: Serum levels of CRP, ESR ,IL-1,IL-6,TNF and Type I interferon

    Measure: Serum levels of CRP, ESR ,IL-1,IL-6,TNF and Type I interferon

    Time: at day 7 and 14 after randimization

    Description: Serum level of COVID19 RNA

    Measure: Serum level of COVID19 RNA

    Time: at day 7 and 14

    Description: less than 250 ng/mL, or less than 0.4 mcg/mL of blood sample

    Measure: d-dimers

    Time: within 14 days

    Description: lymphocyte counts

    Measure: Absolute lymphocyte counts

    Time: at day 7 and 14 after randimization

    Description: To determine the immune correlates of viral clearance (Antibody Titres sufficient for viral clearance and neutralizing ) against future exposure to SARS-CoV-2

    Measure: The immune correlates of protection against future exposure to SARS-CoV-2

    Time: within 14 days

    Description: Number of CD4 HLA-DR+ and CD38+, CD8 lymphocytes

    Measure: Immunological profile

    Time: within 14 days

    Measure: Total duration of mechanical ventilation, ventilatory weaning and curarisation

    Time: at day 7 and 14

    Description: Kidney failure, hypersensitivity with cutaneous or hemodynamic manifestations, aseptic meningitis, hemolytic anemia, leuko-neutropenia, transfusion related acute lung injury (TRALI)

    Measure: Occurrence of adverse event related to immunoglobulins

    Time: at day 14

    Description: serum levels of IgG and IgM against COVID-19

    Measure: IgG, IgA and IgM against COVID-19

    Time: at day 7 and 14

    Description: ACE2 expression in patients with COVID-19 infection

    Measure: ACE2 expression in patients with COVID-19 infection

    Time: at day 7 and 14

    Measure: All cause mortality rate [

    Time: at day 7 and 14

    Measure: Ventilation free days

    Time: at 14 days

    Measure: ICU free days

    Time: at 14 days
    133 A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of AT-527 in Subjects With Moderate COVID-19

    The objectives of this study are to evaluate the safety, tolerability and efficacy of AT-527 in adult subjects ≥18 years of age with moderate COVID-19 and risk factors for poor outcomes (such as obesity (BMI>30), hypertension, diabetes or asthma). Eligible subjects will be randomized to blinded AT-527 (nucleotide analog) tablets or matching placebo tablets to be administered orally for 5 days. Local supportive standard of care (SOC) will be allowed for all subjects. Efficacy and safety observations will be compared for treatment with active AT-527 tablets + SOC vs. placebo tablets + SOC.

    NCT04396106
    Conditions
    1. COVID-19
    Interventions
    1. Drug: AT-527
    2. Other: Placebo

    Primary Outcomes

    Description: Progressive respiratory insufficiency defined as a ≥ 2-tier increase in respiratory support methods required to maintain satisfactory oxygenation (SpO2 ≥ 93%), using the 6-tier hierarchical scale of respiratory support methods

    Measure: Proportions (active vs. placebo) of subjects with progressive respiratory insufficiency.

    Time: Day 14

    Measure: Proportions (active vs. placebo) of subjects experiencing treatment-emergent adverse events

    Time: Day 14

    Secondary Outcomes

    Description: Clinical recovery defined as time from randomization to disease resolution status on an 8 point Clinical Status scale

    Measure: Time to clinical recovery

    Time: Day 14

    Measure: Proportions (active vs. placebo) of subjects with respiratory failure or death

    Time: Day 28
    134 Safety and Efficacy of Post-exposure Prophylaxis With Hydroxychloroquine (HCQ) for the Prevention of COVID-19 in High-risk Older Individuals in Long-term and Specialized Care: A Double-blind Randomized Control Trial

    Older adults are at the highest risk of complications and severe illness for 2019-nCoV infections. Hydroxychloroquine (HCQ), an emerging chemoprophylaxis, which holds clinical and mechanistic plausibility, will help to reduce disease incidence and mitigate disease severity across in-patient settings. This study is designed to assess the safety and efficacy of post-exposure prophylaxis with hydroxychloroquine (HCQ) for the prevention of Coronavirus Infectious Disease-19 (COVID-19) in high-risk older individuals in long-term and specialized care.

    NCT04397328
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Hydroxychloroquine
    2. Drug: Placebo

    Primary Outcomes

    Measure: Incidence of symptomatic fever >37.8, dry cough, or shortness of breath (resident/patient report or nurse observation) respiratory infection with confirmed PCR+ result for SARS-CoV-2.

    Time: baseline through day 90

    Secondary Outcomes

    Measure: Requirement for admission to acute care hospital and/or ICU admission or death

    Time: baseline through day 90

    Measure: Asymptomatic PCR+ SARS-CoV-2 test result

    Time: baseline, days 2, 5, 12, and 19

    Measure: Time to clinical recovery (TTCR).

    Time: baseline through day 90
    135 A Randomized, Double Blind, Placebo-controlled Trial of Mavrilimumab for Acute Respiratory Failure Due to COVID-19 Pneumonia With Hyper-inflammation (the COMBAT-19 Trial)

    This study is a prospective, phase II, multi-center, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of mavrilimumab in hospitalized patients with acute respiratory failure requiring oxygen supplementation in COVID- 19 pneumonia and a hyper-inflammatory status. The study will randomize patients to mavrilimumab or placebo, in addition to standard of care per local practice. The total trial duration will be 12 weeks after single mavrilimumab or placebo dose.

    NCT04397497
    Conditions
    1. Covid-19
    2. Acute Respiratory Failure
    3. ARDS, Human
    4. Sars-CoV2
    5. Viral Pneumonia
    Interventions
    1. Drug: Mavrilimumab
    2. Drug: Placebo
    MeSH:Pneumonia, Viral Pneumonia Respiratory Insufficiency Respiratory Distress Syndrome, Adult Inflammation
    HPO:Pneumonia

    Primary Outcomes

    Description: Time to the absence of need for oxygen supplementation (time to first period of 24 hrs with a SpO2 of 94%) within day 14 of treatment, stated as Kaplan- Mayer estimates of the proportion of patients on room air at day 14 and median time to room air attainment in each arm

    Measure: Reduction in the dependency on oxygen supplementation

    Time: within day 14 of treatment

    Secondary Outcomes

    Description: Response is defined as a 7-point ordinal scale of 3 or less, i.e. no supplemental oxygen

    Measure: Proportion of responders (using the WHO 7-point ordinal scale)

    Time: Day 7, 14, and 28

    Description: Time from date of randomization to the date with a 7-point ordinal scale of 3 or less, i.e. no supplemental oxygen

    Measure: Time to response (using the WHO 7-point ordinal scale)

    Time: Within day 28 of intervention

    Description: Proportion of patients with at least two-point improvement in clinical status

    Measure: Proportion of improving patients (using the WHO 7-point ordinal scale)

    Time: At day 7, 14, and 28

    Description: Time to resolution of fever (for at least 48 hours) in absence of antipyretics, or discharge, whichever is sooner

    Measure: Time to resolution of fever

    Time: Within day 28 of intervention

    Description: COVID-19-related death

    Measure: Reduction in case fatality

    Time: Within day 28 of intervention

    Description: Proportion of hospitalized patients who died or required mechanical ventilation (WHO Categories 6 or 7)

    Measure: Proportion of patient requiring mechanical ventilation/deaths

    Time: Within day 14 of intervention

    Description: Change of the following serological markers over follow-up (C-reactive protein; Ferritin; D-Dimer)

    Measure: Change in biochemical markers

    Time: Within day 28 of intervention or discharge -whatever comes first

    Description: Median changes of NEWS2 score from baseline

    Measure: Median changes in the National Early Warning Score 2 (NEWS2)

    Time: At day 7, 14, and 28

    Description: Time to clinical improvement (as defined as a NEWS2 score of 2 or less maintained for at least 24 hours or discharge, whichever comes first)

    Measure: Time to clinical improvement as evaluated with the National Early Warning Score 2 (NEWS2)

    Time: Within day 28 of intervention or discharge -whatever comes first

    Description: Variations from baseline to subsequent timepoints (when available) in terms of percentage of lung involvement, modifications in the normal parenchyma, ground glass opacities (GGO), crazy paving pattern,parenchymal consolidations, and evolution towards fibrosis.

    Measure: Variations in radiological findings

    Time: Within day 28 of intervention or discharge -whatever comes first

    Description: Number of patients with treatment- related side effects (as assessed by Common Terminology Criteria for Adverse Event (CTCAE) v.5.0), serious adverse events, adverse events of special interest, clinically significant changes in laboratory measurements and vital signs

    Measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

    Time: By day 84

    Other Outcomes

    Description: To evaluate the primary and secondary endpoints in different subgroups of patients: mild respiratory failure: PaO2/FiO2 ≤ 300 and > 200 mmHg; moderate respiratory failure: PaO2/FiO2 ≤ 200 and > 100 mmHg

    Measure: Clinical efficacy of mavrilimumab compared to the control arm by clinical severity

    Time: Within day 28 of intervention

    Description: Median changes in serum IL-6

    Measure: Changes in serum IL-6 (exploratory biomarker)

    Time: By day 84

    Description: Median changes in serum IL-1 receptor antagonist

    Measure: Changes in serum IL-1RA (exploratory biomarker)

    Time: By day 84

    Description: Median changes in serum TNF-alpha

    Measure: Changes in serum TNF-alpha (exploratory biomarker)

    Time: By day 84

    Description: Median variations in haemoglobin and leucocyte counts

    Measure: Changes in CBC + differential (exploratory biomarker)

    Time: By day 84

    Description: Median titres od anti-SARS-CoV2 antibodies

    Measure: Level of anti-SARS-CoV2 antibodies (exploratory biomarker)

    Time: By day 84

    Description: Proportion of patients with a positive swab for SARS-CoV2 by PCR

    Measure: Virus eradication (exploratory biomarker)

    Time: By day 84

    Description: Proportion of patients who developed anti-drug antibodies

    Measure: Anti-drug antibodies (exploratory biomarker)

    Time: By day 84
    136 A Multicenter, Randomized, Double-blind, Placebo-controlled, Adaptively Designed Clinical Trial of the Efficacy and Safety of Levilimab (BCD-089) in Patients With Severe COVID-19

    The objective: to study the efficacy and safety of levilimab in subjects with severe COVID-19.

    NCT04397562
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Levilimab
    2. Drug: Placebo

    Primary Outcomes

    Description: Sustained clinical recovery is defined as either an improvement of at least 2 categories relative to baseline on a 7-Category Ordinal Scale of Clinical Status or reaching categories "Discharged" / "Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care" at day 14.

    Measure: Proportion of patients with sustained clinical recovery

    Time: Day 14

    Secondary Outcomes

    Description: 7-Category Ordinal Scale of Clinical Status: Not hospitalized / Discharged Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise) Hospitalized, requiring supplemental oxygen Hospitalized, requiring non-invasive ventilation or high flow oxygen devices Hospitalized, requiring invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) Death

    Measure: Proportion of patients reporting each category of 7-Category Ordinal Scale of Clinical Status

    Time: Day 30

    Measure: Proportion of patients transferred to the ICU

    Time: Day 60

    Measure: Duration of fever

    Time: Day 60

    Measure: Duration of hospitalization

    Time: Day 60

    Measure: Change in ESR

    Time: Day 30

    Measure: Change in serum CRP level

    Time: Day 30

    Measure: Change in serum IL-6 level

    Time: Day 30
    137 Phase 1b Randomized, Double-Blind, Placebo-Controlled Study Of The Safety Of Therapeutic Treatment With Immunomodulatory Mesenchymal Stem Cells In Adults With COVID-19 Infection Requiring Mechanical Ventilation

    This is a phase 1b randomized, double-blind, placebo-controlled study in adult subjects with Coronavirus Disease 2019 (COVID-19). This clinical trial will evaluate the preliminary safety and efficacy of BM-Allo.MSC vs placebo in treating subjects with severe disease requiring ventilator support during COVID 19 infection.

    NCT04397796
    Conditions
    1. COVID
    Interventions
    1. Biological: BM-Allo.MSC
    2. Biological: Placebo
    MeSH:Infection

    Primary Outcomes

    Description: Incidence of AEs within 30 days of randomization.

    Measure: Incidence of AEs

    Time: 30 days

    Description: Mortality within 30 days of randomization.

    Measure: Mortality

    Time: 30 days

    Description: Cause of death within 30 days of randomization

    Measure: Death

    Time: 30 days

    Description: Number of ventilator-free days within 60 days of randomization.

    Measure: Number of ventilator-free days

    Time: 60 days

    Secondary Outcomes

    Description: Time from randomization to an improvement of one category using the ordinal scale. The ordinal scale is as follows: Death Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) Hospitalized, on non-invasive ventilation or high flow oxygen devices Hospitalized, requiring supplemental oxygen Hospitalized, not requiring supplemental oxygen Not hospitalized, limitation on activities Not hospitalized, no limitations on activities

    Measure: Improvement of one category

    Time: 30 days

    Description: Change in the 7-point ordinal scale from baseline. The ordinal scale is as follows: Death Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) Hospitalized, on non-invasive ventilation or high flow oxygen devices Hospitalized, requiring supplemental oxygen Hospitalized, not requiring supplemental oxygen Not hospitalized, limitation on activities Not hospitalized, no limitations on activities

    Measure: 7-point ordinal scale

    Time: 30 days

    Description: Change in NEWS from baseline. The following 7 clinical parameters will be assessed: Respiration rate Oxygen saturation Any supplemental oxygen Temperature Systolic blood pressure Heart rate Level of consciousness Measurements within normal ranges are assigned a 0. If the measurement in each category is substantially above or below the normal range, it is given a +1, +2, or +3. The more far off than normal, the bigger the number (in each category). A higher number indicates worse outcome. Each category can be 0-3, except for supplemental oxygen which is only 0-2. The highest value a patient can get is 20.

    Measure: NEWS

    Time: 30 days

    Description: Time from randomization to discharge or to a NEWS of ≤ 2 maintained for 24 hours, whichever occurs first.

    Measure: NEWS of ≤ 2

    Time: 30 days

    Description: Change from baseline in Sequential Organ Failure Assessment (SOFA) score on days 8, 15, 22, and 29. System Score for each category is 0-4 with 28 is the maximum score for worst outcome. The following categories are: Respiration Coagulation Liver Cardiovascular Central Nervous System Renal

    Measure: Sequential Organ Failure Assessment (SOFA)

    Time: days 8, 15, 22, and 29

    Description: Number of days requiring oxygen.

    Measure: Oxygen

    Time: 30 days

    Description: Duration of hospitalization from randomization.

    Measure: Hospitalization

    Time: 30 days

    Description: Incidence of SAEs within 30 days of randomization

    Measure: Incidence of SAEs

    Time: 30 days
    138 A Randomized, Observer-Blind, Dose-escalation Phase I/II Clinical Trial of Ad5-nCoV Vaccine in Healthy Adults From 18 to <85 Years of Age in Canada

    This study is a phase I /II adaptive clinical trial to evaluate the safety, tolerability and the Immunogenicity of Ad5-nCoV in healthy adults from 18 to <55 and 65 to <85 years of age,with the randomized, observer-blind, dose-escalation design

    NCT04398147
    Conditions
    1. COVID-19
    Interventions
    1. Biological: Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector)
    2. Biological: Placebo

    Primary Outcomes

    Description: The occurrence of Solicited AE in all groups within 0-6 days after each vaccination;

    Measure: Incidence of the Solicited AE in all groups

    Time: 0-6 days after each vaccination

    Description: The occurrence of Unsolicited AE in all groups within 0-28 days after each vaccination.

    Measure: Incidence of Unsolicited AE in all groups

    Time: 0-28 days after each vaccination

    Description: The occurrence of Serious adverse events (SAE) in all groups within 6 months after the final vaccination.

    Measure: Incidence of Serious adverse events (SAE) in all groups

    Time: 6 months after the final vaccination

    Secondary Outcomes

    Description: Geometric mean titer (GMT) of the IgG antibody against SARS-CoV-2 measured on Day 0, Day 14, Day 28, Day 84 and Day 168 after vaccination in the one dose group and Day 0, 14, 28, 56, 70, 84, and 224 in the two dose group (ELISA method);

    Measure: Geometric mean titer (GMT) of the IgG antibody against SARS-CoV-2 (ELISA method);

    Time: Day 0, Day 14, Day 28, Day 84 and Day 168 after vaccination in the one dose group and Day 0, 14, 28, 56, 70, 84, and 224 in the two dose group

    Description: Seroconversion rate (%of subjects with 4-fold or greater increase in antibody level) of the IgG antibody against SARS-CoV-2 measured on Day 14, Day 28, Day 84 and Day 168 after vaccination in the one dose group and Day 14, 28, 56, 70, 84, and 224 in the two dose group (ELISA method );

    Measure: Seroconversion rate of the IgG antibody against SARS-CoV-2(ELISA method )

    Time: Day 14, Day 28, Day 84 and Day 168 after vaccination in the one dose group and Day 14, 28, 56, 70, 84, and 224 in the two dose group

    Description: Geometric Mean Increase Ratio (GMI) of the specific antibody against SARS-CoV-2 measured on Day 14, Day 28, Day 84 and Day 168 after vaccination in the one dose group and Day 14, 28, 56, 70, 84, and 224 in the two dose group (ELISA method);

    Measure: Geometric Mean Increase Ratio (GMI) of the specific antibody against SARS-CoV-2(ELISA method);

    Time: Day 14, Day 28, Day 84 and Day 168 after vaccination in the one dose group and Day 14, 28, 56, 70, 84, and 224 in the two dose group

    Description: Geometric mean titer (GMT) of the neutralizing antibody against SARS-CoV-2 measured on Day 0, Day 14, Day 28 and Day 168 after vaccination in the one dose group and Day 0, 14, 28, 56, 70, 84, and 224 in the two dose group (Pseudo-viral neutralization assay)

    Measure: Geometric mean titer (GMT) of the neutralizing antibody against SARS-CoV-2(Pseudo-viral neutralization assay)

    Time: Day 0, Day 14, Day 28 and Day 168 after vaccination in the one dose group and Day 0, 14, 28, 56, 70, 84, and 224 in the two dose group

    Description: Seroconversion rate of the neutralizing antibody against SARS-CoV-2 measured on Day 14, Day 28 and Day 168 after vaccination in the one dose group and Day 14, 28, 56, 70, 84, and 224 in the two dose group(Pseudo-viral neutralization assay);

    Measure: Seroconversion rate of the neutralizing antibody against SARS-CoV-2(Pseudo-viral neutralization assay)

    Time: Day 14, Day 28 and Day 168 after vaccination in the one dose group and Day 14, 28, 56, 70, 84, and 224 in the two dose group

    Description: Geometric mean increase ratio (GMI) of neutralizing antibody against SARS-CoV-2 measured on Day 14, Day 28 and Day 168 after vaccination in the one dose group and Day 14, 28, 56, 70, 84, and 224 in the two dose group (Pseudo-viral neutralization assay)

    Measure: Geometric mean increase ratio (GMI) of neutralizing antibody against SARS-CoV-2 (Pseudo-viral neutralization assay)

    Time: Day 14, Day 28 and Day 168 after vaccination in the one dose group and Day 14, 28, 56, 70, 84, and 224 in the two dose group

    Description: Geometric Mean Titer (GMT) of the neutralizing antibody against adenovirus type 5 vector measured on Day 0, Day 14, Day 28, Day 84 and Day 168 after vaccination in the one dose group and Day 0, 14, 28, 56, 70, 84, and 224 in the two dose group;

    Measure: Geometric Mean Titer (GMT) of the neutralizing antibody against adenovirus type 5 vector

    Time: Day 0, Day 14, Day 28, Day 84 and Day 168 after vaccination in the one dose group and Day 0, 14, 28, 56, 70, 84, and 224 in the two dose group

    Description: Geometric mean increase ratio (GMI) of the neutralizing antibody against adenovirus type 5 vector measured on Day 14, Day 28, Day 84 and Day 168 after vaccination in the one dose group and Day 14, 28, 56, 70, 84, and 224 in the two dose group

    Measure: Geometric mean increase ratio (GMI) of the neutralizing antibody against adenovirus type 5 vector

    Time: Day 14, Day 28, Day 84 and Day 168 after vaccination in the one dose group and Day 14, 28, 56, 70, 84, and 224 in the two dose group

    Description: The positive rate of IFN-γ stimulated by S protein overlapping peptide library detected by ELISpot

    Measure: cellular immune response by ELISpot

    Time: on Day 0, Day 14, Day 28 and Day 168 in the one dose group and Day 0, 14, 28, 56, 70, 84, and 224 in the two dose group

    Description: The positive rate of IFN-γ, TNF-α, and IL-2 expressed by CD4+ and CD8+ T lymphocytes stimulated by S protein overlapping peptide library detected by Intracellular Cytokine Staining (ICS);

    Measure: cellular immune response by ICS

    Time: Day 0, Day 14, Day 28 and Day 168 in the one dose group and Day 0, 14, 28, 56, 70, 84, and 224 in the two dose group
    139 A Phase 1/2 Randomized, Placebo-Controlled Trial of ACT-20 in Patients With Severe COVID-19 Pneumonia

    The primary objective of this study is determine the safety and efficacy of ACT-20-MSC (allogenic human umbilical derived mesenchymal stem cells) and ACT-20-CM (allogenic human umbilical derived mesenchymal stem cells in conditioned media) in patients with moderate to severe COVID-19 pneumonia.

    NCT04398303
    Conditions
    1. COVID-19 Pneumonia
    Interventions
    1. Biological: ACT-20-MSC
    2. Biological: ACT-20-CM
    3. Biological: Placebo
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Measure: Mortality at day 30

    Time: 30 days post treatment

    Secondary Outcomes

    Description: Number of ventilator-free days

    Measure: Ventilated Subjects - Ventilator Free Days

    Time: 28 days post treatment

    Description: Improvement in ventilator settings: Minute ventilation, PEEP, FiO2

    Measure: Ventilated Subjects - Improvement in Ventilator Settings

    Time: 28 days post treatment, or until off of ventilator

    Description: Days of step-down O2 therapy as evidenced by: improvement in required volume, change to nasal cannula or face mask delivery or improvement in required concentration.

    Measure: High-Flow O2 Support Subjects - Step-Down O2 Therapy

    Time: 30 days post treatment, or until off of high-flow O2 support

    Description: Respiration Rate < 30 for > 24 hours.

    Measure: High Flow O2 Support Subjects - Respiration Rate

    Time: 30 days post treatment, or until off of high-flow O2 support

    Description: Number of ICU-free days

    Measure: Both Ventilated and High-Flow O2 Support Subjects - ICU-Free Days

    Time: 30 days post treatment, or until off of ventilator or high-flow O2 support

    Description: Improvement in pulmonary function as evidenced by A-A oxygen gradient, O2 saturation

    Measure: Both Ventilated and High-Flow O2 Support Subjects - Pulmonary Function Improvement

    Time: 30 days post treatment, or until off of ventilator or high-flow O2 support

    Description: Increased Berlin Criteria score > 24 hours

    Measure: Both Ventilated and High-Flow O2 Support Subjects - Increased Berlin Score

    Time: 30 days post treatment, or until off of ventilator or high-flow O2 support
    140 Niclosamide for Patients With Mild to Moderate Disease From Novel Coronavirus (COVID-19)

    This study will evaluate the antihelmintic drug, Niclosamide, as a potential treatment for mild to moderate coronavirus disease 2019 (COVID-19).

    NCT04399356
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Niclosamide
    2. Drug: Placebo
    3. Other: Telehealth monitoring

    Primary Outcomes

    Description: Oropharangeal swabs

    Measure: Change in respiratory viral clearance (by PCR)

    Time: Days 3 and 10

    Secondary Outcomes

    Description: Fecal swabs

    Measure: Fecal viral clearance (by PCR)

    Time: Day 14

    Description: Oropharngeal swabs

    Measure: Reduction (change) in respiratory viral shedding (by PCR)

    Time: Days 1,3,7,10,14

    Description: Fecal swabs

    Measure: Reduction (change) in GI viral shedding (by PCR)

    Time: Days 1,3,7,10,14, 21

    Description: Defined as 1) O2 saturation <92% on room air (in two consecutive measurements at least 2 hours apart) OR 2) requirement of hospitalization OR 3) need for artificial ventilation OR 4) death.

    Measure: Progression to severe COVID-19 Disease

    Time: Enrollment through final day of participation

    Description: Days

    Measure: Time to resolution of a fever

    Time: Enrollment through final day of participation

    Other Outcomes

    Description: Composite counts by Adverse Events and Serious Adverse Events

    Measure: Incidence of Adverse Events (AEs)

    Time: Enrollment through 30 days after final day of participation
    141 Efficacy and Safety of Octagam 10% Therapy in COVID-19 Patients With Severe Disease Progression

    This is a randomized, double-blind, placebo-controlled, multicenter, Phase 3 study to evaluate if high-dose Octagam 10% therapy can stabilize or improve clinical status in patients with severe Coronavirus disease

    NCT04400058
    Conditions
    1. Covid-19
    Interventions
    1. Biological: Octagam 10%
    2. Other: Placebo
    MeSH:Disease Progression

    Primary Outcomes

    Description: Proportion of subjects with stabilized or improved clinical status at Day 7 on at least one category on a 6-point clinical status scale. Clinical status categories will be defined as: Hospital discharge or meet discharge criteria (discharge criteria are defined as clinical recovery, i.e. fever, respiratory rate, oxygen saturation return to normal, and cough relief). Hospitalization, not requiring supplemental oxygen. Hospitalization, requiring supplemental oxygen (but not NIV/HFNC). ICU/hospitalization, requiring NIV/HFNC therapy. ICU, requiring Extracorporeal Membrane Oxygenation (ECMO) and/or IMV. Death.

    Measure: Stabilization or Improvement in Clinical Status

    Time: 7 days

    Description: Change from Baseline (Day 1) at Day 7 in terms of the 6-point clinical status scale (descriptive analysis). Clinical status categories will be defined as: Hospital discharge or meet discharge criteria (discharge criteria are defined as clinical recovery, i.e. fever, respiratory rate, oxygen saturation return to normal, and cough relief). Hospitalization, not requiring supplemental oxygen. Hospitalization, requiring supplemental oxygen (but not NIV/HFNC). ICU/hospitalization, requiring NIV/HFNC therapy. ICU, requiring Extracorporeal Membrane Oxygenation (ECMO) and/or IMV. Death.

    Measure: Descriptive Clinical Status Analysis

    Time: 7 days

    Secondary Outcomes

    Description: Proportion of subjects with maintenance or improvement by at least one category on the 6-point clinical status scale on Day 14. (This endpoint will go into formal hypothesis testing procedure) Clinical status categories will be defined as: Hospital discharge or meet discharge criteria (discharge criteria are defined as clinical recovery, i.e. fever, respiratory rate, oxygen saturation return to normal, and cough relief). Hospitalization, not requiring supplemental oxygen. Hospitalization, requiring supplemental oxygen (but not NIV/HFNC). ICU/hospitalization, requiring NIV/HFNC therapy. ICU, requiring Extracorporeal Membrane Oxygenation (ECMO) and/or IMV. Death.

    Measure: Clinical Status Assessment

    Time: 14 days

    Description: Time to death

    Measure: Time to death

    Time: Up to 33 days

    Description: Proportion of subjects requiring invasive mechanical ventilation by Day 33.

    Measure: Mechanical Ventilation Initiation

    Time: Up to 33 days

    Description: Duration of invasive mechanical ventilation

    Measure: Mechanical Ventilation Duration

    Time: Up to 33 days

    Description: Results of RT-PCR for SARS-CoV-2 from nares/throat swab and/or sputum and/or lower respiratory tract sample on Day 7.

    Measure: SARS-CoV-2 Test Result

    Time: 7 days

    Description: Incidence of all AEs

    Measure: Incidence of all AEs

    Time: Up to 33 days

    Description: Incidence of AEs considered related to the IMP

    Measure: Incidence of AEs considered related to the IMP

    Time: Up to 33 days

    Description: Incidence of serious adverse events (SAEs)

    Measure: Incidence of serious adverse events (SAEs)

    Time: Up to 33 days

    Description: Radiological findings (chest CT/chest X-ray)

    Measure: Radiological findings (chest CT/chest X-ray)

    Time: Up to 7 days

    Description: Change from baseline in blood glucose

    Measure: Blood glucose

    Time: Up to 33 daya

    Description: Change from baseline in blood calcium

    Measure: Blood calcium

    Time: Up to 33 days

    Description: Change from baseline in sodium

    Measure: Sodium

    Time: Up to 33 days

    Description: Change from baseline in potassium

    Measure: Potassium

    Time: Up to 33 days

    Description: Change from baseline in carbon dioxide

    Measure: Carbon dioxide

    Time: Up to 33 days

    Description: Change from baseline in chloride

    Measure: Chloride

    Time: Up to 33 days

    Description: Change from baseline in albumin

    Measure: Albumin

    Time: Up to 33 days

    Description: Change from baseline in total protein

    Measure: Total protein

    Time: Up to 33 days

    Description: Change from baseline in alkaline phosphatase

    Measure: Alkaline phosphatase

    Time: Up to 33 days

    Description: Change from baseline in alanine transaminase

    Measure: Alanine transaminase

    Time: Up to 33 days

    Description: Change from baseline in aspartate aminotransferase

    Measure: Aspartate aminotransferase

    Time: Up to 33 days

    Description: Change from baseline in bilirubin

    Measure: Bilirubin

    Time: Up to 33 days

    Description: Change from baseline in blood urea nitrogen

    Measure: Blood urea nitrogen

    Time: Up to 33 days

    Description: Change from baseline in D-dimer

    Measure: D-dimer

    Time: Up to 33 days

    Description: Change from baseline in fibrinogen

    Measure: Fibrinogen

    Time: Up to 33 days

    Description: Change from baseline in PT

    Measure: PT

    Time: Up to 33 days

    Description: Change from baseline in PTT

    Measure: PTT

    Time: Up to 33 days

    Description: Change from baseline in INR

    Measure: INR

    Time: Up to 33 days

    Description: Change from baseline in hsCRP

    Measure: hsCRP

    Time: Up to 33 days

    Description: Change from baseline in ferritin

    Measure: Ferritin

    Time: Up to 33 days

    Description: Change from baseline in LDH

    Measure: LDH

    Time: Up to 33 days

    Description: Change from baseline in IgG

    Measure: IgG

    Time: Up to 33 days

    Description: Change from baseline in IgM

    Measure: IgM

    Time: Up to 33 days

    Description: Change from baseline in IgA

    Measure: IgA

    Time: Up to 33 days

    Description: Change from baseline in IFE

    Measure: IFE

    Time: Up to 33 days

    Description: Change from baseline in troponin

    Measure: Troponin

    Time: Up to 33 days

    Description: Change from baseline in red blood cell count

    Measure: Red blood cell count

    Time: Up to 33 days

    Description: Change from baseline in hemoglobjn

    Measure: Hemoglobin

    Time: Up to 33 days

    Description: Change from baseline in hematocrit

    Measure: Hematocrit

    Time: Up to 33 days

    Description: Change from baseline in mean corpuscular volume

    Measure: Mean corpuscular volume

    Time: Up to 33 days

    Description: Change from baseline in mean corpuscular hemoglobin

    Measure: Mean corpuscular hemoglobin

    Time: Up to 33 days

    Description: Change from baseline in mean corpuscular hemoglobin concentration

    Measure: Mean corpuscular hemoglobin concentration

    Time: Up to 33 days

    Description: Change from baseline in red cell distribution width

    Measure: Red cell distribution width

    Time: Up to 33 days

    Description: Change from baseline in white blood cell count

    Measure: White blood cell count

    Time: Up to 33 days

    Description: Change from baseline in white blood cell differential

    Measure: White blood cell differential

    Time: Up to 33 days

    Description: Change from baseline in platelet count

    Measure: Platelet count

    Time: Up to 33 days

    Description: Change from baseline in mean platelet volume

    Measure: Mean platelet volume

    Time: Up to 33 days

    Description: Change from baseline in platelet distribution width

    Measure: Platelet distribution width

    Time: Up to 33 days

    Description: Change from baseline in SpO2

    Measure: SpO2

    Time: Up to 33 days

    Description: Change from baseline in A-a gradient

    Measure: A-a gradient

    Time: Up to 33 days

    Description: Change from baseline in blood pressure

    Measure: Blood Pressure

    Time: Up to 33 days

    Description: Change from baseline in pulse

    Measure: Pulse

    Time: Up to 33 days

    Description: Change from baseline in respiration rate

    Measure: Respiration Rate

    Time: Up to 33 days

    Description: Change from baseline in body temperature

    Measure: Body Temperature

    Time: Up to 33 days
    142 Randomized Controlled Trial of Angiotensin 1-7 (TXA127) for the Treatment of Severe COVID-19

    The purpose of this study is to determine if administration of angiotensin-(1-7) (TXA127) prevents acute kidney injury and deterioration into multi-organ failure in patients with severe COVID-19. Participants will undergo a 10-day treatment with either placebo or study drug. The drug will be administered intravenously for 3 hours once each day for 10 days consecutively.

    NCT04401423
    Conditions
    1. COVID-19
    Interventions
    1. Drug: TXA127
    2. Drug: Placebo

    Primary Outcomes

    Description: Calculated from baseline (at enrollment) to end of study

    Measure: Change of serum creatinine

    Time: Day 1 and Day 10

    Measure: Number of participants requiring intubation and ventilatory support

    Time: Up to Day 10

    Secondary Outcomes

    Measure: Change in number of deceased participants

    Time: Day 1 and Day 10

    Measure: Number of participants requiring dialysis

    Time: Up to Day 10

    Measure: Number of participants requiring a vasopressors

    Time: Up to Day 10

    Measure: Change in blood inflammatory markers

    Time: Day 1 and Day 10

    Measure: Percent change in supplemental oxygen requirements

    Time: Day 1 and Day 10
    143 A Multicenter, Adaptive, Randomized Blinded Controlled Trial of the Safety and Efficacy of Investigational Therapeutics for the Treatment of COVID-19 in Hospitalized Adults (ACTT-2)

    ACTT-2 will evaluate the combination of baricitinib and remdesivir compared to remdesivir alone. Subjects will be assessed daily while hospitalized. If the subjects are discharged from the hospital, they will have a study visit at Days 15, 22, and 29. For discharged subjects, it is preferred that the Day 15 and 29 visits are in person to obtain safety laboratory tests and oropharyngeal (OP) swab and blood (serum only) samples for secondary research as well as clinical outcome data. However, infection control or other restrictions may limit the ability of the subject to return to the clinic. In this case, these visits may be conducted by phone, and only clinical data will be obtained. The Day 22 visit does not have laboratory tests or collection of samples and is conducted by phone. The primary outcome is time to recovery by Day 29.

    NCT04401579
    Conditions
    1. COVID-19
    Interventions
    1. Other: Placebo
    2. Drug: Remdesivir
    3. Drug: Baricitinib

    Primary Outcomes

    Description: Day of recovery is defined as the first day on which the subject satisfies one of the following three categories from the ordinal scale: 1) Not hospitalized, no limitations on activities; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Hospitalized, not requiring supplemental oxygen and no longer requires ongoing medical care.

    Measure: Time to recovery

    Time: Day 1 through Day 29

    Secondary Outcomes

    Measure: Change from baseline in alanine transaminase (ALT)

    Time: Day 1 through Day 29

    Measure: Change from baseline in aspartate transaminase (AST)

    Time: Day 1 through Day 29

    Measure: Change from baseline in creatinine

    Time: Day 1 through Day 29

    Measure: Change from baseline in glucose

    Time: Day 1 through Day 29

    Measure: Change from baseline in hemoglobin

    Time: Day 1 through Day 29

    Measure: Change from baseline in platelets

    Time: Day 1 through Day 29

    Description: PT reported as international normalized ratio (INR).

    Measure: Change from baseline in prothrombin time (PT)

    Time: Day 1 through Day 29

    Measure: Change from baseline in total bilirubin

    Time: Day 1 through Day 29

    Measure: Change from baseline in white blood cell count (WBC) with differential

    Time: Day 1 through Day 29

    Description: The NEW score has demonstrated an ability to discriminate patients at risk of poor outcomes. This score is based on 7 clinical parameters (respiration rate, oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate, level of consciousness). The NEW Score is being used as an efficacy measure.

    Measure: Change in National Early Warning Score (NEWS) from baseline

    Time: Day 1 through Day 29

    Description: Grade 3 AEs are defined as events that interrupt usual activities of daily living, or significantly affects clinical status, or may require intensive therapeutic intervention. Severe events are usually incapacitating. Grade 4 AEs are defined as events that are potentially life threatening.

    Measure: Cumulative incidence of Grade 3 and 4 clinical and/or laboratory adverse events (AEs)

    Time: Day 1 through Day 29

    Description: An SAE is defined as an AE or suspected adverse reaction is considered serious if, in the view of either the investigator or the sponsor, it results in death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect.

    Measure: Cumulative incidence of serious adverse events (SAEs)

    Time: Day 1 through Day 29

    Description: Measured in days.

    Measure: Duration of hospitalization

    Time: Day 1 through Day 29

    Description: Measured in days.

    Measure: Duration of new non-invasive ventilation or high flow oxygen use

    Time: Day 1 through Day 29

    Description: Measured in days.

    Measure: Duration of new oxygen use

    Time: Day 1 through Day 29

    Description: Measured in days.

    Measure: Duration of new ventilator or extracorporeal membrane oxygenation (ECMO) use

    Time: Day 1 through Day 29

    Description: Measured in days

    Measure: Duration of oxygen use

    Time: Day 1 through Day 29

    Description: For any reason.

    Measure: Incidence of discontinuation or temporary suspension of investigational therapeutics

    Time: Day 1 through Day 10

    Measure: Incidence of new non-invasive ventilation or high flow oxygen use

    Time: Day 1 through Day 29

    Measure: Incidence of new oxygen use

    Time: Day 1 through Day 29

    Measure: Incidence of new ventilator or extracorporeal membrane oxygenation (ECMO) use

    Time: Day 1 through Day 29

    Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.

    Measure: Mean change in the ordinal scale

    Time: Day 1 through Day 29

    Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.

    Measure: Participant's clinical status at Day 15 by ordinal scale

    Time: Day 15

    Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.

    Measure: Percentage of subjects reporting each severity rating on an 8 point ordinal scale

    Time: Days 3, 5, 8, 11, 22, and 29

    Description: Date and cause of death (if applicable).

    Measure: Subject 14-day mortality

    Time: Day 1 through Day 15

    Description: Date and cause of death (if applicable).

    Measure: Subject 28-day mortality

    Time: Day 1 through Day 29

    Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.

    Measure: Time to an improvement of one category using an ordinal scale

    Time: Day 1 through Day 29

    Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.

    Measure: Time to an improvement of two categories using an ordinal scale

    Time: Day 1 through Day 29

    Description: The NEW score has demonstrated an ability to discriminate patients at risk of poor outcomes. This score is based on 7 clinical parameters (respiration rate, oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate, level of consciousness). The NEW Score is being used as an efficacy measure.

    Measure: Time to discharge or to a National Early Warning Score (NEWS) of Time: Day 1 through Day 29

    Measure: Change from baseline in C-reactive protein (CRP)

    Time: Day 1 through Day 29

    Measure: Change from baseline in d-dimer concentration

    Time: Day 1 through Day 29
    144 A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Parallel-group, Multi-center Study of an Inhaled Pan-Janus Kinase Inhibitor, TD-0903, to Treat Symptomatic Acute Lung Injury Associated With COVID-19

    This Phase 2 study will evaluate the efficacy, safety, pharmacodynamics and pharmacokinetics of inhaled TD-0903 compared with a matching placebo in combination with standard of care (SOC) in hospitalized patients with confirmed COVID-19 associated acute lung injury and impaired oxygenation.

    NCT04402866
    Conditions
    1. Acute Lung Injury (ALI) Associated With COVID-19
    2. Lung Inflammation Associated With COVID-19
    Interventions
    1. Drug: TD-0903
    2. Drug: Placebo
    MeSH:Lung Injury Acute Lung Injury Respiratory Distress Syndrome, Adult Pneumonia Inflammation
    HPO:Pneumonia

    Primary Outcomes

    Description: Number of Respiratory Failure-Free Days (RFDs) from randomization through Day 28

    Measure: Part 2: Respiratory Failure-Free Days (RFDs)

    Time: Baseline through Day 28

    Secondary Outcomes

    Description: Proportion of subjects in each category of the 8-point Clinical Status scale. The Clinical Status scale contains 8 different categories that are each assigned a numeric score. The values range from 1 (representing 'Not hospitalized, no limitations on activities') to 8 (representing 'Death'). The various measures describe hospitalization status and the various limitations and requirements for oxygen support.

    Measure: Part 2: Clinical Status Scale

    Time: Day 7, 14, 21 and 28

    Description: Proportion of subjects alive and respiratory failure-free on Day 28

    Measure: Part 2: Subjects alive and respiratory failure-free

    Time: Day 28

    Description: Change from baseline in SaO2/FiO2 ratio on Day 7

    Measure: Part 2: SaO2/FiO2 ratio

    Time: Baseline, Day 7
    145 Pulmozyme to Improve COVID-19 ARDS Outcomes

    This is a randomized double-blind placebo-controlled Phase II trial of recombinant human deoxyribonuclease I (rhDNase I) - Pulmozyme - in mechanically ventilated patients with COVID-19 pneumonia. Patients admitted to the ICU with severe COVID-19 pneumonia who require mechanical ventilation will be invited to participate in this study. Potential subjects will be identified from medical record review or from direct contact with physicians. Investigators will check medical history and confirm eligibility. Informed consent will be obtained from either the patient or designated healthcare proxy. 60 subjects will be enrolled. After obtaining informed consent, patients will be randomized 2:1 to Pulmozyme 2.5 mg BID for up to 28 days or until they are no longer receiving mechanical ventilation, whichever is sooner plus standard of care vs. placebo normal saline 2.5 ml plus standard of care.

    NCT04402944
    Conditions
    1. COVID
    Interventions
    1. Drug: Pulmozyme
    2. Drug: Placebo

    Primary Outcomes

    Description: Primary outcome

    Measure: Ventilator-free days at 28 days

    Time: 28 days

    Secondary Outcomes

    Description: change in airway resistance

    Measure: change in airway resistance

    Time: 28 days

    Description: Change in lung compliance

    Measure: change in lung compliance

    Time: 28 days

    Description: oxygenation

    Measure: oxygenation (PaO2/FiO2 ratio)

    Time: 28 days

    Description: length of stay

    Measure: length of stay (ICU and hospital)

    Time: 28 days

    Description: rate of batotrauma

    Measure: rate of barotrauma

    Time: 28 days

    Description: mortality

    Measure: mortality.

    Time: 28 days
    146 Multicenter, Randomized, Double-Blind, Placebo-Controlled, Proof of Concept Study of LSALT Peptide as Prevention of Acute Respiratory Distress Syndrome (ARDS) and Acute Kidney Injury in Patients Infected With SARS-CoV-2 (COVID-19)

    To evaluate the proportion of subjects alive and free of respiratory failure (e.g. need for non-invasive or invasive mechanical ventilation, high flow oxygen, or ECMO) and free of the need for continued renal replacement therapy (RRT) on Day 28. The need for continued RRT at Day 28 will be defined as either dialysis in the past 3 days (Day 26, 27, or 28) or an eGFR on Day 28 <10 mL/min/1.73 m2.

    NCT04402957
    Conditions
    1. COVID
    2. Severe Acute Respiratory Syndrome
    3. Sars-CoV2
    4. Acute Kidney Injury
    Interventions
    1. Drug: LSALT peptide
    2. Drug: Placebo
    MeSH:Severe Acute Respiratory Syndrome Coronavirus Infections Acute Kidney Injury Syndrome Wounds and Injuries
    HPO:Acute kidney injury

    Primary Outcomes

    Description: To evaluate the efficacy of intravenous LSALT peptide plus standard of care to prevent the progression of COVID-19 to mild, moderate or severe ARDS, acute kidney injury, cardiomyopathy, acute liver injury, coagulopathy, or death in patients infected with SARS-CoV-2 compared with placebo plus standard of care.

    Measure: Development of Acute Respiratory Distress Syndrome (ARDS) and Other Organ Injuries

    Time: 28 days

    Secondary Outcomes

    Description: High-frequency oscillatory ventilation, with its rapid delivery of low tidal volumes and a respiratory rate in the range of 60 to 900 breaths/minute, has also been utilized in ARDS patients.

    Measure: Ventilation-free days

    Time: 28 days

    Description: Oxygen therapy provided as non-invasive therapy for ARDS patients.

    Measure: Time on nasal cannula or oxygen masks

    Time: 28 days

    Description: 28 day mortality - all cause and attributable

    Measure: 28 day mortality - all cause and attributable

    Time: 28 days

    Description: ICU and hospitalization length of stay (days)

    Measure: ICU and hospitalization length of stay (days)

    Time: 28 days

    Description: Swab (nasopharyngeal, nasal, throat, sputum, or lower respiratory tract) at baseline (Day 1) and every 3 days thereafter until eradication → virologic clearance rate

    Measure: SARS-CoV2 testing

    Time: 28 days

    Description: Extracorporeal membrane oxygenation (ECMO) is often used for severe ARDS to allow lung healing/repair and reverse respiratory failure.

    Measure: Need and duration for extracorporeal membrane oxygenation (ECMO)

    Time: 28 days

    Description: Vasopressor free days

    Measure: Vasopressor free days

    Time: 28 days

    Description: Chest X-rays performed at Baseline, Day 3, at clinical improvement, and end-of-treatment (EOT) and study (EOS) to determine presence of bilateral opacities.

    Measure: Radiographic pulmonary assessments

    Time: 28 days

    Description: Change in daily mMRC dyspnea and SOFA scores (0 to 4) with 4 being the most severe outcome

    Measure: Change in modified Medical Research Council (mMRC) dyspnea and Sequential Organ Failure Assessment (SOFA) scores

    Time: 28 days

    Description: Incidence of other organ (non-lung) disorders

    Measure: Incidence of non-lung disorders

    Time: 28 days

    Description: Change in liver function tests (ALT, AST, and total bilirubin levels) from baseline

    Measure: Measures of liver dysfunction

    Time: 28 days

    Description: Change in SCr and eGFR from baseline

    Measure: Measures of kidney dysfunction

    Time: 28 days

    Description: Change in highly-sensitive troponin (hs-troponin) from baseline

    Measure: Measures of cardiac dysfunction

    Time: 28 days

    Description: Change from baseline ACT, aPTT, and/or PT/INR levels

    Measure: Measures of coagulopathies

    Time: 28 days

    Description: Change in baseline antiviral immunoglobulins (IgG, IgM) at EOS.

    Measure: Changes in immunogenic responses

    Time: 28 days

    Description: Changes in total healthcare costs from admission to discharge between treatment groups.

    Measure: Healthcare outcomes

    Time: 28 days

    Description: Change in serum cytokines including IL-1α, IL-1ß, IL-1ra, IL-5, IL-6, IL-8, IL-12, TNFα, CXCL10/IP10, MCP-3, and ferritin drawn at the same time as LSALT peptide levels

    Measure: Molecular changes in pro-inflammatory pathways

    Time: 28 days

    Description: Pharmacokinetics of LSALT peptide over the study period.

    Measure: Pharmacokinetics of LSALT peptide

    Time: 28 days
    147 Hydroxychloroquine and Lopinavir/ Ritonavir for Hospitalization and Mortality Reduction in Patients With COVID-19 and Mild Disease Symptoms: "The Hope Coalition"

    The COVID-19 pandemic has been characterized by high morbidity and mortality, especially in certain subgroups of patients. To date, no treatment has been shown to be effective in controlling this disease in hospitalized patients with moderate and / or severe cases of this disease. Hydroxychloroquine and lopinavir / ritonavir have been shown to inhibit SARS-CoV viral replication in experimental severe acute respiratory symptoms models and have similar activity against SARS-CoV2. Although widely used in studies of critically ill patients, to date, no study has demonstrated its role on the treatment of high-risk, newly diagnosed patients with COVID-19 and mild symptoms.

    NCT04403100
    Conditions
    1. COVID-19
    2. Coronavirus Infection
    3. Virus Disease
    4. Acute Respiratory Infection
    5. SARS-CoV Infection
    Interventions
    1. Drug: Hydroxychloroquine Sulfate Tablets
    2. Drug: Lopinavir/ Ritonavir Oral Tablet
    3. Drug: Hydroxychloroquine Sulfate Tablets plus Lopinavir/ Ritonavir Oral Tablets
    4. Drug: Placebo
    MeSH:Infection Communicable Diseases Respiratory Tract Infections Coronavirus Infections Virus Diseases Severe Acute Respiratory Syndrome
    HPO:Respiratory tract infection

    Primary Outcomes

    Description: Hospitalization is defined as at least 24 hours of acute care in a hospital or similar acute care facility (emergency settings, temporary emergency facilities created for acute care of COVID-19 pandemic)

    Measure: Proportion of participants who were hospitalized for progression of COVID-19 disease

    Time: Measuring during 28-day period since randomization (Intention to treat analysis)

    Measure: Proportion of participants who died due to COVID-19 progression and/ or complications

    Time: Measuring during 28-day period since randomization (Intention to treat analysis)

    Secondary Outcomes

    Description: Viral load change on 03, 07, 10 and 14 after randomization (200 patients per arm)

    Measure: Proportion of participants with viral load change on 03, 07, 10 and 14 after randomization

    Time: Measuring during 14-day period since randomization

    Description: Proportion of participants with clinical improvement, defined as normalization of temperature, Respiratory rate, SaO2, and cough relief (> 50% compared to baseline measured on a visual analog scale) in the last 72 hours.

    Measure: Time to clinical improvement

    Time: Measuring during 28-day period since randomization

    Description: Proportion of participants with clinical improvement, defined as as time to need for hospitalization due to dyspnea, death, need for mechanical ventilation, shock and need for vasoactive amines;

    Measure: Time to clinical failure

    Time: Measuring during 28-day period since randomization

    Description: Proportion of participants with hospitalization for any cause

    Measure: Hospitalization for any cause

    Time: Measuring during 28-day period since randomization

    Measure: Proportion of participants who died due to pulmonary complications

    Time: Measuring during 28-day period since randomization

    Measure: Proportion of participants who died due to cardiovascular complications

    Time: Measuring during 28-day period since randomization

    Description: Evaluation of adverse events evaluated as associated to any of study arms

    Measure: Proportion of participants who presented with adverse events

    Time: Measuring during 28-day period since randomization

    Description: Proportion of participants who presented sustained improvement on respiratory scale defined as at least 48 hours of improvement.

    Measure: Time to improvement on respiratory scale symptoms

    Time: Measuring during 28-day period since randomization

    Measure: proportion of non-adherent participants to any of study drugs

    Time: Measuring during 10-day period since randomization
    148 Randomized Clinical Trial of Açaí Palm Berry Extract as an Intervention in Patients Diagnosed With COVID-19

    The Açaí trial will be testing if the açaí berry extract, a safe natural product with anti-inflammatory properties, can be used as a treatment option in adult patients with COVID-19 in the community.

    NCT04404218
    Conditions
    1. COVID
    Interventions
    1. Dietary Supplement: Açaí palm berry extract - natural product
    2. Other: Placebo

    Primary Outcomes

    Description: Symptom comparison between patients from the treatment vs control group, using an ordinal symptom scale based on the WHO scale. Patients who were hospitalized will be classified according to their worst score over 30 days and non-hospitalized patients according to their score at 30 days.

    Measure: 7-point ordinal symptom scale

    Time: 30 days

    Secondary Outcomes

    Description: First occurrence of all-cause mortality or need for mechanical ventilation

    Measure: The composite of all-cause mortality and need for mechanical ventilation

    Time: 30 days

    Description: First occurrence of all-cause mortality or hospitalization

    Measure: The composite of all-cause mortality and hospitalization

    Time: 30 days

    Description: All-cause mortality

    Measure: All-cause mortality

    Time: 30 days

    Description: Need for mechanical ventilation

    Measure: Need for mechanical ventilation

    Time: 30 days

    Description: Need for hospitalization

    Measure: Need for hospitalization

    Time: 30 days
    149 A Phase 3 Randomized, Double-blind, Placebo-controlled, Multicenter Study of Pacritinib Plus Standard of Care Versus Placebo and Standard of Care in Hospitalized Patients With Severe COVID-19 With or Without Cancer

    This is a Phase 3 randomized, double-blind, placebo-controlled, multicenter study to evaluate the efficacy and safety of pacritinib in hospitalized patients with severe COVID-19 with or without cancer.

    NCT04404361
    Conditions
    1. COVID
    Interventions
    1. Drug: Pacritinib
    2. Drug: Placebo

    Primary Outcomes

    Description: The proportion is calculated as the number of patients who progress divided by the total number of patients in the ITT population.

    Measure: Proportion of patients who progress to IMV and/or ECMO or death during the 28 days following randomization

    Time: 28 days
    150 CACOLAC : Randomized Trial of Citrulline Administration in the Hospital Patient in Intensive Care for COVID-19 Acute Respiratory Distress Syndrome

    Respiratory involvement of SARS-CoV2 leads to acute respiratory distress syndrome (ARDS) and significant immunosuppression (lymphopenia) exposing patients to long ventilation duration and late mortality linked to the acquisition of nosocomial infections. Lymphopenia characteristic of severe forms of ARDS secondary to SARS-CoV2 infection may be linked to expansion of MDSCs and arginine depletion of lymphocytes. Severe forms of COVID-19 pneumonitis are marked by persistent ARDS with acquisition of nosocomial infections as well as by prolonged lymphocytic dysfunction associated with the emergence of MDSC. It has been found in intensive care patients hypoargininaemia, associated with the persistence of organ dysfunction (evaluated by the SOFA score), the occurrence of nosocomial infections and mortality. Also, it has been demonstrated that in these patients, the enteral administration of ARG was not deleterious and increased the synthesis of ornithine, suggesting a preferential use of ARG by the arginase route, without significant increase in argininaemia nor effect on immune functions. L-citrulline (CIT), an endogenous precursor of ARG, is an interesting alternative to increase the availability of ARG. Recent data demonstrate that the administration of CIT in intensive care is not deleterious and that it very significantly reduces mortality in an animal model of sepsis, corrects hypoargininemia, with convincing data on immunological parameters such as lymphopenia, which is associated with mortality, organ dysfunction and the occurrence of nosocomial infections. The availability of ARG directly impacts the mitochondrial metabolism of T lymphocytes and their function. The hypothesis is therefore that CIT supplementation is more effective than the administration of ARG to correct hypoargininaemia, decrease lymphocyte dysfunction, correct immunosuppression and organ dysfunction in septic patients admitted to intensive care. The main objective is to show that, in patients hospitalized in intensive care for ARDS secondary to COVID-19 pneumonia, the group of patients receiving L-citrulline for 7 days, compared to the group receiving placebo, has a score of organ failure decreased on D7 (evaluated by the SOFA score) or by the last known SOFA score if the patient has died or been resuscitated.

    NCT04404426
    Conditions
    1. ARDS Secondary to COVID-19 Pneumonia
    Interventions
    1. Dietary Supplement: L-citrulline
    2. Other: Placebo
    MeSH:Pneumonia Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury
    HPO:Pneumonia

    Primary Outcomes

    Description: SOFA score for organ failures on D7 or last known SOFA score if the patient has died or been resuscitated

    Measure: SOFA

    Time: Day 7

    Secondary Outcomes

    Description: Number and phenotype of lymphocytes on days 1, 3, 7, 10 and 14

    Measure: Number and phenotype of lymphocytes

    Time: Days 1, 3, 7, 10 and 14

    Description: Monocytic expression HLA-DR (Flow cytometry) on days 1, 3, 7, 10 and 14

    Measure: HLA-DR

    Time: Days 1, 3, 7, 10 and 14

    Description: Number of Myeloid-derived suppressor cells (Flow cytometry) on days 1, 3, 7, 10 and 14

    Measure: Number of Myeloid-derived suppressor cells

    Time: Days 1, 3, 7, 10 and 14

    Description: Plasma cytokines / chemokines (IL-6, IL-8, IL-10, IL-7, CXCL10, G-CSF, TNF-alpha, IFN-β) at days 1, 3, 7, 10 and 14

    Measure: Plasma cytokines / chemokines

    Time: Days 1, 3, 7, 10 and 14

    Description: Diversity of the repertoire T at days 1, 3, 7, 10 and 14

    Measure: Repertoire T

    Time: Days 1, 3, 7, 10 and 14

    Description: T lymphocyte exhaustion: measurement of lymphocyte apoptosis and lymphocyte proliferation on days 1, 3, 7, 10 and 14

    Measure: Lymphocyte T exhaustion

    Time: Days 1, 3, 7, 10 and 14

    Description: Measurement of mitochondrial activity (measurement of the number of mitochondria and their membrane potential, measurement of the expression of Beclin1) on days 1, 3, 7, 10 and 14

    Measure: Mitochondrial activity

    Time: Days 1, 3, 7, 10 and 14

    Description: Plasma amino acids (arginine and its metabolites (ornithine, glutamate, glutamine, citrulline, proline) and tryptophan / kynurenine) on days 1, 3, 7, 10 and 14

    Measure: Plasma amino acids

    Time: Days 1, 3, 7, 10 and 14

    Description: SOFA score of organ failures on days 3, 7, 10 and 14

    Measure: SOFA

    Time: Days 3, 7, 10 and 14

    Description: Duration of hospitalization in intensive care (days), up to day 28 maximum

    Measure: Duration of hospitalization in intensive care

    Time: Day 28

    Description: Duration of hospital stay in hospital (days), up to day 28 maximum

    Measure: Duration of hospital stay in hospital

    Time: Day 28

    Description: Duration of mechanical ventilation (days), up to day 28 maximum

    Measure: Duration of mechanical ventilation

    Time: Day 28

    Description: Mortality in intensive care on day 28

    Measure: Mortality in intensive care on day 28

    Time: Day 28

    Description: Hospital mortality on day 28

    Measure: Hospital mortality on day 28

    Time: Day 28

    Description: Measurement of the presence of SARS-CoV2 in the tracheal aspiration by PCR on days 1, 3, 7, 10 and 14

    Measure: Measurement of the presence of SARS-CoV2

    Time: Days 1, 3, 7, 10 and 14

    Description: Incidence of nosocomial infections during the intensive care unit (maximum D28). The diagnosis of nosocomial infections will be made according to the definitions of nosocomial infections of the CDC. An independent committee of experts will validate or not the infections

    Measure: Nosocomial infections

    Time: D28

    Description: Number of days of exposure to each antibiotic per 1000 days of hospitalization (maximum day 28).

    Measure: Number of days of exposure to each antibiotic per 1000 days of hospitalization

    Time: Day 28
    151 A Phase 2a, Randomized, Observer-Blind, Placebo Controlled, Dose-Confirmation Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of mRNA-1273 SARS-COV-2 Vaccine in Adults Aged 18 Years and Older

    This clinical study will assess the safety, reactogenicity, and immunogenicity of 2 dose levels of mRNA-1273 SARS-COV-2 vaccine in adults 18 years of age or older.

    NCT04405076
    Conditions
    1. SARS-CoV-2
    Interventions
    1. Biological: Biological: mRNA-1273: 50 mcg
    2. Other: Placebo
    3. Biological: Biological: mRNA-1273: 100 mcg

    Primary Outcomes

    Measure: Solicited local and systemic adverse reactions (ARs)

    Time: 7 days post-vaccination

    Measure: Unsolicited adverse events (AEs)

    Time: 28 days post-vaccination

    Measure: Medically-attended adverse events (MAAEs)

    Time: Month 0 through Month 13

    Measure: Serious adverse events (SAEs)

    Time: Month 0 through Month 13

    Measure: Change in the measure of clinical safety laboratory values in Cohort 2 from baseline

    Time: Through 1 month after last vaccination

    Measure: The number and percentage of participants with abnormalities in blood pressure, temperature, HR or respiratory rate will be assessed.

    Time: Through 1 year after last vaccination

    Measure: The number and percentage of participants with abnormalities in physical examinations will be assessed

    Time: Through 1 year after last vaccination

    Measure: Evaluate immunogenicity of mRNA-1273 by titer of SARS-CoV-2-specific binding antibody (bAb) measured by enzyme-linked immunosorbent assay (ELISA)

    Time: Through 1 year after the final dose

    Secondary Outcomes

    Measure: Titer of SARS-CoV-2-specific neutralizing antibody (nAb)

    Time: Through 1 year post last vaccination

    Description: Seroconversion as measured by an increase of SARS-CoV-2-specific neutralizing antibody (nAb) titer either from below the limit of detection (LOD) or lower limit of quantification (LLOQ) to equal to or above LOD or LLOQ, or a 4-times higher titer in participants with pre-existing nAb titers.

    Measure: Seroconversion as measured by an increase of SARS-CoV-2-specific neutralizing antibody (nAb) titer

    Time: Through 1 year post last vaccination
    152 Randomized, Double-blind, Placebo-controlled Trial of TAF/FTC for Pre-exposure Prophylaxis of COVID-19 in Healthcare Workers (CoviPrep Study)

    A randomized parallel double-blinded placebo-controlled clinical trial to evaluate the effect of Emtricitabine/Tenofovir alafenamide (FTC/TAF) compared with placebo on the risk of developing SARS-CoV-2 disease (COVID-19) in healthcare workers with high transmission risk in addition to currently recommended control measures.

    NCT04405271
    Conditions
    1. Healthcare Workers
    2. COVID-19
    3. SARS-CoV 2
    Interventions
    1. Drug: Emtricitabine/Tenofovir Alafenamide 200 MG-25 MG Oral Tablet
    2. Drug: Placebo

    Primary Outcomes

    Description: SARS-CoV-2 disease (COVID-19) with or without symptoms at week 12 of treatment as defined by the presence of specific antibodies against the virus. Positive cases will be confirmed by PCR

    Measure: COVID-19 incident cases

    Time: During treatment (12 weeks)

    Secondary Outcomes

    Description: Number of asymptomatic SARS-CoV-2 (Covid-19) infections confirmed by serology

    Measure: Number of asymptomatic SARS-CoV-2 (Covid-19) infections confirmed by serology

    Time: During treatment (12 weeks)

    Description: Severity of symptomatic SARS-CoV-2 (Covid-19) infections as defined by the following categories: Mild symptoms: malaise, fever, cough, arthralgia myalgias, Moderate symptoms: same as above plus shortness of breath Severe symptoms: clinical status requiring admission in Intensive care unit

    Measure: Severity of symptomatic COVID-19

    Time: During treatment (12 weeks)

    Description: Respiratory symptom duration in days

    Measure: Respiratory symptom duration in days

    Time: During treatment (12 weeks)

    Description: Relation between treatments and symptoms duration

    Measure: Relation between treatments and symptoms duration

    Time: During treatment (12 weeks)

    Description: Time course of specific IgM/IgG seroconversion

    Measure: Time course of specific IgM/IgG seroconversion

    Time: During treatment (12 weeks)
    153 Randomized, Placebo Controlled, Double Blind Clinical Trial to Evaluate the Efficacy of Molecule D11AX22 in Adults Patients From Valle Del Cauca, Colombia With Early Stages of SARS COV2 / COVID-19

    Double blind, placebo controlled, randomized clinical trial to evaluate the efficacy of ivermectin in preventing progression of disease in adult patients with early stages of COVID-19

    NCT04405843
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Ivermectin Oral Product
    2. Drug: Placebo

    Primary Outcomes

    Description: Time until resolution of symptoms

    Measure: Time to event

    Time: 21 days

    Secondary Outcomes

    Description: Clinical condition in an ordinal scale of 7 points, on day 2. Higher scores indicate worse outcomes

    Measure: Clinical condition on day 2

    Time: On day 2 (± 1 day) after randomization

    Description: Clinical condition in an ordinal scale of 7 points, on day 5. Higher scores indicate worse outcomes

    Measure: Clinical condition on day 5

    Time: On day 5 (± 1 day) after randomization

    Description: Clinical condition in an ordinal scale of 7 points, on day 8. Higher scores indicate worse outcomes

    Measure: Clinical condition on day 8

    Time: On day 8 (± 1 day) after randomization

    Description: Clinical condition in an ordinal scale of 7 points, on day 11. Higher scores indicate worse outcomes

    Measure: Clinical condition on day 11

    Time: On day 11 (± 1 day) after randomization

    Description: Clinical condition in an ordinal scale of 7 points, on day 15. Higher scores indicate worse outcomes

    Measure: Clinical condition on day 15

    Time: On day 15 (± 1 day) after randomization

    Description: Clinical condition in an ordinal scale of 7 points, on day 21. Higher scores indicate worse outcomes

    Measure: Clinical condition on day 21

    Time: On day 21 (± 1 day) after randomization

    Description: Proportion of subjects who require hospitalization, use of supplementary oxygen for >24 hours or ICU admission

    Measure: Proportion of subjects with additional care

    Time: 21 days

    Description: Proportion of subjects who die

    Measure: Proportion of subjects who die

    Time: From randomization up to 21 days

    Description: Duration of supplementary oxygen, hospitalization, ICU stay

    Measure: Duration of additional care

    Time: 21 days

    Description: Proportion of subjects who develop solicited adverse events

    Measure: Adverse events

    Time: 21 days

    Description: Proportion of subjects who required discontinuation of the intervention due to adverse events

    Measure: Proportion of subjects who discontinue intervention

    Time: 21 days

    Description: Time until deterioration of 2 or more points in an ordinal 7 points scale.

    Measure: Time to event

    Time: 21 days

    Description: Number of days with fever since randomization

    Measure: Duration of fever

    Time: 21 days
    154 Ivermectin and Doxycycline in Combination or Ivermectin Alone for the Treatment of Adult Bangladeshi Patients Hospitalized for COVID-19: a Randomised, Double-blind, Placebo-controlled Trial.

    Burden: Initial outbreak of corona virus disease 2019 (COVID-19) was reported from Wuhan, China in early December 2019.Presently known to be caused by a novel beta-corona virus, named as Severe acute respiratory syndrome corona virus 2 ( SARS-CoV-2). World Health Organization (WHO) declared a pandemic on March. The clinical characteristics of COVID-19 include respiratory symptoms, fever, cough, dyspnoea and pneumonia Infected individuals exhibit: 1. Mostly mild illness (80% +) recover without any treatment (~80%) 2. Moderate illness that needs hospitalization and recovers after standard 3. supportive treatment (~14%) 4. Critical illness (~5%) needs ICU support 5. Death (1-2% ) COVID-19 has now spread >210 countries and territories globally. SARS-CoV-2 is a respiratory virus which spreads primarily through droplets generalized when an infected person coughs or sneezes or through droplets of saliva or discharge from the nose. Symptomatic management remains the mainstay of treatment strategy. Mortality appears to be more common in older individuals and those with co-morbidities, such as chronic lung disease, cardiovascular disease and diabetes. Young people with no comorbidities also appear to be at risk for critical illness including multi-organ failure and death. Seen more in Bangladesh between 21-40 yrs of age. Knowledge Gap: There is no specific treatment against this new virus that WHO has officially declared until now.There are many pharmacologic therapies that are being used or considered for treatment of COVID-19. National Guidelines on Clinical Management of Corona virus Disease 2019 (Covid-19): V 5.0 date 9th April 2020) CDC, DGHS, GoB Thus an RCT is urgently needed in Bangladesh: Based on recent literatures on Rx studies in COVID-19 patients from other countries as well as its availability & affordability of those repurposed medicines

    NCT04407130
    Conditions
    1. COVID-19 Patients
    Interventions
    1. Drug: Ivermectin + Doxycycline + Placebo
    2. Drug: Ivermectin + Placebo
    3. Drug: Placebo

    Primary Outcomes

    Description: • Presence of virus will be negative on Day 7 detected by RT PCR

    Measure: Virological clearance

    Time: within 7 days after enrollment

    Description: • Body temperature will be between 36.1 to 37.2 C by day 7 detected by Infrared thermometer

    Measure: Remission of fever

    Time: within 7 days after enrollment

    Description: • Remission of cough: No signs of cough showing respiratory rate within 12-20/ min, on day7

    Measure: Remission of cough

    Time: within 7 days after enrollment

    Secondary Outcomes

    Description: Detected SPO2 level <94% on Day 7or before by pulse oxymeter

    Measure: Patients requiring oxygen

    Time: within 7 days after enrollment

    Description: Patients who fail to maintain pulse oxymeter detected SpO2 level>93% despite O2 supplementation of 2-6 L/min, on Day 7 or before

    Measure: Patients failing to maintain SpO2 >93% despite oxygenation

    Time: within 7 days after enrollment

    Description: Any number of days on oxygen support on Day 7 or before recorded in CRF

    Measure: Number of days on oxygen support

    Time: within 7 days after enrollment

    Description: Hospital stay ≥7days to ≤14 days as per CRF records

    Measure: Duration of hospitalization

    Time: within 14 days after enrollment

    Description: Death any time during 14 days of study period from any cause recorded in CRF and Hospital death certificate

    Measure: All causes of mortality

    Time: within 14 days after enrollment
    155 Effects of Nicotinamide Riboside on the Clinical Outcome of Covid-19 in the Elderly. A Randomized Double-blind, Placebo-controlled Trial of Nicotinamide Riboside NR-COVID19

    The purpose of this study is to investigate whether nicotinamide riboside supplementation can attenuate the severity of SARS-CoV-2 infections in elderly patients. A major event in aging is the loss of the central metabolite nicotinamide adenine dinucleotide (NAD+) that appear to be important in the proinflammatory environment that occur during aging. Notably, recent work from our and other groups suggest that aging can be ameliorated by even a short-term treatment of the NAD+ precursor nicotinamide riboside. Nicotinamide riboside has recently been shown to be able to return aging tissues to a younger state even after short term treatment. This vitamin B3- analog is naturally occurring, is readily taken up through oral administration and has been tested in human trials with few side effects. In this randomized double blinded case-control trial, the investigators will treat elderly (>70 year old) COVID19 patients with 1 g of nicotinamide riboside (NR-E) or placebo for 2 weeks and investigate if this affects the clinical course of the disease.

    NCT04407390
    Conditions
    1. COVID
    Interventions
    1. Dietary Supplement: Nicotinamide riboside
    2. Dietary Supplement: Placebo

    Primary Outcomes

    Description: Hypoxic respiratory failure as defined by need for oxygen therapy

    Measure: Hypoxic respiratory failure

    Time: Day 1

    Description: Hypoxic respiratory failure as defined by need for oxygen therapy

    Measure: Hypoxic respiratory failure

    Time: Day 7

    Description: Hypoxic respiratory failure as defined by need for oxygen therapy

    Measure: Hypoxic respiratory failure

    Time: Day 14

    Description: Hypoxic respiratory failure as defined by need for oxygen therapy

    Measure: Hypoxic respiratory failure

    Time: Day 90

    Secondary Outcomes

    Description: Overall mortality

    Measure: Mortality

    Time: Day 1

    Description: Overall mortality

    Measure: Mortality

    Time: Day 7

    Description: Overall mortality

    Measure: Mortality

    Time: Day 14

    Description: Overall mortality

    Measure: Mortality

    Time: Day 90

    Description: Sepsis

    Measure: Sepsis

    Time: Day 1

    Description: Sepsis

    Measure: Sepsis

    Time: Day 7

    Description: Sepsis

    Measure: Sepsis

    Time: Day 14

    Description: Sepsis

    Measure: Sepsis

    Time: Day 90

    Description: Circulatory failure as defined by a need for interventions to support the circulatory system.

    Measure: Circulatory failure

    Time: Day 1

    Description: Circulatory failure as defined by a need for interventions to support the circulatory system.

    Measure: Circulatory failure

    Time: Day 7

    Description: Circulatory failure as defined by a need for interventions to support the circulatory system.

    Measure: Circulatory failure

    Time: Day 14

    Description: Circulatory failure as defined by a need for interventions to support the circulatory system.

    Measure: Circulatory failure

    Time: Day 90

    Description: Days in hospital

    Measure: Days in hospital

    Time: Day 1

    Description: Days in hospital

    Measure: Days in hospital

    Time: Day 7

    Description: Days in hospital

    Measure: Days in hospital

    Time: Day 14

    Description: Days in hospital

    Measure: Days in hospital

    Time: Day 90

    Description: Measurements of NAD+ and related metabolite levels by mass spectrometry in whole blood.

    Measure: NAD levels

    Time: Day 1

    Description: Measurements of NAD+ and related metabolite levels by mass spectrometry in whole blood.

    Measure: NAD levels

    Time: Day 7

    Description: Measurements of NAD+ and related metabolite levels by mass spectrometry in whole blood.

    Measure: NAD levels

    Time: Day 14

    Description: Measurements of NAD+ and related metabolite levels by mass spectrometry in whole blood.

    Measure: NAD levels

    Time: Day 90
    156 Multicenter, Double-blind, Randomized, Placebo-controlled Study to Assess the Efficacy, Safety and Tolerability of Ivermectin in Mild Virus-positive Subjects (SARS-CoV)-2 With or Without Symptoms

    This study aims to evaluate the efficacy, safety and tolerability of Ivermectin in patients with mild SARS-CoV-2 infection, in the rate of progression to severe 2019 novel coronavirus disease (COVID-19). The primary efficacy endpoint is the proportion of participants with a disease control status defined as no progression of severe disease Hypothesis (H0): There is no difference between group A (ivermectin + paracetamol) and group B (ivermectin + paracetamol) in terms of the primary endpoint on day 14.

    NCT04407507
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Ivermectin
    2. Drug: Placebo

    Primary Outcomes

    Description: The subject is considered to have progressed to severe illness when one or more of the following criteria are present: Breathing difficulty (≥30 breaths per minute); Resting oxygen saturation ≤93%; Severe complications such as: respiratory failure, need for mechanical ventilation, septic shock, non-respiratory organic failure.

    Measure: Participants with a disease control status defined as no disease progression to severe.

    Time: 14 days
    157 A Multicenter, Randomized, Double-blinded Placebo-controlled Study of Recombinant Interleukin-7 (CYT107) for Immune Restoration of Hospitalized Lymphopenic Patients With Coronavirus COVID-19 Infection in France and Belgium

    Comparison of the effects of CYT107 vs Placebo administered IM at 10μg/ kg twice a week for two weeks on immune reconstitution of lymphopenic COVID-19 patients.

    NCT04407689
    Conditions
    1. COVID-19
    2. Lymphocytopenia
    Interventions
    1. Drug: Interleukin-7
    2. Drug: Placebo
    MeSH:Lymphopenia
    HPO:Lymphopenia

    Primary Outcomes

    Description: A statistically significant increase of the absolute lymphocyte count (ALC) from randomization to day 30 or Hospital Discharge

    Measure: Improvement of the absolute lymphocyte count (ALC) of lymphopenic (ALC≤1000/mm3) COVID-19 infected participants out to approximately 30 days following initial Study drug administration or Hospital discharge (HD), whichever occurs first

    Time: 1 month

    Secondary Outcomes

    Description: The time to clinical improvement to determine if CYT107 will improve the clinical status of hospitalized COVID-19 patients as measured by clinical improvement score

    Measure: "clinical improvement" as defined by a 2 points improvement in a 7-point ordinal scale for Clinical Assessment, through day 30 or HD.

    Time: 1 month

    Description: The decrease of SARS-CoV-2 viral load from measurements at baseline and days of treatment dose 4 and dose 5, Day 21 and Day 30 or HD (whichever occurs first)

    Measure: a significant decline of SARS-CoV-2 viral load through day 30 or HD

    Time: 1 month or HD (whichever occurs first)

    Description: Incidence of secondary infections based on pre-specified criteria as adjudicated by the Secondary Infections Committee (SIC) through Day 45

    Measure: frequency of secondary infections through day 45 compared tp placebo arm

    Time: 45 days

    Description: Number of days of hospitalization during index hospitalization (defined as time from initial Study drug treatment through HD)

    Measure: length of hospitalization compared to placebo arm

    Time: 45 days

    Description: Number of days in ICU during index hospitalization

    Measure: length of stay in ICU compared to placebo arm

    Time: 45 days

    Description: Readmissions to ICU through Day 45

    Measure: number of readmissions to ICU compared to placebo arm

    Time: 45 days

    Description: Organ support free days (OSFDs) during index hospitalization (This includes ventilator assistance free days)

    Measure: organ support free days compared to placebo arm

    Time: 45 days

    Description: Number of readmissions to the hospital through Day 45

    Measure: Frequency of re-hospitalization through day 45 compared to placebo arm

    Time: 45 days

    Description: All-cause mortality through Day 45

    Measure: All-cause mortality through day 45 compared to placebo arm

    Time: 45 days

    Description: Absolute numbers of CD4+ and CD8+ T-cell counts at timepoints indicated on the Schedule of Activities (SoA) through Day 30 or HD

    Measure: CD4+ and CD8+ T cell counts compared to placebo arm

    Time: 30 days

    Description: Track and evaluate other known biomarkers of inflammation, Ferritin, from baseline to day 30

    Measure: level of other known biomarkers of inflammation: Ferritin compared to placebo arm

    Time: 30 days

    Description: Track and evaluate other known biomarkers of inflammation, CRP from baseline to day 30

    Measure: Level of other known biomarkers of inflammation: CRP compared to placebo arm

    Time: 30 days

    Description: Track and evaluate other known biomarkers of inflammation, D-dimer from baseline to day 30

    Measure: Level of other known biomarkers of inflammation: D-dimer compared to placebo arm

    Time: 30 days

    Description: Evaluate improvement of the NEWS2 score value. Score form 0 to 4: NO Risk Score of 7 or more: High risk

    Measure: Physiological status through NEWS2 evaluation compared to Placebo arm

    Time: 30 days

    Other Outcomes

    Description: Incidence and scoring of all grade 3-4 adverse events through Day 45 (using CTCAE Version 5.0 to assess severity)

    Measure: Safety assessment through incidence and scoring of grade 3-4 adverse events

    Time: 45 days
    158 Efficacy, Safety, and Tolerability of GLS-1200 Topical Nasal Spray in the Prevention of Incident Confirmed, Symptomatic SARS-CoV-2 Infection in Healthcare Personnel

    This clinical trial will evaluate the safety, tolerability and effectiveness of topical GLS-1200 nasal spray to reduce the incidence of confirmed, symptomatic SARS-CoV-2 infection.

    NCT04408183
    Conditions
    1. SARS-CoV 2
    2. Infection
    Interventions
    1. Drug: GLS-1200
    2. Drug: Placebo
    MeSH:Infection Communicable Diseases

    Primary Outcomes

    Measure: Evaluate the number of GLS-1200 topical nasal spray adverse events as assessed by CTCAE v5.0

    Time: 4 weeks of treatment

    Measure: Incidence of SARS-CoV-2 infection, confirmed by PCR relative to treatment group

    Time: 4 weeks of treatment

    Secondary Outcomes

    Measure: Symptom score of documented SARS-CoV-2 infection relative to treatment group with a higher score being a worse outcome.

    Time: 4 weeks of treatment
    159 A Phase III, Randomized, Double-Blind, Multicenter Study to Evaluate the Efficacy and Safety of Remdesivir Plus Tocilizumab Compared With Remdesivir Plus Placebo in Hospitalized Patients With Severe COVID-19 Pneumonia

    This study will evaluate the efficacy and safety of combination therapy with remdesivir plus tocilizumab compared with remdesivir plus placebo in hospitalized patients with COVID-19 pneumonia.

    NCT04409262
    Conditions
    1. COVID-19 Pneumonia
    Interventions
    1. Drug: Remdesivir
    2. Drug: Tocilizumab
    3. Drug: Placebo
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Measure: Time from Randomization to Hospital Discharge (or "ready for discharge" as evidenced by normal body temperature and respiratory rate, and stable oxygen saturation on ambient air or Time: Up to Day 28

    Secondary Outcomes

    Measure: Time to Clinical Improvement (TTCI) Defined as Time from Randomization to National Early Warning Score 2 (NEWS2) Score of Time: Up to Day 60

    Measure: Time to Improvement of at Least 2 Categories Relative to Baseline on a 7-Category Ordinal Scale of Clinical Status

    Time: Up to Day 60

    Measure: Clinical Status as Assessed by the Investigator Using a 7-Category Ordinal Scale of Clinical Status on Days 7, 14, 21, and 28

    Time: Days 7, 14, 21, and 28

    Measure: Proportion of Participants Requiring Initiation of Mechanical Ventilation Post-baseline

    Time: Up to Day 60

    Measure: Ventilator-Free Days from Randomization to Day 28

    Time: Up to Day 28

    Measure: Proportion of Participants Requiring Initiation of Intensive Care Unit (ICU) Care Post-baseline

    Time: Up to Day 60

    Measure: Duration of ICU Stay in Days

    Time: Up to Day 60

    Description: For participants entering the study already in ICU or on mechanical ventilation, clinical failure is defined as a one-category worsening on the ordinal scale, withdrawal or death.

    Measure: Time to Clinical Failure, Defined as the Time from Randomization to the First Occurrence of Death, Mechanical Ventilation, ICU Admission, or Withdrawal (whichever occurs first)

    Time: Up to Day 60

    Measure: Mortality up to Day 28 and Day 60

    Time: Days 28 and 60

    Measure: Mortality Rate on Days 7, 14, 21, 28, and 60

    Time: Days 7, 14, 21, 28, and 60

    Measure: Time to Recovery, Defined as Time from Randomization to the Time when a Category of 2, Non-ICU Hospital Ward (or "Ready for Hospital Ward") not Requiring Supplemental Oxygen, or Better is Observed

    Time: Up to Day 28

    Measure: Duration of Supplemental Oxygen Use

    Time: Up to Day 60

    Other Outcomes

    Measure: Percentage of Participants with Adverse Events (AEs)

    Time: Up to 60 days

    Measure: Proportion of Participants with any Post-Treatment Infection

    Time: Up to 60 days

    Measure: Plasma Concentration of Remdesivir

    Time: Days 4 and 7
    160 Randomized Double Blind Placebo-Controlled Study to Determine if Prophylaxis With RTB101 Compared to Placebo Reduces Severity of Lab Confirmed COVID19 in Adults ≥65 Years in a Nursing Home in Which ≥1 Person(s) Have Lab Confirmed COVID19

    The purpose of this study is to determine if prophylaxis with RTB101 decreases the severity of laboratory-confirmed COVID-19 among adults ≥ 65 years who reside in a nursing homes in which one or more residents or staff have laboratory-confirmed COVID-19

    NCT04409327
    Conditions
    1. COVID19
    Interventions
    1. Drug: RTB101
    2. Drug: Placebo

    Primary Outcomes

    Measure: The percentage of subjects who develop laboratory-confirmed COVID-19: - with protocol-defined progressive symptoms OR - are hospitalized OR - die

    Time: Through Week 4

    Secondary Outcomes

    Measure: The percentage of subjects who develop symptomatic laboratory-confirmed COVID-19 infection

    Time: Through Week 4

    Measure: Mortality rate in subjects who develop laboratory-confirmed COVID19

    Time: Through Week 8

    Measure: Percent of subjects who are hospitalized due to having one or more predefined COVID-19 symptoms and laboratory-confirmed SARS-CoV-2

    Time: Through Week 4

    Measure: Percent of subjects who require mechanical ventilation, noninvasive ventilation, high flow nasal canula oxygen delivery or ICU admission during the hospitalization for COVID19

    Time: Through Week 8

    Measure: Safety and tolerability will be assessed by report of AE/SAEs

    Time: Through Week 5 and 8
    161 A Phase 2, Multicenter, Double Blind, Randomized, Placebo-Controlled Study to Evaluate CSL312 in Coronavirus Disease 2019 (COVID 19)

    This is a prospective, phase 2, multicenter, randomized, double blind, placebo controlled, parallel group study to assess the safety and efficacy of CSL312 administered intravenously, in combination with standard of care (SOC) treatment, in patients with Coronavirus disease 2019 (COVID 19)

    NCT04409509
    Conditions
    1. Coronavirus Disease 2019 (COVID-19)
    Interventions
    1. Biological: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody
    2. Drug: Placebo
    MeSH:Coronavirus Infections

    Primary Outcomes

    Measure: The incidence of tracheal intubation or death prior to tracheal intubation

    Time: From randomization to Day 28

    Secondary Outcomes

    Measure: Proportion of subjects with death from all causes

    Time: From randomization to Day 28

    Measure: Proportion of subjects intubated

    Time: From randomization to Day 28

    Measure: Number and proportion of subjects with ≥ 2-point improvement on National Institute of Allergy and Infectious Diseases (NIAID) Ordinal scale

    Time: From randomization to Day 28

    Measure: Number and proportion of subjects within each of the categories of the NIAID

    Time: From randomization to Day 28

    Measure: Proportion of subjects requiring continuous positive airway pressure (CPAP)

    Time: From randomization to Day 28

    Measure: Proportion of subjects requiring bilevel positive airway pressure (BiPAP)

    Time: From randomization to Day 28

    Measure: Proportion of subjects requiring high-flow nasal cannula (HFNC)

    Time: From randomization to Day 28

    Measure: Proportion of subjects requiring extracorporeal membrane oxygenation (ECMO)

    Time: From randomization to Day 28

    Measure: Maximum change from baseline in Sequential Organ Failure Assessment (SOFA) score

    Time: From randomization to Day 28

    Measure: Change from Baseline in SOFA score and in the individual components of SOFA score

    Time: From randomization to Day 28

    Measure: Length of hospital stay

    Time: From randomization to Day 28

    Measure: Number and proportion of subjects experiencing Adverse Events (AEs)

    Time: Up to 28 days after CSL312 or placebo administration

    Measure: Number and proportion of subjects experiencing serious adverse events (SAEs)

    Time: Up to 28 days after CSL312 or placebo administration

    Measure: Number and proportion of subjects with adverse events of special interest (AESIs)

    Time: Up to 28 days after CSL312 or placebo administration

    Measure: Number and proportion of subjects with CSL312 induced anti-CSL312 antibodies

    Time: Up to 28 days after CSL312 or placebo administration

    Measure: Maximum plasma concentration (Cmax) of CSL312

    Time: Up to 28 days after CSL312 administration

    Measure: Time to maximum plasma concentration (Tmax) of CSL312

    Time: Up to 28 days after CSL312 administration

    Measure: Area under the plasma concentration-time curve from time zero to the time of the last measurable concentration (AUC0-last) of CSL312

    Time: Up to 28 days after CSL312 administration

    Measure: Terminal half-life (T1/2) of CSL312

    Time: Up to 28 days after CSL312 administration
    162 Study of the P2Et Extract Obtained From Caesalpinia Spinosa in the Symptomatic Treatment of Subjects With COVID-19 at the Hospital Universitario San Ignacio, Colombia.

    Antioxidants, and particularly polyphenols, have shown protection in respiratory pathologies, which is related to the decrease in the severity of the clinical picture and suppression of inflammation. This suppression of inflammation may be related to the inhibition of NF-kB polyphenols, where its activation is related to the stimulation of 150 stimuli including cytokines (IL-1β, IL-6, THF-α, GM-CSF, MCP-1), TLRs, among others. There may be other additional mechanisms that can help control virus-induced respiratory pathologies, among which are the regulation of reactive oxygen species (ROS) associated with tissue destruction caused by the virus and a selective antiviral action can be reported. direct. The standardized P2Et extract obtained from C. spinosa, by the Immunobiology Group of the Pontificia Universidad Javeriana, is highly antioxidant, decreases lipid peroxidation and tissue damage and induces complete autophagy in stressed or tumor cells. The induction of a full autophagic flow could inhibit the replication of beta-coronaviruses like SARS-CoV-2. Furthermore, P2Et can decrease the factors involved in tissue damage by reducing IL-6 and decrease ILC2 cells of the lung in animals with lung metastases (unpublished data). These antecedents suggest that the supplementation of patients with COVID-19 with the extract P2Et, could improve their general condition and decrease the inflammatory mediators and the viral load.

    NCT04410510
    Conditions
    1. COVID
    2. Coronavirus Infection
    3. SARS-CoV 2
    4. COVID19
    Interventions
    1. Drug: P2Et (Caesalpinia spinosa extract)
    2. Other: Placebo
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome

    Primary Outcomes

    Description: Proportion of patients who reduce the time in the hospital

    Measure: Evaluate the efficacy of P2Et in reducing the length of hospital stay of patients with clinical suspicion or confirmed case of COVID-19

    Time: 30 days

    Secondary Outcomes

    Description: Efficacy of P2Et in reducing the time to clinically significant improvement in patients with clinical suspicion or confirmed case of COVID-19

    Measure: Efficacy of P2Et in reducing the time to clinically significant improvement in patients with clinical suspicion or confirmed case of COVID-19

    Time: 30 days

    Description: Evaluate the efficacy of P2Et in increasing the proportion of patients with clinical suspicion or confirmed case of COVID-19, who achieve clinical improvement after 14 days of treatment

    Measure: Proportion of patients with clinical suspicion or confirmed case of COVID-19, who achieve clinical improvement after 14 days of treatment

    Time: 30 days

    Description: Evaluate the efficacy of P2Et in increasing the proportion of patients with clinical suspicion or confirmed case of COVID-19, who achieve clinical improvement after 28 days of treatment

    Measure: Proportion of patients with clinical suspicion or confirmed case of COVID-19, who achieve clinical improvement after 28 days of treatment

    Time: 30 days

    Description: Assess the efficacy of P2Et in reducing the proportion of hospitalized patients with clinical suspicion or confirmed case of COVID-19 who require admission to the ICU due to worsening clinical symptoms.

    Measure: Efficacy of P2Et in reducing the proportion of hospitalized patients with clinical suspicion or confirmed case of COVID-19 who require admission to the ICU due to worsening clinical symptoms.

    Time: 30 days

    Description: Evaluate the efficacy of P2Et in reducing the proportion of patients with clinical suspicion or confirmed case of COVID-19 who die from the disease.

    Measure: Efficacy of P2Et in reducing the proportion of patients with clinical suspicion or confirmed case of COVID-19 who die from the disease.

    Time: 30 days

    Description: Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) of the P2Et in patients with COVID-19

    Measure: Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) of the P2Et in patients with COVID-19

    Time: 30 days
    163 Hydroxychloroquine Efficacy and Safety in Preventing SARS-CoV-2 Infection and COVID-19 Disease Severity During Pregnancy

    It still unclear how SARS-CoV-2 affects pregnant women and their offspring, as well as which factors may influence obstetrical disease and outcomes, including the timing of maternal viral exposure by gestational age, the effects of parity, age, host immune responses, coexisting medical and obstetrical conditions and the effects of treatment regimens. While further information is gathered, based on the existing evidence from other infections causing pneumonia, pregnant women should be considered to be at high risk for developing severe infection during the current COVID-19 epidemic. Results from clinical trials with HCQ in nonpregnant adults may not be directly extrapolated to pregnant women given the special features of the pregnancy status. Thus, clinical research is urgently needed to improve the care and reduce the risk of poor pregnancy outcomes of women in this and in future epidemics.

    NCT04410562
    Conditions
    1. Pregnancy Related
    2. COVID
    3. Covid-19
    Interventions
    1. Drug: Hydroxychloroquine
    2. Drug: Placebo
    MeSH:Infection

    Primary Outcomes

    Description: Number of PCR-confirmed infected pregnant women assessed from collected nasopharyngeal and oropharyngeal swabs at day 21 after treatment start

    Measure: Number of PCR confirmed cases among pregnant women

    Time: 21 days after intervention

    Secondary Outcomes

    Measure: Incidence of COVID-19 disease during pregnancy

    Time: through study completion, an average of 1 year

    Measure: Incidence of COVID-19-related admissions

    Time: through study completion, an average of 1 year

    Measure: Incidence of all-cause admissions

    Time: through study completion, an average of 1 year

    Measure: Incidence of all-cause outpatient attendances

    Time: through study completion, an average of 1 year

    Measure: Mean duration of symptoms-signs of COVID-19

    Time: through study completion, an average of 1 year

    Measure: Frequency and severity of adverse events

    Time: through study completion, an average of 1 year

    Measure: Incidence of preeclampsia

    Time: through study completion, an average of 1 year

    Measure: Incidence of gestational diabetes

    Time: through study completion, an average of 1 year

    Measure: Incidence of SARS-CoV-2 infections during pregnancy

    Time: through study completion, an average of 1 year

    Measure: Prevalence of intrauterine growth restriction

    Time: through study completion, an average of 1 year

    Measure: Maternal mortality rate

    Time: through study completion, an average of 1 year

    Measure: Proportion of neonates with SARS-CoV-2- intrauterine infection by PCR-confirmed SARS-CoV-2-infection in nasopharyngeal aspirate.

    Time: through study completion, an average of 1 year

    Measure: Proportion of neonates with clinical signs/symptoms of COVID-19

    Time: through study completion, an average of 1 year

    Measure: Prevalence of low birth weight (<10th centile according to local standards)

    Time: through study completion, an average of 1 year

    Measure: Prevalence of preterm birth (<37 weeks of gestational age)

    Time: through study completion, an average of 1 year

    Measure: Prevalence of embryo and foetal losses (miscarriages and stillbirths)

    Time: through study completion, an average of 1 year

    Measure: Frequency of congenital malformations

    Time: through study completion, an average of 1 year

    Measure: Proportion of adverse perinatal outcome

    Time: through study completion, an average of 1 year

    Measure: Neonatal morbidity

    Time: through study completion, an average of 1 year

    Measure: Neonatal mortality rate

    Time: through study completion, an average of 1 year
    164 Randomized Controlled Trial of High Dose of Vitamin D as Compared With Placebo to Prevent Complications Among COVID-19 Patients

    The recent inception of the coronavirus SARS-CoV-2, responsible for the coronavirus disease (COVID-19), has caused thousands of deaths globally. The most frequently reported complications among COVID-19 patients are from respiratory involvement. Vitamin D has immunomodulatory effects that could protect against COVID-19 infection. Indeed, there is good evidence from randomized clinical trials suggesting that high doses of vitamin D administered during cold seasons prevent viral respiratory infections in at risk individual, and more recently, observational studies suggested that the mortality rate from COVID-19 is inversely correlated with levels of serum 25(OH)vitamin D. The hypothesis of the study is that a high dose of vitamin D given orally to patients admitted to the hospital for COVID-19 will prevent the occurrence of respiratory deragement and other adverse clinical events. To evaluate the aforementioned hypothesis, a randomized, controlled, double-blind, clinical trial comparing a 500.000 UI dose of vitamin D versus placebo among COVID-19 patients at moderate risk, requiring hospitalization but without requirements of critical care at admission was designed. The intervention will be one dose of 500.000 UI given orally or matching placebo. The trial has a sequential design with two steps: - The first step, projected to include 200 patients, will assess the effects of the intervention on the respiratory SOFA; and - If there is a detectable effects, the second step, projected to include 1264 patients, will assess the effects on a combined event that includes need of high dose of oxygen or mechanical ventilation. All study outcomes will be measured during the index hospitalization.

    NCT04411446
    Conditions
    1. COVID
    Interventions
    1. Drug: Vitamin D
    2. Drug: Placebo

    Primary Outcomes

    Description: Is the respiratory component of the sequential organ failure assessment score (SOFA score). It is a 4 points scale, each point indicate a deeper respiratory impairment. The score is based on the relationship between the arterial pressure of oxygen (PaO2) and inspired fraction of oxygen (FiO2), as the ratio of both (PaFi). In the cases were arterial blood gas are not measured, the pulse oximetry will be used instead. The respiratory SOFA is as follows: 1: PaO2/FiO2 >=300; 2: PaO2/FiO2 >=200 and <300; 3: PaO2/FiO2 >=100 and <200; 4: PaO2/FiO2 <100. The minimum respiratory SOFA score will be record on daily basis during first week or to death or discharge, whichever occur first. This outcome is the primary outcome of the first study phase.

    Measure: Respiratory SOFA.

    Time: One week

    Description: The start of oxygen supplementation at FiO2 >40% or the initiation of invasive through orotracheal intubation) or non-invasive ventilation (Continuous positive airway pressure or Bilevel positive airway ventilation). This outcome will be recorded during hospitalization to 30 days, the death or discharge, whichever occur first. This is the primary outcome of the second study phase.

    Measure: Need of a high dose of oxygen or mechanical ventilation.

    Time: 30 days

    Secondary Outcomes

    Description: Difference between the oxygen saturation at study entry and the lowest oxygen saturation measured during the first week, the death or discharge, whichever occur first. The oxygen saturation will be measured by pulse oximetry using commercially available devices.

    Measure: Change in oxygen saturation.

    Time: One week

    Description: Oxygen saturation equal or less than 90% in any moment during the hospitalization. This outcome will be measured by pulse oximetry using commercially available devices. The outcome will be measured during the first week, the death or hospital discharge, whichever occur first.

    Measure: Oxygen desaturation.

    Time: One week

    Description: The difference between the Quick SOFA score at study entry and the highest value recorded during the hospitalization. The outcome will be measured during the hospitalization until 30 days, the death or discharge whichever occur first.

    Measure: Change in Quick SOFA score.

    Time: 30 days.

    Description: Myocardial infarction is defined as suspicious symptoms with new Q waves in the EKG and enzymatic elevations compatible with the Fourth MI Definition. The outcome will be measured during the hospitalization until 30 days, the death or discharge whichever occur first.

    Measure: Myocardial infarction.

    Time: 30 days

    Description: Stroke is defined as a focal neurological loss lasting >24 hs as reported by treating physician. The outcome will be measured during the hospitalization until 30 days, the death or discharge whichever occur first.

    Measure: Stroke.

    Time: 30 days

    Description: Acute kidney injury is defined as an increase of at least 50% in serum creatinine levels (as compared with any previous value during the hospitalization). The outcome will be measured during the hospitalization until 30 days, the death or discharge whichever occur first.

    Measure: Acute kidney injury.

    Time: 30 days

    Description: Pulmonary thromboembolism is defined as the presence of suspicious symptoms (i.e. dyspnea) confirmed with objective evidence of a thrombus in the pulmonary tree by CT or MRI or Pulmonary Angiography. The outcome will be measured during the hospitalization until 30 days, the death or discharge whichever occur first.

    Measure: Pulmonary thromboembolism.

    Time: 30 days

    Description: Combined outcome of the aforementioned events, Stroke is defined as a focal neurological loss lasting >24 hs as reported by treating physician. Myocardial infarction is defined as suspicious symptoms with new Q waves in the EKG and enzymatic elevations compatible with the Fourth MI Definition. Pulmonary thromboembolism is defined as the presence of suspicious symptoms (i.e. dyspnea) confirmed with objective evidence of a thrombus in the pulmonary tree by CT or MRI or Pulmonary Angiography. Acute kidney injury is defined as an increase of at least 50% in serum creatinine levels (as compared with any previous value during the hospitalization). The outcome will be measured during the hospitalization until 30 days, the death or discharge whichever occur first.

    Measure: Combined endpoint (stroke, myocardial infarction, acute kidney injury and pulmonary thromboembolism.

    Time: 30 days

    Description: Admission to Intensive Care Unit due to clinical deterioration as judged by the treating physician. The outcome will be measured during the hospitalization until 30 days, the death or discharge whichever occur first.

    Measure: Admission to ICU.

    Time: 30 days

    Description: The start of mechanical ventilation invasive during the hospitalization until 30 days, the death or discharge whichever occur first.

    Measure: Invasive Mechanical Ventilation.

    Time: 30 days

    Description: Total duration of initial hospital stay in days. The outcome will be measured during the hospitalization until 30 days, the death or discharge whichever occur first. In the cases with hospital stays longer than 30 days, it will considered as 30 days.

    Measure: Hospital Length of Stay.

    Time: 30 days.

    Description: Total duration of initial ICU stay in days. The outcome will be measured during the hospitalization until 30 days, the death or discharge whichever occur first. In the cases with ICU stays longer than 30 days, it will considered as 30 days.

    Measure: ICU length of stay.

    Time: 30 days

    Description: Death of any cause during the hospitalization until 30 days or discharge whichever occur first.

    Measure: Death

    Time: 30 days.
    165 A Randomized, Placebo-Controlled, Double-Blind, Sponsor Unblinded, Single Ascending Dose, Phase 1 First in Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Intravenous LY3819253 in Participants Hospitalized for COVID-19

    The purpose of this study is to test the safety and tolerability of LY3819253 when it is given by injection into a vein to participants hospitalized with COVID-19. Blood tests will be done to check how much LY3819253 is in the bloodstream and how long the body takes to eliminate it. Participation could last about 8 weeks and may include up to 15 visits in the hospital or the home.

    NCT04411628
    Conditions
    1. COVID-19
    Interventions
    1. Drug: LY3819253
    2. Drug: Placebo

    Primary Outcomes

    Description: A summary of SAEs and other non-serious adverse events (AEs), regardless of causality, will be reported in the Reported Adverse Events module

    Measure: Number of Participants with One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration

    Time: Baseline through Day 60

    Secondary Outcomes

    Description: PK: AUC of LY3819253

    Measure: Pharmacokinetics (PK): Area Under the Concentration-time Curve (AUC) of LY3819253

    Time: Baseline through Day 29

    Description: PD: Change from Baseline in Viral Load

    Measure: Pharmacodynamics (PD): Change from Baseline to Day 29 in Viral Load

    Time: Baseline, Day 29
    166 A Randomized, Double-blind, Placebo-controlled, Multicenter, Phase 2 Clinical Trial to Evaluate the Efficacy and Safety of CERC-002 in Adults With COVID 19 Pneumonia and Acute Lung Injury

    The study is a prospective, randomized, placebo-controlled, single-blind phase 2 clinical study of the efficacy and safety of CERC-002, a potent inhibitor of LIGHT, for the treatment of patients with COVID-19 pneumonia who have mild to moderate ARDS. LIGHT is a cytokine in the TNF super family (TNFSF14) which drives inflammation and induces many other cytokines including IL-1, IL-6 and GM-CSF. LIGHT levels have been shown to be elevated in COVID-19 infected patients and inhibiting LIGHT is hypothesized to ameliorate the cytokine storm which has shown to be a major factor in progression of ARDS. The study will assess the efficacy and safety of CERC-002 in patients with severe COVID-19 over a 28 day period as single dose on top of standard of care.

    NCT04412057
    Conditions
    1. COVID-19 Pneumonia
    2. Acute Lung Injury
    3. ARDS
    Interventions
    1. Drug: CERC-002
    2. Drug: Placebo
    MeSH:Pneumonia Lung Injury Acute Lung Injury Respiratory Distress Syndrome, Adult Wounds and Injuries
    HPO:Pneumonia

    Primary Outcomes

    Description: Respiratory failure defined based on resource utilization requiring at least one of the following: Endotracheal intubation and mechanical ventilation Oxygen delivered by high-flow nasal cannula (heated, humidified oxygen delivered via reinforced nasal cannula at flow rates >20L/min with fraction of delivered oxygen ≥0.5) Noninvasive positive pressure ventilation, Extracorporeal membrane oxygenation

    Measure: Proportion of patient alive and free of respiratory failure

    Time: Baseline to Day 28

    Secondary Outcomes

    Description: 1-month mortality

    Measure: Proportion of subjects who are alive

    Time: Baseline to Day 28
    167 A MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PARALLEL GROUP STUDY ASSESSING THE SAFETY AND EFFICACY OF TOFACITINIB IN HOSPITALIZED PARTICIPANTS WITH COVID-19 PNEUMONIA WHO ARE RECEIVING STANDARD OF CARE THERAPY

    The study is designed as a multicenter, randomized, double-blind, placebo-controlled, parallel group study of the safety and efficacy of tofacitinib in hospitalized adult participants with COVID-19 pneumonia who are receiving SoC therapy and who are not on HFNC, noninvasive ventilation, invasive mechanical ventilation, or ECMO on Day 1 at the time of randomization. Participants with laboratory confirmed SARS-CoV-2 infection as determined by a positive PCR or other commercially available or public health assay, who have agreed to participate will be screened within 48 hours after hospitalization to determine eligibility. This should be completed within 48 hours prior to Day 1. Eligible participants will be randomized on Day 1 in a 1:1 ratio to the tofacitinib treatment group or the placebo treatment group and will receive treatment for up to 14 days, or until discharge from the hospital, whichever is earlier. If a participant requires intubation prior to the end of the 14-day treatment period, they will continue to receive tofacitinib or matching placebo until Day 14 (or until discharge from the hospital, if earlier than Day 14), if clinically appropriate. Participants will be assessed daily (up to Day 28) while hospitalized for clinical, safety, and laboratory parameters. Follow-up visits will occur on Day 28, 28 to 35 days after the ET/ED/EOT visit, and on Day 60. An independent, external DSMB will be convened to oversee the safety of participants and make recommendations regarding the conduct of the trial in accordance with the Charter.

    NCT04412252
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Tofacitinib
    2. Other: Placebo
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Death or respiratory failure (1, 2, or 3, on an 8-point ordinal scale of disease severity) at Day 28. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.

    Measure: Clinical status using ordinal scale

    Time: Day 28

    Secondary Outcomes

    Description: Ordinal scale of disease severity. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.

    Measure: Clinical status using ordinal scale

    Time: Day 14

    Description: Category 3 to 8 on an ordinal scale of disease severity. The scale is as follows: 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.

    Measure: Status of alive and not using mechanical ventilation or extracorporeal membrane oxygenation (ECMO)

    Time: Day 14 and Day 28

    Description: Category 5 to 8 on an ordinal scale of disease severity. The scale is as follows: 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.

    Measure: Status of discharged or not requiring supplemental oxygen

    Time: Day 28

    Description: Category 1 on an ordinal scale of disease severity. The scale is as follows: 1) Death.

    Measure: Mortality

    Time: Day 60
    168 A Randomized Double-blind Placebo-controlled Study to Evaluate the Safety and Efficacy of ATYR1923 In Adult Patients With Severe Pneumonia Related to SARS-CoV-2 Infection (COVID-19)

    A Phase 2 study to evaluate the safety and preliminary efficacy of ATYR1923, compared to placebo, in hospitalized patients with SARS-CoV-2 (COVID-19) severe pneumonia not requiring mechanical ventilation

    NCT04412668
    Conditions
    1. SARS-CoV-2 (COVID-19) Severe Pneumonia
    Interventions
    1. Drug: ATYR1923 1 mg/kg
    2. Drug: ATYR1923 3 mg/kg
    3. Drug: Placebo
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Measure: Incidence of treatment-emergent adverse events (TEAEs)

    Time: Baseline through Day 60

    Secondary Outcomes

    Measure: Time to hospital discharge

    Time: Baseline through Day 60

    Measure: Time to recovery (World Health Organization [WHO] Ordinal Scale score ≤3)

    Time: Baseline through Day 60

    Measure: Proportion of patients achieving recovery by Day 14 and Day 28

    Time: Baseline through Day 14 and Day 28

    Measure: Duration of supplemental oxygen (O2) requirement

    Time: Baseline through Day 60

    Measure: Number of days with fever (temperature >100.4ºF [38.0ºC])

    Time: Baseline through Day 14 or discharge

    Measure: Change from baseline in World Health Organization (WHO) Ordinal Scale score on Days 5, 7, 14, 28, and 60

    Time: Baseline through Day 60

    Measure: Time to improvement from inpatient hospital admission based on at least a 1 point reduction in WHO Ordinal Scale score

    Time: Baseline through Day 60

    Measure: All-cause mortality at Days 14, 28, and 60

    Time: Baseline through Day 60
    169 A Randomized, Controlled Clinical Trial of the Safety and Efficacy of Tocilizumab for the Treatment of Severe COVID-19

    The overall objective is to evaluate the clinical efficacy and safety of tocilizumab relative to placebo among approximately 300 hospitalized adult patients who have severe COVID-19. The study will be a 2 arm double blinded comparison between tocilizumab 8 mg/kg and matching placebo IV. The dose may be repeated in 8-12 hours if clinical symptoms worsens, (e.g. increase in oxygen requirements). Participants will be followed for 28 days.

    NCT04412772
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Tocilizumab
    2. Drug: Placebo

    Primary Outcomes

    Description: Clinical Status 7-point ordinal scale: Not hospitalized, no limitations on activities Not hospitalized, limitation on activities Hospitalized, not requiring supplemental oxygen Hospitalized, requiring supplemental oxygen Hospitalized, on non-invasive ventilation or high flow oxygen devices Hospitalized, on invasive mechanical ventilation or ECMO Death

    Measure: Clinical status (on a 7-point ordinal scale) at day 28

    Time: up to day 28

    Secondary Outcomes

    Description: ii. Time to clinical improvement, defined as a National Early Warning Score (NEWS) of < 2 maintained for 24 hours iii. Time to clinical improvement of at least 2 categories relative to baseline on a 7-category ordinal scale of clinical status

    Measure: Clinical improvement

    Time: up to day 28

    Description: iv. Incidence of mechanical ventilation v. Ventilator-free days

    Measure: Mechanical Ventilation

    Time: up to day 28

    Description: vi. Duration of time on supplemental oxygen

    Measure: Oxygenation

    Time: up to day 28
    170 A Randomized Clinical Trial for Enhanced Trained Immune Responses Through Bacillus Calmette-Guérin Vaccination to Prevent Infections by COVID-19: The ACTIVATE II Trial

    Based on findings of the interim analysis of the ACTIVATE study showing 53% decrease of the incidence of all new infections with BCG vaccination, a new trial is designed aiming to validate if BCG can protect against COVID-19 (Corona Virus Disease-19).The aim of the study is to demonstrate in a double-blind, placebo-controlled approach if vaccination of participants susceptible to COVID-19 with BCG vaccine may modulate their disease susceptibility for COVID-19. This will be validated using both clinical and immunological criteria. At the same time, a sub-study will be conducted and the mechanism of benefit from BCG vaccination by assessing its effect on vascular endothelial function and mononuclear blood cells will be studied

    NCT04414267
    Conditions
    1. COVID-19
    2. Virus Diseases
    3. Corona Virus Infection
    4. Coronary Heart Disease
    5. Chronic Obstructive Pulmonary Disease
    Interventions
    1. Biological: BCG vaccine
    2. Biological: Placebo
    MeSH:Infection Virus Diseases Coronavirus Infections Severe Acute Respiratory Syndrome Lung Diseases, Obstructive Pulmonary Disease, Chronic Obstructive Heart Diseases Coronary Disease
    HPO:Chronic pulmonary obstruction Pulmonary obstruction

    Primary Outcomes

    Description: This is set on visit 3 (90 ± 5 days from the date of visit 1). The two groups of vaccination are compared for the primary endpoints which is composite. Patients who meet any of the following will be considered to meet the primary endpoint: Positive for the respiratory questionnaire endpoint when at least one of the following combination is met either at visit 2 and/or at visit 3: One situation definitively related to COVID-19 All four questions of symptoms possibly related to COVID-19 At least two questions of symptoms possibly related to COVID-19 as well as need for admission at the emergency department of any hospital and/or need for intake of antibiotics At least four questions of symptoms probably related to COVID-19 one of which is "need for admission at the emergency department of any hospital and/or need for intake of antibiotics" Positive IgG or IgM antibodies against SARS-CoV-2

    Measure: Positive for the respiratory questionnaire consisted of questions concerning the appearance of symptoms possibly, probably and/or definitively related to COVID-19 on visit 3.

    Time: Visit 3 (90 +/- 5 days)

    Secondary Outcomes

    Description: The two groups of vaccination are compared for the primary endpoints which is composite (as defined at primary study endpoint) and meet a positive respiratory questionnaire endpoint on visit 4

    Measure: Positive respiratory questionnaire endpoint consisted of questions concerning the appearance of symptoms possibly, probably and/or definitively related to COVID-19 on visit 4

    Time: Visit 4 (135 +/- 5 days)

    Description: The two groups of vaccination are compared for the primary endpoints which is composite (as defined at primary study endpoint) and meet a positive respiratory questionnaire endpoint (as defined at primary study endpoint) on visit 5

    Measure: Positive respiratory questionnaire endpoint consisted of questions concerning the appearance of symptoms possibly, probably and/or definitively related to COVID-19 on visit 5

    Time: Visit 5 (180 +/- 5 days)

    Description: Prevalence of IgG/IgM against SARS-CoV-2 will be measured among the patients who failed the eligibility procedure and the patients that were eligible and were enrolled

    Measure: Prevalence of IgG/IgM against SARS-CoV-2

    Time: Screening Visit and Visit 3 (90 +/- 5 days)

    Description: Itemized analysis of each of the components of the respiratory questionnaire on each study visit

    Measure: Analysis of each of the components of the respiratory questionnaire consisted of questions concerning the appearance of symptoms possibly, probably and/or definitively related to COVID-19.

    Time: Visit 2 (45 +/- 5 days), Visit 3 (90 +/- 5 days), Visit 4 (135 +/- 5 days), Visit 5 (180 +/- 5 days)

    Description: The impact of new cardiovascular events between the two study groups (placebo and BCG) will be analyzed, though the collection of any cardiovascular events occured to the enrolled patients.

    Measure: The impact of new cardiovascular events between the two study groups

    Time: Visit 2 (45 +/- 5 days), Visit 3 (90 +/- 5 days), Visit 4 (135 +/- 5 days), Visit 5 (180 +/- 5 days)

    Description: Differences in repeated measurements of arterial stiffness in visit 3 between the two sub-study groups (placebo or BCG) will be analyzed through the speed of the pulse wave velocity. Pulse wave velocity is measured in m/sec.

    Measure: Differences in repeated measurements of angiometric parameters (arterial hardness) between the two sub-study groups in Visit 3

    Time: Visit 1 (Day 0), Visit 3 (90 +/- 5 days)

    Description: Differences in repeated measurements of central arterial pressures and reflected waves in visit 3 between the two sub-study groups (placebo or BCG) will be measured non-invasively by pulse wave analysis. Central arterial pressure is measured in mmHg.

    Measure: Differences in repeated measurements of angiometric parameters (central arterial pressures and reflected waves) between the two sub-study groups in Visit 3

    Time: Visit 1 (Day 0), Visit 3 (90 +/- 5 days)

    Description: Differences in repeated measurements of endothelial function in visit 3 between the two sub-study groups (placebo or BCG) will be measured by ultrasound measurement of endothelium-dependent flow-mediated dilatation and by nitrate-mediated dialatation. Endothelial function will be assessed by Flow Mediated Dilatation (FMD). Endothelium-dependent: diameter of the artery prior and after temporary ischemia in is measured in mm, nitrate-mediated: diameter of the artery prior and after nitrate administration is measured in mm

    Measure: Differences in repeated measurements of angiometric parameters (endothelial function) between the two sub-study groups in Visit 3

    Time: Visit 1 (Day 0), Visit 3 (90 +/- 5 days)

    Description: Differences in repeated measurements of thickness of the medial carotid sheath in visit 3 between the two sub-study groups (placebo or BCG) will be measured by B-mode ultrasound examination. Intima-Media Thickness is measured in mm

    Measure: Differences in repeated measurements of angiometric parameters (thickness of the medial carotid sheath) between the two sub-study groups in Visit 3

    Time: Visit 1 (Day 0), Visit 3 (90 +/- 5 days)

    Description: Differences in repeated measurements of arterial stiffness in visit 5 between the two sub-study groups (placebo or BCG) will be analyzed through the speed of the pulse wave velocity. Pulse wave velocity is measured in m/sec.

    Measure: Differences in repeated measurements of angiometric parameters (arterial hardness) between the two sub-study groups in Visit 5

    Time: Visit 1 (Day 0), Visit 3 (90 +/- 5 days), Visit 5 (180 +/- 5 days)

    Description: Differences in repeated measurements of central arterial pressures and reflected waves in visit 5 between the two sub-study groups (placebo or BCG) will be measured non-invasively by pulse wave analysis. Central arterial pressure is measured in mmHg.

    Measure: Differences in repeated measurements of angiometric parameters (central arterial pressures and reflected waves) between the two sub-study groups in Visit 5

    Time: Visit 1 (Day 0), Visit 3 (90 +/- 5 days), Visit 5 (180 +/- 5 days)

    Description: Differences in repeated measurements of thickness of the medial carotid sheath in visit 5 between the two sub-study groups (placebo or BCG) will be measured by B-mode ultrasound examination. Intima-Media Thickness is measured in mm

    Measure: Differences in repeated measurements of angiometric parameters (thickness of the medial carotid sheath) between the two sub-study groups in Visit 5

    Time: Visit 1 (Day 0), Visit 3 (90 +/- 5 days), Visit 5 (180 +/- 5 days)

    Description: Differences in repeated measurements of endothelial function in visit 5 between the two sub-study groups (placebo or BCG) will be measured by ultrasound measurement of endothelium-dependent flow-mediated dilatation and by nitrate-mediated dialatation. Endothelial function will be assessed by Flow Mediated Dilatation (FMD). Endothelium-dependent: diameter of the artery prior and after temporary ischemia in is measured in mm, nitrate-mediated: diameter of the artery prior and after nitrate administration is measured in mm

    Measure: Differences in repeated measurements of angiometric parameters (endothelial function) between the two sub-study groups in Visit 5

    Time: Visit 1 (Day 0), Visit 3 (90 +/- 5 days), Visit 5 (180 +/- 5 days)

    Description: Differences in cardiac ultrasound at visit 5 between the two sub-study groups (placebo or BCG) will be assessed using standard measurements from 2-D and Doppler echocardiography.

    Measure: Differences in cardiac ultrasound at visit 5 between the two sub-study groups

    Time: Visit 1 (Day 0), Visit 3 (90 +/- 5 days), Visit 5 (180 +/- 5 days)

    Description: Changes in the release of cytokines from blood mononuclear cells at visit 3 between the two sub-study groups (placebo or BCG) will be analyzed

    Measure: Changes in the release of cytokines from blood mononuclear cells at visit 3 between the two sub-study groups

    Time: Visit 1 (Day 0), Visit 3 (90 +/- 5 days)
    171 Opaganib, a Sphingosine Kinase-2 (SK2) Inhibitor in COVID-19 Pneumonia: a Randomized, Double-blind, Placebo-Controlled Phase 2a Study, in Adult Subjects Hospitalized With SARS-CoV-2 Positive Pneumonia

    This proof of concept study will take place in the US and other countries in approximately 15 clinical sites and will enroll about 40 hospitalized patients diagnosed with COVID-19 infection who have developed pneumonia and require supplemental oxygen. 20 patients will receive opaganib in addition to standard of care twice each day for 14 days. 20 will receive matching placebo in addition to standard of care unless the patient has been discharged from the hospital without requiring supplemental oxygen, in which case study drug will only be administered for 10 days. All participants will be followed up for 4 weeks after their last dose of study drug.

    NCT04414618
    Conditions
    1. Coronavirus Infections
    Interventions
    1. Drug: Opaganib
    2. Drug: Placebo
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: To compare the total oxygen requirement (area under the curve) for each arm using daily supplemental oxygen flow (L/min) over 14 days

    Measure: Measurement of the oxygen requirement

    Time: 14 days

    Secondary Outcomes

    Description: To comparing the time required between arms to achieve 50% reduction from baseline in supplemental oxygen based on oxygen flow in L/min

    Measure: Measurement of the reduction in oxygen requirement.

    Time: 14 days

    Description: To comparing the proportion of patients in each arm no longer requiring supplemental oxygen for at least 24 hours by Day 14

    Measure: Eliminating supplemental oxygen

    Time: 14 days

    Description: To compare the proportion of afebrile patients in each arm at Day 14 via measurement of temperature.

    Measure: Elimination of fever

    Time: 14 days

    Description: To compare the time in each arm to negative swabs for SARS-CoV-2 by PCR nasopharyngeal or oropharyngeal swab for SARS-CoV-2

    Measure: Time to negative swabs for SARS-CoV-2 by PCR post treatment

    Time: 6 weeks

    Description: To comparing the time in each arm to achieve negative swabs for SARS-CoV-2 by PCR nasopharyngeal or oropharyngeal swab for SARS-CoV-2 during treatment

    Measure: Time to negative swabs for SARS-CoV-2 by PCR at Day 14

    Time: 14 days

    Description: To compare the percentage of patients in each arm who require intubation and mechanical ventilation by Day 14

    Measure: Intubation and mechanical ventilation requirements

    Time: From screening phase and every day from day 1 to day 14 of treatment

    Description: To compare the time in each arm for the patient to require mechanical ventilation.

    Measure: Evaluation of the time to mechanical ventilation

    Time: From screening phase and every day from day 1 to day 14 of treatment

    Description: To compare the proportion of patients in each arm, with at least one measurement of fever at baseline (defined as temperature >38.0 C[100.4 F]), who are afebrile (defined as temperature <37.2C [99 F]) at Day 14

    Measure: Evaluation the proportion of patients, with at least one measurement of fever at baseline who are afebrile at Day 14

    Time: From screening phase and every day from day 1 to day 14 of treatment

    Description: To compare the mortality in each arm 30 days post-baseline.

    Measure: Evaluation of mortality 30 days post-baseline

    Time: 30 days after day 1 of treatment

    Other Outcomes

    Description: To compare the number of all treatment-emergent adverse events in each arm of all treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)

    Measure: Safety

    Time: 6 weeks
    172 A Phase 2, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Axatilimab for the Treatment of Hospitalized Patients With Respiratory Signs and Symptoms Secondary to Novel Coronavirus Disease (COVID-19)

    This is a randomized, double-blind, placebo-controlled, 29-day study to assess the efficacy and safety of axatilimab plus standard of care, compared with placebo plus standard of care, in patients with respiratory signs and symptoms secondary to novel coronavirus disease (COVID-19).

    NCT04415073
    Conditions
    1. Coronavirus
    2. COVID
    3. ARDS
    4. Cytokine Storm
    5. Cytokine Release Syndrome
    Interventions
    1. Drug: SNDX-6352
    2. Drug: Placebo
    MeSH:Coronavirus Infections

    Primary Outcomes

    Description: Respiratory failure as defined by need for mechanical ventilation, extracorporeal membrane oxygenation (ECMO), non-invasive ventilation >6L oxygen/minute, or clinical diagnosis of respiratory failure with initiation of none of these measures only when clinical decision-making is driven solely by resource limitation

    Measure: Proportion of subjects alive and free of respiratory failure

    Time: 29 Days

    Secondary Outcomes

    Description: Proportion of subjects achieving a ≥ 2 category improvement on 7-point ordinal score relative to the baseline on Day 28 as collected on Day 29

    Measure: Secondary clinical improvement outcomes

    Time: 29 Days

    Description: National early warning score (NEWS) of ≤2 maintained for 24 hours

    Measure: Time to clinical improvement (TTCI)

    Time: 29 Days

    Description: Change from baseline to Day 29 or hospital discharge or death, if sooner, in the ratio of peripheral hemoglobin oxygen saturation to fraction of inspired oxygen (SpO2/FiO2)

    Measure: To evaluate improvement in oxygenation in hospitalized adults with respiratory signs and symptoms secondary to COVID 19 treated with axatilimab

    Time: 29 Days

    Description: Serum concentrations of IL 6 and c-reactive protein (CRP) change from baseline to Day 15 or hospital discharge or death

    Measure: To evaluate changes in biomarkers following treatment with axatilimab

    Time: 15 Days

    Description: Frequency and severity of AEs and SAEs

    Measure: To evaluate the safety and tolerability of axatilimab in the same population

    Time: 29 Days

    Description: Proportion of subjects who require initiation of mechanical ventilation after study entry

    Measure: Ventilation outcomes

    Time: 29 Days

    Description: Proportion of subjects who are SARS CoV-2 virus free by Day 15 or hospital discharge, whichever is sooner

    Measure: To evaluate antiviral effect of axatilimab in hospitalized adults with recently diagnosed SARS CoV-2 infection

    Time: Day 15

    Description: Serum concentration of axatilimab and presence of anti-drug antibody

    Measure: To characterize exposure to axatilimab

    Time: 29 Day
    173 Investigation of Tofacitinib to Mitigate the Impact of COVID-19 (I-TOMIC) in Moderate SARS-CoV-2 (MODERATE I-TOMIC)

    The purpose of this randomized, double blinded, placebo controlled study is to assess the efficacy and safety of tofacitinib in hospitalized adult (18-99 years old) patients with SARS-CoV-2 and pneumonia who require supplemental oxygen and have serologic markers of inflammation but do not need mechanical ventilation.

    NCT04415151
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Tofacitinib 10 mg
    2. Drug: Placebo

    Primary Outcomes

    Description: The primary objective of this study is to determine whether tofacitinib improves the clinical outcomes of patients with moderate SARS-CoV-2 infection as determined by the primary outcome measure: Proportion of subjects alive and not needing any form of mechanical ventilation, high flow oxygen, or ECMO by day 14.

    Measure: Disease Severity

    Time: 14 days

    Secondary Outcomes

    Description: Clinical improvement as measured by NIAID 8-point ordinal scale (i.e., 1 = death and 8 = Not hospitalized, no limitations on activities) at day 14. The scale is as follows: Death Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) Hospitalized, on non-invasive ventilation or high flow oxygen devices Hospitalized, requiring supplemental oxygen Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care Not hospitalized, limitation on activities and/or requiring home oxygen Not hospitalized, no limitations on activities.

    Measure: Clinical improvement

    Time: 14 days

    Description: Clinical improvement as measured by NIAID 8-point ordinal scale (i.e., 1 = death and 8 = Not hospitalized, no limitations on activities) (days 3 through day 14): The scale is as follows: Death Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) Hospitalized, on non-invasive ventilation or high flow oxygen devices Hospitalized, requiring supplemental oxygen Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care Not hospitalized, limitation on activities and/or requiring home oxygen Not hospitalized, no limitations on activities.

    Measure: Clinical improvement

    Time: Up to 14 days

    Description: Time to recovery [ Time Frame: Day 1 through Day 14] (Day of recovery is defined as the first day on which the subject satisfies one of the following three categories from the ordinal scale: Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care Not hospitalized, limitation on activities and/or requiring home oxygen Not hospitalized, no limitations on activities)

    Measure: Time to recovery

    Time: Up to 14 days

    Description: Time to clinical improvement (defined as a 2-point increase on the NIAID 8-point ordinal scale (i.e., 1 = death and 8 = Not hospitalized, no limitations on activities). The scale is as follows: Death Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) Hospitalized, on non-invasive ventilation or high flow oxygen devices Hospitalized, requiring supplemental oxygen Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care Not hospitalized, limitation on activities and/or requiring home oxygen Not hospitalized, no limitations on activities.

    Measure: Time to clinical improvement

    Time: 30 days

    Description: Clinical status on the NIAID 8-point ordinal scale at day 30 The scale is as follows: Death Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) Hospitalized, on non-invasive ventilation or high flow oxygen devices Hospitalized, requiring supplemental oxygen Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care Not hospitalized, limitation on activities and/or requiring home oxygen Not hospitalized, no limitations on activities.

    Measure: Clinical status

    Time: 30 Days

    Description: Clinical status on the NIAID 8-point ordinal scale at day 60 The scale is as follows: Death Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) Hospitalized, on non-invasive ventilation or high flow oxygen devices Hospitalized, requiring supplemental oxygen Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care Not hospitalized, limitation on activities and/or requiring home oxygen Not hospitalized, no limitations on activities.

    Measure: Clinical status

    Time: 60 Days

    Description: Clinical status on the NIAID 8-point ordinal scale at day 90 The scale is as follows: Death Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) Hospitalized, on non-invasive ventilation or high flow oxygen devices Hospitalized, requiring supplemental oxygen Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care Not hospitalized, limitation on activities and/or requiring home oxygen Not hospitalized, no limitations on activities.

    Measure: Clinical status

    Time: 90 Days

    Description: Mortality rate at day 30

    Measure: Mortality

    Time: 30 Days

    Description: Mortality rate at day 60

    Measure: Mortality

    Time: 60 Days

    Description: Mortality rate at day 90

    Measure: Mortality

    Time: 90 Days

    Description: Proportion of patients requiring mechanical ventilatory support.

    Measure: Mechanical Ventilatory Support

    Time: Up to 14 Days

    Description: Duration of invasive mechanical ventilation (days).

    Measure: Mechanical Ventilatory Support Duration

    Time: Up to 14 Days

    Description: Invasive mechanical ventilation free days.

    Measure: Freedom from mechanical ventilation

    Time: Up to 14 Days

    Description: Adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug/treatment.

    Measure: Adverse events

    Time: Up to 14 days

    Description: Did the patient receive an intervention with additional immunomodulatory agent (i.e. IL-6 targeting therapy)? (y/n)

    Measure: Additional intervention

    Time: Up to 14 days

    Description: Change in SARS-CoV-2 viral titers during intervention.

    Measure: Viral titer

    Time: Up to 14 days
    174 Reducing Hospital Admission of Elderly in SARS-CoV-2 Pandemic Via the Induction of Trained Immunity by Bacillus Calmette-Guérin Vaccination, a Randomized Controlled Trial

    Bacillus Calmette-Guérin (BCG) vaccine not only protects against tuberculosis, but has also been shown to induce protection against various infections with a viral aetiology, leading to significant reductions in morbidity and mortality. We hypothesize that BCG vaccination might be a potent preventive measure against SARS-CoV-2 infection and/or may reduce disease severity in elderly people, who are known to be at increased risk of illness and death from SARS-CoV-2 infection. Therefore, we will in this placebo-controlled adaptive multi-centre randomized controlled trial evaluate the ability of BCG to reduce hospital admission and its efficacy to improve the clinical course of SARS-CoV-2 infection in elderly people((≥ 60 years of age).

    NCT04417335
    Conditions
    1. COVID-19
    Interventions
    1. Biological: BCG vaccine
    2. Biological: Placebo

    Primary Outcomes

    Measure: SARS-CoV-2 related hospital admission

    Time: Maximum of 1 year

    Secondary Outcomes

    Measure: the duration of hospital admission due to documented COVID-19

    Time: Maximum of 1 year

    Measure: the cumulative incidence of documented SARS-CoV-2 infection

    Time: Maximum of 1 year

    Measure: the cumulative incidence of self-reported acute respiratory symptoms or fever

    Time: Maximum of 1 year

    Measure: the cumulative incidence of death due to documented SARS-CoV-2 infection

    Time: 1 year

    Measure: the cumulative incidence of hospital admission for any reason

    Time: Maximum of 1 year

    Measure: the cumulative incidence of Intensive Care Admission due to documented SARS-CoV-2 infection

    Time: Maximum of 1 year
    175 Synbiotic Therapy of Gastrointestinal Symptoms During Covid-19 Infection: A Randomized, Double-blind, Placebo Controlled, Telemedicine Study (SynCov Study)

    The investigators hypothesize that the intake of Omni-Biotic® 10 AAD can reduce the duration of diarrhea in Covid-19 disease. The investigators further hypothesize that Omni-Biotic® 10 AAD can reduce stool frequency, improve stool consistency, improve other gastrointestinal symptoms of Covid-19, reduce disease duration and severity, reduce intestinal inflammation and can improve dysbiosis. The investigators aim to perform a randomized, double blind, placebo-controlled study using telemedicine in patients with Covid-19 disease.

    NCT04420676
    Conditions
    1. COVID
    Interventions
    1. Dietary Supplement: Omnibiotic AAD
    2. Dietary Supplement: Placebo
    MeSH:Infection

    Primary Outcomes

    Description: Duration of diarrhea (defined as days with 3 or more loose stools)

    Measure: Diarrhea

    Time: 30 days

    Secondary Outcomes

    Description: stool evacuations per days

    Measure: Stool frequency

    Time: 30 days

    Description: Stool consistency according to Bristol stool scale for each evacuation, score 1-7, a higher score means a lower stool consistancy

    Measure: Stool consistency

    Time: 30 days

    Description: presence of anorexia, nausea, vomiting, abdominal pain, bloating (yes/no)

    Measure: Gastrointestinal symptoms

    Time: 30 days

    Description: days patients feel sick, are not able to work or are on sick leave

    Measure: Duration of Covid-19 disease

    Time: 30 days

    Description: mild/moderate/severe

    Measure: Severity of Covid-19 disease

    Time: 30 days

    Description: measured by ELISA

    Measure: Stool Calprotectin

    Time: 30 days

    Description: measured by ELISA

    Measure: Stool Zonulin

    Time: 30 days

    Description: 16S RNA sequencing

    Measure: Microbiome composition

    Time: 30 days
    176 A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Phase 3 Study of Baricitinib in Patients With COVID-19 Infection

    The reason for this study is to see if the study drug baricitinib is effective in hospitalized participants with COVID-19.

    NCT04421027
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Baricitinib
    2. Drug: Placebo

    Primary Outcomes

    Description: Percentage of Participants who Die or Require Non-Invasive Ventilation/High-Flow Oxygen or Invasive Mechanical Ventilation (including ECMO)

    Measure: Percentage of Participants who Die or Require Non-Invasive Ventilation/High-Flow Oxygen or Invasive Mechanical Ventilation (including extracorporeal membrane oxygenation [ECMO])

    Time: Day 1 to Day 28

    Secondary Outcomes

    Description: The National Institute of Allergy and Infectious Diseases ordinal scale (NIAID-OS) is an assessment of clinical status. The scale is as follows: Death; Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); Hospitalized, on non-invasive ventilation or high flow oxygen devices; Hospitalized, requiring supplemental oxygen; Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; Not hospitalized, limitation on activities and/or requiring home oxygen; Not hospitalized, no limitations on activities.

    Measure: Percentage of Participants with at Least 1-Point Improvement on NIAID-OS or Live Discharge from Hospital

    Time: Day 10

    Description: Number of Ventilator-Free Days

    Measure: Number of Ventilator-Free Days

    Time: Day 1 to Day 28

    Description: Recovery assessed by the NIAID-OS.

    Measure: Time to Recovery

    Time: Day 1 to Day 28

    Description: Overall Improvement on the NIAID-OS

    Measure: Overall Improvement on the NIAID-OS

    Time: Day 1 to Day 28

    Description: Duration of Hospitalization

    Measure: Duration of Hospitalization

    Time: Day 1 to Day 28

    Description: Percentage of Participants with a Change in Oxygen Saturation from <94% to ≥94% from Baseline

    Measure: Percentage of Participants with a Change in Oxygen Saturation from <94% to ≥94% from Baseline

    Time: Day 10

    Description: Mortality

    Measure: Mortality

    Time: Day 1 to Day 28

    Description: Duration of Stay in the ICU in Days

    Measure: Duration of Stay in the Intensive Care Unit (ICU) in Days

    Time: Day 1 to Day 28

    Description: Time to Clinical Deterioration (one-category increase on the NIAID-OS)

    Measure: Time to Clinical Deterioration (one-category increase on the NIAID-OS)

    Time: Day 1 to Day 28

    Description: Time to Resolution of Fever, in Participants with Fever at Baseline

    Measure: Time to Resolution of Fever, in Participants with Fever at Baseline

    Time: Day 1 to Day 28

    Description: The NEWS is used to detect and report changes in illness severity in participants with acute illness. The score is determined from six physiological parameters readily measured over time in hospitalized participants: Respiration rate; oxygen saturation; temperature; systolic blood pressure; heart (pulse) rate, and level of consciousness

    Measure: Mean Change from Baseline on the National Early Warning Score (NEWS)

    Time: Baseline, Day 1 to Day 28

    Description: Time to Definitive Extubation

    Measure: Time to Definitive Extubation

    Time: Day 1 to Day 28

    Description: Time to Independence from Non-Invasive Mechanical Ventilation

    Measure: Time to Independence from Non-Invasive Mechanical Ventilation

    Time: Day 1 to Day 28

    Description: Time to Independence from Oxygen Therapy in Days

    Measure: Time to Independence from Oxygen Therapy in Days

    Time: Day 1 to Day 28

    Description: Number of Days with Supplemental Oxygen Use

    Measure: Number of Days with Supplemental Oxygen Use

    Time: Day 1 to Day 28

    Description: Number of Days of Resting Respiratory Rate <24 Breaths per Minute

    Measure: Number of Days of Resting Respiratory Rate <24 Breaths per Minute

    Time: Day 1 to Day 28
    177 A Randomized Controlled Adaptive Study Comparing COVID-19 Convalescent Plasma (CCP) to Non-immune Plasma to Limit Coronavirus-associated Complications in Hospitalized Patients

    The purpose of this study assess the efficacy and safety of anti-SARS-CoV-2 convalescent plasma in hospitalized patients with acute respiratory symptoms up to 14 days after the onset of initial symptoms.

    NCT04421404
    Conditions
    1. COVID-19
    2. Sars-CoV2
    Interventions
    1. Biological: COVID-19 Convalescent Plasma (CCP)
    2. Biological: Placebo
    MeSH:Coronavirus Infections

    Primary Outcomes

    Description: Progression to mechanical ventilation or death within the first 14 days of enrollment.

    Measure: Mechanical Ventilation or Death Endpoint

    Time: Day 14

    Secondary Outcomes

    Description: Progression to mechanical ventilation or death within the first 28 days of enrollment.

    Measure: Mechanical Ventilation or Death Endpoint

    Time: Day 28

    Description: Clinical efficacy of CCP relative to the control arm in adults hospitalized with COVID-19 according to clinical status as assessed by 8-point ordinal scale. Death; Hospitalized, on invasive mechanical ventilation or ECMO; Hospitalized, on non-invasive ventilation or high flow oxygen devices; Hospitalized, requiring supplemental oxygen; Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; Not hospitalized, limitation on activities and/or requiring home oxygen; Not hospitalized, no limitations on activities.

    Measure: 8-Point Ordinal Scale Endpoint

    Time: Day 29
    178 A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of Pulsed, Inhaled Nitric Oxide (iNO) Versus Placebo in Subjects With Mild or Moderate Coronavirus (COVID-19)

    A randomized, double-blind, placebo-controlled study to assess the efficacy and safety of pulsed inhaled iNO compared to placebo in subjects with COVID-19.

    NCT04421508
    Conditions
    1. COVID-19
    2. Coronavirus
    3. Coronavirus Infection
    Interventions
    1. Combination Product: INOpulse
    2. Combination Product: Placebo
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome

    Primary Outcomes

    Measure: The proportion of subjects who died or had respiratory failure

    Time: Through Day 28

    Secondary Outcomes

    Description: The assessment of clinical status at the first assessment of a study day. The scale is: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.

    Measure: Clinical status using National Institute of Allergy and Infectious Diseases (NIAID) 8-point ordinal scale

    Time: Day 7, 14, 28 and day of discharge

    Measure: Proportion of subject to recover, defined as return to room air or baseline O2, or discharged alive

    Time: Through Day 28

    Measure: Proportion of subjects discharged alive from hospital

    Time: Through Day 28

    Measure: Duration of Hospitalization

    Time: Through Day 28

    Measure: Mortality - all cause and cardiopulmonary

    Time: Through Day 28

    Measure: Proportion of subjects with a negative conversion of reverse transcription polymerase chain reaction (RT-PCR) from a nasopharyngeal swab

    Time: Through Day 28

    Other Outcomes

    Measure: Proportion of subjects with adverse events leading to study drug discontinuation

    Time: Through Day 28
    179 Coronavirus Smell Therapy for Anosmia Recovery

    As the COVID-19 pandemic spread around the world, anosmia and dysgeusia were quickly recognized as two of the key presenting symptoms. The probability of return of smell is related to severity of smell loss at presentation, but it appears that the loss of sense of smell and taste seems to persist in approximately 10% of the affected patients after 6 months. As a result of COVID-19, it is estimated that within the next 12 months > 150,000 Americans will suffer permanent loss of smell. The magnitude of this impairment on the health, safety, and quality of life is truly unprecedented and makes post-COVID olfactory disorder a major public health problem. Thus, there is a pressing need to identify effective treatments. The research questions are to determine the effects of steroid nasal saline lavage and olfactory training among adults with post-COVID olfactory dysfunction and identify confounders and modifiers of any observed effects. To answer the research question, the investigators propose a 2 x 2 factorial design blinded randomized clinical trial whereby 220 subjects with documented COVID-19 with anosmia/hyposmia of 12 weeks duration or longer from Missouri, Illinois, and Indiana will be recruited electronically from COVID patient advocacy sites, social media sites, and other internet sources. Enrolled subjects will be randomized to nasal saline lavage with topical budesonide or placebo to address the presumed role of inflammation in the olfactory cleft and each subject will also be randomized to olfactory training with patient-specific, high- or low-concentration essential oil scent to assess the role of olfactory training. Data will be analyzed in a blinded fashion to allow estimation of observed effect size for both anti-inflammatory and olfactory training. This innovative study will exploit the unique opportunities presented by COVID-19. The study will use a high-tech virtual "contactless" research strategy, including eConsent and digital mHealth techniques to obtain rapid answers to the research questions. The interventions are low-cost, readily available, and results of this study can be directly disseminated to the care of COVID-19 patients with anosmia.

    NCT04422275
    Conditions
    1. Anosmia
    Interventions
    1. Drug: Budesonide
    2. Behavioral: High-Concentration Essential Oil
    3. Drug: Placebo
    4. Behavioral: Low-Concentration Essential Oil
    MeSH:Olfaction Disorders
    HPO:Anosmia

    Primary Outcomes

    Description: The University of Pennsylvania Smell Identification Test (UPSIT) (Sensonics, New Jersey)7 is the most widely accepted olfactory identification test in North America. The UPSIT consists of four 10-page booklets, with a total of 40 items. Subjects are asked to scratch each strip with a pencil to release the scents, detect the smell, and identify the smell from the four choice options. The UPSIT comes from a scoring rubric that identifies the normalcy benchmark based on age and gender. Normosmia is defined as ≥34 for males and ≥35 for females, and an increase of 4 points or more from baseline indicates a clinically meaningful improvement. UPSIT has high internal reliability across a wide range of populations.

    Measure: University of Pennsylvania Smell Identification Test (UPSIT)

    Time: The within subject change in UPSIT between baseline and 12- and 24-week assessment time frame.

    Secondary Outcomes

    Description: The Questionnaire of Olfactory Disorders-Negative Statements (QOD-NS) was adapted from the original 52-item Questionnaire of Olfactory Disorders. This short-modified version is a validated 17-item questionnaire about quality of life and impairments related to olfactory dysfunction. The maximum score is 51, and higher values indicate worse quality of life or higher degree of impairment of normal daily activity. Mean scores in anosmics is 19; hyposmics is 8; and normosmics is 0. Prior studies used a cutoff score of 12.5 to reflect normal vs. abnormal scores.The minimum clinically important difference is 5.2.

    Measure: Questionnaire of Olfactory Disorders-Negative Statements (QOD-NS).

    Time: The within subject change in QOD-NS between baseline and assessment time frame.

    Description: The Global Rating of Smell is a single-item, global rating that asks: "Overall, please rate your current sense of smell? Excellent, Very Good, Good, Fair, Poor, Absent."

    Measure: Global Rating of Smell.

    Time: 12 weeks - End of nasal lavage & olfactory training; 24 weeks - Follow-up (12 weeks after completion of lavage & training)

    Description: The Global Rating of Smell Change is a single-item, global rating that asks: "Compared to your sense of smell # weeks ago, how would you rate your change in smell since then? Much better, Somewhat better, Slightly better, Neither better nor worse, Slightly worse, Somewhat worse, or Much worse." The time frame ("#") will be changed to reflect the correct time since enrollment (i.e., 12, or 24 weeks).

    Measure: Global Rating of Smell Change.

    Time: 12 weeks - End of olfactory training; 24 weeks - Follow-up (12 weeks after completion of lavage & training)
    180 A Phase III, Multicentre, Parallel, Randomized, Double-blind Clinical Trial to Assess the Efficacy and Safety of Nitazoxanide 600 mg Compared to Placebo in the Treatment of Hospitalized Patients With COVID-19 in Non-critical Condition

    This is a pivotal phase III study to evaluate the efficacy of nitazoxanide 600 mg BID compared to placebo to treat hospitalized patients with non-critical COVID-19.

    NCT04423861
    Conditions
    1. covid19
    Interventions
    1. Drug: Nitazoxanide
    2. Drug: Placebo

    Primary Outcomes

    Description: Evaluation of change in acute respiratory syndrome using WHO Ordinal Scale for Clinical Improvement that measures illness severity over time (0=uninfected; ambulatory, no limitation of activities=1; ambulatory, limitation of activities=2, hospitalized no oxygen therapy=3; hospitalized oxygen by mask or nasal prongs=4; hospitalized non invasive ventilation or high-flow oxygen=5; hospitalized intubation or mechanical ventilation=6; hospitalized ventilation + additional organ support=7; death=8)

    Measure: Need of mechanical ventilation

    Time: 14 days

    Secondary Outcomes

    Description: Evaluation of change in oximetry, respiratory rate and need for oxygen therapy

    Measure: Change in the pulmonary condition

    Time: Baseline, Day 7 and Day 14

    Description: Evaluation of change in the following symptoms: cough, headache, myalgia and fever, level of consciousness and organ dysfunction

    Measure: Change in Clinical Condition

    Time: Baseline, Day 7 and Day 14

    Description: Evaluation of change in chest CT

    Measure: Change in tomographic pulmonary condition

    Time: Baseline, Day 7

    Description: Evaluation of change in acute respiratory syndrome

    Measure: Rate of mortality within 14-days

    Time: 14 days

    Description: Evaluation of change in inflammatory markers d-dimer and IL-6

    Measure: Change in inflammatory markers

    Time: Baseine, Day 7, Day 14
    181 A Multi-center, Randomized, Double-blind, Placebo-controlled, Phase III Clinical Study Evaluating the Efficacy and Safety of Favipiravir in the Treatment of Adult Patients With COVID-19-Moderate Type

    This is a multi-center, randomized, double-blind, placebo-controlled, phase III clinical study to evaluate the efficacy of Favipiravir combined with supportive care for adult patients with COVID-19-Moderate type.

    NCT04425460
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Favipiravir
    2. Other: Placebo

    Primary Outcomes

    Description: The duration from start of treatment (Favipiravir or placebo) to normalization of pyrexia, respiratory rate and SPO2 and relief of cough (where there are relevant abnormal symptoms at enrolment) that is maintained for at least 72h. Criteria for normalization or relief: Pyrexia (body temperature): axillary ≤37℃,or oral≤37.5℃,or rectal or tympanic ≤38℃; Respiratory rate: ≤24/min without oxygen inhalation; SPO2: >94% without oxygen inhalation; Cough: Subject-perceived improvement or resolution of cough.

    Measure: Time from randomization to clinical recovery

    Time: 28 days

    Secondary Outcomes

    Description: Time from randomization to negativity in RT-PCR nucleic acid test for 2019-nCov within 28 days of randomization;

    Measure: Negativity in RT-PCR nucleic acid test

    Time: 28 days

    Description: Time from randomization to resolution of pyrexia (defined the same as for the primary efficacy variable; applicable to subjects with pyrexia at enrolment) within 28 days of randomization;

    Measure: Time from randomization to resolution of pyrexia

    Time: 28 days

    Description: Time from randomization to relief of cough (defined the same as for the primary efficacy variable; applicable to subjects with cough at enrolment) within 28 days of randomization; It is recommended that the severity of cough be graded as per NCI-CTCAE v5.0: Mild: Requires non-prescription treatment; Moderate: Requires medication treatment; limits instrumental activities of daily living; Severe: Limits self-care activities of daily living;

    Measure: Time from randomization to relief of cough

    Time: 28 days

    Description: Incidence of deterioration/aggravation of pneumonia (defined as SPO2≤93% or PaO2/FiO2 ≤300 mmHg or distressed RR≥30/min without oxygen inhalation and requiring oxygen therapy or more advanced breath support) within 28 days of randomization;

    Measure: Incidence of deterioration/aggravation of pneumonia

    Time: 28 days

    Description: Time from randomization to relief of dyspnoea (defined as subject-perceived improvement or resolution of dyspnoea; applicable to subjects with dyspnoea at enrolment) within 28 days of randomization;

    Measure: Time from randomization to relief of dyspnoea

    Time: 28 days

    Description: Rate of auxiliary oxygen therapy or non-invasive ventilation within 28 days of randomization;

    Measure: Rate of auxiliary oxygen therapy or non-invasive ventilation

    Time: 28 days

    Description: ICU admission rate within 28 days of randomization (except patients already enrolled in ICU which respect eligibility criteria);

    Measure: ICU admission rate within 28 days of randomization

    Time: 28 days

    Description: All-cause mortality within 28 days of randomization.

    Measure: All-cause mortality within 28 days of randomization.

    Time: 28 days
    182 A Master Protocol Assessing the Safety, Tolerability, and Efficacy of Anti-Spike (S) SARS-CoV-2 Monoclonal Antibodies for the Treatment of Ambulatory Patients With COVID-19

    Phase 1 - To evaluate the safety and tolerability of REGN10933+REGN10987 compared to placebo - To evaluate the virologic efficacy of REGN10933+REGN10987 compared to placebo in reducing viral load of SARS-CoV-2 Phase 2 • To evaluate the virologic efficacy of REGN10933+REGN10987 compared to placebo in reducing viral load of SARS-CoV-2 Phase 3 - Cohort 1 (Patients ≥18 Years) • To evaluate the clinical efficacy of REGN10933+REGN10987 compared to placebo, as measured by COVID-19-related medically-attended visits - Cohort 2 (Patients 0 to <18 Years) - To evaluate the safety and tolerability of REGN10933+REGN10987 compared to placebo - To characterize further the concentrations of REGN10933 and REGN10987 in serum over time - To assess the immunogenicity of REGN10933 and REGN10987

    NCT04425629
    Conditions
    1. COVID-19
    Interventions
    1. Drug: REGN10933+REGN10987 combination therapy
    2. Drug: Placebo

    Primary Outcomes

    Description: Primary: Phase 1, Phase 3 (Cohort 2) Secondary: Phase 2, Phase 3 (Cohort 1)

    Measure: Proportion of patients with treatment-emergent serious adverse events (SAEs)

    Time: Through Day 29

    Description: Primary: Phase 1, Phase 3 (Cohort 2) Secondary: Phase 2, Phase 3 (Cohort 1)

    Measure: Proportion of patients with infusion-related reactions

    Time: Through Day 4

    Description: Primary: Phase 1, Phase 3 (Cohort 2) Secondary: Phase 2, Phase 3 (Cohort 1)

    Measure: Proportion of patients with hypersensitivity reactions

    Time: Through Day 29

    Description: Phase 1 Only

    Measure: Time-weighted average change from baseline in viral load (log10 copies/mL), as measured by quantitative reverse transcription quantitative polymerase chain reaction (RT-qPCR) in nasopharyngeal (NP) swab samples

    Time: Baseline up to Day 22

    Description: Primary: Phase 2 Secondary: Phase 3 (Cohort 1), Phase 3 (Cohort 2)

    Measure: Time-weighted average change from baseline in viral load (log10 copies/mL), as measured by RT-qPCR in NP swab samples

    Time: Baseline up to Day 7

    Description: Primary: Phase 3 (Cohort 1) Secondary: Phase 3 (Cohort 2)

    Measure: Cumulative Incidence of COVID-19 related medically attended visits

    Time: Through Day 29

    Description: Primary: Phase 3 (Cohort 2) Secondary: Phase 1, Phase 2, Phase 3 (Cohort 1)

    Measure: Concentration of REGN10933 in serum over time

    Time: Through Day 29

    Description: Primary: Phase 3 (Cohort 2) Secondary: Phase 1, Phase 2, Phase 3 (Cohort 1)

    Measure: Concentration of REGN10987 in serum over time

    Time: Through Day 29

    Description: Primary: Phase 3 (Cohort 2) Secondary: Phase 1, Phase 2, Phase 3 (Cohort 1)

    Measure: Incidence of anti-drug antibodies (ADA) to REGN10933

    Time: Through Day 29

    Description: Primary: Phase 3 (Cohort 2) Secondary: Phase 1, Phase 2, Phase 3 (Cohort 1)

    Measure: Incidence of ADA to REGN10987

    Time: Through Day 29

    Description: Primary: Phase 3 (Cohort 2) Secondary: Phase 3 (Cohort 1)

    Measure: Incidence of neutralizing antibody (NAb) to REGN10933

    Time: Through Day 29

    Description: Primary: Phase 3 (Cohort 2) Secondary: Phase 3 (Cohort 1)

    Measure: Incidence of NAb to REGN10987

    Time: Through Day 29

    Secondary Outcomes

    Description: Phase 1 Only

    Measure: Time-weighted average change from baseline in viral load (log10 copies/mL), as measured by RT-qPCR in saliva samples

    Time: Baseline up to Day 22

    Description: Phase 1 Only

    Measure: Time-weighted average change from baseline in viral load (log10 copies/mL), as measured by RT-qPCR in nasal swab samples

    Time: Baseline up to Day 22

    Description: Phase 1 Only

    Measure: Time to negative RT-qPCR in all tested samples with no subsequent positive RT-qPCR in any tested samples

    Time: Through Day 29

    Description: Phase 2 Only

    Measure: Time to negative RT-qPCR in NP swabs with no subsequent positive RT-qPCR

    Time: Through Day 29

    Description: Phase 1, Phase 2, Phase 3 (Cohort 1), Phase 3 (Cohort 2)

    Measure: Change from baseline in viral load at each visit, as measured by RT-qPCR in NP swabs

    Time: Baseline up to Day 29

    Description: Phase 1 Only

    Measure: Change from baseline in viral load at each visit, as measured by RT-qPCR in saliva samples

    Time: Baseline up to Day 29

    Description: Phase 1 Only

    Measure: Change from baseline in viral load at each visit, as measured by RT-qPCR in nasal swabs

    Time: Baseline up to Day 29

    Description: Phase 1 Only

    Measure: Correlation of RT-qPCR results over time between different sample types (NP, nasal, and saliva)

    Time: Up to Day 29

    Description: Phase 1 Only

    Measure: Concordance of RT-qPCR results over time between different sample types (NP, nasal, and saliva)

    Time: Up to Day 29

    Description: Phase 1, Phase 2

    Measure: Time-weighted average change from baseline in viral load (log10 copies/mL) from day 1 to post-baseline study days

    Time: Day 1 to Day 29

    Description: Phase 1, Phase 2, Phase 3 (Cohort 1), Phase 3 (Cohort 2)

    Measure: Proportion of participants with at least one COVID-19 related medically-attended visit

    Time: Through Day 29

    Description: Phase 1, Phase 2, Phase 3 (Cohort 1), Phase 3 (Cohort 2)

    Measure: Proportion of participants with at least two COVID-19 related medically-attended visit

    Time: Through Day 29

    Description: Phase 1, Phase 2, Phase 3 (Cohort 1), Phase 3 (Cohort 2)

    Measure: Total number of COVID-19 related medically-attended visits

    Time: Through Day 29

    Description: Phase 1, Phase 2

    Measure: Proportion of participants admitted to a hospital due to COVID-19

    Time: Through Day 29

    Description: Phase 2, Phase 3 (Cohort 1), Phase 3 (Cohort 2)

    Measure: Proportion of participants admitted to an intensive care unit (ICU) due to COVID-19

    Time: Through Day 29

    Description: Phase 1, Phase 2

    Measure: Proportion of participants with at least 1 outpatient or telemedicine visit due to COVID-19

    Time: Through Day 29

    Description: Phase 2, Phase 3 (Cohort 1), Phase 3 (Cohort 2)

    Measure: Proportion of participants requiring mechanical ventilation due to COVID-19

    Time: Through Day 29

    Description: Phase 2, Phase 3 (Cohort 1), Phase 3 (Cohort 2)

    Measure: Number of days of hospitalization due to COVID-19

    Time: Through Day 29

    Description: Phase 2 Only

    Measure: Proportion of participants with All-Cause Mortality

    Time: Through Day 29

    Description: Phase 2 Only

    Measure: Time to first onset of symptoms consistent with COVID-19 (asymptomatic cohort only)

    Time: Up to Day 29

    Description: Phase 2 Only

    Measure: Duration of symptoms consistent with COVID-19

    Time: Up to Day 29

    Description: Phase 1 Only

    Measure: Assessment of pharmacokinetic (PK) parameter: maximum serum concentration observed (Cmax) of REGN10933

    Time: Through Day 29

    Description: Phase 1 Only

    Measure: Assessment of PK parameter: maximum serum concentration observed (Cmax) of REGN10987

    Time: Through Day 29

    Description: Phase 1 Only

    Measure: Assessment of PK parameter: Cmax-to-dose ratio (Cmax/dose) of REGN10933

    Time: Through Day 29

    Description: Phase 1 Only

    Measure: Assessment of PK parameter: Cmax-to-dose ratio (Cmax/dose) of REGN10987

    Time: Through Day 29

    Description: Phase 1 Only

    Measure: Assessment of PK parameter: Time to Cmax (tmax) for REGN10933

    Time: Through Day 29

    Description: Phase 1 Only

    Measure: Assessment of PK parameter: Time to Cmax (tmax) for REGN10987

    Time: Through Day 29

    Description: Phase 1 Only

    Measure: Assessment of PK parameter: Area Under the Curve (AUC) computed from time zero to the time of the last positive concentration (AUClast) for REGN10933

    Time: Through Day 29

    Description: Phase 1 Only

    Measure: Assessment of PK parameter: AUC computed from time zero to the time of the last positive concentration (AUClast) for REGN10987

    Time: Through Day 29

    Description: Phase 3 (Cohort 1), Phase 3 (Cohort 2)

    Measure: Cumulative incidence of COVID-19-related hospitalizations or emergency room visits

    Time: Through Day 29

    Description: Phase 3 (Cohort 1), Phase 3 (Cohort 2)

    Measure: Cumulative incidence of COVID-19-related hospitalizations

    Time: Through Day 29

    Description: Phase 3 (Cohort 1), Phase 3 (Cohort 2)

    Measure: Cumulative incidence of COVID-19-related emergency room visits

    Time: Through Day 29

    Description: Phase 3 (Cohort 1), Phase 3 (Cohort 2)

    Measure: Proportion of participants requiring supplemental oxygen due to COVID-19

    Time: Through Day 29

    Description: Phase 2 Only

    Measure: Proportion of participants with high viral load at each visit

    Time: Through Day 29

    Description: Phase 2 Only

    Measure: Proportion of participants with viral loads below the limit of detection at each visit

    Time: Through Day 29

    Description: Phase 2 Only

    Measure: Proportion of participants with viral loads below the lower limit of quantitation at each visit

    Time: Through Day 29

    Description: Phase 3 (Cohort 1), Phase 3 (Cohort 2)

    Measure: Time to All-Cause Mortality

    Time: Through Day 169

    Description: Phase 3 (Cohort 1), Phase 3 (Cohort 2)

    Measure: All-Cause Mortality

    Time: At Day 29, Day 120, and Day 169

    Description: Phase 3 (Cohort 1), Phase 3 (Cohort 2)

    Measure: Viral load over time in participants with COVID-19-related medically-attended visits

    Time: Through Day 29

    Description: Phase 3 (Cohort 1), Phase 3 (Cohort 2)

    Measure: Viral load over time in participants without COVID-19-related medically-attended visits

    Time: Through Day 29
    183 A Study to Assess the Safety, Tolerability, and Pharmacodynamics of Multiple Dose MK-5475 in Participants With Hypoxemia Due to COVID-19 Pneumonia

    The purpose of this study is to evaluate safety, tolerability, and pharmacodynamics of MK-5475 after administration of multiple doses to participants with COVID-19 pneumonia. The primary hypothesis is that MK-5475 when administered to participants with COVID-19 pneumonia and hypoxemia improves arterial oxygenation as measured by the ratio of blood oxygen saturation to fraction of inspired oxygen (SpO2/FiO2 ratio) compared to placebo.

    NCT04425733
    Conditions
    1. Coronavirus Disease 2019 (COVID-19)
    2. Pneumonia
    3. Hypoxemia
    Interventions
    1. Drug: MK-5475
    2. Drug: Placebo
    MeSH:Pneumonia Hypoxia
    HPO:Hypoxemia Pneumonia

    Primary Outcomes

    Description: An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who experience an AE will be reported.

    Measure: Number of Participants Who Experience an Adverse Event (AE)

    Time: Up to ~Day 21

    Description: An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who discontinued study drug due to an AE will be reported.

    Measure: Number of Participants Who Discontinued Study Drug Due to an Adverse Event (AE)

    Time: Up to ~Day 7

    Description: The SpO2/FiO2 ratio is a measure of arterial oxygenation. Noninvasive pulse oximetry will be used to obtain the SpO2/FiO2 ratio. The TWA0-24hrs will be calculated as the area under the curve from 0 to 24 hours post-dose on Day 1 divided by the length of time (24 hrs). Baseline is the Day 1 pre-dose measurement and assessments will be conducted pre-dose and at multiple time points post-dose on Day 1 to determine change from baseline in TWA0-24hrs for SpO2/FiO2 on Day 1.

    Measure: Change From Baseline to Day 1 in the Time-weighted Average from 0 through 24 hours (TWA0-24hrs) for the Ratio of Blood Oxygen Saturation to the Fraction of Inspired Oxygen (SpO2/FiO2)

    Time: Baseline, Day 1 (pre-dose and 2, 6, 12, 18, 24 hours post-dose)

    Description: The SpO2/FiO2 ratio is a measure of arterial oxygenation. Noninvasive pulse oximetry will be used to obtain the SpO2/FiO2 ratio. The TWA0-24hrs will be calculated as the area under the curve from 0 to 24 hours on Day 2 divided by the length of time (24 hrs). Baseline is the Day 1 pre-dose measurement and assessments will be conducted pre-dose and at multiple time points post-dose on Day 2 to determine change from baseline in TWA0-24hrs for SpO2/FiO2 on Day 2.

    Measure: Change From Baseline to Day 2 in the Time-weighted Average from 0 through 24 hours (TWA0-24hrs) for the Ratio of Blood Oxygen Saturation to the Fraction of Inspired Oxygen (SpO2/FiO2)

    Time: Baseline, Day 2 (pre-dose and 2, 6, 12, 18, 24 hours post-dose)

    Description: The SpO2/FiO2 ratio is a measure of arterial oxygenation. Noninvasive pulse oximetry will be used to obtain the SpO2/FiO2 ratio. The TWA0-24hrs will be calculated as the area under the curve from 0 to 24 hours on Day 3 divided by the length of time (24 hrs). Baseline is the Day 1 pre-dose measurement and assessments will be conducted pre-dose and at multiple time points post-dose on Day 3 to determine change from baseline in TWA0-24hrs for SpO2/FiO2 on Day 3.

    Measure: Change From Baseline to Day 3 in the Time-weighted Average from 0 through 24 hours (TWA0-24hrs) for the Ratio of Blood Oxygen Saturation to the Fraction of Inspired Oxygen (SpO2/FiO2)

    Time: Baseline, Day 3 (pre-dose and 2, 6, 12, 18, 24 hours post-dose)

    Description: The SpO2/FiO2 ratio is a measure of arterial oxygenation. Noninvasive pulse oximetry will be used to obtain the SpO2/FiO2 ratio. The TWA0-24hrs will be calculated as the area under the curve from 0 to 24 hours on Day 4 divided by the length of time (24 hrs). Baseline is the Day 1 pre-dose measurement and assessments will be conducted pre-dose and at multiple time points post-dose on Day 4 to determine change from baseline in TWA0-24hrs for SpO2/FiO2 on Day 4.

    Measure: Change From Baseline to Day 4 in the Time-weighted Average from 0 through 24 hours (TWA0-24hrs) for the Ratio of Blood Oxygen Saturation to the Fraction of Inspired Oxygen (SpO2/FiO2)

    Time: Baseline, Day 4 (pre-dose and 2, 6, 12, 18, 24 hours post-dose)

    Description: The SpO2/FiO2 ratio is a measure of arterial oxygenation. Noninvasive pulse oximetry will be used to obtain the SpO2/FiO2 ratio. The TWA0-24hrs will be calculated as the area under the curve from 0 to 24 hours on Day 5 divided by the length of time (24 hrs). Baseline is the Day 1 pre-dose measurement and assessments will be conducted pre-dose and at multiple time points post-dose on Day 5 to determine change from baseline in TWA0-24hrs for SpO2/FiO2 on Day 5.

    Measure: Change From Baseline to Day 5 in the Time-weighted Average from 0 through 24 hours (TWA0-24hrs) for the Ratio of Blood Oxygen Saturation to the Fraction of Inspired Oxygen (SpO2/FiO2)

    Time: Baseline, Day 5 (pre-dose and 2, 6, 12, 18, 24 hours post-dose)

    Description: The SpO2/FiO2 ratio is a measure of arterial oxygenation. Noninvasive pulse oximetry will be used to obtain the SpO2/FiO2 ratio. The TWA0-24hrs will be calculated as the area under the curve from 0 to 24 hours on Day 6 divided by the length of time (24 hrs). Baseline is the Day 1 pre-dose measurement and assessments will be conducted pre-dose and at multiple time points post-dose on Day 6 to determine change from baseline in TWA0-24hrs for SpO2/FiO2 on Day 6.

    Measure: Change From Baseline to Day 6 in the Time-weighted Average from 0 through 24 hours (TWA0-24hrs) for the Ratio of Blood Oxygen Saturation to the Fraction of Inspired Oxygen (SpO2/FiO2)

    Time: Baseline, Day 6 (pre-dose and 2, 6, 12, 18, 24 hours post-dose)

    Description: The SpO2/FiO2 ratio is a measure of arterial oxygenation. Noninvasive pulse oximetry will be used to obtain the SpO2/FiO2 ratio. The TWA0-24hrs will be calculated as the area under the curve from 0 to 24 hours on Day 7 divided by the length of time (24 hrs). Baseline is the Day 1 pre-dose measurement and assessments will be conducted pre-dose and at multiple time points post-dose on Day 7 to determine change from baseline in TWA0-24hrs for SpO2/FiO2 on Day 7.

    Measure: Change From Baseline to Day 7 in the Time-weighted Average from 0 through 24 hours (TWA0-24hrs) for the Ratio of Blood Oxygen Saturation to the Fraction of Inspired Oxygen (SpO2/FiO2)

    Time: Baseline, Day 7 (pre-dose and 2, 6, 12, 18, 24 hours post-dose)
    184 A Multicenter, Randomized, Double-blinded Placebo-controlled Study of Recombinant Interleukin-7 (CYT107) for Immune Restoration of Hospitalized Lymphopenic Patients With Coronavirus COVID-19 Infection. US Oncology Cohort

    Comparison of the effects of CYT107 vs Placebo administered IM at 10μg/kg twice a week for three weeks on immune reconstitution of lymphopenic COVID-19 patients

    NCT04426201
    Conditions
    1. COVID-19
    2. Lymphocytopenia
    Interventions
    1. Drug: CYT107
    2. Drug: Placebo
    MeSH:Lymphopenia
    HPO:Lymphopenia

    Primary Outcomes

    Description: A statistically significant increase of the absolute lymphocyte count (ALC) from randomization to day 30 or HospitalDischarge

    Measure: Improvement of the absolute lymphocyte count (ALC) of lymphopenic (ALC≤1000/mm3) COVID-19 infected participants out to approximately 30 days following initial Study drug administration or Hospital discharge (HD), whichever occurs first

    Time: one month

    Secondary Outcomes

    Description: The time to clinical improvement to determine if CYT107 will improve the clinical status of hospitalized COVID-19 patients as measured by clinical improvement score

    Measure: "clinical improvement" as defined by a 2 points improvement in a 7-point ordinal scale for Clinical Assessment, through day 30 or HD.

    Time: one month

    Description: The decrease of SARS-CoV-2 viral load from measurements at baseline and days of treatment dose 4 and dose 5, Day 21 and Day 30 or HD (whichever occurs first)

    Measure: a significant decline of SARS-CoV-2 viral load through day 30 or HD

    Time: 1 month or HD (whichever occurs first)

    Description: Incidence of secondary infections based on pre-specified criteria as adjudicated by the Secondary Infections Committee (SIC) through Day 45

    Measure: frequency of secondary infections through day 45 compared to placebo arm

    Time: 45 days

    Description: Number of days of hospitalization during index hospitalization (defined as time from initial Study drug treatment through HD)

    Measure: length of hospitalization compared to placebo arm

    Time: 45 days

    Description: Number of days in ICU during index hospitalization

    Measure: length of stay in ICU compared to placebo arm

    Time: 45 days

    Description: Readmissions to ICU through Day 45

    Measure: number of readmissions to ICU compared to placebo arm

    Time: 45 days

    Description: Organ support free days (OSFDs) during index hospitalization (This includes ventilator assistance free days)

    Measure: organ support free days compared to placebo arm

    Time: 45 days

    Description: Number of readmissions to the hospital through Day 45

    Measure: Frequency of re-hospitalization through day 45 compared to placebo arm

    Time: 45 days

    Description: All-cause mortality through Day 45

    Measure: All-cause mortality through day 45 compared to placebo arm

    Time: 45 days

    Description: Absolute numbers of CD4+ and CD8+ T-cell counts at time points indicated on the Schedule of Activities (SoA) through Day 30 or HD

    Measure: CD4+ and CD8+ T cell counts compared to placebo arm

    Time: 30 days

    Description: Track and evaluate other known biomarkers of inflammation, Ferritin, from baseline to day 30

    Measure: level of other known biomarkers of inflammation: Ferritin compared to placebo arm

    Time: 30 days

    Description: Track and evaluate other known biomarkers of inflammation, CRP from baseline to day 30

    Measure: Level of other known biomarkers of inflammation: CRP compared to placebo arm

    Time: 30 days

    Description: Track and evaluate other known biomarkers of inflammation, D-dimer from baseline to day 30

    Measure: Level of other known biomarkers of inflammation: D-dimer compared to placebo arm

    Time: 30 days

    Description: Evaluate improvement of the NEWS2 score value. Score form 0 to 4: NO Risk Score of 7 or more: High risk

    Measure: Physiological status through NEWS2 evaluation compared to Placebo arm

    Time: 30 days

    Other Outcomes

    Description: Incidence and scoring of all grade 3-4 adverse events through Day 45 (using CTCAE Version 5.0) to assess safety

    Measure: Safety assessment through incidence and scoring of grade 3-4 adverse events

    Time: 45 days
    185 A Master Protocol Assessing the Safety, Tolerability, and Efficacy of Anti-Spike (S) SARS-CoV-2 Monoclonal Antibodies for the Treatment of Hospitalized Patients With COVID-19

    The primary objectives are: Phase 1 - To evaluate the safety and tolerability of REGN10933+REGN10987 compared to placebo - To evaluate the virologic efficacy of REGN10933+REGN10987 compared to placebo in reducing viral shedding of SARS-CoV-2 Phase 2 - To evaluate the virologic efficacy of REGN10933+REGN10987 compared to placebo in reducing viral shedding of SARS-CoV-2 - To evaluate the clinical efficacy of REGN10933+REGN10987 compared to placebo in improving clinical status Phase 3 - To evaluate and confirm the clinical efficacy of REGN10933+REGN10987 compared to placebo in improving clinical status

    NCT04426695
    Conditions
    1. COVID-19
    Interventions
    1. Drug: REGN10933+REGN10987 combination therapy
    2. Drug: Placebo

    Primary Outcomes

    Description: Primary: Up to Day 169: Phase 1: C1 Secondary: Up to Day 29: Phase 1: C1, Phase 2: C1A, C1, C2, C3 Up to Day 57: Phase 2: C1A, C1, C2, C3

    Measure: Proportion of patients with treatment-emergent Serious Adverse Events (SAEs)

    Time: Through Day 169

    Description: Primary: Phase 1:C1 Secondary: Phase 2: C1A, C1, C2, C3

    Measure: Proportion of patients with infusion-related reactions

    Time: Through Day 4

    Description: Primary: Phase 1:C1 Secondary: Phase 2: C1A, C1, C2, C3

    Measure: Proportion of patients with hypersensitivity reactions

    Time: Through Day 29

    Description: Phase 1:C1 Phase 2: C1A, C1, C2, C3

    Measure: Time-weighted average change from baseline in viral shedding as measured by quantitative reverse transcription polymerase chain reaction (RT-qPCR) in nasopharyngeal (NP) swab samples

    Time: Baseline up to Day 22

    Description: Primary: Day 8: Phase 2: C1A, C1, Phase 3:C1 Day 22: Phase 2:C2, C3, Phase 3:C2, C3 Secondary: Day 8: Phase 1:C1 Day 29: Phase 1:C1, Phase 2: C1A, C1, C2, C3 7-point Ordinal Scale: Death; Hospitalized, requiring invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); Hospitalized, requiring non-invasive ventilation or high flow oxygen devices; Hospitalized, requiring supplemental oxygen; Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care Not hospitalized

    Measure: Proportion of patients with at least 1-point improvement on a 7-Point Ordinal Scale in clinical status

    Time: From Day 1 up to Day 29

    Secondary Outcomes

    Description: Phase 1: C1

    Measure: Time-weighted average change from baseline in viral shedding as measured by RT-qPCR in saliva samples

    Time: Baseline up to Day 22

    Description: Phase 1: C1

    Measure: Time-weighted average change from baseline in viral shedding as measured by RT-qPCR in nasal samples

    Time: Baseline up to Day 22

    Description: Phase 1: C1

    Measure: Time to negative RT-qPCR in all tested samples with no subsequent positive RT-qPCR in any tested samples

    Time: Through Day 29

    Description: Phase 2: C1A, C1, C2, C3

    Measure: Time to negative RT-qPCR in NP swabs with no subsequent positive RT-qPCR

    Time: Through Day 29

    Description: Phase 1: C1 Phase 2: C1A, C1, C2, C3

    Measure: Change from baseline in viral shedding as measured by RT-qPCR in NP swabs

    Time: Baseline up to Day 29

    Description: Phase 1: C1 Phase 2: C1A, C1, C2, C3

    Measure: Time-weighted average change in viral shedding

    Time: Baseline up to Day 29

    Description: Phase 1: C1

    Measure: Change from baseline in viral shedding as measured by RT-qPCR in saliva samples

    Time: Baseline up to Day 29

    Description: Phase 1: C1

    Measure: Change from baseline in viral shedding as measured by RT-qPCR in nasal swabs

    Time: Baseline up to Day 29

    Description: Phase 1: C1

    Measure: Correlation of RT-qPCR results over time between different sample types

    Time: Up to Day 29

    Description: Phase 1: C1

    Measure: Concordance of RT-qPCR results over time between different sample types

    Time: Up to Day 29

    Description: Phase 1: C1, Phase 2: C1A, C1 Day 8 Phase 2: C2, C3 Day 22 Phase 1: C1, Phase 2: C1A, C1, C2, C3 Day 29

    Measure: Proportion of patients with at least 2-point improvement on a 7-Point Ordinal Scale in clinical status

    Time: From Day 1 up to Day 29

    Description: Phase 1: C1 Phase 2: C1, C2, C3

    Measure: Time to no longer requiring oxygen supplementation

    Time: Through Day 29

    Description: Phase 1: C1 Phase 2: C1A, C1, C2, C3

    Measure: Number of days of supplemental oxygen use

    Time: Through Day 29

    Description: Phase 1: C1 Phase 2: C1A, C1, C2, C3

    Measure: Proportion of patients initiating high-intensity oxygen therapy

    Time: Up to Day 29 or hospital discharge

    Description: Phase 1: C1 Phase 2: C1A, C1, C2, C3

    Measure: Number of days of high-intensity oxygen therapy

    Time: Through Day 29

    Description: Phase 1: C1 Phase 2: C1A, C1, C2, C3

    Measure: Proportion of patients initiating mechanical ventilation

    Time: Up to Day 29 or hospital discharge

    Description: Phase 1: C1 Phase 2: C1A, C1, C2, C3

    Measure: Number of days of mechanical ventilation

    Time: Through Day 29

    Description: Phase 1: C1 Phase 2: C1A, C1, C2, C3

    Measure: Number of Ventilator-free days

    Time: Through Day 29

    Description: Phase 1: C1 Phase 2: C1A, C1, C2, C3

    Measure: Number of days of hospitalization

    Time: Through Day 29

    Description: Phase 1: C1: Through Day 169 Phase 2: C1A, C1, C2, C3: Through Day 57

    Measure: Proportion of patients re-admitted to hospital after discharge through the end of study

    Time: Through Day 169

    Description: Phase 1: C1 Phase 2: C1A, C1, C2, C3

    Measure: Proportion of patients admitted into an intensive care unit (ICU)

    Time: Up to Day 29

    Description: Phase 1: C1 Phase 2: C1A, C1, C2, C3

    Measure: Days of ICU stay

    Time: Up to Day 29

    Description: Phase 1: C1 Through Day 29 and Day 169 Phase 2: C1A, C1, C2, C3 Through Day 29 and Day 57

    Measure: Number of deaths due to any cause (All-Cause Mortality)

    Time: Through Day 169

    Description: Phase 1: C1: Through Day 169 Phase 2: C1A, C1, C2, C3: Through Day 57

    Measure: Overall Survival

    Time: Through Day 169

    Description: Phase 1: C1: Through Day 169 Phase 2: C1A, C1, C2, C3: Through Day 29

    Measure: Serum concentration of REGN10933 over time

    Time: Through Day 169

    Description: Phase 1: C1: Through Day 169 Phase 2: C1A, C1, C2, C3: Through Day 29

    Measure: Serum concentration of REGN10987 over time

    Time: Through Day 169

    Description: Phase 1: C1: Through Day 169 Phase 2: C1A, C1, C2, C3: Through Day 29

    Measure: Incidence of anti-drug antibodies (ADA) to REGN10933

    Time: Through Day 169

    Description: Phase 1: C1: Through Day 169 Phase 2: C1A, C1, C2, C3: Through Day 29

    Measure: Incidence of anti-drug antibodies (ADA) to REGN10987

    Time: Through Day 169

    Description: Phase 1 only

    Measure: Assessment of pharmacokinetic (PK) parameter: maximum serum concentration observed (Cmax) of REGN10933

    Time: Through day 169

    Description: Phase 1 only

    Measure: Assessment of PK parameter: maximum serum concentration observed (Cmax) of REGN10987

    Time: Through day 169

    Description: Phase 1 only

    Measure: Assessment of PK parameter: Cmax-to-dose ratio (Cmax/dose) for REGN10933

    Time: Through Day 169

    Description: Phase 1 only

    Measure: Assessment of PK parameter: Cmax-to-dose ratio (Cmax/dose) for REGN10987

    Time: Through Day 169

    Description: Phase 1 only

    Measure: Assessment of PK parameter: Time to Cmax (tmax) for REGN10933

    Time: Through Day 169

    Description: Phase 1 only

    Measure: Assessment of PK parameter: Time to Cmax (tmax) for REGN10987

    Time: Through Day 169

    Description: Phase 1 only

    Measure: Assessment of PK parameter: Area Under the Curve (AUC) computed from time zero to the time of the last positive concentration (AUClast) for REGN10933

    Time: Through Day 169

    Description: Phase 1 only

    Measure: Assessment of PK parameter: AUC computed from time zero to the time of the last positive concentration (AUClast) for REGN10987

    Time: Through Day 169

    Description: Phase 1 only

    Measure: Assessment of PK parameter: AUC from time zero extrapolated to infinity (AUCinf) for REGN10933

    Time: Through Day 169

    Description: Phase 1 only

    Measure: Assessment of PK parameter: AUC from time zero extrapolated to infinity (AUCinf) for REGN10987

    Time: Through Day 169

    Description: Phase 1 only

    Measure: Assessment of PK parameter: AUCinf-to-dose ratio (AUCinf/dose) of REGN10933

    Time: Through Day 169

    Description: Phase 1 only

    Measure: Assessment of PK parameter: AUCinf-to-dose ratio (AUCinf/dose) of REGN10987

    Time: Through Day 169

    Description: Phase 1 only

    Measure: Assessment of PK parameter: Observed terminal half-life [t1/2] for REGN10933

    Time: Through Day 169

    Description: Phase 1 only

    Measure: Assessment of PK parameter: Observed terminal half-life [t1/2] of REGN10987

    Time: Through Day 169

    Description: Phase 1 only

    Measure: Assessment of PK parameter: Clearance (CL) for REGN10933

    Time: Through Day 169

    Description: Phase 1 only

    Measure: Assessment of PK parameter: Clearance (CL) of REGN10987

    Time: Through Day 169

    Description: Phase 1 only

    Measure: Assessment of PK parameter: Volume of distribution at steady state (Vss) of REGN10933

    Time: Through Day 169

    Description: Phase 1 only

    Measure: Assessment of PK parameter: Volume of distribution at steady state (Vss) of REGN10987

    Time: Through Day 169

    Description: Phase 1 only

    Measure: Assessment of PK parameter: Mean residence time (MRT) of REGN10933

    Time: Through Day 169

    Description: Phase 1 only

    Measure: Assessment of PK parameter: Mean residence time (MRT) of REGN10987

    Time: Through Day 169
    186 A Randomized, Double-blind, Placebo-Controlled, Phase 2/3 Study to Evaluate the Efficacy and Safety of LY3819253 and LY3832479 in Participants With Mild to Moderate COVID-19 Illness

    The purpose of this study is to measure how well LY3819253 and LY3832479 work against the virus that causes COVID-19. LY3819253 and LY3832479 will be given to participants with early symptoms of COVID-19, via an injection into a vein. Samples will be taken from the back of the nose to determine how much virus is in the body at various times during the study. Participation could last about 12 weeks and includes one required visit to the study site, with the remainder of assessments performed in the home or by phone.

    NCT04427501
    Conditions
    1. COVID-19
    Interventions
    1. Drug: LY3819253
    2. Drug: LY3832479
    3. Drug: Placebo

    Primary Outcomes

    Description: Change from Baseline to Day 11 in SARS-CoV-2 Viral Load

    Measure: Change from Baseline to Day 11 in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Viral Load

    Time: Baseline, Day 11

    Description: Percentage of Participants Who Experience COVID-Related Hospitalization or Death

    Measure: Percentage of Participants Who Experience COVID-Related Hospitalization or Death

    Time: Baseline through Day 29

    Description: Percentage of Participants with SARS-CoV-2 Viral Load Greater than a Prespecified Threshold

    Measure: Percentage of Participants with SARS-CoV-2 Viral Load Greater than a Prespecified Threshold

    Time: Day 7

    Secondary Outcomes

    Description: Change from Baseline to Day 11 in SARS-CoV-2 Viral Load Among Participants Enrolled with Recent Symptoms Prior to Randomization

    Measure: Change from Baseline to Day 11 in SARS-CoV-2 Viral Load Among Participants Enrolled with Recent Symptoms Prior to Randomization

    Time: Baseline, Day 11

    Description: Percentage of Participants Demonstrating Symptom Resolution

    Measure: Percentage of Participants Demonstrating Symptom Resolution

    Time: Day 11

    Description: Percentage of Participants Demonstrating Symptom Improvement

    Measure: Percentage of Participants Demonstrating Symptom Improvement

    Time: Day 11

    Description: PK: Mean Concentration of LY3819253 and LY3819253 in the Presence of LY3832479

    Measure: Pharmacokinetics (PK): Mean Concentration of LY3819253 and LY3819253 in the Presence of LY3832479

    Time: Day 29

    Description: PK: Mean Concentration of LY3832479 in the Presence of LY3819253

    Measure: PK: Mean Concentration of LY3832479 in the Presence of LY3819253

    Time: Day 29

    Description: Percentage of Participants Who Experience COVID-Related Hospitalization, COVID-Related ER Visit, or Death

    Measure: Percentage of Participants Who Experience COVID-Related Hospitalization, COVID-Related Emergency Room (ER) Visit, or Death

    Time: Baseline through Day 85

    Description: Change from Baseline to Day 7 in SARS-CoV-2 Viral Load

    Measure: Change from Baseline to Day 7 in SARS-CoV-2 Viral Load

    Time: Baseline, Day 7

    Description: Percentage of Participants Enrolled with Recent Symptoms Prior to Randomization Who Experience COVID-Related Hospitalization or Death

    Measure: Percentage of Participants Enrolled with Recent Symptoms Prior to Randomization Who Experience COVID-Related Hospitalization or Death

    Time: Baseline through Day 29
    187 A Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Efficacy, Safety, Tolerability, Biomarkers and Pharmacokinetics of Ibudilast (MN-166) in COVID-19 Subjects at Risk for Developing Acute Respiratory Distress Syndrome

    The study aims to evaluate MN-166 (ibudilast) in patients with COVID-19 who are at risk of developing acute respiratory distress syndrome. Subjects will be screened, randomly assigned to MN-166 or placebo groups, receive study drug on Days 1-7, and followed up on Day 14 and Day 28.

    NCT04429555
    Conditions
    1. Pneumonia, Viral
    Interventions
    1. Drug: Ibudilast
    2. Drug: Placebo
    MeSH:Pneumonia, Viral Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Proportion of subjects free from respiratory failure as defined by the need for decreased oxygen requirements (invasive mechanical ventilation, non-invasive ventilation, high-flow oxygen, or ECMO, CPAP, BiPAP, nasal cannula) at Day 7

    Measure: Proportion of subjects free from respiratory failure

    Time: 7 days

    Description: Mean change from baseline in clinical status based on the NIAID 8-point scale (1= death, 8= not hospitalized, no limitations on activities) at Day 7. A higher score indicates improvement.

    Measure: Mean change from baseline in clinical status using the NIAID 8-point ordinal scale at Day 7

    Time: 7 days

    Description: Percentage of patients with at least a one-point improvement in clinical status using the NIAID 8-point ordinal scale (1= death, 8= not hospitalized, no limitations on activities) at Day 7. A higher score indicates improvement.

    Measure: Percentage of patients with improvement in clinical status

    Time: 7 days

    Description: Mean change from baseline (baseline = 1-fold; any value above 1.0 indicates elevation in cytokine levels; any value below 1.0 indicates reduction in cytokine levels) in migration inhibitory factor (MIF), (interleukin 1-beta (IL-1β), interleukin 6 (IL-6), tumor necrosis factor (TNF-α), and C-reactive protein (CRP) at Day 7.

    Measure: Change in cytokine levels from baseline

    Time: 7 days

    Secondary Outcomes

    Description: Incidence, frequency, and severity of adverse events at Day 7 and Day 14

    Measure: Adverse event Incidence, severity, relationship to study drug, and study discontinuations

    Time: Days 7, 14

    Description: Incidence of out-of-normal-range values and markedly abnormal change from baseline in laboratory safety test variables by treatment group.

    Measure: Changes in laboratory values from baseline

    Time: 7 days

    Description: Proportion of subjects free from respiratory failure as defined by the need for decreased oxygen requirement (invasive mechanical ventilation, non-invasive ventilation, high-flow oxygen, or ECMO, CPAP, BiPAP, nasal cannula) at Day 14

    Measure: Proportion of subjects free from respiratory failure as defined by the need for decreased oxygen requirement (invasive mechanical ventilation, non-invasive ventilation, high-flow oxygen, or ECMO, CPAP, BiPAP, nasal cannula) at Day 14

    Time: 14 days

    Description: Mean change from baseline in clinical status using the NIAID 8-point ordinal scale at Day 14 and Day 28

    Measure: Mean change from baseline in clinical status

    Time: Days 14, 28

    Description: Proportion of subjects receiving mechanical ventilation or intubation.

    Measure: Incidence of mechanical ventilation or intubation

    Time: Days 7, 14

    Description: Proportion of subjects requiring submission to the intensive care unit

    Measure: Intensive care unit admission

    Time: 7 days

    Description: Blood sample collection to determine plasma concentrations of ibudilast.

    Measure: Plasma concentrations of Ibudilast

    Time: 7 days

    Description: Number of deaths from any cause

    Measure: All cause mortality

    Time: Days 7, 14, 28
    188 Safety and Efficacy of Mesenchymal Stem Cells in the Management of Severe COVID-19

    The disease caused by the new coronavirus, SARS-CoV-2, called COVID-19, it has considered a worldwide pandemia by the WHO. Suddently, it produces a lot of patients severe ill, in a little geographic area, that could surpase the resourses of the any health system in the world. There is no documentation of an effective alternative for the treatment of the severe ill patients, that can reduce the mortality or the adverse events suffered by these people. It is has suggested the usefulness of the Mesenchymal Stem cells (MSC) for the management of these patients, thanks to their direct and indirect antiviral capacity, and its potency as immunomodulator, that could ameliorate the lung disease and the severity of COVID-19.

    NCT04429763
    Conditions
    1. COVID-19
    Interventions
    1. Biological: Umbilical cord derived mesenchymal stem cells
    2. Biological: Placebo

    Primary Outcomes

    Description: Change in two or more degrees in the NEWS scale

    Measure: Clinical deterioration or death

    Time: 4 weeks
    189 Hydroxychloroquine Use in Hospitalized Patients With COVID-19: Impact on Progression to Severe or Critical Disease

    The primary objective is to assess the impact of hydroxychloroquine in hospitalized patients with COVID-19 and risk factors for severe/critical disease.

    NCT04429867
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Hydroxychloroquine
    2. Drug: Placebo
    MeSH:Disease Progression

    Primary Outcomes

    Description: The impact will be evaluated by comparing rates of a composite primary outcome in patients randomized to hydroxychloroquine versus those randomized to placebo. The composite outcome includes progression to severe/critical disease or death (including withdrawal of care/hospice transfer). Progression to severe/critical disease is defined by requiring oxygen delivery via high flow nasal cannula, non-rebreather mask, bipap, or transfer to intensive care (ICU) or intermediate care units (IMCU) due to COVID-19-related complications.

    Measure: Impact of hydroxychloroquine in hospitalized patients with COVID-19 and risk factors for severe/critical disease.

    Time: 30 Days

    Secondary Outcomes

    Measure: Hospital length of stay

    Time: 30 Days

    Measure: 30-Day Mortality

    Time: 30 Days

    Description: Resolution of symptoms will be assessed using standard medical interview procedures with the subject and review of the medical records.

    Measure: Resolution of Symptoms

    Time: 14 Days

    Measure: Incidence of QTc >500ms after initiation of therapy

    Time: 30 Days

    Measure: Incidence of discontinuation of therapy

    Time: 30 Days
    190 Randomized, Double-Blind, Placebo-Controlled Phase 2 Study of the Efficacy and Safety of Intravenous Pamrevlumab, a Monoclonal Antibody Against Connective Tissue Growth Factor (CTGF), in Hospitalized Patients With Acute COVID-19 Disease

    This is a Phase 2 trial to evaluate the efficacy and safety of intravenous (IV) infusions of pamrevlumab as compared to placebo in hospitalized subjects with acute COVID-19 disease.

    NCT04432298
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Pamrevlumab
    2. Drug: Placebo

    Primary Outcomes

    Measure: Proportion of subjects who never received mechanical ventilation and/or ECMO and alive

    Time: Baseline to Day 28

    Secondary Outcomes

    Measure: Proportion of subjects alive, discharged home, and not on supplemental oxygen

    Time: Baseline to Day 28

    Measure: Time to recovery based on a Modified 8-Point Ordinal Scale

    Time: Baseline to Day 28

    Measure: Days in ICU/CCU (either on or off mechanical ventilation and/or ECMO)

    Time: Baseline to Day 28

    Measure: Days on mechanical ventilation and/or ECMO

    Time: Baseline to Day 28

    Measure: Time to death from any cause

    Time: Baseline to Day 28

    Measure: Changes in PaO2/FiO2 ratio, both as categorical and continuous variable

    Time: Baseline to Day 28

    Measure: Change in (non-invasive) oxygen supplementation requirements

    Time: Baseline to Day 28
    191 A Randomized Controlled Trial Assessing the Efficacy of Lianhua Qingwen as an Adjuvant Treatment in Patients With Mild Symptoms of COVID-19

    COVID-19 virus remains in infected patients for extended periods of time. A great resource burden is placed on the healthcare system and society at large to isolate COVID-19 patients for prolonged periods. Thus, being able to increase the rate of viral clearance, thus reducing the duration of COVID-19 infection, would allow patients to be discharged earlier to free up resources for those who require it. The investigators designed a randomized controlled trial, investigating the use of Lianhua Qingwen, a TCM treatment, in COVID-19 infected patients with mild symptoms. The investigators hypothesize that the use of Lianhua Qingwen will increase the proportion of patients who test negative for COVID-19 after 8 days of TCM treatment when compared to the group of patients provided with standard care and placebo. Patients will be recruited from community isolation facilities, and have onset of symptoms within 5 days prior to admission to the isolation facility. The trial also evaluates the time taken for relief of clinical symptoms associated with COVID-19 and assesses the safety of the TCM treatment given to patients.

    NCT04433013
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Lianhua Qingwen
    2. Drug: Placebo

    Primary Outcomes

    Measure: Proportion of participants who test negative for COVID-19

    Time: after 8 days of treatment

    Secondary Outcomes

    Measure: Time taken in days for relief of clinical symptoms

    Time: during the 8-day course of treatment

    Measure: Proportion of participants with mild symptoms of COVID-19 progressing to moderate or severe illness

    Time: after 8 days of treatment and at the end of the trial

    Measure: Proportion of participants who test positive for COVID-19 with Ct value>30

    Time: after 8 days of treatment
    192 RepurpoSing Old Drugs TO SuppRess a Modern Threat: The STORM Trial

    The primary aim of this study is to test whether Doxycycline can benefit patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections by inhibiting the replication of the virus while at the same time blocking the development of cytokine storms or inhibiting cytokine-associated coagulopathy respectively. The investigators hypothesize that Doxycycline will will improve survival and reduce morbidity in SARS-CoV-2 infected patients. A secondary aim is to identify genetic variants that predict either an unusually mild disease or an unusually severe disease - knowledge that can be used to design new and precise medications and to be able to predict patients who might get into early trouble and to therefore hospitalize them.

    NCT04433078
    Conditions
    1. Cytokine Storm
    2. SARS-CoV-2
    Interventions
    1. Drug: Doxycycline
    2. Drug: Placebo

    Primary Outcomes

    Description: Days Alive and Out of Hospital (Composite Endpoint)

    Measure: Time Free of Either Hospitalization, Hypoxemia, ICU Admission or Death

    Time: 21 days

    Secondary Outcomes

    Description: Change From Baseline of Nasopharyngeal Luminex NxTAG CoV (Positive/Negative)

    Measure: NP SARS-CoV-2 PCR

    Time: 21 days

    Description: Change From Baseline of SARS-CoV-2 Serum Quantitative Viral Load

    Measure: SARS-CoV-2 Serum Quantitative Viral Load

    Time: 21 days

    Description: Change From Baseline of SARS-CoV-2 IgM/IgG Antibodies (Positive/Negative)

    Measure: SARS-CoV-2 IgM/IgG Antibodies

    Time: 21 days

    Description: Change From Baseline of White Blood Count (CBC) K/mm3

    Measure: White Blood Cell Count (WBC)

    Time: 21 days

    Description: Change From Baseline of Absolute Lymphocyte Count (ALC) K/mm3

    Measure: Absolute Lymphocyte Count (ALC)

    Time: 21 days

    Description: Change From Baseline of C-Reactive Protein (CRP) mg/dL

    Measure: C-Reactive Protein (CRP)

    Time: 21 days

    Description: Change From Baseline of N-Terminal Pro-B-Type Natriuretic Peptide (Pro-BNP) pg/mL

    Measure: N-Terminal Pro-B-Type Natriuretic Peptide (Pro-BNP)

    Time: 21 days

    Description: Change From Baseline of High Sensitivity Troponin I (hsTnT) ng/mL

    Measure: High Sensitivity Troponin I (hsTnT)

    Time: 21 days

    Description: Change From Baseline of Tumor Necrosis Factor Alpha (TNF-a)

    Measure: Tumor Necrosis Factor Alpha (TNF-a)

    Time: 21 days

    Description: Change From Baseline of IL-1

    Measure: IL-1

    Time: 21 days

    Description: Change From Baseline of IL-1B

    Measure: IL-1B

    Time: 21 days

    Description: Change From Baseline of IL-6

    Measure: IL-6

    Time: 21 days
    193 Efficacy of Pentoxifylline as Add on Therapy in COVID19 Patients

    With potential antiviral effects on severe acute respiratory syndrome (SARS) and as a methyl-xanthine derived inhibitor of phosphodiesterase-4, pentoxifylline basically functions as a hemorrheologic agent for a better circulation and oxygenation and exerts unique effects on immune modulation, inflammation and oxidative stress. As the main regulator of cAMP metabolism, posphodiesterase-4 plays a key role in proinflammatory and immune cells. Pentoxifylline plays its anti-inflammatory role by reducing the production of proinflammatory cytokines such as TNF-a, IL-1 and IL-6. Given its unique impacts on immune modulation, homeostasis and fibrinolysis and its supportive effects on oxidative stress and organ failure, pentoxifylline can constitute a multipurpose and generally-safe adjuvant therapy for COVID-19 patients.

    NCT04433988
    Conditions
    1. COVID
    Interventions
    1. Drug: Pentoxifylline
    2. Drug: Placebo

    Primary Outcomes

    Description: Number of Participants need hospitalization

    Measure: Primary Outcome

    Time: 7 days

    Secondary Outcomes

    Description: Incidence of any acute respiratory infection

    Measure: Respiratory infection

    Time: 7 days

    Description: Absolute and relative frequencies of Serious Adverse Events

    Measure: Serious Adverse Events

    Time: 7 days
    194 Prospective, Randomized, Double-blind, Parallel, Placebo Controlled Study to Evaluate the Safety and Efficacy of Nitazoxanide 600 mg Three Times a Day for Post Exposure Prophylaxis of COVID-19 in Subjects From Vulnerable Communities

    The primary objective of this study is to evaluate the efficacy of the drug nitazoxanide 600 mg, administered three times a day, in relation to placebo in preventing the development of COVID-19 in subjects from vulnerable communities that had direct contact with patients diagnosed with the disease.

    NCT04435314
    Conditions
    1. covid19
    Interventions
    1. Drug: Nitazoxanide
    2. Drug: Placebo

    Primary Outcomes

    Description: PCR will be done to evaluate infection

    Measure: The proportion of subjects with laboratory-confirmed COVID-19 identified after start of treatment and before the end of the study

    Time: 28 days

    Secondary Outcomes

    Description: Number of participants with treatment-related adverse events

    Measure: Incidence of Treatment-Emergent Adverse Events

    Time: 28 days

    Description: Symptomatic PCR positive subjects

    Measure: The proportion of subjects with symptomatic laboratory-confirmed COVID-19 identified after start of treatment and before the end of the study

    Time: 28 days

    Description: Asymptomatic PCR will be done to evaluate infection

    Measure: The proportion of subjects with asymptomatic laboratory-confirmed COVID identified after the start of treatment and before the end of the study

    Time: 28 days

    Description: Subject adherence to treatment will be assessed through study diary record

    Measure: Treatment adherence

    Time: 7 days

    Description: Proportion of patients with severe condition

    Measure: Disease complication

    Time: 28 days

    Description: Proportion of patient that needed undergo an unscheduled visit

    Measure: Incidence of subjects that underwent unscheduled visit

    Time: 28 days
    195 A Phase III, Randomized, Double-blind, Placebo-controlled, Multicentre, Clinical Trial to Assess the Efficacy and Safety of VPM1002 in Reducing Hospital Admissions and/or Severe Respiratory Infectious Diseases in Elderly in the SARS-CoV-2 Pandemic by Modulating the Immune System

    The aim of this study is to investigate whether vaccination of elderly with VPM1002 could reduce hospital admissions and/or severe respiratory infectious diseases in the SARS-CoV-2 pandemic . VPM1002 is a vaccine that is a further development of the old Bacillus Calmette-Guérin (BCG) vaccine, which has been used successfully as a vaccine against tuberculosis for about 100 years, especially in developing countries. VPM1002 has been shown in various clinical studies to be significantly safer than the BCG vaccine. VPM1002 strengthens the body's immune defence and vaccination with BCG reduces the frequency of respiratory diseases. It is therefore assumed that a VPM1002 vaccination could also provide (partial) protection against COVID-19 disease caused by the "new corona virus" SARS-CoV 2.

    NCT04435379
    Conditions
    1. Infection, Respiratory Tract
    Interventions
    1. Biological: VPM1002
    2. Biological: Placebo
    MeSH:Communicable Diseases Infection Respiratory Tract Infections
    HPO:Respiratory tract infection

    Primary Outcomes

    Measure: Number of days with severe respiratory disease at hospital and/or at home

    Time: From day 0 to day 240

    Secondary Outcomes

    Measure: Cumulative incidence of hospital admissions

    Time: From day 0 to day 240

    Measure: Cumulative incidence of documented SARS-CoV-2 infection

    Time: From day 0 to day 240

    Measure: Number of days with self-reported fever (≥ 38 ºC)

    Time: From day 0 to day 240

    Measure: Number of days with self-reported acute respiratory symptoms

    Time: From day 0 to day 240

    Measure: Cumulative incidence of self-reported acute respiratory symptoms

    Time: From day 0 to day 240

    Measure: Cumulative incidence of death for any reason

    Time: From day 0 to day 240

    Measure: Cumulative incidence of death due to documented SARS-CoV-2 infection

    Time: From day 0 to day 240

    Measure: Cumulative incidence of ICU admission for any reason

    Time: From day 0 to day 240

    Measure: Cumulative incidence of ICU admission due to documented SARS-CoV-2 infection

    Time: From day 0 to day 240

    Measure: Cumulative incidence of hospital admission due to documented SARSCoV- 2 infection

    Time: From day 0 to day 240
    196 A Randomized, Double-blind, Placebo-controlled Phase 1/2a Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of Ad26COVS1 in Adults Aged 18 to 55 Years Inclusive and Adults Aged 65 Years and Older

    The purpose of the study is to assess the safety, reactogenicity, and immunogenicity of Ad26.COV2.S at 2 dose levels, administered intramuscularly (IM) as a single-dose or 2-dose schedule, with a single booster vaccination administered in one cohort, in healthy adults aged greater than or equal to 18 to less than or equal to 55 years and in adults aged greater than or equal to 65 years in good health with or without stable underlying conditions.

    NCT04436276
    Conditions
    1. Healthy
    Interventions
    1. Biological: Ad26.COV2.S
    2. Biological: Placebo

    Primary Outcomes

    Description: Solicited local AEs are pre-defined local (at the injection site) adverse events for which participants are specifically questioned and which are noted by participants in their diary for 7 days after first vaccination. Solicited local AEs are: injection site pain/tenderness, erythema, and swelling at the vaccination site. An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product.

    Measure: Cohorts 1, 2, and 3: Number of Participants with Solicited Local Adverse Events (AEs) for 7 Days after First Vaccination

    Time: Day 8 (7 Days after first vaccination on Day 1)

    Description: Solicited local AEs are pre-defined local (at the injection site) adverse events for which participants are specifically questioned and which are noted by participants in their diary for 7 days after second vaccination. Solicited local AEs are: injection site pain/tenderness, erythema, and swelling at the vaccination site. An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product.

    Measure: Cohorts 1, 2, and 3: Number of Participants with Solicited Local Adverse Events (AEs) for 7 Days after Second Vaccination

    Time: Day 64 (7 Days after second vaccination on Day 57)

    Description: Participants will be instructed on how to record daily temperature using a thermometer and also instructed to note signs and symptoms in the diary on a daily basis for 7 days after first vaccination. Solicited systemic AEs are fatigue, headache, nausea, and myalgia.

    Measure: Cohorts 1, 2, and 3: Number of Participants with Solicited Systemic AEs for 7 Days after First Vaccination

    Time: Day 8 (7 Days after first vaccination on Day 1)

    Description: Participants will be instructed on how to record daily temperature using a thermometer and also instructed to note signs and symptoms in the diary on a daily basis for 7 days after second vaccination. Solicited systemic AEs are fatigue, headache, nausea, and myalgia.

    Measure: Cohorts 1, 2, and 3: Number of Participants with Solicited Systemic AEs for 7 Days after Second Vaccination

    Time: Day 64 (7 Days after second vaccination on Day 57)

    Description: Number of participants with unsolicited AEs for 28 days after first vaccination will be reported. Unsolicited AEs are all AEs for which the participant is not specifically questioned.

    Measure: Cohorts 1, 2, and 3: Number of Participants with Unsolicited AEs for 28 Days after First Vaccination

    Time: Day 29 (28 Days after first vaccination on Day1)

    Description: Number of participants with unsolicited AEs for 28 days after second vaccination will be reported. Unsolicited AEs are all AEs for which the participant is not specifically questioned.

    Measure: Cohorts 1, 2, and 3: Number of Participants with Unsolicited AEs for 28 Days after Second Vaccination

    Time: Day 85 (28 Days after second vaccination)

    Description: SAE is an adverse event resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly/birth defect; suspected transmission of any infectious agent via a medicinal product or medically important.

    Measure: Cohort 1 and 3: Number of Participants with Serious Adverse Events (SAEs) from the First Vaccination until 1 Year after the Second Vaccination

    Time: From Day 57 (vaccination 2) up to 1 year

    Description: SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly/birth defect; suspected transmission of any infectious agent via a medicinal product or medically important.

    Measure: Cohort 2: Number of Participants with SAEs from the First Vaccination until 6 Months after the First Vaccination

    Time: Day 1 (vaccination 1) up to 6 Months

    Secondary Outcomes

    Description: Number of participants with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) neutralizing antibody titers as assessed by VNA to measure the humoral immune responses will be reported.

    Measure: Cohorts 1, 2, and 3: Number of Participants With SARS-CoV-2 Neutralizing Antibody Titers as Assessed by Virus Neutralization Assay (VNA)

    Time: Up to 38 Months

    Description: Number of participants with SARS-CoV-2 binding antibodies as assessed by enzyme-linked immunosorbent assay (ELISA) to measure humoral immune response will be reported.

    Measure: Cohorts 1, 2, and 3: Number of Participants with SARS-CoV-2 Binding Antibodies Assessed by ELISA

    Time: Up to 38 Months

    Description: Number of participants with Th-1 and Th-2 immune responses will be reported. Th1 and Th2 immune responses will be assessed by flow cytometry after SARS-CoV-2 S protein peptide stimulation of peripheral blood mononuclear cells (PBMCs) and intracellular staining [ICS] including cluster of differentiation (CD)-4+/CD-8+, Interferons (INF)-gamma, interleukin [IL] 2, Tumor Necrosis Factor (TNF)-alpha, IL-4, IL-5, IL-13, and/or other Th-1/Th-2 markers.

    Measure: Cohorts 1, 2, and 3: Number of Participants with T-helper (Th)-1 and Th-2 Immune Responses as Assessed by Flow Cytometry

    Time: Up to 38 Months
    197 Phase 2, Multicentre, Randomized, Double Blind, 2 Arms Placebo-controlled Study in Adults With Moderate COVID-19 With Gastrointestinal Signs and Symptoms

    This is a Phase 2, multicentre, randomized, double blind, 2 arm placebo-controlled study in adults with moderate COVID-19 with gastrointestinal signs and symptoms.

    NCT04436458
    Conditions
    1. COVID
    Interventions
    1. Drug: Niclosamide Oral Tablet
    2. Drug: Placebo

    Primary Outcomes

    Measure: The primary endpoint is the rate of faecal SARS-CoV-2 virus clearance (rectal swab or stool sample) assessed by RT-PCR in the niclosamide group, compared to the placebo group

    Time: From Day 1 to 42
    198 Randomized, Double-blind, Multi Centre Phase II, Proof of Concept, Dose Finding Clinical Trial on Ivermectin for the Early Treatment of COVID-19

    Prospective, multi-centre, randomized, double-blind trial to assess efficacy and safety of ivermectin for the treatment of initial infection with SARS-CoV2 infection. Study arms: A) placebo B) ivermectin 600 μg/kg daily for 5 consecutive days (I_600) + placebo. C) ivermectin 1200 μg/kg daily at empty stomach with water for 5 consecutive days (I_1200). Patients will be randomized at emergency room of hospitals as well as at outpatient ambulatory care as well as at home, according to routine procedures of recruiting centres. In arm A and B, the number of placebo tablets to be administered will be calculated by the study dedicated pharmacist considering the number of tablets that should be taken in case a patient with the same weight is assigned to arm C.

    NCT04438850
    Conditions
    1. Covid19
    Interventions
    1. Drug: Ivermectin
    2. Other: Placebo

    Primary Outcomes

    Description: Number of serious adverse drug reaction

    Measure: SADR

    Time: 14 days

    Description: Quantitative viral load as measured by quantitative, digital droplet PCR.

    Measure: Viral load

    Time: Assessed at day 7

    Secondary Outcomes

    Description: 1. Trend over time of quantitative viral load at Day 7 and 14 as measured by quantitative, digital droplet PCR.

    Measure: Trend viral load

    Time: Days 7 and 14 from baseline

    Description: Time to clinical resolution (for symptomatic patients).

    Measure: Clinical resolution

    Time: Assessed on Day 30

    Description: Time from diagnosis to documented viral clearance

    Measure: Viral clearance

    Time: assessed on days 14 and 30

    Description: Proportion of patients with virological clearance

    Measure: Virological clearance

    Time: Assessed at day 14 and 30

    Description: rate of hospitalization

    Measure: hospitalization rate

    Time: Day 30

    Description: COVID-19 Severity Score (Coronavirus Diseases 19 Severity Score) - min value 1 ("no limitation of activities), max value 8 ("death"). Higher scores mean worse outcome

    Measure: Severity score

    Time: Assessed at Day 14 and Day 30
    199 Treatment of COVID-19 Pneumonia With Glucocorticoids. A Randomized Controlled Trial

    Around 30% of admitted patients with COVID-19 pneumonia develop a hyper-inflammatory state whose progression to an acute respiratory distress syndrome (ARSD) could be prevented by the early initiation of immune-modulatory agents. The role of glucocorticoids (GC) in this setting remains controversial. This study aims to assess the safety and effectiveness of GC pulses to improve the clinical outcomes of patients with COVID-19 pneumonia with risen inflammatory biomarkers.

    NCT04438980
    Conditions
    1. Covid-19 Pneumonia
    Interventions
    1. Drug: Methylprednisolone
    2. Other: Placebo
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: • Death

    Measure: Proportion of patients developing treatment failure

    Time: At 14 days after randomization

    Description: • Need for admission in an intensive care unit (ICU)

    Measure: Proportion of patients developing treatment failure

    Time: At 14 days after randomization

    Description: • Need for mechanical ventilation

    Measure: Proportion of patients developing treatment failure

    Time: At 14 days after randomization

    Description: • Decrease in SpO2 <90% (in ambient air) or PaO2 <60 mmHg (in ambient air) or PaO2FiO2 <300 mmHg, associated with radiological impairment

    Measure: Proportion of patients developing treatment failure

    Time: At 14 days after randomization

    Secondary Outcomes

    Measure: Mortality at day 28

    Time: At 28 days after randomization

    Measure: Proportion of patients requiring ICU admission

    Time: At 28 days after randomization

    Measure: Proportion of patients requiring rescue-therapy with tocilizumab

    Time: At 14 days after randomization

    Description: Time in days from randomization until the date of hospital discharge.

    Measure: Length of hospital stay

    Time: At 28 days after randomization

    Description: Any undesirable experience related to the use of the studied drugs, which causes patient's death, life-threatening risk, hospitalization or extension of a previous hospitalization, disability or permanent damage, requires intervention to prevent permanent impairment or damage, or is considered medically relevant

    Measure: Proportion of severe adverse events

    Time: At 28 days after randomization

    Measure: Proportion of bacterial, fungal or opportunistic infections

    Time: At 28 days after randomization

    Description: Change in plasma levels of C-reactive protein (CRP)

    Measure: Evolution of inflammatory biomarkers related to COVID-19

    Time: At 14 days after randomization

    Description: Change in plasma levels of ferritin

    Measure: Evolution of inflammatory biomarkers related to COVID-19

    Time: At 14 days after randomization

    Description: Change in plasma levels of interleukin-6 (IL-6)

    Measure: Evolution of inflammatory biomarkers related to COVID-19

    Time: At 14 days after randomization

    Description: Change in plasma levels of lactate dehydrogenase (LDH)

    Measure: Evolution of inflammatory biomarkers related to COVID-19

    Time: At 14 days after randomization

    Description: Change in plasma levels of D-dimer (DD)

    Measure: Evolution of inflammatory biomarkers related to COVID-19

    Time: At 14 days after randomization

    Description: Negativization of RT-PCR for SARS-CoV-2 on nasopharyngeal swab or sputum

    Measure: Proportion of SARS-CoV-2 clearance.

    Time: At 7 days after randomization
    200 A Randomized, Double-blind, Placebo-controlled Phase 3 Study: Efficacy and Safety of VPM1002 in Reducing SARS-CoV-2 Infection Rate and COVID-19 Severity

    Bacille Calmette-Guerin (BCG) is a live attenuated vaccine administered for prevention of tuberculosis. Recently, several groups have hypothesized that BCG may "train" the immune system to respond to a variety of unrelated infections, including viruses and in particular the coronavirus responsible for COVID-19. Trials are currently being conducted in Australia, Netherlands, Germany and the United Kingdom to evaluate its effectiveness. Front line workers includes members of municipal and provincial police services, emergency medical personnel, firefighters, public transport employees, health service workers and food manufacturing employees. They are at high risk of infection from COVID-19, with potentially high infection rate. The investigators propose an interventional trial to evaluate the effectiveness of BCG vaccination to prevent COVID-19 infection and reduce its severity in front-line employees in Ontario.

    NCT04439045
    Conditions
    1. SARS-CoV-2 Infection
    Interventions
    1. Biological: VPM1002
    2. Other: Placebo
    MeSH:Infection Communicable Diseases

    Primary Outcomes

    Description: To compare the self-reported incidence of SARS-CoV-2 infection (confirmed by positive test) following vaccination with either VPM1002 or placebo.

    Measure: COVID-19 infection

    Time: 7 months

    Secondary Outcomes

    Description: To compare the incidence of hospitalization in participants with positive COVID-19 test treated with either VPM1002 or placebo

    Measure: Incidence of hospitalization for COVID-19

    Time: 7 months

    Description: To compare the incidence of hospitalization requiring intensive care (ICU admission) in participants with positive COVID-19 test treated with either VPM1002 or placebo

    Measure: Incidence of ICU admission for COVID-19

    Time: 7 months

    Description: To compare the incidence of acute respiratory distress syndrome (ARDS) in participants with positive COVID-19 test treated with either VPM1002 or placebo.

    Measure: Incidence of ARDS

    Time: 7 months

    Description: To compare the incidence of the need for mechanical ventilation in participants with positive COVID-19 test treated with either VPM1002 or placebo.

    Measure: Mechanical ventilation for COVID-19

    Time: 7 months

    Description: To compare the incidence of secondary infection in participants with positive COVID-19 test treated with either VPM1002 or placebo.

    Measure: Secondary infection in COVID-19

    Time: 7 months

    Description: To compare the mortality in participants with positive COVID-19 test treated with either VPM1002 or placebo.

    Measure: COVID-19-related Mortality

    Time: 7 months

    Description: To compare the incidence of deep vein thrombosis, pulmonary embolism, or stroke in participants with positive COVID-19 test treated with either VPM1002 or placebo.

    Measure: Incidence of DVT

    Time: 7 months

    Other Outcomes

    Description: To compare the incidence of COVID-19 in participants who have received BCG vaccination previously vs those not previously vaccinated

    Measure: Incidence of COVID-19 in Participants with Past BCG Vaccination

    Time: 7 months

    Description: To measure cardiac troponin, B-type natriuretic peptide, N-terminal pro b-type natriuretic peptide, C reactive protein, serum amyloid A, and procalcitonin identified as potential biomarkers of COVID-19 infection using blood samples collected prior to the vaccination and at the end of the 7-month follow-up.

    Measure: Measure cardiac troponin, B-type natriuretic peptide, N-terminal pro b-type natriuretic peptide, C reactive protein, serum amyloid A, and procalcitonin as biomarkers of COVID-19

    Time: 7 months

    Description: To compare adverse event profile in participants following administration of VPM1002 or placebo when used for prevention of COVID-19.

    Measure: Adverse events following BCG vaccine

    Time: 7 months

    Description: Compare the priming of the innate trained immunity (i.e. induction of Th1 and Th17 responses to unrelated stimuli) in participants following administration of VPM1002 or placebo when used for prevention of COVID-19.

    Measure: Innate Trained Immunity

    Time: 7 months
    201 Evaluation of the Efficacy and Safety of PTC299 in Hospitalized Subjects With COVID-19 (FITE19)

    This is a randomized, double-blind, placebo-controlled, multicenter, 28-day study of adult participants hospitalized with COVID-19, with a safety follow-up telephone call at Day 60.

    NCT04439071
    Conditions
    1. Pneumonia
    2. COVID-19
    3. Coronavirus
    Interventions
    1. Drug: PTC299
    2. Other: SOC
    3. Drug: Placebo
    MeSH:Coronavirus Infections Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Respiratory improvement is defined as sustained peripheral oxygen saturation (SpO2) ≥94% on room air.

    Measure: Time from Randomization to Respiratory Improvement

    Time: up to Day 28

    Secondary Outcomes

    Measure: Percentage of Participants Requiring Invasive Ventilation

    Time: up to Day 28

    Measure: Percentage of Participants Requiring Supplemental Oxygen or Non-Invasive Ventilation in Participants who did not Require Supplemental Oxygen at Baseline

    Time: up to Day 28

    Measure: Time from Randomization to Defervescence in Participants Presenting With Fever at Enrollment (Temperature of ≥37.6℃ Axilla, ≥38.0℃ Oral, or ≥38.6°C Tympanic or Rectal)

    Time: up to Day 28

    Measure: Time from Randomization to Respiratory Rate ≤ 24 Breaths per Minute on Room Air

    Time: up to Day 28

    Description: Cough will be rated on a scale of severe, moderate, mild, absent, in those with cough at enrollment rated severe or moderate.

    Measure: Time from Randomization to Cough Reported as Mild or Absent

    Time: up to Day 28

    Description: Dyspnea will be rated on a scale of severe, moderate, mild, absent, in those with dyspnea at enrollment rated as severe or moderate.

    Measure: Time from Randomization to Dyspnea Reported as Mild or Absent

    Time: up to Day 28

    Measure: Reduction of Immune Responses

    Time: up to Day 28

    Measure: Reduction in Viral Load

    Time: up to Day 28

    Measure: Duration of Hospitalization

    Time: up to Day 28

    Measure: Number of Mortalities

    Time: Day 28

    Measure: Number of Participants with Treatment-Emergent Adverse Events (TEAEs)

    Time: up to Day 28
    202 Randomized Controlled Single Blind Cross Over Trial Evaluating the Impact of Botox Treatment Into the Upper One Third of the Face an Area on Mood and Self -Appearance Satisfaction in a Post Covid Period.

    Botox treatment into the upper one third of the face (glabella, forehead lines and/or lateral canthal lines) to analyze mood and self -appearance satisfaction in a Post Covid period on non-naïve Botox patients

    NCT04439825
    Conditions
    1. Mood
    Interventions
    1. Drug: Botulinum Neurotoxin
    2. Drug: Placebo

    Primary Outcomes

    Description: Treatment with Botox into the glabellar furrows increase the self- satisfaction with appearance once optimal correction is achieved beyond baseline in non -naïve users as compared to a control group and to themselves.

    Measure: Self- perception of mood before treatment and after achieving an optimal cosmetic result as determined by the PI.

    Time: 1 month

    Description: Treatment with Botox into the glabellar furrows increase the happiness levels once optimal correction is achieved beyond baseline in non -naïve users as compared to a control group and to themselves.

    Measure: Happiness levels before treatment and after achieving an optimal cosmetic result as determined by the PI.

    Time: 1 month

    Secondary Outcomes

    Description: Do non-naïve patients of Botox who have a baseline wrinkle severity score of 2 or 3 on the severity scale following an extended interval since last treatment of greater than 20 weeks achieve a two-point improvement 2 to 4 weeks after treatment.

    Measure: Measurement of the Glabellar Wrinkle Severity Scores before treatment. The onset of effect and maximum efficacy compared to previous BOTOX Cosmetic injections will also be assessed by questionnaires.

    Time: 1 month
    203 Prospective, Randomized, Double-blind, Parallel, Placebo Controlled Study to Evaluate the Safety and Efficacy of Nitazoxanide 600 mg Three Times a Day to Treat Ambulatory Adult Subjects Diagnosed With COVID-19 With Mild Symptoms Assisted in the Public Health System of the City of Mesquita -RJ

    The aim is to demonstrate a decrease in complications among ambulatory patients who are diagnosed with mild COVID-19 by treating them with nitazoxanide for 7 to 14 days on top of standard care compared to patients who receive standard care and placebo only.

    NCT04441398
    Conditions
    1. covid19
    Interventions
    1. Drug: Nitazoxanide
    2. Drug: Placebo

    Primary Outcomes

    Description: Symptoms will be assessed using a 5 point scale (1- excellent, 2- good, 3- fair, 4 - poor 5 - very poor).

    Measure: Change in signs and symptoms scale

    Time: 21 days

    Secondary Outcomes

    Description: Number of participants with treatment-related adverse events

    Measure: Incidence of Treatment-Emergent Adverse Events

    Time: 21 days

    Description: Change in clinical condition - WHO Ordinal Scale for Clinical Improvement that measures illness severity over time (0=uninfected; ambulatory, no limitation of activities=1; ambulatory, limitation of activities=2, hospitalized no oxygen therapy=3; hospitalized oxygen by mask or nasal prongs=4; hospitalized non invasive ventilation or high-flow oxygen=5; hospitalized intubation or mechanical ventilation=6; hospitalized ventilation + additional organ support=7; death=8)

    Measure: The proportion of subjects hospitalized after start of treatment and before the end of the study

    Time: 21 days

    Description: Change in clinical condition - WHO Ordinal Scale for Clinical Improvement that measures illness severity over time (0=uninfected; ambulatory, no limitation of activities=1; ambulatory, limitation of activities=2, hospitalized no oxygen therapy=3; hospitalized oxygen by mask or nasal prongs=4; hospitalized non invasive ventilation or high-flow oxygen=5; hospitalized intubation or mechanical ventilation=6; hospitalized ventilation + additional organ support=7; death=8)

    Measure: The proportion of subjects that need mechanical ventilation after start of treatment and before the end of the study

    Time: 21 days

    Description: Time required (days) to full symptom recovery

    Measure: Duration of symptoms

    Time: 21 days

    Description: Evaluation of change in acute respiratory syndrome

    Measure: Rate of mortality within 21-days

    Time: 21 days
    204 A Multicenter, Randomized, Double-blinded Placebo-controlled Study of Recombinant Interleukin-7 (CYT107) for Immune Restoration of Hospitalized Lymphopenic Patients With Coronavirus COVID-19 Infection. US Infectious Cohort

    Comparison of the effects of CYT107 vs Placebo administered IM at 10μg/kg twice a week for three weeks on immune reconstitution of lymphopenic COVID-19 patients

    NCT04442178
    Conditions
    1. COVID-19
    2. Lymphocytopenia
    Interventions
    1. Drug: CYT107
    2. Drug: Placebo
    MeSH:Lymphopenia
    HPO:Lymphopenia

    Primary Outcomes

    Description: A statistically significant increase of the absolute lymphocyte count (ALC) from randomization to day 30 or Hospital Discharge

    Measure: Improvement of the absolute lymphocyte count (ALC) of lymphopenic (ALC≤1000/mm3) COVID-19 infected participants out to approximately 30 days following initial Study drug administration or Hospital discharge (HD), whichever occurs first

    Time: one month

    Secondary Outcomes

    Description: The time to clinical improvement to determine if CYT107 will improve the clinical status of hospitalized COVID-19 patients as measured by clinical improvement score

    Measure: "clinical improvement" as defined by a 2 points improvement in a 7-point ordinal scale for Clinical Assessment, through day 30 or HD.

    Time: one month

    Description: The decrease of SARS-CoV-2 viral load from measurements at baseline and days of treatment dose 4 and dose 5, Day 21 and Day 30 or HD (whichever occurs first)

    Measure: a significant decline of SARS-CoV-2 viral load through day 30 or HD

    Time: one month

    Description: Incidence of secondary infections based on pre-specified criteria as adjudicated by the Secondary Infections Committee (SIC) through Day 45

    Measure: frequency of secondary infections through day 45 compared to placebo arm

    Time: 45 days

    Description: Number of days of hospitalization during index hospitalization (defined as time from initial Study drug treatment through HD)

    Measure: length of hospitalization compared to placebo arm

    Time: 45 days

    Description: Number of days in ICU during index hospitalization

    Measure: Length of stay in ICU compared to placebo arm

    Time: 45 days

    Description: Readmissions to ICU through Day 45

    Measure: number of readmissions to ICU compared to placebo arm

    Time: 45 days

    Description: Organ support free days (OSFDs) during index hospitalization (This includes ventilator assistance free days)

    Measure: organ support free days compared to placebo arm

    Time: 45 days

    Description: Number of readmissions to the hospital through Day 45

    Measure: Frequency of re-hospitalization through day 45 compared to placebo arm

    Time: 45 days

    Description: All-cause mortality through Day 45

    Measure: All-cause mortality through day 45 compared to placebo arm

    Time: 45 days

    Description: Absolute numbers of CD4+ and CD8+ T-cell counts at time points indicated on the Schedule of Activities (SoA)through Day 30 or HD

    Measure: CD4+ and CD8+ T cell counts compared to placebo arm

    Time: 30 days

    Description: Track and evaluate other known biomarkers of inflammation, Ferritin, from baseline to day 30

    Measure: level of other known biomarkers of inflammation: Ferritin compared to placebo a

    Time: 30 days

    Description: Level of other known biomarkers of inflammation: CRP compared to placebo arm

    Measure: Level of other known biomarkers of inflammation: CRP compared to placebo arm

    Time: 30 days

    Description: Track and evaluate other known biomarkers of inflammation, D-dimer from baseline to day 30

    Measure: Level of other known biomarkers of inflammation: D-dimer compared to placebo arm

    Time: 30 days

    Description: Evaluate improvement of the NEWS2 score value. Score form 0 to 4: NO Risk Score of 7 or more: High risk

    Measure: Physiological status through NEWS2 evaluation compared to Placebo arm

    Time: 30 days

    Other Outcomes

    Description: Incidence and scoring of all grade 3-4 adverse events through Day 45 (using CTCAE Version 5.0) to assess safety

    Measure: Safety assessment through incidence and scoring of grade 3-4 adverse events

    Time: 45 days
    205 Infusion of Convalescent Plasma for the Treatment of Patients Infected With Severe Acute Respiratory Syndrome-Coronavirus-2 (COVID-19): A Double-blinded, Placebo-controlled, Proof-of-concept Study

    Patients who are ill with COVID-19 may benefit from receiving convalescent plasma infusions containing antibodies from donors who have recovered from the disease and are proven to no longer be infected. Given the current public health emergency due to COVID-19, the FDA has recently fast-tracked the use of convalescent plasma. The purpose for this study is to assess if convalescent plasma collected from donors previously infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, can provide clinical benefit to those acutely ill with the virus and to evaluate if such treatment is safe. There will be two arms in the interventional study, where subjects will either be treated with convalescent plasma or fresh frozen plasma in a randomized and blinded manner. As an additional comparison, the clinical course of subjects enrolled during the period of the study who do not receive an alternative treatment for COVID-19 will be assessed.

    NCT04442191
    Conditions
    1. COVID-19
    Interventions
    1. Biological: Convalescent plasma
    2. Biological: Placebo

    Primary Outcomes

    Description: The primary endpoint will be clinical response at 8 days, defined as no need for oxygen supplementation for the previous 24 hours.

    Measure: Oxygen supplementation

    Time: 8 days

    Secondary Outcomes

    Description: Mortality rate during the 28 days of follow-up and during the subjects' initial hospital stays

    Measure: 28-day and in-hospital mortality rate

    Time: 28 days

    Description: Transfer to an ICU bed during the 28 days following study enrollment

    Measure: Number of participants transferred to the Intensive Care Unit (ICU)

    Time: 28 days

    Description: Intubation within the 28 days following study enrollment

    Measure: Number of participants intubated

    Time: 28 days

    Description: Number of days admitted to the hospital during the 28-day follow-up period

    Measure: Length of hospital stay in days

    Time: 28 days

    Description: Type of respiratory support required during the 28-day follow-up period: intubation, high-flow oxygen by nasal canula, nasal canula

    Measure: Type of respiratory support

    Time: 28 days

    Description: Change in CRP following treatment

    Measure: C-reactive Protein (CRP)

    Time: 28 days

    Description: Change in lymphocyte count following treatment

    Measure: Lymphocyte count

    Time: 28 days

    Description: Number of days respiratory support is required

    Measure: Length or respiratory support required, in days

    Time: 28 days

    Description: Change in LDH following treatment

    Measure: Lactate dehydrogenase (LDH)

    Time: 28 days

    Description: Change in Ferritin level following treatment

    Measure: Ferritin

    Time: 28 days

    Description: Change in D-Dimer level following treatment

    Measure: D-Dimer

    Time: 28 days

    Description: Change in WBC count following treatment

    Measure: White Blood Cell (WBC) Count

    Time: 28 days

    Other Outcomes

    Description: Severe transfusion reaction will be defined as having any of the following occur within 6 hours of the infusion of blood product and not attributable to the underlying disease: 1) an increase of 2 L/minutes or more in supplemental oxygen requirement compared to the baseline requirement before transfusion, 2) oxygen saturations <93% despite oxygen via nasal canula, or 3) need for transfer to the ICU.

    Measure: Safety endpoint: Severe transfusion reaction

    Time: 6 hours following transfusion

    Description: Cumulative incidence of adverse events during the study period: transfusion reaction (fever, rash), transfusion related acute lung injury (TRALI), transfusion associated circulatory overload (TACO), transfusion related infection.

    Measure: Safety endpoint two: adverse events

    Time: 24 hours following transfusion
    206 Phase 2, Double-blind, Randomized, Placebo-controlled Study of NasoVAX in the Prevention of Clinical Worsening in Patients With Early Coronavirus Infectious Disease 2019 (COVID-19)

    The purpose of this study is to evaluate the safety and effectiveness of NasoVAX in preventing worsening of symptoms and hospitalization in patients with early COVID-19.

    NCT04442230
    Conditions
    1. Coronavirus Infection
    Interventions
    1. Biological: NasoVAX
    2. Other: Placebo
    MeSH:Communicable Diseases Infection Coronavirus Infections Severe Acute Respiratory Syndrome

    Primary Outcomes

    Description: Decrease from baseline in mean resting SpO2

    Measure: Proportion of patients with clinical worsening

    Time: Day 1 to Day 14

    Secondary Outcomes

    Description: Proportion of patients requiring hospitalization

    Measure: Maximal severity of COVID-19 after treatment

    Time: Day 1 to Day 42

    Measure: All-cause mortality

    Time: Day 1 to Day 42
    207 Prospective, Randomized Phase 2 Clinical Trial of Mesenchymal Stem Cells(MSCs) for the Treatment of Coronavirus Disease 2019(COVID-19)

    Since the outbreak of coronavirusdisease2019(COVID-19), many researchers in China have carried out/published clinical trials on treatment based on Western medicine, traditional Chinese medicine or a combination of the two. Trials on treatment modalities have mainly used antivirals, interferon, glucocorticoids in addition to traditional Chinese medicine. There are also clinical trials exploring hydroxyquinoline/chloroquine sulphate, immunoglobulins, Vitamin-C, washed microbiota, nebulized interferon, teicoplanin as well as Mesenchymal stem cells. However, most of these trials were small (median sample size 100) and the bulk of potential therapeutic strategies remain in the experimental phase and currently there is no effective specific antiviral with high-level evidence.The aim of this study is assess the efficacy of MSCs as an add-on therapy to standard supportive treatment for patients with moderate/severe COVID-19.

    NCT04444271
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Mesenchymal stem cells
    2. Other: Placebo

    Primary Outcomes

    Description: Assessment of Overall survival at 30 days post intervention

    Measure: Overall survival

    Time: 30 days post intervention

    Secondary Outcomes

    Description: days required for oxygen support independence after intervention

    Measure: Clinical improvement

    Time: 30 days

    Description: PCR testing to check PCR negativity

    Measure: Time of COVID19 PCR negativity

    Time: day 1,3,7,10, 14

    Description: Computed tomography Chest assesment will be done to assess improvment in radiological findings of COVID-19

    Measure: Radiological improvement (day 15 and day 30 assessment)

    Time: day 15 and day30

    Description: number of days required for discharge from hospital

    Measure: days required to discharge from hospital

    Time: 30 days post admission
    208 Prasugrel in the Prevention of Severe SARS-CoV2 Pneumonia in Hospitalised Patients

    Inflammatory diseases favour the onset of venous thromboembolic events in hospitalized patients. Thromboprophylaxis with a fixed dose of heparin/low molecular weight heparin (LMWH) is recommended if concomitant inflammatory disease. In severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) pneumonia an inflammation-dependent thrombotic process occurs and platelet activation may promote thrombosis and amplify inflammation, as indicated by previous experimental evidence , and the similarities with atherothrombosis and thrombotic microangiopathies. Antiplatelet agents represent the cornerstone in the prevention and treatment of atherosclerotic arterial thromboembolism, with limited efficacy in the context of venous thromboembolism. The use of purinergic receptor P2Y12 inhibitors in pneumococcal pneumonia may improve inflammation and respiratory function in humans. There are no validated protocols for thrombosis prevention in Covid-19. There is scientific rationale to consider a P2Y12 inhibitor for the prevention of thrombosis in the pulmonary circulation and attenuation of inflammation. This is supported by numerous demonstrations of the anti-inflammatory activity of P2Y12 inhibitors and the evidence of improvement in respiratory function both in human and experimental pathology. Prasugrel could be considered as an ideal candidate drug for Covid-19 patients because of higher efficacy and limited Interactions with drugs used in the treatment of Sars-CoV2. The hypothesis underlying the present study project is that in Covid-19 platelet activation occurs through an inflammation-dependent mechanism and that early antithrombotic prophylaxis in non-critical patients could reduce the incidence of pulmonary thrombosis and respiratory and multi-organ failure improving clinical outcome in patients with SARS-CoV2 pneumonia. The prevention of thrombogenic platelet activity with a P2Y12 inhibitor could be superior to fixed dose enoxaparin alone. The proposed treatment is feasible in all coronavirus disease 2019 (COVID-19) patients, regardless of the treatment regimen (antivirals, anti-inflammatory drugs, antibiotics), except for specific contraindications.

    NCT04445623
    Conditions
    1. COVID19
    2. Thrombosis
    Interventions
    1. Drug: Prasugrel Hydrochloride 10 MG Oral Tablet
    2. Drug: Placebo
    MeSH:Pneumonia Thrombosis
    HPO:Pneumonia

    Primary Outcomes

    Description: PaO2/FiO2 ratio (arterial oxygen tension divided by the fraction of inspired oxygen) detected after 7 days of treatment

    Measure: P/F ratio at day 7

    Time: day 7

    Secondary Outcomes

    Description: PaO2/FiO2 ratio (arterial oxygen tension divided by the fraction of inspired oxygen) detected daily for 15 days

    Measure: Daily P/F ratio

    Time: 15 days

    Description: daily need for oxygen supply for 15 days

    Measure: Daily need for oxygen supply

    Time: 15 days

    Description: Number of patients requiring transfer to the intensive care unit (ICU) by treatment arm

    Measure: Need for ICU

    Time: day 15 and day 30

    Description: death by day 15 and day 30 by treatment arm

    Measure: Death

    Time: 15 day and day 30

    Description: Multi-organ failure (MOF) by day 15 and day 30 assessed using sequential organ failure assessment score (SOFA) score (Units 0-4 better outcome, over 30 worse outcome) by treatment arm

    Measure: MOF

    Time: day 15 and day 30

    Description: Number of patients discharged after improvement by day 15 and day 30 by treatment arm

    Measure: Discharge

    Time: day 15 and day 30

    Description: Clinical progression of the disease evaluated by SOFA score (Units 0-6 better outcome, 15-24 worse outcome) by day 15 and day 30

    Measure: Clinical progression of the disease SOFA score

    Time: day 15 and day 30

    Description: Clinical progression of the disease evaluated by Acute Physiology And Chronic Health Evaluation (APACHE II) score (Units 1-5 better outcome, over 30 worse outcome) by day 15 and day 30

    Measure: Clinical progression of the disease APACHE II

    Time: day 15 and day 30

    Description: Number of patients with venous thrombosis/ pulmonary embolism/thrombosis by day 15 and day 30

    Measure: Venous thrombosis/ pulmonary embolism/thrombosis

    Time: day 15 and day 30

    Description: Number of patients requiring computerized tomography (CT) imaging due to worsening of respiratory function by treatment arm

    Measure: Need for CT imaging

    Time: day 15

    Description: Body temperature measured twice daily for 15 days, C°

    Measure: Daily Temperature

    Time: 15 days

    Description: Blood pressure measured twice daily for 15 days, mmHg

    Measure: Daily blood pressure

    Time: 15 days

    Description: Total blood count measured in venous blood for 15 days, Hemoglobin, g/L (cell/mcL

    Measure: Daily total blood count Hemoglobin

    Time: 15 days

    Description: Total blood count measured in venous blood for 15 days, Red Blood cells (cell/mcL)

    Measure: Daily total blood count Red Blood Cells

    Time: 15 days

    Description: Total blood count measured in venous blood for 15 days, Leukocytes (cell/mcL)

    Measure: Daily total blood count Leukocytes

    Time: 15 days

    Description: Total blood count measured in venous blood for 15 days, platelets (cell/mcL)

    Measure: Daily total blood count Platelets

    Time: 15 days

    Description: ALT U/L in venous blood

    Measure: Daily indices of organ damage Liver

    Time: 15 days

    Description: C-reactive protein microg/L in venous blood

    Measure: Indices of inflammation C-reactive protein

    Time: day 1, 2, 7, 15

    Description: PT ratio in venous blood by treatment arm

    Measure: Indices of haemostasis PT

    Time: day 1, 2, 7,15

    Description: progression of lung infiltrates as detected by chest-X-ray by treatment arm

    Measure: Daily progression at imaging (chest-X-ray)

    Time: 15 days

    Description: Major and/or clinically relevant bleeding according to International Society of Thrombosis and Haemostasis (ISTH) bleeding scale (Unit 0 better outcome, 4 worse outcome, 11 items) during treatment.

    Measure: Major bleeding

    Time: day 1, 2, 7, 15, 30

    Description: Total bleeding according to International Society of Thrombosis and Haemostasis (ISTH bleeding) scale (Unit 0 better outcome, 4 worse outcome, 11 items) during treatment.

    Measure: Total bleeding

    Time: day 1, 2, 7, 15, 30

    Description: Number of unexpected changes in clinical or laboratory findings not included in the predefined list of outcomes during treatment. .

    Measure: Unexpected clinical or laboratory findings

    Time: day 1, 2, 7, 15

    Description: D-dimer microg/L in venous blood

    Measure: Indices of inflammation D-dimer

    Time: day 1, 2, 7, 15

    Description: Fibrinogen g/L in venous blood

    Measure: Indices of inflammation Fibrinogen

    Time: day 1, 2, 7, 15

    Description: Interleukin (IL)-6 pg/mL in venous blood by treatment arm

    Measure: Indices of inflammation IL-6

    Time: day 1, 2, 7, 15

    Description: Interleukin (IL)-1 pg/mL in venous blood by treatment arm

    Measure: Indices of inflammation IL-1

    Time: day 1, 2, 7, 15

    Description: serum creatinine micromol/L by treatment arm

    Measure: Daily indices of organ damage kidney

    Time: 15 days

    Description: troponin t ng/L by treatment arm

    Measure: Daily indices of organ damage heart

    Time: 15 days

    Description: aPTT ratio by treatment arm

    Measure: Haemostasis aPTT

    Time: day 1, 2, 7,15

    Description: Vasodilator stimulated phosphoprotein (VASP) phosphorylation (PRI) % by treatment arm

    Measure: Haemostasis VASP PRI

    Time: day 1, 2, 7,15

    Description: Platelet-leukocytes aggregates % in peripheral by treatment arm

    Measure: Haemostasis platelet-leukocytes aggregates

    Time: day 1, 2, 7,15
    209 A Multicenter, Double-blind, Randomized, Placebo-controlled Clinical Trial to Protect Health Workers Against COVID-19 by Using Previfenon® as Chemoprophylaxis During a SARS-CoV-2 Outbreak. The HERD Study

    The purpose of this clinical trial is to determine the efficacy of Previfenon® (EGCG) to prevent COVID-19, enhance systemic immunity, and decrease the frequency and intensity of selected symptoms when used as pre-exposure chemoprophylaxis to SARS-CoV-2.

    NCT04446065
    Conditions
    1. COVID-19
    2. SARS-CoV2
    Interventions
    1. Drug: Previfenon®
    2. Drug: Placebo

    Primary Outcomes

    Description: A positive case or event of COVID-19 is defined as a patient with acute respiratory illness presenting fever (37.8º C); at least one of the following symptoms: odynophagia, cough, myalgia, or dyspnea; and a specific positive rtPCR test for SARS-CoV-2.

    Measure: Event of clinical acute respiratory disease with a diagnosis of COVID-19 confirmed with rtPCR

    Time: The date for censoring a case will be defined as that date when the rtPCR test results positive minus 4 days, with the aim to calculate the time free of clinically defined COVID-19 infection over 40 to 70 days of intervention

    Secondary Outcomes

    Description: Rate of positive cases for IgM and IgG anti-SARS-CoV-2 measured by immunochromatographic test in treatment and placebo group at the end of the study

    Measure: Rate of positive cases for IgM and IgG anti-SARS-CoV-2

    Time: Positive cases in each two-week examination and to the end of the study over 40 to 70 days of intervention

    Description: Rate of asymptomatic cases defined as a positive rtPCR for SARS-CoV-2 viral RNA but with no symptoms of COVID-19 in treatment and placebo group at the end of the study, and a composite outcome considering symptomatic and asymptomatic cases (i.e. all cases with positive rtPCR test)

    Measure: Composite outcome considering symptomatic and asymptomatic cases with positive rtPCR test

    Time: Positive cases in each two-weeks examination and to the end of the study over 40 to 70 days of intervention

    Description: Rate of hospitalizations due to any acute respiratory infection at the end of the study

    Measure: Hospitalization due to any acute respiratory infection

    Time: Positive cases in each two-week examination visit and to the end of the study over 40 to 70 days of intervention

    Description: Global frequency of events of upper and lower airway respiratory infections

    Measure: Event of upper and lower airway respiratory infection

    Time: Positive cases in each two-week examination and to the end of the study over 40 to 70 days of intervention

    Other Outcomes

    Description: Registry of Visual Analogue Scale (VAS) in the log diary of every healthcare worker for the following selected symptoms: cough, muscle pain (myalgia); difficulty breathing (dyspnea); loss of smell (anosmia); loss of taste (ageusia); pain when swallowing (odynophagia, sore throat); and finally headache

    Measure: Exploratory outcome: Frequency and intensity of selected symptoms for COVID-19

    Time: Different VAS scores calculated each two-week examination visit over 40 to 70 days of intervention

    Description: Elevation of liver enzymes over 5 times the normal value

    Measure: Primary safety outcome: event of major hepatic harm

    Time: Cases accounted by liver profile lab test in each two-week examination visit over 40 to 70 days of intervention.

    Description: Elevation of liver enzymes over 5 times the normal value

    Measure: Event of liver enzymes over 3 times the normal value

    Time: Cases accounted by liver profile lab test in each two-week examination visit over 40 to 70 days of intervention

    Description: Any adverse event reported over the intervention period

    Measure: Frequency of adverse events

    Time: Records of self-reported adverse effects on log dairy accounted in each examination visit over 40 to 70 days of intervention
    210 A Phase II Randomized, Double-Blind, Placebo-Controlled Study of LAM-002A for the Prevention of Progression of COVID-19

    This is a clinical trial to evaluate the efficacy of LAM-002A compared to placebo treatment in adults with a confirmed SARS-CoV-2 infection who are receiving standards supportive care in an outpatient setting.

    NCT04446377
    Conditions
    1. COVID-19 Disease
    Interventions
    1. Drug: Apilimod Dimesylate Capsule
    2. Other: Placebo
    MeSH:Disease Progression

    Primary Outcomes

    Description: The primary efficacy outcome measure evaluates change in SARS-CoV-2 viral load at Day 4 from Day 1, of LAM-002A or placebo-treated participants. SARS-CoV-2 viral load will be measured by a qRT-PCR test of nasopharyngeal samples. Analysis will focus on log10 viral load on Day 4 compared to baseline viral load at Day 1 in participants with baseline viral load >100,000 copies/mL

    Measure: Viral Load Change

    Time: 4 Days

    Secondary Outcomes

    Description: The proportion of LAM 002A-treated participants who develop TEAEs compared to placebo

    Measure: Safety and Tolerability

    Time: 28 Days

    Description: The proportion of participants treated with LAM-002A compared to placebo, who have disease progression by Day 28 as defined by the occurrence of: Hospitalization Death

    Measure: Clinical Efficacy

    Time: 28 Days

    Description: To evaluate change in COVID-19 clinical status, as defined by the ordinal scale, of participants treated with LAM-002A compared to placebo at Day 28, in participants who become hospitalized and continue LAM-002A/placebo treatment, based on the following scores: Not in the hospital Hospitalized, requiring low flow supplemental oxygen (such as nasal cannula) Hospitalized, not on invasive ventilation (such as 100% non-rebreather, BIPAP), (pre-ICU) Hospitalized, in the ICU, on invasive ventilation or ECMO Dead

    Measure: Change in COVID-19 Clinical Status

    Time: 28 Days

    Description: To compare the proportion of participants at or above 95% oxygen saturation (O2 sat) between LAM-002A versus placebo treatment groups as measured on Days 1, 4, and 11.

    Measure: Oxygen Saturation

    Time: 11 Days

    Other Outcomes

    Description: To potentially evaluate the change from baseline (Day 1, Pre-dose) of SARS-CoV-2 viral load as measured by a qRT-PCR test from saliva samples on Day 4, compared between the LAM-002A arm and the placebo arm in participants with a baseline viral load >100,000 copies/mL

    Measure: Viral Clearance

    Time: 4 Days

    Description: To potentially evaluate the change from baseline (Day 1, Pre-dose) of SARS-CoV-2 viral load as measured by a qRT-PCR test from saliva samples on Day 11, compared between the LAM-002A arm and the placebo arm in participants with a baseline viral load >100,000 copies/mL

    Measure: Viral Clearance

    Time: 11 Days

    Description: To potentially evaluate the change from baseline (Day 1, Pre-dose) of SARS-CoV-2 viral load as measured by a qRT-PCR test from saliva samples on Day 28, compared between the LAM-002A arm and the placebo arm in participants with a baseline viral load >100,000 copies/mL

    Measure: Viral Clearance

    Time: 28 Days

    Description: To potentially evaluate the difference in SARS-CoV-2 viral load as measured by a qRT-PCR test from saliva samples based on AUC(Day1-Day11), between the LAM-002A arm and the placebo arm in participants with a baseline viral load >100,000 copies/mL.

    Measure: Viral Clearance AUC

    Time: 11 Days

    Description: To potentially evaluate the difference in SARS-CoV-2 viral load as measured by a qRT-PCR test from saliva samples based on AUC(Day1-Day28), between the LAM-002A arm and the placebo arm in participants with a baseline viral load >100,000 copies/mL.

    Measure: Viral Clearance AUC

    Time: 28 Days

    Description: To potentially evaluate the difference in proportion of participants with a SARS-CoV-2 viral load less than Measure: Proportion of participants with viral load < lower limit of detection

    Time: 4 Days
    211 Randomized, Doubled-blind Phase II Trial Evaluating the Use of Ivermectin Plus Losartan for Prophylaxis of Severe Events in Cancer Patients With Recent Diagnosis of COVID-19

    Ivermectin plus losartan as prophilaxy to severe events in patients with cancer with recent diagnosis of COVID-19

    NCT04447235
    Conditions
    1. Cancer
    2. COVID
    3. Coronavirus Infection
    Interventions
    1. Drug: Placebo
    2. Drug: Ivermectin
    3. Drug: Losartan
    MeSH:Infection Coronavirus Infections Severe Acute Respiratory Syndrome

    Primary Outcomes

    Description: Incidence of severe complications due COVID-19 infection defined as need for ICU admission, need for mechanical ventilation, or death

    Measure: Incidence of severe complications due COVID-19 infection

    Time: 28 days

    Secondary Outcomes

    Description: Severe Acute Respiratory Syndrome defined as oxygen saturation less than 93%

    Measure: Incidence of Severe Acute Respiratory Syndrome

    Time: 28 days

    Description: Severe Acute Respiratory Syndrome defined as respiratory rate higher than 24 incursion per minute

    Measure: Incidence of Severe Acute Respiratory Syndrome

    Time: 28 days

    Description: Incidence of hepatic toxicity (elevation of ALT, AST above the upper limit of normal, measured by U/L)

    Measure: Adverse events

    Time: 28 days

    Description: Incidence of hepatic toxicity (elevation of bilirubin above the upper limit of normal, measured by mg/dL)

    Measure: Adverse events

    Time: 28 days

    Description: Incidence of renal toxicity (elevation of serum creatinine levels above the upper limit of normal, measured by mg/dL)

    Measure: Adverse events

    Time: 28 days

    Description: Incidence of symptomatic postural hypotension, diagnosed by clinical assessment of reduction of > 20 mmHG of arterial systolic pressure after measurement in prone position and orthostatic position.

    Measure: Adverse events

    Time: 28 days

    Description: Death of any cause since protocol enrollment

    Measure: Overall survival

    Time: 28 days
    212 A Randomized, Double-Blind, Placebo Controlled Study to Evaluate Safety and Efficacy of DUR-928 in Subjects Infected With SARS-CoV-2 With Acute Liver or Kidney Injury

    Evaluate safety and efficacy of DUR-928 in treatment of acute organ failure in subjects infected with SARS-CoV-2

    NCT04447404
    Conditions
    1. SARS-CoV 2
    Interventions
    1. Drug: DUR-928
    2. Drug: Placebo

    Primary Outcomes

    Description: Free of mechanical ventilation, free of renal replacement therapy and free of acute liver failure

    Measure: Composite endpoint of alive and free of organ failure

    Time: Day 28

    Measure: Occurrence of serious adverse events following treatment

    Time: Day 1 to Day 60

    Secondary Outcomes

    Measure: Alive at days 28 and 60

    Time: Days 28 and 60

    Measure: Alive and out of ICU

    Time: Day 28

    Measure: Alive and out of hospital

    Time: Day 28 and Day 60
    213 A Phase 2/3, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Mavrilimumab (KPL-301) Treatment in Adult Subjects Hospitalized With Severe COVID-19 Pneumonia and Hyper-inflammation

    Interventional, randomized, double-blind, placebo-controlled study encompassing 2 development phases (Phase 2 and Phase 3).

    NCT04447469
    Conditions
    1. COVID
    Interventions
    1. Drug: mavrilimumab
    2. Other: Placebo
    MeSH:Pneumonia Inflammation
    HPO:Pneumonia

    Primary Outcomes

    Description: Respiratory failure is defined as the need for high flow oxygen (HFO), non-invasive ventilation (NIV), invasive mechanical ventilation (IMV), or extracorporeal membrane oxygenation (ECMO).

    Measure: Cohort 1: Proportion of Participants Alive and Without Respiratory Failure at Day 15

    Time: Day 15

    Description: Mortality rate is defined as the proportion of participants who die.

    Measure: Cohort 2: Mortality Rate at Day 15

    Time: Day 15

    Secondary Outcomes

    Description: Return to room air is defined as time from the date of randomization to the start of a period of 24 hours while breathing room air (National Institute of Allergy and Infectious Diseases [NIAID] scale ≥ 5), or discharge from the hospital, whichever occurs first. The NIAID is an 8-point ordinal scale of clinical outcomes: 1=death; 2=hospitalized, on invasive mechanical ventilation or ECMO; 3=hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5=hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID 19 related or otherwise); 6=hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7=not hospitalized, limitation on activities and/or requiring home oxygen; 8=not hospitalized, no limitations on activities.

    Measure: Cohort 1: Time to Return to Room Air by Day 15

    Time: up to Day 15

    Description: Clinical Improvement, defined as time from randomization to a 2-point improvement on the NIAID scale, or discharge from the hospital, whichever comes first. The NIAID is an 8-point ordinal scale of clinical outcomes: 1=death; 2=hospitalized, on invasive mechanical ventilation or ECMO; 3=hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5=hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID 19 related or otherwise); 6=hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7=not hospitalized, limitation on activities and/or requiring home oxygen; 8=not hospitalized, no limitations on activities.

    Measure: Cohort 1: Time to 2-point Clinical Improvement by Day 15

    Time: up to Day 15

    Description: Mortality rate is defined as the proportion of participants who die.

    Measure: Cohort 1: Mortality Rate at Day 29

    Time: Day 29

    Description: Clinical improvement, defined as time from randomization to a 1-point improvement on the NIAID scale, or discharge from the hospital, whichever comes first. The NIAID is an 8-point ordinal scale of clinical outcomes: 1=death; 2=hospitalized, on invasive mechanical ventilation or ECMO; 3=hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5=hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID 19 related or otherwise); 6=hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7=not hospitalized, limitation on activities and/or requiring home oxygen; 8=not hospitalized, no limitations on activities.

    Measure: Cohort 1: Time to 1-Point Clinical Improvement by Day 15

    Time: up to Day 15

    Description: Mortality rate is defined as the proportion of participants who die.

    Measure: Cohort 2: Mortality Rate at Day 29

    Time: Day 29

    Description: Respiratory failure is defined as the need for HFO, NIV, IMV, or ECMO.

    Measure: Cohort 2: Proportion of Participants Alive and Without Respiratory Failure at Day 15

    Time: Day 15

    Description: Respiratory failure is defined as the need for HFO, NIV, IMV, or ECMO

    Measure: Cohorts 1 and 2: Proportion of Participants Alive and Without Respiratory Failure At Day 29

    Time: Day 29

    Description: Return to room air is defined as time from the date of randomization to the start of a period of 24 hours while breathing room air (NIAID scale ≥ 5), or discharge from the hospital, whichever occurs first. The NIAID is an 8-point ordinal scale of clinical outcomes: 1=death; 2=hospitalized, on invasive mechanical ventilation or ECMO; 3=hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5=hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID 19 related or otherwise); 6=hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7=not hospitalized, limitation on activities and/or requiring home oxygen; 8=not hospitalized, no limitations on activities.

    Measure: Cohorts 1 and 2: Time to Return to Room Air by Day 29

    Time: up to Day 29

    Description: Clinical Improvement, defined as time from randomization to a 2-point improvement on the NIAID scale, or discharge from the hospital, whichever comes first. The NIAID is an 8-point ordinal scale of clinical outcomes: 1=death; 2=hospitalized, on invasive mechanical ventilation or ECMO; 3=hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5=hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID 19 related or otherwise); 6=hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7=not hospitalized, limitation on activities and/or requiring home oxygen; 8=not hospitalized, no limitations on activities.

    Measure: Cohort 2: Time to 2-point Clinical Improvement by Day 15

    Time: up to Day 15

    Description: Clinical Improvement, defined as time from randomization to a 1-point improvement on the NIAID scale, or discharge from the hospital, whichever comes first. The NIAID is an 8-point ordinal scale of clinical outcomes: 1=death; 2=hospitalized, on invasive mechanical ventilation or ECMO; 3=hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5=hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID 19 related or otherwise); 6=hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7=not hospitalized, limitation on activities and/or requiring home oxygen; 8=not hospitalized, no limitations on activities.

    Measure: Cohorts 1 and 2: Time to 1-point Clinical Improvement by Day 29

    Time: up to Day 29

    Description: Clinical Improvement, defined as time from randomization to a 2-point improvement on the NIAID scale, or discharge from the hospital, whichever comes first. The NIAID is an 8-point ordinal scale of clinical outcomes: 1=death; 2=hospitalized, on invasive mechanical ventilation or ECMO; 3=hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5=hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID 19 related or otherwise); 6=hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7=not hospitalized, limitation on activities and/or requiring home oxygen; 8=not hospitalized, no limitations on activities.

    Measure: Cohorts 1 and 2: Time to 2-point Clinical Improvement by Day 29

    Time: up to Day 29

    Description: Respiratory failure is defined as the need for HFO, NIV, IMV, or ECMO.

    Measure: Cohort 1: Respiratory Failure-Free Survival by Day 15

    Time: up to Day 15

    Description: Respiratory failure is defined as the need for HFO, NIV, IMV, or ECMO

    Measure: Cohort 1: Respiratory Failure-Free Survival by Day 29

    Time: up to Day 29

    Description: Return to room air is defined as time from the date of randomization to the start of a period of 24 hours while breathing room air (NIAID scale ≥ 5), or discharge from the hospital, whichever occurs first. The NIAID is an 8-point ordinal scale of clinical outcomes: 1=death; 2=hospitalized, on invasive mechanical ventilation or ECMO; 3=hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5=hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID 19 related or otherwise); 6=hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7=not hospitalized, limitation on activities and/or requiring home oxygen; 8=not hospitalized, no limitations on activities.

    Measure: Cohort 1: Proportion of Participants Who Return to Room Air by Day 15

    Time: up to Day 15

    Description: Return to room air is defined as time from the date of randomization to the start of a period of 24 hours while breathing room air (NIAID scale ≥ 5), or discharge from the hospital, whichever occurs first. The NIAID is an 8-point ordinal scale of clinical outcomes: 1=death; 2=hospitalized, on invasive mechanical ventilation or ECMO; 3=hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5=hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID 19 related or otherwise); 6=hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7=not hospitalized, limitation on activities and/or requiring home oxygen; 8=not hospitalized, no limitations on activities.

    Measure: Cohorts 1 and 2: Proportion of Participants Who Return to Room Air by Day 29

    Time: up to Day 29

    Description: Mortality rate is defined as the proportion of participants who die.

    Measure: Cohort 1: Mortality Rate at Day 15

    Time: Day 15

    Description: Overall survival is defined as time from date of randomization to the date of death.

    Measure: Cohorts 1 and 2: Overall Survival by Day 29

    Time: up to Day 29

    Description: Clinical status, based on the NIAID 8-point ordinal scale. The NIAID is an 8-point ordinal scale of clinical outcomes: 1=death; 2=hospitalized, on invasive mechanical ventilation or ECMO; 3=hospitalized, on non-invasive ventilation or high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5=hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID 19 related or otherwise); 6=hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7=not hospitalized, limitation on activities and/or requiring home oxygen; 8=not hospitalized, no limitations on activities.

    Measure: Cohorts 1 and 2: Clinical Status Over Time

    Time: Days 4, 8, 15, 22, and 29

    Measure: Cohorts 1 and 2: Number of Days Alive and Out of Hospital Through Day 90

    Time: through Day 90
    214 A Phase II, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety and Efficacy of M5049 in Hospitalized Participants With COVID-19 Pneumonia

    The study will evaluate the safety and efficacy of orally-administered M5049 in COVID-19 pneumonia participants who are hospitalized but not on mechanical ventilation.

    NCT04448756
    Conditions
    1. Coronavirus Disease 2019
    Interventions
    1. Drug: M5049
    2. Drug: M5049
    3. Drug: Placebo
    MeSH:Coronavirus Infections Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Measure: Percentage of Participants Alive and not Requiring Supplemental Oxygenation

    Time: Day 14

    Measure: Occurrence of Treatment-Emergent Adverse Events (TEAEs), Adverse Events of Special Interests (AESIs), TEAEs Leading to Treatment Discontinuation and Serious AEs (SAEs)

    Time: Day 1 through Day 60

    Measure: Number of Participants With Clinically Significant Changes in Laboratory Parameters and Electrocardiogram Findings

    Time: Day 1 through Day 28

    Secondary Outcomes

    Description: A nine point ordinal scale - 0: Uninfected No limitation of activities Limitation of activities Hospitalized, mild disease on, no oxygen therapy Hospitalized, with oxygen by mask or nasal prongs Hospitalized, severe disease: noninvasive ventilation or high flow oxygen Hospitalized, severe disease: intubation and mechanical ventilation Hospitalized, severe disease: ventilation plus additional organ support - example, vasopressors, Extracorporeal membrane oxygenation (ECMO) Death.

    Measure: Clinical Status of Participants on a 9-Point Ordinal Scale

    Time: Day 1 through Day 60

    Description: Normal oxygen exchange in room air.

    Measure: Time to Reach Peripheral Capillary Oxygen Saturation (SpO2) Greater Than or Equal to 94 Percent for at Least 24 Hours on Room Air

    Time: Day 1 through Day 28

    Description: Percentage of Participants who die for any reason.

    Measure: Percentage of Participants With All-Cause Mortality

    Time: Day 1 through Day 28

    Description: Clinical Deterioration

    Measure: Clinical Deterioration: Time to Intensive Care Unit (ICU) Admission

    Time: Day 1 through Day 28

    Description: Clinical Deterioration

    Measure: Clinical Deterioration: Time to Invasive Mechanical Ventilation

    Time: Day 1 through Day 28

    Description: Clinical Deterioration

    Measure: Clinical Deterioration: Time to Non-Invasive Mechanical Ventilation

    Time: Day 1 through Day 28

    Measure: Total Length of Stay in Intensive Care Unit (ICU)

    Time: Day 1 through Day 60

    Measure: Total Length of Hospitalization Stay

    Time: Day 1 through Day 60

    Measure: Percentage of Participants Alive and not Requiring Supplemental Oxygenation

    Time: Day 1 through Day 28

    Measure: Percentage Change From Baseline in Inflammatory Biomarkers

    Time: Day 1 through Day 28

    Measure: Percentage Change From Baseline in Cytokine Biomarkers

    Time: Day 1 through Day 28

    Description: Relapse refers to rehospitalization due to worsening oxygenation, with either a positive result of any respiratory pathogenic nucleic acid test, or worsening lesions on chest imaging.

    Measure: Percentage of Participants With Relapse

    Time: Day 5 through Day 60

    Description: Percentage or participants who are re-hospitalized for any reason.

    Measure: Percentage of Participants who are Re-Hospitalized

    Time: Day 5 through Day 60

    Description: Only the first 15 participants will be evaluated for Pharmacokinetic parameters.

    Measure: Maximum Observed Concentration (Cmax) of M5049

    Time: Day 1 and Day 7

    Measure: Time to Reach the Maximum Observed Concentration (tmax) of M5049

    Time: Day 1 and Day 7

    Measure: Terminal Rate Constant (Lambda z) of M5049

    Time: Day 1 and Day 7

    Measure: Apparent Elimination Half-Life (t1/2) of M5049

    Time: Day 1 and Day 7

    Measure: Area Under the Plasma Concentration-Time Curve From Time of Dosing to the Time of the Last Observation (AUC0-t) of M5049

    Time: Day 1 and Day 7

    Measure: Area Under Plasma Concentration-Time Curve From Time of Dosing to 12 Hours Post-Dose (AUC0-12h) of M5049

    Time: Day 1 and Day 7

    Measure: Area Under the Plasma Concentration-Time Curve From Time of Dosing to Infinity (AUC0-Infinity) of M5049

    Time: Day 1 and Day 7

    Measure: Apparent Total Body Clearance (CL/F) of M5049

    Time: Day 1 and Day 7

    Measure: Apparent Volume of Distribution During the Terminal Phase Following Extravascular Administration (Vz/F) of M5049

    Time: Day 1 and Day 7

    Measure: Dose-Normalized Maximum Observed Concentration (Cmax/Dose) of M5049

    Time: Day 1 and Day 7

    Measure: Dose-Normalized Area Under the Plasma Concentration-Time Curve From Time of Dosing to the Time of the Last Observation (AUC0-t/Dose) of M5049

    Time: Day 1 and Day 7

    Measure: Dose-Normalized Area Under Plasma Concentration-Time Curve From Time of Dosing to 12 Hours Post-Dose (AUC0-12h/Dose) of M5049

    Time: Day 1 and Day 7

    Measure: Dose-Normalized Area Under the Plasma Concentration-Time Curve From Time of Dosing to Infinity (AUC0-Infinity/Dose) of M5049

    Time: Day 1 and Day 7

    Measure: Accumulation Ratio for Area Under Plasma Concentration-Time Curve From Time of Dosing to 12 Hours Post-Dose [Racc(AUC0- 12h)] of M5049

    Time: Day 1 and Day 7

    Measure: Accumulation Ratio for Maximum Observed Concentration [Racc(Cmax)] of M5049

    Time: Day 1 and Day 7
    215 COVID-19: A Phase 1, Partially Blind, Placebo-controlled, Dose Escalation, First-in-human, Clinical Trial to Evaluate the Safety, Reactogenicity and Immunogenicity After 1 and 2 Doses of the Investigational SARS-CoV-2 mRNA Vaccine CVnCoV Administered Intramuscularly in Healthy Adults

    This study aims to evaluate the safety and reactogenicity profile after 1 and 2 dose administrations of CVnCoV at different dose levels.

    NCT04449276
    Conditions
    1. Severe Acute Respiratory Syndrome
    2. Coronavirus
    3. SARS-CoV-2
    4. COVID-19
    Interventions
    1. Biological: CVnCoV Vaccine
    2. Drug: Placebo
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome

    Primary Outcomes

    Description: This data will be collected for decisions on subsequent vaccination of an additional open-label sentinel group with the same dose level.

    Measure: Number of Participants With Grade 3 Adverse Reactions or any Serious Adverse Event (SAE) Considered Related to Trial Vaccine Within at Least 24 Hours After the First Vaccination

    Time: Up to 24 hours after vaccination on Day 1

    Description: This data will be collected for decisions on dose escalation as well as continuation of enrollment at the same dose level in the observer-blind placebo-controlled part of the trial.

    Measure: Number of Participants With Grade 3 Adverse Reactions or any Serious Adverse Event (SAE) Considered Related to Trial Vaccine Within at Least 60 Hours After the First Vaccination

    Time: Up to 60 hours after vaccination on Day 1

    Measure: Number of Participants with Solicited Local Adverse Events

    Time: 7 days after vaccination

    Measure: Intensity of Solicited Local Adverse Events per the FDA Toxicity Grading Scale

    Time: 7 days after vaccination

    Measure: Duration of Solicited Local Adverse Events

    Time: 7 days after vaccination

    Measure: Number of Participants with Solicited Systemic Adverse Events

    Time: 7 days after vaccination

    Measure: Intensity of Solicited Systemic Adverse Events per the FDA Toxicity Grading Scale

    Time: 7 days after vaccination

    Measure: Duration of Solicited Systemic Adverse Events

    Time: 7 days after vaccination

    Measure: Number of Participants with Solicited Systemic Adverse Events Considered Related to Trial Vaccine

    Time: 7 days after vaccination

    Measure: Number of Participants with Unsolicited Adverse Events

    Time: 28 days after vaccination

    Measure: Intensity of Unsolicited Adverse Events Assessed by the Investigator

    Time: 28 days after vaccination

    Measure: Number of Participants with Unsolicited Adverse Events Considered Related to Trial Vaccine

    Time: 28 days after vaccination

    Measure: Number of Participants with One or More Serious Adverse events (SAEs)

    Time: Baseline to Day 393

    Measure: Number of Participants with One or More Serious Adverse events (SAEs) Considered Related to Trial Vaccine

    Time: Baseline to Day 393

    Measure: Number of Participants with One or More Adverse Events of Special Interest (AESIs)

    Time: Baseline to Day 393

    Measure: Number of Participants with One or More Adverse Events of Special Interest (AESIs) Considered Related to Trial Vaccine

    Time: Baseline to Day 393

    Secondary Outcomes

    Description: Measured using Enzyme-Linked Immunosorbent Assay (ELISA).

    Measure: Number of Participants Seroconverting for SARS-CoV-2 Spike Protein Antibodies

    Time: Baseline and on Day 8, Day 15, Day 29, Day 36, Day 43, Day 57, Day 120, Day 211 and Day 393

    Description: Measured using Enzyme-Linked Immunosorbent Assay (ELISA).

    Measure: Individual SARS-CoV-2 Spike Protein-Specific Antibody Levels in Serum

    Time: On Day 8, Day 15, Day 29, Day 36, Day 43, Day 57, Day 120, Day 211 and Day 393

    Description: Measured using Enzyme-Linked Immunosorbent Assay (ELISA).

    Measure: Geometric Mean Titers (GMTs) of Serum SARS-CoV-2 Spike Protein Antibodies

    Time: On Day 8, Day 15, Day 29, Day 36, Day 43, Day 57, Day 120, Day 211 and Day 393

    Description: Measured using an activity assay.

    Measure: Number of Participants Seroconverting for SARS-CoV-2 Neutralizing Antibodies

    Time: Baseline and on Day 8, Day 15, Day 29, Day 36, Day 43, Day 57, Day 120, Day 211 and Day 393

    Description: Measured using an activity assay.

    Measure: Individual SARS-CoV-2 Neutralizing Antibody Levels in Serum

    Time: On Day 8, Day 15, Day 29, Day 36, Day 43, Day 57, Day 120, Day 211 and Day 393

    Description: Measured using an activity assay.

    Measure: Geometric Mean Titers (GMTs) of Serum SARS-CoV-2 Neutralizing Antibodies

    Time: On Day 8, Day 15, Day 29, Day 36, Day 43, Day 57, Day 120, Day 211 and Day 393
    216 Vitamin D Supplementation in Patients With COVID-19: A Randomized, Double-blind, Placebo-controlled Trial

    Coronavirus disease 2019 (COVID-19) was declared an emergency public health problem by the World Health Organization (WHO) in March 2020. Since then, several initiatives by the medical and scientific community have sought alternatives to treat infected individuals, as well as identifying risk or protective factors for the contamination and prognosis of patients. In this perspective, vitamin D supplementation can improve some important outcomes in critically ill patients, being considered a potent immunomodulatory agent. Vitamin D deficiency is a common outcome in critically ill patients, thus making it a modifiable risk factor with great potential for reducing hospital stay and intensive care and mortality. The investigators speculate that vitamin D supplementation could have therapeutic effects in patients with COVID-19.

    NCT04449718
    Conditions
    1. COVID-19
    Interventions
    1. Dietary Supplement: Vitamin D
    2. Dietary Supplement: Placebo

    Primary Outcomes

    Description: total number of days that patient remained hospitalized

    Measure: Length of hospitalization

    Time: From date of randomization until the date of hospital discharge or death, which is usually less than 1 month

    Secondary Outcomes

    Description: number of patients that died

    Measure: Mortality

    Time: From date of randomization until the date of hospital discharge or death, which is usually less than 1 month

    Description: total number of days that patient remained in ICU

    Measure: Number of cases admitted to Intensive Care Unit (ICU)

    Time: From date of randomization until the date of hospital discharge or death, which is usually less than 1 month

    Description: total number of days that patient remained in mechanic ventilator

    Measure: Length of use of mechanic ventilator

    Time: From date of randomization until the date of hospital discharge or death, which is usually less than 1 month

    Measure: Number and severity of symptoms

    Time: From date of randomization until the date of hospital discharge or death, which is usually less than 1 month

    Description: C-reactive protein, IL-1alpha (pg/ml), IL-1beta (pg/ml), IL-6 (pg/ml), TNF-alpha (pg/ml), IL-1ra (pg/ml), IL-10 (pg/ml) concentration in the serum

    Measure: Inflammatory markers

    Time: Baseline, 14 days after hospitalization and at the moment of hospital discharge or death (usually less than 1 month)

    Description: serum concentration

    Measure: C-reactive protein

    Time: Baseline, 14 days after hospitalization and at the moment of hospital discharge or death (usually less than 1 month)

    Description: serum concentration

    Measure: Vitamin D

    Time: Baseline, 14 days after hospitalization and at the moment of hospital discharge or death (usually less than 1 month)

    Description: serum concentration

    Measure: Creatinine

    Time: Baseline, 14 days after hospitalization and at the moment of hospital discharge or death (usually less than 1 month)

    Description: serum concentration

    Measure: Calcium

    Time: Baseline, 14 days after hospitalization and at the moment of hospital discharge or death (usually less than 1 month)

    Description: Baecke questionnaire (higher scores mean a higher physical activity level)

    Measure: Physical activity

    Time: Baseline
    217 The Efficacy of Topical Povidone-Iodine Rinses in the Management of the Coronavirus Disease 2019 (COVID-19)

    The aim of this study is to determine if Povidone iodine (PVP-I) rinses and throat gargles or a PVP-I gel forming nasal spray compared to a placebo (a treatment that has no physical effect to a person) is an effective treatment for patients diagnosed with COVID-19. These patients have been diagnosed with mild/moderate COVID-19 symptoms and sent home for self-isolation. Patients will be instructed to take either of the two treatments or placebo twice daily for two weeks and have follow up visits 2 and 4 weeks after. The participants will also complete study related procedures such as saliva sample collection, and two questionnaires throughout the study period. The investigators hypothesize that COVID 19 positive participants who use either of the Povidone - Iodine treatment will have a reduction in their viral load, develop a negative oral mucosa sample and improve their clinical symptoms.

    NCT04449965
    Conditions
    1. Covid19
    Interventions
    1. Drug: Povidone-iodine
    2. Drug: Placebo

    Primary Outcomes

    Description: A saliva sample will be analyzed to monitor the duration of positivity and when test becomes negative for SARS-CoV-2.

    Measure: Change in SARS-CoV-2 positivity in the saliva

    Time: A saliva sample will be taken every 2 days for 2 weeks, and again at 4 and 6 weeks

    Description: Quantify the amount of SAR-CoV-2 viral load present in the saliva.

    Measure: Change in the SAR-CoV-2 viral load in the saliva

    Time: A saliva sample will be taken every 2 days for 2 weeks, and again at 4 and 6 weeks

    Secondary Outcomes

    Description: This is a 44 question, quality of life survey designed to measure different aspects affected by the common cold.

    Measure: Change in Wisconsin Upper Respiratory Symptom Survey (WURSS-44)

    Time: daily for 2 weeks, 4 weeks, and 6 weeks

    Description: That includes 22 questions about symptoms and social/emotional consequences of your nasal disorder.

    Measure: Change Sino nasal Outcome Test (SNOT-22)

    Time: baseline, 2 weeks, 4 weeks, 6 weeks

    Description: We will record and worsening of clinical condition such as, need for hospitalization/oxygen support.

    Measure: Change in clinical condition

    Time: daily for 2 weeks, 4 weeks, and 6 weeks
    218 A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Assessing the Efficacy and Safety of Anti-Spike SARS-CoV-2 Monoclonal Antibodies in Preventing SARS-CoV-2 Infection in Household Contacts of Individuals Infected With SARS-CoV-2

    Primary Objective: - To evaluate the efficacy of REGN10933+REGN10987 compared to placebo in preventing symptomatic SARS-CoV-2 infection (strict-term) confirmed by RT-qPCR - To evaluate the efficacy of REGN10933+REGN10987 compared to placebo in preventing asymptomatic or symptomatic SARS-CoV-2 infection confirmed by RT-qPCR - To evaluate the safety and tolerability of REGN10933+REGN10987 following subcutaneous (SC) administration compared to placebo

    NCT04452318
    Conditions
    1. Healthy Participants
    Interventions
    1. Drug: REGN10933 + REGN10987
    2. Drug: Placebo
    MeSH:Infection

    Primary Outcomes

    Description: Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline

    Measure: Proportion of participants who have a positive SARS-CoV-2 RT-qPCR (based on central lab test) and signs and symptoms (strict-term) of SARS-CoV-2 infection during the Efficacy assessment period (EAP)

    Time: Up to 1 month

    Description: Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline

    Measure: Proportion of participants who have a RT-qPCR confirmed SARS-CoV-2 infection (either symptomatic or asymptomatic) during the EAP

    Time: Up to 1 month

    Description: Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline

    Measure: Proportion of participants with treatment-emergent adverse events (TEAEs) and severity of TEAEs

    Time: Up to 8 months

    Secondary Outcomes

    Description: Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline

    Measure: Proportion of participants who have a symptomatic RT-qPCR confirmed SARS-CoV-2 infection (broad term) during the EAP

    Time: Up to 1 month

    Description: Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline

    Measure: Proportion of participants who have a positive SARS-CoV-2 RT-qPCR and absence of signs and symptoms (strict term) during the EAP

    Time: Up to 1 month

    Description: Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline

    Measure: Proportion of participants who have a positive SARS-CoV-2 RT-qPCR and absence of signs and symptoms (broad term) during the EAP

    Time: Up to 1 month

    Description: Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline

    Measure: Number of days of symptomatic SARS-CoV-2 infection (strict-term) from the first day of the first sign or symptom until the last day of the last sign or symptom associated with the first positive SARS-CoV-2 RT-PCR that occurs during the EAP

    Time: Up to 8 months

    Description: Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline

    Measure: Number of days of symptomatic SARS-CoV-2 infection (broad-term) from the first day of the first sign or symptom until the last day of the last sign or symptom associated with the first positive SARS-CoV-2 RT-PCR that occurs during the EAP

    Time: Up to 8 months

    Description: Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline

    Measure: Time-weighted average of viral shedding (log10 copies/mL) from the first positive SARS CoV-2 RT-qPCR Nasopharyngeal (NP) swab sample (with an onset during the EAP) until the visit within the window including 22 days after the positive test during the EAP

    Time: Up to 1 month

    Description: Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline

    Measure: Maximum SARS-CoV-2 RT-qPCR log10 viral copies/mL in Nasopharyngeal (NP) swab samples among individuals with ≥1 RT-qPCR positive that has an onset during the EAP

    Time: Up to 8 months

    Description: Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline

    Measure: Area under the curve (AUC) in viral shedding (log10 copies/mL) from the first positive SARS-CoV-2 RT-qPCR NP swab sample until the first confirmed negative test, that has an onset during the EAP

    Time: Up to 8 months

    Description: Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline

    Measure: Number of medically attended visits in emergency rooms or urgent care centers related to a RT-qPCR confirmed SARS-CoV-2 infection that has an onset during the EAP

    Time: Up to 8 months

    Description: Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline

    Measure: Proportion of participants requiring medically attended visits in emergency rooms or urgent care centers related to a RT-qPCR confirmed SARS CoV-2 infection that has an onset during the EAP

    Time: Up to 8 months

    Description: Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline

    Measure: Proportion of participants hospitalized related to a RT-qPCR confirmed SARS-CoV-2 infection that has an onset during the EAP

    Time: Up to 8 months

    Description: Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline

    Measure: Number of days of hospital and intensive care unit (ICU) stay in participants hospitalized for a RT-qPCR confirmed SARS-CoV-2 infection that has an onset during the EAP

    Time: Up to 8 months

    Description: Daily responsibilities including work (employed adults) or school (matriculating students), or family obligations/responsibilities (childcare or eldercare) Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline

    Measure: Number of days missed for daily responsibilities due to a RT-qPCR confirmed SARS-CoV-2 infection that has an onset during the EAP

    Time: Up to 8 months

    Description: Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline

    Measure: Incidence of symptomatic SARS-CoV-2 infection in seronegative and seropositive participants (based on central lab test) in both the EAP and follow-up periods

    Time: Up to 8 months

    Description: Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline

    Measure: Severity of symptomatic SARS-CoV-2 infection in seronegative and seropositive participants (based on central lab test) in both the EAP and follow-up periods

    Time: Up to 8 months

    Description: Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline

    Measure: Proportion of baseline seropositive subjects (based on central lab test) with TEAEs and severity of TEAEs

    Time: Up to 8 months

    Description: Pharmacokinetic (PK) parameters may include, but are not limited to: - Maximum observed plasma concentration (Cmax) - Cmax/Dose - Time of maximum observed plasma concentration (tmax) - Time of Clast (tlast) - Last measurable plasma concentration (Clast) - Area under plasma concentration-time curve from time 0 to infinity (AUCinf) - AUCinf/Dose - Elimination half-life (t1/2) - Concentration in serum 28 days (C28) after dosing) Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline Cohort B: SARS-CoV-2 RT-qPCR Positive at Baseline

    Measure: Concentrations of REGN10933 in serum over time and selected PK parameters

    Time: Up to 8 months

    Description: Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline Cohort B: SARS-CoV-2 RT-qPCR Positive at Baseline

    Measure: Concentrations of REGN10987 in serum over time and selected PK parameters

    Time: Up to 8 months

    Description: Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline Cohort B: SARS-CoV-2 RT-qPCR Positive at Baseline

    Measure: Immunogenicity as measured by anti-drug antibodies (ADA) to REGN10933 over time

    Time: Up to 8 months

    Description: Cohort A: SARS-CoV-2 RT-qPCR Negative at Baseline Cohort B: SARS-CoV-2 RT-qPCR Positive at Baseline

    Measure: Immunogenicity as measured by anti-drug antibodies (ADA) to REGN10987 over time

    Time: Up to 8 months

    Description: Cohort B: SARS-CoV-2 RT-qPCR Positive at Baseline

    Measure: Proportion of participants who subsequently develop signs and symptoms (strict-term) of symptomatic SARS-CoV-2 infection during EAP

    Time: Within 14 and 28 days of a positive RT-qPCR

    Description: Cohort B: SARS-CoV-2 RT-qPCR Positive at Baseline

    Measure: Proportion of participants who subsequently develop signs and symptoms (broad-term) of symptomatic SARS-CoV-2 infection during EAP

    Time: Within 14 and 28 days of a positive RT-qPCR

    Description: Cohort B: SARS-CoV-2 RT-qPCR Positive at Baseline

    Measure: Number of days of symptomatic SARS CoV-2 infection (strict-term)

    Time: Up to 8 months

    Description: Cohort B: SARS-CoV-2 RT-qPCR Positive at Baseline

    Measure: Number of days of symptomatic SARS CoV-2 infection (broad-term)

    Time: Up to 8 months

    Description: Cohort B: SARS-CoV-2 RT-qPCR Positive at Baseline

    Measure: Time-weighted average change from baseline in viral shedding in NP swab samples until the visit within the window including day 23

    Time: Until day 23

    Description: Cohort B: SARS-CoV-2 RT-qPCR Positive at Baseline

    Measure: Area under the curve (AUC) in viral shedding (log10 copies/mL) in NP swab samples until the first confirmed negative test

    Time: Up to 8 months

    Description: Cohort B: SARS-CoV-2 RT-qPCR Positive at Baseline

    Measure: Maximum SARS-CoV-2 RT-qPCR log10 viral copies/mL in NP swab samples

    Time: Up to 8 months

    Description: Cohort B: SARS-CoV-2 RT-qPCR Positive at Baseline

    Measure: Number of medically attended visits in emergency rooms or urgent care centers related to RT-qPCR confirmed SARS-CoV-2 infection

    Time: Up to 8 months

    Description: Cohort B: SARS-CoV-2 RT-qPCR Positive at Baseline

    Measure: Proportion of participants requiring medically attended visits in emergency rooms or urgent care centers related to a RT-qPCR confirmed SARS CoV-2 infection

    Time: Up to 8 months

    Description: Cohort B: SARS-CoV-2 RT-qPCR Positive at Baseline

    Measure: Proportion of participants hospitalized related to a RT-qPCR confirmed SARS-CoV-2 infection

    Time: Up to 8 months

    Description: Cohort B: SARS-CoV-2 RT-qPCR Positive at Baseline

    Measure: Number of days of hospital and intensive care unit (ICU) stay in participants hospitalized for a RT-qPCR confirmed SARS-CoV-2 infection

    Time: Up to 8 months

    Description: Daily responsibilities including work (employed adults) or school (matriculating students), or family obligations/responsibilities (childcare or eldercare) Cohort B: SARS-CoV-2 RT-qPCR Positive at Baseline

    Measure: Number of days missed for daily responsibilities due to a RT-qPCR confirmed SARS-CoV-2 infection

    Time: Up to 8 months

    Description: Cohort B: SARS-CoV-2 RT-qPCR Positive at Baseline

    Measure: Proportion of participants with TEAEs and severity of TEAEs

    Time: Up to 8 months

    Description: Cohort B: SARS-CoV-2 RT-qPCR Positive at Baseline

    Measure: Incidence of symptomatic SARS-CoV-2 infection in both the EAP and follow-up periods

    Time: Up to 8 months

    Description: Cohort B: SARS-CoV-2 RT-qPCR Positive at Baseline

    Measure: Severity of symptomatic SARS-CoV-2 infection in both the EAP and follow-up periods

    Time: Up to 8 months
    219 A Randomised, Double-blind, Placebo-controlled, Phase 2 Trial Investigating the Safety and Efficacy of C21 in Hospitalised Subjects With COVID-19 Infection Not Requiring Mechanical Ventilation

    This is a randomised, double-blind, placebo-controlled phase 2 trial investigating the safety and efficacy of C21 in subjects who are hospitalised with COVID-19 infection, but not in need of mechanical invasive or non-invasive ventilation. In total, approximately 100 subjects will be enrolled and randomised to receive twice daily oral administration of either standard of care (SoC) + placebo (N=50) or SoC + C21 (N=50). Subjects will be treated for 7 days.

    NCT04452435
    Conditions
    1. COVID-19
    Interventions
    1. Drug: C21
    2. Drug: Placebo

    Primary Outcomes

    Description: Primary endpoint

    Measure: Change from baseline in C-reactive protein (CRP) after treatment with C21 200 mg daily dose (100 mg b.i.d.)

    Time: Treatment period of 7 days
    220 A Multicenter, Randomized, Double-blind, Adaptive, Placebo-controlled Study of the Efficacy and Safety of a Single Administration of Olokizumab vs. Placebo in Addition to Standard Treatment in Patients With Severe SARS-CoV-2 Infection (COVID-19)

    The primary objective of the study is to evaluate the efficacy of a single dose of OKZ (64 mg) vs placebo in addition to standard therapy in patients with severe SARS-CoV-2 infection (COVID-19) at Day 29.

    NCT04452474
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Olokizumab 64 mg
    2. Drug: Placebo
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome

    Primary Outcomes

    Description: Difference between OKZ and placebo groups in the percentage of subjects with an improvement of at least 2 categories of the 5-points clinical status scale relative to baseline or in the "Not hospitalized" category. The points of the scale are: 1. Not hospitalized; 2.Hospitalized, not requiring supplemental oxygen; 3.Hospitalized, supplemental oxygen, spontaneous breathing;4. Hospitalized, mechanical ventilation (invasive/non-invasive) or extracorporeal membrane oxygenation (ECMO); 5. Death

    Measure: Percentage of subjects achieving a change in their clinical status defined as improvement for at least 2 categories of the 5-points clinical status scale relative to baseline or in the "Not hospitalized" category

    Time: at Day 29

    Secondary Outcomes

    Description: Subjects' clinical status distribution based on 5-point clinical status scale during the study

    Measure: Subjects' clinical status distribution based on 5-point clinical status scale during the study

    Time: from Day 2 tо Day 15, Day 29, Day 60

    Description: 28-day case fatality rates

    Measure: 28-day case fatality rates

    Time: from Day 1 to Day 29

    Other Outcomes

    Description: Case fatality rates during the intensive care unit (ICU) stay at Days 7, 15, and 60

    Measure: Case fatality rates during the intensive care unit (ICU) stay, at Days 7, 15, and 60

    Time: from Day 1 to Day 60

    Description: Duration of oxygen support (if applicable)

    Measure: Duration of oxygen support

    Time: From Day 1 to Day 60

    Description: The time period until SpO2 ≥ 94% at ambient air during 2 consequence days is reached

    Measure: The time period until SpO2 ≥ 94% at ambient air during 2 consequence days is reached

    Time: from Day 2 to Day 60

    Description: Changes of oxygenation index PaO2/FiO2 from baseline (if applicable)

    Measure: Changes of oxygenation index PaO2/FiO2 from baseline

    Time: from Day 2 to Day 60

    Description: Duration of oxygen support (if applicable), in days

    Measure: Duration of oxygen support (if applicable)

    Time: from Day 1 to Day 60

    Description: Duration of mechanical ventilation and/or ECMO (if applicable), in days

    Measure: Duration of mechanical ventilation and/or ECMO (if applicable)

    Time: from Day 1 to Day 60

    Description: Duration of ICU stay (if applicable)

    Measure: Duration of ICU stay (if applicable)

    Time: from Day 1 to Day 60

    Description: Changes from baseline of COVID-19 cytokine storm surrogate marker: white blood count

    Measure: Changes from baseline of COVID-19 cytokine storm surrogate marker: white blood count

    Time: from Day 2 and until the end of hospitalization, Day 29 as a maximum

    Description: Changes from baseline of COVID-19 cytokine storm surrogate marker: lymphocyte counts

    Measure: Changes from baseline of COVID-19 cytokine storm surrogate marker: lymphocyte count

    Time: from Day 2 and until the end of hospitalization, Day 29 as a maximum

    Description: Changes from baseline of COVID-19 cytokine storm surrogate marker: neutrophils count

    Measure: Changes from baseline of COVID-19 cytokine storm surrogate marker: neutrophils count

    Time: from Day 2 and until the end of hospitalization, Day 29 as a maximum

    Description: Changes from baseline of COVID-19 cytokine storm surrogate marker: C-reactive protein (CRP)

    Measure: Changes from baseline of COVID-19 cytokine storm surrogate marker: C-reactive protein (CRP)

    Time: from Day 2 and until the end of hospitalization, Day 29 as a maximum

    Description: Changes from baseline of COVID-19 cytokine storm surrogate marker: ferritin

    Measure: Changes from baseline of COVID-19 cytokine storm surrogate marker: ferritin

    Time: from Day 2 and until the end of hospitalization, Day 29 as a maximum

    Description: Changes from baseline of COVID-19 cytokine storm surrogate marker:D-dimer

    Measure: Changes from baseline of COVID-19 cytokine storm surrogate marker:D-dimer

    Time: from Day 2 and until the end of hospitalization, Day 29 as a maximum

    Description: Changes from baseline of COVID-19 cytokine storm surrogate marker:platelets

    Measure: Changes from baseline of COVID-19 cytokine storm surrogate marker:platelets

    Time: from Day 2 and until the end of hospitalization, Day 29 as a maximum

    Description: Changes from baseline of COVID-19 cytokine storm surrogate marker: triglycerides

    Measure: Changes from baseline of COVID-19 cytokine storm surrogate marker: triglycerides

    Time: from Day 2 and until the end of hospitalization, Day 29 as a maximum

    Description: The time period until National Early Warning Score 2 (NEWS2) ≤ 2 during 2 consequent days is reached

    Measure: The time period until National Early Warning Score 2 (NEWS2) ≤ 2 during 2 consequent days is reached

    Time: from Day 1 and until the end of hospitalization, Day 29 as a maximum

    Description: The time period until National Early Warning Score 2 (NEWS2) ≤ 4 during 2 consequent days is reached

    Measure: The time period until National Early Warning Score 2 (NEWS2) ≤ 4 during 2 consequent days is reached

    Time: from Day 1 and until the end of hospitalization, Day 29 as a maximum
    221 Prospective, Multicenter, Randomized, Double-blind, Placebo-controlled Clinical Trial on the Efficacy of BACMUNE (MV130) in the Prevention of Disease Due to SARS-CoV-2 Infection in Healthcare Personnel

    The purpose of this trial is to assess the effect of immunotherapy with the bacterial preparation MV130 on the spread and course of SARS-CoV-2 infection in highly exposed subjets, as is the case with healthcare personnel.

    NCT04452643
    Conditions
    1. Covid19
    Interventions
    1. Biological: BACMUNE (MV130)
    2. Other: Placebo
    MeSH:Infection

    Primary Outcomes

    Description: Incidence of subjects with COVID-19, defined by the presence of: Fever Any of the respiratory signs and/or symptoms: cough, dyspnea, respiratory failure, runny nose/nasal obstruction. Positive test for SARS-COV-2 (PCR o serology)

    Measure: Incidence of subjects with COVID-19

    Time: 60 days

    Description: Incidence of severe COVID-19, defined by CURB > 2 and/or death

    Measure: Severity of COVID-19

    Time: 60 days

    Secondary Outcomes

    Description: Rate of subjects with seroconversion to SARS-CoV-2 (negative serology at the beginning of the study and positive at the end of the study

    Measure: Seroconversion to SARS-CoV-2

    Time: 60 days

    Description: Rate of subjects with any symptoms, whether confirmed, probable or suspected, according to the WHO definition

    Measure: Subjects with symptoms

    Time: 60 days

    Description: The effect of the treatment on the severity of the disease will be measured based on the rate of subjects requiring hospital admission for COVID-19

    Measure: Hospital admission due to COVID-19

    Time: 60 days

    Description: The effect of the treatment on the severity of the disease will be measured based on the rate of subjects who require admission to an intensive care unit for COVID-19 • Time from confirmation of SARS-CoV-2 infection to the appearance of symptoms.

    Measure: Admission to an intensive care unit due to COVID-19

    Time: 60 days

    Description: Elapsed time until the first symptoms of COVID-19 appears to hospitalization due to COVID-19.

    Measure: Elapsed time until hospitalization

    Time: 60 days

    Description: Elapsed time until the first symptoms of COVID-19 appears to admission into an intensive care unit pro COVID-19.

    Measure: Elapsed time until admission into an care unit for COVID-19

    Time: 60 days

    Description: Elapsed time until the first symptoms of COVID-19 appears to death from any cause not related to COVID-19.

    Measure: Elapsed time until death not related to COVID-19

    Time: 60 days
    222 Double-blind, Randomized, Placebo-Controlled Clinical Trial to Evaluate the Efficacy of the Manremyc® Food Supplement to Prevent SARS-CoV-2 Infection

    The purpose of this study is to assess the efficacy of Manremyc® food supplement for reduce the incidence of SARS-CoV-2 infection in a high risk population, as healthcare workers.

    NCT04452773
    Conditions
    1. COVID19
    Interventions
    1. Dietary Supplement: Manremyc
    2. Dietary Supplement: Placebo
    MeSH:Infection

    Primary Outcomes

    Description: % of positive serology at the end of the study or positive PCR test in the course of routine clinical practice

    Measure: Documented cumulative incidence of SARS-CoV-2 infection

    Time: up to 4 months

    Secondary Outcomes

    Description: Number of days Documented as sick leave for SARS-CoV-2

    Measure: Documented sick leave for SARS-CoV-2

    Time: up to 4 months (cumulative)

    Description: Number of days off work due to the quarantine imposed as a consequence to have acute respiratory symptoms, fever or infection documented by SARS-CoV-2

    Measure: days off work due to the quarantine

    Time: up to 4 months

    Description: Number of days in quarantine imposed by close contact outside the center with SARS-CoV-2 positive

    Measure: Quarantine imposed by close contact outside the center with SARS-CoV-2 positive

    Time: up to 4 months

    Description: Number of days of self-reported fever (≥38 ºC)

    Measure: Fever

    Time: Up to 4 months

    Description: Cumulative incidence of self-reported acute respiratory symptoms

    Measure: Cumulative incidence of self-reported acute respiratory symptoms

    Time: up to 4 months

    Description: Number of days of self-reported acute respiratory symptoms

    Measure: Number of days of self-reported acute respiratory symptoms

    Time: up to 4 months

    Description: Number of participants with pneumonia confirmed by X-ray

    Measure: Incidence of pneumonia

    Time: up to 4 months

    Description: Cumulative incidence of death from documented SARS-CoV-2 infection

    Measure: Cumulative incidence of death from documented SARS-CoV-2 infection

    Time: Up to 4 months

    Description: Cumulative incidence of admissions to intensive care unit for documented SARS-CoV-2 infection

    Measure: Incidence of admission to ICU

    Time: Up to 4 months

    Description: Number of days admitted to the ICU for documented SARS-CoV-2 infection

    Measure: Days in IUC

    Time: Up to 4 months

    Description: Cumulative incidence of need for mechanical ventilation due to documented SARS-CoV-2 infection

    Measure: Incidence of mechanical ventilation

    Time: Up to 4 months

    Description: Cumulative incidence of hospital admissions for documented SARS-CoV-2 infection

    Measure: Incidence of hospital admissions

    Time: Up to 4 months

    Description: Number of days of hospitalization for documented SARS-CoV-2 infection

    Measure: Days of hospitalization

    Time: Up to 4 months

    Description: Levels of IgG

    Measure: Levels of IgG

    Time: Up to 4 months

    Description: Levels of IgM

    Measure: Levels of IgM

    Time: Up to 4 months

    Description: Levels of SARS-CoV-2 antibodies at the end of the study period

    Measure: Levels of SARS-CoV-2 antibodies at the end of the study period

    Time: Up to 4 months

    Other Outcomes

    Description: All adverse events reported by the subjects, both serious and non-serious, will be collected. All events related to a SARS-CoV-2 infection will be exempted from collection, as they will be collected as part of the associated symptoms

    Measure: AEs

    Time: Up to 4 months

    Description: All thoseAdverse Events that lead to hospitalization of the patient, that endanger his life or cause or may cause death.

    Measure: SAEs

    Time: Up to 4 moths
    223 A Randomized, Double-blind, Placebo-controlled Phase 2 (2a and 2b) Study to Evaluate the Safety and Efficacy of XAV-19 in Patients With COVID-19 Induced Moderate Pneumonia

    Early inhibition of entry and replication of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a very promising therapeutic approach. Polyclonal neutralizing antibodies offers many advantages such as providing immediate immunity, consequently blunt an early pro-inflammatory pathogenic endogenous antibody response and lack of drug-drug interactions1-3. Because a suboptimal endogenous early antibody response with regard to SARS-CoV-2 replication in severe cases is observed, neutralising antibody treatment can be very interesting for patient with COVID-19 induced moderate pneumonia4,5. Convalescent plasma to treat infected patients is therefore an interesting therapeutic option currently under evaluation. However, the difficulties of collecting plasma and its safety aspects are not adapted to many patients. A new polyclonal humanized anti-SARS-CoV2 antibodies (XAV-19) is being developed by Xenothera, which can be administered as intravenous treatment. XAV-19 is a heterologous swine glyco-humanized polyclonal antibody (GH-pAb) raised against the spike protein of SARS-CoV-2, inhibiting infection of ACE-2 positive human cells with SARS-CoV-2. Pharmacokinetic and pharmacodynamic studies have been performed in preclinical models including primates and a First In Human study with another fully representative GH-pAb from Xenothera is ongoing in volunteer patients recipients of a kidney graft. These studies indicated that 5 consecutive administrations of GH-pAbs can be safely performed in humans. The objective of this 2-steps phase 2 randomized double-blind, placebo-controlled study is 1) to define the optimal and safety XAV-19 dose to administrate in patients with COVID-19 induced moderate pneumonia ; 2) to show the clinical benefit of selected dose of XAV-19 when administered to patients with COVID-19 induced moderate pneumonia.

    NCT04453384
    Conditions
    1. SARS Virus
    Interventions
    1. Drug: XAV-19
    2. Drug: Placebo
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: The primary endpoint is measurement of the antibody titer XAV-19 in all treated patients and in all patients in the placebo group at Day 8

    Measure: Phase 2a: XAV-19 antibody titers

    Time: Day 8

    Description: Adverse events of XAV-19 between the two groups of treated patients and vs. placebo over 29 days

    Measure: Phase 2a: Adverse events of XAV-19

    Time: Day 29

    Description: Efficacy is defined by the proportion of patients who die or develop respiratory failure in the two groups of treatment between baseline and Day 15. Patient with respiratory failure will be patient requiring noninvasive ventilation, high-flow oxygen devices or invasive mechanical ventilation (corresponding to 8-point ordinal scale ≥ 6).

    Measure: Phase 2b: Time to weaning of supplemental oxygen.

    Time: Day 15

    Secondary Outcomes

    Description: XAV-19 Antibody titer over the time

    Measure: Phase 2a: Pharmacokinetic analysis

    Time: Day 1 (pre-dose, post-dose), at Day 5 (pre-dose, post-dose), Day 8, Day 15, and Day 29

    Description: The antibody titer of XAV-19 measurements in Group 1 treated patients and Group 2 treated patients

    Measure: Phase 2a: Antibody titer between the two groups

    Time: day 15

    Description: Duration of supplemental oxygen

    Measure: Phase 2a: Supplemental oxygen

    Time: Day 1 to Day 29

    Description: Transfer to intensive care unit with need for invasive mechanical ventilation or high flow oxygen

    Measure: Phase 2a: Evaluation of Transfer to intensive care

    Time: Day 1 to Day 29

    Description: Normalization of fever ≥ 24 hours: clinical assessment every day from Day 1 to Day 14. Evaluation to be performed between 8 and 12 am, Day X evaluation will consider the higher value during Day X-1

    Measure: Phase 2a: Normalization of Fever

    Time: Day 1 to Day 29

    Description: Biomarkers : CRP, Ferritin

    Measure: Phase 2a: Biomarkers

    Time: Day 1 to Day 29

    Description: Evaluation of Hospital length of stay

    Measure: Phase 2a: Hospital length of stay

    Time: Day 1 to Day 29

    Description: a) Proportion of patients who die, develop respiratory failure (requiring noninvasive ventilation, high-flow oxygen devices or invasive mechanical ventilation) between baseline and Day 8, then between baseline and D29

    Measure: Phase 2b: Efficacy of XAV-19

    Time: Day 8 and Day 29

    Description: b) National Early Warning Score (NEWS) at Day 15 and difference in NEWS between baseline and D8 / D15 / D29

    Measure: Phase 2b: National Early Warning Score (NEWS)

    Time: Day 8, Day 15 and Day 29

    Description: c) Clinical status using the 8-point ordinal scale assessed and difference between baseline and D3, D5, D8, D15, and D29

    Measure: Phase 2b: clinical status

    Time: Day 3, Day 5, Day 8, Day15, and Day 29

    Description: d) Time to improvement of one category from admission using the 8-point ordinal scale. This scale is rated 0 to 8 with score 0 being the better score (no clinical impact) and 8 being the worst score (death)

    Measure: Phase 2b: Time to improvement

    Time: 29 Days

    Description: e) Time to first fever normalization (criteria for normalization: temperature < 36.6°C armpit, < 37.2°C oral, < 37.8°C rectal or tympanic)

    Measure: Phase 2b: fever normalization

    Time: 29 Days

    Description: f) Duration of oxygen therapy

    Measure: Phase 2b: Oxygen therapy

    Time: 29 Days

    Description: g) Comparison of oxygen requirement between the two groups

    Measure: Phase 2b: oxygen requirement

    Time: 29 Days

    Description: h) Time to weaning in supplemental oxygen and proportion without O2 requirement at Day 8, D15 and Day 29, according to baseline (D1) oxygen requirement (≤ 4 L/min or 4 L/min)

    Measure: Phase 2b: Time to weaning

    Time: Day8, Day 15 and Day 29

    Description: i) Incidence and duration of non-invasive ventilation or high flow oxygen devices, of invasive mechanical ventilation during the study

    Measure: Phase 2b: Ventilation

    Time: 29 Days

    Description: j) Evaluation of hospital length of stay

    Measure: Phase 2b: Hospital length of stay

    Time: 29 Days

    Description: k) All cause mortality

    Measure: Phase 2b: mortality

    Time: 29 Days

    Description: l) Occurrence of all suspected XAV-19 related adverse effects or Incidence of serious adverse events Proportion of participants with treatment emergent adverse events leading to study drug discontinuation Incidence of major or opportunistic bacterial or fungal infections Incidence of hypersensitivity reactions and infusion reactions White cell count, hemoglobin, platelets, creatinine, ALT, AST, on D1, D3, D5, D8, D11, D15 and D29 SARS-CoV-2 viral load over time (D1-D29), as collected by nasopharyngeal swab samples Time to RT-PCR virus negativity in nasopharyngeal swab samples

    Measure: Phase 2b: safety

    Time: 29 Days
    224 Double-blind, Randomized, Placebo-controlled Clinical Trial to Evaluate the Efficacy of the RUTI® Vaccine to Prevent SARS-CoV-2 Infection

    The purpose of this study is to assess the efficacy of RUTI® vaccine preventing SARS-CoV-2 infection (COVID-19) in healthcare workers.

    NCT04453488
    Conditions
    1. Covid-19
    2. Sars-CoV2
    Interventions
    1. Biological: RUTI® vaccine
    2. Biological: Placebo
    MeSH:Infection

    Primary Outcomes

    Description: % positive serology at the end of the study or positive PCR test in the course of routine clinical practice

    Measure: Documented cumulative incidence of SARS-CoV-2 infection

    Time: Up to 4 months

    Secondary Outcomes

    Description: Number of days of documented sick leave for SARS-CoV-2

    Measure: Sick leave for SARS-CoV-2

    Time: Up to 4 months

    Description: The number of days off work due to the quarantine imposed as a consequence to have acute respiratory symptoms, fever or infection documented by SARS-CoV-2

    Measure: Days off work due to the quarantine

    Time: Up to 4 months

    Description: Number of days of quarantine imposed by close contact outside the center with SARS-CoV-2 positive

    Measure: Quarantine imposed by close contact outside the center with SARS-CoV-2 positive

    Time: Up to 4 months

    Description: Number of MD, nursing, personnel management and services, etc.

    Measure: Professional category

    Time: Up to 4 months

    Description: Number of days of self-reported fever (≥38 ºC)

    Measure: Fever

    Time: Up to 4 months

    Description: Cumulative incidence of self-reported acute respiratory symptoms

    Measure: Incidence of self-reported acute respiratory symptoms

    Time: Up to 4 months

    Description: Number of days of self-reported acute respiratory symptoms

    Measure: Days of self-reported acute respiratory symptoms

    Time: Up to 4 months

    Description: Number of participants with pneumonia confirmed by X-ray

    Measure: Incidence of pneumonia

    Time: Up to 4 months

    Description: Cumulative incidence of death from documented SARS-CoV-2 infection

    Measure: Incidence of death from SARS-CoV-2 infection

    Time: Up to 4 months

    Description: Cumulative incidence of admissions to intensive care unit for documented SARS-CoV-2 infection

    Measure: Incidence of admissions to Intensive Care Unit (ICU)

    Time: Up to 4 months

    Description: Number of days admitted to the ICU for documented SARS-CoV-2 infection

    Measure: Days in ICU

    Time: Up to 4 months

    Description: Cumulative incidence of need for mechanical ventilation due to documented SARS-CoV-2 infection

    Measure: Incidence of mechanical ventilation

    Time: Up to 4 months

    Description: Cumulative incidence of hospital admissions for documented SARS-CoV-2 infection

    Measure: Incidence of hospital admissions

    Time: Up to 4 months

    Description: Number of days of hospitalization for documented SARS-CoV-2 infection

    Measure: Days of hospitalization

    Time: Up to 4 months

    Description: Incidence of SARS-CoV-2 antibodies at the end of the study period

    Measure: Incidence of SARS-CoV-2 antibodies

    Time: Final visit

    Description: Frequency and levels of immunoglobulin IgG and immunoglobulin IgM

    Measure: Types of antibodies detected

    Time: Final visit

    Description: Levels of SARS-CoV-2 antibodies at the end of the study period

    Measure: Levels of SARS-CoV-2 antibodies

    Time: Final visit

    Other Outcomes

    Description: All adverse events reported by the subjects, both serious and non-serious, will be collected. All events related to a SARS-CoV-2 infection will be exempted from collection as part of the associated symptoms.

    Measure: AEs

    Time: Up to 4 months

    Description: All those Adverse Events that lead to hospitalization of the patient, that endanger his life or cause or may cause death.

    Measure: SAEs

    Time: Up to 4 months
    225 A Randomized, Placebo-controlled Study to Evaluate the Safety, Pharmacokinetics and Efficacy of a Single Dose of STI-1499 (COVI-GUARD™) in Hospitalized Patients With Moderate COVID-19

    Randomized, placebo-controlled study to evaluate the safety, pharmacokinetics and efficacy of a single dose of STI-1499 (COVI-GUARD™) in hospitalized patients with moderate COVID-19

    NCT04454398
    Conditions
    1. Covid-19
    Interventions
    1. Biological: COVI-GUARD
    2. Other: Standard of Care
    3. Drug: Placebo

    Primary Outcomes

    Description: Types, frequencies, and severities of adverse events and their relationships to COVI-GUARD

    Measure: Incidence of adverse events (safety)

    Time: Randomization through study completion through Day 60

    Description: Types, frequencies, and severities of treatment-emergent adverse events and their relationships to COVI-GUARD

    Measure: Incidence of treatment-emergent adverse events (safety)

    Time: Randomization through study completion through Day 60

    Description: Types, frequencies, and severities of serious adverse events and their relationships to COVI-GUARD

    Measure: Incidence of serious adverse events (safety)

    Time: Randomization through study completion through Day 60

    Description: All-cause mortality at 29 and 60 days

    Measure: All-cause mortality at 29 and 60 days

    Time: Randomization through Day 29 and Day 60

    Description: Dose-limiting toxicities, particularly presence of acute or delayed hypersensitivity reactions

    Measure: Incidence of dose-limiting toxicities (safety)

    Time: Randomization through study completion through Day 60

    Description: Clinically meaningful laboratory abnormalities

    Measure: Incidence of laboratory abnormalities (safety)

    Time: Randomization through study completion through Day 60

    Description: Plasma samples and salivary samples are taken to correlate viral load with nasopharyngeal testing at various timepoints; stool or rectal swab samples are taken if possible for additional virologic assessments

    Measure: SARS-CoV-2 viral load as assessed using various sample types

    Time: Randomization through study completion through Day 60

    Description: Time from onset of COVID-19 symptoms to hospitalization and to treatment on Day 1, and if applicable, time to ICU admission, discharge from ICU and discharge from hospital

    Measure: Time to hospitalization, treatment, ICU admission, and discharge from ICU and/or hospital

    Time: Randomization up to study completion through Day 60

    Description: Presence and levels of anti-drug antibodies (ADA) directed to COVI-GUARD

    Measure: Anti-drug antibodies

    Time: Randomization through study completion through Day 60

    Description: Levels of cytokines including EGF, IFNγ, IL-1β, IL-6, IL-8, IL-10, and TNFα

    Measure: Cytokine levels

    Time: Randomization through study completion through Day 60

    Secondary Outcomes

    Description: Area under the serum concentration-time curve (AUC) of COVI-GUARD

    Measure: AUC of COVI-GUARD (PK)

    Time: Randomization through study completion through Day 60

    Description: Maximum observed serum concentration (Cmax) of COVI-GUARD

    Measure: Cmax of COVI-GUARD (PK)

    Time: Randomization through study completion through Day 60

    Description: Apparent serum terminal elimination half life (t½) of COVI-GUARD

    Measure: t½ of COVI-GUARD (PK)

    Time: Randomization through study completion through Day 60

    Description: Time to Cmax (Tmax) of COVI-GUARD

    Measure: Tmax of COVI-GUARD (PK)

    Time: Randomization through study completion through Day 60
    226 Pilot Double Blinded Randomized Placebo Controlled Multi Central Clinical Trial on Inflammatory Regulation Effect of NAC on COVID-19

    Study times to evaluate the efficacy of N-Acetylcysteine therapy in the management of adult admitted patients with COVID-19.

    NCT04455243
    Conditions
    1. COVID-19
    Interventions
    1. Drug: N-Acetyl cysteine
    2. Drug: Placebo

    Primary Outcomes

    Description: Day of recovery is defined as the first day on which of the following three categories from The Ordinal Scale on Covid-19 Clinical Improvement Not-Hospitalized, No limitation on activity. Not Hospitalized, with limitation on activity. Hospitalized, Not requiring supplemental Oxygen

    Measure: Time to Recovery

    Time: 28 days
    227 Double-Blind, Randomized, Placebo-Controlled Phase III Clinical Trial to Evaluate Efficacy and Safety in Healthcare Professionals of the Adsorbed COVID-19 (Inactivated) Vaccine Manufactured by Sinovac

    This is a phase III clinical trial to assess efficacy and safety of the Adsorbed COVID-19 (inactivated) vaccine manufactured by Sinovac in health care professionals

    NCT04456595
    Conditions
    1. COVID-19
    Interventions
    1. Biological: Adsorbed COVID-19 (inactivated) Vaccine
    2. Biological: Placebo

    Primary Outcomes

    Description: Number of virologically-confirmed symptomatic COVID-19 two weeks after second dose of vaccine

    Measure: Incidence of COVID-19 cases after two-doses immunization schedule

    Time: Two weeks after second dose up to one year after first dose

    Description: Frequency of adverse reaction in the seven days following each immunization per age group

    Measure: Frequency of adverse events up to seven days after immunization

    Time: Seven days after each immunization

    Secondary Outcomes

    Description: Number of virologically-confirmed symptomatic COVID-19 two weeks after second dose of vaccine according to previous exposure to SARS-CoV-2

    Measure: Incidence of COVID-19 cases after two-doses immunization schedule according to previous exposure

    Time: Two weeks after first dose up to one year after first dose

    Description: Number of virologically-confirmed symptomatic COVID-19 two weeks after first dose of vaccine, regardless the vaccination schedule was completed

    Measure: Incidence of COVID-19 cases after 14-days of first immunization

    Time: Two weeks after last dose uup to one year after first dose

    Description: Number of virologically-confirmed and or serologically-confirmed SARS-CoV-2 infections two weeks after first dose of vaccine

    Measure: Combined incidence of SARS-CoV-2 infection

    Time: Two weeks after second dose up to one year after first dose

    Description: Number of virologically-confirmed severe COVID-19 two weeks after second dose of vaccine

    Measure: Incidence of severe COVID-19 cases after two-doses immunization schedule

    Time: Two weeks after second dose up to one year after first dose

    Description: Frequency of adverse reaction in the 28 days following each immunization per age group

    Measure: Frequency of adverse events up to 28 days after immunization

    Time: 28 days after each immunization

    Description: Frequency of virologically-confirmed severe COVID-19 cases after receiving, at least, one dose of the vaccine

    Measure: Frequency of severe COVID-19 cases

    Time: From first vaccination up to one year after first dose

    Description: Frequency of adverse events of special interest after receiving, at least, one dose of the vaccine

    Measure: Frequency of adverse events of special interest after immunization

    Time: From first vaccination up to one year after first dose

    Description: Number of seroconversion responses to SARS-CoV-2 in the second week after each vaccination per age group in a subset of participants

    Measure: Seroconversion rate

    Time: Two weeks after each vaccination

    Description: Number of cell-mediated immune response against SARS-CoV-2 in the week two and four after the second vaccination per age group in a subset of participants

    Measure: Cell-mediated immune profile

    Time: Two and four weeks afer each vaccination

    Description: Number of seropositive responses to SARS-CoV-2 in the second week after each vaccination per age group in a subset of participants

    Measure: Seropositivity rate

    Time: Two weeks after second vaccination
    228 A Double-Blind, Placebo-Controlled Phase 2 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of OP-101 (Dendrimer N-acetyl-cysteine) in Patients With Severe COVID-19

    The primary purpose is to evaluate the safety and tolerability of OP-101 and secondary purpose is to determine the effect of OP-101 reducing proinflammatory cytokines after a single dose in severe COVID-19 Patients.

    NCT04458298
    Conditions
    1. COVID-19
    Interventions
    1. Drug: OP-101
    2. Drug: Placebo

    Primary Outcomes

    Description: Number of participants with treatment emergent adverse events will be evaluated as a measure of safety and tolerability of OP-101 by monitoring and documenting all adverse events, which include laboratory test variables.

    Measure: Number of Participants with Treatment Emergent Adverse Events Graded as Assessed by CTCAE Version 4.0

    Time: Up to Day 60

    Secondary Outcomes

    Description: WHO-7 is a 7 point ordinal scale for clinical improvement with scores ranging from 0 to 7 where 0= uninfected, 1= no limitation of activities (ambulatory), 2= limitation of activities (ambulatory), 3= hospitalized, no oxygen therapy (hospitalized mild disease), 4= Hospitalized, oxygen by mask or nasal prongs (hospitalized mild disease), 5= Hospitalized, noninvasive ventilation or high-flow oxygen (hospitalized severe disease), 6= Hospitalized, intubation and mechanical ventilation (hospitalized severe disease), 7= Hospitalized, ventilation + additional organ support - pressors, renal replacement therapy, ECMO.

    Measure: Time to Improvement (2 points) in Clinical Status Assessment Using the World Health Organization 7-Point Ordinal Scale (WHO 7OS)

    Time: Up to Day 30

    Measure: Time to Resolution of Fever for at least 48 hours Without Antipyretics for Patients with Documented Fever (>=37.2 degree celsius [oral], or >=37.8 degree celsius [rectal], or >=38.0 degree celsius [tympanic])

    Time: Up to Day 30

    Description: Improvement in oxygenation is defined by increase in pulse oxygen saturation/fraction of inspired oxygen (SpO2/FiO2) of >=50 compared with nadir SpO2/FiO2.

    Measure: Time to Improvement in Oxygenation for at least 48 hours

    Time: Up to Day 30

    Description: WHO-7 is a 7 point ordinal scale for clinical improvement with scores ranging from 0 to 7 where 0= uninfected, 1= no limitation of activities (ambulatory), 2= limitation of activities (ambulatory), 3= hospitalized, no oxygen therapy (hospitalized mild disease), 4= Hospitalized, oxygen by mask or nasal prongs (hospitalized mild disease), 5= Hospitalized, noninvasive ventilation or high-flow oxygen (hospitalized severe disease), 6= Hospitalized, intubation and mechanical ventilation (hospitalized severe disease), 7= Hospitalized, ventilation + additional organ support - pressors, renal replacement therapy, ECMO.

    Measure: Change from Baseline in the World Health Organization (WHO)-7 Point Ordinal Scale

    Time: Baseline up to Day 30

    Description: NEWS2 consists of: Physiological Parameters: Respiration rate (per minute), SpO2 Scale 1 (%), SpO2 Scale 2 (%), Use of Air or oxygen, Systolic blood pressure (mmHg), Pulse (per minute), Consciousness, Temperature (°C).

    Measure: Time to Discharge from Clinic or Hospital or to National Early Warning Score 2 (NEWS2) of <=2 and maintained for 24 hours

    Time: Up to Day 30

    Measure: Percentage of Patients Alive and not Using Supplemental Oxygen at Time of Discharge from Hospital/Clinic or Day 30

    Time: Up to Day 30

    Measure: Number of Days of Resting Respiratory Rate of more than 24 breath/min

    Time: Up to Day 30

    Description: Hypoxemia is defined by Saturation of Peripheral Oxygen (SpO2) of less than (<) 95 percent (%) on room air or acute respiratory distress syndrome (ARDS).

    Measure: Number of Days with Hypoxemia

    Time: Up to Day 30

    Measure: Number of Days of Supplemental Oxygen use

    Time: Up to Day 30

    Measure: Number of Ventilator-free Days

    Time: Up to Day 28

    Measure: Number of Days in Intensive Care Unit (ICU)

    Time: Up to Day 30

    Measure: Number of Days of Hospitalization for Survivors

    Time: Up to Day 30

    Measure: Number of Participants with all cause deaths

    Time: Up to Day 30

    Description: Percent change from baseline in proinflammatory cytokines (C-reactive protein [CRP], ferritin, and interleukin-6 [IL-6]) will be reported.

    Measure: Percent change from baseline in Proinflammatory Cytokines

    Time: Baseline up to Day 30

    Measure: Incidence of Drug-related Serious Adverse Events (SAEs)

    Time: Up to Day 60
    229 A Phase 1b, Randomized, Double-blind, Single and Repeat Dosing Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Lanadelumab When Added to Standard-of-Care in Subjects Hospitalized With COVID-19 Pneumonia

    The purpose of this study is to evaluate the safety, pharmacokinetic and pharmacodynamics of lanadelumab administered by intravenous (IV) infusion when added to standard-of-care (SoC) in adults hospitalized with COVID-19 pneumonia.

    NCT04460105
    Conditions
    1. COVID-19 Pneumonia
    Interventions
    1. Drug: Lanadelumab
    2. Other: Placebo
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Treatment-emergent adverse events are defined as Adverse events (AEs) with onset at the time of or following the start of treatment with study medication, or medical conditions present prior to the start of treatment but increasing in severity or relationship at the time of or following the start of treatment. SAE is any untoward clinical manifestation of signs, symptoms or outcomes (whether considered related to investigational product or not and at any dose: results in death, is lifethreatening, requires inpatient hospitalization or prolongation of hospitalization, results in persistent or significant disability/incapacity, congenital abnormality/birth defect, an important medical event. AESI will include hypersensitivity reactions, events of disordered coagulation such as bleeding AESI, hypercoagulable AESI. Number of participants with TEAEs including AESI and SAE will be assessed.

    Measure: Number of Participants with Treatment emergent adverse events (TEAEs)

    Time: From start of study drug administration to follow-up (up to Day 29)

    Secondary Outcomes

    Description: Pharmacokinetic plasma concentrations of lanadelumab after a single and repeat intravenous (IV) doses will be assessed.

    Measure: Pharmacokinetic (PK) Plasma Concentrations of Lanadelumab

    Time: Single-dose Cohort: Pre-dose, 1, 24, 72, 144, 216, 336 hours post-dose; Repeat-dose Cohort: Pre-dose, 1, 24, 72, 73, 144, 216, 336 hours post-dose

    Description: Percentage change from baseline in pKal activity to assess pharmacodynamics (PD) of lanadelumab.

    Measure: Percentage Change from Baseline in Plasma Kallikrein Activity (pKal)

    Time: Single-dose Cohort: Pre-dose, 1, 24, 72, 144, 216, 336 hours post-dose; Repeat-dose Cohort: Pre-dose, 72, 144, 216, 336 hours post-dose

    Description: Percentage change from baseline in cHMWK levels to assess PD of lanadelumab.

    Measure: Percentage Change from Baseline in Cleaved High Molecular Weight Kininogen (cHMWK)

    Time: Single-dose Cohort: Pre-dose, 1, 24, 72, 144, 216, 336 hours post-dose; Repeat-dose Cohort: Pre-dose, 72, 144, 216, 336 hours post-dose

    Description: Percentage change from baseline in functional C1-INH levels to assess PD of lanadelumab.

    Measure: Percentage Change from Baseline in Functional C1-Inhibitor (C1-INH)

    Time: Single-dose Cohort: Pre-dose, 1, 24, 72, 144, 216, 336 hours post-dose; Repeat-dose Cohort: Pre-dose, 72, 144, 216, 336 hours post-dose
    230 PREPARE-IT. Prevention of COVID19 With EPA in Healthcare Providers at Risk - Intervention Trial

    The PREPARE-IT trial is a simple, pragmatic and universally applicable strategy with icosapent ethyl (IPE) at high doses intended to reduce infection rate and subsequent morbidity and mortality among subjects at high risk of infection due to COVID-19.

    NCT04460651
    Conditions
    1. COVID19
    Interventions
    1. Drug: Icosapent ethyl (IPE)
    2. Drug: Placebo

    Primary Outcomes

    Description: SARS-CoV-2 positive subjects are defined as subjects with positive tests for SARS-CoV-2 RT-PCR or for SARS-CoV-2 lgG antibodies after developing COVID-19 disease at any stage within the follow-up period (including those subjects with or without symptomatic COVID-19 evaluated before the final visit) or those individuals who test positive for SARS-CoV-2 RT-PCR or for SARS-CoV-2 lgG antibodies at the final visit (day 60).

    Measure: Percentage of SARS-CoV-2 positive subjects

    Time: 60 days

    Measure: Highest mean WHO descriptive score of COVID-19 in the active treatment group compared to the placebo group.

    Time: 60 days

    Secondary Outcomes

    Measure: Highest mean WHO score up to day 60 for the active treatment group as compared to placebo among subjects with a positive test received at any moment during the study after the first visit

    Time: 60 days

    Description: Mean change from baseline will be computed

    Measure: Total cholesterol, LDL, HDL, triglycerides (mg/dL) at baseline and at day 60

    Time: baseline, 60 days

    Description: Mean change from baseline will be computed

    Measure: Ultrasensitive C-reactive Protein (mg/dL) at baseline and at day 60

    Time: baseline, 60 days

    Measure: Difference in hospital length of stay between groups

    Time: 60 days

    Measure: Difference in duration of mechanical ventilation in both groups

    Time: 60 days

    Measure: Rate of hospital admissions due to SARS (Severe Acute Respiratory Syndrome) in patients who were negative for SARS CoV-2 upon admission

    Time: 60 days

    Measure: Mean highest WHO descriptive score in active treatment versus placebo groups up to day 60 among hospitalized patients (WHO grades 3 or more) without serum evidence / PCR detecting SARS-CoV-2 infection

    Time: 60 days

    Measure: Rate of total events, non-fatal myocardial infarction or non-fatal stroke or death (initial and subsequent), up to day 60

    Time: 60 days
    231 A Phase 1 Randomized Double Blind Placebo Controlled, Single-Dose, Dose-Escalation Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Orally Inhaled Aerosolized Hydroxychloroquine Sulfate in Healthy Adult Volunteers

    This study is 'A Randomized Phase 1 Double Blind Placebo Controlled, Single-Dose, Dose-Escalation Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Orally Inhaled Aerosolized Hydroxychloroquine Sulfate in Healthy Adult Volunteers.' The primary objectives are as follows: - To assess the safety and tolerability of AHCQ administered as a single dose by oral inhalation in healthy individuals at escalating doses until either the maximum tolerated dose (MTD) is identified or 1 mL of a 50 mg/mL solution is administered. - To determine the recommended Phase 2a dose (RP2D). Secondary objectives: • To characterize pharmacokinetics (PK) of single dose AHCQ in healthy individuals.

    NCT04461353
    Conditions
    1. Severe Acute Respiratory Syndrome Coronavirus 2
    Interventions
    1. Drug: Aerolized Hydroxychloroquine Sulfate
    2. Other: Placebo
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome

    Primary Outcomes

    Description: TEAEs (defined as AEs with onset after study drug administration or existing AEs that worsen in severity after study drug administration)

    Measure: Incidences of treatment-emergent adverse events (TEAEs) as assessed by TGSHAAV (September 2007) or CTCAE version 5.0

    Time: after treatment (Day 1) through to Day 30

    Description: Blood sample collected for CBC with differential will be assessed from baseline (at screening)

    Measure: Change from baseline in clinical laboratory test results for CBC with differential

    Time: Screening and Day 8

    Description: Screening blood sample collected for CBC with differential, counting the number of abnormal clinical tests

    Measure: Incidence of abnormal laboratory test results for CBC with differential at Screening

    Time: Screening

    Description: Day 8 blood sample collected for CBC with differential

    Measure: Incidence of abnormal laboratory test results for CBC with differential - Day 8

    Time: Day 8

    Description: Blood sample collected for blood glucose and measured with a glucometer

    Measure: Changes from baseline for blood glucose

    Time: Screening and Day 1

    Description: Blood sample collected for chemistry panel (albumin, total protein, ALP, ALT, AST, direct and indirect bilirubin, GGT, BUN, creatinine, glucose, bicarbonate, calcium, chloride, magnesium, phosphate, potassium, sodium, and LDH)

    Measure: Incidence of abnormal laboratory test results for chemistry -Screening

    Time: Screening

    Description: Blood sample collected for chemistry panel (albumin, total protein, ALP, ALT, AST, direct and indirect bilirubin, GGT, BUN, creatinine, glucose, bicarbonate, calcium, chloride, magnesium, phosphate, potassium, sodium, and LDH)

    Measure: Incidence of abnormal laboratory tests results for chemistry - Day 8

    Time: Day 8

    Description: Collection of urine sample to test pH, specific gravity, protein, glucose, ketones, urobilinogen, bilirubin, leukocyte esterase, squamous cells, epithelial cells, clarity, bacteria, blood

    Measure: Incidence of abnormal laboratory tests results for urinalysis - Screening

    Time: Screening

    Description: Collection of urine sample to test pH, specific gravity, protein, glucose, ketones, urobilinogen, bilirubin, leukocyte esterase, squamous cells, epithelial cells, clarity, bacteria, blood

    Measure: Incidence of abnormal laboratory tests results for urinalysis- Day 8

    Time: Day 8

    Description: The Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventative Vaccine Clinical Trials (September 2007) (TGSHAAV) will be used as the primary criteria for assessment of clinical abnormalities. Mild (17-20 breaths per minute) to Potentially Life Threatening (intubation)

    Measure: Changes in vital signs from baseline (pre-dose) - respiratory rate

    Time: Screening, Day 1, Day 2 and Day 8

    Description: Oral temperature

    Measure: Changes in vital signs from baseline (pre-dose)- temperature

    Time: Screening, Day 1, Day 2 and Day 8

    Description: Systolic and diastolic blood pressure

    Measure: Changes in vital signs from baseline (pre-dose) - seated blood pressure

    Time: Screening, Day 1, Day 2 and Day 8

    Description: Heart rate measure by radial pulse rate (beats/min)

    Measure: Changes in vital signs from baseline (pre-dose) - pulse

    Time: Screening, Day 1, Day 2 and Day 8

    Description: O2 saturation (%), measured by pulse oximeter. Graded as per TGSHAAV (September 2007) from Moderate (pulse oximeter <92%) to Potentially Life Threatening (Life-threatening airway compromise; urgent intervention indicated)

    Measure: Changes in vital signs from baseline (pre-dose) - O2 saturation

    Time: Screening, Day 1, Day 2 and Day 8

    Description: Physical exam by clinician. A directed physical examination will be conducted

    Measure: Incidence of abnormal and physical examinations findings during Screening- general appearance

    Time: Screening

    Description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted

    Measure: Incidence of abnormal and physical examinations findings on Day 1 - general appearance

    Time: Day 1

    Description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted

    Measure: Incidence of abnormal and physical examinations findings on Day 2- general appearance

    Time: Day 2

    Description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted

    Measure: Incidence of abnormal and physical examinations findings on Day 8- general appearance

    Time: Day 8

    Description: Physical exam by clinician. A directed physical examination will be conducted

    Measure: Incidence of abnormal and physical examinations findings during Screening- neurological

    Time: Screening

    Description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted

    Measure: Incidence of abnormal and physical examinations findings on Day 1- neurological

    Time: Day 1

    Description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted

    Measure: Incidence of abnormal and physical examinations findings on Day 2- neurological

    Time: Day 2

    Description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted

    Measure: Incidence of abnormal and physical examinations findings on Day 8- neurological

    Time: Day 8

    Description: Physical exam by clinician. A directed physical examination will be conducted

    Measure: Incidence of abnormal and physical examinations findings during Screening - heart/cardiovascular

    Time: Screening

    Description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted

    Measure: Incidence of abnormal and physical examinations findings on Day 1 - heart/cardiovascular

    Time: Day 1 (pre-dose, within 3 hours of dose)

    Description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted

    Measure: Incidence of abnormal and physical examinations findings on Day 2 - heart/cardiovascular

    Time: Day 2

    Description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted

    Measure: Incidence of abnormal and physical examinations findings on Day 8 - heart/cardiovascular

    Time: Day 8

    Description: Physical exam by clinician. A directed physical examination will be conducted

    Measure: Incidence of abnormal and physical examinations findings during Screening - lungs

    Time: Screening

    Description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted

    Measure: Incidence of abnormal and physical examinations findings on Day 1 - lungs

    Time: Day 1

    Description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted

    Measure: Incidence of abnormal and physical examinations findings on Day 2 - lungs

    Time: Day 2

    Description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted

    Measure: Incidence of abnormal and physical examinations findings on Day 8 - lungs

    Time: Day 8

    Description: Physical exam by clinician. A directed physical examination will be conducted

    Measure: Incidence of abnormal and physical examinations findings during Screening- abdomen

    Time: Screening

    Description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted

    Measure: Incidence of abnormal and physical examinations findings on Day 1 - abdomen

    Time: Day 1

    Description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted

    Measure: Incidence of abnormal and physical examinations findings on Day 2- abdomen

    Time: Day 2

    Description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted

    Measure: Incidence of abnormal and physical examinations findings on Day 8- abdomen

    Time: Day 8

    Description: Physical exam by clinician. A directed physical examination will be conducted

    Measure: Incidence of abnormal and physical examinations findings during screening- endocrine

    Time: Screening

    Description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted

    Measure: Incidence of abnormal and physical examinations findings on Day 1 - endocrine

    Time: Day 1

    Description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted

    Measure: Incidence of abnormal and physical examinations findings on Day 2- endocrine

    Time: Day 2

    Description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted

    Measure: Incidence of abnormal and physical examinations findings on Day 8- endocrine

    Time: Day 8

    Description: Physical exam by clinician. A directed physical examination will be conducted

    Measure: Incidence of abnormal and physical examinations findings during Screening- extremities

    Time: Screening

    Description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted

    Measure: Incidence of abnormal and physical examinations findings on Day 1- extremities

    Time: Day 1

    Description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted

    Measure: Incidence of abnormal and physical examinations findings on Day 2- extremities

    Time: Day 2

    Description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted

    Measure: Incidence of abnormal and physical examinations findings on Day 8- extremities

    Time: Day 8

    Description: Physical exam by clinician. A directed physical examination will be conducted

    Measure: Incidence of abnormal and physical examinations findings during Screening- lymphatic

    Time: Screening

    Description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted

    Measure: Incidence of abnormal and physical examinations findings on Day 1- lymphatic

    Time: Day 1

    Description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted

    Measure: Incidence of abnormal and physical examinations findings on Day 2 - lymphatic

    Time: Day 2

    Description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted

    Measure: Incidence of abnormal and physical examinations findings on Day 8- lymphatic

    Time: Day 8

    Description: A directed physical examination will be conducted

    Measure: Incidence of abnormal and physical examinations findings during screening - skin

    Time: Screening

    Description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted

    Measure: Incidence of abnormal and physical examinations findings on Day 1 - skin

    Time: Day 1

    Description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted

    Measure: Incidence of abnormal and physical examinations findings on Day 2 - skin

    Time: Day 2

    Description: Physical exam by clinician. A directed physical examination assessing and documenting changes from the previous visit, including any new abnormalities, will be conducted

    Measure: Incidence of abnormal and physical examinations findings on Day 8 - skin

    Time: Day 8

    Description: Pulmonary function testing and recording of FEV1, both actual and percent predicted

    Measure: Changes from baseline for pulmonary function tests (PFTs) - FEV1

    Time: Screening, Day 1 at pre-dose (within 25 minutes of dose) and at +15 minutes, +1, +3 and +6 hours after study treatment, and on Day 2 and Day 8.

    Description: Pulmonary function testing and recording of FVC, , both actual and percent predicted

    Measure: Changes from baseline for pulmonary function tests (PFTs) - FVC

    Time: Screening, Day 1 at pre-dose (within 25 minutes of dose) and at +15 minutes, +1, +3 and +6 hours after study treatment, and on Day 2 and Day 8.

    Description: Pulmonary function testing and recording of FEV1/FVC

    Measure: Changes from baseline for pulmonary function tests (PFTs) - FEV1/FVC

    Time: creening, Day 1 at pre-dose (within 25 minutes of dose) and at +15 minutes, +1, +3 and +6 hours after study treatment, and on Day 2 and Day 8.

    Description: The ECG will be performed after the participant is allowed to rest seated for at least 5 minutes, before transferring to the examination bed/table for the ECG. ECG will be performed before PFTs or blood drawing. ECG QT Interval (msec) will be the assessment parameter.

    Measure: Changes from baseline for ECG readings - QT interval

    Time: Screening and on Day 1 pre-dose (within 3 hours of dose) and approximately +2 and +6 hours, and on Days 2 and 8.

    Description: The ECG will be performed after the participant is allowed to rest seated for at least 5 minutes, before transferring to the examination bed/table for the ECG. ECG will be performed before PFTs or blood drawing. ECG QTcB interval (msec) will be the assessment parameter.

    Measure: Changes from baseline for ECG readings - QTcB Interval

    Time: Screening and on Day 1 pre-dose (within 3 hours of dose) and approximately +2 and +6 hours, and on Days 2 and 8.

    Description: The ECG will be performed after the participant is allowed to rest seated for at least 5 minutes, before transferring to the examination bed/table for the ECG. ECG will be performed before PFTs or blood drawing. ECG QRS duration (msec) will be the assessment parameter.

    Measure: Changes from baseline for ECG readings - QRS duration

    Time: Screening and on Day 1 pre-dose (within 3 hours of dose) and approximately +2 and +6 hours, and on Days 2 and 8.

    Description: The ECG will be performed after the participant is allowed to rest seated for at least 5 minutes, before transferring to the examination bed/table for the ECG. ECG will be performed before PFTs or blood drawing. ECG PR interval (msec) will be the assessment parameter.

    Measure: Changes from baseline for ECG readings - PR interval

    Time: Screening and on Day 1 pre-dose (within 3 hours of dose) and approximately +2 and +6 hours, and on Days 2 and 8.

    Description: The ECG will be performed after the participant is allowed to rest seated for at least 5 minutes, before transferring to the examination bed/table for the ECG. ECG will be performed before PFTs or blood drawing. ECG heart rate (beats/min) will be the assessment parameter.

    Measure: Changes from baseline for ECG readings - heart rate

    Time: Screening and on Day 1 pre-dose (within 3 hours of dose) and approximately +2 and +6 hours, and on Days 2 and 8.

    Description: The ECG will be performed after the participant is allowed to rest seated for at least 5 minutes, before transferring to the examination bed/table for the ECG. ECG will be performed before PFTs or blood drawing. ECG QT Interval will be the assessment parameter.

    Measure: Incidence of abnormal ECG - Screening

    Time: Screening

    Description: The ECG will be performed after the participant is allowed to rest seated for at least 5 minutes, before transferring to the examination bed/table for the ECG. ECG will be performed before PFTs or blood drawing. ECG QT Interval will be the assessment parameter.

    Measure: Incidence of abnormal ECG- Day 1

    Time: Day 1 pre-dose (within 3 hours of dose) and +2 and +6 hours

    Description: The ECG will be performed after the participant is allowed to rest seated for at least 5 minutes, before transferring to the examination bed/table for the ECG. ECG will be performed before PFTs or blood drawing. ECG QT Interval will be the assessment parameter.

    Measure: Incidence of abnormal ECG - Day 2

    Time: Days 2

    Description: The ECG will be performed after the participant is allowed to rest seated for at least 5 minutes, before transferring to the examination bed/table for the ECG. ECG will be performed before PFTs or blood drawing. ECG QT Interval will be the assessment parameter.

    Measure: Incidence of abnormal ECG - Day 8

    Time: Days 8.

    Secondary Outcomes

    Description: Blood samples for PK analysis will be collected via indwelling catheter or via direct venipuncture.

    Measure: HCQ concentration in whole blood versus time profiles

    Time: Day 1 pre-dose (time 0) and +2, +3, +5, and +15 minutes after dose, and also +1, +2, +4 and +6 hours post-dose completion. Day 2 (+24±4 hours post dose) and Day 8.
    232 Prevention, Efficacy and Safety of BCG Vaccine in COVID-19- Randomized Clinical Trial

    In Mexico the total number of confirmed cases of COVID-19 is 232, 000 and 28,510 deaths. Health workers are at high risk of COVID-19 infection. Their absence from work dramatically limits the ability to contain the disease. There is currently no vaccine to prevent the disease. Since the introduction to the vaccination schedule of the Bacillus Calmette-Guerin (BCG) live attenuated vaccine directed towards tuberculosis prevention, a decrease in infant mortality has been reported, not related only to tuberculosis. BCG vaccine has been hypothesized to have a non-specific role towards other unrelated pathogens such as viruses that cause airway disease, with reduced morbidity and mortality. In murine as well as in human models it has been shown to decrease the incidence of acute respiratory influenza infections. Likewise, in countries with a high endemicity for tuberculosis, the BCG vaccine reduces the incidence of respiratory infections by up to 80% . In healthy subjects, the BCG vaccine increases the production of proinflammatory cytokines in monocytes. Likewise, it increases the epigenetic response, causing an increase in the transcription of genes important in the antimicrobial response, as well as an improvement in cellular function. This is the first national clinical trial to evaluate prospectively the effect that the BCG vaccine offers towards the prevention and reduction of severity in cases of COVID-19.

    NCT04461379
    Conditions
    1. BCG
    2. COVID-19
    3. SARS-CoV2
    4. Corona Virus Infection
    Interventions
    1. Biological: BCG vaccine
    2. Other: Placebo
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome

    Primary Outcomes

    Description: Cumulative incidence of infection in 6 months: disease defined as positive SARS-Cov-2 test (serology), plus fever (using self-reported questionnaire), or at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure (using self-reported questionnaire)

    Measure: Demonstrate COVID- 19 disease incidence among Health care workers:

    Time: During the 6 months study period

    Description: Cumulative incidence of hospitalization for COVID-19

    Measure: Demonstrate cumulative incidence of hospitalization for COVID-19 among Health care workers:

    Time: During the 6 months study period

    Description: Incidence of specific Antibodies (IgG and IgM) against SARS-CoV-2 will be measured at 3 and 6 months

    Measure: Demonstrate the Incidence of specific Antibodies against SARS-CoV-2 at 3 and 6 months in health care workers

    Time: During the 6 months study period

    Description: Number of participants who needed hospitalization

    Measure: Hospitalization of severe disease COVID-19

    Time: During the 6 months study period

    Description: Number of participants who Need for oxygen supplementation (nasal cannulas, masks, high flow oxygen) in hospitalized patients

    Measure: Oxygen supplementation in severe disease COVID-19

    Time: During the 6 months study period

    Description: Number of participants who Need for intubation or non-invasive ventilation in hospitalized patients

    Measure: Need for intubation or non-invasive ventilation for the patient.

    Time: During the 6 months study period

    Description: Number of participants in Critical care admission with SARS-CoV2 in hospitalized patients

    Measure: Critical care admission with SARS-CoV2

    Time: During the 6 months study period

    Description: Mortality associated to progressive pulmonary disease in hospitalized patients

    Measure: Mortality associated to progressive pulmonary disease

    Time: During the 6 months study period

    Secondary Outcomes

    Measure: Evaluate the safety of the vaccine by measuring the incidence rates of local and systemic adverse effects that occur after one month its application.

    Time: 1 month after vaccine/placebo application

    Measure: Calculate the incidence of COVID-19 complications

    Time: During the 6 months study period

    Measure: Determine the mean days of hospitalization and days in intensive care unit by COIVD-19

    Time: During the 6 months study period

    Measure: Calculate the cost associated with in-hospital medical care

    Time: During the 6 months study period

    Description: SOFA score: PaO2/FIO2 (mm Hg), SaO2/FIO2, Platelets (×10³/µL), Bilirubin (mg/dL), Hypotension, Glasgow Coma Score and Creatinine (mg/dL) or urine output (mL/d).

    Measure: Determine the scores of the Clinical Prediction Rules associated with mortality using Sequential Organ Failure Assessment (SOFA score) at the patient's hospital admission:

    Time: During the 6 months study period

    Description: APACHE: History of severe organ failure or immunocompromise Heart Failure Class IV, cirrhosis, chronic lung disease, or dialysis-dependent, Age, Temperature (C°), Mean arterial pressure (mmHg), pH, Sodium (mEq/L), Potassium (mEq/L), Creatinine (mg/dL), Hematocrit (%), WBC (x 109/L)

    Measure: Determine the scores of the Clinical Prediction Rules associated with mortality using Acute Physiology and Chronic Health disease Classification System (APACHE) at the patient's hospital admission:

    Time: During the 6 months study period

    Description: CPR, ESR, Ferritin, D-dimer, LDH,Troponins, Procalcitonin, Interleukin-6, Hemoglobin, Hematocrit, Erythrocytes, Leukocytes, MCV, HCM, MCHC, Lymphocytes, Monocytes, Eosinophils, Basophils, Platelets, Glucose, Urea, Creatinine, BUN, Sodium, Potassium, Chlorine, Calcium, Serum albumin, Direct bilirubin, Indirect bilirubin, Alkaline phosphatase, AST, ALT, bleeding time, Prothrombin Time, Activated partial thromboplastin time, Arterial / Venous Blood Gasometry, pH, pCO2, HCO3, pO2, SaO2%, Lactate.

    Measure: Evaluate and determine the alteration profile in laboratory studies at the patient's hospital admission

    Time: During the 6 months study period

    Measure: Registration of chronic medications

    Time: During the 6 months study period

    Measure: Need for vasopressors

    Time: During the 6 months study period
    233 Efficacy and Safety Study of Nitazoxanide (NTX) in the Treatment of Patients With SARS-CoC-2 Virus Infection (COVID-19). A Pilot, Randomized, Simple Blind, Placebo-controlled, Parallel-group Study

    Evaluation of the efficacy and safety of NTX in adult patients (≥18 years and <60 years), with SARS-CoV-2 infection with mild symptoms of COVID-19, compared to a placebo control arm. 135 patients will be randomized to either Nitazoxanide (n=90) or placebo (n=45) (2:1). Simple blind design. Primary endpoint: eradication of virus from patients' respiratory tract secretions by the 7th day of treatment.

    NCT04463264
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Nitazoxanide
    2. Drug: Placebo
    MeSH:Infection Virus Diseases

    Primary Outcomes

    Description: Erradication will be considered a reduction of the viral load on day 7 greater than 35% with respect to placebo. Extraction of genomic material will be performed using a QIAgen mini kit (QIAmp viral RNA) validated by the CDC (United States Center for Disease Control and Prevention (https://www.fda.gov/media/134922/download) (CDC-006-00019) Viral load will be quantified with the following detection kits: Commercial Kit: PCR-EUA-CDC-nCoV-IFU. Commercial KIT SENTINEL - STAT-NAT Covid 19B (Berlín). Rational: In mild cases of COVID-19, 50% of the patients eradicated the virus within a period of 3 weeks, 25% eradicated the virus before the 13th day, 75% during the first month and the rest were " late eradicators." This latter subgroup of patients has been associated with severe cases of COVID-19 disease.

    Measure: Eradication of SARS COV-2 from patients' respiratory tract secretions by treatment day 7th.

    Time: 7 day

    Secondary Outcomes

    Description: Consequently, in mild cases, viral eradication will likely occur more frequently during the first to second week of COVID-19 disease; less than 15% could eradicate the virus during the first week of symptom onset. From an epidemiological point of view, increasing the viral eradication rate from less than 15% to more than 35% during the first two weeks of treatment would be clinically relevant.(seven), 14 (fourteen) and 35 (thirty-five) after starting treatment compared to the baseline measurement.

    Measure: Comparative decrease of the viral load

    Time: 3 - 35 days

    Description: Clinical improvement according to the WHO COVID-19 ordinal scale. Minimun 0 (zero), (best), maximum 8 (eight) (worst)

    Measure: Clinical improvement

    Time: 1 - 35 days

    Description: Percentage of pneumonia patients meeting severity criteria.

    Measure: Pneumonia patients meeting severity criteria.

    Time: 1 - 35 days

    Description: Number of days with fever (axillary temperature higher than 37.5°C).

    Measure: Number of days with fever

    Time: 1 - 35 days

    Other Outcomes

    Description: Percentage of patients requiring mechanical ventilation through orotracheal intubation (OT) and/or ICU hospitalization.

    Measure: Patients requiring mechanical ventilation

    Time: 1 - 35 days

    Description: Mortality rate.

    Measure: Mortality rate.

    Time: 1- 35 days

    Description: Lymphocyte recovery (absolute lymphocyte count > 1000 / mm3).

    Measure: Lymphocyte recovery

    Time: 7 day

    Description: Days of ICU hospitalization.

    Measure: ICU hospitalization.

    Time: 1 - 35 days

    Description: Oxygen saturation (SpO2) > 92% (at ambient FiO2).

    Measure: Oxygen saturation

    Time: 1 - 35 days

    Description: Days of hospitalization

    Measure: Days of hospitalization

    Time: 1 - 35 days

    Description: Respiratory rate per minute (in afebrile state conditions).

    Measure: Respiratory rate

    Time: 1 - 35 days
    234 Safety and Efficacy of PHR 160 Spray on the Outcomes of Patients With COVID-19 a Multi-center Randomized Blinding Clinical Trial Study

    This study is a multi-center randomized, controlled, and blinded clinical trial study that will be performed in four medical-educational centers. In this study, the samples will be selected from among patients with SARS-CoV-2 as easy access and based on entry criteria and will be randomly divided into two groups, including a control group and an intervention group. The study will be conducted in four medical centers. From each center, 56 definitive Corona patients will be selected, who will be randomly divided into two groups of 28, for a total of 224 patients will enter the study. In the intervention group, in addition to receiving the test spray, Patients will also receive standard treatment

    NCT04463420
    Conditions
    1. COVID-19
    Interventions
    1. Drug: PHR160 Spray
    2. Drug: Placebo
    3. Drug: Standard treatment

    Primary Outcomes

    Description: shortness of breath measured by Visual analog scale (VAS) dyspnea score. The minimum score is zero means shortness of breath and the highest score is 10 means the maximum intensity of shortness of breath.

    Measure: Dyspnea

    Time: up to 14 days

    Secondary Outcomes

    Description: The length of time the patient is hospitalized after the diagnosis of COVID-19

    Measure: long of hospitalization

    Time: up to 28 days

    Description: CT scans help determine how much the lungs are affected by COVID-19.

    Measure: Radiological Treatment Response

    Time: up to 14 days

    Description: In-hospital mortality

    Measure: Mortality

    Time: Up to 28 days

    Description: There will be known allergic reactions to the drugs.

    Measure: Allergic drug

    Time: up to 14 days

    Description: Normal blood cell count and CRP count (normal laboratory range)

    Measure: Laboratory Treatment Response

    Time: up to 14 days

    Description: Using an oximeter pulse, the amount of oxygen saturation is measured. If the patient is receiving oxygen, first cut off the oxygen for 5 minutes and then measure. If the oxygen drops below 90 degrees, oxygen therapy will be re-established immediately.

    Measure: O2 saturation without supplemental oxygen

    Time: up to 14 days

    Description: Complications in both groups should be evaluated and evaluated during treatment. protective response that serves to clear the trachea, bronchi, and/or lungs of irritants and secretions that measured by Physical examination.

    Measure: drug reactions Adverse

    Time: Up to 14 days
    235 A Trial of Favipiravir Therapy in Adults With Mild Coronavirus Disease COVID-19

    Favipiravir is a selective and potent inhibitor of influenza viral RNA polymerase. It acts as a purine analogue, which selectively inhibits viral RNA-dependent RNA polymerase (RdRps). It has the characteristic of acting on RNA viruses including Ebola and Coronaviruses especially novel coronavirus (2019-nCoV). The purpose of this study is to evaluate the clinical efficacy and safety of Favipiravir in comparison to placebo in the treatment of mild COVID-19 cases. It is a Multicenter, randomized double-blinded, parallel-group trial.

    NCT04464408
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Favipiravir
    2. Drug: Placebo

    Primary Outcomes

    Description: Time from randomization to negativity in RT-PCR nucleic acid test for COVID-19 within 15 days of randomization

    Measure: PCR negative

    Time: 15 days

    Secondary Outcomes

    Description: The duration from start of treatment (Favipiravir or placebo) to normalization of pyrexia, respiratory symptoms, and relief of cough (or other relevant symptoms at enrollment) that is maintained for at least 72 hours.

    Measure: Time from randomization to clinical recovery

    Time: 15 days

    Measure: Symptoms progression based on clinical evaluation using simple scoring system.

    Time: 28 days

    Measure: Rate of daily requirement of using antipyretics, analgesics, or antibiotics.

    Time: 15 days

    Measure: 28 days mortality.

    Time: 28 days

    Measure: Rate of requirement of hospitalization, ICU admission or Mechanical ventilation.

    Time: 28 days

    Description: incidence of GI symptoms secondary to the study drug.

    Measure: Incidence of Treatment-related Adverse Events [Safety and Tolerability]

    Time: 15 days
    236 Multi-center, Randomized, Placebo Controlled, Interventional Phase 2A Clinical Trial Evaluating the Safety and Potential Efficacy of Multiple Dosing of Mesenchymal Stromal Cells in Patients With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-Cov-2)

    This is a multi-center, randomized, placebo controlled, interventional phase 2A trial to evaluate the safety profile and potential efficacy of multi-dosing of mesenchymal stromal cells (MSC) for patients with SARS-CoV-2 associated Acute Respiratory Distress Syndrome (ARDS). After informed consent, treatment assignment will be made by computer-generated randomization to administer either MSC or vehicle placebo control with a 2:1 allocation to the MSC: placebo arm.

    NCT04466098
    Conditions
    1. Acute Respiratory Distress Syndrome
    2. ARDS (Moderate or Severe)
    3. COVID-19 Pneumonia
    Interventions
    1. Biological: Mesenchymal stromal cells
    2. Other: Placebo
    MeSH:Pneumonia Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome
    HPO:Pneumonia

    Primary Outcomes

    Measure: Incidence of grade 3-5 infusional toxicities and predefined hemodynamic or respiratory adverse events related to the infusion of MSC

    Time: Within 6 hours of the start of the infusion

    Secondary Outcomes

    Measure: Incidence of a reduction in one or more biomarkers of inflammation by day 7

    Time: Day 7 after first infusion

    Measure: Trend changes in PaO2:FiO2 ratio

    Time: On the day of screening and on days 3, 7 and 14 after first infusion

    Measure: Trend changes in Mean Airway Pressure

    Time: On the day of screening and on days 3, 7 and 14 after first infusion

    Measure: Trend changes in peak pressure

    Time: On the day of screening and on days 3, 7 and 14 after first infusion

    Measure: Trend changes in plateau pressure

    Time: On the day of screening (baseline) and on days 3, 7 and 14 after first infusion

    Measure: Trend changes in Positive end-expiratory airway pressure (PEEP)

    Time: On the day of screening and on days 3, 7 and 14 after first infusion

    Measure: Incidence of mortality

    Time: 28 days after first infusion

    Measure: Incidence of mortality

    Time: 100 days after first infusion

    Measure: Number of ICU-free days

    Time: 28 days after first infusion

    Measure: Number of days alive and ventilator free composite score 3

    Time: 28 days after first infusion

    Description: Acute Lung Injury Score is a composite 4 point scoring system validated by the NHLBI ARDS Network that considers PaO2/FiO2, the level of positive end-expiratory airway pressure, respiratory compliance, and the extent of pulmonary infiltrates on the chest radiograph

    Measure: Change in acute lung injury (ALI) score 2

    Time: Baseline and Day 28 after first infusion

    Measure: Incidence of serious adverse events

    Time: 28 days after first infusion

    Measure: Number of days alive off supplemental oxygen

    Time: 100 days after first infusion
    237 Pragmatic, Double-blind, Placebo-controlled Randomized Clinical Trial, Evaluating Hydroxychloroquine for Prevention of Hospitalization and Respiratory Complications in Non-hospitalized Patients With Confirmed or Probable COVID-19

    In December 2019, a group of patients with pneumonia of unknown cause was identified in Wuhan, in the Hubei province, China. Despite the need of target specific therapeutic options for COVID-19, until now there is no proof of effectiveness of any specific intervention. Some limited observational trials and also evidence from randomized trials have shown no benefit of hydroxychloroquine in inpatient context. Thus, studies evaluating interventions in an outpatient setting in non-severe patients can provide important information related to prognosis and safety. In this way, the present study will evaluate the effectiveness and safety of the use of hydroxychloroquine in COVID-19 outpatients by means of a Randomized, double-blind, placebo-controlled trial

    NCT04466540
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Hydroxychloroquine
    2. Drug: Placebo

    Primary Outcomes

    Description: To assess if the treatment is able to avoid hospitalization due to a COVID-19-related clinical reason within 30 days of randomization in an outpatient setting. Hospitalization is considered to be hospital stay for a period > 24h or an additional hospitalized calendar day.

    Measure: Hospitalization

    Time: 30 days from randomization

    Secondary Outcomes

    Description: Affirmative answer in three or four items of the Global Initiative for Asthma (GINA) questionnaire

    Measure: Uncontrolled asthma after ≥ 5 days of starting study medication

    Time: within 30 days from randomization

    Description: Defined by clinical-radiological criteria - a history of cough and one or more of the following symptoms: sputum, dyspnea, chest pain, sweating or fever (T> 37.8o C) + Chest CT scan showing ground-glass opacity, focal consolidations or mixed opacities (including reverse halo sign), uni or bilateral

    Measure: Pneumonia

    Time: within 30 days from randomization

    Description: Defined by clinical criteria - Fever (T> 37.8o C) and otalgia + bulging of the tympanic membrane

    Measure: Otitis media

    Time: within 30 days from randomization

    Description: Day 0 of fever resolution will be defined as the first afebrile day (T <37.5o C) after inclusion in the study followed by at least two consecutive days. The temperature will be obtained through the participant report in the patient's diary

    Measure: Fever resolution time

    Time: within 30 days from randomization

    Description: Time to improve respiratory symptoms (cough, runny nose)

    Measure: Time to improve respiratory symptoms

    Time: within 30 days from randomization

    Description: Admission to ICU due to clinical reasons related to COVID-19

    Measure: Hospitalization in the Intensive Care Unit

    Time: within 30 days from randomization

    Description: Clinical need for Orotracheal Intubation as assessed by the physician responsible for the case

    Measure: Need for Orotracheal Intubation

    Time: within 30 days from randomization

    Description: Number of days on mechanical ventilation until extubation or death

    Measure: Mechanical Ventilation Time

    Time: within 30 days from randomization

    Description: Death due to any cause that occurred within 30 days after inclusion in the study

    Measure: Mortality

    Time: within 30 days from randomization

    Other Outcomes

    Description: Change in the frequency of hypoglycemic episodes in diabetic patients using hypoglycemic medication, perceived by clinical signs or symptoms or measured in a capillary or blood glucose device

    Measure: Hypoglycemia

    Time: within 30 days from randomization

    Description: Presence of cardiac arrhythmias in patients without known history of prolongation of the measure between Q wave and T wave in the heart's electrical cycle (QTc) or pre-existing heart disease;

    Measure: Palpitations

    Time: within 30 days from randomization

    Description: Change in visual acuity or new diagnosis of retinal disease not previously documented

    Measure: Reduced visual acuity

    Time: within 30 days from randomization

    Description: Change in bowel habit greater than three (3) diarrheal episodes per day during the use of hydroxychloroquine medication and 3 days after its end

    Measure: Diarrhea

    Time: within 30 days from randomization

    Description: Change in appetite during medication use hydroxychloroquine and 3 days after the end of treatment

    Measure: Anorexia

    Time: within 30 days from randomization

    Description: Perception of change in emotional lability (mood swings) during hydroxychloroquine use and 3 days after the end of treatment

    Measure: Emotional lability

    Time: within 30 days from randomization

    Description: Time from randomization to hospitalization

    Measure: Time to hospitalization after randomization

    Time: within 30 days from randomization

    Description: Clinical and vital signs assessed when admitted to hospital

    Measure: Assessment of the patient clinical status at the time of hospitalization

    Time: within 30 days from randomization
    238 A Randomized, Double-blind, Placebo-controlled Trial of Anti-SARS-CoV-2 Plasma in Hospitalized Non-ICU Patients With COVID-19

    The purpose of this study is to assess the efficacy and safety of the administration of anti-SARS-CoV-2 convalescent plasma in COVID-19 patients who are sick enough to warrant hospitalization, but not yet admitted to the ICU (prior to the onset of overwhelming disease including a systemic inflammatory response, sepsis, and/or ARDS).

    NCT04467151
    Conditions
    1. COVID-19
    Interventions
    1. Drug: anti-SARS-CoV-2 plasma
    2. Other: Placebo

    Primary Outcomes

    Description: Disease progression from the state at randomization (with a "3" or "4" on the WHO Ordinal Scale for Clinical Improvement) to requiring invasive mechanical ventilation (which is "6" or greater on the WHO scale) during the study period

    Measure: Disease progression measured by WHO scale

    Time: Day 0 through Day 28 (or hospital discharge)

    Secondary Outcomes

    Description: Comparison of the number of participants reaching a maximum daily WHO score of 5, 7, and 8 during the study period per group

    Measure: Comparison of maximum WHO score per group

    Time: Day 0 through Day 28 (or hospital discharge)

    Description: Comparison of the median and maximum daily WHO scores during the study period per group

    Measure: Comparison of decrease of median and maximum WHO score per group

    Time: Day 0 through Day 28 (or hospital discharge)

    Description: Comparison of time to clinical improvement, defined as time between randomization and time to improvement (WHO Ordinal Scale "2" first reached for at least 1 day)

    Measure: Comparison of time to clinical improvement per group

    Time: Day 0 through Day 28 (or hospital discharge)

    Description: Evaluate the time to reach score of at least 6 within 28 days

    Measure: Comparison of time to reach score of "6" or greater on the WHO scale

    Time: Day 0 through Day 28 (or hospital discharge)

    Other Outcomes

    Description: Evaluate number of days hospitalized

    Measure: Comparison of hospital length of stay per group

    Time: Day 0 through Day 28 (or hospital discharge)

    Description: Evaluate number of hours in the ICU

    Measure: Comparison of ICU length of stay per group

    Time: Day 0 through Day 28 (or hospital discharge)
    239 Opaganib, a Sphingosine Kinase-2 (SK2) Inhibitor in COVID-19 Pneumonia: a Randomized, Double-blind, Placebo-Controlled Phase 2/3 Study, in Adult Subjects Hospitalized With Severe SARS-CoV-2 Positive Pneumonia

    A phase 2/3 multi-center randomized, double-blind, parallel arm, placebo- controlled study in Adult Subjects Hospitalized with Severe SARS-CoV-2 Positive Pneumonia to determine the potential of opaganib to improve and/or stabilize the clinical status of the patient.

    NCT04467840
    Conditions
    1. COVID-19
    2. Lung Infection
    Interventions
    1. Drug: Opaganib
    2. Drug: Placebo
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: To compare the proportion of patients requiring intubation and mechanical ventilation by Day 14 between subjects taking opaganib and those on placebo.

    Measure: Intubation and mechanical ventilation

    Time: 14 days

    Secondary Outcomes

    Description: Compare scores of subjects taking opaganib and those on placebo, lower scores indicate improvement.

    Measure: WHO Ordinal Scale for Clinical Improvement with a scale ranging from 8 down to 0

    Time: 14 days

    Description: To compare the time to intubation and mechanical ventilation between subjects taking opaganib and those on placebo.

    Measure: Time to intubation and mechanical ventilation

    Time: 14 days

    Description: To compare the time to low oxygen flow via nasal cannula e.g. from high oxygen flow via nasal cannula or CPAP, if high oxygen flow is not an available option between subjects taking opaganib and those on placebo.

    Measure: Time to low oxygen flow via nasal cannula

    Time: 14 days

    Description: To compare the proportion of patients no longer requiring supplemental oxygen for at least 24 hours by Day 14 between subjects taking opaganib and those on placebo.

    Measure: Supplemental oxygen requirement

    Time: 14 days

    Description: To compare the total oxygen requirement (area under the curve) using daily supplemental oxygen flow (L/min) over 14 days (Day 1 to Day 14) between subjects taking opaganib and those on placebo.

    Measure: Total daily oxygen requirement

    Time: 14 days

    Description: To compare the time to two consecutive negative swabs for SARS-CoV-2 by PCR between subjects taking opaganib and those on placebo.

    Measure: Time to negative swabs for SARS-CoV-2

    Time: 14 days

    Description: To compare the proportion of patients with two consecutive negative swabs for SARS-CoV-2 by PCR at Day 14 between subjects taking opaganib and those on placebo.

    Measure: Negative swabs for SARS-CoV-2 at day 14

    Time: 14 days

    Description: To compare the proportion of patients, with at least one measurement of fever at baseline (defined as temperature >38.0 C [100.4 F]), who are afebrile (defined as temperature <37.2C [99 F]) at Day 14 between subjects taking opaganib and those on placebo.

    Measure: Fever

    Time: 14 days

    Description: To compare mortality 30 days post-baseline between subjects taking opaganib and those taking placebo

    Measure: Mortality

    Time: 30 days post baseline

    Other Outcomes

    Description: To compare the number of adverse events in patients with severe COVID-19 pneumonia between subjects taking opaganib and subjects taking placebo

    Measure: Adverse events

    Time: Up to 14 days and at the end of the 4 weeks follow-up after the end of treatment

    Description: To compare the change in the systemic marker of inflammation, D-dimer, over the treatment period between subjects taking opaganib and those on placebo.

    Measure: Inflammatory markers - D-dimer

    Time: 14 days

    Description: To compare the change in the systemic marker of inflammation, cardiac troponin, over the treatment period between subjects taking opaganib and those on placebo.

    Measure: Inflammatory markers - cardiac troponin

    Time: 14 days

    Description: To compare the change in the systemic marker of inflammation, C-reactive protein [CRP], over the treatment period between subjects taking opaganib and those on placebo.

    Measure: Inflammatory markers - C-reactive protein

    Time: 14 days

    Description: To compare the change in the systemic marker of inflammation lactate dehydrogenase [LDH] over the treatment period between subjects taking opaganib and those on placebo.

    Measure: Inflammatory markers - lactate dehydrogenase

    Time: 14 days

    Description: To compare the change in the systemic marker of inflammation ferritin over the treatment period between subjects taking opaganib and those on placebo.

    Measure: Inflammatory markers - ferritin

    Time: 14 days
    240 Phase 1 Double-Blinded, Randomized, Placebo Controlled Safety and Early Efficacy Trial of Cryopreserved Cord Blood Derived T-Regulatory Cell Infusions (CK0802) In The Treatment Of COVID-19 Induced Acute Respiratory Distress Syndrome (ARDS)

    To assess the safety and efficacy of CK0802 in treatment of patients with COVID-19 induced moderate-to-severe PNA-ARDS.

    NCT04468971
    Conditions
    1. COVID19
    2. ARDS
    Interventions
    1. Biological: CK0802
    2. Drug: Placebo

    Primary Outcomes

    Description: Regimen related ≥ grade 3 toxicity within 48 hours of first infusion (DLT)

    Measure: Regimen related ≥ grade 3 toxicity within 48 hours of first infusion

    Time: 48 hours

    Description: Alive and not intubated 28 days after the date of first infusion

    Measure: 28-day treatment success, defined as S28

    Time: 28 days

    Secondary Outcomes

    Description: Time to extubation

    Measure: Time to extubation

    Time: 28 days

    Description: Oxygenation requirement (PaO2/FiO2) change between day 0 and day +11

    Measure: Oxygenation improvement

    Time: 11 days

    Description: Ventilator free days measured at day 28

    Measure: Ventilator free days

    Time: 28 days

    Description: Organ failure free days measured at day 28

    Measure: Organ failure free days

    Time: 28 days

    Description: ICU free days measured at day 28

    Measure: ICU free days

    Time: 28 days

    Description: All-cause mortality at day 28

    Measure: All-cause mortality

    Time: 28 days
    241 A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-design Trial of Tofacitinib in Hospitalized Participants With COVID-19 Pneumonia

    Tofacitinib suppresses pro-inflammatory signaling that may be important pathogenetically to progression to more severe lung disease and acute respiratory distress syndrome (ARDS) in patients with COVID-19. The purpose of the study is to assess the safety and efficacy of tofacitinib plus standard pharmacologic and supportive measures in treating hospitalized participants with COVID-19 pneumonia.

    NCT04469114
    Conditions
    1. Covid19
    Interventions
    1. Drug: Tofacitinib 10 mg
    2. Drug: Placebo
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: 1, 2 or 3 on the 8-point National Institute of Allergy and Infectious Diseases (NIAID) ordinal scale of disease severity. The minimum value is 1 (worst outcome) and the maximum value is 8 (best outcome). Death. Hospitalized, on invasive mechanical ventilation or ECMO. Hospitalized, on non-invasive ventilation or high-flow oxygen devices. Hospitalized, requiring supplemental oxygen. Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise). Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care. Not hospitalized, limitation on activities and/or requiring home oxygen. Not hospitalized, with no limitations on activities.

    Measure: Death or respiratory failure ate Day 28

    Time: 28 days

    Secondary Outcomes

    Description: NIAID ordinal scale of disease severity

    Measure: National Institute of Allergy and Infectious Diseases (NIAID) ordinal scale of disease severity at Day 14

    Time: 14 days

    Description: Categories 3 to 8 in the National Institute of Allergy and Infectious Diseases (NIAID) ordinal scale of disease severity at Day 14 and Day 28

    Measure: Status of alive and not on mechanical ventilation or ECMO at Day 14 and 28 NIAID ordinal scale of disease severity at Day 14

    Time: 14 and 28 days

    Description: Categories 1 to 4 in the National Institute of Allergy and Infectious Diseases (NIAID) ordinal scale of disease severity

    Measure: Status of requiring supplemental oxygen at Day 28

    Time: 28 days

    Description: Categories 7 and 8 in the National Institute of Allergy and Infectious Diseases (NIAID) ordinal scale of disease severity

    Measure: Status of being alive and not hospitalized at Day 14 and 28

    Time: 14 and 28 days

    Description: NIAID ordinal scale of disease severity

    Measure: National Institute of Allergy and Infectious Diseases (NIAID) ordinal scale of disease severity at Day 14 NIAID ordinal scale of disease severity at Day 28

    Time: 28 days

    Description: Number of patients with resolution of fever, cough, and need for ventilatory or oxygen support.

    Measure: Number of patients with cure

    Time: 28 days

    Description: Number of patients at the ICU or on ventilatory support

    Measure: Number of patients at the ICU or on ventilatory support at Day 28

    Time: 28 days

    Description: Number of days free from mechanical ventilation

    Measure: Number of days free from mechanical ventilation at 28 days

    Time: 28 days

    Description: Number of days in hospital

    Measure: Number of days in hospital

    Time: 28 days

    Description: Number of days in ICU

    Measure: Number of days in ICU

    Time: 28 days
    242 A Phase 1b, Randomized, Double-blinded, Placebo-controlled Study to Evaluate the Safety and Immunomodulatory Effect of the RIPK1 Inhibitor SAR443122 in Hospitalized Patients With Severe COVID-19

    Primary Objective: To evaluate the effect of SAR443122 relative to the control arm on the hyperinflammatory state as measured by C-reactive protein (CRP) levels in adult patients hospitalized with severe coronavirus disease 2019 (COVID-19) Secondary Objectives: - To evaluate the time to onset of effect of SAR443122 relative to the control arm on the hyperinflammatory state as measured by CRP levels - To evaluate the time to onset of effect of SAR443122 relative to the control arm on oxygenation status - To evaluate the effect of SAR443122 relative to the control arm on oxygenation status - To evaluate the effect of SAR443122 relative to the control arm on total duration of supplemental oxygen requirement - To evaluate the effect of SAR443122 relative to the control arm on length of ventilator support needed - To evaluate the effect of SAR443122 relative to the control arm on laboratory markers of severe COVID-19 - To evaluate the effect of SAR443122 relative to the control arm on mortality - To evaluate the effect of SAR443122 relative to the control arm on need for thrombolytic therapy - To evaluate the effect of SAR443122 relative to the control arm on need for vasopressor treatment - To evaluate the safety of SAR443122 as compared to the control arm up to End of Study - To evaluate the effect of SAR443122 relative to the control arm on total duration without high flow supplemental oxygen requirements

    NCT04469621
    Conditions
    1. Corona Virus Infection
    Interventions
    1. Drug: SAR443122
    2. Drug: Placebo
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome

    Primary Outcomes

    Description: Relative change from baseline in CRP level on Day 7

    Measure: Relative change from baseline in CRP level

    Time: Day 7

    Secondary Outcomes

    Description: The time to 50% decrease from baseline in CRP level

    Measure: Time to 50% decrease from baseline in CRP level

    Time: Baseline to Day 28

    Description: The time to improvement of oxygenation as measured by oxygen saturation >/=92% breathing room air over 48 hrs or until discharge

    Measure: Time to improvement of oxygenation

    Time: Baseline to Day 28

    Description: Change from baseline in SPO2/FiO2 ratio at Day 7

    Measure: Change from baseline in SPO2/FiO2 ratio

    Time: Day 7

    Description: Number of Days without need for oxygen support and alive (oxygen saturation >=92% breathing room air) up to Day 28

    Measure: Number of Days without need for oxygen support and alive

    Time: Baseline to Day 28

    Description: Numbers of Ventilator-free days and alive up to Day 28

    Measure: Numbers of Ventilator-free days and alive

    Time: Baseline to Day 28

    Description: Change from baseline in white blood cell count and differential blood lymphocytes at Day 7 and End of treatment (EOT)

    Measure: Change from baseline in markers of inflammation: white blood cell count and differential blood lymphocytes

    Time: Day 7 and Day 15

    Description: Change from baseline in neutrophil to lymphocyte ratio at Day 7 and EOT

    Measure: Change from baseline in marker of inflammation: neutrophil to lymphocyte ratio

    Time: Day 7 and Day 15

    Description: Change from baseline in IL-6 at Day 7 and EOT

    Measure: Change from baseline in marker of inflammation: interleukin 6 (IL-6)

    Time: Day 7 and Day 15

    Description: Change from baseline in D-Dimer at Day 7 and EOT

    Measure: Change from baseline in D-Dimer

    Time: Day 7 and Day 15

    Description: Incidence of Deaths up to Day 28

    Measure: Incidence of Deaths

    Time: Baseline to Day 28

    Description: Percentage of participants receiving thrombolytic treatment up to Day 28

    Measure: Percentage of participants receiving thrombolytic treatment

    Time: Baseline to Day 28

    Description: Percentage of participants receiving vasopressor treatment up to Day 28

    Measure: Percentage of participants receiving vasopressor treatment

    Time: Baseline to Day 28

    Measure: Incidence of serious adverse events (SAEs), adverse events of special interest (AESI) and treatment-emergent adverse events (TEAEs) leading to treatment discontinuation

    Time: Baseline to Day 28

    Measure: Incidence of TEAEs leading to study discontinuation (primary reason)

    Time: Baseline to Day 28

    Description: Numbers of Respiratory Failure-Free Days (RFFD) and alive up to Day 28

    Measure: Numbers of Respiratory Failure-Free Days (RFFD) and alive

    Time: Baseline to Day 28
    243 A Phase 3, Randomized, Stratified, Observer-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, and Immunogenicity of mRNA-1273 SARS-CoV-2 Vaccine in Adults Aged 18 Years and Older

    The mRNA-1273 vaccine is being developed to prevent COVID-19, the disease resulting from Severe Acute Respiratory Syndrome coronavirus (SARS-CoV-2) infection. The study is designed to primarily evaluate the efficacy, safety, and immunogenicity of mRNA-1273 to prevent COVID-19 for up to 2 years after the second dose of mRNA-1273.

    NCT04470427
    Conditions
    1. SARS-CoV-2
    Interventions
    1. Biological: mRNA-1273
    2. Biological: Placebo

    Primary Outcomes

    Measure: Number of Participants with a First Occurrence of COVID-19 Starting 14 Days after Second Dose of mRNA-1273

    Time: Day 29 (second dose) up to Day 759 (2 years after second dose)

    Measure: Number of Participants with Adverse Events (AEs) or Medically Attended AEs (MAAEs) Leading to Withdrawal

    Time: Up to Day 759 (2 years after second dose)

    Measure: Number of Participants with Solicited Local and Systemic Adverse Reactions (ARs)

    Time: Up to Day 8 (7 days after first dose) and up to Day 36 (7 days after second dose)

    Measure: Number of Participants with Unsolicited AEs

    Time: Up to Day 57 (28 days after each dose)

    Secondary Outcomes

    Description: Clinical signs indicative of severe COVID-19 as predefined for the study.

    Measure: Number of Participants with a First Occurrence of Severe COVID-19 Starting 14 Days after Second Dose of mRNA-1273

    Time: Day 29 (second dose) up to Day 759 (2 years after second dose)

    Description: Clinical signs indicative of COVID-19 and SARS-CoV-2 Infection as predefined for the study.

    Measure: Number of Participants with a First Occurrence of Either COVID-19 or SARS-CoV-2 Infection regardless of symptomatology or Severity Starting 14 Days after Second Dose of mRNA-1273 or Placebo

    Time: Day 29 (second dose) up to Day 759 (2 years after second dose)]

    Description: Clinical signs indicative of secondary case definition of COVID-19 as predefined for the study.

    Measure: Number of Participants with a Secondary Case Definition of COVID-19 Starting 14 days after Second Dose of mRNA-1273 or Placebo

    Time: Day 29 (second dose) up to Day 759 (2 years after second dose)

    Description: Clinical signs indicative of COVID-19 as predefined for the study.

    Measure: Number of Participants with a First Occurrence of COVID-19 Starting 14 days after First Dose of mRNA-1273 or Placebo

    Time: Day 1 (first dose) up to Day 759 (2 years after second dose)

    Description: Clinical signs indicative of COVID-19 and SARS-CoV-2 infection as predefined for the study.

    Measure: Number of Participants with a First Occurrence of COVID-19 Starting 14 days after Second Dose of mRNA-1273 or Placebo regardless of evidence of prior SARS-CoV-2 Infection

    Time: Day 29 (second dose) up to Day 759 (2 years after second dose)

    Description: Clinical signs indicative of COVID-19 and SARS-CoV-2 infection as predefined for the study.

    Measure: Number of Participants with a First Occurrence of SARS-CoV-2 Infection in the Absence of Symptoms Defining COVID-19 Starting 14 days after Second Dose of mRNA-1273 or Placebo

    Time: Day 29 (second dose) up to Day 759 (2 years after second dose)

    Measure: Geometric Mean Titer (GMT) of SARS-CoV-2 Specific Neutralizing Antibody (nAb)

    Time: Day 1, Day 29, Day 57, Day 209, Day 394, and Day 759

    Measure: Geometric Mean Fold Rise (GMFR) of SARS-CoV-2 Specific nAb

    Time: Day 1, Day 29, Day 57, Day 209, Day 394, and Day 759

    Measure: Quantified Levels or GMT of S Protein-Specific Binding Antibody (bAb)

    Time: Day 1, Day 29, Day 57, Day 209, Day 394, and Day 759

    Measure: GMFR of S Protein Specific bAb

    Time: Day 1, Day 29, Day 57, Day 209, Day 394, and Day 759
    244 Phase 2, Randomized, Double-Blind Placebo Controlled Study of Intravenous Abatacept in the Treatment of Hospitalized COVID-19 Participants With Respiratory Compromise

    The purpose of this study is to evaluate the efficacy and safety of intravenous abatacept administered to hospitalized COVID-19 participants with respiratory compromise.

    NCT04472494
    Conditions
    1. COVID-19
    2. SARS-CoV-2
    Interventions
    1. Biological: Abatacept
    2. Other: Placebo

    Primary Outcomes

    Measure: Proportion of participants with composite end point of mechanical ventilation or death prior to or on Day 28

    Time: Up to 28 days

    Secondary Outcomes

    Measure: Change from baseline in the Ordinal 8-point Outcome Scale on Day 28

    Time: Day 28

    Measure: All-cause mortality on Day 28

    Time: Day 28

    Measure: Proportion of participants alive and free of respiratory failure on Day 28

    Time: Day 28

    Measure: Proportion of participants returned to room air by Day 28

    Time: Up to 28 days

    Measure: Proportion of participants alive and discharged home by Day 28

    Time: Up to 28 days

    Measure: Proportion of participants with Serious Adverse Events (SAEs)

    Time: Up to 60 days

    Measure: Proportion of participants with serious infections

    Time: Up to 60 days
    245 Sub-cutaneous Ivermectin in Combination With and Without Oral Zinc and Nigella Sativa: a Placebo Randomized Control Trial on Mild to Moderate COVID-19 Patients

    To measure the effect of Ivermectin (sub-cutaneous) with or without zinc and Nigella sativa in treating the COVID-19 patients to clear viral load of SARS-CoV-2 along with reduction in severity of symptoms and length of hospitalization of patients with COVID-19.

    NCT04472585
    Conditions
    1. Coronavirus Infection
    2. COVID
    3. Sars-CoV2
    Interventions
    1. Drug: Nigella Sativa / Black Cumin
    2. Drug: Ivermectin Injectable Solution
    3. Other: Placebo
    4. Drug: Zinc
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome

    Primary Outcomes

    Description: time needed to turn positive COVID-19 PCR to negative

    Measure: qRT-PCR

    Time: 14 days

    Secondary Outcomes

    Description: time needed to make patients clinically better

    Measure: Severity of symptoms

    Time: 14 days
    246 Adaptive Design Phase 2 to 3, Randomized, Double-blind, to Evaluate Safety, Efficacy, Pharmacokinetics and Pharmacodynamics of BIO101 in the Prevention of the Respiratory Deterioration in Hospitalized COVID-19 Patients

    The COVA clinical study is a global multicentric, double-blind, placebo-controlled, group sequential and adaptive 2 parts phase 2-3 study targeting in patients with SARS-CoV-2 pneumonia. Part 1 is a Phase 2 exploratory Proof of Concept (PoC) study to provide preliminary data on the activity, safety and tolerability of BIO101 in the target population. Part 2 is a phase 3 pivotal randomized study to provide further evidence of safety and efficacy of BIO101 after 28 days of double-blind dosing. BIO101 is the investigational new drug that activates the Mas receptor (MasR) through the protective arm of the Renin Angiotensin System (RAS).

    NCT04472728
    Conditions
    1. Covid-19
    2. SARS-CoV2
    Interventions
    1. Drug: BIO101
    2. Drug: Placebo

    Primary Outcomes

    Description: For interim analysis intended to obtain indication of activity of BIO101. Primary endpoint: • Proportion of subjects with negative events, of either of the following: All-cause mortality Respiratory failure, defined as any of the following: Requiring mechanical ventilation (including cases that will not be intubated due to resource restrictions and triage) Requiring ECMO Requiring high-flow oxygen

    Measure: End-of-Part 1 interim analysis: Proportion of subjects with all cause mortality or with respiratory failure.

    Time: up to 28 days

    Description: For sample size re-assessment for part 2, time frame - up to 28 days: • Proportion of participants with negative events, of either of the following: All-cause mortality Respiratory failure, defined as any of the following: Requiring mechanical ventilation (including cases that will not be intubated due to resource restrictions and triage) Requiring high-flow oxygen

    Measure: For part-2 sample size interim analysis: Proportion of subjects with all cause mortality or with respiratory failure.

    Time: up to 28 days

    Description: • Proportion of participants with of subjects with negative events, of either of the following. All-cause mortality Respiratory failure, defined as any of the following: Mechanical ventilation (including cases that will not be intubated due to resource restrictions and triage) Requiring ECMO Requiring high-flow oxygen

    Measure: For the final analysis: Proportion of subjects with all cause mortality or respiratory failure.

    Time: up to 28 days

    Secondary Outcomes

    Description: • SpO2/FiO2

    Measure: Interim analysis; indication of activity of BIO101: Oxygen saturation by pulse oximetry (SpO2) SpO2 / Fraction of inspired oxygen (FiO2) ratio

    Time: 28 days

    Description: • Inflammatory markers including: IL 6 TNFα D-dimer

    Measure: Interim analysis; indication of activity of BIO101: Inflammatory markers

    Time: 28 days

    Description: • Renin Angiotensin System biomarkers: Angiotensin 2 Angiotensin-converting enzyme (ACE) levels

    Measure: Interim analysis; indication of activity of BIO101: Renin Angiotensin System biomarkers

    Time: 28 days

    Description: Proportion of participants with events of all-cause mortality Proportion of participants with 'positive' events: o official discharge from hospital care by the department due to improvement in patient condition (self-discharge by patient is not considered a positive event) Proportion of participants with events of respiratory failure, defined as any of the following: Requiring mechanical ventilation (including cases that will not be intubated due to resource restrictions and triage) Requiring ECMO Requiring high-flow oxygen

    Measure: Key secondary endpoint for final analysis: Proportion of participants with positive or negative events

    Time: 28 days

    Description: Oxygen saturation in arterial blood, measured by pulse-oximetry (SpO2) SpO2/FiO2 Proportion of participants with CPAP/BiPAP events, defined as requiring CPAP/BiPAP in participants entering the study on low flow oxygen)

    Measure: Additional secondary endpoints for final analysis: Respiratory function

    Time: 28 days

    Description: For participants who experienced a positive event: proportion of participants with with sustained positive outcome (to asesss durability of effect after those participants discontinued study medication). Time to event: official discharge from hospital care due to improvement

    Measure: Additional secondary endpoints for final analysis:proportion of patients who experienced positive event

    Time: 28 days

    Description: Time to events, of either of the following: All-cause mortality Respiratory failure, defined as any of the following: Requiring mechanical ventilation (including cases that will not be intubated due to resource restrictions and triage); Requiring ECMO; Requiring high-flow oxygen • Proportion of participants with CPAP/BiPAP events, defined as requiring CPAP/BiPAP in participants entering the study on low flow oxygen)

    Measure: Additional secondary endpoints for final analysis:proportion of patients who experienced negative events

    Time: 28 days

    Description: National Early Warning Score 2 (NewS2): scores: 0-7

    Measure: Additional secondary endpoint for final analysis: The National Early Warning Score 2 (NewS2):

    Time: 28 days

    Description: Cmax: Peak Plasma concentration

    Measure: Additional secondary endpoint for final analysis: Population Pharmacokinetics study (pop-PK)

    Time: 1day

    Description: tmax: Time to reach peak plasma concentration

    Measure: Additional secondary endpoint : Population Pharmacokinetics study (pop-PK)

    Time: 1 day

    Description: AUC: Area under the plasma concentration versus time curve

    Measure: Secondary endpoint: Population Pharmacokinetics study (pop-PK)

    Time: 1 day
    247 Efficacy of Iodine Complex in Mild to Moderate COVID-19 Patients

    The objective of this study is to measure the effect of Iodine complex in treating the COVID-19 patients to clear viral load of SARS-CoV-2 along with reduction in severity of symptoms and length of hospitalization of patients with COVID-19.

    NCT04473261
    Conditions
    1. Covid19
    2. SARS-CoV-2
    3. Corona Virus Infection
    Interventions
    1. Drug: Iodine Complex
    2. Drug: Iodine Complex
    3. Drug: Placebo
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome

    Primary Outcomes

    Description: Time taken for viral load clearance

    Measure: qRT-PCR

    Time: 14 days

    Secondary Outcomes

    Description: Time taken for symptomatic response in patients

    Measure: Severity of Symptoms

    Time: 14 days
    248 A First-in-human, Observer-blinded, Randomized, Placebo-controlled, Parallel Group Study to Evaluate the Safety and Immunogenicity of KBP-COVID-19 SARS-CoV-2 Vaccine With Adjuvant in Healthy Seronegative Adults Aged 18-49 and 50-70

    This is an First In Human (FIH), observer-blinded, randomized, placebo-controlled, parallel group study to evaluate the safety and immunogenicity of KBP-COVID-19 vaccine in healthy CoV-2seronegative adult subjects in 2 age groups, Part A (18-49 years) and Part B (50-70 years).

    NCT04473690
    Conditions
    1. Covid19
    Interventions
    1. Biological: Low Dose of KBP-COVID-19
    2. Biological: High Dose of KBP-COVID-19
    3. Biological: Placebo

    Primary Outcomes

    Description: Occurrence of Adverse Events

    Measure: Solicited Administration site reactions

    Time: 7 days after vaccination

    Description: Occurrence of Adverse Events

    Measure: Solicited systemic events

    Time: 7 days after vaccination

    Secondary Outcomes

    Description: Safety Endpoints

    Measure: Unsolicited Adverse Events and medically attended adverse events

    Time: 43 days after vaccination

    Description: Safety Endpoints

    Measure: Serious Adverse Events, Medically Attended Adverse Events and New Onset Chronic Diseae

    Time: 365 days after vaccination

    Description: Immunogenicity

    Measure: Vaccine ELISA and neutralizing antibody titers for each treatment group

    Time: Baseline, Day 8, 15, 22, 29, 43, 90, 181, 273, 365

    Description: Immunogenicity

    Measure: Seroconversion rates

    Time: Days 8, 15, 22, 29, 43, 90, 181, 273, 365
    249 A Multi-center, Randomized, Double-blind, Parallel, Placebo-Controlled, Phase Ⅱ Clinical Trial to Evaluate Efficacy and Safety of Pyramax in Mild to Moderate COVID-19 Patients

    This study is a multi-center, randomized, double-blind, parallel, placebo-controlled, phase Ⅱ clinical trial to evaluate efficacy and safety of Pyramax in mild to moderate COVID-19 patients.

    NCT04475107
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Pyronaridine-Artesunate
    2. Drug: Placebo

    Primary Outcomes

    Description: * Patients who are rRT-PCR negative for COVID-19

    Measure: Proportion (%) of patients with virological clearance of SARS-CoV-2 at day 7 post-dose*

    Time: Day 7

    Secondary Outcomes

    Measure: Viral load reduction of SARS-CoV-2 at Day 3, 7, 10, and 14 post-dose compared to the baseline

    Time: Day 3, 7, 10, 14

    Description: * Patients who are rRT-PCR negative for COVID-19

    Measure: Proportion (%) of patients with virological clearance of SARS-CoV-2 at Day 3, 10, and 14 post-dose*

    Time: Day 3, 10, 14

    Measure: Change in WHO Ordinal Scale for Clinical Improvement at Day 3, 7, 10, 14, and 28 post-dose from the baseline

    Time: Day 3, 7, 10, 14, 28

    Measure: Change in NEWS score at Day 3, 7, 10, 14, and 28 post-dose from the baseline

    Time: Day 3, 7, 10, 14, 28

    Measure: Time to achieve normalization of body temperature, post-dose

    Time: Day 3, 7, 10, 14, 28

    Measure: Time to achieve normalization of respiratory rate, post-dose

    Time: Day 3, 7, 10, 14, 28

    Measure: Time to achieve normalization of oxygen saturation, post-dose

    Time: Day 3, 7, 10, 14, 28
    250 Reducing Asymptomatic Infection With Vitamin D in Coronavirus Disease

    This study is intended to address whether oral daily vitamin D supplementation reduces infection with SARS-CoV-2 in healthy young adults. The primary aim of the study is to demonstrate a reduction in 'silent' seroconversion rates, consistent with asymptomatic transmission of SARS-CoV-2, in a young healthy adult population following 24 weeks of taking oral vitamin D supplemented at a dose of 1000 I.U. daily, versus matching placebo. The secondary aims of this study are to explore: 1. Any effect on symptomatic illness. 2. The background 'point' prevalence and subsequent rate of increase in seropositivity for SARS-CoV-2 in healthy young adults. 3. The individual reductions in seropositivity to SARS-CoV-2 over time, and changes in seropositivity in a defined young adult population over time. 4. Where salivary Immunoglobulin A (IgA) may be used to provide an alternative/ complementary serological method 5. The effect (if any) of vitamin D supplementation on seroconversion rates stratified by: i) level of baseline vitamin D 'deficiency/ insufficiency/ sufficiency' status; ii) extent of BMI-defined normal/overweight/obesity cut-offs and iii) gender.

    NCT04476680
    Conditions
    1. SARS-CoV Infection
    2. Vitamin D Deficiency
    3. Covid19
    4. Acute Respiratory Tract Infection
    Interventions
    1. Dietary Supplement: Vitamin D 1000 IU
    2. Drug: Placebo
    MeSH:Infection Communicable Diseases Respiratory Tract Infections Coronavirus Infections Severe Acute Respiratory Syndrome Vitamin D Deficiency Asymptomatic Infections
    HPO:Low levels of vitamin D Respiratory tract infection

    Primary Outcomes

    Description: asymptomatic seroconversion for SARS-CoV-2

    Measure: Seroconversion

    Time: 24 weeks

    Description: asymptomatic seroconversion for SARS-CoV-2

    Measure: Interim analysis - seropositivity at 12 weeks

    Time: 12 weeks

    Secondary Outcomes

    Description: Sensitivity and specificity of dried blood spot assay compared with venous blood serology

    Measure: Dried Blood Spot performance

    Time: 24 weeks

    Description: Sensitivity and specificity of salivary IgA compared with venous blood serology

    Measure: Salivary IgA performance

    Time: 24 weeks

    Description: The background 'point' prevalence and subsequent rate of increase in seropositivity for SARS-CoV-2 in healthy young adults.

    Measure: Prevalence of SARS-CoV-2

    Time: 24 weeks

    Description: The individual reductions in seropositivity to SARS-CoV-2 over time, and changes in seropositivity in a defined young adult population over time

    Measure: Change in seropositivity

    Time: 24 weeks

    Description: The effect of vitamin D supplementation on seroconversion rates stratified by: i) level of baseline vitamin D 'deficiency/ insufficiency/ sufficiency' status; ii) extent of BMI-defined normal/overweight/obesity cut-offs, iii) gender iv) ethnicity

    Measure: Change in seroconversion rate

    Time: 24 weeks
    251 COVID-FISETIN: A Phase 2 Placebo-Controlled Pilot Study in Covid-19 of Fisetin to Alleviate Dysfunction and Excessive Inflammatory Response in Hospitalized Adults

    The purpose of this study is to test whether Fisetin, a senolytic drug, can assist in preventing an increase in the disease's progression and alleviate complications of coronavirus due to an excessive inflammatory reaction.

    NCT04476953
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Placebo
    2. Drug: Fisetin

    Primary Outcomes

    Description: Number of participants to experience serious adverse events and hypersensitivity reactions.

    Measure: Serious Adverse Events

    Time: 6 months

    Description: change in oxygenation levels as measured by S/F ratio (SPO2/FiO2)

    Measure: Change in oxygenation status

    Time: baseline, Day 3, 7, 10, 14, 17 and 30; Months 3 and 6

    Secondary Outcomes

    Description: Number of participants to progress to severe or critical classification measure by the WHO/ NIH Baseline Severity Classification criteria descriptions of SARS-CoV-2 infection without symptoms, Mild COVID-19 (CoV), Moderate CoV, Severe CoV and Critical CoV

    Measure: COVID-19 Severity Category

    Time: 6 months
    252 Randomized, Double-Blind Clinical Trial of Ruxolitinib in Patients With Acute Respiratory Disorder Syndrome Due to SARS-CoV-2 Infection

    The COVID-19 pandemic has had a dramatic effect in public health worldwide. In Brazil, there have been more than 2 million confirmed cases and over 75,000 deaths since February 26, 2020. Based on reports of a hyperinflammatory state associated with COVID-19, the use of immunosuppressive drugs may be efficacious in the treatment of this disease. JAK inhibitors have been shown to harness inflammation in a number of different pathologic conditions. The aim of the present study is to evaluate the efficacy and safety of JAK inhibitor ruxolitinib in patients with acute respiratory distress syndrome due to COVID-19.

    NCT04477993
    Conditions
    1. Severe Acute Respiratory Syndrome Coronavirus 2
    2. SARS-CoV2
    Interventions
    1. Drug: Janus Kinase Inhibitor (ruxolitinib)
    2. Other: Placebo
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Respiration Disorders Respiratory Tract Diseases Syndrome

    Primary Outcomes

    Measure: A composite outcome of death or ICU admission or mechanical ventilation at day 14.

    Time: 14 days

    Secondary Outcomes

    Measure: A composite outcome of death or ICU admission or mechanical ventilation at day 28

    Time: 28 days

    Description: ICU admission, mechanical ventilation, death or consent withdrawal

    Measure: Time to treatment failure

    Time: 28 days

    Measure: Overall survival at days 14 and 28

    Time: 14 and 28 days

    Measure: Cumulative incidence of ICU admission rate at days 14 and 28

    Time: 14 and 28 days

    Measure: Cumulative incidence of mechanical ventilation at days 14 and 28

    Time: 14 and 28 days

    Measure: Duration of hospital stay

    Time: 28 days

    Measure: Duration of ICU stay

    Time: 28 days

    Measure: Duration of mechanical ventilation

    Time: 28 days

    Measure: Duration of non-invasive ventilation

    Time: 28 days

    Measure: Secondary hemophagocytic syndrome rate

    Time: 28 days

    Measure: Cumulative incidence nosocomial infection rate at days 14 and 28

    Time: 14 and 28 days

    Measure: Incidence of discontinuation of oxygen supplementation at days 14 and 28

    Time: 14 and 28 days

    Measure: Rate of grade 1-2 and 3-5 emerging adverse events at day 28

    Time: 28 days

    Measure: Cumulative dose of methylprednisolone at days 14 and 28

    Time: 14 and 28 days

    Measure: Change in PaO2/FiO2 ratio from baseline to days 14 and 28

    Time: 14 and 28 days

    Measure: Change in interleukin 6 levels [pg/mL] from baseline to days 14 and 28

    Time: 14 and 28 days

    Measure: Change in d-dimer levels [ng/mL] from baseline to days 14 and 28

    Time: 14 and 28 days

    Measure: Change in fibrinogen levels [mg/dL] from baseline to days 14 and 28

    Time: 14 and 28 days

    Measure: Change in ferritin levels [ng/mL] from baseline to days 14 and 28

    Time: 14 and 28 days

    Measure: Change in C reactive protein levels [mg/L] from baseline to days 14 and 28

    Time: 14 and 28 days

    Measure: Change in alanine aminotransferase [U/L] from baseline to days 14 and 28

    Time: 14 and 28 days

    Measure: Change in aspartate aminotransferase [U/L] from baseline to days 14 and 28

    Time: 14 and 28 days

    Measure: Change in creatinine levels [mg/dL] from baseline to days 14 and 28

    Time: 14 and 28 days

    Measure: Change in glucose levels [mg/dL] from baseline to days 14 and 28

    Time: 14 and 28 days

    Measure: Change in hemoglobin levels [g/dL] from baseline to days 14 and 28

    Time: 14 and 28 days

    Measure: Change in platelet count [x10ˆ3/mmˆ3] from baseline to days 14 and 28

    Time: 14 and 28 days

    Measure: Change in absolute neutrophil count [x10ˆ3/mmˆ3] from baseline to days 14 and 28

    Time: 14 and 28 days

    Measure: Change in absolute neutrophil count [/mmˆ3] from baseline to days 14 and 28

    Time: 14 and 28 days

    Measure: Change in absolute lymphocyte count [/mmˆ3] from baseline to days 14 and 28

    Time: 14 and 28 days

    Measure: Change in prothrombin time ratio from baseline to days 14 and 28

    Time: 14 and 28 days

    Measure: Change in partial thromboplastin time ratio from baseline to days 14 and 28

    Time: 14 and 28 days

    Measure: Change in bilirubin [mg/dl] from baseline to days 14 and 28

    Time: 14 and 28 days

    Measure: Change in lactate dehydrogenase [U/L] from baseline to days 14 and 28

    Time: 14 and 28 days

    Measure: Change in CPK-MB [ng/mL] from baseline to days 14 and 28

    Time: 14 and 28 days

    Measure: Change in troponin [ng/mL] from baseline to days 14 and 28

    Time: 14 and 28 days

    Measure: Change in von Willebrand factor antigen level (VWF:Ag) [%] from baseline to days 14 and 28

    Time: 14 and 28 days

    Measure: Change in von Willebrand factor activity (ristocetin cofactor) [%] from baseline to days 14 and 28

    Time: 14 and 28 days

    Measure: Change in ADAMTS-13 [%] from baseline to days 14 and 28

    Time: 14 and 28 days

    Measure: Change in von Willebrand multimeters from baseline to days 14 and 28

    Time: 14 and 28 days

    Measure: Change in plasminogen activator inhibitor-1 levels [ng/mL] from baseline to days 14 and 28

    Time: 14 and 28 days

    Measure: Change in E-selectin levels [ng/mL] from baseline to days 14 and 28

    Time: 14 and 28 days

    Measure: Change in P-selectin levels [ng/mL] from baseline to days 14 and 28

    Time: 14 and 28 days

    Measure: Change in endothelin [fmol/mL] from baseline to days 14 and 28

    Time: 14 and 28 days

    Measure: Change in circulating microparticles from baseline to days 14 and 28

    Time: 14 and 28 days

    Measure: Change in thromboelastography from baseline to days 14 and 28

    Time: 14 and 28 days
    253 Prevention of Severe Covid-19 in Infected Elderly by Early Administration of Convalescent Plasma With High-titers of Antibody Against SARS-CoV2.

    Trial design. Randomized, double-blind, placebo-controlled trial in a catchment population of 2,020,860 age-appropriate subjects in the state of Buenos Aires and 235,000 in the city of Buenos Aires. Institutions. Hospitals San Juan de Dios, Simplemente Evita, Dr. Carlos Bocalandro, Evita Pueblo, Sanatorio Antartida, Hospital Central de San Isidro, Clinica Olivos in the state of Buenos Aires with 38 regional and town hospitals acting as referral centers, and Hospital Militar Central, Sanatorio de Los Arcos, Hospital Universitario CEMIC, Sanatorio Sagrado Corazon, Sanatorio Finochietto, Sanatorio Anchorena, Centro Gallego, and in the city of Buenos Aires in Argentina. Study population. Subjects >= 75 years of age irrespective of presenting comorbidities or between 65-74 years of age with at least one comorbidity (hypertension, diabetes, obesity, chronic renal failure, and COPD) who experience the following signs and symptoms for less than 48 hours at the time of screening for SARS CoV2 by RT-PCR: (a) a temperature >=37.5°C and/or unexplained sweating and/or chills and (b) at least one of the following: dry cough, dyspnea, fatigue, myalgia, anorexia, sore throat, loss of taste and/or smell, rhinorrhea. Subjects consenting to screening will be tested by reverse-transcriptase-polymerase-chain-reaction (RT-PCR) for SARS-CoV-2 in a nasopharyngeal and an oropharyngeal swab and invited to participate when RNA for the virus is detected. Intervention. Eligible, consenting patients will be randomized using an electronic system to receive 250 ml of convalescent plasma with an IgG titer against SARS-CoV2 spike (S) protein >1:1,000 (COVIDAR IgG, Insituto Leloir, Argentina) or placebo (normal saline 0.9%) administered in a 1:1 ratio. Both treatment and placebo will be concealed using dark bags and tape to cover the infusion line. Treatment will be administered <72 hours from initiation of symptoms. Subjects will be monitored for 12 hours after treatment for adverse events. Clinical and laboratory monitoring. All participating subjects will be admitted to the hospital upon enrollment. Twenty-four hours after completing the infusion, a sample of venous blood (5 ml) will be obtained from all participants to measure anti-S IgG SARS-CoV2 in serum (COVIDAR IgG, Leloir) and preserved at -20°C until completion of the study. Patient evolution will be assessed daily by study physicians during hospitalization until day 25 and/or at home until day 15, in the event of earlier discharge from the hospital. Study physicians will use predesigned questionnaires to collect clinical information. An Independent Data Safety Monitoring Board (DSMB) will supervise participating subjects during the study. Endpoints. The primary endpoint of the trial is development of severe respiratory disease defined as a respiratory rate (RR)>30 and/or an O2 sat<93% when breathing room air determined using a predefined protocol. Three other clinical endpoints include (a) life threatening respiratory disease, defined as need for 100% oxygen supplementation and/or non-invasive or invasive ventilation and/or admission to intensive care; (b) critical systemic illness, defined as respiratory failure (PaO2/FiO2 ≤ 200 mm Hg) and/or shock and/or multiorganic distress syndrome; and (c) death. Statistical analysis. The study is designed to have one interim analysis when the outcome results for 50% of the subjects is obtained. The minimally clinically important difference was set at a 40% relative reduction for an expected outcome rate of 50% in the control group reduced to 30% in the intervention group. A total sample size of 210 subjects (105 per trial arm) was estimated to have 80% power at a significance level (alpha) of 0.05 using a two-sided z-test with continuity correction. Ethical considerations. The trial has been approved by the institutional review boards of participating institutions and the Central Ethics Committee of the state of Buenos Aires. The study will be conducted in accordance with the principles of the Declaration of Helsinki and the Good Clinical Practice guidelines of the International Conference on Harmonization. Written informed consent will be obtained from all patients for screening and enrollment.

    NCT04479163
    Conditions
    1. COVID
    Interventions
    1. Biological: Convalescent Plasma
    2. Other: Placebo

    Primary Outcomes

    Measure: Development of severe respiratory disease defined as a respiratory rate (RR)>30 and/or an O2 sat<93%

    Time: From 12 hours post infusion to day 15 post infusion

    Secondary Outcomes

    Measure: Life threatening respiratory disease

    Time: From 12 hours post infusion to day 25 post infusion

    Measure: Critical systemic illness, defined as respiratory failure

    Time: From 12 hours post infusion to day 25 post infusion

    Measure: Death

    Time: From 12 hours post infusion to day 25 post infusion

    Measure: Combination of secondary outcomes #2 (Life threatening respiratory disease) and/or #3 (Critical systemic illness, defined as respiratory failure) and//or #4 (death)

    Time: From 12 hours post infusion to day 25 post infusion

    Measure: Duration of oxygen support requirement in patients with covid-19 due to saturation in ambient air <93%.

    Time: From 12 hours post infusion to day 25 post infusion
    254 A Phase 1 Randomized, Single-blind, Placebo-controlled, Single Ascending Dose Escalation Study of the Safety, Tolerability, and Pharmacokinetics of Human Monoclonal Antibody, BRII-196 Administered Intravenously to Healthy Adult Volunteers

    This is a phase 1 study in which healthy adult volunteers will receive BRII-196 or placebo and will be assessed for safety, tolerability, and pharmacokinetics.

    NCT04479631
    Conditions
    1. COVID-19
    Interventions
    1. Drug: BRII-196
    2. Drug: Placebo

    Primary Outcomes

    Measure: Incidence of adverse events (AEs) by CTCAE v5.0

    Time: up to 24 weeks

    Measure: Proportion of subjects with SAEs

    Time: up to 24 weeks

    Measure: Proportion of subjects with infusion-related reactions

    Time: up to 24 weeks

    Measure: Proportion of subjects with hypersensitivity reactions

    Time: up to 24 weeks

    Secondary Outcomes

    Measure: Serum Concentration of BRII-196

    Time: up to 24 weeks
    255 A Phase 1 Randomized, Single-blind, Placebo-controlled, Single Ascending Dose Escalation Study of the Safety, Tolerability, and Pharmacokinetics of Human Monoclonal Antibody, BRII-198 Administered Intravenously to Healthy Adult Volunteers

    This is a phase 1 study in which healthy adult volunteers will receive BRII-198 or placebo and will be assessed for safety, tolerability, and pharmacokinetics.

    NCT04479644
    Conditions
    1. COVID-19
    Interventions
    1. Drug: BRII-198
    2. Drug: Placebo

    Primary Outcomes

    Measure: Incidence of adverse events (AEs) by CTCAE v5.0

    Time: up to 24 weeks

    Measure: Proportion of subjects with SAEs

    Time: up to 24 weeks

    Measure: Proportion of subjects with infusion-related reactions

    Time: up to 24 weeks

    Measure: Proportion of subjects with hypersensitivity reactions

    Time: up to 24 weeks

    Secondary Outcomes

    Measure: Serum Concentration of BRII-198

    Time: up to 24 weeks
    256 A Phase 1/2 Randomised, Double Blinded, Placebo Controlled, Ascending Dose Study to Assess the Safety, Tolerability, and Immunogenicity of ARCT-021 in Healthy Adult Subjects

    Determine safety and tolerability and immungenicity of investigational vaccine ARCT-021 in healthy adult volunteers.

    NCT04480957
    Conditions
    1. SARS-CoV-2
    Interventions
    1. Biological: ARCT-021 Dose 1
    2. Biological: ARCT-021 Dose 2
    3. Biological: ARCT-021 Dose 3
    4. Biological: ARCT-021 Dose 4
    5. Biological: ARCT-021 Dose Regimen 1
    6. Biological: ARCT-021 Dose Regimen 2
    7. Other: Placebo

    Primary Outcomes

    Description: Safety and tolerability of ARCT-021 assessed by determining the incidence, severity and dose-relationship of AEs by dose

    Measure: Incidence, severity and dose-relationship of AEs

    Time: 56 days

    Secondary Outcomes

    Description: SARS-CoV-2-specific serum neutralizing antibody levels, expressed as GMT

    Measure: Geometric mean titre for SARS-CoV-2-specific serum neutralizing antibody

    Time: Up to 56 days

    Description: SARS-CoV-2-specific serum neutralizing antibody levels, expressed as mean titer

    Measure: Mean titre for SARS-CoV-2-specific serum neutralizing antibody levels

    Time: Up to 56 days

    Description: GMFR in titre for SARS-CoV-2-spike protein specific neutralizing antibodies from before vaccination to each subsequent time point

    Measure: Geometric mean fold rise in titre for SARS-CoV-2-spike protein specific neutralizing antibody levels

    Time: Up to 56 days

    Other Outcomes

    Description: GMFR in SARS-CoV-2--spike protein-specific binding antibody levels from before vaccination to each subsequent time point

    Measure: Increase in SARS-CoV-2--spike protein-specific binding antibody levels

    Time: Up to 56 days

    Description: GMT for SARS-CoV-2--spike protein-specific binding antibody levels

    Measure: Geometric mean SARS-CoV-2--spike protein-specific binding antibody titre

    Time: Up to 56 days

    Description: Mean titer for SARS-CoV-2--spike protein-specific binding antibody levels

    Measure: Mean SARS-CoV-2--spike protein-specific binding antibody titre

    Time: Up to 56 days

    Description: Proportion of participants that are seronegative before vaccination achieving a titer of greater than or equal to 20 for SARS-CoV-2-specific serum neutralizing antibodies

    Measure: SARS-CoV-2-specific serum neutralizing antibody seroconversion rate

    Time: 56 days

    Description: Proportion of participants that are seropositive before vaccination achieving a greater than or equal to 4-fold rise from before vaccination in SARS-CoV-2-specific serum neutralizing antibody levels

    Measure: SARS-CoV-2-specific serum neutralizing antibody seroconversion rate (seropositive baseline)

    Time: 56 days
    257 A Double-blind, Randomized, Controlled Trial of ATI-450 in Patients With Moderate-severe COVID-19

    COVID-19 morbidity and mortality has been associated with Cytokine Release Syndrome (CRS) and Acute Respiratory Distress Syndrome (ARDS). ATI-450 is an oral small molecule MAPKAPK2 (MK2) inhibitor that potently inhibits multiple inflammatory cytokines. The investigator hypothesizes that MK2 pathway blockade during active COVID-19 infection in hospitalized participants will result in improvement in respiratory-failure free survival.

    NCT04481685
    Conditions
    1. Covid19
    Interventions
    1. Drug: ATI-450
    2. Drug: Placebo

    Primary Outcomes

    Description: Participants medical record

    Measure: Respiratory failure-free survival in participants with moderate-severe COVID-19 who are treated with ATI-450

    Time: Study day 14

    Secondary Outcomes

    Description: Using World Health Organization (WHO) COVID-19 Ordinal scale measuring: Proportion and time to participants with greater than 2 point improvement on the 7 point categorical scale. This scale measures illness severity over time and has a range of 0-7. 0- Uninfected: No clinical or virological evidence of infection. 1- Ambulatory: No limitation of activities. 2- Ambulatory: Limitation of activities. 3- Hospitalized, mild disease: Hospitalized, no oxygen. 4- Hospitalized, mild disease: Oxygen by mask or nasal prongs. 5- Hospitalized, severe disease: Non- invasive ventilation or high- flow oxygen. 6- Hospitalized, severe disease: Intubation and mechanical ventilation. 7- Hospitalized, severe disease: Ventilation + organ support; pressors, Renal Replacement Therapy (RRT), Extracorporeal Membrane Oxygenation (ECMO).

    Measure: Change in 7 point-ordinal scale

    Time: Baseline, Day 7, Day 14, Day 28 and follow-up up to 9 months

    Description: Peripheral capillary pulse oximeter to measure: Oxygen Saturation (SpO2)/Fraction of Inspired Oxygen (FiO2) ratio over time, sustainment of normalization in 24 hours, and relative shifts in SpO2/FiO2 categories (<235, between 235 and 315, greater than 315) over time

    Measure: Change in oxygen saturation-normalization

    Time: Baseline and continuous throughout hospitalization up to 14 days

    Description: Derived from medical record

    Measure: Need for advanced respiratory care

    Time: Baseline and continuous throughout hospitalization up to 14 days

    Description: Noted in participant medical record

    Measure: All-cause mortality

    Time: Baseline and through day 60

    Description: CTCAE v5.0

    Measure: Percentage of adverse events (AEs)

    Time: Baseline through day 14 or at discharge

    Description: CTCAE v5.0

    Measure: Percentage of serious adverse events (SAEs)

    Time: Baseline through day 14 or at discharge

    Description: Standard daily temperature measurement and obtained from participant medical record

    Measure: Proportion of participants with normalization of fever for 24 hours

    Time: Baseline through day 14 or at discharge

    Description: Noted in participant medical record

    Measure: Number of participants who develop new bacterial infection

    Time: Continuous throughout hospitalization up to 14 days

    Description: Noted in participant medical record

    Measure: Number of participants who develop new fungal infection

    Time: Continuous throughout hospitalization up to 14 days

    Description: Noted in participant medical record

    Measure: Incidence of Adult Respiratory distress Syndrome (ARDS2)

    Time: From day 1 though day 14 or at discharge

    Description: Serum collected from blood and assayed on Luminex panel performed by University of Kansas Medical Center (KUMC) Biobanking and Biomarker Validation (BBV) Core

    Measure: Change in serum cytokine Interleukin (IL)-6

    Time: Baseline, day 3, day 7 (or discharge day 7 and

    Description: Serum collected from blood and assayed on Luminex panel performed by KUMC BBV Core

    Measure: Change in serum cytokine IL-8

    Time: Baseline, day 3, day 7 (or discharge day 7 and

    Description: Serum collected from blood and assayed on Luminex panel performed by KUMC BBV Core

    Measure: Change in serum cytokines IL-1β

    Time: Baseline, day 3, day 7 (or discharge day 7 and

    Description: Serum collected from blood and assayed on Luminex panel performed by KUMC BBV Core

    Measure: Change in serum cytokine Tumor Necrosis Factor (TNF-α)

    Time: Baseline, day 3, day 7 (or discharge day 7 and
    258 A Phase 2 Study of BIO 300 Oral Suspension in Discharged COVID-19 Patients

    Randomized, double-blinded, placebo-controlled, two-arm study to evaluate the effectiveness and safety of BIO 300 Oral Suspension (BIO 300) for the mitigation of impaired pulmonary function in 2019 Coronavirus Disease (COVID-19) patients recently discharged from the hospital. Patients will be randomized 1:1 to receive BIO 300 or placebo. All patients will receive the same background current standard of care.

    NCT04482595
    Conditions
    1. Pulmonary Fibrosis
    Interventions
    1. Drug: BIO 300 Oral Suspension
    2. Drug: Placebo
    MeSH:Pulmonary Fibrosis
    HPO:Pulmonary fibrosis

    Primary Outcomes

    Description: Diffusing capacity of the lungs for carbon monoxide (DLCO)

    Measure: Change in DLCO

    Time: 12 Weeks

    Description: 6 minute walk test (6MWT)

    Measure: Change in 6 Minute Walk Test

    Time: 12 Weeks

    Secondary Outcomes

    Description: Forced vital capacity (FVC)

    Measure: Change in FVC

    Time: 12 Weeks, 6 Months and 12 Months

    Description: Patient reported outcome to measure impact on overall health, daily life, and perceived well-being in patients with impaired pulmonary function. Scores range from 0-100 with higher scores indicating more limitations.

    Measure: Change in St. George's Respiratory Questionnaire (SGRQ) Scores

    Time: 12 Weeks, 6 Months and 12 Months

    Description: Evidence of pulmonary fibrosis on high resolution computerized tomography (HRCT) scans of the lungs based on a 4-point Likert scale, where 0 is no evidence of fibrosis and 3 is severe fibrosis

    Measure: Change in Pulmonary Fibrosis on HRCT Scan

    Time: 12 Weeks, 6 Months and 12 Months

    Description: Incidence of hospitalization after initial discharge and initiating treatment

    Measure: Incidence of Re-Hospitalization

    Time: 12 Months

    Description: Mortality at 12 months after initiating treatment

    Measure: All-Cause Mortality

    Time: 12 Months

    Description: Forced expiratory volume in one second (FEV1)

    Measure: Change in FEV1

    Time: 12 Weeks, 6 Months and 12 Months

    Description: Ratio of forced expiratory volume in one second (FEV1) to forced vital capacity (FVC)

    Measure: Change in FEV1/FVC Ratio

    Time: 12 Weeks, 6 Months and 12 Months

    Description: 6 minute walk test (6MWT)

    Measure: Change in 6 Minute Walk Test

    Time: 6 Months and 12 Months

    Description: Oxygen saturation (pulse oximetry) at rest and during the 6 minute walk test (6MWT)

    Measure: Change in Pulse Oximetry at Rest and During the 6MWT

    Time: 12 Weeks, 6 Months and 12 Months

    Description: Diffusing capacity of the lungs for carbon monoxide (DLCO)

    Measure: Change in DLCO

    Time: 6 Months and 12 Months

    Description: Evaluate the safety of BIO 300 Oral Suspension treatment

    Measure: Adverse Events Related to BIO 300 Oral Suspension

    Time: 12 Months

    Description: Monitoring of blood serum levels for bilirubin, C-reactive protein (CRP), creatinine, blood urea nitrogen (BUN), cholesterol and triglycerides (all reported as mg/dL)

    Measure: Change in Clinical Laboratory Values

    Time: 4 Weeks, 8 Weeks, 12 Weeks, 6 Months and 12 Months

    Description: Monitoring of blood serum levels for troponin T, d-dimer and ferritin (all reported as ng/mL)

    Measure: Change in Clinical Laboratory Values

    Time: 4 Weeks, 8 Weeks, 12 Weeks, 6 Months and 12 Months

    Description: Monitoring of blood serum levels for albumin (g/dL)

    Measure: Change in Clinical Laboratory Values for Albumin

    Time: 4 Weeks, 8 Weeks, 12 Weeks, 6 Months and 12 Months

    Description: Monitoring of blood serum levels for alkaline phosphatase (ALP), alanine transaminase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) (all reported as Units/L)

    Measure: Change in Clinical Laboratory Values for Serum Enzymes

    Time: 4 Weeks, 8 Weeks, 12 Weeks, 6 Months and 12 Months

    Description: Monitoring of white blood cell, red blood cell and platelet counts

    Measure: Change in Complete Blood Counts with Differential

    Time: 4 Weeks, 8 Weeks, 12 Weeks, 6 Months and 12 Months

    Other Outcomes

    Description: Prescribed supplemental oxygen flow rate at night, rest and exertion

    Measure: Change in Supplemental Oxygen Use

    Time: 12 Weeks, 6 Months and 12 Months

    Description: Duration of supplemental oxygen use

    Measure: Change in Duration of Supplemental Oxygen Use

    Time: 12 Weeks, 6 Months and 12 Months

    Description: Expression levels of serum-derived cytokines (IL-1b, IL-6, IL-8, TNFa, and TGFb1)

    Measure: Change in Serum Cytokine Expression

    Time: 4 Weeks, 8 Weeks, 12 Weeks, 6 Months and 12 Months
    259 Phase I/Phase II Trial of Off-the-Shelf Allogeneic Hybrid TREG/Th2 Cell (RAPA-501-ALLO) Therapy for Severe, Post-Intubation Stage 3 COVID-19 Disease

    The first-in-human Phase 1 study component will evaluate two dose levels of RAPA-501-ALLO off the shelf cells in patients with post-intubation, stage 3 COVID-19 disease, with key endpoints of safety, biologic and potential disease-modifying effects. The randomized, double-blind, placebo-controlled Phase 2b study component will evaluate infusion of RAPA-501 ALLO off the shelf cells or a control infusion, with the primary endpoint assessing whether RAPA-501 cells reduce 30-day mortality. The COVID-19 pandemic is a disaster playing out with progressive morbidity and mortality. As of December 15, 2020, an estimated 73.3 million people have contracted the virus and 1,630,000 deaths have resulted globally. The United States has the highest totals with an estimated 16.6 million people diagnosed and 302,000 deaths. In stages 1 and 2 of COVID-19, viral propagation within the patient is predominant. As such, therapeutic interventions focus on immune molecules (convalescent serum, monoclonal antibodies) and anti-viral medications (remdesivir). In marked contrast, the most severe and deadly form of COVID-19, stage 3, is driven not by viral propagation, but by an out-of-control immune response (hyperinflammation) caused by increases in immune molecules known as cytokines and chemokines. As such, therapeutic interventions for stage 3 disease focus on anti-inflammatory medications such as anti-cytokine therapy (anti-IL-6 drugs) or corticosteroid therapy. Unfortunately, such interventions do not address the full pathogenesis of stage 3 COVID-19, which includes hyperinflammation due to "cytokine storm" and "chemokine storm," tissue damage, hypercoagulation, and multi-organ failure (including lung, heart, kidney and brain). The pulmonary component of stage 3 disease includes acute respiratory distress syndrome (ARDS), which is a final-common-pathway of patient death due to a myriad of conditions, including pneumonia, sepsis, and trauma. There is a dire need for novel cellular treatments that can deliver both a broad-based immune modulation effect and a tissue regenerative effect, such as RAPA-501-ALLO off-the-shelf allogeneic hybrid TREG/Th2 Cells. Stage 3 COVID-19 carries an estimated 30-day mortality of over 50% in spite of ICU utilization, mechanical ventilation, and supportive care therapies to manage ARDS and multiorgan failure. Narrowly acting targeted anti-inflammatory approaches such as anti-IL-6 therapeutics have not been particularly effective in stage 3 COVID-19 and the broad anti-inflammatory pharmaceutical approach of corticosteroid therapy, has only modestly tempered stage 3 disease in some studies. Cell therapy is also being evaluated in stage 3 COVID-19, in particular, mesenchymal stromal cells (MSC) and now, with the current RAPA-501-ALLO protocol, regulatory T (TREG) cells. TREG therapy has a mechanism of action that includes a multi-faceted anti-inflammatory effect, which puts TREG therapy at the forefront of future curative therapy of a wide range of autoimmune and neurodegenerative diseases, plus transplant complications, such as graft-versus-host disease (GVHD) and graft rejection. In addition, TREG therapy can provide a tissue regenerative effect, which places TREG cell therapy at the lead of novel regenerative medicine efforts to repair a myriad of tissue-based diseases, such as diseases of the skin, muscle, lung, liver, intestine, heart (myocardial infarction) and brain (stroke). RAPA-501-ALLO off-the-shelf cell therapy offers this potential dual threat mechanism of action that incorporates both anti-inflammatory and tissue repair effects for effective treatment of COVID-19 and multiple lethal conditions. RAPA-501-ALLO cells are generated from healthy volunteers, cryopreserved, banked, and are then available for off-the-shelf therapy anytime. During manufacturing, T cells are "reprogrammed" ex vivo using a novel, patented 7-day two-step process that involves T cell de-differentiation and subsequent re-differentiation towards the two key anti-inflammatory programs, the TREG and Th2 pathways, thus creating a "hybrid" product. The hybrid phenotype inhibits inflammatory pathways operational in COVID-19, including modulation of multiple cytokines and chemokines, which attract inflammatory cells into tissue for initiation of multi-organ damage. The hybrid TREG and Th2 phenotype of RAPA-501-ALLO cells cross-regulates Th1 and Th17 populations that initiate hyperinflammation of COVID-19. RAPA-501 immune modulation occurs in a T cell receptor independent manner, thus permitting off-the-shelf cell therapy. Finally, in experimental models of viral pneumonia and ARDS, TREG cells mediate a protective effect on the lung alveolar tissue. Because of this unique mechanism of action that involves both anti-inflammatory and tissue protective effects, the allogeneic RAPA-501 T cell product is particularly suited for evaluation in the setting of post-intubation, Stage 3 COVID-19.

    NCT04482699
    Conditions
    1. Severe COVID-19 Disease
    Interventions
    1. Biological: RAPA-501-Allo off-the-shelf Therapy of COVID-19
    2. Other: Placebo

    Primary Outcomes

    Description: On the phase 1 study component, determine the safety of allogeneic RAPA-501 cells when administered at dose level 1 (Cohort 1, 40 x 106 cells) and dose level 2 (Cohort 2, 160 x 106 cells).

    Measure: Dose-Limiting Toxicity (DLT)

    Time: 30 days after the first infusion of allogeneic RAPA-501 cells.

    Description: On the phase II study component, determine whether allogeneic RAPA-501 cells result in a mortality rate that is reduced relative to the randomized placebo-control cohort.

    Measure: Mortality Rate

    Time: 30 days after the first infusion of allogeneic RAPA-501 cells.

    Secondary Outcomes

    Description: Number of days requiring ventilation support.

    Measure: Ventilation Support

    Time: 90 days after the infusion of allogeneic RAPA-501 cells.

    Description: Number of days of hospitalization among survivors.

    Measure: Days of Hospitalization

    Time: 90 days after the infusion of allogeneic RAPA-501 cells.

    Description: Number of deaths due to any cause.

    Measure: Number of Deaths

    Time: 90 days after the infusion of allogeneic RAPA-501 cells.

    Description: Incidence of severe or life-threatening bacterial, invasive fungal, or opportunistic infection.

    Measure: Incidence of Infection

    Time: 90 days after the infusion of allogeneic RAPA-501 cells.

    Description: GVHD incidence and severity.

    Measure: GVHD Incidence

    Time: 90 days after the infusion of allogeneic RAPA-501 cells.

    Other Outcomes

    Description: COVID-19 viral load, as determined by standard reverse transcriptase polymerase chain reaction (RT-PCR) assay or equivalent test on nasopharyngeal and/or endotracheal tube swab samples.

    Measure: Viral Load

    Time: Six months after treatment initiation.

    Description: Development of potentially protective host immunity to COVID-19, as determined by serologic studies.

    Measure: Host Immunity

    Time: Six months after treatment initiation.

    Description: Peripheral blood immune counts, including CD4+ and CD8+ T cells, NK cells, and B cells.

    Measure: Peripheral Blood Immune Counts

    Time: Six months after treatment initiation.

    Description: T cell expression of co-stimulation molecules (including CD28) and checkpoint receptor molecules (including PD-1).

    Measure: T Cell Expression

    Time: Six months after treatment initiation.

    Description: Peripheral blood micro-chimerism, as determined by PCR amplification of donor and host STR loci.

    Measure: Peripheral Blood Micro-chimerism

    Time: Six months after treatment initiation.
    260 Effects of mTOR Inhibition With Sirolimus (RAPA) in Patients With COVID-19 to Moderate the Progression of Acute Respiratory Distress Syndrome (RAPA-CARDS)

    This study assesses the clinical effectiveness of mammalian target of rapamycin (mTOR) inhibition with rapamycin in minimizing or decreasing the severity of acute lung injury/acute respiratory distress syndrome (ALI/ARDS) in participants infected with mild to moderate COVID-19 virus.

    NCT04482712
    Conditions
    1. Acute Lung Injury/Acute Respiratory Distress Syndrome (ARDS)
    2. Respiratory Failure
    3. Sars-CoV2
    Interventions
    1. Drug: Rapamycin
    2. Drug: Placebo
    MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Respiratory Insufficiency Acute Lung Injury Lung Injury Syndrome

    Primary Outcomes

    Description: The proportion of participants who survive without respiratory failure

    Measure: Survival rate

    Time: 4 weeks

    Secondary Outcomes

    Description: The WHO ordinal scale is a measure of clinical improvement using a scale score of 0-8, where 0 indicates a better outcome and 8 indicates death: Uninfected, no clinical oor virological evidence of infection 0 Ambulatory, no limitation of activities 1 Ambulatory, limitation of activities 2 Hospitalized Mild disease, no oxygen therapy 3 Hospitalized mild disease, oxygen by mask or nasal prongs 4 Hospitalized Severe Disease, non-invasive ventilation 5 Hospitalized severe disease, intubation and mechanical ventilation 6 Hospitalized severe disease, ventilation+organ support 7 Death 8

    Measure: Change in Clinical Status assessed by the World Health Organization (WHO) scale

    Time: Baseline to 4 weeks

    Description: An ordinal scale for clinical improvement scored from 1 to 8, where 1 represents death and 8 represents recovery to discharge from hospital with no limitation on activities: Death (1) Hospitalized, on invasive mechanical ventilation of extracorporeal membrane oxygenation (ECMO) (2) Hospitalized, on non-invasive ventilation or high flow oxygen devices (3) Hospitalized, requiring supplemental oxygen (4) Hospitalized, not requiring supplemental oxygen or ongoing medical care (6) Not hospitalized, limitation on activities &/or requiring supplemental home oxygen (7) Not hospitalized, no limitation on activities (8)

    Measure: Change in Clinical Status assessed by the National Institute of Allergy and Infectious Disease (NIAID) scale

    Time: Baseline to 4 weeks

    Other Outcomes

    Description: Total number of deaths during the study period

    Measure: All cause mortality

    Time: 4 weeks

    Description: Number of days on ECMO

    Measure: Duration of ECMO

    Time: Up to 4 weeks

    Description: Number of days participants are on supplemental oxygen

    Measure: Duration of supplemental oxygen

    Time: Up to 4 weeks

    Description: Days of hospitalization

    Measure: Length of hospital stay

    Time: Up to 4 weeks

    Description: Number of days until there is a negative response to the reverse transcriptase-polymerase chain reaction test (RT-PCR)

    Measure: Length of time to SARS-CoV2 negativity

    Time: Up to 4 weeks
    261 A Randomized, Double-blinded, Placebo-controlled, Single Ascending Dose, Phase I Study to Evaluate the Tolerability, Safety, Pharmacokinetics of SCTA01 in Healthy Subjects

    The purpose of this study is to evaluate the tolerability, safety, pharmacokinetics of SCTA01(anti-SARS-CoV-2 monoclonal antibody) in Healthy Chinese Subjects.

    NCT04483375
    Conditions
    1. Coronavirus Disease 2019(COVID-19)
    Interventions
    1. Biological: SCTA01
    2. Other: Placebo
    MeSH:Coronavirus Infections

    Primary Outcomes

    Description: DLT will be assessed by DAIDS v2.1. The measurements include clinical symptoms and abnormal vital signs, abnormal laboratory tests (complete blood cell count, serum chemistry, routine urinalysis, coagulation function, etc.) and 12-lead ECGs

    Measure: Dose-limiting toxicity(DLT)

    Time: 7 days

    Description: MTD will be assessed by DAIDS v2.1. The measurements include clinical symptoms and abnormal vital signs, abnormal laboratory tests (complete blood cell count, serum chemistry, routine urinalysis, coagulation function, etc.) and 12-lead ECGs.

    Measure: Maximal Tolerable Dose(MTD)

    Time: 12 weeks

    Secondary Outcomes

    Description: Area under the curve from the time of dosing to the last measurable concentration time t (AUC0-t)

    Measure: AUC0-t

    Time: 12 weeks

    Description: Area Under the Concentration Time Curve (AUC) From Time Zero to Infinity (AUC 0-∞)

    Measure: AUC0-∞

    Time: 12 weeks

    Description: Elimination Phase Half-life(t1/2)

    Measure: t1/2

    Time: 12 weeks

    Description: Time to the Maximum Concentration(Tmax)

    Measure: Tmax

    Time: 12 weeks

    Description: Positive rate of anti-SCT A01 antibody

    Measure: Anti-drug antibody(ADA)

    Time: 12 weeks

    Description: Adverse events as assessed by DAIDS v2.1, including clinical symptoms and abnormal vital signs, abnormal laboratory tests (complete blood cell count, serum chemistry, routine urinalysis, coagulation function, etc.) and 12-lead ECGs

    Measure: Adverse events

    Time: 12 weeks
    262 PROTECT RCT (PRevention of COVID-19 With Oral Vitamin D Supplemental Therapy in Essential healthCare Teams

    In this 16-week randomized control study, health care workers will receive a bolus dose followed by a weekly dose of vitamin D or a placebo bolus and weekly dose. This study will test whether high-dose of vitamin D supplementation decreases the incidence of laboratory-confirmed COVID19 infection (primary outcome), reduces illness severity, duration, as well as work absenteeism among health care workers (HCW) in setting at high-risk of contact with COVID-19 cases in high COVID-19 incidence areas.

    NCT04483635
    Conditions
    1. COVID-19
    Interventions
    1. Dietary Supplement: Placebo
    2. Dietary Supplement: Vitamin D

    Primary Outcomes

    Description: documented by salivary or NP samples obtained clinically for screening or diagnostic purposes throughout the study period, self-obtained salivary samples at endpoint, analysed by RT-qPCR or COVID-19 seroconversion at endpoints

    Measure: Change in incidence of laboratory-confirmed COVID-19 infection

    Time: 16 weeks

    Secondary Outcomes

    Description: 5-category ordinal variable [asymptomatic, mild (managed at home); moderate (hospitalisation without supplemental oxygen; severe (oxygen supplementation); critical (mechanical ventilation/death)

    Measure: Distribution of disease severity

    Time: up to 16 weeks

    Description: For asymptomatic positive COVID-19 participants, symptoms will be recorded in a daily diary up to 14 days. Symptomatic positive COVID-19 participants will record their symptoms in a daily diary up to 48 hours after the resolution of symptoms

    Measure: Duration of symptoms in COVID-19 positive participants

    Time: up to 16 weeks

    Description: SARS-CoV-2 IgG Diasorin on Liaison XL platform

    Measure: Number of participants with COVID-19 positive IgG serology

    Time: 16 weeks

    Description: Participant-reported; reported by Direction of Human Resource (or for physicians, Direction des services professionnelles) databases

    Measure: Number of workday absences due to COVID-19 suspected/confirmed infection

    Time: 16 weeks

    Description: Participant-reported; reported by Direction of Human Resource (or for physicians, Direction des services professionnelles) databases

    Measure: Number of workday absences for any reason

    Time: 16 weeks

    Description: Number and distribution of adverse health events

    Measure: Adverse health events

    Time: 16 weeks
    263 Sulodexide in the Treatment of Early Stages of COVID-19

    Problem: The COVID- 19 pandemic has not only affected our healthcare system, but the impact on the worldwide financial systems and our "normal" way of life is still to be determined. Although the percentage of patients infected with COVID-19 that need hospital care is low, Its high rate of contagiousness makes the total number of patients in need of hospital care cripple any healthcare system, limiting the space available for other patients in need of critical care, who cannot be admitted or even prefer not to attend the hospital in fear of infection. Early investigations report an Increase risk of thromboembolic complications, and a systemic inflammatory response not clearly understood. There is a possible vascular endothelial dysfunction due to chronic comorbidities (Hypertension, diabetes, obesity, chronic kidney disease, lung disease) as a risk factor for a more severe presentation. Justification: Sulodexide is a two-compound drug, each of them with different endothelial action that can be beneficial in COVID-19 patients. Glycosaminoglycans: Can help restore venous and arterial endothelial glycocalyx which can downregulate or limit the response to inflammatory molecules, by maintaining the integrity lost in certain chronic diseases (high blood pressure, diabetes). Heparin compound: It has an antithrombotic effect that could help reduce the incidence of thromboembolic complications, and also add to the anti-inflammatory response due to it anti-thrombin action (similar or a bit less to that of low molecular weight heparin) with less risk of major bleeding. It's a medication that can be used orally with minimal adverse effects and is less expensive than low molecular weight heparin. Hypothesis: We hypothesize that sulodexide instituted early in populations at significant risk and symptomatic patients affected with COVID-19 (shortness of breath, fever, weakness, diarrhoea) and risk factors of diabetes, hypertension, COPD, atherosclerosis, chronic kidney disease, will provide improvement in endothelial integrity, decrease inflammatory responses, and improved clinical outcomes with decreased hospital admission, decrease VTE and arterial complications, morbidity, and mortality. Objective: To use sulodexide in patients that have early onset of COVID-19 symptoms to mitigate the progression of the disease process that can allow them to recover at home, and limit the need of hospital care and a more severe clinical manifestation

    NCT04483830
    Conditions
    1. Covid19
    Interventions
    1. Drug: Sulodexide
    2. Drug: Placebo

    Primary Outcomes

    Description: need for hospital care admission

    Measure: hospital care

    Time: 21 days since start of trial participation

    Description: number of total days in hospital care

    Measure: days of hospital care

    Time: 21 days since start of trial participation

    Description: total days in need of supplemental oxigen via facial mask or nasal

    Measure: days of need suplemental oxigen

    Time: 21 days since the start of trial participation

    Description: total value in ng/dl of d-dimmer

    Measure: serum level of d-dimmer

    Time: change betwen basal level and at 14 day follow-up

    Description: total value in mg/dl

    Measure: serum level of creatinine

    Time: change between basal level ans at 14 day followup

    Secondary Outcomes

    Description: presence of a tromboembolic event

    Measure: thromboembolic event

    Time: 21 days from start of trial

    Description: the need for the use of endotraqueal tube mechanical ventilation

    Measure: need for mechanical ventilation

    Time: 21 days from the start of the trial
    264 A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Dose Escalation Study to Evaluate the Safety and Efficacy of SPI-1005 in Severe COVID-19 Patients

    The study is a randomized, double-blind, placebo-controlled, dose escalation, multi-center clinical trial (RCT) of SPI-1005 in adult subjects with positive PCR test for novel SARS-CoV-2 (nCoV2) and severe symptoms of COVID-19 disease.

    NCT04483973
    Conditions
    1. Covid19
    2. Coronavirus
    3. Coronavirus Infection
    4. Corona Virus Infection
    Interventions
    1. Drug: Ebselen
    2. Drug: Placebo
    MeSH:Infection Communicable Diseases Coronavirus Infections Severe Acute Respiratory Syndrome

    Primary Outcomes

    Measure: Number of participants with treatment-related adverse events

    Time: 30 days

    Secondary Outcomes

    Description: Clinical outcome assessed by WHO Ordinal Scale for Clinical Improvement. Scale is 0-8 where higher score is worse outcome.

    Measure: WHO Ordinal Scale

    Time: 30 days

    Description: Respiratory status assessed by degree of supplemental oxygen (e.g. mask oxygen, mechanical ventilation)

    Measure: Degree of supplemental oxygen

    Time: 30 days

    Description: Peripheral oxygen saturation measured by pulse oximetry

    Measure: Peripheral Oxygen Saturation (SpO2)

    Time: 30 days
    265 A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Dose Escalation Study to Evaluate the Safety and Efficacy of SPI-1005 in Moderate COVID-19 Patients

    The study is a randomized, double-blind, placebo-controlled, dose escalation, multi-center clinical trial (RCT) of SPI-1005 in adult subjects with positive PCR test for novel SARS-CoV-2 (nCoV2) and moderate symptoms of COVID-19 disease.

    NCT04484025
    Conditions
    1. Covid19
    2. Corona Virus Infection
    3. Coronavirus
    4. Coronavirus Infection
    Interventions
    1. Drug: Ebselen
    2. Drug: Placebo
    MeSH:Infection Communicable Diseases Coronavirus Infections Severe Acute Respiratory Syndrome

    Primary Outcomes

    Measure: Number of participants with treatment-related adverse events

    Time: 30 days

    Secondary Outcomes

    Description: Clinical outcome assessed by WHO Ordinal Scale for Clinical Improvement. Scale is 0-8 where higher score is worse outcome.

    Measure: WHO Ordinal Scale

    Time: 30 days

    Description: Respiratory status assessed by degree of supplemental oxygen (e.g. mask oxygen, mechanical ventilation)

    Measure: Degree of supplemental oxygen

    Time: 30 days

    Description: Peripheral oxygen saturation measured by pulse oximetry

    Measure: Peripheral Oxygen Saturation (SpO2)

    Time: 30 days
    266 DISulfiram for COvid-19 (DISCO) Trial: A Phase 2 Double-Blind, Randomized Placebo-Controlled Trial of Disulfiram Compared to Standard Supportive Care in Outpatients With Symptomatic COVID-19

    Disulfiram (DSF) a safe, easily dosed, FDA-approved drug for the treatment of alcohol dependence has been identified to be a potential therapeutic target for SARS-CoV-2 infection. Disulfiram may have both antiviral (inhibiting viral replication via blocking the Mpro protease and zinc ejection) and anti-inflammatory effects (via inhibition of NF-kB-induced and NLRP inflammasome-induced cytokine release) on SARS-CoV-2. We will study oral disulfiram given for 5 consecutive days (1000 mg/day in cohort 1; 2000 mg/day in cohort 2) in 60 symptomatic COVID+ individuals in a randomized (2:1) randomized, double blind placebo-controlled trial evaluating disulfiram's effect on COVID-19 symptom severity, SARS-CoV-2 viral load, and biomarkers of inflammation and pyroptosis (aberrant pro-inflammatory cell death) over 31 days.

    NCT04485130
    Conditions
    1. Covid19
    Interventions
    1. Drug: Disulfiram
    2. Drug: Placebo

    Primary Outcomes

    Description: Change in plasma inflammatory biomarker levels (e.g., IL-6, IL-1b) at days 5, 15, and 31.

    Measure: Immunologic impact of 5 days of disulfiram, as measured by the fold-change in plasma levels of pro-inflammatory cytokines (e.g, interleukin 6, interleukin 1-beta, etc.).

    Time: 31 days

    Secondary Outcomes

    Description: Change in SARS-CoV-2 PCR quantitative viral load at days 5, 15, and 31

    Measure: Virologic impact of 5 days of disulfiram, as measured by the fold-change in copies of SARS-CoV-2 virus per million cells between Baseline and Day 31.

    Time: 31 days

    Description: The safety and tolerability of a 5 day course of disulfiram. The number of adverse events and their grade will be determined for each participant.

    Measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

    Time: 31 days

    Description: The severity of COVID-19 symptoms will be recorded on a 5-point symptom severity scale at each visit for each participant.

    Measure: Change in COVID-19 symptom severity score as assessed by a 5-point adapted somatic symptom severity score (SSS-8)

    Time: 31 days
    267 Phase 3, Randomized, Double-Blind, Placebo-Controlled, Trial to Evaluate Efficacy and Safety of Nitazoxanide in the Treatment of Mild or Moderate COVID-19

    Trial to Evaluate Efficacy and Safety of Nitazoxanide in the Treatment of Mild or Moderate COVID-19

    NCT04486313
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Nitazoxanide
    2. Drug: Placebo
    3. Dietary Supplement: Vitamin Super B-Complex

    Primary Outcomes

    Description: To evaluate the effect of nitazoxanide in reducing the time to sustained response compared to placebo in subjects with mild or moderate COVID-19

    Measure: Reducing the Time to Sustained Response

    Time: Up to 21 days

    Secondary Outcomes

    Description: To evaluate the effect of nitazoxanide in reducing the rate of progression to severe COVID-19 illness compared to placebo

    Measure: Reducing the Rate of Progression

    Time: Up to 21 days
    268 A Multicenter, Adaptive, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy and Safety of XC221, Tablets, 100 mg in Patients With COVID-19

    The innovative drug XC221 100 mg tablet is designed for the treatment of COVID-19 (SARS-CoV-2 infection). A multicenter, adaptive, randomized, double-blind, placebo-controlled Phase III clinical study is aimed to assess the efficacy and safety of XC221 100 mg tablet, in COVID-19 patients during a 14-day treatment. The primary objective of the study is to demonstrate the efficacy of XC221 100 mg tablet (200 mg daily dose) in achieving clinical improvement of COVID-19 symptoms. The secondary objective of the study is to evaluate the safety of XC221 100 mg tablet (200 mg daily dose) in COVID-19 patients.

    NCT04487574
    Conditions
    1. SARS-CoV-2 Infection
    Interventions
    1. Drug: XC221
    2. Drug: Placebo

    Primary Outcomes

    Description: The scale of the patient's clinical condition, proposed by the WHO, will be used to assess the severity of patient general condition. Ranges for patient's clinical condition: 0 points (no infection) - 8 points (death).

    Measure: Patient rate with a transition to category 3 or lower according to the WHO scale by Day 14 after the beginning of drug administration.

    Time: Day 1 - Day 14

    Secondary Outcomes

    Description: Body temperature ≤ 37.5°C without using NSAIDs and / or paracetamol; RR ≤ 22 / min without oxygen therapy; SpO2 ≥ 95% without oxygen therapy.

    Measure: Time till clinical improvement, which is described by presence of all of the following factors during 48 hours in a row.

    Time: Day 1 - Day 28

    Description: Body temperature ≤ 37.5°C without using NSAIDs and / or paracetamol; RR ≤ 22 / min without oxygen therapy; SpO2 ≥ 95% without oxygen therapy.

    Measure: Patient rate with clinical improvement by day 2-28. Presence of all of the following factors during 48 hours in a row.

    Time: Day 1 - Day 28

    Measure: Patient rate with a negative test result for SARS-CoV-2 by Day 7±1, 15±1, 21 ±1 and 28 ± 1.

    Time: Day 1 - Day 28

    Measure: Duration of hospitalization.

    Time: Day 1 - Day 28

    Measure: Patient rate transferred to the intensive care unit (ICU) during hospitalization.

    Time: Day 1 - Day 28

    Measure: Duration of ICU stay.

    Time: Day 1 - Day 28

    Measure: Patient rate with ARDS during hospitalization.

    Time: Day 1 - Day 28

    Measure: Presence of a fatal outcome.

    Time: Day 1 - Day 28

    Measure: Patient rate requiring oxygen therapy by Day 2-28.

    Time: Day 1 - Day 28

    Measure: Patient rate requiring high-flow oxygen therapy by Day 2-28.

    Time: Day 1 - Day 28

    Measure: Patient rate requiring non-invasive ventilation by Day 2-28.

    Time: Day 1 - Day 28

    Measure: Patient rate requiring invasive ventilation by Day 2-28.

    Time: Day 1 - Day 28

    Measure: Patient rate requiring extracorporeal membrane oxygenation (EMO) by Day 2-28.

    Time: Day 1 - Day 28

    Measure: The total duration of oxygen therapy by the last day of hospitalization.

    Time: Day 1 - Day 28

    Measure: The total duration of high-flow oxygen therapy by the last day of hospitalization.

    Time: Day 1 - Day 28

    Measure: The total duration of non-invasive ventilation by the last day of hospitalization.

    Time: Day 1 - Day 28

    Measure: The total duration of invasive ventilation of lungs by the last day of hospitalization.

    Time: Day 1 - Day 28

    Measure: The total duration of EMO by the last day of hospitalization.

    Time: Day 1 - Day 28

    Measure: Patient rate with Sp02 > 95% by Day 2-28.

    Time: Day 1 - Day 28

    Measure: Average alteration of Sp02 by Day 2-28 from baseline.

    Time: Day 1 - Day 28

    Measure: Average time to reach SpO2 ≥ 95%.

    Time: Day 1 - Day 28

    Measure: Patient rate with RR < 22 / min by Day 2-28.

    Time: Day 1 - Day 28

    Measure: Average alteration in RR by Day 2-28 from baseline.

    Time: Day 1 - Day 28

    Measure: Average time to reach RR ≤ 22 / min.

    Time: Day 1 - Day 28

    Measure: Patient rate with body temperature < 37.5°C by Day 2-28.

    Time: Day 1 - Day 28

    Measure: Average alteration in body temperature by Day 2-28 from baseline.

    Time: Day 1 - Day 28

    Measure: Average time until the patient reaches a body temperature of ≤37.5°C.

    Time: Day 1 - Day 28

    Measure: Patient rate with CT-1 according to CT data by Day 2-28.

    Time: Day 1 - Day 28

    Measure: Average alteration in CT data by 1 point in terms of severity (CT-1, CT-2, CT-3, CT-4) by Day 7, 10, 15, 18, 21 and 28 compared to the baseline value.

    Time: Day 1 - Day 28

    Measure: Average time to reach CT-1 according to CT data.

    Time: Day 1 - Day 28

    Description: The Daytime and Nighttime Cough Scale will be used to assess the dynamics of cough during the study. Ranges for assess: 0 points (no cough) - 6 points (severe cough that makes daytime activity impossible).

    Measure: Patient rate with a score < 2 according to the Daytime and Nighttime Cough Scale by Day 2-28.

    Time: Day 1 - Day 28

    Description: The Daytime and Nighttime Cough Scale will be used to assess the dynamics of cough during the study. Ranges for assess: 0 points (no cough) - 6 points (severe cough that makes daytime activity impossible).

    Measure: Mean change in Daytime and Nighttime Cough scores by Day 2-28 from baseline.

    Time: Day 1 - Day 28

    Description: The Daytime and Nighttime Cough Scale will be used to assess the dynamics of cough during the study. Ranges for assess: 0 points (no cough) - 6 points (severe cough that makes daytime activity impossible).

    Measure: Average time to reach < 2 points when assessed according to the Daytime and Nighttime Cough Scale.

    Time: Day 1 - Day 28

    Description: The Symptom Rating Scale will be used to assess the individuals' subjective ratings the severity of 6 symptoms of COVID-19. Ranges for each symptom: 0 points (no symptoms) - 3 points (the most severe). Total score (ranges from 0 to 18 points) is a sum of points for each symptom.

    Measure: Patient rate with a score < 1 for each symptom (general fatigue, chest congestion, sore throat, decreased sense of smell and taste, nasal congestion) according to a 4-point scale by Day 2-28.

    Time: Day 1 - Day 28

    Description: The Symptom Rating Scale will be used to assess the individuals' subjective ratings the severity of 6 symptoms of COVID-19. Ranges for each symptom: 0 points (no symptoms) - 3 points (the most severe). Total score (ranges from 0 to 18 points) is a sum of points for each symptom.

    Measure: Average change in score for each symptom (general fatigue, chest congestion, sore throat, decreased sense of smell and taste, nasal congestion) according to a 4-point scale by Day 2-28 from baseline.

    Time: Day 1 - Day 28

    Description: The Symptom Rating Scale will be used to assess the individuals' subjective ratings the severity of 6 symptoms of COVID-19. Ranges for each symptom: 0 points (no symptoms) - 3 points (the most severe). Total score (ranges from 0 to 18 points) is a sum of points for each symptom.

    Measure: Average time to reach a score of < 1 for each symptom (general fatigue, feeling of congestion in the chest, sore throat, decreased sense of smell and taste, nasal congestion) according to a 4-point scale.

    Time: Day 1 - Day 28

    Description: The scale of the patient's clinical condition, proposed by the WHO, will be used to assess the severity of patient general condition. Ranges for patient's clinical condition: 0 points (no infection) - 8 points (death).

    Measure: Patient rate with a transition decrease to category 3 or lower according to the WHO scale by Day 2-13 and Day 15-28.

    Time: Day 1 - Day 28

    Description: The scale of the patient's clinical condition, proposed by the WHO, will be used to assess the severity of patient general condition. Ranges for patient's clinical condition: 0 points (no infection) - 8 points (death).

    Measure: Mean WHO grade change by Day 2-28 from baseline.

    Time: Day 1 - Day 28

    Description: The scale of the patient's clinical condition, proposed by the WHO, will be used to assess the severity of patient general condition. Ranges for patient's clinical condition: 0 points (no infection) - 8 points (death).

    Measure: Average time to reach the 3rd category or below according to the WHO scale.

    Time: Day 1 - Day 28

    Description: Parameters will be assessed according to the National Early Warning Score only during hospitalization. During the treatment period, the assessment will be performed 2 times a day. During the follow-up period, the assessment will be performed once a day. The worst result for each period is to be chosen.

    Measure: Patient rate with a NEWS score < 2 by Day 2-28.

    Time: Day 1 - Day 28

    Description: Parameters will be assessed according to the National Early Warning Score only during hospitalization. During the treatment period, the assessment will be performed 2 times a day. During the follow-up period, the assessment will be performed once a day. The worst result for each period is to be chosen.

    Measure: Average change in NEWS score by Day 2-28 from baseline.

    Time: Day 1 - Day 28

    Description: Parameters will be assessed according to the National Early Warning Score only during hospitalization. During the treatment period, the assessment will be performed 2 times a day. During the follow-up period, the assessment will be performed once a day. The worst result for each period is to be chosen.

    Measure: Average time to reach a NEWS score ≤ 2.

    Time: Day 1 - Day 28

    Other Outcomes

    Description: (Search Outcome)

    Measure: Concentration of IL-6 on Days 3 ± 1, 7 ± 1, 15 ± 1.

    Time: Day 1 - Day 15
    269 Duvelisib Ameliorates Manifestations of Pneumonia in Established Novel Coronavirus Infection

    In this study, a total of 80 patients with severe coronavirus disease 2019 (COVID-19) infection will be randomized to receive Duvelisib or a placebo. Participants will be enrolled at Emory University Hospital and at the University of Pennsylvania and will be identified and recruited by their treating physician and research team.

    NCT04487886
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Duvelisib
    2. Drug: Placebo
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: This is a composite endpoint of the number of participants who require mechanical ventilation or who die within four weeks of randomization.

    Measure: Number of Participants Requiring Mechanical Ventilation or Dying

    Time: Up to Day 29

    Secondary Outcomes

    Description: Time to recovery (in days) is defined as a score of greater than 5 from the following eight categories from the NIAID ordinal scale. The scale is as follows: 1. Death; 2. Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3. Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4. Hospitalized, requiring supplemental oxygen; 5. Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6. Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7. Not hospitalized, limitation on activities and/or requiring home oxygen; 8. Not hospitalized, no limitations on activities.

    Measure: Days to Recovery

    Time: Up to Day 29

    Description: The number of days spent hospitalized will be compared between study arms.

    Measure: Duration of Hospitalization

    Time: Up to Day 29

    Description: The incidence of death within 29 days of randomization will be compared between study arms.

    Measure: Incidence of Death

    Time: Up to Day 29

    Description: Comparing the proportion of subjects in each group requiring ICU transfer within 29 days of randomization

    Measure: Proportion of Participants Transferred to ICU

    Time: Up to Day 29

    Description: The ECOG Performance Status instrument includes a single item assessing overall physical status. Health status is rated on a scale of 0 to 5 where 0 = fully active and 5 = dead. Median ECOG performance will be compared between study arms.

    Measure: Change in Eastern Cooperative Oncology Group (ECOG) Performance Status Score

    Time: Day 15, Day 29

    Description: The incidence of grade III-V adverse events or Serious Adverse Events (SAEs), as defined by Common Terminology Criteria for Adverse Events (CTCAE) version 5, will be compared between study arms.

    Measure: Incidence of Grade III-V Adverse Events

    Time: Up to Day 29

    Description: The incidence of documented secondary bacterial or viral infections among participants will be compared between study arms.

    Measure: Incidence of Secondary Bacterial or Viral Infections

    Time: Up to Day 29

    Description: The mean frequency of Th1 T cells in blood mononuclear cells will be compared between study arms.

    Measure: Change in Th1 T Cell Frequency

    Time: Weeks 1, 2, and 4

    Description: The mean frequency of Th17 T cells in blood mononuclear cells will be compared between study arms.

    Measure: Change in Th17 T Cell Frequency

    Time: Weeks 1, 2, and 4

    Description: Mean levels of the inflammatory serum biomarker IL-2 will be compared between study arms.

    Measure: Change in Interleukin-2 (IL-2)

    Time: Weeks 1, 2, and 4

    Description: Mean levels of the inflammatory serum biomarker IL-2R will be compared between study arms.

    Measure: Change in Interleukin-2 receptor (IL-2R)

    Time: Weeks 1, 2, and 4

    Description: Mean levels of the inflammatory serum biomarker IL-6 will be compared between study arms.

    Measure: Change in Interleukin-6 (IL-6)

    Time: Weeks 1, 2, and 4

    Description: Mean levels of the inflammatory serum biomarker IL-7 will be compared between study arms.

    Measure: Change in Interleukin-7 (IL-7)

    Time: Weeks 1, 2, and 4

    Description: Mean levels of the inflammatory serum biomarker IL-8 will be compared between study arms.

    Measure: Change in Interleukin-8 (IL-8)

    Time: Weeks 1, 2, and 4

    Description: Mean levels of the inflammatory serum biomarker IL-10 will be compared between study arms.

    Measure: Change in Interleukin-10 (IL-10)

    Time: Weeks 1, 2, and 4

    Description: Mean levels of the inflammatory serum biomarker IP-10 will be compared between study arms.

    Measure: Change in Interferon gamma-induced Protein 10 (IP-10)

    Time: Weeks 1, 2, and 4

    Description: Mean levels of the inflammatory serum biomarker MIP-1a will be compared between study arms.

    Measure: Change in Macrophage Inflammatory Protein 1alpha (MIP-1a)

    Time: Weeks 1, 2, and 4

    Description: Mean levels of the inflammatory serum biomarker MCP-1 will be compared between study arms.

    Measure: Change in Monocyte Chemoattractant Protein-1 (MCP-1)

    Time: Weeks 1, 2, and 4

    Description: Mean levels of the inflammatory serum biomarker G-CSF will be compared between study arms.

    Measure: Change in Granulocyte Colony-stimulating Factor (G-CSF)

    Time: Weeks 1, 2, and 4

    Description: Mean levels of the inflammatory serum biomarker TNF-alpha will be compared between study arms.

    Measure: Change in Tumor Necrosis Factor (TNF)-alpha

    Time: Weeks 1, 2, and 4

    Description: VIP is a peptide hormone with immunosuppressive properties. Mean levels VIP will be compared between study arms.

    Measure: Change in Vasoactive Intestinal Peptide (VIP)

    Time: Weeks 1, 2, and 4

    Description: Mean levels of the Tregs will be compared between study arms.

    Measure: Change in Gene Expression Profile of Regulatory T Cells (Tregs)

    Time: Weeks 1, 2, and 4

    Description: Mean levels of CD8+IFNg+GM-CSF+ will be compared between study arms.

    Measure: Change in Gene Expression Profile of cluster of differentiation 8 (CD8)+Interferon Gamma (IFNg)+ Granulocyte-macrophage colony-stimulating factor (GM-CSF)+

    Time: Weeks 1, 2, and 4

    Description: Mean levels of CD8+Tim3+PD-1+ will be compared between study arms.

    Measure: Change in Gene Expression Profile of CD8+ T cell immunoglobulin and mucin domain-containing protein 3 (Tim3)+ Programmed cell death protein 1 (PD-1)+

    Time: Weeks 1, 2, and 4

    Description: Mean levels of CD14+CD16+ monocytes will be compared between study arms.

    Measure: Change in Gene Expression Profile of cluster of differentiation 14 (CD14)+ cluster of differentiation (CD16)+ monocytes

    Time: Weeks 1, 2, and 4

    Description: Mean levels of SARS-CoV-2 viremia in respiratory specimens will be compared between study arms.

    Measure: Change in SARS-CoV-2 Viremia

    Time: Weeks 1, 2, and 4

    Description: Median titers of IgG antibodies to SARS-CoV-2 will be compared between study arms.

    Measure: Change in Immunoglobulin G (IgG) Antibodies

    Time: Weeks 1, 2, and 4

    Description: Median titers of IgM antibodies to SARS-CoV-2 will be compared between study arms.

    Measure: Change in Immunoglobulin M (IgM) Antibodies

    Time: Weeks 1, 2, and 4

    Description: Overall survival is defined as days from randomization to death and censored at last follow up.

    Measure: Overall Survival

    Time: Up to Day 29
    270 A Phase 2 Double-blind Placebo-controlled Study Investigating the Safety and Efficacy of EDP1815 in the Treatment of Patients Hospitalized With SARS-CoV-2 Infection

    Evelo will investigate the safety and efficacy of EDP1815 in the treatment of patients hospitalized with SARS-CoV-2 Infection

    NCT04488575
    Conditions
    1. Covid19
    Interventions
    1. Drug: EDP1815
    2. Drug: Placebo
    MeSH:Infection

    Primary Outcomes

    Description: Pulmonary function as measured by the change in Oxygen Saturation (SpO2) / Fraction of Inspired Oxygen (FiO2) [S/F ratio]

    Measure: Change from baseline to the lowest S/F oxygen ratio

    Time: 14 days

    Secondary Outcomes

    Description: The effect of 1815 on the development and severity of complications of COVID-19 infection will be measured using change in S/F ratio at days 4, 7, 10 and 14/discharge day.

    Measure: Change in S/F Ratio

    Time: 14 days

    Description: The effect of 1815 on the development and severity of complications of COVID-19 infection will be measured using percentage change in S/F ratio at days 4, 7, 10 and 14/discharge day.

    Measure: Percentage change in S/F Ratio

    Time: 14 days

    Description: The effect of 1815 on the development and severity of complications of COVID-19 infection will be measured using percentage of participants at each level on the WHO OSCI score at days 4, 7, 14, 21 and 42

    Measure: Percentage of participants at each level on the WHO OSCI score

    Time: 42 days

    Description: The effect of 1815 on the development and severity of complications of COVID-19 infection will be measured using percentage of participants with shifts from each level of the WHO OSCI score at baseline at days 4, 7, 14, 21 and 42

    Measure: Percentage of participants with shifts from each level of the WHO OSCI score at baseline

    Time: 42 days

    Description: The effect of 1815 on the development and severity of complications of COVID-19 infection will be measured using percentage of participants remaining at their baseline score on the WHO OSCI (or lower) at days 4, 7, 14, 21 and 42

    Measure: Percentage of participants remaining at their baseline score on the WHO OSCI (or lower)

    Time: 42 days

    Description: The effect of 1815 on the development and severity of complications of COVID-19 infection will be measured using percentage of participants reporting each level of the WHO OSCI score at their worst post-baseline day

    Measure: Percentage of participants reporting each level of the WHO OSCI score at their worst post-baseline day

    Time: 42 days

    Description: The effect of 1815 on the development and severity of complications of COVID-19 infection will be measured using the time in days spent at each participant's worst reported WHO OSCI score (excluding death).

    Measure: The time in days spent at each participant's worst reported WHO OSCI score (excluding death).

    Time: 42 days

    Description: The effect of 1815 on the development and severity of complications of COVID-19 infection will be measured using the intubation and mechanical-ventilation free survival, defined as the time in days from start of treatment to first occurrence of a WHO OSCI score of 6 or more.

    Measure: Intubation and mechanical-ventilation free survival

    Time: 42 days

    Description: The effect of 1815 on the development and severity of complications of COVID-19 infection will be measured using overall survival, defined as the time in days from start of treatment to death by any cause

    Measure: Overall survival

    Time: 42 days

    Description: The effect of 1815 on the development and severity of complications of COVID-19 infection will be measured using number of days requiring oxygen therapy

    Measure: Number of days requiring oxygen therapy

    Time: 42 days

    Description: The effect of 1815 on the development and severity of complications of COVID-19 infection will be measured using number of days with pyrexia ≥ 38C

    Measure: Number of days with pyrexia

    Time: 42 days

    Description: The effect of 1815 on the development and severity of complications of COVID-19 infection will be measured using maximum daily temperature

    Measure: Maximum daily temperature

    Time: 42 days

    Description: The effect of 1815 on the development and severity of complications of COVID-19 infection will be measured using minimum and maximum SpO2 levels

    Measure: SpO2 level

    Time: 42 days

    Description: The effect of EDP1815 on length of hospitalization and recovery in participants with COVID-19 will be measured using time to discharge, defined as the time in days from start of treatment to first occurrence of a WHO OSCI score of 2 or less.

    Measure: Time to discharge

    Time: 42 days

    Description: The effect of EDP1815 on length of hospitalization and recovery in participants with COVID-19 will be measured using time to oxygen saturation (SpO2) ≥94% on room air without further requirement for oxygen therapy.

    Measure: Time to oxygen saturation (SpO2) ≥94%

    Time: 42 days

    Description: The effect of EDP1815 on length of hospitalization and recovery in participants with COVID-19 will be measured using time to recovery, defined as the time in days from symptom onset to alleviation of all COVID-19 symptoms.

    Measure: Time to recovery

    Time: 42 days

    Description: The safety and tolerability of EDP1815 in participants with COVID-19 will be measured using the number of participants experiencing AEs by seriousness and relationship to treatment

    Measure: Number of participants experiencing AEs by seriousness and relationship to treatment

    Time: 42 days

    Description: The safety and tolerability of EDP1815 in participants with COVID-19 will be measured using the number of participants experiencing clinically significant abnormal changes in safety lab parameters

    Measure: Incidence of clinically significant abnormal lab parameters

    Time: 42 days
    271 Sildenafil for Treating Patients With COVID-19 and Perfusion Mismatch: A Pilot Randomised Trial

    This randomised trial aims to assess the role of sildenafil in improving oxygenation amongst hospitalised patients with COVID19.

    NCT04489446
    Conditions
    1. Covid19
    2. SARS-COV2 Infection
    Interventions
    1. Drug: Sildenafil
    2. Drug: Placebo
    MeSH:Infection

    Primary Outcomes

    Description: Mean difference in alveolar oxygen pressure to inspired oxygen fraction (Pa/Fi) ratios.

    Measure: Arterial Oxygenation

    Time: One hour after sildenafil administration

    Description: Mean difference in alveolar oxygen pressure to inspired oxygen fraction (Pa/Fi) ratios.

    Measure: Arterial Oxygenation

    Time: Daily until the end of follow-up (up to 15 days after randomisation)

    Description: Mean difference in the alveolo-arterial gradient between study groups.

    Measure: Alveolo-arterial gradient

    Time: One hour after sildenafil administration

    Description: Mean difference in the alveolo-arterial gradient between study groups.

    Measure: Alveolo-arterial gradient

    Time: Daily until the end of follow-up (up to 15 days after randomisation)

    Secondary Outcomes

    Description: Proportion of patients requiring admission to an intensive care unit in each study group

    Measure: Intensive care unit admission

    Time: Up to two weeks after randomisation

    Description: Proportion of patients requiring noninvasive mechanical ventilation o high-flow nasal cannula unit in each study group

    Measure: Noninvasive Mechanical Ventilation or Requirement of High-Flow Nasal Cannula

    Time: Up to two weeks after randomisation

    Description: Proportion of patients requiring invasive mechanical ventilation in each study group

    Measure: Invasive mechanical ventilation

    Time: Up to two weeks after randomisation

    Description: Proportion of patients that survived COVID19 in each study group

    Measure: Survival

    Time: Up to two weeks after randomisation

    Other Outcomes

    Description: Adverse events attributable to sildenafil use.

    Measure: Adverse events

    Time: Up to two weeks after randomisation
    272 Phase I, Randomized, Double Blinded, Placebo Control Study to Evaluate the Safety and Potential Efficacy of Intravenous Infusion of Umbilical Cord Tissue (UC) Derived Mesenchymal Stem Cells (MSCs) Versus Placebo to Treat Acute Pulmonary Inflammation Due to COVID-19 With Moderate to Severe Symptoms

    The purpose of this study is to demonstrate the safety of Umbilical Cord Tissue Derived Mesenchymal Stem Cells (UCMSCs) administered intravenously in patients with acute pulmonary inflammation due to COVID-19 with moderately severe symptoms

    NCT04490486
    Conditions
    1. COVID-19
    2. Acute Respiratory Distress Syndrome
    3. Corona Virus Infection
    Interventions
    1. Biological: UCMSCs
    2. Other: Placebo
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Pneumonia Inflammation
    HPO:Pneumonia

    Primary Outcomes

    Description: Safety of UCMSCs will be reported as the percentage of participants in each treatment group that experienced a treatment related SAEs.

    Measure: Percent of participants with treatment related Serious Adverse Events (SAE)

    Time: 12 months

    Secondary Outcomes

    Description: Change in serum inflammatory marker levels including Interleukin (IL) IL-6, IL-2, Tumor Necrosis Factor Alpha (TNF-a) and procalcitonin will be evaluated in ng/L.

    Measure: Change in inflammatory marker levels

    Time: Baseline, Day 30

    Description: Change in serum systemic inflammatory marker levels including D-dimer, high sensitivity C-reactive protein (hsCRP) and ferritin will be evaluated in mg/L.

    Measure: Change in systemic inflammatory marker levels

    Time: Baseline, Day 30

    Description: Assessed using blood samples or nose/throat swabs.

    Measure: COVID-19 Viral Load

    Time: Up to 30 Days

    Description: Sequential Organ Failure Assessment (SOFA) will be used to assess organ failure including the cardiovascular system, coagulation system, liver, kidney and other extra-pulmonary organs. SOFA score ranges from 0-24 with the higher score indicating worse outcomes.

    Measure: Change in SOFA score

    Time: Baseline, Up to 30 Days

    Description: Sodium, Potassium, Chloride and Carbon Dioxide (CO2) will be evaluated in mmol/L. Changes from baseline to Day 30 will be compared between groups.

    Measure: Change in electrolytes levels

    Time: Baseline, Up to 30 Days

    Description: Serum Lactate Dehydrogenase (LDH) levels assessed in U/L. Changes in LDH from baseline to Day 30 will be compared between groups.

    Measure: Change in LDH levels

    Time: Baseline, Up to 30 Days

    Description: ICU monitoring status will be reported as the number of subjects discharged from the ICU within 7 days.

    Measure: Number of subjects discharged from the ICU

    Time: Up to 7 Days

    Description: Percentage of participants requiring less use of vasoactive agents will be reported.

    Measure: Percentage of participants with less requirement for vasoactive agents

    Time: Up to 30 Days

    Description: Percentage of participant deaths throughout the study period.

    Measure: Rate of Mortality

    Time: Up to 30 Days

    Description: The percentage of participants with changes in serum immune marker levels including Cluster of Differentiation (CD) CD 4+ and CD 8+, as evaluated by treating physician will be reported.

    Measure: Percentage of participants with changes in immune marker expression

    Time: Up to 30 Days

    Description: Percentage of participants with changes in their chest imaging such as ground-glass opacity, local patch shadowing, bilateral patch shadowing and interstitial abnormalities will be reported. Imaging will be assessed by treating physician using chest radiography or chest Computed Tomography (CT).

    Measure: Percentage of participants with changes in radiologic findings

    Time: Up to 30 Days

    Description: Percentage of participants showing less pneumonia symptoms will be reported as evaluated by treating physician using chest radiography or chest CT.

    Measure: Percentage of participants with less pneumonia symptoms

    Time: Up to 30 Days
    273 A Multicenter, Adaptive, Randomized Blinded Controlled Trial of the Safety and Efficacy of Investigational Therapeutics for the Treatment of COVID-19 in Hospitalized Adults (ACTT-3)

    ACTT-3 will evaluate the combination of interferon beta-1a and remdesivir compared to remdesivir alone. Subjects will be assessed daily while hospitalized. If the subjects are discharged from the hospital, they will have a study visit at Days 15, 22, and 29. For discharged subjects, it is preferred that the Day 15 and 29 visits are in person to obtain safety laboratory tests and oropharyngeal (OP) swab and blood (serum only) samples for secondary research as well as clinical outcome data. However, infection control or other restrictions may limit the ability of the subject to return to the clinic. In this case, these visits may be conducted by phone, and only clinical data will be obtained. The Day 22 visit does not have laboratory tests or collection of samples and is conducted by phone. The primary outcome is time to recovery by Day 29.

    NCT04492475
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Interferon beta-1a
    2. Other: Placebo
    3. Drug: Remdesivir

    Primary Outcomes

    Description: Day of recovery is defined as the first day on which the subject satisfies one of the following three categories from the ordinal scale: 1) Not hospitalized, no limitations on activities; 2) Not hospitalized, but new or increased limitation on activities and/or new or increased requirement for home oxygen; 3) Hospitalized, not requiring supplemental oxygen and no longer requires ongoing medical care.

    Measure: Time to recovery for patients with baseline ordinal score 4, 5, and 6

    Time: Day 1 through Day 29

    Secondary Outcomes

    Description: Assessed overall and by baseline ordinal scale category (categories 4 and 5 versus category 6).

    Measure: Change from baseline in alanine aminotransferase (ALT)

    Time: Day 1 through Day 29

    Description: Assessed overall and by baseline ordinal scale category (categories 4 and 5 versus category 6).

    Measure: Change from baseline in aspartate aminotransferase (AST)

    Time: Day 1 through Day 29

    Measure: Change from baseline in C-reactive protein (CRP)

    Time: Day 1 through Day 29

    Description: Assessed overall and by baseline ordinal scale category (categories 4 and 5 versus category 6).

    Measure: Change from baseline in creatinine

    Time: Day 1 through Day 29

    Measure: Change from baseline in d-dimer concentration

    Time: Day 1 through Day 29

    Description: Assessed overall and by baseline ordinal scale category (categories 4 and 5 versus category 6).

    Measure: Change from baseline in hemoglobin

    Time: Day 1 through Day 29

    Description: Assessed overall and by baseline ordinal scale category (categories 4 and 5 versus category 6).

    Measure: Change from baseline in international normalized ratio (INR)

    Time: Day 1 through Day 29

    Description: Assessed overall and by baseline ordinal scale category (categories 4 and 5 versus category 6).

    Measure: Change from baseline in platelets

    Time: Day 1 through Day 29

    Description: Assessed overall and by baseline ordinal scale category (categories 4 and 5 versus category 6).

    Measure: Change from baseline in total bilirubin

    Time: Day 1 through Day 29

    Description: Assessed overall and by baseline ordinal scale category (categories 4 and 5 versus category 6).

    Measure: Change from baseline in white blood cell count (WBC) with differential

    Time: Day 1 through Day 29

    Description: The NEW score has demonstrated an ability to discriminate patients at risk of poor outcomes. This score is based on 7 clinical parameters (respiration rate, oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate, level of consciousness). The NEW Score is being used as an efficacy measure.

    Measure: Change in National Early Warning Score (NEWS) from baseline

    Time: Day 1 through Day 29

    Description: Assessed overall and by baseline ordinal scale category (categories 4 and 5 versus category 6). Grade 3 AEs are defined as events that interrupt usual activities of daily living, or significantly affects clinical status, or may require intensive therapeutic intervention. Severe events are usually incapacitating. Grade 4 AEs are defined as events that are potentially life threatening.

    Measure: Cumulative incidence of Grade 3 and 4 clinical and/or laboratory adverse events (AEs)

    Time: Day 1 through Day 29

    Description: Assessed overall and by baseline ordinal scale category (categories 4 and 5 versus category 6). An SAE is defined as an AE or suspected adverse reaction is considered serious if, in the view of either the investigator or the sponsor, it results in death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect.

    Measure: Cumulative incidence of serious adverse events (SAEs)

    Time: Day 1 through Day 29

    Description: Measured in days.

    Measure: Duration of hospitalization

    Time: Day 1 through Day 29

    Description: Measured in days.

    Measure: Duration of invasive mechanical ventilation

    Time: Day 1 through Day 29

    Description: Measured in days.

    Measure: Duration of new non-invasive ventilation or high flow oxygen use

    Time: Day 1 through Day 29

    Description: Measured in days.

    Measure: Duration of new oxygen use

    Time: Day 1 through Day 29

    Description: Measured in days.

    Measure: Duration of new ventilator or extracorporeal membrane oxygenation (ECMO) use

    Time: Day 1 through Day 29

    Description: Measured in days.

    Measure: Duration of non invasive ventilation or high flow oxygen use

    Time: Day 1 through Day 29

    Description: Measured in days

    Measure: Duration of oxygen use

    Time: Day 1 through Day 29

    Description: For any reason. Assessed overall and by baseline ordinal scale category (categories 4 and 5 versus category 6).

    Measure: Incidence of discontinuation or temporary suspension of study product administration

    Time: Day 1 through Day 10

    Measure: Incidence of new non-invasive ventilation or high flow oxygen use

    Time: Day 1 through Day 29

    Measure: Incidence of new oxygen use

    Time: Day 1 through Day 29

    Measure: Incidence of new ventilator or extracorporeal membrane oxygenation (ECMO) use

    Time: Day 1 through Day 29

    Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Not hospitalized, no limitations on activities; 2) Not hospitalized, but new or increased limitation on activities and/or new or increased requirement for home oxygen; 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 5) Hospitalized, requiring supplemental oxygen; 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 8) Death.

    Measure: Mean change from baseline in the ordinal scale

    Time: Day 1 through Day 29

    Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Not hospitalized, no limitations on activities; 2) Not hospitalized, but new or increased limitation on activities and/or new or increased requirement for home oxygen; 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 5) Hospitalized, requiring supplemental oxygen; 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 8) Death.

    Measure: Participant's clinical status at Day 15 by ordinal scale for patients with baseline ordinal score 4 and 5

    Time: Day 15

    Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Not hospitalized, no limitations on activities; 2) Not hospitalized, but new or increased limitation on activities and/or new or increased requirement for home oxygen; 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 5) Hospitalized, requiring supplemental oxygen; 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 8) Death.

    Measure: Percentage of subjects reporting each severity rating on an 8 point ordinal scale

    Time: Days 3, 5, 8, 11, 22, and 29

    Description: Date and cause of death (if applicable).

    Measure: Subject 14-day mortality

    Time: Day 1 through Day 15

    Description: Date and cause of death (if applicable).

    Measure: Subject 28-day mortality

    Time: Day 1 through Day 29

    Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Not hospitalized, no limitations on activities; 2) Not hospitalized, but new or increased limitation on activities and/or new or increased requirement for home oxygen; 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 5) Hospitalized, requiring supplemental oxygen; 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 8) Death.

    Measure: Time to an improvement of one category using an ordinal scale

    Time: Day 1 through Day 29

    Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Not hospitalized, no limitations on activities; 2) Not hospitalized, but new or increased limitation on activities and/or new or increased requirement for home oxygen; 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 5) Hospitalized, requiring supplemental oxygen; 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 8) Death.

    Measure: Time to an improvement of two categories using an ordinal scale

    Time: Day 1 through Day 29

    Description: The NEW score has demonstrated an ability to discriminate patients at risk of poor outcomes. This score is based on 7 clinical parameters (respiration rate, oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate, level of consciousness). The NEW Score is being used as an efficacy measure.

    Measure: Time to discharge or to a National Early Warning Score (NEWS) of Time: Day 1 through Day 29

    Description: Day of recovery is defined as the first day on which the subject satisfies one of the following three categories from the ordinal scale: 1) Not hospitalized, no limitations on activities; 2) Not hospitalized, but new or increased limitation on activities and/or new or increased requirement for home oxygen; 3) Hospitalized, not requiring supplemental oxygen and no longer requires ongoing medical care.

    Measure: Time to recovery for patients with a baseline ordinal score of 4 and 5

    Time: Day 1 through Day 29
    274 Mavrilimumab to Reduce Progression of Acute Respiratory Failure in COVID-19 Pneumonia and Systemic Hyper-inflammation

    The purpose of this prospective, Phase 2, multicenter, blinded, randomized placebo controlled study is to demonstrate that early treatment with mavrilimumab prevents progression of respiratory failure in patients with severe COVID-19 pneumonia and clinical and biological features of hyper-inflammation.

    NCT04492514
    Conditions
    1. COVID 19
    2. SARS-CoV 2
    3. Pneumonia
    Interventions
    1. Drug: Mavrilimumab
    2. Drug: Placebo
    MeSH:Pneumonia Respiratory Insufficiency
    HPO:Pneumonia

    Primary Outcomes

    Description: Proportion of subjects alive and off oxygen at day14

    Measure: Primary Outcome Measure:

    Time: Day 14

    Secondary Outcomes

    Description: Proportion of subjects alive and without respiratory failure at 28 days

    Measure: Secondary Outcome Measures:

    Time: 28 days
    275 BARCONA: A Phase II/III, Randomized, Double-blind, Placebo-controlled, Multi-center Study of the Effects of Bardoxolone Methyl in Participants With SARS-Corona Virus-2 (COVID-19)

    This multi-center, double-blind, placebo-controlled, randomized Phase 2/3 trial will study the safety, tolerability, and efficacy of bardoxolone methyl in approximately 400-440 patients hospitalized with confirmed COVID-19. The Phase 2 portion of the trial will include approximately 40 patients and is designed to provide an early interim analysis of safety. The Phase 3 portion of the trial will include approximately 360-400 additional patients, and is designed to determine whether bardoxolone methyl increases the probability of recovery at Day 29 when compared with matching placebo. Patients will be randomized using permuted block randomization in a 1:1 fashion to either once-daily administration of bardoxolone methyl (20 mg) or matching placebo and treatment will be administered for the duration of hospitalization (until recovery), with a maximum treatment duration of 29 days.

    NCT04494646
    Conditions
    1. Covid19
    Interventions
    1. Drug: Bardoxolone methyl
    2. Drug: Placebo
    MeSH:Coronavirus Infections

    Primary Outcomes

    Measure: Incidence of Serious Adverse Events in Phase 2

    Time: Day 29

    Description: Recovery is defined as alive, free of respiratory failure (e.g., need for noninvasive, or invasive mechanical ventilation, high flow oxygen, or ECMO) and free of renal replacement therapy (RRT).

    Measure: Proportion of participants who have recovered in Phase 3

    Time: Day 29

    Secondary Outcomes

    Measure: Average number of renal replacement therapy (RRT)-free days

    Time: Day 29

    Measure: Average number of mechanical ventilation-free days

    Time: Day 29

    Measure: Incidence of All-Cause Mortality

    Time: Day 29

    Description: Deterioration is defined by a 1-point worsening scale: 0- Uninfected; no viral RNA detected, 1- Asymptomatic; viral RNA detected, 2- Symptomatic; Independent, 3- Symptomatic; assistance needed, 4- Hospitalized; no oxygen therapy, 5- Hospitalized; oxygen by mask or nasal prongs, 6- Hospitalized; oxygen by NIV or High flow, 7- Intubation & Mechanical ventilation; pO2/FIO2 >/= 150 or SpO2/FIO2 >/=200, 8- Mechanical ventilation pO2/FIO2 < 150 (SpO2/FIO2 <200) or vasopressors, 9- Mechanical ventilation pO2/FIO2 < 150 and vasopressors, dialysis or ECMO, 10- Death

    Measure: Proportion of participants who experienced deterioration from baseline

    Time: Day 29
    276 A Phase 2 Trial to Evaluate the Safety and Tolerability of Clazakizumab® [Anti-Interleukin (IL)-6 Monoclonal] Compared to Placebo for the Treatment of COVID-19 Infection

    The purpose of this study is to investigate the effectiveness and safety of treatment with clazakizumab compared to a placebo (inactive substance). We are proposing to try this drug to treat coronavirus disease 2019 (COVID-19) infection. Patients with COVID-19 infection have been shown to have increases in certain inflammatory processes. Clazakizumab is an antibody (immune system protein) that blocks certain inflammatory processes. The treatment plan is to attempt to inhibit or block these inflammatory processes in order to try to limit the damage COVID-19 causes to the lungs.

    NCT04494724
    Conditions
    1. COVID-19 Infection
    Interventions
    1. Drug: Clazakizumab
    2. Drug: Placebo
    MeSH:Infection Communicable Diseases

    Primary Outcomes

    Description: Proportion of participants who experience treatment-related adverse events (TEAE) ≥ Grade 3 (CTCAE v5.0) during the first 24 hours after infusion of clazakizumab or placebo

    Measure: Primary Endpoint

    Time: 24 hours

    Secondary Outcomes

    Description: Proportion of participants who need mechanical ventilation and/or extracorporeal membrane oxygenation (ECMO) after the first dose of clazakizumab or placebo

    Measure: Requirement for mechanical ventilation and/or extracorporeal membrane oxygenation (ECMO)

    Time: 14 days

    Description: Proportion of participants who experience infusion-related reactions during the first 24 hours after infusion of clazakizumab or placebo

    Measure: Infusion-related reactions during 24 hours from the time of infusion

    Time: 24 hours

    Description: Proportion of participants alive at day 28 after the first dose of clazakizumab or placebo

    Measure: Patient survival at 28 days

    Time: 28 days

    Description: Proportion of participants alive at day 60 after the first dose of clazakizumab or placebo

    Measure: Patient survival at 60 days

    Time: 60 days

    Description: Proportion of participants who require an open-label dose of clazakizumab

    Measure: Requirement for open-label clazakizumab

    Time: 14 days

    Description: Number of days in the ICU following the first dose of clazakizumab or placebo

    Measure: Time in the intensive care unit (ICU)

    Time: 60 days

    Description: Number of days in the hospital following the first dose of clazakizumab or placebo

    Measure: Time in the hospital

    Time: 60 days

    Description: Number of days from first dose of clazakizumab or placebo to requiring mechanical ventilation

    Measure: Time to mechanical ventilation

    Time: 60 days

    Description: Difference in WHO Clinical Progression Scale between clazakizumab and placebo

    Measure: Clinical status improvement assessed by the World Health Organization (WHO) Clinical Progression Scale at day 14

    Time: 14 days

    Description: Difference in WHO Clinical Progression Scale between clazakizumab and placebo

    Measure: Clinical status improvement assessed by World Health Organization (WHO) Clinical Progression Scale at day 28

    Time: 28 days

    Description: Difference in mean or median change in radiologic assessment of lung edema (RALE) score at day 14 from baseline between clazakizumab or placebo

    Measure: Change in Radiologic Assessment of Lung Edema (RALE) at day 14

    Time: 14 days

    Description: Difference in mean or median change in radiologic assessment of lung edema (RALE) score at day 28 from baseline between clazakizumab or placebo

    Measure: Change in Radiologic Assessment of Lung Edema (RALE) at day 28

    Time: 28 days
    277 A Stage 2/3, Adaptive, Randomized, Controlled, Double-blind Study to Investigate the Pharmacokinetics, Efficacy and Safety of the Hyperimmune Equine Serum (INM005) in Adult Patients With Moderate to Severe Confirmed SARS-CoV2 Disease.

    This study aims to analyze the efficacy and safety of passive immunotherapy by administering an equine hyperimmune serum (INM005) against the SARS-CoV2 RBD to Covid19 patients. Improvement of the clinical course 28 days after the start of treatment will be evaluated.

    NCT04494984
    Conditions
    1. Covid19
    Interventions
    1. Drug: INM005
    2. Drug: Placebo

    Primary Outcomes

    Description: The primary endpoint will be the proportion of patients who show a change in symptoms 28 days after the administration of the first dose. A responding subject is defined as a subject with improvement in at least 2 categories on the 8-point World Health Organization (WHO) ordinal scale of clinical status or a subject who is discharged.

    Measure: Clinical changes in COVID-19 symptoms

    Time: 4 weeks

    Secondary Outcomes

    Description: INM005 product concentration in serum at different time points after dosing

    Measure: Pharmacokinetics evaluation of INM005

    Time: 1 week

    Description: Time to achieve a change in at least 2 categories on the 8-point WHO ordinal scale of clinical status. Time to discharge (days). Time to intensive care unit (ICU) discharge (days).

    Measure: Time to progression of disease

    Time: 4 weeks

    Description: Proportion of patients who present change in at least 2 categories on the 8-point WHO ordinal scale of clinical status at 7 and 14 days after the start of the treatment.

    Measure: Disease progression

    Time: up to 2 weeks

    Description: Proportion of patients discharged at 28 days

    Measure: Discharge

    Time: up to 4 weeks

    Description: Proportion of patients who require ICU hospitalization

    Measure: Intensive care unit (ICU) hospitalization

    Time: up to 4 weeks

    Description: Proportion of patients who require MVA

    Measure: Mechanical ventilation assistance (MVA)

    Time: up to 4 weeks

    Description: Proportion of patients who die due to complications from COVID19

    Measure: Mortality

    Time: up to 4 weeks

    Description: Change in viral load from baseline to 7 and 21 days after the start of the treatment.

    Measure: Changes in viral load

    Time: up to 3 weeks

    Other Outcomes

    Description: Measurement of anti SARS-CoV2 antibodies titer levels. IgG (0, 21 days)

    Measure: Anti SARS-CoV2 antibodies levels

    Time: 3 weeks

    Description: Changes in Troponin T levels will be evaluated at 7 and 21 days as a measurement of disease progression

    Measure: Changes in Troponin T levels

    Time: 3 weeks

    Description: Changes in D-dimer levels will be evaluated at 7 and 21 days as a measurement of disease progression

    Measure: Changes in D-dimer levels

    Time: 3 weeks

    Description: Changes in Ferritin levels will be evaluated at 7 and 21 days as a measurement of disease progression

    Measure: Changes in Ferritin levels

    Time: 3 weeks

    Description: Changes in LDH levels will be evaluated at 7 and 21 days as a measurement of disease progression

    Measure: Changes in LDH levels

    Time: 3 weeks

    Description: Changes in C-reactive protein levels will be evaluated at 7 and 21 days as a measurement of disease progression

    Measure: Changes in C-reactive protein levels

    Time: 3 weeks

    Description: Measurement of anti-INM005 antibodies: baseline and 21 days

    Measure: Immunogenicity

    Time: 3 weeks
    278 A Phase 1, Randomised, Double-Blind, Placebo-Controlled, Dosage-Escalation, Single Centre Study to Evaluate the Safety and Immunogenicity of an Adjuvanted SARS-CoV-2 Sclamp Protein Subunit Vaccine in Healthy Adults Aged 18 to 55 Years Old and Healthy Older Adults, Aged 56 Years and Over

    This study is being conducted to look at the safety and immune response (how the immune system of the human body reacts) to a vaccine for SARS-CoV-2 (the virus responsible for COVID-19 infection) when administered as an intramuscular injection (an injection directly into the muscle) to the upper arm of healthy participants, on two occasions at least 28 days apart.

    NCT04495933
    Conditions
    1. SARS-CoV2
    2. Covid19
    Interventions
    1. Biological: MF59 adjuvanted SARS-CoV-2 Sclamp vaccine 5mcg
    2. Biological: MF59 adjuvanted SARS-CoV-2 Sclamp vaccine 15mcg
    3. Biological: MF59 adjuvanted SARS-CoV-2 Sclamp vaccine 45mcg
    4. Other: Placebo

    Primary Outcomes

    Description: - the frequency of solicited local reactogenicity adverse events (AEs)

    Measure: Frequency of Solicited local reactogenicity adverse events (AEs)

    Time: 7 days following each vaccination (at Days 1 and 29)

    Description: - the frequency of solicited systemic reactogenicity AEs

    Measure: Frequency of Solicited systemic reactogenicity adverse events (AEs)

    Time: 7 days following each vaccination (at Days 1 and 29)

    Description: - the grading of solicited local reactogenicity adverse events (AEs)

    Measure: Grading of Solicited local reactogenicity adverse events (AEs)

    Time: 7 days following each vaccination (at Days 1 and 29)

    Description: - the grading of solicited systemic reactogenicity AEs

    Measure: Grading of Solicited systemic reactogenicity adverse events (AEs)

    Time: 7 days following each vaccination (at Days 1 and 29)

    Description: - the frequency, duration, intensity and relationship to vaccination of unsolicited local adverse events (AEs)

    Measure: Unsolicited adverse events (AEs)

    Time: 28 days following each vaccination (at Days 1 and 29)

    Description: - the frequency, duration, intensity and relationship to vaccination of Serious adverse events (SAEs), Medically attended adverse events (MAAEs) and any Adverse events (AEs) leading to study withdrawal at any time during the study (including decision by the Principal Investigator [PI] not to proceed with the second dose) at any time during the study

    Measure: Serious adverse events (SAEs), Medically attended adverse events (MAAEs) and any Adverse events (AEs) leading to study withdrawal at any time during the study

    Time: through study completion (394 days)

    Description: - Geometric mean titre (GMT) of the serum antibody response compared to placebo

    Measure: Geometric Mean Titer (GMT) of the serum antibody response

    Time: 28 days following each vaccination (Days 29 and 57)

    Description: GMT of the serum NAb titres to SARS-CoV-2 virus compared to placebo

    Measure: Geometric Mean Titer (GMT) of the serum neutralizing antibody (NAb) response to SARS-CoV-2 virus

    Time: 28 days following each vaccination (Days 29 and 57)

    Secondary Outcomes

    Description: GMT of the serum antibody response compared to placebo

    Measure: Total serum antibody immune responses

    Time: through study completion (394 days)

    Description: proportion of participants with greater than or equal to 4 fold increase in titre above baseline compared to placebo.

    Measure: proportion of participants with ≥ 4 fold increase in titer above baseline

    Time: through study completion (394 days)

    Description: GMT of the serum neutralizing antibody (NAb) immune responses compared to placebo

    Measure: GMT of the serum neutralizing antibody (NAb) titres

    Time: through study completion (394 days)
    279 A Randomized, Placebo-controlled Trial, to Evaluate the Safety and Immunogenicity of the COVID-19 Vaccine, a Measles Vector-based Vaccine Candidate Against COVID-19 in Healthy Volunteers Consisting of an Unblinded Dose Escalation and a Blinded Treatment Phase

    This is a randomized, placebo-controlled, two center, Phase I trial in healthy adult volunteer participants consisting of two phases, an unblinded dose escalation and a double blind treatment phase to investigate the safety, tolerability and immunogenicity of a novel measles-vector based vaccine candidate against SARS-CoV-2 infection (TMV-083).

    NCT04497298
    Conditions
    1. COVID-19
    Interventions
    1. Biological: Two COVID-19 vaccine candidate (TMV-083) administrations - Low dose
    2. Biological: Two COVID-19 vaccine candidate (TMV-083) administrations - High dose
    3. Biological: One COVID-19 vaccine candidate (TMV-083) administration - High dose
    4. Other: Placebo

    Primary Outcomes

    Description: Rate of solicited Adverse Event up to 14 days after each injection. Rate of unsolicited AE up to 28 days after the last injection. Rate of serious adverse events (SAEs), serious adverse reactions (SARs), suspected unexpected serious adverse reactions (SUSARs) and adverse events of special interest (AESI) all along the study period.

    Measure: To assess the safety and tolerability of the COVID-19 vaccine following one or two consecutive intramuscular injections in healthy volunteers

    Time: Day 390

    Secondary Outcomes

    Description: SARS-CoV-2 specific antibodies up to study day 390 as measured by spike protein-specific ELISA

    Measure: To assess induction of SARS-CoV-2 spike protein-binding antibodies upon one or two administrations of the COVID-19 vaccine by means of ELISA up to study day 390

    Time: Day 390

    Description: SARS-CoV-2 specific antibodies up to study day 390 for each cohort as measured by serum neutralization assay

    Measure: To assess induction of SARS-CoV-2 neutralizing antibodies upon one or two administrations of the COVID-19 vaccine by means of serum neutralization assay up to study day 390

    Time: Day 390

    Description: SARS-CoV-2 spike protein-specific cell-mediated immune response up to study day 390 induced by one or two doses as measured by intracellular staining and flow cytometry

    Measure: To assess SARS-CoV-2 spike protein-specific, cell-mediated immune responses up to study day 390, induced by one or two doses of vaccine, by means of intracellular staining and flow cytometry.

    Time: up to Day 390

    Description: Occurrence of measles virus shedding as evidenced by a positive RT-PCR for saliva, nasal swab, urine, or blood sample in sentinel groups.

    Measure: To assess potential measles virus shedding by means of RT-qPCR of saliva, nasal swab, urine, or blood samples in sentinel groups on day 0 and up to day 42

    Time: up to Day 42

    Other Outcomes

    Description: Measles virus antibody levels as assessed by standard ELISA assays on day 0 and day 28.

    Measure: To assess the anti-measles antibody levels at baseline and on day 28 by ELISA

    Time: up to Day 28

    Description: SARS-CoV-2 N protein specific antibody up to study day 390 as measured by ELISA to differentiate the response to the COVID-19 vaccine from infection

    Measure: To assess the natural exposure of the subjects to SARS-CoV-2 during the duration of the trial by means of N protein-specific ELISA

    Time: Day 390

    Description: Occurrence of confirmed COVID-19 (i.e. asymptomatic, paucisymptomatic or symptomatic) cases in the study participant all along the study period

    Measure: To assess the occurrence of COVID-19 cases in study participants all along the duration of the study

    Time: Day 390
    280 A Phase 3 Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Efficacy and Safety of LY3819253 in Preventing SARS-CoV-2 Infection and COVID-19 in Skilled Nursing and Assisted Living Facility Residents and Staff; a NIAID and Lilly Collaborative Study

    The purpose of this study is to evaluate whether LY3819253 prevents severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease - 2019 (COVID-19) in facility staff and residents in contracted skilled nursing and assisted living facility networks with a high risk of SARS-CoV-2 exposure. Participants with a high risk of SARS-CoV-2 exposure will receive LY3819253 or placebo via an injection into a vein. Samples will be taken from the nose. Blood samples will be drawn. Participation could last up to 25 weeks and may include up to 19 visits.

    NCT04497987
    Conditions
    1. COVID-19
    2. SARS-CoV2
    Interventions
    1. Drug: LY3819253
    2. Drug: Placebo
    MeSH:Infection

    Primary Outcomes

    Description: Percentage of Participants with SARS-CoV-2 Infection

    Measure: Percentage of Participants with SARS-CoV-2 Infection

    Time: Week 4

    Secondary Outcomes

    Description: Percentage of Participants with Moderate or Worse Severity COVID-19

    Measure: Percentage of Participants with Moderate or Worse Severity COVID-19

    Time: Week 8

    Description: Percentage of Participants with Mild or Worse Severity COVID-19

    Measure: Percentage of Participants with Mild or Worse Severity COVID-19

    Time: Week 8

    Description: Percentage of Participants Who are Hospitalized due to COVID-19

    Measure: Percentage of Participants Who are Hospitalized due to COVID-19

    Time: Week 8

    Description: Percentage of Participants who Experience COVID-19-Related Hospitalization, COVID-19 Related Emergency Room Visit, or Death

    Measure: Percentage of Participants who Experience COVID-19-Related Hospitalization, COVID-19 Related Emergency Room Visit, or Death

    Time: Week 8

    Description: Percentage of Participants Who Die Due to COVID-19

    Measure: Percentage of Participants Who Die Due to COVID-19

    Time: Week 8
    281 A Phase 1/Phase 2, Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging Trial to Evaluate the Safety, Tolerability and Immunogenicity of V591 (COVID-19 Vaccine) in Healthy Younger and Older Participants

    The primary objective of this early Phase 1 study is to identify the V591 dose that achieves the target immune response in humans based on preclinical or early clinical data.

    NCT04498247
    Conditions
    1. Coronavirus Disease (COVID-19)
    Interventions
    1. Biological: V591
    2. Other: Placebo
    MeSH:Coronavirus Infections

    Primary Outcomes

    Description: An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.

    Measure: Percentage of Participants with at Least 1 Solicited Injection Site Adverse Event

    Time: Up to ~5 days after vaccination

    Description: An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.

    Measure: Percentage of Participants with at Least 1 Solicited Systemic Adverse Event

    Time: Up to ~14 days after vaccination

    Description: An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.

    Measure: Percentage of Participants with at Least 1 Unsolicited Adverse Event

    Time: Up to ~28 days after vaccination

    Description: A serious adverse event is "life threatening," requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity and is a congenital anomaly/birth defect.

    Measure: Percentage of Participants with at Least 1 Serious Adverse Event

    Time: Up to ~365 days (±14 days) after vaccination

    Description: An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.

    Measure: Percentage of Participants who Discontinued Study Treatment due to an Adverse Event

    Time: Up to ~365 days (±7 days) after vaccination

    Description: A medically attended adverse event (MAAE) is an AE in which medical attention is received during an unscheduled, non-routine outpatient visit, such as an emergency room visit, office visit, or an urgent care visit with any medical personnel for any reason.

    Measure: Percentage of Participants with at Least 1 Medically Attended Adverse Event

    Time: Up to ~365 days (±14 days) after vaccination

    Secondary Outcomes

    Description: Serum samples will be collected and the presence of serum neutralization antibodies will be assessed using PRNT.

    Measure: Geometric Mean Titers for Serum Neutralizing Antibodies (nAb) as Measured by Plaque Reduction Neutralization Test (PRNT): All Panels

    Time: Day 29

    Description: Serum samples will be collected and the total anti-spike IgG antibodies will be assessed using ELISA.

    Measure: Geometric Mean Concentration of Total Anti-Spike Immunoglobulin G (IgG) Antibodies as Measured by Enzyme-Linked Immunosorbent Assay (ELISA): All Panels

    Time: Day 29

    Description: Serum samples will be collected and the presence of serum neutralization antibodies will be assessed using PRNT.

    Measure: Geometric Mean Titers for Serum Neutralizing Antibodies as Measured by PRNT: Panels A,B, I and J

    Time: Day 85

    Description: Serum samples will be collected and the total anti-spike IgG antibodies will be assessed using ELISA.

    Measure: Geometric Mean Concentration of Total Anti-Spike IgG Antibodies as Measured by ELISA: Panels A,B, I and J

    Time: Day 85

    Description: Serum samples will be collected and the presence of serum neutralization antibodies will be assessed using PRNT.

    Measure: Geometric Mean Titers for Serum Neutralizing Antibodies as Measured by PRNT: Panels K and L

    Time: Day 197

    Description: Serum samples will be collected and the total anti-spike IgG antibodies will be assessed using ELISA.

    Measure: Geometric Mean Concentration of Total Anti-Spike IgG Antibodies as Measured by ELISA: Panels K and L

    Time: Day 197

    Description: Serum samples will be collected and the presence of serum neutralization antibodies will be assessed using PRNT.

    Measure: Geometric Mean Titers for Serum nAb as Measured by PRNT

    Time: Panels C-E and G-H: Days 1, 15, 29, 57, 85, 115, 211, and 365; Panels A,B, I and J: Days 1, 15, 29, 57, 71, 85, 115, 211, and 422; Panels F, K and L: Days 1, 15, 29, 85, 169, 197, 365 and 534

    Description: Serum samples will be collected and the total anti-spike IgG antibodies will be assessed using ELISA.

    Measure: Geometric Mean Concentration of Total Anti-Spike IgG Antibodies as Measured by ELISA

    Time: Panels C-E and G-H: Days 1, 15, 29, 57, 85, 115, 211, and 365; Panels A,B, I and J: Days 1, 15, 29, 57, 71, 85, 115, 211, and 422; Panels F, K and L: Days 1, 15, 29, 85, 169, 197, 365 and 534
    282 COVID-19 Outpatient Thrombosis Prevention Trial: A Multi-center Adaptive Randomized Placebo-controlled Platform Trial Evaluating the Efficacy and Safety of Anti-thrombotic Strategies in COVID-19 Adults Not Requiring Hospitalization at Time of Diagnosis

    A multi-center adaptive randomized placebo-controlled platform trial evaluating the efficacy and safety of anti-thrombotic strategies in COVID-19 adults not requiring hospitalization at time of diagnosis

    NCT04498273
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Apixaban 2.5 MG
    2. Drug: Apixaban 5MG
    3. Drug: Aspirin
    4. Drug: Placebo
    MeSH:Thrombosis

    Primary Outcomes

    Description: The primary outcome will be a composite endpoint of need for hospitalization for cardiovascular/pulmonary events, symptomatic deep venous thrombosis, pulmonary embolism, arterial thromboembolism, myocardial infarction, ischemic stroke, and all-cause mortality for up to 45 days after initiation of assigned treatment.

    Measure: Hospitalization for cardiovascular/pulmonary events

    Time: 45 days
    283 A Phase I and Pilot Study Evaluating the Effect of NT-I7, a Long Acting Interleukin-7, to Increase Lymphocyte Counts and Enhance Immune Clearance of SARS-CoV-2

    Lymphopenia is common in patients with COVID-19 and is associated with worse clinical outcomes. NT-I7 is a long-acting human interleukin-7 (IL-7) that has been shown to increase absolute lymphocyte count (ALC) and CD4+ and CD8+ T cell counts with a well-tolerated safety profile in humans. In this study, patients who have tested positive for SARS-CoV-2 by PCR testing without severe disease and with ALC <1500 cells/mm3 will be enrolled.

    NCT04498325
    Conditions
    1. COVID-19
    2. SARS-CoV-2
    Interventions
    1. Drug: NT-I7
    2. Drug: Placebo
    3. Procedure: Blood for research purposes
    4. Procedure: Blood for pharmacokinetic samples
    5. Procedure: Nasopharyngeal, oropharyngeal, or saliva swab
    6. Procedure: Blood for anti-drug antibody (ADA)

    Primary Outcomes

    Description: The safe tolerated dose is defined as the dose level immediately below the dose level at which 1 patient of a cohort of 3 patients experiences dose-limiting toxicity within 14 days after administration of NT-I7 Dose limiting toxicities (DLT) are defined as: A serious adverse event that is at least possibly related to NT-I7 A grade 3 or higher adverse event that is at least possibly related to NT-I7 (excluding injection site swelling, irritation or discomfort) A clinically significant lab abnormality that is at least possibly related to NT-I7

    Measure: Safe and tolerable dose of NT-I7 (Phase I only)

    Time: Completion of DLT assessment window of Phase I portion of study (estimated to be 8 months)

    Measure: Percent change in absolute lymphocyte count (ALC)

    Time: From baseline to Day 14

    Secondary Outcomes

    Measure: Percent change in absolute lymphocyte count (ALC)

    Time: From baseline through Day 21

    Description: -Using PCR from nasopharyngeal swab, oropharyngeal swab or saliva

    Measure: Change in SARS-CoV-2 viral load

    Time: From baseline to Day 7

    Description: -Using PCR from nasopharyngeal swab, oropharyngeal swab or saliva

    Measure: Change in SARS-CoV-2 viral load

    Time: From baseline to Day 14

    Measure: COVID-19 Symptom severity as measured by WHO Ordinal Scale for clinical improvement

    Time: From baseline, day 7, day 14, and day 21

    Measure: Time to resolution of COVID-19 symptoms

    Time: From baseline through Day 21

    Description: -A treatment emergent adverse event (TEAE) is defined as any event that begins or worsens on or after date of first dose of study treatment.

    Measure: Incidence of treatment-emergent adverse events

    Time: From baseline through Day 21

    Description: -If quantitative PCR is not available

    Measure: Number of participants by PCR result status (positive or negative)

    Time: -From baseline to Day 7

    Description: -If quantitative PCR is not available

    Measure: Number of participants by PCR result status (positive or negative)

    Time: From baseline to Day 14
    284 A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation, Multicenter Study to Evaluate the Efficacy and Safety of F-652 (IL-22:IgG2 Fusion Protein) in Patients With Moderate to Severe COVID-19

    This is an interventional, multicenter, 2-arm, parallel-group, randomized, double-blind, placebo controlled, dose-escalation, safety and efficacy study of F-652 treatment versus placebo in patients aged 18 years or older with a COVID-19 diagnosis confirmed by PCR. Eligible patients will have moderate to severe COVID-19 symptoms within 5 days post hospitalization and a positive COVID-19 testing.

    NCT04498377
    Conditions
    1. Covid19
    Interventions
    1. Biological: F-652
    2. Biological: Placebo

    Primary Outcomes

    Description: The proportion of patients with a greater or equal 2-point change in the NIAID 8-point ordinal scale from baseline to Day 29

    Measure: NIAID 8-point ordinal scale

    Time: Study day 1 before dose to day 29
    285 Charité Trial of Cenicriviroc (CVC) Treatment for COVID-19 Patients

    The aim of this study is to test Cenicriviroc (CVC) as a means to reduce the severity of the lung disease COVID-19 caused by an infection with SARS-CoV-2. The safety of CVC, when administered to COVID-19 patients, will also be assessed. Furthermore, the clinical trial aims to answer the question of whether patients with pre-existing conditions, who have an increased risk of severe COVID-19 progression, benefit more and particularly from CVC. CVC is an orally available dual inhibitor of the chemokine receptors CCR2 and CCR5, which is expected to reduce (hyper-) inflammation in COVID-19. The main goal of the study is to determine whether CVC helps increase the number of patients who are symptom-free and not hospitalized after 14 days compared to a placebo. Approximately 66.7% of the patients enrolled in the study will receive CVC and 33.3% will get an optically identical pill (placebo). Subjects will be assessed daily while hospitalized. Discharged patients will be asked to attend study visits at Days 8, 15, 22, and 29 and 85. All subjects will undergo a series of clinical, safety, and laboratory assessments. Blood samples and oropharyngeal (OP) swabs will be obtained on Day 1; 3, 5 (while hospitalized); and Day 8, 15 and 29 (if able to return to clinic or still hospitalized). The presence of anti-SARS-CoV-2 antibodies will be determined on Days 29 and 85.

    NCT04500418
    Conditions
    1. Covid19
    Interventions
    1. Drug: Cenicriviroc (CVC)
    2. Drug: Placebo

    Primary Outcomes

    Description: The Primary Endpoint will be the subject's responder status defined by achieving a score of "1" or "2" (discharged from hospital e.g.) on Day 15 on the following 7-point scale: Not hospitalized, no limitations on activities; Not hospitalized, limitation on activities; Hospitalized, not requiring supplemental oxygen; Hospitalized, requiring supplemental oxygen; Hospitalized, on non-invasive ventilation or high-flow oxygen devices; Hospitalized, on invasive mechanical ventilation or ECMO (Extracorporeal membrane oxygenation); Death.

    Measure: Subject´s Responder status (score on the 7-point ordinal scale on Day 15)

    Time: 14 days after enrollment (Day 15)

    Secondary Outcomes

    Description: 7-point ordinal scale to be assessed on Day 15 (and Day 1 for baseline comparison), analyses of ordinal change of 2 or more, compared with baseline ordinal change of 1 or more, compared with baseline

    Measure: Evaluation of change in clinical condition based on the 7-point ordinal scale

    Time: day of enrollment and 15 days after enrollment

    Description: 7-point ordinal scale assessed on: Days 8, 22, 29 (and Day 1 for baseline comparison), analyses of: Responder status (achieving a score of a "1" or a "2") ordinal change of 2 or more, compared with baseline ordinal change of 1 or more, compared with baseline

    Measure: Evaluation of change in clinical condition based on the 7-point ordinal scale and Responder Status

    Time: day of enrollment, 8 days, 22 days and 29 days after enrollment

    Description: Analysis of: Length of time spent in the ICU (days) Length of time spent in the hospital (days) Days alive and out of hospital through Day 29 Days free of endotracheal tube-based ventilation through Day 29

    Measure: Hospital resource utilization comparison

    Time: 29 days after enrollment, 85 days after enrollment
    286 A Multicenter, Adaptive, Randomized, Blinded Controlled Trial of the Safety and Efficacy of Investigational Therapeutics for Hospitalized Patients With COVID-19

    This study looks at the safety and effectiveness of different drugs in treating COVID-19 in people who have been hospitalized with the infection. Participants in the study will be treated with either a study drug plus current standard of care (SOC), or with placebo plus current SOC.

    NCT04501978
    Conditions
    1. Covid19
    Interventions
    1. Drug: LY3819253
    2. Drug: Placebo
    3. Drug: Remdesivir

    Primary Outcomes

    Description: Oxygen requirements measured by 7 categories (1 = least severe, 7 = most severe). The participant's highest (i.e. most severe) observed score is used.

    Measure: Pulmonary ordinal outcome (Stage 1)

    Time: Day 5

    Description: Extrapulmonary complications and respiratory dysfunction measured by 7 categories (1= least severe, 7 = most severe). The participant's highest (i.e. most severe) observed score is used.

    Measure: Pulmonary+ ordinal outcome (Stage 1)

    Time: Day 5

    Description: Sustained recovery defined as being discharged from the index hospitalization, followed by being alive and home for 14 consecutive days prior to Day 90.

    Measure: Time from randomization to sustained recovery (Stage 2)

    Time: Up to Day 90

    Secondary Outcomes

    Measure: All-cause mortality

    Time: Thru Day 90

    Measure: Composite of time to sustained recovery and mortality

    Time: Thru Day 90

    Measure: Days alive outside short-term acute care hospital

    Time: Up to Day 90

    Description: Oxygen requirements measured by 7 categories (1 = least severe, 7 = most severe). The participant's highest (i.e. most severe) observed score is used.

    Measure: Pulmonary ordinal outcome

    Time: Days 1-7, 14 and 28

    Description: Extrapulmonary complications and respiratory dysfunction measured by 7 categories (1= least severe, 7 = most severe). The participant's highest (i.e. most severe) observed score is used.

    Measure: Pulmonary+ ordinal outcome

    Time: Days 1-7

    Description: Total of: Respiratory rate (breaths per minute) scored from 0 to +3; Oxygen saturation (%) scored from 0 to +3; Any supplemental oxygen scored from 0 to +2; Temperature scored from 0 to +3; Systolic BP scored from 0 to +3; Heart rate (beats per minute) scored from 0 to +3.; and AVPU (alert, voice, pain, unresponsive) scored from 0 to +3. A higher score denotes a worse outcome.

    Measure: Change in New Early Warning (NEW) Score

    Time: Baseline to Day 5

    Measure: Incidence of clinical organ failure

    Time: Thru Day 28

    Measure: Composite of death or serious clinical COVID-19 related events

    Time: Thru Day 90

    Measure: Composite of cardiovascular events and thromboembolic events

    Time: Thru Day 90

    Measure: Composite of grade 3 and 4 clinical adverse events, serious adverse events (SAEs) or death

    Time: Thru Days 5 and 28

    Measure: Incidence of infusion reactions

    Time: Thru Day 0

    Measure: Composite of SAEs or death

    Time: Thru Day 90

    Measure: Change in SARS-CoV-2 neutralizing antibody levels

    Time: Baseline to Days 1, 3, 5, 28 and 90

    Measure: Change in overall titers of antibodies

    Time: Baseline to Days 1, 3, 5, 28 and 90

    Measure: Change in neutralizing antibody levels

    Time: Baseline to Days 1, 3, 5, 28 and 90
    287 A Randomized, Controlled, Phase 2b Study to Evaluate Safety and Efficacy of Rivaroxaban (Xarelto®) for High Risk People With Mild COVID-19

    The purpose of this study is to assess safety and clinical efficacy of rivaroxaban in people with mild Coronavirus Disease 2019 who are at increased risk of disease progression.

    NCT04504032
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Rivaroxaban
    2. Drug: Placebo

    Primary Outcomes

    Measure: Number of Participants With Grade 3 or Grade 4 Adverse Events (AEs)

    Time: Up to approximately 35 days

    Measure: Number of Participants With AEs Leading to Study Discontinuation

    Time: Up to approximately 35 days

    Measure: Number of Participants With Serious Adverse Events (SAEs)

    Time: Up to approximately 35 days

    Description: Disease progression is defined as the proportion of participants who progress to moderate or severe disease category or higher (Gates Medical Research Institute ordinal scale ≥3). The assessments will be performed using Gates Medical Research Institute ordinal scale.

    Measure: Proportion of Participants With Disease Progression

    Time: Up to Day 28

    Secondary Outcomes

    Description: Time to disease resolution is defined as symptoms resolution (new onset Coronavirus Disease 2019 [COVID-19] symptoms resolved, and pre-existing symptoms returned to baseline) with viral clearance (two consecutive negative diagnostic tests) through Day 28. Baseline refers to health status prior to contracting new onset COVID-19 symptoms.

    Measure: Median Time to Disease Resolution

    Time: Up to Day 28

    Description: Time to disease resolution is defined as symptoms resolution only (new onset COVID-19 symptoms resolved, and preexisting symptoms returned to baseline) through Day 28. Baseline refers to health status prior to contracting new onset COVID-19 symptoms.

    Measure: Median Time to Disease Resolution

    Time: Up to Day 28

    Measure: Proportion of Participants With Disease Progression

    Time: Days 8, 14, and 21

    Measure: Proportion of Participants Who Achieve Disease Resolution

    Time: Days 8, 14, 21, and 28

    Measure: Mean Gates Medical Research Institute Ordinal Scale Score

    Time: Days 8, 14, 21, and 28

    Measure: Change From Baseline in Gates Medical Research Institute Ordinal Scale Score

    Time: Days 8, 14, 21, and 28

    Measure: Mean World Health Organization Ordinal Scale Score

    Time: Days 8, 14, 21, and 28

    Measure: Change From Baseline in World Health Organization Ordinal Scale Score

    Time: Days 8, 14, 21, and 28

    Measure: Incidence of Hospitalization

    Time: Days 8, 14, 21, and 28

    Measure: Number of Days of Hospitalization

    Time: Days 8, 14, 21, and 28
    288 Multi-Center, Randomized, Double-Blind, Placebo-Controlled Study of Bucillamine in Patients With Mild-Moderate COVID-19

    This is a Phase 3, multi-center, randomized, double blind, placebo controlled, clinical study of bucillamine (2 dosage levels) in patients with mild-moderate COVID-19. Patients will be randomized 1:1:1 to receive bucillamine 100 mg 3 times a day (TID), bucillamine 200 mg TID or placebo TID for up to 14 days. After the first interim analysis when a single dose is selected, patients will then be randomized 2:1 to the selected bucillamine dose or placebo The study will be overseen by an independent Data and Safety Monitoring Board (DSMB). Up to 10 centers in the United States will conduct this study. Up to 1000 patients will be enrolled in this study. Patients will participate in the study approximately 45 days.

    NCT04504734
    Conditions
    1. Covid19
    Interventions
    1. Drug: Bucillamine
    2. Drug: Placebo
    3. Drug: Bucillamine

    Primary Outcomes

    Description: Proportion of patients meeting a composite endpoint of hospitalization or death

    Measure: Efficacy: Frequency of hospitalization or death

    Time: From time of first dose through Day 28 following randomization

    Secondary Outcomes

    Description: Number of adverse events

    Measure: Safety: Changes in adverse events from baseline to end of study

    Time: From time of first dose through Day 28 following randomization
    289 Tenecteplase With Concomitant Anticoagulation for Severe Acute Respiratory Failure in Patients With COVID-19

    This is a placebo-controlled, double blind, randomized, Phase II dose escalation study intended to evaluate the potential safety and efficacy of tenecteplase for the treatment of COVID-19 associated respiratory failure. The hypothesis is that administration of the drug, in conjunction with heparin anticoagulation, will improve patients' clinical outcomes.

    NCT04505592
    Conditions
    1. COVID-19
    2. Respiratory Failure
    3. ARDS
    Interventions
    1. Drug: Tenecteplase
    2. Drug: Placebo
    MeSH:Respiratory Insufficiency

    Primary Outcomes

    Description: The number of patients free of respiratory failure defined as not requiring high flow nasal cannula, non-rebreather, noninvasive positive pressure ventilation, or mechanical ventilation at 28 days

    Measure: Number of participants free of respiratory failure

    Time: 28 Days

    Description: Safety as assessed by number of occurrences of intracranial bleeding or major bleeding

    Measure: Number of occurrences of bleeding

    Time: 28 days

    Secondary Outcomes

    Measure: Number of participants with in-hospital deaths at 14 days

    Time: 14 days

    Measure: Number of participants with death at 28 days

    Time: 28 days

    Measure: Number of ventilator-free days

    Time: 28 days

    Description: Respiratory failure-free defined as not requiring high flow nasal cannula, non-rebreather, noninvasive positive pressure ventilation, or mechanical ventilation

    Measure: Number of respiratory failure-free days

    Time: 28 days

    Measure: Number of vasopressor-free days

    Time: 28 days

    Measure: Vasopressor doses at 24 hours

    Time: 24 hours

    Measure: Vasopressor doses at 72 hours

    Time: 72 hours

    Description: The P/F ratio equals the arterial pO2 ("P") from the ABG divided by the FIO2 ("F") - the fraction (percent) of inspired oxygen that the patient is receiving expressed as a decimal (40% oxygen = FIO2 of 0.40).

    Measure: P/F ratio at 24 hours

    Time: 24 hours

    Description: The P/F ratio equals the arterial pO2 ("P") from the ABG divided by the FIO2 ("F") - the fraction (percent) of inspired oxygen that the patient is receiving expressed as a decimal (40% oxygen = FIO2 of 0.40).

    Measure: P/F ratio at 72 hours

    Time: 72 hours

    Measure: Number of ICU-free days

    Time: 28 days

    Measure: Hospital length of stay

    Time: 28 days

    Measure: Number of participants with new-onset renal failure

    Time: 28 days

    Measure: Number of participants with need for renal replacement therapy

    Time: 28 days
    290 A Randomized, Double-blind, Placebo-controlled Phase 3 Study to Assess the Efficacy and Safety of Ad26.COV2.S for the Prevention of SARS-CoV-2-mediated COVID-19 in Adults Aged 18 Years and Older

    The study will enroll up to 60,000 participants in order to evaluate the efficacy of Ad26.COV2.S in the prevention of molecularly confirmed moderate to severe/critical COVID-19, as compared to placebo, in adult participants.

    NCT04505722
    Conditions
    1. Participants With or Without Stable Co-morbidities Associated With Progression to Severe COVID-19 at Different Stages of the Protocol
    Interventions
    1. Biological: Ad26.COV2.S
    2. Other: Placebo
    MeSH:Disease Progression

    Primary Outcomes

    Description: Moderate defined as one sign or symptom from a list of signs and symptoms, such as respiratory rate greater than or equal to (>=) 20 breaths per minute and symptoms such as shortness of breath or two signs or symptoms from a list of sign and symptoms or severe COVID-19 defined in FDA guidance.

    Measure: Number of Participants with First Occurrence of Molecularly Confirmed Moderate to Severe/Critical Coronavirus Disease (COVID-19) with Seronegative Status

    Time: 14 Days post-vaccination (Day 15) to end of study (2.1 Years)

    Secondary Outcomes

    Description: Moderate defined as one sign or symptom from a list of signs and symptoms, such as respiratory rate >= 20 breaths per minute and symptoms such as shortness of breath or two signs or symptoms from a list of sign and symptoms or severe COVID-19 defined in FDA guidance.

    Measure: Number of Participants with First Occurrence of Molecularly Confirmed Moderate to Severe/Critical COVID-19 Regardless of their Serostatus

    Time: 1 Day post-vaccination (Day 2) to end of study (2.1 Years)

    Description: Moderate defined as one sign or symptom from a list of signs and symptoms, such as respiratory rate >= 20 breaths per minute and symptoms such as shortness of breath or two signs or symptoms from a list of sign and symptoms or severe COVID-19 defined in FDA guidance.

    Measure: Number of Participants with First Occurrence of Molecularly Confirmed Moderate to Severe/Critical Coronavirus Disease COVID-19 Regardless of Their Serostatus

    Time: 14 Days post-vaccination (Day 15) to end of study (2.1 Years)

    Description: Moderate defined as one sign or symptom from a list of signs and symptoms, such as respiratory rate greater than or equal to (>=) 20 breaths per minute and symptoms such as shortness of breath or two signs or symptoms from a list of sign and symptoms or severe COVID-19 defined in FDA guidance.

    Measure: Number of Participants with First Occurrence of Molecularly Confirmed Moderate to Severe/Critical Coronavirus Disease (COVID-19)

    Time: 1 Day post-vaccination (Day 2) to end of study (2.1 Years)

    Description: Number of participants with first occurrence of COVID-19 requiring medical intervention (such as a composite endpoint of hospitalization, intensive care unit (ICU) admission, mechanical ventilation, and extracorporeal membrane oxygenation (ECMO), linked to objective measures such as decreased oxygenation, X-ray or CT findings) or linked to any molecularly confirmed, COVID-19 at least 14 days post vaccination will be reported.

    Measure: Number of Participants with First Occurrence of COVID-19 Requiring Medical Intervention

    Time: 14 Days post-vaccination (Day 15) to end of study (2.1 Years)

    Description: The viral load of SARS-CoV-2 will be assessed in confirmed COVID-19 cases using RT-PCR. Nasal swabs will be used to detect and/or quantify SARS-CoV-2.

    Measure: SARS-CoV-2 Viral Load as Assessed by Quantitative Reverse-Transcriptase Polymerase Chain Reaction (RT-PCR) in Participants with Molecularly Confirmed, Moderate to Severe/Critical COVID-19

    Time: 14 Days post-vaccination (Day 15) to end of study (2.1 Years)

    Description: Molecularly confirmed mild COVID-19 is defined as a SARS-CoV-2 positive RT-PCR or molecular test result from any available respiratory tract sample (example, nasal swab sample, sputum sample, throat swab sample, saliva sample) or other sample. Mild COVID-19 includes: Fever, sore throat, malaise, headache, muscle pain, gastrointestinal symptoms, cough, chest congestion, runny nose, wheezing, skin rash, eye irritation or discharge, or chills, without shortness of breath or dyspnea.

    Measure: Number of Participants with First Occurrence of Molecularly Confirmed Mild COVID-19

    Time: 14 Days post-vaccination (Day 15) to end of study (2.1 Years)

    Description: Molecularly confirmed moderate and severe/critical COVID-19 defined as a positive SARS-CoV-2 positive RT-PCR or molecular test result from any available respiratory tract sample (example, nasal swab sample, sputum sample, throat swab sample, saliva sample) or other sample; and COVID-19 symptoms consistent with those defined by the US FDA harmonized case Definition at the time of finalization of this protocol: fever or chills, cough, shortness of breath or difficulty breathing, fatigue, muscle or body aches, headache, new loss of taste or smell, sore throat, congestion or runny nose, nausea or vomiting, diarrhea.

    Measure: Number of Participants with First Occurrence of Molecularly Confirmed COVID-19 Defined by the US Food and Drug Administration (FDA) Harmonized case Definition

    Time: 14 Days post-vaccination (Day 15) to end of study (2.1 Years)

    Description: BOD will be evaluated based on the first occurrence of molecularly confirmed COVID-19, including mild, moderate or severe/critical COVID-19 case.

    Measure: Burden of Disease (BOD) Based on First Occurrence of Molecularly Confirmed Symptomatic COVID-19

    Time: 14 Days post-vaccination (Day 15) to end of study (2.1 Years)

    Description: Serologic conversion between baseline and (Day 1; pre-vaccination), Day 71, 6 Months, 1 year post-vaccination using an ELISA and/or SARS-CoV- 2 immunoglobulin assay that is dependent on the SARS-CoV-2 nucleocapsid (N) protein will be reported.

    Measure: Serologic Conversion Between Baseline and (Day 1; Pre-vaccination), Day 71, 6 Months and 1- Year Post-vaccination using an Enzyme-linked Immunosorbent Assay (ELISA)

    Time: Between baseline (Day 1; pre-vaccination) and Day 71, 6 Months, 1-Year post-vaccination (up to 52 Weeks)

    Description: Number of participants with first occurrence of SARS-CoV-2 infection (serologically and/or molecularly confirmed) with onset at least 14 days after vaccination (Day 15) to end of Study (2.1 Years) will be reported.

    Measure: Number of Participants with First Occurrence of SARS-CoV-2 Infection (Serologically and/or Molecularly Confirmed)

    Time: 14 Days post-vaccination (Day 15) to end of study (2.1 Years)

    Description: SAE is any untoward medical occurrence that at any dose may result in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a suspected transmission of any infectious agent via a medicinal product.

    Measure: Number of Participants with Serious Adverse Events (SAEs)

    Time: Up to 104 Weeks

    Description: MAAEs are defined as AEs with medically-attended visits including hospital, emergency room, urgent care clinic, or other visits to or from medical personnel for any reason.

    Measure: Number of Participants with Medically-Attended Adverse Events (MAAEs)

    Time: Up to 6 Months

    Description: MAAEs are defined as AEs with medically-attended visits including hospital, emergency room, urgent care clinic, or other visits to or from medical personnel for any reason. Routine study visits will not be considered medically-attended visits. New onset of chronic diseases will be collected as part of the MAAEs.

    Measure: Number of Participants with Medically-Attended Adverse Events (MAAEs) Leading to Study Discontinuation

    Time: Up to 104 Weeks

    Description: Participants will be asked to note in the e-Diary occurrences of injection site pain/tenderness, erythema, and swelling at the study vaccine injection site daily for 7 days post-vaccination (day of vaccination and the subsequent 7 days).

    Measure: Number of Participants with Solicited Local Adverse Events (AEs) During 7 Days Following Vaccination

    Time: Up to Day 8 (7 Days after first vaccination on Day 1)

    Description: Participants will be instructed on how to record daily temperature using a thermometer provided for home use. Participants should record the temperature in the e-Diary in the evening of the day of vaccination, and then daily for the next 7 days approximately at the same time each day. If more than 1 measurement is made on any given day, the highest temperature of that day will be recorded in the e-Diary. Fever is defined as endogenous elevation of body temperature >= 38.0 degree Celsius or >=100.4-degree Fahrenheit, as recorded in at least 1 measurement. Participants will also be instructed on how to note signs and symptoms in the e-Diary on a daily basis for 7 days post-vaccination (day of vaccination and the subsequent 7 days), for the following events: fatigue, headache, nausea, myalgia.

    Measure: Number of Participants with Solicited Systemic AEs During 7 Days Following Vaccination

    Time: Up to Day 8 (7 Days after first vaccination on Day 1)

    Description: Unsolicited AEs are all AEs for which the participant is not specifically questioned in the participant diary.

    Measure: Number of Participants with Unsolicited Local Adverse Events (AEs) During 28 Days Post-vaccination

    Time: Up to Day 29 (28 Days after first vaccination on Day 1)

    Description: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) neutralizing antibody titers as assessed by VNA to measure the humoral immune responses will be reported

    Measure: SARS-CoV-2 Neutralizing Antibody Titers as Assessed by Virus Neutralization Assay (VNA)

    Time: Up to 104 Weeks

    Description: SARS-CoV-2 binding antibodies as assessed by enzyme-linked immunosorbent assay (ELISA) to measure humoral immune response will be reported.

    Measure: SARS-CoV-2 Binding Antibodies Assessed by ELISA

    Time: Up to 104 Weeks
    291 A Phase I Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability and Pharmacokinetics of AZD7442 in Healthy Adults

    In this first-in-humans dose escalation study, AZD7442 (AZD8895 + AZD1061) will be evaluated for safety, tolerability, pharmacokinetics, and generation of anti-drug antibodies (ADAs). The study is intended to enable future studies of AZD7442's efficacy in preventing and treating COVID-19.

    NCT04507256
    Conditions
    1. COVID-19
    Interventions
    1. Combination Product: AZD7442
    2. Other: Placebo

    Primary Outcomes

    Description: Safety and tolerability will be evaluated in terms of number of participants with AEs/SAEs, abnormal values of vital signs, safety laboratory parameters, 12 lead safety electrocardiogram, injection site reactions, and physical examination.

    Measure: Number of participants with adverse events (AEs) and serious AEs

    Time: From Day 1 up to last follow-up day (Day 361)

    Secondary Outcomes

    Description: Cmax will be assessed after sequential or co-administration (AZD8895 + AZD1061 mixed into a single infusion) of AZD7442 (IV infusion) using noncompartmental methods with Phoenix® WinNonlin® Version 8.1, or higher.

    Measure: Observed maximum concentration (Cmax) (IV infusion)

    Time: From Day 1 up to last follow-up day (Day 361)

    Description: Tmax will be assessed after sequential or co-administration (AZD8895 + AZD1061 mixed into a single infusion) of AZD7442 (IV infusion) using noncompartmental methods with Phoenix® WinNonlin® Version 8.1, or higher.

    Measure: Time to reach maximum concentration (Tmax) (IV infusion)

    Time: From Day 1 up to last follow-up day (Day 361)

    Description: t½λz will be assessed after sequential or co-administration (AZD8895 + AZD1061 mixed into a single infusion) of AZD7442 (IV infusion) using noncompartmental methods with Phoenix® WinNonlin® Version 8.1, or higher.

    Measure: Terminal elimination half life, estimated as (ln2)/λz (t½λz) (IV infusion)

    Time: From Day 1 up to last follow-up day (Day 361)

    Description: AUClast will be assessed after sequential or co-administration (AZD8895 + AZD1061 mixed into a single infusion) of AZD7442 (IV infusion) using noncompartmental methods with Phoenix® WinNonlin® Version 8.1, or higher.

    Measure: Area under the concentration curve from time zero to the time of last quantifiable concentration (AUClast) (IV infusion)

    Time: From Day 1 up to last follow-up day (Day 361)

    Description: AUCinf will be assessed after sequential or co-administration (AZD8895 + AZD1061 mixed into a single infusion) of AZD7442 (IV infusion) using noncompartmental methods with Phoenix® WinNonlin® Version 8.1, or higher.

    Measure: Area under the concentration time curve from time zero extrapolated to infinity (AUCinf) (IV infusion)

    Time: From Day 1 up to last follow-up day (Day 361)

    Description: Vss will be assessed after sequential or co-administration (AZD8895 + AZD1061 mixed into a single infusion) of AZD7442 (IV infusion) using noncompartmental methods with Phoenix® WinNonlin® Version 8.1, or higher.

    Measure: Volume of distribution at steady state (Vss) (IV infusion)

    Time: From Day 1 up to last follow-up day (Day 361)

    Description: Vz will be assessed after sequential or co-administration (AZD8895 + AZD1061 mixed into a single infusion) of AZD7442 (IV infusion) using noncompartmental methods with Phoenix® WinNonlin® Version 8.1, or higher.

    Measure: Volume of distribution at terminal phase (Vz) (IV infusion)

    Time: From Day 1 up to last follow-up day (Day 361)

    Description: CL will be assessed after sequential or co-administration (AZD8895 + AZD1061 mixed into a single infusion) of AZD7442 (IV infusion) using noncompartmental methods with Phoenix® WinNonlin® Version 8.1, or higher.

    Measure: Systemic clearance (CL) (IV infusion)

    Time: From Day 1 up to last follow-up day (Day 361)

    Description: Cmax will be assessed after sequential or co-administration (AZD8895 + AZD1061 mixed into a single infusion) of AZD7442 (IM injection) using noncompartmental methods with Phoenix® WinNonlin® Version 8.1, or higher.

    Measure: Cmax (IM injection)

    Time: From Day 1 up to last follow-up day (Day 361)

    Description: Tmax will be assessed after sequential or co-administration (AZD8895 + AZD1061 mixed into a single infusion) of AZD7442 (IM injection) using noncompartmental methods with Phoenix® WinNonlin® Version 8.1, or higher.

    Measure: Tmax (IM injection)

    Time: From Day 1 up to last follow-up day (Day 361)

    Description: t½λz will be assessed after sequential or co-administration (AZD8895 + AZD1061 mixed into a single infusion) of AZD7442 (IM injection) using noncompartmental methods with Phoenix® WinNonlin® Version 8.1, or higher.

    Measure: t½λz (IM injection)

    Time: From Day 1 up to last follow-up day (Day 361)

    Description: AUClast will be assessed after sequential or co-administration (AZD8895 + AZD1061 mixed into a single infusion) of AZD7442 (IM injection) using noncompartmental methods with Phoenix® WinNonlin® Version 8.1, or higher.

    Measure: AUClast (IM injection)

    Time: From Day 1 up to last follow-up day (Day 361)

    Description: AUCinf will be assessed after sequential or co-administration (AZD8895 + AZD1061 mixed into a single infusion) of AZD7442 (IM injection) using noncompartmental methods with Phoenix® WinNonlin® Version 8.1, or higher.

    Measure: AUCinf (IM injection)

    Time: From Day 1 up to last follow-up day (Day 361)

    Description: CL/F will be assessed after sequential or co-administration (AZD8895 + AZD1061 mixed into a single infusion) of AZD7442 (IM injection) using noncompartmental methods with Phoenix® WinNonlin® Version 8.1, or higher.

    Measure: Extravascular systemic clearance (CL/F) (IM injection)

    Time: From Day 1 up to last follow-up day (Day 361)

    Description: F will be assessed after sequential or co-administration (AZD8895 + AZD1061 mixed into a single infusion) of AZD7442 (IM injection) using noncompartmental methods with Phoenix® WinNonlin® Version 8.1, or higher.

    Measure: Bioavailability (F) (IM injection)

    Time: From Day 1 up to last follow-up day (Day 361)

    Description: Vz/F will be assessed after sequential or co-administration (AZD8895 + AZD1061 mixed into a single infusion) of AZD7442 (IM injection) using noncompartmental methods with Phoenix® WinNonlin® Version 8.1, or higher.

    Measure: Extravascular terminal-phase volume of distribution (Vz/F) (IM injection)

    Time: From Day 1 up to last follow-up day (Day 361)

    Description: The incidence of ADAs to AZD7442 in serum will be summarised by number and percentage of participants who are ADA positive. The ADA titer will be listed by participant at different time points.

    Measure: Number and percentage of participants who are ADA positive

    Time: From Day 1 up to last follow-up day (Day 361)
    292 A Multicenter, Randomized, Placebo-Controlled, Pragmatic Phase 3 Study Investigating the Efficacy and Safety of Rivaroxaban to Reduce the Risk of Major Venous and Arterial Thrombotic Events, Hospitalization and Death in Medically Ill Outpatients With Acute, Symptomatic COVID-19 Infection

    The purpose of this study is to evaluate whether rivaroxaban reduces the risk of a composite endpoint of major venous and arterial thrombotic events, all-cause hospitalization, and all-cause mortality compared with placebo in outpatients with acute, symptomatic Coronavirus Disease 2019 (COVID-19) Infection.

    NCT04508023
    Conditions
    1. Coronavirus Disease 2019 (COVID-19)
    Interventions
    1. Drug: Rivaroxaban
    2. Other: Placebo
    3. Other: Standard of Care (SOC)
    MeSH:Coronavirus Infections

    Primary Outcomes

    Description: Time to first occurrence of a composite endpoint of symptomatic venous thromboembolism (VTE), myocardial infarction (MI), ischemic stroke, acute limb ischemia, noncentral nervous system (non-CNS) systemic embolization, all-cause hospitalization, and all-cause mortality will be assessed.

    Measure: Time to First Occurrence of a Composite Endpoint of Symptomatic VTE, MI, Ischemic Stroke, Acute Limb Ischemia, Non-CNS Systemic Embolization, All-cause Hospitalization and All-cause Mortality

    Time: Up to Day 35

    Secondary Outcomes

    Description: Time to first occurrence of a composite endpoint of symptomatic VTE, MI, ischemic stroke, acute limb ischemia, non-CNS systemic embolization, and all-cause mortality will be assessed.

    Measure: Time to First Occurrence of a Composite Endpoint of Symptomatic VTE, MI, Ischemic Stroke, Acute Limb Ischemia, Non-CNS Systemic Embolization, and All-cause Mortality

    Time: Up to Day 35

    Description: Time to first occurrence of all-cause hospitalization will be assessed.

    Measure: Time to First Occurrence of All-cause Hospitalization

    Time: Up to Day 35

    Description: Time to first occurrence of symptomatic VTE which includes DVT or pulmonary embolism (PE) will be assessed.

    Measure: Time to First Occurrence of Symptomatic VTE

    Time: Up to Day 35

    Description: Time to first occurrence of an ER visit will be assessed.

    Measure: Time to First Occurrence of an Emergency Room (ER) Visit

    Time: Up to Day 35

    Description: Time to first occurrence of symptomatic VTE, MI, ischemic stroke, acute limb ischemia, non-CNS systemic embolization, and all-cause hospitalization will be assessed.

    Measure: Time to First Occurrence of Symptomatic VTE, MI, Ischemic Stroke, Acute Limb Ischemia, Non-CNS Systemic Embolization, and All-cause Hospitalization

    Time: Up to Day 35

    Description: Percentage of participants who are hospitalized or dead from any cause at Day 35 will be assessed.

    Measure: Percentage of Participants who are Hospitalized or Dead From Any Cause

    Time: Day 35

    Description: Time to all-cause mortality up to Day 35 will be assessed.

    Measure: Time to All-cause Mortality up to Day 35

    Time: Up to Day 35

    Description: Time to first occurrence of ISTH critical site and fatal bleeding will be assessed.

    Measure: Time to First Occurrence of International Society on Thrombosis and Hemostasis (ISTH) Critical Site and Fatal Bleeding

    Time: Up to 37 Days (last dose on Day 35 plus 2 Days)

    Description: Time to first occurrence of ISTH major bleeding will be assessed. Major bleeding is defined as clinically overt bleeding that is associated with a reduction in hemoglobin of 2 gram per deciliter (g/dL) or more, or a transfusion of 2 or more units of packed red blood cells or whole blood, or occurrence at a critical site defined as intracranial, intra-spinal, intraocular, pericardial, intra-articular, intra-muscular with compartment syndrome, retroperitoneal, or fatal outcome.

    Measure: Time to First Occurrence of ISTH Major Bleeding Events

    Time: Up to 37 Days (last dose on Day 35 plus 2 Days)

    Description: Time to first occurrence of clinically relevant non-major bleeding will be assessed. Clinically relevant non-major bleeding is defined as overt bleeding not meeting the criteria for major bleeding but associated with medical intervention, or unscheduled contact with a physician, or temporary cessation of study treatment, or discomfort such as pain, or impairment of activities of daily life.

    Measure: Time to First Occurrence of Clinically Relevant Non-major Bleeding

    Time: Up to 37 Days (last dose on Day 35 plus 2 Days)
    293 A Phase III, Observer-blind, Randomized, Placebo-controlled Study of the Efficacy, Safety and Immunogenicity of SARS-CoV-2 Inactivated Vaccine in Healthy Adults Aged 18-59 Years in Indonesia

    This phase III trial aims to assess the efficacy, safety and immunogenicity of SARS-CoV-2 Vaccine (inactivated) and lot-to-lot consistency evaluation

    NCT04508075
    Conditions
    1. SARS-CoV2 Infection
    Interventions
    1. Biological: SARS-CoV-2 vaccine (inactivated)
    2. Biological: Placebo
    MeSH:Infection

    Primary Outcomes

    Description: Percentage of laboratory-confirmed COVID-19 cases

    Measure: Incidence of laboratory-confirmed COVID-19 after the second dose

    Time: 14 days to 6 months after the second dose

    Secondary Outcomes

    Description: Percentage of suspected COVID-19 cases

    Measure: Incidence of suspected COVID-19 cases

    Time: within 14 days to 6 months after the second dose.

    Description: Percentage of laboratory-confirmed cases (severe, critical, death)

    Measure: Incidence of laboratory-confirmed cases (severe, critical and death)

    Time: within 14 days to 6 months after the second dose

    Description: Percentage of subjects with four-fold increasing anti-S antibody IgG titer (ELISA) compare to baseline and between batches

    Measure: Seroconversion rate anti-S antibody IgG titer (ELISA)

    Time: 14 days after two doses of vaccination

    Description: Percentage of subjects with four-fold increasing anti-S antibody IgG titer (ELISA) compare to baseline and between batches

    Measure: Seroconversion rate anti-S antibody IgG titer (ELISA)

    Time: 6 months after two doses of vaccination

    Description: Percentage of subjects with four-fold increasing serum neutralizing antibody compared to baseline and between batches

    Measure: Seropositive rate of neutralizing antibodies

    Time: 14 days after two doses of vaccination

    Description: Percentage of subjects with four-fold increasing serum neutralizing antibody compared to baseline and between batches

    Measure: Seropositive rate of neutralizing antibodies

    Time: 6 months after two doses of vaccination

    Other Outcomes

    Description: Number of Local reactions and systemic events

    Measure: Local reaction and systemic events

    Time: 30 minutes to 14 days after each vaccination

    Description: Number of Local reactions and systemic events

    Measure: Local reaction and systemic events occurring after the last vaccination

    Time: 14 days to 28 days following last vaccination

    Description: Number of any SAE occur

    Measure: Serious adverse events during study

    Time: 6 months after the last dose
    294 A Randomized, Double-blind, Placebo-controlled Phase 1 Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of Ad26.COV2.S in Adults

    The purpose of this study is to assess the safety and reactogenicity of Ad26.COV2.S administered intramuscularly (IM) at 2-dose levels, as 2-dose schedule in healthy participants aged greater than or equal to 20 to less than or equal to 55 years and greater than or equal to 65 years in good health with or without stable underlying conditions.

    NCT04509947
    Conditions
    1. Healthy
    Interventions
    1. Biological: Ad26.COV2.S
    2. Biological: Placebo

    Primary Outcomes

    Description: Solicited local AEs are pre-defined local (at the injection site) AEs for which participants are specifically questioned and which are noted by participants in their diary for 7 days post first vaccination. Solicited local AEs are: injection site pain/tenderness, erythema, swelling and induration at the vaccination site. An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product.

    Measure: Number of Participants with Solicited Local Adverse Events (AEs) for 7 days after First Vaccination

    Time: Day 8 (7 days after first vaccination on Day 1)

    Description: Solicited local AEs are pre-defined local (at the injection site) AEs for which participants are specifically questioned and which are noted by participants in their diary for 7 days post second vaccination. Solicited local AEs are: injection site pain/tenderness, erythema, swelling and induration at the vaccination site. An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product.

    Measure: Number of Participants with Solicited Local AEs for 7 days after Second Vaccination

    Time: Day 64 (7 days after second vaccination on Day 57)

    Description: Participants will be instructed on how to note signs and symptoms in the diary on a daily basis for 7 days post-vaccination (Day of vaccination and the subsequent 7 days) for solicited systemic AEs. Solicited systemic events include fatigue, headache, nausea and myalgia.

    Measure: Number of Participants with Solicited Systemic AEs for 7 days after First Vaccination

    Time: Day 8 (7 days after first vaccination on Day 1)

    Description: Participants will be instructed on how to note signs and symptoms in the diary on a daily basis for 7 days post-vaccination (Day of vaccination and the subsequent 7 days) for solicited systemic AEs. Solicited systemic events include fatigue, headache, nausea and myalgia.

    Measure: Number of Participants with Solicited Systemic AEs for 7 days after Second Vaccination

    Time: Day 64 (7 days after second vaccination on Day 57)

    Description: Number of participants with unsolicited AEs for 28 days after first vaccination will be reported. Unsolicited AEs are all AEs for which the participant is not specifically questioned.

    Measure: Number of Participants with Unsolicited AEs for 28 days after First Vaccination

    Time: Day 29 (28 days after first vaccination on Day 1)

    Description: Number of participants with unsolicited AEs for 28 days after second vaccination will be reported. Unsolicited AEs are all AEs for which the participant is not specifically questioned.

    Measure: Number of Participants with Unsolicited AEs for 28 days after Second Vaccination

    Time: Day 85 (28 days after second vaccination on Day 57)

    Description: SAE is an adverse event resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly/birth defect; suspected transmission of any infectious agent via a medicinal product or medically important.

    Measure: Number of Participants with Serious Adverse Events (SAEs)

    Time: Up to 12 months

    Secondary Outcomes

    Description: SARS-CoV-2 neutralization will be measured by VNA to analyse the neutralizing antibodies to the wild-type virus and/or pseudovirion expressing S protein.

    Measure: Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Neutralization as measured by Virus Neutralization Assay (VNA)

    Time: Up to 12 months

    Description: SARS-CoV-2 binding antibodies will be measured by ELISA to analyse the antibodies binding to the SARS-CoV-2 S protein.

    Measure: SARS-CoV-2-Binding Antibodies as Measured by Enzyme-Linked Immunosorbent Assay (ELISA)

    Time: Up to 12 months
    295 Randomized Trial of Bicalutamide to Block TMPRSS2 in Males With COVID-19 Infection

    COVID-19 outcomes are worse in male patients. Androgen signaling, therefore, is a target for clinical exploration. TMPRSS2 is a membrane protease required for COVID pathogenesis that is regulated by androgens. Blocking TMPRSS2 with bicalutamide may reduce viral replication and improve the clinical outcome. Therefore, the study proposes to test bicalutamide at 150 mg oral daily dosing in a double-blind placebo-controlled randomized trial in male patients with early symptomatic COVID-19 disease.

    NCT04509999
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Bicalutamide 150 Mg Oral Tablet
    2. Drug: Placebo
    MeSH:Infection

    Primary Outcomes

    Description: COVID-19 symptom relief at day 28, and % of COVID-19 symptom relief and its 95% confidence interval (CI) will be calculated using the exact binomial distribution and compared using Fisher's exact test.

    Measure: Proportion x 100 = percent of patients with improved COVID-19 symptoms

    Time: Day 28
    296 MET-Covid Trial - Metformin for Outpatient Treatment and Post-exposure Prophylaxis (PEP) of COVID-19

    The purpose of this trial is to conduct a Stage 1 Substudy powered to detect a difference in continuous laboratory outcomes: 1. Test if metformin treatment in non-hospitalized adults with SARS-CoV-2 can improve laboratory outcomes associated with Covid-19 severity 2. Test if metformin treatment in non-hospitalized adults with SARS-CoV-2 infection can prevent emergency department utilization for Covid-19. 3. Test if metformin treatment in non-hospitalized adults with SARS-CoV-2 disease can prevent Covid-19 disease progression.

    NCT04510194
    Conditions
    1. Covid19
    2. SARS-CoV Infection
    Interventions
    1. Drug: Metformin
    2. Drug: Placebo
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome

    Primary Outcomes

    Description: This is one of the primary outcomes for the stage 1 trial. Outcome is reported as the change in serum concentrations of c-reactive protein (mg/L) from baseline to 5 days and baseline to 10 days.

    Measure: Change in C-Reactive Protein

    Time: 10 days

    Description: This is one of the primary outcomes for the stage 1 trial. Outcome is reported as the change in serum concentrations of albumin (g/dL) from baseline to 5 days and baseline to 10 days.

    Measure: Change in Albumin

    Time: 10 days

    Description: This is one of the primary outcomes for the stage 1 trial. Outcome is reported as the change in serum viral load (copies per ml of blood) from baseline to 5 days and baseline to 10 days.

    Measure: Change in Viral load

    Time: 10 days

    Secondary Outcomes

    Description: For Covid-19 Symptoms (as defined by current CDC definition of Covid-19 symptoms).

    Measure: Emergency Department Utilization

    Time: 14 days, 28 days

    Description: Assessed with Symptom Scale Recommended by FDA for Industry 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.

    Measure: Incidence of Possible COVID-19 Symptoms

    Time: 14 days, 28 days

    Description: Incidence of hospitalization for Covid-19 Incidence of oxygen therapy needed Incidence of mechanical ventilation Incidence of death

    Measure: WHO Disease Progression Scale

    Time: 14 days, 28 days.
    297 Multicenter, Randomized, Double Blind, Parallel Placebo Controlled, Phase III Clinical Trial to Evaluate the Protective Efficacy, Safety and Immunogenicity of Inactivated SARS-CoV-2 Vaccines (Vero Cell) in Healthy Population Aged 18 Years Old and Above

    This is a multicenter, randomized, double blind, parallel placebo controlled, phase 3 clinical trial to evaluate the protective efficacy, safety and immunogenicity of inactivated SARS-CoV-2 vaccines in healthy population 18 years old and above.

    NCT04510207
    Conditions
    1. COVID-19
    Interventions
    1. Biological: Inactivated SARS-CoV-2 Vaccine (Vero cell)
    2. Biological: Inactivated SARS-CoV-2 Vaccine (Vero cell)
    3. Biological: Placebo

    Primary Outcomes

    Measure: The incidence of COVID-19 cases after two-doses of vaccination

    Time: From14 days after the second dose to 6 month after the second dose

    Secondary Outcomes

    Measure: The incidence of severe cases of SARS-CoV-2 pneumonia and deaths accompanied by COVID-19 after two-doses of vaccination

    Time: From14 day after the second dose to 6 month after the second dose

    Measure: The incidence of any adverse reactions/events

    Time: 28 days after each immunization

    Measure: The incidence of serious adverse events (SAE)

    Time: From the beginning of the first dose to 12 months after the second immunization

    Measure: The Geometric Mean Titer (GMT) of anti-SARS-CoV-2 neutralizing antibody

    Time: 14 days after full course of immunization

    Measure: The four-fold increase rate of anti-SARS-CoV-2 neutralizing antibody

    Time: 14 days after full course of immunization

    Measure: The Geometric Mean Fold Rise (GMFR) of anti-SARS-CoV-2 neutralizing antibody

    Time: 14 days after full course of immunization

    Measure: The Geometric Mean Titer (GMT) of anti-SARS-CoV-2 neutralizing antibody

    Time: 28 days, 3rd month, 6th month, 9th month, and 12th month after 2 doses of immunization

    Measure: The 4-fold increase rate of anti-SARS-CoV-2 neutralizing antibody

    Time: 28 days, 3rd month, 6th month, 9th month, and 12th month after 2 doses of immunization

    Measure: The Geometric Mean Fold Rise (GMFR) of anti-SARS-CoV-2 neutralizing antibody

    Time: 28 days, 3rd month, 6th month, 9th month, and 12th month after 2 doses of immunization

    Other Outcomes

    Measure: the anti-SARS-CoV-2 neutralizing antibody protective level against COVID-19

    Time: 14 days after 2 doses of vaccination

    Measure: The occurrence of ADE

    Time: From the beginning of the first dose to 12 months after the second immunization
    298 Canakinumab in Patients With COVID-19 and Type 2 Diabetes - CanCovDia Trial

    The purpose of this study is to evaluate whether Canakinumab has beneficial effects on patients with Type 2 diabetes mellitus and coronavirus disease 19 (COVID19).

    NCT04510493
    Conditions
    1. Coronavirus Infection
    2. Diabetes Mellitus, Type 2
    Interventions
    1. Drug: Canakinumab
    2. Drug: Placebo
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Diabetes Mellitus Diabetes Mellitus, Type 2
    HPO:Diabetes mellitus Type II diabetes mellitus

    Primary Outcomes

    Description: Treatment and placebo will be compared on the basis of the unmatched win-ratio approach of Pocock. When comparing two patients, the winner will be determined by the first component in which the two patients differ (4 weeks after randomization): longer survival time longer ventilation-free time longer ICU-free time shorter hospitalization time If there is no difference between treatment and Placebo: the win ratio is 1. If there is a difference between treatment and Placebo: the win ratio is not 1.

    Measure: unmatched win ratio after treatment with canakinumab compared to Placebo (composite endpoint)

    Time: within 4 weeks after treatment with canakinumab or placebo

    Secondary Outcomes

    Description: Time to clinical improvement, defined as the time from randomization to either an improvement of two points on a seven-category ordinal scale or discharge from the hospital, whichever comes first. "The seven-category ordinal scale consists of the following categories: not hospitalized with resumption of normal activities; not hospitalized, but unable to resume normal activities; hospitalized, not requiring supplemental oxygen; hospitalized, requiring supplemental oxygen; hospitalized, requiring nasal high-flow oxygen therapy, noninvasive mechanical ventilation, or both; hospitalized, requiring extracorporeal membrane oxygenation (ECMO), invasive mechanical ventilation, or both; and death"

    Measure: Time to clinical improvement

    Time: From randomization up to 4 weeks

    Description: Death rate during the 4-week period after study treatment

    Measure: Death rate

    Time: 4 weeks

    Description: Admission to the intensive care unit from the medical ward during the 4-week period after study treatment

    Measure: Admission to intensive care unit (ICU)

    Time: 4 weeks

    Description: Secondary worsening of disease (i.e., development of Acute respiratory distress Syndrome (ARDS), increase of oxygen demand after 72h of treatment)

    Measure: Secondary worsening of disease

    Time: 4 weeks

    Description: Prolonged hospital stay > 3 weeks

    Measure: Prolonged hospital stay

    Time: >3 weeks

    Description: Ratio to baseline in the glycated hemoglobin

    Measure: Change in ratio to baseline in the glycated hemoglobin

    Time: Baseline, Day 29 and Day 90

    Description: Ratio to baseline in the fasting glucose

    Measure: Change in ratio to baseline in the fasting glucose

    Time: Baseline, Day 29

    Description: Ratio to baseline in the fasting insulin

    Measure: Change in ratio to baseline in the fasting insulin

    Time: Baseline, Day 29

    Description: Ratio to baseline in the fasting c-peptide

    Measure: Change in ratio to baseline in the fasting c-peptide

    Time: Baseline, Day 29

    Description: Ratio to baseline in the C-reactive protein (CRP)

    Measure: Ratio to baseline in the C-reactive protein (CRP)

    Time: Baseline, Day 29 and Day 90

    Description: Ratio to baseline in the D-dimer

    Measure: Change in ratio to baseline in the D-dimer

    Time: Baseline, Day 29

    Description: Ratio to baseline in the Natriuretic peptide (NTproBNP)

    Measure: Change in ratio to baseline in the Natriuretic peptide (NTproBNP)

    Time: Baseline, Day 29 and Day 90

    Description: Ratio to baseline in the Glomerular Filtration Rate Renal (eGFR)

    Measure: Change in ratio to baseline in the Glomerular Filtration Rate Renal (eGFR)

    Time: Baseline, Day 29 and Day 90

    Description: Type of antidiabetic treatment at Day 29

    Measure: Type of antidiabetic treatment at Day 29

    Time: Day 29

    Description: Number of antidiabetic treatment at Day 29

    Measure: Number of antidiabetic treatment at Day 29

    Time: Day 29

    Description: Type of antidiabetic treatment at three months

    Measure: Type of antidiabetic treatment at three months

    Time: Month 3

    Description: Number of antidiabetic treatment at three months

    Measure: Number of antidiabetic treatment at three months

    Time: Month 3
    299 Pilot Study to Evaluate Safety and Efficacy of Anti-SARS-CoV-2 Equine Immunoglobulin F(ab')2 Fragments (INOSARS) in Hospitalized Patients With COVID-19

    This is a two-center, randomized, placebo-controlled pilot study of anti-SARS-CoV-2 equine immunoglobulin fragments F(ab')2 (INOSARS) to evaluate safety and preliminary efficacy in the treatment of hospitalized COVID-19 patients. Clinical improvement at 28 days from the start of treatment will be evaluated.

    NCT04514302
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Placebo
    2. Drug: Anti-SARS-CoV-2 equine immunoglobulin fragments (INOSARS)

    Primary Outcomes

    Description: The primary endpoint is the proportion of patients with clinical improvement at 28 days after treatment. Clinical improvement is defined as (whichever is first): a) hospital discharge or b) reduction of 1 point in the NIAID 8-point ordinal scale. Scale categories as follows: 1 = not hospitalized; 2 = not hospitalized with limitation of activities and/or oxygen requirement; 3 = hospitalized not requiring supplemental oxygen and not requiring active medical care, 4 = hospitalized requiring active medical care without requiring oxygen supplementation; 5 = hospitalized requiring oxygen supplementation; 6 = hospitalized requiring high-flow oxygen or non-invasive mechanical ventilation; 7 = hospitalized requiring invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 8 = death.

    Measure: Proportion of patients with improvement in clinical status

    Time: 28 days

    Secondary Outcomes

    Description: Time from the day of treatment until the first day with clinical improvement, defined as (whichever is first): a) hospital discharge or b) reduction of 1 point in the NIAID 8-point ordinal scale.

    Measure: Time to clinical improvement

    Time: 28 days

    Description: Proportion of participant death or non-invasive or invasive mechanical ventilation or extracorporeal membrane oxygenation requirement.

    Measure: Proportion of patients that reach a score of 6, 7 or 8 in the NIAID 8-point ordinal scale

    Time: 28 days

    Description: Measured in days

    Measure: Duration of hospitalization

    Time: 28 days

    Description: Proportion of patients that have a negative polymerase chain reaction assay for SARS-CoV-2 at 72 hrs from start of treatment.

    Measure: SARS-CoV-2 PCR negativization rate

    Time: 3 days

    Description: Proportion of patients with clinical improvement at day 7. Clinical improvement is defined as (whichever is first): a) hospital discharge or b) reduction of 1 point in the NIAID 8-point ordinal scale

    Measure: Proportion of patients with clinical improvement at day 7

    Time: 7 days

    Description: Proportion of patients that present within 24 hours of treatment with immediate adverse events defined as: skin rash and/or respiratory findings (dyspnea, wheezing, bronchospasm, hypoxia) and/or circulatory compromise (reduction of blood pressure or associated symptoms, i.e. syncope).

    Measure: Proportion of patients with immediate adverse events (< 24 hours)

    Time: 24 hours

    Description: Proportion of patients that present events associated with serum sickness (type 3 hypersensitivity), vasculitis, glomerulonephritis, arthritis.

    Measure: Proportion of patients with late adverse events (1 - 28 days)

    Time: 28 days
    300 A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose, First-In-Human Study Evaluating the Safety, Tolerability, and Pharmacokinetics of AK119 in Healthy Subjects

    This is a first-in-human (FIH), Phase 1, single-center, randomized, double-blind, placebo-controlled, single ascending dose study to evaluate the safety, tolerability, PK and immunogenicity of AK119, a humanized monoclonal antibody targeting the CD73. The study will consist of 4 cohorts of healthy subjects. Eight subjects will be enrolled per cohort, randomized in a 3:1 ratio to receive a single dose of either the active drug AK119 (N=6) or matching placebo (N=2). Approximately 32 subjects (24 receiving active drug and 8 receiving placebo) will participate in this study.

    NCT04516564
    Conditions
    1. Coronavirus Disease 2019 (COVID-19)
    Interventions
    1. Drug: AK119
    2. Drug: Placebo
    MeSH:Coronavirus Infections

    Primary Outcomes

    Measure: Incidence of treatment-emergent AEs

    Time: From signing of informed consent till end of study (approximately 64 days postdose)

    Secondary Outcomes

    Measure: Maximum serum concentration (Cmax) of AK119

    Time: From baseline till end of study (approximately 64 days postdose)

    Measure: Area under the concentration-time curve (AUC) of serum concentration of AK119

    Time: From baseline till end of study (approximately 64 days postdose)

    Measure: Percentage of subjects who develop detectable anti-drug antibodies (ADAs)

    Time: From baseline till end of study (approximately 64 days postdose)
    301 A Phase III Randomized, Double-blind, Placebo-controlled Multicenter Study in Adults to Determine the Safety, Efficacy, and Immunogenicity of AZD1222, a Non-replicating ChAdOx1 Vector Vaccine, for the Prevention of COVID-19

    The aim of the study is to assess the safety, efficacy, and immunogenicity of AZD1222 for the prevention of COVID-19.

    NCT04516746
    Conditions
    1. COVID-19
    2. SARS-CoV-2
    Interventions
    1. Biological: AZD1222
    2. Biological: Placebo

    Primary Outcomes

    Description: A binary response, whereby a participant is defined as a COVID-19 case if their first case of SARS-CoV-2 RT-PCR-positive symptomatic illness occurs ≥ 15 days post second dose of study intervention. Otherwise, a participant is not defined as a COVID-19 case.

    Measure: The efficacy of 2 IM doses of AZD1222 compared to placebo for the prevention of COVID-19 in adults ≥ 18 years of age

    Time: 1 year

    Description: Incidence of adverse events. Incidence of serious adverse events, medically attended adverse events, and adverse events of special interest.

    Measure: The safety and tolerability of 2 IM doses of AZD1222 compared to placebo in adults ≥ 18 years of age

    Time: a: 28 days post each dose of study Intervention. / b: from Day 1 post-treatment through Day 730.

    Description: Incidence of local and systemic solicited adverse events.

    Measure: The reactogenicity of 2 IM doses of AZD1222 compared to placebo in adults ≥ 18 years of age (Substudy only)

    Time: 7 days post each dose of study intervention.

    Secondary Outcomes

    Description: The proportion of participants who have a post-treatment response (negative at baseline to positive post treatment with study intervention) for SARS-CoV-2 Nucleocapsid antibodies over time.

    Measure: The efficacy of 2 IM doses of AZD1222 compared to placebo for the prevention of SARS-CoV-2 infection

    Time: 1 year

    Description: The incidence of the first case of SARS-CoV-2 RT-PCR-positive symptomatic illness for a participant occurring at or after 15 days post second dose of study intervention using criteria from the CDC.

    Measure: The efficacy of 2 IM doses of AZD1222 compared to placebo for the prevention of symptomatic COVID-19 using CDC criteria

    Time: 1 year

    Description: The incidence of the first case of SARS-CoV-2 RT-PCR positive symptomatic illness occurring ≥ 15 days post second dose of study intervention using University of Oxford defined symptom criteria.

    Measure: The efficacy of 2 IM doses of AZD1222 compared to placebo for the prevention of University of Oxford defined symptomatic COVID-19

    Time: 1 year

    Description: The incidence of SARS-CoV-RT-PCR-positive severe or critical symptomatic illness occurring 15 days or more post second dose of study intervention.

    Measure: The efficacy of 2 IM doses of AZD12222 compared to placebo for the prevention of severe or critical symptomatic COVID-19.

    Time: 1 year

    Description: The incidence of COVID-19-related Emergency Department visits occurring ≥ 15 days post second dose of study intervention

    Measure: The efficacy of 2 IM doses of AZD1222 compared to placebo for the prevention of COVID-19-related Emergency Department visits

    Time: 1 year

    Description: Post-treatment GMTs and GMFRs in SARS-CoV-2 S, RBD antibodies (MSD serology assay); The proportion of participants who have a post-treatment seroresponse (≥ 4-fold rise in titers) to the S, RBD antigens of AZD1222 (MSD serology assay)

    Measure: Antibody responses to AZD1222 S antigen following 2 IM doses of AZD1222 or placebo (Substudy and Illness Visits only)

    Time: 28 days post each dose

    Description: Post-treatment GMTs and GMFRs in SARS-CoV-2 neutralizing antibodies (wild-type assay or pseudo-neutralization assay); Proportion of participants who have a post-treatment seroresponse (≥ 4-fold rise in titers) to AZD1222 as measured by SARS-CoV-2 neutralizing antibodies (wild-type assay or pseudo-neutralization assay)

    Measure: Anti-SARS-CoV-2 neutralizing antibody levels in serum following 2 IM doses of AZD1222 or placebo (Sub-study and Illness Visits only)

    Time: 28 days post each dose
    302 A Phase II, Randomised, Double-blind, Placebo-controlled Clinical Trial to Assess the Safety and Efficacy of AZD1656 in Diabetic Patients Hospitalised With Suspected or Confirmed COVID-19

    The ARCADIA Trial is a randomised, double-blind, placebo-controlled clinical trial to assess the safety and efficacy of AZD1656 in patients with either Type 1 or Type 2 diabetes, hospitalised with COVID-19.

    NCT04516759
    Conditions
    1. Covid19
    Interventions
    1. Drug: AZD1656
    2. Other: Placebo

    Primary Outcomes

    Description: Clinical Improvement measured as the percentage of subjects at Day 14 who are in categories 1-3 according to the WHO 8-point Ordinal Scale for Clinical Improvement, comparing AZD1656 treatment to placebo

    Measure: Clinical Improvement by Day 14

    Time: Day 1 to Day 14

    Secondary Outcomes

    Description: Clinical Improvement measured as the percentage of patients categorised at each severity rating on the WHO 8-point Ordinal Scale at Day 7, Day 14 and Day 21 versus baseline, comparing AZD1656 treatment with placebo.

    Measure: *Title: Clinical Improvement at Day 7, 14 and 21

    Time: Day 1 to Day 21

    Description: Degree of glycaemic control as measured by the need to increase baseline medication requirements or the need to add additional diabetic medications to maintain appropriate blood glucose levels in patients receiving AZD1656 compared with placebo

    Measure: Glycaemic Control

    Time: Day 1 to Day 21

    Description: Proportion of Treatment Emergent Adverse Events (TEAEs) leading to study drug discontinuation in patients receiving AZD1656 compared with placebo

    Measure: Occurrence of Adverse Events

    Time: Day 1 to Day 28

    Description: Proportion of Serious Adverse Events (SAEs) in patients receiving AZD1656 compared with placebo

    Measure: Occurrence of Serious Adverse Events

    Time: Day 1 to Day 28

    Description: Time from hospital admission to hospital discharge (in hours) in patients receiving AZD1656 compared with placebo

    Measure: Duration of Hospitalisation

    Time: Day 1 to Day 21

    Description: Time from hospital admission to receiving intubation/mechanical ventilation in patients receiving AZD1656 compared with placebo

    Measure: Time to Intubation/ Mechanical Intervention

    Time: Day 1 to Day 21

    Description: Mortality rate in patients receiving AZD1656 compared with placebo.

    Measure: Mortality Rate

    Time: Day 1 to Day 28

    Other Outcomes

    Description: Plasma AZD1656 levels during first 7 days of treatment in patients receiving AZD1656 compared with placebo.

    Measure: Pharmacokinetic Analysis

    Time: Day 1 to Day 7

    Description: Immunophenotyping panel to be conducted by Flow Cytometry: between group comparison (AZD1656 versus placebo)

    Measure: Immunophenotyping Analysis

    Time: Day 1 to Day 21

    Description: Immunochemistry panel to be conducted using the Meso Scale Discovery (MSD) U-Plex multiplex assay.

    Measure: Immunochemistry Analysis

    Time: Day 1 to Day 21

    Description: Measurement of hsTroponin and NTproBNP to determine extent of cardiac injury in patients receiving AZD1656 compared with placebo

    Measure: Cardiac Injury

    Time: Day 1 to Day 21

    Description: Measurement of 25-hydroxyvitamin D levels before treatment to determine whether there is any correlation between baseline vitamin D level and clinical improvement in patients treated with AZD1656 versus placebo.

    Measure: Correlation of clinical outcomes with pre-treatment vitamin D levels (by measurement of 25-hydroxyvitamin D levels).

    Time: Day 1 to Day 21

    Description: Sub group analysis of patient ethnicity, to determine whether there is any correlation between patient ethnicity and clinical improvement in patients treated with AZD1656 versus placebo.

    Measure: Correlation of patient ethnicity with clinical improvement

    Time: Day 1 to Day 21
    303 FEnofibRate as a Metabolic INtervention for Coronavirus Disease 2019

    The severe acute respiratory syndrome coronavirus 2 (SARS-CoC-2), the virus responsible for coronavirus disease 2019 (COVID-19), is associated with a high incidence of acute respiratory distress syndrome (ARDS) and death. Aging, obesity, diabetes, hypertension and other risk factors associated with abnormal lipid and carbohydrate metabolism are risk factors for death in COVID-19. Recent studies suggest that COVID-19 progression is dependent on metabolic mechanisms. Moreover, gene expression analyses in cultured human bronchial cells infected with SARS-CoV-2 and lung tissue from patients with COVID-19, indicated a marked shift in cellular metabolism, with excessive intracellular lipid generation. In this cell culture system, fenofibrate (a widely available low-cost generic drug approved by the FDA and multiple other regulatory agencies around the world to treat dyslipemias) at concentrations that can be achieved clinically, markedly inhibited SARS-CoV-2 viral replication. Fenofibrate also has immunomodulatory effects that may be beneficial in the setting of COVID-19. The aim of this trial is to assess the clinical impact of fenofibrate (145 mg/d of Tricor or dose-equivalent preparations for 10 days, with dose adjustment in chronic kidney disease ([CKD]) to improve clinical outcomes in patients with COVID-19.

    NCT04517396
    Conditions
    1. Covid19
    Interventions
    1. Other: Fenofibrate
    2. Other: Placebo
    3. Other: Usual care

    Primary Outcomes

    Description: The primary endpoint of the trial will be a global rank score that ranks patient outcomes according to 5 factors: (1) time to death; (2) the number of days supported by invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); (3) The inspired concentration of oxygen/percent oxygen saturation (FiO2/SpO2) ratio area under the curve; (4) For participants enrolled as outpatients who are subsequently hospitalized, the number of days out of the hospital during the 30 day-period following randomization; (5) For participants enrolled as outpatients who don't get hospitalized during the 30-day observation period, the modified Borg dyspnea scale

    Measure: Hierarchical composite endpoint

    Time: Up to 30 days

    Secondary Outcomes

    Measure: Number of days alive, out of the intensive care unit, free of mechanical ventilation/extracorporeal membrane oxygenation, or maximal available respiratory support in the 30 days following randomization

    Time: Up to 30 days

    Description: A seven-category ordinal scale consisting of the following categories: 1, not hospitalized with resumption of normal activities; 2, not hospitalized, but unable to resume normal activities; 3, hospitalized, not requiring supplemental oxygen; 4, hospitalized, requiring supplemental oxygen; 5, hospitalized, requiring nasal high-flow oxygen therapy, noninvasive mechanical ventilation, or both; 6, hospitalized, requiring extracorporeal membrane oxygenation (ECMO), invasive mechanical ventilation, or both; and 7, death.

    Measure: Seven-category ordinal scale

    Time: At 15 days

    Description: A global rank score similar to the primary endpoint, but using a more comprehensive COVID-19 symptom scale instead of the dyspnea Borg scale

    Measure: Hierarchical composite endpoint

    Time: Up to 30 days

    Other Outcomes

    Measure: All-Cause Death

    Time: Up to 30 days

    Measure: Number of days alive and out of the hospital during the 30 days following randomization

    Time: Up to 30 days

    Description: A global rank score similar to the primary endpoint, but built only with factors 1-4 of the primary endpoint

    Measure: Hierarchical composite endpoint

    Time: Up to 30 days
    304 Efficacy and Safety of Lactobacillus Plantarum and Pediococcus Acidilactici as Co-adjuvant Therapy for Reducing the Risk of Severe Disease in Adults With SARS-CoV-2 and Its Modulation of the Fecal Microbiota: A Randomized Clinical Trial

    Clinical research focused to evaluate the effect as coadyuvant of a combination of L. plantarum and P. acidilactici in adults positive for SARS-CoV-2 with mild clinical COVID-19 symptoms. Main objective is to evaluate how this combination of probiotics reduce the risk to progress to moderate or severe COVID and associated advantages such as reduce the risk of death. Adittionnally this RCT is launching to explore the benefits of this combination of strains to modulate fecal microbiome and explore how this correlate with clinical improvement.

    NCT04517422
    Conditions
    1. SARS-CoV Infection
    Interventions
    1. Dietary Supplement: Probiotics
    2. Other: Placebo
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome

    Primary Outcomes

    Description: Frequency of randomized subjects who progress from mild to moderate or severe COVID-19, as evaluated by WHO Clinical Progression Scale

    Measure: Severity progression of COVID-19

    Time: 30 days

    Description: Length of stay at Intensive care unit

    Measure: Stay at ICU

    Time: 30 days

    Description: Mortality ratio for all the causes related to COVID-19

    Measure: Mortality ratio

    Time: 30 days

    Secondary Outcomes

    Description: Frequency of lung abnormalities clasified by severity and measured by x-ray and artificial intelligence

    Measure: Lung abnormalities

    Time: 30 days

    Description: Description of SARS-Cov-2 viral load evaluated by RT-PCR at screening and on days 15 and 30

    Measure: Viral load

    Time: 30 days

    Description: Levels of Immunoglobulin G and Immunoglobulin M evaluated on day 15 and 30

    Measure: Levels of immunoglobulins

    Time: 30 days

    Description: Frequency and severity of gastrointestinal manifestation evaluated by Gastrointestinal Symptom Rating Scale (GSRS)

    Measure: Gastrointestinal manifestations, where 0 means good health status and 5 worse status

    Time: 30 days

    Description: Changes on fecal microbiome evaluated by 16S analysis on day 1st and 30th

    Measure: Fecal microbiome

    Time: 30 days

    Description: Frequency of adverse events reported on dairy report form after randomization and until day 30

    Measure: Adverse events

    Time: 30 days

    Description: Change on C-reactive high sensitivity protein (hsCRP) and D-Dimer

    Measure: Change on Serum Biomarkers

    Time: Days 1st, 15th and 30th after randomization
    305 Adaptive Platform Treatment Trial for Outpatients With COVID-19 (Adapt Out COVID)

    Drug studies often look at the effect one or two drugs have on a medical condition, and involve one company. There is currently an urgent need for one study to efficiently test multiple drugs from more than one company, in people who have tested positive for COVID-19 but who do not currently need hospitalization. This could help prevent disease progression to more serious symptoms and complications, and spread of COVID-19 in the community. This study looks at the safety and effectiveness of different drugs in treating COVID-19 in outpatients. Participants in the study will be treated with either a study drug or with placebo.

    NCT04518410
    Conditions
    1. Coronavirus
    2. Covid19
    Interventions
    1. Drug: LY3819253
    2. Drug: Placebo
    MeSH:Coronavirus Infections

    Primary Outcomes

    Description: Symptoms: Fever or feeling feverish; cough, shortness of breath or difficulty breathing at rest or with activity; sore throat; body pain or muscle pain/aches; fatigue; headache, chills, nasal obstruction or congestion; nasal discharge (runny nose); nausea or vomiting; and diarrhea. Each symptom is scored daily by the participant as absent (score 0), mild (1), moderate (2) or severe (3)

    Measure: Duration of COVID-19 symptoms (Phase 2)

    Time: Up to Day 28

    Description: Measured as detectable or undetectable, from site-collected NP (nasopharyngeal) swabs

    Measure: Post-treatment presence of SARS-CoV-2 RNA at Day 3 (Phase 2)

    Time: Day 3

    Description: Measured as detectable or undetectable, from site-collected NP (nasopharyngeal) swabs

    Measure: Post-treatment presence of SARS-CoV-2 RNA at Day 7 (Phase 2)

    Time: Day 7

    Description: Measured as detectable or undetectable, from site-collected NP (nasopharyngeal) swabs

    Measure: Post-treatment presence of SARS-CoV-2 RNA at Day 14 (Phase 2)

    Time: Day 14

    Description: Measured as detectable or undetectable, from site-collected NP (nasopharyngeal) swabs

    Measure: Post-treatment presence of SARS-CoV-2 RNA at Day 21 (Phase 2)

    Time: Day 21

    Description: Measured as detectable or undetectable, from site-collected NP (nasopharyngeal) swabs

    Measure: Post-treatment presence of SARS-CoV-2 RNA at Day 28 (Phase 2)

    Time: Day 28

    Measure: Incidence of new adverse event (AE) ≥ Grade 3 (Phase 2)

    Time: Thru Day 28

    Description: ≥24 hours of acute care in a hospital or similar acute care facility, including Emergency Rooms or temporary facilities instituted ton address medical needs of those with severe COVID-19

    Measure: Cumulative incidence of death from any cause or hospitalization (Phase 3)

    Time: Thru Day 28

    Measure: Proportion of participants with new adverse event (AE) ≥ Grade 3 (Phase 3)

    Time: Thru Day 28

    Secondary Outcomes

    Description: ≥24 hours of acute care in a hospital or similar acute care facility, including Emergency Rooms or temporary facilities instituted ton address medical needs of those with severe COVID-19

    Measure: Cumulative incidence of death from any cause or hospitalization (Phase 2)

    Time: Thru Day 28

    Description: Symptoms: Fever or feeling feverish; cough, shortness of breath or difficulty breathing at rest or with activity; sore throat; body pain or muscle pain/aches; fatigue; headache, chills, nasal obstruction or congestion; nasal discharge (runny nose); nausea or vomiting; and diarrhea. Each symptom is scored daily by the participant as absent (score 0), mild (1), moderate (2) or severe (3)

    Measure: Duration of COVID-19 symptoms (Phase 3)

    Time: Up to Day 28

    Description: Measured as detectable or undetectable, from participant-collected nasal swabs

    Measure: Presence of SARS-CoV-2 RNA (Phases 2 and 3)

    Time: Thru Day 28

    Description: Measured from participant-collected nasal swabs

    Measure: Level of SARS-Cov-2 RNA (Phases 2 and 3)

    Time: Thru Day 28

    Description: Based on symptom severity scores. Symptoms: Fever or feeling feverish; cough, shortness of breath or difficulty breathing at rest or with activity; sore throat; body pain or muscle pain/aches; fatigue; headache, chills, nasal obstruction or congestion; nasal discharge (runny nose); nausea or vomiting; and diarrhea. Each symptom is scored daily by the participant as absent (score 0), mild (1), moderate (2) or severe (3). For participants who are alive at 28 days and not previously hospitalized, the severity ranking will be based on the area under the curve (AUC) of the symptom score associated with COVID-19 disease over time. Participants hospitalized or who die during follow-up through 28 days will be ranked as worse than those alive and never hospitalized as follows (in worsening rank order): alive and not hospitalized at 28 days; hospitalized but alive at 28 days; and died at or before 28 days.

    Measure: COVID-19 severity ranking (Phases 2 and 3)

    Time: From Day 0 thru Day 28

    Description: Progression of one or more COVID-19-associated symptoms to a worse status than recorded at study entry, prior to start of investigational product or placebo

    Measure: Incidence of ≥1 worsening symptom of COVID-19 (Phases 2 and 3)

    Time: Thru Day 28

    Description: Defined as the last day in the participant's study diary on which a temperature ≥ 38°C (100.4°F) was recorded or a potentially antipyretic drug was taken.

    Measure: Duration of fever (Phases 2 and 3)

    Time: Thru Day 28

    Description: As recorded in participant's study diary

    Measure: Time to self-report return to usual (pre-COVID-19) health (Phases 2 and 3)

    Time: Thru Day 28

    Measure: Cumulative incidence of death from any cause or hospitalization (Phases 2 and 3)

    Time: Day 0 thru Week 24

    Description: Measured by pulse oximeter and categorized as <96% versus ≥96%

    Measure: Oxygen saturation level (Phase 2)

    Time: Thru Day 28

    Description: Measured by AUC and above assay lower limit of quantification

    Measure: Level of SARS-CoV-2 RNA from site-collected NP swabs (Phase 2)

    Time: Days 0, 3, 7, 14, 21 and 28

    Description: Measured by AUC and above assay lower limit of quantification

    Measure: Level of SARS-CoV-2 RNA from saliva (Phase 2)

    Time: Days 0, 3, 7, 14, 21 and 28

    Description: Measured by AUC and above assay lower limit of quantification

    Measure: Level of SARS-CoV-2 RNA from self-collected nasal swabs (Phase 2)

    Time: Daily at Days 0-14, plus Days 21 and 28

    Description: From site-collected NP swabs

    Measure: Level of SARS-CoV-2 RNA (Phase 2)

    Time: Days 3, 7, 14, 21 and 28

    Description: Measured as detectable or undetectable

    Measure: Post-treatment presence of SARS-CoV-2 RNA in saliva (Phase 2)

    Time: Days 3, 7, 14, 21 and 28

    Description: Measured from saliva samples

    Measure: Post-treatment level of SARS-CoV-2 RNA (Phase 2)

    Time: Days 3, 7, 14, 21 and 28

    Measure: Incidence of new adverse event (AE) ≥ Grade 3 (Phase 3)

    Time: Thru Week 24

    Description: Analyses of plasma samples collected from placebo-treated participants are not planned

    Measure: Concentration of investigational agent (Phase 2 - LY3819253)

    Time: Days 0, 14, 28, Week 12, Week 24

    Description: Analyses of plasma samples collected from placebo-treated participants are not planned

    Measure: Level of anti-drug antibodies (Phase 2 - LY3819253)

    Time: Days 0, 14, 28, Week 12, Week 24

    Description: Area under the concentration-time curve. Analyses of plasma samples collected from placebo-treated participants are not planned

    Measure: AUC (Phase 2 - LY3819253)

    Time: Days 0, 14, 28, Week 12, Week 24

    Description: Analyses of plasma samples collected from placebo-treated participants are not planned

    Measure: Total body clearance (CL) (Phase 2 - LY3819253)

    Time: Days 0, 14, 28, Week 12, Week 24

    Description: T1/2. Analyses of plasma samples collected from placebo-treated participants are not planned

    Measure: Elimination half-life (Phase 2 - LY3819253)

    Time: Days 0, 14, 28, Week 12, Week 24

    Description: Maximum plasma concentration of LY3819253. Analyses of samples collected from placebo-treated participants are not planned

    Measure: Cmax (Phase 2 - LY3819253)

    Time: Days 0, 14, 28, Week 12, Week 24

    Description: Minimum plasma concentration of LY3819253. Analyses of samples collected from placebo-treated participants are not planned

    Measure: Cmin (Phase 2 - LY3819253)

    Time: Days 0, 14, 28, Week 12, Week 24
    306 A Phase 2, Multicenter, Double-blind, Randomized, Placebo-controlled Study to Evaluate CSL324 in Coronavirus Disease 2019 (COVID-19)

    This is a phase 2, prospective, multicenter, randomized, double blind, placebo controlled, parallel group study to evaluate the safety and efficacy of intravenous (IV) administration of CSL324, administered in combination with SOC treatment, in subjects with COVID 19. For the purposes of this study, standard of care (SOC) may include any written or established treatment protocol followed at the study site for the treatment of severe COVID-19 or its complications, including off-label use of marketed pharmaceutical products and / or products with emergency use authorization granted for the treatment of COVID-19 (ie, not yet marketed) (eg, remdesivir).

    NCT04519424
    Conditions
    1. Coronavirus Disease 2019 (COVID-19)
    Interventions
    1. Biological: CSL324
    2. Drug: Placebo
    MeSH:Coronavirus Infections

    Primary Outcomes

    Measure: Proportion of subjects progressing to endotracheal intubation or death prior to endotracheal intubation

    Time: Randomization to Day 28

    Secondary Outcomes

    Measure: Proportion of deaths from all causes

    Time: Randomization to Day 28

    Measure: Proportion of subjects intubated

    Time: Randomization to Day 28

    Measure: Median length of stay in hospital

    Time: Randomization to Day 28

    Measure: Number and proportion of subjects with at least a 2-point improvement in the National Institute of Allergy and Infectious Diseases (NIAID) ordinal scale

    Time: Randomization to Day 28

    Measure: Number and proportion of subjects within each of the categories of the NIAID ordinal scale

    Time: Daily up to Day 28

    Measure: Proportion of subjects using continuous positive airway pressure (CPAP) or bilevel positive airway pressure (BiPAP)

    Time: Randomization to Day 28

    Measure: Proportion of subjects using high-flow nasal cannula (HFNC)

    Time: Randomization to Day 28

    Measure: Proportion of subjects using extracorporeal membrane oxygenation (ECMO)

    Time: Randomization to Day 28

    Measure: Maximum Change in Sequential Organ Failure Assessment (SOFA) score

    Time: Randomization to Day 28

    Measure: Change in SOFA score and in individual components of the SOFA score

    Time: Baseline to Day 28

    Measure: Number and proportion of subjects experiencing adverse events (AEs)

    Time: Up to 60 days

    Measure: Number and proportion of subjects experiencing serious adverse events (SAEs)

    Time: Up to 60 days

    Measure: Number and proportion of subjects experiencing adverse events of special interest (AESIs)

    Time: Up to 60 days

    Measure: Presence of anti-CSL324 antibodies

    Time: Up to 28 days

    Measure: Maximum concentration (Cmax) of CSL324

    Time: Up to 28 days

    Measure: Time to reach maximum concentration (Tmax) of CSL324

    Time: Up to 28 days

    Measure: Area under the concentration-time curve (AUC0-last) of CSL324

    Time: Up to 28 days

    Measure: Trough concentration (Ctrough) of CSL324

    Time: Before dose on Day 4 and Day 8
    307 A Phase 1, Randomized, Double-Blind, Placebo-Controlled Study Assessing the Safety, Tolerability, Pharmacokinetics, and Immunogenicity of Repeated Subcutaneous Doses of Anti-Spike (S) SARS-CoV-2 Monoclonal Antibodies (REGN10933+REGN10987) in Adult Volunteers

    The primary objectives are: - To assess the occurrence of adverse events of special interest (AESIs) in participants treated with repeated subcutaneous (SC) doses of REGN10933+REGN10987 compared to placebo - To assess the concentrations of REGN10933 and REGN10987 in serum over time after single and repeated SC administration The secondary objectives are: - To assess the safety and tolerability of repeated SC doses of REGN10933+REGN10987 compared to placebo - To assess attainment of target concentrations of REGN10933 and REGN10987 in serum after single and repeated SC administration - To assess the immunogenicity of REGN10933 and REGN10987

    NCT04519437
    Conditions
    1. Healthy
    2. Chronic Stable Illness
    Interventions
    1. Drug: REGN10933+REGN10987
    2. Drug: Placebo

    Primary Outcomes

    Measure: Incidence of adverse event of special interests (AESIs) that occur within 4 days of study drug administration

    Time: Within 4 days postdose at Baseline

    Measure: Incidence of adverse event of special interests (AESIs) that occur within 4 days of study drug administration

    Time: Within 4 days postdose at Day 29

    Measure: Incidence of adverse event of special interests (AESIs) that occur within 4 days of study drug administration

    Time: Within 4 days postdose at Day 57

    Measure: Incidence of adverse event of special interests (AESIs) that occur within 4 days of study drug administration

    Time: Within 4 days postdose at Day 85

    Measure: Incidence of adverse event of special interests (AESIs) that occur within 4 days of study drug administration

    Time: Within 4 days postdose at Day 113

    Measure: Incidence of adverse event of special interests (AESIs) that occur within 4 days of study drug administration

    Time: Within 4 days postdose at Day 141

    Measure: Concentrations of REGN10933 in serum over time

    Time: Up to 52 weeks

    Measure: Concentrations of REGN10987 in serum over time

    Time: Up to 52 weeks

    Secondary Outcomes

    Measure: Proportion of participants with treatment-emergent adverse events (TEAEs)

    Time: Up to 52 weeks

    Measure: Severity of TEAEs

    Time: Up to 52 weeks

    Measure: Proportion of participants who achieve or exceed target concentration in serum of REGN10933

    Time: Up to 52 weeks

    Measure: Proportion of participants who achieve or exceed target concentration in serum of REGN10987

    Time: Up to 52 weeks

    Measure: Immunogenicity as measured by anti-drug antibodies (ADA) to REGN10933

    Time: Up to 52 weeks

    Measure: Immunogenicity as measured by anti-drug antibodies (ADA) to REGN10987

    Time: Up to 52 weeks
    308 A Double-blind, Randomized, Placebo-controlled, Multi-center, Phase II Study to Evaluate the Efficacy and Safety of DWJ1248 in Patients With Mild to Moderate COVID-19

    To evaluate the efficacy and safety after administration of DWJ1248 in patients with mild to moderate COVID-19 compared to the placebo.

    NCT04521296
    Conditions
    1. Mild to Moderate COVID-19
    Interventions
    1. Drug: DWJ1248
    2. Drug: Placebo

    Primary Outcomes

    Description: Time to reach undetectable SARS-CoV-2 RNA level

    Measure: Time to SARS-CoV-2 eradication

    Time: Up to 28 days

    Secondary Outcomes

    Description: Percent of patients with undetectable SARS-CoV-2 RNA level

    Measure: Rate of SARS-CoV-2 eradication

    Time: Days 4, 7, 10, and 14

    Measure: Time to clinical improvement of subjective symptoms

    Time: Up to 28 days
    309 A Double-blind, Placebo-controlled, Phase 2 Trial of Sublingual Low-Dose Thimerosal in Adults With Symptomatic SARS-CoV-2 Infection

    Clinical trial to compare sublingual low does thimerosal in adults that have symptoms of SARS-CoV-2 Infection against placebo to show a difference in physical characteristics and viral levels.

    NCT04522830
    Conditions
    1. SARS-CoV-2 Infection
    Interventions
    1. Drug: BTL-TML-COVID
    2. Drug: Placebo
    MeSH:Infection

    Primary Outcomes

    Description: Change from baseline in the physical component summary of the short form-36 Quality of Life Instrument

    Measure: Mean duration and severity of disease

    Time: Two days

    Secondary Outcomes

    Description: AEs will be assessed by the investigator as to severity, duration and relationship to treatment

    Measure: Incidence/Safety of Adverse Events

    Time: Baseline through 10 days
    310 The C3 Nitazoxanide for Mild to Moderate COVID-19 in HIV-infected and HIV-uninfected Adults With Enhanced Risk: a Double-blind, Randomised, Placebo-controlled Trial in a Resource-poor Setting

    COVID-19 due to SARS-CoV-2 infection is a rapidly escalating global pandemic for which there is no proven effective treatment. COVID-19 is multi-dimensional disease caused by viral cytopathic effects and host-mediated immunopathology. Therapeutic approaches should logically be based on interventions that have direct anti-viral effects and favourably modulate the host immune response. Thus, an optimal drug regimen in ambulatory patients should collectively (i) target and reduce viral replication, (ii) upregulate host innate immune anti-viral responses, (iii) have favourable immunomodulatory properties, and (iv) minimise disease progression to hospitalisation thus circumventing the 'cytokine storm' that likely underpins ARDS and multi-organ failure. Nitazoxanide (NTZ) is an antiprotozoal drug that is FDA-approved for treating Cryptosporidium and Giardia and has an excellent safety record for a variety of indications, but primarily as an anti-parasitic agent. It has proven broad anti-viral activity as it amplifies cytoplasmic RNA sensing, potently augments type I interferon and autophagy-mediated anti-viral responses, has immunomodulatory properties e.g inhibits macrophage IL-6 production, and interferes with SARS-CoV-2 glycosylation. It has been shown to have anti-viral activity against several viruses including Ebola, influenza, hepatitis B and C, rotavirus and norovirus. With regard to respiratory viral infections, NTZ was evaluated in uncomplicated influenza and demonstrated a reduction in the median time to symptom recovery. By contrast, NTZ failed to show benefit in hospitalised patients with severe influenza suggesting that, as with oseltamivir (Tamiflu), it likely needs to be administered early in the course of the disease. NTZ has proven in vitro activity against SARS-CoV-2. NTZ inhibited the SARs-CoV-2 at a low-micromolar concentrations and in vivo evaluation in patients with COVID-19 has been strongly recommended. NTZ has an excellent drug-drug interaction profile. No clinically significant interactions are expected with commonly used antihypertensive agents, antidiabetics drugs, antiretroviral agents, steroids or commonly prescribed analgesics / anti-inflammatory agents. The investigators propose NTZ for the treatment of mild COVID-19 in non-hospitalised patients with HIV co-infection and/or enhanced risk for progression to severe disease (age > 50 years and/ or with comorbidity). The investigators will perform a randomised controlled trial enrolling 960 patients with mild disease. The primary outcome measure will be the proportion progressing to severe disease (hospitalisation) based on the WHO clinical progression scale (progression to stage 4 and beyond). Secondary outcome measures will include disease rates in contacts and effect on viral load, productive infectiousness using viral cultures, and ability to abrogate the generation of infectious aerosols using novel cough aerosol sampling technology. Recruitment is stratified and thus the study is powered to detect progression to severe disease in HIV-infected persons.

    NCT04523090
    Conditions
    1. Covid19
    Interventions
    1. Drug: Nitazoxanide
    2. Drug: Placebo

    Primary Outcomes

    Description: Time-specific (30- and 60-day) disease severity based on the WHO clinical progression scale

    Measure: Time specific disease severity

    Time: 60 days

    Secondary Outcomes

    Description: Need for hospitalisation and length of hospital stay (in those admitted to hospital because of disease progression).

    Measure: Progression to severe disease

    Time: 60 days

    Description: Length of time on high flow nasal oxygen or in the ventilator.

    Measure: Need for respiratory support (high flow nasal oxygen, non-invasive ventilation, or intubation) in those admitted to hospital because of disease progression.

    Time: 60 days

    Description: Time-specific all cause of mortality

    Measure: In-hospital and 30- and 60-day all-cause mortality. available).

    Time: 60 days

    Description: SARS-CoV-2 viral parameters [duration and burden of viral load and duration of viral culture positivity (viral shedding)

    Measure: Time-specific viral load as measured by RT-PCR using NP swabs and sputum (where available).

    Time: 60 days

    Description: Assessment of SARS-CoV-2 presence in droplets and aerosols generated COVID-19 positive participants ( and infectiousness)

    Measure: Cough aerosol sampling positivity

    Time: 60 days
    311 A Phase 2 Randomized, Double-blind, Placebo-controlled, Proof of Concept Study to Evaluate the Safety and Efficacy of Antroquinonol in Hospitalized Patients With Mild to Moderate Pneumonia Due to COVID-19

    To evaluate the safety andefficacy of antroquinonol treatment of mild to moderate pneumonia due to COVID-19, as measured by the proportion of patients alive and free of respiratory failure.

    NCT04523181
    Conditions
    1. Covid-19
    Interventions
    1. Drug: Antroquinonol
    2. Drug: Placebo

    Primary Outcomes

    Description: The proportion of patients who are alive and free of respiratory failure (e.g., no need for invasive mechanical ventilation, non invasive ventilation, high flow oxygen, or ECMO) on Day 14

    Measure: recover ratio

    Time: 14 day

    Secondary Outcomes

    Description: Clinical change score as measured by the WHO COVID-19 Clinical Improvement Ordinal Scale

    Measure: Time to 2-point improvement

    Time: 28 day

    Description: time for patient discharge

    Measure: Duration of hospitalization

    Time: 28 day

    Description: measured as study days from start of treatment to first negative SARS CoV 2 PCR test

    Measure: Time to virological clearance

    Time: 28 day
    312 Safety and Immunogenicity of SARS-CoV-2 mRNA Vaccine (BNT162b1) in Chinese Healthy Subjects: A Phase I, Randomized, Placebo-controlled, Observer-blind Study

    This is a phase I, randomized, placebo-controlled, observer-blind study, for evaluation of safety and immunogenicity of SARS-CoV-2 mRNA vaccine (BNT162b1) in Chinese healthy population. After randomization, the trial for each subject will last for approximately 12 months. Screening period is 2 weeks prior to randomization (Day -14 to Day 0), and each dose of either SARS-CoV-2 vaccine (BNT162b1) or placebo will be given intramuscularly (IM).

    NCT04523571
    Conditions
    1. SARS-CoV-2
    Interventions
    1. Biological: BNT162b1
    2. Other: Placebo

    Primary Outcomes

    Measure: Occurrence of solicited local reactions in the subjects (e.g., vaccination sites: pain/tenderness, erythema/redness, induration/swelling) during the 14-days after each dose of BNT162b1 or placebo.

    Time: 14 days following each dose administration

    Measure: Occurrence of solicited systematic reactions (e.g., nausea, vomiting, diarrhea, headache, fatigue, myalgia, arthralgia, chills, loss of appetite, malaise, and fever) during 14-day after each dose of BNT162b1 or placebo.

    Time: 14 days following each dose administration

    Measure: Occurrence of adverse event (AE) associated with vaccination in subjects during the 21-day period after prime vaccination of BNT162b1 or placebo.

    Time: 21-day period after prime vaccination

    Measure: Occurrence of AE associated with vaccination in subjects during the 28-day period after boost dose of BNT162b1 or placebo.

    Time: 28-day period after boost dose

    Secondary Outcomes

    Measure: The proportion of subjects experiencing serious adverse events (SAEs), occurring up to Day 21 after prime vaccination and Day 28 after boost vaccination, up to Month 3, 6 and 12.

    Time: Day 21 after prime vaccination, Day 28 after boost vaccination, and Month 3, 6 and 12

    Measure: The proportion of subjects experiencing AE associated with BNT162b1, occurring up to Month 3, 6 and 12.

    Time: up to Month 3, 6 and 12

    Measure: The proportion of subjects experiencing abnormal markers of hematology, blood chemistry and urine analysis, occurring at Hour 24 and Day 7 after prime vaccination and Day 7 period after boost dose of BNT162b1 or placebo.

    Time: Hour 24 and Day 7 after prime vaccination and Day 7 after boost dose

    Measure: Geometric mean titer (GMT) of anti-S1 IgG antibody at Day 7, Day 21 after prime vaccination, at Day 7, Day 21 after boost vaccination, and at Month 3, 6 and 12.

    Time: Day 7, Day 21 after prime vaccination, Day 7, Day 21 after boost vaccination, and Month 3, 6 and 12

    Measure: GMT of anti-receptor binding domain (RBD) immunoglobulin G (IgG) antibody at Day 7, Day 21 after prime vaccination, at Day 7, Day 21 after boost vaccination, and at Month 3, 6 and 12.

    Time: Day 7, Day 21 after prime vaccination, Day 7, Day 21 after boost vaccination, and Month 3, 6 and 12

    Measure: GMT of SARS-CoV-2 neutralizing antibody (including true virus-based SARS-CoV-2 neutralizing test) at Day 7, Day 21 after prime vaccination, at Day 7, Day 21 after boost vaccination, and at Month 3, 6 and 12.

    Time: Day 7, Day 21 after prime vaccination, Day 7, Day 21 after boost vaccination, and Month 3, 6 and 12

    Measure: Fold increase in antibody anti-S1 IgG antibody titers, as compared to baseline, at Day 7, Day 21 after prime vaccination, at Day 7, Day 21 after boost vaccination, and at Month 3, 6 and 12.

    Time: Day 7, Day 21 after prime vaccination, Day 7, Day 21 after boost vaccination, and Month 3, 6 and 12

    Measure: Fold increase in antibody anti-RBD IgG antibody titers, as compared to baseline, at Day 7, Day 21 after prime vaccination, at Day 7, Day 21 after boost vaccination, and at Month 3, 6 and 12.

    Time: Day 7, Day 21 after prime vaccination, Day 7, Day 21 after boost vaccination, and Month 3, 6 and 12

    Measure: Fold increase in SARS-CoV-2 neutralizing antibody titers (virus neutralizing test), as compared to baseline, at Day 7, Day 21 after prime vaccination, at Day 7, Day 21 after boost vaccination, and at Month 3, 6 and 12.

    Time: Day 7, Day 21 after prime vaccination, Day 7, Day 21 after boost vaccination, and Month 3, 6 and 12

    Measure: Seroconversion rates (SCR) defined as a minimum of 4-fold increase of antibody titers, as compared to baseline, at Day 7, Day 21 after prime vaccination, and at Day 7, Day 21 after boost vaccination.

    Time: Day 7, Day 21 after prime vaccination, and Day 7, Day 21 after boost vaccination
    313 Phase I Study to Evaluate the Safety, Tolerability, Pharmacodynamics (PD) and Pharmacokinetics (PK) of DWRX2003 (Niclosamide IM Depot) Injection Following Intramuscular Administration in Healthy Volunteers

    This study is to assess the safety, tolerability, pharmacodynamics, and pharmacokinetics of Niclosamide (DWRX2003) following escalating doses of DWRX2003 administered as an intramuscular injection in healthy volunteers.

    NCT04524052
    Conditions
    1. Healthy
    Interventions
    1. Drug: DWRX2003
    2. Drug: Placebo

    Primary Outcomes

    Description: AE rate, incidence, severity and causality of adverse events (AEs) and serious adverse events (SAEs)

    Measure: Incidence of Treatment-Emergent Adverse Events

    Time: follow-up 48 days after dosing

    Secondary Outcomes

    Description: Maximum measured plasma concentration over the time span specified

    Measure: pharmacokinetic changes of niclosamide from baseline in each dose group: Cmax

    Time: follow-up 48 days after dosing

    Description: Time of the maximum measured plasma concentration

    Measure: pharmacokinetic changes of niclosamide from baseline in each dose group: Tmax

    Time: follow-up 48 days after dosing

    Description: Change in C reactive protein levels

    Measure: pharmcodynamic analysis of niclosamide from baseline in each dose group and time point: CRP

    Time: on Day 3, 7, 10 and 14
    314 A Phase 2 Randomized, Double Blinded, Placebo Controlled Study of Oral Camostat Mesilate Compared to Standard of Care in Subjects With Mild-Moderate COVID-19

    This study will evaluate the efficacy of oral Foipan® (camostat mesilate) compared with the current standard of care in reducing the duration of viral shedding of SARS-CoV-2 virus in patients with mild-moderate COVID-19 disease. Patients will attend 4 study visits over a period of up to 28 days.

    NCT04524663
    Conditions
    1. Covid19
    Interventions
    1. Drug: Camostat Mesilate
    2. Drug: Placebo
    3. Other: Standard of Care Treatment

    Primary Outcomes

    Description: This outcome is defined as the time in days from randomization to the first of two consecutive negative RT-PCR results of self-collected nasal swabs.

    Measure: Time until cessation of shedding of SARS-CoV-2 virus

    Time: Up to 28 days

    Secondary Outcomes

    Description: Number of symptomatic patients with clinical worsening, defined as the development of respiratory distress or symptoms that require hospitalization.

    Measure: Clinical worsening of COVID-19 disease in symptomatic patients

    Time: Up to 28 days

    Description: Number of patients that develop antibodies to SARS-CoV-2.

    Measure: Development of antibodies to SARS-CoV-2

    Time: Up to 28 days

    Description: This outcome is defined as absence of moderate or severe symptoms for at least 24 hours for those reporting moderate or severe symptoms at baseline

    Measure: Time until resolution of symptoms

    Time: Up to 28 days

    Description: Progression of respiratory symptoms defined as a two-level increase of a symptom on the Daily Symptom Status Questionnaire within a 24 hour period, or a one-level increase of a symptom on the Daily Symptom Status Questionnaire observed/sustained for a consecutive 48 hour period.

    Measure: Time until progression of symptoms

    Time: Up to 28 days

    Measure: Drug level on day five, one hour after a dose taken on an empty stomach

    Time: Day 5, 1 hour post dose
    315 A Phase 1, Randomized, Double-blind, Placebo-controlled, Parallel Group, Single Ascending Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics of CT-P59 in Healthy Subjects

    This is a Phase I study that randomized, double-blind, Placebo-controlled, Parallel Group, Single Ascending Dose Study to evaluate Safety, Tolerability and Pharmacokinetics of CT-P59 in Healthy Subjects.

    NCT04525079
    Conditions
    1. SARS-CoV-2 Infection
    Interventions
    1. Drug: CT-P59
    2. Drug: Placebo

    Primary Outcomes

    Description: Proportion of patients with Treatment Emergent Adverse Events (TEAEs) Proportion of patients with Treatment Emergent Serious Adverse Events (TESAEs) Proportion of patients with TEAEs of special interest (IRR hypersensitivity/anaphylactic reaction

    Measure: Primary safety outcome

    Time: Day 14

    Secondary Outcomes

    Description: Proportion of patients with Treatment Emergent Adverse Events (TEAEs) Proportion of patients with Treatment Emergent Serious Adverse Events (TESAEs) Proportion of patients with TEAEs of special interest (IRR including hypersensitivity/anaphylactic reaction) Incidence of ADA and NAbs to CT-P59 (positive or negative)

    Measure: To evaluate the safety of CT-P59

    Time: Up to 90 Days

    Description: 1. Pharmacokinetic (PK) parameter: Area under the serum concentration-time curve from time zero to infinity, calculated using the linear up and low down trapezoidal rule(AUC0-inf) of CT-P59

    Measure: To evaluate the Pharmacokinetic(PK) of CT-P59

    Time: Up to 90 Days

    Description: 2. PK parameter: Dose normalized AUC0-inf (normalized to total body dose)(AUC0-inf/Dose) of CT-P59

    Measure: To evaluate the Pharmacokinetic(PK) of CT-P59

    Time: Up to 90 Days

    Description: 3. PK parameter: AUC from time zero to the last quantifiable concentration, calculated using the linear up and log down trapezoidal rule(AUC0-last) of CT-P59

    Measure: To evaluate the Pharmacokinetic(PK) of CT-P59

    Time: Up to 90 Days

    Description: 4. PK parameter: Dose normalized AUC0-last (normalized to total body dose)(AUC0-last/Dose) of CT-P59

    Measure: To evaluate the Pharmacokinetic(PK) of CT-P59

    Time: Up to 90 Days

    Description: 5. PK parameter: Maximum observed serum concentration(Cmax) of CT-P59

    Measure: To evaluate the Pharmacokinetic(PK) of CT-P59

    Time: Up to 90 Days

    Description: 6. PK parameter: Dose normalized Cmax(normalized to total body dose)(Cmax/Dose) of CT-P59

    Measure: To evaluate the Pharmacokinetic(PK) of CT-P59

    Time: Up to 90 Days

    Description: 7. PK parameter: Time to Cmax(Tmax) of CT-P59

    Measure: To evaluate the Pharmacokinetic(PK) of CT-P59

    Time: Up to 90 Days

    Description: 8. PK parameter: Terminal elimination half-life(t1/2) of CT-P59

    Measure: To evaluate the Pharmacokinetic(PK) of CT-P59

    Time: Up to 90 Days

    Description: 9. PK parameter: Percentage of the area extrapolated for calculation of AUC0-inf(%AUCext) of CT-P59

    Measure: To evaluate the Pharmacokinetic(PK) of CT-P59

    Time: Up to 90 Days

    Description: 10. PK parameter: Terminal elimination rate constant estimated from the linear regression of the natural log-transformed concentration over time at the terminal phase(λz) of CT-P59

    Measure: To evaluate the Pharmacokinetic(PK) of CT-P59

    Time: Up to 90 Days

    Description: 11. PK parameter: Total body clearance(CL) of CT-P59

    Measure: To evaluate the Pharmacokinetic(PK) of CT-P59

    Time: Up to 90 Days

    Description: 12. PK parameter: Volume of distribution during the terminal phase(Vz) of CT-P59

    Measure: To evaluate the Pharmacokinetic(PK) of CT-P59

    Time: Up to 90 Days
    316 High Dose Vitamin-D Substitution in Patients With COVID-19: a Randomized Controlled, Multi Center Study

    The world is currently facing a pandemic with the coronavirus (SARS-CoV-2) which leads to the disease of COVID-19. Risk factors for a poor outcome of COVID-19 have so far been identified as older age and co-morbidity including chronic respiratory conditions such as chronic obstructive pulmonary disease (COPD) and current smoking status. Previous studies found, that vitamin D deficiency is more prevalent among patients with these risk factors. There are observational studies reporting independent associations between low serum concentrations of 25-hydroxyvitamin D (the major circulating vitamin D metabolite) and susceptibility to acute respiratory tract infection. Vitamin D substitution in patients with COVID-19 who show a vitamin D deficiency should therefore be investigated for efficacy and safety. The study is designed as a randomized, placebo-controlled, double blind study. The objective of the study is to test the hypothesis that patients with vitamin D deficiency suffering from COVID-19 treated under standardized conditions in hospital will recover faster when additionally treated with a single high dose of vitamin D compared to standard treatment only.

    NCT04525820
    Conditions
    1. Covid19
    2. Vitamin D Deficiency
    3. Corona Virus Infection
    4. ARDS
    5. Coronavirus
    6. SARS-CoV Infection
    Interventions
    1. Drug: Single high dose vitamin D
    2. Drug: Placebo
    3. Drug: Treatment as usual vitamin D
    MeSH:Infection Communicable Diseases Coronavirus Infections Severe Acute Respiratory Syndrome Vitamin D Deficiency
    HPO:Low levels of vitamin D

    Primary Outcomes

    Description: Overall duration of the hospitalization from day of admission until the day of discharge or fatality

    Measure: Length of hospitalization

    Time: Administration to Discharge from hospital care (mean duration is between 14 and 22 days for Patients with COVID 19)

    Secondary Outcomes

    Description: Did the patient need a intensive care treatment during the hospitalization (yes/no)

    Measure: Need of intensive care

    Time: Until discharge or fatality (mean duration is between 14 and 22 days for Patients with COVID-19)

    Description: Day of admission to ICU until discharge or fatality

    Measure: Lenght of the Intensive Care Treatment

    Time: Until discharge or fatality (mean duration is between 14 and 22 days for Patients with COVID-19)

    Description: Percentage of patient died during hospitalization

    Measure: Overall mortality

    Time: During the length of hospitalisation (mean duration is between 14 and 22 days for Patients with COVID-19)

    Description: percentage of patients with 25-hydroxyvitamin D > 50nmol/L (>20ng/mL) at day 7 - The values of calcium, phosphorus, 24-hydroxyvitamin D, 1.25-dihydroxyvitamin D, parathyroid hormone.

    Measure: Development of vitamin D levels

    Time: Day 1 (Baseline) and Day 7 after the first administration of the high dose vitamin D or the placebo and at discharge (mean hospital stay is between 14 and 22 days for Patients with COVID-19)

    Description: percentage of patients developing a sepsis

    Measure: Development of sepsis

    Time: During the length of hospitalization (mean duration is between 14 and 22 days for Patients with COVID-19)

    Other Outcomes

    Description: We assess every other complications which occurs due to COVID-19

    Measure: Complications due to COVID-19

    Time: During the length of hospitalization (mean duration is between 14 and 22 days for Patients with COVID-19)

    Description: The BP will be assessed daily in mmHg

    Measure: Blood pressure (BP)

    Time: Daily until discharge or fatality (mean duration is between 14 and 22 days for Patients with COVID-19)

    Description: The heart rate will be assessed daily in bpm

    Measure: Heart rate

    Time: Daily until discharge or fatality (mean duration is between 14 and 22 days for Patients with COVID-19)

    Description: The SpO2 will be assessed daily in %

    Measure: Peripheral oxygen saturation (SpO2)

    Time: Daily until discharge or fatality (mean duration is between 14 and 22 days for Patients with COVID 19)

    Description: Requirement for oxygen will be assessed daily (yes/no) if yes how many liters per minute

    Measure: Percentage of patients who require oxygen

    Time: Daily until discharge or fatality (mean duration is between 14 and 22 days for Patients with COVID 19)

    Description: Breathing frequence will be assessed daily in breaths per minute

    Measure: Breathing frequency

    Time: Daily until discharge or fatality (mean duration is between 14 and 22 days for Patients with COVID 19)

    Description: GCS will be assessed daily 3 to 15 points. It describes the extent of impaired consciousness. 15 points means no impairment, 3 points means severe impairment of consciousness.

    Measure: Glasgow Coma Scale (GCS)

    Time: Daily until discharge or fatality (mean duration is between 14 and 22 days for Patients with COVID 19)

    Description: Assessing the history of smoking in pack years (PY). the assessment will be made with the following options for answering Current smoker: Smoking for how many years? Cigarettes per day? Former smoker, how many years smoked? How many cigarettes per day Life-long non-smoker

    Measure: Percentage of patients are smokers, former smokers or lifelong non-smokers

    Time: Assessing of the smoking Status at Basleine

    Description: Assessed in No/ Mild/ Moderate /Severe

    Measure: Current Symptoms

    Time: Daily until discharge or fatality (mean duration is between 14 and 22 days for Patients with COVID 19)

    Description: Temperature will be assessed daily in degrees celsius

    Measure: Temperature

    Time: Daily until discharge or fatality (mean duration is between 14 and 22 days for Patients with COVID 19)
    317 A Proof of Concept Study of the Safety and Efficacy of VIB7734 for the Treatment and Prevention of Acute Lung Injury (ALI) in Patients With SARS-CoV-2 Infection

    The study aims to assess the potential benefit and evaluate the safety and tolerability of a single subcutaneous (SC) dose of VIB7734 in hospitalized patients with documented infection of severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) with pulmonary involvement. Subjects will be administered a single dose of VIB7734 injected under the skin, assessed for efficacy for 28 days and followed for an additional 42 days.

    NCT04526912
    Conditions
    1. Acute Lung Injury
    Interventions
    1. Drug: VIB7734
    2. Drug: Placebo
    MeSH:Lung Injury Acute Lung Injury Respiratory Distress Syndrome, Adult Wounds and Injuries

    Primary Outcomes

    Description: Critical illness is defined by respiratory failure (requiring any of the following: endotracheal intubation, oxygen delivered by high flow nasal cannula, non-invasive positive pressure ventilation, extracorporeal membrane oxygenation or clinical diagnosis of respiratory failure) or shock (systolic blood pressure < 90 mm Hg, or diastolic blood pressure < 60 mm Hg, or requiring vasopressors)

    Measure: The proportion of patients who achieve treatment success through Day 28, defined as avoidance of death and critical illness

    Time: Day 1 (Baseline) through Day 28

    Secondary Outcomes

    Description: Defined as measure of safety

    Measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs), Treatment-emergent fatal and life-threatening SAEs, Treatment-emergent Serious Adverse Events

    Time: Day 1 (Baseline) through Day 70

    Description: Safety evaluation via review of labs (white blood cell (WBC) with differential counts, hemoglobin, platelet count, liver function tests (aspartate aminotransferase [AST], alanine aminotransferase [ALT], and total bilirubin levels), serum chemistry, cardiac troponin coagulation markers (prothrombin time [PT], partial thromboplastin time [PTT], D dimer, fibrinogen), and urinalysis)

    Measure: Change in safety laboratory parameters

    Time: Day 1 (Baseline) through Day 70
    318 A Global Multicenter, Randomized, Double-blind, Placebo -Controlled, Adaptive Designed Phase Ⅲ Clinical Trial to Evaluate the Efficacy, Safety and Immunogenicity of Ad5-nCoV in Adults 18 Years of Age and Older

    This study is a global multicenter, randomized, double-blind, placebo -controlled, adaptive designed phase Ⅲ clinical trial, in order to evaluate the efficacy, safety and immunogenicity of Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector) in adults 18 years old and above.

    NCT04526990
    Conditions
    1. COVID-19
    Interventions
    1. Biological: Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector)
    2. Biological: Placebo

    Primary Outcomes

    Description: The efficacy of Ad5-nCoV in preventing virologically confirmed (PCR positive) COVID-19 disease

    Measure: Incidence of COVID-19 cases

    Time: day 28 to 12 months post vaccination

    Description: Evaluate the incidence of severe adverse events (SAE)

    Measure: Incidence of SAE

    Time: Within 12 months

    Secondary Outcomes

    Description: Evaluate the efficacy of Ad5-nCoV in preventing severe COVID-19 disease caused by SARS-CoV-2 infection

    Measure: Incidence of severe COVID-19 cases

    Time: Day 14 to 12 months post vaccination

    Description: Incidence of solicited adverse reactions within 7 days after vaccination, in a subset

    Measure: Incidence of solicited adverse reactions

    Time: Day 0-7 post vaccination

    Description: Incidence of unsolicited adverse events within 28 days after vaccination in a subset

    Measure: Incidence of unsolicited adverse events

    Time: Day 0-28 post vaccination

    Description: The seroconversion rate of S-RBD IgG antibody post vaccination

    Measure: Immunogencity of S-RBD IgG antibody (ELISA method)

    Time: Day 28 post vaccination

    Description: The seroconversion rate of neutralizing antibody

    Measure: Immunogencity of neutralizing antibody

    Time: Day 28 post vaccination

    Description: Number of cell-mediated immune response against SARS-CoV-2

    Measure: Cell-mediated immune profile

    Time: Day 28 post vaccination
    319 Multicenter, Randomized, Double-blind, Placebo-controlled Pilot Study of Treamid Efficacy and Safety in the Rehabilitation of Patients After COVID-19 Pneumonia

    The innovative drug Treamid is planned for use in the rehabilitation of patients after COVID-19 pneumonia in a pilot, multicenter, randomized, double-blind, placebo-controlled Phase II clinical study to assess the efficacy and safety of Treamid, tablets, 50 mg in patients with fibrotic changes in the lungs after COVID-19 pneumonia during a 28-day treatment. The primary objective of the study is to demonstrate the efficacy of Treamid tablet, 50 mg in change in forced vital capacity (FVC) and/or diffusing capacity of lung for carbon monoxide (DLCO) at Week 4. The secondary objective of the study is to evaluate the safety of Treamid tablet, 50 mg and pharmacokinetics (PK).

    NCT04527354
    Conditions
    1. SARS-CoV-2 Infection
    2. Fibrosis Lung
    Interventions
    1. Drug: Treamid
    2. Drug: Placebo
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Clinically significant changes include a relative ≥ 10% increase in FVC or a relative increase in FVC within the range from ≥ 5% to <10% and a relative ≥ 15% in DLCO

    Measure: Rate of clinically significant change in FVC and/or DLCO at Week 4 relative to the baseline value

    Time: Day 1- Day 28

    Secondary Outcomes

    Measure: Change in distance covered for 6 minutes (6MWD) at Weeks 2 and 4 from the baseline value (based on 6-minute walk test)

    Time: Day 1- Day 28

    Measure: Change in the score of the Borg scale at Weeks 2 and 4 from the baseline value (based on the 6-minute walk test)

    Time: Day 1- Day 28

    Measure: Change in forced expiratory volume for the first second (FEV1) according to spirometry data at Weeks 1, 2, 3 and 4 relative to the baseline values

    Time: Day 1- Day 28

    Measure: Change in FVC according to spirometry data at Weeks 1, 2, 3 and 4 relative to the baseline values

    Time: Day 1- Day 28

    Measure: Change in FEV1/FVC according to spirometry data at Weeks 1, 2, 3 and 4 relative to the baseline values

    Time: Day 1- Day 28

    Measure: Change in DLCO according to bodyplethysmography at Week 2 and Week 4 relative to baseline values

    Time: Day 1- Day 28

    Measure: Change in Total Lung Capacity (TLC) according to bodyplethysmography at Week 2 and Week 4 relative to baseline values

    Time: Day 1- Day 28

    Measure: Change in Functional Residual Capacity (FRC) according to bodyplethysmography at Week 2 and Week 4 relative to baseline values

    Time: Day 1- Day 28

    Description: Classification of lung damage includes the following stages: CT-0 (norm), CT-1 (< 25% of lung damage), CT-2 (25-50% of lung damage), CT-3 (50-75% of lung damage), CT-4 (> 75% of lung damage)

    Measure: The rate of reduction in the lung damage degree based on the computed tomography (CT) at Week 4 relative to the baseline value

    Time: Day 1- Day 28

    Measure: Change in mMRC Dyspnea Score in Week 1, Week 2, Week 3, and Week 4 from the baseline value

    Time: Day 1- Day 28

    Measure: Change in the overall score of the KBILD Questionnaire at Week 2 and Week 4 relative to the baseline value

    Time: Day 1- Day 28

    Other Outcomes

    Measure: The rate of adverse events (AEs)

    Time: Day 1- Day 28

    Measure: The rate of serious adverse events (SAEs)

    Time: Day 1- Day 28

    Description: Blood sampling for the PK study of the parameter Сtrough will be performed for all patients prior to administration of the Treamid / Placebo at Week 0, Week 2, and Week 4 visits.

    Measure: Residual concentration Ctrough of the active substance of Treamid

    Time: Day 1- Day 28
    320 Colchicine in Moderate Symptomatic COVID-19 Patients: Double Blind, Randomized, Placebo Controlled Trial to Observe the Efficacy

    This is a prospective, double blind, randomized, placebo controlled clinical trial. The participants will be randomized into two groups (group A and group B). Patients of group-A are the treatment group. They will be treated with optimal treatment based on the algorithm proposed in National Guidelines on Clinical Management of Coronavirus Disease 2019 (Covid-19) Version 7.0, 28 May 2020, along with Colchicine for 14 days. The patients in group-B will be controlled group. They will be treated with optimal treatment based on the algorithm proposed in National Guideline along with a placebo.

    NCT04527562
    Conditions
    1. Covid19
    Interventions
    1. Drug: Colchicine
    2. Drug: Placebo

    Primary Outcomes

    Description: Seven-category ordinal scale. The scale is recommended by the WHO R&D Blueprint expert group. The seven-category ordinal scale consisted of the following categories: 1, not hospitalized with resumption of normal activities; 2, not hospitalized, but unable to resume normal activities; 3, hospitalized, not requiring supplemental oxygen; 4, hospitalized, requiring supplemental oxygen; 5, hospitalized, requiring nasal high-flow oxygen therapy, noninvasive mechanical ventilation, or both; 6, hospitalized, requiring ECMO, invasive mechanical ventilation, or both; and 7, death

    Measure: Time to develop clinical deterioration, defined as the time from randomization to a deterioration of two points (from the status at randomization) on a Seven-category ordinal scale.

    Time: 14 days following randomization

    Secondary Outcomes

    Measure: Length of hospital stay

    Time: 14 days following randomization

    Measure: Number of participant requiring increased amount of supplemental oxygen

    Time: 14 days following randomization

    Measure: Number of participants requiring mechanical ventilation

    Time: 14 days following randomization

    Measure: Number of participants who die

    Time: 14 days following randomization
    321 A Phase 2, Randomized, Double-Blind, Placebo-controlled Study of the Safety and Efficacy of STI-5656 (Abivertinib Maleate) in Subjects Hospitalized Due to COVID-19

    A phase 2, placebo-controlled study of the safety and efficacy of STI-5656 (Abivertinib Maleate) in subjects hospitalized due to COVID-19

    NCT04528667
    Conditions
    1. Covid19
    Interventions
    1. Drug: STI-5656
    2. Drug: Placebo

    Primary Outcomes

    Description: Proportion of subjects whoa re alive and discharged from the hospital by Day 29

    Measure: Proportion of subjects discharged from hospital

    Time: Randomization through Day 29

    Secondary Outcomes

    Description: Types, frequencies, and severities of adverse events and their relationships to STI-5656, including serious adverse events

    Measure: Incidence of adverse events (safety)

    Time: Randomization through study completion through Day 36

    Description: Time from onset of COVID-19 symptoms to hospital admission, time from hospitalization to start of treatment (D1), and time from D1 to hospital discharge

    Measure: Time to hospital admission, treatment, and discharge

    Time: Randomization through study completion through Day 36

    Description: Number of days hospitalized from randomization through Day 36

    Measure: Number of days hospitalized

    Time: Randomization to Day 36

    Description: Change in clinical status as assessed using a 0-8 ordinal scale, where a lower score equals better outcome, at Days 3, 10, and 36

    Measure: Change in clinical status as assessed using a 0-8 ordinal scale

    Time: Randomization to Day 3, Day 10, and Day 36

    Description: Change in RT-PCR test results (or equivalent) at Days 3, 10, and 36

    Measure: Change in RT-PCR test results

    Time: Randomization to Day 3, Day 10, and Day 36

    Description: Change in C-reactive protein (CRP) levels at Day 3 and Day 10

    Measure: Change in C-reactive protein levels

    Time: Randomization to Day 3 and Day 10

    Description: Area under the serum concentration-time curve (AUC) of STI-5656

    Measure: AUC of STI-5656 (PK)

    Time: Randomization through Day 8

    Description: Maximum observed serum concentration (Cmax) of STI-5656

    Measure: Cmax of STI-5656 (PK)

    Time: Randomization through Day 8

    Description: Apparent serum terminal elimination half life (t½) of STI-5656

    Measure: t½ of STI-5656 (PK)

    Time: Randomization through Day 8

    Description: Change in cytokine levels (including IL-6, TNF-a, IFNγ, IL1β) at Day 3 and Day 10

    Measure: Change in cytokine levels

    Time: Randomization to Day 3 and Day 10

    Description: Time to Cmax (Tmax) of STI-5656

    Measure: Tmax of STI-5656 (PK)

    Time: Randomization through Day 8
    322 Ivermectin to Prevent Hospitalizations in COVID-19: Randomized, Double-blind, Placebo-controlled

    It is a single-center, prospective, randomized, double-blind, placebo-controlled study carried out by the Ministry of Public Health of the Province of Corrientes, Argentina, in coordination with the Corrientes Institute of Cardiology "Juana F. Cabral". Patients who meet all the inclusion criteria and none of the exclusion criteria are randomized via the web system to receive placebo or ivermectin. The need for hospitalization in patients with COVID-19 is assessed as the primary end point. As secondary end points are evaluated: time to hospitalization (in days); use of invasive mechanical ventilation; time to invasive mechanical ventilation (in days); dialysis; all-cause mortality; negative of the swab at 3 ± 1 days and 12 ± 2 days after entering the study and ivermectin safety. Intermediate internal analyzes of study objectives and serious adverse events will be performed, including 125; 250 and 375 patients in order to assess the possible need for early termination of the study. For these intermediate internal analyzes, the Haybittle-Peto rule will be followed, therefore a value of p <0.001 will be considered significant

    NCT04529525
    Conditions
    1. Covid19
    Interventions
    1. Drug: Ivermectin
    2. Drug: Placebo

    Primary Outcomes

    Description: Hospitalization will be considered when at least 24 hours have elapsed in a health institution, in any of its services.

    Measure: Percentage of Hospitalization of medical cause in patients with COVID-19 in each arm

    Time: through study completion, an average of 30 days

    Secondary Outcomes

    Description: Number of days elapsed

    Measure: Time to hospitalization

    Time: through study completion, an average of 30 days

    Description: All patients who are connected to invasive mechanical ventilation support

    Measure: Percentage of Use of invasive mechanical ventilation support in each arm

    Time: through study completion, an average of 30 days

    Description: Number of days elapsed

    Measure: Time to invasive mechanical ventilation support

    Time: through study completion, an average of 30 days

    Description: All patients who require temporary or permanent renal replacement therapy

    Measure: Percentage of dialysis in each arm

    Time: through study completion, an average of 30 days

    Description: Death of the patient, from any cause.

    Measure: All-cause mortality

    Time: through study completion, an average of 30 days

    Description: Negative Nasal Swab Using Polymerase Chain Reaction Technique

    Measure: Negative of the swab at 3±1 days and 12±2 days after entering the study

    Time: At days 3±1 and 12±2

    Description: According to the adverse events that patients may present.

    Measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability])

    Time: through study completion, an average of 30 days
    323 Randomized, Blind, Placebo-controlled Phase- i Study and Randomized, Open Phase Phase-ii Study of QAZCOVID-IN®- COVID-19 Inactivated Vaccine in Healthy Adult Volunteers From 18 Years Old and Elder

    Randomized, blind, placebo-controlled phase- i study and randomized, open phase phase-ii study of QAZCOVID-IN®- COVID-19 inactivated vaccine in healthy adult volunteers from 18 years old and elder

    NCT04530357
    Conditions
    1. Covid19
    2. SARS-CoV Infection
    3. Vaccine Adverse Reaction
    Interventions
    1. Biological: QazCovid-in® - COVID-19 inactivated vaccine
    2. Other: Placebo
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome

    Primary Outcomes

    Description: Frequency of adverse reaction in the seven days following each immunization per age group

    Measure: Frequency of adverse events up to seven days after immunization

    Time: Seven days after each immunization

    Description: Frequency of adverse reaction in the 21 days following each immunization per age group

    Measure: Frequency of adverse events up to 21 days after immunization

    Time: 21 days after each immunization

    Description: The proportion of volunteers with increased levels of the immune response of specific neutralizing antibody titers in ELISA greater than ≥ 4 times 21 days following the second vaccination compared with a placebo.

    Measure: The proportion of volunteers with increased levels of the immune response of specific neutralizing antibody titers in ELISA following the vaccination, compared with a placebo

    Time: at days 0, 21, 27, 42

    Secondary Outcomes

    Description: Incidence of serious adverse events during the study.

    Measure: Incidence of serious adverse events during the study

    Time: throughout the study, an average of 42 days

    Description: Cell-mediated immune profile

    Measure: Cell-mediated immune profile

    Time: at days 0, 7, 21, 27, 42
    324 Outpatient Use of Ivermectin in COVID-19

    Covid 19, a novel coronavirus, causes infection that, while mild to moderate in many people, can lead to severe disease in a significant portion. Currently, it is expected that the majority, 81%, of patients with COVID-19 will have mild to moderate disease, with 14% having more severe disease (2). There exists a number of candidate drugs that may inhibit SARS-CoV-2 infection or progression of disease. Simple, safe and low-cost strategies that may be the best solution to inhibit infection and limit transmission and spread of infection. Ivermectin is a drug initially synthesized and used as an anthelmintic. It has been found to have activity against several RNA viruses such as the SARS-CoV-2 by mechanisms that inhibit importin α/β-mediated nuclear transport that may prevent viral proteins from entering the nucleus to alter host cell function. A recent in vitro study showed that a single dose of ivermectin could kill COVID-19 in vitro within 48 hours. A recent multi-continent retrospective study of 1,400 patients demonstrated an association of ivermectin use with lower in-hospital mortality 1.4% versus 8.5%. Given these findings and its safety profile, cost and ease of administration, Ivermectin warrants study as a potential treatment to prevent progression of COVID 19 infection.

    NCT04530474
    Conditions
    1. Covid19
    Interventions
    1. Drug: Ivermectin Pill
    2. Drug: Placebo

    Primary Outcomes

    Description: Clinical Improvement as measured by a standardized scale

    Measure: Clinical Improvement

    Time: 28 days
    325 The Effect of Melatonin and Vitamin C on COVID-19

    This is a double-blind placebo controlled trial that seeks to evaluate the impact of melatonin and vitamin C on symptoms and outcomes of patients with COVID-19.

    NCT04530539
    Conditions
    1. Covid19
    2. SARS-CoV Infection
    Interventions
    1. Dietary Supplement: Vitamin C
    2. Dietary Supplement: melatonin
    3. Dietary Supplement: Placebo
    4. Other: Symptom Survey
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome

    Primary Outcomes

    Description: Symptom severity will be tracked electronically

    Measure: Symptom Severity

    Time: 14 days

    Secondary Outcomes

    Description: Determine symptom course of those with moderate or severe symptoms

    Measure: Symptom progression

    Time: 14 days
    326 Selective Estrogen Modulation and Melatonin in Early COVID-19

    This study is a randomized, double-blind, controlled clinical trial to evaluate the effects of toremifene and/or melatonin in adults with mild COVID-19.

    NCT04531748
    Conditions
    1. Covid19
    Interventions
    1. Drug: Toremifene
    2. Drug: Melatonin
    3. Other: Placebo

    Primary Outcomes

    Description: Score total of 0-12 assessed daily. Each category based on severity of symptoms of Cough, Shortness of breath, Fatigue/tiredness and daily temperature on a rating scale of 0-3.

    Measure: Peak increase in COVID-19 Sign and Symptom score

    Time: Screening to 28 days

    Secondary Outcomes

    Description: Daily mean values

    Measure: Nadir Oxygen Saturation

    Time: Day 1 through day 14

    Description: Daily mean values

    Measure: Peak Heart Rate

    Time: Day 1 through day 14

    Description: Score total of 0-12 assessed daily. Each category based on severity of symptoms of Cough, Shortness of breath, Fatigue/tiredness and daily temperature on a rating scale of 0-3.

    Measure: Time to COVID-19 Sign and Symptom score resolution

    Time: Screening to 28 days

    Description: not hospitalized, no limitation of activities (or resumption of normal activity) not hospitalized but limitation on activities hospitalized, not requiring supplemental oxygen hospitalized, requiring supplemental oxygen (low-flow, e.g., nasal prong) hospitalized, requiring non-invasive ventilation and/or high-flow oxygen hospitalized, on invasive ventilation or ECMO death

    Measure: Time to WHO 7-point ordinal scale score of 3 or higher

    Time: Day 1 to Day 30
    327 A First-in-Human, Randomized, Double-Blind, Placebo Controlled, Single Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Immunogenicity of SARS-CoV-2 Neutralizing Antibody BGB-DXP593 in Healthy Subjects

    The primary purpose of this study is to investigate the safety and tolerability of BGB-DXP593 administered intravenously as a single dose in healthy participants

    NCT04532294
    Conditions
    1. Covid19
    Interventions
    1. Drug: BGB DXP593
    2. Drug: Placebo

    Primary Outcomes

    Measure: Number of participants experiencing Treatment Emergent Adverse Events (TEAEs)

    Time: Up to 113 days

    Measure: Number of participants experiencing Serious Adverse Events (SAEs)

    Time: Up to 113 days

    Secondary Outcomes

    Measure: Maximum observed plasma concentration (Cmax) of BGB-DXP593

    Time: Up to 113 days

    Measure: Area under the plasma concentration-time curve (AUC) from time zero to the time of the last quantifiable concentration (AUCt) of BGB-DXP593

    Time: Up to 113 days

    Measure: AUC from time zero to infinity (AUCinf) of BGB-DXP593

    Time: Up to 113 days

    Measure: AUC from time zero to Day 29 (AUC0-29) of BGB-DXP593

    Time: Up to Day 29

    Measure: Time to maximum observed plasma concentration (tmax) of BGB-DXP593

    Time: Up to 113 days

    Measure: Terminal half life (t1/2) of BGB-DXP593

    Time: Up to 113 days

    Measure: Clearance (CL) of BGB-DXP593

    Time: Up to 113 days

    Measure: Volume of distribution (Vz) of BGB-DXP593

    Time: Up to 113 days

    Measure: Immunogenic response to BGB-DXP593 as assessed by the Detection of antidrug antibodies (ADA)

    Time: Up to 113 days
    328 The Impact of Growth Hormone in Obese Cases With Covid-19

    The use of growth hormone in obese cases with COVID-19 may help them to recover earlier.

    NCT04532554
    Conditions
    1. Covid19
    Interventions
    1. Drug: Growth Hormone
    2. Drug: Placebo

    Primary Outcomes

    Description: need to be hospitalized due to deterioration

    Measure: Need for hospitalization

    Time: one to two weeks

    Secondary Outcomes

    Description: Time to recovery from symptoms and signs

    Measure: Time to recovery

    Time: one to four weeks

    Description: Percentage of reduction in CRP

    Measure: Percentage of reduction in CRP

    Time: one to two weeks

    Description: Percentage of reduction in LDH

    Measure: Percentage of reduction in LDH

    Time: one to two weeks

    Description: Percentage of reduction in Ferritin

    Measure: Percentage of reduction in Ferritin

    Time: one to two weeks

    Description: Time to recovery from leucopenia

    Measure: Time to recovery from leucopenia

    Time: one to two weeks
    329 A Double-blind Placebo-controlled Study to Assess the Efficacy and Safety of Oral Tafenoquine Versus Placebo in Patients With Mild to Moderate COVID-19 Disease

    A clinical study to assess the efficacy and safety of oral tafenoquine compared to placebo in patients with mild to moderate COVID 19 disease.

    NCT04533347
    Conditions
    1. COVID 19 Disease
    Interventions
    1. Drug: Tafenoquine Oral Tablet
    2. Drug: Placebo

    Primary Outcomes

    Measure: Proportion of patients with clinical recovery of COVID-19 symptoms on Day 12 [± 1 day]

    Time: Day 12 [± 1 day]

    Secondary Outcomes

    Measure: Proportion of patients with negative SARS-CoV-2 RT-PCR on Day 12 [± 1 day]

    Time: Day 12 [± 1 day]

    Measure: Hospitalization rates due to COVID-19 symptoms (excluding admittance only for administrative or observations purposes)

    Time: Up to 28 Days

    Measure: Number of COVID-19-related medical follow up visits [Doctor's office or emergency room (ER) visit]

    Time: Up to 28 Days

    Measure: Proportion of patients with COVID-19 symptoms at Day 12 by individual symptoms

    Time: Day 12 [± 1 day]
    330 A Phase 2A/B, Randomized, Observer-blinded, Placebo-controlled Study to Evaluate the Efficacy, Immunogenicity, and Safety of a SARS-CoV-2 Recombinant Spike Protein Nanoparticle Vaccine (SARS-CoV-2 rS) With Matrix-M1™ Adjuvant in South African Adult Subjects Living Without HIV; and Safety and Immunogenicity in Adults Living With HIV

    This is a study to evaluate the effectiveness and safety of a coronavirus disease 2019 (COVID-19) vaccine called SARS-CoV-2 rS with Matrix-M1 adjuvant in a minimum of approximately 2,960 to a maximum of approximately 4,164 healthy HIV-negative (HIV-) adult participants and in approximately 240 medically stable HIV-positive (HIV+) adult participants in up to 15 sites across South Africa. A vaccine causes the body to have an immune response that may help prevent the infection or reduce the severity of symptoms. An adjuvant is something that can make a vaccine work better. This study will look at the protective effect, body's immune response, and safety of SARS-CoV-2 rS with Matrix-M1 adjuvant in these study populations. Participants in the study will randomly be assigned to receive SARS-CoV-2 rS with Matrix-M1 adjuvant or placebo. Each participant in the study will receive a total of 2 intramuscular injections over the course of the study.

    NCT04533399
    Conditions
    1. SARS-CoV-2 Infection
    2. COVID-19
    Interventions
    1. Biological: SARS-CoV-2 rS/Matrix-M1 Adjuvant
    2. Other: Placebo

    Primary Outcomes

    Description: Number of human immunodeficiency virus negative (HIV-) participants with first occurrence of positive (+) polymerase chain reaction (PCR), (+) PCR-confirmed, SARS-CoV-2 illness with symptomatic mild, moderate, or severe COVID-19 assessed from Day 28 (7 days after second vaccination dose) through the length of the study.

    Measure: Cohort 1: HIV- Participants with Symptomatic Mild, Moderate, or Severe COVID-19

    Time: Day 28 to Day 386

    Description: Number of HIV- participants with first occurrence of (+) PCR-confirmed SARS-CoV-2 illness with symptomatic moderate or severe COVID-19 assessed from Day 28 (7 days after second vaccination) through the length of the study.

    Measure: Cohort 1: HIV- Participants with Symptomatic Moderate or Severe COVID-19

    Time: Day 28 to Day 386

    Description: Numbers and percentages (with 95% confidence intervals [CIs]) of HIV- participants with solicited AEs, local and systemic, for 7 days following each vaccination (Days 0 and 21) by severity score, duration, and peak intensity.

    Measure: Cohort 1: HIV- Participants with Solicited Adverse Events (AEs)

    Time: 28 days

    Description: Numbers and percentages (with 95% CI) of HIV- participants with unsolicited AEs (eg, treatment-emergent, serious, suspected unexpected serious, those of special interest, MAAEs) through Day 35 by Medical Dictionary for Regulatory Activities (MedDRA) classification, severity score, and relatedness.

    Measure: Cohort 1: HIV- Participants with Unsolicited AEs

    Time: 35 days

    Description: Numbers and percentages (with 95% CIs) of HIV+ participants with solicited AEs, local and systemic, for 7 days following each vaccination (Days 0 and 21) by severity score, duration, and peak intensity.

    Measure: Cohort 2: HIV+ Participants with Solicited AEs

    Time: 28 days

    Description: Numbers and percentages (with 95% CI) of HIV+ participants with unsolicited AEs (eg, treatment-emergent, serious, suspected unexpected serious, those of special interest, MAAEs) through Day 35 by MedDRA classification, severity score, and relatedness.

    Measure: Cohort 2: HIV+ Participants with Unsolicited AEs

    Time: 35 days

    Description: Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by enzyme-linked immunosorbent assay (ELISA) expressed as GMTs at Day 35.

    Measure: Cohort 2: Serum Immunoglobulin G (IgG) Antibody Levels Expressed as Geometric Mean Titers (GMTs)

    Time: Day 35

    Description: Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as GMFRs at Day 35.

    Measure: Cohort 2: Serum IgG Antibody Levels Expressed as Geometric Mean Fold Rises (GMFRs)

    Time: Day 35

    Description: Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as SCR at Day 35. SCR is defined as the percentage of participants with a post-vaccination titer ≥ 4 fold over naïve background and ≥ 2 fold over pre existing titer.

    Measure: Cohort 2: Serum IgG Antibody Levels Expressed as Seroconversion Rates (SCRs)

    Time: Day 35

    Secondary Outcomes

    Description: Number of HIV- participants with first occurrence of (+) PCR-confirmed SARS-CoV-2 illness in terms of individual strata of symptomatic virologically confirmed, mild, moderate, or severe COVID-19.

    Measure: Cohort 1: HIV- Participants with Individual Strata of Symptomatic Virologically Confirmed, Mild, Moderate, or Severe COVID-19

    Time: Day 28 to Day 386

    Description: Number of HIV- participants with first occurrence of (+) PCR-confirmed SARS-CoV-2 illness with COVID-19 requiring hospitalization.

    Measure: Cohort 1: HIV- Participants with COVID-19 Requiring Hospitalization

    Time: Day 28 to Day 386

    Description: Incidence, maximum severity score, and symptom duration of SARS-CoV-2 infection by classification of symptomatic virologically confirmed, mild, moderate, and/or severe disease in HIV- participants.

    Measure: Cohort 1: Incidence, Maximum Severity Score, and Symptom Duration of SARS-CoV-2 Infection by Severity Classification

    Time: Day 28 to Day 386

    Description: Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as GMTs at Days 0 (baseline), 21 (post first dose), and at 3 and 6 months after the last vaccination in HIV- participants.

    Measure: Cohort 1: Serum IgG Antibody Levels at Multiple Time Points Expressed as GMTs

    Time: Day 0 to 6 months after the last vaccination

    Description: Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as GMFRs at Days 0 (baseline), 21 (post first dose), and at 3 and 6 months after the last vaccination in HIV- participants.

    Measure: Cohort 1: Serum IgG Antibody Levels at Multiple Time Points Expressed as GMFRs

    Time: Day 0 to 6 months after the last vaccination

    Description: Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as SCRs at Days 0 (baseline), 21 (post first dose), and at 3 and 6 months after the last vaccination in HIV- participants. SCR is defined as the percentage of participants with a post-vaccination titer ≥ 4 fold over naïve background and ≥ 2 fold over pre-existing titer.

    Measure: Cohort 1: Serum IgG Antibody Levels at Multiple Time Points Expressed as SCRs

    Time: Day 0 to 6 months after the last vaccination

    Description: Epitope-specific immune responses to the SARS-CoV-2 rS protein receptor binding as detected by ACE2 receptor binding inhibition assay expressed as GMTs at Days 0 (baseline), 21 (post first dose), 35 (post second dose), and at 3 and 6 months after the last vaccination in HIV- participants.

    Measure: Cohort 1: Angiotensin-Converting Enzyme 2 (ACE2) Receptor Binding Inhibition Assay Expressed as GMTs

    Time: Day 0 to 6 months after the last vaccination

    Description: Epitope-specific immune responses to the SARS-CoV-2 rS protein receptor binding as detected by ACE2 receptor binding inhibition assay expressed as GMFRs at Days 0 (baseline), 21 (post first dose), 35 (post second dose), and at 3 and 6 months after the last vaccination in HIV- participants.

    Measure: Cohort 1: ACE2 Receptor Binding Inhibition Assay Expressed as GMFRs

    Time: Day 0 to 6 months after the last vaccination

    Description: Epitope-specific immune responses to the SARS-CoV-2 rS protein receptor binding as detected by ACE2 receptor binding inhibition assay expressed as SCRs at Days 0 (baseline), 21 (post first dose), 35 (post second dose), and at 3 and 6 months after the last vaccination in HIV- participants.

    Measure: Cohort 1: ACE2 Receptor Binding Inhibition Assay Expressed as SCRs

    Time: Day 0 to 6 months after the last vaccination

    Description: Epitope-specific immune responses to the SARS-CoV-2 rS protein receptor binding as detected by ACE2 receptor binding inhibition assay expressed as SRRs at Days 0 (baseline), 21 (post first dose), 35 (post second dose), and at 3 and 6 months after the last vaccination in HIV- participants. SRR is defined as the proportion of participants with rises in titers exceeding the 95th percentile of placebo participants at the same time point and based on prior SARS-CoV-2 exposure.

    Measure: Cohort 1: ACE2 Receptor Binding Inhibition Assay Expressed as Seroresponse Rates (SRRs)

    Time: Day 0 to 6 months after the last vaccination

    Description: Neutralizing antibody activity as detected by microneutralization assay (MN) as expressed as GMTs at Days 0 (baseline), 35 (post second dose), and at 3 and 6 months after the last vaccination in HIV- participants.

    Measure: Cohort 1: Neutralizing Antibody Activity Expressed as GMTs

    Time: Day 0 to 6 months after the last vaccination

    Description: Neutralizing antibody activity as detected by MN expressed as GMFRs at Days 0 (baseline), 35 (post second dose), and at 3 and 6 months after the last vaccination in HIV-participants.

    Measure: Cohort 1: Neutralizing Antibody Activity Expressed as GMFRs

    Time: Day 0 to 6 months after the last vaccination

    Description: Neutralizing antibody activity as detected by MN expressed as SCRs (≥ 4 fold change) at Days 0 (baseline), 35 (post second dose), and at 3 and 6 months after the last vaccination in HIV- participants.

    Measure: Cohort 1: Neutralizing Antibody Activity Expressed as SCRs

    Time: Day 0 to 6 months after the last vaccination

    Description: Neutralizing antibody activity as detected by MN expressed as SRRs at Days 0 (baseline), 35 (post second dose), and at 3 and 6 months after the last vaccination in HIV-participants.

    Measure: Cohort 1: Neutralizing Antibody Activity Expressed as SRRs

    Time: Day 0 to 6 months after the last vaccination

    Description: Numbers and percentages (with 95% CI) of participants with MAAEs, AESI, or SAE through End of Study by MedDRA classification, severity score, and relatedness in HIV- participants.

    Measure: Cohort 1: HIV- Participants with Medically Attended Adverse Events (MAAEs), Adverse Events of Special Interest (AESIs), and Serious Adverse Events (SAEs)

    Time: 386 days

    Description: Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as GMTs at Days 0 (baseline), 21 (post first dose), and at 3 and 6 months after the last vaccination in HIV+ participants.

    Measure: Cohort 2: Serum IgG Antibody Levels at Multiple Time Points Expressed as GMTs

    Time: Day 0 to 6 months after the last vaccination

    Description: Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as GMFRs at Days 0 (baseline), 21 (post first dose), and at 3 and 6 months after the last vaccination in HIV+ participants.

    Measure: Cohort 2: Serum IgG Antibody Levels at Multiple Time Points Expressed as GMFRs

    Time: Day 0 to 6 months after the last vaccination

    Description: Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as SCRs at Days 0 (baseline), 21 (post first dose), and at 3 and 6 months after the last vaccination in HIV+ participants. SCR is defined as the percentage of participants with a post-vaccination titer ≥ 4 fold over naïve background and ≥ 2 fold over pre-existing titer.

    Measure: Cohort 2: Serum IgG Antibody Levels at Multiple Time Points Expressed as SCRs

    Time: Day 0 to 6 months after the last vaccination

    Description: Epitope-specific immune responses to the SARS-CoV-2 rS protein receptor binding as detected by ACE2 receptor binding inhibition assay expressed as GMTs at Days 0 (baseline), 21 (post first dose), 35 (post second dose), and at 3 and 6 months after the last vaccination in HIV+ participants.

    Measure: Cohort 2: ACE2 Receptor Binding Inhibition Assay Expressed as GMTs

    Time: Day 0 to 6 months after the last vaccination

    Description: Epitope-specific immune responses to the SARS-CoV-2 rS protein receptor binding as detected by ACE2 receptor binding inhibition assay expressed as GMFRs at Days 0 (baseline), 21 (post first dose), 35 (post second dose), and at 3 and 6 months after the last vaccination in HIV+ participants.

    Measure: Cohort 2: ACE2 Receptor Binding Inhibition Assay Expressed as GMFRs

    Time: Day 0 to 6 months after the last vaccination

    Description: Epitope-specific immune responses to the SARS-CoV-2 rS protein receptor binding as detected by ACE2 receptor binding inhibition assay expressed as SCRs at Days 0 (baseline), 21 (post first dose), 35 (post second dose), and at 3 and 6 months after the last vaccination in HIV+ participants.

    Measure: Cohort 2: ACE2 Receptor Binding Inhibition Assay Expressed as SCRs

    Time: Day 0 to 6 months after the last vaccination

    Description: Epitope-specific immune responses to the SARS-CoV-2 rS protein receptor binding as detected by ACE2 receptor binding inhibition assay expressed as SRRs at Days 0 (baseline), 21 (post first dose), 35 (post second dose), and at 3 and 6 months after the last vaccination in HIV+ participants. SRR is defined as the proportion of participants with rises in titers exceeding the 95th percentile of placebo participants at the same time point and based on prior SARS-CoV-2 exposure.

    Measure: Cohort 2: ACE2 Receptor Binding Inhibition Assay Expressed as SRRs

    Time: Day 0 to 6 months after the last vaccination

    Description: Neutralizing antibody activity as detected by MN as expressed as GMTs at Days 0 (baseline), 35 (post second dose), and at 3 and 6 months after the last vaccination in HIV+ participants.

    Measure: Cohort 2: Neutralizing Antibody Activity Expressed as GMTs

    Time: Day 0 to 6 months after the last vaccination

    Description: Neutralizing antibody activity as detected by MN expressed as GMFRs at Days 0 (baseline), 35 (post second dose), and at 3 and 6 months after the last vaccination in HIV+ participants.

    Measure: Cohort 2: Neutralizing Antibody Activity Expressed as GMFRs

    Time: Day 0 to 6 months after the last vaccination

    Description: Neutralizing antibody activity as detected by MN expressed as SCRs (≥ 4 fold change) at Days 0 (baseline), 35 (post second dose), and at 3 and 6 months after the last vaccination in HIV+ participants.

    Measure: Cohort 2: Neutralizing Antibody Activity Expressed as SCRs

    Time: Day 0 to 6 months after the last vaccination

    Description: Neutralizing antibody activity as detected by MN expressed as SRRs at Days 0 (baseline), 35 (post second dose), and at 3 and 6 months after the last vaccination in HIV+ participants.

    Measure: Cohort 2: Neutralizing Antibody Activity Expressed as SRRs

    Time: Day 0 to 6 months after the last vaccination

    Description: Numbers and percentages (with 95% CI) of participants with MAAEs, AESI, or SAE through End of Study by MedDRA classification, severity score, and relatedness in HIV+ participants.

    Measure: Cohort 2: HIV+ Participants with MAAEs, AESIs, and SAEs

    Time: 386 days

    Description: Counts and proportions of symptomatic virologically confirmed, mild, moderate, and severe COVID-19 outcomes in HIV+ participants as previously described in the second primary efficacy endpoint for Cohort 1 (HIV- participants).

    Measure: Cohort 2: HIV+ Participants with Symptomatic Virologically Confirmed, Mild, Moderate, or Severe COVID-19

    Time: Day 28 to Day 385

    Description: Incidence, maximum severity score, and symptom duration of SARS-CoV-2 infection by classification of symptomatic virologically confirmed, mild, moderate, and/or severe disease in HIV+ participants.

    Measure: Cohort 2: Incidence, Maximum Severity Score, and Symptom Duration of SARS-CoV-2 Infection by Severity Classification

    Time: Day 28 to Day 385
    331 Bacillus Calmette-Guerin Against Covid-19 for Prevention and Amelioration of Severity Trial

    The purpose of this study is to assess the efficacy of Bacille Calmette-Guérin (BCG) vaccination compared to placebo in reducing severe Covid-19 disease among elderly residents of skilled nursing facilities. The investigators hypothesize that BCG vaccination can reduce severity of Covid-19 disease. Patients who are residents of participating long-term care facilities (LTCFs), with the ability to understand and cooperate with study procedures, who agree to participate in the study will be randomly assigned to receive BCG vaccination or a placebo. Participants will be followed for up to twelve months to assess severity of Covid-19 outcomes.

    NCT04534803
    Conditions
    1. Covid19
    Interventions
    1. Drug: BCG Vaccine
    2. Other: Placebo

    Primary Outcomes

    Description: Number of people diagnosed with severe Covid-19 disease as documented in the electronic heath record; severe Covid-19 disease is defined as any instance of death, hospitalization, or non-hospitalization but requiring new administration of supplemental oxygen or having a decline in oxygen saturation of 10%, change from ambulant to non-ambulant for 3 or more days, or any new change in mental health status.

    Measure: To assess the efficacy of BCG vaccination compared to placebo in reducing severe Covid-19 disease among elderly residents of skilled nursing facilities.

    Time: 12 months

    Secondary Outcomes

    Description: Number of cases of any COVID-19 disease, defined as a positive SARS-Cov-2 test (per PCR or serology), plus fever (as documented in EHR) or at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure (as documented in EHR.) Number of cases of asymptomatic SARS-CoV-2 infection, defined as evidence of SARS-CoV-2 infection (by PCR or seroconversion), absence of associated respiratory illness (as documented in EHR), and no evidence of exposure prior to randomization (baseline serology will be negative). Number of cases of critical care admissions with SARS-CoV-2, defined as the number of admissions to critical care associated with a positive SARS-CoV-2 test. Number of cases of critical care admission duration with SARS-CoV-2, defined as the number of days admitted to critical care (using medical/hospital records) associated with a positive SARS-CoV-2 test.

    Measure: To assess the efficacy of BCG vaccination compared to placebo in reducing the following among elderly residents of skilled nursing facilities (by number of cases)

    Time: 12 months

    Description: 5. Number of cases of critical care admissions, defined as the number of admissions to critical care. 6. Number of cases of mechanical ventilation with SARS-CoV-2, defined as the number of participants needing mechanical ventilation (as documented by EHR) and associated with a positive SARS-CoV-2 test. 7. Number of cases of mechanical ventilation, defined as the number of participants needing mechanical ventilation. 8. Number of cases of All-Cause Mortality, defined as death reported by the long-term care facility. 9. Number of cases of any fever or respiratory illness, defined as fever (as documented in EHR), or at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure (as documented in EHR).

    Measure: To assess the efficacy of BCG vaccination compared to placebo in reducing the following among elderly residents of skilled nursing facilities (by number of cases), continued

    Time: 12 months

    Description: Number of episodes of fever or respiratory illness, defined as fever (as documented in EHR), or at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure (as documented in EHR). Number of episodes of any COVID-19 disease, defined as a positive SARS-Cov-2 test (per PCR or serology), plus fever (as documented in EHR) or at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure (as documented in EHR.) Number of episodes of local and systemic adverse events to BCG vaccination measured over the 3 months following randomization (type and severity of local and systemic adverse events will be collected and graded using toxicity grading scale).

    Measure: To assess the efficacy of BCG vaccination compared to placebo in reducing the following among elderly residents of skilled nursing facilities (by number of episodes)

    Time: 12 months

    Description: Number of days of symptom duration of fever or respiratory illness, defined as number of days with symptoms in any episode of illness that meets the case definition for fever or respiratory illness, defined as fever (as documented in EHR), or at least one sign or symptom of respiratory disease including cough, shortness of breath, respiratory distress/failure (as documented in EHR). Number of days of COVID-19 symptom duration, defined as the number of days with symptoms in any episode of illness that meets the case definition for any COVID-19 disease.

    Measure: To assess the efficacy of BCG vaccination compared to placebo in reducing the following among elderly residents of skilled nursing facilities (by number of days)

    Time: 12 months
    332 A PHASE 1B, 2-PART, DOUBLE-BLIND, PLACEBO-CONTROLLED, SPONSOR-OPEN STUDY, TO EVALUATE THE SAFETY, TOLERABILITY AND PHARMACOKINETICS OF SINGLE ASCENDING (24-HOUR, PART 1) AND EXTENDED (120-HOUR, PART 2) INTRAVENOUS INFUSIONS OF PF-07304814 IN HOSPITALIZED PARTICIPANTS WITH COVID-19

    It is Phase 1b, 2-part, double-blind, placebo-controlled study to evaluate safety, tolerability, and pharmacokinetics of PF-07304814, in patients with SARS-CoV-2 virus infection and with mild-to-moderate symptoms.

    NCT04535167
    Conditions
    1. Viral Disease
    Interventions
    1. Drug: PF-07304814
    2. Drug: Placebo
    MeSH:Virus Diseases

    Primary Outcomes

    Description: Adverse Events (AEs)

    Measure: Frequency of treatment-emergent adverse events (TEAEs)

    Time: 0 hours up to 41 days

    Description: Adverse Events

    Measure: Number of participants who withdraw due to treatment-emergent adverse events (TEAEs)

    Time: 0 hours up to 41 days

    Description: Adverse Events

    Measure: Frequency of treatment-emergent adverse events (TEAEs), causally related to study intervention

    Time: 0 hours up to 41 days

    Description: Serious Adverse Events

    Measure: Frequency of treatment-emergent serious adverse events

    Time: 0 hours up to 41 days

    Description: Adverse Events

    Measure: Frequency of treatment-emergent infusion site reactions

    Time: 0 hours up to 41 days

    Description: Percent change in laboratory parameters

    Measure: Magnitude of abnormal hematologic laboratory findings

    Time: 0 hours up to 41 days

    Description: Adverse Events

    Measure: Frequency of abnormal chemistry values

    Time: 0 hours up to 41 days

    Description: Adverse Events

    Measure: Frequency of abnormal hematologic laboratory findings

    Time: 0 hours up to 41 days

    Description: Percent change in urinalysis parameters

    Measure: Magnitude of abnormal urinalysis findings

    Time: 0 hours up to 41 days

    Description: ECG parameters

    Measure: Change from baseline in PR values

    Time: 0 hours up to 41 days

    Description: ECG parameters

    Measure: Change from baseline in RR values

    Time: 0 hours up to 41 days

    Description: ECG parameters

    Measure: Change from baseline in QTc values

    Time: 0 hours up to 41 days

    Description: ECG parameters

    Measure: Change from baseline in QTcF values

    Time: 0 hours up to 41 days

    Description: ECG parameters

    Measure: Change from baseline in QRS values

    Time: 0 hours up to 41 days

    Description: Vital sign measurements

    Measure: Change from baseline in pulse rate measurements

    Time: 0 hours up to 41 days

    Description: Vital sign measurements

    Measure: Change from baseline in temperature values

    Time: 0 hours up to 41 days

    Description: Vital sign measurements

    Measure: Change from baseline in respiratory rate values

    Time: 0 hours up to 41 days

    Description: Vital sign measurements

    Measure: Change from baseline in systolic blood pressure

    Time: 0 hours up to 41 days

    Description: Vital sign measurements

    Measure: Change from baseline in diastolic blood pressure

    Time: 0 hours up to 41 days

    Description: Vital sign measurements

    Measure: Change from baseline in pulse oximetry/SpO2 measurement

    Time: 0 hours up to 41 days

    Secondary Outcomes

    Description: plasma PK parameters

    Measure: Change in concentration at 24 hours (C24[end of infusion]) of PF-07304814 and PF-00835231

    Time: 0 to 32 hours

    Description: plasma PK parameters

    Measure: Change in concentration, dose normalised, at 24 hours (C24 (dn) [end of infusion]) of PF-07304814 and PF-00835231

    Time: 0 to 32 hours

    Description: plasma PK parameters

    Measure: Change in concentration at 120 hours (C120[end of infusion]) of PF-07304814 and PF-00835231

    Time: 0 to 32 hours

    Description: plasma PK parameters

    Measure: Change in maximum observed concentration (Cmax) of PF-07304814 and PF-00835231

    Time: 0 to 32 hours

    Description: plasma PK parameters

    Measure: Change in maximum observed concentration, dose normalised (Cmax [dn]) of PF-07304814 and PF-00835231

    Time: 0 to 32 hours

    Description: plasma PK parameters

    Measure: Change in concentration at steady state (Css) of PF-07304814 and PF-00835231

    Time: 0 to 32 hours

    Description: plasma PK parameters

    Measure: Change in concentration at steady state, dose normalised (Css [dn]) of PF-07304814 and PF-00835231

    Time: 0 to 32 hours

    Description: plasma PK parameters

    Measure: Change in terminal half life (t1/2) of PF-07304814 and PF-00835231

    Time: 0 to 32 hours

    Description: plasma PK parameters

    Measure: Change in clearance (CL) of PF-07304814

    Time: 0 to 32 hours

    Description: plasma PK parameters

    Measure: Change in area-under-the-curve plasma concentration from 0 to time extrapolated to infinity (AUCinf) of PF-07304814 and PF-00835231

    Time: 0 to 32 hours

    Description: plasma PK parameters

    Measure: Change in area-under-the-curve plasma concentration from 0 to last quantifiable concentration (AUClast) of PF-07304814 and PF-00835231

    Time: 0 to 32 hours

    Description: plasma PK parameters

    Measure: Change in area-under-the-curve plasma concentration from 0 to time extrapolated to infinity, dose normalised (AUCinf [dn]) of PF-07304814 and PF-00835231

    Time: 0 to 32 hours

    Description: plasma PK parameters

    Measure: Change in steady state volume of distribution (Vss) of PF-00835231

    Time: 0 to 32 hours

    Description: urinary PK parameters (Cohort 2 only)

    Measure: Cumulative amount of unchanged drug excreted into urine (Ae)

    Time: 0 to 36 hours

    Description: urinary PK parameters (Cohort 2 only)

    Measure: Percent of dose excreted as unchanged drug (Ae%) over dosing period

    Time: 0 to 36 hours
    333 Therapeutic Study to Evaluate the Safety and Efficacy of DW-MSC in COVID-19 Patients: Randomized, Double-blind, and Placebo-controlled

    This is a phase 1 clinical trial to verify the safety and efficacy of DW-MSC in COVID-19 patients. A total of 9 subjects are randomly allocated. Subjects who meet the final inclusion and exclusion criteria are randomized to the test groups (low-dose group and high-dose group) or control group (placebo group) in a ratio of 1:1:1. Subjects assigned to the test groups were administered intravenously once with 5 x 10^7cells of DW-MSC for the low-dose group or 1 x 10^8cells for the high-dose group after registration. Subjects assigned to the control group were administered with placebo in the same manner as the test drug (DW-MSC). At this time, all of the existing standard co-treatment are allowed. DW-MSC is adjunct therapy to standard therapy. This clinical trial is a double-blind trial, in which a randomized method will be used. To maintain the double-blindness of the study, statistician who do not participate in this study independently generate randomization code. Subjects will be randomized to the test groups (low-dose group and high-dose group) or the control group (placebo group) in a 1:1:1 ratio. After the completion of the trial, the randomization code will be disclosed after unlocking the database and unblinding procedures. Follow Up period: observed for 28 days after a single administration

    NCT04535856
    Conditions
    1. Covid19
    2. Corona Virus Infection
    3. SAR
    Interventions
    1. Drug: allogeneic mesenchymal stem cell
    2. Other: Placebo
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome

    Primary Outcomes

    Description: Incidence of TEAE* in Treatment group * TEAE: Treatment-Emergent Adverse Event All adverse reactions will be organized according to System Organ Class (SOC) and Preferred Term (PT) using MedDRA (Medical Dictionary for Regulatory Activities), and the incidence of treatment-emergent adverse events will be summarized for the coded adverse reactions.

    Measure: Incidence of TEAE* in Treatment group

    Time: 28 days

    Secondary Outcomes

    Description: Survival rate is defined as the rate of subjects surviving until Day 14 and Day 28, and the number and rate of surviving subjects for each administration group is given.

    Measure: Survival rate

    Time: until Day 14 and Day 28

    Description: Duration of hospitalization is defined as the number of days in the hospital until Day 28, and descriptive statistics (number of subjects, mean, standard deviation, median, minimum, maximum) are given for each administration group.

    Measure: Duration of hospitalization

    Time: 28 days

    Description: Clinical improvement measured by Ordinal scale change for clinical improvement from baseline to Day 14 and 28

    Measure: Clinical improvement Ordinal scale

    Time: from baseline to Day 14 and Day 28

    Description: Clinical improvement measured by National EWS (National Early Warning Score) change from baseline to Day 7, 14, 28. EWS Points, Risk and Interpretation as follows: 0~4: Low clinical risk; interpretation= Ward-based response 3~4 : Low~medium clinical risk; interpretation= Urgent ward-based response 5~6: Medium clinical risk; interpretation= Key threshold for urgent response

    Measure: Clinical improvement National EWS

    Time: from baseline to Day 7, 14 and Day 28

    Description: Clinical improvement measured by Oxygenation index (PaO2/FiO2) change from baseline (Day 1, 3, 7, 10, 14, 28)

    Measure: Clinical improvement Oxygenation index

    Time: Day 1, 3, 7, 10, 14, 28

    Description: Clinical improvement measured by Lung involvement change by Imaging from baseline (Day 7, 14, 28)

    Measure: Clinical improvement Lung involvement change

    Time: Day 7, 14, 28

    Description: Inflammation markers change from baseline for WBC

    Measure: Clinical improvement Inflammation markers change

    Time: Day 7, 14, 28

    Description: Inflammation markers change from baseline for Lymphocytes

    Measure: Clinical improvement Inflammation markers change

    Time: Day 7, 14, 28

    Description: Inflammation markers change from baseline for ESR

    Measure: Clinical improvement Inflammation markers change

    Time: Day 7, 14, 28

    Description: Inflammation markers change from baseline for CRP

    Measure: Clinical improvement Inflammation markers change

    Time: Day 7, 14, 28

    Description: Inflammation markers change from baseline for Fibrinogen

    Measure: Clinical improvement Inflammation markers change

    Time: Day 7, 14, 28

    Description: Inflammation markers change from baseline for IL-6, TNF-α, IL-1β, IF-γ (Day 7, 14, 28)

    Measure: Clinical improvement Inflammation markers change

    Time: Day 7, 14, 28
    334 A Cluster-Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy of Vitamin D3 Supplementation to Reduce Disease Severity in Persons With Newly Diagnosed COVID-19 Infection and to Prevent Infection in Household Members

    The Vitamin D and COVID-19 Trial (VIVID) is a nationwide randomized clinical trial in 2700 U.S. men and women to investigate whether taking a daily dietary supplement of vitamin D for 4 weeks reduces the risk of hospitalization and/or death in participants newly diagnosed with COVID-19, and reduces the risk of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in their closest household contacts (as documented by seroconversion).

    NCT04536298
    Conditions
    1. COVID-19
    Interventions
    1. Dietary Supplement: vitamin D
    2. Dietary Supplement: Placebo

    Primary Outcomes

    Measure: Hospitalization or death in index cases

    Time: 4 weeks

    Secondary Outcomes

    Description: Severity: 1=no COVID-19 illness; 2=COVID-19 illness with no hospitalization; 3=COVID-19 illness with hospitalization or death

    Measure: Self-reported disease severity in index cases

    Time: 4 weeks

    Measure: Time to hospitalization or death in index cases

    Time: 4 weeks

    Measure: ICU admission/ventilation support in index cases

    Time: 4 weeks

    Measure: SARS-CoV-2 infection in close household contacts

    Time: 4 weeks

    Description: Severity: 1=no COVID-19 illness; 2=COVID-19 illness with no hospitalization; 3=COVID-19 illness with hospitalization or death

    Measure: Self-reported disease severity in close household contacts

    Time: 4 weeks
    335 COVID-FIS: A Phase 2 Placebo-Controlled Pilot Study in COVID-19 of Fisetin to Alleviate Dysfunction and Excessive Inflammatory Response in Older Adults in Nursing Homes

    The purpose of this study is to test whether Fisetin, a senolytic drug, can assist in preventing an increase in the disease's progression and alleviate complications of coronavirus due to an excessive inflammatory reaction.

    NCT04537299
    Conditions
    1. Covid19
    2. SARS-CoV Infection
    Interventions
    1. Drug: Fisetin
    2. Drug: Placebo
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome

    Primary Outcomes

    Description: Ordinal Scale for Clinical Improvement (minimum=0 and maximum=8; higher score = worse outcome)

    Measure: Change in COVID-19 Severity

    Time: baseline, Day 2, 7, 10, 14, 17, 30, 90 and 180
    336 Bacillus Calmette-Guérin Vaccination To Prevent Serious Respiratory Tract Infection And Covid-19 In Vulnerable Elderly - An Adaptive Randomized Controlled Trial

    On March 11 2020 the World Health Organization (WHO) declared the coronavirus (SARS-CoV-2) outbreak a pandemic. Worldwide, the number of confirmed cases continues to rise, leading to significant morbidity and mortality. In the Netherlands, although the incidence is currently low due to social distancing measures, recurrence of infections is expected once measures are going to be lifted. Although individuals of any age can acquire SARS-CoV-2, adults of middle and older age are at highest risk for developing severe COVID-19 disease. Moreover, recent reports demonstrate that mortality rates rise significantly among patients 60 years and older. Therefore, strategies to prevent SARS-CoV-2 infection or to reduce its clinical consequences in vulnerable populations are urgently needed. Bacille Calmette-Guérin (BCG) vaccine not only protects against tuberculosis, but also induces protection against various respiratory infections, including those with a viral etiology. We hypothesize that BCG vaccination reduces clinically relevant respiratory tract infections requiring medical intervention, including COVID-19, in vulnerable elderly. The objective of this trial is to determine the impact of BCG vaccination on the incidence of clinically relevant respiratory infections or COVID-19 in vulnerable elderly. The trial is designed as an adaptive multi-center double-blind randomized placebo-controlled trial. The attempt is to include 5,200 to 7,000 vulnerable elderly, defined as ≥60 years of age being discharged from hospital in the last 6 weeks, or visiting a medical outpatient clinic, thrombosis care services, or chronic renal replacement departments. Patients with contraindications to BCG vaccination as stipulated in the Summary of Product Characteristics (SPC) and patients with a history of COVID-19 will be excluded. Participants will be randomized between intracutaneous administration of BCG vaccine (Danish strain 1331) or placebo (0.1ml 0.9% NaCl) in a 1:1 ratio.The trial has an adaptive primary endpoint. Based on accrual of the two endpoints, the primary endpoint will be either (a) COVID-19 or (b) clinically relevant respiratory tract infection requiring medical intervention, potentially including COVID-19 episodes. The other will be declared secondary endpoint. Other secondary endpoints include: all SARS-CoV-2 infections (including asymptomatic infections), influenza infection, acute respiratory infection (ARI; all infections regardless of medical intervention), ARI-related hospital admission, COVID-19 related hospital admission, pneumonia, mental, physical and social functioning, serious adverse events and adverse events, and death.

    NCT04537663
    Conditions
    1. Respiratory Tract Infections
    2. Covid19
    Interventions
    1. Drug: Bacille Calmette-Guérin (BCG)
    2. Drug: Placebo
    MeSH:Infection Communicable Diseases Respiratory Tract Infections
    HPO:Respiratory tract infection

    Primary Outcomes

    Description: Clinically relevant relevant respiratory tract infection is composed of clinical symptoms in combination with the need for medical intervention. Exact criteria for clinically relevant respiratory tract infection and COVID-19 are described in the protocol. A blinded adjudication committee will determine the status of the primary endpoints of all participants with a potential primary endpoint, based on information provided in a standardized narrative using data reported by the participant and from GP and hospital medical records when relevant. For detection of ARI, symptoms are checked on a weekly (from week 1-4) or bi-weekly basis (from week 4 onward).

    Measure: The trial has an adaptive primary endpoint. Based on predefined objective and quantitative criteria the primary endpoint will be either a clinically relevant respiratory tract infection, or COVID-19.

    Time: 180 days

    Secondary Outcomes

    Description: Cumulative incidence of SARS-CoV-2 infection regardless of symptomatology defined as having had COVID-19 as described under primary endpoints above and/or SARS-CoV-2 positive test in real time as part of the test-and-trace program of the Dutch government and/of documented SARS-CoV-2 seroconversion at 6 months. Seroconversion will be defined as antibody-positive at 6 months but negative at baseline.

    Measure: Cumulative incidence of SARS-CoV-2 infection (irrespective the presence of symptoms)

    Time: 180 days

    Measure: Cumulative incidence of asymptomatic, mild/moderate, and severe (requiring hospitalization) SARS-CoV-2 infection.

    Time: 180 days

    Description: Defined as either of 1) ARI + microbiological evidence of influenza infection, 2) seroconversion of influenza between enrolment and month 6.

    Measure: Influenza infection

    Time: 180 days

    Description: Meeting the definition stated in the primary outcome. Irrespective of requiring an intervention.

    Measure: An acute respiratory tract infection

    Time: 180 days

    Description: Meeting the definition stated in the primary outcome including the requirement of an intervention.

    Measure: Medically attended acute respiratory tract infection

    Time: 180 days

    Description: Meeting the definition stated in the primary outcome including the need of hospitalization.

    Measure: Acute respiratory tract infection related hospital admission

    Time: 180 days

    Measure: Pneumonia diagnosed by a GP or medical specialist

    Time: 180 days

    Description: Using the Katz Activities of Daily Living (ADL) scale, from A (fully independent) to G (dependent in feeding, continence, transferring, going to toilet, dressing, and bathing)

    Measure: Functioning in daily activities

    Time: 180 days

    Measure: Serious adverse events and adverse events.

    Time: 180 days

    Measure: Major cardiovascular events

    Time: 180 days

    Measure: All cause 6-month mortality

    Time: 180 days

    Measure: History of falls

    Time: 180 days

    Description: Using the EQ5D quality of life instrument, with questions on 4 domains (mobility, self-care, usual activities, pain discomfort) and the percepted health of the participant with 100 meaning the best health you can imagine, and 0 meaning the worst health you can imagine

    Measure: Quality of life using the EQ5D quality of life instrument

    Time: 180 days

    Description: Using the 6-item Lawton Activities of Daily Living questionnaire, with scores ranging from 0 (low function, dependent) to 8 (high function, independent) for women (0 through 5 for men)

    Measure: Activities in daily living

    Time: 180 days
    337 A Study of Brexanolone for Acute Respiratory Distress Syndrome Due to COVID-19

    The purpose of this study is to evaluate the efficacy and safety of brexanolone in participants on ventilator support for acute respiratory distress syndrome (ARDS) due to COVID-19.

    NCT04537806
    Conditions
    1. Acute Respiratory Distress Syndrome
    2. COVID-19
    Interventions
    1. Drug: Brexanolone
    2. Drug: Placebo
    MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

    Primary Outcomes

    Description: Respiratory failure is defined based on resource utilization, requiring at least one of the following: endotracheal intubation and mechanical ventilation; oxygen delivered by high-flow nasal cannula; noninvasive positive pressure ventilation or extracorporeal membrane oxygenation (ECMO).

    Measure: Percentage of Participants Who are Alive and Free of Respiratory Failure at Day 28

    Time: Day 28

    Secondary Outcomes

    Measure: Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE)

    Time: Up to Day 28

    Measure: All-cause Mortality Through Day 28

    Time: Up to Day 28
    338 A Phase 1b/2a Study in Participants With Early Stage COVID-19 to Evaluate the Safety, Efficacy, and Pharmacokinetics of Remdesivir Administered by Inhalation

    The primary objective of this study is to characterize the impact of inhaled remdesivir (RDV) on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load in participants with early stage coronavirus disease 2019 (COVID-19).

    NCT04539262
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Remdesivir (RDV)
    2. Drug: Placebo
    MeSH:Respiratory Aspiration

    Primary Outcomes

    Description: Time-weighted Average Change in SARS-CoV-2 viral load is defined as area under the concentration versus time curve (AUC) of viral load change divided by time between baseline through Day 7

    Measure: Time-weighted Average Change From Baseline in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Viral Load Through Day 7

    Time: Baseline, Day 7

    Secondary Outcomes

    Measure: Proportion of Participants Experiencing any Treatment-Emergent Adverse Events

    Time: First dose date up to 5 days plus 30 days

    Measure: Proportion of Participants Experiencing any Treatment-Emergent Graded Laboratory Abnormalities

    Time: First dose date up to 5 days plus 30 days

    Measure: Proportion of Participants Experiencing any Treatment-Emergent Adverse Events Leading to Study Treatment Discontinuation

    Time: First dose date up to 5 days plus 30 days

    Measure: Proportion of Participants Progressing From Early Stage Coronavirus Disease 2019 (COVID-19) to Hospitalization or Death by Day 14

    Time: Day 14

    Description: AUC0-24h is defined as the concentration of drug over time between time 0 to time 24 hours. Time Frame for PK samples: Sparse PK (all participants): Day 1 (end of nebulization, and optional 2-hour post nebulization), and Day 3 (predose and end of nebulization); Intensive PK (Up to 6 participants/group in Part A & Part B): Day 1 and an additional sample at Day 3 or Day 5 at the following time points: 0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization.

    Measure: Pharmacokinetic (PK) Parameter: AUC0-24h of Remdesivir (RDV) and its Metabolites (GS-441524 and GS-704277)

    Time: Sparse PK: Day 1 (end of nebulization) and Day 3 (predose and end of nebulization); Intensive PK: Day 1 and Day 3 or Day 5 (0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization); Nebulization duration: 17-34 minutes.

    Description: AUClast is defined as the concentration of drug from time zero to the last observable concentration. Time Frame for PK samples: Sparse PK (all participants): Day 1 (end of nebulization, and optional 2-hour post nebulization), and Day 3 (predose and end of nebulization); Intensive PK (Up to 6 participants/group in Part A & Part B): Day 1 and an additional sample at Day 3 or Day 5 at the following time points: 0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization.

    Measure: PK Parameter: AUClast of RDV and its Metabolites (GS-441524 and GS-704277)

    Time: Sparse PK: Day 1 (end of nebulization) and Day 3 (predose and end of nebulization); Intensive PK: Day 1 and Day 3 or Day 5 (0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization); Nebulization duration: 17-34 minutes.

    Description: CLss/F is defined as apparent oral clearance at steady state after administration of the drug. CLss/F = Dose/AUCtau, where "Dose" is the dose of the drug Time Frame for PK samples: Sparse PK (all participants): Day 1 (end of nebulization, and optional 2-hour post nebulization), and Day 3 (predose and end of nebulization); Intensive PK (Up to 6 participants/group in Part A & Part B): Day 1 and an additional sample at Day 3 or Day 5 at the following time points: 0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization.

    Measure: PK Parameter: CLss/F of RDV and its Metabolites (GS-441524 and GS-704277)

    Time: Sparse PK: Day 1 (end of nebulization) and Day 3 (predose and end of nebulization); Intensive PK: Day 1 and Day 3 or Day 5 (0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization); Nebulization duration: 17-34 minutes.

    Description: t1/2 is defined as the estimate of the terminal elimination half-life of the drug. Time Frame for PK samples: Sparse PK (all participants): Day 1 (end of nebulization, and optional 2-hour post nebulization), and Day 3 (predose and end of nebulization); Intensive PK (Up to 6 participants/group in Part A & Part B): Day 1 and an additional sample at Day 3 or Day 5 at the following time points: 0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization.

    Measure: PK Parameter: t1/2 of RDV and its Metabolites (GS-441524 and GS-704277)

    Time: Sparse PK: Day 1 (end of nebulization) and Day 3 (predose and end of nebulization); Intensive PK: Day 1 and Day 3 or Day 5 (0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization); Nebulization duration: 17-34 minutes.

    Description: Vz/F is defined as the apparent volume of distribution of the drug. Time Frame for PK samples: Sparse PK (all participants): Day 1 (end of nebulization, and optional 2-hour post nebulization), and Day 3 (predose and end of nebulization); Intensive PK (Up to 6 participants/group in Part A & Part B): Day 1 and an additional sample at Day 3 or Day 5 at the following time points: 0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization.

    Measure: PK Parameter: Vz/F of RDV and its Metabolites (GS-441524 and GS-704277)

    Time: Sparse PK: Day 1 (end of nebulization) and Day 3 (predose and end of nebulization); Intensive PK: Day 1 and Day 3 or Day 5 (0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization); Nebulization duration: 17-34 minutes.

    Description: Cmax is defined as the maximum observed concentration of drug. Time Frame for PK samples: Sparse PK (all participants): Day 1 (end of nebulization, and optional 2-hour post nebulization), and Day 3 (predose and end of nebulization); Intensive PK (Up to 6 participants/group in Part A & Part B): Day 1 and an additional sample at Day 3 or Day 5 at the following time points: 0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization.

    Measure: PK Parameter: Cmax of RDV and its Metabolites (GS-441524 and GS-704277)

    Time: Sparse PK: Day 1 (end of nebulization) and Day 3 (predose and end of nebulization); Intensive PK: Day 1 and Day 3 or Day 5 (0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization); Nebulization duration: 17-34 minutes.

    Description: Tmax is defined as the time (observed time point) of Cmax. Time Frame for PK samples: Sparse PK (all participants): Day 1 (end of nebulization, and optional 2-hour post nebulization), and Day 3 (predose and end of nebulization); Intensive PK (Up to 6 participants/group in Part A & Part B): Day 1 and an additional sample at Day 3 or Day 5 at the following time points: 0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization.

    Measure: PK Parameter: Tmax of RDV and its Metabolites (GS-441524 and GS-704277)

    Time: Sparse PK: Day 1 (end of nebulization) and Day 3 (predose and end of nebulization); Intensive PK: Day 1 and Day 3 or Day 5 (0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization); Nebulization duration: 17-34 minutes.

    Description: Clast is defined as the last observable concentration of drug. Time Frame for PK samples: Sparse PK (all participants): Day 1 (end of nebulization, and optional 2-hour post nebulization), and Day 3 (predose and end of nebulization); Intensive PK (Up to 6 participants/group in Part A & Part B): Day 1 and an additional sample at Day 3 or Day 5 at the following time points: 0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization.

    Measure: PK Parameter: Clast of RDV and its Metabolites (GS-441524 and GS-704277)

    Time: Sparse PK: Day 1 (end of nebulization) and Day 3 (predose and end of nebulization); Intensive PK: Day 1 and Day 3 or Day 5 (0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization); Nebulization duration: 17-34 minutes.

    Description: Tlast is defined as the time (observed time point) of Clast. Time Frame for PK samples: Sparse PK (all participants): Day 1 (end of nebulization, and optional 2-hour post nebulization), and Day 3 (predose and end of nebulization); Intensive PK (Up to 6 participants/group in Part A & Part B): Day 1 and an additional sample at Day 3 or Day 5 at the following time points: 0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization.

    Measure: PK Parameter: Tlast of RDV and its Metabolites (GS-441524 and GS-704277)

    Time: Sparse PK: Day 1 (end of nebulization) and Day 3 (predose and end of nebulization); Intensive PK: Day 1 and Day 3 or Day 5 (0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization); Nebulization duration: 17-34 minutes.

    Description: AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval). Time Frame for PK samples: Sparse PK (all participants): Day 1 (end of nebulization, and optional 2-hour post nebulization), and Day 3 (predose and end of nebulization); Intensive PK (Up to 6 participants/group in Part A & Part B): Day 1 and an additional sample at Day 3 or Day 5 at the following time points: 0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization.

    Measure: PK Parameter: AUCtau of RDV and its Metabolites (GS-441524 and GS-704277)

    Time: Sparse PK: Day 1 (end of nebulization) and Day 3 (predose and end of nebulization); Intensive PK: Day 1 and Day 3 or Day 5 (0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization); Nebulization duration: 17-34 minutes.

    Description: λz is defined as the terminal elimination rate constant, estimated by linear regression of the terminal elimination phase of the log plasma concentration of drug versus time curve of the drug. Time Frame for PK samples: Sparse PK (all participants): Day 1 (end of nebulization, and optional 2-hour post nebulization), and Day 3 (predose and end of nebulization); Intensive PK (Up to 6 participants/group in Part A & Part B): Day 1 and an additional sample at Day 3 or Day 5 at the following time points: 0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization.

    Measure: PK Parameter: λz of RDV and its Metabolites (GS-441524 and GS-704277)

    Time: Sparse PK: Day 1 (end of nebulization) and Day 3 (predose and end of nebulization); Intensive PK: Day 1 and Day 3 or Day 5 (0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization); Nebulization duration: 17-34 minutes.

    Description: Ctau is defined as the observed drug concentration at the end of the dosing interval. Time Frame for PK samples: Sparse PK (all participants): Day 1 (end of nebulization, and optional 2-hour post nebulization), and Day 3 (predose and end of nebulization); Intensive PK (Up to 6 participants/group in Part A & Part B): Day 1 and an additional sample at Day 3 or Day 5 at the following time points: 0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization.

    Measure: PK Parameter: Ctau of RDV and its Metabolites (GS-441524 and GS-704277)

    Time: Sparse PK: Day 1 (end of nebulization) and Day 3 (predose and end of nebulization); Intensive PK: Day 1 and Day 3 or Day 5 (0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, and 24 hours post end of nebulization); Nebulization duration: 17-34 minutes.

    Measure: Change in SARS-CoV-2 Viral Load From Baseline to Day 4

    Time: Baseline, Day 4

    Measure: Change in SARS-CoV-2 Viral Load From Baseline to Day 7

    Time: Baseline, Day 7

    Measure: Change in SARS-CoV-2 Viral Load From Baseline to Day 14

    Time: Baseline, Day 14

    Measure: Time to Negative SARS-CoV-2 Polymerase Chain Reaction (PCR)

    Time: First dose date up to 14 days
    339 A Phase Ib/II, Single Center, Placebo-Controlled, Randomized, Blinded Study in Adult Patients (> 18 Years) With COVID-19 Respiratory Disease, to Evaluate, Safety, Tolerability and Mechanistic Effect of Alvelestat on Top of Standard of Care (COSTA)

    The purpose of this study is to determine the safety, tolerability and pharmacokinetics (PK), and explore the mechanistic and clinical effect of alvelestat (an oral neutrophil elastase inhibitor) orally twice per day for 10 days added to standard of care in adult patients (≥18 years) with COVID-19 respiratory disease.

    NCT04539795
    Conditions
    1. Covid19
    Interventions
    1. Drug: Alvelestat
    2. Drug: Placebo

    Primary Outcomes

    Description: Safety Outcome Assessment

    Measure: Numbers and % of subjects who experience at least 1 treatment-emergent adverse event

    Time: to day 60

    Measure: Mortality rate

    Time: to Day 90

    Description: clinically significant safety monitoring labs tests

    Measure: Adverse events of special interest

    Time: to Day 14 (acute treatment period) or EoT

    Secondary Outcomes

    Description: neutrophil elastase

    Measure: Effect of alvelestat on blood pharmacodynamic biomarkers of inflammation

    Time: to day 10
    340 Multicenter, Randomized, Double Blind, Placebo Controlled Parallel Group Study Evaluating Efficacy, Reactogenicity and Safety of Recombinant Vaccine Ad5-nCoV Against Novel Coronavirus Infection in Adult Volunteers

    This study is a phase III clinical trial to evaluate efficacy, reactogenicity and safety of the vaccine Ad5-nCoV compared with placebo in volunteers at the age from 18 to 85 years,with the randomized, double-blind design

    NCT04540419
    Conditions
    1. Covid19
    Interventions
    1. Biological: Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector)
    2. Biological: Placebo
    MeSH:Coronavirus Infections

    Primary Outcomes

    Description: Proportion of subjects with four-fold and higher increment of anti-receptor-binding domain antibodies [receptor-binding domain, RBD] of S-protein SARS-CoV-2).

    Measure: Superiority of the vaccine Ad5-nCoV to placebo by the level of seroconversion

    Time: Day 28 after vaccination

    Secondary Outcomes

    Description: Geometric mean titer of RBD и S-protein SARS-CoV-2 antibodies.

    Measure: Immunogenicity of the vaccine Ad5-nCoV compared with placebo (titer of SARS-CoV-2 antibodies)

    Time: Day 14, 28 and after 6 months after vaccination.

    Description: Level of seroconversion (proportion of persons with four-fold and higher increment of RBD и S-protein SARS-CoV-2 antibodies).

    Measure: Immunogenicity of the vaccine Ad5-nCoV compared with placebo (level of seroconversion)

    Time: Day 14, 28 and after 6 months after vaccination.

    Description: Geometric mean fold rise of RBD и S-protein SARS-CoV-2 antibodies.

    Measure: Immunogenicity of the vaccine Ad5-nCoV compared with placebo (rise of SARS-CoV-2 antibodies)

    Time: Day 14, 28 and after 6 months after vaccination.

    Description: Quantity of T-cells.

    Measure: Immunogenicity of the vaccine Ad5-nCoV compared with placebo (T-cell response)

    Time: Day 14, 28 and after 6 months after vaccination.

    Description: Frequency of confirmed COVID-19 (confirmed case of COVID-19: presence of clinical signs and positive result of laboratory test for RNA of virus SARS-CoV-2) (exploratory analysis).

    Measure: Frequency of confirmed COVID-19

    Time: Within 6 months after vaccination (except for COVID-19 cases within 14 days after vaccination)

    Description: Frequency of confirmed cases of COVID-19, requiring hospitalization. (confirmed case of COVID-19: presence of clinical signs and positive result of laboratory test for RNA of virus SARS-CoV-2) (exploratory analysis).

    Measure: Frequency of confirmed cases of COVID-19, requiring hospitalization

    Time: Within 6 months after vaccination (except for COVID-19 cases within 14 days after vaccination)

    Description: Frequency of cases with severe course of COVID-19 (confirmed case of COVID-19: presence of clinical signs and positive result of laboratory test for RNA of virus SARS-CoV-2) (exploratory analysis).

    Measure: Frequency of cases with severe course of COVID-19

    Time: Within 6 months after vaccination (except for COVID-19 cases within 14 days after vaccination)

    Description: Frequency of death due to COVID-19 (exploratory analysis).

    Measure: Frequency of death due to COVID-19.

    Time: Within 6 months after vaccination (except for COVID-19 cases within 14 days after vaccination)

    Description: Frequency and character of general and local postvaccinal reactions.

    Measure: Reactogenicity of the vaccine Ad5-nCoV compared with placebo

    Time: Day 0 (day of vaccination), Day 2, Day 7

    Description: Frequency and character of adverse events and serious adverse events.

    Measure: Frequency and character of adverse events and serious adverse events.

    Time: Day 0 - Month 6

    Description: Results of evaluation of vital parameters: Systolic blood pressure Diastolic blood pressure The researcher evaluates each of the vital parameter in the normal / abnormal categories. Clinically significant abnormalities should be reported as adverse events.

    Measure: To evaluate safety of the vaccine Ad5-nCoV by its effect on vital parameters (blood pressure)

    Time: Day -7-1 (Screening), Day 0, Day 2, Day 7, Day 14, Day 28, Month 6

    Description: Results of evaluation of vital parameters: • Heart rate. The researcher evaluates each of the vital parameter in the normal / abnormal categories. Clinically significant abnormalities should be reported as adverse events.

    Measure: To evaluate safety of the vaccine Ad5-nCoV by its effect on vital parameters (heart rate)

    Time: Day -7-1 (Screening), Day 0, Day 2, Day 7, Day 14, Day 28, Month 6

    Description: Results of evaluation of vital parameters: • Respiratory rate. The researcher evaluates each of the vital parameter in the normal / abnormal categories. Clinically significant abnormalities should be reported as adverse events.

    Measure: To evaluate safety of the vaccine Ad5-nCoV by its effect on vital parameters (respiratory rate)

    Time: Day -7-1 (Screening), Day 0, Day 2, Day 7, Day 14, Day 28, Month 6

    Description: Results of physical examination includes examination of organs and systems: General state Ears, nose, throat Skin and examination of the injection site The lymph nodes The cardiovascular system Respiratory system Nervous system Abdominal organs Kidneys and urinary system Musculoskeletal system. During the physical examination, the researcher evaluates each of the systems in the normal / abnormal categories. Clinically significant abnormalities should be reported as adverse events.

    Measure: To evaluate safety of the vaccine Ad5-nCoV by its effect on results of physical examination

    Time: Day -7-1 (Screening), Day 0, Day 2, Day 7, Day 14, Day 28, Month 6

    Description: Results of electrocardiography: • Heart rate (HR) The researcher evaluates each of the parameter in the normal / abnormal categories. Clinically significant abnormalities should be reported as adverse events.

    Measure: To evaluate safety of the vaccine Ad5-nCoV by its effect on results of electrocardiography (Heart rate)

    Time: Day -7-1 (Screening), Day 2

    Description: Results of electrocardiography: Intervals RR, PQ, QT QRS complex Corrected QT interval (QTcF). The researcher evaluates each of the parameter in the normal / abnormal categories. Clinically significant abnormalities should be reported as adverse events.

    Measure: To evaluate safety of the vaccine Ad5-nCoV by its effect on results of electrocardiography

    Time: Day -7-1 (Screening), Day 2

    Description: Results of serum chemistry: alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH). The researcher evaluates each of the parameter in the normal / abnormal categories. Clinically significant abnormalities should be reported as adverse events.

    Measure: To evaluate safety of the vaccine Ad5-nCoV by its effect on results of serum chemistry (enzymes)

    Time: Day -7-1 (Screening), Day 2, Day 28

    Description: Results of serum chemistry: total bilirubin, creatinine, urea, fasting glucose. The researcher evaluates each of the parameter in the normal / abnormal categories. Clinically significant abnormalities should be reported as adverse events.

    Measure: To evaluate safety of the vaccine Ad5-nCoV by its effect on results of serum chemistry

    Time: Day -7-1 (Screening), Day 2, Day 28

    Description: Results of serum chemistry: total protein, C-reactive protein. The researcher evaluates each of the parameter in the normal / abnormal categories. Clinically significant abnormalities should be reported as adverse events.

    Measure: To evaluate safety of the vaccine Ad5-nCoV by its effect on results of serum chemistry

    Time: Day -7-1 (Screening), Day 2, Day 28

    Description: Results of complete blood count: hemoglobin The researcher evaluates each of the parameter in the normal / abnormal categories. Clinically significant abnormalities should be reported as adverse events.

    Measure: To evaluate safety of the vaccine Ad5-nCoV by its effect on results of complete blood count (hemoglobin)

    Time: Day -7-1 (Screening), Day 2, Day 28

    Description: Results of complete blood count: hematocrit. The researcher evaluates each of the parameter in the normal / abnormal categories. Clinically significant abnormalities should be reported as adverse events.

    Measure: To evaluate safety of the vaccine Ad5-nCoV by its effect on results of complete blood count (hematocrit)

    Time: Day -7-1 (Screening), Day 2, Day 28

    Description: Results of complete blood count: erythrocytes. The researcher evaluates each of the parameter in the normal / abnormal categories. Clinically significant abnormalities should be reported as adverse events.

    Measure: To evaluate safety of the vaccine Ad5-nCoV by its effect on results of complete blood count (erythrocytes)

    Time: Day -7-1 (Screening), Day 2, Day 28

    Description: Results of complete blood count: platelets, leukocytes and leukocyte formula (neutrophils, lymphocytes, monocytes, eosinophils, basophils (absolute number). The researcher evaluates each of the parameter in the normal / abnormal categories. Clinically significant abnormalities should be reported as adverse events.

    Measure: To evaluate safety of the vaccine Ad5-nCoV by its effect on results of complete blood count

    Time: Day -7-1 (Screening), Day 2, Day 28

    Description: Results of complete blood count: erythrocyte sedimentation rate The researcher evaluates each of the parameter in the normal / abnormal categories. Clinically significant abnormalities should be reported as adverse events.

    Measure: To evaluate safety of the vaccine Ad5-nCoV by its effect on results of complete blood count (erythrocyte sedimentation rate)

    Time: Day -7-1 (Screening), Day 2, Day 28

    Description: Results of coagulogram: activated partial thromboplastin time, prothrombin time. The researcher evaluates each of the parameter in the normal / abnormal categories. Clinically significant abnormalities should be reported as adverse events.

    Measure: To evaluate safety of the vaccine Ad5-nCoV by its effect on results of coagulogram

    Time: Day -7-1 (Screening), Day 2, Day 28

    Description: Results of coagulogram: fibrinogen. The researcher evaluates each of the parameter in the normal / abnormal categories. Clinically significant abnormalities should be reported as adverse events.

    Measure: To evaluate safety of the vaccine Ad5-nCoV by its effect on results of coagulogram (fibrinogen)

    Time: Day -7-1 (Screening), Day 2, Day 28

    Description: Results of clinical urinalysis: relative density. The researcher evaluates each of the parameter in the normal / abnormal categories. Clinically significant abnormalities should be reported as adverse events.

    Measure: To evaluate safety of the vaccine Ad5-nCoV by its effect on results of clinical urinalysis (relative density)

    Time: Day -7-1 (Screening), Day 2, Day 28

    Description: Results of clinical urinalysis: pH. The researcher evaluates each of the parameter in the normal / abnormal categories. Clinically significant abnormalities should be reported as adverse events.

    Measure: To evaluate safety of the vaccine Ad5-nCoV by its effect on results of clinical urinalysis (pH)

    Time: Day -7-1 (Screening), Day 2, Day 28

    Description: Results of clinical urinalysis: leukocytes, erythrocytes, cylinders . The researcher evaluates each of the parameter in the normal / abnormal categories. Clinically significant abnormalities should be reported as adverse events.

    Measure: To evaluate safety of the vaccine Ad5-nCoV by its effect on results of clinical urinalysis

    Time: Day -7-1 (Screening), Day 2, Day 28

    Description: Results of clinical urinalysis: protein . The researcher evaluates each of the parameter in the normal / abnormal categories. Clinically significant abnormalities should be reported as adverse events.

    Measure: To evaluate safety of the vaccine Ad5-nCoV by its effect on results of clinical urinalysis (protein)

    Time: Day -7-1 (Screening), Day 2, Day 28

    Description: Results of clinical urinalysis:glucose . The researcher evaluates each of the parameter in the normal / abnormal categories. Clinically significant abnormalities should be reported as adverse events.

    Measure: To evaluate safety of the vaccine Ad5-nCoV by its effect on results of clinical urinalysis (glucose)

    Time: Day -7-1 (Screening), Day 2, Day 28

    Description: Results of determination of immunoglobulin E serum concentrations.

    Measure: To evaluate safety of the vaccine Ad5-nCoV by its effect on results of determination of immunoglobulin E serum concentrations.

    Time: Day -7-1 (Screening), Day 28
    341 Phase I Study to Evaluate the Safety, Tolerability, and Pharmacodynamics (PD) of DWRX2003 (Niclosamide IM Depot) Injection Following Intramuscular Administration in COVID-19 Patients

    This study is designed to assess the safety and tolerability of single doses of DWRX2003 in COVID-19 patients.

    NCT04541485
    Conditions
    1. COVID-19 Patients
    Interventions
    1. Drug: DWRX2003
    2. Drug: Placebo

    Primary Outcomes

    Description: Incidence, severity and causality of adverse events (AEs) and serious adverse events (SAEs)

    Measure: Incidence of Treatment-Emergent Adverse Events

    Time: follow-up 42 days after dosing

    Secondary Outcomes

    Measure: Time to SARS-CoV-2 eradication (days) by Nasopharyngeal specimen

    Time: follow-up 42 days after dosing

    Measure: Rate of SARS-CoV-2 eradication by Nasopharyngeal specimen

    Time: at Day 3, 7, 10 and 14
    342 "Nintedanib for the Treatment of SARS-Cov-2 Induced Pulmonary Fibrosis"

    Currently, there is no approved treatment for COVID-19 in France, either for the acute phase, nor for the late chronic phase. the investigator suggest that nintedanib has the potential to block the development of lung fibrosis when initiated early enough to inhibit the activation of mesenchymal cells and the progression of virus-induced pulmonary fibrosis. Computerized Tomography (CT) manifestations of fibrosis or fibrous stripes are described in COVID-19 (Ye, Eur Radiol 2020). Pan et al observed fibrous stripes in 17% patients in the early phase of the disease (Pan, Eur Radiol 2020). Ye et al observed bronchiectasis in 2 patients (15.4%) and evidence of pulmonary fibrosis in 3 patients (23.7%) at HRCT performed at 4 weeks (Ye, Eur Radiol 2020). Long term data are still lacking in patients with COVID-19 and the investigators do not know how many patients will have fibrotic sequelae from the acute illness.

    NCT04541680
    Conditions
    1. SARS-Cov-2 Induced Pulmonary Fibrosis
    Interventions
    1. Drug: Nintedanib 150 MG [Ofev]
    2. Other: Placebo
    MeSH:Pulmonary Fibrosis Fibrosis
    HPO:Pulmonary fibrosis

    Primary Outcomes

    Description: Change in Forced Vital Capacity over 12 months assessed by Annual Rate of Decline in FVC in Overall Population

    Measure: The primary objective is to assess whether nintedanib slows the progression of lung fibrosis in COVID-19 survivors as assessed by the decline in the forced vital capacity (FVC) over 12 months compared to placebo.

    Time: at inclusion and 12 months.

    Secondary Outcomes

    Description: Rate of decline in DLCO estimated by linear regression of DLCO from baseline to 12 months from DLCO measurement at inclusion, 6 and 12 months

    Measure: compare the rate of decline of DLCO over 12 months

    Time: at inclusion, 6 and 12 months

    Description: Absolute change from baseline in the Six-minute walk test (6MWT) at 12 months

    Measure: compare exercise capacity at 12 months

    Time: at 12 months

    Description: HRCT fibrosis score and HRCT fibrosis extension (visual and computer-based assessment) at inclusion and 12 months

    Measure: compare high resolution CT (HRCT) lung opacities extension at 12 months

    Time: at inclusion and 12 months

    Description: Absolute change from baseline in the total score on the St. George's Respiratory Questionnaire questionnaire at 12 months

    Measure: compare change in health-related quality of life

    Time: at 12 months

    Description: Absolute change from baseline in the Dyspnea score (Multidimensional Dyspnea Profile and mMRC score) at 3, 6, 9 and 12 months

    Measure: compare the evolution of dyspnea over time

    Time: at 3, 6, 9 and 12 months

    Description: The absolute change from baseline Hospital Anxiety and Depression score at 3, 6, 9 and 12 months

    Measure: compare change in Depression and anxiety over time

    Time: at 3, 6, 9 and 12 months

    Description: Biomarker assay (KL-6, NT-proBNP, CRP, D-dimers) at inclusion and 12 months

    Measure: compare change in lung injury, pulmonary hypertension and inflammation biomarkers

    Time: at inclusion and 12 months

    Description: Percentage of patients with a tricuspid regurgitation velocity > 2.5, 2.8 and 3.4 m/sec evaluated at baseline and at 12 months.

    Measure: pulmonary hypertension prevalence at inclusion and 12 months

    Time: at inclusion and 12 months

    Description: MUC5B at risk allele detection at inclusion

    Measure: association between genetic susceptibility (MUC5B polymorphism) and lung fibrosis in COVID-19 survivors

    Time: at inclusion

    Description: Incidence of clinical or biological adverse events with nintedanib versus placebo over 12 months

    Measure: safety of nintedanib

    Time: over 12 months
    343 A Phase 2 Randomized Double Blind, Placebo-controlled Study on the Safety and Efficacy of Niclosamide in Patients With COVID-19

    This is a two-part, Phase 2, multicentre, randomized, double blind, 2-arm placebo-controlled study in adults with moderate COVID-19 with gastrointestinal signs and symptoms

    NCT04542434
    Conditions
    1. Covid19
    Interventions
    1. Drug: Niclosamide Oral Tablet
    2. Drug: Placebo

    Primary Outcomes

    Description: All-cause mortality

    Measure: Mortality

    Time: From Day 1 to 6 weeks

    Description: Proportion of patients with Treatment Emergent Adverse Events (TEAE) leading to study drug discontinuation

    Measure: TEAE

    Time: From Day 1 to 6 weeks

    Description: Serious adverse event (SAE) coded by System Organ Class (SOC) and Preferred Term (PT), using the Medical Dictionary for Regulatory Activities (MedDRA)

    Measure: SAEs

    Time: From Day 1 to end of study

    Description: Change in safety laboratory tests from baseline to 6 weeks, the number of subjects with values low, normal, and high compared to the normal ranges pretreatment versus post-treatment will be provided

    Measure: Safety laboratory

    Time: From Day 1 to 6 weeks

    Description: Change in sitting systolic and diastolic blood pressure from baseline to 6 weeks summarized descriptively by visit and presented as shift tables

    Measure: Blood pressure

    Time: From Day 1 to 6 weeks

    Description: time to fecal RNA virus clearance (rectal swab or stool sample) assessed by RT-qPCR in the niclosamide group, compared to the placebo group (Part 2 only)

    Measure: fecal RNA virus clearance

    Time: From Day 1 to 6 weeks

    Description: Change in body temperature from baseline to 6 weeks summarized descriptively by visit and presented as shift tables

    Measure: Body temperature

    Time: From Day 1 to 6 weeks

    Description: Change in heart rate from baseline to 6 weeks summarized descriptively by visit and presented as shift tables

    Measure: Heart rate

    Time: From Day 1 to 6 weeks

    Description: Change in SaO2 from baseline to 6 weeks summarized descriptively by visit and presented as shift tables

    Measure: SaO2

    Time: From Day 1 to 6 weeks

    Description: Change in ECG parameters including: 1. PR interval 2. RR interval 3. QRS interval 4 QT interval 5. HR interval 6. QtcF interval. All intervals summarized descriptively by visit from baseline to 6 weeks

    Measure: ECG

    Time: From Day 1 to 6 weeks
    344 A Randomized, Multi-center, Double-blind, Placebo-controlled Study to Assess the Safety and Efficacy of Monoclonal Antibody VIR-7831 for the Early Treatment of Coronavirus Disease 2019 (COVID-19) in Non-hospitalized Patients

    This is a phase 2/3 study in which subjects with coronavirus disease 2019 (COVID-19) will receive VIR-7831 or placebo and will be assessed for safety, tolerability, efficacy, and pharmacokinetics.

    NCT04545060
    Conditions
    1. Covid19
    Interventions
    1. Biological: VIR-7831
    2. Drug: Placebo

    Primary Outcomes

    Measure: Proportion of participants who have progression of COVID-19 through Day 29

    Time: Up to Day 29

    Secondary Outcomes

    Measure: Occurence of of adverse events (AEs)

    Time: Up to 24 weeks

    Measure: Occurrence of serious adverse events (SAEs)

    Time: Up to 24 weeks

    Measure: Occurrence of adverse events of special interest (AESI)

    Time: Up to 24 weeks

    Measure: Incidence and titers (if applicable) of serum ADA to VIR-7831

    Time: Up to 24 weeks

    Measure: Cmax

    Time: Up to 24 weeks

    Measure: Clast

    Time: Up to 24 weeks

    Measure: Tmax

    Time: Up to 24 weeks

    Measure: Tlast

    Time: Up to 24 weeks

    Measure: AUCinf

    Time: Up to 24 weeks

    Measure: AUClast

    Time: Up to 24 weeks

    Measure: %AUCextrap

    Time: Up to 24 weeks

    Measure: t1/2

    Time: Up to 24 weeks

    Measure: Vz

    Time: Up to 24 weeks

    Measure: Vss

    Time: Up to 24 weeks

    Measure: CL

    Time: Up to 24 weeks

    Measure: Proportion of participants who have progression of COVID-19 as defined by hospitalization >24 hrs or death at Day 8, Day 15, or Day 22

    Time: Up to Day 22

    Measure: Proportion of participants who progress to develop severe and/or critical respiratory COVID-19 as manifest by requirement for and method of supplemental oxygen at Day 8, Day 15, Day 22, or Day 29

    Time: Up to Day 29

    Description: Severity and duration of participant-reported symptoms of COVID-19 related illness using the 34-item COVID-19 adapted FLU-PRO (Influenza Patient-reported outcome) instrument. Higher scores mean worse outcome.

    Measure: Severity and duration of participant-reported symptoms of COVID-19 related illness using the FLU-PRO patient-reported outcome instrument

    Time: Up to 12 weeks

    Measure: Detection of SARS-CoV-2 in nasal secretions by PCR at baseline and during follow-up period through Day 29

    Time: Up to Day 29

    Measure: 29-day, 60-day, and 90-day all-cause mortality

    Time: Up to 90 days
    345 An International Multicenter, Adaptive, Randomized Double-Blind, Placebo-Controlled Trial of the Safety, Tolerability and Efficacy of Anti-Coronavirus Hyperimmune Intravenous Immunoglobulin for the Treatment of Adult Hospitalized Patients at Onset of Clinical Progression of COVID-19

    This protocol will serve as a platform for assessing treatments for adult patients hospitalized for medical management of COVID-19 without related serious end-organ failure. Trials will involve sites around the world strategically chosen to ensure rapid enrollment. This trial will compare hyperimmune intravenous immunoglobulin (hIVIG) with matched placebo, when added to standard of care (SOC), for preventing further disease progression and mortality related to COVID-19. SOC will include remdesivir unless it is contraindicated for an individual patient.

    NCT04546581
    Conditions
    1. COVID
    2. COVID-19
    3. SARS-CoV-2
    4. SARS (Severe Acute Respiratory Syndrome)
    Interventions
    1. Drug: Hyperimmune immunoglobulin to SARS-CoV-2 (hIVIG)
    2. Other: Placebo
    3. Drug: Remdesivir
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome

    Primary Outcomes

    Description: The primary objective is to compare the clinical status of patients in each group on day 7 of follow-up using the primary ordinal outcome with 7 mutually exclusive categories: 7. Death 6. End-organ failure 5. Life-threatening end-organ dysfunction 4. Serious end-organ dysfunction 3. Moderate end-organ dysfunction 2. Limiting symptoms due to COVID-19 1. No limiting symptoms due to COVID-19 Outcome is reported as the percent of participants in each of 7 categories.

    Measure: Ordinal Outcome Scale - Day 7

    Time: 7 days

    Secondary Outcomes

    Description: Outcome reported as the percent of participants who expire for any reason by day 28 post treatment.

    Measure: All-cause mortality through Day 28

    Time: 28 days

    Description: A secondary outcome is to compare the clinical status of patients in each group on day 3, 5, 14, and 28 of follow-up using the primary ordinal outcome. Outcome is reported as the percent of participants in each of 7 categories.

    Measure: Ordinal Outcome Scale

    Time: 3 days, 5 days, 14 days, and 28 days

    Description: The National Early Warning Score (NEWS) is used to determine the degree of illness of a patient and prompt critical care intervention. The score takes into account respiratory rate, oxygen saturation, use of respiratory support, body temperature, blood pressure, and heart rate. These data are entered into a program to calculate a NEW score. Scores range from -3 to +3 with scores closer to zero representing a lower degree of illness. Scores will be collected at baseline and day 7 and the change in score at these 2 time points will be reported.

    Measure: Change in National Early Warning Score (NEWS)

    Time: 7 days

    Description: Time to worsening is defined as the 3 least favorable categories on the primary ordinal scale. Outcome is reported as the percent of participants in each arm who are characterized as categories 5, 6, and 7 on the primary ordinal scale at 7, 14, and 28 days post treatment.

    Measure: Time to Worsening

    Time: 7 days, 14 days, and 28 days

    Description: Outcome is reported as the percent of participants in each arm who are alive and discharged from the hospital to home or rehabilitation at days 7, 14, and 28 post treatment.

    Measure: Discharge Status

    Time: 7 days, 14 days, and 28 days

    Description: Outcome is reported as the mean number of days alive and outside the hospital from study entry to Day 28 for participants in each arm.

    Measure: Days Alive Outside the Hospital

    Time: 28 days

    Description: A secondary outcome is to compare the clinical status of patients in each group on day 3, 5, 7, 14, and 28 post treatment limited to using the pulmonary elements of the primary ordinal outcome (e.g., requirement for invasive ventilation). Outcome is reported as the percent of participants in each arm who fall into each of the 7 categories of the primary ordinal outcome with regard to their pulmonary dysfunction only.

    Measure: Pulmonary-only Components of the Primary Ordinal Outcome

    Time: 3 days, 5 days, 7 days, 14 days, and 28 days

    Description: A secondary outcome is to compare the clinical status of patients in each group on day 3, 5, 7, 14, and 28 post treatment limited to using the thrombotic conditions (e.g., arterial thrombosis) in the primary ordinal outcome. Outcome is reported as the percent of participants in each arm who fall in each of the 7 categories of the primary ordinal outcome with regard to thrombotic conditions only.

    Measure: Thrombotic Components of the Primary Ordinal Outcome

    Time: 3 days, 5 days, 7 days, 14 days, and 28 days

    Description: Time to recovery is defined as the 2 most favorable categories on the primary ordinal scale. Outcome is reported as the percent of participants in each arm who are characterized as categories 1 or 2 at 7, 14, and 28 days post treatment.

    Measure: Time to recovery

    Time: 7 days, 14 days, and 28 days

    Description: Clinical organ dysfunction is defined by new onset of any one or more of the following. Outcome is reported as the percent of participants in each arm who meet any 1 of the following criteria by day 28 post treatment. A) Respiratory dysfunction B) Cardiac and vascular dysfunction C) Renal dysfunction D) Hepatic dysfunction E) Neurological dysfunction F) Haematological dysfunction G) Serious infection

    Measure: Clinical Organ Dysfunction

    Time: 28 days

    Description: Outcome is reported as the percent of participants in each arm who experience a new grade 3 or 4 event, a serious adverse event (SAE), or death through day 7 (primary safety endpoint) post treatment.

    Measure: Safety and Tolerability - Adverse Events

    Time: 7 days

    Description: Outcome is reported as the percent of participants in each arm for who had any grade of reaction during the infusion or within 2 hours afterwards, for whom the infusion is interrupted prior to completion, or for whom the infusion is stopped prior to completion.

    Measure: Safety and Tolerability - Infusion Reactions, Interruptions, or Cessation

    Time: approximately 2 hours

    Description: Outcome is reported as the percent of participants in each arm who experience a serious adverse event (SAE) or death through day 28 post treatment.

    Measure: Safety and Tolerability - Serious Adverse Events

    Time: 28 days

    Description: Outcome is reported as the percent of participants in each arm who experience an adverse event (AE) of any grade present (new or continuing) on days 1, 3, 7, and 28 post treatment.

    Measure: Safety and Tolerability - Prevalence of Adverse Events

    Time: 1 day, 3 days, 7 days, and 28 days

    Description: Outcome reported as the change in anti-SARS-CoV-2 IgG antibody level in blood from baseline to 1, 3, 7, and 28 days post treatment. Outcome is reported in units of antibody titer.

    Measure: Change in Neutralizing Antibody Level

    Time: 1 day, 3 days, 7 days, and 28 days
    346 A Multicenter, Randomized, Double-blind, Placebo-Controlled, Parallel Group Study to Evaluate the Safety and Efficacy of Liquid Alpha1-Proteinase Inhibitor (Human) Plus Standard Medical Treatment (SMT) Versus Placebo Plus SMT in Hospitalized Subjects With COVID-19

    The purpose of the study is to determine if liquid alpha1-proteinase inhibitor (human) (liquid alpha1-PI) plus SMT can reduce the proportion of participants dying or requiring intensive care unit (ICU) admission on or before Day 29 or who are dependent on high flow oxygen devices or invasive mechanical ventilation on Day 29 versus placebo plus SMT in hospitalized participants with COVID-19.

    NCT04547140
    Conditions
    1. COVID-19
    Interventions
    1. Biological: Liquid Alpha1-Proteinase Inhibitor (Human)
    2. Drug: Placebo
    3. Drug: Standard Medical Treatment
    MeSH:Alpha 1-Antitrypsin Deficiency

    Primary Outcomes

    Measure: Percentage of Participants Dying or Requiring ICU Admission

    Time: Up to Day 29

    Measure: Percentage of Participants Who are Dependent on High Flow Oxygen Devices or Invasive Mechanical Ventilation

    Time: Day 29

    Secondary Outcomes

    Measure: Change from Baseline in National Early Warning Score (NEWS)

    Time: Day 1 through Day 29

    Measure: Time to Clinical Response as Assessed by: NEWS ≤ 2 Maintained for 24 hours

    Time: Day 1 through Day 29

    Measure: Time to Hospital Discharge

    Time: Day 1 through Day 29

    Measure: Duration of ICU Stay

    Time: Up to Day 29

    Measure: Duration of Any Oxygen Use

    Time: Day 1 through Day 29

    Measure: Duration of Mechanical Ventilation

    Time: Up to Day 29

    Measure: Mean Change from Baseline in Ordinal Scale

    Time: Day 1 through Day 29

    Measure: Absolute Value Change from Baseline in Ordinal Scale

    Time: Day 1 through Day 29

    Measure: Percentage of Participants in Each Severity Category of the 7-point Ordinal Scale

    Time: Day 15 and Day 29

    Measure: Time to Sustained Normalization of Temperature

    Time: Up to Day 29

    Measure: Percentage of Participants with Normalization of Fever

    Time: Up to Day 29

    Measure: Number of Participants who Develop Acute Respiratory Distress Syndrome (ARDS)

    Time: Up to Day 29

    Measure: Length of Time to Clinical Progression

    Time: Up to Day 29
    347 Antiviral Effects of Tranexamic Acid (TXA) as a Preventative Treatment Following COVID-19 Exposure

    A recent report in Physiolological Reviews proposed that the endogenous protease plasmin acts on SARS-CoV-2 by cleaving a newly inserted furin site in the S protein portion of the virus resulting in increased infectivity and virulence. A logical treatment that might blunt this process would be the inhibition of the conversion of plasminogen to plasmin. Fortunately, there is an inexpensive, commonly used drug, tranexamic acid, TXA, which suppresses this conversion and could be re-purposed for the treatment of COVID-19. TXA is a synthetic analog of the amino acid lysine which reversibly binds four to five lysine receptor sites on plasminogen. This reduces conversion of plasminogen to plasmin, and is normally used to prevent fibrin degradation. TXA is FDA approved for the outpatient treatment of heavy menstrual bleeding (typical dose 1300 mg p.o. TID x 5 days) and off-label use for many other indications. TXA is used perioperatively as a standard-of-care at UAB for orthopedic and cardiac bypass surgeries. It has a long track record of safety such that it is used over-the-counter in other countries as an antiviral and for the treatment of cosmetic dermatological disorders. Given the potential benefit and limited toxicity of TXA it would appear warranted to perform randomized, double-blind placebo controlled exploratory trial at UAB as a prophylactic antiviral treatment following exposure to COVID-19 in order to determine whether it reduces infectivity and virulence of the SARS-CoV-2 virus as hypothesized. Involvement of each patient is only for 7 days before primary endpoints and 30 days for final data collection.

    NCT04550338
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Tranexamic acid
    2. Drug: Placebo

    Primary Outcomes

    Description: RNA testing of nasopharyngeal swabs

    Measure: Conversion from negative to positive COVID-19 test

    Time: Repeat testing after 7 days
    348 The Safety and Efficacy Outcome of Ivermectin Plus Doxycycline in Treatment of RT-PCR Positive Adult Mild Covid-19 Cases: a Randomized Double Blind Placebo Controlled Trial

    A randomized double blind control trial will be done. Total 188 Covid-19 patients will be enrolled in this trial who are RT-PCR confirmed case of mild cases. Before enrollment, base line investigations will be done and as per eligibility criteria 188 (one hundred eighty eight) patients of mild symptoms will be selected by random sampling. Ninety four diagnosed patients (Group-A) of Covid-19 will be in the experimental group and 94 Covid-19 diagnosed patients (Group-B) will be in the control group. Group -A will be given combination treatment of Tab Ivermectin and Cap Doxycycline along with standard therapy and Group -B will be treated by standard therapy with placebo. Follow up will be done every day in both group with all the parameters as stated above and will be documented. On 5th day of treatment, if fever subsides final outcome will be measured by result of RT-PCR test preferably from one designated lab with sample of nasal swab for all. Subject to RT-PCR test negative result again on 6th day another RT-PCR test will be done at 24 hours apart. But if RT-PCR test result remain positive on 5th day, again on 10th day same test is to be done and also on 11th day subject to test result as negative on 10th day. Death of the patients will be documented as well. Regarding safety issues of the drugs we shall monitor for any SAE and would report to the DSMB for proper management guideline

    NCT04551755
    Conditions
    1. Covid19
    Interventions
    1. Drug: Ivermectin and Doxycycline
    2. Other: Placebo

    Primary Outcomes

    Description: Outcome measure of symptoms associated with covid, fever and cough

    Measure: Time to outcome measure of fever (<100.40F)and cough

    Time: 10 days

    Description: If the result of RT-PCR test is negative, then 24 hours apart another RT-PCR test will be done. Subject to 2 consecutive negative tests patient will be declared as cured

    Measure: Negative RT-PCR test on day 5 of treatment

    Time: 10 days
    349 A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of SARS-CoV-2 Neutralizing Antibody BGB-DXP593 in Patients WithMild-to-Moderate COVID-19

    The primary objective of this study is to investigate the safety and tolerability of BGB-DXP593 administered intravenously as a single dose in participants with mild-to-moderate COVID-19.

    NCT04551898
    Conditions
    1. Covid19
    Interventions
    1. Drug: BGB-DXP593
    2. Drug: Placebo

    Primary Outcomes

    Measure: Change from baseline to Day 8 in SARS-CoV-2 viral shedding as measured by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in nasopharyngeal swab samples

    Time: Up to 8 days

    Secondary Outcomes

    Measure: Time-weighted average change in viral shedding as measured by RT-qPCR in nasopharyngeal swab samples

    Time: Baseline to Day 15

    Measure: Change from baseline to Day 15 in SARS-CoV-2 viral shedding as measured by RT-qPCR in nasopharyngeal swab samples

    Time: Baseline to Day 15

    Measure: Time to negative RT-qPCR in all tested samples with no subsequent positive RT-qPCR in any tested samples

    Time: Up to 15 days

    Measure: Number of participants requiring hospitalization due to worsened COVID-19

    Time: Up to 29 days

    Measure: Time to resolution of all COVID-19-related symptoms

    Time: Up to 29 days

    Measure: All-cause mortality rate at Day 29

    Time: Up to 29 days

    Measure: Number of participants experiencing Adverse Events (AEs)

    Time: Up to 85 days

    Measure: Number of participants experiencing Serious Adverse Events (SAEs)

    Time: Up to 85 days
    350 A Randomized, Double-Blind Placebo-Controlled Study to Evaluate the Safety and Efficacy of Rayaldee (Calcifediol) Extended-release Capsules to Treat Symptomatic Patients Infected With SARS-CoV-2 (REsCue)

    This is a phase 2, single or multi-center, randomized, double-blind placebo-controlled study to evaluate the safety and efficacy of Rayaldee (CTAP101 Capsules) to treat adult subjects with mild to moderate COVID-19 who test positive for SARS-CoV-2 via nasopharynx swab and subsequent reverse transcription polymerase chain reaction (RT-PCR).

    NCT04551911
    Conditions
    1. Covid19
    2. Coronavirus
    3. SARS-CoV-2 Infection
    Interventions
    1. Drug: Rayaldee 30Mcg Extended-Release (ER) Capsule
    2. Drug: Placebo
    MeSH:Coronavirus Infections

    Primary Outcomes

    Description: The FLU- PRO© questionnaire was specifically designed and validated to evaluate in clinical trials the presence, severity and duration of symptoms associated with viral infections. It contains 32 items (eg, felt hot, sweating, headache), grouped into 6 domains, that provide a comprehensive evaluation of such symptoms, using 5-point scales (values ranging from 0 to 4) with higher scores indicating worse symptoms.

    Measure: Severity and duration of disease as evidenced by COVID-19 symptoms using the FLU-PRO© questionnaire.

    Time: 42 days

    Measure: Concentration of serum total 25-hydroxyvitamin D maintained at or above 50 ng/mL.

    Time: 28 days
    351 Effects of Nitazoxanide Administration to Patients in the Initial Phase of COVID-19

    Multicenter, randomized, placebo-controlled, parallel, blinded, interventional, treatment clinical trial with two arms. Population: 392 Patients with COVID-19 (Coronavirus Disease-19), confirmed by RT-PCR (Real Time polymerase chain reaction), symptomatic in the early phase of the disease. Experimental group: 196 patients, nitazoxanide 500mg 8 / 8 hours for 5 days. Control group: 196 patients, placebo 8/8 hours for 5 days.

    NCT04552483
    Conditions
    1. Covid19
    2. Coronavirus
    Interventions
    1. Drug: Nitazoxanide
    2. Drug: Placebo
    MeSH:Coronavirus Infections

    Primary Outcomes

    Description: Reduction in the duration of fever of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide compared to patients treated with placebo; verified through the collection of information with the patient; quantified by the number of days that presented the symptom.

    Measure: Days with fever

    Time: Day8

    Description: Reduction in the duration of cough of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide compared to patients treated with placebo; verified through the collection of information with the patient; quantified by the number of days that presented the symptom.

    Measure: Days with cough

    Time: Day8

    Description: Reduction in the duration of asthenia of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide compared to patients treated with placebo; verified through the collection of information with the patient; quantified by the number of days that presented the symptom.

    Measure: Days with asthenia

    Time: Day8

    Secondary Outcomes

    Description: Compare the evolution of viral load in naso- and oropharyngeal swab in patients with COVID-19 treated with nitazoxanide or placebo on day 1; verified using the RT-PCR technique; quantified by the absolute number

    Measure: SARS-COV-2 viral load - absolute number

    Time: Day1

    Description: Compare the evolution of viral load in naso- and oropharyngeal swab in patients with COVID-19 treated with nitazoxanide or placebo on day 8; verified using the RT-PCR technique; quantified by the absolute number.

    Measure: SARS-COV-2 viral load - absolute number

    Time: Day8

    Description: Compare the evolution of viral load in naso- and oropharyngeal swab in patients with COVID-19 treated with nitazoxanide or placebo on day 1; verified using the RT-PCR technique; quantified by the percentage change between the two groups.

    Measure: SARS-COV-2 viral load - percentage

    Time: Day 1

    Description: Compare the evolution of viral load in naso- and oropharyngeal swab in patients with COVID-19 treated with nitazoxanide or placebo on day 8; verified using the RT-PCR technique; quantified by the percentage change between the two groups.

    Measure: SARS-COV-2 viral load - percentage

    Time: Day 8

    Description: Compare the hospital admission rate of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, in the period of 8 days; verified by information actively collected from patients or family members; quantified by absolute number.

    Measure: Hospital admission rate - absolute number

    Time: Day8

    Description: Compare the hospital admission rate of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, in the period of 8 days; verified by information actively collected from patients or family members; quantified by percentage.

    Measure: Hospital admission rate - percentage

    Time: Day8

    Description: Compare the levels of inflammatory mediators: (interleukin [IL] -6 from patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 3; verified by the measurement of cytokines in patient serum by the ELISA technique; quantified by the absolute number between the two groups.

    Measure: Serum Interleukin-6

    Time: Day 3

    Description: Compare the levels of inflammatory mediators: (interleukin [IL] -6 from patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 8; verified by the measurement of cytokines in patient serum by the ELISA technique; quantified by the absolute number between the two groups.

    Measure: Serum Interleukin-6

    Time: Day 8

    Description: Compare the levels of inflammatory mediators: IL-1-beta from patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 3; verified by the measurement of cytokines in patient serum by the ELISA technique; quantified by the absolute number between the two groups.

    Measure: Serum Interleukin-1-beta

    Time: Day 3

    Description: Compare the levels of inflammatory mediators: IL-1-beta from patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 8; verified by the measurement of cytokines in patient serum by the ELISA technique; quantified by the absolute number between the two groups.

    Measure: Serum Interleukin-1-beta

    Time: Day 8

    Description: Compare the levels of inflammatory mediators: IL-8 from patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 3; verified by the measurement of cytokines in patient serum by the ELISA technique; quantified by the absolute number between the two groups.

    Measure: Serum Interleukin-8

    Time: Day 3

    Description: Compare the levels of inflammatory mediators: IL-8 from patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 8; verified by the measurement of cytokines in patient serum by the ELISA technique; quantified by the absolute number between the two groups.

    Measure: Serum Interleukin-8

    Time: Day 8

    Description: Compare the levels of inflammatory mediators: tumor necrosis factor (TNF)-alfa from patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 3; verified by the measurement of cytokines in patient serum by the ELISA technique; quantified by the absolute number between the two groups.

    Measure: Serum tumor necrosis factor (TNF)-alfa

    Time: Day 3

    Description: Compare the levels of inflammatory mediators: tumor necrosis factor (TNF)-alfa from patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 8; verified by the measurement of cytokines in patient serum by the ELISA technique; quantified by the absolute number between the two groups.

    Measure: Serum tumor necrosis factor (TNF)-alfa

    Time: Day 8

    Description: Compare the levels of inflammatory mediators: interferon-gamma from patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 3; verified by the measurement of cytokines in patient serum by the ELISA technique; quantified by the absolute number between the two groups.

    Measure: Serum interferon-gamma

    Time: Day 3

    Description: Compare the levels of inflammatory mediators: interferon-gamma from patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 8; verified by the measurement of cytokines in patient serum by the ELISA technique; quantified by the absolute number between the two groups.

    Measure: Serum interferon-gamma

    Time: Day 8

    Description: Compare the levels of inflammatory mediators: monocyte chemoattractant protein (MCP)-1 from patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 3; verified by the measurement of cytokines in patient serum by the ELISA technique; quantified by the absolute number between the two groups.

    Measure: Serum monocyte chemoattractant protein (MCP)-1

    Time: Day 3

    Description: Compare the levels of inflammatory mediators: monocyte chemoattractant protein (MCP)-1 from patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 8; verified by the measurement of cytokines in patient serum by the ELISA technique; quantified by the absolute number between the two groups.

    Measure: Serum monocyte chemoattractant protein (MCP)-1

    Time: Day 8

    Description: Evaluate evolution of complete blood count with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 3; verified by laboratory tests and expressed by the absolute number between the two groups.

    Measure: Complete blood count

    Time: Day 3

    Description: Evaluate evolution of complete blood count with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 8; verified by laboratory tests and expressed by the absolute number between the two groups.

    Measure: Complete blood count

    Time: Day 8

    Description: To evaluate the levels of C-reactive protein (CRP) of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 3; verified by laboratory tests and expressed by the absolute number between the two groups.

    Measure: C-reactive protein - absolute number

    Time: Day 3

    Description: To evaluate the levels of C-reactive protein (CRP) of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 8; verified by laboratory tests and expressed by the absolute number between the two groups.

    Measure: C-reactive protein - absolute number

    Time: Day 8

    Description: To evaluate the levels of C-reactive protein (CRP) of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 3; verified by laboratory tests and expressed by the percentage between the two group.

    Measure: C-reactive protein - percentage

    Time: Day 3

    Description: To evaluate the levels of C-reactive protein (CRP) of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 8; verified by laboratory tests and expressed by the percentage between the two groups.

    Measure: C-reactive protein - percentage

    Time: Day 8

    Other Outcomes

    Description: Assess the incidence and profile of adverse events reported throughout the study, by treatment group; verified by information actively collected from patients or family members; quantified by percentage.

    Measure: Adverse events - percentage

    Time: Day 8

    Description: Assess the incidence and profile of adverse events reported throughout the study, by treatment group; verified by information actively collected from patients or family members; quantified by absolute number.

    Measure: Adverse events - absolute number

    Time: Day8

    Description: Assess the rate of treatment discontinuation due to adverse events; verified by information actively collected from patients or family members; quantified by absolute number.

    Measure: Treatment discontinuation rate - absolute number

    Time: Day8

    Description: Assess the rate of treatment discontinuation due to adverse events; verified by information actively collected from patients or family members; quantified by percentage.

    Measure: Treatment discontinuation rate - percentage

    Time: Day8
    352 A Pilot, Randomized, Placebo-Controlled Trial of GC4419 (Avasopasem Manganese) in Patients With Critical Illness Due to SARS-CoV-2 Infection (COVID-19)

    A Trial of GC4419 in Patients with Critical Illness due to COVID-19

    NCT04555096
    Conditions
    1. Covid19
    2. SARS-CoV-2 Infection
    Interventions
    1. Drug: GC4419
    2. Drug: Placebo
    MeSH:Infection Critical Illness

    Primary Outcomes

    Measure: 28 day all-cause mortality

    Time: 28 days
    353 A Prospective, Open-label, Randomized, Multi-center, Phase 2a Study to Evaluation the Dose Response, Efficacy and Safety of Hyper-Ig (Hyper-immunoglobulin) GC5131 in Patients With COVID-19

    The objective of this study is to evaluate the efficacy and safety of 5131A for hospitalized patients of COVID-19.

    NCT04555148
    Conditions
    1. Covid19
    Interventions
    1. Biological: GC5131
    2. Other: Placebo

    Primary Outcomes

    Description: The percent of participants reduced by 2 points or more

    Measure: Ordinal scale outcome

    Time: 7, 14, 21, 28 days

    Secondary Outcomes

    Description: The percents of negative patients for COVID-19 virus

    Measure: Viral negative

    Time: 1, 3, 5, 7, 10 days

    Description: The change of NEWS from baseline

    Measure: Change in NEWS

    Time: 7, 14, 21, 28 days

    Description: The percent of participants

    Measure: mortality

    Time: 28 days
    354 A Phase III, Randomized, Placebo-controlled, Clinical Trial to Evaluate the Efficacy and Safety of Co-administered Niclosamide in Patients Treated With an Established Regimen for Novel Coronavirus Infectious Disease (COVID-19)

    This study aims to investigate the potential antiviral efficacy and safety of a novel formulation of Niclosamide; a well-known antihelmintic agent, together with an established COVID-19 treatment regimen in patients. The aim of this study is to evaluate the safety and efficacy profile of niclosamide from the test product (Niclosamide 200 mg/10 mL Suspension) in patients treated for the novel coronavirus infectious disease (COVID-19) in a placebo controlled phase III trial. Both treatment groups will receive an established treatment regimen against COVID-19 together with either niclosamide or placebo. The efficacy and safety of the molecule is well-known and the properties of novel formulation is well-established. The promising in vitro results of niclosamide as an antiviral compound is well documented and make it an ideal candidate as a therapy against SARS-CoV 2 infection. A good safety profile is expected with solid antiviral activity.

    NCT04558021
    Conditions
    1. Covid19
    Interventions
    1. Drug: Niclosamide suspension
    2. Other: Placebo

    Primary Outcomes

    Description: The physician will check for the following symptoms: Fever: axillary temperature ≤36.6°C or oral temperature ≤37.2 °C; Respiratory rate: ≤24/minute on room air; Oxygen saturation: >94% on room air; Cough: mild or absent on a patient reported scale of severe, moderate, mild, absent.)

    Measure: Physician's judgment on clinical recovery from the time of admission

    Time: Day 1 to day 19

    Secondary Outcomes

    Description: (National Early Warning Score 2) to 0 to 3 (Improvement in fever, respiratory rate, oxygen saturation,alleviation of cough scores to 3 points to 0 in 72 hours)

    Measure: Clinical improvement in NEWS2

    Time: 3 days from admission

    Description: An elevated D-dimer,ferritin, thrombocyte, PT, aPTT, troponine and fibrinogen were associated with a poor outcome in COVID19. These parameters will be checked on day 1 and day 3.

    Measure: Improvement in serum biomarkers

    Time: Day 1 to day 3

    Description: Requirement for indotracheal intubation is a key outcome for unsuccesful treatment

    Measure: Requirement for indotracheal intubation

    Time: Day 1 to day 19

    Description: Occurrence of Macrophage Activation Syndrome(MAS) will alert the physician that the patients condition is worsening.

    Measure: Occurrence of Macrophage Activation Syndrome(MAS)

    Time: Day 1 to day 19

    Description: Occurrence of Coagulopathy will alert the physician that the patients condition is worsening.

    Measure: Occurrence of Coagulopathy

    Time: Day 1 to day 19

    Other Outcomes

    Description: The assessment of safety will be based on CTCAE v4.0

    Measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

    Time: Day 1 to day 19
    355 A Randomized, Double-Blind, Placebo-Controlled, Dose Escalation Phase I Clinical Study to Evaluate Safety and Pharmacokinetics of HLX70 in Healthy Adult Volunteers

    A Randomized, Double-Blind, Placebo-Controlled, Dose Escalation Phase I Clinical Study to Evaluate Safety and Pharmacokinetics of HLX70 in Healthy Adult Volunteers

    NCT04561076
    Conditions
    1. COVID 19
    Interventions
    1. Drug: HLX70
    2. Other: Placebo

    Primary Outcomes

    Measure: Number of participants with adverse events, serious adverse event and infusion-related reactions as assessed by CTCAE v5.0

    Time: up to 92 days

    Description: The proportion of subjects undergoing DLT events

    Measure: Safety evaluation- proportion of subjects undergoing DLT events

    Time: Days 1 to 7

    Secondary Outcomes

    Measure: PK parameters-Areas under the concentration-time curves

    Time: pre-infusion (pre-dose), immediately post-infusion, 3 hours, 6 hours and 10 hours post-infusion, Days 2, 3, 5, 8, 11, 15, 22, 29, 43, 57, 71 and 92.

    Measure: PK parameters-Maximum measured concentration

    Time: pre-infusion (pre-dose), immediately post-infusion, 3 hours, 6 hours and 10 hours post-infusion, Days 2, 3, 5, 8, 11, 15, 22, 29, 43, 57, 71 and 92.

    Measure: PK parameters-Time from dosing to maximum measured concentration

    Time: pre-infusion (pre-dose), immediately post-infusion, 3 hours, 6 hours and 10 hours post-infusion, Days 2, 3, 5, 8, 11, 15, 22, 29, 43, 57, 71 and 92.

    Measure: PK parameters-Terminal phase elimination rate constant

    Time: pre-infusion (pre-dose), immediately post-infusion, 3 hours, 6 hours and 10 hours post-infusion, Days 2, 3, 5, 8, 11, 15, 22, 29, 43, 57, 71 and 92.

    Measure: PK parameters-Terminal phase elimination half life

    Time: pre-infusion (pre-dose), immediately post-infusion, 3 hours, 6 hours and 10 hours post-infusion, Days 2, 3, 5, 8, 11, 15, 22, 29, 43, 57, 71 and 92.

    Measure: PK parameters-Clearance

    Time: pre-infusion (pre-dose), immediately post-infusion, 3 hours, 6 hours and 10 hours post-infusion, Days 2, 3, 5, 8, 11, 15, 22, 29, 43, 57, 71 and 92.

    Measure: PK parameters-Volume of distribution during terminal phase and at steady state

    Time: pre-infusion (pre-dose), immediately post-infusion, 3 hours, 6 hours and 10 hours post-infusion, Days 2, 3, 5, 8, 11, 15, 22, 29, 43, 57, 71 and 92.

    Measure: PK parameters-Mean residence time

    Time: pre-infusion (pre-dose), immediately post-infusion, 3 hours, 6 hours and 10 hours post-infusion, Days 2, 3, 5, 8, 11, 15, 22, 29, 43, 57, 71 and 92.

    Description: The number of presence subjects that develop of anti-durg antibody (immunogenicity)

    Measure: Anti-drug antibody

    Time: pre-infusion and Days 15, day 29, day 57, and day 92
    356 Nitazoxanide for Moderate to Severe COVID-19 Pneumonia: a Multicenter, Randomized, Placebo-controlled, Double-Blind Clinical Trial

    Multicenter, randomized, placebo-controlled, parallel, blinded, interventional, treatment clinical trial with two arms. Population: 500 Hospitalized patients with pneumonia derived from COVID-19 (Coronavirus Disease-19), either confirmed by RT-PCR (Real Time polymerase chain reaction), or suggested by typical findings on the computed tomography scan symptomatic. Experimental group: nitazoxanide 500mg 8 / 8 hours for 5 days. Control group: placebo 8/8 hours for 5 days.

    NCT04561219
    Conditions
    1. Covid19
    2. Corona Virus Infection
    3. Pneumonia, Viral
    Interventions
    1. Drug: Nitazoxanide
    2. Drug: Placebo
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia, Viral Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Compare the intubation rate of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, in the period of 14 days; verified by clinical evolution; quantified by percentage.

    Measure: Orotracheal intubation rate

    Time: 14 days

    Description: Compare the number of days patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, stayed free of mechanical ventilation, in the period of 14 days; verified by clinical evolution; quantified by absolute number.

    Measure: Mechanical ventilation free days

    Time: 14 days

    Secondary Outcomes

    Description: Compare the number of days patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, stayed at the hospital, in the period of 14 days; verified by clinical evolution; quantified by absolute number.

    Measure: Hospitalisation days

    Time: 14 days

    Description: Compare the number of days patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, stayed at the ICU, in the period of 14 days; verified by clinical evolution; quantified by absolute number.

    Measure: ICU days

    Time: 14 days

    Description: Compare the number of days patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, stayed with the support of oxygen nasal cannula, in the period of 14 days; verified by clinical evolution; quantified by absolute number.

    Measure: Intranasal oxygen support days

    Time: 14 days

    Description: Compare the mortality rate of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, in the period of 14 days; verified by clinical evolution; quantified by absolute number.

    Measure: Mortality rate

    Time: 14 days

    Description: Reduction in the duration of fever of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide compared to patients treated with placebo; verified through the collection of clinica data; quantified by the number of days that presented the symptom.

    Measure: Days with fever

    Time: 14 days

    Description: Reduction in the duration of cough of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide compared to patients treated with placebo; verified through the collection of clinica data; quantified by the number of days that presented the symptom.

    Measure: Days with cough

    Time: 14 days

    Description: Reduction in the duration of dyspnea of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide compared to patients treated with placebo; verified through the collection of clinica data; quantified by the number of days that presented the symptom.

    Measure: Days with dyspnea

    Time: 14 days

    Description: Compare chest tomographic findings of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide compared to patients treated with placebo; verified through the collection of radiologic data; quantified by the number of patients that presented the a list of alterations.

    Measure: Radiologic findings

    Time: Day1

    Description: Compare chest tomographic findings of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide compared to patients treated with placebo; verified through the collection of radiologic data; quantified by the number of patients that presented the a list of alterations.

    Measure: Radiologic findings

    Time: Day7

    Description: Compare echocardiographic findings of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide compared to patients treated with placebo; verified through the collection of echocardiographic data; quantified by the number of patients that presented the a list of alterations.

    Measure: Cardiologic findings

    Time: Day1

    Description: Compare echocardiographic findings of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide compared to patients treated with placebo; verified through the collection of echocardiographic data; quantified by the number of patients that presented the a list of alterations.

    Measure: Cardiologic findings

    Time: Day7

    Description: To evaluate the levels of C-reactive protein (CRP) of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 1; verified by laboratory tests and expressed by the absolute number between the two groups.

    Measure: C-reactive protein - absolute number

    Time: Day 1

    Description: To evaluate the levels of C-reactive protein (CRP) of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 3; verified by laboratory tests and expressed by the absolute number between the two groups.

    Measure: C-reactive protein serum levels

    Time: Day 3

    Description: To evaluate the levels of C-reactive protein (CRP) of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 7; verified by laboratory tests and expressed by the absolute number between the two groups.

    Measure: C-reactive protein serum levels

    Time: Day 7

    Description: To evaluate the levels of lactate dehydrogenase (LDH) of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 1; verified by laboratory tests and expressed by the absolute number between the two groups.

    Measure: Lactate dehydrogenase (LDH) serum levels

    Time: Day 1

    Description: To evaluate the levels of lactate dehydrogenase (LDH) of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 3; verified by laboratory tests and expressed by the absolute number between the two groups.

    Measure: Lactate dehydrogenase (LDH) serum levels

    Time: Day 3

    Description: To evaluate the levels of lactate dehydrogenase (LDH) of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 7; verified by laboratory tests and expressed by the absolute number between the two groups.

    Measure: Lactate dehydrogenase (LDH) serum levels

    Time: Day 7

    Description: To evaluate the levels of troponin of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 1; verified by laboratory tests and expressed by the absolute number between the two groups.

    Measure: Troponin serum levels

    Time: Day 1

    Description: To evaluate the levels of troponin of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 3; verified by laboratory tests and expressed by the absolute number between the two groups.

    Measure: Troponin serum levels

    Time: Day 3

    Description: To evaluate the levels of troponin of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 7; verified by laboratory tests and expressed by the absolute number between the two groups.

    Measure: Troponin serum levels

    Time: Day 7

    Description: To evaluate the levels of electrolytes of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 1; verified by laboratory tests and expressed by the absolute number between the two groups.

    Measure: Electrolytes serum levels

    Time: Day 1

    Description: To evaluate the levels of electrolytes of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 3; verified by laboratory tests and expressed by the absolute number between the two groups.

    Measure: Electrolytes serum levels

    Time: Day 3

    Description: To evaluate the levels of electrolytes of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 7; verified by laboratory tests and expressed by the absolute number between the two groups.

    Measure: Electrolytes serum levels

    Time: Day 7

    Description: To evaluate the levels of glucose of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 1; verified by laboratory tests and expressed by the absolute number between the two groups.

    Measure: Glucose serum levels

    Time: Day 1

    Description: To evaluate the levels of glucose of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 3; verified by laboratory tests and expressed by the absolute number between the two groups.

    Measure: Glucose serum levels

    Time: Day 3

    Description: To evaluate the levels of glucose of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 7; verified by laboratory tests and expressed by the absolute number between the two groups.

    Measure: Glucose serum levels

    Time: Day 7

    Description: To evaluate renal function of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 1; verified by laboratory tests and expressed by the absolute number between the two groups.

    Measure: Renal function

    Time: Day 1

    Description: To evaluate renal function of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 3; verified by laboratory tests and expressed by the absolute number between the two groups.

    Measure: Renal function

    Time: Day 3

    Description: To evaluate renal function of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 7; verified by laboratory tests and expressed by the absolute number between the two groups.

    Measure: Renal function

    Time: Day 7

    Description: To evaluate coagulogram of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 1; verified by laboratory tests and expressed by the absolute number between the two groups.

    Measure: Coagulogram

    Time: Day 1

    Description: To evaluate coagulogram of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 3; verified by laboratory tests and expressed by the absolute number between the two groups.

    Measure: Coagulogram

    Time: Day 3

    Description: To evaluate coagulogram of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 7; verified by laboratory tests and expressed by the absolute number between the two groups.

    Measure: Coagulogram

    Time: Day 7

    Description: To evaluate liver function panel of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 1; verified by laboratory tests and expressed by the absolute number between the two groups.

    Measure: Liver function panel

    Time: Day 1

    Description: To evaluate liver function panel of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 3; verified by laboratory tests and expressed by the absolute number between the two groups.

    Measure: Liver function panel

    Time: Day 3

    Description: To evaluate liver function panel of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 7; verified by laboratory tests and expressed by the absolute number between the two groups.

    Measure: Liver function panel

    Time: Day 7

    Description: To evaluate ferritin of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 1; verified by laboratory tests and expressed by the absolute number between the two groups.

    Measure: Ferritin

    Time: Day 1

    Description: To evaluate ferritin of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 3; verified by laboratory tests and expressed by the absolute number between the two groups.

    Measure: Ferritin

    Time: Day 3

    Description: To evaluate ferritin of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 7; verified by laboratory tests and expressed by the absolute number between the two groups.

    Measure: Ferritin

    Time: Day 7

    Description: To evaluate D-dimer of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 1; verified by laboratory tests and expressed by the absolute number between the two groups.

    Measure: D-dimer

    Time: Day 1

    Description: To evaluate D-dimer of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 3; verified by laboratory tests and expressed by the absolute number between the two groups.

    Measure: D-dimer

    Time: Day 3

    Description: To evaluate D-dimer of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 7; verified by laboratory tests and expressed by the absolute number between the two groups.

    Measure: D-dimer

    Time: Day 7

    Description: To evaluate blood cell count of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, for 7 days; verified by laboratory tests and expressed by the absolute number between the two groups.

    Measure: Blood cell count

    Time: 7 days

    Description: To evaluate D-dimer of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 1; verified by laboratory tests and expressed by the absolute number between the two groups.

    Measure: Inflammatory mediators

    Time: Day 1

    Description: To evaluate D-dimer of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 3; verified by laboratory tests and expressed by the absolute number between the two groups.

    Measure: Inflammatory mediators

    Time: Day 3

    Description: To evaluate D-dimer of patients with COVID-19 submitted to the therapeutic protocol with nitazoxanide with patients with COVID-19 treated with placebo, on day 7; verified by laboratory tests and expressed by the absolute number between the two groups.

    Measure: Inflammatory mediators

    Time: Day 7

    Other Outcomes

    Description: Assess the incidence and profile of adverse events reported throughout the study, by treatment group; verified by information actively collected from patients or family members; quantified by percentage.

    Measure: Adverse events - percentage

    Time: Day 14

    Description: Assess the incidence and profile of adverse events reported throughout the study, by treatment group; verified by information actively collected from patients or family members; quantified by absolute number.

    Measure: Adverse events - absolute number

    Time: Day 14

    Description: Assess the rate of treatment discontinuation due to adverse events; verified by information actively collected from patients or family members; quantified by absolute number.

    Measure: Treatment discontinuation rate - absolute number

    Time: Day 14

    Description: Assess the rate of treatment discontinuation due to adverse events; verified by information actively collected from patients or family members; quantified by percentage.

    Measure: Treatment discontinuation rate - percentage

    Time: Day 14
    357 A Randomized, Double-Blind, Study Comparing the Efficacy, Safety, and Tolerability of Oral Administration of Ribavirin (RBV) and Nitazoxamide (NTZ)Versus Placebo in SARS-CoV-2 Virus Infected Participants (DuACT)

    This is a single center, randomized, double-blind, 2-arm, parallel-group study of DuACT in participants with clinical symptoms of COVID-19 that have begun within the past 48 hours prior to testing.

    NCT04563208
    Conditions
    1. Covid19
    2. SARS-CoV Infection
    Interventions
    1. Drug: Placebo
    2. Drug: DuACT
    MeSH:Coronavirus Infections Severe A Severe Acute Respiratory Syndrome

    Primary Outcomes

    Description: Rate of decline in viral load over the 10 days after randomization between participants treated with RBV and NTZ for COVID-19 and placebo

    Measure: Rate of decline in viral load

    Time: 10 days

    Secondary Outcomes

    Description: Time to resolution of viral load, defined by reduction of virus below LLOQ and maintaining it for 2 days.

    Measure: Time to resolution of viral load

    Time: 28 days

    Description: Comparison of proportion of subjects who are asymptomatic and symptomatic at day 10

    Measure: Comparison of proportion of subjects who are asymptomatic and symptomatic

    Time: 10 days

    Description: To assess the rate of decline in viral load over days 3 and 6 after randomization

    Measure: Rate of decline in viral load

    Time: Days 3 and 6

    Description: Assess change in modified National Early Warning System-2 items on a scale of 0 to 20. HIgher scores meaning greater clinical risk.

    Measure: Change in modified NEWS-2

    Time: 28 days

    Description: Proportion of subjects with treatment emergent adverse events leading to study drug discontinuation

    Measure: Proportion of subjects with treatment emergent adverse events

    Time: 28 days
    358 Сlinical Trial of Efficacy, Safety and Immunogenicity of Combined Vector Vaccine Gam-COVID-Vac in SARS-СoV-2 Infection Prophylactic Treatment in Republic of Belarus

    Randomized, double-blind (blinded for the trial subject and the study physician), placebo controlled, multi-center clinical trial in parallel assignment of efficacy, immunogenicity, and safety of the Gam-COVID-Vac combined vector vaccine against the SARS-CoV-2-induced coronavirus infection in adults in the SARS-СoV-2 infection prophylactic treatment.

    NCT04564716
    Conditions
    1. Covid19
    Interventions
    1. Biological: Gam-COVID-Vac
    2. Other: Placebo

    Primary Outcomes

    Description: Demonstrate the superiority of Gam-COVID-Vac combined vector vaccine against the SARS-CoV-2-induced coronavirus infection compared to placebo, based on the percentage of trial subjects with coronavirus disease 2019 (COVID-19) developed within 6 months after the second dose of the study drug/placebo, as confirmed with the method of polymerase chain reaction (PCR)

    Measure: percentage of trial subjects with coronavirus disease 2019 (COVID-19) developed within 6 months after the first dose

    Time: through the whole study, an average of 180 days

    Secondary Outcomes

    Description: Assess the efficacy of the Gam-COVID-Vac combined vector vaccine against the SARS-CoV-2-induced coronavirus compared to placebo, based on the severity of the clinical course of COVID-19

    Measure: the severity of the clinical course of COVID-19

    Time: through the whole study, an average of 180 days

    Description: Assess the immunogenicity of the Gam-COVID-Vac combined vector vaccine against the SARS-CoV-2-induced coronavirus infection compared to placebo, based on the geometric mean titer of SARS-CoV-2 glycoprotein-specific antibodies

    Measure: Changing of antibody levels against the SARS-CoV-2 glycoprotein S

    Time: day before injecting the first dose of the study drug/placebo and 42±2 and 180±14 days after the first dose

    Description: Incidence of adverse events in trial subjects compared to placebo

    Measure: Incidence of adverse events in trial subjects

    Time: through the whole study, an average of 180 days

    Description: Severity of adverse events in trial subjects compared to placebo

    Measure: Severity of adverse events in trial subjects

    Time: through the whole study, an average of 180 days
    359 A Randomized, Double-blind, Dose-ranging, Placebo Controlled, Phase 2a Evaluation of the Safety, Tolerability, and Pharmacokinetics of PLN-74809 in Participants With Acute Respiratory Distress Syndrome (ARDS) Associated With at Least Severe COVID-19 (INTEGRIS-ARDS)

    Evaluation of the safety, tolerability, and pharmacokinetics of PLN-74809 in participants with acute respiratory distress syndrome (ARDS) associated with at least severe COVID-19

    NCT04565249
    Conditions
    1. Acute Respiratory Distress Syndrome
    2. SARS-CoV-2
    Interventions
    1. Drug: PLN-74809
    2. Drug: Placebo
    MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

    Primary Outcomes

    Measure: Number of participants with treatment-related adverse events and laboratory abnormalities, assessed by CTCAE V5.0

    Time: Up to 90 days

    Secondary Outcomes

    Measure: Assessment of PLN-74809 plasma concentrations

    Time: up to 14 days

    Other Outcomes

    Measure: Number of participants alive and free of invasive mechanical ventilation

    Time: up to 28 days

    Measure: Number of participants alive and discharged from hospital

    Time: Up to 28 days

    Measure: Number of participants alive and discharged from hospital

    Time: Up to 90 days
    360 A Randomized, Double Blind, Placebo-controlled, Phase 2 Clinical Trial to Investigate the Efficacy and Safety of 2 Doses of NuSepin® Intravenous Infusion in COVID-19 Pneumonia Patients

    A randomized, double blind, placebo-controlled, phase 2 clinical trial to investigate the efficacy and safety of 2 doses of NuSepin® intravenous infusion in COVID-19 pneumonia patients

    NCT04565379
    Conditions
    1. COVID19 Pneumonia
    Interventions
    1. Drug: NuSepin® 0.1 mg
    2. Drug: NuSepin® 0.2 mg
    3. Drug: Placebo
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Measure: Difference in Time to Clinical Improvement (TTCI) between the 2 treatments and the placebo group (in days)

    Time: Day 29

    Secondary Outcomes

    Measure: Percentage of patients with CRP < 10 mg/L or < 30% decreases from baseline

    Time: Day 15 and Day 29

    Description: Minimum value being 1, Maximum value being 6. Smaller the number, better the clinical status & outcome

    Measure: Clinical Status assessed by the six-category ordinal scale at fixed time points

    Time: Day 1, 4, 9, 15 and 29

    Measure: Time to complete clinical remission OR NEWS2 (National Early Warning Score 2) of ≤ 2 maintained for 24 hours

    Time: Up to Day 29

    Measure: All-cause mortality

    Time: Up to Day 29

    Measure: Duration (days) of mechanical ventilation

    Time: Up to Day 29

    Measure: Duration (days) of extracorporeal membrane oxygenation

    Time: Up to Day 29

    Measure: Duration (days) of supplemental oxygenation

    Time: Up to Day 29

    Measure: Length of hospital stay (days)

    Time: Up to Day 29

    Measure: Length of ICU stay (days)

    Time: Up to Day 29

    Measure: Number of incidence of treatment emergent adverse events (TEAEs) in 3 treatment groups

    Time: Day 15 and Day 29

    Other Outcomes

    Measure: Serum level of TNF-α in pg/ml

    Time: Day 0, 4, 9, 15 and 29

    Measure: Serum level of IL-1β in pg/ml

    Time: Day 0, 4, 9, 15 and 29

    Measure: Serum level of IL-6 in pg/ml

    Time: Day 0, 4, 9, 15 and 29

    Measure: Serum level of IL-8 in pg/ml

    Time: Day 0, 4, 9, 15 and 29
    361 A Phase 1 Study in Healthy Participants to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single -Ascending and Multiple Doses of an Anti-Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Chicken Egg Antibody (IgY)

    The primary objective of Part 1 (Single Ascending Dose) is to assess the safety and tolerability of anti-SARS-CoV-2 IgY when given as single-ascending doses administered intranasally to healthy participants. The primary objective of Part 2 (Multiple Dose) is to assess the safety and tolerability of anti-SARS-CoV-2 IgY when given as multiple doses administered intranasally to healthy participants. A secondary objective is to assess the pharmacokinetics of anti-SARS-CoV-2 IgY when given as multiple doses administered intranasally to healthy participants. Safety will be evaluated using adverse event (AE), physical examination (including vital signs), electrocardiogram, and clinical laboratory data. Pharmacokinetics will be evaluated by serum anti-SARS-CoV-2 IgY concentration.

    NCT04567810
    Conditions
    1. Covid19
    Interventions
    1. Drug: anti-SARS-CoV-2 IgY
    2. Drug: Placebo
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome

    Primary Outcomes

    Measure: Number of participants with treatment-related adverse events

    Time: up to 21 days

    Secondary Outcomes

    Measure: Number of Participants With Vital Sign Findings Reported as TEAEs

    Time: up to 21 days

    Description: Clinically significant in the judgement of the investigator.

    Measure: Number of Participants With Clinically Significant Findings in Physical Examinations

    Time: up to 21 days

    Description: Clinically significant in the judgement of the investigator.

    Measure: Number of Participants With Clinically Significant Changes From Baseline in ECG Data

    Time: up to 21 days

    Description: Clinically significant in the judgement of the investigator.

    Measure: Number of participants with Clinically Significant Changes from Baseline in Clinical Laboratory Parameters

    Time: up to 21 days

    Measure: Number of Participants with Presence of Serum anti-SARS-CoV-2 IgY

    Time: up to 21 days
    362 Phase 2, Multi-center, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety and Efficacy of EC-18 in Preventing the Progression of COVID-19 Infection to Severe Pneumonia or ARDS

    A trial of EC-18 in patients with mild/moderate pneumonia due to COVID-19

    NCT04569227
    Conditions
    1. Covid19 Pneumonia
    Interventions
    1. Drug: EC-18
    2. Drug: Placebo
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Measure: Proportion of patients alive and free of respiratory failure through at Day 28

    Time: 28 days

    Secondary Outcomes

    Measure: Probability of progression of mild pneumonia patients to severe pneumonia or ARDS within 28 days

    Time: 28 days

    Measure: Assessment of all-cause mortality

    Time: 28 days

    Description: Endotracheal intubation and mechanical ventilation Oxygen delivered by high-flow nasal cannula (heated, humidified, oxygen delivered via reinforced nasal cannula at flow rates > 20L/min with a fraction of delivered oxygen ≥ 0.5) Non-invasive positive pressure ventilation Extracorporeal membrane oxygenation

    Measure: Respiratory failure defined based on resource utilization requiring at least 1 of the following:

    Time: 28 days

    Measure: Proportion of patients alive and free of invasive mechanical ventilation at a pre-specified timepoint

    Time: 28 days

    Measure: Proportion of patients alive and discharged from the hospital at a pre-specified timepoint

    Time: 28 days

    Measure: Lengths of ICU stay

    Time: 28 days

    Measure: Lengths of alive and respiratory failure-free days

    Time: 28 days

    Measure: Proportion of patients with objective measures of improvement (returning to room air) at time points (days 7, 14, and 28)

    Time: 7, 14, and 28 days

    Description: o Check for changes in symptoms on a daily basis for 28 days compared to the baseline at day 1

    Measure: Confirmation of changes in subject's subjective clinical symptoms (e.g., patient questionnaire)

    Time: 28 days
    363 A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging Trial to Evaluate the Safety and Immunogenicity of V590 in Healthy Adults

    The primary objectives of this study is to evaluate the safety and tolerability of V590 versus placebo and to assess the immunogenicity of V590 on Day 28. The primary hypothesis is that at least one well-tolerated dose of V590 increases the geometric mean titers (GMTs) of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike serum neutralizing antibody, as measured by plaque reduction neutralization test (PRNT), compared to placebo.

    NCT04569786
    Conditions
    1. Coronavirus Disease (COVID-19)
    Interventions
    1. Biological: V590
    2. Other: Placebo
    MeSH:Coronavirus Infections

    Primary Outcomes

    Description: An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Solicited injection-site AEs (redness, swelling, and tenderness/pain) will be assessed.

    Measure: Percentage of Participants with at Least 1 Solicited Injection Site Adverse Event

    Time: Up to 5 days post-vaccination

    Description: An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Solicited systemic AEs (muscle pain, joint pain, headache, tiredness, fatigue, rash, nausea, joint swelling, oral lesions, and sweating more than usual) will be assessed.

    Measure: Percentage of Participants with at Least 1 Solicited Systemic Adverse Event

    Time: Up to 28 days post-vaccination

    Description: An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Unsolicited AEs will be assessed.

    Measure: Percentage of Participants with at Least 1 Unsolicited Adverse Event

    Time: Up to 28 days post-vaccination

    Description: A medically attended adverse event (MAAE) is an AE in which medical attention is received during an unscheduled, non-routine outpatient visit, such as an emergency room visit, office visit, or an urgent care visit with any medical personnel for any reason. Any MAAE will be assessed.

    Measure: Percentage of Participants with at Least 1 Medically Attended Adverse Event

    Time: Up to 180 days post-vaccination

    Description: A serious adverse event is "life threatening," requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity and is a congenital anomaly/birth defect. Any SAE will be assessed.

    Measure: Percentage of Participants with at Least 1 Serious Adverse Event

    Time: Up to 365 days post-vaccination

    Description: Serum samples will be collected and the presence of serum neutralization antibodies (SNAs) will be assessed using plaque reduction neutralization test (PRNT).

    Measure: Geometric Mean Titers for Serum Neutralizing Antibodies as Measured by Plaque Reduction Neutralization Test (Panels A - H)

    Time: Day 28 post-vaccination

    Secondary Outcomes

    Description: Serum samples will be collected and the presence of SNAs will be assessed using PRNT.

    Measure: Geometric Mean Titers for SNAs as Measured by PRNT (Panels A-H)

    Time: Days 7, 14, 90, 180, 270, and 365 post-vaccination

    Description: Serum samples will be collected and the total anti-spike IgG antibodies will be assessed using enzyme-linked immunosorbent assay (ELISA).

    Measure: Geometric Mean Concentration of Total Anti-SARS-CoV-2 Spike SNAs as Measured by Enzyme-Linked Immunosorbent Assay (Panels A-H)

    Time: Days 7, 14, 28, 90, 180, 270, and 365 post-vaccination

    Description: The percentage of participants with viremia detected by reverse transcription polymerase chain reaction (RT-PCR) of blood specimens will be assessed.

    Measure: Percentage of Participants with Vaccine Viremia as Measured by Reverse Transcription-Polymerase Chain Reaction

    Time: Days 1, 2, 3, 4, 5, 6, 7, 14 and 28 post-vaccination

    Description: The percentage of participants with viral shedding detected by RT-PCR in urine or saliva specimens will be assessed.

    Measure: Percentage of Participants with Vaccine Shedding in Saliva or Urine as Measured by RT-PCR

    Time: Days 1, 2, 3, 4, 5, 6, 7, 14, and 28 post-vaccination

    Description: The percentage of participants with vaccine shedding in stool as measured by RT-PCR will be assessed. Total of 2 stool samples collected if produced: one sample on Days 2 to 4; one sample on Days 5 to 7.

    Measure: Percentage of Participants with Vaccine Shedding in Stool as Measured by RT-PCR

    Time: Days 2-4, 5-7 post-vaccination
    364 Prospective, Randomized, Double-Blind, Placebo-Controlled Phase II Trial of Intravenous L-Citrulline (Turnobi) to Delay and Potentially Prevent the Need for Invasive Mechanical Ventilation for Acute Hypoxemic Respiratory Failure in Patients With COVID-19 (SARS-CoV-2) Illness

    Prospective, Randomized, Double-Blind, Placebo-Controlled Phase II Trial of Intravenous L-Citrulline (Turnobi) to Delay and Potentially Prevent the Need for Invasive Mechanical Ventilation for Acute Hypoxemic Respiratory Failure in Patients with COVID-19 (SARS-CoV2) Illness. To evaluate safety and efficacy of a bolus loading dose and continuous intravenous infusion of L-Citrulline compared to placebo in patients hospitalized with COVID-19 infection (SARS-CoV-2).

    NCT04570384
    Conditions
    1. Acute Hypoxemic Respiratory Failure
    Interventions
    1. Drug: L-Citrulline
    2. Drug: Placebo
    MeSH:Respiratory Insufficiency

    Primary Outcomes

    Description: The primary biochemical objective of this trial is to evaluate the effects of intravenous L-Citrulline on plasma levels of citrulline and arginine in patients admitted to the hospital with COVID-19 infection (SARS-CoV2) and acute hypoxemic respiratory symptoms requiring oxygen therapy. An association of plasma amino acid levels to clinical outcomes may serve as surrogate marker for response. Also measured is time on vent and time in ICU along with hospital stay

    Measure: Primary Biochemical Objective to measure levels of citrulline and arginine in the Blood

    Time: Day 1 through Day 60 Follow up

    Description: Hemodynamic measurements will be converted to a vasopressor dependency index (VDI) for analysis through day 10

    Measure: The primary safety objective is a beneficial effect of intravenous L-Citrulline on hemodynamic status.

    Time: Day 1 through Day 10

    Description: The primary clinical objective is to evaluate the difference in the length of time to an intubation event in hours from the start of study infusion between the study arms.

    Measure: Primary Clinical Objective

    Time: Day 1 through day 60 Follow-up

    Secondary Outcomes

    Description: To evaluate the safety of intravenous L-Citrulline compared to placebo as measured by incidence of reported adverse events.

    Measure: Evaluate the Safety of L-Citrulline

    Time: Day 1 through Day 60 Follow-up

    Description: To evaluate the effect of intravenous L-Citrulline compared to placebo as measured by the total length of all mechanical ventilation, including non-invasive modalities such as high flow nasal cannula and BiPAP and oxygen therapy.

    Measure: Evaluate the effect of intravenous L-Citrulline compared to placebo as measured by the total length of all mechanical ventilation

    Time: Dat 1 through Day 12

    Description: To evaluate the effect of intravenous L-Citrulline compared to placebo on Hospital all-cause mortality

    Measure: Evaluate the Effect of IV L-Citrulline to Placebo for Hospital all cause mortality

    Time: Day 1 through day 12

    Description: To evaluate the effect of intravenous L-Citrulline compared to placebo on lengths of ICU and hospital stay

    Measure: Evaluate the Effect of IV L-Citrulline to Placebo on length of ICU and Hospital Stay

    Time: Day 1 through Day 12 (DC)

    Description: To evaluate overall difference in intubation rates

    Measure: Evaluate overall difference in intubation rates

    Time: Day 1 to Day 10

    Description: To evaluate overall duration of mechanical ventilation from consent and post-infusion

    Measure: Evaluate overall duration of mechanical ventilation from consent and post-infusion

    Time: Day 1 through day 10
    365 Pilot Randomized Controlled Trial: Fluoxetine to Reduce Hospitalization From COVID-19 Infection (FloR COVID-19)

    The current research is a pilot study to determine the feasibility of recruiting and retaining 40 participants diagnosed with COVID-19. The purpose is to observe the early use of fluoxetine (commonly known as Prozac) to reduce the severity of the COVID-19 illness. Fluoxetine is a drug that has been approved by the U.S. Food and Drug Administration (FDA) since 1987 for various mental health disorders.

    NCT04570449
    Conditions
    1. Covid19
    Interventions
    1. Drug: Fluoxetine
    2. Drug: Placebo
    MeSH:Infection

    Primary Outcomes

    Description: Measures number of subjects hospitalized for COVID-19 symptoms

    Measure: Rate of hospitalization

    Time: 8 weeks

    Description: The 23-item daily symptom checklist measures the presence or absence of COVID-related symptoms (e.g. shortness of breath, fever, chills) and other possible symptoms (e.g. ear pain, vomit, seizures).

    Measure: Physical symptoms assessed through daily checklist

    Time: 8 weeks

    Secondary Outcomes

    Description: Measures number of subjects intubated for COVID-19 symptoms

    Measure: Rate of intubation

    Time: 8 weeks

    Description: Measures number of subjects who die from COVID-19 symptoms

    Measure: Rate of death

    Time: 8 weeks

    Description: Measured using the 9-item Patient Health Questionnaire (PHQ-9) each item rated on a scale of 0-3, where 0=no depressive symptoms and 3=depressive symptoms present nearly every day. A high score indicates severe depression.

    Measure: Depressive symptoms assessed weekly

    Time: 8 weeks

    Description: Measured using the 4-item SPAN assessment rated on a scale from 0-4 where 0=not at all distressing and 4=extremely distressing. A score greater than 5 indicates the presence of PTSD.

    Measure: Post traumatic stress disorder symptoms assessed weekly

    Time: 8 weeks

    Description: Measured using the 7-item General Anxiety Disorder Scale (GAD-7) rated from 0-3, where 0=no anxiety symptoms and 3=anxiety symptoms present nearly ever day. A high score indicates severe anxiety.

    Measure: Anxiety symptoms assessed weekly

    Time: 8 weeks

    Description: Measured using the 6-item Columbia-Suicide Severity Rating Scale (C-SSRS), a semi-structured interview on the presence or absence of suicidal ideation.

    Measure: Suicidality assessed daily

    Time: 8 weeks
    366 A Multi-Center, Randomized, Double-Blind, Placebo Controlled Study of the Safety and Efficacy of Angiotensin (1-7) for the Treatment of COVID-19 in Hospitalized Patients

    The primary objective is to evaluate the safety and efficacy of intravenous (IV) infusion of Ang (1-7) compared to placebo with respect to time to recovery, disease severity, need for mechanical ventilation or extracorporeal membrane oxygenation (ECMO), and mortality in patients with COVID 19.

    NCT04570501
    Conditions
    1. Covid19
    Interventions
    1. Drug: Angiotensin-(1-7)
    2. Drug: Placebo

    Primary Outcomes

    Description: Time to recovery, defined as attaining a score of 6, 7, or 8 on the COVID-19 disease severity scale, an 8 point ordinal scale used in the NIH Adaptive COVID-19 Treatment Trial (ACTT; NCT04280705). = Death; = Hospitalized and on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); = Hospitalized and on non-invasive ventilation or high-flow oxygen devices; = Hospitalized and requiring supplemental oxygen; = Hospitalized and not requiring supplemental oxygen but requiring ongoing medical care (COVID-19-related or otherwise); = Hospitalized and not requiring supplemental oxygen and no longer requiring ongoing medical care; = Not hospitalized, limitation on activities and/or requiring home oxygen; = Not hospitalized, no limitation on activities

    Measure: Time to recovery

    Time: Up to 29 days

    Secondary Outcomes

    Measure: Incidence of mortality at Day 29

    Time: 29 days

    Measure: Number of days alive and not on mechanical ventilator or ECMO in the 28 days following first dose

    Time: Up to 29 days

    Measure: Number of participants requiring mechanical ventilation or ECMO, or dying, through Day 29

    Time: Up to 29 days

    Description: COVID-19 disease severity scale (range; 1-8, higher scores correspond to better health state).

    Measure: COVID-19 disease severity scale score on Day 8

    Time: Day 8

    Description: COVID-19 disease severity scale (range; 1-8, higher scores correspond to better health state).

    Measure: COVID-19 disease severity scale score on Day 15

    Time: Day 15

    Description: COVID-19 disease severity scale (range; 1-8, higher scores correspond to better health state).

    Measure: COVID-19 disease severity scale score on Day 22

    Time: Day 22

    Description: COVID-19 disease severity scale (range; 1-8, higher scores correspond to better health state).

    Measure: COVID-19 disease severity scale score on Day 29

    Time: Day 29
    367 A Pilot Phase Study Evaluating the Effects of a Single Mesenchymal Stem Cell Injection in Patients With Suspected or Confirmed COVID-19 Infection and Healthcare Providers Exposed to Coronavirus Patients

    This double blind, placebo controlled, multi-arm, multi-site study investigates the safety and efficacy of stem cell therapy for the treatment of patients admitted to hospital suffering complications from COVID-19 and the treatment of healthy subjects (healthcare providers) for prophylactic effect following those patients.

    NCT04573270
    Conditions
    1. Covid19
    2. Prophylaxis
    Interventions
    1. Biological: PrimePro
    2. Other: Placebo

    Primary Outcomes

    Description: Survival Rate in COVID-19 infected patients admitted to hospital for complications

    Measure: Survival Rates

    Time: 30 Days

    Description: Contraction Rate of COVID-19 in healthy healthcare workers following patients admitted to hospital for complications due to COVID-19

    Measure: Contraction Rates

    Time: 30 Days
    368 Acute Effects of Oral Ketone Ester on Cardiac Function in Patients With COVID-19

    Based on Chinese studies, cardiac injury occurs in 20-30% of hospitalized patients and contributes to 40% of deaths. There are many possible mechanisms of cardiac injury in COVID-19 patients and increased myocardial oxygen demand and decreased myocardial oxygen supply are likely contributors to increased risk of myocardial infarction and heart failure. Interventions reducing the risk of cardiac injury are needed. Ketone bodies, such as 3-hydroxybutyrate and acetoacetate, can maintain ATP production in the heart and brain during starvation. It has been suggested that ketone bodies are more efficient substrates of energy metabolism than glucose, with a lower oxygen consumption per ATP-molecule produced. In addition, the reduction in hospitalizations due to heart failure observed in type 2 diabetes patients treated with sodium-glucose cotransporter 2 inhibitors, is suggested to be partly attributable to increased levels of 3-hydroxybutyrate. Infusion with 3-hydroxybutyrate reaching a plasma level of approximately 3 mM had acute beneficial hemodynamic effects in patients with heart failure and in healthy controls in a study by Nielsen et al. Improved haemodynamics and reduced systemic oxygen consumption might be of great benefit in patients with COVID-19. The primary endpoint is left ventricular ejection fraction. Secondary endpoints are conventional echocardiography parameters, peripheral blood oxygen saturation, venous blood oxygen saturation and urine creatinine clearance. The study population are twelve hospitalized patients with COVID-19 The study design is a randomized placebo-controlled double-blinded crossed-over acute intervention study.

    NCT04573764
    Conditions
    1. COVID-19
    Interventions
    1. Dietary Supplement: D-beta-hydroxybutyrate-(R)-1,3 butanediol monoester
    2. Dietary Supplement: Placebo

    Primary Outcomes

    Description: Echocardiography

    Measure: Left Ventricular ejection fraction

    Time: 1 hour

    Secondary Outcomes

    Description: Echocardiography

    Measure: Global longitudinal strain

    Time: 1 hour

    Description: Echocardiography

    Measure: Cardiac output

    Time: 1 hour

    Description: Pulse oximetry

    Measure: Peripheral blood oxygen saturation

    Time: 5 minutes

    Description: blood gas analysis

    Measure: Venous blood oxygen saturation

    Time: 5 minutes

    Description: Urine will be collected during the two cross-over sessions and urine creatinine will be measured on these two volumes. Creatinine clearance in ml/min/1.73m2 will then be estimated and compared with plasma creatinine for estimating kidney function.

    Measure: Urine creatinine clearance

    Time: 12 hours
    369 A Randomized, Double-Blind, Placebo-Controlled, Two-Part Study to Evaluate the Safety, Tolerability, Preliminary Efficacy, PK, & PD of RLS-0071 in Patients With Acute Lung Injury Due to COVID-19 Pneumonia in Early Respiratory Failure

    The aim of this study will test the safety, tolerability, and efficacy of RLS-0071 for approximately 28 days in comparison to a placebo control in patients with acute lung injury due to COVID-19 pneumonia in early respiratory failure. Patients will be randomized and double-blinded for two parts, a single-ascending dose (SAD) part and a multiple-ascending dose (MAD) part. The name of the study drug involved in this study is: RLS-0071.

    NCT04574869
    Conditions
    1. Acute Lung Injury
    2. ALI
    3. COVID-19
    Interventions
    1. Drug: RLS-0071
    2. Drug: RLS-0071
    3. Drug: Placebo
    4. Drug: RLS-0071
    5. Drug: RLS-0071
    6. Drug: Placebo
    MeSH:Pneumonia Respiratory Insufficiency Lung Injury Acute Lung Injury Respiratory Distress Syndrome, Adult Wounds and Injuries
    HPO:Pneumonia

    Primary Outcomes

    Measure: Frequency and severity of Adverse Events, including Serious Adverse Events, by treatment group and dose level, including the frequency of premature discontinuation of study intervention due to Adverse Events.

    Time: Through study completion at Day 28 following last dose.

    Secondary Outcomes

    Measure: Incidence of clinically significant changes from baseline in clinical laboratory values, ADA, autoantibody panel, vital signs, physical examination, ECG, radiography, and concomitant medications.

    Time: Through study completion at Day 28 following last dose; (if positive ADA/antibodies, Day 90 and Day 180 following last dose).

    Measure: Number of patients with positive ADA titers after receiving a single dose (Part A) or multiple doses (Part B) of RLS-0071.

    Time: Through study completion at Day 28 following last dose; (if positive ADA/antibodies, Day 90 and Day 180 following last dose).

    Measure: Estimates of single-dose maximum plasma concentration (Cmax) for RLS-0071.

    Time: Pre-Dose (within 30 minutes before start of dosing), 5 and 30 minutes after start of dosing, and 1, 2, 3, 4, 5, 6, 7, 8,12, 18, 24, 36, and 48 hours after the start of dosing, up to 28 days following last dose.

    Measure: Estimates of single-dose time to maximum plasma concentration (Tmax) for RLS-0071.

    Time: Pre-Dose (within 30 minutes before start of dosing), 5 and 30 minutes after start of dosing, and 1, 2, 3, 4, 5, 6, 7, 8,12, 18, 24, 36, and 48 hours after the start of dosing, up to 28 days following last dose.

    Measure: Estimates of single-dose minimum plasma concentration (Cmin) for RLS-0071.

    Time: Pre-Dose (within 30 minutes before start of dosing), 5 and 30 minutes after start of dosing, and 1, 2, 3, 4, 5, 6, 7, 8,12, 18, 24, 36, and 48 hours after the start of dosing, up to 28 days following last dose.

    Measure: Estimates of single-dose area under the plasma concentration-time curve (AUC) for RLS-0071.

    Time: Pre-Dose (within 30 minutes before start of dosing), 5 and 30 minutes after start of dosing, and 1, 2, 3, 4, 5, 6, 7, 8,12, 18, 24, 36, and 48 hours after the start of dosing, up to 28 days following last dose.

    Measure: Estimates of single-dose apparent total volume of distribution for RLS-0071.

    Time: Pre-Dose (within 30 minutes before start of dosing), 5 and 30 minutes after start of dosing, and 1, 2, 3, 4, 5, 6, 7, 8,12, 18, 24, 36, and 48 hours after the start of dosing, up to 28 days following last dose.

    Measure: Estimates of single-dose apparent total body clearance for RLS-0071.

    Time: Pre-Dose (within 30 minutes before start of dosing), 5 and 30 minutes after start of dosing, and 1, 2, 3, 4, 5, 6, 7, 8,12, 18, 24, 36, and 48 hours after the start of dosing, up to 28 days following last dose.

    Measure: Estimates of single-dose apparent first-order terminal elimination half-life for RLS-0071.

    Time: Pre-Dose (within 30 minutes before start of dosing), 5 and 30 minutes after start of dosing, and 1, 2, 3, 4, 5, 6, 7, 8,12, 18, 24, 36, and 48 hours after the start of dosing, up to 28 days following last dose.

    Measure: Estimates of multiple-dose maximum plasma concentration (Cmax) for RLS-0071.

    Time: Pre-Dose (within 30 minutes before start of dosing); 30 minutes after the start of dosing; and 1, 2, 4, 6, 12, 18, 24, 36, and 48 hours after the start of dosing. The last PK sample will be taken 48 hours following the last dosing (the 9th infusion).

    Measure: Estimates of multiple-dose peak time to maximum plasma concentration (Tmax) for RLS-0071.

    Time: Pre-Dose (within 30 minutes before start of dosing); 30 minutes after the start of dosing; and 1, 2, 4, 6, 12, 18, 24, 36, and 48 hours after the start of dosing. The last PK sample will be taken 48 hours following the last dosing (the 9th infusion).

    Measure: Estimates of multiple-dose area under the plasma concentration-time curve (AUC) for RLS-0071.

    Time: Pre-Dose (within 30 minutes before start of dosing); 30 minutes after the start of dosing; and 1, 2, 4, 6, 12, 18, 24, 36, and 48 hours after the start of dosing. The last PK sample will be taken 48 hours following the last dosing (the 9th infusion).

    Measure: Estimates of multiple-dose average plasma drug concentration observed (Cavg) for RLS-0071.

    Time: Pre-Dose (within 30 minutes before start of dosing); 30 minutes after the start of dosing; and 1, 2, 4, 6, 12, 18, 24, 36, and 48 hours after the start of dosing. The last PK sample will be taken 48 hours following the last dosing (the 9th infusion).

    Measure: Estimates of multiple-dose trough concentration prior to dose administration (Ctrough).

    Time: Pre-Dose (within 30 minutes before start of dosing); 30 minutes after the start of dosing; and 1, 2, 4, 6, 12, 18, 24, 36, and 48 hours after the start of dosing. The last PK sample will be taken 48 hours following the last dosing (the 9th infusion).

    Measure: Estimates of multiple-dose apparent total volume of distribution for RLS-0071.

    Time: Pre-Dose (within 30 minutes before start of dosing); 30 minutes after the start of dosing; and 1, 2, 4, 6, 12, 18, 24, 36, and 48 hours after the start of dosing. The last PK sample will be taken 48 hours following the last dosing (the 9th infusion).

    Measure: Estimates of multiple-dose apparent total body clearance for RLS-0071.

    Time: Pre-Dose (within 30 minutes before start of dosing); 30 minutes after the start of dosing; and 1, 2, 4, 6, 12, 18, 24, 36, and 48 hours after the start of dosing. The last PK sample will be taken 48 hours following the last dosing (the 9th infusion).

    Measure: Estimates of multiple-dose apparent first-order terminal elimination half-life for RLS-0071.

    Time: Pre-Dose (within 30 minutes before start of dosing); 30 minutes after the start of dosing; and 1, 2, 4, 6, 12, 18, 24, 36, and 48 hours after the start of dosing. The last PK sample will be taken 48 hours following the last dosing (the 9th infusion).

    Measure: Assessment of dose response relationship of single and multiple doses of RLS-0071 on C1q levels and the complement activity assay.

    Time: Through study completion at Day 28 following last dose.

    Measure: Overall survival.

    Time: Through Day 15 and through study completion at Day 28 following last dose.

    Measure: Incidence of progression to respiratory failure requiring mechanical ventilation.

    Time: Days on ventilation while in the hospital through study completion at Day 28.

    Measure: Incidence of transfer to the ICU.

    Time: Through Day 15 following last dose; through study completion at Day 28 following last dose; and duration of ICU stay days in the hospital post-dose through study completion at Day 28.

    Measure: Duration of hospitalization after treatment (days).

    Time: Through study completion at Day 28 following last dose.

    Measure: Incidence, severity, and duration after treatment (days) of fever (≥ 39.0°C).

    Time: Through study completion at Day 28 following last dose.

    Measure: Incidence, severity, and duration after treatment (days) of cough per investigator assessment of CTCAE's latest version.

    Time: Through study completion at Day 28 following last dose.

    Measure: Duration of requirement for supplemental oxygen after treatment (days).

    Time: Through study completion at Day 28 following last dose.

    Measure: PaO2/FiO2

    Time: Through study completion at Day 28 following last dose.

    Measure: Incidence, severity, and duration after treatment (days) of new cardiovascular events as assessed by the investigator (e.g. myocardial infarction, stroke, TIA, ischemic limb) with CTCAE's latest version.

    Time: Through Day 15 and through study completion at Day 28 following last dose.

    Measure: Incidence, severity, and duration after treatment (days) of respiratory acidosis as assessed by the investigator with CTCAE's latest version.

    Time: Through Day 15 and through study completion at Day 28 following last dose.

    Description: Dialysis will be assessed by the investigator with CTCAE's latest version.

    Measure: Incidence and duration after treatment (days) of dialysis.

    Time: Through Day 15 and through study completion at Day 28 following last dose.

    Measure: Levels of complement activity (eg, CH50).

    Time: Through study completion at Day 28 following last dose.

    Measure: Levels of C1q (free and bound to RLS-0071).

    Time: Through study completion at Day 28 following last dose.
    370 A Randomized, Double-Blind, Placebo-Controlled, Two-Part Study to Evaluate the Safety, Tolerability, Preliminary Efficacy, PK, & PD of RLS-0071 in Patients With Acute Lung Injury Due to COVID-19 Pneumonia in Early Respiratory Failure

    The aim of this study will test the safety, tolerability, and efficacy of RLS-0071 for approximately 28 days in comparison to a placebo control in patients with acute lung injury due to COVID-19 pneumonia in early respiratory failure. Patients will be randomized and double-blinded for two parts, a single-ascending dose (SAD) part and a multiple-ascending dose (MAD) part. The name of the study drug involved in this study is: RLS-0071.

    NCT04574869
    Conditions
    1. Acute Lung Injury
    2. ALI
    3. COVID-19
    Interventions
    1. Drug: RLS-0071
    2. Drug: RLS-0071
    3. Drug: Placebo
    4. Drug: RLS-0071
    5. Drug: RLS-0071
    6. Drug: Placebo
    MeSH:Pneumonia Respiratory Insufficiency Lung Injury Acute Lung Injury Respiratory Distress Syndrome, Adult Wounds and Injuries
    HPO:Pneumonia

    Primary Outcomes

    Measure: Frequency and severity of Adverse Events, including Serious Adverse Events, by treatment group and dose level, including the frequency of premature discontinuation of study intervention due to Adverse Events.

    Time: Through study completion at Day 28 following last dose.

    Secondary Outcomes

    Measure: Incidence of clinically significant changes from baseline in clinical laboratory values, ADA, autoantibody panel, vital signs, physical examination, ECG, radiography, and concomitant medications.

    Time: Through study completion at Day 28 following last dose; (if positive ADA/antibodies, Day 90 and Day 180 following last dose).

    Measure: Number of patients with positive ADA titers after receiving a single dose (Part A) or multiple doses (Part B) of RLS-0071.

    Time: Through study completion at Day 28 following last dose; (if positive ADA/antibodies, Day 90 and Day 180 following last dose).

    Measure: Estimates of single-dose maximum plasma concentration (Cmax) for RLS-0071.

    Time: Pre-Dose (within 30 minutes before start of dosing), 5 and 30 minutes after start of dosing, and 1, 2, 3, 4, 5, 6, 7, 8,12, 18, 24, 36, and 48 hours after the start of dosing, up to 28 days following last dose.

    Measure: Estimates of single-dose time to maximum plasma concentration (Tmax) for RLS-0071.

    Time: Pre-Dose (within 30 minutes before start of dosing), 5 and 30 minutes after start of dosing, and 1, 2, 3, 4, 5, 6, 7, 8,12, 18, 24, 36, and 48 hours after the start of dosing, up to 28 days following last dose.

    Measure: Estimates of single-dose minimum plasma concentration (Cmin) for RLS-0071.

    Time: Pre-Dose (within 30 minutes before start of dosing), 5 and 30 minutes after start of dosing, and 1, 2, 3, 4, 5, 6, 7, 8,12, 18, 24, 36, and 48 hours after the start of dosing, up to 28 days following last dose.

    Measure: Estimates of single-dose area under the plasma concentration-time curve (AUC) for RLS-0071.

    Time: Pre-Dose (within 30 minutes before start of dosing), 5 and 30 minutes after start of dosing, and 1, 2, 3, 4, 5, 6, 7, 8,12, 18, 24, 36, and 48 hours after the start of dosing, up to 28 days following last dose.

    Measure: Estimates of single-dose apparent total volume of distribution for RLS-0071.

    Time: Pre-Dose (within 30 minutes before start of dosing), 5 and 30 minutes after start of dosing, and 1, 2, 3, 4, 5, 6, 7, 8,12, 18, 24, 36, and 48 hours after the start of dosing, up to 28 days following last dose.

    Measure: Estimates of single-dose apparent total body clearance for RLS-0071.

    Time: Pre-Dose (within 30 minutes before start of dosing), 5 and 30 minutes after start of dosing, and 1, 2, 3, 4, 5, 6, 7, 8,12, 18, 24, 36, and 48 hours after the start of dosing, up to 28 days following last dose.

    Measure: Estimates of single-dose apparent first-order terminal elimination half-life for RLS-0071.

    Time: Pre-Dose (within 30 minutes before start of dosing), 5 and 30 minutes after start of dosing, and 1, 2, 3, 4, 5, 6, 7, 8,12, 18, 24, 36, and 48 hours after the start of dosing, up to 28 days following last dose.

    Measure: Estimates of multiple-dose maximum plasma concentration (Cmax) for RLS-0071.

    Time: Pre-Dose (within 30 minutes before start of dosing); 30 minutes after the start of dosing; and 1, 2, 4, 6, 12, 18, 24, 36, and 48 hours after the start of dosing. The last PK sample will be taken 48 hours following the last dosing (the 9th infusion).

    Measure: Estimates of multiple-dose peak time to maximum plasma concentration (Tmax) for RLS-0071.

    Time: Pre-Dose (within 30 minutes before start of dosing); 30 minutes after the start of dosing; and 1, 2, 4, 6, 12, 18, 24, 36, and 48 hours after the start of dosing. The last PK sample will be taken 48 hours following the last dosing (the 9th infusion).

    Measure: Estimates of multiple-dose area under the plasma concentration-time curve (AUC) for RLS-0071.

    Time: Pre-Dose (within 30 minutes before start of dosing); 30 minutes after the start of dosing; and 1, 2, 4, 6, 12, 18, 24, 36, and 48 hours after the start of dosing. The last PK sample will be taken 48 hours following the last dosing (the 9th infusion).

    Measure: Estimates of multiple-dose average plasma drug concentration observed (Cavg) for RLS-0071.

    Time: Pre-Dose (within 30 minutes before start of dosing); 30 minutes after the start of dosing; and 1, 2, 4, 6, 12, 18, 24, 36, and 48 hours after the start of dosing. The last PK sample will be taken 48 hours following the last dosing (the 9th infusion).

    Measure: Estimates of multiple-dose trough concentration prior to dose administration (Ctrough).

    Time: Pre-Dose (within 30 minutes before start of dosing); 30 minutes after the start of dosing; and 1, 2, 4, 6, 12, 18, 24, 36, and 48 hours after the start of dosing. The last PK sample will be taken 48 hours following the last dosing (the 9th infusion).

    Measure: Estimates of multiple-dose apparent total volume of distribution for RLS-0071.

    Time: Pre-Dose (within 30 minutes before start of dosing); 30 minutes after the start of dosing; and 1, 2, 4, 6, 12, 18, 24, 36, and 48 hours after the start of dosing. The last PK sample will be taken 48 hours following the last dosing (the 9th infusion).

    Measure: Estimates of multiple-dose apparent total body clearance for RLS-0071.

    Time: Pre-Dose (within 30 minutes before start of dosing); 30 minutes after the start of dosing; and 1, 2, 4, 6, 12, 18, 24, 36, and 48 hours after the start of dosing. The last PK sample will be taken 48 hours following the last dosing (the 9th infusion).

    Measure: Estimates of multiple-dose apparent first-order terminal elimination half-life for RLS-0071.

    Time: Pre-Dose (within 30 minutes before start of dosing); 30 minutes after the start of dosing; and 1, 2, 4, 6, 12, 18, 24, 36, and 48 hours after the start of dosing. The last PK sample will be taken 48 hours following the last dosing (the 9th infusion).

    Measure: Assessment of dose response relationship of single and multiple doses of RLS-0071 on C1q levels and the complement activity assay.

    Time: Through study completion at Day 28 following last dose.

    Measure: Overall survival.

    Time: Through Day 15 and through study completion at Day 28 following last dose.

    Measure: Incidence of progression to respiratory failure requiring mechanical ventilation.

    Time: Days on ventilation while in the hospital through study completion at Day 28.

    Measure: Incidence of transfer to the ICU.

    Time: Through Day 15 following last dose; through study completion at Day 28 following last dose; and duration of ICU stay days in the hospital post-dose through study completion at Day 28.

    Measure: Duration of hospitalization after treatment (days).

    Time: Through study completion at Day 28 following last dose.

    Measure: Incidence, severity, and duration after treatment (days) of fever (≥ 39.0°C).

    Time: Through study completion at Day 28 following last dose.

    Measure: Incidence, severity, and duration after treatment (days) of cough per investigator assessment of CTCAE's latest version.

    Time: Through study completion at Day 28 following last dose.

    Measure: Duration of requirement for supplemental oxygen after treatment (days).

    Time: Through study completion at Day 28 following last dose.

    Measure: PaO2/FiO2

    Time: Through study completion at Day 28 following last dose.

    Measure: Incidence, severity, and duration after treatment (days) of new cardiovascular events as assessed by the investigator (e.g. myocardial infarction, stroke, TIA, ischemic limb) with CTCAE's latest version.

    Time: Through Day 15 and through study completion at Day 28 following last dose.

    Measure: Incidence, severity, and duration after treatment (days) of respiratory acidosis as assessed by the investigator with CTCAE's latest version.

    Time: Through Day 15 and through study completion at Day 28 following last dose.

    Description: Dialysis will be assessed by the investigator with CTCAE's latest version.

    Measure: Incidence and duration after treatment (days) of dialysis.

    Time: Through Day 15 and through study completion at Day 28 following last dose.

    Measure: Levels of complement activity (eg, CH50).

    Time: Through study completion at Day 28 following last dose.

    Measure: Levels of C1q (free and bound to RLS-0071).

    Time: Through study completion at Day 28 following last dose.
    371 The CRISIS2 Study: A Phase 2, Randomized, Double Blind, Placebo-controlled, Multi-center Study Assessing the Safety and Anti-coronavirus Response of Suppression of Host Nucleotide Synthesis in Out-patient Adults With SARS-CoV-2

    This study will assess the efficacy and safety of DHODHi (brequinar) as an antiviral via 5 days of treatment of participants with positive COVID-19 and at least one symptom of COVI019 in an out-patient setting. The study is multi-center, randomized, and placebo-controlled.

    NCT04575038
    Conditions
    1. COVID-19 Infection
    Interventions
    1. Drug: Brequinar
    2. Drug: Placebo

    Primary Outcomes

    Description: Quantitative SARS-CoV-2 viral load

    Measure: SARS-CoV-2 viral load

    Time: Day 29

    Secondary Outcomes

    Description: Safety measured by rates of AEs and SAEs including laboratory assessments

    Measure: Rates of AEs and SAEs including laboratory assessments

    Time: Day 29

    Description: Duration of viral shedding

    Measure: Viral shedding duration

    Time: Day 29

    Description: Percentage of subjects requiring admission as an inpatient for >24 hours

    Measure: Hospital Admission

    Time: Day 29
    372 A Phase 2/3, Randomized, Placebo-Controlled, Double-Blind Clinical Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of MK-4482 in Hospitalized Adults With COVID-19

    This study aims to evaluate the safety, tolerability and efficacy of molnupiravir (MK-4482) compared to placebo. The primary hypothesis is that molnupiravir is superior to placebo as assessed by the rate of sustained recovery through Day 29.

    NCT04575584
    Conditions
    1. Coronavirus Disease (COVID-19)
    Interventions
    1. Drug: Molnupiravir
    2. Drug: Placebo
    MeSH:Coronavirus Infections

    Primary Outcomes

    Description: Sustained recovery is defined as: the participant is alive and not hospitalized; or the participant is alive and medically ready for discharge as determined by the investigator.

    Measure: Time-to-sustained recovery

    Time: Up to 29 days

    Description: An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.

    Measure: Percentage of participants with an adverse event (AE)

    Time: Up to 19 days

    Description: An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.

    Measure: Percentage of participants who discontinued study intervention due to an AE

    Time: Up to 6 days

    Secondary Outcomes

    Description: All-cause mortality is death due to any cause

    Measure: Percentage of participants with all-cause mortality

    Time: Up to 29 days

    Description: Pulmonary score is a score on an ordinal scale which focuses on respiratory sequalae based on oxygen requirements using 7 mutually exclusive categories. The score ranges from 1 to 7 with a higher score indicating more severe respiratory sequalae.

    Measure: Pulmonary score on a scale

    Time: Up to 29 days

    Description: Pulmonary+ score is a score on an ordinal scale which is a 7-category assessment that captures the range of disease severity, including coagulation-related complications and respiratory dysfunction. The score ranges from 1 to 7 with a higher score indicating more severe sequalae.

    Measure: Pulmonary+ score on a scale

    Time: Up to 29 days

    Description: The National Early Warning Score assesses a participant's degree of illness as assessed by clinical risk prediction categories for poor clinical outcomes including mortality within 24 hours of a set of vital sign measurements. There are 7 physiological parameters, of which 6 are assigned a point value ranging from 0 to 3, and 1 is assigned a point value ranging from 0 to 2. The total aggregate score may range from 0 to 20 with an increasing aggregate score indicating increasing clinical risk.

    Measure: National Early Warning Score on a scale

    Time: End of Treatment (EOT) (Up to 6 days)

    Description: The World Health Organization (WHO) outcome scale is an 11-point ordinal score that categorizes clinical progression. Score ranges from 0 to 10 with higher score indicating clinical progression.

    Measure: WHO 11-point outcomes score on a scale

    Time: Up to 29 days
    373 A Phase 2/3, Randomized, Placebo-Controlled, Double-Blind Clinical Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of MK-4482 in Non-Hospitalized Adults With COVID-19.

    This study aims to evaluate the safety, tolerability and efficacy of molnupiravir (MK-4482) compared to placebo. The primary hypothesis is that molnupiravir is superior to placebo as assessed by the percentage of participants who are hospitalized and/or die through Day 29

    NCT04575597
    Conditions
    1. Coronavirus Disease (COVID-19)
    Interventions
    1. Drug: Molnupiravir
    2. Drug: Placebo
    MeSH:Coronavirus Infections

    Primary Outcomes

    Description: Hospitalization (all cause) is ≥24 hours of acute care in a hospital or similar acute care facility. Death is due to any cause.

    Measure: Percentage of participants who are hospitalized and/or die

    Time: Up to 29 days

    Description: An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.

    Measure: Percentage of participants with an adverse event (AE)

    Time: Up to 19 days

    Description: An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.

    Measure: Percentage of participants who discontinued study intervention due to an AE

    Time: Up to 6 days

    Secondary Outcomes

    Description: The number of days from randomization to the first day on or before study Day 29 by which the targeted self-reported signs/symptoms improve or resolve.

    Measure: Time to improvement or resolution of targeted COVID-19 signs/symptoms

    Time: Up to 29 days

    Description: The number of days from randomization to the first day on or before study Day 29 by which the targeted self-reported signs/symptoms are newly reported or worsen.

    Measure: Time to progression of targeted COVID-19 signs/symptoms

    Time: Up to 29 days

    Description: The World Health Organization (WHO) outcome scale is an 11-point ordinal score that categorizes clinical progression. Score ranges from 0 to 10 with higher score indicating clinical progression.

    Measure: WHO 11-point outcomes score on a scale

    Time: Up to 29 days
    374 Investigation of IRAK4 Inhibition to Mitigate the Impact of COVID-19 in Severe SARS-CoV-2 (I-RAMIC)

    The purpose of this study is to assess the efficacy of PF-06650833 in addition to standard-of-care compared to standard-of-care treatment alone in improving outcomes in patients with COVID-19.

    NCT04575610
    Conditions
    1. COVID-19
    Interventions
    1. Drug: PF-06650833
    2. Drug: Placebo

    Primary Outcomes

    Description: All-cause mortality at Day 29 (end of planned treatment period).

    Measure: All-cause mortality at Day 29

    Time: Up to 29 days

    Secondary Outcomes

    Description: Proportion of patients alive, extubated, and receiving no more than low flow oxygen supplementation by nasal cannula or face mask (excluding extubation for compassionate purposes in terminal patients). This would correspond to an at least 2 point decrease in the NIAID ordinal scale. The NIAID scale is as follows: Not hospitalized, no limitations on activities Not hospitalized, limitations on activities and/or requiring home oxygen Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise) Hospitalized, requiring supplemental oxygen Hospitalized, on non-invasive ventilation or high-flow oxygen devices Hospitalized, on invasive mechanical ventilation or ECMO Death

    Measure: Disease Severity (8 point scale)

    Time: 29 days

    Description: Proportion of patients alive, extubated, and receiving no more than low flow oxygen supplementation by nasal cannula or face mask (excluding extubation for compassionate purposes in terminal patients). This would correspond to an at least 2 point decrease in the NIAID ordinal scale (1 = not hospitalized, no limitations on activities, and 8 = death) at Day 61.

    Measure: Disease Severity (8 point scale)

    Time: 61 days

    Description: Proportion of patients alive, extubated, and receiving any level oxygen supplementation, including non-invasive positive pressure ventilation or high flow oxygen device (excluding extubation for compassionate purposes in terminal patients). This would correspond to an at least 1-point decrease in the NIAID ordinal scale (1 = not hospitalized, no limitations on activities, and 8 = death) at Day 29.

    Measure: Disease Severity (8 point scale)

    Time: 29 days

    Description: Proportion of patients alive, extubated, and receiving any level oxygen supplementation, including non-invasive positive pressure ventilation or high flow oxygen device (excluding extubation for compassionate purposes in terminal patients). This would correspond to an at least 1-point decrease in the NIAID ordinal scale (1 = not hospitalized, no limitations on activities, and 8 = death) at Day 61.

    Measure: Disease Severity (8 point scale)

    Time: 61 days

    Description: Percentage of patients in each category of the NIAID 8-point ordinal scale of disease severity at Day 8. The ordinal scale is an assessment of the clinical status at the first assessment of a given study day in which 1 = not hospitalized, no limitations on activities, and 8 = death.

    Measure: Disease Severity (8 point scale)

    Time: 8 days

    Description: Percentage of patients in each category of the NIAID 8-point ordinal scale of disease severity at Day 15. The ordinal scale is an assessment of the clinical status at the first assessment of a given study day in which 1 = not hospitalized, no limitations on activities, and 8 = death.

    Measure: Disease Severity (8 point scale)

    Time: 15 days

    Description: Percentage of patients in each category of the NIAID 8-point ordinal scale of disease severity at Day 22. The ordinal scale is an assessment of the clinical status at the first assessment of a given study day in which 1 = not hospitalized, no limitations on activities, and 8 = death.

    Measure: Disease Severity (8 point scale)

    Time: 22 days

    Description: Percentage of patients in each category of the NIAID 8-point ordinal scale of disease severity at Day 29. The ordinal scale is an assessment of the clinical status at the first assessment of a given study day in which 1 = not hospitalized, no limitations on activities, and 8 = death.

    Measure: Disease Severity (8 point scale)

    Time: 29 days

    Description: Percentage of patients in each category of the NIAID 8-point ordinal scale of disease severity at Day 61. The ordinal scale is an assessment of the clinical status at the first assessment of a given study day in which 1 = not hospitalized, no limitations on activities, and 8 = death.

    Measure: Disease Severity (8 point scale)

    Time: 61 days

    Description: Mortality rate at day 61

    Measure: Mortality

    Time: 61 days

    Description: Time to a 1-point decrease in the NIAID 8-point ordinal scale of disease severity (1 = not hospitalized, no limitations on activities, and 8 = death).

    Measure: Disease Severity (8 point scale)

    Time: 29 days

    Description: Time to a 2-point decrease in the NIAID 8-point ordinal scale of disease severity.

    Measure: Disease Severity (8 point scale)

    Time: 29 days

    Description: Change from baseline in the ordinal scale from Day 1 to Days 3.

    Measure: Disease Severity (8 point scale)

    Time: 3 days

    Description: Change from baseline in the ordinal scale from Day 1 to Days 5.

    Measure: Disease Severity (8 point scale)

    Time: 5 days

    Description: Change from baseline in the ordinal scale from Day 1 to Days 8.

    Measure: Disease Severity (8 point scale)

    Time: 8 days

    Description: Change from baseline in the ordinal scale from Day 1 to Days 11.

    Measure: Disease Severity (8 point scale)

    Time: 11 days

    Description: Change from baseline in the ordinal scale from Day 1 to Days 15.

    Measure: Disease Severity (8 point scale)

    Time: 15 days

    Description: Change from baseline in the ordinal scale from Day 1 to Days 22.

    Measure: Disease Severity (8 point scale)

    Time: 22 days

    Description: Change from baseline in the ordinal scale from Day 1 to Days 29.

    Measure: Disease Severity (8 point scale)

    Time: 29 days

    Description: PaO2 (partial pressure of oxygen) / FiO2 (fraction of inspired oxygen, FiO2) ratio (or P/F ratio)

    Measure: P/F ratio

    Time: Up to 29 days

    Description: The SOFA evaluates 6 variables, each representing an organ system (one for the respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems), and scored from 0 (normal) to 4 (high degree of dysfunction/failure). Thus, the maximum score may range from 0 to 24.

    Measure: Change of the SOFA score.

    Time: Up to 29 days

    Description: The duration is days spent on mechanical ventilation.

    Measure: Duration (days) of mechanical ventilation

    Time: Up to 29 days

    Description: The number of days hospitalized not on a ventilator.

    Measure: Ventilator free days.

    Time: Up to 29 days

    Measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

    Time: Up to 29 days
    375 A Phase II Study Evaluating Fostamatinib for Hospitalized Adults With COVID-19

    Background: COVID-19 is a new disease caused by SARS-CoV-2 that was identified in 2019. Some people who get sick with COVID-19 become ill requiring hospitalization. There are some medicines that may help with recovery. Researchers want to see if a drug called fostamatinib may help people who are hospitalized with COVID-19. Objective: To learn if fostamatinib is safe in patients who are hospitalized with COVID-19 and gain earlier insight into whether it improves outcomes. Eligibility: Adults age 18 and older who are hospitalized with COVID-19. Design: Participants will be screened with a physical exam, including vital signs and weight. They will have a blood test and chest x-ray. They will have a COVID-19 test as a swab of either the back of the throat or the back of the nose. They will take a pregnancy test if needed. Participants will be randomly assigned, to take either fostamatinib pills or a placebo twice daily for up to 14 days in addition to standard of care for COVID-19. If they can swallow, they will take the pills by mouth with water. If they cannot swallow or are on mechanical ventilation, the pills will be crushed, mixed with water, and given through a tube placed through the nostril, or placed in the mouth, down the esophagus, and into the stomach. Blood samples will be taken daily. Participants will return to the Clinical Center for safety follow-up visits. At these visits, they will have a physical exam and blood tests. If they cannot visit the Clinical Center, they will be contacted by phone or have a telehealth visit. Participation will last for about two months

    NCT04579393
    Conditions
    1. Coronavirus Disease 2019
    Interventions
    1. Drug: Placebo
    2. Drug: fostamatinib
    MeSH:Coronavirus Infections

    Primary Outcomes

    Description: The safety primary endpoint is cumulative incidence of SAEs through day 29

    Measure: Cumulative Incidence of SAEs

    Time: Day 29

    Secondary Outcomes

    Measure: Number of days in the ICU

    Time: entire hospitalization

    Measure: Change in CRP, IL-6, d-dimer, ferritin, fibrinogen, absolute lymphocyte count, absolute neutrophil count, and platelet count from baseline

    Time: day 3, 5, 8, 11, 15, 29

    Measure: Ordinal scale

    Time: day 15, 29

    Measure: Days of hospitalization

    Time: entire hospitalization

    Measure: Time to recovery

    Time: day 29

    Measure: Number of days free of mechanical ventilation [entire hospitalization cohort 1]

    Time: entire hospitalization

    Measure: Number of days on oxygen

    Time: entire hospitalization

    Measure: Change in SOFA score from baseline

    Time: day 3, 5, 8, 11, 15, 29

    Measure: Days free of renal failure

    Time: entire hospitalization

    Measure: Clinically relevant deep vein thrombosis

    Time: entire hospitalization

    Measure: Relative change in PaO2/FiO2 or SpO2/FiO2 ratio

    Time: day 1,3,5,8,15,22 and 29

    Measure: Mortality

    Time: day 14, 18

    Measure: Grade 3 and 4 AE

    Time: through day 60
    376 A Pragmatic, Individually Randomised, Double-blind, Placebo-controlled Trial of Triazavirin (TZV) for the Treatment of Mild-moderate SARS-CoV-2 Infection A Phase II and III Clinical Trial

    A) Phase II: Early viral responses to triazavirin In hospitalised patients with mild-moderate COVID-19, in addition to standard of care therapy, treatment with triazavirin 250mg three times daily for five days, the slope of increase of the Ct values of serial nasopharyngeal swabs to 12 days after initiation of treatment will be ≥24% higher than in hospitalised patients receiving standard of care treatment only. B) Phase III: Efficacy of triazavirin to improve clinical outcomes In hospitalised patients with mild-moderate laboratory proven COVID-19, in addition to standard of care therapy, treatment with triazavirin 250mg three times daily for five days will reduce a composite outcome - death; ICU admission or mechanical ventilation; or prolonged duration of admission- by ≥29% when compared to the composite outcome in hospitalised patients receiving standard of care therapy only.

    NCT04581915
    Conditions
    1. Covid19
    Interventions
    1. Drug: Triazavirin (Riamilovir)
    2. Other: Placebo

    Primary Outcomes

    Description: To ascertain that indeed there is a biological effect of Triazavirin, we will compare slope of cycle threshold (Ct) values of nasopharyngeal swabs taken from all patients in the Phase II part of the trial. We require at least a 24% difference in slope.

    Measure: To compare the slope of cycle threshold(Ct) values of nasopharyngeal swabs in people receiving Triazavirin versus placebo

    Time: 11 days per patient

    Description: We have selected a composite measure including three adverse outcomes, all of which have serious implications for the patient and the health system. We will combine: deaths; ICU admissions or mechanical ventilation; and prolonged hospital stays -defined in this study as >14 days.

    Measure: To assess the proportion of patients who progress to severe COVID-19 and the proportion who need ICU or die.

    Time: 1 month per patient

    Description: We will compare rates of grade 3 and worse adverse events that occur whilst on treatment, and for up to 30 days after randomisation. We will also report on tolerability, by comparing the proportions by arm of those who had placebo/Triazavirin withheld permanently.

    Measure: To determine the proportion of patients who develop grade 3 or grade 4 adverse events on treatment

    Time: 1 month per patient

    Description: We will report on tolerability by comparing the proportions by arm who had placebo/Triazavirin withheld permanently.

    Measure: To determine the proportion of patients who stop taking either placebo/Triazavirin

    Time: 1 month per patient
    377 A Randomized, Double Blind, Placebo Controlled, Combined Phase 1/2 Single Dose and Multiple Dose Study to Assess the Safety, Tolerability, and Pharmacokinetics of NGM621 in Healthy Volunteers and the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy in Subjects With Confirmed SARS-CoV-2 Infection

    This study is a combined Phase 1 and Phase 2 study with IV infusion of NGM621 to evaluate the safety, tolerability, and PK in healthy volunteers (Part 1), and safety, tolerability, PK and efficacy in subjects with confirmed SARS-CoV-2 infection (Part 2).

    NCT04582318
    Conditions
    1. SARS-CoV-2 Infection
    Interventions
    1. Biological: NGM621
    2. Biological: Placebo
    MeSH:Infection

    Primary Outcomes

    Description: TEAEs in subjects receiving NGM621 compared to placebo

    Measure: Treatment emergent adverse events - Part 1

    Time: 85 days

    Description: TEAEs in subjects receiving NGM621 compared to placebo

    Measure: Treatment emergent adverse events - Part 2

    Time: 91 days

    Description: Clnical status (on an 8-point ordinal scale) in NGM621 group versus placebo group

    Measure: Clinical status at Day 15 and Day 29 - Part 2

    Time: 29 days

    Secondary Outcomes

    Measure: Maxiumum Serum Concentration [Cmax]

    Time: 91 days

    Measure: Mortality at Day 29

    Time: 29 days

    Measure: Duration of Supplemental Oxygen Requirement

    Time: 91 days

    Measure: Change in Hemolytic Assays (CH50 and AH50) from Baseline

    Time: 91 days
    378 Randomized, Double-Blind, Placebo-Controlled Phase III Clinical Trial For Evaluation of Efficacy and Safety of SARS-CoV-2 Vaccine (Vero Cell), Inactivated

    This study is a randomized, double-blinded, and placebo controlled phase III clinical trial of the SARS-CoV-2 inactivated vaccine manufactured by Sinovac Research & Development Co., Ltd. The purpose of this study is to evaluate the efficacy, safety and immunogenicity of the experimental vaccine in healthy adults aged 18~59 Years.

    NCT04582344
    Conditions
    1. COVID-19
    Interventions
    1. Biological: CoronaVac
    2. Biological: Placebo

    Primary Outcomes

    Description: The protection rate of a two-dose of SARS-CoV-2 (Vero Cell) vaccine against RT-PCR confirmed symptomatic COVID-19

    Measure: Protection Indexes of Two Vaccine Doses For Symptomatic COVID-19

    Time: 2 weeks after the second dose of vaccination

    Secondary Outcomes

    Description: The protection rate of, at least, one dose of SARS-CoV-2 (Vero Cell) vaccine against RT-PCR confirmed symptomatic COVID-19 Two weeks after the last dose vaccination.

    Measure: Protection Indexes of One Vaccine Dose For Symptomatic COVID-19

    Time: 2 weeks after the second dose of vaccination

    Description: The protection rate of a two-dose of SARS-CoV-2 (Vero Cell) vaccine against rates of hospitalization, disease severity/and death two weeks after the second dose of vaccination

    Measure: Protection Indexes of Second Vaccine Dose For Hospitalization, Disease Severity/and Death

    Time: 2 weeks after the second dose of vaccination

    Description: The protection rate of a two dose of SARS-CoV-2 (Vero Cell) vaccine against RT-PCR confirmed SARS-CoV-2 infection two weeks after the second dose of vaccination

    Measure: Protection Indexes of Two Vaccine Doses For SARS-CoV-2 infection

    Time: 2 weeks after the second dose of vaccination

    Description: The incidence of adverse reactions from the day of first vaccination to 28 days after the second dose of vaccination.

    Measure: Safety indexes of adverse reactions in 28 days

    Time: 28 days after the second dose of vaccination

    Description: The incidence of adverse reactions within 7 days after each dose of vaccination

    Measure: Safety indexes of adverse reactions in 7 days

    Time: 7 days after each dose of vaccination

    Description: The incidence of SAEs from the first vaccination to one year after the second dose vaccination

    Measure: Safety indexes of serious adverse events in 1 year

    Time: 1 year after second dose of vaccination

    Description: The seroconversion rate, seropositivity rate 14 days after each dose vaccination

    Measure: Immunogenicity parameters (seroconversion rate, seropositivity rate) in 14 days

    Time: 14 days after each dose vaccination

    Description: The seroconversion rate, seropositive rate 28 days after the second dose vaccination

    Measure: Immunogenicity parameters (seroconversion rate, seropositivity rate) in 28 days

    Time: 28 days after the second dose vaccination

    Description: GMT and GMI of neutralizing antibody and IgG 14 days after each dose vaccination

    Measure: Immunogenicity parameters (GMT and GMI of neutralizing antibody and IgG) in 14 days

    Time: 14 days after each dose vaccination

    Description: GMT and GMI of neutralizing antibody and IgG 28 days after the second dose vaccination

    Measure: Immunogenicity parameters (GMT and GMI of neutralizing antibody and IgG) in 28 days

    Time: 28 days after the second dose vaccination
    379 A Randomized, Double-Blind, Placebo-Controlled, Dose-Escalating Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacodynamics, Pharmacokinetics, and Immunogenicity of HLX71 in Healthy Adult Subjects

    A Randomized, Double-Blind, Placebo-Controlled, Dose-Escalating Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacodynamics, Pharmacokinetics, and Immunogenicity of HLX71 in Healthy Adult Subjects

    NCT04583228
    Conditions
    1. COVID 19
    Interventions
    1. Drug: HLX71
    2. Other: Placebo

    Primary Outcomes

    Measure: Number of participants with adverse events, serious adverse event and infusion-related reactions as assessed by CTCAE v5.0

    Time: up to 28 days

    Measure: The proportion of subjects undergoing DLT events in each dose cohorts during the DLT observation period

    Time: Days 1 to 7

    Secondary Outcomes

    Measure: PK parameters-Peak concentration

    Time: Pre-infusion, immediately post-infusion(0 hours), 1, 2.5, 4, 10, 24 hours after end of infusion and on days 3, 4, 6, 8, 10, 12, 15, 18, 22 and 29

    Measure: PK parameters-Time to peak

    Time: Pre-infusion, immediately post-infusion(0 hours), 1, 2.5, 4, 10, 24 hours after end of infusion and on days 3, 4, 6, 8, 10, 12, 15, 18, 22 and 29

    Measure: PK parameters-Areas under the concentration-time curves

    Time: Pre-infusion, immediately post-infusion(0 hours), 1, 2.5, 4, 10, 24 hours after end of infusion and on days 3, 4, 6, 8, 10, 12, 15, 18, 22 and 29

    Measure: PK parameters-Terminal elimination rate constant

    Time: Pre-infusion, immediately post-infusion(0 hours), 1, 2.5, 4, 10, 24 hours after end of infusion and on days 3, 4, 6, 8, 10, 12, 15, 18, 22 and 29

    Measure: PK parameters-Elimination half-life

    Time: Pre-infusion, immediately post-infusion(0 hours), 1, 2.5, 4, 10, 24 hours after end of infusion and on days 3, 4, 6, 8, 10, 12, 15, 18, 22 and 29

    Measure: PK parameters-Clearance (CL)

    Time: Pre-infusion, immediately post-infusion(0 hours), 1, 2.5, 4, 10, 24 hours after end of infusion and on days 3, 4, 6, 8, 10, 12, 15, 18, 22 and 29

    Measure: PK parameters-Volume of distribution

    Time: Pre-infusion, immediately post-infusion(0 hours), 1, 2.5, 4, 10, 24 hours after end of infusion and on days 3, 4, 6, 8, 10, 12, 15, 18, 22 and 29

    Measure: The concentration-time curves of plasma Ang1-10

    Time: Pre infusion, immediately post-infusion(0 hours), 1, 4, 10, 24 hours after end of infusion and on days 3, 8, 15 and 29

    Measure: The concentration-time curves of plasma Ang1-9

    Time: Pre infusion, immediately post-infusion(0 hours), 1, 4, 10, 24 hours after end of infusion and on days 3, 8, 15 and 29

    Measure: The concentration-time curves of plasma Ang1-8

    Time: Pre infusion, immediately post-infusion(0 hours), 1, 4, 10, 24 hours after end of infusion and on days 3, 8, 15 and 29

    Measure: The concentration-time curves of plasma Ang1-7

    Time: Pre infusion, immediately post-infusion(0 hours), 1, 4, 10, 24 hours after end of infusion and on days 3, 8, 15 and 29

    Measure: The concentration-time curves of plasma aldosterone

    Time: Pre infusion, immediately post-infusion(0 hours), 1, 4, 10, 24 hours after end of infusion and on days 3, 8, 15 and 29

    Measure: ADA positive rate

    Time: Day 15 and 29

    Measure: NAb positive rate

    Time: Day 15 and 29
    380 A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of the Efficacy of Camostat Mesilate for Treatment of COVID-19 in Outpatients

    This is a randomized, double-blind, placebo-controlled study of camostat mesilate in ambulatory patients with confirmed COVID-19 with at least one risk factor for severe illness.

    NCT04583592
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Camostat Mesilate
    2. Drug: Placebo

    Primary Outcomes

    Description: Disease progression will be defined as the proportion of participants requiring hospitalization (including emergency room visit) or who die due to any cause within 28 days of randomization.

    Measure: Disease Progression at Day 28

    Time: 28 days

    Secondary Outcomes

    Description: The overall survival rate (the proportion of randomized participants who survive up to Day 15 and Day 28).

    Measure: Survival Rate

    Time: Up to Day 15 and Day 28

    Description: Time (in hours) from initiation of study treatment until normalization of fever (≤ 37.2 °C oral or tympanic) and sustained for at least 72 hours only assessed in participants who experienced a fever within 24 hours of enrollment up to Day 28.

    Measure: Time to Fever Resolution

    Time: Up to 28 days

    Description: Time to disease progression is defined as the time from randomization to either hospitalization or death up to Day 28.

    Measure: Time to Disease Progression

    Time: Up to 28 days

    Description: Proportion of participants with no viral shedding (yes/no) using reverse transcriptase-polymerase chain reaction (RT-PCR) at Day 7, Day 15, and at early termination.

    Measure: Resolution of Viral Shedding

    Time: Day 1, Day 7 and Day 15

    Description: Incidence of adverse events (AEs) and serious adverse events (SAEs) of any grade from randomization up to Day 28.

    Measure: Rate of Adverse Events and Serious Adverse Events

    Time: 28 days

    Description: Cumulative incidence of grade 3 and 4 AEs from randomization up to Day 28.

    Measure: Cumulative Rate of Grade 3 and 4 Adverse Events

    Time: 28 days

    Description: Incidence of discontinuation from study due to an AE/SAE (discontinued participants will be followed up to Day 28).

    Measure: Rate of Discontinuation

    Time: 28 days

    Description: Change from baseline in clinical laboratory value of platelet count.

    Measure: Change in Laboratory Parameter - Platelet Count

    Time: Day 1 and Day 15

    Description: Change from baseline in clinical laboratory value of potassium level.

    Measure: Change in Laboratory Parameter - Potassium Level

    Time: Day 1 and Day 15

    Description: Change from baseline in clinical laboratory value of AST.

    Measure: Change in Laboratory Parameter - Aspartate Aminotransferase (AST)

    Time: Day 1 and Day 15

    Description: Change from baseline in clinical laboratory value of ALT.

    Measure: Change in Laboratory Parameter - Alanine Aminotransferase (ALT)

    Time: Day 1 and Day 15

    Description: Change from baseline in clinical laboratory value of ALP.

    Measure: Change in Laboratory Parameter - Alkaline Phosphatase (ALP)

    Time: Day 1 and Day 15

    Description: Change from baseline in clinical laboratory value of GGT.

    Measure: Change in Laboratory Parameter - Gamma-Glutamyl Transferase (GGT)

    Time: Day 1 and Day 15

    Description: Change from baseline in clinical laboratory value of albumin.

    Measure: Change in Laboratory Parameter - Albumin

    Time: Day 1 and Day 15

    Description: Change from baseline in clinical laboratory value of bilirubin.

    Measure: Change in Laboratory Parameter - Bilirubin

    Time: Day 1 and Day 15

    Description: Change from baseline in heart rate.

    Measure: Change in Vital Signs - Heart Rate

    Time: Day 1, Day 7 and Day 15

    Description: Change from baseline in blood pressure.

    Measure: Change in Vital Signs - Blood Pressure

    Time: Day 1, Day 7 and Day 15

    Description: Change from baseline in SpO2.

    Measure: Change in Vital Signs - Peripheral Capillary Oxygen Saturation (SpO2)

    Time: Day 1, Day 7 and Day 15
    381 A Multicenter Platform Trial of Putative Therapeutics for the Treatment of COVID-19 in Hospitalized Adults

    This is a platform trial to conduct a series of randomized, double-blind, placebo-controlled trials using common assessments and endpoints in hospitalized adults diagnosed with COVID-19. BET is a proof-of-concept study with the intent of identifying promising treatments to enter a more definitive study. The study will be conducted in up to 40 sites throughout the US. The study will compare different investigational therapeutic agents to a common control arm and determine which have relatively large effects. In order to maintain the double blind, each intervention will have a matched placebo. However, the control arm will be shared between interventions and may include participants receiving the matched placebo for a different intervention. The goal is not to determine clear statistical significance for an intervention, but rather to determine which products have clinical data suggestive of efficacy and should be moved quickly into larger studies. Estimates produced from BET will provide an improved basis for designing the larger trial, in terms of sample size and endpoint selection. Products with little indication of efficacy will be dropped on the basis of interim evaluations. In addition, some interventions may be discontinued on the basis of interim futility or efficacy analyses. One or more interventions may be started at any time. The number of interventions enrolling are programmatic decisions and will be based on the number of sites and the pace of enrollment. At the time of enrollment, subjects will be randomized to receive any one of the active arms they are eligible for or placebo. Approximately 100 subjects will be assigned to each arm entering the platform and a given site will generally have no more than 3 interventions at once. The BET-A stage will evaluate the combination of remdesivir with risankizumab vs remdesivir with a risankizumab placebo. The primary objective is to evaluate the clinical efficacy of different investigational therapeutics relative to the control arm in adults hospitalized with COVID-19 according to clinical status (8-point ordinal scale) at Day 8.

    NCT04583956
    Conditions
    1. COVID-19
    Interventions
    1. Other: Placebo
    2. Drug: Remdesivir
    3. Biological: Risankizumab

    Primary Outcomes

    Description: Clinical status assessed using ordinal scale: 1) Not hospitalized, no limitations on activities; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Hospitalized, not requiring supplemental oxygen and no longer requires ongoing medical care; 4) Hospitalized, not requiring supplemental oxygen but requiring ongoing medical care (COVID-19 related or otherwise); 5) Hospitalized, requiring supplemental oxygen; 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 8) Death.

    Measure: Clinical efficacy in adults hospitalized with COVID-19 according to clinical status on an 8-point ordinal scale.

    Time: Day 8

    Secondary Outcomes

    Measure: Change from baseline in C-reactive protein (CRP) concentration

    Time: Day 1 through Day 29

    Measure: Change from baseline in d-dimer concentration

    Time: Day 1 through Day 29

    Measure: Change from baseline in ferritin concentration

    Time: Day 1 through Day 29

    Measure: Change from baseline in fibrinogen concentration

    Time: Day 1 through Day 29

    Measure: Change from baseline in troponin concentration

    Time: Day 1 through Day 29

    Measure: Change in alanine aminotransferase (ALT) over time

    Time: Day 1 through Day 29

    Measure: Change in aspartate aminotransferase (AST) over time

    Time: Day 1 through Day 29

    Measure: Change in creatinine over time

    Time: Day 1 through Day 29

    Measure: Change in hemoglobin over time

    Time: Day 1 through Day 29

    Measure: Change in international normalized ratio (INR) over time

    Time: Day 1 through Day 29

    Description: The NEW score has demonstrated an ability to discriminate patients at risk of poor outcomes. This score is based on 7 clinical parameters (respiration rate, oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate, level of consciousness). The NEW Score is being used as an efficacy measure.

    Measure: Change in National Early Warning Score (NEWS) from baseline

    Time: Day 1 through Day 29

    Measure: Change in platelets over time

    Time: Day 1 through Day 29

    Measure: Change in total bilirubin over time

    Time: Day 1 through Day 29

    Measure: Change in white blood cell (WBC) count with differential over time

    Time: Day 1 through Day 29

    Description: Day of recovery is defined as the first day on which the subject satisfies one of the following three categories from the ordinal scale: 1) Not hospitalized, no limitations on activities; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care.

    Measure: Clinical efficacy, as assessed by time to recovery

    Time: Day 1 through Day 29

    Measure: Cumulative incidence of Grade 3 and 4 clinical and/or laboratory adverse events (AEs)

    Time: Day 1 through Day 60

    Measure: Cumulative incidence of serious adverse events (SAEs)

    Time: Day 1 through Day 60

    Description: For any reason.

    Measure: Discontinuation or temporary suspension of study product administration

    Time: Day 1 through Day 29

    Description: Measured in days.

    Measure: Duration of hospitalization

    Time: Day 1 through Day 29

    Description: Measured in days.

    Measure: Duration of new mechanical ventilation or extracorporeal membrane oxygenation (ECMO) use

    Time: Day 1 through Day 29

    Description: Measured in days.

    Measure: Duration of new non-invasive ventilation or high flow oxygen use during the study

    Time: Day 1 through Day 29

    Description: Measured in days; supplemental oxygen concentration or flow rate will be measured.

    Measure: Duration of new oxygen use

    Time: Day 1 through Day 29

    Description: Measured in days.

    Measure: Duration of non-invasive ventilation/high flow oxygen use

    Time: Day 1 through Day 29

    Measure: Incidence of new mechanical ventilation or extracorporeal membrane oxygenation (ECMO) use

    Time: Day 1 through Day 29

    Measure: Incidence of new non-invasive ventilation or high flow oxygen use

    Time: Day 1 through Day 29

    Description: Supplemental oxygen concentration or flow rate will be measured.

    Measure: Incidence of new oxygen use

    Time: Day 1 through Day 29

    Description: Clinical outcome assessed using ordinal scale: 1) Not hospitalized, no limitations on activities; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Hospitalized, not requiring supplemental oxygen and no longer requires ongoing medical care; 4) Hospitalized, not requiring supplemental oxygen but requiring ongoing medical care (COVID-19 related or otherwise); 5) Hospitalized, requiring supplemental oxygen; 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 8) Death.

    Measure: Mean change in the ordinal scale

    Time: Day 1 through Day 29

    Description: Measured in days; supplemental oxygen concentration or flow rate will be measured.

    Measure: Oxygenation use

    Time: Day 1 through Day 29

    Description: A subject who is "alive and without respiratory failure" is defined as meeting any one of the following five categories from the ordinal scale: 1) Not hospitalized, no limitations on activities; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3)Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 5) Hospitalized, requiring supplemental oxygen.

    Measure: Proportion of subjects alive and without respiratory failure

    Time: Day 1 to Day 29

    Description: Date and cause of death (if applicable).

    Measure: Subject 14-day mortality

    Time: Day 1 through Day 15

    Description: Date and cause of death (if applicable).

    Measure: Subject 29-day mortality

    Time: Day 1 through Day 29

    Description: Clinical outcome assessed using ordinal scale: 1) Not hospitalized, no limitations on activities; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Hospitalized, not requiring supplemental oxygen and no longer requires ongoing medical care; 4) Hospitalized, not requiring supplemental oxygen but requiring ongoing medical care (COVID-19 related or otherwise); 5) Hospitalized, requiring supplemental oxygen; 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 8) Death.

    Measure: Time to an improvement of one category using an ordinal scale

    Time: Day 1 through Day 29

    Description: Clinical outcome assessed using ordinal scale: 1) Not hospitalized, no limitations on activities; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Hospitalized, not requiring supplemental oxygen and no longer requires ongoing medical care; 4) Hospitalized, not requiring supplemental oxygen but requiring ongoing medical care (COVID-19 related or otherwise); 5) Hospitalized, requiring supplemental oxygen; 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 8) Death.

    Measure: Time to an improvement of two categories using an ordinal scale

    Time: Day 1 through Day 29

    Measure: Time to death

    Time: Day 1 through Day 29

    Description: The NEW score has demonstrated an ability to discriminate patients at risk of poor outcomes. This score is based on 7 clinical parameters (respiration rate, oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate, level of consciousness). The NEW Score is being used as an efficacy measure.

    Measure: Time to discharge or to a National Early Warning Score (NEWS) of < / = 2 and maintained for 24 hours, whichever occurs first

    Time: Day 1 through Day 29

    Description: Measured in days.

    Measure: Ventilator/ extracorporeal membrane oxygenation (ECMO) use

    Time: Day 1 through Day 29
    382 A Multicenter Platform Trial of Putative Therapeutics for the Treatment of COVID-19 in Hospitalized Adults

    This is a platform trial to conduct a series of randomized, double-blind, placebo-controlled trials using common assessments and endpoints in hospitalized adults diagnosed with COVID-19. BET is a proof-of-concept study with the intent of identifying promising treatments to enter a more definitive study. The study will be conducted in up to 40 sites throughout the US. The study will compare different investigational therapeutic agents to a common control arm and determine which have relatively large effects. In order to maintain the double blind, each intervention will have a matched placebo. However, the control arm will be shared between interventions and may include participants receiving the matched placebo for a different intervention. The goal is not to determine clear statistical significance for an intervention, but rather to determine which products have clinical data suggestive of efficacy and should be moved quickly into larger studies. Estimates produced from BET will provide an improved basis for designing the larger trial, in terms of sample size and endpoint selection. Products with little indication of efficacy will be dropped on the basis of interim evaluations. In addition, some interventions may be discontinued on the basis of interim futility or efficacy analyses. One or more interventions may be started at any time. The number of interventions enrolling are programmatic decisions and will be based on the number of sites and the pace of enrollment. At the time of enrollment, subjects will be randomized to receive any one of the active arms they are eligible for or placebo. Approximately 100 subjects will be assigned to each arm entering the platform and a given site will generally have no more than 3 interventions at once. The BET-B stage will evaluate the combination of remdesivir with lenzilumab vs remdesivir with a lenzilumab placebo. The primary objective is to evaluate the clinical efficacy of different investigational therapeutics relative to the control arm in adults hospitalized with COVID-19 according to clinical status (8-point ordinal scale) at Day 8.

    NCT04583969
    Conditions
    1. COVID-19
    Interventions
    1. Biological: Lenzilumab
    2. Other: Placebo
    3. Drug: Remdesivir

    Primary Outcomes

    Description: Clinical status assessed using ordinal scale: 1) Not hospitalized, no limitations on activities; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Hospitalized, not requiring supplemental oxygen and no longer requires ongoing medical care; 4) Hospitalized, not requiring supplemental oxygen but requiring ongoing medical care (COVID-19 related or otherwise); 5) Hospitalized, requiring supplemental oxygen; 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 8) Death.

    Measure: Clinical efficacy in adults hospitalized with COVID-19 according to clinical status on an 8-point ordinal scale

    Time: Day 8

    Secondary Outcomes

    Measure: Change from baseline in C-reactive protein (CRP) concentration

    Time: Day 1 through Day 29

    Measure: Change from baseline in d-dimer concentration

    Time: Day 1 through Day 29

    Measure: Change from baseline in ferritin concentration

    Time: Day 1 through Day 29

    Measure: Change from baseline in fibrinogen concentration

    Time: Day 1 through Day 29

    Measure: Change from baseline in lactate dehydrogenase (LDH) concentration

    Time: Day 1 through Day 29

    Measure: Change from baseline in troponin concentration

    Time: Day 1 through Day 29

    Measure: Change in alanine aminotransferase (ALT) over time

    Time: Day 1 through Day 29

    Measure: Change in aspartate aminotransferase (AST) over time

    Time: Day 1 through Day 29

    Measure: Change in creatinine over time

    Time: Day 1 through Day 29

    Measure: Change in hemoglobin over time

    Time: Day 1 through Day 29

    Measure: Change in international normalized ratio (INR) over time

    Time: Day 1 through Day 29

    Description: The NEW score has demonstrated an ability to discriminate patients at risk of poor outcomes. This score is based on 7 clinical parameters (respiration rate, oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate, level of consciousness). The NEW Score is being used as an efficacy measure.

    Measure: Change in National Early Warning Score (NEWS) from baseline

    Time: Day 1 through Day 29

    Measure: Change in platelets over time

    Time: Day 1 through Day 29

    Measure: Change in total bilirubin over time

    Time: Day 1 through Day 29

    Measure: Change in white blood cell (WBC) count with differential over time

    Time: Day 1 through Day 29

    Description: Day of recovery is defined as the first day on which the subject satisfies one of the following three categories from the ordinal scale: 1) Not hospitalized, no limitations on activities; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care.

    Measure: Clinical efficacy, as assessed by time to recovery

    Time: Day 1 through Day 29

    Measure: Cumulative incidence of Grade 3 and 4 clinical and/or laboratory adverse events (AEs)

    Time: Day 1 through Day 60

    Measure: Cumulative incidence of serious adverse events (SAEs)

    Time: Day 1 through Day 60

    Description: For any reason.

    Measure: Discontinuation or temporary suspension of study product administration

    Time: Day 1 through Day 29

    Description: Measured in days.

    Measure: Duration of hospitalization

    Time: Day 1 through Day 29

    Description: Measured in days.

    Measure: Duration of new mechanical ventilation or extracorporeal membrane oxygenation (ECMO) use

    Time: Day 1 through Day 29

    Description: Measured in days.

    Measure: Duration of new non-invasive ventilation or high flow oxygen use during the study

    Time: Day 1 through Day 29

    Description: Measured in days; supplemental oxygen concentration or flow rate will be measured.

    Measure: Duration of new oxygen use

    Time: Day 1 through Day 29

    Description: Measured in days.

    Measure: Duration of non-invasive ventilation/high flow oxygen use

    Time: Day 1 through Day 29

    Measure: Incidence of new mechanical ventilation or extracorporeal membrane oxygenation (ECMO) use

    Time: Day 1 through Day 29

    Measure: Incidence of new non-invasive ventilation or high flow oxygen use

    Time: Day 1 through Day 29

    Description: Supplemental oxygen concentration or flow rate will be measured.

    Measure: Incidence of new oxygen use

    Time: Day 1 through Day 29

    Description: Measured in days.

    Measure: Incidence of ventilator/ extracorporeal membrane oxygenation (ECMO) use

    Time: Day 1 through Day 29

    Description: Clinical outcome assessed using ordinal scale: 1) Not hospitalized, no limitations on activities; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Hospitalized, not requiring supplemental oxygen and no longer requires ongoing medical care; 4) Hospitalized, not requiring supplemental oxygen but requiring ongoing medical care (COVID-19 related or otherwise); 5) Hospitalized, requiring supplemental oxygen; 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 8) Death.

    Measure: Mean change in the ordinal scale

    Time: Day 1 through Day 29

    Description: Measured in days; supplemental oxygen concentration or flow rate will be measured.

    Measure: Oxygenation use

    Time: Day 1 through Day 29

    Description: A subject who is "alive and without respiratory failure" is defined as meeting any one of the following five categories from the ordinal scale: 1) Not hospitalized, no limitations on activities; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3)Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 5) Hospitalized, requiring supplemental oxygen.

    Measure: Proportion of subjects alive and without respiratory failure

    Time: Day 1 through Day 29

    Description: Date and cause of death (if applicable).

    Measure: Subject 14-day mortality

    Time: Day 1 through Day 15

    Description: Date and cause of death (if applicable).

    Measure: Subject 29-day mortality

    Time: Day 1 through Day 29

    Description: Clinical outcome assessed using ordinal scale: 1) Not hospitalized, no limitations on activities; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Hospitalized, not requiring supplemental oxygen and no longer requires ongoing medical care; 4) Hospitalized, not requiring supplemental oxygen but requiring ongoing medical care (COVID-19 related or otherwise); 5) Hospitalized, requiring supplemental oxygen; 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 8) Death.

    Measure: Time to an improvement of one category using an ordinal scale

    Time: Day 1 through Day 29

    Description: Clinical outcome assessed using ordinal scale: 1) Not hospitalized, no limitations on activities; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Hospitalized, not requiring supplemental oxygen and no longer requires ongoing medical care; 4) Hospitalized, not requiring supplemental oxygen but requiring ongoing medical care (COVID-19 related or otherwise); 5) Hospitalized, requiring supplemental oxygen; 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 8) Death.

    Measure: Time to an improvement of two categories using an ordinal scale

    Time: Day 1 through Day 29

    Measure: Time to death

    Time: Day 1 through Day 29

    Description: The NEW score has demonstrated an ability to discriminate patients at risk of poor outcomes. This score is based on 7 clinical parameters (respiration rate, oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate, level of consciousness). The NEW Score is being used as an efficacy measure.

    Measure: Time to discharge or to a National Early Warning Score (NEWS) of < / = 2 and maintained for 24 hours, whichever occurs first

    Time: Day 1 through Day 29
    383 A Phase 3, Randomised, Observer-Blinded, Placebo-Controlled Trial to Evaluate the Efficacy and Safety of a SARS-CoV-2 Recombinant Spike Protein Nanoparticle Vaccine (SARS-CoV-2 rS) With Matrix-M1™ Adjuvant in Adult Participants 18-84 Years of Age in the United Kingdom

    This is a study to evaluate the efficacy, immune response, and safety of a coronavirus disease 2019 (COVID-19) vaccine called SARS-CoV-2 rS with Matrix-M1 adjuvant in adults aged 18-84 years in the United Kingdom. A vaccine causes the body to have an immune response that may help prevent the infection or reduce the severity of symptoms. An adjuvant is something that can make a vaccine work better. This study will look at the protective effect, body's immune response, and safety of SARS-CoV-2 rS with Matrix-M1 adjuvant in the study population. Participants in the study will randomly be assigned to receive SARS-CoV-2 rS with Matrix-M1 adjuvant or placebo. Each participant in the study will receive a total of 2 intramuscular injections over the course of the study. Approximately 15,000 participants will take part in the study. The first 400 participants who meet additional criteria will receive a flu vaccine, in addition to the SARS-CoV-2 rS vaccine or placebo, as part of a sub-study. An effort will be made to enroll a target of at least 25% of participants who are ≥ 65 years of age, as well as prioritizing other groups that are most affected by COVID-19, including racial and ethnic minorities.

    NCT04583995
    Conditions
    1. SARS-CoV-2 Infection
    2. COVID-19
    Interventions
    1. Biological: SARS-CoV-2 rS/Matrix M1-Adjuvant
    2. Other: Placebo
    3. Biological: Licensed seasonal influenza vaccine

    Primary Outcomes

    Description: Number of participants, testing serologically negative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at baseline, with first occurrence of positive (+) polymerase chain reaction (PCR)-confirmed SARS-CoV-2 illness with symptomatic mild, moderate, or severe COVID-19 with onset from Day 28 through the length of the study.

    Measure: Participants with Symptomatic Mild, Moderate, or Severe Coronavirus Disease 2019 (COVID-19)

    Time: From Day 28 to Day 386

    Secondary Outcomes

    Description: Number of participants, testing serologically negative for SARS-CoV-2 at baseline with first occurrence of (+) PCR-confirmed, SARS-CoV-2 illness with symptomatic moderate or severe COVID-19 with onset from Day 28 through the length of the study.

    Measure: Participants with Symptomatic Moderate or Severe COVID-19

    Time: From Day 28 to Day 386

    Description: Number of participants, regardless of serostatus at baseline, with first occurrence of (+) PCR-confirmed, SARS-CoV-2 illness with symptomatic mild, moderate, or severe COVID-19 assessed from Day 28 through the length of the study.

    Measure: Participants with Symptomatic Mild, Moderate, or Severe COVID-19 Regardless of Baseline Serostatus

    Time: From Day 28 to Day 386

    Description: Number of participants, regardless of serostatus at baseline, with first occurrence of (+) PCR-confirmed, or nucleocapsid protein serologically confirmed, SARS-CoV-2 illness with asymptomatic or symptomatic COVID-19 with onset from Day 28 through the length of the study.

    Measure: Participants with Asymptomatic or Symptomatic COVID-19

    Time: From Day 28 to Day 386

    Description: Number of participants, regardless of serostatus at baseline, with first occurrence of (+) PCR-confirmed, SARS-CoV-2 illness with COVID-19 with onset from Day 28 through the length of the study.

    Measure: Participants with COVID-19 requiring Hospitalization, Intensive Care Unit (ICU), or Mechanical Ventilation

    Time: From Day 28 to Day 386

    Description: Number of participants, regardless of serostatus at baseline, with first occurrence of (+) PCR-confirmed, SARS-CoV-2 illness with symptomatic mild COVID-19 (with no progression to moderate or severe COVID-19 during the course of the COVID-19 episode) with onset from Day 28 through the length of the study.

    Measure: Participants with Symptomatic Mild COVID-19

    Time: From Day 28 to Day 386

    Description: Serum IgG antibody levels specific for the SARS-CoV-2 rS protein antigen(s) as detected by enzyme-linked immunosorbent assay (ELISA) expressed as GMEUs at Day 0 and Day 35.

    Measure: Serum IgG Antibody Levels at Multiple Time Points Expressed as Geometric Mean ELISA Units (GMEUs)

    Time: Day 0 to Day 35

    Description: Number of participants with SAEs through the length of the study by Medical Dictionary for Regulatory Activities (MedDRA) classification and relationship to study vaccination.

    Measure: Participants with Serious Adverse Events (SAEs)

    Time: 386 days

    Description: Number of participants with MAAEs related to study vaccination through the length of the study by MedDRA classification.

    Measure: Participants with Medically Attended Adverse Events (MAAEs) Related to Study Vaccination

    Time: 386 days

    Description: Number of participants with AESIs, which include potential immune-mediated medical conditions (PIMMCs) and AESIs relevant to COVID-19 such as possible vaccine-enhanced disease by MedDRA classification through the length of the study.

    Measure: Participants with Adverse Events of Special Interest (AESIs)

    Time: 386 days

    Description: Number of participants with solicited local and systemic AEs for 7 days after each study vaccination.

    Measure: Participants with Solicited Local and Systemic Adverse Events (AEs)

    Time: 28 days

    Description: Number of participants with all MAAEs through Day 35 by MedDRA classification and relationship to study vaccination.

    Measure: Participants with All MAAEs Through Day 35

    Time: 35 days

    Description: Number of participants with unsolicited AEs through Day 49 by MedDRA classification and relationship to study vaccination.

    Measure: Participants with Unsolicited AEs Through Day 49

    Time: 49 days
    384 A Randomized, Placebo-controlled Study to Evaluate the Safety, Pharmacokinetics and Efficacy of a Single Dose of STI-2020 (COVI-AMG™) in Outpatients With COVID-19 Who Are Asymptomatic or Have Mild Symptoms

    This is a randomized, placebo-controlled study to assess the safety, PK profile, and efficacy of COVI-AMG in subjects with COVID-19.

    NCT04584697
    Conditions
    1. Covid19
    Interventions
    1. Biological: COVI-AMG
    2. Drug: Placebo

    Primary Outcomes

    Description: Safety as assessed by incidence of adverse events by type, frequency, severity, and causality

    Measure: Incidence of adverse events by type, frequency, severity, and causality (safety)

    Time: Randomization through study completion at Day 60

    Description: Safety as assessed by incidence of treatment-emergent adverse events by type, frequency, severity, and causality

    Measure: Incidence of treatment-emergent adverse events by type, frequency, severity, and causality (safety)

    Time: Randomization through study completion at Day 60

    Description: Safety as assessed by incidence of serious adverse events by type, frequency, severity, and causality

    Measure: Incidence of serious adverse events by type, frequency, severity, and causality (safety)

    Time: Randomization through study completion at Day 60

    Description: Safety as assessed by incidence of dose-limiting toxicities

    Measure: Incidence of dose-limiting toxicities (safety)

    Time: Randomization through study completion at Day 60

    Description: Safety as assessed by incidence of clinically meaningful laboratory abnormalities

    Measure: Incidence of clinically meaningful laboratory abnormalities (safety)

    Time: Randomization through study completion at Day 60

    Description: Viral load as assessed using plasma and salivary samples at various timepoints correlated with nasopharyngeal testing

    Measure: Viral load as assessed using plasma and salivary samples at various timepoints

    Time: Randomization through study completion at Day 60

    Description: Time from onset of COVID-19 symptoms to treatment (Day 1)

    Measure: Time from onset of COVID-19 symptoms to treatment (Day 1)

    Time: Day 1

    Description: Presence and levels of anti-drug antibodies directed to COVI-AMG

    Measure: Presence and levels of anti-drug antibodies directed to COVI-AMG

    Time: Randomization through study completion at Day 60

    Description: Cytokine levels post-treatment including EGF, IFNγ, IL-1β, IL-6, IL-8, IL-10, and TNFα will be measured by ELISA

    Measure: Cytokine levels post-treatment

    Time: Randomization through study completion at Day 60

    Secondary Outcomes

    Description: Area under the serum concentration-time curve (AUC) of COVI-AMG

    Measure: AUC of COVI-AMG (PK)

    Time: Randomization through study completion at Day 60

    Description: Maximum observed serum concentration (Cmax) of COVI-AMG

    Measure: Cmax of COVI-AMG (PK)

    Time: Randomization through study completion at Day 60

    Description: Time to Cmax (Tmax) of COVI-AMG

    Measure: Tmax of COVI-AMG (PK)

    Time: Randomization through study completion at Day 60

    Description: Apparent serum terminal elimination half life (t½) of COVI-AMG

    Measure: t½ of COVI-AMG (PK)

    Time: Randomization through study completion at Day 60
    385 A Randomized, Double-Blind, Placebo-Controlled Phase 2a Study of RTB101 as COVID-19 Post-Exposure Prophylaxis in Adults Age ≥65 Years

    The proposed trial will obtain preliminary data on the feasibility of studying RTB101 as compared to placebo for COVID-19 post-exposure prophylaxis in adults age ≥ 65 years to inform the design of a subsequent pivotal trial.

    NCT04584710
    Conditions
    1. Covid19
    Interventions
    1. Drug: RTB101
    2. Drug: Placebo

    Primary Outcomes

    Description: The number of days from the date of receipt of a positive SARS-CoV-2 swab test result to the date of first dose of study drug in asymptomatic subjects who: have SARS-CoV-2 detected on a surveillance nasal or nasopharyngeal swab OR live in the same house or apartment as someone who has laboratory-confirmed symptomatic COVID-19

    Measure: To determine the length of time from date of receipt of a positive SARS-CoV2 test result to date of first dose of study drug in asymptomatic adults age ≥ 65 years

    Time: Beginning of randomization through Week 2

    Secondary Outcomes

    Description: Study drug compliance determined from the number of capsules of study drug taken by the subject based on data reported in an eDiary

    Measure: To determine the feasibility of using an eDiary to assess study drug compliance in the study drug population

    Time: Beginning of randomization through Week 2

    Description: Study drug compliance determined from the number of capsules of study drug taken by the subject based on data from twice weekly phone calls

    Measure: To determine the feasibility of using an eDiary to assess study drug compliance in the study drug population

    Time: Beginning of randomization through Week 2

    Description: Study drug compliance determined from the number of capsules of study drug taken by the subject based on a pill count done by phone when subjects complete study drug treatment

    Measure: To determine the feasibility of using an eDiary to assess study drug compliance in the study drug population

    Time: Beginning of randomization through Week 2

    Description: Incidence and severity of COVID-19 symptoms based on data reported in an eDiary

    Measure: To determine the feasibility of using an eDiary to assess COVID-19 symptoms in the study population

    Time: From time of first dose through Week 3

    Description: Incidence and severity of COVID-19 symptoms based on data from twice weekly phone calls

    Measure: To determine the feasibility of using an eDiary to assess COVID-19 symptoms in the study population

    Time: From time of first dose through Week 3

    Description: Safety and tolerability will be assessed by report of AE/SAEs from first dose of study drug through Week 3

    Measure: To assess the incidence of treatment-emergent of AEs and SAEs in subjects assigned to RTB101 as compared to placebo

    Time: From time of first dose through Week 3

    Description: The percentage of subjects who have SARS-CoV-2 detected on nasal or nasopharyngeal swab and who develop 2 or more concurrent symptoms of COVID-19 from first dose of study drug through Day 14

    Measure: To determine the percentage of subjects treated with RTB101 as compared to placebo who develop symptomatic laboratory-confirmed COVID-19 from first dose through Day 14

    Time: From time of first dose through Week 2

    Description: The percentage of subjects who die from any cause from first dose of study drug through Day 14 and 21

    Measure: To determine the percentage of subjects treated with RTB101 as compared to placebo who die from any cause from first dose of study drug through Day 14 and 21

    Time: From time of first dose through Week 3

    Description: The percentage of subjects who develop laboratory-confirmed COVID-19 from first dose of study drug through Day 14 and are subsequently hospitalized for any reason through Day 21

    Measure: To determine the percentage of subjects treated with RTB101 as compared to placebo who develop laboratory-confirmed COVID-19 from first dose through Day 14 and are subsequently hospitalized for any reason through Day 21

    Time: From time of first dose through Week 3

    Description: The percentage of subjects who have SARS-CoV-2 detected on nasal or nasopharyngeal swab regardless of symptoms from first dose of study drug through Day 7, 14, and 21 among subjects who are not SARS-CoV-2 positive at screening or baseline

    Measure: To determine the percent of subjects treated with RTB101 or placebo who have laboratory-confirmed SARS-CoV-2 infection regardless of symptoms from first dose of study drug through Days 7, 14, 21.

    Time: From time of first dose through Week 3
    386 A PHASE 1/2, PLACEBO-CONTROLLED, RANDOMIZED, AND OBSERVER-BLIND STUDY TO EVALUATE THE SAFETY, TOLERABILITY, AND IMMUNOGENICITY OF A SARS-COV-2 RNA VACCINE CANDIDATE AGAINST COVID-19 IN HEALTHY JAPANESE ADULTS

    This is a Phase 1/2, randomized, placebo-controlled, and observer-blind study in healthy Japanese adults. The study will evaluate the safety, tolerability, and immunogenicity of the SARS-CoV-2 RNA vaccine candidate against COVID-19: - As 2 doses, separated by 21 days - At a single dose level - In adults 20 to 85 years of age

    NCT04588480
    Conditions
    1. SARS-CoV-2 Infection
    2. COVID-19
    Interventions
    1. Biological: BNT162b2
    2. Other: Placebo

    Primary Outcomes

    Description: Pain at the injection site, redness, and swelling as self-reported on electronic diaries.

    Measure: Percentage of participants reporting local reactions

    Time: For 7 days after dose 1 and dose 2

    Description: Fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain as self-reported on electronic diaries.

    Measure: Percentage of participants reporting systemic events

    Time: For 7 days after dose 1 and dose 2

    Description: As elicited by investigational site staff

    Measure: Percentage of participants reporting adverse events

    Time: From dose 1 through 1 month after the last dose

    Description: As elicited by investigational site staff

    Measure: Percentage of participants reporting serious adverse events

    Time: From dose 1 through 12 months after the last dose

    Description: As measured at the local laboratory

    Measure: Percentage of subset participants with abnormal hematology and chemistry laboratory values

    Time: 1 day after dose 1

    Description: As measured at the local laboratory

    Measure: Percentage of subset participants with abnormal hematology and chemistry laboratory values

    Time: 7 days after dose 1

    Description: As measured at the local laboratory

    Measure: Percentage of subset participants with abnormal hematology and chemistry laboratory values

    Time: 7 days after dose 2

    Description: As measured at the local laboratory

    Measure: Percentage of subset participants with grading shifts in hematology and chemistry laboratory assessments

    Time: Between baseline and 1 day after dose 1

    Description: As measured at the local laboratory

    Measure: Percentage of subset participants with grading shifts in hematology and chemistry laboratory assessments

    Time: Between baseline and 7 days after dose 1

    Description: As measured at the local laboratory

    Measure: Percentage of subset participants with grading shifts in hematology and chemistry laboratory assessments

    Time: Between before dose 2 and 7 days after dose 2

    Description: As measured at the central laboratory

    Measure: SARS-CoV-2 serum neutralizing antibody levels, expressed as GMTs

    Time: 1 month after dose 2

    Description: As measured at the central laboratory

    Measure: GMFR in SARS-CoV-2 serum neutralizing titers

    Time: From before vaccination to 1 month after dose 2

    Description: as measured at the central laboratory

    Measure: SARS-CoV-2 S1-binding IgG levels, expressed as GMCs

    Time: 1 month after dose 2

    Description: as measured at the central laboratory

    Measure: GMFR in SARS-CoV-2 S1-binding IgG levels

    Time: From before vaccination to 1 month after dose 2

    Secondary Outcomes

    Description: As measured at the central laboratory

    Measure: SARS-CoV-2 serum neutralizing antibody levels, expressed as GMTs

    Time: Through 1 year after dose 2

    Description: As measured at the central laboratory

    Measure: GMFR in SARS-CoV-2 serum neutralizing titers from before vaccination to each subsequent time point

    Time: Through 1 year after dose 2 from baseline

    Description: As measured at the central laboratory

    Measure: SARS-CoV-2 S1-binding IgG levels, expressed as GMCs

    Time: Through 1 year after dose 2

    Description: As measured at the central laboratory

    Measure: GMFR in SARS-CoV-2 S1-binding IgG levels from before vaccination to each subsequent time point

    Time: Through 1 year after dose 2 from baseline

    Description: As measured at the central laboratory

    Measure: GMR of the geometric mean of SARS-CoV-2 serum neutralizing titers to the geometric mean of SARS CoV 2 S1-binding IgG levels

    Time: Through 1 year after dose 2
    387 A Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose First-in-Human Study Investigating the Safety, Tolerability, and Pharmacokinetics of Intravenously Administered HFB30132A, a Monoclonal Antibody Directed Against SARS-CoV-2, in Healthy Adult Subjects

    The purpose of this study is to test the safety and tolerability of HFB30132A when it is given by intravenously to healthy participants. Blood tests will be done to check how much HFB30132A is in the bloodstream and how long the body takes to eliminate it. Participation may include up to ten visits to the study center.

    NCT04590430
    Conditions
    1. Healthy
    Interventions
    1. Drug: HFB30132A
    2. Other: Placebo

    Primary Outcomes

    Description: Number of participants experiencing TEAEs

    Measure: Number of participants with treatment emergent serious adverse events (TESAEs)

    Time: From Day 1 to up to Day 30 of the last enrolled subject

    Description: Safety and tolerability will be evaluated in terms of number of participants with TEAEs of special interest (hypersensitivity / anaphylactic reaction / local tolerability)

    Measure: Number of participants with treatment emergent adverse events (TEAE) of special interest

    Time: From Day 1 to up to Day 30 of the last enrolled subject

    Description: Safety and tolerability will be evaluated in terms of number of participants with TEAE

    Measure: Number of participants with treatment-emergent adverse events (TEAE)

    Time: From Day 1 to up to Day 30 of the last enrolled subject

    Measure: Maximum observed serum concentration (Cmax)

    Time: From Day 1 to up to Day 30 of the last enrolled subject

    Measure: Minimum observed serum concentration (Cmin)

    Time: From Day 1 to up to Day 30 of the last enrolled subject

    Measure: Time of maximum serum concentration (Tmax)

    Time: From Day 1 to up to Day 30 of the last enrolled subject

    Measure: Area under the concentration vs. time curve (AUC0-last), AUC0-∞)

    Time: From Day 1 to up to Day 30 of the last enrolled subject

    Measure: Terminal half-life (T1/2)

    Time: From Day 1 to up to Day 30 of the last enrolled subject

    Measure: Systemic clearance (CL)

    Time: From Day 1 to up to Day 30 of the last enrolled subject

    Measure: Steady-state volume of distribution (Vss)

    Time: From Day 1 to up to Day 30 of the last enrolled subject

    Secondary Outcomes

    Description: Safety and tolerability will be evaluated in terms of number of participants with TEAEs

    Measure: Number of participants with treatment-emergent adverse events (TEAEs)

    Time: From Day 1 to up to last follow-up day (Day 270)

    Description: Safety and tolerability will be evaluated in terms of number of participants with TESAEs

    Measure: Number of participants with treatment-emergent serious adverse events (TESAEs)

    Time: From Day 1 to up to last follow-up day (Day 270)

    Measure: Maximum observed serum HFB30132A concentration (Cmax) in nasal and oral secretions

    Time: From Day 1 to up to last follow-up day (Day 270)

    Measure: Minimum observed serum HFB30132A concentration (Cmin) in nasal and oral secretions

    Time: From Day 1 to up to last follow-up day (Day 270)

    Measure: Time of maximum serum HFB30132A concentration (Tmax) in nasal and oral secretions

    Time: From Day 1 to up to last follow-up day (Day 270)

    Measure: Area under the concentration vs. time curve (AUC0-last), AUC0-∞) in nasal and oral secretions

    Time: From Day 1 to up to last follow-up day (Day 270)

    Measure: Terminal half-life (T1/2) of HFB30132A in nasal and oral secretions

    Time: From Day 1 to up to last follow-up day (Day 270)

    Measure: Systemic clearance (CL) of HFB30132A in nasal and oral secretions

    Time: From Day 1 to up to last follow-up day (Day 270)

    Measure: Steady-state volume of distribution (Vss) of HFB30132A in nasal and oral secretions

    Time: From Day 1 to up to last follow-up day (Day 270)

    Description: Presence or absence of antibodies against HFB30132A over time

    Measure: HFB30132A Anti-drug antibodies

    Time: From Day 1 to up to last follow-up day (Day 270)
    388 Safety, Tolerability and Efficacy of GLS-1027 in the Prevention of Severe Pneumonitis Caused by SARS-CoV-2 Infection

    This clinical trial will evaluate the safety, tolerability and efficacy of GLS-1027 in the prevention of severe pneumonitis caused by SARS-CoV-2 infection

    NCT04590547
    Conditions
    1. Pneumonitis
    2. SARS-CoV Infection
    Interventions
    1. Drug: GLS-1027
    2. Drug: Placebo
    MeSH:Infection Communicable Diseases Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Measure: Incidence of serious adverse events relative to treatment group

    Time: 56 days

    Measure: Incidence of progression to WHO Classification of ≥6 to include intubation with mechanical ventilation, need for ECMO, or death relative to treatment group

    Time: 56 days

    Secondary Outcomes

    Measure: Assess the number of days requiring ICU care relative to treatment group

    Time: 56 days

    Measure: Assess the number of days of mechanical ventilation relative to treatment group

    Time: 56 days
    389 Industry Alliance Platform Trial to Assess the Efficacy and Safety of Multiple Candidate Agents for the Treatment of COVID-19 in Hospitalized Patients

    The primary objective of this study is to evaluate the time to confirmed clinical recovery in participants hospitalized with COVID-19. Candidate agents will be evaluated frequently for efficacy and safety, with candidate agents being added to and/or removed from the study on an ongoing basis, depending on the results of their evaluation.

    NCT04590586
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Standard of care
    2. Drug: Apremilast
    3. Drug: Placebo

    Primary Outcomes

    Description: Confirmed clinical recovery means the participant is fit for discharge from hospital. Fit for discharge is defined by achieving a score of 6, 7, or 8 on the 8-point ordinal scale of clinical severity status, without being re-hospitalized prior to Day 29. 8-point ordinal scale of clinical severity status scores are: Death Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) Hospitalized, on noninvasive ventilation or high-flow oxygen devices Hospitalized, requiring supplemental oxygen Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care (COVID-19 related or otherwise) Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care Not hospitalized, limitation on activities and/or requiring home oxygen Not hospitalized, no limitations on activities

    Measure: Time to confirmed clinical recovery

    Time: Up to Day 29

    Secondary Outcomes

    Description: Oxygen-free recovery is defined as participants who are alive, discharged, and not receiving supplement oxygen

    Measure: Number of participants who achieve oxygen-free recovery at Day 29

    Time: Day 29

    Description: Fit for discharge is defined by achieving a score of 6, 7, or 8 on the 8-point ordinal scale of clinical severity status, without being re-hospitalized prior to Day 29. 8-point ordinal scale of clinical severity status scores are: Death Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) Hospitalized, on noninvasive ventilation or high-flow oxygen devices Hospitalized, requiring supplemental oxygen Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care (COVID-19 related or otherwise) Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care Not hospitalized, limitation on activities and/or requiring home oxygen Not hospitalized, no limitations on activities

    Measure: Number of participants who experience ≥2-point improvement from baseline or assessed as fit-for-discharge on the ordinal scale at Day 29

    Time: Baseline to Day 29

    Measure: Incidence of all-cause mortality

    Time: Up to Day 29

    Description: 8-point ordinal scale of clinical severity status scores are: Death Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) Hospitalized, on noninvasive ventilation or high flow oxygen devices Hospitalized, requiring supplemental oxygen Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care (COVID-19 related or otherwise) Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care Not hospitalized, limitation on activities and/or requiring home oxygen Not hospitalized, no limitations on activities

    Measure: Distribution of participants across the 8-point ordinal scale of clinical severity status scores at Day 8, Day 15 and Day 29

    Time: Day 8, Day 15 and Day 29

    Description: 8-point ordinal scale of clinical severity status scores are: Death Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) Hospitalized, on noninvasive ventilation or high flow oxygen devices Hospitalized, requiring supplemental oxygen Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care (COVID-19 related or otherwise) Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care Not hospitalized, limitation on activities and/or requiring home oxygen Not hospitalized, no limitations on activities

    Measure: Worst post-baseline score on the 8-point ordinal scale of clinical severity status

    Time: Up to Day 29

    Measure: Number of intensive care unit (ICU) days

    Time: Day 1 to Day 29

    Measure: Number of invasive mechanical ventilator days

    Time: Day 1 to Day 29

    Description: Clinical recovery is defined by achieving a score of 6, 7 or 8 on the 8-point ordinal scale of clinical severity status. 8-point ordinal scale of clinical severity status scores are Death Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) Hospitalized, on noninvasive ventilation or high flow oxygen devices Hospitalized, requiring supplemental oxygen Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care (COVID-19 related or otherwise) Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care Not hospitalized, limitation on activities and/or requiring home oxygen Not hospitalized, no limitations on activities

    Measure: Number of participants who achieve clinical recovery at Day 8, Day 15, and Day 29

    Time: Day 8, Day 15, and Day 29

    Description: Sustained clinical recovery is defined by achieving a score of 6, 7 or 8 on the 8-point ordinal scale of clinical severity status at follow-up visit (Day 60). 8-point ordinal scale of clinical severity status scores are Death Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) Hospitalized, on noninvasive ventilation or high flow oxygen devices Hospitalized, requiring supplemental oxygen Hospitalized, not requiring supplemental oxygen, requiring ongoing medical care (COVID-19 related or otherwise) Hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care Not hospitalized, limitation on activities and/or requiring home oxygen Not hospitalized, no limitations on activities

    Measure: Number of participants who achieve sustained clinical recovery at Day 60

    Time: Day 60

    Measure: Number of participants who experience one or more treatment-emergent adverse events (TEAEs)

    Time: Baseline to Day 60

    Measure: Number of participants who experience one or more serious adverse events (SAEs)

    Time: Baseline to Day 60

    Measure: Number of participants who experience one or more common terminology criteria for adverse events (CTCAE) grade 3 or higher

    Time: Baseline to Day 60

    Measure: Number of participants who experience one or more adverse events (AEs) leading to dose modification

    Time: Baseline to Day 60

    Measure: Number of participants who experience one or more adverse events (AEs) leading to discontinuation

    Time: Baseline to Day 60
    390 A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Dose Escalation Study to Evaluate the Safety, Pharmacokinetics, and Immunogenicity of ADM03820 in Adults

    ADM03820 is indicated for the treatment and prevention of SARS-CoV-2 (COVID-19) in adults. The primary purpose of this study is to assess the safety of ADM03820 in healthy male and female subjects compared to placebo.

    NCT04592549
    Conditions
    1. SARS-CoV-2
    Interventions
    1. Drug: ADM03820
    2. Other: Placebo

    Primary Outcomes

    Measure: The number of participants with Serious Adverse Events following administration of ADM03820 to the final visit

    Time: 540 days

    Measure: The number of participants with AEs from administration of ADM03820 to the final visit

    Time: 540 days

    Secondary Outcomes

    Measure: The assessment of Peak Plasma Concentration (Cmax) for total antibodies of ADM03820 as measured by enzyme-linked immunosorbent assay (ELISA) methods designed for total monoclonal antibody in the Drug Product.

    Time: 540 days

    Measure: The assessment of Tmax for total antibodies of ADM03820 as measured by enzyme-linked immunosorbent assay (ELISA) methods designed for total monoclonal antibody in the Drug Product.

    Time: 540 days

    Measure: The assessment of the Area under the plasma concentration (AUC(0-t)) for total antibodies of ADM03820 as measured by enzyme-linked immunosorbent assay (ELISA) methods designed for total monoclonal antibody in the Drug Product.

    Time: 540 days

    Measure: To assess the anti-drug antibody levels

    Time: 540 days
    391 A Randomized, Double-blind, Placebo-controlled Safety and Clinical Outcomes Study of Disulfiram in Subjects With Moderate COVID-19

    This clinical trial evaluates the safety, efficacy, and biomarker levels of FDA-approved drug disulfiram in the treatment of adult subjects hospitalized with moderate COVID-19. Disulfiram may limit the hyperinflammatory response associated with COVID-19 and reduce the risk of progression to severe illness. Subjects will be screened and randomized to receive either daily administration of oral disulfiram or placebo for 14 days. Subjects will be followed up on Day 28.

    NCT04594343
    Conditions
    1. Covid19
    Interventions
    1. Drug: Disulfiram
    2. Drug: Placebo

    Primary Outcomes

    Measure: Change from baseline to day 7 for cytokine IL-18

    Time: Baseline to Day 7

    Secondary Outcomes

    Measure: Percentage of subjects that do not require invasive mechanical ventilation

    Time: 14 Days

    Measure: Mean number of days of invasive mechanical ventilation for those subjects requiring invasive mechanical ventilation

    Time: 14 Days

    Measure: Mean number of days of non-invasive ventilation for those subjects requiring non-invasive ventilation

    Time: 14 Days

    Measure: Mean number of days of supplemental oxygen

    Time: 14 Days

    Measure: Percentage of subjects that deteriorate 1 or more points in the 7-point WHO Ordinal Scale from baseline to Day 14

    Time: Baseline to Day 14

    Measure: Percentage of subjects that are not admitted to the Intensive Care Unit (ICU)

    Time: 14 Days

    Measure: 28-day mortality

    Time: At Day 28

    Other Outcomes

    Measure: Percent change in neutrophil count from baseline to Day 7 and 14

    Time: Baseline to Day 7 and baseline to Day 14

    Measure: Percent change in total lymphocyte count from baseline to Day 7 and 14

    Time: Baseline to Day 7 and baseline to Day 14

    Measure: Change from baseline to Day 7 and 14 for neutrophil-derived circulating free DNA (cf-DNA/NETs)

    Time: Baseline to Day 7 and baseline to Day 14

    Measure: Change from baseline to Day 7 and 14 for Cytokine TNF-α

    Time: Baseline to Day 7 and baseline to Day 14

    Measure: Change from baseline to Day 7 and 14 for cytokine IL-1β

    Time: Baseline to Day 7 and baseline to Day 14

    Measure: Change from baseline to Day 7 and 14 for cytokine IL-1RA

    Time: Baseline to Day 7 and baseline to Day 14

    Measure: Change from baseline to Day 7 and 14 for cytokine IL-6

    Time: Baseline to Day 7 and baseline to Day 14

    Measure: Change from baseline to Day 7 and 14 for cytokine IL-8

    Time: Baseline to Day 7 and baseline to Day 14

    Measure: Change from baseline to Day 7 and 14 for cytokine IL-10

    Time: Baseline to Day 7 and baseline to Day 14

    Measure: Change from baseline to Day 7 and 14 for Lactate Dehydrogenase (LDH)

    Time: Baseline to Day 7 and baseline to Day 14

    Measure: Change from baseline to Day 7 and 14 for D-dimer

    Time: Baseline to Day 7 and baseline to Day 14

    Measure: Change from baseline to Day 14 for cytokine IL-18

    Time: Baseline to Day 14
    392 Favipiravir for Patients With Mild to Moderate Disease From Novel Coronavirus (COVID-19)

    Double-blinded, placebo controlled, randomized, phase 3 trial evaluating the antiviral drug favipiravir as potential therapy for mild to moderate COVID-19 in adult outpatients who are not requiring hospitalization and who have had a recently positive COVID-19 test prior to study enrollment.

    NCT04600895
    Conditions
    1. Covid19
    Interventions
    1. Drug: Favipiravir
    2. Drug: Placebo

    Primary Outcomes

    Description: The endpoint will be considered to have been met at the earliest time point at which the associated symptoms over a continuous period of 48 hours.

    Measure: Time to sustained clinical recovery

    Time: From Day 0 to Day 21

    Secondary Outcomes

    Description: Time (number of days) to negative conversion of detectable SARS-CoV-2 viral RNA in negative Reverse Transcription-Polymerase Chain Reaction (RT-PCR) assays of saliva

    Measure: Time of Negative Conversion of SARS-CoV2 RNA

    Time: From Day 0 to Day 10

    Description: Proportion of patients showing negative conversion of detectable SARS-CoV-2 viral RNA in saliva

    Measure: Proportion of Negative Conversion of SARS-CoV2 RNA

    Time: Day 2, 4, 6, 8 and 10

    Description: Proportion of patients showing Alleviation of Symptoms fever, chills, cough, sore throat, malaise, headache, muscle pain, diarrhea, vomiting, shortness of breath

    Measure: Proportion of patients showing Alleviation of Symptoms

    Time: Day 4, 7, 10, 14 and 21

    Description: Progression to severe COVID-19 (severe COVID-19 defined as O2 saturation of <94% at rest, all cause hospitalization, or death)

    Measure: Proportion of patients that progress to severe COVID-19

    Time: Day 21

    Description: Proportion of patients dying a. from any cause, b. from a COVID-19 associated complication

    Measure: Reduction in Death Related to COVID-19

    Time: Day 21

    Description: Proportion of patients hospitalized: a. from any cause, b. from a COVID-19 associated complication

    Measure: Reduction in Patient Hospitalization

    Time: Day 21

    Description: Incidence of hospitalization for respiratory distress or O2 saturation <93%

    Measure: Reduction in incidence of hospitalization for respiratory distress or O2 saturation

    Time: Day 21

    Other Outcomes

    Description: Number (and proportion) of patients reporting treatment emergent adverse events by MedDRA system organ class and preferred term

    Measure: Safety / Adverse Events

    Time: Day 21

    Description: Changes of parameters for heart rate (beats per minutes) at each assessment during the study/follow-up period, compared to baseline

    Measure: Vitals (Heart rate)

    Time: Day 21

    Description: Changes of parameters for body temperature (°C) at each assessment during the study/follow-up period, compared to baseline

    Measure: Vitals (Body Temperature)

    Time: Day 21

    Description: Changes of parameters for oxygen saturation (%) at each assessment during the study/follow-up period, compared to baseline

    Measure: Vitals (Oxygen Saturation)

    Time: Day 21
    393 Pilot Study: The Evaluation of Nitric Oxide Generating Lozenges on Outcome in Newly Diagnosed COVID-19 Patient of African American Origin

    This study is a multi-center, randomized, double blinded, prospective, placebo controlled study. Patients upon diagnosis of COVID-19 (Corona Virus Disease-19) will be eligible to participate in the study. The purpose of this study is to find out the side effects and ability to take the study drug, Nitric Oxide (NO) lozenges when taken twice daily by mouth. If this study shows that the drug has no or few, acceptable side effects, it will then include up to 840 participants to find out if the drug can reduce bad outcomes of COVID-19 infection (hospitalization, ICU admission, death). In each part of the study, half of the subjects will receive the study drug and the other half will be given a placebo (inactive pill).

    NCT04601077
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Nitric Oxide lozenges, 30 mg
    2. Drug: Placebo

    Primary Outcomes

    Description: Blood pressure under 90 mmHg

    Measure: Low blood pressure

    Time: 30 days

    Description: Incidence of self reported dizziness

    Measure: dizziness

    Time: 30 days

    Secondary Outcomes

    Description: The effects of NO therapy on incidence of hospitalization, intubation, ICU admission, dialysis and death in treated patients vs. those receiving placebo therapy.

    Measure: Incidence of hospitalization, ICU admission, intubation, dialysis and death

    Time: 30 Days
    394 Ivermectin in Adults With Severe COVID-19. Double-blind Randomized Clinical Trial

    Since the onset of the disease, more than 40.5 million people have been diagnosed with COVID-19 and nearly 1.2 million people have died (October 21, 2020). There is no complete understanding of the pathogenesis of SARS-CoV-2 infection and to this day there is no specific therapy or vaccine available. Thus, patient care is based on symptomatic therapy and treatment of complications. Ivermectin has been used for more than 30 years for the treatment of several diseases. More than one million doses of the drug are administered daily, particularly in low- and middle-income countries. Due to the low prevalence of adverse events with the use of this drug, ivermectin is considered to have a good safety profile and its potential benefit in other diseases is currently under investigation. An in vitro study of ivermectin in SARS-CoV-2 in Australia showed a significant reduction of viral load in infected cells. Subsequently, a descriptive study of 704 critical patients with COVID-19 showed a reduction in mortality, hospitalization, and intensive care unit length-of-stay in those patients who received the drug. Unfortunately, this study was withdrawn by its authors, leaving more questions than answers. Some countries in Latin America have authorized its use for the management of patients with COVID-19 even in the absence of solid evidence, and several other countries are conducting clinical trials to evaluate its efficacy for the treatment of moderate and severe disease. Since there is no specific treatment for COVID-19 and the therapeutic options are scarce, the researchers believe it is completely plausible, urgent, and necessary to evaluate if ivermectin use reduces the risk of admission to an intensive care unit (ICU) in hospitalized adults with severe COVID-19. The proposal is a randomized, double-blind clinical trial, conducted at CES Clinic, Medellin-Colombia. The investigators will randomize 100 patients with severe, non-critical illness, into two groups, one group will receive ivermectin in addition to standard management and the other group will receive placebo plus standard management. Clinical outcomes to evaluate will be ICU admission, need for mechanical ventilation, length of hospital stay, days in the ICU and mechanical ventilation, and finally, the incidence of adverse events related to the intervention. The estimated time to complete the study is approximately five months.

    NCT04602507
    Conditions
    1. Covid19
    2. Severe Acute Respiratory Syndrome
    Interventions
    1. Drug: Ivermectin
    2. Other: Placebo
    MeSH:Severe Acute Respiratory Syndrome Coronavirus Infections

    Primary Outcomes

    Description: Cumulative incidence of ICU admission.

    Measure: Admission to the intensive care unit.

    Time: 21 days

    Secondary Outcomes

    Description: Duration of hospitalization (days).

    Measure: Hospital length of stay.

    Time: 21 days

    Description: 21-day mortality.

    Measure: Mortality rate.

    Time: 21 days

    Description: Number of days in ICU.

    Measure: ICU length of stay.

    Time: 21 days

    Description: Number of days with mechanical ventilator.

    Measure: Length of stay in ventilator time.

    Time: 21 days

    Description: Cumulative incidence of adverse effects: headache, rash, pruritus, arthralgia, tachycardia, dizziness, hypotension, uveitis, Steven Johnson Syndrome.

    Measure: Adverse effects of ivermectin.

    Time: 21 days
    395 A Phase 2/3 Randomized and Placebo-Controlled Study of ANA001 in Moderate COVID-19 Patients

    Study of ANA001 in Moderate COVID-19 Patients

    NCT04603924
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Niclosamide
    2. Drug: Placebo

    Primary Outcomes

    Description: Incidence of treatment emergent adverse events (TEAE's)

    Measure: Safety and Tolerability of ANA001 as measured by the incidence of treatment emergent adverse events (TEAE's) (Part 1 and Part 2)

    Time: Randomization to Day 28

    Description: Median time to hospital discharge

    Measure: Efficacy as measured by median time to hospital discharge (Part 2)

    Time: Randomization to Day 60

    Secondary Outcomes

    Description: Median time to hospital discharge

    Measure: Efficacy as measured by median time to hospital discharge (Part 1)

    Time: Randomization to Day 60

    Description: Plasma concentrations of ANA001

    Measure: Pharmacokinetics (PK) of ANA001 as measured by plasma concentrations (Part 1)

    Time: Day 1, 2, 3 or 4

    Description: Mean change from baseline in National Early Warning Score (NEWS 2) score

    Measure: Efficacy of ANA001 as measured by mean change from baseline in the National Early Warning Score (NEWS 2) (Part 2)

    Time: Day 8, Day 15

    Description: Mean number of days on rescue therapy

    Measure: Efficacy of ANA001 as measured by mean number of days on rescue therapy (Part 2)

    Time: Within 15 days after enrollment
    396 BI 764198 Efficacy and Safety in Prevention/Progression of ARDS and ARDS-related Complications Secondary to COVID-19 (ACTION ON COVID-19)

    This study is open to adults with COVID-19 infection who are in hospital and receive oxygen. Participants need to be 50 years of age or older and need to be at risk of further worsening of their condition. The purpose of the study is to find out whether a medicine called BI 764198 helps people with COVID-19 infection and breathing problems. BI 764198 may prevent cell death and swelling of the lung tissue and therefore help patients with COVID-19 infection. Participants are put into 2 groups by chance. One group of participants gets BI 764198 capsules and the other group gets placebo capsules. The placebo capsules look exactly like the BI 764198 capsules but do not contain any medicine. Participants take 1 capsule per day. Participants are in the study for about a month. At study end, doctors compare the 2 groups for the number of patients that are alive and do not need mechanical breathing support. During the study, the doctors collect information on any health problems of the participants.

    NCT04604184
    Conditions
    1. COVID-19
    Interventions
    1. Drug: BI 764198
    2. Drug: Placebo

    Primary Outcomes

    Measure: Patients alive and free of mechanical ventilation

    Time: At Day 29

    Secondary Outcomes

    Measure: Patients alive and discharged free of oxygen

    Time: At Day 29

    Measure: Patients with occurrence of any component of composite: In-hospital mortality or intensive care unit (ICU) admission or mechanical ventilation

    Time: At Day 29

    Description: Clinical improvement of at least 2 points (from randomisation) on the World Health Organization Clinical Progression Scale, discharge from the hospital, or considered fit for discharge (a score of 0, 1, 2, or 3 on the Clinical Progression Scale), whichever comes first. The scale provides a measure of illness severity across a range from 0 (not infected) to 10 (dead).

    Measure: Time to response

    Time: Up to Day 29

    Measure: Number of ventilator free days

    Time: Up to Day 29

    Measure: Mortality

    Time: At Day 15, 29, 60 and 90
    397 Phase-II Randomized Clinical Trial to Evaluate the Effect of Pirfenidone Compared to Placebo in Post-COVID19 Pulmonary Fibrosis

    Study population: Patients with fibrotic lung sequelae after recovery from acute phase of severe COVID19 pneumonia Objectives: To evaluate the effect of pirfenidone administered for 24 weeks in patients who have pulmonary fibrotic changes after suffering severe COVID19 pneumonia, analysed by - % change in forced vital capacity (FVC) - % fibrosis in high resolution computed tomography (HRCT) of the lung

    NCT04607928
    Conditions
    1. Fibrotic Pulmonary Sequelae Post-COVID19 Infection
    Interventions
    1. Drug: Pirfenidone
    2. Drug: Placebo
    MeSH:Pulmonary Fibrosis
    HPO:Pulmonary fibrosis

    Primary Outcomes

    Description: To investigate the effect of pirfenidone administered for 24 weeks measuring the number of patients who have pulmonary fibrotic changes from baseline after suffering severe COVID19 pneumonia, analysed by Change From Baseline in % in forced vital capacity (FVC) Change From Baseline % fibrosis in high resolution computed tomography (HRCT) of the lung

    Measure: To investigate the effect of pirfenidone on fibrotic signs induced by COVID19 infection

    Time: 24 weeks

    Secondary Outcomes

    Description: Number of patients who show maintenance of stability or functional improvement: stability will be considered when the FVC does not increase more than 10% or does not decrease more than 10% and the DLCO does not increase more than 15% or decreases more than 15%. An increase in% FVC greater than 10% or in DLCO greater than 15% will be considered significant improvement.

    Measure: Maintenance of stability or functional improvement FVC

    Time: 24 weeks

    Description: Rate of decreased oxygen requirement for physical activity in patients

    Measure: Decreased oxygen requirement for physical activity

    Time: 24 weeks

    Description: Number of patients who have improved exercise capacity (> 50 meter improvement or less decrease in% oxygen saturation) in the TM6m

    Measure: Improved exercise capacity (> 50 meter improvement or less decrease in% oxygen saturation) in the TM6m

    Time: 24 weeks

    Description: Number of Hospitalizations (general and due to respiratory problems)

    Measure: Hospitalizations (general and due to respiratory problems)

    Time: 24 weeks

    Description: Number of Visits to the Emergency or Day Hospital for respiratory causes

    Measure: Visits to the Emergency or Day Hospital for respiratory causes

    Time: 24 weeks

    Description: Number of patients who need Lung transplantation

    Measure: Lung transplantation

    Time: 24 weeks

    Description: Number of patients who die

    Measure: Death

    Time: 24 weeks
    398 A Multicenter Randomized Trial to Evaluate the Efficacy and Safety of Camostat Mesylate for the Treatment of SARS-CoV-2 Infection - COVID-19 in Ambulatory Adult Patients (CAMOVID)

    The overall objective of the study is to determine the therapeutic effect and tolerance of Camostat mesylate, compared to placebo in adult patients with ambulatory COVID-19 disease, presenting with risk factors of severe COVID-19. Camostat mesylate is a serine protease TMPRSS2 (Transmembrane Serine Protease 2) inhibitor which has been successfully and safely used to treat pancreatitis-associated pain and post-operative reflux oesophagitis in Japan. More recently, it has been shown to inhibit SARS-CoV-2 viral entry and reduce infection of human primary pneumocytes and lung cell lines. Camostat mesylate or placebo will be administered to consenting adult patients with virologically confirmed COVID-19, not requiring initial hospitalization. All patients will receive standard of care along with randomized treatments. Outcomes of included patients will be compared between the 2 groups.

    NCT04608266
    Conditions
    1. Covid19
    Interventions
    1. Drug: Camostat Mesylate
    2. Drug: Placebo
    MeSH:Infection

    Primary Outcomes

    Description: Proportion of patients hospitalized for COVID-19 deterioration or who died without hospitalization

    Measure: Hospitalization for COVID-19 deterioration or death without hospitalization

    Time: Day 21

    Secondary Outcomes

    Description: Number of patients with at least one adverse event

    Measure: Adverse events

    Time: Day 21

    Description: Number of patients with at least one serious adverse event

    Measure: Serious adverse events

    Time: Day 21

    Description: Number of patients who discontinued the investigational medication

    Measure: Investigational medication discontinuation

    Time: Day 21

    Description: Proportion of patients hospitalized for COVID-19 deterioration (reviewed by independent adjudication comitter) or who died without hospitalization

    Measure: Hospitalization for COVID-19 deterioration or death without hospitalization, evaluated by independent adjudication comittee

    Time: Day 21

    Description: WHO clinical scale: Uninfected - No clinical or virological evidence of infection: 0; Ambulatory - No limitation of activities: 1; Ambulatory - limitation of activities: 2; Hospitalized - no oxygen therapy: 3; Hospitalized - oxygen by mask or nasal prongs: 4; Hospitalized; oxygen by non invasive ventilation or High flow: 5; Intubation and Mechanical ventilation: 6; Mechanical ventilation + additional organ support (pressors, Renal replacement therapy, ECMO):7; Dead: 8

    Measure: Clinical improvement using the Word Health Organization (WHO) COVID-19 scale

    Time: Day 7, 14, 21

    Description: Proportion of patients admitted to an intensive care unit

    Measure: Need for intensive care

    Time: Day 21

    Description: Number of days alive without hospitalization up to day 21

    Measure: Duration of hospitalization

    Time: Day 21

    Description: Proportion of patients with initiation of invasive mechanical ventilation

    Measure: Need for invasive mechanical ventilation for severe COVID-19

    Time: Day 21

    Description: Proportion of patients with initiation of oxygen therapy

    Measure: Need for oxygen therapy for COVID-19

    Time: Day 21

    Description: Proportion of patients alive at day 90

    Measure: Overall survival

    Time: Day 90

    Description: Number of days alive without symptoms at day 21

    Measure: Duration of symptoms

    Time: Day 21

    Description: By Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) on nasal swab and droplet quantification of SARS-CoV2 ribonucleic acid-emia (RNAemia)

    Measure: SARS-CoV-2 virological assessment

    Time: Day 7, 14, 21

    Description: SARS-CoV2 antibodies quantification in blood

    Measure: SARS-CoV-2 serological assessment

    Time: Day 7, 14, 21 and 90

    Description: Peripheral blood lymphocyte phenotyping with telomere length measurement

    Measure: Peripheral blood lymphocyte phenotyping

    Time: Day 1, 14, 90

    Description: Acute kidney failure defined as at least serum creatinine increase of 0.3mg/dl or 1.5-1.9 times baseline and/or oliguria < 0.5ml/kg/h

    Measure: Acute kidney failure

    Time: Day 21

    Description: estimated glomerular filtration rate

    Measure: Renal function

    Time: Day 7, 14 and 21

    Description: Uricemia in mmol/L or mg/dL

    Measure: Concentration of urea in blood

    Time: Day 7, 14 and 21

    Description: Kaliemia in mmol/L

    Measure: Concentration of potassium in blood

    Time: Day 7, 14 and 21

    Description: Liver transaminases dosage on blood sample

    Measure: Liver function

    Time: Day 7, 14 and 21

    Description: Gamma-glutamyl transferase (gamma-GT) dosage on blood sample

    Measure: Liver function (2)

    Time: Day 7, 14 and 21

    Other Outcomes

    Description: Biobanking of blood samples for predictive biomarker assessment

    Measure: Biobanking for biomarker assessment

    Time: Day 1, 7, 14, 21, 90
    399 A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy and Safety of ZnAg Liquid Solution to Treat COVID-19 in Acutely Symptomatic Non-Hospitalized Participants

    This is a multi-site, randomized, double-blind, placebo-controlled study assessing the efficacy and safety of ZnAg liquid solution in symptomatic participants with acute COVID-19 that are not hospitalized at the time of enrollment.

    NCT04610138
    Conditions
    1. Covid19
    Interventions
    1. Drug: CNM-ZnAg
    2. Drug: Placebo

    Primary Outcomes

    Description: Confirmed symptom resolution over a continuous period ≥ 48 hours, defined as PGI-Severity of 'Normal' in Participants whose Baseline PGI-Severity value was 'Mild'; or, a PGI-Severity of 'Normal' or 'Mild' in participants whose Baseline PGI-Severity value was 'Moderate' or 'Severe'.

    Measure: Time to substantial alleviation of COVID-19 symptoms

    Time: Up to 28 days.

    Secondary Outcomes

    Description: Hospitalization will be determined by Investigator's clinical judgement. Where applicable, Investigators should follow local recommendations for hospitalization of patients with COVID-19 within their institution.

    Measure: The proportion of participants who require COVID-19 related hospitalization, are hospitalized for COVID-19 related medical support, or are deceased within 28-days following randomization.

    Time: Up to 28 days.

    Other Outcomes

    Description: Days from baseline participant remains alive.

    Measure: Number of alive hospital free days at Day 28.

    Time: 28 days

    Description: Cycle Thresholds assessed by RT-qPCR.

    Measure: Mean change from Baseline to Day 14, Day 21, and Day 28 in SARS-CoV-2 viral load.

    Time: Up to 28 days

    Description: Oxygen saturation will be obtained after the participant has been resting for 5 minutes.

    Measure: Change from Baseline to Day 8, Day 14, Day 21, and 28 in the slope of oxygen saturation levels (SpO2) assessed per protocol.

    Time: up to 28 days

    Description: Measured by changes in participant rated Clinical Global Impression.

    Measure: Clinical Global Impression (CGI) Severity and Change measures from Baseline to Day 8, Day 14, Day 21, and 28.

    Time: Up to 28 days

    Description: Measured by changes in participant rated Patient Global Impression.

    Measure: Patient Global Impression (PGI) Severity and Change measures from Baseline to Day 8, Day 14, Day 21, and 28.

    Time: Up to 28 days

    Description: Summary measure integrating semi-daily serial assessments of a subject's symptom count and severity over the duration of the study.

    Measure: Change in the area under the curve for Net Symptom Burden from Baseline to Day 8, Day 14, Day 21, and 28.

    Time: Up to 28 days

    Description: Assessed by the Clinical Status Ordinal Scale established in the remdesivir ACTT study. Scale is 1-8, with 1 being the least severe and 8 being the most severe (death).

    Measure: Change in clinical status from Baseline to Day 8, Day 14, Day 21, and Day 28.

    Time: Up to 28 days

    Description: Rate of deceased participants at day 28.

    Measure: All-cause mortality rate at Day 28.

    Time: 28 days
    400 A Phase 3, Randomized, Observer-Blinded, Placebo-Controlled Study to Evaluate the Efficacy, Safety, and Immunogenicity of a SARS-CoV-2 Recombinant Spike Protein Nanoparticle Vaccine (SARS-CoV-2 rS) With Matrix-M1™ Adjuvant in Adult Participants ≥ 18 Years

    This is a study to evaluate the effectiveness, immune response, and safety of a coronavirus disease 2019 (COVID-19) vaccine called SARS-CoV-2 rS with Matrix-M1 adjuvant in adults 18 years of age and older in the United States and Mexico. A vaccine causes the body to have an immune response that may help prevent the infection or reduce the severity of symptoms. An adjuvant is something that can make a vaccine work better. This study will look at the protective effect, body's immune response, and safety of SARS-CoV-2 rS with Matrix-M1 adjuvant in the study population. Participants in the study will randomly be assigned to receive SARS-CoV-2 rS with Matrix-M1 adjuvant or placebo. Each participant in the study will receive a total of 2 intramuscular injections over the course of the study. Up to 30,000 participants will take part in the study.

    NCT04611802
    Conditions
    1. SARS-CoV Infection
    2. Covid19
    Interventions
    1. Biological: SARS-CoV-2 rS/Matrix-M1 Adjuvant
    2. Other: Placebo
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome

    Primary Outcomes

    Description: Number of participants with first occurrence of positive (+) polymerase chain reaction (PCR)-confirmed SARS-CoV-2 illness with symptomatic mild, moderate, or severe COVID-19, with each symptom lasting for at least 2 consecutive days, with onset from Day 28 (7 days after second vaccination dose) through the length of the study.

    Measure: Participants with Symptomatic Mild, Moderate, or Severe Coronavirus Disease 2019 (COVID-19)

    Time: Day 28 to Day 750

    Secondary Outcomes

    Description: Number of participants with first occurrence of (+) PCR-confirmed SARS-CoV-2 illness with symptomatic moderate or severe COVID-19, with each symptom lasting for at least 2 consecutive days, with onset from Day 28 (7 days after second vaccination dose) through the length of the study.

    Measure: Participants with Symptomatic Moderate or Severe COVID-19

    Time: Day 28 to Day 750

    Description: Number of participants with first occurrence of (+) PCR-confirmed SARS-CoV-2 illness with any symptomatic COVID-19, with each symptom lasting for at least 2 consecutive days, with onset from Day 28 (7 days after second vaccination dose) through the length of the study.

    Measure: Participants with Any Symptomatic COVID-19

    Time: Day 28 to Day 750

    Description: Neutralizing antibody activity as detected by microneutralization assay (MN) as expressed as GMTs at Days 0, 35 and Month 3.

    Measure: Neutralizing Antibody Activity Expressed as Geometric Mean Titers (GMTs)

    Time: Day 0 to Day 105

    Description: Neutralizing antibody activity as detected by MN as expressed as GMFRs at Days 0, 35 and Month 3.

    Measure: Neutralizing Antibody Activity Expressed as Geometric Mean Fold Rises (GMFRs)

    Time: Day 0 to Day 105

    Description: Serum IgG antibody levels specific to SARS-CoV-2 rS protein antigen(s) as detected by enzyme-linked immunosorbent assay (ELISA) expressed as GMTs at Days 0, 35 and Month 3.

    Measure: Serum Immunoglobulin G (IgG) Antibody Levels Expressed as GMTs

    Time: Day 0 to Day 105

    Description: Serum IgG antibody levels specific to SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as GMFRs at Days 0, 35 and Month 3.

    Measure: Serum IgG Antibody Levels Expressed as GMFRs

    Time: Day 0 to Day 105

    Description: Epitope-specific immune responses to the SARS-CoV-2 rS protein receptor binding as detected by hACE2 receptor binding inhibition assay expressed as GMTs at Days 0, 35 and Month 3.

    Measure: Human Angiotensin-Converting Enzyme 2 (hACE2) Receptor Binding Inhibition Assay Expressed as GMTs

    Time: Day 0 to Day 105

    Description: Epitope-specific immune responses to the SARS-CoV-2 rS protein receptor binding as detected by hACE2 receptor binding inhibition assay expressed as GMFRs at Days 0, 35 and Month 3.

    Measure: hACE2 Receptor Binding Inhibition Assay Expressed as GMFRs

    Time: Day 0 to Day 105

    Description: Serum IgG antibody levels specific to SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as GMTs at Months 6, 12, 18, and 24.

    Measure: Serum Immunoglobulin G (IgG) Antibody Levels Expressed as GMTs at Later Time Points

    Time: Day 165 to Day 750

    Description: Serum IgG antibody levels specific to SARS-CoV-2 rS protein antigen(s) as detected by ELISA expressed as GMFRs at Months 6, 12, 18, and 24.

    Measure: Serum Immunoglobulin G (IgG) Antibody Levels Expressed as GMFRs at Later Time Points

    Time: Day 165 to Day 750

    Description: Epitope-specific immune responses to the SARS-CoV-2 rS protein receptor binding as detected by hACE2 receptor binding inhibition assay expressed as GMTs at Months 6, 12, 18, and 24.

    Measure: hACE2 Receptor Binding Inhibition Assay Expressed as GMTs at Later Time Points

    Time: Day 165 to Day 750

    Description: Epitope-specific immune responses to the SARS-CoV-2 rS protein receptor binding as detected by hACE2 receptor binding inhibition assay expressed as GMFRs at Months 6, 12, 18, and 24.

    Measure: hACE2 Receptor Binding Inhibition Assay Expressed as GMFRs at Later Time Points

    Time: Day 165 to Day 750

    Description: Neutralizing antibody activity as detected by MN as expressed as GMTs at Months 6, 12, 18, and 24.

    Measure: Neutralizing Antibody Activity Expressed as GMTs at Later Time Points

    Time: Day 165 to Day 750

    Description: Neutralizing antibody activity as detected by MN as expressed as GMFRs at Months 6, 12, 18, and 24.

    Measure: Neutralizing Antibody Activity Expressed as GMFRs at Later Time Points

    Time: Day 165 to Day 750

    Description: Description of course, treatment and severity of COVID-19 reported after a PCR-confirmed case via the Endpoint Form.

    Measure: Description of Course, Treatment and Severity of COVID-19

    Time: Day 28 to Day 750

    Description: Reactogenicity incidence and severity (mild, moderate or severe) recorded by all participants on their electronic patient-reported outcome diary application (eDiary) on days of vaccination and subsequent 6 days (total 7 days after each vaccine injection).

    Measure: Reactogenicity Incidence and Severity

    Time: Day 0 to Day 27

    Description: Number of participants with mild, moderate, or severe MAAEs through Day 49.

    Measure: Incidence and Severity of Medically Attended Adverse Events (MAAEs) Through Day 49.

    Time: Day 0 to Day 49

    Description: Number of participants with mild, moderate, or severe AEs through Day 49.

    Measure: Incidence and Severity of Unsolicited Adverse Events (AEs) Through Day 49.

    Time: Day 0 to Day 49

    Description: Number of participants with mild, moderate, or severe MAAEs attributed to study vaccine through Month 12.

    Measure: Incidence and Severity of MAAEs Attributed to Study Vaccine Through Month 12.

    Time: Day 0 to Day 375

    Description: Number of participants with mild, moderate, or severe SAEs through Month 12.

    Measure: Incidence and Severity of Serious Adverse Events (SAEs) Through Month 12.

    Time: Day 0 to Day 375

    Description: Number of participants with mild, moderate, or severe AESIs through Month 12.

    Measure: Incidence and Severity of Adverse Events of Special Interest (AESIs) Through Month 12.

    Time: Day 0 to Day 375

    Description: Number of participants with mild, moderate, or severe SAEs from Month 12 to Month 24.

    Measure: Incidence and Severity of SAEs from Month 12 to Month 24.

    Time: Day 360 to Day 750

    Description: Number of participants with mild, moderate, or severe MAAEs attributed to study vaccine from Month 12 to Month 24.

    Measure: Incidence and Severity of MAAEs Attributed to Study Vaccine from Month 12 to Month 24.

    Time: Day 360 to Day 750

    Description: Number of participants with mild, moderate, or severe AESIs attributed to study vaccine from Month 12 to Month 24.

    Measure: Incidence and Severity of AESIs from Month 12 to Month 24.

    Time: Day 360 to Day 750

    Description: Number of participants who died during the study due to any cause.

    Measure: Deaths Due to Any Cause

    Time: Day 0 to Day 750

    Description: Number of participants with antibodies to SARS-CoV-2 NP at Days 0 and 35, or Months 3, 6, 12, 18 and 24 to determine natural infection and to determine the incidence of asymptomatic infection acquired during study follow-up.

    Measure: Antibodies to SARS-CoV-2 Nucleoprotein (NP) at Specific Time Points

    Time: Day 0 to Day 750

    Description: Number of participants with antibodies to SARS-CoV-2 NP, regardless of whether the infection was symptomatic.

    Measure: Antibodies to SARS-CoV-2 Nucleoprotein (NP) at Any Time Point

    Time: Day 0 to Day 750
    401 A Randomized, Double-blind, Placebo-controlled Phase 3 Study to Assess the Efficacy and Safety of Ad26.COV2.S for the Prevention of SARS-CoV-2-mediated COVID-19 in Adults Aged 18 Years and Older

    The study will enroll up to 30,000 participants in order to evaluate the efficacy of Ad26.COV2.S in the prevention of molecularly confirmed moderate to severe/critical coronavirus disease-2019 (COVID-19), as compared to placebo, in adult participants.

    NCT04614948
    Conditions
    1. Participants With or Without Stable Co-morbidities Associated With Progression to Severe COVID-19 at Different Stages of the Protocol
    Interventions
    1. Biological: Ad26.COV2.S
    2. Other: Placebo
    MeSH:Disease Progression

    Primary Outcomes

    Description: Moderate defined as one sign or symptom from a list of signs and symptoms, such as respiratory rate greater than or equal to (>=) 20 breaths per minute and symptoms such as shortness of breath or two signs or symptoms from a list of signs and symptoms or severe COVID-19 defined in Food and Drug Administration (FDA) guidance.

    Measure: Number of Participants with First Occurrence of Molecularly Confirmed Moderate to Severe/Critical COVID-19 and who were Seronegative at Baseline

    Time: At least 14 days after the 2nd vaccination (Day 71) to end of study (2 years and 3 months)

    Secondary Outcomes

    Description: Moderate defined as one sign or symptom from a list of signs and symptoms, such as respiratory rate >= 20 breaths per minute and symptoms such as shortness of breath or two signs or symptoms from a list of sign and symptoms or severe COVID-19 defined in FDA guidance.

    Measure: Number of Participants with First Occurrence of Molecularly Confirmed Moderate to Severe/Critical COVID-19 Regardless of their Serostatus

    Time: 1 day after the 1st vaccination (Day 2) to end of study (2 years and 3 months)

    Description: Moderate defined as one sign or symptom from a list of signs and symptoms, such as respiratory rate >= 20 breaths per minute and symptoms such as shortness of breath or two signs or symptoms from a list of sign and symptoms or severe COVID-19 defined in FDA guidance.

    Measure: Number of Participants with First Occurrence of Molecularly Confirmed Moderate to Severe/Critical COVID-19 Regardless of their Serostatus

    Time: 14 days after the 2nd vaccination (Day 71) to end of study (2 years and 3 months)

    Description: Moderate defined as one sign or symptom from a list of signs and symptoms, such as respiratory rate >= 20 breaths per minute and symptoms such as shortness of breath or two signs or symptoms from a list of sign and symptoms or severe COVID-19 defined in FDA guidance.

    Measure: Number of Participants with First Occurrence of Molecularly Confirmed Moderate to Severe/Critical COVID-19 and who were Seronegative at Baseline

    Time: 1 day after the 1st vaccination (Day 2) to end of study (2 years and 3 months)

    Description: Moderate defined as one sign or symptom from a list of signs and symptoms, such as respiratory rate >= 20 breaths per minute and symptoms such as shortness of breath or two signs or symptoms from a list of sign and symptoms or severe COVID-19 defined in FDA guidance.

    Measure: Number of Participants with First Occurrence of Molecularly Confirmed Moderate to Severe/Critical COVID-19 and who were Seronegative at Baseline

    Time: 14 days after the 1st vaccination (Day 15) to end of study (2 years and 3 months)

    Description: Number of participants with first occurrence of COVID-19 requiring medical intervention (such as a composite endpoint of hospitalization, intensive care unit (ICU) admission, mechanical ventilation, and extracorporeal membrane oxygenation (ECMO), linked to objective measures such as decreased oxygenation, X-ray, computed tomographic [CT] findings) and linked to any molecularly confirmed COVID-19 at least 14 days after the second vaccination will be reported.

    Measure: Number of Participants with First Occurrence of COVID-19 Requiring Medical Intervention

    Time: At least 14 days after the 2nd vaccination (Day 71) to end of study (2 years and 3 months)

    Description: The viral load of SARS-CoV-2 will be assessed in confirmed COVID-19 cases using RT-PCR. Nasal swabs will be used to detect and/or quantify SARS-CoV-2.

    Measure: SARS-CoV-2 Viral Load as Assessed by Quantitative Reverse-Transcriptase Polymerase Chain Reaction (RT-PCR) in Participants with Molecularly Confirmed, Moderate to Severe/Critical COVID-19

    Time: At least 14 days after the 2nd vaccination (Day 71) to end of study (2 years and 3 months)

    Description: Molecularly confirmed mild COVID-19 is defined as a SARS-CoV-2 positive RT-PCR or molecular test result from any available respiratory tract sample (example, nasal swab sample, sputum sample, throat swab sample, saliva sample) or other sample. Mild COVID-19 includes: Fever, sore throat, malaise, headache, muscle pain, gastrointestinal symptoms, cough, chest congestion, runny nose, wheezing, skin rash, eye irritation or discharge, or chills, without shortness of breath or dyspnea.

    Measure: Number of Participants with First Occurrence of Molecularly Confirmed Mild COVID-19

    Time: At least 14 days after the 2nd vaccination (Day 71) to end of study (2 years and 3 months)

    Description: Molecularly confirmed moderate and severe/critical COVID-19 defined as a positive SARS-CoV-2 positive RT-PCR or molecular test result from any available respiratory tract sample (example, nasal swab sample, sputum sample, throat swab sample, saliva sample) or other sample; and COVID-19 symptoms consistent with those defined by the US FDA harmonized case definition at the time of finalization of this protocol: fever or chills, cough, shortness of breath or difficulty breathing, fatigue, muscle or body aches, headache, new loss of taste or smell, sore throat, congestion or runny nose, nausea or vomiting, diarrhea.

    Measure: Number of Participants with First Occurrence of Molecularly confirmed COVID-19 Defined by the US FDA Harmonized Case Definition

    Time: At least 14 days after the 2nd vaccination (Day 71) to end of study (2 years and 3 months)

    Description: BOD will be evaluated based on the first occurrence of molecularly confirmed COVID-19, including mild, moderate, or severe/critical COVID-19 case.

    Measure: Burden of Disease (BOD) Based on First Occurrence of Molecularly Confirmed Symptomatic COVID-19

    Time: At least 14 days after the 2nd vaccination (Day 71) to end of study (2 years and 3 months)

    Description: Serologic conversion between baseline (Day 1) and 14 days, 6 months, and 1 year after the 2nd vaccination using an ELISA and/or SARS-CoV- 2 immunoglobulin assay that is dependent on the SARS-CoV-2 nucleocapsid (N) protein will be reported.

    Measure: Serologic Conversion Between Baseline (Day 1) and 14 days, 6 months, and 1 year after the 2nd vaccination Using an Enzyme-linked Immunosorbent Assay (ELISA)

    Time: Between baseline (Day 1) and 14 days, 6 months, and 1 year after the 2nd vaccination

    Description: Number of participants with first occurrence of SARS-CoV-2 infection (serologically and/or molecularly confirmed) with onset at least 14 days after second vaccination (Day 71) to end of Study (2.3 years) will be reported.

    Measure: Number of Participants with First Occurrence of SARS-CoV-2 Infection (Serologically and/or Molecularly Confirmed)

    Time: At least 14 days after the 2nd vaccination (Day 71) to end of study (2 years and 3 months)

    Description: SAE is any untoward medical occurrence that at any dose may result in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a suspected transmission of any infectious agent via a medicinal product.

    Measure: Number of Participants with Serious Adverse Events (SAEs)

    Time: Up to 2 years and 3 months

    Description: MAAEs are defined as AEs with medically-attended visits including hospital, emergency room, urgent care clinic, or other visits to or from medical personnel for any reason. Routine study visits will not be considered medically-attended visits. New onset of chronic diseases will be collected as part of the MAAEs.

    Measure: Number of Participants with Medically-attended Adverse Events (MAAEs)

    Time: 6 months after second vaccination (Up to 34 weeks)

    Description: MAAEs are defined as AEs with medically-attended visits including hospital, emergency room, urgent care clinic, or other visits to or from medical personnel for any reason. Routine study visits will not be considered medically-attended visits. New onset of chronic diseases will be collected as part of the MAAEs.

    Measure: Number of Participants with Medically-attended Adverse Events (MAAEs) Leading to Study Discontinuation

    Time: Up to 2 years and 3 months

    Description: Participants will be asked to note in the e-Diary occurrences of injection site pain/tenderness, erythema, and swelling at the study vaccine injection site daily for 7 days post each vaccination (day of each vaccination and the subsequent 7 days).

    Measure: Number of Participants with Solicited Local Adverse Events (AEs) During 7 Days Following Each Vaccination

    Time: Up to Day 8 (7 days after first vaccination on Day 1), up to Day 64 (7 days after second vaccination on Day 57)

    Description: Participants will be instructed on how to record daily temperature using a thermometer provided for home use. Participants should record the temperature in the e-Diary in the evening of the day of each vaccination, and then daily for the next 7 days approximately at the same time each day. If more than 1 measurement is made on any given day, the highest temperature of that day will be recorded in the e-Diary. Fever is defined as endogenous elevation of body temperature >= 38.0 degree Celsius or >=100.4-degree Fahrenheit, as recorded in at least 1 measurement. Participants will also be instructed on how to note signs and symptoms in the e-Diary on a daily basis for 7 days post each vaccination (day of each vaccination and the subsequent 7 days), for the following events: fatigue, headache, nausea, myalgia.

    Measure: Number of Participants with Solicited Systemic AEs During 7 Days Following Each Vaccination

    Time: Up to Day 8 (7 days after first vaccination on Day 1), up to Day 64 (7 days after second vaccination on Day 57)

    Description: Unsolicited AEs are all AEs for which the participant is not specifically questioned in the participant diary.

    Measure: Number of Participants with Unsolicited Local Adverse Events (AEs) During 28 Days Post-vaccination

    Time: Up to Day 29 (28 days after first vaccination on Day 1), up to Day 85 (28 days after second vaccination on Day 57)

    Description: SARS-CoV-2 binding antibodies as assessed ELISA to measure humoral immune response will be reported.

    Measure: SARS-CoV-2 Binding Antibodies Assessed by ELISA

    Time: Up to 2 years and 3 months

    Description: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) neutralizing antibody titers as assessed by VNA to measure the humoral immune responses will be reported

    Measure: SARS-CoV-2 Neutralizing Antibody Titers as Assessed by Virus Neutralization Assay (VNA)

    Time: Up to 2 years and 3 months
    402 Double-blind, Randomized, Controlled, Clinical Trial to Assess the Efficacy of Allogenic Mesenchymal Stromal Cells in Patients With Acute Respiratory Distress Syndrome Due to COVID-19

    A double-blind, randomized, controlled, clinical trial to evaluate the efficacy and safety of MSC (mesenchymal stromal cells) intravenous administration in patients with COVID-induced ARDS compared to a control arm.

    NCT04615429
    Conditions
    1. Acute Respiratory Distress Syndrome
    2. COVID-19 Pneumonia
    Interventions
    1. Biological: Mesenchymal stromal cells
    2. Other: Placebo
    MeSH:Pneumonia Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome
    HPO:Pneumonia

    Primary Outcomes

    Description: Primary endpoint

    Measure: Change in the PaO2/FiO2* ratio from baseline to day 7 of treatment administration

    Time: 7 days

    Secondary Outcomes

    Description: Secondary endpoint

    Measure: All-cause mortality

    Time: Days 7, 14, and 28 after treatment

    Description: Secondary endpoint

    Measure: Time to PaO2/FiO2 ratio greater than 200 mmHg

    Time: 12 months

    Description: Secondary endpoint. Categories: Not hospitalized, no limitations on activities. Not hospitalized, limitation on activities. Hospitalized, not requiring supplemental oxygen. Hospitalized, requiring supplemental oxygen. Hospitalized, on non-invasive ventilation or high flow oxygen devices. Hospitalized, on invasive mechanical ventilation or ECMO . Death.

    Measure: Clinical status on the World Health Organization ordinal scale

    Time: Baseline, daily until day 14, and on day 28 after treatment

    Description: Secondary endpoint

    Measure: PaO2/FiO2 ratio

    Time: Baseline and days 2, 4, 14 and 28 after treatment

    Description: Secondary endpoint Sequential Organ Failure Assessment score (0-24)

    Measure: SOFA score

    Time: Baseline and days 2, 4, 7, 14 and 28 after treatment

    Description: Secondary endpoint

    Measure: Oxygen therapy-free days

    Time: Day 28

    Description: Secondary endpoint

    Measure: Duration of hospitalization

    Time: 12 months

    Description: Secondary endpoint

    Measure: Duration of ICU admission

    Time: 12 months

    Description: Secondary endpoint Proportion of patients with non-invasive ventilation

    Measure: Incidence of non-invasive ventilation

    Time: Day 28

    Description: Secondary endpoint Proportion of patients with invasive mechanical ventilation

    Measure: Incidence of invasive mechanical ventilation

    Time: Day 28

    Description: Secondary endpoint (number of days)

    Measure: Duration of non-invasive ventilation

    Time: Day 28

    Description: Secondary endpoint (number of days)

    Measure: Duration of invasive mechanical ventilation

    Time: Day 28

    Description: Secondary endpoint

    Measure: Mechanical ventilation-free days

    Time: Day 28

    Description: Secondary endpoint

    Measure: Survival rate

    Time: 3 and 12 months.

    Description: Secondary endpoint

    Measure: Cumulative incidence SAEs, Grade 3 and 4 AEs, ADR and AEs of special interest.

    Time: 12 months

    Other Outcomes

    Description: Exploratory endpoint Analytical markers (e.g., neutrophil and lymphocyte counts). Changes from baseline to set time points will be calculated.

    Measure: Analytical endpoints

    Time: Baseline and days 2, 4, 7, 14 and 28 after treatment
    403 Study to Evaluate the Efficacy and Safety of CardiolRx™ in Patients With COVID-19 and Cardiovascular Disease or Risk Factors A Double-blind, Placebo-controlled Trial

    Non-critical patients, hospitalized within the previous 24 hours who tested positive for COVID-19 and have a prior history of cardiovascular disease (CVD) and/or significant risk factors for CVD will be treated for 28 days.

    NCT04615949
    Conditions
    1. COVID-19
    2. Cardiovascular Diseases
    3. Cardiovascular Risk Factor
    Interventions
    1. Drug: Cannabidiol, pharmaceutically produced with < 5 ppm THC
    2. Drug: Placebo
    MeSH:Cardiovascular Diseases
    HPO:Abnormality of the cardiovascular system

    Primary Outcomes

    Description: proportions of patients not surviving

    Measure: All-cause mortality

    Time: 28 days post randomization

    Description: Proportions of patients needing ICU admission and/or ventilatory support

    Measure: Requirement for ICU admission and/or ventilatory support

    Time: 28 days post randomization

    Description: HF, AMI, myocarditis, new sustained arrhythmia or stroke

    Measure: CV complications

    Time: 28 days
    404 First-in-human, Randomised, Double-blind, Placebo-controlled, Dose-escalation Study in Healthy Young Adults Evaluating the Safety and Immunogenicity of COVI-VAC, a Live Attenuated Vaccine Candidate for Prevention of COVID-19

    This is the first study of COVI-VAC in humans. The purpose of the study is to evaluate the safety and immune response of COVI-VAC (a live attenuated vaccine to prevent COVID-19) in healthy adults aged 18 to 30 years. Approximately 48 participants will be enrolled into 1 of 3 dose groups (low, medium, high). Within each of these dose groups, participants will be assigned randomly to receive either 2 doses of COVI-VAC 28 days apart, 2 doses of placebo (saline), or 1 dose of COVI-VAC and 1 dose of placebo. COVI-VAC or placebo is administered by drops into each nostril. Neither the participants nor the researchers will know whether COVI-VAC or placebo has been received. To assess the safety of the vaccine, each participant will record symptoms and oral temperature in a diary daily for 14 days after each dose. Safety laboratory tests, physical exams, ECGs, and a chest X-ray will also be performed, and peak expiratory flow and vital signs will be measured. Adverse events and medication use will be recorded. Blood samples and intranasal samples will be collected to assess the immune response from the vaccine.

    NCT04619628
    Conditions
    1. COVID-19
    Interventions
    1. Biological: COVI-VAC
    2. Other: Placebo

    Primary Outcomes

    Description: Percentage of subjects with reactogenicity events

    Measure: Reactogenicity

    Time: 14 days after each dose

    Description: Percentage of subjects with adverse events

    Measure: Adverse events

    Time: Days 1 through 57

    Description: Percentage of subjects with serious adverse events

    Measure: Serious adverse events

    Time: Days 1-400

    Secondary Outcomes

    Description: IgG titre measured by ELISA in serum collected on Days 1, 15, 29, 43, 57, 120, 210, and 400

    Measure: IgG titre

    Time: Days 1, 15, 29, 43, 57, 120, 210, and 400

    Description: Neutralising antibody level measured by microneutralisation assay in serum

    Measure: Neutralizing antibody titre

    Time: Days 1, 15, 29, 43, 57, 120, 210, and 400
    405 Early Nintedanib Deployment in COVID-19 Interstitial Fibrosis

    This is a collaborative study between Icahn School of Medicine at Mount Sinai and Boehringer Ingelheim Pharmaceuticals to determine the effect of Nintedanib on slowing the rate of lung fibrosis in patients who have been diagnosed with COVID-19, and have ongoing lung injury more than 4 weeks out from their diagnosis.

    NCT04619680
    Conditions
    1. Pulmonary Fibrosis
    2. Interstitial Lung Disease
    3. Respiratory Disease
    Interventions
    1. Drug: Nintedanib
    2. Drug: Placebo
    MeSH:Lung Diseases Pulmonary Fibrosis Lung Diseases, Interstitial Respiration Disorders Respiratory Tract Diseases Fibrosis
    HPO:Abnormal lung morphology Abnormal pulmonary Interstitial morphology Interstitial pneumonitis Pulmonary fibrosis

    Primary Outcomes

    Description: Change in Forced Vital Capacity (FVC) at 180 days as compared to baseline. Forced vital capacity (FVC) is the amount of air that can be forcibly exhaled from your lungs after taking the deepest breath possible, as measured by spirometry.

    Measure: Change in Forced Vital Capacity (FVC)

    Time: Baseline and 180 days

    Secondary Outcomes

    Description: Death within 90 days and 180 days from enrollment due to a respiratory cause

    Measure: Number of deaths due to respiratory cause

    Time: within 90-180 days

    Description: Quantitative Change in chest CT visual score graded by blinded chest radiologists. Data driven texture analysis (DTA) is a patented deep learning method to quantify lung fibrosis. DTA score is reported in percentage ranging from 0% to 100%. A minimally clinical important difference when comparing CT scans from the same subject is 4%. A higher percentage suggests worsening lung injury.

    Measure: Chest CT visual score

    Time: 180 days

    Description: The Saint George's Respiratory Questionnaire (SGRQ) is a self-reported disease-specific, health-related quality of life (QOL) questionnaire. 50-item instrument. Scores range from 0 to 100, with higher scores indicating more limitations.

    Measure: St. George's Respiratory Questionnaire (SGRQ)

    Time: Day 90

    Description: The Saint George's Respiratory Questionnaire (SGRQ) is a self-reported disease-specific, health-related quality of life (QOL) questionnaire. 50-item instrument. Scores range from 0 to 100, with higher scores indicating more limitations.

    Measure: St. George's Respiratory Questionnaire (SGRQ)

    Time: Day 180

    Description: The King's Brief Interstitial Lung Disease (KBILD) questionnaire is a self-administered, ILD-specific measure of health-related quality of life, comprising 15 items with three domains (Psychological (KBILD-P), Breathlessness and activities (KBILD-B), and Chest symptoms (KBILD-C)) combined in a total score (KBILD-T). The KBILD domain and total score ranges are 0-100; 100 represents best health status.

    Measure: King's Brief Interstitial Lung Disease (KBILD)

    Time: Day 90

    Description: The King's Brief Interstitial Lung Disease (KBILD) questionnaire is a self-administered, ILD-specific measure of health-related quality of life, comprising 15 items with three domains (Psychological (KBILD-P), Breathlessness and activities (KBILD-B), and Chest symptoms (KBILD-C)) combined in a total score (KBILD-T). The KBILD domain and total score ranges are 0-100; 100 represents best health status.

    Measure: King's Brief ILD (KBILD)

    Time: Day 180

    Description: The LCQ is a 19 item questionnaire that assesses cough-related QOL. It has 3 domains (physical, psychological and social). The domain scores range from 1-7 and total score range is 3-21 with a higher score indicating a better quality of life.

    Measure: Leicester Cough Questionnaire (LCQ)

    Time: Day 90

    Description: The LCQ is a 19 item questionnaire that assesses cough-related QOL. It has 3 domains (physical, psychological and social). The domain scores range from 1-7 and total score range is 3-21 with a higher score indicating a better quality of life.

    Measure: Leicester Cough Questionnaire

    Time: Day 180

    Description: The (36) Health Survey is a 36-item, patient-reported survey of patient health. The SF-36 is a measure of health status. Scores range from 0 - 100, with higher scores indicating less disability.

    Measure: Short Form (SF) 36 Health Survey

    Time: Day 90

    Description: The (36) Health Survey is a 36-item, patient-reported survey of patient health. The SF-36 is a measure of health status. Scores range from 0 - 100, with higher scores indicating less disability.

    Measure: SF 36 Health Survey

    Time: Day 180

    Description: Questionnaire with 7 items for anxiety and 7 items for depression, each item is scored on a 4 point response 0 - 3, with full range from 0 to 42, with higher score indicating more severe anxiety or depression. 14-items scale with responses scored from 0-3, scores for each subscale from 0 (normal) to 21 (severe symptoms). Scores for the entire scale is 0 to 42, with higher score indicating more distress.

    Measure: Hospital Anxiety and Depression Scale (HADS)

    Time: Day 90

    Description: Questionnaire with 7 items for anxiety and 7 items for depression, each item is scored on a 4 point response 0 - 3, with full range from 0 to 42, with higher score indicating more severe anxiety or depression. 14-items scale with responses scored from 0-3, scores for each subscale from 0 (normal) to 21 (severe symptoms). Scores for the entire scale is 0 to 42, with higher score indicating more distress.

    Measure: Hospital Anxiety and Depression Scale (HADS)

    Time: Day 180

    Description: Number of participants with Increase in liver transaminases

    Measure: Number of participants with Increase in liver transaminases (AST and ALT) > 3 times the upper limit of normal

    Time: day 90

    Description: Number of participants with Increase in liver transaminases

    Measure: Number of participants with Increase in liver transaminases (AST and ALT) > 3 times the upper limit of normal

    Time: day 180

    Description: Number of participants with Thrombotic events: venous or arterial thrombosis

    Measure: Number of participants with Thrombotic events

    Time: day 90

    Description: Number of participants with Thrombotic events: venous or arterial thrombosis

    Measure: Number of participants with Thrombotic events

    Time: day 180

    Description: Number of participants with 10% weight loss

    Measure: Number of participants with 10% weight loss over 90 days

    Time: day 90

    Description: Number of participants with 10% weight loss

    Measure: Number of participants with 10% weight loss over 90 days

    Time: day 180

    Description: Number of participants with Nausea/emesis/diarrhea not responsive to anti-emetics and anti-motility agents

    Measure: Number of participants with GI events

    Time: day 90

    Description: Number of participants with Nausea/emesis/diarrhea not responsive to anti-emetics and anti-motility agents

    Measure: Number of participants with GI events

    Time: day 180
    406 A Randomized, Double-Blind, Placebo-Controlled, Multicenter Phase IIA Study of FSD201 (Ultramicronized PEA) + Standard of Care (SOC) Vs SOC in the Treatment of Hospitalized Patients With COVID-19

    This study will measure the effect of FSD201 (ultramicronized PEA) + SoC vs placebo + SoC on Day 28, on disease progression in the confirmed coronavirus disease 2019 (COVID-19) patient population.

    NCT04619706
    Conditions
    1. COVID-19
    Interventions
    1. Drug: FSD201
    2. Drug: Placebo

    Primary Outcomes

    Description: Disease progression will be defined as the percentage of participants who are not alive or who have respiratory failure. Respiratory failure will be defined as the need for invasive or non-invasive mechanical ventilation, high-flow oxygen, or extracorporeal membraneoxygenation (ECMO).

    Measure: Percentage of Participants With Disease Progression at Day 28

    Time: Day 28

    Secondary Outcomes

    Description: Disease resolution will be defined as participants alive and not requiring supplemental oxygen (at home or in the hospital).

    Measure: Percentage of Participants With Disease Resolution at Day 28

    Time: Day 28

    Measure: Percentage of Participants Requiring Invasive Mechanical Ventilation or ExtraCorporeal Membrane Oxygenation (ECMO) or who are not Alive on Day 28

    Time: Day 28

    Description: Oxygen use will be assessed by change in the type of oxygen use between the following categories: no oxygen, supplemental oxygen, non-invasive mechanical ventilation or high-flow oxygen, invasive mechanical ventilation/ECMO.

    Measure: Change From Baseline in Oxygen use

    Time: Baseline, Day 15, and Day 28

    Measure: Change From Baseline in Saturation of Oxygen (SpO2) percent (%)

    Time: Baseline through Day 28

    Description: Clinical status will be measured with the 9-point ordinal scale ranging (1-9; 1 being death and 9 being not hospitalized, not requiring supplemental home oxygen, and no limitations on activities).

    Measure: Change From Baseline in Clinical Status Related to COVID-19

    Time: Baseline, Day 15, and Day 28

    Description: Mortality rate will be defined as the percentage of participants who die.

    Measure: Percentage of Participants who Die (Mortality Rate) at Day 28

    Time: Day 28

    Description: COVID-19 testing by standard standard reverse transcription-polymerase chain reaction (RT-PCR) assay or equivalent test.

    Measure: Percentage of Participants Testing Negative for COVID-19 at Day 28

    Time: Day 28

    Description: Number of participants with AEs and SAEs will be summarized and reported by seriousness, severity, relationship to the study medication, outcome, and duration.

    Measure: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)

    Time: From the signing of the informed consent to Day 60 (approximately 9 months)

    Description: The number of participants with clinically significant changes in vital signs, laboratory parameters and electrocardiogram findings, and physical findings will be reported.

    Measure: Number of Participants With Clinically Significant Changes in Vital Signs, Laboratory Parameters, Electrocardiogram Findings and Physical Examination Findings

    Time: Baseline through Day 28

    Description: Plasma concentrations will be measured in participants who give optional consent will be collected relative to the first dose on Day 1 and the first dose on Day 14. Samples on Day 1 and Day 14 will be collected predose (within 10 minutes before the first daily dose) and post dose at 2 hours (±30 minutes), 12 hours (±30 minutes) (before the evening dose), and 24 hours (±30 minutes)(before the next morning dose).

    Measure: Plasma Concentrations of FSD201

    Time: Day 1 and Day 14

    Description: Cmax is defined as maximum observed plasma concentration.

    Measure: Maximum Observed Plasma Concentration (Cmax) of FSD201

    Time: Day 1 and Day 14

    Description: Area under the concentration-time curve (AUC).

    Measure: Area Under the Concentration-Time Curve (AUC) of FSD201

    Time: Day 1 and Day 14

    Description: Elimination half-life (t1/2) of FSD201.

    Measure: Elimination Half-Life (t1/2)

    Time: Day 1 and Day 14

    Description: CL/F is the apparent total body clearance of FSD201 in plasma.

    Measure: Apparent Total Body Clearance (CL/F) of FSD201

    Time: Day 1 and Day 14

    Description: Vz/F is the apparent volume of distribution of FSD201 in plasma.

    Measure: Apparent Volume of Distribution (Vz/F) of FSD201

    Time: Day 1 and Day 14

    Description: Cav is average plasma concentration over a dosing interval.

    Measure: Average Observed Plasma Concentration at Steady State (Cav) of FSD201

    Time: Day 1 and Day 14
    407 A Randomized, Placebo-Controlled Study Evaluating the Efficacy of Zinc for the Treatment of COVID-19 in the Outpatient Setting

    This is a randomized, double-blind, placebo-controlled trial to assess the efficacy of zinc in a higher risk COVID-19 positive outpatient population.

    NCT04621461
    Conditions
    1. Corona Virus Infection
    Interventions
    1. Dietary Supplement: Zinc Sulfate 220 MG
    2. Drug: Placebo
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome

    Primary Outcomes

    Description: COVID-19 related complications that require the participant to be hospitalized or have an emergency room visit

    Measure: Number of participants hospitalized and/or requiring repeat emergency room visits

    Time: 21 days

    Description: If hospitalized, number of participants admitted to the ICU, and number of days in the ICU

    Measure: Number of participants admitted to the Intensive care unit (ICU)

    Time: 30 days

    Description: If placed on ventilator, number of days on a ventilator

    Measure: Number of participants on a ventilator

    Time: 30 days

    Secondary Outcomes

    Description: Total number of deaths in the cohort.

    Measure: All-cause mortality

    Time: Up to 30 days

    Description: Time at which the patient is completely symptom free.

    Measure: Time to resolution of COVID-19 symptoms

    Time: Evaluated at day 2, 6, day 14, and day 21

    Description: Scored by the participant for feverishness, sore throat, cough, shortness of breath, myalgias. (0 =none; 1 = mild; 2 = moderate; 3 = severe)

    Measure: Severity of symptoms

    Time: Evaluated at day 2, 6, day 14, and day 21
    408 Efficacy of Clarithromycin in Comparison to Azithromycin in Treatment of Mild COVID-19 Infection, Randomized Controlled Trial

    The current study was conducted at Qena Governorate, Egypt, during the period from May 2020, to July 2020. The study included 305 COVID-19 cases diagnosed by PCR, patients were randomly assigned to one of three study limps, Azithromycin 500 mg/24 h for 7 days, Clarithromycin 500 /12 h for 7 days, or a control group with no antibiotics, All three groups received only symptomatic treatment for control of fever and cough

    NCT04622891
    Conditions
    1. Covid19
    Interventions
    1. Drug: Clarithromycin 500mg
    2. Drug: Azithromycin
    3. Drug: Placebo
    MeSH:Infection

    Primary Outcomes

    Description: time to complete resolution of fever

    Measure: time to fever control

    Time: 15 days

    Secondary Outcomes

    Description: time to PCR conversion from first positive PCR for COVID-19 to negative PCR

    Measure: PCR conversion

    Time: 15 days
    409 A Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of Intravenous Infusion of CAP-1002 in Patients With COVID-19 (INSPIRE)

    This is a randomized, double-blind, placebo-controlled study that will enroll subjects with a clinical diagnosis of COVID-19 confirmed by laboratory testing and who are in severe or critical condition as indicated by life-support measures.

    NCT04623671
    Conditions
    1. Covid19
    Interventions
    1. Biological: CAP-1002
    2. Biological: Placebo

    Primary Outcomes

    Description: Number of adverse events from start of treatment

    Measure: Safety of CAP-1002

    Time: 90 days

    Description: Cytokine absolute values and changes from start of treatment to Day 30.

    Measure: Efficacy of CAP-1002 on Cytokine

    Time: 30 days

    Description: Biomarker absolute values and changes from start of treatment to Day 30.

    Measure: Efficacy of CAP-1002 on Laboratory Biomarker

    Time: 30 days

    Other Outcomes

    Description: Number of all cause mortality cases within 30 days from start of treatment

    Measure: All cause mortality

    Time: 30 days

    Description: Number of Intensive Care Unit (ICU) discharges within 30 days from start of treatment

    Measure: ICU Discharge

    Time: 30 days

    Description: Duration in ICU from start of treatment (up to 90 days)

    Measure: Duration in ICU

    Time: 90 days

    Description: Number of hospital discharges within 30 days from start of treatment

    Measure: Hospital Discharge

    Time: 30 days

    Description: Duration in hospital from start of treatment up to Day 90

    Measure: Hospitalization length

    Time: 90 days

    Description: Duration of time on supplemental oxygen or mechanical ventilation from start of treatment up to Day 90

    Measure: Ventilatory status

    Time: 90 days

    Description: Severity of ARDS as defined by the Berlin criteria, absolute values and changes from start of treatment to Day 30.

    Measure: Acute Respiratory Distress

    Time: 30 days

    Description: Absolute values and changes from start of treatment to Day 30.

    Measure: Ordinal Scale of Clinical Improvement

    Time: 30 days

    Description: Time to a 1-point decrease (indicative of improvement) on the WHO Ordinal Scale of Clinical Improvement from start of treatment

    Measure: WHO Ordinal Improvement

    Time: 90 days

    Description: Area under the severity versus time curve, where severity is defined by the Ordinal Scale of Clinical Improvement and time is measured from start of treatment to Day 30

    Measure: Severity vs. Time

    Time: 30 days
    410 The Potential of Oral Camostat in Early COVID-19 Disease in an Ambulatory Setting to Reduce Viral Load and Disease Burden

    The investigators are conducting a pilot trial where they will study safety, efficacy and compliance in a cohort of ambulatory patients in the Ghent region with confirmed COVID-19 infection, in both an early stage of disease, defined as less than 5 days of symptoms and who at presentation do not meet any criteria for hospitalisation as well as asymptomatic individuals with a PCR CT value below 30. The primary endpoint is to assess the efficacy of the drug in terms of change from day 0 to day 5 in respiratory (oropharyngeal swab RT-PCR) log10 viral load. The aim of the study is to assess whether Camostat, a serine protease inhibitor available in an oral formulation has the potential to be studied as an antiviral drug in a large scale ambulatory setting to prevent transmission by decreasing viral load, to prevent symptoms after exposure (PEP) in asymptomatic individuals or to prevent disease progression in the occurrence of early symptomatology.

    NCT04625114
    Conditions
    1. Covid19
    Interventions
    1. Drug: Camostat
    2. Drug: Placebo
    3. Drug: Camostat
    4. Drug: Placebo

    Primary Outcomes

    Description: The primary endpoint is to assess the efficacy of the drug in terms of change from day 0 to day 5 in respiratory (oropharyngeal swab RT-PCR) log10 viral load. Surrogate market CT value will be used as well.

    Measure: Efficacy in terms of viral load or surrogate

    Time: 5 days
    411 The Potential of Oral Camostat in Early COVID-19 Disease in an Ambulatory Setting to Reduce Viral Load and Disease Burden

    The investigators are conducting a pilot trial where they will study safety, efficacy and compliance in a cohort of ambulatory patients in the Ghent region with confirmed COVID-19 infection, in both an early stage of disease, defined as less than 5 days of symptoms and who at presentation do not meet any criteria for hospitalisation as well as asymptomatic individuals with a PCR CT value below 30. The primary endpoint is to assess the efficacy of the drug in terms of change from day 0 to day 5 in respiratory (oropharyngeal swab RT-PCR) log10 viral load. The aim of the study is to assess whether Camostat, a serine protease inhibitor available in an oral formulation has the potential to be studied as an antiviral drug in a large scale ambulatory setting to prevent transmission by decreasing viral load, to prevent symptoms after exposure (PEP) in asymptomatic individuals or to prevent disease progression in the occurrence of early symptomatology.

    NCT04625114
    Conditions
    1. Covid19
    Interventions
    1. Drug: Camostat
    2. Drug: Placebo
    3. Drug: Camostat
    4. Drug: Placebo

    Primary Outcomes

    Description: The primary endpoint is to assess the efficacy of the drug in terms of change from day 0 to day 5 in respiratory (oropharyngeal swab RT-PCR) log10 viral load. Surrogate market CT value will be used as well.

    Measure: Efficacy in terms of viral load or surrogate

    Time: 5 days
    412 A Phase III Randomized, Double-blind, Placebo-controlled, Multi-center Study in Adults to Determine the Safety and Efficacy of AZD7442, a Combination Product of Two Monoclonal Antibodies (AZD8895 and AZD1061), for Pre-exposure Prophylaxis of COVID-19.

    This study will assess the safety and efficacy of a single dose of AZD7442(× 2 IM injections) compared to placebo for the prevention of COVID-19.

    NCT04625725
    Conditions
    1. COVID-19
    Interventions
    1. Drug: AZD7442
    2. Drug: Placebo

    Primary Outcomes

    Description: To estimate the efficacy of a single IM dose of AZD7442 compared to placebo for the prevention of COVID-19 through Day 183

    Measure: The incidence of the first case of SARS CoV-2 RT PCR positive symptomatic illness

    Time: Day 183

    Description: To assess the safety and tolerability of a single IM dose of AZD7442 compared to placebo

    Measure: AEs, SAEs, MAAEs, and AESIs through 365 days post dose of IMP

    Time: 1 year

    Secondary Outcomes

    Description: To estimate the efficacy of a single IM dose of AZD7442 compared to placebo for the prevention of COVID-19 through Day 366

    Measure: The incidence of the first case of SARS-CoV-2 RT-PCR-positive symptomatic illness occurring after dosing with IMP through Day 366

    Time: 1 year

    Description: To estimate the efficacy of a single IM dose of AZD7442 compared to placebo for the prevention of SARS-CoV-2 infection

    Measure: The incidence of participants who have a post-treatment response (negative at baseline to positive at any time post-baseline) for SARS-CoV-2 nucleocapsid antibodies

    Time: 1 year

    Description: To estimate the efficacy of a single IM dose of AZD7442 compared to placebo for the prevention of severe or critical symptomatic COVID-19

    Measure: The incidence of SARS-CoV-2 RT-PCR-positive severe or critical symptomatic illness occurring after dosing with IMP

    Time: 1 year

    Description: To estimate the efficacy of a single IM dose of AZD7442 compared to placebo for the prevention of COVID-19-related Emergency Department visits

    Measure: The incidence of COVID-19-related Emergency Department visits occurring after dosing with IMP

    Time: 1 year

    Description: To assess the pharmacokinetics of AZD7442 administered as a single dose of 300 mg IM

    Measure: Serum AZD7442 concentrations, PK parameters if data permit.

    Time: 1 year

    Description: To evaluate ADA responses to AZD7442 in serum

    Measure: Incidence of ADA to AZD7442 in serum.

    Time: 1 year
    413 Efficacy of Infusions of Mesenchymal Stem Cells From Wharton Jelly in the Moderate to Severe SARS-Cov-2 Related Acute Respiratory Distress Syndrome (COVID-19): A Phase IIa Double-blind Randomized Controlled Trial

    Mesenchymal stem cells (MSCs) are of potential help in acute respiratory distress syndrome (ARDS), due to their anti-inflammatory properties. The investigators will analyze the effect of 3 iterative infusions of ex vivo expanded Wharton's Jelly MSCs (total dose 2.10^6/kg) in patients with ARDS due to COVID19, who require mechanical ventilation.

    NCT04625738
    Conditions
    1. COVID19 ARDS
    Interventions
    1. Biological: Ex vivo expanded Wharton's Jelly Mesenchymal Stem Cells
    2. Biological: Placebo
    MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury

    Primary Outcomes

    Description: The primary endpoint is the percentage of patients with a PaO2/FiO2 ratio > 200 at D10 of treatment with MSC-GW or placebo.

    Measure: PaO2 / FiO2 ratio

    Time: day 10

    Secondary Outcomes

    Description: The evolution of the PaO2/FiO2 ratio between Day 0 (or Day 1) and Day 14 of treatment with MSC-GW or placebo is a secondary endpoint.

    Measure: respiratory function evolution

    Time: between Day 0 (or Day 1) and Day 14 of treatment

    Description: The effect of WJ-MSC on respiratory assistance is evaluated by the proportion of days without invasive respiratory assistance during the hospital stay and maximum on Day 28 (number of days without invasive respiratory assistance / number of hospital days until Day 28)

    Measure: respiratory assistance

    Time: between day 0 (or 1) and day 28 (or last day of hospitalization if before day 28)

    Description: Difference in sequential organ failure assessment score (SOFA score), grading 0 (best) to 4 (worst), between Day 5-Day 0 and D14-Day 0

    Measure: organ failures 1

    Time: Day 0 to day 14

    Description: number of days without extra-renal treatment treatment / number of days of hospitalization until Day 28)

    Measure: organ failures 2

    Time: day 0 to day 28

    Description: number of days without vasopressor support

    Measure: organ failures 3

    Time: day 0 to day 28

    Description: The duration of stay in intensive care unit

    Measure: duration of intensive care

    Time: day 0 to 90

    Description: Cause of death during the stay in intensive care unit and during the hospital stay, on Day 28 and Day 90

    Measure: Cause of death

    Time: day 0 to 90

    Description: respiratory morbidity on Day 90

    Measure: respiratory morbidity (TDM, functional respiratory measures)

    Time: day 90

    Description: The evolution of the viral load is evaluated by RT PCR SARS-Cov-2 monitoring on a nasopharyngeal swab (or any other sample) at diagnosis, at Day 7, Day 14, Day 21, Day 28 or on the last day of hospitalisation

    Measure: viral load

    Time: day 0 to day 28 (or last day of hospitalization if before day 28)

    Description: - The anti-HLA antibody rate measured on Day 0 (before initiating treatment), on Day 28 and on Day 90

    Measure: Anti-HLA antibody rate

    Time: day 0 to day 90

    Description: The occurrence of immediate hypersensitivity reactions (chills, hyperthermia associated with hypotension) within 4 to 6 hours of the WJ MSC or placebo infusion.

    Measure: immediate hypersensitivity reactions

    Time: day 0, day 3, day 5 (+/- 1day)

    Description: The thromboembolic risks monitored biologically by routinely daily monitoring of hemostasis (TP, TCA, Fibrinogen, D-dimers)

    Measure: thromboembolic adverse events 1

    Time: day 0 to day 14

    Description: daily monitoring of transthoracic echocardiography

    Measure: thromboembolic adverse events 2

    Time: day 0 to day 14

    Description: blood cultures in case of T° > 38,5°C

    Measure: infectious adverse events

    Time: day 0 to day 14
    414 A Phase III Randomized, Double-blind, Placebo-controlled, Multi-center Study in Adults to Determine the Safety and Efficacy of AZD7442, a Combination Product of Two Monoclonal Antibodies (AZD8895 and AZD1061), for Post-exposure Prophylaxis of COVID-19

    This study will assess the efficacy of AZD7442 for the post-exposure prophylaxis of COVID-19 in Adults.

    NCT04625972
    Conditions
    1. COVID-19
    Interventions
    1. Drug: AZD7442
    2. Drug: Placebo

    Primary Outcomes

    Description: To estimate the efficacy of a single IM dose of AZD7442 compared to placebo for the prevention of COVID-19

    Measure: The incidence of the first case of SARS CoV-2 RT PCR positive symptomatic illness

    Time: Day 183

    Description: To assess the safety and tolerability of a single IM dose of AZD7442 compared to placebo

    Measure: AEs, SAEs, MAAEs, and AESIs through 365 days post dose of IMP

    Time: 1 year

    Secondary Outcomes

    Description: To estimate the efficacy of a single IM dose of AZD7442 compared to placebo for the prevention of severe or critical symptomatic COVID-19

    Measure: The incidence of SARS-CoV-2 RT-PCR-positive severe or critical symptomatic illness occurring after dosing with IMP

    Time: Day 183

    Description: To estimate the efficacy of a single IM dose of AZD7442 compared to placebo for the prevention of SARS-CoV-2 infection

    Measure: The incidence of participants who have a post-treatment response (negative at baseline to positive at any time post-baseline) for SARSCoV- 2 nucleocapsid antibodies

    Time: 1 year

    Description: To estimate the efficacy of a single IM dose of AZD7442 compared to placebo for the prevention of COVID-19-related death

    Measure: The incidence of COVID-19-related death occurring after dosing with IMP

    Time: 1 year

    Description: To estimate the efficacy of a single IM dose of AZD7442 compared to placebo for the prevention of all-cause mortality

    Measure: The incidence of all-cause mortality occurring after dosing with IMP

    Time: 1 year

    Description: To assess the pharmacokinetics of AZD7442 administered as a single dose of 300 mg IM

    Measure: Serum AZD7442 concentrations, PK parameters if data permit.

    Time: 1 year

    Description: To evaluate ADA responses to AZD7442 in serum

    Measure: Incidence of ADA to AZD7442 in serum

    Time: 1 year
    415 The Clinical Trial of Application of Ezrin Peptide (HEP-1) for Treatment of Coronavirus Disease (COVID-19) Infection

    Currently, SARS-CoV-2 the novel member of the corona virus family, affecting the world leading to COVID-19 disease. It can result life-threatening condition by developing severe acute respiratory distress syndrome (ARDS). Based on previous evidence a group of patients with severe COVID-19 develop a cytokine storm syndrome which leads to hyper-inflammation lung tissue damage. Supportive care is the current management of COVID-19 is and management of ARDS as a main cause of mortality has been remained challenging. Therefore, an urgent effective treatment of COVID-19 regarding hyper-inflammation mechanism is required. Currently, development of novel anti-viral agents and vaccines are the main issues. However, it needs long time, from months to years, until suitable new medications and vaccines have been developed. An immune-modulatory tetra deca peptide (14-mer peptide) named Human Ezrin Peptide 1 (HEP-1) (trade name Gepon) was introduced by the group of Ataullakhanov in Russia. Regarding its proved anti-viral and anti-inflammatory effect, Russian authorities approved Gepon for treatment of ulcerative colitis treatment and Hepatitis -C. In this regard, it seems that Hep-1 is a very safe immune-modulatory agent which can be effective in the management of COVID-19 infection without any adverse effect for the patient.

    NCT04627233
    Conditions
    1. Covid19
    2. Treatment
    3. Corona Virus Infection
    Interventions
    1. Drug: Human Ezrin Peptide 1 (HEP1)
    2. Drug: Placebo
    MeSH:Infection Communicable Diseases Coronavirus Infections Severe Acute Respiratory Syndrome

    Primary Outcomes

    Measure: Time to clinical improvement of disease symptoms

    Time: 7 days

    Measure: Duration of Hospitalization

    Time: 28 days

    Measure: Duration of artificial ventilation

    Time: 28 days

    Secondary Outcomes

    Description: Range 0-40

    Measure: CT Severity score

    Time: 28 days

    Measure: CBC

    Time: 28 days

    Measure: IL-1

    Time: 28 days

    Measure: IL-6

    Time: 28 days

    Measure: TNF

    Time: 28 days

    Measure: CRP

    Time: 28 days
    416 A Phase 1 Double-blinded, Randomized, Placebo-controlled Study for COVID-19 and Influenza Virus-Elicited Acute Respiratory Distress Syndrome (ARDS) Using Longeveron Mesenchymal Stem Cells (LMSCs)

    A Phase I, double- blinded, randomized, placebo- controlled study to test the safety of LMSCs in Adults suffering from mild to severe acute respiratory distress syndrome (ARDS) due to COVID-19 resultant from 2019-nCoV coronavirus infection, or resultant from influenza virus infection.

    NCT04629105
    Conditions
    1. ARDS, Human
    2. Covid19
    Interventions
    1. Biological: Longeveron Mesenchymal Stem Cells (LMSCs)
    2. Other: Placebo
    MeSH:Respiratory Distress Syndrome, Adult

    Primary Outcomes

    Description: Incidence of treatment-emergent serious adverse events (TE-SAEs) within 4 weeks after treatment, defined as one or more of the following untoward medical occurrences happening within the first 4 weeks after treatment. i. Life-threatening event (e.g., stroke or non-fatal pulmonary embolism). ii. Event requiring inpatient hospitalization or prolongation of existing hospitalization (e.g., for worsening dyspnea). iii. Event resulting in persistent or significant disability/incapacity. iv. Event resulting in death. v. Event leading to other clinically significant untoward laboratory test result(s) or medical condition(s), as determined by the Investigator.

    Measure: Incidence of Treatment-Emergent Serious Adverse Events

    Time: Within 4 weeks after treatment

    Description: Number of Participants with Abnormal Clinical Significant Lab Values in the Hematology testing will be assessed at Baseline and 6 Months.

    Measure: Number of Participants with Abnormal Clinical Significant Laboratory Values in Hematology.

    Time: Baseline to 6 Months

    Description: Overall Assessment Normal vs Abnormal will be collected at Baseline and 6 months, this change in overall assessment will be the outcome in numbers of particants with a change.

    Measure: Number of Participants with Changes in Echocardiography Overall Assessment

    Time: Baseline to 6 Months

    Description: Number of Participants with changes to Overall Assessment Normal vs Abnormal will be collected at Baseline and 6 Months

    Measure: Number of Participants with Changes to overall assessment of Electrocardiogram

    Time: Baseline to 6 Months

    Description: Time to recovery of Sp02 to 90% or higher on room air (or the oxygen concentration the patient had before acute illness) after 10 minutes of spontaneous breathing.

    Measure: Time to recovery of Sp02

    Time: Baseline to 6 Months

    Description: Number of Participants with Abnormal Clinical Significant Lab Values in Blood Chemistry testing will be assessed at Baseline and 6 Months.

    Measure: Number of Participants with Abnormal Clinical Significant Lab Values in the Blood Chemistry testing.

    Time: Baseline to 6 months

    Description: Number of Participants with Abnormal Clinical Significant Lab Values in the Coagulation testing will be assessed at Baseline and 6 Months.

    Measure: Number of Participants with Abnormal Clinical Significant Lab Values in the Coagulation.

    Time: Baseline to 6 months

    Description: Number of Participants with Abnormal Clinical Significant Lab Values in the Hematology testing will be assessed at Baseline and 6 Months.

    Measure: Number of Participants with Abnormal Clinical Significant Lab Values in the Urinalysis

    Time: Baseline to 6 months

    Secondary Outcomes

    Description: Geometric mean titer

    Measure: Immunity

    Time: Baseline to 6 Months

    Description: Change in overall assessment via Lung imaging via chest X-ray will be assessed and compared between baseline and 6 months

    Measure: Change in Imaging via X-ray

    Time: Baseline to 6 Months

    Description: Change in overall assessment via Lung imaging via computerized tomography will be assessed and compared between baseline and 6 months

    Measure: Change in Imaging via Computerized Tomography

    Time: Baseline to 6 Months
    417 Double-Blind, Randomized, Placebo-Controlled, Adaptive Design, Multi-Center Phase 3 Study to Evaluate the Efficacy and Safety of Fostamatinib in COVID-19 Subjects

    The study is a double-blind, randomized, placebo-controlled, adaptive design, multi-center, Phase 3 study to evaluate the efficacy and safety of fostamatinib in COVID-19 subjects.

    NCT04629703
    Conditions
    1. Covid19
    2. SARS (Severe Acute Respiratory Syndrome)
    3. SARS Pneumonia
    4. SARS-Associated Coronavirus as Cause of Disease Classified Elsewhere
    5. Pneumonia
    6. Pneumonia, Viral
    Interventions
    1. Drug: Fostamatinib
    2. Drug: Placebo
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia, Viral Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Progression to severe/critical disease within 29 days of first dose of study treatment

    Measure: Progression to severe/critical disease within 29 days of first dose of study treatment

    Time: 29 days

    Secondary Outcomes

    Description: Proportion of subjects transferred into the intensive care unit (ICU) or who died prior to Day 29

    Measure: Proportion of subjects transferred into the intensive care unit (ICU) or who died prior to Day 29

    Time: 29 days

    Description: Total number of calendar days hospitalized through Day 29

    Measure: Total number of calendar days hospitalized through Day 29

    Time: 29 days
    418 A Phase 1b, Randomized, Double-Blind, Placebo-Controlled, Dose Escalation Trial of Intravenous Zotatifin in Adults With Mild or Moderate Coronavirus Disease 2019 (COVID-19)

    To evaluate the safety and tolerability, the antiviral activity, and plasma pharmacokinetics (PK) of zotatifin administered intravenously (IV) to adults with mild or moderate COVID-19.

    NCT04632381
    Conditions
    1. Corona Virus Infection
    Interventions
    1. Drug: Zotatifin
    2. Drug: Placebo
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome

    Primary Outcomes

    Description: Incidence of Treatment Emergent Adverse Events and Serious Adverse Events

    Measure: Safety as assessed by the incidence of Treatment Emergent Adverse Events and Serious Adverse Events

    Time: 52 days

    Description: Adverse Events of Special Interest to be assessed: Incidence of hospitalizations incidence of cytokine release syndrome hemophagocytic lymphohistiocytosis acute respiratory distress syndrome need for oxygen supplementation

    Measure: Safety as assessed by the incidence of adverse events of special interest:

    Time: 52 days

    Description: Changes as assessed by respiration rate

    Measure: Tolerability as assessed by changes in vital signs from baseline (Day 1)

    Time: 22 days

    Description: Changes as assessed by heart rate

    Measure: Tolerability as assessed by changes in vital signs from baseline (Day 1)

    Time: 22 days

    Description: Changes as assessed by oxygen saturation

    Measure: Tolerability as assessed by changes in vital signs from baseline (Day 1)

    Time: 22 days

    Description: Changes as assessed by temperature

    Measure: Tolerability as assessed by changes in vital signs from baseline (Day 1)

    Time: 22 days

    Description: Changes as assessed by blood pressure

    Measure: Tolerability as assessed by changes in vital signs from baseline (Day 1)

    Time: 22 days

    Description: Changes as assessed by physical exam

    Measure: Tolerability as assessed by changes in clinical symptoms from baseline (Day 1)

    Time: 22 days

    Description: Changes as assessed by serum chemistry

    Measure: Tolerability as assessed by changes in clinical laboratory tests from baseline (Day 1)

    Time: 22 days

    Description: Changes as assessed by hematology

    Measure: Tolerability as assessed by changes in clinical laboratory tests from baseline (Day 1)

    Time: 22 days

    Description: Changes as assessed by coagulation

    Measure: Tolerability as assessed by changes in clinical laboratory tests from baseline (Day 1)

    Time: 22 days

    Description: Changes as assessed by urinalysis

    Measure: Tolerability as assessed by changes in clinical laboratory tests from baseline (Day 1)

    Time: 22 days

    Secondary Outcomes

    Description: Defined as the time to the first of 2 consecutive negative SARS-CoV-2 measurements assessed from swab specimen

    Measure: Time to viral load undetectability;

    Time: 22 days

    Description: Assessed by swab specimen

    Measure: Proportion of patients with SARS-CoV-2 viral load below the level of detectability;

    Time: 22 days

    Description: Assessed by swab specimen

    Measure: Mean change in SARS-CoV-2 viral load;

    Time: 22 days

    Description: Defined as resolution of symptoms on the WHO 9-point ordinal scale for clinical improvement.

    Measure: The time to clinical resolution;

    Time: 52 days

    Description: Concentrations at end of infusion, end of dosing interval, and on defined timepoint periods.

    Measure: Zotatifin plasma concentrations

    Time: 15 days

    Other Outcomes

    Description: Time to the first of 2 consecutive negative SARS-CoV-2 measurements assessed from daily samples

    Measure: Time to viral load undetectability

    Time: 22 days

    Description: Assessed from daily saliva and anterior nasal samples

    Measure: Proportion of patients below the limit of detection

    Time: 22 days

    Description: Assessed from daily saliva and anterior nasal samples

    Measure: Mean change in viral load in saliva and nasal samples

    Time: 22 days

    Description: Assessed from plasma collected

    Measure: Mean change in viral load in plasma

    Time: 22 days

    Description: Assessed by plaque-based or comparable assay

    Measure: Assessment and quantification of infectious virus

    Time: 22 days

    Description: According Virus Analysis Plan

    Measure: Virus resistance

    Time: 22 days

    Description: Assessed in change from baseline to post infusion

    Measure: Change in the WHO 9-point ordinal scale for clinical improvement

    Time: 38 days
    419 A Randomised, Double-Blind, Placebo-Controlled, Exploratory Phase I Trial Assessing the Pharmacokinetic Profile, Safety and Tolerability of a Continuous Daily Dosing Regimen of Active IMP in Healthy Volunteers

    An early stage trial to check how safe and tolerable, as well as how the body handles continuous daily use of Active IMP over 28 days in healthy volunteers to help with coronavirus infection (COVID-19).

    NCT04632706
    Conditions
    1. Covid19
    Interventions
    1. Drug: Ivermectin
    2. Drug: Placebo

    Primary Outcomes

    Description: Maximum plasma concentration (Cmax)

    Measure: Pharmacokinetic concentrations - (Maximum Plasma Concentration [Cmax])

    Time: Study day 42 (at 14 days post the final dose)

    Description: Time to reach Cmax (tmax)

    Measure: Pharmacokinetic concentrations - (Time to Reach Cmax [Tmax])

    Time: Study day 42 (at 14 days post the final dose)

    Description: trough plasma concentration (Ctrough)

    Measure: Pharmacokinetic concentrations - (Trough Plasma Concentration [Ctrough])

    Time: Study day 42 (at 14 days post the final dose)

    Description: area under the plasma concentration-time curve from zero to 24 hours (AUC0-24h) concentration-time curve from zero to 24 hours (AUC0-24h)

    Measure: Pharmacokinetic concentrations - (Area under the plasma concentration-time curve from zero to 24 hours [AUC0-24h])

    Time: Study day 42 (at 14 days post the final dose)

    Description: area under the plasma concentration-time curve from zero to 48 hours (AUC0-48h)

    Measure: Pharmacokinetic concentrations - (Area under the plasma concentration-time curve from zero to 48 hours [AUC0-48h])

    Time: Study day 42 (at 14 days post the final dose)

    Description: average plasma concentration at steady state (Cavg ss)

    Measure: Pharmacokinetic concentrations - (Average Plasma Concentration at steady state [Cavg ss])

    Time: Study day 42 (at 14 days post the final dose)

    Description: apparent terminal half-life (t1/2)

    Measure: Pharmacokinetic concentrations - (Apparent Terminal Half-Life [T1/2])

    Time: Study day 42 (at 14 days post the final dose)

    Secondary Outcomes

    Description: Clinical safety data from adverse event (AE) reporting

    Measure: Safety and Tolerability - Number of participants with treatment emergent adverse events (TEAEs)

    Time: Study day 42 (at 14 days post the final dose)

    Description: Assessment of cardiac electrical activity

    Measure: Safety and Tolerability - Number of participants with abnormal electrocardiograms (ECG)

    Time: Study day 42 (at 14 days post the final dose)

    Description: Assessment of neurological function

    Measure: Safety and Tolerability - Number of participants with abnormal clinical neurological exam, as assessed by the investigator

    Time: Study day 42 (at 14 days post the final dose)

    Description: Assessment of clinical laboratory results

    Measure: Safety and Tolerability - Number of participants with abnormal urine and/or blood test, as compared to reference laboratory values

    Time: Study day 42 (at 14 days post the final dose)

    Description: Assessment of physical examination results

    Measure: Safety and Tolerability - Number of participants with abnormal physical exams, as assessed by the investigator

    Time: Study day 42 (at 14 days post the final dose)
    420 Randomized Clinical Trial Phase I/II for the Use of Angiotensin-(1-7) in the Treatment of Severe Infection by Sars-CoV-2

    The renin-angiotensin system (RAS) has a relevant role in COVID-19, as the virus will enter host's cells via the angiotensin-converting enzyme 2 (ACE2); RAS disequilibrium might also play a key role in the modulation of the inflammatory response that characterizes the lung involvement. Angiotensin-(1-7) is a peptide that could be altered in COVID-19 patient and its supplementation may potentially helpful in this setting.

    NCT04633772
    Conditions
    1. Infection, Coronavirus
    2. Respiratory Failure
    Interventions
    1. Drug: Angiotensin-(1-7)
    2. Drug: Placebo
    MeSH:Infection Coronavirus Infections Respiratory Insufficiency

    Primary Outcomes

    Description: 28 - x, where x = number of days on which the patient is released from supplemental oxygen therapy after start

    Measure: supplemental oxygen-free days (SOFDs)

    Time: 28 days

    Secondary Outcomes

    Description: Hospital length of stay

    Measure: Hospital length of stay

    Time: through study completion, on average 60 days

    Description: composite outcome of mortality and necessity of mechanical ventilation

    Measure: ventilator free days

    Time: 28 days

    Description: number of days free from intensive care unit

    Measure: ICU free days

    Time: through study completion, on average 40 days

    Description: Ang II and Ang-(1-7) circulating levels using mass spectrometry

    Measure: RAS effectors levels

    Time: Baseline, 3 and 24 hours after randomization and 72 hours after randomization

    Description: CT scan evolutions compared to baseline including findings compatible with late pulmonary fibrosis.

    Measure: CT scan findings

    Time: through study completion, on average 30 days

    Description: C-reactive protein levels daily measurements

    Measure: Changes in inflammatory markers: C reactive protein

    Time: through study completion, on average 30 days

    Description: use of vasopressors during hospitalization

    Measure: Changes in clinical state: vasopressors usage

    Time: through study completion, on average 30 days

    Description: Chest X-ray modifications until hospital discharge

    Measure: Chest X ray findings

    Time: through study completion, on average 30 days

    Description: pro-inflammatory chemokine levels (IL-1/IL-6) at baseline day 3 and 7

    Measure: Changes in inflammatory markers: chemokines

    Time: Baseline, 3 and 24 hours after randomization and 72 hours after randomization

    Description: Troponin plasmatic levels

    Measure: Changes in inflammatory markers: troponin

    Time: Baseline, 3 and 24 hours after randomization and 72 hours after randomization

    Description: D-Dimer

    Measure: Changes in thrombotic markers: D-Dimer

    Time: Baseline, 3 and 24 hours after randomization and 72 hours after randomization

    Description: Secondary infections recorded during hospitalization

    Measure: Changes in clinical state: secondary infections

    Time: through study completion, on average 30 days

    Description: deep venous thrombosis recorded during hospitalization

    Measure: Changes in clinical state: deep venous thrombosis

    Time: through study completion, on average 30 days
    421 A Randomized, Double-blind, Placebo-Controlled, Phase 2 Study to Evaluate the Efficacy and Safety of Mono and Combination Therapy With Monoclonal Antibodies in Participants With Mild to Moderate COVID-19 Illness (BLAZE-4)

    The purpose of this study is to measure how well LY3819253 (LY-CoV555) and LY3832479 (LY-CoV016) work against the virus that causes COVID-19. LY3819253 and LY3832479 will be given to participants with early symptoms of COVID-19. Samples will be taken from the back of the nose to determine how much virus is in the body at various times during the study. Participation could last about 12 weeks and includes at least 1 visit to the study site, with the remainder of assessments performed in the home, local clinic, or by phone.

    NCT04634409
    Conditions
    1. COVID-19
    Interventions
    1. Drug: LY3819253
    2. Drug: LY3832479
    3. Drug: Placebo

    Primary Outcomes

    Description: Percentage of Participants with SARS-CoV-2 Viral Load Greater than 5.27

    Measure: Percentage of Participants with SARS-CoV-2 Viral Load Greater than 5.27

    Time: Day 7

    Secondary Outcomes

    Description: Percentage of Participants Who Experience COVID-19 Related Hospitalization or Death

    Measure: Percentage of Participants Who Experience COVID-19 Related Hospitalization or Death

    Time: Baseline through Day 29

    Description: Change from Baseline to Day 7 in SARS-CoV-2 Viral Load

    Measure: Change from Baseline to Day 7 in SARS-CoV-2 Viral Load

    Time: Baseline, Day 7

    Description: Percentage of Participants Demonstrating Symptom Resolution

    Measure: Percentage of Participants Demonstrating Symptom Resolution

    Time: Day 7

    Description: Percentage of Participants Demonstrating Symptom Improvement

    Measure: Percentage of Participants Demonstrating Symptom Improvement

    Time: Day 7

    Description: Percentage of Participants Who Experience COVID-Related Hospitalization, COVID-19 Related Emergency Room Visit, or Death

    Measure: Percentage of Participants Who Experience COVID-Related Hospitalization, COVID-19 Related Emergency Room Visit, or Death

    Time: Baseline through Day 22

    Description: Pharmacokinetics (PK): Mean Concentration of LY3819253 and LY3832479

    Measure: Pharmacokinetics (PK): Mean Concentration of LY3819253 and LY3832479

    Time: Day 29
    422 Study To antagOnize Plasminogen Activator Inhibitor-1 in Severe COVID-19 (STOP Severe COVID-19)

    This is a single-center, randomized double blind placebo controlled trial to evaluate the efficacy and safety of novel PAI-1 inhibitor (TM5614) for high-risk patients hospitalized with severe COVID-19 at Northwestern Memorial Hospital. The patients will be randomized in a 1:1 ratio to receive standard of care plus TM5614 or standard of care plus placebo.

    NCT04634799
    Conditions
    1. Covid19
    Interventions
    1. Drug: TM5614
    2. Other: Placebo

    Primary Outcomes

    Description: Change of at least 2 points in the NIAID-defined ordinal scale (higher scores indicate improved outcome),: Death Hospitalized, receiving invasive mechanical ventilation or ECMO Hospitalized, receiving noninvasive ventilation or high-flow oxygen devices Hospitalized, requiring low-flow supplemental oxygen Hospitalized, not requiring supplemental oxygen but receiving ongoing medical care (related or not related to Covid-19) Hospitalized, requiring neither supplemental oxygen nor ongoing medical care (other than that specified in the protocol) Not hospitalized

    Measure: Clinical improvement

    Time: 7 Days

    Secondary Outcomes

    Description: Change in degree of organ dysfunction as defined by the Sequential Organ Failure Assessment (SOFA) Score. The SOFA score ranges from 0 to 24 (higher scores indicate more severe organ failure), with 0 to 4 points assigned for each of 6 organ dysfunctions (ie, central nervous system, cardiovascular, respiratory, renal, coagulation, and liver).

    Measure: Sequential organ failure assessment (SOFA) score change

    Time: 7 Days

    Description: Change in circulating levels

    Measure: PAI-1 Levels

    Time: 48 hours

    Description: For subjects who received mechanical ventilation, total number of days the subject was not on mechanical or non invasive mechanical ventilation while in the hospital

    Measure: Ventilator free days

    Time: 14 days
    423 Randomized Phase IIA Clinical Trial to Compare the Efficacy of Ivermectin Versus Placebo to Obtain Negative PCR Results in Patients With Early Phase COVID-19

    SAINT-PERU is a triple-blind, randomized controlled trial with two parallel groups to compare the efficacy of ivermectin versus placebo to obtain negative PCR results in patients with early phase COVID-19. The trial is currently planned at a single center in Lima.

    NCT04635943
    Conditions
    1. Covid19
    2. Coronavirus Infection
    3. SARS-CoV Infection
    Interventions
    1. Drug: Ivermectin
    2. Drug: Placebo
    MeSH:Infection Communicable Diseases Coronavirus Infections Severe Acute Respiratory Syndrome

    Primary Outcomes

    Description: Proportion of patients with a positive SARS-CoV-2 PCR from a nasopharyngeal swab at day 7 post-treatment

    Measure: Proportion of patients with a positive SARS-CoV-2 PCR.

    Time: 7 days post-treatment

    Secondary Outcomes

    Description: Change from baseline quantitative and semi-quantitative PCR in nasopharyngeal swab

    Measure: Mean viral load

    Time: Baseline and on days 4, 7, 14 and 21

    Description: Proportion of patients with fever and cough at days 4, 7, 14 and 21 as well as proportion of patients progressing to severe disease or death during the trial

    Measure: Fever and cough progression

    Time: Up to and including day 21

    Description: Proportion of participants with positive IgG at day 21

    Measure: Seroconversion at day 21

    Time: Up to and including day 21

    Description: Proportion of drug-related adverse events

    Measure: Proportion of drug-related adverse events

    Time: 7 days post treatment

    Measure: Levels of IgG, IgM and IgA

    Time: Up to and including day 21

    Description: Frequency (% over total PBMC) of innate immune cells (myeloid and plasmacytoid dendritic cells, NK cell, classical, intermediate and pro-inflammatory macrophages) measured in cryopreserved PBMC by flow cytometry

    Measure: Frequency of innate immune cells

    Time: Up to and including day 7

    Description: Frequency of CD4+ T and CD8+ T cells (% over total CD4+T and CD8+ T) expressing any functional marker upon in vitro stimulation of PBMC with SARS-CoV-2 peptides, measured by flow cytometry

    Measure: Frequency SARS-CoV-2-specific CD4+ T and and CD8+ T cells

    Time: Up to and including day 7

    Description: Concentration (all in pg/mL) of epidermal growth factor (EGF), fibroblast growth factor (FGF), granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), tumour necrosis factor (TNF), interferon (IFN)-α, IFN-γ, interleukin (IL)-1RA, IL-1β, IL-2, IL-2R, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12(p40/p70), IL-13, IL-15, IL-17, IFN-γ induced protein (IP-10), monocyte chemoattractant protein (MCP-1), monokine induced by IFN-γ (MIG), macrophage inflammatory protein (MIP)-1α, MIP-1β in plasma measured by a Luminex assay using a commercially available kit (Cytokine Human Magnetic 30-Plex Panel from ThermoFisher)

    Measure: Results from cytokine Human Magnetic 30-Plex Panel

    Time: Up to and including day 21

    Description: Proportion and parasitic load of intestinal helminths by quantitative Kato-katz and Baerman method

    Measure: Presence of intestinal helminths

    Time: Baseline and on day 14.
    424 Vitamin D Supplementation and Covid-19: a Randomised, Double- Blind, Controlled Study

    The objective of the study is to evaluate the clinical efficacy and safety of vitamin D supplementation in hospitalized patients with COVID-19.

    NCT04636086
    Conditions
    1. Covid19
    Interventions
    1. Drug: Cholecalciferol
    2. Other: Placebo

    Primary Outcomes

    Description: Mean change from screening to end of treatment phase in 25(OH)D3 serum concentration

    Measure: Vitamin D serum concentration

    Time: Baseline, on days 8, 15, 22, 29 (+/-1 day), or last day of hospitalization, and finally at day 15 to 30 after hospital discharge

    Secondary Outcomes

    Description: Ordinal scale for clinical improvement as recommended by WHO

    Measure: Clinical improvement

    Time: Baseline and up to 4 weeks after randomization on days 8, 15, 22, 29 (+/-1 day), or last day of hospitalization, and finally at day 15 to 30 after hospital discharge

    Description: Hospital length of stay.

    Measure: Hospital length of stay.

    Time: at day 15 to 30 after hospital discharge

    Description: Intensive care unit length of stay.

    Measure: Intensive care unit length of stay.

    Time: at day 15 to 30 after hospital discharge

    Description: Number of patients requiring supplemental oxygen, non-invasive ventilation or high flow oxygen devices, invasive mechanical ventilation or additional organ support (pressors, renal replacement therapy, extracorporeal membrane oxygenation).

    Measure: Supplemental oxygen, non-invasive or invasive ventilation or organ support

    Time: Baseline and up to 4 weeks after randomization on days 8, 15, 22, 29 (+/-1 day), or last day of hospitalization, and finally at day 15 to 30 after hospital discharge

    Description: Duration of any organ support

    Measure: Duration of supplemental oxygen, non-invasive or invasive ventilation or organ support

    Time: at day 15 to 30 after hospital discharge

    Description: Time until absence of fever for more than 48h without antipyretics.

    Measure: Absence of fever

    Time: Last day of hospitalization, or at at day 15 to 30 after hospital discharge

    Description: Time until negative laboratory SARS-CoV-2 test.

    Measure: Time until negative laboratory SARS-CoV-2 test.

    Time: Last day of hospitalization , or at at day 15 to 30 after hospital discharge

    Description: Mortality all causes.

    Measure: Mortality all causes.

    Time: Last day of hospitalization , or at at day 15 to 30 after hospital discharge

    Description: Mortality related to Covid-19.

    Measure: Mortality related to Covid-19.

    Time: Last day of hospitalization , or at at day 15 to 30 after hospital discharge

    Description: Blood levels of C-reactive protein, interleukin 6 and 10, cathelicidin, white blood cells, creatinin and 1,25(OH)2-D3

    Measure: Biological markers

    Time: Baseline, on days 8, 15, 22, 29 (+/-1 day), or last day of hospitalization, and finally at day 15 to 30 after hospital discharge
    425 A Multicenter, Adaptive, Randomized Blinded Controlled Trial of the Safety and Efficacy of Investigational Therapeutics for the Treatment of COVID-19 in Hospitalized Adults (ACTT-4)

    ACTT-4 will evaluate the combination of baricitinib and remdesivir compared to dexamethasone and remdesivir. Subjects will be assessed daily while hospitalized. If the subjects are discharged from the hospital, they will have a study visit at Days 15, 22, and 29. For discharged subjects, it is preferred that the Day 15 and 29 visits are in person to obtain safety laboratory tests, oropharyngeal (OP) swabs, plasma (Day 29), and serum for secondary research as well as clinical outcome data. However, if infection control or other restrictions limit the ability of the subject to return to the clinic, these visits may be conducted by phone, and only clinical data will be obtained. The Day 22 visit does not have laboratory tests or collection of samples and is conducted by phone. The primary objective is to evaluate the clinical efficacy of baricitinib + remdesivir versus dexamethasone + remdesivir as assessed by the mechanical ventilation free survival by Day 29.

    NCT04640168
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Baricitinib
    2. Drug: Dexamethasone
    3. Other: Placebo
    4. Drug: Remdesivir

    Primary Outcomes

    Measure: The proportion of subjects not meeting criteria for one of the following two ordinal scale categories at any time: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO)

    Time: Day 1 through Day 29

    Secondary Outcomes

    Measure: Change from baseline in alanine aminotransferase (ALT)

    Time: Day 1 through Day 29

    Measure: Change from baseline in aspartate aminotransferase (AST)

    Time: Day 1 through Day 29

    Measure: Change from baseline in C-reactive protein (CRP)

    Time: Day 1 through Day 29

    Measure: Change from baseline in creatinine

    Time: Day 1 through Day 29

    Measure: Change from baseline in d-dimer concentration

    Time: Day 1 through Day 29

    Measure: Change from baseline in glucose

    Time: Day 1 through Day 29

    Measure: Change from baseline in hemoglobin

    Time: Day 1 through Day 29

    Measure: Change from baseline in platelets

    Time: Day 1 through Day 29

    Description: Reported as international normalized ratio (INR)

    Measure: Change from baseline in prothrombin time (PT)

    Time: Day 1 through Day 29

    Measure: Change from baseline in total bilirubin

    Time: Day 1 through Day 29

    Measure: Change from baseline in white blood cell count (WBC) with differential

    Time: Day 1 through Day 29

    Description: Grade 3 AEs are defined as events that interrupt usual activities of daily living, or significantly affects clinical status, or may require intensive therapeutic intervention. Severe events are usually incapacitating. Grade 4 AEs are defined as events that are potentially life threatening.

    Measure: Cumulative incidence of Grade 3 and 4 clinical and/or laboratory adverse events (AEs)

    Time: Day 1 through Day 29

    Description: An SAE is defined as an AE or suspected adverse reaction is considered serious if, in the view of either the investigator or the sponsor, it results in death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect.

    Measure: Cumulative incidence of serious adverse events (SAEs)

    Time: Day 1 through Day 29

    Measure: Days of invasive mechanical ventilation/ extracorporeal membrane oxygenation (ECMO) (if applicable)

    Time: Day 1 through Day 29

    Measure: Days of non-invasive ventilation/high flow oxygen (if applicable)

    Time: Day 1 through Day 29

    Measure: Days of supplemental oxygen (if applicable)

    Time: Day 1 through Day 29

    Description: Desirability of Outcome Ranking (DOOR) based on ordinal scale: 1) Recovered (category 1, 2 or 3 on ordinal scale); 2) Improved (> / = 1 category improvement of ordinal scale compared with baseline) & no serious adverse event (SAE); 3) Improved (> / = 1 category improvement of the ordinal scale compared with baseline) & SAE (related or unrelated); 4) No change in ordinal scale from baseline & no SAE; 5) No change in ordinal scale from baseline & SAE (related or unrelated); 6) Worsening (> / = 1 category worse in ordinal scale from baseline); 7) Death.

    Measure: Desirability of Outcome Ranking (DOOR)

    Time: Day 15 through Day 29

    Description: Measured in days.

    Measure: Duration of hospitalization

    Time: Day 1 through Day 29

    Description: For any reason.

    Measure: Incidence of discontinuation or temporary suspension of study product administration

    Time: Day 1 through Day 10

    Description: Date of death (if applicable).

    Measure: Subject 14-day mortality

    Time: Day 1 through Day 15

    Description: Date of death (if applicable).

    Measure: Subject 28-day mortality

    Time: Day 1 through Day 29

    Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or ECMO; 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, but has new or increased limitation on activities and/or new or increased requirement for home oxygen over baseline, pre-COVID-19 status; 1) Not hospitalized, patient is back to their baseline, pre-COVID-19 status, that is, no new or increased limitations on activities and no new or increased oxygen use.

    Measure: Subject clinical status

    Time: Days 3, 5, 8, 11, 15, 22, and 29

    Description: The ordinal scale categories are defined as: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or ECMO; 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, but has new or increased limitation on activities and/or new or increased requirement for home oxygen over baseline, pre-COVID-19 status; 1) Not hospitalized, patient is back to their baseline, pre-COVID-19 status, that is, no new or increased limitations on activities and no new or increased oxygen use.

    Measure: The proportion of subjects meeting criteria for one of the 8 ordinal scale categories

    Time: Day 15

    Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or ECMO; 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, but has new or increased limitation on activities and/or new or increased requirement for home oxygen over baseline, pre-COVID-19 status; 1) Not hospitalized, patient is back to their baseline, pre-COVID-19 status, that is, no new or increased limitations on activities and no new or increased oxygen use.

    Measure: Time to an improvement of one category from baseline using an ordinal scale

    Time: Day 1 through Day 29

    Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or ECMO; 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, but has new or increased limitation on activities and/or new or increased requirement for home oxygen over baseline, pre-COVID-19 status; 1) Not hospitalized, patient is back to their baseline, pre-COVID-19 status, that is, no new or increased limitations on activities and no new or increased oxygen use.

    Measure: Time to an improvement of two categories from baseline using an ordinal scale

    Time: Day 1 through Day 29

    Description: Day of recovery is defined as the first day on which the subject satisfies one of the following three ordinal scale categories: 3) Hospitalized, not requiring supplemental oxygen and no longer requires ongoing medical care; 2) Not hospitalized, but has new or increased limitation on activities and/or new or increased requirement for home oxygen over baseline, pre-COVID-19 status; 1) Not hospitalized, patient is back to their baseline, pre-COVID-19 status, that is, no new or increased limitations on activities and no new or increased oxygen use.

    Measure: Time to recovery

    Time: Day 1 through Day 29
    426 Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Phase II/III Adaptive Clinical Trial to Assess the Safety and Immunogenicity of Gam-COVID-Vac Combined Vector Vaccine for SARS-Сov-2 Infection in Indian Healthy Subjects

    Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multi-Centre Phase II/III Adaptive Clinical Trial to Assess the Safety and Immunogenicity of Gam-COVID-Vac Combined Vector Vaccine for SARS-Сov-2 Infection in Indian Healthy Subjects.

    NCT04640233
    Conditions
    1. COVID-19 Prevention
    Interventions
    1. Biological: Gam-COVID-Vac
    2. Other: Placebo
    MeSH:Infection

    Primary Outcomes

    Description: For Phase II study - - Incidence & severity of adverse events (AEs) after first dose of IMP/Placebo For Phase III study - - Incidence of related serious adverse events (SAEs) following vaccination during the study

    Measure: Adverse Events

    Time: For Phase II study - at Day 28; For Phase III study - till day 180 after first dose

    Description: For Phase II study - - Seroconversion rate of SARS-CoV-2 glycoprotein-specific antibodies in immunogenicity group

    Measure: Immunogenicity

    Time: For Phase II study - Day 28 after first dose

    Description: For Phase III study - Geometric mean titre ratio of SARS-CoV-2 glycoprotein-specific antibodies between IMP and placebo in immunogenicity group

    Measure: Immunogenicity

    Time: For Phase III study - Day 42 after first dose

    Secondary Outcomes

    Description: Incidence and severity of adverse events after injecting the first dose of the IMP/placebo Incidence of SAE following vaccination

    Measure: Adverse Events

    Time: Baseline to Day 180

    Description: Seroconversion rate of SARS-CoV-2 glycoprotein-specific antibodies in immunogenicity group Seroconversion rate of SARS-CoV-2 virus-neutralizing antibodies in immunogenicity group

    Measure: Immunogenicity assessment

    Time: Baseline, Day 21, Day 28, Day 42, Day 90, and Day 180

    Description: Geometric mean virus-neutralizing antibodies titre in immunogenicity group

    Measure: Immunogenicity assessment

    Time: Baseline, Day 21, Day 28, Day 42, Day 90, and Day 180

    Description: Interferon gamma concentration in T-cells after restimulation with the SARS-CoV-2 glycoprotein in cell mediated immunogenicity group

    Measure: Immunogenicity assessment

    Time: Baseline, Day 28, Day 42, Day 90 and Day 180

    Description: The number of proliferating cluster of differentiation 4 (CD4) cell and cluster of differentiation 8 (CD8) cells in response to mitogen stimulation in cell mediated immunogenicity group

    Measure: Immunogenicity assessment

    Time: Baseline, Day 28, Day 42, Day 90 and Day 180

    Description: Comparing percentage of subjects developing COVID-19 disease between Gam-COVID-Vac combined vector vaccine and placebo based on severity course

    Measure: Percentage of subjects with mild, moderate, severe coronavirus disease 2019 (COVID-19) developed within 6 months after the first dose of the vaccine/placebo

    Time: Baseline to Day 180

    Description: Comparing incidence of COVID-19 disease between Gam-COVID-Vac combined vector vaccine and placebo

    Measure: Incidence of coronavirus disease 2019 (COVID-19) developed within 6 months after the first dose in trial subjects

    Time: Baseline to Day 180
    427 A Randomized Trial to Determine the Effect of Vitamin D and Zinc Supplementation for Improving Treatment Outcomes Among COVID-19 Patients in India

    The purpose of this study is to assess the effect of vitamin D and/or zinc supplementation on improving COVID-19 treatment outcomes. The effects of vitamin D, zinc, and both vitamin D and zinc together will be investigated among COVID-19 patients in India.

    NCT04641195
    Conditions
    1. COVID-19
    Interventions
    1. Dietary Supplement: Vitamin D3 (cholecalciferol)
    2. Dietary Supplement: Zinc (zinc gluconate)
    3. Dietary Supplement: Zinc (zinc gluconate) & Vitamin D (cholecalciferol)
    4. Other: Placebo

    Primary Outcomes

    Description: Defined as resolution of fever, cough and shortness of breath relative to baseline

    Measure: Time to recovery

    Time: Up to 8 weeks

    Secondary Outcomes

    Measure: All-cause mortality

    Time: Up to 8 weeks

    Measure: Necessity for assisted ventilation

    Time: Up to 8 weeks

    Measure: Individual symptoms duration

    Time: Up to 8 weeks

    Measure: Vitamin D

    Time: At 8 weeks

    Measure: Zinc

    Time: At 8 weeks

    Measure: Interleukin 6 (IL-6)

    Time: At 8 weeks

    Measure: Angiopoietin-2

    Time: At 8 weeks

    Measure: sTREM-1

    Time: At 8 weeks

    Measure: Immunoglobulin M (IgM)

    Time: At 8 weeks

    Measure: Immunoglobulin (IgG)

    Time: At 8 weeks
    428 An Event-Driven, Phase 3, Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate Efficacy, Safety, Immunogenicity, Lot-to-Lot Consistency of BBV152, a Whole-Virion Inactivated SARS-CoV-2 Vaccine in Adults≥18 Yrs of Age

    The BBV152 vaccine is being developed to prevent COVID-19, the disease resulting from Severe Acute Respiratory Syndrome coronavirus (SARS-CoV-2) infection. The study is designed to primarily evaluate the efficacy, safety, and immunogenicity of BBV152 to prevent COVID-19 for up to 1 year after the second dose of BBV152.

    NCT04641481
    Conditions
    1. Covid19
    2. SARS-CoV Infection
    Interventions
    1. Biological: BBV152
    2. Biological: Placebo
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome

    Primary Outcomes

    Description: (RT-PCR positive) symptomatic cases of COVID-19.

    Measure: First occurrence of Virologically confirmed (RT-PCR positive) symptomatic cases of COVID-19.

    Time: Day 42 to Month 12

    Secondary Outcomes

    Description: (RT-PCR positive) symptomatic cases of COVID-19.

    Measure: First occurence of Virologically confirmed (RT-PCR positive) symptomatic cases of COVID-19 based on the case definition for the secondary efficacy symptomatic endpoint.

    Time: Day 42 to Month 12

    Description: (RT-PCR positive) severe symptomatic cases of COVID-19.

    Measure: Virologically confirmed (RT-PCR positive) severe cases of COVID-19

    Time: Day 42 to Month 12

    Description: (RT-PCR positive) symptomatic cases of COVID-19

    Measure: Virologically confirmed COVID-19 cases of any severity occurring among participants 18 through 59 years of age and ≥60 years of age.

    Time: Day 42 to Month 12

    Description: (RT-PCR positive) asymptomatic/symptomatic cases of COVID-19.

    Measure: Virologically confirmed COVID-19 asymptomatic and symptomatic cases occurring from two weeks after the second vaccination.

    Time: Day 42 to Month 12

    Description: Solicited, Unsolicited, Serious Adverse Events

    Measure: Reactogenicity and Safety

    Time: Day 42 to Month 12

    Description: Reported by participant/documented in hospital records throughout the trial.

    Measure: The occurrence of enhanced respiratory disease episodes.

    Time: Day 42 to Month 12

    Description: Assessed based Wild-type SARS-CoV-2 Specific Neutralizing Antibody (nAb)

    Measure: Immunogenicity: Lot-to-Lot consistency of three consecutive GMP Lots

    Time: Day 0 to Day 42

    Description: Specific Neutralizing Antibody (nAb)

    Measure: Geometric Mean Titer (GMT) of SARS-CoV-2 Specific Neutralizing Antibody (nAb)

    Time: Day 0 to Month 12
    429 Randomized, Double-blind, Placebo Controlled, Clinical Trial of the Immunogenicity, Safety, and Efficacy of the Gam-COVID-Vac Combined Vector Vaccine in Prophylactic Treatment for SARS-СoV-2 Infection

    Randomized, double-blind, placebo controlled clinical trial of immunogenicity, safety and efficacy of the Gam-COVID-Vac combined vector vaccine against the SARS-CoV-2-induced coronavirus infection in adults.

    NCT04642339
    Conditions
    1. Covid19
    Interventions
    1. Biological: Gam-COVID-Vac
    2. Biological: Placebo

    Primary Outcomes

    Description: Percentage of trial subjects with fourfold or more increase in the titer of SARS-CoV-2 glycoprotein-specific antibodies in 2,000 trial subjects on the drug administration day before injecting the first dose of the study drug/placebo and 42±2 and 180±14 days after the first dose

    Measure: Seroconversion rate

    Time: 42 day, 180 day

    Secondary Outcomes

    Description: Incidence and severity of adverse events in trial subjects within 6 months after injecting the first dose of the study drug/placebo

    Measure: Incidence and severity of adverse events

    Time: through the study (till day 180)

    Description: Geometric mean virus-neutralizing antibodies titer in 500 trial subjects on the drug administration day before injecting the first dose of the study drug/placebo and 42±2 days after the first dose

    Measure: Virus-neutralizing antibody levels against the SARS-CoV-2

    Time: 42 day

    Description: Geometric mean titer of the SARS-CoV-2 glycoprotein-specific antibodies in 2,000 trial subjects on the drug administration day before injecting the first dose of the study drug/placebo and 42±2 and 180±14 days after the first dose

    Measure: Antibody levels against the SARS-CoV-2 glycoprotein

    Time: 42 day, 180 day

    Description: Percentage of trial subjects with coronavirus disease 2019 (COVID-19) developed within 6 months, as confirmed with the method of polymerase chain reaction (PCR)

    Measure: Percentage of trial subjects with coronavirus disease 2019 (COVID-19)

    Time: through the study (till day 180)
    430 Phase 2/3 Randomized, Blinded, Placebo-Controlled Trial to Evaluate the Safety, Immunogenicity, and Efficacy of INO-4800, a Prophylactic Vaccine Against COVID-19 Disease, Administered Intradermally Followed by Electroporation in Healthy Seronegative Adults at High Risk of SARS-CoV-2 Exposure

    This is a Phase 2/3, randomized, placebo-controlled, multi-center trial to evaluate the safety, immunogenicity and efficacy of INO-4800 administered by intradermal (ID) injection followed by electroporation (EP) using CELLECTRA® 2000 device to prevent COVID-19 disease in participants at high risk of exposure to SARS-CoV-2. The Phase 2 segment will evaluate immunogenicity and safety in approximately 400 participants at two dose levels across three age groups. Safety and immunogenicity information from the Phase 2 segment will be used to determine the dose level for the Phase 3 efficacy segment of the study involving approximately 6178 participants.

    NCT04642638
    Conditions
    1. Coronavirus Infection
    2. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)
    3. COVID-19 Disease
    Interventions
    1. Drug: INO-4800
    2. Device: CELLECTRA® 2000
    3. Drug: Placebo
    4. Device: CELLECTRA® 2000
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome

    Primary Outcomes

    Measure: Phase 2: Change From Baseline in Antigen-specific Cellular Immune Response Measured by Interferon-gamma (IFN-γ) Enzyme-linked Immunospot (ELISpot) Assay

    Time: Baseline up to Day 393

    Measure: Phase 2: Change From Baseline in Neutralizing Antibody Response Measured by a Pseudovirus-based Neutralization Assay

    Time: Baseline up to Day 393

    Measure: Phase 3: Percentage of Participants With Virologically-confirmed COVID-19 Disease

    Time: From 14 days after completion of the 2-dose regimen up to 12 months post-dose 2 (i.e. Day 42 up to Day 393)

    Secondary Outcomes

    Measure: Phase 2 and 3: Percentage of Participants With Solicited and Unsolicited Injection Site Reactions

    Time: From time of consent up to 28 days post-dose 2 (up to Day 56)

    Measure: Phase 2 and 3: Percentage of Participants With Solicited and Unsolicited Systemic Adverse Events (AEs)

    Time: From time of consent up to 28 days post-dose 2 (up to Day 56)

    Measure: Phase 2 and 3: Percentage of Participants With Serious Adverse Events (SAEs)

    Time: Baseline up to Day 393

    Measure: Phase 2 and 3: Percentage of Participants With Adverse Events of Special Interest (AESIs)

    Time: Baseline up to Day 393

    Measure: Phase 3: Percentage of Participants With Death From All Causes

    Time: Baseline up to Day 393

    Measure: Phase 3: Percentage of Participants With Non-Severe COVID-19 Disease

    Time: From 14 days after completion of the 2-dose regimen up to 12 months post-dose 2 (i.e. Day 42 up to Day 393)

    Measure: Phase 3: Percentage of Participants With Severe COVID-19 Disease

    Time: From 14 days after completion of the 2-dose regimen up to 12 months post-dose 2 (i.e. Day 42 up to Day 393)

    Measure: Phase 3: Percentage of Participants With Death From COVID-19 Disease

    Time: From 14 days after completion of the 2-dose regimen up to 12 months post-dose 2 (i.e. Day 42 up to Day 393)

    Measure: Phase 3: Percentage of Participants With Virologically-Confirmed SARS-CoV-2 Infections

    Time: From 14 days after completion of the 2-dose regimen up to 12 months post-dose 2 (i.e. Day 42 up to Day 393)

    Measure: Phase 3: Days to Symptom Resolution in Participants With COVID-19 Disease

    Time: From 14 days after completion of the 2-dose regimen up to 12 months post-dose 2 (i.e. Day 42 up to Day 393)

    Measure: Phase 3: Change From Baseline in Antigen-specific Cellular Immune Response Measured by IFN-gamma ELISpot Assay

    Time: Baseline up to Day 393

    Measure: Phase 3: Change From Baseline in Neutralizing Antibody Response Measured by a Pseudovirus-based Neutralization Assay

    Time: Baseline up to Day 393
    431 A Phase II/III Study of Sargramostim in Patients With Coronavirus Disease-2019 (COVID-19)

    This is a randomized, placebo-controlled, double-blind, group comparison, multicenter study to evaluate the efficacy and safety of inhalation administration of sargramostim for 5 days, in principle (up to 10 days) as Add-on treatment to the standard treatment in COVID-19 patients.

    NCT04642950
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Sargramostim
    2. Drug: Placebo

    Primary Outcomes

    Description: Number of days to achieve at least 2-rank improvement on a 7-point ordinal scale from baseline until Day 28.

    Measure: 2-rank improvement on a 7-point ordinal scale

    Time: Period until Day 28 (including the case after discharge).

    Secondary Outcomes

    Description: Changes in alveolar-arterial oxygen partial pressure gradient (A-aDO) on Day 5 and Day 10 from baseline.

    Measure: Changes in alveolar-arterial oxygen partial pressure gradient (A-aDO)

    Time: Period until Day 28 (including the case after discharge).

    Description: Number of days until discharge from baseline (days of shifting to Category 7 on a 7-point ordinal scale).

    Measure: Number of days until discharge from baseline

    Time: Period until Day 28 (including the case after discharge).

    Description: Proportion of subjects whose category has shifted to Category 1 or 2 on a 7-point ordinal scale from baseline until Day 28

    Measure: Proportion of subjects whose category has shifted to Category 1 or 2

    Time: Period until Day 28 (including the case after discharge).
    432 A Multicenter, Adaptive, Randomized, Double-blinded, Placebo-controlled Phase II/III Trial to Evaluate the Efficacy and Safety of Monoclonal Antibody SCTA01 Against SARS-CoV-2 in Hospitalized Patients With Severe COVID-19

    The study is a multicenter, adaptive, randomized, double-blinded and placebo-controlled Phase II/III trial, and will be conducted in approximately 40 sites globally. The study is comprised of two parts: dose selection (Phase II) and pivotal treatment effect (Phase III).

    NCT04644185
    Conditions
    1. Covid19
    Interventions
    1. Drug: SCTA01
    2. Other: Placebo

    Primary Outcomes

    Description: As measured by RT-qPCR

    Measure: The virologic efficacy of SCTA01 (Phase II)

    Time: Day 8

    Description: As assessed by time to clinical improvement (TTCI)

    Measure: The clinical efficacy of SCTA01 (Phase III)

    Time: Day 29

    Secondary Outcomes

    Description: TTCI

    Measure: Clinical efficacy of SCTA01(Phase II)

    Time: Day 29

    Description: Cumulative incidence of serious adverse events in both Phase II and III

    Measure: Cumulative incidence of SAEs(Phase II, III)

    Time: 3 Months

    Description: Change from baseline in viral shedding as measured by RT-qPCR in in NP swab samples

    Measure: Change from baseline in viral shedding as measured by RT-qPCR(Phase III)

    Time: Day 85

    Description: AUC0-t through Day 85

    Measure: area under the curve (AUC0-t)(Phase II)

    Time: Day 85

    Description: AUC0-∞ through Day 85

    Measure: AUC0-∞(Phase II)

    Time: Day 85

    Description: t1/2 through Day 85

    Measure: Half-life time (t1/2)(Phase II)

    Time: Day 85

    Description: Cmax through Day 85

    Measure: Maximum concentration (Cmax)(Phase II)

    Time: Day 85

    Description: Tmax through Day 85

    Measure: Peak time (Tmax)(Phase II)

    Time: Day 85

    Description: CL through Day 85

    Measure: Clearance (CL)(Phase II)

    Time: Day 85

    Description: Vd through Day 85

    Measure: Apparent volume of distribution (Vd)(Phase II)

    Time: Day 85

    Description: λz through Day 85

    Measure: Elimination rate constant (λz)(Phase II)

    Time: Day 85

    Description: ADA against SCTA01 at baseline and Day 29

    Measure: Immunogenicity as measured by anti-drug antibodies (ADA) (Phase II, III)

    Time: Day 29
    433 A 3-part Study to Investigate the Safety and Pharmacokinetics of a Novel Niclosamide Solution as a Treatment Option for COVID-19 in Combination With Camostat

    Niclosamide is a well-established substance that is a promising candidate for a repurposing approach to treat COVID-19. Niclosamide is currently marketed as a chewing tablet for the treatment of intestinal worm infections. The marketed formulation is optimized for minimal drug substance absorption. A niclosamide solution has been developed that is expected to release the drug substance more readily and more reproducibly. Camostat is approved for oral treatment of chronic pancreatitis and reflux oesophagitis in Japan. Camostat has been shown to effectively block viral replication in a SARS-CoV-2 animal model. Since the mechanisms of actions are different, it was hypothesized that a combination of both substances might have an additive or even synergistic effect in the treatment of COVID-19 patients. This 3-part study is designed to investigate (1) safety and pharmacokinetics of single ascending doses of the new niclosamide solution after fasted and fed conditions, (2) the relative bioavailability of the niclosamide solution compared to the chewing tablet, and (3) safety and pharmacokinetics of the combination of niclosamide solution and camostat after multiple doses in healthy volunteers.

    NCT04644705
    Conditions
    1. Healthy Volunteers
    Interventions
    1. Drug: Niclosamide
    2. Drug: Placebo

    Primary Outcomes

    Description: Assessment of severity of an AE will be based on CTCAE Version 5.0

    Measure: Treatment emergent number of Adverse Events

    Time: up to 14 days

    Description: Measurement will start at Day 1

    Measure: Maximum plasma concentration of niclosamide (µg/ml)

    Time: from predose until 24 hours after intervention

    Description: Measurement will start at Day 1

    Measure: Area Under the Plasma Concentration Time Curve from predose until last detectable concentration of niclosamide(AUC0-last) of niclosamide [µg/ml*h]

    Time: from predose until 24 hours after intervention

    Secondary Outcomes

    Description: Measurement will start at Day 1 after a standard high fat breakfast

    Measure: Food effect on maximum plasma concentration of niclosamide (µg/ml)

    Time: from predose until 24 hours after intervention

    Description: Measurement will start at Day 1 after a standard high fat breakfast

    Measure: Food effect on Area Under the Plasma Concentration Time Curve from predose until last detectable concentration of niclosamide (AUC0-last) [µg/ml*h]

    Time: from predose until 24 hours after intervention

    Measure: Maximum plasma concentration of niclosamide (µg/ml) at steady state after multiple dosing

    Time: from predose until Day 9

    Measure: Area Under the Plasma Concentration Time Curve between two dosing intervals (AUC tau ss) of niclosamide [µg/ml*h] at steady state after multiple dosing

    Time: from predose until Day 9
    434 A Phase 1b, Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of Bempegaldesleukin (BEMPEG; NKTR-214) Plus Standard of Care Versus Placebo Plus Standard of Care in Adults With Mild COVID-19

    The main purpose of this phase-1b, multicenter, randomized double-blind, placebo-controlled, trial is to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of bempegaldesleukin (BEMPEG; NKTR-214) in combination with standard of care (SOC) in adult patients with mild COVID-19 (coronavirus disease 2019). The trial will also define the recommended phase 2 dose (RP2D) of bempegaldesleukin in patients with mild COVID-19.

    NCT04646044
    Conditions
    1. Covid-19
    2. Coronavirus Disease 2019
    Interventions
    1. Drug: Bempegaldesleukin
    2. Drug: Standard of Care
    3. Other: Placebo
    MeSH:Coronavirus Infections

    Primary Outcomes

    Description: Area under the serum concentration-time curve (AUC) of BEMPEG /SOC.

    Measure: AUC of BEMPEG/standard of care (SOC) (PK).

    Time: Approximately 30 days

    Description: Maximum observed serum concentration (Cmax) of BEMPEG /SOC.

    Measure: Cmax of BEMPEG /SOC (PK).

    Time: Approximately 30 days

    Description: Time to Cmax (Tmax) of BEMPEG /SOC.

    Measure: Tmax of BEMPEG /SOC (PK).

    Time: Approximately 30 days

    Measure: Incidence of adverse events.

    Time: Approximately 30 days

    Measure: Incidence of treatment emergent adverse events (TEAEs).

    Time: Approximately 30 days

    Measure: Incidence of serious adverse events (SAEs).

    Time: Approximately 30 days

    Measure: Incidence of dose limiting toxicities (DLT) for BEMPEG.

    Time: Approximately 30 days

    Measure: Presence and levels of anti-drug antibodies directed to BEMPEG.

    Time: Approximately 30 days

    Measure: Fold change from baseline in absolute lymphocyte count by Central Laboratory.

    Time: Approximately 30 days

    Secondary Outcomes

    Measure: Percentage of patients who require supplemental oxygen.

    Time: Approximately 30 days

    Description: The WHO Clinical Progression Scale scores and descriptors are as follows: 0- Uninfected; no viral RNA detected; 1- Asymptomatic; viral RNA detected; 2- Symptomatic; independent; 3- Symptomatic; assistance needed; 4- Hospitalized, no oxygen therapy; 5- Hospitalized; oxygen by mask or nasal prongs ; 6- Hospitalized; oxygen by non-invasive ventilation or high-flow; 7- Intubation and mechanical ventilation, PaO2/FiO2 ≥ 150 or SpO2/FiO2 ≥ 200; 8- Mechanical ventilation, PaO2/FiO2 < 150 (SpO2/FiO2 < 200) or vasopressors; 9- Mechanical ventilation, PaO2/FiO2 < 150 and vasopressors, dialysis, or ECMO; 10- Death Abbreviations: ECMO = extracorporeal membrane oxygenation; FiO2 = fraction of inspired oxygen; PaO2 = partial pressure of arterial oxygen; SpO2 = oxygen saturation If hospitalized for isolation only, record status as for ambulatory patient. Source: WHO 2020.

    Measure: Change from baseline on the daily collection World Health Organization (WHO) Clinical Progression Scale, an 11-point clinical status ordinal scale.

    Time: Approximately 30 days
    435 A Combined Phase Ib Double-Blind Randomized Placebo Controlled/IIa, Randomized, Double-blind, Placebo Controlled, Multi-center Study to Assess the Safety, Pharmacokinetics, Pharmacodynamics and Efficacy of MRG-001 in Subjects Infected With SARS-CoV-2

    The Study is Designed as A Combined Phase I Double-Blind Randomized Placebo controlled/IIa, Randomized, Double-blind, Placebo controlled, Multi-center Study to Assess the Safety, Pharmacokinetics, Pharmacodynamics and Efficacy of MRG-001 in Subjects Infected with SARS-CoV-2. Part A: To determine the safety and tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) profiles of MRG-001 in asymptomatic SARS-CoV-2 infected subjects. Part B: To determine the safety and efficacy profile of MRG-001 in patients with moderate-to-severe COVID-19. A total of 132 subjects will be enrolled and randomized in 1:1 ratio to receive MRG-001 or placebo. All subjects will be treated with the best available treatment. The follow-up period is up to 28 days.

    NCT04646603
    Conditions
    1. COVID19
    Interventions
    1. Drug: MRG-001
    2. Drug: Placebo

    Primary Outcomes

    Description: Change from baseline in the proportion of subjects experiencing any treatment emergent adverse event (TEAE) associated with MRG-001 to Day 12.

    Measure: Phase Ib

    Time: 12 days

    Description: Time to clinical improvement from randomization to Day 28 by at least 2 points on the 8-point ordinal scale of WHO clinical improvement scale (1 = discharged; 8 = death).

    Measure: Phase IIa

    Time: 28 days

    Secondary Outcomes

    Measure: Change in percentages from baseline in circulating white blood cell subpopulations

    Time: 12 days

    Measure: Proportion of subjects changing from the WHO 8-point ordinal scale for clinical improvement Scale 1 to WHO Scale 2, 3, or 4 which corresponds to mild and moderate disease on the NIH COVID-19 severity scale.

    Time: 12 days

    Measure: Change in Plerixafor concentration (ng/ml) from baseline in blood

    Time: 12 days

    Measure: Change in Tacrolimus concentration (ng/ml) from baseline in blood

    Time: 12 days

    Measure: Change in percentage from baseline of IgG antibodies against SARS CoV-2 in serum

    Time: 12 days

    Measure: Change from baseline in ALT, AST

    Time: 12 days

    Measure: Change in percentages from baseline in circulating stem cells and immune cells

    Time: 12 days

    Measure: Change from baseline in platelets

    Time: 12 days

    Measure: Change from baseline in total Bilirubin

    Time: 12 days

    Measure: Change from baseline in LDH

    Time: 12 days

    Measure: Change from baseline in blood urea nitrogen (BUN)

    Time: 12 days

    Measure: Change from baseline in glomerular filtration rate (GFR)

    Time: 12 days

    Measure: Change from baseline in percentages in interleukin-1β

    Time: 12 days

    Measure: Change from baseline in percentages in interleukin-6

    Time: 12 days

    Measure: Change from baseline in percentages in interleukin TNF- α

    Time: 12 days

    Measure: Change from baseline in percentages in interferon-gamma-inducible protein-10 (IP-10)

    Time: 12 days

    Measure: Change from baseline in percentages in CRP

    Time: 12 days

    Measure: Change from baseline in percentages in D-dimer levels

    Time: 12 days

    Measure: Change from baseline in hemoglobin

    Time: 12 days

    Measure: Change in from baseline in SARS-CoV-2 viral load

    Time: 12 days
    436 Safety and Immunogenicity of SARS-CoV-2 mRNA Vaccine (BNT162b2) in Chinese Healthy Population: A Phase II, Randomized, Placebo-controlled, Observer-blinded Study

    This is a phase II, randomized, placebo-controlled, observer-blinded study of the safety and immunogenicity of SARS-CoV-2 messenger RNA (mRNA) vaccine (BNT162b2) in Chinese healthy population. After randomization, the trial for each participant will last for approximately 13 months. Screening period is 2 weeks prior to randomization (Day -14 to Day 0), and two doses of either SARS-CoV-2 vaccine (BNT162b2) or placebo will be given intramuscularly (IM) separated by 21 days.

    NCT04649021
    Conditions
    1. SARS-CoV-2
    Interventions
    1. Biological: BNT162b2
    2. Other: Placebo

    Primary Outcomes

    Description: SCR of SARS-CoV-2 serum neutralizing titers at 1-month after dose 2. Seroconversion is defined as ≥4-fold rise from before vaccination to 1-month post dose 2.

    Measure: SARS-CoV-2 serum neutralizing titers - Seroconversion rates (SCR)

    Time: 1 Month after Dose 2

    Measure: The geometric mean titer (GMT) of SARS-CoV-2 serum neutralizing titers at 1 month after dose 2

    Time: 1 Month after Dose 2

    Secondary Outcomes

    Description: Compared with baseline before Vaccination 1, SCR of SARS-CoV-2 serum neutralizing titers at 1 week, 6 and 12 months after dose 2.

    Measure: SARS-CoV-2 serum neutralizing titers - SCR

    Time: 1 Week, 6 and 12 Months after Dose 2

    Description: GMT of SARS-CoV-2 serum neutralizing titers at 1 week, 6 and 12 months after dose 2.

    Measure: SARS-CoV-2 serum neutralizing titers - GMT

    Time: 1 Week, 6 and 12 Months after Dose 2

    Description: Compared with baseline before Vaccination 1, SCR of SARS-CoV-2 anti-S1 IgG antibody level at 1 week, 1, 6 and 12 months after dose 2.

    Measure: SARS-CoV-2 anti-S1 immunoglobulin G (IgG) antibody level - SCR

    Time: 1 Week, 1, 6 and 12 Months after Dose 2

    Description: GMT of SARS-CoV-2 anti-S1 IgG antibody level at 1 week, 1, 6 and 12 months after dose 2.

    Measure: SARS-CoV-2 anti-S1 IgG antibody level - GMT

    Time: 1 Week, 1, 6 and 12 Months after Dose 2

    Description: Compared with baseline before Vaccination 1, the GMFR of SARS-CoV-2 serum neutralizing antibody titers at 1 week, 1, 6 and 12 months after dose 2.

    Measure: SARS-CoV-2 serum neutralizing antibody level - Geometric mean fold rise (GMFR)

    Time: 1 Week, 1, 6 and 12 Months after Dose 2

    Description: Compared with baseline before Vaccination 1, GMFR of SARS-CoV-2 anti-S1 IgG antibody level at 1 week, 1, 6 and 12 months after dose 2.

    Measure: SARS-CoV-2 anti-S1 IgG antibody level - GMFR

    Time: 1 Week, 1, 6 and 12 Months after Dose 2

    Description: Pain at the injection site, redness, and swelling as self-reported on diary cards.

    Measure: Percentage of participants reporting local reactions

    Time: Within 7 Days and 14 Days after each vaccination

    Description: Fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain as self-reported on diary cards.

    Measure: Percentage of participants reporting systemic events

    Time: Within 7 Days and 14 Days after each vaccination

    Description: Percentage of participants with abnormal hematology laboratory values 1 and 7 days after dose 1, before dose 2, and 7 days after dose 2.

    Measure: Hematology laboratory assessments

    Time: Day 1 and 7 Days after Dose 1, before Dose 2, and 7 Days after Dose 2

    Description: Percentage of participants with abnormal chemistry laboratory values 1 and 7 days after dose 1, before dose 2, and 7 days after dose 2.

    Measure: Chemistry laboratory assessments

    Time: Day 1 and 7 Days after Dose 1, before Dose 2, and 7 Days after Dose 2

    Description: Percentage of participants with grading shifts in hematology laboratory assessments between baseline and 1 and 7 days after dose 1; and before dose 2 and 7 days after dose 2.

    Measure: Hematology laboratory assessments

    Time: Day 1 and 7 Days after Dose 1; and before Dose 2 and 7 Days after Dose 2

    Description: Percentage of participants with grading shifts in chemistry laboratory assessments between baseline and 1 and 7 days after dose 1; and before dose 2 and 7 days after dose 2.

    Measure: Chemistry laboratory assessments

    Time: Day 1 and 7 Days after Dose 1; and before Dose 2 and 7 Days after Dose 2

    Description: AEs from dose 1 to 1 month after the last dose.

    Measure: Adverse events (AEs)

    Time: From Dose 1 through 1 Month after the last Dose

    Description: SAEs from dose 1 to 6 months after the last dose.

    Measure: Serious AEs (SAEs)

    Time: From Dose 1 through 6 Months after the last Dose
    437 A Phase 2/3, Randomized, Observer-Blind, Placebo Controlled Study to Evaluate the Safety, Reactogenicity, and Effectiveness of mRNA-1273 SARS CoV 2 Vaccine in Healthy Adolescents 12 to <18 Years of Age

    The mRNA-1273 vaccine is being developed to prevent COVID-19, the disease resulting from Severe Acute Respiratory Syndrome coronavirus (SARS-CoV-2) infection. The study is designed to primarily evaluate the safety and reactogenicity of a single dose level of mRNA-1273 vaccine administered in 2 doses 28 days apart to an adolescent population.

    NCT04649151
    Conditions
    1. SARS-CoV-2
    Interventions
    1. Biological: mRNA-1273
    2. Biological: Placebo

    Primary Outcomes

    Measure: Number of Participants with Solicited Local and Systemic Adverse Reactions (ARs)

    Time: Up to Day 8 (7 days after first dose) and up to Day 36 (7 days after second dose)

    Measure: Number of Participants with Unsolicited Adverse Events (AEs)

    Time: Up to Day 57 (28 days after each dose)

    Measure: Number of Participants with Serious Adverse Events (SAEs), Medically Attended AEs (MAAEs), or Adverse Events of Special Interest (AESI)

    Time: Up to Day 394 (1 year after second dose)

    Description: Acceptable serum Ab threshold as predefined for the study.

    Measure: Number of Participants Who have Reached the Acceptable Threshold for the Serum Ab Level at Day 57

    Time: Day 57 (28 days after second dose)

    Measure: Comparison of the Geometric Mean of the Serum Neutralizing Antibody (nAb) level against the Geometric Mean of the Serum nAb level in Study mRNA-1273-P301 (NCT04470427)

    Time: Day 57 (28 days after second dose)

    Secondary Outcomes

    Measure: Geometric Mean Value of SARS-CoV-2 Spike Protein (S2P)-specific binding antibody (bAb)

    Time: Day 1, Day 57 (1 month after dose 2), Day 209 (6 months after dose 2), and Day 394 (1 year after dose 2)

    Measure: Geometric Mean Value of SARS-CoV-2-specific nAb

    Time: Day 1, Day 57 (1 month after dose 2), Day 209 (6 months after dose 2), and Day 394 (1 year after dose 2)

    Description: Clinical signs indicative of SARS-CoV-2 infection as predefined for the study.

    Measure: Number of Participants with a SARS-CoV-2 Infection Starting on Day 57

    Time: Day 57 up to Day 394

    Description: Clinical signs indicative of COVID-19 as predefined for the study.

    Measure: Number of Participants with a First Occurrence of COVID-19 Starting 14 days after Second Dose of mRNA-1273 or Placebo

    Time: Day 29 (second dose) up to Day 394 (1 year after second dose)
    438 COVID-19 Post-hospital Thrombosis Prevention Trial: An Adaptive, Multicenter, Prospective, Randomized Platform Trial Evaluating the Efficacy and Safety of Antithrombotic Strategies in Patients With COVID-19 Following Hospital Discharge

    A multicenter, adaptive, randomized platform trial evaluating the efficacy and safety of antithrombotic strategies in patients with COVID-19 following hospital discharge

    NCT04650087
    Conditions
    1. Covid19
    Interventions
    1. Drug: Apixaban 2.5 MG
    2. Drug: Placebo
    MeSH:Thrombosis

    Primary Outcomes

    Measure: Composite outcome of symptomatic deep vein thrombosis, pulmonary embolism, other venous thromboembolism, ischemic stroke, myocardial infarction, other arterial thromboembolism, and all-cause mortality as measured by hospital records.

    Time: 30 days after hospital discharge

    Secondary Outcomes

    Measure: The composite outcome of symptomatic deep vein thrombosis, pulmonary embolism, other venous thromboembolism, ischemic stroke, myocardial infarction, other arterial thromboembolism, and all-cause mortality as measured by hospital records.

    Time: 45 days after hospital discharge

    Measure: The composite outcome of symptomatic deep vein thrombosis, pulmonary embolism, other venous thromboembolism, ischemic stroke, myocardial infarction, other arterial thromboembolism, and all-cause mortality as measured by hospital records.

    Time: 90 days after hospital discharge

    Measure: New, symptomatic VTE (inclusive of DVT, PE, or other venous thrombosis) for up to 30 days after randomization as measured by hospital records.

    Time: 30 days after reandomization

    Measure: New, symptomatic ATE (inclusive of ischemic stroke, MI, or peripheral arterial thromboembolism) for up to 30 days after randomization as measured by hospital records.

    Time: 30 days after randomization

    Other Outcomes

    Measure: The incidence of all-cause mortality

    Time: 30 days following discharge from hospital

    Measure: The incidence of all-cause rehospitalization for up to 30 days after randomization

    Time: 30 days following discharge from hospital
    439 Multi-center, Phase 3, Double-blind, Randomized, Placebo-controlled, Clinical Study to Evaluate the Efficacy, Safety, and Immunogenicity of an Inactivated Vaccine Against the SARS-CoV-2 Infection in High Risk of Infection Adults

    The study will evaluate the efficacy, safety, and immunogenicity of an inactivated vaccine against the SARS-CoV-2 infection in high risk of infection adults. Two doses of the vaccine or placebo will be administered in an 0 and 14 days schedule. Follow-up of safety and efficacy will be implemented by 12 months after the first dose. Immunogenicity will be studied in a subgroup of participants.

    NCT04651790
    Conditions
    1. Covid19
    2. Vaccines
    Interventions
    1. Biological: SARS-CoV-2 inactivated vaccine
    2. Other: Placebo
    MeSH:Infection

    Primary Outcomes

    Description: Vaccine efficacy to prevent virologically confirmed COVID-19 two weeks after the second vaccination will be determined

    Measure: Incidence of symptomatic cases of virologically confirmed COVID-19 two weeks after the second vaccination

    Time: Two weeks after second dose up to one year after first dose

    Description: The frequency of solicited and unsolicited local and systemic adverse reactions will be registered. This will be measured during the first 7 days after each vaccination. These adverse reactions will be registered according to the age group in adult (18-59 years old) and elder (60 years of age or older) subjects.

    Measure: Frequency of solicited and unsolicited local and systemic adverse reactions during the period of one week after vaccination according to age group in adult (18-59 years old) and elder (60 years of age or older) subjects.

    Time: During the first 7 days after each dose of vaccine/placebo

    Secondary Outcomes

    Description: The incidence of cases confirmed through PCR for COVID-19 after administration of at least one dose of vaccine/placebo will be determined.

    Measure: Incidence of cases of virologically confirmed COVID-19 after administration of at least one dose of vaccine/placebo

    Time: Since first dose and up to 12 months after

    Description: The incidence of severe cases of COVID-19, confirmed through PCR, two weeks after the second vaccination, will be determined.

    Measure: Incidence of severe cases of COVID-19 virologically confirmed two weeks after the second vaccination

    Time: Since two weeks after the second dose up 12 month after first dose

    Description: The incidence of hospitalized cases of COVID-19 two weeks after the second vaccination will be determined.

    Measure: Incidence of hospitalized cases of COVID-19 two weeks after the second vaccination

    Time: Since two weeks after the second dose and up 12 month after first dose

    Description: The incidence of deaths due to COVID-19 two weeks after the second vaccination will be determined.

    Measure: Incidence of deaths due to COVID-19 two weeks after the second vaccination

    Time: Since two weeks after the second dose up 12 month after first dose

    Description: The incidence of adverse reactions to the vaccine, both local and systemic, solicited and unsolicited will be determined. These adverse reactions will be measured within the period of four weeks after each dose of vaccination. These adverse reactions will be registered according to the age group in adult (18-59 years old) and elder (60 years of age or older) subjects.

    Measure: Incidence of adverse reactions to the vaccine, local and systemic, solicited and unsolicited, within the period of four weeks after each dose of vaccination, according to the age group, adults (18-59 years old) and elder (60 years or older) subjects.

    Time: Four weeks after each dose of vaccine/placebo

    Description: The frequency of severe COVID-19 cases in participants who received at least one dose of vaccine/placebo will be determined.

    Measure: Frequency of severe COVID-19 cases in participants who received at least one dose of vaccine/placebo

    Time: Since first dose up to 12 month after

    Description: The occurrence of serious adverse events (SAE) and adverse events of special interest in participants who have received at least one dose of the vaccine, will be determined.

    Measure: Incidence of serious adverse events (SAE) and adverse events in participants who have received at least one dose of the vaccine

    Time: Since first dose up to 12 month after

    Description: The cellular immune response in a subgroup of participants, before and two and four weeks after the administration of each dose of the vaccine, will be evaluated.

    Measure: Percentage of participants that show a significant increase in SARS-CoV-2 specific T cells after vaccination, determined by flow Cytometry and ELISPOT

    Time: Since first dose up to 4 weeks after second dose

    Description: The presence of anti-SARS-CoV-2 antibodies in a subgroup of participants, before and two weeks after the administration of each dose of the vaccine, will be evaluated.

    Measure: Percentage of participants with a significant increase of anti-SARS-CoV-2 antibodies, determined by ELISA

    Time: Since first dose up to 2 weeks after second dose
    440 A Phase 2b/3, Randomized, Observer-Blinded, Placebo-Controlled, Multicenter Clinical Study Evaluating the Efficacy and Safety of Investigational SARS-CoV-2 mRNA Vaccine CVnCoV in Adults 18 Years of Age and Older

    This study aims to: - Demonstrate the efficacy of a 2-dose schedule of CVnCoV in the prevention of first episodes of virologically-confirmed cases of COVID-19 of any severity in SARS-CoV-2 naïve participants. - Demonstrate the efficacy of a 2-dose schedule of CVnCoV in the prevention of first episode of virologically-confirmed moderate to severe cases of COVID-19 in SARS-CoV-2 naïve participants.

    NCT04652102
    Conditions
    1. Covid19
    2. SARS-CoV-2
    Interventions
    1. Biological: CVnCoV
    2. Biological: Placebo

    Primary Outcomes

    Measure: Number of participants who experience a first episode of virologically-confirmed {reverse transcription polymerase chain reaction (RT-PCR) positive} case of COVID-19 of any severity

    Time: Day 1 to Day 393

    Measure: Number of participants who experience a first episode of virologically-confirmed {reverse transcription polymerase chain reaction (RT-PCR) positive} case of moderate to severe COVID-19

    Time: Day 1 to Day 393

    Measure: Number of participants who experience one or more medically-attended adverse events (AEs)

    Time: Day 29 to Day 211

    Measure: Intensity grading of medically-attended adverse events (AEs) per FDA toxicity grading scale

    Time: Day 29 to Day 211

    Measure: Number of participants who experience one or more treatment-related medically-attended adverse events (AEs)

    Time: Day 29 to Day 211

    Measure: Number of participants who experience one or more serious adverse events (SAEs)

    Time: Day 29 to Day 393

    Measure: Intensity grading of serious adverse events (SAEs) per FDA toxicity grading scale

    Time: Day 29 to Day 393

    Measure: Number of participants who experience one or more treatment-related serious adverse events (SAEs)

    Time: Day 29 to Day 393

    Measure: Number of participants who experience one or more adverse events of special interest (AESI)

    Time: Day 29 to Day 393

    Measure: Intensity grading of adverse events of special interest (AESI) per FDA toxicity grading scale

    Time: Day 29 to Day 393

    Measure: Number of participants who experience one or more treatment-related adverse events of special interest (AESI)

    Time: Day 29 to Day 393

    Measure: Number of participants who experience a fatal serious adverse event (SAE)

    Time: Day 29 to Day 393

    Secondary Outcomes

    Measure: Number of participants who experience a first episode of virologically-confirmed {reverse transcription polymerase chain reaction (RT-PCR) positive} severe case of COVID-19

    Time: Day 1 to Day 393

    Description: Seroconversion is defined as detectable SARS-CoV-2 N protein antibodies in the serum of asymptomatic seronegative participants who tested seronegative on Day 1 and on Day 43.

    Measure: Number of participants with seroconversion to the nucleocapsid (N) protein of SARS-CoV-2 ≥ 15 days after the second study vaccination

    Time: Days 1, 43, 211 and 393

    Measure: Number of participants aged ≥ 61 who experience a first episode of virologically-confirmed {reverse transcription polymerase chain reaction (RT-PCR) positive} case of COVID-19 of any severity

    Time: Day 1 to Day 393

    Measure: Number of participants who experience a virologically-confirmed {reverse transcription polymerase chain reaction (RT-PCR) positive} SARS-CoV-2 infection, with or without symptoms

    Time: Day 1 to Day 393

    Measure: Burden of disease (BoD) based on first episodes of virologically-confirmed {reverse transcription polymerase chain reaction (RT-PCR) positive} cases of COVID-19

    Time: Day 1 to Day 393

    Measure: Number of participants who experience a virologically-confirmed {reverse transcription polymerase chain reaction (RT-PCR) positive} case of COVID-19 of any severity with symptom onset at any time after the first study vaccination

    Time: Post vaccination on Day 1 up to Day 393

    Description: S protein will be measured by enzyme-linked immunosorbent assay (ELISA).

    Measure: Number of participants with serum antibodies to SARS-CoV-2 spike (S) protein

    Time: Days 1, 29, 43, 57, 120, 211 and 393

    Description: S protein will be measured by enzyme-linked immunosorbent assay (ELISA). Seroconversion is defined as detectable SARS-CoV-2 S protein antibodies in the serum of participants who tested seronegative on Day 1.

    Measure: Number of participants who experience seroconversion to SARS-CoV-2 spike (S) protein

    Time: Days 1, 29, 43, 57, 120, 211 and 393

    Description: Serum vital neutralizing antibodies to SARS-CoV-2 virus will be measured by a viral neutralizing antibody assay.

    Measure: Number of participants with serum vital neutralizing antibodies to SARS-CoV-2 virus

    Time: Days 1, 29, 43, 57, 120, 211 and 393

    Description: Seroconversion to SARS-CoV-2 virus will be measured by a viral neutralizing antibody assay. Seroconversion is defined as detectable SARS-CoV-2 viral neutralizing antibodies in the serum of participants who tested seronegative on Day 1.

    Measure: Number of participants who experience seroconversion to SARS-CoV-2 virus

    Time: Days 1, 29, 43, 57, 120, 211 and 393

    Measure: Phase 2b participants only: Number of participants who experience one or more solicited local adverse events (AEs)

    Time: 7 days after vaccination

    Measure: Phase 2b participants only: Intensity grading of solicited local adverse events (AEs) per FDA toxicity grading scale

    Time: 7 days after vaccination

    Measure: Phase 2b participants only: Duration of solicited local adverse events (AEs)

    Time: 7 days after vaccination

    Measure: Phase 2b participants only: Number of participants who experience one or more solicited systemic adverse events (AE)

    Time: 7 days after vaccination

    Measure: Phase 2b participants only: Intensity grading of solicited systemic adverse events (AEs)

    Time: 7 days after vaccination

    Measure: Phase 2b participants only: Duration of solicited systemic adverse events (AEs)

    Time: 7 days after vaccination

    Measure: Phase 2b participants only: Number of participants who experience one or more unsolicited adverse events (AEs)

    Time: 28 days after vaccination

    Measure: Phase 2b participants only: Intensity grading of unsolicited adverse events (AEs)

    Time: 28 days after vaccination

    Measure: Phase 2b participants only: Number of participants who experience one or more treatment-related unsolicited adverse events (AEs)

    Time: 28 days after vaccination

    Measure: Number of participants who experience one or more adverse events (AEs) leading to vaccine withdrawal or trial discontinuation

    Time: Day 29 to Day 393
    441 A Phase 2 Randomized, Double-blind, Placebo-controlled Safety and Efficacy Trial of Deupirfenidone (LYT-100) in Post-acute COVID-19 Respiratory Disease

    This study is a randomized, double-blind, parallel arm study to evaluate the safety and efficacy of LYT-100 compared to placebo in adults with post-acute COVID-19 respiratory complications

    NCT04652518
    Conditions
    1. Covid19
    Interventions
    1. Drug: LYT-100
    2. Other: Placebo
    MeSH:Respiration Disorders Respiratory Tract Diseases

    Primary Outcomes

    Description: The 6MWT is a validated endpoint commonly used in clinical trial research

    Measure: Change in distance walked on the six-minute walk test (6MWT)

    Time: Baseline to Day 91

    Secondary Outcomes

    Description: The mBDS is an assessment tool that analyzes breathlessness under exertion

    Measure: Change in Modified Borg Dyspnoea Scale (mBDS) score

    Time: Baseline to Day 91

    Description: The SF-36 (v2) is a self-administered questionnaire containing 36 items that measures functional status, well-being and overall evaluation of health in 8 domains

    Measure: Quality of Life assessment as collected using the SF-36

    Time: Baseline to Day 91
    442 A Placebo-controlled, Multicenter, Double-blind, Randomized, Parallel-group Comparative Study in SARS-CoV-2 Infection (COVID-19)

    To assess the efficacy and safety of FOY-305 in patients with SARS-CoV-2 infection (COVID-19) in a placebo-controlled, multicenter, double-blind, randomized, parallel-group comparative study.

    NCT04657497
    Conditions
    1. SARS-CoV-2 Infection (COVID-19)
    Interventions
    1. Drug: FOY-305
    2. Drug: Placebo
    MeSH:Infection Communicable Diseases

    Primary Outcomes

    Description: Time to SARS-CoV-2 negative test as assessed by the local laboratory

    Measure: Time to SARS-CoV-2 negative test

    Time: Up to 14 days

    Secondary Outcomes

    Description: Time to SARS-CoV-2 negative test as assessed by the central laboratory

    Measure: Time to SARS-CoV-2 negative test

    Time: Up to 14 days

    Description: Proportion of subjects who test negative for SARS-CoV-2 (as assessed by the local and central laboratories)

    Measure: Proportion of subjects who test negative for SARS-CoV-2

    Time: Up to 14 days

    Description: Ordinal scale for severity. The minimum score is 0: No clinical or virological evidence of infection, representing the better outcome, and the maximum value is 8: Death, representing the worse outcome.

    Measure: Ordinal scale for severity

    Time: Up to 14 days

    Description: Proportion of subjects on mechanical ventilator

    Measure: Proportion of subjects on mechanical ventilator

    Time: Up to 14 days

    Description: Proportion of subjects alive or death

    Measure: Survival status (alive/death)

    Time: Up to 14 days
    443 A Randomized, Double Blind, Multicenter, Placebo Controlled, Parallel Group, Exploratory Efficacy and Safety Study of Glenzocimab in SARS-Cov-2-related Acute Respiratory Distress Syndrome

    A randomized, double blind, multicenter, placebo-controlled, parallel group, fixed dose, phase II study to evaluate the efficacy and safety of glenzocimab in ARDS.

    NCT04659109
    Conditions
    1. SARS-CoV Infection
    2. Acute Respiratory Distress Syndrome
    3. COVID-19
    4. ARDS
    Interventions
    1. Drug: glenzocimab
    2. Drug: Placebo
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acu Acute Lung Injury Syndrome

    Primary Outcomes

    Description: Progression from moderate to severe assessed at Day 4 is a composite failure endpoint defined as the occurrence of at least one of the following failure events : Respiratory rate (RR) ≥ 30/min, or Oxygen Saturation (SpO2) ≤ 93% in resting state, or Oxygen Pressure/ Inspired fraction (PaO2/FiO2) ≤ 200mmHg Death occurring prior to or on Day 4

    Measure: Progression from moderate to severe respiratory distress assessed at Day 4

    Time: Day 4

    Secondary Outcomes

    Measure: All cause mortality at day 40

    Time: Day 40 (maximum)

    Description: WHO COVID-19 Ordinal Scoring Scale is 9 point ordinal scale

    Measure: WHO-COVID-19 Scale

    Time: Up to Day 40

    Description: Determines the degree of illness of a patient and prompts critical care intervention (recommended by NHS over original NEWS): total possible score ranges from 0 to 20. The higher the scores the greater the clinical risk.

    Measure: NEWS-2 Scale

    Time: Up to Day 40

    Description: Respiratory Rate status defined as:: o Normal:<20/min, Mild:20/min≤RR<24/min, Moderate:24/min≤RR<30/min, o Severe:≥30/min, Death.

    Measure: Respiratory Rate status (RR)

    Time: Up to Day 40

    Description: Hypoxemia status defined as:: o Normal:>300mmHg, Mild: 200 mmHg < PaO2/FiO2 ≤ 300 mmHg, Moderate:100mmHg Measure: Hypoxemia status

    Time: Up to Day 40

    Description: SpO2 status defined as: o Normal:>95% Mild:93% Measure: SpO2 status

    Time: Up to Day 40

    Measure: CHEST CT-Scan (or in exceptional cases, chest radiogram)

    Time: Day 4

    Measure: Oxygen-free days

    Time: Up to Day 40

    Measure: Admission to the ICU

    Time: Up to Day 40

    Measure: ICU-free days

    Time: Up to Day 40

    Measure: Hospital-free days

    Time: Up to Day 40

    Measure: Clinical recovery and Time to Clinical recovery

    Time: Up to Day 40

    Measure: Cure and Time-to-cure

    Time: Up to Day 40

    Measure: Incidence, nature and severity of Adverse Events, SAEs, SUSARs and Treatment-Emergent Adverse Events (TEAEs)

    Time: Up to Day 40

    Measure: Incidence of bleeding-related events

    Time: Up to Day 40

    Measure: Incidence of hypersensitivity reactions

    Time: Up to Day 40

    Measure: Changes from baseline on blood pressure

    Time: Up to Day 40

    Measure: Changes from baseline on heart rate

    Time: Up to Day 40

    Measure: Changes from baseline on NFS

    Time: Up to Day 40

    Measure: Changes from baseline on INR/PTT

    Time: Up to Day 40

    Measure: Changes from baseline on platelet count

    Time: Up to Day 40

    Measure: Changes from baseline on plasma fibrinogen level

    Time: Up to Day 40

    Measure: Changes from baseline on plasma D-Dimers level

    Time: Up to Day 40

    Measure: Changes from baseline on serum-glucose level

    Time: Up to Day 40

    Measure: Changes from baseline on urea level

    Time: Up to Day 40

    Measure: Changes from baseline on creatinemia

    Time: Up to Day 40

    Measure: Changes from baseline on LFTs (ASAT/ALAT)

    Time: Up to Day 40

    Measure: Changes from baseline on CRP level

    Time: Up to Day 40

    Measure: Changes from baseline on LDH level

    Time: Up to Day 40

    Measure: Changes from baseline on IL6 level

    Time: Up to Day 40

    Measure: Changes from baseline on Tnt

    Time: Up to Day 40

    Measure: Changes from baseline on NT proBNP

    Time: Up to Day 40

    Measure: Changes from baseline on procalcitonin level

    Time: Up to Day 40

    Measure: Changes from baseline on ferritin level

    Time: Up to Day 40

    Description: Changes in one or several of the usual ECG parameters compared to baseline or screening, i.e. sinusal rhythm, cardiac axis, QRS value, QT/QTc segment, Wave direction, and any abnormality.

    Measure: ECG over the course of the study versus screening

    Time: Up to Day 40
    444 A Randomized, Double-Blinded, Placebo Controlled Phase III Clinical Trial of SARS-CoV-2 Vaccine, Inactivated (Vero Cell) in Adults Aged 18 Years and Above

    This is a randomized, double-blinded, placebo controlled phase III clinical trial to evaluate the efficacy, safety and immunogenicity of SARS-CoV-2 Vaccine, Inactivated (Vero Cell) in adults aged 18 years and above after 2-dose schedule.

    NCT04659239
    Conditions
    1. COVID-19
    Interventions
    1. Biological: Inactivated SARS-CoV-2 Vaccine (Vero cell)
    2. Biological: Placebo

    Primary Outcomes

    Description: The incidence of the symptomatic and laboratory-confirmed COVID-19 cases starting from Day 14 after the second dose.

    Measure: The incidence of COVID-19 cases after two-doses of vaccination

    Time: From 14 days after the second dose to 1 year after the second dose.

    Description: The incidence of solicited AEs at the inoculation site (local) and solicited AEs at the non-inoculation site (systemic) within 7 days after each dose

    Measure: The incidence of solicited AEs.

    Time: 7 days after each dose

    Secondary Outcomes

    Description: The incidence of the symptomatic and laboratory-confirmed COVID-19 cases after at least one dose of immunization.

    Measure: The incidence of COVID-19 cases after at least one dose of immunization.

    Time: From the first dose to 1 year after the second dose.

    Description: The Geometric Mean Titer (GMT) of neutralizing antibody against SARS-CoV-2 14 days after the whole-course immunization.

    Measure: The Geometric Mean Titer (GMT) of neutralizing antibody

    Time: 14 days after the whole-course immunization

    Description: The Geometric Mean Titer (GMT) of IgG antibody (ELISA method) against SARS-CoV-2 14 days after the whole-course immunization.

    Measure: The Geometric Mean Titer (GMT) of IgG antibody

    Time: 14 days after the whole-course immunization

    Description: The positive rates of neutralizing antibody against SARS-CoV-2 14 days after the whole-course immunization.

    Measure: The positive rates of neutralizing antibody

    Time: 14 days after the whole-course immunization

    Description: The positive rates of IgG antibody (ELISA method) against SARS-CoV-2 14 days after the whole-course immunization.

    Measure: The positive rates of IgG antibody

    Time: 14 days after the whole-course immunization

    Description: The seroconversion rates of neutralizing antibody against SARS-CoV-2 14 days after the whole-course immunization.

    Measure: The seroconversion rates of neutralizing antibody

    Time: 14 days after the whole-course immunization

    Description: The seroconversion rates of IgG antibody (ELISA method) against SARS-CoV-2 14 days after the whole-course immunization.

    Measure: The seroconversion rates of IgG antibody

    Time: 14 days after the whole-course immunization

    Description: The positive rates of neutralizing antibody against SARS-CoV-2 6 months and 12 months after whole-course immunization.

    Measure: The positive rates of neutralizing antibody

    Time: 6 months and 12 months after whole-course immunization.

    Description: The positive rates of IgG antibody (ELISA method) against SARS-CoV-2 6 months and 12 months after whole-course immunization.

    Measure: The positive rates of IgG antibody

    Time: 6 months and 12 months after whole-course immunization.

    Description: The Geometric Mean Titer (GMT) of neutralizing antibody against SARS-CoV-2 6 months and 12 months after whole-course immunization.

    Measure: The Geometric Mean Titer (GMT) of neutralizing antibody

    Time: 6 months and 12 months after whole-course immunization.

    Description: The Geometric Mean Titer (GMT) of IgG antibody (ELISA method) against SARS-CoV-2 6 months and 12 months after whole-course immunization.

    Measure: The Geometric Mean Titer (GMT) of IgG antibody

    Time: 6 months and 12 months after whole-course immunization.

    Description: Detecting specific T cells with ELISPOT assay 6 months and 12 months after the whole-course immunization

    Measure: Specific T cells with ELISPOT assay

    Time: 6 months and 12 months after the whole-course immunization

    Description: The incidence of AEs from the first dose to 28 days after whole-course immunization

    Measure: The incidence of AEs

    Time: From the first dose to 28 days after whole-course immunization.

    Description: The incidence of SAEs from the first dose to at least 12 months after whole-course immunization.

    Measure: The incidence of SAEs

    Time: From the first dose to at least 12 months after whole-course immunization.

    Description: The occurrence of Antibody Dependent Enhancement (ADE)/ Vaccine Enhanced Disease(VED) that probably related to the laboratory-confirmed COVID-19 from 14 days after the second dose till the end of trial.

    Measure: The occurrence of Antibody Dependent Enhancement (ADE)/ Vaccine Enhanced Disease(VED)

    Time: From 14 days after the second dose to 1 year after the second dose.

    Other Outcomes

    Description: The correlation between the efficacy of the vaccine and the levels of neutralizing antibody and IgG antibody against SARS-CoV-2.

    Measure: The surrogate endpoint of immunogenicity

    Time: From 14 days after the second dose to 1 year after the second dose.
    445 A Randomized Placebo-Controlled Safety And Dose-Finding Study For The Use Of The Il-6 Inhibitor Clazakizumab in Patients With Life-Threatening COVID-19 Infection

    The purpose of this study is to investigate the safety of treatment with an investigational drug called clazakizumab compared to a placebo (inactive substance) in critically ill patients.

    NCT04659772
    Conditions
    1. Covid19
    2. Respiratory Failure
    Interventions
    1. Drug: Clazakizumab
    2. Drug: Placebo
    MeSH:Respiratory Insufficiency

    Primary Outcomes

    Description: Total number of adverse events associated with clazakizumab or placebo

    Measure: Adverse Events

    Time: 60 days
    446 A Single-Blind Dose-Ranging Pharmacodynamic Study of Auxora for the Treatment of Patients With Critical COVID-19 Pneumonia

    This is a single-blind study consisting of up to 3 cohorts Patients will be randomized 3:1 to Auxora or Placebo. The first 4 patients will be enrolled in Cohort 1. If dose escalation occurs, the next 8 patients will be enrolled in Cohort 2 If dose escalation occurs, the next 8 patients will be enrolled in Cohort 3. The decision to escalate dosing will be made by CalciMedica in consultation with the PI and after the review of safety events in Cohorts 1 and 2.

    NCT04661540
    Conditions
    1. Pneumonia
    Interventions
    1. Drug: CM4620-IE (Injectable Emulsion)
    2. Drug: Placebo
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Measure: Decrease in interferon-gamma producing T-cells in Broncoalveolar lavage (BAL) fluid

    Time: Baseline Assessment up to 120 hours

    Secondary Outcomes

    Measure: Number of Days in the Hospital after randomization

    Time: From randomization until discharge from the hospital assessed up to 30 days

    Measure: Number of Days in the Intensive Care Unit (ICU) after randomization

    Time: From randomization until discharge from ICU assessed up to 30 days

    Measure: Incidence of Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

    Time: From randomization up to 30 days

    Measure: Intensity and relationship of TEAEs and SAEs

    Time: From randomization up to 30 days

    Description: Changes in cardiac conduction are defined as: QTcF interval of ≥ 500 msec; QTcF prolongation of ≥ 60 msec as compared to baseline; Mobitz Type II second degree atrioventricular (AV) block; Third degree or high grade AV block; or Polymorphic Ventricular Tachycardia

    Measure: Pre-defined changes in cardiac conduction assessed by ECG

    Time: From screening up to 144 hours

    Measure: Mortality

    Time: Randomization up to 30 days

    Description: Concentration of Auxora from blood samples and fluid collected from BAL

    Measure: Plasma Levels of CM4620

    Time: From end of first infusion of study drug up to 144 hours
    447 Controlled Trial of Fenofibrate for Patients With COVID-19 Requiring Hospitalization

    This is an open-label run-in followed by a randomized, double-blind drug treatment study of COVID-19 infected patients requiring inpatient hospital admission.

    NCT04661930
    Conditions
    1. Corona Virus Disease (COVID-19)
    2. Respiratory Distress Syndrome
    3. SARS-CoV-2 Infection
    Interventions
    1. Drug: TriCor® 145mg tablets
    2. Other: Usual Care
    3. Other: Placebo
    MeSH:Virus Diseases Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult

    Primary Outcomes

    Description: Blood will be collected every third day for the duration of study participation. D-dimer Neutrophils Lymphocytes Platelets (PLT) Glucose Lactate C-Reactive Protein (CRP) Cardiac Troponin (TRO) Ferritin

    Measure: Difference in Plasma markers at 14 days

    Time: 14 days

    Description: Outcome reported as the number of participants who have expired at 14 days post enrollment.

    Measure: 14-Day Mortality

    Time: 14 days

    Description: Outcome calculated from the partial pressure of oxygen or peripheral saturation of oxygen by pulse oximetry divided by the fraction of inspired oxygen (PaO2 or SaO2 : FiO2 ratio). PaO2 is preferentially used if available.

    Measure: Difference in Estimated P/F Ratio at 14 days

    Time: 14 days

    Description: Nasopharyngeal swabs will be collected every fourth day for the duration of study participation. as number of viral genetic copies per mL.

    Measure: Viral Clearance by Nasopharyngeal Swab

    Time: 14 days

    Secondary Outcomes

    Description: Outcome reported as the mean number of days participants in each arm had 2 or more abnormal plasma levels of: D-dimer Neutrophils Lymphocytes Platelets (PLT) Glucose Lactate C-Reactive Protein (CRP) Cardiac Troponin (TRO) Ferritin

    Measure: Number of Abnormal Biomarker Days

    Time: 14 days

    Description: Outcome calculated from the partial pressure of oxygen or peripheral saturation of oxygen by pulse oximetry divided by the fraction of inspired oxygen (PaO2 or SaO2 : FiO2 ratio) and Expiratory Pressure.

    Measure: Difference in Estimated PEEP adjusted P/F Ratio at 14 days

    Time: 14 days

    Description: PaO2 or SaO2 and FiO2. Partial pressure of oxygen or peripheral saturation of oxygen by pulse oximetry. FiO₂ is estimated from oxygen flow/delivery rates

    Measure: Difference in Oxygenation at 14 days

    Time: 14 days

    Description: Outcome reported as the mean number of daily hypotensive episodes (MAP < 65 mmHg) prompting intervention (indicated by a fluid bolus >=500 mL, new treatment with pressures, increase in 50% pressure or fluid rate) per participant in each arm.

    Measure: Daily Hypotensive Episodes

    Time: 14 days

    Description: Outcome reported as the number of participants in each arm requiring the use of vasopressors for hypotension.

    Measure: Hypotension Requiring Vasopressors

    Time: 14 days

    Description: Outcome reported as the number of participants in each arm who experience acute kidney injury as defined by the Kidney Disease Improving Global Outcomes (KDIGO) guidelines: Increase in serum creatinine by 0.3mg/dL or more within 48 hours OR Increase in serum creatinine to 1.5 times baseline or more within the last 7 days OR Urine output less than 0.5 mL/kg/h for 6 hours.

    Measure: Acute Kidney Injury

    Time: 14 days

    Description: The SOFA assessment is used to track a person's risk status during stay in the Intensive Care Unit (ICU). The score is based on six different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal, and neurological systems. Each organ system is assigned a point value from 0 (normal) to 4 (high degree of dysfunction/failure). Total score is calculated by entering patient data into a SOFA calculator, a widely available software. Total scores range from 0-24, with higher scores indicating greater risk of mortality.

    Measure: Sequential Organ Failure Assessment (SOFA) Total Score

    Time: 14 days

    Description: Oxygen saturation (percent) is measured by pulse oximeter. Fraction of inspired oxygen (FiO2) (unitless) is the volumetric fraction of oxygen to other gases in respiratory support. The F/S ratio is unitless.

    Measure: Oxygen Saturation / Fractional Inhaled Oxygen (F/S)

    Time: 14 days

    Description: Outcome reported as the number of participants who have expired at 28 days post enrollment.

    Measure: 28-Day Mortality

    Time: 28 days

    Description: Outcome reported as the number of participants who have expired at 90 days post enrollment.

    Measure: 90-Day Mortality

    Time: 90 days

    Description: Outcome reported as the number of participants in each arm who require admission to the Intensive Care Unit (ICU).

    Measure: ICU Admission

    Time: 14 days

    Description: Outcome reported as the mean number of days participants in each arm did not require mechanical ventilation during an in-patient hospital admission.

    Measure: Number of Ventilator-Free Days

    Time: 14 days

    Description: Outcome reported as the mean number of days participants in each arm did not require therapeutic oxygen usage during an in-patient hospital admission.

    Measure: Number of Therapeutic Oxygen-Free Days

    Time: 14 days

    Description: Outcome reported as the mean number of days participants in each arm did not require vasopressor usage during an in-patient hospital admission.

    Measure: Number of Vasopressor-Free Days

    Time: 14 days

    Description: Outcome reported as the mean length of stay (in days) in the Intensive Care Unit (ICU) for participants in each arm.

    Measure: Length of ICU Stay

    Time: 14 days

    Description: Outcome reported as the mean length of in-patient hospital stay (in days) for participants in each arm.

    Measure: Length of Hospital Stay

    Time: 14 days

    Description: Outcome reported as the number of participants requiring BiPAP OR high flow nasal cannula OR mechanical ventilation OR extracorporeal membranous oxygenation (ECMO) utilization during in-patient hospital care in each arm.

    Measure: Incidence of Respiratory Failure

    Time: 14 days

    Description: The PROMIS Dyspnea (shortness of breath) item banks and pools assess self-reported Functional Limitations, Severity, Activity Motivation, Activity Requirements, Airborne Exposure, Assistant Devices Resources, Characteristics, Emotional Response, Task Avoidance and Time Extension as they related to dyspnea. In the 33-item Functional Limitations bank, 33 daily activities are rated in terms of degree of difficulty while engaging in the activity over the past 7 days (0 = no difficulty, 1 = a little difficulty, 2 = some difficulty, 3 = much difficulty). Total scores range from 0 to 99, with higher scores reflecting greater functional limitations.

    Measure: Change in PROMIS Dyspnea Functional Limitations

    Time: 14 days

    Description: The PROMIS Dyspnea (shortness of breath) item banks and pools assess self-reported Functional Limitations, Severity, Activity Motivation, Activity Requirements, Airborne Exposure, Assistant Devices Resources, Characteristics, Emotional Response, Task Avoidance and Time Extension as they related to dyspnea. The 33-item Severity bank assesses the severity of difficulty breathing during various specific activities (the same 33 activities assessed in Dyspnea Functional Limitations). Each activity is rated in terms of degree of dyspnea (0 = no shortness of breath, 1 = mildly short of breath, 2 = moderately short of breath, 3 = severely short of breath) while engaging in the activity over the past 7 days. Total scores range from 0 to 99 with higher scores reflecting greater levels of dyspnea during daily activity.

    Measure: Change in PROMIS Dyspnea Severity

    Time: 14 days

    Description: Outcome reported as the number of participants in each arm who fall into each of 7 categories. Lower scores indicate greater condition severity. The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen; 6) Not hospitalized, limitation on activities; 7) Not hospitalized, no limitations on activities.

    Measure: Disease Severity Rating

    Time: 14 days

    Description: Nasopharyngeal swabs will be collected every fourth day for the duration of study participation. Viral load is measured as number of viral genetic copies per mL.

    Measure: Viral Load by Nasopharyngeal Swab

    Time: 14 days

    Description: Blood will be collected every third day for viral load assessment for the duration of study participation. Viral load is measured as number of viral genetic copies per mL.

    Measure: Viral Load by Blood

    Time: 14 days

    Description: Blood will be collected every third day for viral load assessment for the duration of study participation. clearance is measured as fold change in viral genetic copies per mL.

    Measure: Viral Clearance by Blood

    Time: 14 days
    448 COVID-19 Outpatient Pragmatic Platform Study (COPPS): A Pragmatic Multi-arm, Adaptive, Phase 2, Blinded, Randomized Placebo-controlled Platform Trial to Assess the Efficacy of Different Investigational Therapeutics in Reducing Time to Disease Resolution or Viral Load Cessation, as Compared to Standard Supportive Care in Outpatients With COVID-19

    The overall objective of this study is to efficiently evaluate the clinical efficacy and safety of different investigational therapeutics among adults who have COVID-19 but are not yet sick enough to require hospitalization. The overall hypothesis is that through an adaptive trial design, potential effective therapies (single and combination) may be identified for this group of patients. COVID-19 Outpatient Pragmatic Platform Study (COPPS) is a pragmatic platform protocol designed to evaluate COVID-19 treatments by assessing their ability to reduce viral shedding (Viral Domain) or improve clinical outcomes (Clinical Domain). To be included into the platform, every investigational product will collect data for both Domain primary endpoints. Individual treatments to be evaluated in the platform will be described in separate sub-protocols.

    NCT04662060
    Conditions
    1. Covid19
    Interventions
    1. Drug: Acebilustat
    2. Drug: Placebo

    Primary Outcomes

    Description: Defined as the time in days from randomization to the first of two consecutive negative RT-PCR results of self-collected nasal swabs

    Measure: For Viral Domain:Time until cessation of shedding of SARS-CoV-2 virus

    Time: 28 days

    Description: Resolution is defined as the first study day where no symptoms are self-reported for 48 hours, not including sense of taste or smell, and defining recovery for fatigue and cough as mild or none. Participants who never experienced resolution will be censored at their last survey completion day.

    Measure: For Clinical Domain: Time from randomization to sustained symptom resolution assessed over a 28-day period

    Time: 28 days

    Secondary Outcomes

    Description: Defined as the first study day where no symptoms are self-reported, not including sense of taste or smell, and defining recovery for fatigue and cough as mild or none.

    Measure: Time to first resolution

    Time: 28 days

    Measure: Indicator of SARS-CoV-2 related hospitalizations, ED visits, or death in outpatients with COVID-19 disease.

    Time: 28 days

    Measure: Indicator participant has developed antibodies to SARS-CoV-2

    Time: 28 days

    Measure: Time to event from randomization to worsening of symptoms or disease progression

    Time: 28 days
    449 COVID-19 Outpatient Pragmatic Platform Study (COPPS): A Pragmatic Multi-arm, Adaptive, Phase 2, Blinded, Randomized Placebo-controlled Platform Trial to Assess the Efficacy of Different Investigational Therapeutics in Reducing Time to Disease Resolution or Viral Load Cessation, as Compared to Standard Supportive Care in Outpatients With COVID-19

    The overall objective of this study is to efficiently evaluate the clinical efficacy and safety of different investigational therapeutics among adults who have COVID-19 but are not yet sick enough to require hospitalization. The overall hypothesis is that through an adaptive trial design, potential effective therapies (single and combination) may be identified for this group of patients. COVID-19 Outpatient Pragmatic Platform Study (COPPS) is a pragmatic platform protocol designed to evaluate COVID-19 treatments by assessing their ability to reduce viral shedding (Viral Domain) or improve clinical outcomes (Clinical Domain). To be included into the platform, every investigational product will collect data for both Domain primary endpoints. Individual treatments to be evaluated in the platform will be described in separate sub-protocols.

    NCT04662073
    Conditions
    1. Covid19
    Interventions
    1. Drug: Camostat
    2. Drug: Placebo

    Primary Outcomes

    Description: Defined as the time in days from randomization to the first of two consecutive negative RT-PCR results of self-collected nasal swabs

    Measure: For Viral Domain:Time until cessation of shedding of SARS-CoV-2 virus

    Time: 28 days

    Description: Resolution is defined as the first study day where no symptoms are self-reported for 48 hours, not including sense of taste or smell, and defining recovery for fatigue and cough as mild or none. Participants who never experienced resolution will be censored at their last survey completion day.

    Measure: For Clinical Domain: Time from randomization to sustained symptom resolution assessed over a 28-day period

    Time: 28 days

    Secondary Outcomes

    Description: Defined as the first study day where no symptoms are self-reported, not including sense of taste or smell, and defining recovery for fatigue and cough as mild or none.

    Measure: Time to first resolution

    Time: 28 days

    Measure: Indicator of SARS-CoV-2 related hospitalizations, ED visits, or death in outpatients with COVID-19 disease.

    Time: 28 days

    Measure: Indicator participant has developed antibodies to SARS-CoV-2

    Time: 28 days

    Measure: Time to event from randomization to worsening of symptoms or disease progression

    Time: 28 days
    450 A Phase 2 Study to Assess the Virologic Efficacy of REGN10933+REGN10987 Across Different Dose Regimens in Outpatients With SARS-CoV-2 Infection

    The primary objective of the study is to assess the virologic efficacy of REGN10933+REGN10987 across different intravenous and subcutaneous doses compared to placebo. The secondary objectives of the study are: - To evaluate additional indicators of virologic efficacy of REGN10933+REGN10987 compared to placebo - To evaluate the safety and tolerability of REGN10933+REGN10987 compared to placebo - To assess the concentrations of REGN10933 and REGN10987 in serum over time

    NCT04666441
    Conditions
    1. COVID-19
    Interventions
    1. Drug: REGN10933+REGN10987 combination therapy
    2. Drug: Placebo
    MeSH:Infection

    Primary Outcomes

    Description: Measured in patients who have a central-lab determined RT-qPCR positive test and are seronegative at baseline

    Measure: Time-weighted average daily change from baseline in viral load (log10 copies/mL), as measured by reverse transcription quantitative polymerase chain reaction (RT-qPCR) in nasopharyngeal (NP) swab samples

    Time: Baseline to day 7

    Secondary Outcomes

    Measure: Time-weighted average daily change from baseline in viral load (log10 copies/mL)

    Time: Baseline to day 5

    Measure: Time-weighted average daily change from baseline in viral load (log10 copies/mL) in patients with high viral load

    Time: Baseline to day 7

    Measure: Time-weighted average daily change from baseline in viral load (log10 copies/mL) in patients with high viral load

    Time: Baseline to day 5

    Measure: Proportion of patients with high viral load

    Time: At each visit, through day 22

    Measure: Proportion of patients with viral loads below the limit of detection

    Time: At each visit, through day 22

    Measure: Proportion of patients with viral loads below the lower limit of quantitation

    Time: At each visit, through day 22

    Measure: Time-weighted average daily change from baseline in cycle threshold (Ct) as measured by RT-qPCR in NP samples

    Time: Baseline to day 7

    Measure: Time-weighted average daily change from baseline in Ct from day 1 to day 5, as measured by RT-qPCR in NP samples

    Time: Baseline to day 5

    Measure: Change from baseline in Ct as measured by RT-qPCR in NP samples

    Time: At each visit, Baseline through day 22

    Measure: Change from baseline in viral load as measured by RT-qPCR in NP samples

    Time: At each visit, Baseline through day 22

    Measure: Proportion of patients with treatment-emergent serious adverse events (SAEs)

    Time: Through day 29

    Measure: Proportion of patients with infusion-related reactions (grade ≥2)

    Time: Through day 4

    Measure: Proportion of patients with injection-site reactions (grade ≥2)

    Time: Through day 4

    Measure: Proportion of patients with hypersensitivity reactions (grade ≥2)

    Time: Through day 29

    Measure: Concentrations of REGN10933 in serum

    Time: Through day 22

    Measure: Concentrations of REGN10987 in serum

    Time: Through day 22
    451 Fluvoxamine for Early Treatment of Covid-19: a Fully-remote, Randomized Placebo Controlled Trial

    The purpose of this research study is to determine if a drug called fluvoxamine can be used early in the course of the COVID-19 infection to prevent more serious complications like shortness of breath. Fluvoxamine is an anti-depressant drug approved by the FDA for the treatment of obsessive-compulsive disorder. The use of fluvoxamine for the treatment of COVID-19 is considered investigational, which means the US Food and Drug Administration has not approved it for this use. This study is fully-remote, which means that there is no face-to-face contact; study materials including study drug will be shipped to participants' houses. People around the United States and Canada can participate.

    NCT04668950
    Conditions
    1. Covid19
    2. Coronavirus
    Interventions
    1. Drug: Fluvoxamine
    2. Drug: Placebo
    MeSH:Coronavirus Infections

    Primary Outcomes

    Description: Defined as both of the following: 1)Presence of dyspnea and/or hospitalization for shortness of breath or pneumonia, 2)) decrease in O2 saturation (<92% on room air) and/or supplemental oxygen requirement to keep O2 saturation ≥92%).

    Measure: Clinical deterioration

    Time: RCT-approximately 15 days

    Secondary Outcomes

    Description: Self report post Covid Functioning using the PROMIS Global Health Scale. It is a 10-item patient-reported questionnaire in which the response options are presented as 5-point, and one 11-point, rating scales. Higher scores indicate better health.

    Measure: Post Covid Functioning

    Time: Day 15 and Day 90
    452 NOVATION-1: A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Aerosolized Novaferon + SOC vs. Placebo + SOC in Hospitalized Adult Patients With Moderate to Severe COVID-19

    This study is a randomized, double-blind, multicenter, placebo-controlled trial to evaluate the safety and efficacy of a novel therapeutic agent, Novaferon, in hospitalized adult patients diagnosed with COVID-19. The study is comprised of two cohorts: - Cohort A: This is a blinded safety lead-in comprising two arms. 40 patients will be randomized on a 1:1 basis to receive either Novaferon or matched placebo via a commercial nebulizer, plus Standard of Care (SOC) - Cohort B: This is the main portion of the study, which comprises two arms. Up to 874 patients will be randomized on a 1:1 basis to receive either Novaferon or matched placebo via a commercial nebulizer, plus SOC

    NCT04669015
    Conditions
    1. Covid19
    Interventions
    1. Biological: Novaferon
    2. Biological: Placebo

    Primary Outcomes

    Description: Proportion of patients requiring mechanical ventilation or that die (defined as WHO categories 6, 7, or 8)

    Measure: Rate of clinical deterioration

    Time: From enrollment to Day 28

    Secondary Outcomes

    Description: Proportion of patients demonstrating clinical improvement (defined as WHO categories 0, 1, 2, or 3)

    Measure: Rate of recovery

    Time: From enrollment to Day 28

    Description: Rate of non-hospitalized alive patients

    Measure: Hospital discharge rate

    Time: At Day 28

    Description: Mortality rate

    Measure: Mortality rate

    Time: At Day 28

    Description: Number of days hospitalized

    Measure: Duration of hospitalization

    Time: Up to Day 28

    Description: Adverse event incidence, type and severity

    Measure: Adverse events

    Time: From first dose to Day 56
    453 A Phase 3, Randomized, Multicenter, Placebo-controlled, Double-blind Clinical Study of the Safety and Efficacy of Carrimycin for Treatment of Severe COVID-19 in Hospitalized Patients

    This is a randomized, multicenter, placebo-controlled, double-blind clinical study in patients hospitalized due to severe Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection.

    NCT04672564
    Conditions
    1. Coronavirus Disease 2019
    Interventions
    1. Drug: Carrimycin
    2. Drug: Placebo
    MeSH:Coronavirus Infections

    Primary Outcomes

    Description: To evaluate the efficacy and safety of carrimycin compared to SOC in patients hospitalized with severe SARS-CoV-2 pneumonia.

    Measure: Percentage of patients alive without need for supplemental oxygen and ongoing in patient-medical care (SOC treatment for COVID-19) at Day 28

    Time: At Day 28

    Secondary Outcomes

    Description: To evaluate efficacy of carrimycin administered for treatment of severe COVID-19 in hospitalized patients between patients receiving carrimycin vs placebo. Time to recovery is defined as time point when a patient reaches level 3 or lower on the 8-Category ordinal scale and does not return to a level > 3 during the 28-day period. The 8-Category ordinal scale score ranges from 1 to 8. Score 1: Not hospitalized, no limitations on activities; 2: Not hospitalized, limitation on activities, home oxygen requirement or both; 3: Hospitalized, not requiring supplemental oxygen and no longer requiring ongoing medical care; 4: Hospitalized, not requiring supplemental oxygen but requiring ongoing medical care; 5: Hospitalized, requiring supplemental oxygen; 6: Hospitalized, requiring noninvasive ventilation or high flow oxygen devices; 7: Hospitalized, receiving invasive mechanical ventilation or extracorporeal membrane oxygenation and score 8: Death. Higher scores indicate worse outcome.

    Measure: Time to recovery

    Time: From screening Day (Day -2 to Day -1) until Day 28

    Description: To evaluate the efficacy of carrimycin administered for the treatment of severe COVID-19 in hospitalized patients between patients receiving carrimycin vs placebo. The 8-Category ordinal scale score ranges from 1 to 8. Score 1 indicates: Not hospitalized, no limitations on activities; 2: Not hospitalized, limitation on activities, home oxygen requirement or both; 3: Hospitalized, not requiring supplemental oxygen and no longer requiring ongoing medical care; 4: Hospitalized, not requiring supplemental oxygen but requiring ongoing medical care; 5: Hospitalized, requiring supplemental oxygen; 6: Hospitalized, requiring noninvasive ventilation or high flow oxygen devices; 7: Hospitalized, receiving invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) and score 8 indicates: Death. Higher scores indicate worse outcome

    Measure: Mean difference from baseline (Days -2 to -1) to Day 28 as per the 8 category ordinal scale

    Time: Screening Day (Day -2 to Day -1) until Day 28

    Description: To evaluate the efficacy of carrimycin administered for the treatment of severe COVID-19 in hospitalized patients between patients receiving carrimycin vs placebo. Radiological imaging (lung computed tomography scan and chest X-ray) will be used to determine change in lung imaging.

    Measure: Change in lung imaging

    Time: Days 7, 14 and 28

    Description: To evaluate the efficacy of carrimycin administered for the treatment of severe COVID-19 in hospitalized patients between patients receiving carrimycin vs placebo. To evaluate the change in viral load between treatment arms and to evaluate the relationship between change in viral load over time with time to clinical recovery.

    Measure: Negative conversion ratio of SARS-CoV-2 RNA in nasopharyngeal samples after treatment.

    Time: Days 3, 7 and 14

    Description: To evaluate the efficacy of carrimycin administered for the treatment of severe COVID-19 in hospitalized patients between patients receiving carrimycin vs placebo. The SOFA score ranges from 0 to 4. Lower score predicts better organ functioning and higher score represents severe organ failure.

    Measure: Improvement in sequential organ failure assessment (SOFA) score

    Time: Days 3, 7, 10, 14 and 28 after treatment

    Description: To evaluate length of hospital stay and to evaluate time to successful discharge between patients receiving carrimycin vs placebo.

    Measure: Length of hospital stay (in days)

    Time: From Screening Day (Day -2 to Day -1) until Day 60 or Early Withdrawal

    Description: To evaluate mortality rates between patients receiving carrimycin vs placebo.

    Measure: Number of patients with all cause mortality at Days 14 and 28

    Time: From Screening Day (Day -2 to Day -1) until Day 60 or Early Withdrawal

    Description: To evaluate the safety and tolerability of the carrimycin and to describe the safety profile of treatments as reflected by AEs and SAEs.

    Measure: Number of patients with adverse event (AEs) and Serious adverse events (SAEs)

    Time: Day 28 and Day 60

    Description: To evaluate the safety and tolerability of the carrimycin and to describe the safety profile of treatments. The routine ECG will include heart rate, QTc interval, ST segment and T wave changes

    Measure: Number of patients with changes in routine electrocardiogram (ECG) from Day 1 up to Day 14

    Time: Day 1 until Day 14
    454 Multicenter, Randomized, Combined Phase I Dose-escalation and Phase IIa Double-blind, Placebo-controlled Study of the Safety, Tolerability, and Immunogenicity of GLS-5310 DNA Vaccine, Administered Intradermally Against SARS-CoV-2 in Healthy Adults

    This clinical trial will evaluate the safety, tolerability and immunogenicity of GLS-5310 DNA vaccine against SARS-CoV-2(COVID-19) in healthy volunteers.

    NCT04673149
    Conditions
    1. SARS-CoV-2
    Interventions
    1. Biological: GLS-5310
    2. Biological: Placebo

    Primary Outcomes

    Description: solicited/unsolicited local and systemic AEs after vaccination

    Measure: Incidence of adverse events

    Time: Through 48 weeks post vaccination

    Description: Endpoint titer of binding antibody in serum

    Measure: Geometric mean titer (GMT) of antigen-specific binding antibody titers

    Time: Through 48 weeks post vaccination

    Secondary Outcomes

    Description: T-cell response of antigen-specific interferon - gamma (IFN-γ) secretion in PBMC at each timepoint

    Measure: Evaluation of positive response rate of T cell responses induced by GLS-5310 DNA vaccine

    Time: Through 48 weeks post vaccination

    Description: Plaque-reduction neutralizing titer(PRNT) in serum at each timepoint

    Measure: Geometric mean titer (GMT) of neutralizing antibody titers

    Time: Through 48 weeks post vaccination

    Other Outcomes

    Description: Endpoint titer of binding antibody in serum at each timepoint

    Measure: Determine IgG antibody responses after a single dose of vaccine related to treatment arm

    Time: Through 1 year post vaccination

    Description: Survival rate

    Measure: Measure survival rate of animals administered immune serum from vaccinated individuals and later challenged with SARS-CoV-2.

    Time: Through 1 year post vaccination

    Description: Endpoint titer of binding antibody in serum at each timepoint Plaque-reduction neutralizing titer in serum at each timepoint T-cell response of antigen-specific interferon - gamma (IFN-γ) secretion in PBMC at each timepoint

    Measure: Persistence of immune responses following vaccination with GLS-5310

    Time: Through 1 year post vaccination

    Description: Change from baseline in binding antibody titers Change from baseline in T-cell response of antigen-specific interferon - gamma (IFN-γ) Change from baseline in plaque-reduction neutralizing titer(PRNT) in serum

    Measure: Determine the extent of immune boosting for participants who are seropositive at baseline following vaccination with GLS-5310

    Time: Through 1 year post vaccination

    Description: viral load measurement of blood and major organs

    Measure: Measure viral load in organs, including blood, of animals administered immune serum from vaccinated individuals and later challenged with SARS-CoV-2.

    Time: Through 1 year post vaccination

    Description: pathological examination of organs

    Measure: Perform histologic examination of organs of animals administered immune serum from vaccinated individuals and later challenged with SARS-CoV-2.

    Time: Through 1 year post vaccination
    455 A Phase 3, Randomized, Observer-Blinded, Placebo-Controlled Clinical Study Evaluating the Safety and Immunogenicity of Investigational SARS-CoV-2 mRNA Vaccine CVnCoV in Adult Health Care Workers in Mainz (Germany)

    This study aims to evaluate the safety (in all participants) and reactogenicity (in a subset of participants) of CVnCoV administered as a 2-dose schedule to adult participants 18 years of age or older. The study also aims to assess antibody responses to the receptor-binding domain (RBD) of spike (S) protein of SARS-CoV-2 after 1 and 2 doses of CVnCoV in adults 18 years of age or older included in a subset of participants.

    NCT04674189
    Conditions
    1. Coronavirus
    2. Covid19
    3. SARS-CoV-2
    4. Severe Acute Respiratory Syndrome
    Interventions
    1. Biological: CVnCoV Vaccine
    2. Drug: Placebo
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome

    Primary Outcomes

    Measure: Number of Participants with Medically-attended Adverse Events

    Time: Day 29 to Day 211

    Measure: Intensity of Medically-attended Adverse Events per Investigator's Assessment

    Time: Day 29 to Day 211

    Measure: Number of Participants with Medically-attended Adverse Events Considered Related to Trial Vaccine

    Time: Day 29 to Day 211

    Measure: Number of Participants with One or More Serious Adverse Events (SAEs)

    Time: Day 29 to Day 393

    Measure: Intensity of Serious Adverse Events (SAEs) per Investigator's Assessment

    Time: Day 29 to Day 393

    Measure: Number of Participants with One or More Serious Adverse Events (SAEs) Considered Related to Trial Vaccine

    Time: Day 29 to Day 393

    Measure: Number of Participants with One or More Adverse Events of Special Interest (AESIs)

    Time: Day 29 to Day 393

    Measure: Intensity of Adverse Events of Special Interest (AESIs) per Investigator's Assessment

    Time: Day 29 to Day 393

    Measure: Number of Participants with One or More Serious Adverse Events of Special Interest (AESIs) Considered Related to Trial Vaccine

    Time: Day 29 to Day 393

    Measure: Number of Participants with Death due to a Serious Adverse Event (SAE)

    Time: Day 29 to Day 393

    Measure: Number of Participants with Adverse Events (AEs) Leading to Vaccine Withdrawal or Study Disctontinuation

    Time: Day 29 to Day 393

    Measure: Number of Participants with Solicited Local Adverse Events

    Time: 7 days after vaccination

    Measure: Intensity of Solicited Local Adverse Events per the FDA Toxicity Grading Scale

    Time: 7 days after vaccination

    Measure: Duration of Solicited Local Adverse Events

    Time: 7 days after vaccination

    Measure: Number of Participants with Solicited Systemic Adverse Events

    Time: 7 days after vaccination

    Measure: Intensity of Solicited Systemic Adverse Events per the FDA Toxicity Grading Scale

    Time: 7 days after vaccination

    Measure: Duration of Solicited Systemic Adverse Events

    Time: 7 days after vaccination

    Measure: Number of Participants with Unsolicited Adverse Events

    Time: 28 days after vaccination

    Measure: Intensity of Unsolicited Adverse Events per the Investigator's Assessment

    Time: 28 days after vaccination

    Measure: Number of Participants with Unsolicited Adverse Events Considered Related to Trial Vaccine

    Time: 28 days after vaccination

    Description: Measured using Enzyme-Linked Immunosorbent Assay (ELISA).

    Measure: Individual SARS-CoV-2 Spike (S) Protein-Specific Antibody Levels in Serum

    Time: Days 1, 29, 43, 57, 120, 211 and 393

    Description: Measured using Enzyme-Linked Immunosorbent Assay (ELISA). Seroconversion is defined as detectable SARS-CoV-2 RBD of S protein antibodies in the serum of participants who tested seronegative on prior to vaccination on Day 1.

    Measure: Number of Participants Seroconverting for SARS-CoV-2 Spike (S) Protein Antibodies

    Time: Days 1, 29, 43, 57, 120, 211 and 393

    Secondary Outcomes

    Measure: Number of Participants that Contract COVID-19 of Any Severity

    Time: Day 1 to Day 393

    Measure: Number of Participants that Contract Mild, Moderate, Severe and Moderate to Severe COVID-19

    Time: Day 1 to Day 393

    Description: Seroconversion is defined as detectable SARS-CoV-2 N protein antibodies in the serum of subjects on Day 211 and/or Day 393 of the trial, who tested seronegative at prior to vaccination on Day 1 and Day 43.

    Measure: Number of Participants Seroconverting to the Nucleocapsid (N) Protein of SARS-SoV-2

    Time: Day 1, 43, 211 and 393

    Measure: Burden of Disease (BoD) Score Based on First Episodes of Virologically-confirmed Cases of COVID-19

    Time: Day 1 to Day 393

    Description: Measured by a virus neutralizing assay in a subset of participants.

    Measure: Individual SARS-CoV-2 Neutralizing Antibody Levels in Serum

    Time: Days 1, 29, 43, 57, 120, 211 and 393

    Description: Measured by a virus neutralizing assay in a subset of participants.

    Measure: Number of Participants Seroconverting to SARS-CoV-2

    Time: Days 1, 29, 43, 57, 120, 211 and 393

    Description: Measured by a virus neutralizing assay in a subset of participants.

    Measure: Individual Serum Antibodies to Spike (S) Protein of SARS-CoV-2

    Time: Days 43, 57, 120, 211 and 393
    456 Randomized, Double-blind, Placebo Controlled, Parallel Group, Multi-centre, First-in-human, Phase Ib/II Study to Assess Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, Immunogenicity, and Efficacy of COR-101 in Hospitalized Patients

    Primary objectives Part 1: - To evaluate the safety and tolerability of COR-101 compared to placebo Secondary objectives Part 1: - To evaluate the preliminary efficacy of COR-101 compared to placebo in hospitalized patients with moderate to severe COVID-19 - To assess the pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of COR-101

    NCT04674566
    Conditions
    1. Covid19
    Interventions
    1. Drug: COR-101
    2. Drug: Placebo

    Primary Outcomes

    Measure: Proportion of patients with Treatment-Emergent Adverse Events (TEAEs)

    Time: through Day 28

    Measure: Proportion of patients with Serious Adverse Events (SAEs)

    Time: through Day 28

    Measure: Proportion of patients with Adverse Events of Special Interest (AESI)

    Time: through Day 28

    Secondary Outcomes

    Description: Proportion of patients who are not alive or have respiratory failure

    Measure: Secondary efficacy endpoint: Proportion of patients with disease progression

    Time: through Day 28

    Measure: Secondary efficacy endpoint: Time to negative RT-PCR for SARS-CoV-2

    Time: through Day 28

    Measure: Assessment of pharmacokinetic (PK) parameter: maximum serum concentration observed (Cmax) of COR-101

    Time: through Day 60

    Measure: Assessment of PK parameter: Time to Cmax (tmax) for COR-101

    Time: through Day 60

    Measure: Assessment of PK parameter: AUC from time zero extrapolated to infinity (AUCinf) for COR-101

    Time: through Day 60

    Measure: Assessment of PK parameter: Clearance (CL) for COR-101

    Time: through Day 60

    Measure: Assessment of PK parameter: Mean residence time (MRT) of COR-101

    Time: through Day 60

    Measure: Secondary PD endpoint: Change of the viral load of SARS-CoV-2 from baseline, as measured from nasopharyngeal swab samples by qRT-PCR

    Time: through Day 21

    Measure: Secondary immunogenicity endpoint: Percentage of patients with detectable neutralizing antibodies to COR-101

    Time: through Day 60
    457 A Double-blind, Placebo-controlled, Phase 2a Proof-of-concept Trial of Dalcetrapib in Patients With Confirmed Mild to Moderate COVID-19

    This study is a placebo-controlled, Phase 2a proof-of-concept clinical study which will evaluate efficacy and safety of dalcetrapib in outpatients patients with mild to moderate, symptomatic, confirmed COVID 19.

    NCT04676867
    Conditions
    1. Covid19
    Interventions
    1. Drug: Dalcetrapib
    2. Other: Placebo

    Primary Outcomes

    Description: Sustained clinical resolution is defined as occurring when no key COVID-19 related symptom has a score higher than 1 over a 72-hour period (as documented using an electronic patient-reported outcome [ePRO] instrument), except for sense of smell and taste where the score should be 0 over a 72-hour period. The time to resolution will be taken as the time from randomization until the first day of the last 72 hour period where the patient meets the definition of resolution within 28 days. Patients who do not meet the definition of resolution 28 days after randomization will be considered not resolved.

    Measure: To evaluate the time to sustained clinical resolution of symptoms of COVID-19

    Time: 28 Days
    458 A Phase 1/2, Randomized, Observer-Blind, Placebo-Controlled Trial to Evaluate the Safety and Immunogenicity of TAK-919 by Intramuscular Injection in Healthy Japanese Male and Female Adults Aged 20 Years and Older (COVID-19)

    The purpose of this study is to evaluate the safety and immunogenicity of 2 doses of TAK-919 by intramuscular (IM) injection in healthy Japanese male and female adults.

    NCT04677660
    Conditions
    1. Prevention of Infectious Disease Caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2)
    Interventions
    1. Biological: TAK-919
    2. Biological: Placebo
    MeSH:Communicable Diseases Infection Coronavirus Infections Severe Acute Respiratory Syndrome

    Primary Outcomes

    Description: An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation subject administered an investigational medicinal product (IMP); it does not necessarily have to have a causal relationship with IMP administration. Reported solicited local AEs are defined as injection site pain, erythema/redness, swelling, induration, and axillary (underarm) swelling or tenderness ipsilateral to the side of injection.

    Measure: Percentage of Participants with Reported Solicited Local Adverse Events (AEs) for 7 Days Following Each Vaccination

    Time: Up to Day 7 after each vaccination

    Description: Solicited systemic AEs are defined as headache, fatigue, myalgia, arthralgia, nausea/vomiting, chills, and fever.

    Measure: Percentage of Participants with Solicited Systemic AEs for 7 Days Following Each Vaccination

    Time: Up to Day 7 after each vaccination

    Description: Unsolicited AEs defines as other AEs than solicited local AEs and solicited systemic AEs.

    Measure: Percentage of Participants with Unsolicited AEs for 28 Days After Each Vaccination

    Time: Up to Day 28 after each vaccination

    Description: An SAE is defined as any untoward medical occurrence that: Results in death, Is life-threatening, Requires inpatient hospitalization or prolongation of existing hospitalization, Results in persistent or significant disability/incapacity, Leads to a congenital anomaly/birth defect in the offspring of a participant, or Is an important medical event.

    Measure: Percentage of Participants with Serious AE (SAE) until Day 57

    Time: Up to Day 57

    Measure: Percentage of Participants with Medically-Attended Adverse Events (MAAEs) until Day 57

    Time: Up to Day 57

    Measure: Percentage of Participants with Any AE Leading to Discontinuation of Vaccination

    Time: Up to Day 57 (up to discontinuation of vaccination)

    Measure: Percentage of Participants with Any AE Leading to Participant's Withdrawal from the Trial until Day 57

    Time: Up to Day 57

    Measure: Percentage of Participants with SARS-CoV-2 Infection until Day 57

    Time: Up to Day 57

    Description: GMT of serum bAb against SARS-CoV-2 will be measured by ligand-binding assay specific to the SARS-CoV-2 S protein.

    Measure: Geometric Mean Titers (GMT) of Serum binding antibody (bAb) Against SARS-CoV-2 on Day 57

    Time: Day 57

    Description: GMFR of serum bAb against SARS-CoV-2 will be measured by ligand-binding assay specific to the SARS-CoV-2 S protein.

    Measure: Geometric Mean Fold Rise (GMFR) of Serum bAb Against SARS-CoV-2 on Day 57

    Time: Day 57

    Description: SCR of serum bAb against SARS-CoV-2 will be measured by ligand-binding assay specific to the SARS-CoV-2 S protein. SCR is defined at percentage of participants with a change from below the limit of detection (LOD) to equal to or above LOD, OR, >= 4-fold rises from baseline.

    Measure: Seroconversion Rate (SCR) of Serum bAb Against SARS-CoV-2 on Day 57

    Time: Day 57

    Secondary Outcomes

    Measure: Percentage of Participants with SAE throughout the Trial

    Time: Up to Day 394

    Measure: Percentage of Participants with MAAEs throughout the Trial

    Time: Up to Day 394

    Measure: Percentage of Participants with Any AE Leading to Participant's Withdrawal from the Trial from the Day of Vaccination throughout the Trial

    Time: Up to Day 394

    Measure: Percentage of Participants with SARS-CoV-2 Infection throughout the Trial

    Time: Up to Day 394

    Description: GMT of serum bAb against SARS-CoV-2 will be measured by ligand-binding assay specific to the SARS-CoV-2 S protein.

    Measure: GMT of Serum bAb Against SARS-CoV-2 on Day 29, Day 43, Day 209 and Day 394

    Time: Day 29, Day 43, Day 209 and Day 394

    Description: GMFR of serum bAb against SARS-CoV-2 will be measured by ligand-binding assay specific to the SARS-CoV-2 S protein.

    Measure: GMFR of Serum bAb Against SARS-CoV-2 on Day 29, Day 43, Day 209 and Day 394

    Time: Day 29, Day 43, Day 209 and Day 394

    Description: SCR of serum bAb against SARS-CoV-2 will be measured by ligand-binding assay specific to the SARS-CoV-2 S protein. SCR is defined at percentage of participants with a change from below the LOD to equal to or above LOD, OR, >= 4-fold rises from baseline.

    Measure: SCR of Serum bAb Against SARS-CoV-2 on Day 29, Day 43, Day 209 and Day 394

    Time: Day 29, Day 43, Day 209 and Day 394

    Description: GMT of serum nAb against SARS-CoV-2 will be measured by assay specific to wild-type virus.

    Measure: GMT of serum neutralizing antibody (nAb) against SARS-CoV-2 on Day 29, Day 43, Day 57, Day 209, and Day 394

    Time: Day 29, Day 43, Day 57, Day 209, and Day 394

    Description: GMFR of serum nAb against SARS-CoV-2 will be measured by assay specific to wild-type virus.

    Measure: GMFR of serum nAb against SARS-CoV-2 on Day 29, Day 43, Day 57, Day 209, and Day 394

    Time: Day 29, Day 43, Day 57, Day 209, and Day 394

    Description: SCR of serum nAb against SARS-CoV-2 will be measured by assay specific to wild-type virus. SCR is defined at percentage of subjects with a change from below the lower limit of quantification (LLOQ) to equal to or above LLOQ, OR, >= 4-fold rises from baseline.

    Measure: SCR of serum nAb against SARS-CoV-2 on Day 29, Day 43, Day 57, Day 209, and Day 394

    Time: Day 29, Day 43, Day 57, Day 209, and Day 394
    459 A Phase 1, Double-blind, Randomized, Placebo-controlled, First-in-Human Study of the Safety and Immunogenicity of AdCOVID Administered as One or Two Doses

    A study to evaluate the immune response and safety of AdCOVID administered as an intranasal spray in healthy adults.

    NCT04679909
    Conditions
    1. Healthy Volunteers
    Interventions
    1. Biological: AdCOVID
    2. Other: Placebo

    Primary Outcomes

    Description: Counts and percentages of subjects with local and systemic events

    Measure: Reactogenicity

    Time: For 7 days after vaccination

    Description: Counts and percentages of subjects with AEs

    Measure: Adverse Events (AEs)

    Time: Day 1 to Day 57

    Secondary Outcomes

    Measure: Anti-SARS-CoV-2 spike IgG antibody levels

    Time: Day 1 to Day 366

    Measure: Neutralizing antibody titer against live and/or pseudotyped SARS-CoV-2 virus

    Time: Day 1 to Day 366

    Other Outcomes

    Measure: Anti-SARS-CoV-2 RBD T cell responses by interferon (IFN)-gamma enzyme-linked immunosorbent spot (ELISpot)

    Time: Day 1 to Day 366

    Measure: Mucosal antibody responses in nasopharyngeal swabs (anti-SARS-CoV-2 spike IgA titers)

    Time: Day 1 to Day 366

    Related HPO nodes (Using clinical trials)


    HP:0002088: Abnormal lung morphology
    Genes 1425
    KMT2D SMARCB1 ABCA12 MAT2A TNFSF11 TRAIP MAGEL2 DNAAF1 NFE2L2 MITF NFKB2 LCK MAGEL2 SGCG ALG9 TECPR2 GTF2IRD1 CALCRL KAT6B CHAMP1 OFD1 CTRC SCNN1G CD247 MGP TGFBR2 SPINK5 CTPS1 RASA2 NHLRC2 PHGDH RTEL1 NTRK1 NGLY1 ARVCF SLC2A10 RELB ZNF341 RSPH9 FCN3 NELFA RREB1 NAA10 MALT1 HPGD CFTR GLI1 OCA2 LETM1 NPHP3 PIK3CD FSHR FMO3 USP9X TCF4 WDR35 PRSS1 HLA-DPA1 DNAH11 RIT1 ZAP70 STK11 NKX2-5 UNC119 CDC45 BUB1B SNAI2 WAS SIM1 GNPTAB DYNC2H1 FOXH1 CFAP221 TARS1 NF1 NEB LAMB2 TTC7A CCR6 RARA ACTL6B MYO5A CD81 ADNP TNFRSF13B SEC24C TBX1 MYH6 COL3A1 TSC1 CYBA HLA-DPB1 TERT GNS FOXH1 EVC2 LIPN KATNIP TPM2 RRAS2 TSC1 EPHB4 COL6A1 NIPBL SPAG1 FLNB IL17RA HSPG2 ITGA8 GAS1 SLC12A6 EFEMP2 CRLF1 SLC26A2 GMNN DGCR8 ACTA2 CTLA4 SLC35A1 ADAMTS3 TAPBP SLC25A24 PRKCD SPECC1L CCR6 CXCR4 HOXD13 BLM RNU4ATAC CFAP300 FOXP1 CDON CD79A TTC21B CBL RAG1 VPS51 DISP1 USB1 NUP107 NEPRO COL11A2 FLNA CR2 ACVRL1 LAMTOR2 NEK1 SNORD115-1 GLE1 MAP3K20 DNMT3B SLC26A2 FAS MKRN3-AS1 LYST PIK3R1 ACADVL LIFR TDGF1 TAPT1 RFX5 VPS33A MYRF MDM4 HRAS TBC1D24 NGLY1 GLI2 FGF8 ODAD4 CCDC40 MYH11 C11ORF95 MCM4 CTLA4 CRELD1 ZBTB24 TINF2 ECM1 CAV1 NAA10 LRRC6 PUF60 CFTR FLCN COL11A2 CR2 FOXE1 CCBE1 ELP1 TFRC AGA SMPD1 PWRN1 MMP21 IPW GATA6 LACC1 TCIRG1 SERPINF2 BLNK IFT80 FLI1 UBB KIF20A STAT1 DLL4 MBTPS2 PAX3 ELP1 SNRPN DISP1 RMRP TGFBR2 KRAS STAG2 IRF8 SIX3 SOX10 KIF1A RYR1 IGHM BTK NOTCH3 DICER1 CYP4F22 CXCR4 RSPH1 MEFV CCBE1 DNAH11 ZIC2 WDFY3 CCND1 CSF2RA POLR3A BCL6 LAMA2 SMAD4 SKIV2L STAT1 SNX10 TERT FGF8 BRAF SFTPC FOXJ1 ATP11A AICDA SHH RYR1 ODAD1 SCARB2 SIK1 HACD1 CHRNG CREBBP TNFRSF13B CITED2 OCA2 MYBPC3 NODAL NOTCH2 CFAP298 SELENON CEP57 CTLA4 TRIM28 ZIC2 ALMS1 DOK7 ODAD4 IDUA DLL1 ELN SBDS COG6 TBX6 RFXAP PEX13 TCTN3 PTPN22 DGCR6 SFTPC RAG1 INTU EDNRB FGF20 MAGEL2 DNASE1L3 RASGRP1 STRA6 IFT81 COG4 MARS1 EPM2A MESP2 TTC12 SOS1 TBC1D23 IL12A-AS1 ENG SCNN1B CSF2RA TGFB1 CCN2 FBXW11 MAN2B1 HLA-DRB1 PTCH1 NPM1 EPG5 UGP2 GLI2 GAS2L2 TSC2 PPP1CB RANBP2 SCN11A GPKOW CBL CTLA4 IL12A MESP2 IL21R CRELD1 IL17RC UMPS TERT SLC18A3 MYSM1 DSE TRPS1 PEX1 MKRN3 RTEL1 RPGR DYNC2H1 PRKG1 DSG1 ACP5 FLT4 JAK3 TCF20 EXOSC9 MIR140 DNAL1 NCF4 ACTC1 IFT80 FGFR3 ALG14 VAMP1 RTL1 ESS2 WRN TGFB1 MKS1 DYNC2LI1 EWSR1 FGF20 CD3E POU6F2 ELN IDUA SFTPA2 SFTPB ATP5F1A FANCF PLCG2 SLC29A3 NDN PIGL RAG2 RAG2 SLC46A1 SLC2A10 RET PGM3 GBA IL2RG SULT2B1 DNAJB13 JMJD1C TP53 SDR9C7 BUB1 MSN MYOD1 FCGR3A SHROOM4 PNP COQ7 ACTA1 ERF MYSM1 ZEB2 ETFDH AGTR1 LEPR TBX1 PIGT FLNC DGCR2 NCF4 ODAD2 IFT172 RFXANK KAT6B DNAI1 GBA NEK10 DNAI1 KIAA0586 MPLKIP CCNQ MDM2 AGA LAMC2 RAG2 LEPR IL17F DCLRE1C SPIDR LIMK1 PEPD CCN2 ITGA3 MYT1L ZBTB24 STAT5B NCF1 CD3D EP300 RIT1 IL2RB GLI2 DICER1 COL6A3 FBLN5 TASP1 DCLRE1C FARSA CDC42 PYROXD1 IL7R TBC1D24 PLCG2 GAA ODAD3 STAT4 LTBP4 NFKBIA PKHD1 IL17RA KRAS MCTP2 BPTF IGLL1 SCNN1A ODAD3 TK2 PSMC3IP TPM3 RNF113A MBTPS2 IGHM PDGFRB RAF1 FASLG CCDC39 MUSK FAM111B NDUFAF6 TRIP4 MS4A1 SMN1 MUSK PRKAG2 SMARCC2 HLA-DRB1 CFH LEP CYBB LMNA PSMD12 NEU1 CD3E PTPRC STAT3 PLG CHRNA1 FOXH1 TNNI3 PRKAR1A TYK2 LOX FLCN NEK9 ORC6 RNF168 PTPN11 CARD11 CD3G LONP1 TGFBR1 CC2D2A GNPTAB IDUA TREX1 CYBB NBN NRAS LPIN2 DNAAF6 TGIF1 WAC ADA FBN1 STAT3 SETBP1 ACTA1 STRA6 CD3D STAT3 ZMIZ1 ETFB RSPH4A SFTPC HLA-B TBX5 TSC1 DNMT3B A2ML1 RPL10 RPL10 MEFV TP53 ITCH BRCA2 IRF2BP2 GAS1 ASXL1 NEK10 CCDC22 SAMD9 MYH7 WNT4 DOCK3 CD247 CFI RCBTB1 UFD1 TREX1 ASAH1 INPPL1 NOTCH2 SERPINF2 MECP2 DKC1 KAT6B MEFV GLDN CHRNG HYDIN CDT1 DNAAF2 IL6R LAMB3 NFKB1 RUNX2 IL1RN GLI3 IRAK1 KANSL1 DLL3 PTCH1 TGFBR1 NDUFB10 REN TDGF1 ABCA3 RAG1 KIF11 FGFR1 UBE2A MYOD1 NFKB2 PIK3CD SMN1 FREM2 TGIF1 LAT HELLS ZEB2 RSPH9 NSDHL SERPINH1 MTHFD1 FAM13A SETD2 PAX6 SOX18 SMARCD1 OCRL SLC52A3 BMPR2 DZIP1L TDGF1 WDR1 ALB CD28 ADA2 RAPSN DLL1 RBPJ WDR19 HLA-DRB1 SHH BMPER MYLK TMEM94 SIX3 PML TGFB3 MYL2 STAG2 TBL1XR1 FBN1 EFL1 TERC BUB3 HES7 FOXC2 RBM10 CFAP410 MASP2 TRIP13 GLB1 MEG3 MYH3 LIG4 PARN RHOH NFKB2 EDARADD DNAAF6 BCR RNF125 TLL1 DCLRE1C SCNN1A GPC3 ASAH1 SNAP25 NR5A1 NHP2 DNAAF5 DLL1 EXTL3 PRPS1 MAN2B1 FANCB COMT ZMYND10 FOXN1 PRKCD BLNK NTNG1 IL2RG IL7R EMG1 TRPV4 SMPD1 ETFA IRF5 NODAL WT1 NECTIN1 LAMTOR2 RAG2 ROR2 ADA FCGR2A IER3IP1 CYTB KDM6A BTNL2 WNT3 TLL1 ALOXE3 TGIF1 ASCC1 PIGN BNC1 RIPPLY2 BAP1 NOS1 NXN DSP DNAH1 ITPR1 IGH PIEZO1 CSPP1 COL3A1 ARHGAP31 MS4A1 NODAL USB1 LRRC56 NPM1 TSC2 ATP6V0A2 DHCR7 ZBTB16 EPG5 TINF2 CASP8 PRPS1 IKBKB ARID2 SHH ARID1B RLIM EGFR CDKN2A LAMA3 SFTPA1 IKZF1 CAV1 PLOD1 PRKDC LMNA JAK3 BMP2 AKT1 CFTR ELN AGT DNAAF4 ATP6V1E1 IFT140 BTK BTNL2 COPA PEPD SCNN1B KCNJ6 GAA MCIDAS PTEN SOX4 ZMYND10 UNG GATA6 DYNC2I1 PSAT1 GATA4 SLC26A2 NDN BCOR NAB2 CD81 NKX2-1 PLOD1 PLEC FUZ CRTAP FGF8 GAS1 ABCA12 REST B3GLCT IGH CLIP2 SCNN1B H19 CYBC1 ELN RAG1 ALDH18A1 MYT1L KLHL41 ACE RSPO2 CLEC7A HIRA GP1BB DRC1 GDF1 TP53 GLI3 SVBP TCIRG1 FRAS1 IRF5 GDF1 PMM2 PAFAH1B1 ZMPSTE24 TGM1 DLL1 SIX3 CCNQ TIMM8A ELN PTEN FUCA1 MYD88 SPAG1 ARID1B AGGF1 THOC2 ABCA3 ARSB CFB PORCN HFE SOX11 NOTCH1 FOXP3 TERC USP9X P4HTM DRC1 AP3B1 CBL POLA1 CDON PKHD1 TAF1 COLQ SON TRPV3 TSC1 DVL3 TCF3 TRIP4 CHEK2 FLNB STAT5B STXBP2 CREBBP NPAP1 FAM20C STK36 DOCK8 SLC7A7 DDR2 TTC37 CD8A DOCK6 CD46 CCDC65 BCL2 INPPL1 DIS3L2 MFAP5 TNFRSF13C KNSTRN RPS15A GLA SELENON LRRC6 KMT2E SLC5A7 TERT GRIP1 DYNC2I2 PTPN22 FAT4 SHH IFIH1 IL7R PARN ARHGAP31 CSF2RB CHST14 TANC2 CIITA ZIC2 FLNA G6PC3 MARS1 BACH2 ZNHIT3 DNAJC21 SH2D1A CCNO COL13A1 DISP1 IL21 HYDIN MGP IL2RA MED25 GSN FOXH1 SLC35C1 PNP PRTN3 SP110 ARID1A MEFV NOD2 SERPINA1 NHP2 MED13 FRAS1 NBN MCIDAS FCGR2B KLHL40 BLM RAG1 RRAS TAP1 SNRPN ADGRG6 NADK2 SLC26A2 DDR2 ZAP70 MAGT1 FGFR1 GATA2 ALOX12B TMEM260 IFNGR1 SMAD4 SLC7A7 NFKB1 RB1 RARB APOE GATA6 DOCK8 AP3D1 SOS2 STING1 CASP10 B2M FLCN SRP54 ZEB2 TNFRSF13C FADD C4A TTC12 TAP2 KPTN STN1 LBR SNRPN DNAI2 MRAS COL2A1 RNF168 CHRM3 CCNO CHRNG RAC1 FGFR3 LGI4 ADA NUP88 TBX20 ODAD2 BCL10 FLNA SLC25A22 ELN SMO GBA TGFB2 NUMA1 RAG2 GATA4 DNAH9 SMARCA4 TNFRSF11A IRAK4 GUSB CD40LG SCNN1G SLC34A2 DHCR7 MIF GUSB KITLG KIAA0586 GRIP1 NSD2 DPF2 SLC35A1 EIF2AK4 GBA SPP1 NCF2 MKKS GAS2L2 MYH3 TBCD HLA-DRB1 PTPN22 RAC2 DDX6 CEP57 RELA PTCH1 DNAI2 ZFPM2 TPP2 RAG1 STAT6 IFT43 KANSL1 PURA LRRC56 DNAAF1 SCNN1G IL6ST ACP5 XIAP IL2RG FANCB IGLL1 AFF4 SCNN1B BCORL1 BTK PCNT MUC5B MRPS22 CDON COG4 PRKCD PTPN11 LRRC8A PHGDH BGN DVL3 PSAP HLA-DQA1 DYNC2I2 SLC35C1 PWAR1 SLC1A4 CR2 TBCE AGRN CTCF FBLN5 VANGL1 TRIP11 NKX2-5 TSC2 GFI1 TNFSF12 GAS8 MAPK1 SLC11A1 IFNG FBN1 DNAAF2 SCNN1A ACTA1 MESP2 HABP2 NDN SLCO2A1 FOXE3 IDS PANK2 FGFR1 CHD7 DNAAF3 NABP1 DNAAF3 CFI DPM2 OCA2 PCGF2 SFTPB MANBA TNNT2 SRP54 PLVAP CD79B SOX18 INVS DYNC2LI1 RARB CD19 FOXJ1 BMPR2 PIGN LEP PKD1L1 NHLRC1 GPC6 ITCH APC2 GATA6 SCNN1A SERPINA1 ATM GBA DNAJB13 CEP120 TNFRSF1A KIAA0319L CLCN7 NSD1 CACNA1C SPEF2 PIEZO2 DYNC2I1 NKX2-5 CREBBP TBX1 TNFSF12 COL6A2 EFEMP2 RAC2 PRSS2 TBL2 CFTR IL10 CFAP298 DONSON RSPH3 ABL1 EVC SDCCAG8 DNAH5 WIPF1 PARN PDGFRA TINF2 NCF2 TNFRSF1B CEP120 FOXP1 RFC2 NPHP3 BCOR GATA4 SNORD116-1 POLR2A NOP10 CCDC103 OFD1 DNAAF5 GATA6 IL6 POLA1 PDHA1 LMNA CD19 SFTPC SIX3 LTBP3 SMPD1 SMARCD2 RIPK4 CSF2RB PSMB8 HPS4 CRKL PTH1R EP300 RSPH1 PERP ATM ABCA3 DCTN4 CLCA4 CTSC STAT3 CCND1 POLR3H TRIP13 FCGR2A MST1 MUC5B DNAH5 CDON TRAF3IP2 IDS SRSF2 SLC18A3 TRIM28 CD79A PIK3R1 GRHL3 NOP10 HPS6 WNT3 RPGR DPP9 RAF1 SCNN1G CD79B RSPO2 BCL11B IVNS1ABP ACTL6A ZIC2 AFF4 SMAD3 ITGA7 CITED2 ERCC2 RAB3GAP2 TRIP11 IL23R SPINK1 TERC RTEL1 CYBA TSC2 CITED2 GLE1 GPC3 TGFB2 SCN9A RASGRP1 FGF8 SNRPN DYNC2I1 CARD11 POLE ICOS FADD NME8 HLA-DQB1 LMNA PGM3 EOGT CDCA7 WT1 SAMD9L SMC1A ICOS GLI3 SREBF1 CHAT RFX5 FOXF1 TDGF1 CHST14 CCDC40 SMARCE1 DCLRE1C ALMS1 TLR4 NCF1 RSPH3 CYBC1 SLC25A1 PTCH1 IL2RG B3GALT6 GLI2 GAS1 TNFRSF13B TET2 NRAS WAS ZMPSTE24 EHMT1 WRAP53 FAS WDR35 HPS1 NSMCE3 TGIF1 GLUL SH3KBP1 RFXAP CARMIL2 BCOR GTF2I TNFRSF1A MAGEL2 STAT4 HGSNAT SMAD3 FBLN5 MYO9A GTF2H5 NEK8 TERT RUNX1 RYR1 FAT4 CLPB RIPK1 COL13A1 JAGN1 CIITA TBX20 CSPP1 DNAAF4 CCR1 HK1 MINPP1 UBAC2 NFIX RNU4ATAC BIRC3 WNT4 IKBKB CD27 FAS NLRC4 SFTPA2 NDN AARS2 TGFB1 DHCR24 PIK3R1 HYLS1 CREBBP CHRND ALPL ITK VHL CCDC103 GREB1L ERAP1 FARSB RAB27A NAGLU ODAD1 CTC1 ZCCHC8 TRMT1 SNRPN CEP55 PRPS1 DLL3 LYST KEAP1 GBA JAG1 NME8 MYPN STX1A TNFRSF13C FIP1L1 HERC2 ELANE CORO1A SYT2 CCDC39 CFTR GPC4 ITGA8 ICOS RFXANK KLRC4 DNASE1 DICER1 EP300 PRKAR1A MAGEL2 MLXIPL LZTR1 PIGN BMP15 HLA-DRB1 COL2A1 ADAMTS2 WDR19 ALG12 AK2 CD55 HLA-DRB1 GAS8 DKC1 NKX2-1 DLK1 SCN10A DYNC2I2 HELLPAR LMOD3 FLCN WT1 NODAL LRBA ELANE GTF2E2 SGSH GPR35 BAZ1B SFTPB TRAPPC4 PLP1 CACNA1B RSPH4A FSHR TERT CCDC65 WT1 TERC MID1 NR2F2 DHCR24 ERCC3 WASHC5 NIPAL4 LFNG VPS33A CD19 RLIM GALNS OSTM1 XIAP ASAH1 HLA-B DISP1 NAA10
    HP:0001626: Abnormality of the cardiovascular system
    Genes 4425
    MERTK SLC25A26 TRNK MTHFR ALDH18A1 SCN9A B3GLCT GNPTAB MITF GJB4 NDUFS4 MEGF8 SCYL1 TREX1 SLFN14 LMNA DOLK SDHA RANGRF SCNN1G CD247 EFTUD2 KRT16 SLC25A4 NTRK1 ATP6V1A CTNND2 ARVCF SIX3 ND1 WDR11 ANTXR1 CTSB NBEAL2 RREB1 TOPORS NOS1AP RRM2B CAV3 LETM1 GNA11 KIF3B IFT172 NPHP3 COG4 ELMO2 ANTXR1 PEX11B DNAH11 KRT2 APOB RPS6KA3 PRKAG2 GJB6 CDSN ZAP70 HRAS ZIC3 NKX2-5 BUB1B FLRT3 NXN RAF1 NKX2-6 KCTD1 TTC7A SPATA5 DNAH1 BRIP1 FGA SGO1 VPS13B TKFC CRYAB CNBP SEC24C CDK8 TULP1 MYH6 B3GALT6 TWNK PLEC SLC37A4 PIGA TSC1 ATRX FOXF1 FOXC1 WAC GNS TERC MPL THSD1 EVC2 DLST CRB2 FLNB ATP6V0A2 TPM2 AK2 ACTN4 SPAG1 RTL1 ITGA8 EFEMP2 C8ORF37 IL7 KRAS ECE1 XYLT1 VPS45 SLC25A24 POMT2 TPM2 CCR6 KCNE1 PLAGL1 AHI1 SNTA1 PALB2 FOXP1 KDSR RELN CAV1 ARL3 MYF6 IGF2 COL3A1 CBL ATP6V1E1 COL5A1 ACD PPP1R15B ACVRL1 AMMECR1 HNF4A ADA2 CDKN2B ERCC8 SBDS SOX3 FANCL NDUFB11 CPLX1 PRKAR1A LYST PRPH2 SLC18A2 RINT1 COX10 SLC2A1 VPS33A LDB3 XK TTN NKX2-5 GJA1 NGLY1 GLI2 ODAD4 MYH11 MAF FLI1 SMG9 SDHA AGPAT2 CAV1 MKS1 TAF2 LRRC6 COL11A2 HOXA13 CASK CCBE1 SMPD1 BTD KCNMB1 TDGF1 PIK3CA WDPCP LACC1 KCNJ2 ND4 RPS19 CHRNA7 IGF2 KAT6A AIRE DISP1 MYD88 DHDDS GNAI3 DOCK6 KRAS IRF8 ERMARD BAP1 APP RPE65 SLURP1 CALR FN1 SLC19A3 ALX4 TSPYL1 PEX13 SLC39A4 NDUFB11 TTN FOXC1 RBCK1 HNRNPA2B1 TRPM4 ZIC2 WDFY3 KYNU PSMB9 CD2AP APOE SMAD4 ITGB3 TRNK KCNQ1 SNX10 KCNJ2 HMBS FKBP14 FGF8 BRAF SC5D SHH ALOXE3 FAS SCARB2 HACD1 CREBBP CITED2 MMP2 HADH NEXN NODAL ABCC6 PORCN CEP57 PIK3R2 RAD21 SCYL1 VCP KCNE2 USH2A TCTN3 PTPN22 ESR1 TRNS2 CDON TIMMDC1 C1R STRA6 IL10 DLD SCNN1A DNM2 SOS1 CDKN1C TGM1 TNNC1 LPIN2 CCN2 MAP3K7 HLA-DRB1 FRG1 TSC2 PPP2R5D GLI2 SLC2A1 EYS FDFT1 IFNG ANK1 SYNE2 ARL6 IRF6 TAB2 PCSK9 TP63 CARS1 HABP2 MYSM1 ERGIC1 ALOX12B DYNC2H1 DSG1 NSUN2 FLT4 FERMT1 DNAL1 CRYAB PPARG GNB5 TRNE TSFM MEIS2 DYNC2LI1 TRNL1 NT5E EWSR1 POU6F2 CSGALNACT1 ELN PRCD FBN2 KAT6B PLCG2 THBD PEX5 SLC2A10 SPOP GBA CYP17A1 SHANK3 SGCG TRNK PNP ACTA1 AGTR1 FERMT1 SIM1 GNA11 DGCR2 NCF4 ODAD2 FMR1 CYTB HCCS GBA SNIP1 DNAI1 LMNA PSMD12 NBEAL2 MKKS LMNA WAS DMD NDUFA10 ITGA3 HESX1 PIGL SDHAF1 POMK MKS1 CYP11B2 ATAD3A IL2RB CACNA1S GLI2 RNU4ATAC NEU1 TASP1 PMS1 RNASEH2A FAH BRCA2 ODAD3 FKTN FHL1 IL17RA C2CD3 CALM2 MCTP2 PDE11A IGLL1 ODAD3 ATN1 TPM3 MYOT SMOC1 PUF60 SOX10 RYR1 NDUFAF6 TRIP4 IQSEC2 GATB ADAM17 SDHB GLMN LRRC32 TMEM216 NLRP3 CISD2 BAP1 MED12 CYBB COL1A1 STAC3 BSCL2 PTPRC VWF CHST3 FOXH1 NDUFA2 TNNI3 YWHAE SNX10 COX3 COG8 LRRK2 FBP1 TMTC3 GNPTAB CTSK TREX1 XPR1 HADHB ZFPM2 SCNN1A PCARE STRA6 NDUFAF2 IL17RD RBM20 FANCB GLI2 CLCNKB CCDC141 RPGRIP1L PHKG2 F7 RPL10 COL4A1 WDR26 HMBS EGFR ABCC8 PLAGL1 BCR NDUFAF2 CCDC22 SAMD9 DMPK ERCC5 SCN5A USP18 HYMAI C1QBP PRRX1 SLC29A3 ARMC5 PLAG1 COLGALT1 KAT6B MEFV DNAAF2 ITGA2B KDM3B GJB2 NFKB1 IL1RN EED IRAK1 FHL1 TGFBR1 REN ABCB4 COL4A2 MDH2 CALM1 UBE2A SP110 PIK3CD SRD5A3 ENG MAX ATP6 NSDHL HSPA9 PROK2 SETD2 CTLA4 SMARCD1 SOX2 ND5 PQBP1 TELO2 F10 DZIP1L JAG1 GATA6 JAM2 MYH7 KRT14 ALB PEX5 TTC8 ADA2 BPGM RIPK4 FRG1 CIB1 KCNH2 CHCHD2 TSR2 POLR1A WNT5A TET2 RGR SOX9 TGFB3 TMEM67 BMP2 CEP41 GYPC ZNF462 GPC4 FBN1 DDRGK1 COX6B1 RBM10 CFAP410 FGFR2 GDF6 TF MAP3K1 ATP2C1 BMPR1A BBS12 DPM1 MDM2 PARN RHOH NFKB2 RFWD3 VHL H19 TBX1 LIAS MOG TLL1 PPARG DCLRE1C NAXD ABL1 CFHR1 SELENOI GNAS NRL KCNE3 NHP2 CYP11B2 TGFBR3 KRAS NTNG1 OSTM1 SLC17A5 SDHB ABCG8 COL5A2 NODAL F13B SDHC TNFRSF11B IVD F9 IRX5 GDF2 PSMB4 PCNA PIGU SAMHD1 NXN DSP ANTXR1 UBR1 FGFR2 PEX6 NKX2-5 COL3A1 TRNL1 ARHGAP31 MS4A1 NODAL USB1 BBIP1 F13B CASP8 CAVIN1 CYP11B2 ASXL1 IFNG FGFR1 ARX PLAU PROC RLIM DTNBP1 ZNF408 SFTPA1 TRNS2 ITPA JAK3 BMP2 BAP1 NBAS FZD2 ATP6V1E1 BTK ATM CACNA1S HADHA MCIDAS NOS3 NODAL PTEN ZMYND10 NFIA ACTA1 PSAT1 SYNE1 BCOR ABCC9 CYLD CD81 COL3A1 GJA8 FGF8 RPGR SCN3B COX3 RPGRIP1 CPLANE1 CYBC1 FANCD2 FGFR2 RAG1 CRLF1 SMARCA2 NPHP1 MYT1L ACE CLEC7A GLI3 CYP27A1 FRAS1 NFU1 PMM2 PAFAH1B1 ZMPSTE24 CEP41 DLL1 FERMT3 CCNQ PTEN EYA4 NPHP1 KCNN4 PRDM5 HFE MPL SIK3 SLC40A1 TERC RPL27 SEC23B TRPV3 PPOX TCF3 SUMF1 SDHAF1 COL1A1 STAT5B SUFU CREBBP SOX9 STK36 BBS4 SLC7A7 GJA1 ADD1 DOCK6 CD46 DIS3L2 MFAP5 KNSTRN ARX TNNT2 SF3B1 KMT2E INPP5E BANF1 GYG1 ARHGAP31 ZFPM2 RMND1 ZIC2 G6PC3 NDUFB10 DNAJC21 PEX26 XYLT1 ERF PEX19 ENPP1 MED25 NCAPG2 FOXH1 HJV SEMA3E AIP IKBKG IQCB1 MRPL3 SP110 NAGA MED13 LIG4 NDP HPSE2 TRPM4 FZD4 FLNB FCGR2B LHX4 INPP5E KATNIP TRIP11 TTC8 PSAP TREX1 ND2 ND5 IDH2 BRCA1 RPS6KA3 FHL1 USP8 SLC25A11 MASP1 LMNA LMNA WDR37 TRPM4 PEX3 TRNF OTC FADD OTC TMEM126A MTAP PPARG TRNQ KIAA0586 ZMPSTE24 RAI1 ELN KPTN LBR KDM6B SON AGXT TRNS1 PDCD10 CYP7B1 TRDN DMXL2 SPATA7 NPHP3 TRAPPC11 ELN PTCH2 MAP1B TGFB2 ARHGEF18 JAK2 SUMF1 GUSB ADCY5 IFNGR1 DHCR7 GUSB KITLG HADHB BVES C12ORF57 SDHB GBA MPIG6B FOXP3 RAC2 STIM1 KRT83 RPL35A AKT1 MYH6 ZFPM2 GJB6 CHST3 KANSL1 PURA SATB2 PITX2 COL4A1 FN1 GLRX5 ADAMTS10 CDK4 AFF4 ZFP57 ERCC1 SCARF2 PCNT PRPF8 NPHP4 LRRC8A RPL26 RMRP ACTG1 TTN OTUD6B KDM6A ECHS1 KCNQ1 ATP5F1E CTCF TGDS CNGB3 TMEM107 GAS8 POLG DNAAF2 SCNN1A ACTA1 MTM1 FLNA POMP HABP2 MTTP TRNL1 FGFR1 TGFBR2 FKRP OTX2 PTPN22 CFI LRP2 PHF21A ZIC2 EOGT RNF6 PLIN1 INSR WRN KRT5 PIGN NDUFA10 FKBP14 WWOX PPA2 LDLR GATA4 GATA6 TBX1 ENG POLH NSMF ARID1A KCNK3 NSD1 F5 KCNN3 REEP6 NKX2-5 CREBBP KIT ZFPM2 CDH23 PDE6D ATP6V1A TMEM231 MTFMT PROS1 XYLT2 EPCAM KCNQ1 P2RY12 IL10 PDGFRB SLC4A1 LRP6 NDUFS8 GCK SDHD DCAF8 STRADA PNPLA2 NDUFB11 DDRGK1 FUCA1 RNASEH1 RNASEH2C ND4 NF1 AKAP9 NOTCH3 FLNC DNAAF5 PEX5 PDHA1 SMARCE1 ERCC4 MYH9 CCDC22 COL1A2 STAT3 CCND1 TMPO ND6 IMPG2 CALM1 CCDC8 TGIF1 NEUROD2 DNAH5 ABCA4 TRAF3IP2 ARFGEF2 TBX1 KISS1R SSR4 ALG8 DDX3X TRNS1 KDSR HAAO RIN2 TUB MKKS RSPO2 DNMT3A ETV6 GNB3 HK1 AFF4 GBA RAB3GAP2 PPCS FGB IL23R DVL1 F8 FBXW11 APOA2 CYBA RAI1 MYH11 CITED2 PEX12 TFAP2B HADH SCN9A FGF8 CASR POLE LOXL1 ICOS FADD AMMECR1 SCN5A LMNA TNNI3 CDON PDE6G SDHD MANBA PIGT TDGF1 DYSF CCDC40 ALMS1 FGA ANO5 PARS2 RPGRIP1L TERT GJB3 CDIN1 KCNE1 FOXH1 SOS1 NRAS CACNA1D WAS CASR DHODH F2 PNPLA2 EHMT1 NF2 TCIRG1 DYRK1A NDUFS1 FAS MYH7 TOP3A SAMHD1 WDR35 NSMCE3 PTEN TGIF1 G6PC1 CCDC28B KRAS GTF2I TNFRSF1A FBN2 TWNK HGSNAT GNAQ PRDM6 APOA1 DSC2 SRD5A3 IFIH1 FTO KCNJ11 GNAS AMER1 SETD5 LIPC COX2 MINPP1 NFIX RNU4ATAC OFD1 RASA1 AIP COL6A3 WDR35 FAS ACVR2B RNF135 CDH2 SFTPA2 MKS1 UPF3B ANTXR2 PRF1 KRT1 AARS2 TSHR TRNT1 SCN5A GATA1 NRAS GREB1L ERAP1 RAB27A SCN10A MC4R PACS1 PRKACA GLI3 LYST GBA GATA4 TKT TBX4 MYMK COL4A4 SCN2B CEP290 KLRC4 SCAPER MMP1 KRT9 F13A1 VIPAS39 PRPF31 PIGN HLA-DRB1 AIPL1 MPL ADAMTS2 TMEM237 CD55 MVK NKX2-1 DLK1 TPI1 APOE GNAO1 WT1 ELANE GTF2E2 PKP2 ABCC9 GPR35 CIITA TRAPPC4 MED12 CDKN1A CLCC1 CRPPA GJB3 MEIS2 RAF1 MIPEP PEX1 COX3 COX7B NEBL SH2B3 ERCC3 ERCC2 KCNAB2 TAB2 CTNS SETX ANGPTL6 CD19 TRIO STK4 POLH ERCC5 GALNS POMT2 NFKBIL1 ADAM17 TET2 NAA10 SF3B1 SLC26A3 GFI1B KMT2D ABCA12 LRP5 UBR1 PEX3 FEZF1 COL7A1 HSPG2 TRPM4 TRNK NDUFAF4 C12ORF57 MYBPC3 GTF2IRD1 CAVIN1 KRAS PIGY VWF TGFBR2 SPINK5 RASA2 APC PHGDH SLC25A24 NGLY1 LARP7 STAG1 RYR2 CCND2 FANCM UCP2 RPL10 CDKN2A DSG2 ANO10 NELFA NLRP3 KCNJ11 PIK3C2A GLI1 CTCF KCNQ1 LRP5 TCF4 CFHR3 POLG TBX5 SHPK HLA-DPA1 TMEM43 SETBP1 LMNA RIT1 SVBP CEP164 AKAP9 ATP6 FKRP CYP27A1 CACNB2 WAS SDHA NF1 LAMB2 BAG3 RARA ACTL6B TREX1 ABCC6 COL11A1 HSPG2 KCND3 CNGA3 IL36RN SLC19A2 CYP1B1 COL3A1 CD96 CYBA ERCC8 TET2 GLIS3 DLD TERT PEX2 FOXH1 SURF1 ATOH7 GFI1B HRAS CASP10 TSC1 TNPO3 NIPBL PITX2 WDR19 GAS1 MYCN TXNRD2 IL10RA ATP7A MYH9 ACTA2 TRNW GDNF CTLA4 PDE4D SPTB ADAMTS3 GLB1 SGCD ERCC3 F7 HLA-B COL5A1 CBS SNCA FGFR2 LIG4 RNU4ATAC CLN3 GNE AKR1D1 ADA2 KCNJ1 FGFR1 CFI ERCC2 DISP1 FKTN ATP6AP2 NLRP3 FGFR2 COQ2 SPECC1L ARL6IP6 FAH ND5 NR0B1 LIG4 MAP3K20 POMT1 FOXE3 PDGFB GYS1 SDHAF2 SLC26A2 FAS PRKAR1A SERPINC1 RLBP1 TCIRG1 CALR PIK3R1 LIFR KCNQ1 SDHD ZNF687 SLC35A2 FGF8 CCDC40 CTLA4 SCN5A HBA2 ARSA DCAF17 CFTR SCNN1G ESCO2 GJB4 ITGA2B KIF1B BEST1 RP2 GATA6 BBS9 ARNT2 KCNJ18 HTRA2 SPRY2 STAT1 GTPBP3 FGF8 SCNN1A SNRPN MYOC GPR101 ATP5MK HNF1A MAX LRIG2 LONP1 PLEC CXCR4 ERCC8 COQ9 PTDSS1 SLMAP STIM1 CCND1 KCNQ1OT1 AHCY ATPAF2 FANCC POLR3A SKIV2L PADI4 CYTB MAF TERT SFTPC FOXJ1 NPC1 AICDA FANCI CALM3 NDUFS2 EDA LDLRAP1 TFAP2B CALM3 PEX6 CFAP298 CSTA SELENON TRIM28 ZIC2 KLHL7 NPC2 TBX22 ALMS1 GPD1L FGF8 ELN SBDS CERKL CYP11A1 KDM6A LAMP2 B9D1 MAFB DTNA NDUFS2 PEX14 LEMD3 GJA1 FGF20 SGCB MMEL1 DNASE1L3 TGFB3 CCDC141 FANCA LIPN FLT4 MYH7 RDH5 SCNN1B FBXW11 MAN2B1 SCN5A LTBP3 PTCH1 MGME1 EPG5 NKX2-5 GAS2L2 PPP1CB F13A1 PDE6H HIC1 CBL CWC27 PDE3A FLNA CHRM3 POLG2 JPH2 IRF5 IL17RC GNAQ SMARCA4 APP PIGM HPS5 TMC8 COL4A5 LYZ NFIX RTEL1 PRKG1 PLN ATAD3A MPI BRAF IFT172 FMR1 ALG14 PAH WRN TGFB1 RBM8A NDUFB9 SFTPA2 CDH23 FGFR3 RET NR2F2 JMJD1C TNNC1 SLC30A10 GLI2 BUB1 GMPPB NRXN1 COQ7 OCLN VCL TMEM237 TFAP2B TBX1 WDR19 RRM2B COX4I2 KAT6B FLNA DNAI1 HCCS NOTCH1 IFT140 FOXA2 MPLKIP PROS1 LZTR1 SOS2 NDUFS2 CACNA1H TPI1 FECH CYP11B1 GNA14 MADD GCDH PEPD MYT1L MYO18B GTPBP3 SDHA IDH1 CDKN2A SCN4B SOX10 FBLN5 YY1AP1 CDKL5 RPS10 TANGO2 NPPA GAA AKAP9 NDUFS2 PIGO MAP3K7 LMNA MEOX1 KRAS TMEM216 RBBP8 KLF1 SCN1B BPTF SMARCB1 SOX10 BRCA2 SPTB ANK2 RNF113A BRAF MBTPS2 RAF1 COL6A1 FASLG TNNT2 CCDC39 DNAJC19 PYCR1 SMN1 EYS TNXB CFH DEAF1 LMNA PSMD12 TK2 INTU ATP6AP1 PEX6 POGZ STAT3 PLG CHRNA1 ACTN2 NEK9 ESCO2 LONP1 TGFBR1 ACAD9 CDH2 POLG TMEM127 LPIN2 KYNU PRDM16 SETBP1 SNRNP200 CFH UVSSA UBE3A MYH7 PRRX1 CPLANE1 TBX20 SFTPC SLX4 CARD9 ARL2BP RECQL4 LEMD3 TNNI3 RPL10 FGFR2 FHL2 GABRD IRF2BP2 EHMT1 NEK10 ABCG5 MYH7 RPL5 CRYAB MKS1 DOCK3 NODAL ABCC9 TFAP2A RPS24 VPS33B RPL35A FGFR2 SGCA RET COQ2 ARL13B IDH3B MGME1 ASAH1 NOTCH2 UBE2T CENPE CHRNG ATRX SNTA1 PRPF3 ERCC6 HBB MED13L KCNQ1 MRE11 JAG1 RECQL4 RPL27 DNAJC19 TDGF1 TALDO1 RNF213 RAI1 HFE NDUFS2 NR2E3 PCARE MAK PHKA2 LAT STXBP1 ZEB2 KDM5B PIGO MAP2K1 PIBF1 PAX6 ERCC4 SOX18 ERBB3 SIX3 ROR2 ND4 BMPR2 CENPF PEX16 PDX1 DUX4 PEX19 FLNA DIS3L2 DLL1 CDON SHH TPM3 CPT2 H19-ICR TBCK MTRR BMPR1A MYL2 HBA2 JAK2 FOXC1 TBL1XR1 GDAP1 RAD51C CACNA1C RRAS2 PRPF6 LIG4 AGK DNAAF6 PIGS RNF125 BIN1 NR3C2 FANCA PRKAR1A GDNF MYPN NOTCH3 IGF2 RUNX1 PRKCD BLNK KRT1 PRPF3 FCGR2C KAT6A FBLN5 ABCC9 GCLC WDPCP IRF5 WT1 LIPA RAB27A KIT TMEM43 ADA AUTS2 CYTB SALL1 SERPING1 CYP24A1 TGIF1 ASCC1 DNAH1 CSRP3 GNE CST3 IGH FAT4 JAK2 PSEN1 G6PD ACADS MYH11 TMEM43 INSR ERCC6 PQBP1 ARID1B ARL3 PDE6A SH2B3 PPOX TP63 SHH PLOD1 AKT1 TTR COPA PEPD SRY SCNN1B FBN1 SNRPB RBP3 GAA CALM2 GATA6 DYNC2I1 CASR ZNF423 RAD51C GALE SDHB HPS3 REST TGFBR2 SCNN1B TAZ PKD1 TPM1 PRKACG HIRA ACTG1 DRC1 SVBP GPC6 GDF1 HOXA1 BAP1 COX1 CSPP1 ELN MGMT ARSB PEX6 RPL11 PET100 RIPK1 CASQ2 ACTB MSX2 ND2 FOXP3 USP9X ND4 SOX4 SLC39A13 PKHD1 CHKB COLQ TTR SPEG RPL11 GLRX5 PAM16 NOTCH2NLC TET2 SCN5A AKT3 PTPN11 MEOX1 RP9 F2 ENPP1 RHO POLR1D TDGF1 TNFRSF13C GLA SELENON HSD17B10 RPL15 TULP1 NF1 ADGRE2 FGB MED13L GATA5 AGL DDC TRMU BACH2 DLX5 ZNF513 IL12RB1 SH2D1A KRAS SLC25A4 SCN5A NDUFA11 GSN CAP2 ALDH18A1 SMAD6 VPS13A EXT2 ITGA2B SLC4A1 FRAS1 NDUFA12 MFAP5 CYSLTR2 CEP55 AGXT FGF17 CLDN1 PDE8B MAGT1 FGFR1 IFNGR1 DES SMAD4 ZNF469 ND1 DOCK8 KMT2D SOS2 SLC19A2 ND5 LAMA4 CTNNA3 FOXRED1 LIPA MICOS13 CSPP1 ACAT1 RORC STING1 DCHS1 GATA3 MEGF8 HLA-DRB1 ZEB2 ARID2 CHN1 PIK3R2 RPL18 STN1 HTRA1 AP1B1 PCCA EXT1 CCND1 CYLD PDGFRA RAC1 KIF15 TBX20 FIG4 SLC20A2 BIN1 LIPA ODAD2 FLNA TRAF3IP1 SMO SLC4A1 PDHA1 DNAH9 TMEM231 GLA SCNN1G NOS3 MBTPS2 EVC NSD2 HS6ST1 DPF2 ITGA2 MAN2B1 PIK3CA LRP5 PKD1 KIF1B APP TNNT2 TNFSF15 PTCH1 LRP5 RBP4 MMP2 LMNA NLRP3 CHD4 LRRC56 FGG ABCC9 CYP11A1 RNASEH2A CIZ1 TNFSF4 ODC1 POLR3A AGPAT2 TWIST1 MMP1 NDUFA4 ND1 IDUA COG4 TP63 PAFAH1B1 PTCH1 PEX7 LCAT COX8A GP9 ABCD3 PRPH2 TP63 DISP1 TCTN2 TNXB SCN1B PPP1CB VANGL1 NR5A1 NKX2-5 TSC2 ACTA2 DGUOK GFI1 MAPK1 IFNG COL1A2 NDUFS3 PHYH MESP2 RPS28 FASTKD2 FOXE3 NLRP3 MRPS16 RAI1 NABP1 SCN9A PCGF2 FLCN DNAJC13 SFTPB ACTC1 PLVAP HBB RPS20 RPSA RAD21 INVS LYST NDUFA11 RARB CD19 BMPR2 DZIP1 APOA1 GATA1 PEX7 NEK2 ATM LMX1B GBA APOE TGFBR2 MYH11 CANT1 RECQL4 HYOU1 IGSF3 TOR1A ATP8B1 CFTR EVC FANCE PARN PRKAR1A TGFB1 MYLK WWOX MTOR RFC2 WDPCP GATA4 RRM2B CCDC103 SETD1A NEB MPLKIP POLA1 FLT1 CD19 CALM1 SIX3 SMPD1 B9D2 SERPINC1 SELENON SPARC HPS4 PTH1R SRCAP ATM MNS1 KRIT1 MYH6 SH3PXD2B GNAT2 CLCN7 TRIP13 HAND2 COL18A1 MST1 ANKS6 RPS6KA3 MEF2A ALDOA FGB FKRP NOP10 AVPR2 COG6 TRNQ BCL11B PRDM16 IVNS1ABP STOX1 ASAH1 ACTL6A NDUFS7 SMAD3 TALDO1 NUBPL CITED2 ERCC2 TAF1A COL4A1 COX15 TEK STEAP3 HADHA ALX4 ACTA1 DSP NDUFB3 EIF4G1 GATAD1 ACTA1 HBB RERE FLNA MAD2L2 CLRN1 LTBP4 PNPLA6 TMEM237 AIP DDX58 POR PGM3 DCC ABCB11 KCNJ8 EOGT VHL PIK3CA MTFMT TEK PLD1 SLC25A4 SDHC DCLRE1C SEC31A TLR4 RSPH3 APOA5 COX7B CYBC1 DCHS1 KCNH1 FANCB BBS2 HBB SRCAP GAS1 TNFRSF13B LMNA CRB1 ZMPSTE24 ANOS1 SMARCE1 KCNQ1 BCOR WARS2 KLHL3 STAT4 SMAD3 GTF2H5 TRNV RUNX1 LRP2 OPA1 PRKAG2 DNAAF4 UBAC2 MAP2K1 RIN2 THOC6 DLEC1 BIRC3 COL4A3 FGA TTC8 SCN1B GATA4 TMEM138 CD27 BMPR1A ALKBH8 CFHR3 MTHFR NSMCE2 VCL MITF QRSL1 DHCR24 CAV1 BNC2 SNAP29 ITK BICC1 RECQL4 THOC6 NAGLU TRMT1 AKT1 JAG1 RERE GDF6 DMD F2 FIP1L1 GJA5 C2CD3 ND5 ATP2C1 APC NFIX NDNF B9D1 ICOS GFM2 SARDH ND6 HLA-B PRKAR1A KCNJ18 MAGEL2 GMPPB NF1 MAP3K7 DLL1 RPS29 NODAL LRBA RDH12 PLP1 RSPH4A TERT FBN1 F5 NAGA RHO ATP6V1B2 RET HSD11B2 WASHC5 TCTN2 DMD GANAB TMEM67 C8ORF37 SLC39A13 CD46 ADAMTSL4 VPS33A DPF2 PIGQ INS SDHA MVK SMARCB1 RPS7 WT1 TRAIP NDUFB11 DNAAF1 TOP3A PRCD CUL7 TCOF1 ALG9 TRNC CALCRL F5 KAT6B POMGNT1 TTN OFD1 EPB41 TERT BRAF CLCN2 APP SLC2A10 RPS15A APP KRT14 GJC2 PTF1A MALT1 HPGD NID1 SOX3 KCNH2 ABCG5 FSHR MAFB DSE GATA6 CFC1 EFTUD2 HBB MYL3 RPL15 PPCS STK11 ALB CDC45 SNAI2 PCNT FOXH1 ESPN TPK1 IDH3A ANKRD11 COL1A2 TARS1 PKLR CEP290 WNK4 CCR6 SH2B3 ALAS2 DNAH9 HSD3B7 PLIN1 BRAF ADNP DSG2 UROS RLBP1 EXT2 TBX1 SMCHD1 PIK3CA TCAP RS1 ATP5F1A GATA6 FANCG SCN5A GP1BA NDUFV2 GMPPA NOTCH1 MAB21L1 ADAMTSL1 AKT2 MCCC2 ND6 DNMT3A SIN3A THPO NOD2 MYH6 WASHC5 CPOX FOXC2 HAMP GJA1 ANKRD26 ACTA2 CYB561 SCN1B PIGT VPS13B PRKCD HYLS1 SUFU PTCH1 DNAJB11 HOXD13 IGF2 TRRAP CFAP300 COL1A2 GDF1 MTO1 IFT27 INTS1 PHKG2 PEX19 MAP2K2 WT1 DLK1 PPP1R17 SMC3 CR2 STX11 F12 MED25 MADD COL6A2 RAB23 SHH ACADVL FAN1 TET2 TKT MYRF HRAS DLL4 F8 MVK CRELD1 GALNT3 SCN5A TPM1 KIAA0753 SCO2 SOX2 ATP8 SLC26A2 PUF60 RYR1 ELP1 AGA BEST1 NLRP3 FANCF VWF FBN1 MMP21 TCIRG1 PNKP F2 CPT1A FLI1 ZIC2 SLC29A3 KIF20A DLL4 IMPDH1 MBTPS2 POLG KRAS SIX3 PEX12 PRKCSH TCTN3 SOX10 SMARCB1 TRNN SCO1 BTK MSH6 KRAS BSCL2 RSPH1 SMAD9 CCBE1 GK DNAH11 AGTR1 ATR CSF2RA NADSYN1 UMPS CDC42 GJA1 LAMA2 SMAD4 SACS TCOF1 NTRK1 DES POMT2 SLC22A5 MCFD2 MYBPC3 XPNPEP3 NOTCH2 SKI SEC23A TTN LORICRIN MRPS14 SYT1 ODAD4 ECHS1 IDUA CACNB2 DLL1 ND1 RNF113A TBX6 RERE FLNA CASK DGCR6 TTC7A SFTPC RAG1 UROS INTU CKAP2L EDNRB NLRP1 IFT81 ABCD4 EPHX2 COG4 EED SIK1 ETHE1 RPS19 IL12A-AS1 ENG CDKN1B HLA-DRB1 HYLS1 NPM1 NDUFS4 MC1R SCN11A TACO1 RB1 CTLA4 PRG4 CEP19 KLF1 C1S CRELD1 PHYH DSE PEX1 ERBB3 RPGR TCF20 LIMS2 GUCY1A1 GALC TUBB RET JUP NLRP3 ALDH3A2 DHX38 IFT80 FGFR3 FXN FGA MKS1 SEMA3A HBA2 NPHP3 WFS1 VHL PMM2 COL4A3 BRAF ABCB6 IDUA MNX1 PRPH2 RPGRIP1L EYA4 FBN1 HBG2 SLC29A3 CNTNAP2 RAG2 CAPN5 CTSA PGM3 CHRNA7 FANCE MPL COL7A1 NDUFS6 HIBCH FKTN ZEB2 XPA NEK1 GJA1 TRDN FLNC ENG AKAP10 KIAA0586 CCNQ PLN NDP AGA LAMC2 RAG2 IL17F VAMP7 CEP104 FANCC SNCA PYGL CCN2 TPM3 TWNK GGCX COQ2 FOXE3 NCF1 CD3D ABCA4 TAF2 RIT1 MGAT2 SAA1 KIZ IL7R TBC1D24 TTC37 LTBP4 SPTA1 MLX COL1A2 IDH1 SMAD3 TGM5 FOXRED1 PEX16 NOS3 GHR DDX11 HYMAI GDF2 PRKAG2 HLA-DRB1 MRPL44 NDUFA1 DNMT3A NEU1 ATIC EDN3 FLNC CPS1 PRKAR1A APRT GPIHBP1 DNMT3B IDH2 SCN3B PTPN11 EDN1 MECP2 AGK NDUFV2 USF3 ACVRL1 TFR2 FLNA MTTP NRAS OTX2 CC2D2A DNAAF6 FGF23 CLCN7 ANK2 NOTCH1 FBN1 NUP188 NDUFAF3 STAT3 PEX2 PEX10 CARD11 TBX5 BAG3 ERCC6 STX16 SMAD4 SLC25A13 PGM1 LRP1 JAK2 HMGA2 AHI1 RPL31 ELOVL4 AQP2 PIK3CA TP53 CNGA1 BRCA2 PALB2 GAS1 PSAP PTCH1 CFI PTEN STAT3 TMEM67 SCN10A KBTBD13 TREX1 AHI1 ACTC1 JAK2 ISG15 MYH7 ACTG2 BEST1 TMEM126B MAP2K2 ACADM DLL3 RYR1 FUT8 PEX12 ASXL2 KIF11 GP1BB MSL3 HADHA TERF2IP SH3BP2 HNRNPK NFKB2 FREM2 IFT172 HIBCH PIGY ANK1 TGIF1 CAV3 IDS AVPR2 NEK9 SELENON PSTPIP1 CCM2 LEMD3 ATAD3A GATA4 NR3C1 NEUROG3 SCN2B TBX1 POU2AF1 TDGF1 PRKACA ADNP CA4 CD28 CDC73 SIX3 PML BLOC1S3 KCNJ5 CHD7 POLR1C POR TNFRSF11A FH ATRX HES7 FOXC2 NKX2-6 FOS GLB1 CC2D2A DSP MYH3 KRAS HSD3B7 ALDH18A1 ALOX5AP PEX11B SDHD DVL3 SLC12A1 SCNN1A PSEN1 WFS1 GPC3 DCTN1 ALG9 DNAAF5 JUP ZMYND10 CACNA1D IL2RG IL7R PTH1R SMPD1 HLA-A ROR2 GP1BA SMAD4 KDM6A NONO INVS TLL1 RIPPLY2 CLCN7 MYLK NODAL ND6 SERPINA6 GNE BAG3 MEN1 LRRC56 GATA1 TSC2 VPS35 DHCR7 WARS2 NDE1 SLC20A2 WNT10A SLC7A14 GSN RP1 KCNJ5 BMPR1A LBR ARID2 BBS1 SDHD ZNF513 RET CNGB1 KCNJ5 SETD5 NKX2-5 CAV1 ABCG8 DCAF17 DSG2 TF GPD1L AGT GATA1 CTBP1 BTNL2 RYR1 SNX14 CHST3 RAD21 SOX4 SAG ERCC6 TP53 IGF2 BBS10 FUZ SUFU CRTAP PSAP PEX13 GAS1 B3GLCT ABCC6 PLEKHM1 ADAMTS10 ELN RET GATA5 ALDH18A1 CALM2 GATA5 EPB42 GP1BB TCIRG1 DIS3L2 CAV3 TPM2 EMD SCO2 TXNRD2 IKBKG FUCA1 SPAG1 ARID1B GNAS AGGF1 F8 ABCA3 ND4L NLRP12 TGFBR1 NDUFAF5 NOTCH1 PMS2 SEMA5A CAV1 NDUFS8 CD28 CDON GPX4 CA2 CC2D2A PDGFRB GREM1 KIF7 STXBP2 TGM5 ADCY5 EPHB4 ESCO2 FHL1 NEDD4L BCS1L IFT88 CITED2 NDUFB11 BCL2 INPPL1 KRAS CYTB KIT MYBPC3 RPGR CALM1 GRIP1 ATP5F1D FANCD2 PTPN22 FAT4 IFIH1 IL7R LMNA JUP GPC4 FECH H19-ICR SMARCAL1 NAGA GBA CEP290 PDCD10 DISP1 HYDIN SPRY4 MAP2K2 IL2RA FGD1 CDK13 CTC1 PDSS1 PNP PRTN3 ARID1A EPB42 XYLT2 MYH6 FRA16E GP1BB RSPRY1 TRNS1 SDHD BLM CASQ2 CALM3 RRAS SALL4 FANCI LMNA DDR2 ZAP70 ALDOB MNX1 LMNA AIP ND4L C3 IFIH1 TMEM260 NRXN1 USP8 FGFRL1 DPH1 APOE C8ORF37 AP3D1 SALL4 BRCC3 ABCA1 CDK10 KDR TECRL AAAS TBXAS1 C4A MYH7 SH2B1 ERCC6 SBDS DNAI2 NKAP TBC1D24 PEX1 LIPC CHRM3 MTHFR MYL2 TRNE COA6 SERPING1 GATA6 BCL10 PRF1 RAG2 SCN4B GBA GATA4 SMARCA4 GM2A CD40LG KCNQ1 MSH2 TRMT10C MMACHC MIF HES7 GP1BB HLA-DQB1 TRIM32 NKX2-5 GMPPB SLC35A1 AMER1 EIF2AK4 SPP1 XYLT2 KIF7 LBR NCF2 MKKS PTPN22 TMC6 CEP57 FGFR2 DNAI2 SDHA SDHB TRNF TPP2 SDCCAG8 SOX5 PCNA ZNF469 RAG1 CDKN1C CDC73 IFT43 CEP120 HAVCR2 HMGCL KCNJ2 HBB MIB1 SLC4A1 ACP5 XIAP CFAP53 IL2RG ATP7A RNASEH1 FANCB CYP11B1 KAT8 BTK SDHB TTN TMEM231 OFD1 TET3 KLHL7 CDON PTPN11 TXNL4A PHGDH LRP5 FLNA PIEZO1 PIK3CA NNT ABHD5 DVL3 KCNE3 AEBP1 RYR1 CDHR1 HCN4 STRADA PSMD12 CUL3 SLC25A3 ANAPC1 LONP1 ERCC4 FBLN5 ATP6 FBN1 CLRN1 PEX16 FLT4 NIPBL SMAD4 LIPT1 SLCO2A1 NOTCH3 CD109 RPE65 CHD7 SLC37A4 COQ2 TNNT2 SRP54 CD79B SOX18 SGCD TSHR AQP5 TNNT2 CDKN2C MMP14 MED12 TGDS CCDC47 PKD1L1 ND2 ADAT3 CPOX RPS17 APC2 MYH8 TRAF7 KIF7 MYH7 SCNN1A GPD1 DHX37 VEGFC KRT5 TNFRSF1A KIAA0319L CLCN7 YARS2 TBX1 PDE11A SMC1A PIEZO2 TMEM237 NDUFS7 PDGFB TBX1 KCNA5 AKT1 TNFSF12 EFEMP2 PGAP3 ABL1 PIK3CA EHMT1 PDGFRA CTNS SDHD NCF2 NDUFAF5 TNFRSF1B WNT10A FOXP1 PSTPIP1 BCOR TMCO1 GYG1 KDM1A SDHB NDUFS1 NSD2 TECRL F13A1 B3GALT6 CLCNKB TRPS1 BBS1 CSF2RB MPL PERP FAM149B1 COL1A1 HESX1 FCGR2A EDNRA IDS TRIM28 WDPCP CACNA2D1 CD79A PIK3R1 FGFR1 PIGP HNRNPU HPS6 SCNN1G MAP2K1 PDE6A CTSA CPT2 LMAN1 GPR101 SYNE1 TFAP2A COX2 RTL1 CCDC174 COQ2 NR2F2 OFD1 ND6 KCNH2 TSC2 KCNN3 RASGRP1 SP7 GBE1 NDP GATA1 COL3A1 POGZ ENPP1 POMGNT1 SEC23B TCTN3 GLI3 SREBF1 ITGA2B SMARCE1 POU3F4 GIGYF2 SIX6 F11 SEMA3A CDAN1 KIF5A MVK ARMC5 SDHA NDP PTPN14 HAMP CNGA1 PEX26 RYR2 HEXA TP53 HPS1 TET2 COL2A1 FBN1 SCN2A DMD GATA4 FMR1 NKX2-5 ELOVL4 DMRT3 FBLN5 GUCA1B NEK8 TMEM127 CLPB LDB3 RNASEH2C TWNK TBX20 CCR1 HADHA POR WNT4 ELAC2 MEG3 GP1BA TRDN SKI NEXN RAD51 DUSP6 OTUD6B USH2A NDUFA9 MMUT HYLS1 NPHP1 HBA1 CHRND PKP2 PDE6C XRCC2 FSCN2 VHL CCDC103 ERCC6 ZDHHC9 FARSB ODAD1 CYP11B1 ANK1 JAK2 NME8 AHR VHL SLC25A22 LETM1 SLC25A3 ELANE RFWD3 XPA GPC4 ITGA8 GNAQ CDKN1B GNAS ERCC8 C4A DYRK1B TRPC6 DNASE1 CA2 PROKR2 MLXIPL LZTR1 STX3 ALG12 AK2 IDH2 SLC52A2 PDE3A HELLPAR HSD3B2 GP9 SGSH BAZ1B ALG1 WT1 TANGO2 MID1 GP1BA XPC LDB3 NR2F2 DNAL1 TGFB3 SGCB CTSH CTSB DISP1 PRKAR1A TRNL1 UBE3B LCAT MAT2A FIBP CYP11B2 TNFSF11 DSP PET100 LMNA ABCA4 KCNA1 NFE2L2 EPHB2 SGCG PROC IARS2 KCND3 D2HGDH MGP TRDN NHLRC2 SOX9 PGAP2 NAGA PUF60 FKRP CTNNB1 SDHD KCNE2 RSPH9 NOTCH2 PACS1 GNAI2 NAA10 GNB5 GGCX KRT10 CD70 ND1 PIK3CD FMO3 ASS1 EXT1 USP9X PSAP GUCY1A1 LMNA WT1 PIEZO2 GJA5 STN1 DCX KCNE5 GPC1 PROKR2 EBP GNPTAB NLRP3 CFAP221 COA5 JUP GJB2 TP63 TBX3 AP1S1 HBA1 ROBO4 CERKL RPL26 DES EDA2R OFD1 CD81 TNFRSF13B POLG2 FIG4 DDX59 MYH7 NSD1 MTHFR HLA-DPB1 AGT RYR1 CFHR1 BRF1 SLC22A4 SLC25A20 MAPRE2 AKT1 RRAS2 EPHB4 MEN1 XRCC4 COX7B HSPG2 CEP290 CCDC115 LTBP2 DLK1 PROP1 SHOC2 FLT4 ACTB DGCR8 FBP1 NEB SLC35A1 EPAS1 COL1A1 MRAP SPECC1L PSEN2 CDH23 BLM PKD2 CDON PKD2 NPHP1 CST3 RAG1 SNRPB PRKG1 USB1 MYOCD GATA4 TMEM70 NDUFAF6 FLNA STAT2 ZNF365 MEFV PYGM RASA1 NEK1 SOX6 NF1 FKTN NF1 CSRP3 RPL35 HCN4 SRY MYOT TDGF1 GATA4 GGCX TAPT1 TMEM216 COX15 SLC4A1 ROM1 PAX8 COX1 MCM4 TINF2 CD40 TOPORS ERCC2 SDHC NAA10 MPL POT1 CR2 COL1A1 FGG FOXE1 NLRC4 TFRC TRIM37 EXT2 LMNA KMT2A ITGB3 TBX3 STXBP1 DNM2 NCKAP1L ATXN7 ACADVL SERPINF2 LDB3 TPM2 PLEKHM1 PAX3 ELP1 IRF8 RMRP TGFBR2 STAG2 UQCRFS1 LMX1B SALL4 CFAP300 SIX3 BMPR1A DDB2 IGHM GJA1 HPGD MEFV KCNH2 KCNQ2 PALLD RNASEH2B NDUFAF8 MSX1 NOTCH3 BCL6 ISCU ABCC8 ATP11A FAM111A DBH ODAD1 SDHC CHRNG HBB SALL4 CTLA4 ATP7A RNF213 LOX PIGV CP POLR1A NMNAT1 ALPK3 GPC3 WNT5A CYP26C1 PTEN PPARG BBS7 DDX6 ABCC9 PQBP1 COG5 LMNA ETHE1 LDLR DVL1 RASGRP1 CHD7 TTC12 VCL GABRA3 KRT18 PROC KLLN IARS1 GPI GAS1 KIF23 ACTA2 KCNQ1OT1 WIPI2 THPO FGF8 GLI2 LBR PLCB4 ARID1B BRAF DSP IDUA ANKRD1 BCOR IL12A MMUT SF3B4 PEX7 CFB SCN1B UMPS SERPIND1 PLOD3 KIAA1109 TERT XPC SMCHD1 CD96 MYH7 ACP5 SPEG NT5E DNAJC21 MYCN IGBP1 LMNB1 ACTC1 OTX2 RHBDF2 RTL1 ESS2 FYB1 EXOC6B RPS26 SLC39A4 PIGA MID1 ARL2BP EPHB4 SFTPB ODC1 ASCL1 TTPA PIGL PEX10 ND2 GBE1 TP63 JAK1 DHPS RAI1 XPNPEP2 DNAJB13 COL2A1 AGBL5 CPT2 PROM1 PALB2 IL12B SDHC PDE6G LEPR JAK2 FGG PIGT TSPYL1 STAMBP FASLG KLF13 PIEZO1 EZH2 EPB41 RUNX1 B2M CORIN SPTA1 NR3C2 MYH6 KLHL41 PROP1 ADA2 LIMK1 DSP RPL5 HMGA2 KRAS CCM2 NDUFAF1 ERCC3 IDH3A EP300 NDUFA6 MCCC1 DCLRE1C FARSA CDC42 PLCG2 ACTC1 STAT4 C2 VAC14 PKHD1 DMD ND3 SIN3A COL7A1 CYP3A5 BRAT1 ZMIZ1 NUP107 PTCH1 LMNB1 HNRNPK ND1 IGHM TNNI3K TGIF1 TUBB GJA5 POLG FLNC HAVCR2 SMARCC2 ERCC2 TXNL4A RAB23 CD3E MLH1 BCHE SULT2B1 DISP1 PEX1 LOX DES PIK3R2 BPTF TNNC1 PPP2CA RNF168 TMEM126B FSCN2 ARCN1 PIGV IDUA NKX2-5 IGH CYBB COL5A2 BCOR JAK2 SERPING1 SLC12A3 DOLK NEU1 TGIF1 ADA STAT3 FIBP B4GALT7 ZMIZ1 HLA-B HDAC4 ECE1 CYP17A1 TSC1 ATP6V0A2 A2ML1 DPM3 RP1L1 PKDCC RPS26 MEFV ORAI1 CLIC2 ITCH SEMA4A ASXL1 TRIM8 WNT4 RPS27 SURF1 UFD1 RAF1 SERPINF2 SRP54 SCNN1B GBA DKC1 MYH7 COG7 TCIRG1 ALOXE3 BBS5 SF3B4 LAMB3 VANGL2 MYPN GLI3 LIPT1 KANSL1 PTCH1 EIF2AK3 PPA2 NDUFB10 FBN1 ARL6 ABCA3 STEAP3 GCH1 UNC13D FGFR1 FZD4 HTRA1 SALL1 CPT1A HLA-DQB1 SMC1A PCCB NDUFAF4 FAM13A NEXN KCNN4 LARS2 CTU2 CYP21A2 HSD17B10 TWIST1 SMC3 COG1 ARPC1B FBN1 CALR GATA1 WDR1 ACTC1 PRNP RHAG DOLK RBPJ INF2 HLA-DRB1 HNRNPA1 PHOX2B DPH1 MYLK TMEM94 PRPF4 ADAR SARS2 HDAC8 MLH3 COL4A1 STAG2 LRAT CITED2 EFL1 KIAA1549 TERC BUB3 CRX ITGB3 NSD1 BOLA3 KIAA1549 ATF6 TRIP13 MEG3 PRDM16 KMT2C AIRE MED13L ATP7B AMMECR1 BCR BBS2 GLB1 ABCC8 ACAD8 DSP CYP7B1 MYPN DLL1 VHL EXTL3 SH3PXD2B KCNE5 ARL6 MAN2B1 COMT MYORG ARX EMG1 AIP CSRP3 RHAG RAG2 FCGR2A GJA5 TMEM67 BTNL2 ADAMTSL2 WNT3 DSP SOX18 PIGN PAFAH1B1 HGD ITPR1 FN1 FBN1 PIEZO1 ACTN2 COL1A1 YY1AP1 NPM1 ATP6V0A2 ZBTB16 AHCY EPG5 COL7A1 DDB2 SHH CACNA1C KIT EGFR OSGEP LAMA3 TBX2 SPECC1L IKZF1 SPECC1L SAMD9 LMNA YY1 PIK3C2A LMBRD1 ELN IFT172 PDSS2 DNAAF4 SH2B3 HBG1 NDUFA2 LZTFL1 MYO5B KCNJ11 EVC2 CEP120 SEC63 UNG PTEN MYC GATA4 SLC26A2 SCNN1G NKX2-1 PLOD1 PLEC DLL1 FHL1 MUC1 KYNU ABCA1 TTC8 IGH CLIP2 H19 APOB LAMA4 PLCB3 IL6 GNAQ KCNE1 IGF1R SLC25A4 DYNC2LI1 GNAS GDF1 MYOZ2 IRF5 DST LMX1B ARMC9 NRAS KCNE1 MEN1 SIX3 HJV MYD88 THOC2 PORCN SNRNP200 SOX11 GNB5 SHOC2 CKAP2L SDCCAG8 AP3B1 POLG PDGFB CBL APOC2 POLA1 COL2A1 LPL MLYCD SON TSC1 MIR17HG DVL3 RGR HESX1 LAMP2 RANBP2 SCNN1B ALX1 IFT122 GNPTG NRAS ARL6 FGB STK11 PEX2 MRPS22 GPX4 PCCA TTC37 DACT1 WT1 SMAD4 DAXX KRT14 PACS2 RPS15A RAF1 LRRC6 TRNW DYNC2I2 TNFRSF1B SHH PDE6B WNK1 PKP1 CHST14 TRNV TANC2 KIT FLNA NFIX SLC12A3 ACAD8 PRKCH TBXA2R TRAC TJP2 CCNO FGFR2 IDUA MGP KIT NDUFS3 GBA HRAS FAM161A KCNQ1 NOD2 NOD2 ADK MYCN SLC25A20 POU1F1 TRNH GAS1 AKT3 RAG1 PTPN11 SLC26A2 GATA2 STAR HMCN1 IDH3B SLC7A7 CACNA1S RARB GATA6 DPP6 FGA CBS SUFU TKFC PCCB CASP10 SRP54 SUGCT TNFRSF13C RPS17 B3GAT3 EBP ATP6 PLN TCAP CHRNA3 KCNH1 KRT5 MED12 MRAS LMOD1 TNFSF11 MYLK2 DCDC2 CAT FGFR3 CYP11B1 P2RY11 FLAD1 ADA XRCC4 MECP2 KCTD1 ND3 ACAD9 GBA CLCF1 NUMA1 TNFRSF11A FBXL4 ASXL1 GDF3 F5 MRAS ROR2 NUP107 HCN4 TNFRSF11A TWIST1 CEP290 IRF8 HLA-DRB1 DDX6 TAZ ZIC3 SEMA4A SCN4A NDUFV1 DNAAF1 LPL HOXA11 TRAF7 ERCC4 CACNA2D1 SPTB FGFR1 RBM20 NDUFA13 BCORL1 PIGW SMOC1 KRT5 ATRX ACTG2 FOXH1 COG7 MUC5B GATAD1 PRKCD HSD11B2 BGN STAG2 NPPA NDUFAF3 MYPN PSAP ABCA1 PTEN TNNI3 KCNJ2 RBM10 GANAB TACR3 CD244 PEX14 KANSL1 TNFSF12 MAP3K7 DBH COG2 SDHB IDS DNAAF3 DNAAF3 MC2R BSCL2 TNFRSF4 NAGS MYMK B2M LDLRAP1 CPN1 CAV1 DYRK1A MYOC HLCS ALPK1 KCNJ5 SCN5A SMO NONO FLT4 MAPT LEP CYP7A1 GPC6 CASQ2 TAB2 CPOX ITCH USP45 RYR2 DPM3 ZNF423 CRYAB CEP120 KIF1B SPIB NKX2-5 SELENOI PIGL FGFR1 NDUFS8 NDUFB8 CACNA1C SPEF2 NECTIN1 PBX1 AEBP1 POMT1 RAC2 JAK2 SCN5A COQ4 TBL2 BMP2 BBS2 GINS1 CFAP298 AKR1D1 TBX19 SYNE2 ACTA2 METTL5 DNAH5 WIPF1 POMT1 TLL1 CSNK2A1 MEG3 FGG LMNA KRIT1 OFD1 GATA6 IL12A TPM3 IL6 TRNT LMNA PPP2R1A SURF1 BRCA1 PSMB8 CACNA1C STAG2 CRKL SEC23A CACNA1D CDKN2B GATC SGCD LRP5 ALX3 TAZ COL5A1 MUC5B SEMA3E MRPL12 TCTN1 CDON PROS1 SRSF2 BAP1 FXN PIK3CA FOXRED1 DPP9 ARF1 RAF1 CD79B HEXB SDHC XRCC2 FGFR2 MYPN ZIC2 CALR ITGA7 LTBP2 RPGRIP1 TRIP11 APC SOX2 ABCA1 EXT2 NF1 SPINK5 DSG4 RTEL1 TNNI3 GPC3 TGFB2 SMAD4 DYNC2I1 TPM1 DMPK POMT2 DCDC2 SKI PIK3CA EBP WT1 ANKRD11 NR3C1 HFE SAMD9L TRNW SMC1A KCNE2 ICOS RTTN RB1 HGD F5 FOXF1 CHST14 GLB1 KRAS NCF1 SMAD6 PTCH1 IL2RG B3GALT6 SF3B4 GLI2 RP1L1 OTULIN F8 TET2 SEC23B ZNF148 COX3 OBSL1 WRAP53 ACTN2 PAX3 NDUFV1 ATP7A HGSNAT GLUL CARMIL2 PDGFB ABCC6 STIM1 KDSR DGUOK PTEN TERT FAT4 ALG1 PSEN2 MYL4 COX14 ITGB3 IGFBP7 PHOX2B CHD7 RBM8A ROM1 NLRC4 F10 PTGIS TMEM70 POLD1 EMD TDP2 CACNA1S PRKCSH NUP155 ALPL PKLR TRNL1 CTC1 PEX5 SDHB GATA6 MYPN ALG10B MEN1 NDUFV2 SDHD CCDC39 HEPHL1 HSD17B10 WHCR ACSL4 GP6 MTMR14 COX1 NAA10 FGFR3 EP300 TNNI3 GMPPB NDUFS4 LZTFL1 CTNNB1 INPP5E KCNJ8 HCRT HLA-DRB1 DKC1 TERT SCN10A GGCX KRT8 ERCC4 SFTPB LMBR1 NDUFAF1 RFT1 CCDC65 HDAC8 HBA1 POMT1 SEC61A1 SLC25A11 FLII CLIC2 CPT2 ATP6 DHCR24 COA8 CAV3 LFNG RLIM SUZ12 MARS2 NEU1 XIAP HLA-B BTD SREBF1 FGFR2
    HP:0000819: Diabetes mellitus
    Genes 567
    LHX1 BLK MERTK PROK2 UBR1 MTHFR MAGEL2 UBR1 NODAL ND6 NDUFS4 RETN TRNL1 MAGEL2 TRNK POLA1 GTF2IRD1 TRNC SLC7A14 RP1 HNF1A CTRC CAVIN1 BRAF RTL1 BBS1 FGFR1 PDE6A CNGB1 LIPE ZNF408 HNF1B TRNS2 GCK HNF4A SHH CTNNB1 BMP2 HYMAI DCAF17 PTF1A TOPORS CFTR KCNJ11 OCA2 SPINK1 ENPP1 AMACR MTNR1B ND1 TCF4 RBP3 ELMO2 PRSS1 SAG MAPK8IP1 PAX4 TP53 NDN FUZ DLL1 PROKR2 RTL1 PCNT SIM1 CLIP2 ABCC8 ELN KCTD1 PIK3R1 TTC7A IRS2 IGF1R GNAS EDA2R ABCC8 PIK3R1 OFD1 PLIN1 CNBP PEX10 COX1 ELN KLF11 SLC19A2 TULP1 LMNB2 PEX6 AKT2 NDUFV2 NDUFAF5 HFE GLIS3 SNRNP200 INS FOXP3 HMGA1 LIPE TRMT10A XRCC4 NEUROD1 HESX1 PTRH2 MTHFR PDE4D NSMCE2 GLRX5 HAMP HNF1B TRNW NPAP1 PPARG SUFU RP9 IFT88 IRS1 RHO PLAGL1 BLM TDGF1 PRSS1 AKT2 PDX1 TRNW ARL3 RPGR HNF4A GPD2 LMNA PDE6B USB1 MEG3 NDUFB10 SNORD115-1 ZNF513 DNAJC21 WFS1 XRCC4 SOX3 SLC25A4 IL2RA RLBP1 NDUFA11 MKRN3-AS1 PRKAR1A NDUFS3 HJV TKT FAM161A GCK LIG4 ROM1 GJA1 TRNS1 TRNH BLM COX1 SNRPN TTC8 PDE8B AGPAT2 TREX1 TINF2 LMNA AIP DCAF17 ND2 IFIH1 BRCA1 IDH3B DNM1L PDE4D GJB4 USP8 BEST1 PWRN1 GATA6 IPW RP2 ND1 GATA6 ARNT2 SLC19A2 APPL1 ND4 PDX1 FOXRED1 TRNF STAT1 INSR IMPDH1 GATA3 SLC2A2 DHDDS EIF2S3 IL6 CNOT1 HLA-DRB1 GPR101 PPARG TRNQ GCK RPE65 ATP6 SNRPN ZBTB20 CISD2 TRNS1 INS CAT SPATA7 RAC1 NDUFB11 HNF4A PALLD RNASEH2B TRNE XRCC4 NDUFAF8 ARHGEF18 STAT1 CYTB LIPC GCK EDA HBB MMP2 OCA2 ZFYVE26 FOXP3 TRNF KLHL7 ALMS1 CP SEMA4A USH2A FGF8 SBDS HBB CERKL INS CYP19A1 APPL1 RNASEH2A TRNS2 ZFP57 GJA1 CDON TIMMDC1 FGFR1 POLR3A AGPAT2 MAGEL2 HNF4A ZFP57 ND1 FOXH1 PRPF8 IARS1 SPINK1 PAX4 HNF1A NDUFAF3 GAS1 CDHR1 NPM1 STUB1 PWAR1 CPA1 KCNJ11 EYS HNF1A IL18BP DISP1 PDX1 VANGL1 CEP19 POLG2 CARS1 CLRN1 HNF1B NDN MKRN3 KCNJ11 BSCL2 OCA2 ZIC2 SRP54 CAV1 CFTR DHX38 IFT172 PPARG FXN WRN PLIN1 INSR WRN NDUFB9 WFS1 DLK1 MMP14 LEP PTPN1 ARL2BP PRCD EIF2AK3 CIDEC ITCH PRPH2 CDH23 NEK2 ATM PTRH2 TTPA SLC29A3 NDN NKX2-5 PDE11A NDUFS8 REEP6 AGBL5 ZMPSTE24 PROM1 NDUFS6 TRNK AEBP1 PRSS2 LEPR TBL2 BBS2 COL2A1 LRP6 GCK POC1A PDX1 CTNS CORIN PNPLA2 IFT140 PPP1R15B FOXP1 RFC2 CTRC NDUFS1 LMNA PTPN22 SNORD116-1 LEPR RNASEH2C RRM2B LIMK1 BLK NOTCH3 HMGA2 TWNK CNOT1 FLT1 NEUROD1 KCNJ11 ABCA4 IDH3A CDKN2A NDUFA6 KIZ ABCC8 ATM BRCA2 ND6 NDUFS2 LMNA ND3 IMPG2 MST1 TGIF1 PAX4 WFS1 KCNJ11 FXN NOP10 KDSR MEG3 OPA1 TRNQ TUB HYMAI CISD2 DNAJC3 STOX1 IL2RA NDUFS7 NDUFA1 NUBPL BSCL2 PEX1 COX2 SPINK1 PAX4 RTEL1 INS NDUFB3 COX3 CASR SMAD4 GCK ITPR3 SNRPN HBB POLG NDP OTX2 SLC12A3 TRNE PNPLA6 APOA5 LMNA GCK STAT3 POMGNT1 PDE6G WFS1 GLI2 CLCNKB ALMS1 AHI1 LEMD3 HNF1A BBS2 GJB3 ABCC8 TP53 ITCH RP1L1 PLAGL1 LMNA PALB2 NDUFAF2 CRB1 CNGA1 DMPK PPP1R3A PNPLA2 PTCH1 WRAP53 STAT3 SAMHD1 HYMAI NDUFV1 HGSNAT HNF1B HNF4A SLC29A3 ARMC5 CCDC28B KRAS GTF2I MAGEL2 TWNK HNF1A PRPF3 VANGL2 GUCA1B TMEM126B EIF2AK3 TRNV TERT KCNJ11 PTF1A FBN1 IGF2BP2 ARL6 COX2 HFE AIP NR2E3 PCARE MAK KCNJ11 HLA-DQB1 ABCC8 NDN PLCD1 NDUFAF4 POLD1 CEL VANGL2 NSMCE2 PSTPIP1 SOX2 SIX3 ND5 TCF7L2 NEUROG3 MKKS CAV1 SMPD4 SLC16A2 PDX1 FSCN2 PRKACA CA4 MC4R TRNL1 PRKACA CTC1 ADA2 PRSS2 SNRPN RGR AHR DMXL2 PRPF4 KLF11 ADAR SARS2 MOG MEN1 HERC2 CP ND5 INSR LRAT MAFA EFL1 HNF1A TERC FOXC2 SCAPER FOS CRX DLK1 KIAA1549 MAGEL2 MLXIPL DNAJC3 PRPF31 AIRE PRPF6 PARN DKC1 NEUROD1 APOE PPARG WFS1 ABCC8 LRBA AR NRL NHP2 GPR35 BAZ1B RDH12 ERGIC1 ARL6 NDUFAF1 SLC30A8 PDX1 COX3 ABCC8 INS C8ORF37 IER3IP1 PRKAR1A KCNJ11 CEL INS TRNL1
    HP:0002094: Dyspnea
    Genes 438
    TLL1 MAT2A TRNK DSP CHRNA1 LMNA CSPP1 TRPV6 AIFM1 NPM1 ZBTB16 EFTUD2 TGFBR2 LAMA3 SFTPA1 SH2B3 IKZF1 ND1 DNAJB6 BTNL2 COPA KCNJ6 USP9X GAA MEGF10 KRT16 GATA6 GATA4 FGFR2 APOB CASR MYL3 ZIC3 NKX2-1 PLEC PURA AIMP2 DCTN1 DOK7 KCNA1 SCNN1B SCN4A CDC6 LAMB2 DYNC2LI1 RARA ALAS2 VAPB IRF5 PMM2 STT3B ADNP SCO2 MUSK MYH6 ABCA3 TSC1 ATRX FOXF1 CHRNA1 ORC4 FOXP3 TERC USP9X CAV1 ND4 CBL COLQ COL2A1 EPHB4 FGFR1 NOD2 STAT5B MAPT COL2A1 TARDBP CREBBP FBP1 ACTA2 BMPER SLC35A1 SOX9 MATR3 CCR6 PRRT2 MFAP5 GLA RELN CHRNE AK9 SLC5A7 CHRNB1 COL13A1 CSF2RB SCN4A DISC1 TRNV PRPH FGFR2 ACVRL1 PYGM TRMU RNF13 CHRNE NDUFB11 SLC25A4 DNA2 NAGS ACADVL MRPL3 VPS33A TRPM4 NGLY1 MYH11 NEFH TRIP11 CRELD1 SCN5A SCO2 CAV1 ND5 ORC6 PUF60 SMAD4 SMPD1 CYB5R3 GATA6 XYLT1 KAT6A KIF20A EDA SNRPN RPS28 GNAI3 CCNF TTN CDC45 ZMPSTE24 STN1 PRKCSH SBDS TRNN VCP MYL2 VCP TBX20 CSF2RA ND3 TRNK GBA ISCU TGFB2 NUMA1 GATA4 TERT SCNN1G MMACHC SFTPC ATP11A NKX2-5 HBB EIF2AK4 SPP1 CITED2 LDLRAP1 MMAA MYBPC3 ERBB4 DAO ZFPM2 ALMS1 CHRND ORC1 PURA SCN4A TUBB4A SFTPC ALDH7A1 LDLR DNASE1L3 IFT81 MUC5B MARS1 SSR4 EPHA4 CHCHD10 CHMP2B ENG MPC1 NPPA CCN2 ARX MGME1 DPM2 TSC2 PLCB4 AGRN TAF15 NUP214 TRIP11 NKX2-5 TSC2 MMUT PCSK9 OPTN POLG2 JPH2 DBH SCN1B TERT SLC18A3 FOXE3 TRNL1 RTEL1 PRKG1 OTX2 NABP1 DNAAF3 DPM2 DNAJC21 NAGS GALC SFTPB LIFR TNNT2 RUNX2 GLE1 HLCS ACTC1 VAMP1 TRNE BMPR2 ADAMTS13 ND2 UNC13A SLC25A1 ELN SFTPA2 TBK1 GATA6 SFTPB SCNN1A SERPINA1 PFN1 RAPSN LYRM4 CHRND MYH11 CRLF1 EOMES SLC2A10 NDUFB8 GBA MMUT POMT1 COQ7 ERF VCL UBE3B ETFDH SCN5A PON2 CFTR FLNC SDCCAG8 WIPF1 PARN HCCS BCOR GYG1 LAMC2 RRM2B ITGA3 GATA6 GTPBP3 FIG4 NEB TWNK STAT5B SFTPC SURF1 LTBP3 CSF2RB COL1A2 ABCA3 TBC1D24 GAA STAT4 SIK1 C9ORF72 DNA2 MUC5B TK2 SRSF2 TRNS1 DPP9 SMAD3 CITED2 CFAP410 FLNC STAT3 TNNI3 PRKAR1A CHRNE LOX TNNC1 TRAK1 ORC6 CYB5R3 CHRNB1 EDN1 FAM20C PON1 HNRNPA1 FBP1 HBB POLG STT3B DMPK SLC12A3 TRNE FBN1 SETBP1 NDUFAF3 ATXN2 PRRX1 TRNW ETFB RNU4ATAC SFTPC CNTNAP1 HLA-B CHAT PIGT TSC1 STX16 CLCNKB PGM1 CDT1 COX7B SLC25A1 B3GALT6 RPS26 IRF2BP2 TRMT5 TET2 ASXL1 ABCG5 WAS LGI4 PSAP PNKD SURF1 LRP4 PRRX1 TET2 GLT8D1 MGME1 ASAH1 DHX16 SRP54 GBA LAMB3 MYO9A MMAB IL1RN DSC2 ACADM IRAK1 RUNX1 TGFBR1 CYB5A COL13A1 ANG GNAS GMNN KLHL7 TBX20 ABCA3 ANXA11 NDUFS2 EPOR IFT52 UBQLN2 SFTPA2 FAM13A PON3 SLC52A3 KRT17 KRT6A ADCY6 HLA-DRB1 TET2 BMPER CPT2 MYLK PML MYPN TGFB3 AGRN SLC25A3 TBX4 FIP1L1 JAK2 KRT6B NEK1 SYT2 TBL1XR1 TREM2 GNAS ND6 FGFR2 EP300 MAPT ORC1 PPARGC1A DPM1 FGFR2 SQSTM1 HLA-DRB1 SOD1 HLA-DRB1 NKX2-1 TLL1 SNAP25 GNAS TERT FUS ATP6 ABCG8 NR2F2 COA8 ETFA VPS33A SERPING1 BTNL2 CHAT PRKAR1A
    Protein Mutations 0
    SNP 0
    HP:0001945: Fever
    Genes 374
    NLRP3 PSMB4 CHD7 NABP1 PTPN22 TRNK MTHFR ND6 GALC IGH SCYL1 LIFR TREX1 BCAP31 EIF2B5 G6PD NPM1 ZBTB16 ABCC2 EPB41 CTRC DDB2 CD247 ADAMTS13 POU6F2 ND2 IFNG NTRK1 LAMA3 SCNN1A IKZF1 ND1 SLC29A3 TNFRSF1A RAG2 NLRP3 CFTR CRLF1 TP53 MALT1 CD70 ATM CACNA1S TCF4 SLC19A3 PRSS1 IL12B HLA-DPA1 JAK2 XPA CPT2 PRSS2 CFTR IL10 NAB2 ATP13A2 NCF4 REST WIPF1 NLRP3 NCF2 IGH SPTA1 SCNN1B CHEK2 H19 PTPN3 CYBC1 HTR1A BCOR LAMC2 RYR1 RAG2 TMEM165 RNASEH2C RARA DST IL6 PMM2 NCF1 CYP11B2 CD3D COX1 UNC93B1 RB1 TRAF3 MPL PSMB8 EIF2B4 IL36RN MYD88 GCH1 TH TSC1 GAA CYBA HLA-DPB1 RIPK1 NLRP12 STAT4 SPTA1 MLX TRIP13 AVP CFHR1 ELANE MPL AVPR2 P4HTM ND4 IGLL1 MST1 SLC22A4 PTS LPIN1 TRIM28 TCF3 HNRNPK IGHM CD79A PIK3R1 NOD2 MTHFR RANBP2 RYR1 LACC1 AVPR2 STAT5B STXBP2 TRNW CD79B CTLA4 NLRP3 TET2 SPTB EIF2B2 HAVCR2 HLA-DRB1 ERCC3 CYBB CD3E BCL2 DIS3L2 FOXP1 IL23R COX2 SPINK1 STAT3 GLA PRKAR1A KCNJ1 RNF168 COX3 IL7R NLRP3 TRNV FBP1 STAT2 HBB IGH GALC STX11 MEFV SLC12A3 BACH2 LPIN2 STAT3 ATP1A2 CFH CALR SLC35C1 WT1 LIFR PEX6 TRNW PRTN3 EPB42 HMGCL MEFV NOD2 HLA-B TRNS1 DCLRE1C NGLY1 IBA57 TLR4 TRNH JAK2 RAG1 ORAI1 PMP22 CYBC1 MVK AQP2 PRNP ATP1A3 CACNA1A TREX1 MEFV GATA2 ERCC2 BRCA2 OTULIN BCR ND5 IRF2BP2 IFIH1 IFNGR1 WAS RYR1 CASK NLRC4 PSAP ERCC5 ZFHX2 NLRP3 SAMHD1 COL1A1 ND1 SH3KBP1 ASAH1 SLC29A3 LACC1 TCIRG1 ND4 TNFRSF1A MEFV ACAT1 STING1 STAT4 EDA SRP54 ELP1 LAMB3 VANGL2 RMRP IRF8 IRAK1 C4A QDPR TRNQ COL1A1 KLHL7 CCND1 CCR1 UNC13D EIF2B1 UBAC2 BTK BIRC3 HNRNPK MEFV CD27 TP53 ADA RNASEH2B FAS NLRC4 CFHR3 PSMB9 BCL10 TNFAIP3 PRF1 TICAM1 ND3 VANGL2 PSTPIP1 BCL6 SLC4A1 NUMA1 PADI4 CACNA1S JAK2 HMBS TRNT1 CYP21A2 SCNN1G F5 MIF NTRK1 EIF2B3 ALPL ITK CALR ERAP1 RAB27A WDR1 HBB SPP1 MYD88 TRNL1 TLR3 ADA2 LBR IRF8 HLA-DRB1 PTPN22 TET2 STIM1 KIF1B LYST PML TRIM28 TRNF ADAR NLRP3 GYPC FIP1L1 RAG1 STAT6 TBK1 ELANE ND5 HAVCR2 HMGCL TBL1XR1 COG6 KLRC4 PTPN22 AQP2 XIAP ND6 HLA-B RNASEH2A TRNS2 IL2RG SPTB NLRP1 POLR3A HLA-DRB1 LIG4 AK2 IL10 HLA-DRB1 PRKCD MVK NKX2-1 KRT18 LRRC8A SLC12A1 IL12A-AS1 ABL1 KRT8 GPC3 ELANE LPIN2 GPR35 CYP11B2 CIITA RUNX1 BLNK TSC2 WT1 IL2RG IL7R ERCC4 ATP6 ANK1 SH2B3 IL12A CD244 LIPA RAB27A GFI1 NGF SLC11A1 CYTB POMP NFKBIL1 BTNL2 XPC HLA-B TRNL1 PRKAR1A
    Protein Mutations 0
    SNP 0
    HP:0002090: Pneumonia
    Genes 280
    TLL1 CHD7 TGIF1 KMT2D ACP5 PIGN JAK3 NOS1 SFTPB SRP54 MS4A1 NODAL USB1 CD79B SGCG ACTC1 CASP8 TGFB1 OFD1 CD19 CD247 NHLRC1 SHH NTRK1 EGFR LAMA3 PLOD1 FANCF JAK3 RAG2 PGM3 CACNA1C BTK IL2RG PIK3CD CREBBP KCNJ6 FMO3 ACTA1 TNFSF12 GATA6 ZAP70 PLOD1 UNC119 FGF8 GAS1 DNAI1 WAS GNPTAB FOXH1 CYBC1 LAMC2 RAG1 PEPD PDHA1 PMM2 PAFAH1B1 CD19 CD3D SIX3 CD81 DLL1 LTBP3 EP300 TNFRSF13B SIX3 GLI2 SMARCD2 TIMM8A MYH6 DCLRE1C ABCA3 IL7R TBC1D24 STAT3 CFB FOXH1 FOXP3 FCGR2A P4HTM AP3B1 POLA1 TK2 CDON PKHD1 TAF1 CDON NIPBL GRHL3 GAS1 EFEMP2 CRLF1 SLC35A1 SLC25A24 DOCK8 ZIC2 LEP AFF4 DDR2 CD3E PTPRC BLM RNU4ATAC TNFRSF13C KNSTRN CDON SELENON FOXH1 ORC6 RAG1 RNF168 SHH DISP1 CYBA IL7R CARD11 LONP1 COL11A2 CR2 FGF8 ZIC2 CARD11 CYBB NBN ICOS DNAJC21 DNMT3B DISP1 TGIF1 HLA-DQB1 ADA SETBP1 MED25 FOXH1 SLC35C1 ACADVL TDGF1 PNP SP110 SMC1A ICOS SREBF1 TDGF1 NBN DCLRE1C ALMS1 GLI2 MCIDAS FGF8 NCF1 RAG1 PTCH1 NADK2 IL2RG ZBTB24 ZAP70 GLI2 FGFR1 GAS1 TNFRSF13B GAS1 IFNGR1 CFTR COL11A2 CR2 SAMD9 CD247 TGIF1 TREX1 CARMIL2 TCIRG1 BLNK UBB SRP54 LAMB3 DISP1 RMRP TNFRSF13C NFKB1 STAG2 IRF8 PTCH1 SIX3 KPTN TBX20 TDGF1 CSPP1 IGHM BTK NFIX RNU4ATAC CXCR4 NFKB2 RAC1 CD27 TGIF1 ADA TBX20 ZIC2 MTHFD1 RAG2 GATA4 TNFRSF11A DZIP1L FGF8 KIAA0586 SHH TDGF1 RYR1 ODAD1 WDR1 CREBBP CITED2 DLL1 NCF2 TBCD SHH NODAL RAC2 SIX3 GBA PTCH1 DNAI2 ZIC2 TNFRSF13C ALMS1 PURA STAG2 DLL1 SBDS ICOS EFL1 ACP5 SFTPC CFAP410 MASP2 IL2RG IGLL1 AFF4 BTK LIG4 NFKB2 WDR19 CD55 CDON GAS8 EPM2A NKX2-1 RNF125 DCLRE1C NODAL LRBA ELANE MAN2B1 DLL1 PTCH1 HLA-DQA1 EXTL3 SLC35C1 MAN2B1 FOXN1 PRKCD GLI2 RANBP2 MID1 IL2RG FBLN5 NKX2-5 NODAL GFI1 TNFSF12 RAG2 ADA IL21R KDM6A OSTM1 ASAH1 DISP1 PANK2 FGFR1
    SNP 0
    HP:0011947: Respiratory tract infection
    Genes 816
    KMT2D SMARCB1 ABCA12 TNFSF11 TRAIP MAGEL2 DNAAF1 NFE2L2 NFKB2 LCK MAGEL2 SGCG TECPR2 GTF2IRD1 CHAMP1 OFD1 SCNN1G CD247 MGP SPINK5 CTPS1 NTRK1 NGLY1 RELB ZNF341 RSPH9 FCN3 NELFA MALT1 CFTR OCA2 LETM1 PIK3CD FMO3 USP9X HLA-DPA1 DNAH11 ZAP70 UNC119 WAS SIM1 GNPTAB FOXH1 CFAP221 TARS1 LAMB2 MYO5A CD81 ADNP TNFRSF13B MYH6 TSC1 CYBA HLA-DPB1 GNS FOXH1 LIPN KATNIP TPM2 COL6A1 NIPBL SPAG1 IL17RA GAS1 SLC12A6 EFEMP2 CRLF1 GMNN CTLA4 SLC35A1 ADAMTS3 TAPBP SLC25A24 CXCR4 BLM RNU4ATAC CFAP300 FOXP1 CDON CD79A RAG1 VPS51 DISP1 USB1 NEPRO COL11A2 CR2 LAMTOR2 SNORD115-1 MAP3K20 DNMT3B MKRN3-AS1 LYST PIK3R1 ACADVL TDGF1 RFX5 VPS33A MDM4 TBC1D24 NGLY1 GLI2 FGF8 ODAD4 CCDC40 MCM4 CRELD1 ZBTB24 TINF2 ECM1 LRRC6 CFTR COL11A2 CR2 ELP1 TFRC AGA SMPD1 PWRN1 IPW TCIRG1 BLNK FLI1 UBB KIF20A STAT1 MBTPS2 ELP1 SNRPN DISP1 RMRP STAG2 IRF8 SIX3 KIF1A RYR1 IGHM BTK CYP4F22 CXCR4 RSPH1 CCBE1 DNAH11 ZIC2 CSF2RA POLR3A LAMA2 STAT1 SNX10 FGF8 FOXJ1 AICDA SHH RYR1 ODAD1 SIK1 HACD1 CREBBP TNFRSF13B CITED2 OCA2 NODAL NOTCH2 CFAP298 SELENON ZIC2 ALMS1 ODAD4 IDUA DLL1 SBDS COG6 TBX6 RFXAP PEX13 TCTN3 PTPN22 SFTPC MAGEL2 COG4 EPM2A MESP2 TTC12 TBC1D23 SCNN1B TGFB1 MAN2B1 PTCH1 NPM1 EPG5 UGP2 GLI2 GAS2L2 TSC2 RANBP2 SCN11A CTLA4 MESP2 IL21R IL17RC UMPS SLC18A3 MYSM1 TRPS1 MKRN3 RPGR DSG1 ACP5 JAK3 EXOSC9 MIR140 DNAL1 NCF4 ACTC1 VAMP1 TGFB1 CD3E IDUA FANCF PLCG2 SLC29A3 NDN RAG2 RAG2 SLC46A1 PGM3 GBA IL2RG SULT2B1 DNAJB13 SDR9C7 MSN MYOD1 FCGR3A SHROOM4 PNP ACTA1 ERF MYSM1 LEPR FLNC NCF4 ODAD2 RFXANK KAT6B DNAI1 NEK10 DNAI1 MPLKIP AGA LAMC2 RAG2 LEPR IL17F DCLRE1C LIMK1 PEPD ITGA3 ZBTB24 NCF1 CD3D EP300 IL2RB GLI2 COL6A3 FBLN5 TASP1 DCLRE1C PYROXD1 IL7R TBC1D24 PLCG2 GAA ODAD3 NFKBIA IL17RA KRAS IGLL1 SCNN1A ODAD3 TK2 TPM3 RNF113A IGHM CCDC39 MS4A1 SMN1 SMARCC2 LEP CYBB NEU1 CD3E PTPRC PLG FOXH1 TNNI3 TYK2 ORC6 RNF168 CARD11 CD3G LONP1 GNPTAB IDUA CYBB NBN NRAS DNAAF6 TGIF1 WAC ADA STAT3 SETBP1 CD3D STAT3 RSPH4A HLA-B TSC1 DNMT3B ITCH GAS1 NEK10 CCDC22 SAMD9 CD247 CFI TREX1 ASAH1 INPPL1 MECP2 HYDIN DNAAF2 IL6R LAMB3 NFKB1 RUNX2 KANSL1 PTCH1 TDGF1 RAG1 UBE2A NFKB2 PIK3CD SMN1 TGIF1 HELLS RSPH9 MTHFD1 SMARCD1 OCRL SLC52A3 DZIP1L TDGF1 WDR1 ALB ADA2 DLL1 SHH SIX3 MYL2 STAG2 EFL1 TERC CFAP410 MASP2 GLB1 LIG4 PARN NFKB2 EDARADD DNAAF6 BCR RNF125 TLL1 DCLRE1C SCNN1A ASAH1 SNAP25 NHP2 DNAAF5 DLL1 EXTL3 PRPS1 MAN2B1 ZMYND10 FOXN1 PRKCD BLNK IL2RG IL7R SMPD1 NODAL NECTIN1 LAMTOR2 RAG2 ROR2 ADA IER3IP1 KDM6A TLL1 ALOXE3 TGIF1 PIGN NOS1 NXN DNAH1 MS4A1 NODAL USB1 LRRC56 ATP6V0A2 EPG5 CASP8 PRPS1 IKBKB ARID2 SHH ARID1B EGFR LAMA3 IKZF1 PLOD1 PRKDC JAK3 DNAAF4 BTK PEPD SCNN1B KCNJ6 GAA MCIDAS SOX4 ZMYND10 UNG GATA6 GATA4 SLC26A2 NDN CD81 NKX2-1 PLOD1 PLEC FGF8 GAS1 ABCA12 IGH CLIP2 SCNN1B CYBC1 RAG1 CLEC7A DRC1 TCIRG1 PMM2 PAFAH1B1 TGM1 DLL1 SIX3 TIMM8A ELN FUCA1 SPAG1 ARID1B ABCA3 ARSB CFB SOX11 FOXP3 USP9X P4HTM AP3B1 POLA1 CDON PKHD1 TAF1 COLQ TCF3 TRIP4 STXBP2 CREBBP NPAP1 STK36 DOCK8 DDR2 CD8A CCDC65 INPPL1 TNFRSF13C KNSTRN SELENON LRRC6 SLC5A7 SHH IFIH1 IL7R CIITA ZIC2 FLNA G6PC3 BACH2 ZNHIT3 DNAJC21 SH2D1A CCNO COL13A1 DISP1 IL21 HYDIN MGP IL2RA MED25 GSN FOXH1 SLC35C1 PNP PRTN3 SP110 ARID1A NBN MCIDAS RAG1 TAP1 SNRPN NADK2 ZAP70 MAGT1 FGFR1 GATA2 ALOX12B IFNGR1 NFKB1 DOCK8 AP3D1 STING1 B2M SRP54 TNFRSF13C TTC12 TAP2 KPTN SNRPN DNAI2 CHRM3 CCNO RAC1 ADA TBX20 ODAD2 BCL10 FLNA SLC25A22 RAG2 GATA4 DNAH9 SMARCA4 TNFRSF11A IRAK4 GUSB CD40LG SCNN1G GUSB KIAA0586 NSD2 DPF2 GBA NCF2 GAS2L2 MYH3 TBCD PTPN22 RAC2 PTCH1 DNAI2 TPP2 RAG1 KANSL1 PURA LRRC56 DNAAF1 SCNN1G IL6ST ACP5 XIAP IL2RG IGLL1 AFF4 SCNN1B BTK PCNT CDON COG4 PRKCD LRRC8A PSAP HLA-DQA1 DYNC2I2 SLC35C1 PWAR1 SLC1A4 CR2 TBCE AGRN CTCF FBLN5 TRIP11 NKX2-5 TSC2 GFI1 TNFSF12 GAS8 MAPK1 DNAAF2 SCNN1A ACTA1 NDN IDS PANK2 FGFR1 CHD7 DNAAF3 DNAAF3 DPM2 OCA2 PCGF2 SFTPB MANBA TNNT2 SRP54 CD79B CD19 FOXJ1 LEP NHLRC1 GATA6 SCNN1A SERPINA1 ATM DNAJB13 CLCN7 CACNA1C SPEF2 CREBBP TNFSF12 COL6A2 RAC2 TBL2 CFTR CFAP298 RSPH3 SDCCAG8 DNAH5 WIPF1 NCF2 FOXP1 RFC2 SNORD116-1 POLR2A CCDC103 OFD1 DNAAF5 PDHA1 CD19 SIX3 LTBP3 SMARCD2 CSF2RB PSMB8 CRKL EP300 RSPH1 ATM DCTN4 CLCA4 CTSC STAT3 FCGR2A DNAH5 CDON TRAF3IP2 IDS CD79A PIK3R1 GRHL3 NOP10 HPS6 RPGR SCNN1G CD79B IVNS1ABP ZIC2 AFF4 ITGA7 ERCC2 RAB3GAP2 RTEL1 CYBA SCN9A RASGRP1 FGF8 SNRPN CARD11 POLE ICOS NME8 HLA-DQB1 PGM3 CDCA7 SAMD9L SMC1A ICOS GLI3 SREBF1 CHAT RFX5 TDGF1 CCDC40 SMARCE1 DCLRE1C ALMS1 NCF1 RSPH3 CYBC1 SLC25A1 PTCH1 IL2RG GLI2 GAS1 TNFRSF13B WAS EHMT1 WRAP53 TGIF1 GLUL SH3KBP1 RFXAP CARMIL2 GTF2I TNFRSF1A MAGEL2 HGSNAT MYO9A GTF2H5 TERT RYR1 FAT4 RIPK1 COL13A1 JAGN1 CIITA TBX20 CSPP1 DNAAF4 HK1 NFIX RNU4ATAC BIRC3 IKBKB CD27 NDN TGFB1 PIK3R1 CREBBP ALPL CCDC103 NAGLU ODAD1 CTC1 SNRPN PRPS1 DLL3 LYST GBA NME8 MYPN STX1A TNFRSF13C HERC2 ELANE CORO1A SYT2 CCDC39 CFTR ICOS RFXANK EP300 MAGEL2 WDR19 ALG12 AK2 CD55 GAS8 DKC1 NKX2-1 SCN10A NODAL LRBA ELANE GTF2E2 SGSH BAZ1B PLP1 CACNA1B RSPH4A CCDC65 MID1 NR2F2 ERCC3 WASHC5 NIPAL4 VPS33A CD19 GALNS OSTM1 XIAP ASAH1 DISP1
    Protein Mutations 1
    H275Y
    SNP 0

    HPO

    Alphabetical listing of all HPO terms. Navigate: Correlations   Clinical Trials


    Related HPO nodes (Using clinical trials)


    HP:0002088: Abnormal lung morphology
    Genes 1425
    KMT2D SMARCB1 ABCA12 MAT2A TNFSF11 TRAIP MAGEL2 DNAAF1 NFE2L2 MITF NFKB2 LCK MAGEL2 SGCG ALG9 TECPR2 GTF2IRD1 CALCRL KAT6B CHAMP1 OFD1 CTRC SCNN1G CD247 MGP TGFBR2 SPINK5 CTPS1 RASA2 NHLRC2 PHGDH RTEL1 NTRK1 NGLY1 ARVCF SLC2A10 RELB ZNF341 RSPH9 FCN3 NELFA RREB1 NAA10 MALT1 HPGD CFTR GLI1 OCA2 LETM1 NPHP3 PIK3CD FSHR FMO3 USP9X TCF4 WDR35 PRSS1 HLA-DPA1 DNAH11 RIT1 ZAP70 STK11 NKX2-5 UNC119 CDC45 BUB1B SNAI2 WAS SIM1 GNPTAB DYNC2H1 FOXH1 CFAP221 TARS1 NF1 NEB LAMB2 TTC7A CCR6 RARA ACTL6B MYO5A CD81 ADNP TNFRSF13B SEC24C TBX1 MYH6 COL3A1 TSC1 CYBA HLA-DPB1 TERT GNS FOXH1 EVC2 LIPN KATNIP TPM2 RRAS2 TSC1 EPHB4 COL6A1 NIPBL SPAG1 FLNB IL17RA HSPG2 ITGA8 GAS1 SLC12A6 EFEMP2 CRLF1 SLC26A2 GMNN DGCR8 ACTA2 CTLA4 SLC35A1 ADAMTS3 TAPBP SLC25A24 PRKCD SPECC1L CCR6 CXCR4 HOXD13 BLM RNU4ATAC CFAP300 FOXP1 CDON CD79A TTC21B CBL RAG1 VPS51 DISP1 USB1 NUP107 NEPRO COL11A2 FLNA CR2 ACVRL1 LAMTOR2 NEK1 SNORD115-1 GLE1 MAP3K20 DNMT3B SLC26A2 FAS MKRN3-AS1 LYST PIK3R1 ACADVL LIFR TDGF1 TAPT1 RFX5 VPS33A MYRF MDM4 HRAS TBC1D24 NGLY1 GLI2 FGF8 ODAD4 CCDC40 MYH11 C11ORF95 MCM4 CTLA4 CRELD1 ZBTB24 TINF2 ECM1 CAV1 NAA10 LRRC6 PUF60 CFTR FLCN COL11A2 CR2 FOXE1 CCBE1 ELP1 TFRC AGA SMPD1 PWRN1 MMP21 IPW GATA6 LACC1 TCIRG1 SERPINF2 BLNK IFT80 FLI1 UBB KIF20A STAT1 DLL4 MBTPS2 PAX3 ELP1 SNRPN DISP1 RMRP TGFBR2 KRAS STAG2 IRF8 SIX3 SOX10 KIF1A RYR1 IGHM BTK NOTCH3 DICER1 CYP4F22 CXCR4 RSPH1 MEFV CCBE1 DNAH11 ZIC2 WDFY3 CCND1 CSF2RA POLR3A BCL6 LAMA2 SMAD4 SKIV2L STAT1 SNX10 TERT FGF8 BRAF SFTPC FOXJ1 ATP11A AICDA SHH RYR1 ODAD1 SCARB2 SIK1 HACD1 CHRNG CREBBP TNFRSF13B CITED2 OCA2 MYBPC3 NODAL NOTCH2 CFAP298 SELENON CEP57 CTLA4 TRIM28 ZIC2 ALMS1 DOK7 ODAD4 IDUA DLL1 ELN SBDS COG6 TBX6 RFXAP PEX13 TCTN3 PTPN22 DGCR6 SFTPC RAG1 INTU EDNRB FGF20 MAGEL2 DNASE1L3 RASGRP1 STRA6 IFT81 COG4 MARS1 EPM2A MESP2 TTC12 SOS1 TBC1D23 IL12A-AS1 ENG SCNN1B CSF2RA TGFB1 CCN2 FBXW11 MAN2B1 HLA-DRB1 PTCH1 NPM1 EPG5 UGP2 GLI2 GAS2L2 TSC2 PPP1CB RANBP2 SCN11A GPKOW CBL CTLA4 IL12A MESP2 IL21R CRELD1 IL17RC UMPS TERT SLC18A3 MYSM1 DSE TRPS1 PEX1 MKRN3 RTEL1 RPGR DYNC2H1 PRKG1 DSG1 ACP5 FLT4 JAK3 TCF20 EXOSC9 MIR140 DNAL1 NCF4 ACTC1 IFT80 FGFR3 ALG14 VAMP1 RTL1 ESS2 WRN TGFB1 MKS1 DYNC2LI1 EWSR1 FGF20 CD3E POU6F2 ELN IDUA SFTPA2 SFTPB ATP5F1A FANCF PLCG2 SLC29A3 NDN PIGL RAG2 RAG2 SLC46A1 SLC2A10 RET PGM3 GBA IL2RG SULT2B1 DNAJB13 JMJD1C TP53 SDR9C7 BUB1 MSN MYOD1 FCGR3A SHROOM4 PNP COQ7 ACTA1 ERF MYSM1 ZEB2 ETFDH AGTR1 LEPR TBX1 PIGT FLNC DGCR2 NCF4 ODAD2 IFT172 RFXANK KAT6B DNAI1 GBA NEK10 DNAI1 KIAA0586 MPLKIP CCNQ MDM2 AGA LAMC2 RAG2 LEPR IL17F DCLRE1C SPIDR LIMK1 PEPD CCN2 ITGA3 MYT1L ZBTB24 STAT5B NCF1 CD3D EP300 RIT1 IL2RB GLI2 DICER1 COL6A3 FBLN5 TASP1 DCLRE1C FARSA CDC42 PYROXD1 IL7R TBC1D24 PLCG2 GAA ODAD3 STAT4 LTBP4 NFKBIA PKHD1 IL17RA KRAS MCTP2 BPTF IGLL1 SCNN1A ODAD3 TK2 PSMC3IP TPM3 RNF113A MBTPS2 IGHM PDGFRB RAF1 FASLG CCDC39 MUSK FAM111B NDUFAF6 TRIP4 MS4A1 SMN1 MUSK PRKAG2 SMARCC2 HLA-DRB1 CFH LEP CYBB LMNA PSMD12 NEU1 CD3E PTPRC STAT3 PLG CHRNA1 FOXH1 TNNI3 PRKAR1A TYK2 LOX FLCN NEK9 ORC6 RNF168 PTPN11 CARD11 CD3G LONP1 TGFBR1 CC2D2A GNPTAB IDUA TREX1 CYBB NBN NRAS LPIN2 DNAAF6 TGIF1 WAC ADA FBN1 STAT3 SETBP1 ACTA1 STRA6 CD3D STAT3 ZMIZ1 ETFB RSPH4A SFTPC HLA-B TBX5 TSC1 DNMT3B A2ML1 RPL10 RPL10 MEFV TP53 ITCH BRCA2 IRF2BP2 GAS1 ASXL1 NEK10 CCDC22 SAMD9 MYH7 WNT4 DOCK3 CD247 CFI RCBTB1 UFD1 TREX1 ASAH1 INPPL1 NOTCH2 SERPINF2 MECP2 DKC1 KAT6B MEFV GLDN CHRNG HYDIN CDT1 DNAAF2 IL6R LAMB3 NFKB1 RUNX2 IL1RN GLI3 IRAK1 KANSL1 DLL3 PTCH1 TGFBR1 NDUFB10 REN TDGF1 ABCA3 RAG1 KIF11 FGFR1 UBE2A MYOD1 NFKB2 PIK3CD SMN1 FREM2 TGIF1 LAT HELLS ZEB2 RSPH9 NSDHL SERPINH1 MTHFD1 FAM13A SETD2 PAX6 SOX18 SMARCD1 OCRL SLC52A3 BMPR2 DZIP1L TDGF1 WDR1 ALB CD28 ADA2 RAPSN DLL1 RBPJ WDR19 HLA-DRB1 SHH BMPER MYLK TMEM94 SIX3 PML TGFB3 MYL2 STAG2 TBL1XR1 FBN1 EFL1 TERC BUB3 HES7 FOXC2 RBM10 CFAP410 MASP2 TRIP13 GLB1 MEG3 MYH3 LIG4 PARN RHOH NFKB2 EDARADD DNAAF6 BCR RNF125 TLL1 DCLRE1C SCNN1A GPC3 ASAH1 SNAP25 NR5A1 NHP2 DNAAF5 DLL1 EXTL3 PRPS1 MAN2B1 FANCB COMT ZMYND10 FOXN1 PRKCD BLNK NTNG1 IL2RG IL7R EMG1 TRPV4 SMPD1 ETFA IRF5 NODAL WT1 NECTIN1 LAMTOR2 RAG2 ROR2 ADA FCGR2A IER3IP1 CYTB KDM6A BTNL2 WNT3 TLL1 ALOXE3 TGIF1 ASCC1 PIGN BNC1 RIPPLY2 BAP1 NOS1 NXN DSP DNAH1 ITPR1 IGH PIEZO1 CSPP1 COL3A1 ARHGAP31 MS4A1 NODAL USB1 LRRC56 NPM1 TSC2 ATP6V0A2 DHCR7 ZBTB16 EPG5 TINF2 CASP8 PRPS1 IKBKB ARID2 SHH ARID1B RLIM EGFR CDKN2A LAMA3 SFTPA1 IKZF1 CAV1 PLOD1 PRKDC LMNA JAK3 BMP2 AKT1 CFTR ELN AGT DNAAF4 ATP6V1E1 IFT140 BTK BTNL2 COPA PEPD SCNN1B KCNJ6 GAA MCIDAS PTEN SOX4 ZMYND10 UNG GATA6 DYNC2I1 PSAT1 GATA4 SLC26A2 NDN BCOR NAB2 CD81 NKX2-1 PLOD1 PLEC FUZ CRTAP FGF8 GAS1 ABCA12 REST B3GLCT IGH CLIP2 SCNN1B H19 CYBC1 ELN RAG1 ALDH18A1 MYT1L KLHL41 ACE RSPO2 CLEC7A HIRA GP1BB DRC1 GDF1 TP53 GLI3 SVBP TCIRG1 FRAS1 IRF5 GDF1 PMM2 PAFAH1B1 ZMPSTE24 TGM1 DLL1 SIX3 CCNQ TIMM8A ELN PTEN FUCA1 MYD88 SPAG1 ARID1B AGGF1 THOC2 ABCA3 ARSB CFB PORCN HFE SOX11 NOTCH1 FOXP3 TERC USP9X P4HTM DRC1 AP3B1 CBL POLA1 CDON PKHD1 TAF1 COLQ SON TRPV3 TSC1 DVL3 TCF3 TRIP4 CHEK2 FLNB STAT5B STXBP2 CREBBP NPAP1 FAM20C STK36 DOCK8 SLC7A7 DDR2 TTC37 CD8A DOCK6 CD46 CCDC65 BCL2 INPPL1 DIS3L2 MFAP5 TNFRSF13C KNSTRN RPS15A GLA SELENON LRRC6 KMT2E SLC5A7 TERT GRIP1 DYNC2I2 PTPN22 FAT4 SHH IFIH1 IL7R PARN ARHGAP31 CSF2RB CHST14 TANC2 CIITA ZIC2 FLNA G6PC3 MARS1 BACH2 ZNHIT3 DNAJC21 SH2D1A CCNO COL13A1 DISP1 IL21 HYDIN MGP IL2RA MED25 GSN FOXH1 SLC35C1 PNP PRTN3 SP110 ARID1A MEFV NOD2 SERPINA1 NHP2 MED13 FRAS1 NBN MCIDAS FCGR2B KLHL40 BLM RAG1 RRAS TAP1 SNRPN ADGRG6 NADK2 SLC26A2 DDR2 ZAP70 MAGT1 FGFR1 GATA2 ALOX12B TMEM260 IFNGR1 SMAD4 SLC7A7 NFKB1 RB1 RARB APOE GATA6 DOCK8 AP3D1 SOS2 STING1 CASP10 B2M FLCN SRP54 ZEB2 TNFRSF13C FADD C4A TTC12 TAP2 KPTN STN1 LBR SNRPN DNAI2 MRAS COL2A1 RNF168 CHRM3 CCNO CHRNG RAC1 FGFR3 LGI4 ADA NUP88 TBX20 ODAD2 BCL10 FLNA SLC25A22 ELN SMO GBA TGFB2 NUMA1 RAG2 GATA4 DNAH9 SMARCA4 TNFRSF11A IRAK4 GUSB CD40LG SCNN1G SLC34A2 DHCR7 MIF GUSB KITLG KIAA0586 GRIP1 NSD2 DPF2 SLC35A1 EIF2AK4 GBA SPP1 NCF2 MKKS GAS2L2 MYH3 TBCD HLA-DRB1 PTPN22 RAC2 DDX6 CEP57 RELA PTCH1 DNAI2 ZFPM2 TPP2 RAG1 STAT6 IFT43 KANSL1 PURA LRRC56 DNAAF1 SCNN1G IL6ST ACP5 XIAP IL2RG FANCB IGLL1 AFF4 SCNN1B BCORL1 BTK PCNT MUC5B MRPS22 CDON COG4 PRKCD PTPN11 LRRC8A PHGDH BGN DVL3 PSAP HLA-DQA1 DYNC2I2 SLC35C1 PWAR1 SLC1A4 CR2 TBCE AGRN CTCF FBLN5 VANGL1 TRIP11 NKX2-5 TSC2 GFI1 TNFSF12 GAS8 MAPK1 SLC11A1 IFNG FBN1 DNAAF2 SCNN1A ACTA1 MESP2 HABP2 NDN SLCO2A1 FOXE3 IDS PANK2 FGFR1 CHD7 DNAAF3 NABP1 DNAAF3 CFI DPM2 OCA2 PCGF2 SFTPB MANBA TNNT2 SRP54 PLVAP CD79B SOX18 INVS DYNC2LI1 RARB CD19 FOXJ1 BMPR2 PIGN LEP PKD1L1 NHLRC1 GPC6 ITCH APC2 GATA6 SCNN1A SERPINA1 ATM GBA DNAJB13 CEP120 TNFRSF1A KIAA0319L CLCN7 NSD1 CACNA1C SPEF2 PIEZO2 DYNC2I1 NKX2-5 CREBBP TBX1 TNFSF12 COL6A2 EFEMP2 RAC2 PRSS2 TBL2 CFTR IL10 CFAP298 DONSON RSPH3 ABL1 EVC SDCCAG8 DNAH5 WIPF1 PARN PDGFRA TINF2 NCF2 TNFRSF1B CEP120 FOXP1 RFC2 NPHP3 BCOR GATA4 SNORD116-1 POLR2A NOP10 CCDC103 OFD1 DNAAF5 GATA6 IL6 POLA1 PDHA1 LMNA CD19 SFTPC SIX3 LTBP3 SMPD1 SMARCD2 RIPK4 CSF2RB PSMB8 HPS4 CRKL PTH1R EP300 RSPH1 PERP ATM ABCA3 DCTN4 CLCA4 CTSC STAT3 CCND1 POLR3H TRIP13 FCGR2A MST1 MUC5B DNAH5 CDON TRAF3IP2 IDS SRSF2 SLC18A3 TRIM28 CD79A PIK3R1 GRHL3 NOP10 HPS6 WNT3 RPGR DPP9 RAF1 SCNN1G CD79B RSPO2 BCL11B IVNS1ABP ACTL6A ZIC2 AFF4 SMAD3 ITGA7 CITED2 ERCC2 RAB3GAP2 TRIP11 IL23R SPINK1 TERC RTEL1 CYBA TSC2 CITED2 GLE1 GPC3 TGFB2 SCN9A RASGRP1 FGF8 SNRPN DYNC2I1 CARD11 POLE ICOS FADD NME8 HLA-DQB1 LMNA PGM3 EOGT CDCA7 WT1 SAMD9L SMC1A ICOS GLI3 SREBF1 CHAT RFX5 FOXF1 TDGF1 CHST14 CCDC40 SMARCE1 DCLRE1C ALMS1 TLR4 NCF1 RSPH3 CYBC1 SLC25A1 PTCH1 IL2RG B3GALT6 GLI2 GAS1 TNFRSF13B TET2 NRAS WAS ZMPSTE24 EHMT1 WRAP53 FAS WDR35 HPS1 NSMCE3 TGIF1 GLUL SH3KBP1 RFXAP CARMIL2 BCOR GTF2I TNFRSF1A MAGEL2 STAT4 HGSNAT SMAD3 FBLN5 MYO9A GTF2H5 NEK8 TERT RUNX1 RYR1 FAT4 CLPB RIPK1 COL13A1 JAGN1 CIITA TBX20 CSPP1 DNAAF4 CCR1 HK1 MINPP1 UBAC2 NFIX RNU4ATAC BIRC3 WNT4 IKBKB CD27 FAS NLRC4 SFTPA2 NDN AARS2 TGFB1 DHCR24 PIK3R1 HYLS1 CREBBP CHRND ALPL ITK VHL CCDC103 GREB1L ERAP1 FARSB RAB27A NAGLU ODAD1 CTC1 ZCCHC8 TRMT1 SNRPN CEP55 PRPS1 DLL3 LYST KEAP1 GBA JAG1 NME8 MYPN STX1A TNFRSF13C FIP1L1 HERC2 ELANE CORO1A SYT2 CCDC39 CFTR GPC4 ITGA8 ICOS RFXANK KLRC4 DNASE1 DICER1 EP300 PRKAR1A MAGEL2 MLXIPL LZTR1 PIGN BMP15 HLA-DRB1 COL2A1 ADAMTS2 WDR19 ALG12 AK2 CD55 HLA-DRB1 GAS8 DKC1 NKX2-1 DLK1 SCN10A DYNC2I2 HELLPAR LMOD3 FLCN WT1 NODAL LRBA ELANE GTF2E2 SGSH GPR35 BAZ1B SFTPB TRAPPC4 PLP1 CACNA1B RSPH4A FSHR TERT CCDC65 WT1 TERC MID1 NR2F2 DHCR24 ERCC3 WASHC5 NIPAL4 LFNG VPS33A CD19 RLIM GALNS OSTM1 XIAP ASAH1 HLA-B DISP1 NAA10
    HP:0001626: Abnormality of the cardiovascular system
    Genes 4425
    MERTK SLC25A26 TRNK MTHFR ALDH18A1 SCN9A B3GLCT GNPTAB MITF GJB4 NDUFS4 MEGF8 SCYL1 TREX1 SLFN14 LMNA DOLK SDHA RANGRF SCNN1G CD247 EFTUD2 KRT16 SLC25A4 NTRK1 ATP6V1A CTNND2 ARVCF SIX3 ND1 WDR11 ANTXR1 CTSB NBEAL2 RREB1 TOPORS NOS1AP RRM2B CAV3 LETM1 GNA11 KIF3B IFT172 NPHP3 COG4 ELMO2 ANTXR1 PEX11B DNAH11 KRT2 APOB RPS6KA3 PRKAG2 GJB6 CDSN ZAP70 HRAS ZIC3 NKX2-5 BUB1B FLRT3 NXN RAF1 NKX2-6 KCTD1 TTC7A SPATA5 DNAH1 BRIP1 FGA SGO1 VPS13B TKFC CRYAB CNBP SEC24C CDK8 TULP1 MYH6 B3GALT6 TWNK PLEC SLC37A4 PIGA TSC1 ATRX FOXF1 FOXC1 WAC GNS TERC MPL THSD1 EVC2 DLST CRB2 FLNB ATP6V0A2 TPM2 AK2 ACTN4 SPAG1 RTL1 ITGA8 EFEMP2 C8ORF37 IL7 KRAS ECE1 XYLT1 VPS45 SLC25A24 POMT2 TPM2 CCR6 KCNE1 PLAGL1 AHI1 SNTA1 PALB2 FOXP1 KDSR RELN CAV1 ARL3 MYF6 IGF2 COL3A1 CBL ATP6V1E1 COL5A1 ACD PPP1R15B ACVRL1 AMMECR1 HNF4A ADA2 CDKN2B ERCC8 SBDS SOX3 FANCL NDUFB11 CPLX1 PRKAR1A LYST PRPH2 SLC18A2 RINT1 COX10 SLC2A1 VPS33A LDB3 XK TTN NKX2-5 GJA1 NGLY1 GLI2 ODAD4 MYH11 MAF FLI1 SMG9 SDHA AGPAT2 CAV1 MKS1 TAF2 LRRC6 COL11A2 HOXA13 CASK CCBE1 SMPD1 BTD KCNMB1 TDGF1 PIK3CA WDPCP LACC1 KCNJ2 ND4 RPS19 CHRNA7 IGF2 KAT6A AIRE DISP1 MYD88 DHDDS GNAI3 DOCK6 KRAS IRF8 ERMARD BAP1 APP RPE65 SLURP1 CALR FN1 SLC19A3 ALX4 TSPYL1 PEX13 SLC39A4 NDUFB11 TTN FOXC1 RBCK1 HNRNPA2B1 TRPM4 ZIC2 WDFY3 KYNU PSMB9 CD2AP APOE SMAD4 ITGB3 TRNK KCNQ1 SNX10 KCNJ2 HMBS FKBP14 FGF8 BRAF SC5D SHH ALOXE3 FAS SCARB2 HACD1 CREBBP CITED2 MMP2 HADH NEXN NODAL ABCC6 PORCN CEP57 PIK3R2 RAD21 SCYL1 VCP KCNE2 USH2A TCTN3 PTPN22 ESR1 TRNS2 CDON TIMMDC1 C1R STRA6 IL10 DLD SCNN1A DNM2 SOS1 CDKN1C TGM1 TNNC1 LPIN2 CCN2 MAP3K7 HLA-DRB1 FRG1 TSC2 PPP2R5D GLI2 SLC2A1 EYS FDFT1 IFNG ANK1 SYNE2 ARL6 IRF6 TAB2 PCSK9 TP63 CARS1 HABP2 MYSM1 ERGIC1 ALOX12B DYNC2H1 DSG1 NSUN2 FLT4 FERMT1 DNAL1 CRYAB PPARG GNB5 TRNE TSFM MEIS2 DYNC2LI1 TRNL1 NT5E EWSR1 POU6F2 CSGALNACT1 ELN PRCD FBN2 KAT6B PLCG2 THBD PEX5 SLC2A10 SPOP GBA CYP17A1 SHANK3 SGCG TRNK PNP ACTA1 AGTR1 FERMT1 SIM1 GNA11 DGCR2 NCF4 ODAD2 FMR1 CYTB HCCS GBA SNIP1 DNAI1 LMNA PSMD12 NBEAL2 MKKS LMNA WAS DMD NDUFA10 ITGA3 HESX1 PIGL SDHAF1 POMK MKS1 CYP11B2 ATAD3A IL2RB CACNA1S GLI2 RNU4ATAC NEU1 TASP1 PMS1 RNASEH2A FAH BRCA2 ODAD3 FKTN FHL1 IL17RA C2CD3 CALM2 MCTP2 PDE11A IGLL1 ODAD3 ATN1 TPM3 MYOT SMOC1 PUF60 SOX10 RYR1 NDUFAF6 TRIP4 IQSEC2 GATB ADAM17 SDHB GLMN LRRC32 TMEM216 NLRP3 CISD2 BAP1 MED12 CYBB COL1A1 STAC3 BSCL2 PTPRC VWF CHST3 FOXH1 NDUFA2 TNNI3 YWHAE SNX10 COX3 COG8 LRRK2 FBP1 TMTC3 GNPTAB CTSK TREX1 XPR1 HADHB ZFPM2 SCNN1A PCARE STRA6 NDUFAF2 IL17RD RBM20 FANCB GLI2 CLCNKB CCDC141 RPGRIP1L PHKG2 F7 RPL10 COL4A1 WDR26 HMBS EGFR ABCC8 PLAGL1 BCR NDUFAF2 CCDC22 SAMD9 DMPK ERCC5 SCN5A USP18 HYMAI C1QBP PRRX1 SLC29A3 ARMC5 PLAG1 COLGALT1 KAT6B MEFV DNAAF2 ITGA2B KDM3B GJB2 NFKB1 IL1RN EED IRAK1 FHL1 TGFBR1 REN ABCB4 COL4A2 MDH2 CALM1 UBE2A SP110 PIK3CD SRD5A3 ENG MAX ATP6 NSDHL HSPA9 PROK2 SETD2 CTLA4 SMARCD1 SOX2 ND5 PQBP1 TELO2 F10 DZIP1L JAG1 GATA6 JAM2 MYH7 KRT14 ALB PEX5 TTC8 ADA2 BPGM RIPK4 FRG1 CIB1 KCNH2 CHCHD2 TSR2 POLR1A WNT5A TET2 RGR SOX9 TGFB3 TMEM67 BMP2 CEP41 GYPC ZNF462 GPC4 FBN1 DDRGK1 COX6B1 RBM10 CFAP410 FGFR2 GDF6 TF MAP3K1 ATP2C1 BMPR1A BBS12 DPM1 MDM2 PARN RHOH NFKB2 RFWD3 VHL H19 TBX1 LIAS MOG TLL1 PPARG DCLRE1C NAXD ABL1 CFHR1 SELENOI GNAS NRL KCNE3 NHP2 CYP11B2 TGFBR3 KRAS NTNG1 OSTM1 SLC17A5 SDHB ABCG8 COL5A2 NODAL F13B SDHC TNFRSF11B IVD F9 IRX5 GDF2 PSMB4 PCNA PIGU SAMHD1 NXN DSP ANTXR1 UBR1 FGFR2 PEX6 NKX2-5 COL3A1 TRNL1 ARHGAP31 MS4A1 NODAL USB1 BBIP1 F13B CASP8 CAVIN1 CYP11B2 ASXL1 IFNG FGFR1 ARX PLAU PROC RLIM DTNBP1 ZNF408 SFTPA1 TRNS2 ITPA JAK3 BMP2 BAP1 NBAS FZD2 ATP6V1E1 BTK ATM CACNA1S HADHA MCIDAS NOS3 NODAL PTEN ZMYND10 NFIA ACTA1 PSAT1 SYNE1 BCOR ABCC9 CYLD CD81 COL3A1 GJA8 FGF8 RPGR SCN3B COX3 RPGRIP1 CPLANE1 CYBC1 FANCD2 FGFR2 RAG1 CRLF1 SMARCA2 NPHP1 MYT1L ACE CLEC7A GLI3 CYP27A1 FRAS1 NFU1 PMM2 PAFAH1B1 ZMPSTE24 CEP41 DLL1 FERMT3 CCNQ PTEN EYA4 NPHP1 KCNN4 PRDM5 HFE MPL SIK3 SLC40A1 TERC RPL27 SEC23B TRPV3 PPOX TCF3 SUMF1 SDHAF1 COL1A1 STAT5B SUFU CREBBP SOX9 STK36 BBS4 SLC7A7 GJA1 ADD1 DOCK6 CD46 DIS3L2 MFAP5 KNSTRN ARX TNNT2 SF3B1 KMT2E INPP5E BANF1 GYG1 ARHGAP31 ZFPM2 RMND1 ZIC2 G6PC3 NDUFB10 DNAJC21 PEX26 XYLT1 ERF PEX19 ENPP1 MED25 NCAPG2 FOXH1 HJV SEMA3E AIP IKBKG IQCB1 MRPL3 SP110 NAGA MED13 LIG4 NDP HPSE2 TRPM4 FZD4 FLNB FCGR2B LHX4 INPP5E KATNIP TRIP11 TTC8 PSAP TREX1 ND2 ND5 IDH2 BRCA1 RPS6KA3 FHL1 USP8 SLC25A11 MASP1 LMNA LMNA WDR37 TRPM4 PEX3 TRNF OTC FADD OTC TMEM126A MTAP PPARG TRNQ KIAA0586 ZMPSTE24 RAI1 ELN KPTN LBR KDM6B SON AGXT TRNS1 PDCD10 CYP7B1 TRDN DMXL2 SPATA7 NPHP3 TRAPPC11 ELN PTCH2 MAP1B TGFB2 ARHGEF18 JAK2 SUMF1 GUSB ADCY5 IFNGR1 DHCR7 GUSB KITLG HADHB BVES C12ORF57 SDHB GBA MPIG6B FOXP3 RAC2 STIM1 KRT83 RPL35A AKT1 MYH6 ZFPM2 GJB6 CHST3 KANSL1 PURA SATB2 PITX2 COL4A1 FN1 GLRX5 ADAMTS10 CDK4 AFF4 ZFP57 ERCC1 SCARF2 PCNT PRPF8 NPHP4 LRRC8A RPL26 RMRP ACTG1 TTN OTUD6B KDM6A ECHS1 KCNQ1 ATP5F1E CTCF TGDS CNGB3 TMEM107 GAS8 POLG DNAAF2 SCNN1A ACTA1 MTM1 FLNA POMP HABP2 MTTP TRNL1 FGFR1 TGFBR2 FKRP OTX2 PTPN22 CFI LRP2 PHF21A ZIC2 EOGT RNF6 PLIN1 INSR WRN KRT5 PIGN NDUFA10 FKBP14 WWOX PPA2 LDLR GATA4 GATA6 TBX1 ENG POLH NSMF ARID1A KCNK3 NSD1 F5 KCNN3 REEP6 NKX2-5 CREBBP KIT ZFPM2 CDH23 PDE6D ATP6V1A TMEM231 MTFMT PROS1 XYLT2 EPCAM KCNQ1 P2RY12 IL10 PDGFRB SLC4A1 LRP6 NDUFS8 GCK SDHD DCAF8 STRADA PNPLA2 NDUFB11 DDRGK1 FUCA1 RNASEH1 RNASEH2C ND4 NF1 AKAP9 NOTCH3 FLNC DNAAF5 PEX5 PDHA1 SMARCE1 ERCC4 MYH9 CCDC22 COL1A2 STAT3 CCND1 TMPO ND6 IMPG2 CALM1 CCDC8 TGIF1 NEUROD2 DNAH5 ABCA4 TRAF3IP2 ARFGEF2 TBX1 KISS1R SSR4 ALG8 DDX3X TRNS1 KDSR HAAO RIN2 TUB MKKS RSPO2 DNMT3A ETV6 GNB3 HK1 AFF4 GBA RAB3GAP2 PPCS FGB IL23R DVL1 F8 FBXW11 APOA2 CYBA RAI1 MYH11 CITED2 PEX12 TFAP2B HADH SCN9A FGF8 CASR POLE LOXL1 ICOS FADD AMMECR1 SCN5A LMNA TNNI3 CDON PDE6G SDHD MANBA PIGT TDGF1 DYSF CCDC40 ALMS1 FGA ANO5 PARS2 RPGRIP1L TERT GJB3 CDIN1 KCNE1 FOXH1 SOS1 NRAS CACNA1D WAS CASR DHODH F2 PNPLA2 EHMT1 NF2 TCIRG1 DYRK1A NDUFS1 FAS MYH7 TOP3A SAMHD1 WDR35 NSMCE3 PTEN TGIF1 G6PC1 CCDC28B KRAS GTF2I TNFRSF1A FBN2 TWNK HGSNAT GNAQ PRDM6 APOA1 DSC2 SRD5A3 IFIH1 FTO KCNJ11 GNAS AMER1 SETD5 LIPC COX2 MINPP1 NFIX RNU4ATAC OFD1 RASA1 AIP COL6A3 WDR35 FAS ACVR2B RNF135 CDH2 SFTPA2 MKS1 UPF3B ANTXR2 PRF1 KRT1 AARS2 TSHR TRNT1 SCN5A GATA1 NRAS GREB1L ERAP1 RAB27A SCN10A MC4R PACS1 PRKACA GLI3 LYST GBA GATA4 TKT TBX4 MYMK COL4A4 SCN2B CEP290 KLRC4 SCAPER MMP1 KRT9 F13A1 VIPAS39 PRPF31 PIGN HLA-DRB1 AIPL1 MPL ADAMTS2 TMEM237 CD55 MVK NKX2-1 DLK1 TPI1 APOE GNAO1 WT1 ELANE GTF2E2 PKP2 ABCC9 GPR35 CIITA TRAPPC4 MED12 CDKN1A CLCC1 CRPPA GJB3 MEIS2 RAF1 MIPEP PEX1 COX3 COX7B NEBL SH2B3 ERCC3 ERCC2 KCNAB2 TAB2 CTNS SETX ANGPTL6 CD19 TRIO STK4 POLH ERCC5 GALNS POMT2 NFKBIL1 ADAM17 TET2 NAA10 SF3B1 SLC26A3 GFI1B KMT2D ABCA12 LRP5 UBR1 PEX3 FEZF1 COL7A1 HSPG2 TRPM4 TRNK NDUFAF4 C12ORF57 MYBPC3 GTF2IRD1 CAVIN1 KRAS PIGY VWF TGFBR2 SPINK5 RASA2 APC PHGDH SLC25A24 NGLY1 LARP7 STAG1 RYR2 CCND2 FANCM UCP2 RPL10 CDKN2A DSG2 ANO10 NELFA NLRP3 KCNJ11 PIK3C2A GLI1 CTCF KCNQ1 LRP5 TCF4 CFHR3 POLG TBX5 SHPK HLA-DPA1 TMEM43 SETBP1 LMNA RIT1 SVBP CEP164 AKAP9 ATP6 FKRP CYP27A1 CACNB2 WAS SDHA NF1 LAMB2 BAG3 RARA ACTL6B TREX1 ABCC6 COL11A1 HSPG2 KCND3 CNGA3 IL36RN SLC19A2 CYP1B1 COL3A1 CD96 CYBA ERCC8 TET2 GLIS3 DLD TERT PEX2 FOXH1 SURF1 ATOH7 GFI1B HRAS CASP10 TSC1 TNPO3 NIPBL PITX2 WDR19 GAS1 MYCN TXNRD2 IL10RA ATP7A MYH9 ACTA2 TRNW GDNF CTLA4 PDE4D SPTB ADAMTS3 GLB1 SGCD ERCC3 F7 HLA-B COL5A1 CBS SNCA FGFR2 LIG4 RNU4ATAC CLN3 GNE AKR1D1 ADA2 KCNJ1 FGFR1 CFI ERCC2 DISP1 FKTN ATP6AP2 NLRP3 FGFR2 COQ2 SPECC1L ARL6IP6 FAH ND5 NR0B1 LIG4 MAP3K20 POMT1 FOXE3 PDGFB GYS1 SDHAF2 SLC26A2 FAS PRKAR1A SERPINC1 RLBP1 TCIRG1 CALR PIK3R1 LIFR KCNQ1 SDHD ZNF687 SLC35A2 FGF8 CCDC40 CTLA4 SCN5A HBA2 ARSA DCAF17 CFTR SCNN1G ESCO2 GJB4 ITGA2B KIF1B BEST1 RP2 GATA6 BBS9 ARNT2 KCNJ18 HTRA2 SPRY2 STAT1 GTPBP3 FGF8 SCNN1A SNRPN MYOC GPR101 ATP5MK HNF1A MAX LRIG2 LONP1 PLEC CXCR4 ERCC8 COQ9 PTDSS1 SLMAP STIM1 CCND1 KCNQ1OT1 AHCY ATPAF2 FANCC POLR3A SKIV2L PADI4 CYTB MAF TERT SFTPC FOXJ1 NPC1 AICDA FANCI CALM3 NDUFS2 EDA LDLRAP1 TFAP2B CALM3 PEX6 CFAP298 CSTA SELENON TRIM28 ZIC2 KLHL7 NPC2 TBX22 ALMS1 GPD1L FGF8 ELN SBDS CERKL CYP11A1 KDM6A LAMP2 B9D1 MAFB DTNA NDUFS2 PEX14 LEMD3 GJA1 FGF20 SGCB MMEL1 DNASE1L3 TGFB3 CCDC141 FANCA LIPN FLT4 MYH7 RDH5 SCNN1B FBXW11 MAN2B1 SCN5A LTBP3 PTCH1 MGME1 EPG5 NKX2-5 GAS2L2 PPP1CB F13A1 PDE6H HIC1 CBL CWC27 PDE3A FLNA CHRM3 POLG2 JPH2 IRF5 IL17RC GNAQ SMARCA4 APP PIGM HPS5 TMC8 COL4A5 LYZ NFIX RTEL1 PRKG1 PLN ATAD3A MPI BRAF IFT172 FMR1 ALG14 PAH WRN TGFB1 RBM8A NDUFB9 SFTPA2 CDH23 FGFR3 RET NR2F2 JMJD1C TNNC1 SLC30A10 GLI2 BUB1 GMPPB NRXN1 COQ7 OCLN VCL TMEM237 TFAP2B TBX1 WDR19 RRM2B COX4I2 KAT6B FLNA DNAI1 HCCS NOTCH1 IFT140 FOXA2 MPLKIP PROS1 LZTR1 SOS2 NDUFS2 CACNA1H TPI1 FECH CYP11B1 GNA14 MADD GCDH PEPD MYT1L MYO18B GTPBP3 SDHA IDH1 CDKN2A SCN4B SOX10 FBLN5 YY1AP1 CDKL5 RPS10 TANGO2 NPPA GAA AKAP9 NDUFS2 PIGO MAP3K7 LMNA MEOX1 KRAS TMEM216 RBBP8 KLF1 SCN1B BPTF SMARCB1 SOX10 BRCA2 SPTB ANK2 RNF113A BRAF MBTPS2 RAF1 COL6A1 FASLG TNNT2 CCDC39 DNAJC19 PYCR1 SMN1 EYS TNXB CFH DEAF1 LMNA PSMD12 TK2 INTU ATP6AP1 PEX6 POGZ STAT3 PLG CHRNA1 ACTN2 NEK9 ESCO2 LONP1 TGFBR1 ACAD9 CDH2 POLG TMEM127 LPIN2 KYNU PRDM16 SETBP1 SNRNP200 CFH UVSSA UBE3A MYH7 PRRX1 CPLANE1 TBX20 SFTPC SLX4 CARD9 ARL2BP RECQL4 LEMD3 TNNI3 RPL10 FGFR2 FHL2 GABRD IRF2BP2 EHMT1 NEK10 ABCG5 MYH7 RPL5 CRYAB MKS1 DOCK3 NODAL ABCC9 TFAP2A RPS24 VPS33B RPL35A FGFR2 SGCA RET COQ2 ARL13B IDH3B MGME1 ASAH1 NOTCH2 UBE2T CENPE CHRNG ATRX SNTA1 PRPF3 ERCC6 HBB MED13L KCNQ1 MRE11 JAG1 RECQL4 RPL27 DNAJC19 TDGF1 TALDO1 RNF213 RAI1 HFE NDUFS2 NR2E3 PCARE MAK PHKA2 LAT STXBP1 ZEB2 KDM5B PIGO MAP2K1 PIBF1 PAX6 ERCC4 SOX18 ERBB3 SIX3 ROR2 ND4 BMPR2 CENPF PEX16 PDX1 DUX4 PEX19 FLNA DIS3L2 DLL1 CDON SHH TPM3 CPT2 H19-ICR TBCK MTRR BMPR1A MYL2 HBA2 JAK2 FOXC1 TBL1XR1 GDAP1 RAD51C CACNA1C RRAS2 PRPF6 LIG4 AGK DNAAF6 PIGS RNF125 BIN1 NR3C2 FANCA PRKAR1A GDNF MYPN NOTCH3 IGF2 RUNX1 PRKCD BLNK KRT1 PRPF3 FCGR2C KAT6A FBLN5 ABCC9 GCLC WDPCP IRF5 WT1 LIPA RAB27A KIT TMEM43 ADA AUTS2 CYTB SALL1 SERPING1 CYP24A1 TGIF1 ASCC1 DNAH1 CSRP3 GNE CST3 IGH FAT4 JAK2 PSEN1 G6PD ACADS MYH11 TMEM43 INSR ERCC6 PQBP1 ARID1B ARL3 PDE6A SH2B3 PPOX TP63 SHH PLOD1 AKT1 TTR COPA PEPD SRY SCNN1B FBN1 SNRPB RBP3 GAA CALM2 GATA6 DYNC2I1 CASR ZNF423 RAD51C GALE SDHB HPS3 REST TGFBR2 SCNN1B TAZ PKD1 TPM1 PRKACG HIRA ACTG1 DRC1 SVBP GPC6 GDF1 HOXA1 BAP1 COX1 CSPP1 ELN MGMT ARSB PEX6 RPL11 PET100 RIPK1 CASQ2 ACTB MSX2 ND2 FOXP3 USP9X ND4 SOX4 SLC39A13 PKHD1 CHKB COLQ TTR SPEG RPL11 GLRX5 PAM16 NOTCH2NLC TET2 SCN5A AKT3 PTPN11 MEOX1 RP9 F2 ENPP1 RHO POLR1D TDGF1 TNFRSF13C GLA SELENON HSD17B10 RPL15 TULP1 NF1 ADGRE2 FGB MED13L GATA5 AGL DDC TRMU BACH2 DLX5 ZNF513 IL12RB1 SH2D1A KRAS SLC25A4 SCN5A NDUFA11 GSN CAP2 ALDH18A1 SMAD6 VPS13A EXT2 ITGA2B SLC4A1 FRAS1 NDUFA12 MFAP5 CYSLTR2 CEP55 AGXT FGF17 CLDN1 PDE8B MAGT1 FGFR1 IFNGR1 DES SMAD4 ZNF469 ND1 DOCK8 KMT2D SOS2 SLC19A2 ND5 LAMA4 CTNNA3 FOXRED1 LIPA MICOS13 CSPP1 ACAT1 RORC STING1 DCHS1 GATA3 MEGF8 HLA-DRB1 ZEB2 ARID2 CHN1 PIK3R2 RPL18 STN1 HTRA1 AP1B1 PCCA EXT1 CCND1 CYLD PDGFRA RAC1 KIF15 TBX20 FIG4 SLC20A2 BIN1 LIPA ODAD2 FLNA TRAF3IP1 SMO SLC4A1 PDHA1 DNAH9 TMEM231 GLA SCNN1G NOS3 MBTPS2 EVC NSD2 HS6ST1 DPF2 ITGA2 MAN2B1 PIK3CA LRP5 PKD1 KIF1B APP TNNT2 TNFSF15 PTCH1 LRP5 RBP4 MMP2 LMNA NLRP3 CHD4 LRRC56 FGG ABCC9 CYP11A1 RNASEH2A CIZ1 TNFSF4 ODC1 POLR3A AGPAT2 TWIST1 MMP1 NDUFA4 ND1 IDUA COG4 TP63 PAFAH1B1 PTCH1 PEX7 LCAT COX8A GP9 ABCD3 PRPH2 TP63 DISP1 TCTN2 TNXB SCN1B PPP1CB VANGL1 NR5A1 NKX2-5 TSC2 ACTA2 DGUOK GFI1 MAPK1 IFNG COL1A2 NDUFS3 PHYH MESP2 RPS28 FASTKD2 FOXE3 NLRP3 MRPS16 RAI1 NABP1 SCN9A PCGF2 FLCN DNAJC13 SFTPB ACTC1 PLVAP HBB RPS20 RPSA RAD21 INVS LYST NDUFA11 RARB CD19 BMPR2 DZIP1 APOA1 GATA1 PEX7 NEK2 ATM LMX1B GBA APOE TGFBR2 MYH11 CANT1 RECQL4 HYOU1 IGSF3 TOR1A ATP8B1 CFTR EVC FANCE PARN PRKAR1A TGFB1 MYLK WWOX MTOR RFC2 WDPCP GATA4 RRM2B CCDC103 SETD1A NEB MPLKIP POLA1 FLT1 CD19 CALM1 SIX3 SMPD1 B9D2 SERPINC1 SELENON SPARC HPS4 PTH1R SRCAP ATM MNS1 KRIT1 MYH6 SH3PXD2B GNAT2 CLCN7 TRIP13 HAND2 COL18A1 MST1 ANKS6 RPS6KA3 MEF2A ALDOA FGB FKRP NOP10 AVPR2 COG6 TRNQ BCL11B PRDM16 IVNS1ABP STOX1 ASAH1 ACTL6A NDUFS7 SMAD3 TALDO1 NUBPL CITED2 ERCC2 TAF1A COL4A1 COX15 TEK STEAP3 HADHA ALX4 ACTA1 DSP NDUFB3 EIF4G1 GATAD1 ACTA1 HBB RERE FLNA MAD2L2 CLRN1 LTBP4 PNPLA6 TMEM237 AIP DDX58 POR PGM3 DCC ABCB11 KCNJ8 EOGT VHL PIK3CA MTFMT TEK PLD1 SLC25A4 SDHC DCLRE1C SEC31A TLR4 RSPH3 APOA5 COX7B CYBC1 DCHS1 KCNH1 FANCB BBS2 HBB SRCAP GAS1 TNFRSF13B LMNA CRB1 ZMPSTE24 ANOS1 SMARCE1 KCNQ1 BCOR WARS2 KLHL3 STAT4 SMAD3 GTF2H5 TRNV RUNX1 LRP2 OPA1 PRKAG2 DNAAF4 UBAC2 MAP2K1 RIN2 THOC6 DLEC1 BIRC3 COL4A3 FGA TTC8 SCN1B GATA4 TMEM138 CD27 BMPR1A ALKBH8 CFHR3 MTHFR NSMCE2 VCL MITF QRSL1 DHCR24 CAV1 BNC2 SNAP29 ITK BICC1 RECQL4 THOC6 NAGLU TRMT1 AKT1 JAG1 RERE GDF6 DMD F2 FIP1L1 GJA5 C2CD3 ND5 ATP2C1 APC NFIX NDNF B9D1 ICOS GFM2 SARDH ND6 HLA-B PRKAR1A KCNJ18 MAGEL2 GMPPB NF1 MAP3K7 DLL1 RPS29 NODAL LRBA RDH12 PLP1 RSPH4A TERT FBN1 F5 NAGA RHO ATP6V1B2 RET HSD11B2 WASHC5 TCTN2 DMD GANAB TMEM67 C8ORF37 SLC39A13 CD46 ADAMTSL4 VPS33A DPF2 PIGQ INS SDHA MVK SMARCB1 RPS7 WT1 TRAIP NDUFB11 DNAAF1 TOP3A PRCD CUL7 TCOF1 ALG9 TRNC CALCRL F5 KAT6B POMGNT1 TTN OFD1 EPB41 TERT BRAF CLCN2 APP SLC2A10 RPS15A APP KRT14 GJC2 PTF1A MALT1 HPGD NID1 SOX3 KCNH2 ABCG5 FSHR MAFB DSE GATA6 CFC1 EFTUD2 HBB MYL3 RPL15 PPCS STK11 ALB CDC45 SNAI2 PCNT FOXH1 ESPN TPK1 IDH3A ANKRD11 COL1A2 TARS1 PKLR CEP290 WNK4 CCR6 SH2B3 ALAS2 DNAH9 HSD3B7 PLIN1 BRAF ADNP DSG2 UROS RLBP1 EXT2 TBX1 SMCHD1 PIK3CA TCAP RS1 ATP5F1A GATA6 FANCG SCN5A GP1BA NDUFV2 GMPPA NOTCH1 MAB21L1 ADAMTSL1 AKT2 MCCC2 ND6 DNMT3A SIN3A THPO NOD2 MYH6 WASHC5 CPOX FOXC2 HAMP GJA1 ANKRD26 ACTA2 CYB561 SCN1B PIGT VPS13B PRKCD HYLS1 SUFU PTCH1 DNAJB11 HOXD13 IGF2 TRRAP CFAP300 COL1A2 GDF1 MTO1 IFT27 INTS1 PHKG2 PEX19 MAP2K2 WT1 DLK1 PPP1R17 SMC3 CR2 STX11 F12 MED25 MADD COL6A2 RAB23 SHH ACADVL FAN1 TET2 TKT MYRF HRAS DLL4 F8 MVK CRELD1 GALNT3 SCN5A TPM1 KIAA0753 SCO2 SOX2 ATP8 SLC26A2 PUF60 RYR1 ELP1 AGA BEST1 NLRP3 FANCF VWF FBN1 MMP21 TCIRG1 PNKP F2 CPT1A FLI1 ZIC2 SLC29A3 KIF20A DLL4 IMPDH1 MBTPS2 POLG KRAS SIX3 PEX12 PRKCSH TCTN3 SOX10 SMARCB1 TRNN SCO1 BTK MSH6 KRAS BSCL2 RSPH1 SMAD9 CCBE1 GK DNAH11 AGTR1 ATR CSF2RA NADSYN1 UMPS CDC42 GJA1 LAMA2 SMAD4 SACS TCOF1 NTRK1 DES POMT2 SLC22A5 MCFD2 MYBPC3 XPNPEP3 NOTCH2 SKI SEC23A TTN LORICRIN MRPS14 SYT1 ODAD4 ECHS1 IDUA CACNB2 DLL1 ND1 RNF113A TBX6 RERE FLNA CASK DGCR6 TTC7A SFTPC RAG1 UROS INTU CKAP2L EDNRB NLRP1 IFT81 ABCD4 EPHX2 COG4 EED SIK1 ETHE1 RPS19 IL12A-AS1 ENG CDKN1B HLA-DRB1 HYLS1 NPM1 NDUFS4 MC1R SCN11A TACO1 RB1 CTLA4 PRG4 CEP19 KLF1 C1S CRELD1 PHYH DSE PEX1 ERBB3 RPGR TCF20 LIMS2 GUCY1A1 GALC TUBB RET JUP NLRP3 ALDH3A2 DHX38 IFT80 FGFR3 FXN FGA MKS1 SEMA3A HBA2 NPHP3 WFS1 VHL PMM2 COL4A3 BRAF ABCB6 IDUA MNX1 PRPH2 RPGRIP1L EYA4 FBN1 HBG2 SLC29A3 CNTNAP2 RAG2 CAPN5 CTSA PGM3 CHRNA7 FANCE MPL COL7A1 NDUFS6 HIBCH FKTN ZEB2 XPA NEK1 GJA1 TRDN FLNC ENG AKAP10 KIAA0586 CCNQ PLN NDP AGA LAMC2 RAG2 IL17F VAMP7 CEP104 FANCC SNCA PYGL CCN2 TPM3 TWNK GGCX COQ2 FOXE3 NCF1 CD3D ABCA4 TAF2 RIT1 MGAT2 SAA1 KIZ IL7R TBC1D24 TTC37 LTBP4 SPTA1 MLX COL1A2 IDH1 SMAD3 TGM5 FOXRED1 PEX16 NOS3 GHR DDX11 HYMAI GDF2 PRKAG2 HLA-DRB1 MRPL44 NDUFA1 DNMT3A NEU1 ATIC EDN3 FLNC CPS1 PRKAR1A APRT GPIHBP1 DNMT3B IDH2 SCN3B PTPN11 EDN1 MECP2 AGK NDUFV2 USF3 ACVRL1 TFR2 FLNA MTTP NRAS OTX2 CC2D2A DNAAF6 FGF23 CLCN7 ANK2 NOTCH1 FBN1 NUP188 NDUFAF3 STAT3 PEX2 PEX10 CARD11 TBX5 BAG3 ERCC6 STX16 SMAD4 SLC25A13 PGM1 LRP1 JAK2 HMGA2 AHI1 RPL31 ELOVL4 AQP2 PIK3CA TP53 CNGA1 BRCA2 PALB2 GAS1 PSAP PTCH1 CFI PTEN STAT3 TMEM67 SCN10A KBTBD13 TREX1 AHI1 ACTC1 JAK2 ISG15 MYH7 ACTG2 BEST1 TMEM126B MAP2K2 ACADM DLL3 RYR1 FUT8 PEX12 ASXL2 KIF11 GP1BB MSL3 HADHA TERF2IP SH3BP2 HNRNPK NFKB2 FREM2 IFT172 HIBCH PIGY ANK1 TGIF1 CAV3 IDS AVPR2 NEK9 SELENON PSTPIP1 CCM2 LEMD3 ATAD3A GATA4 NR3C1 NEUROG3 SCN2B TBX1 POU2AF1 TDGF1 PRKACA ADNP CA4 CD28 CDC73 SIX3 PML BLOC1S3 KCNJ5 CHD7 POLR1C POR TNFRSF11A FH ATRX HES7 FOXC2 NKX2-6 FOS GLB1 CC2D2A DSP MYH3 KRAS HSD3B7 ALDH18A1 ALOX5AP PEX11B SDHD DVL3 SLC12A1 SCNN1A PSEN1 WFS1 GPC3 DCTN1 ALG9 DNAAF5 JUP ZMYND10 CACNA1D IL2RG IL7R PTH1R SMPD1 HLA-A ROR2 GP1BA SMAD4 KDM6A NONO INVS TLL1 RIPPLY2 CLCN7 MYLK NODAL ND6 SERPINA6 GNE BAG3 MEN1 LRRC56 GATA1 TSC2 VPS35 DHCR7 WARS2 NDE1 SLC20A2 WNT10A SLC7A14 GSN RP1 KCNJ5 BMPR1A LBR ARID2 BBS1 SDHD ZNF513 RET CNGB1 KCNJ5 SETD5 NKX2-5 CAV1 ABCG8 DCAF17 DSG2 TF GPD1L AGT GATA1 CTBP1 BTNL2 RYR1 SNX14 CHST3 RAD21 SOX4 SAG ERCC6 TP53 IGF2 BBS10 FUZ SUFU CRTAP PSAP PEX13 GAS1 B3GLCT ABCC6 PLEKHM1 ADAMTS10 ELN RET GATA5 ALDH18A1 CALM2 GATA5 EPB42 GP1BB TCIRG1 DIS3L2 CAV3 TPM2 EMD SCO2 TXNRD2 IKBKG FUCA1 SPAG1 ARID1B GNAS AGGF1 F8 ABCA3 ND4L NLRP12 TGFBR1 NDUFAF5 NOTCH1 PMS2 SEMA5A CAV1 NDUFS8 CD28 CDON GPX4 CA2 CC2D2A PDGFRB GREM1 KIF7 STXBP2 TGM5 ADCY5 EPHB4 ESCO2 FHL1 NEDD4L BCS1L IFT88 CITED2 NDUFB11 BCL2 INPPL1 KRAS CYTB KIT MYBPC3 RPGR CALM1 GRIP1 ATP5F1D FANCD2 PTPN22 FAT4 IFIH1 IL7R LMNA JUP GPC4 FECH H19-ICR SMARCAL1 NAGA GBA CEP290 PDCD10 DISP1 HYDIN SPRY4 MAP2K2 IL2RA FGD1 CDK13 CTC1 PDSS1 PNP PRTN3 ARID1A EPB42 XYLT2 MYH6 FRA16E GP1BB RSPRY1 TRNS1 SDHD BLM CASQ2 CALM3 RRAS SALL4 FANCI LMNA DDR2 ZAP70 ALDOB MNX1 LMNA AIP ND4L C3 IFIH1 TMEM260 NRXN1 USP8 FGFRL1 DPH1 APOE C8ORF37 AP3D1 SALL4 BRCC3 ABCA1 CDK10 KDR TECRL AAAS TBXAS1 C4A MYH7 SH2B1 ERCC6 SBDS DNAI2 NKAP TBC1D24 PEX1 LIPC CHRM3 MTHFR MYL2 TRNE COA6 SERPING1 GATA6 BCL10 PRF1 RAG2 SCN4B GBA GATA4 SMARCA4 GM2A CD40LG KCNQ1 MSH2 TRMT10C MMACHC MIF HES7 GP1BB HLA-DQB1 TRIM32 NKX2-5 GMPPB SLC35A1 AMER1 EIF2AK4 SPP1 XYLT2 KIF7 LBR NCF2 MKKS PTPN22 TMC6 CEP57 FGFR2 DNAI2 SDHA SDHB TRNF TPP2 SDCCAG8 SOX5 PCNA ZNF469 RAG1 CDKN1C CDC73 IFT43 CEP120 HAVCR2 HMGCL KCNJ2 HBB MIB1 SLC4A1 ACP5 XIAP CFAP53 IL2RG ATP7A RNASEH1 FANCB CYP11B1 KAT8 BTK SDHB TTN TMEM231 OFD1 TET3 KLHL7 CDON PTPN11 TXNL4A PHGDH LRP5 FLNA PIEZO1 PIK3CA NNT ABHD5 DVL3 KCNE3 AEBP1 RYR1 CDHR1 HCN4 STRADA PSMD12 CUL3 SLC25A3 ANAPC1 LONP1 ERCC4 FBLN5 ATP6 FBN1 CLRN1 PEX16 FLT4 NIPBL SMAD4 LIPT1 SLCO2A1 NOTCH3 CD109 RPE65 CHD7 SLC37A4 COQ2 TNNT2 SRP54 CD79B SOX18 SGCD TSHR AQP5 TNNT2 CDKN2C MMP14 MED12 TGDS CCDC47 PKD1L1 ND2 ADAT3 CPOX RPS17 APC2 MYH8 TRAF7 KIF7 MYH7 SCNN1A GPD1 DHX37 VEGFC KRT5 TNFRSF1A KIAA0319L CLCN7 YARS2 TBX1 PDE11A SMC1A PIEZO2 TMEM237 NDUFS7 PDGFB TBX1 KCNA5 AKT1 TNFSF12 EFEMP2 PGAP3 ABL1 PIK3CA EHMT1 PDGFRA CTNS SDHD NCF2 NDUFAF5 TNFRSF1B WNT10A FOXP1 PSTPIP1 BCOR TMCO1 GYG1 KDM1A SDHB NDUFS1 NSD2 TECRL F13A1 B3GALT6 CLCNKB TRPS1 BBS1 CSF2RB MPL PERP FAM149B1 COL1A1 HESX1 FCGR2A EDNRA IDS TRIM28 WDPCP CACNA2D1 CD79A PIK3R1 FGFR1 PIGP HNRNPU HPS6 SCNN1G MAP2K1 PDE6A CTSA CPT2 LMAN1 GPR101 SYNE1 TFAP2A COX2 RTL1 CCDC174 COQ2 NR2F2 OFD1 ND6 KCNH2 TSC2 KCNN3 RASGRP1 SP7 GBE1 NDP GATA1 COL3A1 POGZ ENPP1 POMGNT1 SEC23B TCTN3 GLI3 SREBF1 ITGA2B SMARCE1 POU3F4 GIGYF2 SIX6 F11 SEMA3A CDAN1 KIF5A MVK ARMC5 SDHA NDP PTPN14 HAMP CNGA1 PEX26 RYR2 HEXA TP53 HPS1 TET2 COL2A1 FBN1 SCN2A DMD GATA4 FMR1 NKX2-5 ELOVL4 DMRT3 FBLN5 GUCA1B NEK8 TMEM127 CLPB LDB3 RNASEH2C TWNK TBX20 CCR1 HADHA POR WNT4 ELAC2 MEG3 GP1BA TRDN SKI NEXN RAD51 DUSP6 OTUD6B USH2A NDUFA9 MMUT HYLS1 NPHP1 HBA1 CHRND PKP2 PDE6C XRCC2 FSCN2 VHL CCDC103 ERCC6 ZDHHC9 FARSB ODAD1 CYP11B1 ANK1 JAK2 NME8 AHR VHL SLC25A22 LETM1 SLC25A3 ELANE RFWD3 XPA GPC4 ITGA8 GNAQ CDKN1B GNAS ERCC8 C4A DYRK1B TRPC6 DNASE1 CA2 PROKR2 MLXIPL LZTR1 STX3 ALG12 AK2 IDH2 SLC52A2 PDE3A HELLPAR HSD3B2 GP9 SGSH BAZ1B ALG1 WT1 TANGO2 MID1 GP1BA XPC LDB3 NR2F2 DNAL1 TGFB3 SGCB CTSH CTSB DISP1 PRKAR1A TRNL1 UBE3B LCAT MAT2A FIBP CYP11B2 TNFSF11 DSP PET100 LMNA ABCA4 KCNA1 NFE2L2 EPHB2 SGCG PROC IARS2 KCND3 D2HGDH MGP TRDN NHLRC2 SOX9 PGAP2 NAGA PUF60 FKRP CTNNB1 SDHD KCNE2 RSPH9 NOTCH2 PACS1 GNAI2 NAA10 GNB5 GGCX KRT10 CD70 ND1 PIK3CD FMO3 ASS1 EXT1 USP9X PSAP GUCY1A1 LMNA WT1 PIEZO2 GJA5 STN1 DCX KCNE5 GPC1 PROKR2 EBP GNPTAB NLRP3 CFAP221 COA5 JUP GJB2 TP63 TBX3 AP1S1 HBA1 ROBO4 CERKL RPL26 DES EDA2R OFD1 CD81 TNFRSF13B POLG2 FIG4 DDX59 MYH7 NSD1 MTHFR HLA-DPB1 AGT RYR1 CFHR1 BRF1 SLC22A4 SLC25A20 MAPRE2 AKT1 RRAS2 EPHB4 MEN1 XRCC4 COX7B HSPG2 CEP290 CCDC115 LTBP2 DLK1 PROP1 SHOC2 FLT4 ACTB DGCR8 FBP1 NEB SLC35A1 EPAS1 COL1A1 MRAP SPECC1L PSEN2 CDH23 BLM PKD2 CDON PKD2 NPHP1 CST3 RAG1 SNRPB PRKG1 USB1 MYOCD GATA4 TMEM70 NDUFAF6 FLNA STAT2 ZNF365 MEFV PYGM RASA1 NEK1 SOX6 NF1 FKTN NF1 CSRP3 RPL35 HCN4 SRY MYOT TDGF1 GATA4 GGCX TAPT1 TMEM216 COX15 SLC4A1 ROM1 PAX8 COX1 MCM4 TINF2 CD40 TOPORS ERCC2 SDHC NAA10 MPL POT1 CR2 COL1A1 FGG FOXE1 NLRC4 TFRC TRIM37 EXT2 LMNA KMT2A ITGB3 TBX3 STXBP1 DNM2 NCKAP1L ATXN7 ACADVL SERPINF2 LDB3 TPM2 PLEKHM1 PAX3 ELP1 IRF8 RMRP TGFBR2 STAG2 UQCRFS1 LMX1B SALL4 CFAP300 SIX3 BMPR1A DDB2 IGHM GJA1 HPGD MEFV KCNH2 KCNQ2 PALLD RNASEH2B NDUFAF8 MSX1 NOTCH3 BCL6 ISCU ABCC8 ATP11A FAM111A DBH ODAD1 SDHC CHRNG HBB SALL4 CTLA4 ATP7A RNF213 LOX PIGV CP POLR1A NMNAT1 ALPK3 GPC3 WNT5A CYP26C1 PTEN PPARG BBS7 DDX6 ABCC9 PQBP1 COG5 LMNA ETHE1 LDLR DVL1 RASGRP1 CHD7 TTC12 VCL GABRA3 KRT18 PROC KLLN IARS1 GPI GAS1 KIF23 ACTA2 KCNQ1OT1 WIPI2 THPO FGF8 GLI2 LBR PLCB4 ARID1B BRAF DSP IDUA ANKRD1 BCOR IL12A MMUT SF3B4 PEX7 CFB SCN1B UMPS SERPIND1 PLOD3 KIAA1109 TERT XPC SMCHD1 CD96 MYH7 ACP5 SPEG NT5E DNAJC21 MYCN IGBP1 LMNB1 ACTC1 OTX2 RHBDF2 RTL1 ESS2 FYB1 EXOC6B RPS26 SLC39A4 PIGA MID1 ARL2BP EPHB4 SFTPB ODC1 ASCL1 TTPA PIGL PEX10 ND2 GBE1 TP63 JAK1 DHPS RAI1 XPNPEP2 DNAJB13 COL2A1 AGBL5 CPT2 PROM1 PALB2 IL12B SDHC PDE6G LEPR JAK2 FGG PIGT TSPYL1 STAMBP FASLG KLF13 PIEZO1 EZH2 EPB41 RUNX1 B2M CORIN SPTA1 NR3C2 MYH6 KLHL41 PROP1 ADA2 LIMK1 DSP RPL5 HMGA2 KRAS CCM2 NDUFAF1 ERCC3 IDH3A EP300 NDUFA6 MCCC1 DCLRE1C FARSA CDC42 PLCG2 ACTC1 STAT4 C2 VAC14 PKHD1 DMD ND3 SIN3A COL7A1 CYP3A5 BRAT1 ZMIZ1 NUP107 PTCH1 LMNB1 HNRNPK ND1 IGHM TNNI3K TGIF1 TUBB GJA5 POLG FLNC HAVCR2 SMARCC2 ERCC2 TXNL4A RAB23 CD3E MLH1 BCHE SULT2B1 DISP1 PEX1 LOX DES PIK3R2 BPTF TNNC1 PPP2CA RNF168 TMEM126B FSCN2 ARCN1 PIGV IDUA NKX2-5 IGH CYBB COL5A2 BCOR JAK2 SERPING1 SLC12A3 DOLK NEU1 TGIF1 ADA STAT3 FIBP B4GALT7 ZMIZ1 HLA-B HDAC4 ECE1 CYP17A1 TSC1 ATP6V0A2 A2ML1 DPM3 RP1L1 PKDCC RPS26 MEFV ORAI1 CLIC2 ITCH SEMA4A ASXL1 TRIM8 WNT4 RPS27 SURF1 UFD1 RAF1 SERPINF2 SRP54 SCNN1B GBA DKC1 MYH7 COG7 TCIRG1 ALOXE3 BBS5 SF3B4 LAMB3 VANGL2 MYPN GLI3 LIPT1 KANSL1 PTCH1 EIF2AK3 PPA2 NDUFB10 FBN1 ARL6 ABCA3 STEAP3 GCH1 UNC13D FGFR1 FZD4 HTRA1 SALL1 CPT1A HLA-DQB1 SMC1A PCCB NDUFAF4 FAM13A NEXN KCNN4 LARS2 CTU2 CYP21A2 HSD17B10 TWIST1 SMC3 COG1 ARPC1B FBN1 CALR GATA1 WDR1 ACTC1 PRNP RHAG DOLK RBPJ INF2 HLA-DRB1 HNRNPA1 PHOX2B DPH1 MYLK TMEM94 PRPF4 ADAR SARS2 HDAC8 MLH3 COL4A1 STAG2 LRAT CITED2 EFL1 KIAA1549 TERC BUB3 CRX ITGB3 NSD1 BOLA3 KIAA1549 ATF6 TRIP13 MEG3 PRDM16 KMT2C AIRE MED13L ATP7B AMMECR1 BCR BBS2 GLB1 ABCC8 ACAD8 DSP CYP7B1 MYPN DLL1 VHL EXTL3 SH3PXD2B KCNE5 ARL6 MAN2B1 COMT MYORG ARX EMG1 AIP CSRP3 RHAG RAG2 FCGR2A GJA5 TMEM67 BTNL2 ADAMTSL2 WNT3 DSP SOX18 PIGN PAFAH1B1 HGD ITPR1 FN1 FBN1 PIEZO1 ACTN2 COL1A1 YY1AP1 NPM1 ATP6V0A2 ZBTB16 AHCY EPG5 COL7A1 DDB2 SHH CACNA1C KIT EGFR OSGEP LAMA3 TBX2 SPECC1L IKZF1 SPECC1L SAMD9 LMNA YY1 PIK3C2A LMBRD1 ELN IFT172 PDSS2 DNAAF4 SH2B3 HBG1 NDUFA2 LZTFL1 MYO5B KCNJ11 EVC2 CEP120 SEC63 UNG PTEN MYC GATA4 SLC26A2 SCNN1G NKX2-1 PLOD1 PLEC DLL1 FHL1 MUC1 KYNU ABCA1 TTC8 IGH CLIP2 H19 APOB LAMA4 PLCB3 IL6 GNAQ KCNE1 IGF1R SLC25A4 DYNC2LI1 GNAS GDF1 MYOZ2 IRF5 DST LMX1B ARMC9 NRAS KCNE1 MEN1 SIX3 HJV MYD88 THOC2 PORCN SNRNP200 SOX11 GNB5 SHOC2 CKAP2L SDCCAG8 AP3B1 POLG PDGFB CBL APOC2 POLA1 COL2A1 LPL MLYCD SON TSC1 MIR17HG DVL3 RGR HESX1 LAMP2 RANBP2 SCNN1B ALX1 IFT122 GNPTG NRAS ARL6 FGB STK11 PEX2 MRPS22 GPX4 PCCA TTC37 DACT1 WT1 SMAD4 DAXX KRT14 PACS2 RPS15A RAF1 LRRC6 TRNW DYNC2I2 TNFRSF1B SHH PDE6B WNK1 PKP1 CHST14 TRNV TANC2 KIT FLNA NFIX SLC12A3 ACAD8 PRKCH TBXA2R TRAC TJP2 CCNO FGFR2 IDUA MGP KIT NDUFS3 GBA HRAS FAM161A KCNQ1 NOD2 NOD2 ADK MYCN SLC25A20 POU1F1 TRNH GAS1 AKT3 RAG1 PTPN11 SLC26A2 GATA2 STAR HMCN1 IDH3B SLC7A7 CACNA1S RARB GATA6 DPP6 FGA CBS SUFU TKFC PCCB CASP10 SRP54 SUGCT TNFRSF13C RPS17 B3GAT3 EBP ATP6 PLN TCAP CHRNA3 KCNH1 KRT5 MED12 MRAS LMOD1 TNFSF11 MYLK2 DCDC2 CAT FGFR3 CYP11B1 P2RY11 FLAD1 ADA XRCC4 MECP2 KCTD1 ND3 ACAD9 GBA CLCF1 NUMA1 TNFRSF11A FBXL4 ASXL1 GDF3 F5 MRAS ROR2 NUP107 HCN4 TNFRSF11A TWIST1 CEP290 IRF8 HLA-DRB1 DDX6 TAZ ZIC3 SEMA4A SCN4A NDUFV1 DNAAF1 LPL HOXA11 TRAF7 ERCC4 CACNA2D1 SPTB FGFR1 RBM20 NDUFA13 BCORL1 PIGW SMOC1 KRT5 ATRX ACTG2 FOXH1 COG7 MUC5B GATAD1 PRKCD HSD11B2 BGN STAG2 NPPA NDUFAF3 MYPN PSAP ABCA1 PTEN TNNI3 KCNJ2 RBM10 GANAB TACR3 CD244 PEX14 KANSL1 TNFSF12 MAP3K7 DBH COG2 SDHB IDS DNAAF3 DNAAF3 MC2R BSCL2 TNFRSF4 NAGS MYMK B2M LDLRAP1 CPN1 CAV1 DYRK1A MYOC HLCS ALPK1 KCNJ5 SCN5A SMO NONO FLT4 MAPT LEP CYP7A1 GPC6 CASQ2 TAB2 CPOX ITCH USP45 RYR2 DPM3 ZNF423 CRYAB CEP120 KIF1B SPIB NKX2-5 SELENOI PIGL FGFR1 NDUFS8 NDUFB8 CACNA1C SPEF2 NECTIN1 PBX1 AEBP1 POMT1 RAC2 JAK2 SCN5A COQ4 TBL2 BMP2 BBS2 GINS1 CFAP298 AKR1D1 TBX19 SYNE2 ACTA2 METTL5 DNAH5 WIPF1 POMT1 TLL1 CSNK2A1 MEG3 FGG LMNA KRIT1 OFD1 GATA6 IL12A TPM3 IL6 TRNT LMNA PPP2R1A SURF1 BRCA1 PSMB8 CACNA1C STAG2 CRKL SEC23A CACNA1D CDKN2B GATC SGCD LRP5 ALX3 TAZ COL5A1 MUC5B SEMA3E MRPL12 TCTN1 CDON PROS1 SRSF2 BAP1 FXN PIK3CA FOXRED1 DPP9 ARF1 RAF1 CD79B HEXB SDHC XRCC2 FGFR2 MYPN ZIC2 CALR ITGA7 LTBP2 RPGRIP1 TRIP11 APC SOX2 ABCA1 EXT2 NF1 SPINK5 DSG4 RTEL1 TNNI3 GPC3 TGFB2 SMAD4 DYNC2I1 TPM1 DMPK POMT2 DCDC2 SKI PIK3CA EBP WT1 ANKRD11 NR3C1 HFE SAMD9L TRNW SMC1A KCNE2 ICOS RTTN RB1 HGD F5 FOXF1 CHST14 GLB1 KRAS NCF1 SMAD6 PTCH1 IL2RG B3GALT6 SF3B4 GLI2 RP1L1 OTULIN F8 TET2 SEC23B ZNF148 COX3 OBSL1 WRAP53 ACTN2 PAX3 NDUFV1 ATP7A HGSNAT GLUL CARMIL2 PDGFB ABCC6 STIM1 KDSR DGUOK PTEN TERT FAT4 ALG1 PSEN2 MYL4 COX14 ITGB3 IGFBP7 PHOX2B CHD7 RBM8A ROM1 NLRC4 F10 PTGIS TMEM70 POLD1 EMD TDP2 CACNA1S PRKCSH NUP155 ALPL PKLR TRNL1 CTC1 PEX5 SDHB GATA6 MYPN ALG10B MEN1 NDUFV2 SDHD CCDC39 HEPHL1 HSD17B10 WHCR ACSL4 GP6 MTMR14 COX1 NAA10 FGFR3 EP300 TNNI3 GMPPB NDUFS4 LZTFL1 CTNNB1 INPP5E KCNJ8 HCRT HLA-DRB1 DKC1 TERT SCN10A GGCX KRT8 ERCC4 SFTPB LMBR1 NDUFAF1 RFT1 CCDC65 HDAC8 HBA1 POMT1 SEC61A1 SLC25A11 FLII CLIC2 CPT2 ATP6 DHCR24 COA8 CAV3 LFNG RLIM SUZ12 MARS2 NEU1 XIAP HLA-B BTD SREBF1 FGFR2
    HP:0000819: Diabetes mellitus
    Genes 567
    LHX1 BLK MERTK PROK2 UBR1 MTHFR MAGEL2 UBR1 NODAL ND6 NDUFS4 RETN TRNL1 MAGEL2 TRNK POLA1 GTF2IRD1 TRNC SLC7A14 RP1 HNF1A CTRC CAVIN1 BRAF RTL1 BBS1 FGFR1 PDE6A CNGB1 LIPE ZNF408 HNF1B TRNS2 GCK HNF4A SHH CTNNB1 BMP2 HYMAI DCAF17 PTF1A TOPORS CFTR KCNJ11 OCA2 SPINK1 ENPP1 AMACR MTNR1B ND1 TCF4 RBP3 ELMO2 PRSS1 SAG MAPK8IP1 PAX4 TP53 NDN FUZ DLL1 PROKR2 RTL1 PCNT SIM1 CLIP2 ABCC8 ELN KCTD1 PIK3R1 TTC7A IRS2 IGF1R GNAS EDA2R ABCC8 PIK3R1 OFD1 PLIN1 CNBP PEX10 COX1 ELN KLF11 SLC19A2 TULP1 LMNB2 PEX6 AKT2 NDUFV2 NDUFAF5 HFE GLIS3 SNRNP200 INS FOXP3 HMGA1 LIPE TRMT10A XRCC4 NEUROD1 HESX1 PTRH2 MTHFR PDE4D NSMCE2 GLRX5 HAMP HNF1B TRNW NPAP1 PPARG SUFU RP9 IFT88 IRS1 RHO PLAGL1 BLM TDGF1 PRSS1 AKT2 PDX1 TRNW ARL3 RPGR HNF4A GPD2 LMNA PDE6B USB1 MEG3 NDUFB10 SNORD115-1 ZNF513 DNAJC21 WFS1 XRCC4 SOX3 SLC25A4 IL2RA RLBP1 NDUFA11 MKRN3-AS1 PRKAR1A NDUFS3 HJV TKT FAM161A GCK LIG4 ROM1 GJA1 TRNS1 TRNH BLM COX1 SNRPN TTC8 PDE8B AGPAT2 TREX1 TINF2 LMNA AIP DCAF17 ND2 IFIH1 BRCA1 IDH3B DNM1L PDE4D GJB4 USP8 BEST1 PWRN1 GATA6 IPW RP2 ND1 GATA6 ARNT2 SLC19A2 APPL1 ND4 PDX1 FOXRED1 TRNF STAT1 INSR IMPDH1 GATA3 SLC2A2 DHDDS EIF2S3 IL6 CNOT1 HLA-DRB1 GPR101 PPARG TRNQ GCK RPE65 ATP6 SNRPN ZBTB20 CISD2 TRNS1 INS CAT SPATA7 RAC1 NDUFB11 HNF4A PALLD RNASEH2B TRNE XRCC4 NDUFAF8 ARHGEF18 STAT1 CYTB LIPC GCK EDA HBB MMP2 OCA2 ZFYVE26 FOXP3 TRNF KLHL7 ALMS1 CP SEMA4A USH2A FGF8 SBDS HBB CERKL INS CYP19A1 APPL1 RNASEH2A TRNS2 ZFP57 GJA1 CDON TIMMDC1 FGFR1 POLR3A AGPAT2 MAGEL2 HNF4A ZFP57 ND1 FOXH1 PRPF8 IARS1 SPINK1 PAX4 HNF1A NDUFAF3 GAS1 CDHR1 NPM1 STUB1 PWAR1 CPA1 KCNJ11 EYS HNF1A IL18BP DISP1 PDX1 VANGL1 CEP19 POLG2 CARS1 CLRN1 HNF1B NDN MKRN3 KCNJ11 BSCL2 OCA2 ZIC2 SRP54 CAV1 CFTR DHX38 IFT172 PPARG FXN WRN PLIN1 INSR WRN NDUFB9 WFS1 DLK1 MMP14 LEP PTPN1 ARL2BP PRCD EIF2AK3 CIDEC ITCH PRPH2 CDH23 NEK2 ATM PTRH2 TTPA SLC29A3 NDN NKX2-5 PDE11A NDUFS8 REEP6 AGBL5 ZMPSTE24 PROM1 NDUFS6 TRNK AEBP1 PRSS2 LEPR TBL2 BBS2 COL2A1 LRP6 GCK POC1A PDX1 CTNS CORIN PNPLA2 IFT140 PPP1R15B FOXP1 RFC2 CTRC NDUFS1 LMNA PTPN22 SNORD116-1 LEPR RNASEH2C RRM2B LIMK1 BLK NOTCH3 HMGA2 TWNK CNOT1 FLT1 NEUROD1 KCNJ11 ABCA4 IDH3A CDKN2A NDUFA6 KIZ ABCC8 ATM BRCA2 ND6 NDUFS2 LMNA ND3 IMPG2 MST1 TGIF1 PAX4 WFS1 KCNJ11 FXN NOP10 KDSR MEG3 OPA1 TRNQ TUB HYMAI CISD2 DNAJC3 STOX1 IL2RA NDUFS7 NDUFA1 NUBPL BSCL2 PEX1 COX2 SPINK1 PAX4 RTEL1 INS NDUFB3 COX3 CASR SMAD4 GCK ITPR3 SNRPN HBB POLG NDP OTX2 SLC12A3 TRNE PNPLA6 APOA5 LMNA GCK STAT3 POMGNT1 PDE6G WFS1 GLI2 CLCNKB ALMS1 AHI1 LEMD3 HNF1A BBS2 GJB3 ABCC8 TP53 ITCH RP1L1 PLAGL1 LMNA PALB2 NDUFAF2 CRB1 CNGA1 DMPK PPP1R3A PNPLA2 PTCH1 WRAP53 STAT3 SAMHD1 HYMAI NDUFV1 HGSNAT HNF1B HNF4A SLC29A3 ARMC5 CCDC28B KRAS GTF2I MAGEL2 TWNK HNF1A PRPF3 VANGL2 GUCA1B TMEM126B EIF2AK3 TRNV TERT KCNJ11 PTF1A FBN1 IGF2BP2 ARL6 COX2 HFE AIP NR2E3 PCARE MAK KCNJ11 HLA-DQB1 ABCC8 NDN PLCD1 NDUFAF4 POLD1 CEL VANGL2 NSMCE2 PSTPIP1 SOX2 SIX3 ND5 TCF7L2 NEUROG3 MKKS CAV1 SMPD4 SLC16A2 PDX1 FSCN2 PRKACA CA4 MC4R TRNL1 PRKACA CTC1 ADA2 PRSS2 SNRPN RGR AHR DMXL2 PRPF4 KLF11 ADAR SARS2 MOG MEN1 HERC2 CP ND5 INSR LRAT MAFA EFL1 HNF1A TERC FOXC2 SCAPER FOS CRX DLK1 KIAA1549 MAGEL2 MLXIPL DNAJC3 PRPF31 AIRE PRPF6 PARN DKC1 NEUROD1 APOE PPARG WFS1 ABCC8 LRBA AR NRL NHP2 GPR35 BAZ1B RDH12 ERGIC1 ARL6 NDUFAF1 SLC30A8 PDX1 COX3 ABCC8 INS C8ORF37 IER3IP1 PRKAR1A KCNJ11 CEL INS TRNL1
    HP:0002094: Dyspnea
    Genes 438
    TLL1 MAT2A TRNK DSP CHRNA1 LMNA CSPP1 TRPV6 AIFM1 NPM1 ZBTB16 EFTUD2 TGFBR2 LAMA3 SFTPA1 SH2B3 IKZF1 ND1 DNAJB6 BTNL2 COPA KCNJ6 USP9X GAA MEGF10 KRT16 GATA6 GATA4 FGFR2 APOB CASR MYL3 ZIC3 NKX2-1 PLEC PURA AIMP2 DCTN1 DOK7 KCNA1 SCNN1B SCN4A CDC6 LAMB2 DYNC2LI1 RARA ALAS2 VAPB IRF5 PMM2 STT3B ADNP SCO2 MUSK MYH6 ABCA3 TSC1 ATRX FOXF1 CHRNA1 ORC4 FOXP3 TERC USP9X CAV1 ND4 CBL COLQ COL2A1 EPHB4 FGFR1 NOD2 STAT5B MAPT COL2A1 TARDBP CREBBP FBP1 ACTA2 BMPER SLC35A1 SOX9 MATR3 CCR6 PRRT2 MFAP5 GLA RELN CHRNE AK9 SLC5A7 CHRNB1 COL13A1 CSF2RB SCN4A DISC1 TRNV PRPH FGFR2 ACVRL1 PYGM TRMU RNF13 CHRNE NDUFB11 SLC25A4 DNA2 NAGS ACADVL MRPL3 VPS33A TRPM4 NGLY1 MYH11 NEFH TRIP11 CRELD1 SCN5A SCO2 CAV1 ND5 ORC6 PUF60 SMAD4 SMPD1 CYB5R3 GATA6 XYLT1 KAT6A KIF20A EDA SNRPN RPS28 GNAI3 CCNF TTN CDC45 ZMPSTE24 STN1 PRKCSH SBDS TRNN VCP MYL2 VCP TBX20 CSF2RA ND3 TRNK GBA ISCU TGFB2 NUMA1 GATA4 TERT SCNN1G MMACHC SFTPC ATP11A NKX2-5 HBB EIF2AK4 SPP1 CITED2 LDLRAP1 MMAA MYBPC3 ERBB4 DAO ZFPM2 ALMS1 CHRND ORC1 PURA SCN4A TUBB4A SFTPC ALDH7A1 LDLR DNASE1L3 IFT81 MUC5B MARS1 SSR4 EPHA4 CHCHD10 CHMP2B ENG MPC1 NPPA CCN2 ARX MGME1 DPM2 TSC2 PLCB4 AGRN TAF15 NUP214 TRIP11 NKX2-5 TSC2 MMUT PCSK9 OPTN POLG2 JPH2 DBH SCN1B TERT SLC18A3 FOXE3 TRNL1 RTEL1 PRKG1 OTX2 NABP1 DNAAF3 DPM2 DNAJC21 NAGS GALC SFTPB LIFR TNNT2 RUNX2 GLE1 HLCS ACTC1 VAMP1 TRNE BMPR2 ADAMTS13 ND2 UNC13A SLC25A1 ELN SFTPA2 TBK1 GATA6 SFTPB SCNN1A SERPINA1 PFN1 RAPSN LYRM4 CHRND MYH11 CRLF1 EOMES SLC2A10 NDUFB8 GBA MMUT POMT1 COQ7 ERF VCL UBE3B ETFDH SCN5A PON2 CFTR FLNC SDCCAG8 WIPF1 PARN HCCS BCOR GYG1 LAMC2 RRM2B ITGA3 GATA6 GTPBP3 FIG4 NEB TWNK STAT5B SFTPC SURF1 LTBP3 CSF2RB COL1A2 ABCA3 TBC1D24 GAA STAT4 SIK1 C9ORF72 DNA2 MUC5B TK2 SRSF2 TRNS1 DPP9 SMAD3 CITED2 CFAP410 FLNC STAT3 TNNI3 PRKAR1A CHRNE LOX TNNC1 TRAK1 ORC6 CYB5R3 CHRNB1 EDN1 FAM20C PON1 HNRNPA1 FBP1 HBB POLG STT3B DMPK SLC12A3 TRNE FBN1 SETBP1 NDUFAF3 ATXN2 PRRX1 TRNW ETFB RNU4ATAC SFTPC CNTNAP1 HLA-B CHAT PIGT TSC1 STX16 CLCNKB PGM1 CDT1 COX7B SLC25A1 B3GALT6 RPS26 IRF2BP2 TRMT5 TET2 ASXL1 ABCG5 WAS LGI4 PSAP PNKD SURF1 LRP4 PRRX1 TET2 GLT8D1 MGME1 ASAH1 DHX16 SRP54 GBA LAMB3 MYO9A MMAB IL1RN DSC2 ACADM IRAK1 RUNX1 TGFBR1 CYB5A COL13A1 ANG GNAS GMNN KLHL7 TBX20 ABCA3 ANXA11 NDUFS2 EPOR IFT52 UBQLN2 SFTPA2 FAM13A PON3 SLC52A3 KRT17 KRT6A ADCY6 HLA-DRB1 TET2 BMPER CPT2 MYLK PML MYPN TGFB3 AGRN SLC25A3 TBX4 FIP1L1 JAK2 KRT6B NEK1 SYT2 TBL1XR1 TREM2 GNAS ND6 FGFR2 EP300 MAPT ORC1 PPARGC1A DPM1 FGFR2 SQSTM1 HLA-DRB1 SOD1 HLA-DRB1 NKX2-1 TLL1 SNAP25 GNAS TERT FUS ATP6 ABCG8 NR2F2 COA8 ETFA VPS33A SERPING1 BTNL2 CHAT PRKAR1A
    Protein Mutations 0
    SNP 0
    HP:0001945: Fever
    Genes 374
    NLRP3 PSMB4 CHD7 NABP1 PTPN22 TRNK MTHFR ND6 GALC IGH SCYL1 LIFR TREX1 BCAP31 EIF2B5 G6PD NPM1 ZBTB16 ABCC2 EPB41 CTRC DDB2 CD247 ADAMTS13 POU6F2 ND2 IFNG NTRK1 LAMA3 SCNN1A IKZF1 ND1 SLC29A3 TNFRSF1A RAG2 NLRP3 CFTR CRLF1 TP53 MALT1 CD70 ATM CACNA1S TCF4 SLC19A3 PRSS1 IL12B HLA-DPA1 JAK2 XPA CPT2 PRSS2 CFTR IL10 NAB2 ATP13A2 NCF4 REST WIPF1 NLRP3 NCF2 IGH SPTA1 SCNN1B CHEK2 H19 PTPN3 CYBC1 HTR1A BCOR LAMC2 RYR1 RAG2 TMEM165 RNASEH2C RARA DST IL6 PMM2 NCF1 CYP11B2 CD3D COX1 UNC93B1 RB1 TRAF3 MPL PSMB8 EIF2B4 IL36RN MYD88 GCH1 TH TSC1 GAA CYBA HLA-DPB1 RIPK1 NLRP12 STAT4 SPTA1 MLX TRIP13 AVP CFHR1 ELANE MPL AVPR2 P4HTM ND4 IGLL1 MST1 SLC22A4 PTS LPIN1 TRIM28 TCF3 HNRNPK IGHM CD79A PIK3R1 NOD2 MTHFR RANBP2 RYR1 LACC1 AVPR2 STAT5B STXBP2 TRNW CD79B CTLA4 NLRP3 TET2 SPTB EIF2B2 HAVCR2 HLA-DRB1 ERCC3 CYBB CD3E BCL2 DIS3L2 FOXP1 IL23R COX2 SPINK1 STAT3 GLA PRKAR1A KCNJ1 RNF168 COX3 IL7R NLRP3 TRNV FBP1 STAT2 HBB IGH GALC STX11 MEFV SLC12A3 BACH2 LPIN2 STAT3 ATP1A2 CFH CALR SLC35C1 WT1 LIFR PEX6 TRNW PRTN3 EPB42 HMGCL MEFV NOD2 HLA-B TRNS1 DCLRE1C NGLY1 IBA57 TLR4 TRNH JAK2 RAG1 ORAI1 PMP22 CYBC1 MVK AQP2 PRNP ATP1A3 CACNA1A TREX1 MEFV GATA2 ERCC2 BRCA2 OTULIN BCR ND5 IRF2BP2 IFIH1 IFNGR1 WAS RYR1 CASK NLRC4 PSAP ERCC5 ZFHX2 NLRP3 SAMHD1 COL1A1 ND1 SH3KBP1 ASAH1 SLC29A3 LACC1 TCIRG1 ND4 TNFRSF1A MEFV ACAT1 STING1 STAT4 EDA SRP54 ELP1 LAMB3 VANGL2 RMRP IRF8 IRAK1 C4A QDPR TRNQ COL1A1 KLHL7 CCND1 CCR1 UNC13D EIF2B1 UBAC2 BTK BIRC3 HNRNPK MEFV CD27 TP53 ADA RNASEH2B FAS NLRC4 CFHR3 PSMB9 BCL10 TNFAIP3 PRF1 TICAM1 ND3 VANGL2 PSTPIP1 BCL6 SLC4A1 NUMA1 PADI4 CACNA1S JAK2 HMBS TRNT1 CYP21A2 SCNN1G F5 MIF NTRK1 EIF2B3 ALPL ITK CALR ERAP1 RAB27A WDR1 HBB SPP1 MYD88 TRNL1 TLR3 ADA2 LBR IRF8 HLA-DRB1 PTPN22 TET2 STIM1 KIF1B LYST PML TRIM28 TRNF ADAR NLRP3 GYPC FIP1L1 RAG1 STAT6 TBK1 ELANE ND5 HAVCR2 HMGCL TBL1XR1 COG6 KLRC4 PTPN22 AQP2 XIAP ND6 HLA-B RNASEH2A TRNS2 IL2RG SPTB NLRP1 POLR3A HLA-DRB1 LIG4 AK2 IL10 HLA-DRB1 PRKCD MVK NKX2-1 KRT18 LRRC8A SLC12A1 IL12A-AS1 ABL1 KRT8 GPC3 ELANE LPIN2 GPR35 CYP11B2 CIITA RUNX1 BLNK TSC2 WT1 IL2RG IL7R ERCC4 ATP6 ANK1 SH2B3 IL12A CD244 LIPA RAB27A GFI1 NGF SLC11A1 CYTB POMP NFKBIL1 BTNL2 XPC HLA-B TRNL1 PRKAR1A
    Protein Mutations 0
    SNP 0
    HP:0002090: Pneumonia
    Genes 280
    TLL1 CHD7 TGIF1 KMT2D ACP5 PIGN JAK3 NOS1 SFTPB SRP54 MS4A1 NODAL USB1 CD79B SGCG ACTC1 CASP8 TGFB1 OFD1 CD19 CD247 NHLRC1 SHH NTRK1 EGFR LAMA3 PLOD1 FANCF JAK3 RAG2 PGM3 CACNA1C BTK IL2RG PIK3CD CREBBP KCNJ6 FMO3 ACTA1 TNFSF12 GATA6 ZAP70 PLOD1 UNC119 FGF8 GAS1 DNAI1 WAS GNPTAB FOXH1 CYBC1 LAMC2 RAG1 PEPD PDHA1 PMM2 PAFAH1B1 CD19 CD3D SIX3 CD81 DLL1 LTBP3 EP300 TNFRSF13B SIX3 GLI2 SMARCD2 TIMM8A MYH6 DCLRE1C ABCA3 IL7R TBC1D24 STAT3 CFB FOXH1 FOXP3 FCGR2A P4HTM AP3B1 POLA1 TK2 CDON PKHD1 TAF1 CDON NIPBL GRHL3 GAS1 EFEMP2 CRLF1 SLC35A1 SLC25A24 DOCK8 ZIC2 LEP AFF4 DDR2 CD3E PTPRC BLM RNU4ATAC TNFRSF13C KNSTRN CDON SELENON FOXH1 ORC6 RAG1 RNF168 SHH DISP1 CYBA IL7R CARD11 LONP1 COL11A2 CR2 FGF8 ZIC2 CARD11 CYBB NBN ICOS DNAJC21 DNMT3B DISP1 TGIF1 HLA-DQB1 ADA SETBP1 MED25 FOXH1 SLC35C1 ACADVL TDGF1 PNP SP110 SMC1A ICOS SREBF1 TDGF1 NBN DCLRE1C ALMS1 GLI2 MCIDAS FGF8 NCF1 RAG1 PTCH1 NADK2 IL2RG ZBTB24 ZAP70 GLI2 FGFR1 GAS1 TNFRSF13B GAS1 IFNGR1 CFTR COL11A2 CR2 SAMD9 CD247 TGIF1 TREX1 CARMIL2 TCIRG1 BLNK UBB SRP54 LAMB3 DISP1 RMRP TNFRSF13C NFKB1 STAG2 IRF8 PTCH1 SIX3 KPTN TBX20 TDGF1 CSPP1 IGHM BTK NFIX RNU4ATAC CXCR4 NFKB2 RAC1 CD27 TGIF1 ADA TBX20 ZIC2 MTHFD1 RAG2 GATA4 TNFRSF11A DZIP1L FGF8 KIAA0586 SHH TDGF1 RYR1 ODAD1 WDR1 CREBBP CITED2 DLL1 NCF2 TBCD SHH NODAL RAC2 SIX3 GBA PTCH1 DNAI2 ZIC2 TNFRSF13C ALMS1 PURA STAG2 DLL1 SBDS ICOS EFL1 ACP5 SFTPC CFAP410 MASP2 IL2RG IGLL1 AFF4 BTK LIG4 NFKB2 WDR19 CD55 CDON GAS8 EPM2A NKX2-1 RNF125 DCLRE1C NODAL LRBA ELANE MAN2B1 DLL1 PTCH1 HLA-DQA1 EXTL3 SLC35C1 MAN2B1 FOXN1 PRKCD GLI2 RANBP2 MID1 IL2RG FBLN5 NKX2-5 NODAL GFI1 TNFSF12 RAG2 ADA IL21R KDM6A OSTM1 ASAH1 DISP1 PANK2 FGFR1
    SNP 0
    HP:0011947: Respiratory tract infection
    Genes 816
    KMT2D SMARCB1 ABCA12 TNFSF11 TRAIP MAGEL2 DNAAF1 NFE2L2 NFKB2 LCK MAGEL2 SGCG TECPR2 GTF2IRD1 CHAMP1 OFD1 SCNN1G CD247 MGP SPINK5 CTPS1 NTRK1 NGLY1 RELB ZNF341 RSPH9 FCN3 NELFA MALT1 CFTR OCA2 LETM1 PIK3CD FMO3 USP9X HLA-DPA1 DNAH11 ZAP70 UNC119 WAS SIM1 GNPTAB FOXH1 CFAP221 TARS1 LAMB2 MYO5A CD81 ADNP TNFRSF13B MYH6 TSC1 CYBA HLA-DPB1 GNS FOXH1 LIPN KATNIP TPM2 COL6A1 NIPBL SPAG1 IL17RA GAS1 SLC12A6 EFEMP2 CRLF1 GMNN CTLA4 SLC35A1 ADAMTS3 TAPBP SLC25A24 CXCR4 BLM RNU4ATAC CFAP300 FOXP1 CDON CD79A RAG1 VPS51 DISP1 USB1 NEPRO COL11A2 CR2 LAMTOR2 SNORD115-1 MAP3K20 DNMT3B MKRN3-AS1 LYST PIK3R1 ACADVL TDGF1 RFX5 VPS33A MDM4 TBC1D24 NGLY1 GLI2 FGF8 ODAD4 CCDC40 MCM4 CRELD1 ZBTB24 TINF2 ECM1 LRRC6 CFTR COL11A2 CR2 ELP1 TFRC AGA SMPD1 PWRN1 IPW TCIRG1 BLNK FLI1 UBB KIF20A STAT1 MBTPS2 ELP1 SNRPN DISP1 RMRP STAG2 IRF8 SIX3 KIF1A RYR1 IGHM BTK CYP4F22 CXCR4 RSPH1 CCBE1 DNAH11 ZIC2 CSF2RA POLR3A LAMA2 STAT1 SNX10 FGF8 FOXJ1 AICDA SHH RYR1 ODAD1 SIK1 HACD1 CREBBP TNFRSF13B CITED2 OCA2 NODAL NOTCH2 CFAP298 SELENON ZIC2 ALMS1 ODAD4 IDUA DLL1 SBDS COG6 TBX6 RFXAP PEX13 TCTN3 PTPN22 SFTPC MAGEL2 COG4 EPM2A MESP2 TTC12 TBC1D23 SCNN1B TGFB1 MAN2B1 PTCH1 NPM1 EPG5 UGP2 GLI2 GAS2L2 TSC2 RANBP2 SCN11A CTLA4 MESP2 IL21R IL17RC UMPS SLC18A3 MYSM1 TRPS1 MKRN3 RPGR DSG1 ACP5 JAK3 EXOSC9 MIR140 DNAL1 NCF4 ACTC1 VAMP1 TGFB1 CD3E IDUA FANCF PLCG2 SLC29A3 NDN RAG2 RAG2 SLC46A1 PGM3 GBA IL2RG SULT2B1 DNAJB13 SDR9C7 MSN MYOD1 FCGR3A SHROOM4 PNP ACTA1 ERF MYSM1 LEPR FLNC NCF4 ODAD2 RFXANK KAT6B DNAI1 NEK10 DNAI1 MPLKIP AGA LAMC2 RAG2 LEPR IL17F DCLRE1C LIMK1 PEPD ITGA3 ZBTB24 NCF1 CD3D EP300 IL2RB GLI2 COL6A3 FBLN5 TASP1 DCLRE1C PYROXD1 IL7R TBC1D24 PLCG2 GAA ODAD3 NFKBIA IL17RA KRAS IGLL1 SCNN1A ODAD3 TK2 TPM3 RNF113A IGHM CCDC39 MS4A1 SMN1 SMARCC2 LEP CYBB NEU1 CD3E PTPRC PLG FOXH1 TNNI3 TYK2 ORC6 RNF168 CARD11 CD3G LONP1 GNPTAB IDUA CYBB NBN NRAS DNAAF6 TGIF1 WAC ADA STAT3 SETBP1 CD3D STAT3 RSPH4A HLA-B TSC1 DNMT3B ITCH GAS1 NEK10 CCDC22 SAMD9 CD247 CFI TREX1 ASAH1 INPPL1 MECP2 HYDIN DNAAF2 IL6R LAMB3 NFKB1 RUNX2 KANSL1 PTCH1 TDGF1 RAG1 UBE2A NFKB2 PIK3CD SMN1 TGIF1 HELLS RSPH9 MTHFD1 SMARCD1 OCRL SLC52A3 DZIP1L TDGF1 WDR1 ALB ADA2 DLL1 SHH SIX3 MYL2 STAG2 EFL1 TERC CFAP410 MASP2 GLB1 LIG4 PARN NFKB2 EDARADD DNAAF6 BCR RNF125 TLL1 DCLRE1C SCNN1A ASAH1 SNAP25 NHP2 DNAAF5 DLL1 EXTL3 PRPS1 MAN2B1 ZMYND10 FOXN1 PRKCD BLNK IL2RG IL7R SMPD1 NODAL NECTIN1 LAMTOR2 RAG2 ROR2 ADA IER3IP1 KDM6A TLL1 ALOXE3 TGIF1 PIGN NOS1 NXN DNAH1 MS4A1 NODAL USB1 LRRC56 ATP6V0A2 EPG5 CASP8 PRPS1 IKBKB ARID2 SHH ARID1B EGFR LAMA3 IKZF1 PLOD1 PRKDC JAK3 DNAAF4 BTK PEPD SCNN1B KCNJ6 GAA MCIDAS SOX4 ZMYND10 UNG GATA6 GATA4 SLC26A2 NDN CD81 NKX2-1 PLOD1 PLEC FGF8 GAS1 ABCA12 IGH CLIP2 SCNN1B CYBC1 RAG1 CLEC7A DRC1 TCIRG1 PMM2 PAFAH1B1 TGM1 DLL1 SIX3 TIMM8A ELN FUCA1 SPAG1 ARID1B ABCA3 ARSB CFB SOX11 FOXP3 USP9X P4HTM AP3B1 POLA1 CDON PKHD1 TAF1 COLQ TCF3 TRIP4 STXBP2 CREBBP NPAP1 STK36 DOCK8 DDR2 CD8A CCDC65 INPPL1 TNFRSF13C KNSTRN SELENON LRRC6 SLC5A7 SHH IFIH1 IL7R CIITA ZIC2 FLNA G6PC3 BACH2 ZNHIT3 DNAJC21 SH2D1A CCNO COL13A1 DISP1 IL21 HYDIN MGP IL2RA MED25 GSN FOXH1 SLC35C1 PNP PRTN3 SP110 ARID1A NBN MCIDAS RAG1 TAP1 SNRPN NADK2 ZAP70 MAGT1 FGFR1 GATA2 ALOX12B IFNGR1 NFKB1 DOCK8 AP3D1 STING1 B2M SRP54 TNFRSF13C TTC12 TAP2 KPTN SNRPN DNAI2 CHRM3 CCNO RAC1 ADA TBX20 ODAD2 BCL10 FLNA SLC25A22 RAG2 GATA4 DNAH9 SMARCA4 TNFRSF11A IRAK4 GUSB CD40LG SCNN1G GUSB KIAA0586 NSD2 DPF2 GBA NCF2 GAS2L2 MYH3 TBCD PTPN22 RAC2 PTCH1 DNAI2 TPP2 RAG1 KANSL1 PURA LRRC56 DNAAF1 SCNN1G IL6ST ACP5 XIAP IL2RG IGLL1 AFF4 SCNN1B BTK PCNT CDON COG4 PRKCD LRRC8A PSAP HLA-DQA1 DYNC2I2 SLC35C1 PWAR1 SLC1A4 CR2 TBCE AGRN CTCF FBLN5 TRIP11 NKX2-5 TSC2 GFI1 TNFSF12 GAS8 MAPK1 DNAAF2 SCNN1A ACTA1 NDN IDS PANK2 FGFR1 CHD7 DNAAF3 DNAAF3 DPM2 OCA2 PCGF2 SFTPB MANBA TNNT2 SRP54 CD79B CD19 FOXJ1 LEP NHLRC1 GATA6 SCNN1A SERPINA1 ATM DNAJB13 CLCN7 CACNA1C SPEF2 CREBBP TNFSF12 COL6A2 RAC2 TBL2 CFTR CFAP298 RSPH3 SDCCAG8 DNAH5 WIPF1 NCF2 FOXP1 RFC2 SNORD116-1 POLR2A CCDC103 OFD1 DNAAF5 PDHA1 CD19 SIX3 LTBP3 SMARCD2 CSF2RB PSMB8 CRKL EP300 RSPH1 ATM DCTN4 CLCA4 CTSC STAT3 FCGR2A DNAH5 CDON TRAF3IP2 IDS CD79A PIK3R1 GRHL3 NOP10 HPS6 RPGR SCNN1G CD79B IVNS1ABP ZIC2 AFF4 ITGA7 ERCC2 RAB3GAP2 RTEL1 CYBA SCN9A RASGRP1 FGF8 SNRPN CARD11 POLE ICOS NME8 HLA-DQB1 PGM3 CDCA7 SAMD9L SMC1A ICOS GLI3 SREBF1 CHAT RFX5 TDGF1 CCDC40 SMARCE1 DCLRE1C ALMS1 NCF1 RSPH3 CYBC1 SLC25A1 PTCH1 IL2RG GLI2 GAS1 TNFRSF13B WAS EHMT1 WRAP53 TGIF1 GLUL SH3KBP1 RFXAP CARMIL2 GTF2I TNFRSF1A MAGEL2 HGSNAT MYO9A GTF2H5 TERT RYR1 FAT4 RIPK1 COL13A1 JAGN1 CIITA TBX20 CSPP1 DNAAF4 HK1 NFIX RNU4ATAC BIRC3 IKBKB CD27 NDN TGFB1 PIK3R1 CREBBP ALPL CCDC103 NAGLU ODAD1 CTC1 SNRPN PRPS1 DLL3 LYST GBA NME8 MYPN STX1A TNFRSF13C HERC2 ELANE CORO1A SYT2 CCDC39 CFTR ICOS RFXANK EP300 MAGEL2 WDR19 ALG12 AK2 CD55 GAS8 DKC1 NKX2-1 SCN10A NODAL LRBA ELANE GTF2E2 SGSH BAZ1B PLP1 CACNA1B RSPH4A CCDC65 MID1 NR2F2 ERCC3 WASHC5 NIPAL4 VPS33A CD19 GALNS OSTM1 XIAP ASAH1 DISP1
    Protein Mutations 1
    H275Y
    SNP 0

    Reports

    Data processed on December 13, 2020.

    An HTML report was created for each of the unique drugs, MeSH, and HPO terms associated with COVID-19 clinical trials. Each report contains a list of either the drug, the MeSH terms, or the HPO terms. All of the terms in a category are displayed on the left-hand side of the report to enable easy navigation, and the reports contain a list of correlated drugs, MeSH, and HPO terms. Further, all reports contain the details of the clinical trials in which the term is referenced. Every clinical trial report shows the mapped HPO and MeSH terms, which are also hyperlinked. Related HPO terms, with their associated genes, protein mutations, and SNPs are also referenced in the report.

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