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  • HP:0002090: Pneumonia
  • Pneumonia (359) Respiratory tract infection (38) Neoplasm (36) Abnormality of the cardiovascular system (34) Diabetes mellitus (33) Depressivity (29) Acute kidney injury (27) Hypoxemia (26) Hypertension (24) Abnormal lung morphology (24) Thromboembolism (22) Anosmia (20) Myocardial infarction (20) Arthritis (19) Type II diabetes mellitus (18) Stroke (16) Pulmonary embolism (16) Mental deterioration (15) Abnormality of coagulation (15) Pulmonary fibrosis (15) Chronic pulmonary obstruction (15) Abnormality of the kidney (14) Autistic behavior (14) Rheumatoid arthritis (14) Leukemia (14) Interstitial pneumonitis (14) Pulmonary obstruction (14) Asthma (13) Chronic pain (13) Congestive heart failure (12) Deep venous thrombosis (12) Neoplasm of the lung (12) Autism (11) Obesity (11) Respiratory distress (11) Colitis (11) Ulcerative colitis (11) Crohn's disease (11) Type I diabetes mellitus (10) Abnormality of the liver (9) Coronary artery atherosclerosis (9) Inflammation of the large intestine (9) Pulmonary insufficiency (9) Chronic kidney disease (9) Myocarditis (9) Behavioral abnormality (8) Psychosis (8) Dementia (8) Alzheimer disease (8) Carcinoma (8) Low levels of vitamin D (8) Sepsis (8) Infertility (7) Peripheral arterial stenosis (7) Renal insufficiency (6) Lymphopenia (6) Dysphagia (6) Lymphoma (6) Systemic lupus erythematosus (6) Osteoarthritis (6) Breast carcinoma (6) Psoriasiform dermatitis (6) Abnormality of the gastrointestinal tract (6) Fatigue (6) Encephalopathy (5) Premature birth (5) Bronchiectasis (5) Difficulty walking (5) Gastroparesis (5) Immunodeficiency (5) Obstructive sleep apnea (5) Autoimmunity (5) Knee osteoarthritis (5) Sleep apnea (5) Prostate cancer (5) Allergy (5) Non-small cell lung carcinoma (5) Schizophrenia (5) Neoplasm of the large intestine (5) Seizure (4) Hepatic fibrosis (4) Cardiac arrest (4) Weight loss (4) Migraine (4) Pulmonary arterial hypertension (4) Abnormal intestine morphology (4) Neoplasm of the pancreas (4) Colon cancer (4) Malnutrition (4) Paroxysmal atrial fibrillation (4) Disseminated intravascular coagulation (4) Attention deficit hyperactivity disorder (4) Inflammatory abnormality of the skin (4) Neoplasm of head and neck (4) Endometriosis (4) Addictive behavior (4) Hypercoagulability (4) Insomnia (4) Obsessive-compulsive behavior (3) Eczema (3) Atopic dermatitis (3) Spastic diplegia (3) Abnormal heart morphology (3) Cardiomyopathy (3) Fever (3) Hypothermia (3) Headache (3) Celiac disease (3) Reduced factor VIII activity (3) Lymphoid leukemia (3) Renal cell carcinoma (3) Abnormal anterior horn cell morphology (3) Amyotrophic lateral sclerosis (3) Cystoid macular edema (3) Arrhythmia (3) Cutaneous melanoma (3) Pulmonary edema (3) Ovarian neoplasm (3) Neuroendocrine neoplasm (3) Hypogeusia (2) Hearing impairment (2) Abnormality of the eye (2) Visual impairment (2) Conjunctivitis (2) Cataract (2) Uveitis (2) Agoraphobia (2) Abnormality of the endocrine system (2) Abnormality of the skin (2) Jaundice (2) Lymphedema (2) Spasticity (2) Meningitis (2) Abnormal joint morphology (2) Hepatic steatosis (2) Hepatic failure (2) Tachycardia (2) Angina pectoris (2) Pancreatitis (2) Abnormality of blood and blood-forming tissues (2) Thrombocytopenia (2) Autoimmune thrombocytopenia (2) Gout (2) Diarrhea (2) Gastroesophageal reflux (2) Apnea (2) Neurodegeneration (2) Alopecia of scalp (2) Mutism (2) Transient ischemic attack (2) Hyperkinetic movements (2) Polyphagia (2) Hypotension (2) Atherosclerosis (2) Hypoventilation (2) Squamous cell carcinoma (2) Myelodysplasia (2) Back pain (2) Low back pain (2) Muscular dystrophy (2) Stillbirth (2) Acute myeloid leukemia (2) Lymphoproliferative disorder (2) Myeloproliferative disorder (2) Multiple myeloma (2) Intervertebral disc degeneration (2) Stridor (2) Postprandial hyperglycemia (2) Hemeralopia (2) Arteritis (2) Hepatitis (2) Glioblastoma multiforme (2) Cervix cancer (2) Small cell lung carcinoma (2) Endocarditis (2) Toxemia of pregnancy (2) Myositis (2) Mania (2) Urinary retention (1) Urinary incontinence (1) Nephritis (1) Menorrhagia (1) Xerostomia (1) Otitis media (1) Conductive hearing impairment (1) Amblyopia (1) Periodontitis (1) IgA deposition in the glomerulus (1) Enuresis (1) Hypoparathyroidism (1) Adrenal insufficiency (1) Hyperaldosteronism (1) Osteopenia (1) Urticaria (1) Angiokeratoma corporis diffusum (1) Cholecystitis (1) Keratoconjunctivitis (1) Intellectual disability (1) Hemiparesis (1) Polyneuropathy (1) Syncope (1) Cerebral hemorrhage (1) Hepatocellular carcinoma (1) Intrauterine growth retardation (1) Hoarse voice (1) Dysphonia (1) Weak voice (1) Sudden cardiac death (1) Aortic valve stenosis (1) Bradycardia (1) Torsade de pointes (1) Atrioventricular block (1) Premature rupture of membranes (1) Dehydration (1) Constipation (1) Anorexia (1) Esophageal varix (1) Chorea (1) Status epilepticus (1) Subarachnoid hemorrhage (1) Abnormality of the spinal cord (1) Memory impairment (1) Encephalitis (1) Spina bifida (1) Language impairment (1) Waddling gait (1) Increased intracranial pressure (1) Biliary cirrhosis (1) Dilatation (1) Osteomyelitis (1) Central apnea (1) Hypokalemia (1) Hyponatremia (1) Hyperphosphatemia (1) Skeletal muscle atrophy (1) Male infertility (1) Spondylolisthesis (1) Myalgia (1) Bruxism (1) Neonatal death (1) Increased body weight (1) Intermittent claudication (1) Thrombophlebitis (1) Chronic bronchitis (1) Ventricular tachycardia (1) Acute myelomonocytic leukemia (1) Dilatation of the cerebral artery (1) Coronary artery stenosis (1) Venous insufficiency (1) Chronic lymphatic leukemia (1) Abnormality of bone marrow cell morphology (1) Hypersensitivity pneumonitis (1) Intraalveolar phospholipid accumulation (1) Neoplasm of the genitourinary tract (1) Neoplasm of the skin (1) Female infertility (1) Benign prostatic hyperplasia (1) Hip osteoarthritis (1) Bladder neoplasm (1) Stomatitis (1) Uterine neoplasm (1) Intestinal atresia (1) Placental abruption (1) Sinus tachycardia (1) Bronchiolitis (1) Erythroid hypoplasia (1) Asterixis (1) Hodgkin lymphoma (1) B-cell lymphoma (1) Ciliary dyskinesia (1) Myeloid leukemia (1) Chronic myelomonocytic leukemia (1) Morphea (1) Bronchitis (1) Hypercapnia (1) Pain (1) Retinal vein occlusion (1) Vasovagal syncope (1) Heart block (1) Cough (1) Neonatal asphyxia (1) Dyspareunia (1) Heart murmur (1) Cardiogenic shock (1) Cholangitis (1) Cholangiocarcinoma (1) Vulvar neoplasm (1) Neonatal sepsis (1) Glue ear (1) Abnormality of movement (1) Subdural hemorrhage (1) Biliary tract neoplasm (1) Nasal polyposis (1) Eclampsia (1) Esophagitis (1) Vaginal neoplasm (1) Cellulitis (1) Angioedema (1) Self-injurious behavior (1) Gastrointestinal stroma tumor (1) Bulimia (1) Neoplasm of the rectum (1) Chest pain (1) Atelectasis (1) Lymphocytosis (1) Polymenorrhea (1)

    HP:0002090: Pneumonia

    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 (576)


    Name (Synonyms) Correlation
    drug2916 Placebo Wiki 0.16
    drug2365 Methylprednisolone Wiki 0.13
    drug4025 Tocilizumab Wiki 0.11
    Name (Synonyms) Correlation
    drug3069 Prednisone Wiki 0.11
    drug2298 Mavrilimumab Wiki 0.11
    drug4122 UC-MSCs Wiki 0.09
    drug421 Azithromycin Wiki 0.09
    drug2710 Opaganib Wiki 0.08
    drug3638 SivoMixx (200 billion) Wiki 0.07
    drug1197 Dexamethasone injection Wiki 0.07
    drug2965 Placebo inhalation Wiki 0.07
    drug2200 Low molecular weight heparin Wiki 0.07
    drug182 Abidol hydrochloride Wiki 0.07
    drug4639 oxygen therapy Wiki 0.07
    drug1295 EC-18 Wiki 0.07
    drug1327 EXO 1 inhalation Wiki 0.07
    drug3488 SOC + Placebo Wiki 0.07
    drug517 Baricitinib Oral Tablet Wiki 0.07
    drug4036 Tofacitinib Wiki 0.07
    drug1328 EXO 2 inhalation Wiki 0.07
    drug3321 Remdesivir placebo Wiki 0.07
    drug4809 vv-ECMO + cytokine adsorption (Cytosorb adsorber) Wiki 0.07
    drug2181 Low Dose Radiation Therapy Wiki 0.07
    drug4810 vv-ECMO only (no cytokine adsorption) Wiki 0.07
    drug4510 hydroxychloroquine Wiki 0.07
    drug2220 Lung ultrasound Wiki 0.07
    drug2174 Lopinavir/ritonavir Wiki 0.07
    drug1775 Hydroxychloroquine Wiki 0.06
    drug2351 Mesenchymal stromal cells Wiki 0.06
    drug942 Clopidogrel Wiki 0.06
    drug1712 Heparin Wiki 0.06
    drug1795 Hydroxychloroquine Sulfate Wiki 0.06
    drug3107 Prone Positioning Wiki 0.06
    drug340 Apremilast Wiki 0.06
    drug2729 Oseltamivir Wiki 0.06
    drug1396 Enoxaparin Wiki 0.06
    drug4650 placebo Wiki 0.05
    drug3924 Telehealth Consultation Wiki 0.05
    drug476 BIOMARKERS IN THE LONG TERM IMPACT OF CORONAVIRUS INFECTION IN THE CARDIORRESPIRATORY SYSTEM Wiki 0.05
    drug4578 methylprednisolone Wiki 0.05
    drug1412 EpiVacCorona (EpiVacCorona vaccine based on peptide antigens for the prevention of COVID-19) Wiki 0.05
    drug507 Bacterial species isolated Wiki 0.05
    drug3064 Predictive factors for clinical response in patients with COVID-19. Wiki 0.05
    drug2194 Low dose Radiotherapy Wiki 0.05
    drug1226 Digital Health Literacy Intervention Wiki 0.05
    drug3430 SARS-CoV-2 convalescent plasma treatment Wiki 0.05
    drug2420 Molgramostim nebuliser solution Wiki 0.05
    drug2180 Low Dose (10 mg) Control Wiki 0.05
    drug2354 MetaNeb® System Wiki 0.05
    drug3189 Quercetin Prophylaxis Wiki 0.05
    drug4504 hormones Wiki 0.05
    drug308 Anti-SARS-CoV-2 equine immunoglobulin fragments (INOSARS) Wiki 0.05
    drug1783 Hydroxychloroquine + lopinavir/ritonavir Wiki 0.05
    drug4818 Оxygen therapy Wiki 0.05
    drug2456 MySafeRx Inspire Flex Wiki 0.05
    drug3485 SOC Wiki 0.05
    drug2589 No special intervention Wiki 0.05
    drug2032 Ivermectin + Doxycycline + Placebo Wiki 0.05
    drug2457 MySafeRx Inspire Plus Wiki 0.05
    drug1626 Gas exchange measurement Wiki 0.05
    drug2842 Patients with the treatment agains COVID19 Wiki 0.05
    drug1134 DB-001 Wiki 0.05
    drug379 Asunercept Wiki 0.05
    drug1570 Fondaparinux Wiki 0.05
    drug2645 NİCaS Wiki 0.05
    drug209 Activity Wiki 0.05
    drug4568 mavrilimumab Wiki 0.05
    drug906 Chloroquine Phosphate Tablets Wiki 0.05
    drug2914 Piperacillin/tazobactam Wiki 0.05
    drug458 BDB-001 Injection Wiki 0.05
    drug2534 Neutral writing control Wiki 0.05
    drug4511 hydroxychloroquine + azithromycin Wiki 0.05
    drug107 AI model Wiki 0.05
    drug4316 XAV-19 Wiki 0.05
    drug3156 Pulse CO-Oximetry Hemoglobin measurement transcutaneous Wiki 0.05
    drug1782 Hydroxychloroquine + azithromycin + / - tocilizumab Wiki 0.05
    drug1500 FX06 Wiki 0.05
    drug2572 No Personal protective equipment (PPE) Wiki 0.05
    drug289 Angiography scanner Wiki 0.05
    drug1541 Five-days oseltamivir Wiki 0.05
    drug1745 Home Sleep Apnea Testing or In-hospital Polysomnography Wiki 0.05
    drug987 Combined use of a respiratory broad panel multiplex PCR and procalcitonin Wiki 0.05
    drug2197 Low dose whole lung radiotherapy for older patients with COVID-19 pneumonitis Wiki 0.05
    drug1877 Ibudilast Wiki 0.05
    drug2323 Mefloquine Wiki 0.05
    drug2495 Nafamostat Mesylate Wiki 0.05
    drug623 Bone Marrow Harvest Wiki 0.05
    drug1643 Glycine Wiki 0.05
    drug3088 Pro BNP , Vitamin D Wiki 0.05
    drug4808 vv-ECMO Wiki 0.05
    drug4567 management strategy of outpatient with mild to moderate SARS-CoV-2 pneumonia Wiki 0.05
    drug3381 Ritonavir+Oseltamivir Wiki 0.05
    drug2649 OPT101 Wiki 0.05
    drug1055 Convalescent Plasma of patients with COVID-19 Wiki 0.05
    drug2936 Placebo Control Wiki 0.05
    drug1059 Convalescent anti-SARS-CoV-2 plasma Wiki 0.05
    drug2011 Invasive mechanical ventilation using the Unisabana-Herons Ventilator during 24 hours Wiki 0.05
    drug3486 SOC + IFX-1 Wiki 0.05
    drug3845 Symptomatic treatment (paracetamol or best symptomatic treatment based on doctor recommendations) Wiki 0.05
    drug2271 Macrolide administered for 3-5 days Wiki 0.05
    drug1544 Fixed-duration Hydrocortisone Wiki 0.05
    drug4517 hyperimmune plasma Wiki 0.05
    drug2500 Nasal Brushing Wiki 0.05
    drug4651 placebo (hartmann plus albumine) Wiki 0.05
    drug3304 Regadenoson Wiki 0.05
    drug4327 Yinhu Qingwen Granula Wiki 0.05
    drug1135 DFV890 Wiki 0.05
    drug2254 MSCs Wiki 0.05
    drug4321 Xiyanping injection Wiki 0.05
    drug2633 NuSepin® 0.1 mg Wiki 0.05
    drug3183 Quantitative analysis of SARS-CoV-2 antibodies Wiki 0.05
    drug2789 PROTECTIVE VENTILATION Wiki 0.05
    drug1066 Conventional medicines (Oxygen therapy, alfa interferon via aerosol inhalation, and lopinavir/ritonavir) and Traditional Chinese Medicines (TCMs) granules Wiki 0.05
    drug1896 Imatinib tablets Wiki 0.05
    drug2222 LungFit™ Wiki 0.05
    drug872 Centrum Adult (under 50) multivitamin Wiki 0.05
    drug2462 N-acetyl cysteine Wiki 0.05
    drug149 ATYR1923 3 mg/kg Wiki 0.05
    drug4597 mycophenolic acid Wiki 0.05
    drug4570 mechanical ventilation Wiki 0.05
    drug2037 Ivermectin 5 mg/mL oral solution, Dexamethasone 4-mg injection, Aspirin 250 mg tablets Wiki 0.05
    drug148 ATYR1923 1 mg/kg Wiki 0.05
    drug2195 Low dose radiation 35 cGy Wiki 0.05
    drug527 Bedside lung ultrasound Wiki 0.05
    drug3952 Ten-days oseltamivir Wiki 0.05
    drug2091 LY3127804 Wiki 0.05
    drug1680 HFNO Wiki 0.05
    drug3218 RDV Wiki 0.05
    drug3084 Previfenon® Wiki 0.05
    drug506 Bactek-R Wiki 0.05
    drug3777 Stem Cell Educator-Treated Mononuclear Cells Apheresis Wiki 0.05
    drug2563 Nitric Oxide-Continuous and Sessions Wiki 0.05
    drug1173 Decitabine Wiki 0.05
    drug3763 Standard therapy recommended by the Ministry of Health of the Russian Federation. Wiki 0.05
    drug430 Azithromycin with amoxicillin/clavulanate Wiki 0.05
    drug3710 Standard Of Care (SOC) + Placebo Wiki 0.05
    drug1418 Esflurbiprofen hydrogel patch 165 mg (EFHP) Wiki 0.05
    drug2718 Optimized Management of Covid-19 Positive Kidney Transplant Recipients: Single Center Experience from the Middle East Wiki 0.05
    drug689 CD55 Wiki 0.05
    drug2877 Personal protective equipment (PPE) Wiki 0.05
    drug1115 Cyclosporin A Wiki 0.05
    drug338 Application of tele-rehabilitation Wiki 0.05
    drug2999 Placenta-Derived MMSCs; Cryopreserved Placenta-Derived Multipotent Mesenchymal Stromal Cells Wiki 0.05
    drug1082 Corticosteroid injection Wiki 0.05
    drug3332 Remote pulmonary rehabilitation Wiki 0.05
    drug3056 Prasugrel Wiki 0.05
    drug512 Bariatric procedures Wiki 0.05
    drug3878 TD139 Wiki 0.05
    drug2897 Physical Exercises Wiki 0.05
    drug3153 Pulmonary ultrasound Wiki 0.05
    drug4501 high-titer anti-Sars-CoV-2 plasma Wiki 0.05
    drug2025 Isotretinoin Only Product in Oral Dose Form Wiki 0.05
    drug409 Auxora Wiki 0.05
    drug193 Access to training facility Wiki 0.05
    drug2324 Mefloquine + azithromycin + / - tocilizumab Wiki 0.05
    drug2484 NO intervention planned due to the observational study design - only a diagnostic testing Wiki 0.05
    drug4743 spirometry, thoracic CT, CPET, 6 minute walking test, SF-36 questionnaire Wiki 0.05
    drug2159 Lopinavir 200 MG / Ritonavir 50 MG [Kaletra] Wiki 0.05
    drug2901 Physician Survey Wiki 0.05
    drug86 ACE Inhibitors and Calcium Channel Blockers Wiki 0.05
    drug919 Chronic Hypersensitivity Pneumonitis Health Related Quality of Life Survey Instrument Wiki 0.05
    drug3969 Thalidomide Wiki 0.05
    drug896 Chest MRI Wiki 0.05
    drug3858 T89 Wiki 0.05
    drug1575 Fostamatinib Wiki 0.05
    drug2930 Placebo 0.20 mg + 2.00 mg/kg Wiki 0.05
    drug4649 pirfenidone Wiki 0.05
    drug2003 Intravenous Immunoglobulin Wiki 0.05
    drug4333 Zavegepant (BHV-3500) Wiki 0.05
    drug4576 mesenchymal stem cells Wiki 0.05
    drug756 COVID-19 Specific T Cell derived exosomes (CSTC-Exo) Wiki 0.05
    drug3125 Protocolised mechanical ventilation strategy Wiki 0.05
    drug3285 Recombinant Human Interferon α2b Spray Wiki 0.05
    drug2744 Oxygen supply Wiki 0.05
    drug4019 Tirofiban Injection Wiki 0.05
    drug181 Abidol Hydrochloride combined with Interferon atomization Wiki 0.05
    drug2992 Placebo- 2.00 mg/kg Wiki 0.05
    drug239 AirGo Respiratory Monitor Wiki 0.05
    drug4595 mycophenolate mofetil Wiki 0.05
    drug76 80 ppm Nitric Oxide delivered through LungFit Delivery System Wiki 0.05
    drug2173 Lopinavir/Ritonavir 400 mg/100 mg Wiki 0.05
    drug798 CT of the chest Wiki 0.05
    drug2158 Lopinavir / ritonavir, alpha-interferon nebulization,Abidor Hydrochloride Wiki 0.05
    drug2745 Oxygen-ozone therapy, probiotic supplementation and Standard of care Wiki 0.05
    drug3082 Prevenar 7 and Prevenar 13 Wiki 0.05
    drug1156 Darunavir/Cobicistat Wiki 0.05
    drug233 Aerosolized All trans retinoic acid Wiki 0.05
    drug258 Almitrine Wiki 0.05
    drug1270 Drug: GS-5734 - 2.00 mg/kg Wiki 0.05
    drug271 Amoxicillin-clavulanate Wiki 0.05
    drug3382 Ritonavir/lopinavir Wiki 0.05
    drug1706 Helmet Continuous Positive Airway Pressure (CPAP) Wiki 0.05
    drug3503 Saline Control Wiki 0.05
    drug2634 NuSepin® 0.2 mg Wiki 0.05
    drug641 Breath test Wiki 0.05
    drug4558 low-molecular-weight heparin Wiki 0.05
    drug2990 Placebo- 0.20 mg/kg Wiki 0.05
    drug2511 Nasopharyngeal and throat/oropharyngeal swabs analyses by RT-PCR and ddPCR Wiki 0.05
    drug2853 Pembrolizumab (MK-3475) Wiki 0.05
    drug1721 Hidroxicloroquine Wiki 0.05
    drug4018 Tinzaparin or unfractionated heparin Wiki 0.05
    drug1506 Family Nurture Intervention (FNI) Wiki 0.05
    drug2196 Low dose radiation therapy Wiki 0.05
    drug2799 PTSD Wiki 0.05
    drug3731 Standard of Care (SOC) + ANG-3777 Wiki 0.05
    drug3151 Pulmonary function testing Wiki 0.05
    drug301 Anti SARS-CoV 2 Convalescent Plasma in severe COVID-19 patients Wiki 0.05
    drug4394 biological assays in particular on the lipid metabolism Wiki 0.05
    drug1065 Conventional medicines (Oxygen therapy, alfa interferon via aerosol inhalation, and lopinavir/ritonavir) Wiki 0.05
    drug743 COVID-19 Convalscent Plasma Wiki 0.05
    drug344 Arbidol Hydrochloride Granules Wiki 0.05
    drug4678 pulmonary anomalies 4 months after documented COVID-19 pneumonia Wiki 0.05
    drug2939 Placebo EC-18 Wiki 0.05
    drug1895 Imatinib Mesylate Wiki 0.05
    drug1393 Enhanced hygiene measures Wiki 0.05
    drug668 Burnout Wiki 0.05
    drug3345 Respiratory Training Wiki 0.05
    drug4125 ULTRAPROTECTIVE VENTILATION Wiki 0.05
    drug3608 Sham Device Treatment Wiki 0.05
    drug4794 unfractionated heparin Wiki 0.05
    drug4385 avdoralimab Wiki 0.05
    drug1723 High Flow Nasal Oxygen (HFNO) Wiki 0.05
    drug2537 New screening strategy Wiki 0.05
    drug2126 Lianhua Qingwen Wiki 0.05
    drug256 Allogenic pooled olfactory mucosa-derived mesenchymal stem cells Wiki 0.05
    drug816 CYNK-001 Wiki 0.05
    drug658 Bromhexine Hydrochloride Tablets Wiki 0.05
    drug4488 favipiravir tablets+chloroquine phosphatetablets tablets Wiki 0.05
    drug3043 Povidone-Iodine 0.5% Wiki 0.05
    drug3339 ResCure™ Wiki 0.05
    drug4377 antithymocyte globulin (rabbit) Wiki 0.05
    drug905 Chloroquine Diphosphate Wiki 0.05
    drug4467 ePNa-CheXED Wiki 0.05
    drug3853 T memory cells and NK cells Wiki 0.05
    drug321 Anticoagulant Therapy Wiki 0.05
    drug3360 RhACE2 APN01 Wiki 0.05
    drug4732 severe covid-19 pneumonia with ET Wiki 0.05
    drug3436 SARS-CoV-2 rS/Matrix M1-Adjuvant Wiki 0.05
    drug2748 Ozone auto-hemotherapy Wiki 0.05
    drug1492 FNC dummy tablet+Standard of Care Wiki 0.05
    drug553 Bevacizumab Wiki 0.05
    drug909 Chloroquine diphosphate Wiki 0.05
    drug2252 MSC Treatment Wiki 0.05
    drug4757 standardized Lung Ultrasound (LUS) examination Wiki 0.05
    drug2810 Pamrevlumab Wiki 0.05
    drug794 CPI-006 Wiki 0.05
    drug4370 amoxicillin/clavulanate Wiki 0.05
    drug1460 Exposure (not intervention) - SARS-CoV-2 infection Wiki 0.05
    drug1056 Convalescent SARS COVID-19 plasma Wiki 0.05
    drug2081 LB1148 Wiki 0.05
    drug4776 thalidomide Wiki 0.05
    drug3595 Serology test follow-up Wiki 0.05
    drug227 Aerobic training Wiki 0.05
    drug3873 TCM prescriptions Wiki 0.05
    drug4341 Zinc Sulfate Wiki 0.05
    drug1753 Hormones Wiki 0.05
    drug3593 Serology Test Wiki 0.05
    drug1968 Interferon-β1a Wiki 0.05
    drug4668 predict admission of covid-19 patients to ICU and death with routine and quickly avalaible clinical, biological and radiological variables? Wiki 0.05
    drug1903 Immunoglobulin of cured patients Wiki 0.05
    drug2257 MSTT1041A-matched Placebo Wiki 0.05
    drug516 Baricitinib 4 MG Oral Tablet Wiki 0.05
    drug4033 Tocilizumab Injection [Actemra] Wiki 0.05
    drug937 Clinical, functional and radiological lung involvement evolution Wiki 0.05
    drug297 Angiotensin-Converting Enzyme Inhibitors (ACE-I) and Angiotensin II Receptor Blockers (ARB) Wiki 0.05
    drug3762 Standard therapy recommended by the Ministry of Health of the Russian Federation and Dalargin intramuscular injection combined with Dalargin inhalation Wiki 0.05
    drug4324 Yin Hu Qing Wen Granula(low does) Wiki 0.05
    drug3076 Prescription Opioid Management App Wiki 0.05
    drug2328 Melphalan Wiki 0.05
    drug378 AstroStem-V Wiki 0.05
    drug3209 Quetiapine Wiki 0.05
    drug1563 Folic Acid Wiki 0.05
    drug922 Ciclesonide Inhalation Aerosol Wiki 0.05
    drug1784 Hydroxychloroquine + placebo Wiki 0.05
    drug4627 observation of covid 19 pneumonia Wiki 0.05
    drug861 Ceftaroline Wiki 0.05
    drug1179 Defibrotide Injection Wiki 0.05
    drug3499 STI-5656 Wiki 0.05
    drug4817 γ-Globulin Wiki 0.05
    drug2971 Placebo of FX06 Wiki 0.05
    drug541 Best Available Therapy Wiki 0.05
    drug311 Anti-SARS-CoV2 serological controls and serum neutralization Wiki 0.05
    drug4559 lulizumab pegol Wiki 0.05
    drug3760 Standard therapy recommended by the Ministry of Health of the Russian Federation and Dalargin inhalation Wiki 0.05
    drug1037 Control arm Wiki 0.05
    drug3750 Standard screening strategy Wiki 0.05
    drug1811 Hydroxychloroquine and azithromycin treatment arm. Wiki 0.05
    drug1731 High dose Interferon-beta 1a Wiki 0.05
    drug1989 Intervention group_rehabilitation program Wiki 0.05
    drug2444 MultiStem Wiki 0.05
    drug2949 Placebo Saline Wiki 0.05
    drug4029 Tocilizumab 20 MG/ML Intravenous Solution [ACTEMRA] Wiki 0.05
    drug4414 captopril 25mg Wiki 0.05
    drug196 Acetylsalicylic acid Wiki 0.05
    drug2219 Lung impedance technique Wiki 0.05
    drug404 Autologous Adipose MSC's Wiki 0.05
    drug3001 Plaquenil 200Mg Tablet Wiki 0.05
    drug2154 Lopinavir Wiki 0.05
    drug1949 Inhaled placebo Wiki 0.05
    drug2991 Placebo- 1.00 mg/kg Wiki 0.05
    drug368 Assessment of ventilator-associated pneumonia criteria Wiki 0.05
    drug1576 Fourth Trimester Mobile Tool Wiki 0.05
    drug3190 Quercetin Treatment Wiki 0.05
    drug1279 Drugs: NA-831 (0.10 mg/kg) plus GS-5734 (1.00 mg/kg) Wiki 0.05
    drug1834 Hyperbaric oxygen treatment (HBOT) i.e. inhalation of pressurized oxygen delivered by a hyperbaric chamber (drug/device) Wiki 0.05
    drug4123 UCMSCs Wiki 0.05
    drug3619 Silymarin Wiki 0.05
    drug4747 standard medical treatment Wiki 0.05
    drug2227 MAS825 Wiki 0.05
    drug4520 iNO (inhaled nitric oxide) delivered via the INOpulse Delivery System Wiki 0.05
    drug1579 Froben 100 mg comprimidos revestidos Wiki 0.05
    drug2531 Neuromuscular Electrical Stimulation Wiki 0.05
    drug2611 Non-invasive red LLLT treatment to chest of patient. Wiki 0.05
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    drug2119 Let It Out (LIO)-C Wiki 0.05
    drug110 ALLOCETRA-OTS Wiki 0.05
    drug2170 Lopinavir/Ritonavir Wiki 0.05
    drug3365 Rifaximin Novel Formulation Wiki 0.05
    drug3782 Sterile Water for Injection Wiki 0.05
    drug2184 Low Dose of KBP-COVID-19 Wiki 0.05
    drug1517 Favipiravir + Standard of Care Wiki 0.05
    drug835 Canakinumab 150 MG/ML [Ilaris] Wiki 0.05
    drug2035 Ivermectin 5 MG/ML oral solution, Aspirin 250 mg tablets Wiki 0.05
    drug2065 Kamada Anti-SARS-CoV-2 Wiki 0.05
    drug4368 alveolar recruitment Wiki 0.05
    drug1946 Inhaled budesonide and formoterol Wiki 0.05
    drug4134 Ultra-Low-dose radiotherapy Wiki 0.05
    drug3146 Pulmonary Physiotherapy Techniques Wiki 0.05
    drug30 150 ppm Nitric Oxide delivered through LungFit Delivery System Wiki 0.05
    drug694 CERC-002 Wiki 0.05
    drug2078 L-citrulline Wiki 0.05
    drug1430 Evaluation of clinical, instrumental and laboratory diagnostics tests Wiki 0.05
    drug4171 Usual antibiotic treatment Wiki 0.05
    drug4015 Ticagrelor Wiki 0.05
    drug3761 Standard therapy recommended by the Ministry of Health of the Russian Federation and Dalargin intramuscular injection Wiki 0.05
    drug2191 Low dose CT Wiki 0.05
    drug1771 Hydrocortisone Wiki 0.05
    drug1275 Drug: NA-831 - 0.10 mg/kg Wiki 0.05
    drug1945 Inhaled budesonide Wiki 0.05
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    Correlated MeSH Terms (78)


    Name (Synonyms) Correlation
    D011014 Pneumonia NIH 1.00
    D011024 Pneumonia, Viral NIH 0.45
    D045169 Severe Acute Respiratory Syndrome NIH 0.16
    Name (Synonyms) Correlation
    D018352 Coronavirus Infections NIH 0.16
    D053717 Pneumonia, Ventilator-Associated NIH 0.16
    D017563 Lung Diseases, Interstitial NIH 0.13
    D007249 Inflammation NIH 0.11
    D012128 Respiratory Distress Syndrome, Adult NIH 0.09
    D055371 Acute Lung Injury NIH 0.08
    D011020 Pneumonia, Pneumocystis NIH 0.07
    D000077299 Healthcare-Associated Pneumonia NIH 0.07
    D013577 Syndrome NIH 0.07
    D012127 Respiratory Distress Syndrome, Newborn NIH 0.07
    D008171 Lung Diseases, NIH 0.06
    D055370 Lung Injury NIH 0.06
    D003141 Communicable Diseases NIH 0.05
    D000542 Alveolitis, Extrinsic Allergic NIH 0.05
    D008589 Meningococcal Infections NIH 0.05
    D001261 Pulmonary Atelectasis NIH 0.05
    D011488 Protein Deficiency NIH 0.05
    D001469 Barotrauma NIH 0.05
    D018410 Pneumonia, Bacterial NIH 0.05
    D016769 Embolism and Thrombosis NIH 0.05
    D001768 Blister NIH 0.05
    D012140 Respiratory Tract Diseases NIH 0.05
    D004617 Embolism NIH 0.05
    D007239 Infection NIH 0.05
    D012120 Respiration Disorders NIH 0.05
    D013927 Thrombosis NIH 0.04
    D000860 Hypoxia NIH 0.04
    D053120 Respiratory Aspiration NIH 0.04
    D009767 Obesity, Morbid NIH 0.04
    D030341 Nidovirales Infections NIH 0.04
    D008585 Meningitis, Meningococcal NIH 0.04
    D008581 Meningitis, Mening NIH 0.04
    D001049 Apnea NIH 0.04
    D000075902 Clinical Deterioration NIH 0.04
    D003967 Diarrhea NIH 0.04
    D009410 Nerve Degeneration NIH 0.04
    D004646 Emphysema NIH 0.04
    D007040 Hypoventilation NIH 0.04
    D011665 Pulmonary Valve Insufficiency NIH 0.04
    D012141 Respiratory Tract Infections NIH 0.03
    D004417 Dyspnea NIH 0.03
    D011251 Pregnancy Complications, Infectious NIH 0.03
    D011654 Pulmonary Edema NIH 0.03
    D008173 Lung Diseases, Obstructive NIH 0.03
    D014777 Virus Diseases NIH 0.03
    D020141 Hemostatic Disorders NIH 0.03
    D001778 Blood Coagulation Disorders NIH 0.03
    D011655 Pulmonary Embolism NIH 0.03
    D060085 Coinfection NIH 0.03
    D016638 Critical Illness NIH 0.03
    D013923 Thromboembolism NIH 0.02
    D020181 Sleep Apnea, Obstructive NIH 0.02
    D003693 Delirium NIH 0.02
    D001987 Bronchiectasis NIH 0.02
    D009102 Multiple Organ Failure NIH 0.02
    D006967 Hypersensitivity, NIH 0.02
    D012891 Sleep Apnea, NIH 0.02
    D003333 Coronaviridae Infections NIH 0.02
    D014115 Toxemia NIH 0.02
    D007154 Immune System Diseases NIH 0.02
    D012327 RNA Virus Infections NIH 0.02
    D008231 Lymphopenia NIH 0.02
    D018805 Sepsis NIH 0.02
    D014947 Wounds and Injuries NIH 0.02
    D013313 Stress Disorders, Post-Traumatic NIH 0.02
    D011248 Pregnancy Complications NIH 0.02
    D009765 Obesity NIH 0.02
    D006333 Heart Failure NIH 0.02
    D005355 Fibrosis NIH 0.01
    D009103 Multiple Sclerosis NIH 0.01
    D012598 Scoliosi NIH 0.01
    D007251 Influenza, Human NIH 0.01
    D040921 Stress Disorders, Traumatic NIH 0.01
    D002318 Cardiovascular Diseases NIH 0.01
    D009369 Neoplasms, NIH 0.01

    Correlated HPO Terms (28)


    Name (Synonyms) Correlation
    HP:0006515 Interstitial pneumonitis HPO 0.13
    HP:0002088 Abnormal lung morphology HPO 0.06
    HP:0006516 Hypersensitivity pneumonitis HPO 0.05
    Name (Synonyms) Correlation
    HP:0100750 Atelectasis HPO 0.05
    HP:0001907 Thromboembolism HPO 0.05
    HP:0012418 Hypoxemia HPO 0.04
    HP:0002104 Apnea HPO 0.04
    HP:0002791 Hypoventilation HPO 0.04
    HP:0001287 Meningitis HPO 0.04
    HP:0002014 Diarrhea HPO 0.04
    HP:0002180 Neurodegeneration HPO 0.04
    HP:0010444 Pulmonary insufficiency HPO 0.04
    HP:0011947 Respiratory tract infection HPO 0.03
    HP:0002098 Respiratory distress HPO 0.03
    HP:0100598 Pulmonary edema HPO 0.03
    HP:0006536 Pulmonary obstruction HPO 0.03
    HP:0001928 Abnormality of coagulation HPO 0.03
    HP:0002204 Pulmonary embolism HPO 0.03
    HP:0012393 Allergy HPO 0.02
    HP:0002870 Obstructive sleep apnea HPO 0.02
    HP:0002110 Bronchiectasis HPO 0.02
    HP:0010535 Sleep apnea HPO 0.02
    HP:0001888 Lymphopenia HPO 0.02
    HP:0100806 Sepsis HPO 0.02
    HP:0001513 Obesity HPO 0.02
    HP:0001635 Congestive heart failure HPO 0.02
    HP:0001626 Abnormality of the cardiovascular system HPO 0.01
    HP:0002664 Neoplasm HPO 0.01

    Clinical Trials

    Navigate: Correlations   HPO

    There are 359 clinical trials


    1 Antibiotic Treatment Trial Directed Against Chlamydia Pneumonia in Multiple Sclerosis

    Multiple sclerosis (MS) is an inflammatory, demyelinating disease which affects the central nervous system (CNS). The etiology of MS is unknown, although the immune system appears to play a role. Many different infectious agents have been proposed as potential causes for MS, including Epstein-Barr virus, human herpesvirus 6, and coronaviruses. Recently Dr. Sriram at Vanderbilt University has found evidence for active Chlamydia pneumonia infection in the CNS of MS patients. These findings have been replicated in part by other laboratories. The purpose of the current study is to test whether antibiotic treatment aimed at eradicating Chlamydia infection will reduce the disease activity in MS. The primary outcome measure will be reduction in new enhancing MS lesions on brain MRI. Forty patients will be entered into the trial. To be eligible, patients must have evidence of chlamydia infection in their spinal fluid and enhancing lesions on their pre-randomization MRI scans. Patients who meet these criteria will be randomized to either placebo or antibiotic therapy, and followed for 6 months on treatment.

    NCT00043264
    Conditions
    1. Multiple Sclerosis
    Interventions
    1. Drug: Rifampin
    2. Drug: Azithromycin
    MeSH:Pneumonia Multiple Sclerosis Sclerosis
    HPO:Pneumonia

    2 The Impact of Simultaneous Presence of Viral and Bacterial Pathogens on Therapy and Course of Severe Pneumonia

    The purpose of the study is to determine if the clinical course of pneumonia is more severe when both, bacterial and viral pathogens are find as possible causative agent and how does it affect treatment.

    NCT02203110
    Conditions
    1. Community Acquired Pneumonia
    2. Hospital Acquired Pneumonia
    3. Ventilator Associated Pneumonia
    MeSH:Pneumonia, Ventilator-Associated Healthcare-Associated Pneumonia Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Measure: Rate of changes in empirical antibiotic therapy due to broad microbiological diagnostic

    Time: each patient will be assessed at enrollment and follow-up for 2 months
    3 The Place of Imaging and Microbiology in the Diagnosis of Pneumonia in the Elderly: PneumOldCT

    Diagnosis of pneumonia in the elderly is difficult because of the poor sensitivity and specificity of clinical signs as well as images from chest radiography (RT). New diagnostic tools such as thoracic low-dose computed tomography (CT), which exposes the patient to a weak dose of irradiation, could improve diagnosis. Moreover, low-dose CT could provide additional accuracy in the etiological clarification of pneumonia in elderly people. As a first step, the investigators aim to perform a 1 year (12 months of inclusion + 3 months of follow-up) prospective study including the Divisions of Internal Medicine, Rehabilitation, Geriatrics and Radiology of the University Hospitals of Geneva. In this study, patients >65 years old with a clinical suspicion of low respiratory tract infection (LRTI) will be included. They will be prescribed antimicrobial therapy. Both chest radiography and low-dose thoracic CT will be performed within the first 72 hours after admission, as will blood tests and a nasopharyngeal swab. The clinician's diagnosis, both before and after the results of the CT, will be compared at the end of the study to the adjudication committee's diagnostic opinion which will have access to all available clinical, laboratory and chest X-ray data and which will be considered the gold standard. At the end of the study, all the CT images will be blind-reviewed by two experts in radiology. The impact of CT scanning in the diagnosis of pneumonia will be assessed, both for its sensitivity and specificity in this population. During the first 12 months of the study, all patients will undergo a systematic nasopharyngeal swab at admission and at discharge, from which eluates will be conserved. During the next 12 months, virological and bacteriological polymerase chain reactions (PCR) will be performed, using new diagnostic tools, in order to determine the etiological diagnosis in this population and to evaluate the impact of the new tools in the management of pneumonia for this population. Analysis of these data will allow clinical, radiological and microbiological correlation.

    NCT02467192
    Conditions
    1. Pneumonia
    Interventions
    1. Device: Low dose CT
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Measure: Number of upgraded or downgraded diagnoses

    Time: During the 24 hours after CT

    Secondary Outcomes

    Measure: Number of bacterial and viral pulmonary infections

    Time: During hospitalisation (maximum 3 months)
    4 Effects of Low-dose Corticosteroids on Survival of Severe Community-acquired Pneumonia

    Mortality of severe Community-Acquired Pneumonia (CAP) has not declined over time and is between 25 and 30% in sub-groups of patients. Corticosteroids (CTx) could down-regulate pulmonary and systemic inflammation, accelerate clinical resolution and decrease the rate of inflammation-associated systemic complications. Two recent meta-analyses suggest a positive effect on severe CAP day 28 survival when CTx are added to standard therapy. However they are based on only four trials gathering less than 300 patients, of which only one was positive. Recently published guidelines do not recommend CTx as part of CAP treatment. Therefore a well-powered trial appears necessary to test the hypothesis that CTx - and more specifically hydrocortisone - could improve day 28 survival of critically-ill patients with severe CAP, severity being assessed either on a Pulmonary Severity Index ≥ 130 (Fine class V) or by the use of mechanical ventilation or high-FiO2 high-flow oxygen therapy. A phase-III multicenter add-on randomized controlled double-blind superiority trial assessing the efficacy of hydrocortisone vs. placebo on Day 28 all-causes mortality, in addition to antibiotics and supportive care, including the correction of hypoxemia. Randomization will be stratified on: (i) centers; (ii) use of mechanical ventilation at the time of inclusion.

    NCT02517489
    Conditions
    1. Community Acquired Pneumonia
    Interventions
    1. Drug: Hydrocortisone
    2. Drug: Placebo
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Measure: Day 28 all causes mortality

    Time: at day 28

    Description: For the sub-group of patients included with COVID19, failure is defined as death or need of respiratory support (mechanical ventilation or high-flow oxygen therapy);

    Measure: Day 21 failure

    Time: at day 21

    Secondary Outcomes

    Measure: In patients non-invasively ventilated at inclusion, proportion of patients needing endotracheal intubation

    Time: Participants will be followed for the duration of hospital stay, for a maximum of 28 days

    Measure: In patients non-ventilated at inclusion, proportion of patients requiring non-invasive ventilation

    Time: Participants will be followed for the duration of hospital stay, for a maximum of 28 days

    Measure: In patients non-ventilated at inclusion, proportion of patients needing endotracheal intubation

    Time: Participants will be followed for the duration of hospital stay, for a maximum of 28 days

    Measure: Day 28 ventilator-free-days

    Time: between 0 and day 28

    Measure: Number of patients with vasopressor therapy initiation from inclusion to day 28

    Time: between 0 and day 28

    Measure: Day 28 vasopressor-free-days

    Time: between 0 and day 28

    Measure: ICU and/or intermediate care unit LOS

    Time: Participants will be followed for the duration of hospital stay, for a maximum of 28 days

    Measure: All-causes mortality at day 90

    Time: at day 90

    Measure: SF-36 Health Survey at day 90

    Time: at day 90

    Measure: Biomarkers: procalcitonin at baseline, day 3 and day 7

    Time: at inclusion, day 3 and day 7

    Measure: Biomarkers: C-reactive protein at baseline, day 3 and day 7

    Time: at inclusion, day 3 and day 7

    Measure: Biomarkers: plasmatic concentration of pro-inflammatory cytokines (IL-6, IL-20, IL-22, IL-22BP, HBD2, TNF) at baseline, day 3 and day 7

    Time: at inclusion, day 3 and day 7

    Measure: P/F ratio measured daily from baseline to day 7, at the end of treatment, at the end of ICU-stay and/or day 28

    Time: measured daily from baseline to day 7, at the end of treatment i.e 14 days after the start of treatment, at the end of ICU-stay (for a maximum of 28 days) and/or day 28

    Measure: SOFA calculated daily from baseline to day 7, at the end of treatment, at the end of ICU-stay and/or day 28

    Time: calculated daily from baseline to day 7, at the end of treatment (i.e 14 days after the start of treatment), at the end of ICU-stay (for a maximum of 28 days) and/or day 28

    Measure: Proportion of patients experiencing secondary infection during their ICU-stay

    Time: Participants will be followed for the duration of hospital stay, for a maximum of 28 days

    Measure: Proportion of patients experiencing gastrointestinal bleeding during their ICU-stay

    Time: Participants will be followed for the duration of hospital stay, for a maximum of 28 days

    Measure: Daily amount of insulin administered to the patient from day 1 to day 7

    Time: Patients will be followed from day 1 to day 7

    Measure: Weight-gain at baseline and day 7

    Time: Patients will be followed at baseline and day 7

    Other Outcomes

    Description: Sub-group of patients included with COVID19

    Measure: P/F ratio measured daily from Day1 to Day7, at Day 14 and at Day 21 and/or at the end of ICU-stay

    Time: from day 1 to day 7, at day 14 and day 21 and/or at the end of ICU-stay

    Description: Sub-group of patients included with COVID19

    Measure: Proportion of patients needing endotracheal intubation

    Time: at day 21

    Description: Sub-group of patients included with COVID19

    Measure: Proportion of patients experiencing secondary infection during their ICU-stay

    Time: From baseline to day 21
    5 Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community- Acquired Pneumonia

    REMAP-CAP is a randomised, embedded, multifactorial, adaptive platform trial for community-acquired pneumonia. The purpose of this study is to evaluate the effect of a range of interventions to improve outcome of patients admitted to intensive care with community-acquired pneumonia. In addition, REMAP-CAP provides and adaptive research platform for evaluation of multiple treatment modalities in the event of a respiratory pandemic resulting in critical illness. REMAP-COVID is a sub-platform of REMAP-CAP that evaluates treatments specific to COVID-19.

    NCT02735707
    Conditions
    1. Community-acquired Pneumonia, Influenza, COVID-19
    Interventions
    1. Drug: Fixed-duration Hydrocortisone
    2. Drug: Shock-dependent hydrocortisone
    3. Drug: Ceftriaxone
    4. Drug: Moxifloxacin or Levofloxacin
    5. Drug: Piperacillin-tazobactam
    6. Drug: Ceftaroline
    7. Drug: Amoxicillin-clavulanate
    8. Drug: Macrolide administered for 3-5 days
    9. Drug: Macrolide administered for up to 14 days
    10. Drug: Five-days oseltamivir
    11. Drug: Ten-days oseltamivir
    12. Drug: Lopinavir/ritonavir
    13. Drug: Hydroxychloroquine
    14. Drug: Hydroxychloroquine + lopinavir/ritonavir
    15. Drug: Interferon-β1a
    16. Drug: Anakinra
    17. Drug: Fixed-duration higher dose Hydrocortisone
    18. Drug: Tocilizumab
    19. Drug: Sarilumab
    20. Drug: Vitamin C
    21. Drug: Therapeutic anticoagulation
    22. Drug: Simvastatin
    23. Biological: Convalescent plasma
    24. Other: Protocolised mechanical ventilation strategy
    25. Drug: Eritoran
    26. Drug: Apremilast
    27. Drug: Aspirin
    28. Drug: Clopidogrel
    29. Drug: Prasugrel
    30. Drug: Ticagrelor
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Measure: All-cause mortality

    Time: Day 90

    Description: Primary end-point for patients with suspected or proven COVID-19 pandemic infection

    Measure: Days alive and not receiving organ support in ICU

    Time: Day 21

    Secondary Outcomes

    Measure: ICU Mortality

    Time: Day 90

    Measure: ICU length of stay

    Time: Day 90

    Measure: Hospital length of stay

    Time: Day 90

    Measure: Ventilator free days

    Time: Day 28

    Measure: Organ failure free days

    Time: Day 28

    Measure: All-cause mortality

    Time: 6 months

    Description: EQ5D-5L and WHODAS 2.0 (not completed in all regions)

    Measure: Health-related Quality of life assessment

    Time: 6 months

    Measure: Proportion of intubated patients who receive a tracheostomy

    Time: Day 28

    Description: Characterised as home, rehabilitation hospital, nursing home or long-term care facility, or another acute hospital

    Measure: Destination at time of hospital discharge

    Time: Free text Day 90

    Measure: Readmission to the index ICU during the index hospitalization

    Time: Day 90

    Measure: World Health Organisation 8-point ordinal scale outcome

    Time: Hospital discharge

    Other Outcomes

    Description: Antibiotic Domain specific outcome

    Measure: Occurrence of multi-resistant organism colonisation/infection

    Time: Day 90, censored at hospital discharge

    Description: Antibiotic Domain specific outcome

    Measure: Occurrence clostridium difficile

    Time: Day 90, censored at hospital discharge

    Description: Macrolide Duration domain specific outcome, and COVID-19 Antiviral Domain specific outcome.

    Measure: Occurrence of serious ventricular arrhythmia (including ventricular fibrillation) or sudden unexpected death

    Time: Day 90, censored at hospital discharge

    Description: Antiviral Domain specific outcome. Only required at selected sites.

    Measure: Change from baseline influenza virus levels in upper and lower respiratory tract specimens

    Time: Day 3, up to Day 7

    Description: COVID-19 Antiviral Domain and COVID-19 Immune Modulation Domain specific endpoint

    Measure: Serial detection of SARS-CoV-2 in upper or lower respiratory tract specimens (using only specimens collected for routine clinical testing)

    Time: Day 90, censored at hospital discharge
    6 Trial of Respiratory Infections in Children for Enhanced Diagnostics

    The overall aim of the TREND study is to improve the differential diagnosis of bacterial and viral etiology in children below 5 years of age with clinical community acquired pneumonia. Specific objectives: - To assess the diagnostic accuracy of MxA for viral CAP (sub-study I) - To study etiologies in children with CAP (sub-study II) - To evaluate sensitivity and specificity for MariPOC® Respi test versus PCR for detection of respiratory viruses (sub-study III) - To assess sensitivity and specificity for a novel RPA-based point-of-care test versus PCR for detection of respiratory viruses (sub-study IV) - To assess long-term complications in children with CAP (sub-study V The study takes place at Sachs' Children and Youth hospital in Stockholm.

    NCT03233516
    Conditions
    1. Community-acquired Pneumonia
    MeSH:Respiratory Tract Infections Pneumonia
    HPO:Pneumonia Respiratory tract infection

    Primary Outcomes

    Description: Clinically relevant difference in MxA-levels between cases with viral and bacterial clinical CAP

    Measure: MxA - cases with viral and bacterial clinical CAP

    Time: 2021

    Description: Clinically relevant difference in MxA-levels between cases with viral clinical CAP and controls

    Measure: Mxa viral clinical CAP and controls

    Time: 2021

    Description: Proportion of respiratory pathogens in cases and controls, using real time PCR

    Measure: PCR - respiratory pathogens in cases and controls

    Time: 2020

    Description: Sensitivity and specificity for different respiratory viruses with MariPOC® Respi as compared to real-time PCR

    Measure: Sensitivity and specificity - MariPOC

    Time: 2021

    Description: Sensitivity and specificity for different respiratory viruses with a novel PCR-based point-of-care test as compared to PCR

    Measure: Sensitivity and specificity a novel PCR-based point-of-care test

    Time: 2021

    Description: Difference in asthma prevalence between cases and controls and difference in number of hospital-requiring respiratory infections between cases and controls after 3, 7 and 10 years

    Measure: Difference asthma prevalence and number of hospital-requiring respiratory infections - cases and controls,

    Time: 2027

    Secondary Outcomes

    Description: Clinically relevant difference in MxA-levels comparing cases with viral clinical CAP with cases with atypical and mixed viral-bacterial clinical CAP as well as with controls with and without presence of respiratory viruses by PCR

    Measure: Specific assessment of MxA as a clinical biomarker

    Time: 2021

    Description: Clinically relevant differences in MxA-levels in cases with regard to specific respiratory agents

    Measure: Specific assessment of MxA as a clinical biomarker

    Time: 2021

    Description: Sensitivity and specificity for MxA in identifying viral clinical CAP

    Measure: Specific assessment of MxA as a clinical biomarker

    Time: 2021

    Description: Sensitivity and specificity for identifying viral and bacterial infection respectively for CRP, PCT and combination test of CRP, PCT and MxA

    Measure: Specific assessment of MxA as a clinical biomarker

    Time: 2021

    Description: Difference in CRP and PCT between children with viral, bacterial, atypical bacterial and mixed viral-bacterial infection

    Measure: Assessment of PCT and CRP as clinical biomarkers

    Time: 2021

    Description: Differences in symptom, antibiotic treatment, acute complications, radiologic exams admission rate and length of stay between cases with viral, bacterial, atypical bacterial and mixed viral-bacterial infection

    Measure: Descriptive statistics of study cohort with regard to etiologic agent

    Time: 2020

    Description: Differences in symptom, antibiotic treatment, acute complications, radiologic exams admission rate and length of stay between cases who tested positive for respiratory virus by MariPOC® Respi as compared to those with a negative test

    Measure: Evaluation of MariPOC® Respi in a clinical setting

    Time: 2022

    Description: Number of hospital-requiring respiratory infections in cases and controls

    Measure: Assessment of long-term outcomes of children with CAP

    Time: 2027

    Description: Difference in asthma prevalence between cases with viral and bacterial clinical CAP as compared to an estimate of the prevalence in the general population

    Measure: Assessment of long-term outcomes of children with CAP

    Time: 2027

    Description: Difference in proportion of hospital-requiring respiratory infections between cases with viral, bacterial, atypical and mixed viral-bacterial infection

    Measure: Assessment of long-term outcomes of children with CAP

    Time: 2027

    Description: Difference in MxA-levels between PCR+/MariPOC® Respi+ and PCR+/MariPOC® Respi- study subjects.

    Measure: Evaluation of MariPOC® Respi

    Time: 2022

    Description: Estimation of etiology of cases using two levels of certainty (definitive as well as probable definition).

    Measure: Etiology of cases in TREND study

    Time: 2020
    7 SMART Trial: Steroid Dosing by bioMARker Guided Titration in Critically Ill Patients With Pneumonia

    In community acquired pneumonia, corticosteroids have been shown to have potential benefit. However, the limited and variable use of adjunctive corticosteroids in critically ill patients is largely due to an inability to identify patients that will benefit from the use of anti-inflammatory medications. This study compares usual care to a novel biomarker-tailored steroid dosing algorithm for patients with community acquired pneumonia. In April 2020, in response to the SARS CoV-2 pandemic, we added a COVID-19 arm to this study. The study will evaluate the role of biomarker-titrated adjuvant corticosteroid administration compared to usual care in patients admitted to hospital with SARS CoV-2 (COVID-19) infection and acute respiratory failure.

    NCT03852537
    Conditions
    1. Pneumonia
    Interventions
    1. Drug: Methylprednisolone
    2. Other: Usual Care
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: A percentage of eligible patients adhered to the timely initiation (within 12 hours of emergency room admission) and daily corticosteroid treatment according to ESICM/SCCM clinical practice guideline (control group) or biomarker concordance (intervention group)

    Measure: Feasibility of the timely initiation of corticosteroids and implementation of biomarker-titrated corticosteroid dosing: percentage of eligible patients adhered to the timely initiation

    Time: Within 30 days of enrollment in study.

    Secondary Outcomes

    Description: Death from any cause

    Measure: Mortality

    Time: Within 30 days and 90 days of study enrollment

    Description: Progression of disease is defined by the need for high flow nasal cannula oxygen, noninvasive or invasive ventilation. Given the proliferation of high flow nasal cannula oxygen use in lieu of mechanical ventilation, instead of ventilator-free days the investigators opt for using advanced respiratory support free days where "advanced respiratory support" includes both invasive and noninvasive mechanical ventilation and the high flow nasal cannula oxygen.

    Measure: Progression of disease

    Time: Within hospitalization or 30 days of study enrollment (whichever is sooner)

    Description: Measured by respiratory component of SOFA at time of ICU admission, after 24 hours, after 48 hours and after 72 hours and by the organ failure free days. In the absence of daily arterial blood gas analysis, PaO2/FiO2 ratio will be replaced by SpO2/FiO2 ratio

    Measure: Evolution of respiratory failure

    Time: Within 72 hours of enrollment in study.

    Description: Assessed by renal component of Sequential Organ Failure Assessment (SOFA) Score score. This is a scale from 0-4 (with 0 indicating no renal failure and 4 indicating severe renal failure).

    Measure: Evolution of kidney failure

    Time: Within 72 hours of enrollment in study.

    Description: Assessed by cardiac component of Sequential Organ Failure Assessment (SOFA) Score score. This is a scale from 0-4 (with 0 indicating no cardiovascular failure and 4 indicating severe cardiovascular failure).

    Measure: Evolution of shock

    Time: Within 72 hours of enrollment in study.

    Description: In hospital and in ICU

    Measure: Length of stay

    Time: From time of study enrollment up to discharge from hospital, to a maximum of 1 year.

    Description: Number of participants who have hyperglycemia while receiving corticosteroids. Hyperglycemia is defined as a consistently elevated blood sugar level requiring insulin administration.

    Measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]: Hyperglycemia

    Time: Up to day +5 following study enrollment.

    Description: Number of participants who develop delirium while receiving corticosteroids. Delirium will be assessed by Confusion Assessment Method for the ICU (CAM-ICU) measurement tool. The CAM-ICU is a binary (yes/no) scale for assessing the presence of delirium.

    Measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]: Delirium

    Time: Up to day +5 following study enrollment.

    Description: Number of participants who develop secondary infections during and after steroid therapy. A secondary infection is defined as a new infection that develops after initiation of corticosteroid therapy, until 5 days after steroids are discontinued.

    Measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]: Secondary Infection

    Time: Up to day +14 following study enrollment.
    8 ARrest RESpiraTory Failure From PNEUMONIA (ARREST PNEUMONIA)

    This research study seeks to establish the effectiveness of a combination of an inhaled corticosteroid and a beta agonist compared to placebo for the prevention of acute respiratory failure (ARF) in hospitalized patients with pneumonia and hypoxemia.

    NCT04193878
    Conditions
    1. Pneumonia
    2. Hypoxemia
    3. Acute Respiratory Failure
    Interventions
    1. Drug: Inhaled budesonide and formoterol
    2. Drug: Inhaled placebo
    MeSH:Pneumonia Respiratory Insufficiency Hypoxia
    HPO:Hypoxemia Pneumonia

    Primary Outcomes

    Description: High flow nasal cannula (HFNC) and/or Noninvasive ventilation (NIV) use for greater than 36 hours OR Invasive mechanical ventilation for greater than 36 hours OR Death in a patient placed on respiratory support (HFNC, NIV, ventilator) who dies before 36 hours

    Measure: Acute respiratory failure (ARF)

    Time: within 7 days of randomization

    Secondary Outcomes

    Measure: Hospital length of stay

    Time: within 60 days of randomization

    Measure: Duration of need for supplemental oxygen

    Time: within 60 days of randomization

    Measure: Proportion of patients intubated for respiratory failure

    Time: Within 7 days of randomization
    9 Effects of Traditional Chinese Medicines (TCMs) on Patients With COVID-19 Infection: A Perspective, Open-labeled, Randomized, Controlled Trial

    The aim of this study is to test whether Traditional Chinese Medicines (TCMs) are effective and safe for treating COVID-19 infection. After the enrolment of approximately 30 subjects, the recruitment will be paused, and planned interim analysis will be performed to preliminarily investigate the efficacy and safety of TCMs in patients infected with COVID-19.

    NCT04251871
    Conditions
    1. Pneumonia Caused by Human Coronavirus (Disorder)
    Interventions
    1. Drug: Conventional medicines (Oxygen therapy, alfa interferon via aerosol inhalation, and lopinavir/ritonavir) and Traditional Chinese Medicines (TCMs) granules
    2. Drug: Conventional medicines (Oxygen therapy, alfa interferon via aerosol inhalation, and lopinavir/ritonavir)
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: The incidence rate of acute respiratory distress syndrome (ARDS) development

    Measure: The incidents of acute respiratory distress syndrome (ARDS) development

    Time: 14 days

    Secondary Outcomes

    Description: Time to complete remission of fever in eligible subjects

    Measure: The time to fever resolution rate

    Time: 14 days

    Description: improvement of chest radiographic evidence indirectly reflects recovery in patients infected with COVID-19.

    Measure: Time to recovery of lung injury

    Time: 14 days

    Other Outcomes

    Description: The rate of subject who die will be described.

    Measure: Rate of subjects who die

    Time: 28 days

    Description: The rate of subjects with severe 2019-nCoV infection who receive systematic corticosteroids will be described.

    Measure: Rate of subjects receiving systematic corticosteroids

    Time: 28 days

    Description: The length of hospital stays

    Measure: The length of hospital stays

    Time: 28 days

    Description: The duration of respiratory support including invasive and non-invasive mechanical ventilation

    Measure: The duration of respiratory support

    Time: 28 days
    10 Safety and Efficiency of Mesenchymal Stem Cell in Treating Pneumonia Patients Infected With COVID-19

    The SARS-CoV-2 infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. There is no confirmed antivirus therapy for people infected SARS-CoV-2, 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 Mesenchymal Stem Cells (MSCs) therapy for pneumonia patients infected with SARS-CoV-2.

    NCT04252118
    Conditions
    1. COVID-19
    Interventions
    1. Biological: MSCs
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Evaluation of Pneumonia Improvement

    Measure: Size of lesion area by chest radiograph or CT

    Time: At Baseline , Day 3, Day 6, Day 10, Day 14, Day 21,Day 28

    Description: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

    Measure: Side effects in the MSCs treatment group

    Time: At Baseline , Day 3, Day 6, Day 10, Day 14, Day 21, Day 28, Day 90 and Day 180

    Secondary Outcomes

    Description: Evaluation of Pneumonia Improvement

    Measure: Improvement of Clinical symptoms including duration of fever and respiratory

    Time: At Baseline , Day 3, Day 6, Day 10, Day 14, Day 21, Day 28

    Description: Marker for COVID-19

    Measure: Time of nucleic acid turning negative

    Time: At Baseline , Day 3, Day 6, Day 10, Day 14, Day 21, Day 28, Day 90 and Day 180

    Description: Marker for efficacy of treatment

    Measure: Rate of mortality within 28-days

    Time: Day 28

    Description: Marker of Immunological function

    Measure: CD4+ and CD8+ T celll count

    Time: At Baseline , Day 3, Day 6, Day 10, Day 14, Day 21, Day 28, Day 90 and Day 180

    Description: Markers of organ function

    Measure: Alanine aminotransferase

    Time: At Baseline , Day 3, Day 6, Day 10, Day 14, Day 21, Day 28, Day 90 and Day 180

    Description: Markers of Infection

    Measure: C-reactive protein

    Time: At Baseline , Day 3, Day 6, Day 10, Day 14, Day 21, Day 28, Day 90 and Day 180

    Description: Markers of organ function

    Measure: Creatine kinase

    Time: At Baseline , Day 3, Day 6, Day 10, Day 14, Day 21, Day 28, Day 90 and Day 180
    11 Efficacy and Safety of Darunavir and Cobicistat for Treatment of COVID-19

    The study aims to evaluate the efficacy and safety of darunavir and cobistastat in the treatment of COVID-19 pneumonia

    NCT04252274
    Conditions
    1. Pneumonia, Pneumocystis
    2. Coronavirus
    Interventions
    1. Drug: Darunavir and Cobicistat
    MeSH:Pneumonia, Pneumocystis Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Measure: The virological clearance rate of throat swabs, sputum, or lower respiratory tract secretions at day 7

    Time: 7 days after randomization

    Secondary Outcomes

    Measure: The virological clearance rate of throat swabs, sputum, or lower respiratory tract secretions at day 3

    Time: 3 days after randomization

    Measure: The virological clearance rate of throat swabs, sputum, or lower respiratory tract secretions at day 5

    Time: 5 days after randomization

    Measure: Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

    Time: 14 days after randomization

    Description: The diagnosis of critical illness case was based on the notice on printing and distributing the diagnosis and treatment plan of pneumonia with new coronavirus infection (trial version 4) made by National Health Commission of the People's Republic of China.

    Measure: The critical illness rate of subjects at weeks 2

    Time: 14 days after randomization

    Measure: The mortality rate of subjects at weeks 2

    Time: 14 days after randomization
    12 An Open, Prospective/Retrospective, Randomized Controlled Cohort Study to Compare the Efficacy of Two Therapeutic Schemes(Abidol Hydrochloride,Abidol Hydrochloride Combined With Interferon Atomization)in the Treatment of 2019-nCoV Pneumonia.

    At present, there is no specific and effective antiviral therapy.In this study, an open, prospective/retrospective, randomized controlled cohort study was designed to compare the efficacy of two therapeutic schemes(abidol hydrochloride,abidol hydrochloride combined with interferon atomization)in the treatment of 2019-nCoV viral pneumonia, so as to provide reliable evidence-based medicine for the treatment of viral pneumonia caused by 2019-nCoV.

    NCT04254874
    Conditions
    1. 2019-nCoV
    Interventions
    1. Drug: Abidol hydrochloride
    2. Drug: Abidol Hydrochloride combined with Interferon atomization
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: A: For mild patients : fever, cough and other symptoms relieved with improved lung CT; B:For severe patients : fever, cough and other symptoms relieved with improved lung CT,SPO2> 93% or PaO2/FiO2> 300mmHg (1mmHg=0.133Kpa);

    Measure: Rate of disease remission

    Time: two weeks

    Description: Compare the average time of lung imaging recovery after 2 weeks of treatment in each group.

    Measure: Time for lung recovery

    Time: two weeks

    Secondary Outcomes

    Measure: Rate of no fever

    Time: two weeks

    Measure: Rate of respiratory symptom remission

    Time: two weeks

    Measure: Rate of lung imaging recovery

    Time: two weeks

    Measure: Rate of CRP,ES,Biochemical criterion (CK,ALT,Mb)recovery

    Time: two weeks

    Measure: Rate of undetectable viral RNA

    Time: two weeks
    13 An Open, Prospective/Retrospective, Randomized Controlled Cohort Study to Compare the Efficacy of Three Antiviral Drugs(Abidol Hydrochloride, Oseltamivir and Lopinavir/Ritonavir) in the Treatment of 2019-nCoV Pneumonia.

    At present, there is no specific and effective antiviral therapy.In this study, an open, prospective/retrospective, randomized controlled cohort study was designed to compare the efficacy of three antiviral drugs in the treatment of 2019-nCoV pneumonia by studying the efficacy of abidol hydrochloride, oseltamivir and lopinavir/ritonavir in the treatment of 2019-nCoV viral pneumonia, and to explore effective antiviral drugs for new coronavirus. To provide reliable evidence-based medicine basis for the treatment of viral pneumonia caused by new coronavirus infection.

    NCT04255017
    Conditions
    1. 2019-nCoV
    Interventions
    1. Drug: Abidol hydrochloride
    2. Drug: Oseltamivir
    3. Drug: Lopinavir/ritonavir
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: A: For mild patients : fever, cough and other symptoms relieved with improved lung CT; B:For severe patients : fever, cough and other symptoms relieved with improved lung CT,SPO2> 93% or PaO2/FiO2>300mmHg (1mmHg=0.133Kpa);

    Measure: Rate of disease remission

    Time: two weeks

    Description: Compare the average time of lung imaging recovery after 2 weeks of treatment in each group.

    Measure: Time for lung recovery

    Time: two weeks

    Secondary Outcomes

    Measure: Rate of no fever

    Time: two weeks

    Measure: Rate of respiratory symptom remission

    Time: two weeks

    Measure: Rate of lung imaging recovery

    Time: two weeks

    Measure: Rate of CRP,ES,Biochemical criterion(CK,ALT,Mb) recovery

    Time: two weeks

    Measure: Rate of undetectable viral RNA

    Time: two weeks
    14 A Survey of Psychological Status of Medical Workers and Residents in the Context of 2019 Novel Coronavirus Pneumonia in Wuhan, China

    Due to the outbreak of 2019 Novel Coronavirus Pneumonia in Wuhan, Hubei province, medical staff and residents are facing great psychological pressure, the investigator plan to use electronic questionnaire to carry out investigation research.

    NCT04260308
    Conditions
    1. Virus; Pneumonia
    MeSH:Pneumonia, Viral Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: GHQ-12(general health questionnaire-12): minimal score 0, maximal score 12, higher scores mean a better or worse outcome.

    Measure: GHQ-12(general health questionnaire-12)

    Time: 2 weeks

    Secondary Outcomes

    Description: IES-R(Impact of Event Scale-Revised):score range:0-88, the higher the worse

    Measure: IES-R(Impact of Event Scale-Revised)

    Time: 2 weeks
    15 Randomized, Open, Multicenter Study on the Efficacy and Safety of Arbidol Hydrochloride Tablets in Treating Pneumonia in Patients Infected With Novel Coronavirus (2019-ncov).

    In the absence of 2019-ncov specific therapeutic drugs, arbidol is effective against a variety of coronaviruses in vitro pharmacodynamics. In order to observe the efficacy and safety of arbidol in the treatment of 2019-ncov infected pneumonia, this study is planned.

    NCT04260594
    Conditions
    1. 2019-nCoV
    Interventions
    1. Drug: Arbidol
    2. Other: basic treatment
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Measure: Virus negative conversion rate in the first week

    Time: first week

    Secondary Outcomes

    Description: virus negative conversion rate in second week, overall virus negative conversion rate

    Measure: Virus negative conversion rate

    Time: 14-20 days

    Description: defined as: the rate of Axillary temperature ≤37.5 ℃ for at least 48h

    Measure: Antipyretic rate

    Time: 14-20 days

    Description: time to relieve symptoms of fever, cough, dyspnea, myalgia, etc

    Measure: Symptom relief time

    Time: 14-20 days

    Description: no adjuvant oxygen therapy, resting oxygen saturation>95%, oxygenation index>350

    Measure: Finger oxygen improvement rate

    Time: 14-20 days

    Description: Mild, common type progression to severe or critical illness rate

    Measure: Disease progression rate

    Time: 14-20 days

    Measure: Mortality rate

    Time: 14-20 days

    Measure: Incidence of severe adverse reactions

    Time: 14-20 days

    Measure: Change curve of peripheral blood lymphocyte count

    Time: 14-20 days
    16 A Randomized,Open,Controlled Small Sample Clinical Study to Evaluate the Efficacy and Safety of ASC09/Ritonavir Compound Tablets and Ritonavir for 2019-nCoV Pneumonia

    Based on oseltamivir treatment, evaluate the efficacy and safety of ASC09/ritonavir compound tablets(ASC09F) or ritonavir tablets for 2019-nCoV infection patients.

    NCT04261270
    Conditions
    1. 2019-nCoV Pneumonia
    Interventions
    1. Drug: ASC09F+Oseltamivir
    2. Drug: Ritonavir+Oseltamivir
    3. Drug: Oseltamivir
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: The definition of comprehensive adverse outcome is as follows: SPO2≤93% without oxygen inhalation; PaO2/FiO2≤300mmHg; RR≥30 bpm without oxygen inhalation.

    Measure: Rate of comprehensive adverse outcome

    Time: 14 days

    Secondary Outcomes

    Description: The definition of clinical remission: Based on the symptoms of the disease (fever,cough,diarrhea,myalgia,dyspnea) has been relieved for 48 hours; There is no evidence of disease progression(New dyspnea, SpO2 decreased≥3%,RR≥30 bpm without oxygen inhalation).

    Measure: Time of clinical remission

    Time: 28 days

    Measure: Rate of no fever

    Time: 14 days

    Measure: Rate of no cough

    Time: 14 days

    Measure: Rate of no dyspnea

    Time: 14 days

    Measure: Rate of no need for oxygen inhalation

    Time: 14 days

    Measure: Rate of undetectable viral RNA

    Time: 14 days

    Measure: Rate of mechanical ventilation

    Time: 28 days

    Measure: Rate of ICU admission

    Time: 28 days

    Measure: Rate and time of CRP,ES,Biochemical criterion(CK,ALT,Mb)recovery

    Time: 28 days
    17 A Randomized, Open-label, Controlled, Single-center Study to Evaluate the Efficacy of Intravenous Immunoglobulin Therapy in Patients With Severe 2019- nCoV Pneumonia

    In this single-center, randomized, open-label, controlled study, the investigators will evaluate the efficacy and safety of Intravenous Immunoglobulin (IVIG) in combination with standard care for severe 2019 novel coronavirus (2019-nCoV) pneumonia.

    NCT04261426
    Conditions
    1. 2019-nCoV
    Interventions
    1. Drug: Intravenous Immunoglobulin
    2. Other: Standard care
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: A decline of 2 points on the 7-point scale from admission means better outcome. The 7-category ordinal scale that ranges from 1 (discharged with normal activity) to 7 (death).

    Measure: Clinical improvement based on the 7-point scale

    Time: 28 days after randomization

    Description: Murray lung injury score decrease more than one point means better outcome. The Murray scoring system range from 0 to 4 according to the severity of the condition.

    Measure: Lower Murray lung injury score

    Time: 7 days after randomization

    Description: Murray lung injury score decrease more than one point means better outcome. The Murray scoring system range from 0 to 4 according to the severity of the condition.

    Measure: Lower Murray lung injury score

    Time: 14 days after randomization

    Secondary Outcomes

    Description: Number of deaths during study follow-up

    Measure: 28-day mortality

    Time: Measured from Day 0 through Day 28

    Description: Duration of mechanical ventilation use in days. Multiple mechanical ventilation durations are summed up.

    Measure: Duration of mechanical ventilation

    Time: Measured from Day 0 through Day 28

    Description: Days that a participant spent at the hospital. Multiple hospitalizations are summed up.

    Measure: Duration of hospitalization

    Time: Measured from Day 0 through Day 28

    Description: Proportion of patients with negative RT-PCR results of virus in upper and/or lower respiratory tract samples.

    Measure: Proportion of patients with negative RT-PCR results

    Time: 7 and 14 days after randomization

    Description: Proportion of patients in each category of the 7-point scale, the 7-category ordinal scale that ranges from 1 (discharged with normal activity) to 7 (death).

    Measure: Proportion of patients in each category of the 7-point scale

    Time: 7,14 and 28 days after randomization

    Description: Proportion of patients with different inflammation factors in normalization range.

    Measure: Proportion of patients with normalized inflammation factors

    Time: 7 and 14 days after randomization

    Description: Frequency of Adverse Drug Events

    Measure: Frequency of Adverse Drug Events

    Time: Measured from Day 0 through Day 28

    Description: Frequency of Serious Adverse Drug Events

    Measure: Frequency of Serious Adverse Drug Events

    Time: Measured from Day 0 through Day 28
    18 Efficacy and Safety of Hydroxychloroquine for Treatment of COVID-19

    The study aims to evaluate the efficacy and safety of hydroxychloroquine in the treatment of COVID-19 pneumonia.

    NCT04261517
    Conditions
    1. Pneumonia, Pneumocystis
    2. Coronavirus
    3. COVID-19
    Interventions
    1. Drug: Hydroxychloroquine
    MeSH:Pneumonia, Pneumocystis Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Measure: The virological clearance rate of throat swabs, sputum, or lower respiratory tract secretions at day 3

    Time: 3 days after randomization

    Measure: The virological clearance rate of throat swabs, sputum, or lower respiratory tract secretions at day 5

    Time: 5 days after randomization

    Measure: The virological clearance rate of throat swabs, sputum, or lower respiratory tract secretions at day 7

    Time: 7 days after randomization

    Measure: The mortality rate of subjects at weeks 2

    Time: 14 days after randomization

    Secondary Outcomes

    Measure: Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

    Time: 14 days after randomization

    Description: The diagnosis of critical illness case was based on the notice on printing and distributing the diagnosis and treatment plan of pneumonia with new coronavirus infection (trial version 4) made by National Health Commission of the People's Republic of China.

    Measure: The critical illness rate of subjects at weeks 2

    Time: 14 days after randomization
    19 An Open, Prospective/Retrospective, Randomized Controlled Cohort Study to Compare the Efficacy of Different Hormone Doses in the Treatment of 2019-nCoV Severe Pneumonia

    At present, there is no specific and effective antiviral therapy.In this study, an open, prospective/retrospective, randomized controlled cohort study was designed to compare the efficacy of different hormone doses in the treatment of 2019-nCoV severe Pneumonia.This study explores effective treatment programs for 2019-nCoV severe pneumonia and provides a reliable evidence-based basis for the treatment.

    NCT04263402
    Conditions
    1. 2019-nCoV Severe Pneumonia
    Interventions
    1. Drug: Methylprednisolone
    2. Drug: Methylprednisolone
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: For mild patients: disease remission refers to relieved symptoms with improved lung CT; For severe patients: disease remission refers to relieved symptoms with improved lung CT; or SPO2>93% or PaO2/FiO2 >300mmHg.

    Measure: Rate of disease remission

    Time: day 7

    Description: the critical stage refers to respiratory failure that occurs and requires mechanical ventilation, shock, or having other organ failure that needs ICU monitoring and treatment.

    Measure: Rate and time of entering the critical stage

    Time: day 7

    Secondary Outcomes

    Description: Rate of patients without fever at day 7

    Measure: Rate of normal tempreture

    Time: day 7

    Description: Rate of patients with respiratory symptom remission at day 7

    Measure: Rate of respiratory symptom remission

    Time: day 7

    Description: Rate of patients with lung imaging recovery at day 7

    Measure: Rate of lung imaging recovery

    Time: day 7

    Description: Rate of patients with laboratory indicator recovery at day 7

    Measure: Rate of laboratory indicator recovery

    Time: day 7

    Description: Rate of patients withundetectable viral RNA at day 7

    Measure: Rate of undetectable viral RNA

    Time: day 7
    20 Vitamin C Infusion for the Treatment of Severe 2019-nCoV Infected Pneumonia: a Prospective Randomized Clinical Trial

    2019 new coronavirus (2019-nCoV) infected pneumonia, namely severe acute respiratory infection (SARI) has caused global concern and emergency. There is a lack of effective targeted antiviral drugs, and symptomatic supportive treatment is still the current main treatment for SARI. Vitamin C is significant to human body and plays a role in reducing inflammatory response and preventing common cold. In addtion, a few studies have shown that vitamin C deficiency is related to the increased risk and severity of influenza infections. We hypothize that Vitamin C infusion can help improve the prognosis of patients with SARI. Therefore, it is necessary to study the clinical efficacy and safety of vitamin C for the clinical management of SARI through randomized controlled trials during the current epidemic of SARI.

    NCT04264533
    Conditions
    1. Vitamin C
    2. Pneumonia, Viral
    3. Pneumonia, Ventilator-Associated
    Interventions
    1. Drug: VC
    2. Drug: Sterile Water for Injection
    MeSH:Pneumonia, Ventilator-Associated Pneumonia, Viral Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: days without ventilation support during 28 days after patients' enrollment

    Measure: Ventilation-free days

    Time: on the day 28 after enrollment

    Secondary Outcomes

    Description: wether the patient survives

    Measure: 28-days mortality

    Time: on the day 28 after enrollment

    Description: days of the patients staying in the ICU

    Measure: ICU length of stay

    Time: on the day 28 after enrollment

    Description: the rate of CPR

    Measure: Demand for first aid measuments

    Time: on the day 28 after enrollment

    Description: days of using vasopressors

    Measure: Vasopressor days

    Time: on the day 28 after enrollment

    Description: P O2/Fi O2 which reflects patients' respiratory function

    Measure: Respiratory indexes

    Time: on the day 10 and 28 after enrollment

    Description: Ecmo or ventilator

    Measure: Ventilator parameters

    Time: on the day 10 and 28 after enrollment

    Description: Acute Physiology and Chronic Health Evaluation

    Measure: APACHE II scores

    Time: on the day 10 after enrollment

    Description: Sepsis-related Organ Failure Assessment

    Measure: SOFA scores

    Time: on the day 10 after enrollment
    21 An Exploratory Clinical Study on the Treatment of Acute Severe 2019-nCoV Pneumonia With Immunoglobulin From Cured 2019-nCoV Pneumonia Patients

    The new coronavirus pneumonia is an acute infectious pneumonia. The pathogen is a previously unknown new coronavirus, namely 2019 new coronavirus (2019 novel coronavirus, 2019 nCoV). However, there is no specific anti-viral drug. It has been found that the specific antibodies against virus antigen are produced after these patients were cured, which could block the infection of 2019 nCoV on the host cells. At present, immunoadsorption is the most direct, rapid and effective method to separate immunoglobulin from the cured patients. Therefore, the study aims to prepare the immunoglobulin from 2019-ncov pneumonia cured patients, evaluate the efficacy and safety of the immunoglobulin in 2019-ncov pneumonia cured patients on the treatment of acute severe 2019-ncov pneumonia, and provide a new strategy for the treatment of 2019-ncov pneumonia.

    NCT04264858
    Conditions
    1. 2019-nCoV
    2. Immunoglobulin of Cured Patients
    Interventions
    1. Drug: Immunoglobulin of cured patients
    2. Drug: γ-Globulin
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: TTCI is defined as the time (in days) from initiation of study treatment (active or placebo) until a decline of two categories from admission status on a six-category ordinal scale of clinical status which ranges from 1 (discharged) to 6 (death). Six-category ordinal scale: 6. Death; 5. ICU, requiring ECMO and/or IMV; 4. ICU/hospitalization, requiring NIV/ HFNC therapy; 3. Hospitalization, requiring supplemental oxygen (but not NIV/ HFNC); 2. Hospitalization, not requiring supplemental oxygen; 1. Hospital discharge. Abbreviation: IMV, invasive mechanical ventilation; NIV, non-invasive mechanical ventilation; HFNC, High-flow nasal cannula.

    Measure: Time to Clinical Improvement (TTCI)

    Time: up to 28 days

    Secondary Outcomes

    Description: on days 7, 14, 21, and 28

    Measure: Clinical status assessed by the ordinal scale

    Time: up to 28 days

    Description: 1. No need for supplemental oxygenation; 2. nasal cathete oxygen inhalation;3. Mask oxygen inhalation;4. Noninvasive ventilator oxygen supply;5. Invasive ventilator oxygen supply.

    Measure: The differences in oxygen intake methods

    Time: up to 28 days

    Measure: Duration (days) of supplemental oxygenation

    Time: up to 28 days

    Measure: Duration (days) of mechanical ventilation

    Time: up to 28 days

    Measure: The mean PaO2/FiO2

    Time: up to 28 days

    Description: The detection frequency could be increased according to clinician's decision

    Measure: The lesions of the pulmonary segment numbers involved in pulmonary CT [ every 7 days]

    Time: up to 28 days

    Measure: Time to 2019-nCoV RT-PCR negativity in respiratory tract specimens [every 3 days]

    Time: up to 28 days

    Description: The antibody titer is detected on days 3 and 28

    Measure: Dynamic changes of 2019-nCoV antibody titer in blood

    Time: up to 28 days

    Measure: Length of hospital stay (days)

    Time: up to 28 days

    Measure: All cause mortality

    Time: up to 28 days
    22 Clinical Research Regarding the Availability and Safety of UC-MSCs Treatment for Serious Pneumonia and Critical Pneumonia Caused by the 2019-nCOV Infection

    Serious Pneumonia and Critical Pneumonia caused by the 2019-nCOV infection greatly threats patients' life, UC-MSCs treatment has been proved to play a role in curing multiple diseases. And this study is conducted to find out whether or not it will function in 2019-nCOV infection Pneumonia.

    NCT04269525
    Conditions
    1. Pneumonia, Viral
    2. Pneumonia, Ventilator-Associated
    Interventions
    1. Biological: UC-MSCs
    MeSH:Pneumonia, Ventilator-Associated Pneumonia, Viral Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: partial arterial oxygen pressure (PaO2) / oxygen concentration (FiO2)

    Measure: Oxygenation index

    Time: on the day 14 after enrollment

    Secondary Outcomes

    Description: whether the patient survives

    Measure: 28 day mortality

    Time: on the day 28 after enrollment

    Description: days of the patients in hospital

    Measure: Hospital stay

    Time: up to 6 months

    Description: whether or not the 2019-nCoV antibody is positive

    Measure: 2019-nCoV antibody test

    Time: on the day 7,14,28 after enrollment

    Description: whether or not the 2019-nCoV nucleic acid test is positive

    Measure: 2019-nCoV nucleic acid test

    Time: on the day 7,14,28 after enrollment

    Description: whether lung imaging examinations show the improvement of the pneumonia

    Measure: Improvement of lung imaging examinations

    Time: on the day 7,14,28 after enrollment

    Description: counts of white blood cell in a litre of blood

    Measure: White blood cell count

    Time: on the day 7,14,28 after enrollment

    Description: counts of lymphocyte in a litre (L) of blood

    Measure: Lymphocyte count

    Time: on the day 7,14,28 after enrollment

    Description: procalcitonin in microgram(ug)/L

    Measure: Procalcitonin

    Time: on the day 7,14,28 after enrollment

    Description: IL-2 in picogram(pg)/millilitre(mL)

    Measure: interleukin(IL)-2

    Time: on the day 7,14,28 after enrollment

    Description: IL-4 in pg/mL

    Measure: IL-4

    Time: on the day 7,14,28 after enrollment

    Description: IL-6 in pg/mL

    Measure: IL-6

    Time: on the day 7,14,28 after enrollment

    Description: IL-10 in pg/mL

    Measure: IL-10

    Time: on the day 7,14,28 after enrollment

    Description: TNF-α in nanogram(ng)/L

    Measure: tumor necrosis factor(TNF)-α

    Time: on the day 7,14,28 after enrollment

    Description: γ-IFN in a thousand unit (KU)/L

    Measure: γ-interferon(IFN)

    Time: on the day 7,14,28 after enrollment

    Description: CRP in microgram(μg)/L

    Measure: C-reactive protein(CRP)

    Time: on the day 7,14,28 after enrollment

    Description: counts of CD4+ T-Lymphocytopenia in litre

    Measure: CD4+ T-Lymphocytopenia

    Time: on the day 7,14,28 after enrollment

    Description: counts of CD8+ T-Lymphocytopenia in a litre

    Measure: CD8+ T-Lymphocytopenia

    Time: on the day 7,14,28 after enrollment

    Description: counts of NK in a litre

    Measure: natural killer cell(NK)

    Time: on the day 7,14,28 after enrollment
    23 Efficacy and Safety of Corticosteroids in COVID-19: A Prospective Randomized Controlled Trails

    There is still controversy about the effective of glucocorticoids for the treatment of novel coronavirus pneumonia. This is a prospective randomized controlled trails. The aim is to explore the effectiveness and safety of glucocorticoids in the treatment of novel coronavirus pneumonia.

    NCT04273321
    Conditions
    1. COVID-19
    2. Novel Coronavirus Pneumonia
    Interventions
    1. Drug: Methylprednisolone
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: The clinical symptoms and signs continue to deteriorate, or new pulmonary or extrapulmonary lesions appear, or the chest imaging indicates the progress, and the patient is transferred to ICU or intubation and invasive ventilation or died.

    Measure: the incidence of treatment failure in 14 days

    Time: 14 days

    Secondary Outcomes

    Description: The clinical symptoms and signs improved or alleviated (the temperature be normal , respiratory symptoms improved significantly, imaging showed obvious absorption) and no additional or alternative treatment was needed.

    Measure: clinical cure incidence in 14 days

    Time: 14 days

    Description: the duration from admission to virus negative

    Measure: the duration of virus change to negative

    Time: 30 days

    Description: the patient die in 30 days

    Measure: mortality at day 30

    Time: 30 days

    Description: the patients transform to ICU because of clinical deteriorate in 30 days

    Measure: ICU admission rate in 30 days

    Time: 30 days
    24 The Efficacy and Safety of Thalidomide in the Adjuvant Treatment of Moderate New Coronavirus (COVID-19) Pneumonia: a Prospective, Multicenter, Randomized, Double-blind, Placebo, Parallel Controlled Clinical Study

    In December 2019, Wuhan, in Hubei province, China, became the center of an outbreak of pneumonia of unknown cause. In a short time, Chinese scientists had shared the genome information of a novel coronavirus (2019-nCoV) from these pneumonia patients and developed a real-time reverse transcription PCR (real time RT-PCR) diagnostic assay. In view of the fact that there is currently no effective antiviral therapy, the prevention or treatment of lung injury caused by COVID-19 can be an alternative target for current treatment. Thalidomide has anti-inflammatory, anti-fibrotic, anti-angiogenesis, and immune regulation effects. This study is the first Prospective, Multicenter, Randomized, Double-blind, Placebo, Parallel Controlled Clinical Study at home and abroad to use immunomodulators to treat patients with COVID-19 infection.

    NCT04273529
    Conditions
    1. COVID-19 Thalidomide
    Interventions
    1. Drug: thalidomide
    2. Drug: placebo
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: TTCR is defined as the time (in hours) from initiation of study treatment (active or placebo) until normalisation of fever, respiratory rate, and oxygen saturation, and alleviation of cough, sustained for at least 72 hours. Normalisation and alleviation criteria: Fever - ≤36.6°C or -axilla, ≤37.2 °C oral or ≤37.8°C rectal or tympanic, 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: Time to Clinical recoveryTime to Clinical Recovery (TTCR)

    Time: up to 28 days

    Secondary Outcomes

    Description: baseline SpO2 during screening, PaO2/FiO2 <300mmHg or a respiratory rate ≥ 24 breaths per min without supplemental oxygen

    Measure: All cause mortality

    Time: up to 28 days

    Description: Defined as SPO2≤ 94% on room air or PaO2/FiO2 <300mmHg and requirement for supplemental oxygen or more advanced ventilator support.

    Measure: Frequency of respiratory progression

    Time: up to 28 days

    Description: in those with fever at enrolment

    Measure: Time to defervescence

    Time: up to 28 days

    Other Outcomes

    Description: in those with cough at enrolment rated severe or moderate

    Measure: Time to cough reported as mild or absent

    Time: up to 28 days

    Description: patients with moderate / severe dyspnea when enrolled

    Measure: Respiratory improvement time

    Time: up to 28 days

    Measure: Frequency of requirement for supplemental oxygen or non-invasive ventilation

    Time: up to 28 days

    Measure: Time to 2019-nCoV RT-PCR negative in upper respiratory tract specimen

    Time: up to 28 days

    Measure: Change (reduction) in 2019-nCoV viral load in upper respiratory tract specimen as assessed by area under viral load curve

    Time: up to 28 days

    Measure: Frequency of requirement for mechanical ventilation

    Time: up to 28 days

    Measure: Frequency of serious adverse events

    Time: up to 28 days

    Measure: Serum TNF-α, IL-1β, IL-2, IL-6, IL-7, IL-10, GSCF, IP10,MCP1, MIP1α and other cytokine expression levels before and after treatment

    Time: up to 28 days
    25 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
    26 Evaluating the Efficacy and Safety of Bromhexine Hydrochloride Tablets Combined With Standard Treatment/ Standard Treatment in Patients With Suspected and Mild Novel Coronavirus Pneumonia (COVID-19)

    Compare the efficacy and safety of Bromhexine Hydrochloride Tablets combined with standard treatment/ standard treatment in patients with suspected and mild, or common novel coronavirus pneumonia (COVID-19). Random, open, group sequential design.

    NCT04273763
    Conditions
    1. Novel Coronavirus Pneumonia
    2. 2019-nCoV
    Interventions
    1. Drug: Bromhexine Hydrochloride Tablets
    2. Drug: Arbidol Hydrochloride Granules
    3. Drug: Recombinant Human Interferon α2b Spray
    MeSH:Coronavirus Infections Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Defined as random to fever, respiratory rate return to normal and cough remission over 48 hours.

    Measure: Time to clinical recovery after treatment

    Time: within 14 days from the start of medication

    Description: Aggravation was defined as(one of them): respiratory distress, RR ≥ 30 times / min; SpO2 ≤ 93% in resting state; arterial partial pressure of oxygen (PaO2) /concentration of oxygen (FiO2) ≤ 300mmHg

    Measure: Rate of aggravation

    Time: within 14 days from the start of medication

    Secondary Outcomes

    Description: Clinical remission was defined as (one of them): sustained (more than 48 hours) alleviation of illness based on symptom (fever, cough, dyspnea, myalgia, diarrhea and so on) all being absent and no evidence for progression.

    Measure: Clinical remission rate

    Time: within 14 days from the start of medication

    Description: oxygenation index

    Measure: Dynamic changes of oxygenation index

    Time: within 14 days from the start of medication

    Description: time of Clinical recovery, negative COVID-19 nucleic acid results and CT recovery

    Measure: Time to cure

    Time: within 14 days from the start of medication

    Description: proportion of Clinical recovery, negative COVID-19 nucleic acid results and CT recovery among infected patients

    Measure: rate to cure

    Time: within 14 days from the start of medication

    Description: defervescence is defined as below 37 Celcius degrees(ear temperature)

    Measure: Time to defervescence

    Time: within 14 days from the start of medication

    Measure: Time to cough remission

    Time: within 14 days from the start of medication

    Measure: Time to dyspnea remission

    Time: within 14 days from the start of medication

    Measure: Days of supplemental oxygenation

    Time: within 14 days from the start of medication

    Measure: Rate of patients with requring supplemental oxygen

    Time: within 14 days from the start of medication

    Measure: Rate of patients with mechanical ventilation

    Time: within 14 days from the start of medication

    Measure: Time of negative COVID-19 nucleic acid results

    Time: within 14 days from the start of medication

    Measure: Rate of negative COVID-19 nucleic acid results

    Time: within 14 days from the start of medication

    Measure: Rate of ICU admission

    Time: within 14 days from the start of medication

    Measure: 28-day mortality

    Time: From the first day of screening to the day of follow-up (28 days)
    27 Assessing Health Related Quality of Life in Hypersensitivity Pneumonitis

    The objective of this study is to administer and validate a disease specific health related quality of life (HRQOL) survey for patients with Chronic Hypersensitivity Pneumonitis (CHP).

    NCT04273867
    Conditions
    1. Hypersensitivity Pneumonitis
    2. Chronic Hypersensitivity Pneumonitis
    3. Interstitial Lung Disease
    4. Extrinsic Allergic Alveolitis
    5. Health-related Quality of Life
    Interventions
    1. Other: Chronic Hypersensitivity Pneumonitis Health Related Quality of Life Survey Instrument
    MeSH:Lung Diseases Lung Diseases, Interstitial Pneumonia Alveolitis, Extrinsic Allergic Hypersensitivity
    HPO:Abnormal lung morphology Allergy Hypersensitivity pneumonitis Interstitial pneumonitis Interstitial pulmonary abnormality Pneumonia

    Primary Outcomes

    Description: The newly developed survey that is being validated consists of 42 items that assess the impact that Hypersensitivity Pneumonitis has on daily life for those who have the disease.

    Measure: Validation of a health-related quality of life instrument for patients with Chronic Hypersensitivity Pneumonitis

    Time: Day 0

    Description: This survey will be used to assess the validity of the newly developed health-related quality of life instrument. This survey consists of 12 items. The average score for this survey has been calibrated to 50 with scores below 50 indicating a below average score and scores above 50 indicating an above average score.

    Measure: Validation of a health-related quality of life instrument for patients with Chronic Hypersensitivity Pneumonitis by administering the Short Form (SF-12) Survey

    Time: Day 0

    Description: This survey will be used to assess the validity of the newly developed health-related quality of life instrument. This survey consists of 15 items and is scored from 0-100 with 100 indicating good health.

    Measure: Validation of a health-related quality of life instrument for patients with Chronic Hypersensitivity Pneumonitis by administering the King's Brief Interstitial Lung Disease Questionnaire

    Time: Day 0

    Description: The newly developed survey will be administered again in 2 weeks following the first assessment.

    Measure: Change in Health-related Quality of Life Assessment Score

    Time: 2 weeks following Day 0
    28 Single Center, Single Arm, Open Clinical Study to Access Safety and Initial Efficacy of Anti-CD147 Humanized Meplazumab for Injection to Treat With 2019-nCoV Pneumonia

    To evaluate the safety and efficacy of humanized Meplazumab for Injection in patients infected by 2019-nCoA.

    NCT04275245
    Conditions
    1. 2019-nCoVs Infection Pneumonia
    Interventions
    1. Drug: Meplazumab for Injection
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Virological clearance rate using Real-Time PCR in upper and/or lower respiratory tract samples at day 3, day 7 and day 14 respectively.

    Measure: 2019 nCoV nucleic acid detection

    Time: 14 days

    Secondary Outcomes

    Description: Time (days) from initiation of Meplazumab treatment until normalization of body temperature (≤37℃ axilla)

    Measure: Recovery of body temperature

    Time: 14 days

    Description: Time (days) from initiation of Meplazumab treatment until normalization of resting respiratory rate (≤24/min)

    Measure: Recovery of resting respiratory rate

    Time: 14 days

    Description: Time (days) from initiation of Meplazumab treatment until normalization of SPO2 (>94%)

    Measure: Recovery of SPO2

    Time: 14 days

    Description: Rate of lung imaging recovery

    Measure: Chest CT / chest film changes

    Time: 28 days

    Description: Rate of PaO2 / FiO2 recovery

    Measure: PaO2 / FiO2

    Time: 14 days

    Description: Days to reach the isolation release standard

    Measure: Time to reach the isolation release standard

    Time: 28 days

    Description: Rate of CRP, D-Dimer test recovery

    Measure: Changes of inflammatory immune status

    Time: 14 days
    29 Retrospective Cohort to Evaluate the Effectiveness and Safety of Xiyanping Injection Combined With Conventional Treatment for New Coronavirus Infection Pneumonia (Common Type)

    the investigators conduct a randomized, open-label trial to evaluate and compare the safety and efficacy of Xiyanping injection in patients with 2019-nCoV pneumonia.

    NCT04275388
    Conditions
    1. 2019 Novel Coronavirus Pneumonia
    Interventions
    1. Drug: Xiyanping injection
    2. Drug: Lopinavir / ritonavir, alpha-interferon nebulization,Abidor Hydrochloride
    MeSH:Coronavirus Infections Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: From the beginning of study drug use to fever, respiratory rate, blood oxygen saturation to normal and cough relief, and maintained for at least 72 hours or more, calculated in hours

    Measure: Clinical recovery time

    Time: Up to Day 14

    Secondary Outcomes

    Description: From the beginning of research drug use to body temperature <37.3 ℃ (underarm) or mouth temperature ≤37.5 ° C, or anal or ear temperature ≤37.8 ° C, and maintained for 24h or more

    Measure: Complete fever time

    Time: Up to Day 14

    Description: Cough score "day + night" from the beginning of study medication to cough ≤ 1 point, and maintained for 24 hours and above

    Measure: Cough relief time

    Time: Up to Day 14

    Description: From the beginning of the study drug to two consecutive times (sampling interval of at least 1 day)

    Measure: Virus negative time

    Time: Up to Day 14

    Description: Defined as the proportion of subjects exacerbated during treatment and meeting the diagnostic criteria for severe or critical neocoronavirus pneumonia

    Measure: Incidence of severe or critical neocoronavirus pneumonia

    Time: Up to Day 14
    30 A Pilot Clinical Study on Aerosol Inhalation of the Exosomes Derived From Allogenic Adipose Mesenchymal Stem Cells in the Treatment of Severe Patients With Novel Coronavirus Pneumonia

    In December 2019, a novel coronavirus infectious disease characterized by acute respiratory impairment due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) broke out in Wuhan city of Hubei province in China. So far no specific antiviral therapy can be available for patients with SARS-CoV-2 infection. Although symptomatic and supportive care, even with mechanical ventilation or extracorporeal membrane oxygenation (ECMO), are strongly recommended for severe infected individuals, those with advancing age and co-morbidities such as diabetes and heart disease remain to be at high risk for adverse outcomes. This pilot clinical trial will be performed to explore the safety and efficiency of aerosol inhalation of the exosomes derived from allogenic adipose mesenchymal stem cells (MSCs-Exo) in severe patients with novel coronavirus pneumonia (NCP).

    NCT04276987
    Conditions
    1. Coronavirus
    Interventions
    1. Biological: MSCs-derived exosomes
    MeSH:Coronavirus Infections Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Safety evaluation within 28 days after first treatment, including frequency of adverse reaction (AE) and severe adverse reaction (SAE)

    Measure: Adverse reaction (AE) and severe adverse reaction (SAE)

    Time: Up to 28 days

    Description: Efficiency evaluation within 28 days, including time to clinical improvement (TTIC)

    Measure: Time to clinical improvement (TTIC)

    Time: Up to 28 days

    Secondary Outcomes

    Description: Number of patients weaning from mechanical ventilation within 28 days

    Measure: Number of patients weaning from mechanical ventilation

    Time: Up to 28 days

    Description: Duration (days) of ICU monitoring within 28 days

    Measure: Duration (days) of ICU monitoring

    Time: Up to 28 days

    Description: Duration (days) of vasoactive agents using within 28 days

    Measure: Duration (days) of vasoactive agents usage

    Time: Up to 28 days

    Description: Duration (days) of mechanical ventilation supply among survivors

    Measure: Duration (days) of mechanical ventilation supply

    Time: Up to 28 days

    Description: Number of patients with improved organ failure within 28 days, including cardiovascular system, coagulation system, liver, kidney and other extra-pulmonary organs

    Measure: Number of patients with improved organ failure

    Time: Up to 28 days

    Description: Rate of mortality within 28 days

    Measure: Rate of mortality

    Time: Up to 28 days

    Other Outcomes

    Description: Records of daily sequential organ failure assessment (SOFA) score (From 0 to 24 points, higher scores mean a worse outcome)

    Measure: Sequential organ failure assessment (SOFA) score

    Time: Every day for 28 days

    Description: Records of Blood routine test

    Measure: Lymphocyte Count (10E9/L)

    Time: Day0, Day3, Day7, Day14, Day21, Day28, indicated time points can be added if available

    Measure: C-reactive protein (CRP) (mg/L)

    Time: Day0, Day3, Day7, Day14, Day21, Day28, indicated time points can be added if available

    Measure: Lactate dehydrogenase (U/L)

    Time: Day0, Day3, Day7, Day14, Day21, Day28, indicated time points can be added if available

    Description: Coagulation function

    Measure: D-dimer (mg/L)

    Time: Day0, Day3, Day7, Day14, Day21, Day28, indicated time points can be added if available

    Description: Records of heart failure

    Measure: pro-type B natriuretic peptide (pro-BNP) (pg/ml)

    Time: Day0, Day3, Day7, Day14, Day21, Day28, indicated time points can be added if available

    Description: Record of serum cytokine

    Measure: IL-1β (pg/ml)

    Time: Day0, Day3, Day7, Day14, Day21, Day28, indicated time points can be added if available

    Description: Record of serum cytokine

    Measure: IL-2R (ng/L)

    Time: Day0, Day3, Day7, Day14, Day21, Day28, indicated time points can be added if available

    Description: Record of serum cytokine

    Measure: IL-6 (ng/L)

    Time: Day0, Day3, Day7, Day14, Day21, Day28, indicated time points can be added if available

    Description: Record of serum cytokine

    Measure: IL-8 (ng/L)

    Time: Day0, Day3, Day7, Day14, Day21, Day28, indicated time points can be added if available

    Description: Computed tomography or X-ray

    Measure: Chest imaging

    Time: Day0, Day3, Day7, Day14, Day21, Day28, indicated time points can be added if available

    Description: Time to SARS-CoV-2 RT-PCR negativity in respiratory tract specimens

    Measure: Time to SARS-CoV-2 RT-PCR negativity

    Time: Up to 28 days
    31 Clinical Investigation of Natural Killer Cells Treatment in Pneumonia Patients Infected With 2019 Novel Coronavirus

    Since december 2019, acute respiratory disease due to 2019 novel coronavirus (2019-nCoV) emerged in Wuhan city and rapidly spread throughout China. There is no confirmed antivirus therapy for 2019-nCoV infection. Natural killer (NK) cells are innate lymphocytes that may serve as useful effectors against danger infection. The purpose of this clinical investigation is to evaluate the safety and efficiency of NK Cells in combination with standard therapy for pneumonia patients infected with 2019-nCoV.

    NCT04280224
    Conditions
    1. Novel Coronavirus Pneumonia
    Interventions
    1. Biological: NK Cells
    MeSH:Coronavirus Infections Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Evaluation of pneumonia improvement

    Measure: Improvement of clinical symptoms including duration of fever

    Time: Measured from day 0 through day 28

    Description: Evaluation of pneumonia improvement

    Measure: Improvement of clinical symptoms including respiratory frequency

    Time: Measured from day 0 through day 28

    Description: Safety evaluation

    Measure: Number of participants with treatment-related adverse events evaluated with CTCAE,version 4.0

    Time: Measured from day 0 through day 28

    Secondary Outcomes

    Description: Marker for 2019-nCoV

    Measure: Time of virus nucleic acid test negative

    Time: Measured from day 0 through day 28

    Description: Marker of immunological function

    Measure: CD4+ and CD8+ T cell count

    Time: Measured from day 0 through day 28

    Description: Marker for efficacy of treatment

    Measure: Rate of mortality within 28-days

    Time: Day 28

    Description: Recovery of lung injury

    Measure: Size of lesion area by thoracic imaging

    Time: Measured from day 0 through day 28
    32 Identification of a New Screening Strategy for 2019 Novel Coronavirus Infection

    Since Dec 2019, over 70000 novel coronavirus infection pneumonia (NCIP) patients were confirmed. 2019 novel coronavirus (2019 nCoV) is a RNA virus, which spread mainly from person-to-person contact. Most of the symptoms are non-specific, including fever, fatigue, dry cough. Sever NCIP patients may have shortness of breath and dyspnea, and progress to acute respiratory distress syndrome (ARDS) and multiple organ dysfunction syndrome (MODS). The mortality is reported to be around 2.3%. Thus, early detection and early treatment is very important to the improvement of NCIP patients' prognosis. At present, NCIP RNA detection of pharyngeal swab specimen by RT-PCR is recommended. However, due to the universal susceptibility to 2019 nCoV in general population and limited number of NCIP RNA detection kits available, to identify an efficient screening strategy is urgently needed. This study aim to develop and validate the diagnostic accuracy and screening efficiency of a new NCIP screening strategy, which can benefit the disease prevention and control.

    NCT04281693
    Conditions
    1. Novel Coronavirus Infection Pneumonia
    Interventions
    1. Diagnostic Test: Standard screening strategy
    2. Diagnostic Test: New screening strategy
    MeSH:Infection Communicable Diseases Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: The screening accuracy of the two screening strategies were calculated and compared.

    Measure: Screening accuracy

    Time: 1 month

    Secondary Outcomes

    Description: The costs of the two screening strategies were recorded. Cost-effectiveness analysis were performed and compared.

    Measure: Cost-effectiveness analysis

    Time: 1 month
    33 A Randomized, Open-label Study to Evaluate the Efficacy and Safety of Pirfenidone in Patients With Severe and Critical Novel Coronavirus Infection

    The acute lung injury caused by SARS and 2003 were both related to the inflammatory cytokine storm in patients. The biochemical test showed abnormal increase in related indicators such as interleukin-8, and CT images showed a medical "white" lung". According to the experience of SARS treatment in 2003, the use of hormones will indeed help the patients to alleviate their illness, but patients who survived SARS either had too much hormone at that time and took too long. Although the lungs could recover, but the femoral head was necrotic Either the amount of hormones was very conservative at the time, which kept the lungs in the storm of inflammatory factors, leading to the emergence of irreversible pulmonary fibrosis. So is there a medicine that can anti-inflammatory, reduce the load of hormone use, and have the effect of treating and preventing pulmonary fibrosis complicated by severe viral lung? At present, pirfenidone has achieved encouraging results in the treatment of idiopathic Pulmonary Fibrosis (CTD-ILD) diseases. It is particularly encouraging that the values announced at the 2019 ATS Annual Conference suggest that pirfenidone has more anti-inflammatory and anti-oxidant effects than its own outstanding anti-fibrotic ability. The data shows early use, Its strong anti-SOD activity can effectively inhibit IL-1beta and IL-4, and can open the prevention mode of pulmonary interstitial fibrosis. Based on the above, this project intends to make the following scientific assumptions: based on the homology of the pathogens of the new coronavirus-infected pneumonia and the coronavirus infection of pneumonia in 2003, the similarities in the occurrence and development of the disease, that is, the pulmonary inflammatory storm occurs first, and thereafter The progress of fibrosis and the progressive decline of lung function and mortality are higher than those of ordinary pneumonia. We hope that by adding pirfenidone as a treatment program in addition to standard treatment, it will be a new and severe type of coronavirus infection. Patient clinical treatment provides an effective and practical method.

    NCT04282902
    Conditions
    1. Novel Coronavirus Pneumonia
    2. Pneumonia
    3. Pirfenidone
    Interventions
    1. Drug: pirfenidone
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Lesion area of chest CT image at 4 weeks

    Measure: chest CT

    Time: 4 weeks

    Description: Absolute change in pulse oxygen from baseline

    Measure: Finger pulse oxygen

    Time: 4 weeks

    Description: Absolute change in blood gas from baseline

    Measure: blood gas

    Time: 4 weeks

    Description: Absolute change in total score of King's brief questionnaire for interstitial Absolute change in total score of King's brief questionnaire for interstitial pulmonary disease (k-bild) from baseline at week 4

    Measure: K-BILD

    Time: 4 weeks

    Secondary Outcomes

    Description: Time to death within 4 weeks due to respiratory problems

    Measure: death

    Time: 4 weeks

    Description: Time to disease progression or death within 4 weeks

    Measure: Time to disease progression or death within 4 weeks

    Time: 4 weeks

    Description: lymphocyte count

    Measure: blood

    Time: 4 weeks

    Description: Absolute change in viral nucleic acid from baseline

    Measure: viral nucleic acid

    Time: 4 weeks

    Description: Pulmonary fibrosis survival symptoms absolute changes in dyspnea score from baseline

    Measure: dyspnea score

    Time: 4 weeks

    Description: changes in blood inflammatory indexes

    Measure: blood

    Time: 4 weeks

    Description: Absolute change in cough scores for pulmonary fibrosis survival symptoms from baseline

    Measure: cough scores

    Time: 4 weeks
    34 Study for Clinical Epidemiology and Methods of Diagnosis and Treatment of Novel Coronavirus Pneumonia (NCP)

    To develop practical and effective clinical diagnosis and treatment schemes for the control of novel coronavirus pneumonia.

    NCT04283396
    Conditions
    1. Novel Coronavirus Pneumonia
    Interventions
    1. Combination Product: systemic treatment
    MeSH:Coronavirus Infections Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Number of patients recover from novel coronavirus pneumonia

    Measure: recovery

    Time: up to 24 weeks
    35 CT Scores Predict Mortality in 2019-nCoV Pneumonia

    While 2019-nCoV nucleic acid swab tests has high false positives rate, How to diagnose 2019-nCoV pneumonia and predict prognosis by CT is very important.In this retrospective single-center study, we consecutively included suspected 2019-nCoV pneumonia critical cases in the intensive care unit of Wuhan third hospital from January 31, 2020 to February 16, 2020. The cases were confirmed by real-time RT-PCR, and all patients were evaluated with CT, cutoff values were obtained according to the Yoden index, and were divided into high CT score group and low CT score group. Epidemiological, demographic, clinical, and laboratory data were collected.

    NCT04284046
    Conditions
    1. CT Scores Predict Mortality in 2019-nCoV Pneumonia
    Interventions
    1. Other: CT score
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Measure: 7-day mortality

    Time: 7-day
    36 A Clinical Study to Investigate the Effect of T89 on Improving Oxygen Saturation and Clinical Symptoms in Patients With Coronavirus Disease 2019 (COVID-19)

    This is an open-label, randomized, blank-controlled treatment clinical study. The objective of this study is to investigate the effect of T89 on improving oxygen saturation and clinical symptoms in patients with Coronavirus Disease 2019 (COVID-19). In this study, estimated total of 120-240 male and female patients who have been diagnosed with non-critical type of coronavirus pneumonia (COVID-19) will be enrolled and randomly assigned to one of two study groups, the T89 treatment group and the blank control group, to T89 or nothing on the base of a recommended standard treatment for up to 14 days . The primary efficacy parameters include the time to oxygen saturation recovery to normal level (≥97%), the proportion of patients with normal level of oxygen saturation after treatment, and the total duration of oxygen inhalation, oxygen flow change by time, oxygen concentration change by time during treatment.

    NCT04285190
    Conditions
    1. Coronavirus Disease 2019
    2. Novel Coronavirus Pneumonia
    Interventions
    1. Drug: T89
    MeSH:Coronavirus Infections Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: From screening to the end of treatment, for all patients randomized, oxygen saturation will be assessed for 3 times daily, the time to oxygen saturation recovery to normal level (≥97%) will be calculated finally based on that record and compared between two groups.

    Measure: The time to oxygen saturation recovery to normal level (≥97%)

    Time: Day -1 to 10

    Description: The proportion of patients with normal level of oxygen saturation(≥97%) after treatment will be calculated finally based on that record and compared between two groups.

    Measure: The proportion of patients with normal level of oxygen saturation(≥97%)

    Time: Day -1 to 10

    Secondary Outcomes

    Description: From screening to the end of treatment, for all patients randomized, the symptoms will be assessed 2 times daily, and the time to achievement of remission for each symptom will be calculated finally based on the record and compared between two groups.

    Measure: The degree of remission of symptoms of patients, including: fatigue, nausea, vomiting, chest tightness, shortness of breath, etc.

    Time: Day -1 to 10

    Description: From screening to the end of treatment, for all patients randomized, myocardial enzyme spectrum will be assessed on Day -1, Day 3, 7 and 10 post treatment. The time to the myocardial enzyme spectrum recovery to normal will be calculated finally based on the record and compared between two groups.

    Measure: The time to the myocardial enzyme spectrum recovery to normal after treatment

    Time: Day -1, 3, 7 and 10

    Description: From screening to the end of treatment, for all patients randomized, myocardial enzyme spectrum will be assessed on Day -1, Day 3, 7 and 10 post treatment. The proportion with normal myocardial enzyme spectrum after treatment will be calculated finally based on the record and compared between two groups.

    Measure: The proportion of the patients with normal myocardial enzyme spectrum after treatment

    Time: Day -1, 3, 7 and 10

    Description: From screening to the end of treatment, for all patients randomized, 12-lead electrocardiogram will be assessed on Day -1, Day 3, 7 and 10 post treatment. The time to the myocardial enzyme spectrum recovery to normal level will be calculated finally based on the record and compared between two groups.

    Measure: The time to the electrocardiogram recovery to normal level after treatment

    Time: Day -1, 3, 7 and 10

    Description: From screening to the end of treatment, for all patients randomized, 12-lead electrocardiogram will be assessed on Day -1, Day 3, 7 and 10 post treatment. The proportion with normal electrocardiogram will be calculated finally based on the record and compared between two groups.

    Measure: The proportion of the patients with normal electrocardiogram after treatment

    Time: Day -1, 3, 7 and 10

    Description: From screening to the end of treatment, for all patients randomized, the hemodynamics will be assessed on Day -1, Day 3, 7 and 10 post treatment. The time to the hemodynamics recovery to normal will be calculated finally based on the record and compared between two groups.

    Measure: The time to the hemodynamics recovery to normal after treatment

    Time: Day -1 and 10

    Description: From screening to the end of treatment, for all patients randomized, the hemodynamics will be assessed on Day -1, Day 3, 7 and 10 post treatment. The proportion with normal hemodynamics will be calculated finally based on the record and compared between two groups.

    Measure: The proportion of the patients with normal hemodynamics after treatment

    Time: Day -1 and 10

    Description: From screening to the end of treatment, for all patients randomized, the clinical severity will be assessed 1 time daily. The time to exacerbation or remission of the disease will be calculated finally based on the record and compared between two groups.

    Measure: The time to exacerbation or remission of the disease after treatment;

    Time: Day -1 to 10

    Description: From screening to the end of treatment, for all patients randomized, the clinical severity will be assessed 1 time daily. The proportion of patients whose disease get aggravated or alleviated will be calculated finally based on the record and compared between two groups.

    Measure: The proportion of the patients with exacerbation or remission of disease after treatment

    Time: Day -1 to 10

    Description: From screening to the end of treatment, for all patients randomized, the need for additional treatment will be recorded and compared between two groups.

    Measure: The proportion of patients who need other treatment (e.g. heparin, anticoagulants) due to microcirculation disorders

    Time: Day -1 to 10

    Description: For all patients, the mortality will be recorded in each group and the rate will be compared between two groups.

    Measure: The all-cause mortality rate

    Time: Day -1 to 10

    Description: From screening to the end of treatment, for all patients randomized, the proportion of patients with acidosis will be compared between two groups based on the hemodynamics results.

    Measure: The proportion of patients with acidosis

    Time: Day -1 and 10

    Description: For all patients, the duration of hospitalization will be recorded in each group and compared between two groups.

    Measure: The total duration of the patients in-hospital

    Time: Day -1 to 10

    Description: From screening to the end of treatment, for all patients randomized, the total duration of oxygen inhalation during oxygen treatment will be assessed and compared, if applicable, between two groups.

    Measure: The total duration of oxygen inhalation during treatment

    Time: Day -1 to 10

    Description: From screening to the end of treatment, for all patients randomized, the oxygen flow rate during oxygen treatment will be assessed and compared, if applicable, between two groups.

    Measure: The oxygen flow rate during treatment

    Time: Day -1 to 10

    Description: From screening to the end of treatment, for all patients randomized, the oxygen concentration during oxygen treatment will be assessed and compared, if applicable, between two groups.

    Measure: The oxygen concentration during treatment

    Time: Day -1 to 10
    37 Nitric Oxide Gas Inhalation Therapy in Spontaneous Breathing Patients With Mild/Moderate COVID19 Infection: a Randomized Clinical Trial

    The scientific community is in search for novel therapies that can help to face the ongoing epidemics of novel Coronavirus (COVID-19) originated in China in December 2019. At present, there are no proven interventions to prevent progression of the disease. Some preliminary data on SARS pneumonia suggest that inhaled Nitric Oxide (NO) could have beneficial effects on COVID-19 due to the genomic similarities between this two coronaviruses. In this study we will test whether inhaled NO therapy prevents progression in patients with mild to moderate COVID-19 disease.

    NCT04290858
    Conditions
    1. Coronavirus Infections
    2. Pneumonia, Viral
    3. Dyspnea
    Interventions
    1. Drug: Nitric Oxide
    MeSH:Infection Communicable Diseases Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia, Viral Pneumonia Dyspnea
    HPO:Dyspnea Pneumonia Respiratory distress

    Primary Outcomes

    Description: The primary outcome will be the proportion of patients with mild COVID2019 who deteriorate to a severe form of the disease requiring intubation and mechanical ventilation. Patients with indication to intubation and mechanical ventilation but concomitant DNI (Do Not Intubate) or not intubated for any other reason external to the clinical judgment of the attending physician will be considered as meeting the criteria for the primary endpoint.

    Measure: Reduction in the incidence of intubation and mechanical ventilation

    Time: 28 days

    Secondary Outcomes

    Description: Mortality from all causes

    Measure: Mortality

    Time: 28 days

    Description: Proportion of patients with a negative conversion of RT-PCR from an oropharyngeal or a nasopahryngeal swab

    Measure: Negative conversion of COVID-19 RT-PCR from upper respiratory tract

    Time: 7 days

    Description: Time from initiation of the study to discharge or to normalization of fever (defined as <36.6°C from axillary site, or < 37.2°C from oral site or < 37.8°C from rectal or tympanic site), respiratory rate (< 24 bpm while breathing room air) and alleviation of cough (defined as mild or absent in a patient reported scale of severe >>moderate>>mild>>absent).

    Measure: Time to clinical recovery

    Time: 28 days
    38 Clinical Progressive Characteristics and Treatment Effects of 2019-novel Coronavirus(2019-nCoV)

    Objects: The purpose of this study was to observe the characteristics of morbidity, disease progression and therapeutic effects of 2019-novel coronavirus pneumonia patients with different clinical types. Method: A single center, retrospective and observational study was used to collect COVID-19 patients admitted to Wuhan Infectious Diseases Hospital (Wuhan JinYinTan Hospital) from January 2020 to March 2020. The general information, first clinical symptoms, hospitalization days, laboratory examination, CT examination, antiviral drugs, immune enhancers, traditional Chinese medicine treatment and other clinical intervention measures were recorded, and the nutritional status and prognosis of the patients were recorded. confirm COVID-19 's disease progression, clinical characteristics, disease severity and treatment effects. To compare the characteristics of disease progression, clinical features, disease severity and therapeutic effect of different types of COVID-19. Outcomes: The characteristics of disease progression, clinical features, disease severity and therapeutic effect of different types of COVID-19. Conclusion: The characteristics of disease progression, clinical features and therapeutic effect of different types of COVID-19.

    NCT04292327
    Conditions
    1. Pneumonia Caused by Human Coronavirus
    MeSH:Coronavirus Infections Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: The mortality of COVID-19 in 28 days

    Measure: Mortality

    Time: 28 day

    Description: The time interval of COVID-19 form nucleic acid confirmed to the nucleic acid detection turn into negative.

    Measure: The time interval of Nucleic acid detection become negative

    Time: 28 day
    39 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
    40 Multicenter Clinical Study on the Efficacy and Safety of Xiyanping Injection in the Treatment of New Coronavirus Infection Pneumonia (General and Severe)

    In December 2019, Wuhan, in Hubei province, China, became the center of an outbreak of pneumonia of unknown cause. In a short time, Chinese scientists had shared the genome information of a novel coronavirus (2019-nCoV) from these pneumonia patients and developed a real-time reverse transcription PCR (real time RT-PCR) diagnostic assay. In view of the fact that there is currently no effective antiviral therapy, the prevention or treatment of lung injury caused by COVID-19 can be an alternative target for current treatment. Xiyanping injection has anti-inflammatory and immune regulation effects. This study is a Randomized, Parallel Controlled Clinical Study to treat patients with COVID-19 infection.

    NCT04295551
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Lopinavir / ritonavir tablets combined with Xiyanping injection
    2. Drug: Lopinavir/ritonavir treatment
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: The time from study drug use to complete fever reduction and cough recovery is measured in hours.

    Measure: Clinical recovery time

    Time: Up to Day 28
    41 Analysis of Safety Related Factors of Endotracheal Intubation in Patients With Severe Covid-19 Pneumonia

    To analyze the intubation with severe covid-19 pneumonia, the infection rate of anesthesiologist after intubation, and summarizes the experience of how to avoid the infection of anesthesiologist and ensure the safety of patients with severe covid-19 pneumonia.

    NCT04298814
    Conditions
    1. COVID-19
    2. Endotracheal Intubation
    Interventions
    1. Other: severe covid-19 pneumonia with ET
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: The data of Success rate of intubation with severe COVID-19 pneumonia patients

    Measure: Success rate of intubation

    Time: the time span between 1hour before intubation and 24h after intubation

    Description: Infection rate of Anesthesiologist who performed the endotracheal intubation for severe COVID-19 pneumonia patients

    Measure: Infection rate of Anesthesiologist

    Time: the time span between 1hour before intubation and 14days after intubation

    Secondary Outcomes

    Description: Extubation time of intubated severe COVID-19 pneumonia patients

    Measure: Extubation time

    Time: the time span between 1hour before intubation and 30days after intubation
    42 Clinical Application of Stem Cell Educator Therapy for the Treatment of Viral Inflammation Caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)

    Currently, the growing epidemic of a new coronavirus infectious disease (Covid-19) is wreaking havoc worldwide, which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 is a RNA virus that display high similarity in both genomic and proteomic profiling with SARS-CoV that first emerged in humans in 2003 in China. Therefore, preventing and controlling the pandemic occurrences are extremely urgent as a global top priority. Due to the lack of effective antiviral drugs, patients may be treated by only addressing their symptoms such as reducing fever. Clinical autopsies from SARS-CoV-infected patients demonstrated that there were major pathological changes in the lungs, immune organs, and small systemic blood vessels with vasculitis. However, the detection of SARS-CoV were primarily found in the lung and trachea/bronchus, but was undetectable in spleen, lymph nodes, bone marrow, heart and aorta, highlighting the overreaction of immune responses induced by viral infection were really harmful, resulting in the pathogenesis of lungs, immune organs, and small systemic blood vessels. To this respect, immune modulation strategy may be potentially beneficial to enhance anti-viral immunity and efficiently reduce the viral load, improve clinical outcomes, expedite the patient recovery, and decline the rate of mortality in patients after being infected with SARS-CoV-2. Tianhe Stem Cell Biotechnologies Inc. has developed a novel globally-patented Stem Cell Educator (SCE) technology designed to reverse the autoimmune response in Type 1 diabetes (T1D), Alopecia Areata (AA) and other autoimmune diseases. SCE therapy uses human multipotent cord blood stem cells (CB-SC) from human cord blood. Their properties distinguish CB-SC from other known stem cell types, including mesenchymal stem cells (MSC) and hematopoietic stem cells (HSC). Several clinical studies show that SCE therapy functions via CB-SC induction of immune tolerance in autoimmune T cells and restore immune balance and homeostasis in patients with T1D, AA and other inflammation-associated diseases. To correct the overreaction of overreaction of immune responses, the investigators plan to treat SARS-CoV-2 patients with Stem Cell Educator therapy.

    NCT04299152
    Conditions
    1. Severe Acute Respiratory Syndrome (SARS) Pneumonia
    Interventions
    1. Combination Product: Stem Cell Educator-Treated Mononuclear Cells Apheresis
    MeSH:Severe Acute Respiratory Syndrome Coronavirus Infections Pneumonia Syndrome Inflammation
    HPO:Pneumonia

    Primary Outcomes

    Description: The feasibility will be evaluated by the number of Covid-19 patients who were unable to complete SCE Therapy.

    Measure: Determine the number of Covid-19 patients who were unable to complete SCE Therapy

    Time: 4 weeks

    Secondary Outcomes

    Description: Measurements of immune markers' changes will be preformed by flow cytometry such as activated T cells. Peripheral blood mononuclear cells (PBMC) will be collected at 1, 3, 6, 9, 12, 28 day post the SCE therapy.

    Measure: Examine the percentage of activated T cells after SCE therapy by flow cytometry

    Time: 4 weeks

    Description: Measurements of immune marker's changes will be preformed by flow cytometry such as the percentage of Th17 cells. Peripheral blood mononuclear cells (PBMC) will be collected at 1, 3, 6, 9, 12, 28 day post the SCE therapy.

    Measure: Assess the percentage of Th17 cells after SCE therapy by flow cytometry

    Time: 4 weeks

    Description: Patients will be monitored for their chest imaging every 3 - 5 days for 4 weeks after receiving SCE therapy.

    Measure: Chest imaging changes by computed tomography (CT) scan of the chest

    Time: 4 weeks

    Description: To determine the viral load by real time RT-PCR, samples of blood, sputum, nose / throat swab will be collected from patients during the follow-up studies after receiving SCE therapy.

    Measure: Quantification of the SARS-CoV-2 viral load by real time RT-PCR

    Time: 4 weeks
    43 Clinical Study of Novel Coronavirus Induced Severe Pneumonia Treated by Dental Pulp Mesenchymal Stem Cells

    Evaluation of novel coronavirus induced severe pneumonia by dental pulp mesenchymal stem cells

    NCT04302519
    Conditions
    1. COVID-19
    Interventions
    1. Biological: Dental pulp mesenchymal stem cells
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Kaplan-meier method was used to calculate the median glassy shadow time in all subjects

    Measure: Disppear time of ground-glass shadow in the lungs

    Time: 14 days

    Secondary Outcomes

    Description: Kaplan-meier method was used to calculate the median lung shadow absorption of all subjects on 7, 14, 28, and 360 days

    Measure: Absorption of Lung shadow absorption by CT Scan-Chest

    Time: 7, 14, 28 and 360 days

    Description: T test was used to compare the blood oxygen values of each subject at day 3, 7 and 14

    Measure: Changes of blood oxygen

    Time: 3, 7 and 14 days
    44 Accurate Classification System for Patients With COVID-19 Based on Prognostic Nomogram

    The COVID-19 has a clustering morbidity trend and older people with chronic diseases are more likely to die, such as chronic renal insufficiency and chronic cardiovascular disease. We set up a COVID-19 pneumonia grading scale. The COVID-19 score system was validated to predict the clinical outcome of a patient.

    NCT04302688
    Conditions
    1. Pneumonitis
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: survival status as of February 24, 2020

    Measure: survival status

    Time: 10 December 2019 to 10 February 2020
    45 The Efficacy and Safety of Bevacizumab in Severe or Critical Patients With COVID-19--a Multicenter Randomized Controlled Clinical Trial

    The novel coronavirus (SARS-CoV-2) is a new strain of coronavirus found in human in 2019, which causes epidemic worldwide. Novel coronavirus disease (COVID-19) causes acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) in the severe and critically severe patients. Pulmonary edema is the key detrimental feature of ALI/ARDS. Autopsy of patients died from COVID-19 reported that, pulmonary mucus exudation was severe, more obvious than SARS infection. Pulmonary CT scanning and pathological findings also suggest that pulmonary edema caused by inflammatory exudation is a distinguished feature of COVID-19. However, specific pharmacotherapy is lacking.Vascular endothelial growth factor (VEGF) is known as the most potent inducing factors to increase vascular permeability. Bevacizumab is an anti VEGF recombinant humanized monoclonal antibody, which has been used in anti-tumor treatment for 16 years. Evidence suggest that Bevacizumab is a promising drug for severe and critical COVID-19 patients.

    NCT04305106
    Conditions
    1. COVID-19 Pneumonia
    Interventions
    1. Drug: Bevacizumab
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: The time from randomization to an improvement of two points on a seven-category ordinal scale or live discharge from the hospital

    Measure: The time from randomization to clinical improvement

    Time: No more than 28 days
    46 An Adaptive, Randomized, Double-blind, Parallel-controlled Clinical Trial of Yinhu Qingwen Granula for the Treatment of Severe CoVID-19

    In December 2019, Wuhan, in Hubei province, China, became the center of an outbreak of pneumonia caused by CoVID-19, and the number of cases of infection with CoVID-19 identified in Wuhan increased markedly over the later part of January 2020, with cases identified in multiple other Provinces of China and internationally.Given no specific antiviral therapy for CoVID-19 infection and the availability of Yinhu Qingwen Granula as a potential antiviral Chinese medicine based on vivo antiviral studies in CoVID-19, this adaptive, randomized,double-blind,controlled trial will evaluate the efficacy and safety of Yinhu Qingwen Granula in patients hospitalized with severe CoVID-19.

    NCT04310865
    Conditions
    1. COVID-19
    2. Severe Pneumonia
    3. Chinese Medicine
    Interventions
    1. Drug: Yinhu Qingwen Granula
    2. Drug: Yin Hu Qing Wen Granula(low does)
    3. Other: standard medical treatment
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Measure: changes in the ratio of PaO2 to FiO2 from baseline

    Time: Day 10

    Secondary Outcomes

    Measure: PaO2

    Time: up to 30 days

    Measure: blood oxygen saturation (SpO2)

    Time: up to 30 days

    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; 6) Not hospitalized, limitation on activities; 7) Not hospitalized, no limitations on activities.

    Measure: clinical status rating on the 7-point ordinal scale

    Time: up to 30 days

    Description: TTCI is defined as the time (in days) from initiation of study treatment (Yinhu Qingwen Granula or its low-dose granula) until a decline of two categories from status at randomisation on the 7-point ordinal scale of clinical status which ranges from 0 (death) to 6 (Not hospitalized, no limitations on activities).

    Measure: Time to Clinical Improvement (TTCI)

    Time: up to 30 days

    Measure: Duration (hours) of non-invasive mechanical ventilation or high-flow nasal catheter oxygen inhalation use

    Time: up to 30 days

    Measure: Duration (hours) of invasive mechanical ventilation use

    Time: up to 30 days

    Measure: Duration (hours) of extracorporeal membrane oxygenation (ECMO) use

    Time: up to 30 days

    Measure: Duration (days) of Oxygen use

    Time: up to 30 days

    Measure: The proportion of the patients reporting 2019-nCoV RT-PCR negativity at Day 10 after treatment

    Time: Day 10

    Measure: The counts/percentage of Lymphocyte

    Time: up to 30 days

    Measure: Time to hospital discharge with clinical recovery from the randomisation

    Time: up to 30 days

    Description: Critical status is defined as: 1) respiratory failure with the need of invasive mechanical ventilation; or 2) shock; or 3) other system organ failure with ICU admission.

    Measure: The incidence of critical status conversion in 30 days

    Time: up to 30 days

    Measure: All-cause mortality within 30 days

    Time: up to 30 days

    Measure: Frequency of severe adverse drug events

    Time: up to 30 days
    47 The Benefits of Artificial Intelligence Algorithms (CNNs) for Discriminating Between COVID-19 and Influenza Pneumonitis in an Emergency Department Using Chest X-Ray Examinations

    This project aims to use artificial intelligence (image discrimination) algorithms, specifically convolutional neural networks (CNNs) for scanning chest radiographs in the emergency department (triage) in patients with suspected respiratory symptoms (fever, cough, myalgia) of coronavirus infection COVID 19. The objective is to create and validate a software solution that discriminates on the basis of the chest x-ray between Covid-19 pneumonitis and influenza

    NCT04313946
    Conditions
    1. COVID-19
    2. Pneumonia, Viral
    3. Influenza With Pneumonia
    4. Flu Symptom
    5. Flu Like Illness
    6. Pneumonia, Interstitial
    7. Pneumonia, Ventilator-Associated
    8. Pneumonia Atypical
    Interventions
    1. Diagnostic Test: Scanning Chest X-rays and performing AI algorithms on images
    MeSH:Pneumonia, Ventilator-Associated Influenza, Human Pneumonia, Viral Pneumonia Lung Diseases, Interstitial
    HPO:Interstitial pneumonitis Interstitial pulmonary abnormality Pneumonia

    Primary Outcomes

    Description: Number of participants with pneumonitis on Chest X-Ray and COVID 19 positive

    Measure: COVID-19 positive X-Rays

    Time: 6 months

    Description: Number of participants with pneumonitis on Chest X-Ray and COVID 19 negative

    Measure: COVID-19 negative X-Rays

    Time: 6 months
    48 The Observational Study of Cardiac and Pulmonary Ultrasound and Evaluation of Treatment of Severe Patients With Novel Coronavirus Pneumonia

    Complete the examination of cardio-pulmonary ultrasound in accordance with the a-ccue process of patients with novel coronavirus bedside. To summarize and analyze the characteristics of cardiopulmonary ultrasound in patients with novel coronavirus pneumonia, and assess the relationship between pulmonary ultrasound imaging score and National Early Warning Score(NEWS) and prognosis. Auto line B is a method which is based on artificial intelligence is used to calculate the lungs ultrasonic B line numbers reviewing the status of patients with lung, and also evaluate patients' lungs using the traditional artificial semi-quantitative method, to evaluate those two kinds of evaluation methods for the evaluation of patients with lung condition effects are consistent or not, and verify consistency of ultrasonic evaluation method and the way of CT evaluation.

    NCT04314271
    Conditions
    1. Novel Coronavirus Pneumonia
    MeSH:Coronavirus Infections Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Complete the examination of cardio-pulmonary ultrasound in accordance with the a-ccue process of patients with novel coronavirus bedside. To summarize and analyze the characteristics of cardiopulmonary ultrasound in patients with novel coronavirus pneumonia

    Measure: characteristics of cardiopulmonary ultrasound

    Time: 30 mins

    Secondary Outcomes

    Description: assess the relationship between pulmonary ultrasound imaging score and National Early Warning Score(NEWS) and prognosis.

    Measure: assess the relationship between pulmonary ultrasound imaging score and National Early Warning Score(NEWS) and prognosis.

    Time: 2-3weeks

    Other Outcomes

    Description: Auto line B is a method which is based on artificial intelligence is used to calculate the lungs ultrasonic B line numbers reviewing the status of patients with lung, and also evaluate patients' lungs using the traditional artificial semi-quantitative method, to evaluate those two kinds of evaluation methods for the evaluation of patients with lung condition effects are consistent or not

    Measure: evaluate two kinds of evaluation methods for the evaluation of patients with lung condition effects are consistent or not, and verify consistency of ultrasonic evaluation method and the way of CT evaluation.

    Time: 3 hours
    49 Tocilizumab (RoActemra) as Early Treatment of Patients Affected by SARS-CoV2 (COVID-19) Infection With Severe Multifocal Interstitial Pneumonia

    In a Phase 2 Simon's Optimal Two-Stages Design intravenous tocilizumab will be administered as single 8mg/Kg dose in patients affected by severe multifocal interstitial pneumonia correlated to SARS-CoV2 infection. Aim of the study is to test the hypothesis that an anti-IL6 treatment can be effective in calming the virus-induced cytokine storm, blocking deterioration of lung function or even promoting a rapid improvement of clinical conditions, preventing naso-tracheal intubation and/or death.

    NCT04315480
    Conditions
    1. SARS Pneumonia
    Interventions
    1. Drug: Tocilizumab
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: rate of patients with no need in increase of FiO2 to maintain stable SO2 and no need of intubation

    Measure: arrest in deterioration of pulmonary function

    Time: 7days

    Description: rate of patients with change of oxygen saturation >3 percentage points or >10% or decrease in FiO2 need or reduction in pulmonary consolidations >30% at HR CT-scan

    Measure: improving in pulmonary function

    Time: 7 days

    Secondary Outcomes

    Description: rate of patients needed of intubation

    Measure: need of oro-tracheal intubation

    Time: +7 days

    Description: rate of patients dead

    Measure: death

    Time: 14days
    50 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.
    51 Predictors of Respiratory Failure Requiring ICU Admission Among Hospitalized Patients With SARS-Cov-2 Infection

    The emergence of SARS-CoV-2 is currently engaging and consuming most of resources of efficient healthcare systems in Europe, and several hospitals are currently experiencing a shortage of ICU beds for critically-ill patients with SARS-CoV-2 pneumonia. A risk stratification based on clinical, radiological and laboratory parameters seems necessary in order to better identify those patients who may need ICU admission and/or those who may benefit from a prompt antiviral therapy

    NCT04316949
    Conditions
    1. SARS-CoV-2 Pneumonia
    MeSH:Pneumonia Respiratory Insufficiency
    HPO:Pneumonia

    Primary Outcomes

    Description: Composite of ICU admission or SpO2<92% with 100% FiO2 of oxygen treatment (reservoir mask or CPAP or NIV), respiratory rate >30 bpm, respiratory distress

    Measure: Respiratory failure

    Time: 14 days

    Secondary Outcomes

    Description: Incidence of bacterial superinfection among ventilated patients with SARS-CoV-2 pneumonia

    Measure: Occurence of bacterial superinfection

    Time: 14 days
    52 Multicenter Study on the Efficacy and Tolerability of Tocilizumab in the Treatment of Patients With COVID-19 Pneumonia

    This study project includes a single-arm phase 2 study and a parallel cohort study, enrolling patients with COVID-19 pneumonia.

    NCT04317092
    Conditions
    1. COVID-19 Pneumonia
    Interventions
    1. Drug: Tocilizumab Injection
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: 2-week lethality is defined as the ratio of the number of subjects dead within 14 days from study start out of phase 2 patients with baseline information.

    Measure: Lethality rate two weeks after registration

    Time: up to 15 days

    Description: 1-month lethality is defined as the ratio of the number of subjects dead within 30 days from study start out of phase 2 patients with baseline information.

    Measure: Lethality rate one month after registration

    Time: up to 1 month

    Secondary Outcomes

    Description: IL-6 levels will be assessed using commercial ELISA method.

    Measure: Interleukin-6 level

    Time: baseline, during treatment (cycle 1 and 2 every 12 hours) up to 1 month

    Description: Lymphocyte count assessed by routinely used determination of blood count

    Measure: Lymphocyte count

    Time: baseline, during treatment (cycle 1 and 2 every 12 hours) up to 1 month

    Description: CRP is assessed by routinely used determination of CRP

    Measure: CRP (C-reactive protein) level

    Time: baseline, during treatment (cycle 1 and 2 every 12 hours) up to 1 month

    Description: calculated from arterial blood gas analyses (values from 300 to 100)

    Measure: PaO2 (partial pressure of oxygen) / FiO2 (fraction of inspired oxygen, FiO2) ratio (or P/F ratio)

    Time: baseline, during treatment (cycle 1 and 2 every 12 hours) up to 1 month

    Description: It 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 (Sequential Organ Failure Assessment)

    Time: baseline, during treatment (cycle 1 and 2 every 12 hours) up to 1 month

    Description: graded according to CTCAE citeria (v5.0)

    Measure: Number of participants with treatment-related side effects as assessed by Common Terminology Criteria for Adverse Event (CTCAE) version 5.0

    Time: during treatment and up to 30 days after the last treatment dose

    Description: Thoracic CT scan or Chest XR

    Measure: Radiological response

    Time: at baseline (optional), after seven days and if clinically indicated (up to 1 month)

    Description: Days of hospitalization

    Measure: Duration of hospitalization

    Time: from baseline up to patient's discharge (up to 1 month)

    Description: time to invasive mechanical ventilation (if not previously initiated) calculated from baseline to intubation

    Measure: Remission of respiratory symptoms

    Time: up to 1 month

    Description: time to definitive extubation calculated from intubation (any time occurred) to extubation in days

    Measure: Remission of respiratory symptoms

    Time: up to 1 month

    Description: time to independence from non-invasive mechanical ventilation calculated in days

    Measure: Remission of respiratory symptoms

    Time: up to 1 month

    Description: time to independence from oxygen therapy in days

    Measure: Remission of respiratory symptoms

    Time: up to 1 month
    53 Clinical Trial of Favipiravir Tablets Combine With Chloroquine Phosphate in the Treatment of Novel Coronavirus Pneumonia

    This study is a multi-centered, three-armed, randomized, double-blinded, controlled study, namely, the oral trial drug favipiravir tablets plus chloroquine phosphatetablets tablets group (combined group), the oral trial drug favipiravir tablets group (pirovir group), and the oral placebo treatment group (control group). The total number of enrolled cases in this study was set at 150. During the treatment, the clinical data of the subjects were collected, the changes of viral load and biochemical indicators were detected, and the outcome of the subjects was monitored. The main indicators of efficacy include improvement or recovery of respiratory symptoms and viral nucleic acid shedding. The rate of progression to severe disease, duration of fever, peripheral blood index and improvement time of pulmonary imaging were the secondary indicators to evaluate the efficacy. Statistical analysis was performed at the middle and final stages of the study to evaluate the efficacy and safety of favipiravir tablets combined with chloroquine phosphatetablets tablets in the treatment of novel coronavirus pneumonia.

    NCT04319900
    Conditions
    1. Novel Coronavirus Pnuemonia
    Interventions
    1. Drug: favipiravir tablets+chloroquine phosphatetablets tablets
    2. Drug: Favipiravir tablets
    3. Drug: Placebo
    MeSH:Coronavirus Infections Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Time of improvement or recovery of respiratory symptoms

    Measure: Time of Improvement or recovery of respiratory symptoms

    Time: 10 days during the intervention period

    Description: Number of days from positive to negative for test of swab or sputum virus nucleic acid

    Measure: Number of days virus nucleic acid shedding

    Time: 10 days during the intervention period

    Description: Frequency of improvement or recovery of respiratory symptoms

    Measure: Frequency of Improvement or recovery of respiratory symptoms

    Time: 10 days during the intervention period

    Secondary Outcomes

    Description: Duration of fever after recruitment

    Measure: Duration of fever

    Time: 10 days during the intervention period

    Description: Disease is defined as severe if it meets any of the following criteria: 1.Respiratory rate ≥30/min; 2. Oxygen saturation ≤93%; 3. Arterial partial oxygen pressure (PaO2)/oxygen absorption concentration (FiO2) ≤300 mmHg (1 mmHg=0.133 kPa)

    Measure: Frequencies of progression to severe illness

    Time: 10 days during the intervention period

    Description: Time of improvement of pulmonary imaging

    Measure: Time of improvement of pulmonary imaging

    Time: 10 days during the intervention period

    Description: Peripheral blood c-reactive protein concentration

    Measure: Peripheral blood c-reactive protein concentration

    Time: day-1,3,7,14 after the intervention period

    Description: Absolute value of peripheral blood lymphocytes

    Measure: Absolute value of peripheral blood lymphocytes

    Time: day-1,3,7,14 after the intervention period

    Description: percentage of peripheral blood lymphocytes

    Measure: percentage of peripheral blood lymphocytes

    Time: day-1,3,7,14 after the intervention period
    54 Automated Oxygen Titration - Monitoring and Weaning in Patients With Infectious Pneumonia Requiring Oxygen - Impact on the Number of Interventions for Healthcare Workers. An Innovative Device to Manage Patients With COVID-19 Pneumonia COVID Study (Closed-Loop Oxygen to Verify That Healthcare Workers Interventions Decreaseduring Pneumonia)

    There is a high risk of transmission of COVID-19 to healthcare workers. In a recent cohort, 29% of the patients hospitalized were healthcare workers. Among the WHO's primary strategic objectives for the response to COVID-19, the first was to limit human-to-human transmission, including reducing secondary infections among close contacts and health care workers. Automated oxygen titration, weaning and monitoring (FreeO2 device) may be a solution to reduce the number of interventions of healthcare workers related to oxygen therapy, to reduce complications related to oxygen and to improve monitoring.

    NCT04320056
    Conditions
    1. Coronavirus
    2. Pneumonia
    3. Oxygen Toxicity
    Interventions
    1. Other: Standard administration of oxygen flow
    2. Device: Automated oxygen administration - FreeO2
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: The number of interventions required by healthcare workers to manage oxygen therapy (titration, weaning and monitoring) during 4 hours

    Measure: The number of interventions

    Time: Hour0 to Hour4

    Description: The number of interventions required by healthcare workers to manage oxygen therapy (titration, weaning and monitoring) during 4 hours

    Measure: Duration of interventions

    Time: Hour0 to Hour24

    Secondary Outcomes

    Description: The Mean oxygen flow during study duration to evaluate oxygen consumption

    Measure: Mean oxygen flow

    Time: Hour0 to Hour24 (1 day)

    Description: Time within SpO2 between 90 and 94%

    Measure: Time within theSpO2 target

    Time: Hour0 to Hour24 (1 day)

    Description: Time within SpO2 < 88%

    Measure: Time with hypoxemia

    Time: Hour0 to Hour24 (1 day)

    Description: Time within SpO2 > 96%

    Measure: Time with hyperoxemia

    Time: Hour0 to Hour24 (1 day)

    Description: Rate of ICU admission

    Measure: Rate of ICU admission

    Time: Hour0 to Hour24 (1 day)

    Description: Rate of needed non invasive respiratory support Non invasive ventilation or High Flow Nasal Therapy

    Measure: Rate of needed non invasive respiratory support

    Time: Hour0 to Hour24 (1 day)

    Description: Rate of intubation

    Measure: Rate of intubation

    Time: Hour0 to Hour24 (1 day)

    Description: Evaluation of NEWS 2 score evolution (National Early Warning score) correlate to patient evolution. The NEWS2 score will be calculate but no intervention will be made based on this score. Patient evolution will be compare at NEWS 2 interpretation. Interpretation A low score (NEWS 1-4) should prompt assessment by a competent registered nurse who should decide if a change to frequency of clinical monitoring or an escalation of clinical care is required. A medium score (ie NEWS of 5-6 or a RED score) should consider whether escalation of care to a team with critical-care skills is required (ie critical care outreach team). A high score (NEWS ≥7) should prompt emergency assessment by a clinical team/critical care outreach team with critical-care competencies and usually transfer of the patient to a higher dependency care area.

    Measure: NEWS 2 score evolution

    Time: Hour0 to Hour24 (1 day)

    Description: Evaluation of EWSO2 score(Early Warning ScoreO2) evolution correlate to patient evolution The EWSO2 score will be calculate but no intervention will be made based on this score. Patient evolution will be compare at EWSO2 interpretation. Interpretation Favorable clinical outcome in patients with a score <5.3 A patient with a score >18.6 will experience a poor outcome.

    Measure: EWSO2 score evolution

    Time: Hour0 to Hour24 (1 day)

    Description: Cost effectiveness ratio (cost per SpO2 unit)

    Measure: Cost-effectiveness

    Time: From date of randomization until the date of hospital discharge

    Description: Duration of the hospital length of stay

    Measure: length of stay

    Time: up to 90 days. Hospital stay - hospital admission through hospital discharge or until death if occured
    55 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
    56 Evaluation of the Safety and Clinical Efficacy of Hydroxychloroquine Associated With Azithromycin in Patients With Pneumonia Caused by Infection by the SARS-CoV2 Virus - Coalition COVID-19 Brasil II - SEVERE - Patients

    The Severe Acute Respiratory Syndrome COronaVirus 2 (SARS-CoV2) is a new and recognized infectious disease of the respiratory tract. Around 20% of those infected have severe pneumonia and currently there is no specific or effective therapy to treat this disease. Therapeutic options using malaria drugs chloroquine and hydroxychloroquine have shown promising results in vitro and in vivo test. But those efforts have not involved large, carefully-conducted controlled studies that would provide the global medical community the proof that these drugs work on a significant scale. In this way, the present study will evaluate the effectiveness and safety of the use of hydroxychloroquine combined with azithromycin compared to hydroxychloroquine monotherapy in patients hospitalized with pneumonia by SARS-CoV2 virus.

    NCT04321278
    Conditions
    1. Coronavirus Infections
    2. Pneumonia, Viral
    Interventions
    1. Drug: Hydroxychloroquine + azithromycin
    2. Drug: Hydroxychloroquine
    MeSH:Infection Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia, Viral Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Evaluation of the clinical status of patients on the 15th day after randomization defined by the Ordinal Scale of 6 points (score ranges from 1 to 6, with 6 being the worst score)

    Measure: Evaluation of the clinical status

    Time: 15 days after randomization

    Secondary Outcomes

    Description: All-cause mortality rates at 29 days after randomization

    Measure: All-cause mortality

    Time: 29 days after randomization

    Description: Evaluation of the clinical status of patients on the 7th and 29th day after randomization defined by the Ordinal Scale of 6 points (score ranges from 1 to 6, with 6 being the worst score)

    Measure: Evaluation of the clinical status

    Time: 7 and 29 days after randomization

    Description: Number of days free from mechanical ventilation at 29 days after randomization

    Measure: Number of days free from mechanical ventilation

    Time: 29 days after randomization

    Description: Number of days that the patient was on mechanical ventilation after randomization

    Measure: Duration of mechanical ventilation

    Time: 29 days after randomization

    Description: Length of hospital stay on survivors

    Measure: Duration of hospitalization

    Time: 29 days after randomization

    Description: Presence of other secondary infections

    Measure: Other secondary infections

    Time: 29 days after randomization

    Description: Time from treatment start to death

    Measure: Time from treatment start to death

    Time: 29 days after randomization

    Description: Morbimortality, daily life activities, mental health, and quality of life

    Measure: Medium and long-term outcomes of SARS-CoV2 infection on morbimortality, daily life activities, mental health, and quality of life

    Time: 3, 6, 9 and 12 months

    Description: Leucocyte transcriptome

    Measure: Assess whether the tested therapies may be affected by leucocyte phenotype

    Time: Baseline

    Other Outcomes

    Description: Occurrence of QT interval prolongation

    Measure: QT interval prolongation

    Time: 29 days after randomization

    Description: Occurrence of gastrointestinal intolerance

    Measure: Gastrointestinal intolerance

    Time: 29 days after randomization

    Description: Occurrence of laboratory hematimetric parameters, creatinine and bilirubin

    Measure: Laboratory abnormalities

    Time: 29 days after randomization

    Description: Occurrence of adverse events related to the use of the investigational products

    Measure: Adverse events

    Time: 29 days after randomization
    57 Proposal for International Standardization of the Use of Lung Ultrasound for COVID-19 Patients; a Simple, Quantitative, Reproducible Method

    Growing evidences are showing the usefulness of lung ultrasound in patients with COVID-19. Sars-CoV-2 has now spread in almost every country in the world. In this study, the investigators share their experience and propose a standardized approach in order to optimize the use of lung ultrasound in covid-19 patients. The investigators focus on equipment, procedure, classification and data-sharing.

    NCT04322487
    Conditions
    1. Coronavirus
    2. Epidemic Disease
    3. Pneumonia, Viral
    Interventions
    1. Diagnostic Test: Lung ultrasound
    MeSH:Pneumonia, Viral Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Scoring procedures Score 0: The pleura line is continuous, regular. Horizontal artifacts (A-line) are present. These artifacts are generally referred as A-lines. Score 1: The pleura line is indented. Below the indent, vertical areas of white are visible. Score 2: The pleura line is broken. Below the breaking point, small to large consolidated areas (darker areas) appear with associated areas of white below the consolidated area (white lung). Score 3: The scanned area shows dense and largely extended white lung with or without larger consolidations At the end of the procedure, the clinician will write for each area the highest score obtained.

    Measure: Lung ultrasound grading system for COVID-19 pneumonia

    Time: At enrollment.
    58 Colchicine to Counteract Inflammatory Response in COVID-19 Pneumonia

    Cytokines and chemokines are thought to play an important role in immunity and immunopathology during virus infections [3]. Patients with severe COVID-19 have higher serum levels of pro-inflammatory cytokines (TNF-α, IL-1 and IL-6) and chemokines (IL-8) compared to individuals with mild disease or healthy controls, similar to patients with SARS or MERS . The change of laboratory parameters, including elevated serum cytokine, chemokine levels, and increased NLR in infected patients are correlated with the severity of the disease and adverse outcome, suggesting a possible role for hyper-inflammatory responses in COVID-19 pathogenesis. Importantly, previous studies showed that viroporin E, a component of SARS-associated coronavirus (SARS-CoV), forms Ca2C-permeable ion channels and activates the NLRP3 inflammasome. In addition, another viroporin 3a was found to induce NLRP3 inflammasome activation . The mechanisms are unclear. Colchicine, an old drug used in auto-inflammatory disorders (i.e., Familiar Mediterranean Fever and Bechet disease) and in gout, counteracts the assembly of the NLRP3 inflammasome, thereby reducing the release of IL-1b and an array of other interleukins, including IL-6, that are formed in response to danger signals. Recently, colchicine has been successfully used in two cases of life-threatening post-transplant capillary leak syndrome. These patients had required mechanically ventilation for weeks and hemodialysis, before receiving colchicine, which abruptly restored normal respiratory function and diuresis over 48 hrs [4].

    NCT04322565
    Conditions
    1. Coronavirus Infections
    2. Pneumonia, Viral
    Interventions
    1. Drug: Colchicine
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia, Viral Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Time to clinical improvement: defined as time from randomization to an improvement of two points from the status at randomization on a seven-category ordinary scale

    Measure: Clinical improvement

    Time: Day 28

    Description: Live discharge from the hospital (whatever comes first)

    Measure: Hospital discharge

    Time: Day 28

    Secondary Outcomes

    Description: Number of death patients

    Measure: Death

    Time: Day 28

    Description: 7-category ordinal scale

    Measure: Clinical status

    Time: Day 7, Day 14

    Description: Number of patients with mechanical ventilhation

    Measure: Mechanical ventilhation

    Time: Day 28

    Description: Days of hospitalization

    Measure: Hospitalization

    Time: Day 28

    Description: Days to death from treatment initiation

    Measure: Time from treatment initiation to death

    Time: Day 28

    Description: negativization of two consecutive pharyngo-nasal swab 24-72 hrs apart

    Measure: Time to Negativization COVID 19

    Time: Day 21

    Description: Time to remission of fever in patients with T>37.5°C at enrollment

    Measure: Fever

    Time: Day 1,4,7,14,21,28
    59 Use of Ascorbic Acid in Patients With COVID 19

    Different studies showed that ascorbic acid (vitaminC) positively affects the development and maturation of T-lymphocytes, in particular NK (natural Killer) cells involved in the immune response to viral agents. It also contributes to the inhibition of ROS production and to the remodulation of the cytokine network typical of systemic inflammatory syndrome. Recent studies have also demonstrated the effectiveness of vitamin C administration in terms of reducing mortality, in patients with sepsis hospitalized in intensive care wards. Given this background, in the light of the current COVID-19 emergency, since the investigators cannot carry out a randomized controlled trial, it is their intention to conduct a study in the cohort of hospitalized patients with covid-19 pneumonia, administering 10 gr of vitamin C intravenously in addition to conventional therapy.

    NCT04323514
    Conditions
    1. Hospitalized Patients With Covid-19 Pneumonia
    Interventions
    1. Dietary Supplement: Vitamin C
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Change of hospital mortality

    Measure: In-hospital mortality

    Time: 72 hours

    Secondary Outcomes

    Description: Reduction of PCR levels > 50% in comparison with PCR levels at the admission, within 72 hours after the administration

    Measure: PCR levels

    Time: 72 hours

    Description: Change of the lactate clearance

    Measure: Lactate clearance

    Time: 72 hours

    Description: Change of hospital stay days

    Measure: Hospital stay

    Time: 72 hours

    Description: Resolution of symptoms (Fever, Cough, Shortness of breath or difficulty breathing)

    Measure: Symptoms

    Time: 72 hours

    Description: Change of duration of positive swab (nasopharynx and throat)

    Measure: Positive swab

    Time: 72 hours

    Description: Resolution of tomography imaging (example, patches located in the subpleural regions of the lung)

    Measure: Tomography imaging

    Time: 72 hours
    60 Efficacy and Safety of Chloroquine Diphosphate for the Treatment of Hospitalized Patients With Severe Acute Respiratory Syndrome Secondary to SARS-CoV2: a Phase IIb, Double-blind, Randomized Adaptive Clinical Trial

    In December 2019, the Municipal Health Committee of Wuhan, China, identified an outbreak of viral pneumonia of unknown cause. This new coronavirus was called SARS-CoV-2 and the disease caused by that virus, COVID-19. Recent numbers show that 222,643 infections have been diagnosed with 9115 deaths, worldwide. Currently, there are no approved therapeutic agents available for coronaviruses. In this scenario, the situation of a global public health emergency and evidence about the potential positive effect of chloroquine (CQ) in most coronaviruses, including SARS-CoV-1, and recent data on small trials on SARS-CoV-2, the investigators intend to investigate the efficacy and the safety of CQ diphosphate in the treatment of hospitalized patients with severe acute respiratory syndrome in the scenario of SARS-CoV2. Preliminary in vitro studies and uncontrolled trials with low number of patients of CQ repositioning in the treatment of COVID-19 have been encouraging. The main hypothesis is that CQ diphosphate will reduce mortality in 50% in those with severe acute respiratory syndrome infected by the SARS-COV2. Therefore, the main objective is to assess whether the use of chloroquine diphosphate reduces mortality by 50% in the study population. The primary outcome is mortality in day 28 of follow-up. According to local contingency plan, developed by local government for COVID-19 in the State of Amazonas, the Hospital Pronto-Socorro Delphina Aziz, located in Manaus, is the reference unit for the admission of serious cases of the new virus. The unit currently has 50 ICU beds, with the possibility of expanding to 335 beds, if needed. The hospital also has trained multiprofessional human resources and adequate infrastructure. In total, 440 participants (220 per arm) will receive either high dose chloroquine 600 mg bid regime (4x150 mg tablets, every 12 hours, D1-D10) or low dose chloroquine 450mg bid regime (3x150mg tablets + 1 placebo tablet every 12 hours on D1, 3x150mg tablets + 1 placebo followed by 4 placebo tablets 12h later from D2 to D5, and 4 placebo tablets every 12 hours, D6-D10). Placebo tablets were used to standardize treatment duration and blind research team and patients. All drugs administered orally (or via nasogastric tube in case of orotracheal intubation). Both intervention and placebo drugs will be produced by Farmanguinhos. Clinical and laboratory data during hospitalization will be used to assess efficacy and safety outcomes.

    NCT04323527
    Conditions
    1. SARS-CoV Infection
    2. Severe Acute Respiratory Syndrome (SARS) Pneumonia
    Interventions
    1. Drug: Chloroquine diphosphate
    MeSH:Severe Acute Respiratory Syndrome Coronavirus Infections Pneumonia Syndrome
    HPO:Pneumonia

    Primary Outcomes

    Description: proportion of deaths at day 28 between groups compared

    Measure: Mortality rate reduction of 50% by day 28

    Time: 28 days after randomization

    Secondary Outcomes

    Description: number of deaths at days 7 and 14 between groups compared

    Measure: Absolute mortality on days 7 and 14

    Time: 7 and 14 days after first dose

    Description: clinical status

    Measure: Improvement in overall subject's clinical status assessed in standardized clinical questionnaires on days 14 and 28

    Time: 14 and 28 days after first dose

    Description: clinical status

    Measure: Improvement in daily clinical status assessed in standardized clinical questionnaires during hospitalization

    Time: during and after intervention, up to 28 days

    Description: supplemental oxygen

    Measure: Duration of supplemental oxygen (if applicable)

    Time: during and after intervention, up to 28 days

    Description: mechanical ventilation

    Measure: Duration of mechanical ventilation (if applicable)

    Time: during and after intervention, up to 28 days

    Description: hospitalization

    Measure: Absolute duration of hospital stay in days

    Time: during and after intervention, up to 28 days

    Description: adverse events grade 3 and 4

    Measure: Prevalence of grade 3 and 4 adverse events

    Time: during and after intervention, up to 28 days

    Description: adverse events

    Measure: Prevalence of serious adverse events

    Time: during and after intervention, up to 28 days

    Description: increase or decrease in serum creatinine compared to baseline

    Measure: Change in serum creatinine level

    Time: during and after intervention, up to 28 days

    Description: increase or decrease in serum troponin I compared to baseline

    Measure: Change in serum troponin I level

    Time: during and after intervention, up to 28 days

    Description: increase or decrease in serum aspartate aminotransferase compared to baseline

    Measure: Change in serum aspartate aminotransferase level

    Time: during and after intervention, up to 28 days

    Description: increase or decrease in serum aspartate aminotransferase compared to baseline

    Measure: Change in serum CK-MB level

    Time: during and after intervention, up to 28 days

    Description: virus clearance from respiratory tract secretion

    Measure: Change in detectable viral load in respiratory tract swabs

    Time: during and after intervention, up to 28 days

    Description: viremia in blood detected through RT-PCR

    Measure: Viral concentration in blood samples

    Time: during and after intervention, up to 28 days

    Description: death

    Measure: Absolute number of causes leading to participant death (if applicable)

    Time: during and after intervention, up to 28 days
    61 Prolonged Low Doses of Methylprednisolone for Patients With COVID-19 Severe Acute Respiratory Syndrome

    COVID-19 infection is overwhelming Italian healthcare. There is an urgent need for a solution to the lack of ICU beds and increasing deaths day after day. A recent retrospective Chinese paper (JAMA Intern Med, online March 13, 2020) showed impressive positive effect of methylprednisolone (MP) on survival of SARS-CoV-2 critically ill patients. Moreover, the Italian Infectious Disease leading institution guidelines for COVID-19 clinical management included as an option for patients with "incipient worsening of respiratory functions" methylprednisolone treatment at an approximate dose of 80mg. The main objective of this multi-centre observational trial is to analyse the association of low dose prolonged infusion of methylprednisolone (MP) for patients with severe acute respiratory syndrome with composite primary end-point (ICU referral, need for intubation, in-hospital death at day 28).

    NCT04323592
    Conditions
    1. Severe Acute Respiratory Syndrome (SARS) Pneumonia
    2. Coronavirus Infections
    3. ARDS, Human
    Interventions
    1. Drug: Methylprednisolone
    2. Other: standard care
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia Respiratory Distress Syndrome, Adult Syndrome
    HPO:Pneumonia

    Primary Outcomes

    Description: We reported below the number of participants meeting at least one of three among death or ICU admission or Invasive mechanical ventilation.

    Measure: Composite Primary End-point: Admission to ICU, Need for Invasive Mechanical Ventilation (MV), or All-cause Death by Day 28

    Time: 28 days

    Description: We reported below the number of participants who died within 28 days, during the hospital stay.

    Measure: In-hospital Death Within 28 Days

    Time: 28 days

    Description: We reported below the number of participants admitted to ICU within 28 days.

    Measure: Admission to Intensive Care Unit (ICU)

    Time: 28 days

    Description: We reported below the number of participants who needed endotracheal intubation during ICU admission

    Measure: Endotracheal Intubation (Invasive Mechanical Ventilation)

    Time: 28 days

    Secondary Outcomes

    Description: Change in C-reactive protein after 7 days from baseline. A reduction of CRP reveals a laboratory improvement.

    Measure: Change in C-reactive Protein (CRP)

    Time: 7 days

    Description: number of days free from mechanical ventilation (both invasive and non-invasive) by day 28

    Measure: Number of Days Free From Mechanical Ventilation

    Time: 28 days
    62 Cytokine Adsorption in Severe COVID-19 Pneumonia Requiring Extracorporeal Membrane Oxygenation

    In December 2019 in the city of Wuhan in China, a series of patients with unclear pneumonia was noticed, some of whom have died of it. In virological analyses of samples from the patients' deep respiratory tract, a novel coronavirus was isolated (SARS-CoV-2). The disease spread rapidly in the city of Wuhan at the beginning of 2020 and soon beyond in China and, in the coming weeks, around the world. Initial studies described numerous severe courses, particularly those associated with increased patient age and previous cardiovascular, metabolic and respiratory diseases. A small number of the particularly severely ill patients required not only highly invasive ventilation therapy but also extracorporeal membrane oxygenation (vv-ECMO) to supply the patient's blood with sufficient oxygen. Even under maximum intensive care treatment, a very high mortality rate of approximately 80-100% was observed in this patient group. In addition, high levels of interleukin-6 (IL-6) could be detected in the blood of these severely ill patients, which in turn were associated with poor outcome. From experience in the therapy of severely ill patients with severe infections and respiratory failure, we know that treatment with a CytoSorb® adsorber can lead to a reduction of the circulating pro- and anti-inflammatory cytokines and thus improve the course of the disease and the outcome of the patients. Our primary goal is to investigate the efficacy of treatment with a CytoSorb® adsorber in patients with severe COVID-19 disease requiring venous ECMO over 72 hours after initiation of ECMO. The primary endpoint is the reduction of plasma interleukin-6 levels 72 hours after initiation of ECMO support. As secondary endpoints we investigate 30-day survival, vasopressor and volume requirements, lactate in terms of lactate and platelet function. As safety variables, we further investigate the levels of the applied antibiotics (usually ampicillin and sulbactam).

    NCT04324528
    Conditions
    1. Coronavirus
    2. COVID-19
    3. SARS-CoV Infection
    4. Respiratory Failure
    5. Cytokine Storm
    Interventions
    1. Device: vv-ECMO + cytokine adsorption (Cytosorb adsorber)
    2. Device: vv-ECMO only (no cytokine adsorption)
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia Respiratory Insufficiency
    HPO:Pneumonia

    Primary Outcomes

    Description: measurement of IL-6 levels in patient blood after 72 hours of cytokine adsorption (in relation to level before initiation of cytokine adsorption)

    Measure: interleukin-6 (IL-6) level after 72 hours

    Time: 72 hours

    Secondary Outcomes

    Description: survival after 30 days

    Measure: 30-day-survival

    Time: 72 hours

    Description: needed dosage of norepinephrine and other vasopressors

    Measure: vasopressor dosage

    Time: 72 hours

    Description: fluid balance levels during cytokine adsorption

    Measure: fluid balance

    Time: 72 hours

    Description: serum-lactate levels during cytokine adsorption

    Measure: lactate

    Time: 72 hours
    63 Time of Recovery and Prognostic Factors of COVID-19 Pneumonia

    It has been reported that nearly half of the patients who are hospitalized for Covid-19 pneumonia have on admission old age or comorbidities. In particular, hypertension was present in 30% of the cases, diabetes in 19%, coronary heart disease in 8% and chronic obstructive lung disease in 3% of the patients. Amazingly, in the two major studies published in the Lancet (Zhou F et al Lancet 2020) and in the New England Journal of Medicine (Guan W et al 2020), the weight of the subjects as well their body mass index (BMI) were omitted. However, obesity, alone or in association with diabetes, can be a major predisposition factor for Covid-19 infection. The primary end-point of our prospective, observational study is to assess the recovery rate in patients with diagnosis of Covid-19 pneumonia. Among the other secondary end-points, we intend to find the predictors of the time to clinical improvement or hospital discharge in patients affected by Covid-19 pneumonia.

    NCT04324684
    Conditions
    1. Pneumonia, Viral
    2. Hypertension
    3. Diabetes Mellitus
    4. Obesity
    5. Cardiovascular Diseases
    6. Obstructive Lung Disease
    MeSH:Pneumonia, Viral Pneumonia Lung Diseases Lung Diseases, Obstructive Cardiovascular Diseases
    HPO:Abnormal lung morphology Abnormality of the cardiovascular system Pneumonia Pulmonary obstruction

    Primary Outcomes

    Description: mean rate of recovery in patients with diagnosis of Covid-19 pneumonia, who present with complications at the time of hospital admission (such as diabetes, obesity, cardiovascular disease, hypertension or respiratory failure), with the mean recovery rate in patients without any of the above-mentioned complications.

    Measure: rate of recovery

    Time: 3 weeks

    Secondary Outcomes

    Description: comparison of the survival curves (times to improvement) in the two groups (patients with and without complications) and among patients presenting with different types of complications

    Measure: time to improvement

    Time: 3 weeks

    Description: the efficacy of different pharmaceutical treatment against Covid-19

    Measure: efficacy of treatments

    Time: 3 weeks

    Description: liver, kidney or multiorgan failure, cardiac failure

    Measure: organ failure

    Time: 3 weeks
    64 Proflaxis for Healthcare Professionals Using Hydroxychloroquine Plus Vitamin Combining Vitamins C, D and Zinc During COVID-19 Pandemia: An Observational Study

    Healthcare professionals mainly doctors, nurses and their first degree relatives (spouse, father, mother, sister, brother, child) who have been started hydroxychloroquine(plaquenil) 200mg single dose repeated every three weeks plus vitaminC including zinc once a day were included in the study. Study has conducted on 20th of march. Main purpose of the study was to cover participants those who are facing or treating COVID19 infected patients in Ankara.

    NCT04326725
    Conditions
    1. Pneumonitis
    2. Coronavirus Infection
    Interventions
    1. Drug: Plaquenil 200Mg Tablet
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: persons who took this medication should not have an infection

    Measure: Protection against COVID-19

    Time: 4 months
    65 PCR-COVID-19 Predictors of Positivity in Patients Admitted to ICU for Respiratory Infection: A Prospective Observational Cohort Study

    Coronavirus 2019 (COVID-19) is a respiratory tropism virus transmitted through droplets emitted into the environment of infected persons. The symptoms can be extremely varied and the course can range from spontaneous healing without sequelae to death. Currently, the diagnosis of certainty for resuscitation patients (by definition "severe") is based on searching for a fragment of virus genetic material within the epithelial cells of the respiratory tree, up and/or down, by PCR. It is to be expected that the epidemic peak will make it difficult (if not impossible) to respect the stereotypical path that is currently in place, due to the lack of space in the specific unit. This will require optimization of care pathways and use of the specific sectors. It is therefore necessary to define the simple criteria, available from the moment patients are admitted, to predict the result of the COVID-19 PCR.

    NCT04327180
    Conditions
    1. Infection Viral
    2. Coronavirus
    3. ARDS
    4. Pneumonia
    MeSH:Infection Communicable Diseases Virus Diseases Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Measure: Correlation between nasal and deep PCR positivity for Covid-19 patients performed and all predictors for Covid-19 patients performed within 24 hours of admission to ICU

    Time: within 24 hours of admission to ICU

    Secondary Outcomes

    Description: Assessment of viral, bacterial, fungal and parasitic rate in confirmed and unconfirmed patients for COVID-19

    Measure: Coinfections

    Time: during ICU stay, up to 28 days

    Description: it will be reported the evolution of respiratory dysfunction in patients infected with COVID-19 admitted to ICU during their stay and requiring mechanical ventilation (during, Pao2/FIO2 ratio,,features of artificial ventilation features of extra-bodied respiratory assistance)

    Measure: Respiratory dysfunction requiring mechanical ventilation

    Time: during ICU stay, up to 28 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).

    Measure: Sequential Organ Failure Assessment (SOFA) Score

    Time: during ICU stay, up to 28 days

    Description: APS II was designed to measure the severity of disease for patients admitted to Intensive care units 24 hours after admission to the ICU, the measurement has been completed and resulted in an integer point score between 0 and 163 and a predicted mortality between 0% and 100%.

    Measure: SAPS II score

    Time: at admission

    Description: The DIC Score was developed by the The International Society of Thrombosis and Haemostasis (ISTH.) The DIC score calculator accounts of the following four parameters.Each of the four parameters evaluated above have values that are weighted with a number of points varying from 0 to 3. By summing the points given to the choices, a final result between 0 and 8 is obtained

    Measure: Disseminated Intravascular Coagulation (DIC) score

    Time: during ICU stay, up to 28 days

    Measure: Number of days on vasopressive amines

    Time: during ICU stay, up to 28 days

    Measure: Occurrence of an event of venous or arterial thromboembolic disease

    Time: during ICU stay, up to 28 days

    Measure: Number of days with extra renal treatment (ERA)

    Time: during ICU stay, up to 28 days

    Measure: Number of patients alive after ICU stay less than 28 days will be tracked

    Time: At 28 day

    Description: measuring the long-term impact of confirmed COVID-19 infection. assessment of quality of life according to 8 areas: physical activity (and related limitations), body pain, perception of one's own health, mental health (and related limitations), social life and vitality.

    Measure: Short Form 36

    Time: at 9 months +/- 3 months after ICU stay

    Description: The scale allows to detect anxiety and depression using 14 items rated from 0-3. Measuring the long-term impact of confirmed COVID-19 infection

    Measure: Hospital anxiety and depression scale (HADS)

    Time: at 9 months +/- 3 months after ICU stay

    Description: 22-item self-report measure that assesses subjective distress caused by traumatic events Items are rated on a 5-point scale ranging from 0 ("not at all") to 4 ("extremely"). The IES-R yields a total score (ranging from 0 to 88) Measuring the long-term impact of confirmed COVID-19 infection

    Measure: Impact of Event Scale - revised (IES-R)

    Time: at 9 months +/- 3 months after ICU stay

    Description: Question the stressful experience or event, followed by 20 multiple-choice questions. Measuring the long-term impact of confirmed COVID-19 infection

    Measure: Post-traumatic stress disorder Checklist version DSM-5 (PSL-5)

    Time: at 9 months +/- 3 months after ICU stay

    Description: The mMRC Dyspnea Scale stratifies severity of dyspnea in respiratory diseases Measuring the long-term impact of confirmed COVID-19 infection

    Measure: Modified Medical Research Council (MMRC) Dyspnea Scale

    Time: at 9 months +/- 3 months after ICU stay

    Measure: Correlation between number of patient deaths and all predictors for Covid-19 including anamnestic, clinical, biological, radiological parameters

    Time: until day 28 after admission of ICU

    Description: Evolution of viral clearance in nasal and depp PCR during ICU

    Measure: Viral clearance

    Time: through study completion, an average of 28 days
    66 Non-invasive Detection of Pneumonia in Context of Covid-19 Using Gas Chromatography - Ion Mobility Spectrometry (GC-IMS)

    On Dec 31, 2019, a number of viral pneumonia cases were reported in China. The virus causing pneumonia was then identified as a new coronavirus called SARS-CoV-2. Since this time, the infection called coronavirus disease 2019 (COVID-19) has spread around the world, causing huge stress for health care systems. To diagnose this infection, throat and nose swabs are taken. Unfortunately, the results often take more than 24 hrs to return from a laboratory. Speeding diagnosis up would be of great help. This study aims to look at the breath to find signs that might allow clinicians to diagnose the coronavirus infection at the bedside, without needing to send samples to the laboratory. To do this, the team will be using a machine called a BreathSpec which has been adapted to fit in the hospital for this purpose.

    NCT04329507
    Conditions
    1. COVID-19
    2. Respiratory Disease
    Interventions
    1. Diagnostic Test: Breath test
    MeSH:Pneumonia Respiration Disorders Respiratory Tract Diseases
    HPO:Pneumonia

    Primary Outcomes

    Description: breath sample collection

    Measure: To perform a study in patients with clinical features of pneumonia/chest infection to identify a signature of Covid-19 pneumonia in patients exposed to SARS-CoV-2, compared to unexposed patients or those without.

    Time: up to daily during hospital admission

    Secondary Outcomes

    Description: breath sample collection

    Measure: Detection of markers of Covid-19 pneumonia in non-invasive breath samples.

    Time: multiple samples up to 60 days

    Description: breath sample collection

    Measure: Relationship of this biomarker signature to the presence of SARS-CoV-2 in nasal and throat swabs.

    Time: multiple samples up to 60 days

    Description: breath sample collection

    Measure: Subsequently, the signature's relationship to other biomarkers of SARS-CoV-2 infection which are currently being explored

    Time: multiple samples up to 60 days

    Description: breath sample collection

    Measure: In a smaller group of participants, ideally daily non-invasive breath samples will be collected to determine if there are changes between SARS-CoV-2 positive patients and those that are negative until hospital discharge or undue participant burden .

    Time: multiple samples up to 60 days
    67 Phase 2, Randomized, Open-label Study to Compare Efficacy and Safety of Siltuximab vs. Corticosteroids in Hospitalized Patients With COVID19 Pneumonia

    In our center up to 25% of the hospitalized patients with COVID-19 progress and need an intensive care unit. It is urgent to find measures that can avoid this progression to severe stages of the disease. We hypothesize that the use of anti-inflammatory drugs used at the time they start hyperinflammation episodes could improve symptoms and prognosis of patients and prevent their progression sufficiently to avoid their need for be admitted to an Intensive Care Unit.

    NCT04329650
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Siltuximab
    2. Drug: Methylprednisolone
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Measure: Proportion of patients requiring ICU admission at any time within the study period.

    Time: 29 days

    Secondary Outcomes

    Measure: Days of stay in the ICU during the study period.

    Time: 29 days

    Measure: Days until resolution of fever defined as body temperature (axillary ≤ 36.6 ° C, oral ≤ 37.2 ° C, or rectal or tympanic ≤ 37.8 ° C) for at least 48 hours, without administration of antipyretics or until hospital discharge.

    Time: 29 days

    Measure: Proportion of patients with a worsening requirement of supplemental oxygen at 29 days. days.

    Time: 29 days

    Measure: Days with hypoxemia (SpO2 <93% in ambient air or requiring oxygen supplemental or mechanical ventilation support) at 29 days.

    Time: 29 days

    Measure: Proportion of patients using mechanical ventilation at 29 days.

    Time: 29 days

    Measure: Days with use of mechanical ventilation at 29 days.

    Time: 29 days

    Measure: Days until the start of use of mechanical ventilation, non-invasive ventilation or use of high flow nasal cannula (if the patient have not previously required these interventions at the inclusion of the study) at 29 days.

    Time: 29 days

    Measure: Days of hospitalization among survivors at 29 days.

    Time: 29 days

    Measure: Mortality rate from any cause at 29 days.

    Time: 29 days

    Measure: Proportion of patients with serious adverse events at 29 days.

    Time: 29 days

    Measure: Proportion of patients with invasive bacterial or fungal infections clinically significant or opportunistic with grade 4 neutropenia (count neutrophil absolute <500 / mm3) at 29 days.

    Time: 29 days

    Measure: Proportion of patients with invasive bacterial or fungal infections clinically significant or opportunistic at 29 days.

    Time: 29 days

    Measure: Proportion of patients with grade 2 or higher adverse reactions related to the infusion of the sudy treatments at 29 days.

    Time: 29 days

    Measure: Proportion of patients with hypersensitivity reactions of grade 2 or higher related to the administration of the study treatments at 29 days.

    Time: 29 days

    Measure: Proportion of patients with gastrointestinal perforation at 29 days.

    Time: 29 days

    Measure: Proportion of patients with secondary severe infections confirmed by laboratory or worsening of existing infections at 29 days.

    Time: 29 days

    Measure: Changes from baseline in plasma leukocyte levels at days 1, 3, 5, 7 and 9.

    Time: Days 1, 3, 5, 7 and 9

    Measure: Changes from baseline in plasma hemoglobin levels at days 1, 3, 5, 7 and 9.

    Time: Days 1, 3, 5, 7 and 9

    Measure: Changes from baseline in plasma platelet at days 1, 3, 5, 7 and 9.

    Time: Days 1, 3, 5, 7 and 9

    Measure: Changes from baseline in plasma creatinine levels at days 1, 3, 5, 7 and 9.

    Time: Days 1, 3, 5, 7 and 9

    Measure: Changes from baseline in plasma total bilirubin levels at days 1, 3, 5, 7 and 9.

    Time: Days 1, 3, 5, 7 and 9

    Measure: Proportion of patients with ALT≥ 3 times ULN (for patients with initial values normal) or> 3 times ULN AND at least 2 times more than the initial value (for patients with abnormal initial values) at days 1, 3, 5, 7 and 9.

    Time: Days 1, 3, 5, 7 and 9

    Measure: Changes from baseline in plasma biomarkers (PCR, lymphocytes, ferritin, d-dimer and LDH) at days 1, 3, 5, 7 and 9.

    Time: Days 1, 3, 5, 7 and 9

    Measure: Changes from baseline in chest Rx at days 1, 3 and 5.

    Time: Days 1, 3 and 5
    68 Clinical Characteristics and Outcomes of Children Potentially Infected by Severe Acute Respiratory Distress Syndrome (SARS)-CoV-2 Presenting to Pediatric Emergency Departments

    Rationale: The clinical manifestations of SARS-CoV-2 infection in children are poorly characterized. Preliminary findings indicate that they may be atypical. There is a need to identify the spectrum of clinical presentations, predictors of severe disease (COVID-19) outcomes, and successful treatment strategies in this population. Goals: Primary - Describe and compare characteristics of confirmed SARS-CoV-2 infected children with symptomatic test-negative children. Secondary - 1) Describe and compare confirmed SARS-CoV-2 infected children with mild versus severe COVID-19 outcomes; 2) Describe healthcare resource utilization for, and outcomes of, screening and care of pediatric COVID-19 internationally, alongside regional public health policy changes. Methods: This prospective observational study will occur in 50 emergency departments across 11 countries. We will enroll 12,500 children who meet institutional screening guidelines and undergo SARS-CoV-2 testing. Data collection focuses on epidemiological risk factors, demographics, signs, symptoms, interventions, laboratory testing, imaging, and outcomes. Collection will occur at enrollment, 14 days, and 90 days. Timeline: Recruitment will last for 12 months (worst-case model) and will begin within 7-14 days of funding notification after ongoing expedited review of ethics and data sharing agreements. Impact: Results will be shared in real-time with key policymakers, enabling rapid evidence-based adaptations to pediatric case screening and management.

    NCT04330261
    Conditions
    1. COVID-19
    2. SARS-CoV-2 Infection
    3. Pediatric ALL
    4. Pneumonia, Viral
    5. Pandemic Response
    Interventions
    1. Other: Exposure (not intervention) - SARS-CoV-2 infection
    MeSH:Pneumonia, Viral Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Clinical characteristics among children presenting to a participating hospital's EDs who meet each site's local SARS-CoV-2 screening criteria, will be described and compared between children with confirmed SARS-CoV-2 (i.e. test-positive) versus suspected (i.e. test-negative) infections.

    Measure: Clinical characteristics of children with SARS-CoV-2

    Time: 18 months

    Description: Factors associated with severe outcomes [i.e. positive pressure ventilation (invasive or noninvasive) OR intensive care unit admission with ventilatory or inotropic support OR death; other outcomes may be added as the understanding of the epidemic evolves) will be identified in confirmed paediatric COVID-19 cases.

    Measure: Factors associated with severe COVID-19 outcomes

    Time: 18 months

    Secondary Outcomes

    Description: Health care resource utilization for patient management (e.g. frequencies of isolation, laboratory testing, imaging, and supportive care, with associated costs) of both suspected and confirmed SARS-CoV-2 infected children according to changes in national and regional policies.

    Measure: Health care resource utilization for COVID-19 patient management

    Time: 18 months

    Description: The sensitivity and specificity of various case screening policies for the detection of confirmed symptomatic SARS-CoV-2 infection (i.e. COVID-19) in children (e.g. addition of vomiting/diarrhoea).

    Measure: Sensitivity and specificity of COVID-19 case screening policies

    Time: 18 months
    69 Safety and Efficacy Study of Human Embryonic Stem Cells Derived M Cells (CAStem) for the Treatment of Severe COVID-19 Associated With or Without Acute Respiratory Distress Syndrome (ARDS)

    A phase1/2, open label, dose escalation, safety and early efficacy study of CAStem for the treatment of severe COVID-19 associated with or without ARDS.

    NCT04331613
    Conditions
    1. COVID-19
    2. Acute Respiratory Distress Syndrome
    3. Virus; Pneumonia
    4. Acute Lung Injury
    Interventions
    1. Biological: CAStem
    MeSH:Pneumonia, Viral Pneumonia Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Lung Injury Syndrome
    HPO:Pneumonia

    Primary Outcomes

    Description: Frequency of adverse reaction (AE) and severe adverse reaction (SAE) within 28 days after treatment

    Measure: Adverse reaction (AE) and severe adverse reaction (SAE)

    Time: Within 28 days after treatment

    Description: Evaluation by chest CT

    Measure: Changes of lung imaging examinations

    Time: Within 28 days after treatment

    Secondary Outcomes

    Description: Marker for SARS-CoV-2

    Measure: Time to SARS-CoV-2 RT-PCR negative

    Time: Within 28 days after treatment

    Description: The duration of a fever above 37.3 degrees Celsius

    Measure: Duration of fever (Celsius)

    Time: Within 28 days after treatment

    Description: Marker for efficacy

    Measure: Changes of blood oxygen (%)

    Time: Within 28 days after treatment

    Description: Marker for efficacy

    Measure: Rate of all-cause mortality within 28 days

    Time: Within 28 days after treatment

    Description: Counts of lymphocyte in a litre (L) of blood

    Measure: Lymphocyte count (*10^9/L)

    Time: Within 28 days after treatment

    Description: Alanine aminotransferase in unit (U)/litre(L)

    Measure: Alanine aminotransferase (U/L)

    Time: Within 28 days after treatment

    Description: Creatinine in micromole (umol)/litre(L)

    Measure: Creatinine (umol/L)

    Time: Within 28 days after treatment

    Description: Creatine kinase in U/L

    Measure: Creatine kinase (U/L)

    Time: Within 28 days after treatment

    Description: C-reactive in microgram (mg)/litre(L)

    Measure: C-reactive protein (mg/L)

    Time: Within 28 days after treatment

    Description: Procalcitonin in nanogram (ng)/litre(L)

    Measure: Procalcitonin (ng/L)

    Time: Within 28 days after treatment

    Description: Lactate in millimole(mmol)/litre(L)

    Measure: Lactate (mmol/L)

    Time: Within 28 days after treatment

    Description: IL-1beta in picogram(pg)/millilitre(mL)

    Measure: IL-1beta (pg/mL)

    Time: Within 28 days after treatment

    Description: IL-2 in pg/mL

    Measure: IL-2 (pg/mL)

    Time: Within 28 days after treatment

    Description: IL-6 in pg/mL

    Measure: IL-6 (pg/mL)

    Time: Within 28 days after treatment

    Description: IL-8 in pg/mL

    Measure: IL-8 (pg/mL)

    Time: Within 28 days after treatment
    70 A Single Arm Open-label Clinical Study to Investigate the Efficacy and Safety of Ruxolitinib for the Treatment of COVID-19 Pneumonia

    The purpose of this study is to determine the safety and efficacy of the drug ruxolitinib in people diagnosed with COVID-19 pneumonia by determining the number of people whose conditions worsen (requiring machines to help with breathing or needing supplemental oxygen) while receiving the drug. This is a sub-study of the U-DEPLOY study: UHN Umbrella Trial Defining Coordinated Approach to Pandemic Trials of COVID-19 and Data Harmonization to Accelerate Discovery. U-DEPLOY helps to facilitate timely conduct of studies across the University Health Network and other centers.

    NCT04331665
    Conditions
    1. COVID-19
    2. Pne
    3. Pneumonia
    Interventions
    1. Drug: Ruxolitinib
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Measure: Proportion of patients with COVID-19 pneumonia who become critically ill (defined as requiring mechanical ventilation and/or FiO2 of 60% of more)

    Time: 6 months

    Measure: Number of adverse events

    Time: 9 months

    Secondary Outcomes

    Measure: All cause mortality rate

    Time: 9 months

    Measure: Average duration of hospital stay

    Time: 9 months
    71 Early Institution of Tocilizumab Titration in Non-Critical Hospitalized COVID-19 Pneumonitis

    Coronavirus disease-2019 (COVID-19) has a quoted inpatient mortality as high as 25%. This high mortality may be driven by hyperinflammation resembling cytokine release syndrome (CRS), offering the hope that therapies targeting the interleukin-6 (IL-6) axis therapies commonly used to treat CRS can be used to reduce COVID-19 mortality. Retrospective analysis of severe to critical COVID-19 patients receiving tocilizumab demonstrated that the majority of patients had rapid resolution (i.e., within 24-72 hours following administration) of both clinical and biochemical signs (fever and CRP, respectively) of hyperinflammation with only a single tocilizumab dose. Hypotheses: 1. Tocilizumab is effective in decreasing signs, symptoms, and laboratory evidence of COVID-19 pneumonitis in hospitalized, non-critically ill patients with clinical risk factors for clinical decompensation, intensive care utilization, and death. 2. Low-dose tocilizumab is effective in decreasing signs, symptoms, and laboratory evidence of COVID-19 pneumonitis in hospitalized, non-critically ill patients with and without clinical risk factors for clinical decompensation, intensive care utilization, and death. Objectives: 1. To establish proof of concept that tocilizumab is effective in decreasing signs, symptoms, and laboratory evidence of COVID-19 pneumonitis in hospitalized, non-critically ill patients with clinical risk factors for clinical decompensation, intensive care utilization, and death, as determined by the clinical outcome of resolution of fever and the biochemical outcome measures of time to CRP normalization for the individual patient and the rate of patients whose CRP normalize. 2. To establish proof of concept that low-dose tocilizumab is effective in decreasing signs, symptoms, and laboratory evidence of COVID-19 pneumonitis in hospitalized, non-critically ill patients without clinical risk factors for clinical decompensation, intensive care utilization, and death, as determined by the clinical outcome of resolution of fever and the biochemical outcome measures of time to CRP normalization for the individual patient and the rate of patients whose CRP normalize.

    NCT04331795
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Tocilizumab
    2. Drug: Tocilizumab
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Tmax Response: Resolution of fever (from Tmax > 38C in 24H period to Tmax < 38C in following 24H period, with Tmax measured by commonly accepted clinical methods [forehead, tympanic, oral, axillary, rectal]). Maximum temperature within 24-hour period of time (0:00-23:59) on the day prior to, day of, and every 24 hours after tocilizumab administration. The primary endpoint is absence of Tmax greater than or equal to 38ºC in the 24-hour period following tocilizumab administration.

    Measure: Clinical response

    Time: Assessed for the 24 hour period after tocilizumab administration

    Description: CRP normalization rate: Calculated as the ratio of the number of patients who achieve normal CRP value following tocilizumab administration and total number of patients who receive tocilizumab. Time to CRP normalization: Calculated as the number of hours between tocilizumab administration and first normal CRP value.

    Measure: Biochemical response

    Time: Assessed every 24 hours during patient's hospitalization, up to 4 weeks after tocilizumab administration

    Secondary Outcomes

    Description: 28-Day Overall Survival is defined as the status of the patient at the end of 28 days, beginning from the time of the first dose of tocilizumab.

    Measure: Overall survival

    Time: 28 days

    Description: This will be defined as the percentage of patients who are discharged in stable condition compared to the percentage of patients who die in the hospital. Patients who are discharged to hospice will be excluded from this calculation.

    Measure: Survival to hospital discharge

    Time: Hospitalization, up to 4 weeks after tocilizumab administration

    Description: This will be a binary outcome defined by worsening COVID-19 pneumonitis resulting in transition from clinical Group A or Group B COVID-19 pneumonitis to critical COVID-19 pneumonitis during the course of the patient's COVID-19 infection. This diagnosis will be determined by treating physicians on the basis of worsening pulmonary infiltrates on chest imaging as well as clinical deterioration marked by persistent fever, rising supplemental oxygen requirement, declining PaO2/FiO2 ratio, and the need for intensive care such as mechanical ventilation or vasopressor/inotrope medication(s).

    Measure: Progression of COVID-19 pneumonitis

    Time: Hospitalization, up to 4 weeks after tocilizumab administration

    Description: This will be a binary outcome defined as worsening COVID-19 disease resulting in the use of non-invasive (BiPap, heated high-flow nasal cannula) or invasive positive pressure ventilation during the course of the patient's COVID-19 infection. For patients admitted to the hospital using non-invasive mechanical ventilation, the utilization of mechanical ventilation will count toward this metric, as well. Calculated as the ratio of the number of patients who require non-invasive or invasive positive pressure ventilation during hospitalization and total number of patients who receive tocilizumab.

    Measure: Rate of non-elective mechanical ventilation

    Time: Hospitalization, up to 4 weeks after tocilizumab administration

    Description: This will be a continuous outcome defined by the amount of time between initiation and cessation of mechanical ventilation (invasive and non-invasive).

    Measure: Duration of mechanical ventilation

    Time: Hospitalization, up to 4 weeks after tocilizumab administration

    Description: This will be a continuous outcome defined by the amount of time between tocilizumab dose administration and the initiation of mechanical ventilation. This will be treated as a time-to-event with possible censoring.

    Measure: Time to mechanical ventilation

    Time: Assessed over hospitalization, up to 4 weeks after tocilizumab administration

    Description: This will be a binary outcome defined as utilization of any vasopressor or inotropic medication during the course of the patient's COVID-19 infection. Calculated as the ratio of the number of patients who require vasopressor or inotrope medication during hospitalization and total number of patients who receive tocilizumab.

    Measure: Rate of vasopressor/inotrope utilization

    Time: Hospitalization, up to 4 weeks after tocilizumab administration

    Description: This will be a continuous outcome defined by the amount of time between initiation of first and cessation of last vasopressor or inotrope medication(s).

    Measure: Duration of vasopressor/inotrope utilization

    Time: Hospitalization, up to 4 weeks after tocilizumab administration

    Description: This will be a continuous outcome defined by the amount of time between first tocilizumab dose administration and the initiation of vasopressor or inotropic medication(s). This will be treated as a time-to-event with possible censoring.

    Measure: Time to vasopressor or inotropic utilization

    Time: Assessed over hospitalization, up to 4 weeks after tocilizumab administration

    Description: Number of ICU days is defined as the time period when a patient is admitted to the ICU (defined as the timestamp on the first vital signs collected in an ICU) until they are transferred from the ICU to a non-ICU setting such as a general acute care bed (defined as the timestamp on the first vital signs collected outside an ICU, excepting any "off the floor" vital signs charted from operating rooms or procedure or imaging suites). Death in the ICU will be a competing risk.

    Measure: Number of ICU days

    Time: Hospitalization, up to 4 weeks after tocilizumab administration

    Description: Duration of increased supplemental oxygen requirement from baseline is defined as the time period (number of days) during which the participant requires supplemental oxygen in excess of his/her baseline supplemental oxygen requirement. The supplemental oxygen requirement is defined as the highest liters-per-minute flow of supplemental oxygen required by the patient each day over the course of the hospitalization.

    Measure: Duration of Increased Supplemental Oxygen Requirement from Baseline

    Time: Assessed over hospitalization, up to 4 weeks after tocilizumab administration
    72 Efficacy and Safety of Tocilizumab in the Treatment of Patients With Respiratory Distress Syndrome and Cytokine Release Syndrome Secondary to COVID-19: a Proof of Concept Study

    The current spread of the COrona VIrus Disease-2019 (COVID-19) epidemic in Italy, and the current lack of effective and approved drugs for its treatment, poses the problem of Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infected patients management, especially those who underwent to experience COVID-19 complications, such as CRS. This unmet need becomes more severe if the investigator consider that, the COVID-19 mortality stands around 2% in the general population, but it rises to 49% when considering intensive care unit (ICU) patients. To increase the chances of survival of these patients, the compassionate use of the available drugs is required, based on literature data, to the best of our abilities. ICU patients with cytokine release syndrome (CRS) secondary to COVID-19, show increased production of pro-inflammatory cytokines, including interleukin (IL-6), IL-2, IL-7, IL-10, tumor necrosis factor (TNF)-α and interferon (INF)γ, similar to that found in patients who develop CRS secondary to Chimeric Antigen Receptor-T (CAR-T) therapy. Although immuno-modulatory therapy is not routinely recommended in COVID-19 pneumonia, tocilizumab might have a rationale in those patients who develop CRS, blocking the complications caused by high levels of IL-6, and possibly preventing the development of a multi-organ failure. Reassuring data in this sense, come from the first studies conducted in China. In a Chinese pilot study, Xiaoling Xu and collaborators used tocilizumab (at a dosage of 400 mg iv in a single dose, with a possible second dose in case of no clinical response) in patients with COVID-19 in the presence of one of the following criteria: i) respiratory rate ≥ 30 acts/min; ii) SpO2 ≤ 93% in ambient air; iii) PaO2/FiO2 ≤ 300 mmHg. In the 21 patients treated with tocilizumab a significant reduction in IL-6 levels and fever, with improvement in lung function, was demonstrated. Besides, 90% of treated patients showed an improvement in the radiological picture, in terms of a decrease in the frosted glass areas, and a return to normal lymphocytes count in the peripheral blood. This is a prospective observational clinical study and it is aimed at verifying tocilizumab efficacy and safety in patients with COVID-19 complicated by acute distress respiratory syndrome (ARDS) and CRS.

    NCT04332913
    Conditions
    1. COVID-19 Pneumonia
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Fever normalization criteria: Temperature <36.6 ° C for at least 72 hours; SpO2 normalization criterion: SpO2> 94% for at least 72 hours

    Measure: Percentage of patients with complete recovery defined as fever disappearance and return to normal peripheral oxygen saturation values (SpO2) after 14 days from the end of treatment with tocilizumab.

    Time: 14 days

    Secondary Outcomes

    Measure: Percentage of patients achieving a score <3 on the Brescia-COVID respiratory severity scale (BCRSS) after the last tocilizumab administration.

    Time: 24 hours

    Description: Fever normalization criteria: Temperature <36.6 ° C for at least 72 hours

    Measure: Percentage of patients with partial recovery defined as the disappearance of fever 14 days after the end of treatment with tocilizumab.

    Time: 14 days

    Description: days

    Measure: Duration of hospitalization

    Time: 14 days

    Description: days

    Measure: Time to the first negative SARS-CoV-2 negative RT-PCR test

    Time: 14 days

    Description: number/microliter

    Measure: Changes from the baseline in the white blood cell count

    Time: 7, 14 days

    Description: number/microliter

    Measure: Changes from the baseline in the lymphocyte populations (cluster of differentiation (CD)3+CD4+, CD3+CD8+, CD19+, Th17)

    Time: 7, 14 days

    Measure: Changes from the baseline of c-reactive protein (CRP) values

    Time: 7, 14 days

    Measure: Changes from the baseline of Ferritin values

    Time: 7, 14 days

    Measure: Changes from the baseline of BNP values

    Time: 7,14 days

    Measure: Changes from the baseline of CK-MB values

    Time: 7,14 days

    Measure: Changes from the baseline of Troponin values

    Time: 7,14 days

    Measure: Changes from the baseline of LDH values

    Time: 7,14 days

    Measure: Changes from the baseline of myoglobulin values

    Time: 7,14 days

    Description: (ST segments elevation or depression, T-wave changes)

    Measure: Changes in myocardial ischemia signs at the electrocardiographic trace (YES or NO)

    Time: 7,14 days

    Measure: Rate of adverse events report during and after tocilizumab

    Time: 14 days

    Measure: Mortality (number of Partecipants, cause and timing)

    Time: 12 weeks

    Measure: Percentage of patients who develop autoimmune diseases

    Time: 1 year
    73 Evaluating Convalescent Plasma to Decrease Coronavirus Associated Complications. A Phase I Study Comparing the Efficacy and Safety of High-titer Anti-Sars-CoV-2 Plasma vs Best Supportive Care in Hospitalized Patients With Interstitial Pneumonia Due to COVID-19

    Currently there are no proven treatment option for COVID-19. Human convalescent plasma is an option for COVID-19 treatment and could be available from people who have recovered and can donate plasma.

    NCT04333251
    Conditions
    1. Pneumonia, Interstitial
    Interventions
    1. Biological: high-titer anti-Sars-CoV-2 plasma
    2. Other: oxygen therapy
    MeSH:Pneumonia Lung Diseases, Interstitial
    HPO:Interstitial pneumonitis Interstitial pulmonary abnormality Pneumonia

    Primary Outcomes

    Description: reduction in oxygen and ventilation support

    Measure: reduction in oxygen and ventilation support

    Time: through study completion, an average of 4 weeks
    74 A Pragmatic Adaptive Randomized, Controlled Phase II/III Multicenter Study of IFX-1 in Patients With Severe COVID-19 Pneumonia

    Phase II & Phase III: This is a pragmatic, adaptive, randomized, multicenter phase II/III study evaluating IFX-1 for the treatment of COVID-19 related severe pneumonia. The study consists of two parts: Phase II, an open-label, randomized, 2-arm phase evaluating best supportive care (BSC) + IFX-1 (Arm A) and BSC alone (Arm B); and Phase III, a double-blind, placebo-controlled, randomized phase comparing standard of care (SOC) + IFX-1 (Arm A) versus SOC + placebo-to-match (Arm B)

    NCT04333420
    Conditions
    1. Severe COVID-19 Pneumonia
    Interventions
    1. Drug: SOC + IFX-1
    2. Drug: SOC + Placebo
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: 28-day all-cause mortality

    Measure: Mortality

    Time: Day 28

    Secondary Outcomes

    Description: Frequency, severity, and relatedness to study drug of serious and non-serious TEAEs

    Measure: Treatment Emergent Adverse Events

    Time: Day1 to Day 60

    Description: Proportion of patients with an improvement in the 8-point ordinal scale

    Measure: Safety Parameters

    Time: Day 15, Day 28
    75 Use of a Respiratory Multiplex PCR and Procalcitonin to Reduce Antibiotics Exposure in Patients With Severe Confirmed COVID-19 Pneumonia : a Multicenter, Parallel-group, Open-label, Randomized Controlled Trial

    The novel coronavirus SARS-CoV-2 (COVID-19) is an emerging respiratory virus that causes pneumonia. WHO data reported admission to the intensive care unit (ICU) for 6% of patients, with a mortality rate reaching 45%. To date, apart from therapeutic trials, ICU management is symptomatic, based on organ failure support therapies. In the initial phase, the therapeutic management also includes empiric antimicrobial therapy (90% of patients, in accordance with LRTI guidelines (ATS 2019) and SRLF Guidelines (2020). One challenge for the ICU physicians is the timing for discontinuation of antimicrobial treatment, especially in case of shock or ARDS, considering that a substantial proportion of COVID-19 pneumonia patients may have pulmonary bacterial coinfection/superinfection. In order to avoid unnecessary prolonged antimicrobial therapy, and subsequent selective pressure, two tests could be combined in a personalized antibiotic strategy: - Procalcitonin (PCT): PCT is a useful tool to guide antibiotics discontinuation in community-acquired pneumonia) and viral pneumonia (PMID24612487). - Respiratory multiplex PCR FA-PPP (Biomérieux®): panel has been enlarged, including 8 viruses and 18 bacteria (quantitative analysis). The turnaround time is short. Sensitivity is high (99%, PMID32179139). It may contribute, in combination with conventional tests, to accelerate and improve the microbiological diagnosis during severe COVID-19 pneumonia. The hypothesize of the study is that the combination of the mPCR FA-PPP and PCT could be used to reduce antibiotics exposure in patients with severe confirmed COVID-19 pneumonia, with a higher clinical efficacy and safety as compared with a conventional strategy.

    NCT04334850
    Conditions
    1. Covid19
    2. Pneumonia
    Interventions
    1. Procedure: Combined use of a respiratory broad panel multiplex PCR and procalcitonin
    2. Other: Usual antibiotic treatment
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: the number of days alive without any antibiotics at Day 28. The D28 time point is usual in studies assessing antibiotics saving in ICU patients.

    Measure: Number of antibiotic free days

    Time: Day 28

    Secondary Outcomes

    Measure: Mortality rates

    Time: Day 28 and Day 90

    Measure: Number of defined daily dose (DDD) per 100 patient-days of broad- and narrow-spectrum antibiotics.

    Time: day 28

    Description: Total exposure to antibiotics

    Measure: Antibiotics duration at D28

    Time: Day 28

    Measure: Number of organ-failure free days (based on SOFA)

    Time: Day 28

    Measure: Incidence rates of bacterial super-infections

    Time: day 28

    Measure: Incidence rates of colonization/infection with multidrug resistant bacteria and Clostridium difficile infections

    Time: Day 28

    Measure: ICU and hospital lengths of stay

    Time: Day 28

    Description: using a quality of life questionnaire (EQ5D5L)

    Measure: Quality of life Quality of life

    Time: Day 90
    76 Interest of the Use of Pulmonary Ultrasound in the Referral of Patients With or Suspected COVID-19 +

    The recent pandemic due to the SARS-CoV2 results in a pulmonary infection in major symptomatic patients. Because of the large number of patients and the risk of acute respiratory distress syndrome (which seems to occur in almost 5% of patients), there is a real challenge to improve physician ability to screen between patients those who will require specific surveillance and those who can be sent back home. The recent French official recommendation of the French radiology society prescribe that chest X-ray do not have any place in the COVID-19+ management whereas the WHO stipulate that ultrasound machines may be useful for these patients [1-2]. Moreover, scattered recent publications tend to stress the interest of quick ultrasound imaging for COVID-19 suspected patients for screening purpose [2-5]. The aim of this observational historico-prospective study is to assess the risk of severe clinical outcomes (admission in continuous care unit (USC), invasive respiratory assistance, death) in patients suspected or diagnosed COVID-19+ as a function of initial pulmonary ultrasound abnormalities. These clinical outcomes are assessed through phone calls at D5, D15, M1. The secondary objectives are: - Assessing the concordance between the severity of pulmonary lesions as detected by pulmonary ultrasound devices and the ones detected by CT-scanner, for patients who will undergo these two examinations. - Assessing the compared performances in detecting ultrasound pulmonary lesions for patients suspected or diagnosed COVID-19+, between an experimented operator and a newly trained operator.

    NCT04335019
    Conditions
    1. 2019-nCoV (COVID-19)
    2. Interstitial Pneumonia
    Interventions
    1. Other: Pulmonary ultrasound
    MeSH:Pneumonia Lung Diseases, Interstitial
    HPO:Interstitial pneumonitis Interstitial pulmonary abnormality Pneumonia

    Primary Outcomes

    Description: Association of pulmonary lesions on ultrasound on D0 classified according to three stages of severity There are few B lines at the lung bases Bi-lateralization of B lines, numerous diffuse and / or curtain sign Presence of signs of pulmonary consolidation, hepatization of the lung and air bronchogram)

    Measure: Association of pulmonary lesions on ultrasound on D0 classified according to three stages of severity

    Time: at day0

    Secondary Outcomes

    Measure: Assessment of the agreement between a newly trained operator and an experienced operator of classification in one of the three stages of ultrasound gravity, by Cohen's kappa coefficient.

    Time: at day0

    Measure: Estimate in patients who had a CT-scan on D0, the agreement in the evaluation of the severity of lung lesions via ultrasound vs. CT-scan, by Cohen's kappa coefficient

    Time: at day0

    Measure: Measurement of the cumulative incidence of invasive mechanical ventilation and measurement of survival

    Time: at day5

    Measure: Measurement of the cumulative incidence of invasive mechanical ventilation and measurement of survival

    Time: at day15

    Measure: Measurement of the cumulative incidence of invasive mechanical ventilation and measurement of survival

    Time: at day28
    77 Use of Defibrotide to Reduce Progression of Acute Respiratory Failure Rate in Patients With COVID-19 Pneumonia

    Phase II, prospective, interventional, single-arm, multicentric, open label trial, with a parallel retrospective collection of data on not treated patients from IRCCS, San Raffaele Scientific Institute included in the institutional observational study. A sample of 50 patients with COVID-19 pneumonia will allow to detect an absolute reduction in the rate of Respiratory-failure at day+14 after treatment of 20%, assuming that the actual rate of failure in the corresponding not treated patients is 70% (alpha=5%, power=90%, two-sided test). The software PASS15 was used for calculations. The study will also include a parallel retrospective group of temporally concomitant patients from IRCCS, San Raffaele Scientific Institute, who did not receive an experimental treatment and who are enrolled in an already IRB approved observational study

    NCT04335201
    Conditions
    1. Patients With COVID-19 Pneumonia Will Allow to Detect an Absolute Reduction in the Rate of Respiratory-failure
    Interventions
    1. Drug: Defibrotide Injection
    MeSH:Pneumonia Respiratory Insufficiency
    HPO:Pneumonia

    Primary Outcomes

    Description: To demonstrate that the treatment with Defibrotide administered intravenously in addition to the best available therapy according to institutional guidelines (protease inhibitors antiviral treatment and hydroxychloroquine (HCQ), and if needed, metilprednisolone is able to reduce the progression of acute respiratory failure, the need of mechanical ventilation, the transfer to the intensive care unit or death, in patients with severe COVID-19 pneumonia. Patients with a baseline PaO2/FiO2 >= 200: progression of respiratory failure is defined by: severe gas transfer deficit (PaO2/FiO2 < 200); persistent respiratory distress while receiving oxygen (persistent marked dyspnea, use of accessory respiratory muscles, paradoxical respiratory movements); transfer to the intensive care unit; death. The rate will be calculated as the proportion of patients who experienced at least one of the events above by day+14 from treatment start.

    Measure: to able to reduce the progression of acute respiratory failure

    Time: 14 days

    Secondary Outcomes

    Description: To evaluate the safety of Defibrotide will be analyzed the frequency and incidence of Treatment-Related Adverse Events as Assessed by CTCAE v4.0

    Measure: Adverse events

    Time: 7 days

    Description: evaluate the time of hospitalization that will determine how much and how the administration of defibrotide can resolve the infection

    Measure: duration of hospitalization

    Time: 14 days

    Description: To evaluate the level of PCR, LDH, ferritin, IL-10, IL-6, TNF-alpha, IFN-gamma, PTX3 at day +7 and +14 after start of treatment with Defibrotide. performed per day. Laboratory values performed at day 7 and 14 will be analyzed and compared with each other to understand their progress.

    Measure: systemic inflammation

    Time: 14 days

    Description: To evaluate the overall survival at day+28 after start treatment with Defibrotide

    Measure: overall survival

    Time: 28 days
    78 A Randomized, Controlled, Open-Label, Phase II Trial to Evaluate the Efficacy and Safety of Tocilizumab Combined With Pembrolizumab (MK-3475) in Patients With Coronavirus Disease 2019 (COVID-19)-Pneumonia

    This is a prospective, multicenter, randomized, controlled, open-label, phase 2 clinical trial

    NCT04335305
    Conditions
    1. COVID-19
    2. Pneumonia, Viral
    Interventions
    1. Drug: Tocilizumab
    2. Biological: Pembrolizumab (MK-3475)
    MeSH:Pneumonia, Viral Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Assessed by hospital records

    Measure: Percentage of patients with normalization of SpO2 ≥96% on room air (measured without any respiratory support for at least 15 minutes

    Time: through day 14 after study treatment initiation

    Secondary Outcomes

    Description: Assessed by hospital records

    Measure: Proportion of patients discharged from the emergency department and classified as low risk

    Time: through End of Study, defined as 90 ± 14 days after study entry

    Description: Assessed by hospital records

    Measure: Number of days of patient hospitalization

    Time: through End of Study, defined as 90 ± 14 days after study entry

    Description: The clinical status will be assessed by the SOFA scores

    Measure: Change from baseline in organ failure parameters

    Time: Days 1, 3, 5, 7, 14 (+/- 1 day) and 28 (+/- 2 days) or until discharge whatever it comes first.

    Description: Determined as percentage of dead patients

    Measure: Proportion of mortality rate

    Time: through End of Study, defined as 90 ± 14 days after study entry

    Description: Determined as: Time to invasive mechanical ventilation (if not previously initiated); Time to independence from non-invasive mechanical ventilation; Time to independence from oxygen therapy.

    Measure: Analysis of the remission of respiratory symptoms

    Time: through End of Study, defined as 90 ± 14 days after study entry

    Description: by using the same imaging technique (chest X-ray or thoracic CT scan)

    Measure: Evaluation of the radiological response

    Time: at days 1 and 28 (+/- 2 days)

    Description: determined using oropharyngeal or anal swabs

    Measure: Time to first negative in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RT-PCR test

    Time: within 28 days from study inclusion

    Description: Baseline defined as the value collected at day 1, 2 hours before treatment administration

    Measure: Change from baseline of absolute lymphocyte count (ALC),white blood cell count and white blood cell differential count

    Time: days 3, 5, 7, 10, 14 and 28 after administration of study drug

    Description: Baseline defined as the value collected at day 1, 2 hours before treatment administration

    Measure: Change from baseline of hemoglobin

    Time: days 3, 5, 7, 10, 14 and 28 after administration of study drug

    Description: Baseline defined as the value collected at day 1, 2 hours before treatment administration

    Measure: Change from baseline of platelets

    Time: days 3, 5, 7, 10, 14 and 28 after administration of study drug

    Description: Baseline defined as the value collected at day 1, 2 hours before treatment administration

    Measure: Change from baseline of activated partial thromboplastin time (aPTT)

    Time: days 3, 5, 7, 10, 14 and 28 after administration of study drug

    Description: Baseline defined as the value collected at day 1, 2 hours before treatment administration

    Measure: Change from baseline of Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST)

    Time: days 3, 5, 7, 10, 14 and 28 after administration of study drug

    Description: Baseline defined as the value collected at day 1, 2 hours before treatment administration

    Measure: Change from baseline of creatinine

    Time: days 3, 5, 7, 10, 14 and 28 after administration of study drug

    Description: Baseline defined as the value collected at day 1, 2 hours before treatment administration

    Measure: Change from baseline of glucose

    Time: days 3, 5, 7, 10, 14 and 28 after administration of study drug

    Description: Baseline defined as the value collected at day 1, 2 hours before treatment administration

    Measure: Change from baseline of total bilirubin

    Time: days 3, 5, 7, 10, 14 and 28 after administration of study drug

    Description: Baseline defined as the value collected at day 1, 2 hours before treatment administration

    Measure: Change from baseline of albumin

    Time: days 3, 5, 7, 10, 14 and 28 after administration of study drug

    Description: Evaluated using the Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v.5.0), SOFA scores.

    Measure: Incidence of adverse events (AEs), incidence of prespecified AEs (safety and tolerability)

    Time: Up to End of Study, defined as 90 ± 14 days after study entry
    79 Outcomes of Patients With COVID-19 in the Intensive Care Unit: A National Observational Study (Mexico COVID-19 ICU Study)

    The objective of this study is to evaluate the clinical characteristics and outcomes of critically ill patients with COVID-19 admitted to the intensive care unit. A Multicenter Observational Study.

    NCT04336345
    Conditions
    1. Coronavirus Infections
    2. COVID-19
    3. Viral Pneumonia Human Coronavirus
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia, Viral Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Mortality 30 days following hospital admission

    Measure: Hospital mortality

    Time: 30 days

    Secondary Outcomes

    Description: The number of calendar days from the day of admission (counted as 1 day) to day of intensive care unit discharge

    Measure: Length of stay in the intensive care unit

    Time: Through study completion, an average of 30 days
    80 Accuracy and Inter-observer Variability of Lung Ultrasound in COVID-19 Pneumonia

    COVID-19 is a rapidly spreading and very contagious disease caused by a novel coronavirus that can lead to respiratory insufficiency. In many patients, the chest radiograph at first presentation be normal, and early low-dose CT-scan is advocated to diagnose viral pneumonia. Lung ultrasound (LUS) has similar diagnostic properties as CT for diagnosing pneumonia. However, it has the advantage that it can be performed at point-of-care, minimizing the need to transfer the patient, reducing the number of health care personnel and equipment that come in contact with the patient and thus potentially decrease the risk of spreading the infection. This study has the objective to examine the accuracy of lung ultrasound in patients with proven COVID-19 pneumonia.

    NCT04338568
    Conditions
    1. COVID-19 Pneumonia
    2. Lung Ultrasound
    Interventions
    1. Diagnostic Test: Lung ultrasound
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: The diagnostic accuracy of lung ultrasound is more than 90% compared to low-dose CT or chest X-ray for the detection of viral pneumonia in patients with COVID-19 infection.

    Measure: Accuracy of the diagnosis of interstitial syndrome by lung ultrasound

    Time: within 2 weeks after first subject included

    Description: The interobserver variability by lung ultrasound between the 2 observers for the diagnosis of interstitial syndrome by lung ultrasound is > 0.6 measured by the Kappa score

    Measure: Inter-observer variability

    Time: within 2 weeks after first subject included
    81 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
    82 French Multicentre Observational Study on SARS-Cov-2 Infections (COVID-19) ICU Management: the FRENCH CORONA Study

    Since December 2019, a new agent, the SARS-Cov-2 coronavirus has been rapidly spreading from China to other countries causing an international outbreak of respiratory illnesses named COVID-19. In France, the first cases have been reported at the end of January with more than 60000 cases reported since then. A significant proportion (20-30%) of hospitalized COVID-19 patients will be admitted to intensive care unit. However, few data are available for this special population in France. We conduct a large observational cohort of ICU suspected or proven COVID-19 patients that will enable to describe the initial management of COVID 19 patients admitted to ICU and to identify factors correlated to clinical outcome.

    NCT04340466
    Conditions
    1. Pneumonia, Viral
    2. Critically Ill
    3. Corona Virus Infection
    Interventions
    1. Other: No intervention
    MeSH:Infection Communicable Diseases Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia, Viral Pneumonia Critical Illness
    HPO:Pneumonia

    Primary Outcomes

    Description: Mortality at day 28

    Measure: Mortality at day 28

    Time: day 28

    Secondary Outcomes

    Description: severe complications (pulmonary embolism, acute kidney injury, myocarditis, cardiac arrest, liver failure, ventilator associated pneumonia) Yes / No

    Measure: severe complications

    Time: up to day 28

    Description: Delay in imaging in hours

    Measure: Imaging

    Time: day 1

    Description: delay in microbiological diagnosis in hours

    Measure: Delay in Microbiological diagnosis

    Time: day 1

    Description: Antiviral therapy Yes / no

    Measure: Antiviral therapy

    Time: up to day 28

    Description: Antibiotic therapy Yes / No

    Measure: Antibiotic therapy

    Time: day 28

    Description: Covid-19 treatments Yes / No

    Measure: Covid-19 treatments

    Time: up to day 28

    Description: number

    Measure: Patients receiving renal replacement therapy

    Time: up to day 28

    Description: number

    Measure: Patients receiving mechanical ventilation

    Time: up to day 28

    Description: Patient alive at day 28 : yes / No

    Measure: Vital status

    Time: day 28
    83 "Psychological Burden in ICU Survivors of Severe COVID-19 Pneumonia, Their Relatives and Their Healthcare Providers" "Impact Psychologique de l'épidémie COVID-19 Chez Les Patients, Familles et Soignants de Reanimation" "BURDENCOV"

    Coronavirus disease 2019 (COVID-19) is an infectious disease responsible for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The infection is highly contagious requiring restrictive and stressful measures for patients, family members and ICU healthcare providers. To avoid contagion, patient isolation has become the rule. For patients, these measures add stress to the ICU environment and deprive them of unrestricted family visits. Family members are not only left with fear but also many unanswered questions. In end-of-life situations, many family members are unable to say good-bye and unable to provide support to their loved-one throughout the process. The impact of exclusion or limited inclusion certainly needs to be explored. Moreover, ICU caregivers are having to face new challenges and to work in a unknown situation, juggling with both professional issues such as increased workload, working longer hours and safety issues, and personal issues such as child care and transport as well as family transmission of the virus. The main objective of this study is to demonstrate that the COVID-19 pandemic, as compared to seasonal flu and community acquired pneumonia, significantly increases post-traumatic stress disorder (PTSD) in family members of critically ill patients. PTSD-related symptoms will be assessed in family members using the IES-R (impact of event scale revised) during a telephone interview 90 days after ICU discharge. The IES-R is a 22-item self-report measure that assesses subjective distress caused by traumatic events. It will be compared across the three groups (COVID-19, FLU and CAP).

    NCT04341519
    Conditions
    1. Corona Virus Infection
    2. Post-traumatic Stress Disorder
    Interventions
    1. Behavioral: PTSD
    2. Behavioral: Burnout
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia Stress Disorders, Traumatic Stress Disorders, Post-Traumatic
    HPO:Pneumonia

    Primary Outcomes

    Description: Proportion of Family members with IES-R> 22 PTSD-related symptoms will be assessed in family members using the IES-R (impact of event scale revised) during a telephone interview 90 days after ICU discharge of corresponding patient. It si a scale ranging from 0 to 88. Weiss, DS.; Marmar, CR. The impact of event scale - revised. In: Wilson, JP.; Keane, TM., editors.Assessing psychological trauma and PTSD. New York: Guilford Press; 1997. p. 399-411

    Measure: PTSD Family members sup 22

    Time: 90 days

    Secondary Outcomes

    Description: Among Family members PTSD-related symptoms will be assessed in family members using the IES-R (impact of event scale revised)

    Measure: PTSD Family members

    Time: 90 days

    Description: Among Patients PTSD-related symptoms will be assessed in family members using the IES-R (impact of event scale revised)

    Measure: PTSD Patients

    Time: 90 days

    Description: Among healthcare providers PTSD-related symptoms will be assessed in family members using the IES-R (impact of event scale revised)

    Measure: PTSD healthcare providers

    Time: 2 months after official end of the Covid-19 peak

    Description: Among Family members Symptoms of anxiety and depression using the HADS scale

    Measure: HADS Family members

    Time: 90 days

    Description: Among Patients Symptoms of anxiety and depression using the HADS scale

    Measure: HADS Patients

    Time: 90 days

    Description: Among Patients Mental and physical health-related quality of life as assessed by the SF36

    Measure: SF36 Patients

    Time: 90 days

    Description: Among Family members Questionnaire describing their experience of the patient's ICU hospitalization

    Measure: Questionnaire Family members

    Time: 90 days

    Description: Among Patients Questionnaire describing their experience of the patient's ICU hospitalization

    Measure: Questionnaire Patients

    Time: 90 days

    Description: Among healthcare providers Questionnaire describing their experience of the patient's ICU hospitalization

    Measure: Questionnaire healthcare providers

    Time: 2 months after official end of the Covid-19 peak

    Description: Among healthSymptoms of burnout on MBI scale as assessed by the Maslash Burnout Inventorycare providers

    Measure: MBI healthcare providers

    Time: 2 months after official end of the Covid-19 peak

    Description: Job Strain as assessed by the Karasec instrument

    Measure: Karasec instrument healthcare providers

    Time: 2 months after official end of the Covid-19 peak
    84 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
    85 Prospective Descriptive Study on the Evolution of Pulmonary Ultrasound in Patients Hospitalized for Covid19

    Clinical thoracic ultrasound plays an important role in the exploration, diagnosis and follow-up of thoracic pathologies. The COVID (Coronavirus Disease) epidemic is leading to a large influx of patients in the emergency department with respiratory disorders. The rapid diagnosis of respiratory disorders in infected patients is important for further management. Chest ultrasound has already demonstrated its value in the diagnosis of pneumonia in the emergency department with superiority over chest X-ray. However, there is little data on the thoracic ultrasound semiology of viral pneumonia in general and of COVID in particular.

    NCT04341766
    Conditions
    1. Pneumonia, Viral
    2. COVID-19
    Interventions
    1. Other: No special intervention
    MeSH:Pneumonia, Viral Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: description of ultrasound abnormalities for Covid-19 patients

    Measure: Characteristics of pulmonary ultrasound for Covid-19 patients

    Time: Day one

    Secondary Outcomes

    Description: description of ultrasound abnormalities for Covid-19 patients

    Measure: Characteristics of pulmonary ultrasound for Covid-19 patients

    Time: Day 3

    Description: description of ultrasound abnormalities for Covid-19 patients

    Measure: Characteristics of pulmonary ultrasound for Covid-19 patients

    Time: Day 14

    Description: description of CT-scan abnormalities for Covid-19 patients

    Measure: Charateristics of pulmonary CT-scan for Covid-19 patients

    Time: Day 1

    Description: description of CT-scan abnormalities for Covid-19 patients

    Measure: Charateristics of pulmonary CT-scan for Covid-19 patients

    Time: Day 3

    Description: description of CT-scan abnormalities for Covid-19 patients

    Measure: Charateristics of pulmonary CT-scan for Covid-19 patients

    Time: Day 14
    86 Phase IIb Study to Evaluate the Efficacy and Safety of Chloroquine Diphosphate in the Treatment of Patients With Comorbidities, Without Severe Acute Respiratory Syndrome, Under the New Coronavirus (SARS-CoV2): a Double-blind, Randomized, Placebo-controlled Clinical Trial

    This is a double-blind, randomized, placebo-controlled clinical trial. A total of 210 individuals aged over 18 years old, without a diagnosis of severe respiratory disease, who came to the study site with clinical and radiological suspicion of SARS-CoV2, will be randomized into two treatment groups at a 1:1 ratio to receive a 5-day CQ diphosphate tablets or placebo (tablet without active ingredient produced with the same physical characteristics).

    NCT04342650
    Conditions
    1. COVID-19
    2. SARS-CoV Infection
    3. Severe Acute Respiratory Syndrome (SARS) Pneumonia
    4. Clinical Trial
    Interventions
    1. Drug: Chloroquine Diphosphate
    2. Drug: Placebo oral tablet
    MeSH:Infection Severe Acute Respiratory Syndrome Coronavirus Infections Pneumonia Syndrome
    HPO:Pneumonia

    Primary Outcomes

    Description: Evaluate if CQ diphosphate prevents the onset of SARS in patients on intervention group through standardized questionnaires.

    Measure: Proportion of patients with onset of severe acute respiratory syndrome (SARS)

    Time: 7 days after randomization

    Secondary Outcomes

    Description: Mortality rate between intervention and placebo group on days 7, 14, and 28 after randomization

    Measure: Mortality rate

    Time: after randomization, up to 28 days

    Description: Proportion of participants in need and duration of intensive care support after randomization

    Measure: Number of participants in need of intensive care support

    Time: during and after intervention, up to 28 days

    Description: Viral load change in blood and oropharyngeal swab samples

    Measure: Viral concentration

    Time: After randomization, up to 7 days

    Description: Incidence of serious adverse events during and after treatment

    Measure: Cumulative incidence of serious adverse events

    Time: During and after intervention, up to 28 days

    Description: Incidence of grade 3 and 4 adverse events during and after treatment

    Measure: Cumulative incidence of grade 3 and 4 adverse events

    Time: During and after intervention, up to 28 days

    Description: proportion of discontinuation or temporary suspension of treatment (for any reason)

    Measure: Proportion of patients with discontinued treatment

    Time: after randomization, up to 28 days

    Description: proportion of patients with increased levels of troponin I

    Measure: Incidence of cardiac lesions

    Time: after randomization, up to 120 days

    Description: proportion and magnitude of QTcF interval increases higher than 500ms

    Measure: Incidence of cardiac disfunctions

    Time: after randomization, up to 120 days

    Description: Changes measured on day 120 will be compared to baseline, through spirometry.

    Measure: Change in respiratory capacity

    Time: Day 120 after randomization
    87 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
    88 Efficacy of Injectable Methylprednisolone Sodium Succinate in the Treatment of Patients With Signs of Severe Acute Respiratory Syndrome Under the New Coronavirus (SARS-CoV2): a Phase IIb, Randomized, Double-blind, Placebo-controlled, Clinical Trial.

    This is a double-blind, randomized, placebo-controlled, phase IIb clinical trial to assess the efficacy of injectable methylprednisolone sodium succinate (MP) in patients with severe acute respiratory syndrome (SARS) in COVID-19 infection. A total of 416 individuals of both sexes, aged over 18 years old, with symptoms suggestive or confirmed diagnosis of severe acute respiratory syndrome (SARS), hospitalized at the Hospital and Pronto-Socorro Delphina Rinaldi Abdel Aziz (HPSDRAA), with clinical and radiological findings suggestive of SARS-CoV2 infection, will be randomized at a 1:1 ration to receive either MP (0.5mg/kg of weight, twice daily, for 5 days) or placebo (saline solution, twice daily, for 5 days).

    NCT04343729
    Conditions
    1. SARS-CoV Infection
    2. Severe Acute Respiratory Syndrome (SARS) Pneumonia
    Interventions
    1. Drug: Methylprednisolone Sodium Succinate
    2. Drug: Placebo solution
    MeSH:Severe Acute Respiratory Syndrome Coronavirus Infections Pneumonia Syndrome
    HPO:Pneumonia

    Primary Outcomes

    Description: Mortality rate on day 28, after randomization

    Measure: Mortality rate at day 28

    Time: on day 28, after randomization

    Secondary Outcomes

    Description: Proportion of patient that died on days 7, 14 and 28.

    Measure: Mortality rate on days 7, 14 and 28

    Time: after randomization, up to 28 days.

    Description: proportion of patients requiring orotracheal intubation

    Measure: Incidence of orotracheal intubation

    Time: after randomization, up to 7 days.

    Description: Proportion of patients with oxygenation index (PaO2 / FiO2) < 100 in 7 days.

    Measure: Change in oxygenation index

    Time: after randomization, up to 7 days.
    89 Corticosteroids During Covid-19 Viral Pneumonia Related to SARS-Cov-2 Infection

    Infection with the SARS-Cov-2 virus, responsible of severe acute respiratory distress syndrome (SARS), is an emerging infectious disease called Covid-19 and declared as pandemic by the World Health Organization on March 11, 2020. This pandemic is responsible of significant mortality. In France, several thousand patients are hospitalized in intensive care units, and their number continues to increase. Mortality during Covid-19 is mainly linked to acute respiratory distress syndrome, which frequency is estimated in France to occur in 6% of infected patients. Comorbidities such as cardiovascular conditions, obesity and diabetes increase susceptibility to severe forms of Covid-19 and associated mortality. Therapeutic management has three components: symptomatic management, including supplementary oxygen therapy and in case of respiratory distress mechanical ventilation; the antiviral approach; and immunomodulation, aiming at reducing inflammation associated with viral infection, which is considered to take part in severe presentations of the disease. During Covid-19 viral pneumonia related to SARS-COv-2, there is a significant release of pro-inflammatory cytokines in the acute phase of viral infection, which could participate in viral pneumonia lesions. In children with less mature immune system than adults, SARS-Cov-2 infection is less severe. The current prevailing assumption is that severe forms of Covid-19 may not only be related to high viral replication, but also to an excessive inflammatory response favoring acute lung injury and stimulating infection. The investigators hypothesize that early control of the excessive inflammatory response may help reducing the risk of acute respiratory distress syndrome. The investigators will evaluate the benefit, safety and tolerability of corticosteroid therapy to reduce the rate of subjects hospitalized for Covid-19 viral pneumonia who experience clinical worsening with a need of high-flow supplemental oxygen supplementation or transfer in intensive care units for respiratory support.

    NCT04344288
    Conditions
    1. Viral Pneumonia Human Coronavirus
    2. COVID-19
    Interventions
    1. Drug: Prednisone
    2. Other: Control group
    MeSH:Pneumonia, Viral Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: SpO2 <90% stabilized at rest and under not more than 5 L / min of supplemental oxygen using medium concentration mask. measured twice at 5-15 min intervalsThe average value of the two measurements will be calculated.

    Measure: Number of patients with a theoretical respiratory indication for transfer to intensive care unit evaluated by a SpO2 <90% stabilized at rest and under not more than 5 L / min of supplemental oxygen using medium concentration mask.

    Time: 7 days

    Secondary Outcomes

    Description: level1: not hospitalized no limited activities, level 7: death

    Measure: disease severity assessed on a 7-level ordinal scale

    Time: 7 days

    Measure: number of patients with a supplemental oxygen use

    Time: 7 days

    Description: Reduction of radiological signs on chest imaging

    Measure: radiological signs on chest imaging

    Time: 7 days

    Measure: number of patients transferred to intensive care unit

    Time: 21 days

    Measure: number of patients requiring invasive ventilation

    Time: 21 days

    Description: duration on days

    Measure: Duration of oxygen therapy

    Time: 21 days

    Measure: number of adverse events induced by corticosteroid treatment

    Time: 21 days

    Measure: number of patients with infections other than SARS-CoV-2

    Time: 21 days

    Measure: number of deaths

    Time: 21 days
    90 Management by Hyperbaric Oxygen Therapy of Patients With Hypoxaemic Pneumonia With SARS-CoV-2 (COVID-19)

    Several patients with hypoxaemic SARS-CoV2 pneumonia were able to benefit from hyperbaric oxygen treatment (HBOT) in China. In a clinical case published in the Chinese journal of hyperbaric medicine, treatment with repeated HBO sessions prevented admission to intensive care unit with mechanical ventilation in a patient aged 69 who presented with signs of respiratory decompensation. HBOT is the most powerful oxygenation modality in the body today. HBOT can dramatically increase the amount of dissolved oxygen in the blood. HBOT not only promotes blood transport but also its tissue delivery. Furthermore, HBOT has specific immunomodulatory properties, both humoral and cellular, making it possible, for example, to reduce the intensity of the inflammatory response and to stimulate antioxidant defenses by repeating sessions. A virucidal capacity of HBOT might also be involved. HBOT is generally regarded as safe with very few adverse events. Following this feedback, it is proposed in the context of crisis management related to SARS-CoV2 to assess the value of HBO treatment of patients with CoV2 pneumonia. Indeed, it seems essential to propose therapeutic strategies to limit the risk of respiratory decompensation requiring admission to intensive care unit for patients with SARS-CoV2 pneumonia.

    NCT04344431
    Conditions
    1. Covid-19
    Interventions
    1. Combination Product: Hyperbaric oxygen treatment (HBOT) i.e. inhalation of pressurized oxygen delivered by a hyperbaric chamber (drug/device)
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Time to normalize the oxygen requirement (oxygeno-dependence), i.e. allowing a pulse oximetry value in ambient air greater than or equal to 92% and / or arterial blood gas with a PaO2 value greater than 60mmHg in ambient air.

    Measure: Time to normalize the oxygen requirement (oxygeno-dependence)

    Time: 1 month

    Secondary Outcomes

    Description: Number of days with oxygen need, taking into account the predictors of bad outcome

    Measure: Days of hospitalization between the HBO group and the control group.

    Time: 1 month

    Description: Oxygen flow values to obtain a saturation by pulse oximetry greater than or equal to 92% between the OHB group and the control group.

    Measure: Oxygen flow values to obtain a saturation by pulse oximetry greater than or equal to 92% values between the HBO group and the control group.

    Time: 1 month

    Description: Days on invasive mechanical ventilation

    Measure: Days on invasive mechanical ventilation

    Time: 1 month

    Description: Mortality

    Measure: Mortality

    Time: 1 month

    Other Outcomes

    Description: Number of patients requiring a permanent O2 flow rate greater than 6 liters / min with high-speed nasal mask or oxygen therapy or with invasive or non-invasive ventilation

    Measure: Number of patients requiring a permanent O2 flow rate greater than 6 liters / min with high-speed nasal mask or oxygen therapy or with invasive or non-invasive ventilation

    Time: 1 month
    91 Microbial Etiology of Ventilator-associated Pneumonia (VAP) in COVID-19 Infected Patients

    National multicentric observational retrospective case-control study comparing the relative frequency of the various microorganisms responsible for VAP in patients infected or not by SARS-CoV-2 and their resistance to antibiotics.

    NCT04344509
    Conditions
    1. Ventilator Associated Pneumonia
    Interventions
    1. Other: Bacterial species isolated
    MeSH:Pneumonia, Ventilator-Associated Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Measure: Prevalence of the microorganisms responsible for VAP among patients infected or not by the SARS-CoV-2

    Time: 1 month

    Secondary Outcomes

    Measure: Prevalence of multi-drug resistant bacteria responsible for VAP among patients infected or not by the SARS-CoV-2

    Time: 1 month
    92 Dexamethasone and Oxygen Support Strategies in ICU Patients With Covid-19 pneumonia_COVIDICUS

    The main manifestation of COVID-19 is acute hypoxemic respiratory failure (AHRF). In patients with AHRF, the need for invasive mechanical ventilation is associated with high mortality. Two hypotheses will be tested in this study. The first hypothesis is the benefit of corticosteroid therapy on severe COVID-19 infection admitted in ICU in terms of survival. The second hypothesis is that, in the subset of patients free of mechanical ventilation at admission, either Continuous Positive Airway Pressure (CPAP) or High-Flow Nasal Oxygen (HFNO) allows to reduce intubation rate safely during COVID-19 related acute hypoxemic respiratory failure.

    NCT04344730
    Conditions
    1. Acute Hypoxemic Respiratory Failure
    2. COVID-19
    Interventions
    1. Drug: Dexamethasone injection
    2. Drug: placebo
    3. Procedure: conventional oxygen
    4. Procedure: CPAP
    5. Procedure: HFNO
    6. Procedure: mechanical ventilation
    MeSH:Pneumonia Respiratory Insufficiency
    HPO:Pneumonia

    Primary Outcomes

    Description: The time-to-death from all causes within the first 60 days after randomization.

    Measure: The time-to-death from all causes

    Time: day-60

    Description: the time to need for mechanical ventilation (MV), as defined by any of the 3 criteria for intubation within the first 28 days after randomization.

    Measure: The time to need for mechanical ventilation (MV)

    Time: day-28.

    Secondary Outcomes

    Description: The cycle threshold for SARS-CoV-2 PCR at baseline, day 7 and day 10 in samples of the same origin (preferably subglottic i.e. bronchoalveolar lavage or tracheal aspiration, otherwise nasopharyngeal swab)

    Measure: The viral load in the respiratory tract

    Time: day-10

    Description: Proportion of patients with at least one episode of any healthcare-associated infection between randomization and D28

    Measure: Number of patient with at least one episode of healthcare-associated infections

    Time: day-28

    Description: To compare the exposition to mechanical ventilation

    Measure: Number of days alive without mechanical ventilation

    Time: day-28

    Description: Changes in SOFA (Sepsis-related Organ Failure Assessment) score. (min = 0 for normal status max = 24 for worse status)

    Measure: Measure of SOFA score

    Time: day-28

    Description: to compare the exposition to renal replacement therapy

    Measure: Number of days alive without renal replacement therapy

    Time: day-28

    Description: To compare the lengths of ICU

    Measure: Lengths of ICU-stay

    Time: day-60

    Description: To compare the lengths of hospital-stay

    Measure: Lengths of hospital-stay

    Time: day-60

    Description: Proportion of patients with severe hypoxemia, which is defined as an oxygen saturation of less than 80% during the same interval during the interval between induction and 2 minutes after tracheal intubation

    Measure: Number of patients with severe hypoxemia,

    Time: day 60

    Description: Proportion of patients with cardiac arrest within 1 hour after intubation

    Measure: Number of patients with cardiac arrest within 1 hour after intubation

    Time: day 60
    93 Cohort Multiple Randomized Controlled Trials Open-label of Immune Modulatory Drugs and Other Treatments in COVID-19 Patients CORIMUNO-COAG Trial

    COVID-19 is a respiratory disease caused by a novel coronavirus (SARS-CoV-2) and causes substantial morbidity and mortality. There is currently no vaccine to prevent Covid-19 or infection with SARS-CoV-2 or therapeutic agent to treat COVID-19. This protocol CORIMUNO19-COAG will evaluate the efficacy and safety of active anticoagulation using heparin: Tinzaparin (INNOHEP®) or unfractionated heparin (Calciparine®, Héparine Sodique Choay®) in COVID-19 patients hospitalized in conventional or intensive care units. It will use a phase 2 randomized open-label multicentre clinical trial, where patients will be randomly allocated to anticoagulation versus Standard of Care.

    NCT04344756
    Conditions
    1. COVID19 Pneumonia
    Interventions
    1. Drug: Tinzaparin or unfractionated heparin
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: group 1

    Measure: Survival without ventilation (VNI or mechanical ventilation)

    Time: day 14

    Description: group 2

    Measure: ventilator free survival

    Time: day 28

    Secondary Outcomes

    Description: range from 0 (healthy) to 10 (death) values below or equal to 5 correspond to the absence of any oxygen supply beside nasal or facial mask

    Measure: World Health Organisation(WHO) progression scale ≤5

    Time: day 4

    Description: range from 0 (healthy) to 10 (death)

    Measure: World Health Organisation(WHO) progression scale

    Time: day 4, 7 and 14

    Measure: overall survival

    Time: day 14, 28 and 90

    Measure: Length of hospital stay

    Time: day 28

    Measure: Length of ICU stay

    Time: day 28

    Measure: time to oxygenation supply independency

    Time: day 28

    Measure: time to ventilator (non invasive or invasive)

    Time: day 28

    Description: according to Acute Kidney Injury (AKIN) classification system

    Measure: rate of acute kidney injury

    Time: day 28

    Measure: time to Renal Replacement Therapy (RRT) initiation

    Time: day 28

    Description: confirmed by objective testing

    Measure: rate of clinically overt pulmonary embolism or proximal deep vein thrombosis

    Time: day 14 and day 90

    Description: confirmed by objective testing

    Measure: Rate of clinically overt arterial thrombosis

    Time: day 14 and day 90

    Measure: Rate of unscheduled central venous catheter replacement for catheter dysfunction

    Time: day 28

    Description: as a thrombus extending from the catheter into the lumen of the deep vein where the catheter is inserted diagnosed with radiologic imaging in case of a clinical suspicion of upper/lower limb DVT or pulmonary embolism or compulsory catheter removal

    Measure: Rate of central venous catheter-related deep vein thrombosis (CVC-DVT)

    Time: day 28

    Measure: Rate of unscheduled indwelling arterial catheter replacement for catheter dysfunction

    Time: day 28

    Measure: Rate of acute clotting leading to the replacement the renal replacement therapy circuit stratified by regional citrate anticoagulation or not

    Time: day 28

    Measure: Time to acute clot formation within the oxygenator (acute oxygenator thrombosis, AOT) leading to the exchange of an extracorporeal membrane oxygenation (ECMO) system

    Time: day 28

    Measure: Time to acute clot formation within the pump head (pump head thrombosis, PHT) leading to the exchange of an extracorporeal membrane oxygenation (ECMO) system

    Time: day 28

    Measure: Incidence of adverse events

    Time: day 28
    94 Cohort Multiple Randomized Controlled Trials Open-label of Immune Modulatory Drugs and Other Treatments in COVID-19 Patients CORIMUNO-19- BEVA Trial

    Bevacizumab, ZERIBEV® (Pfizer)/AVASTIN® (Roche) 25 mg/ml ®, is a recombinant humanised monoclonal IgG1 antibody It seems interesting to use bevacizumab in severe patients infected with SARS-CoV-2 requiring hospitalization in conventional unit or in ICU. This protocol CORIMUNO19-BEVA will evaluate the efficacy and safety of AVASTIN®/ ZERIBEV® (bevacizumab) COVID-19 patients hospitalized in conventional units. This phase 2 randomized clinical trial aimed at evaluating the efficacy and safety of AVASTIN®/ ZERIBEV® (bevacizumab) alone versus standard of care (SoC) in patients hospitalized in conventional units.

    NCT04344782
    Conditions
    1. COVID19 Pneumonia
    Interventions
    1. Drug: Bevacizumab Injection
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Measure: Proportion of surviving patients without need for intubation for respiratory support

    Time: day 14

    Secondary Outcomes

    Description: value of a healthy individual occurs between 95 - 100

    Measure: Saturation of Oxygen in the blood (SaO2)

    Time: day 14

    Description: value of a healthy individual occurs between 75-100 mmHg

    Measure: Arterial oxygen partial pressure (paO2)

    Time: day 14

    Description: Normal level should be >500 Index of severity of acute respiratory distress syndrome (ARDS) mild if 200-300 moderate if 100-200 severe if < 200

    Measure: Ratio of arterial oxygen partial pressure to fractional inspired oxygen (paO2/FiO2)

    Time: day 14

    Description: based on a Likert scale with scores ranging from 1 to 5 (1-definitely no; 2-probably no; 3-equivocal; 4-probably yes; 5-definitely yes)

    Measure: CT-scan score

    Time: day 14

    Description: measured on an visual analog scale (VAS), ranging from 0 (no dyspnea) to 10 (major dyspnea)

    Measure: dyspnea

    Time: day 28

    Measure: overall survival

    Time: day 14 and 28

    Measure: admissionn to the intensive care unit (ICU)

    Time: day 14 and day 28

    Measure: incidence of mechanical ventilation

    Time: day 14 and day 28

    Measure: hospital length of stay

    Time: day 28

    Measure: incidence of adverse event

    Time: day 28

    Measure: VEGF plasma concentration

    Time: day 28
    95 Chloroquine Phosphate Against Infection by the Novel Coronavirus SARS-CoV-2 (COVID-19): The HOPE Open-Label, Non Randomized Clinical Trial

    This is an open label clinical study to evaluate the activity of chloroquine phosphate in patients with SARS-CoV-2 virus infection. The study aims to document possible prevention of pneumonia in patients staying at home and in improving the symptoms of SARS-CoV-2 pneumonia in patients who will be hospitalised.

    NCT04344951
    Conditions
    1. Pneumonia, Viral
    2. Covid-19
    Interventions
    1. Drug: UNIKINON (Chloroquine phosphate) 200mg tablets
    MeSH:Pneumonia, Viral Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Achieving 50% reduction in symptom score for patients with lower respiratory tract infection on day 8 visit from study initiation.

    Measure: 50% reduction in symptom score for patients with lower respiratory tract infection

    Time: Day 8 visit from study initiation

    Description: Lack of progression to lower respiratory tract infection in patients enrolled in the study due to upper respiratory tract infection on day 8 visit from study initiation.

    Measure: Lack of progression for patients with upper respiratory tract infection

    Time: Day 8 visit from study initiation

    Secondary Outcomes

    Description: Lower respiratory tract infection rating takes place. The symptoms checked are: Cough, Chest pain, Dyspnea, expectoration. For each symptom score is given from 0 to 3 depending on the intensity and they are summed.

    Measure: Comparison of the primary endpoint with respective patients not receiving the treatment

    Time: Day 14 visit from study initiation

    Description: It is defined as the presence of both of the following: Respiratory quotient (pO2 / FiO2) less than 150 Need for treatment with CPAP or mechanical ventilation

    Measure: Serious respiratory failure until day 14. This will be compared with respective patients not receiving the treatment.

    Time: Day 14 visit from study initiation

    Description: Frequency of AEs and SAEs

    Measure: Frequency of AEs and SAEs

    Time: Day 14 visit from study initiation
    96 Efficacy and Safety of Treatment With Convalescent Plasma for Adults With COVID-19 Pneumonia. A Double-blinded, Randomized, Multicenter Placebo-controlled Trial

    CCAP is an investigator-initiated multicentre, randomized, double blinded, placebo-controlled trial, which aims to assess the safety and efficacy of treatment with convalescent plasma for patients with moderate-severe COVID-19. Participants will be randomized 2:1 to two parallel treatment arms: Convalescent plasma, and intravenous placebo. Primary outcome is a composite endpoint of all-cause mortality or need of invasive mechanical ventilation up to 28 days.

    NCT04345289
    Conditions
    1. COVID
    2. Corona Virus Infection
    3. Viral Pneumonia
    Interventions
    1. Biological: Convalescent anti-SARS-CoV-2 plasma
    2. Other: Infusion placebo
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia, Viral Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Composite outcome

    Measure: All-cause mortality or need of invasive mechanical ventilation

    Time: 28 days

    Secondary Outcomes

    Description: Number of participants with adverse events with possible relation to study drug

    Measure: Frequency of adverse events

    Time: 90 days

    Description: Number of participants with serious adverse events according to International Council of Harmonisation-Good Clinical Practice (ICH-GCP) guidelines

    Measure: Frequency of severe adverse events

    Time: 90 days

    Description: Number of days to improvement of at least 2 categories relative to baseline on the ordinal scale. Categories are as follows: Death; Hospitalized, in intensive care requiring Extracorporeal Membrane Oxygenation (ECMO) or mechanical ventilation; Hospitalized, on non-invasive ventilation or high-flow oxygen device; Hospitalized, requiring supplemental oxygen; Hospitalized, not requiring supplemental oxygen; Not hospitalized, limitation on activities and/or requiring home oxygen; Not hospitalized, no limitations on activities

    Measure: Time to improvement of at least 2 categories relative to baseline on a 7-category ordinal scale of clinical status

    Time: 90 days

    Description: Number of days without mechanical ventilation

    Measure: Ventilator-free days

    Time: 28 days

    Description: Number of days without organ-failure

    Measure: Organ failure-free days

    Time: 28 days

    Description: Number of days in ICU

    Measure: Duration of ICU stay

    Time: 90 days

    Description: Number of deaths by any cause

    Measure: Mortality rate

    Time: 7, 14, 21, 28 and 90 days

    Description: Days from the date of hospital admission for COVID-19 to the date of discharge

    Measure: Length of hospital stay

    Time: 90 days

    Description: Days requiring supplement oxygen

    Measure: Duration of supplemental oxygen

    Time: 90 days
    97 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
    98 Randomized Trial Assessing Efficacy and Safety of Hydroxychloroquine Plus Azithromycin Versus Hydroxychloroquine for Hospitalized Adults With COVID-19 Pneumonia

    Double blinded randomized clinical trial designed to evaluate the efficacy and safety of hydroxychloroquine combined with azithromycin compared to hydroxychloroquine monotherapy in patients hospitalized with confirmed COVID-19 pneumonia.

    NCT04345861
    Conditions
    1. Coronavirus Infection
    2. Pneumonia, Viral
    Interventions
    1. Drug: Hydroxychloroquine + placebo
    2. Drug: hydroxychloroquine + azithromycin
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia, Viral Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Evaluation of the clinical status of patient defined by the Ordinal Scale of 7 points (score range from 1 to 7 , with 7 being the worst score)

    Measure: Time to clinical improvement of at least 1 level on the ordinal scale between Day 1 (day of the first administration of study drug) to Day 11 (day after last day of treatment).

    Time: up to Day 11

    Secondary Outcomes

    Description: Evaluation of the clinical status of patient defined by the Ordinal Scale of 7 points at day 15 and day 29

    Measure: Clinical status assessed by ordinal scale

    Time: up to Day 29

    Description: Necessity for transfer to Intensive care unit

    Measure: transfer to ICU

    Time: up to Day 29

    Description: days from admission to hospital discharge

    Measure: Length of hospital day

    Time: up to Day 29

    Description: incidence of all-cause mortality

    Measure: Hospital Mortality

    Time: Day 29

    Description: Need to mechanical ventilation

    Measure: Need to Mechanical Ventilation

    Time: up to Day 29

    Description: adverse reactions

    Measure: Occurence of grade 3-4 adverse event

    Time: up to Day 29

    Description: ECG

    Measure: QTc Lengthening

    Time: up to Day 11

    Description: Thoracic CT scan : number and size of ground-glass opacifications on day 1 and day 11 Two independent pulmonary imagery experts will assess abnormalities according to a standardized framework

    Measure: Evolution of pulmonary CT scan images

    Time: up to Day 11
    99 Prospective, Phase II, Randomized, Open-label, Parallel Group Study to Evaluate the Efficacy of Hydroxychloroquine Together With Baricitinib, Imatinib or Early Lopinavir / Ritonavir in Patients With SARS Cov2 Pneumonia

    In absence of vaccine and medications specifically designed to treat SARS-CoV-2 disease, identifying treatment options is critical at this time to control the disease outbreak. For this, we have designed a phase II trial of efficacy and safety with 3 branches of different combinations of treatment to identify which is the best early treatment option for patients with pneumonia due to SARS-CoV-2 (Covid-19) Identifying treatment options as early as possible is critical to the SARS-CoV-2 outbreak response. Currently, there is no approved vaccine for the disease and the treatments being used are not specifically designed for the SARS-CoV-2 virus, but are different groups of drugs used for other pathologies with mechanisms of action that justify their use because they inhibit entry of the virus into virus cells or proteases. The study aims to compare lopinavir / ritonavir (200 /50), imatinib 400mg, baricitinib 4mg, in combination with hydroxychloroquine 200mg, administered for 7 days in the setting of SARS-CoV-2 pneumonia treatment. Patients who meet inclusion criteria and do not have any exclusion criteria will be randomized to receive open treatment 1:1:1

    NCT04346147
    Conditions
    1. COVID-19 Pneumonia
    Interventions
    1. Drug: Hidroxicloroquine
    2. Drug: Lopinavir/ritonavir
    3. Drug: Imatinib tablets
    4. Drug: Baricitinib Oral Tablet
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: time from inclusion to improvement by 2 points on the "seven-category ordinal scale" or high, whichever comes first

    Measure: time to clinical improvement

    Time: baseline to day 14

    Secondary Outcomes

    Description: number of serious adverse effects and premature discontinuation of treatment

    Measure: Safety of treatments

    Time: through study completion, an average of 1 month

    Description: Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v5.0

    Measure: Tolerability of treatments

    Time: during treatment and up to 30 days after the last treatment dose

    Other Outcomes

    Description: Possible biomarkers and genetic markers of susceptibility to SARS-CoV-2 using high-performance techniques with serum DNA from the participants

    Measure: Biomarkers and genetic markers of susceptibility to SARS-CoV-2

    Time: baseline
    100 An Open-label Randomized Multicenter Study to Evaluate the Efficacy of Early Administration of Tocilizumab (TCZ) in Patients With COVID-19 Pneumonia

    The clinical study aims at assessing whether early administration of Tocilizumab compared to late administration of Tocilizumab can reduce the number of patients with COVID-19 pneumonia who require mechanical ventilation. The clinical study includes patients with recent-onset COVID-19 pneumonia who require hospital care, but not invasive or semi-invasive mechanical ventilation procedures.

    NCT04346355
    Conditions
    1. COVID-19 Pneumonia
    Interventions
    1. Drug: Tocilizumab
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Entry into Intensive Care with invasive mechanical ventilation or death from any cause or clinical aggravation documented by the finding of a PaO2 / FiO2 ratio <150mm / Hg confirmed by a second arterial blood gas (ABG) measurement within four hours

    Measure: Entry into Intensive Care with invasive mechanical ventilation or death from any cause or clinical aggravation

    Time: two weeks from participants' allocation to study arm

    Secondary Outcomes

    Description: Death

    Measure: Death from any cause

    Time: Two weeks from participants' allocation to study arm

    Description: Adverse events (AE) classified according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) scale

    Measure: Tocilizumab toxicity

    Time: Two weeks from participants' allocation to study arm

    Description: Levels of ferritin, lactate dehydrogenase and D-dimer and their correlation with the effectiveness of the treatment

    Measure: Levels of interleukin-6 and C-reactive protein (CRP) and their correlation with the effectiveness of the treatment

    Time: Two weeks from participants' allocation to study arm

    Description: Changes from baseline of the PaO2 / FiO2 ratio

    Measure: Evaluate the progress of the PaO2 / FiO2 ratio

    Time: Two weeks from participants' allocation to study arm

    Description: Changes from baseline of the lymphocyte count

    Measure: Evaluate the trend over time of the lymphocyte count

    Time: Two weeks from participants' allocation to study arm
    101 A Pilot Study to Explore the Efficacy and Safety of Rescue Theraphy With Antibodies From Convalescent Patients Obtained With Double -Filtration Plasmapheresis (DFPP) and Infused in Critically Ill Ventilated Patients With Coronavirus Disease 2019 (COVID-19)

    The 2019 outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or COVID 19), which originated in Wuhan, China, has become a major concern all over the world. Convalescent plasma or immunoglobulins have been used as a last resort to improve the survival rate of patients with SARS whose condition continued to deteriorate despite any attempted treatment.. Moreover, several studies showed a shorter hospital stay and lower mortality in patients treated with convalescent plasma than those who were not treated with convalescent plasma. Evidence shows that convalescent plasma from patients who have recovered from viral infections can be used effectively as a treatment of patients with active disease. The use of solutions enriched of antiviral antibodies has several important advantages over the convalescent plasma including the high level of neutralizing antibodies supplied. Plasma-exchange is expensive and requires large volumes of substitution fluid. Albumin is better tolerated and less expensive, but exchanges using albumin solutions increase the risk of bleeding because of progressive coagulation factor depletion. With either albumin or fresh frozen plasma, increasing the risk of cardiovascular instability in the plasma donor and in the recipient, which can be detrimental in a critically ill patient with COVID 19 pneumonia. The aforementioned limitations of plasma therapy can be overcome by using selective apheresis methods, such as double-filtration plasmapheresis (DFPP).DFPP is a modality of plasma purification that performs an initial plasma separation from blood, and the subsequent separation of specific molecules, on the basis of their specific molecular weight (cut-off), by using a fractionation filter. The Fractionation Filter 2A20, because of its membrane sieving cut-off, retains larger molecules and returns plasma along with smaller molecules to the circulation, including the major part of the albumin. The selection of the membrane 2A20 is related to the appropriate Sieving Coefficient for IgG that allows to efficiently collect antibodies from patients which are recovered from COVID-19, with negligible fluid losses and limited removal of albumin. The total amount of antibodies obtained during one DFPP session exceeds by three to four times the total amount provided to recipients with one unit of plasma obtained during one plasma-exchange session from one COVID-19 convalescent donor. This should result in more effective viral inhibition and larger benefit for the patient achieved with one unit of enriched immunoglobulin solution obtained with DFPP than with one unit of plasma obtained with plasma exchange. These observations provide the background for a pilot study aimed to explore whether the infusion of antibodies obtained with one single DFPP procedure from voluntary convalescent donors could offer an effective and safe therapeutic option for critically ill patients with severe coronavirus (COVID-19) pneumonia requiring mechanical ventilation.

    NCT04346589
    Conditions
    1. Pneumonia, Ventilator-Associated
    2. Coronavirus Infection
    Interventions
    1. Biological: Anti-coronavirus antibodies (immunoglobulins)obtained with DFPP from convalescent patients
    MeSH:Pneumonia, Ventilator-Associated Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Measure: Number of mechanical ventilation days.

    Time: Through study completion, an average of 6 months.

    Secondary Outcomes

    Measure: Survival

    Time: Through study completion, an average of 6 months.

    Measure: Shift to Continuous Positive Airway Pressure (CPAP) ventilation

    Time: Through study completion, an average of 6 months.

    Measure: Referral to a sub-intensive care unit or discharge

    Time: Through study completion, an average of 6 months.

    Measure: Viral titer

    Time: Changes from before Ig administration, one day and one week after Ig administration and every week after discharge from the intensive care unit through study completion, an average of 6 months.

    Measure: Anti COVID 19 IgG antibodies

    Time: Changes from before Ig administration, one day and one week after Ig administration and every week after discharge from the intensive care unit through study completion, an average of 6 months.

    Measure: Anti COVID 19 IgM antibodies

    Time: Changes from before Ig administration, one day and one week after Ig administration and every week after discharge from the intensive care unit through study completion, an average of 6 months.

    Description: Marker of complement activation in plasma.

    Measure: C5a concentration

    Time: Changes from before Ig administration, one day and one week after Ig administration and every week after discharge from the intensive care unit through study completion, an average of 6 months.

    Description: Marker of complement activation in plasma.

    Measure: C3a concentration

    Time: Changes from before Ig administration, one day and one week after Ig administration and every week after discharge from the intensive care unit through study completion, an average of 6 months.

    Description: Marker of complement activation in plasma.

    Measure: Serum C5b-9 concentration

    Time: Changes from before Ig administration, one day and one week after Ig administration and every week after discharge from the intensive care unit through study completion, an average of 6 months.
    102 An Open Randomized Study of the Effectiveness of the Drug Dalargin for the Prevention and Treatment of Symptoms of Pulmonary Complications in Patients With Coronavirus Infection (SARS-COVID-19)

    The purpose of the study is to evaluate an effectiveness of the drug Dalargin for the prevention and treatment of severe pulmonary complications symptoms associated with severe and critical coronavirus infection cases (SARS COVID19, expanded as Severe acute respiratory syndrome Cоrona Virus Disease 2019 ). Test drug that will be administered to patients are: - Dalargin, solution for inhalation administration, - Dalargin, solution for intravenous and intramuscular administration.

    NCT04346693
    Conditions
    1. Acute Respiratory Tract Infection
    2. Acute Respiratory Insufficiency
    3. Pneumonia
    4. Septic Shock
    5. Hypoxemia
    Interventions
    1. Procedure: Standard therapy recommended by the Ministry of Health of the Russian Federation.
    2. Procedure: Standard therapy recommended by the Ministry of Health of the Russian Federation and Dalargin intramuscular injection
    3. Procedure: Standard therapy recommended by the Ministry of Health of the Russian Federation and Dalargin inhalation
    4. Procedure: Standard therapy recommended by the Ministry of Health of the Russian Federation and Dalargin intramuscular injection combined with Dalargin inhalation
    MeSH:Infection Respiratory Tract Infections Pneumonia Respiratory Insufficiency Pulmonary Valve Insufficiency Hypoxia
    HPO:Hypoxemia Pneumonia Pulmonary insufficiency Respiratory tract infection

    Primary Outcomes

    Description: Estimated by Polymerase chain reaction (PCR)

    Measure: The change of viral load in patients with SARS-COVID-19.

    Time: Upon patient inclusion in the study, after 96 hours and on the 10day;

    Description: Assessed through the entire patient participation in the study

    Measure: The frequency of development of Acute Respiratory Distress Syndrome (ADRS)

    Time: up to 10 days

    Description: The number of days a patient is hospitalized

    Measure: Duration of hospitalization

    Time: up to 10 days

    Description: Early mortality from all causes will be estimated

    Measure: The frequency of early mortality

    Time: up to 30 days

    Description: Late mortality from all causes will be estimated

    Measure: The frequency of late mortality

    Time: up to 90 days

    Description: Clinical status at the time of completion of participation in the study will be estimated based upon the following criteria: Death; Hospitalization is extended, on invasive mechanical ventilation of the lungs with extracorporeal membrane oxygenation; Hospitalization extended, on non-invasive ventilation; Hospitalization is extended, needs additional oxygen; Hospitalization is extended, additional oxygen is not required; Discharged.

    Measure: Clinical status at the time of completion of participation in the study

    Time: an average of 10 days
    103 An Open Randomized Study of the Effectiveness of the Drug Mefloquine, Tablets 250 mg, Produced by FSUE SPC "Farmzashita" of the Federal Medical Biological Agency, FMBA of Russia (Russia) for the Treatment of Patients With COVID19

    Study of the effectiveness and safety of the drug Mefloquine, tablets 250 mg, produced by FSUE "SPC" Farmzaschita " FMBA of Russia (Russia), in comparison with the drug Hydroxychloroquine, tablets 200 mg, for the treatment of patients with coronavirus infection, in the "off-label" mode, to make a decision on the possibility of expanding the indications for use.

    NCT04347031
    Conditions
    1. Pneumonia, Viral
    2. Respiratory Failure
    Interventions
    1. Drug: Mefloquine
    2. Drug: Hydroxychloroquine
    3. Combination Product: Mefloquine + azithromycin + / - tocilizumab
    4. Combination Product: Hydroxychloroquine + azithromycin + / - tocilizumab
    MeSH:Pneumonia, Viral Pneumonia Respiratory Insufficiency
    HPO:Pneumonia

    Primary Outcomes

    Description: The number of patients with development of respiratory failure requiring transfer to the ICU.

    Measure: 1st primary endpoint for group 1

    Time: up to 10 days

    Description: The period of clinical recovery.

    Measure: 2nd primary endpoint for group 1

    Time: up to 10 days

    Description: The period of clinical recovery.

    Measure: 1st primary endpoint for group 2

    Time: up to 10 days

    Description: Frequency of fatal outcomes associated with coronavirus infection disease (COVID19)

    Measure: 2nd primary endpoint for group 2

    Time: through study completion, an average of 3 months

    Secondary Outcomes

    Description: A change in viral load by conducting PCR assay through different timeframes

    Measure: 1st secondary endpoint for group 1

    Time: on days 5 and 10

    Description: Frequency of clinical cure on day 10 from the start of therapy

    Measure: 2nd secondary endpoint for group 1

    Time: on day 10

    Description: The retention time of the reaction temperature from the start of the treatment.

    Measure: 3d secondary endpoint for group 1

    Time: up to 10 days

    Description: Concentration of C-reactive protein in blood plasma.

    Measure: 4th secondary endpoint for group 1

    Time: up to 10 days

    Description: Respiratory index.

    Measure: 5th secondary endpoint for group 1

    Time: up to 10 days

    Description: Frequency appearance unwanted phenomena and serious unwanted phenomena

    Measure: 6th secondary endpoint for group 1

    Time: up to 10 days

    Description: A change in viral load by conducting PCR assay through different timeframes

    Measure: 1st secondary endpoint for group 2

    Time: on days 5 and 10

    Description: Respiratory index.

    Measure: 2nd secondary endpoint for group 2

    Time: up to 10 days

    Description: The retention time of the reaction temperature from the start of treatment.

    Measure: 3d secondary endpoint for group 2

    Time: up to 10 days

    Description: Concentration of C-reactive protein in blood plasma.

    Measure: 4th secondary endpoint for group 2

    Time: up to 10 days

    Description: Number of patients required transition to alternative therapy schedule

    Measure: 5th secondary endpoint for group 2

    Time: up to 10 days

    Description: Frequency of adverse events and serious adverse events

    Measure: 6th secondary endpoint for group 2

    Time: up to 10 days
    104 EVALUATION OF THE EFFICACY OF THE HYDROXYCHLOROQUINE-AZITHROMYCIN COMBINATION IN THE IN THE PREVENTION OF COVID-19 RELATED SDRA

    Since end of December, a new coronavirus, close to the 2002 SARS coronavirus, cause serious pneumonias throughout world. There is currently no strong evidence of an efficient specific treatment. Hydroxychloroquine is an old chloroquine-derived drug, prescribed for auto-immune disorders. It has shown efficacy against Sars-CoV-2 in vitro. Some studies showed that Hydroxychloroquine might improve the clinical status of Sars-CoV-2 infected patients. Azithromycin is a macrolide antibiotic, with immunomodulatory properties. Adding Azithromycin to a hydroxychloroquine-based treatment showed an apparent accelerated viral clearance in infected patients. This study wants to evaluate the clinical impact of adding Azithromycin to Hydroxychloroquine in the treatment of Sars-CoV-2 pneumonia

    NCT04347512
    Conditions
    1. Sars-CoV-2, Community-Acquired Pneumonia,COVID-19
    Interventions
    1. Drug: Hydroxychloroquine and azithromycin treatment arm.
    2. Drug: Hydroxychloroquine
    3. Drug: Control arm
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: A significant hypoxemia is an arterial partial pressure of oxygen of less than 60 mmHg despite an oxygen flow of more than 6 L/min, patient at rest.

    Measure: Rate of patients reaching a significant hypoxemia, in each arms.

    Time: From day 0 to day 7
    105 How COVID-19 Virus Outbreak Affects Antimicrobial Resistance in a Low-middle-income Country's ICU?

    A previous study showed a high incidence of ventilator-associated pneumonia to multidrug resistant pathogens in our ICU. That has been related to lack of compliance to hand hygiene among health care providers in ou ICU.

    NCT04348227
    Conditions
    1. Ventilator Associated Pneumonia
    Interventions
    1. Behavioral: Enhanced hygiene measures
    MeSH:Pneumonia, Ventilator-Associated Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Incidence of MDR bacteria in endotracheal aspirates

    Measure: MDR pathogens in endotracheal aspirates

    Time: 1 year

    Secondary Outcomes

    Description: Incidence of microorganisms in endotracheal aspirates

    Measure: Microorganisms in endotracheal aspirates

    Time: 1 year
    106 Observational Study on the Use of Canakinumab Administered Subcutaneously in the Treatment of Patients With COVID-19 Pneumonia

    The study is configured as a retrospective and prospective observational study. The study will be multi-center and will involve all COVID-19 pneumonia patients treated with canakinumab administered subcutaneously.

    NCT04348448
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Canakinumab 150 MG/ML [Ilaris]
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: percentage of patients treated with canakinumab sc who do not require intensive care treatment during hospitalization for COVID-19

    Measure: intensive care treatment

    Time: 9 months

    Secondary Outcomes

    Description: ICU stay times

    Measure: ICU stay times

    Time: 9 months

    Description: percentage of patients who died 1 month after treatment

    Measure: % died after 1 month after treatment

    Time: 9 months

    Description: time of hospitalization

    Measure: hospitalization

    Time: 9 months

    Description: number of adverse event

    Measure: adverse event

    Time: 9 months
    107 Open Label Randomized Controlled Trial of Ultraprotective Ventilation Without Extracorporeal Circulation in Patients With COVID 19 Pneumonia and Moderate to Severe ARDS

    Mortality of COVID-19 pneumonia with acute respiratory distress syndrome (ARDS) is extremely high in preliminary reports amounting to 50-60%. Duration of mechanical ventilation in these patients appears to exceed standard duration of mechanical ventilation in non-COVID-19 ARDS patients, suggesting that COVID-19 patients may be particularly at risk for ventilator-induced lung injury. Treatment of COVID-19 ARDS patients is to date mainly supportive with protective mechanical ventilation (ventilation with low tidal volume (VT) i.e. 6 ml/kg of predicted body weight (PBW) and plateau pressure control below 30 cm H2O). Mechanical ventilation with VT reduction below 6 ml/kg PBW in ARDS may reduce alveolar strain, driving pressure and hence ventilator-induced lung injury. Investigators recently performed a multicenter pilot study on 34 moderately severe to severe ARDS patients. This study demonstrated that ultraprotective ventilation with ultra-low VT (≤4.2 ml/kg PBW) without extracorporeal circulation may be applied in approximately 2/3 of the patients, with a 4 cmH2O median reduction in driving pressure, at the price of transient episodes of severe acidosis in approximately 1/3 of the patients. Investigators hypothesized that ultraprotective ventilation without extracorporeal circulation may reduce the mortality at day-90 and increase the number of days free from mechanical ventilation (VFD) at day-60, as compared to protective ventilation.

    NCT04349618
    Conditions
    1. Acute Respiratory Distress Syndrome
    2. COVID19
    3. Sars-CoV2
    4. Pneumonia
    Interventions
    1. Other: PROTECTIVE VENTILATION
    2. Other: ULTRAPROTECTIVE VENTILATION
    MeSH:Pneumonia Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury
    HPO:Pneumonia

    Primary Outcomes

    Description: For an alive patient at day 90, the score will be built as follow: a value +1 will be given for comparisons to dead patients and alive patients with a lower number of VFD. For comparisons to alive patients with a higher number of VFD a value -1 will be given and in case of identical number of VFD a value 0 will be given. For a dead patient a value -1 will be given for comparisons to alive patients and 0 for comparisons to dead patients. For a given patients the score will correspond to the sum of values resulting to the comparison to all patients of the other group. A higher score indicates a more favorable result.

    Measure: A composite score based on all-cause mortality and the number of ventilator free-days (VFD)

    Time: Day 90

    Secondary Outcomes

    Description: All-cause mortality with analysis in intention to treat, i.e. each patient will be analyzed in his initial randomization group regardless of whether the allocated strategy was effectively applied or not.

    Measure: All-cause mortality (intention to treat)

    Time: 90-day after inclusion

    Description: VFD will be computed as follows from the day of inclusion: VFD= 0 if the patient dies between inclusion and day 60 VFD = 60-x if the patient is successfully weaned from invasive mechanical ventilation x days after inclusion. Successful weaning from mechanical ventilation is defined by extubation without reintubation within at least 48 hours (or weaning from mechanical ventilation for at least 48 hours in patients with tracheostomy) VFD= 0 if the patient is mechanically ventilated for more than 60 days after inclusion

    Measure: Ventilator-free days (VFD)

    Time: day 60 after inclusion

    Description: Per protocol analysis will be carried out by comparing the group of patients in whom median daily tidal volume from inclusion to weaning of deep sedation will be lower of equal to 4.2 ml/kg of predicted body weight to the group of patients in whom median tidal volume from inclusion to weaning of deep sedation will be greater than 4.2 ml/kg of predicted body weight, whatever the patients' initial randomization group. Weaning of deep sedation is defined by a Richmond Agitation Sedation (RASS) score greater than -3 for at least 48 hours.

    Measure: All-cause mortality with per protocol analysis

    Time: 90-day

    Description: Successful extubation is defined by extubation without reintubation within at least 48 hours (or weaning from mechanical ventilation for at least 48 hours in patients with tracheostomy) Data will be right censored at 60 days and death will be taken into account as a competing risk.

    Measure: Time to successful extubation

    Time: 60 days

    Description: Data will be right censored at 90 days and death will be taken into account as a competing risk.

    Measure: Length of hospital stay

    Time: 90 days

    Description: Weaning of deep sedation is defined by a Richmond Agitation Sedation (RASS) score greater than -3 for at least 48 hours.

    Measure: Respiratory parameters assessed daily from inclusion to weaning of deep sedation or 14 days whichever comes first

    Time: 14 days

    Description: Doses of the following drugs used for deep sedation will be assessed daily: midazolam, propofol and opioid. Opioid dose will be expressed as morphine equivalent with the following conversion factor: 1µg of sufentanil = 10 µg of fentanyl = 1 mg of morphine

    Measure: Daily sedation dose during the first 14 days of the study

    Time: 14 days

    Description: Rescue therapies are any therapy among the following ones: neuromuscular blocking agents, prone position, nitric oxide, recruitment maneuvers, ECMO

    Measure: Rate of use of rescue therapies

    Time: 14 days

    Description: Severe mixed acidosis is defined by the association of pH<7.15 and PaCO2>45 mm Hg.

    Measure: Incidence density rate of severe mixed acidosis

    Time: ICU stay

    Description: Ventilator associated pneumonia will be defined as any pneumonia acquired under mechanical ventilation after inclusion.

    Measure: Incidence density rate of ventilator associated pneumonia

    Time: ICU stay

    Description: Acute cor pulmonale is defined by the association of right ventricle dilatation (right ventricle surface / left ventricle surface >0,6) and septal dyskinesia assessed by echocardiography

    Measure: Incidence density rate of acute cor pulmonale

    Time: ICU stay

    Description: Barotrauma is defined by any pneumothorax OR pneumomediastinum OR subcutaneous emphysema, OR pneumatocele of more than 2 cm detected on image examinations.

    Measure: Incidence density rate of barotrauma

    Time: ICU stay

    Description: Serious adverse event is any life threatening event OR any event resulting in death.

    Measure: Incidence density rate of any serious adverse events

    Time: ICU stay

    Description: The Telephone Montreal Cognitive Assessment score will be assessed by phone call. The total score ranges from 0 to 30; higher scores being associated to a better outcome.

    Measure: Cognitive impairment assessed by phone call using the Telephone Montreal Cognitive Assessment (T-MoCA) test

    Time: Day 365 after inclusion

    Description: The RAND 36-Item Health Survey (SF-36) score will be assessed by phone call. The score ranges from 0 to 100; higher scores being associated to a better outcome.

    Measure: Quality of life assessed by the RAND 36-Item Health Survey (SF-36) score

    Time: Day 365 after inclusion

    Description: The Impact of Event Scale - revised (IES-R) score will be assessed by phone call. The total score ranges from 0 to 88; higher scores being associated to a worse outcome.

    Measure: Post-traumatic stress disorder assessed by the Impact of Event Scale - revised (IES-R) score by phone call

    Time: Day 365 after inclusion

    Description: The cost-efficacy ratio will be computed as the ratio of cost difference on efficacy difference between the intervention arm and the reference arm. The costs taken into account will be the direct hospitalized costs. The efficacy will be assessed as the number of days alive free from mechanical ventilation.

    Measure: Cost-efficacy ratio of the innovative strategy compared to the reference strategy

    Time: Day 90 after inclusion
    108 A Phase 3 Randomized, Placebo-Controlled Study of Lenzilumab in Hospitalized Patients With Severe and Critical COVID-19 Pneumonia

    The primary objective of this study is to assess whether the use of lenzilumab in addition to current standard of care can alleviate the immune-mediated cytokine release syndrome (CRS) and reduce the time to recovery in hospitalized subjects with severe or critical COVID-19 pneumonia.

    NCT04351152
    Conditions
    1. Coronavirus Disease 2019 (COVID-19) Pneumonia
    Interventions
    1. Biological: Lenzilumab
    2. Drug: Standard of Care
    MeSH:Coronavirus Infections Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Time to recovery is defined as the first day on which a subject satisfies one of the following 3 categories from the 8-point 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 28 days

    Secondary Outcomes

    Measure: Incidence of Invasive Mechanical Ventilation and/or Death

    Time: Up to 28 days

    Measure: Incidence of severe acute respiratory distress syndrome (ARDS)

    Time: Up to 28 days

    Measure: Duration of Intensive Care Unit (ICU) Stay

    Time: Up to 28 days

    Measure: Ventilator-free Days

    Time: Up to 60 days

    Measure: Duration of Hospitalization

    Time: Up to 28 days

    Measure: Time to Improvement in 1 or 2 Categories using 8-point Ordinal Scale

    Time: Up to Day 28

    Measure: Time to Death

    Time: Up to Day 28

    Measure: Number of Subjects Alive and Off Oxygen

    Time: Up to 60 days

    Description: Using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0

    Measure: Percentage of Participants Experiencing Adverse Events

    Time: Up to 60 days

    Description: Using the NCI CTCAE version 5.0

    Measure: Percentage of Participants Experiencing Serious Adverse Events

    Time: Up to 60 days

    Measure: Proportion of Subjects Discharged from Hospital

    Time: Up to Day 60

    Measure: All-cause Mortality and Proportion of Subjects Alive

    Time: Day 28 and Day 60

    Measure: Time to improvement in oxygenation for > 48 hours

    Time: Up to Day 28

    Measure: Incidence of Non-invasive Ventilation (or Use of High-flow Oxygen Device)

    Time: Up to Day 28

    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 and temperature (°C)

    Measure: Time to Clinical Improvement, Defined as NEWS2 < 2 Maintained for 24 Hours

    Time: Up to Day 28

    Measure: Change from Baseline to Day 28 in Clinical status Based on the 8-point Ordinal Scale

    Time: Up to Day 28

    Measure: Duration of Time on Low-flow or High-flow Supplemental Oxygen

    Time: Up to Day 28
    109 IV Infusion of Autologous Adipose Derived Mesenchymal Cells for Abatement of Respiratory Compromise in SARS-CoV-2 Pandemic (COVID-19)

    The aim of this study is to evaluate the safety and efficacy of autologous adipose-derived mesenchymal cells for treating confirmed or suspected patients with SARS-CoV-2 and compromised respiratory function requiring hospitalization. The hypothesis of the Study is autologous adipose-derived mesenchymal cells given IV to eligible patients will improve clinical outcomes of COVID 19 positive patients with severe pneumonia or ARDS by reducing or avoiding cytokine storm.

    NCT04352803
    Conditions
    1. Covid-19 Pneumonia
    2. Cyotokine Storm
    Interventions
    1. Biological: Autologous Adipose MSC's
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Incidence of unexpected adverse events within 28 days following IV administration of MSCs.

    Measure: Safety - Incidence of unexpected adverse events

    Time: up to 28 days

    Description: Changes in progression or rate of subjects progressing to mechanical ventilation

    Measure: Efficacy - Frequency of progression to mechanical ventilation

    Time: up to 28 days

    Description: Changes in time subjects remain on mechanical ventilation

    Measure: Efficacy - Changes in length of mechanical ventilation

    Time: up to 28 days

    Description: Changes in length of time subjects wean off of mechanical ventilation

    Measure: Efficacy - Changes in length of weaning of mechanical ventilation

    Time: up to 28 days

    Description: Length of Hospital Stay

    Measure: Efficacy - Changes in length of hospital stay

    Time: up to 28 days

    Description: Mortality rate from all causes

    Measure: Efficacy - Changes in mortality rate

    Time: up to 28 days
    110 A Prospective International Lung UltraSound Analysis (ILUSA) Study in Tertiary Maternity Wards During the SARS-CoV-2 Pandemic

    Currently there is a great need for an accurately and rapid assessment of patients suspected for Covid-19. Like CT, Lung Ultrasound (LUS) examination can potentially help with the initial triage of patients but also help track the evolution of the disease. LUS can be used in every setting, including settings with limited infrastructure, allowing the reduction of disparities in trials participation. LUS is also a practical approach that can be used by obstetricians/gynecologists, who are the primary care givers in the labour and delivery room. The International Lung UltraSound Analysis (ILUSA) Study is an international multicenter prospective explorative observational study to assess the predictive value of LUS in Covid-19 suspected and diagnosed pregnant patients.

    NCT04353141
    Conditions
    1. COVID
    2. Pregnancy Complications, Infectious
    3. Pregnancy Related
    4. Pregnancy, High Risk
    5. Pregnancy Disease
    6. Pneumonia
    7. Pneumonia, Viral
    8. Diagnoses Disease
    Interventions
    1. Diagnostic Test: standardized Lung Ultrasound (LUS) examination
    MeSH:Pregnancy Complications, Infectious Pneumonia, Viral Pneumonia Pregnancy Complications
    HPO:Pneumonia

    Primary Outcomes

    Description: The primary endpoint is diagnostic performance in terms of the area under the receiver operating characteristic curve (AUC, also known as the c-statistic) and sensitivity and specificity with regard to the prediction of poor outcome. Outcome at one week from admission: good outcome includes discharge or inpatient breathing in free air; poor outcome includes patient with oxygen support, patients with CPAP/ high oxygen flow cannula, or patient with endotracheal intubation during the week.

    Measure: Diagnostic performance of LUS to predict poor outcome

    Time: outcome one week after enrollment into the study
    111 Study of Biomarkers in the Long-term Impact of Coronavirus Infection in the Cardiorespiratory System: Effect of Hydroxychloroquine / Azithromycin Combined Therapy

    Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) poses a significant threat to global health. As the disease progresses, a series of acute complications tend to develop in multiple organs. Beyond the supportive care, no specific treatment has been established for COVID-19. The effectiveness, both short-term and long-term, of some promising antivirals, such as the hydroxychloroquine combination with azithromycin, needs to be evaluated. This study aims to investigate the predictive role of cardiac biomarkers and pulmonary symptoms for late complications of COVID-19 coronavirus infection on the heart and lung in patients treated with the hydroxychloroquine / azithromycin combination therapy. Thus, COVID-19 coronavirus patients undergoing hydroxychloroquine / azithromycin combination therapy will be compared to patients not undergoing this therapy. The comparison will be made by the analysis of the relationships between (1) levels of ultrasensitive cardiac troponins collected at the beginning of the infection and cardiac magnetic resonance data in the 3rd and 12th months of troponin collection and (2) findings CT scans and the results of the ergospirometers tests performed in those same periods. It is expected to demonstrate that: (1) cardiac troponin and lung tomographic findings can predict late complications of COVID-19 coronavirus infection in the heart and lung, assessed by cardiac magnetic resonance and ergospirometers one year after the beginning of the infection, and (2) hydroxychloroquine / azithromycin combined therapy can abolish the onset of these complications late. Furthermore, the results may point to the need for more rigorous monitoring of cardiologists and pulmonologists of these patients, due to the risk of hemodynamic complications, arrhythmogenic and respiratory.

    NCT04353245
    Conditions
    1. COVID19
    2. Corona Virus Infection
    3. Myocardial Injury
    4. Pneumonia
    Interventions
    1. Other: BIOMARKERS IN THE LONG TERM IMPACT OF CORONAVIRUS INFECTION IN THE CARDIORRESPIRATORY SYSTEM
    MeSH:Infection Communicable Diseases Coronavirus Infections Virus Diseases Severe Acute Respiratory Syndrome Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: presence of fibrosis on cardiac resonance and / or decreased functional capacity on ergospirometry

    Measure: Fibrosis

    Time: 12 months

    Description: Decreased functional capacity on ergospirometers

    Measure: Ergospirometers

    Time: 12 monthes
    112 Use of Bromhexine and Hydroxychloroquine for Treatment of COVID-19 Pneumonia

    In the current situation it is of great importance to discover a safe, cost-effective and available treatment strategy in order to limit the rapidly spreading SARS-Cov-2. Recent studies have shown that hydroxychloroquine could have a role in the treatment of infected patients. It is however not very likely that hydroxychloroquine alone could be adequate for treatment of Covid-19 disease. Effective therapy that prevents the virus entrance should contain at least TMPRSS2 inhibitor or a competitive inhibitor of viral ACE 2 binding. The use of bromhexine at the dose adequate to selectively inhibit the TMPRSS2, resulting in preventing of viral entrance via TMPRSS2-specific pathway, coud be an effective treatment of Covid-19. In our study we would like to explore the therapeutic potential of bromhexin and hydroxychloroquine in Covid-19 patients. Hypothesis 1. Combined treatment with bromhexin and hydroxychloroquine shortens the course of disease in hospitalized Covid-19 patients compared to hydroxychloroquine alone. 2. Combined treatment with bromhexin and hydroxychloroquine lowers the incidence of secundary pulmonary infections in hospitalized Covid-19 patients compared to hydroxychloroquine alone. 3. Combined treatment with bromhexin and hydroxychloroquine decreases the need for ICU admission in hospitalized Covid-19 patients compared to hydroxychloroquine alone.

    NCT04355026
    Conditions
    1. Covid-19
    Interventions
    1. Drug: Bromhexine Oral Tablet and/or hydroxychloroquine tablet
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: number of days the patient is treated in the hospital

    Measure: Duration of hospitalization

    Time: through study completion, an average of 6 months

    Description: Number of days from the onset of symptoms to hospital discharge

    Measure: Duration of disease

    Time: through study completion, an average of 6 months

    Secondary Outcomes

    Description: Incidence of HAP

    Measure: Hospital-aquired pneumonia

    Time: through study completion, an average of 6 months

    Description: Number of days spent in the ICU

    Measure: ICU stay duration

    Time: through study completion, an average of 6 months

    Description: number of days on oxygene therapy

    Measure: Oxygene therapy duration

    Time: through study completion, an average of 6 months

    Description: Number of hours on mechanical ventilation

    Measure: Mechanical ventilatory support duration

    Time: through study completion, an average of 6 months
    113 Efficacy of Captopril Nebulization in Covid-19 Patients Suffering of SARS CoV-2 Pneumonia. A Randomized Phase II Study

    Captopril being an effective drug available in liquid preparation, administration by nebulization could be of interest for maximizing lung action and minimizing systemic side effects. Such a treatment might be used for "Covid-19" patients with pneumonia in order to avoid ARDS.

    NCT04355429
    Conditions
    1. Pneumonia
    2. Coronavirus Infection
    3. COVID-19
    Interventions
    1. Drug: captopril 25mg
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: To assess determine the efficacy of captopril nebulization addition to standard of care compared to standard of care in term of 14-day ventilation free survival

    Measure: Efficacy of captopril nebulization addition to standard of care compared to standard of care.

    Time: 14 Days
    114 SOLIRIS® (Eculizumab) for the Treatment of Participants With Coronavirus Disease 2019 (COVID 19) - An Expanded Access Program for Hospital-based Emergency Treatment

    This protocol provides access to eculizumab treatment for participants with severe COVID-19.

    NCT04355494
    Conditions
    1. COVID-19
    2. Pneumonia, Viral
    3. Acute Lung Injury/Acute Respiratory Distress Syndrome (ARDS)
    Interventions
    1. Biological: eculizumab
    MeSH:Pneumonia, Viral Pneumonia Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Lung Injury Syndrome
    HPO:Pneumonia

    115 Treatment With Inhaled Corticosteroids in Patients Hospitalized Because of COVID19 Pneumonia

    Randomized, prospective, controlled open label clinical trial aimed at investigating if the addition of inhaled corticosteroids (budesonide) reduces treatment failure (defined as a composite variable by the initiation of treatment with high flow-O2 therapy, non-invasive or invasive ventilation, systemic steroids, use of biologics (anti IL-6 or anti IL-1) and/or death) according to hospital standard of care guidance) at day 15 after initiation of therapeutic intervention.

    NCT04355637
    Conditions
    1. Coronavirus Infection
    Interventions
    1. Drug: Inhaled budesonide
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: composite variable that includes the initiation of treatment with high flow-O2 therapy, non-invasive or invasive ventilation, systemic steroids, use of biologics (anti IL-6 or anti IL-1) and/or death) at day 15 after initiation of therapeutic intervention

    Measure: Proportion of patients in both arms fulfilling the criteria for treatment failure

    Time: 15 days after treatment

    Secondary Outcomes

    Description: Yes/no

    Measure: ICU admission

    Time: baseline, day 3, day 7, day 15, day 30

    Description: yes/no and reason

    Measure: ICU refusal

    Time: baseline, day3, day 7, day 15, day 30

    Description: infectious cardiovascular and /or metabolic complications as well as variation in the 7 point WHO scale.

    Measure: Occurrence of complications

    Time: baseline, day3, day 7, day 15, day 30

    Description: U/L

    Measure: lactate dehydrogenase (LDH)

    Time: at baseline, day 3, day 7, day 15, day 30

    Description: mg/dL

    Measure: C Reactive Protein (CRP)

    Time: at baseline, day 3, day 7, day 15, day 30

    Description: ng/mL

    Measure: ferritin

    Time: at baseline, day 3, day 7, day 15, day 30

    Description: ng/mL

    Measure: D-dimer

    Time: at baseline, day 3, day 7, day 15, day 30

    Description: x10^9/L

    Measure: leukocyte counts

    Time: at baseline, day 3, day 7, day 15, day 30
    116 Non-Invasive Monitoring of Respiratory Function in Spontaneously Breathing Patients With COVID-19 Infection

    This study uses the AirGo band to monitor changes in tidal ventilation in spontaneously breathing patients with COVID-19 associated respiratory failure. It aims to recognize patterns of ventilation associated with worsening respiratory failure in this patient population. If successful, this study will lead to the development of new robust methods for real-time, continuous monitoring of respiratory function in patients with respiratory failure. In turn, such monitoring methods may enable improvements in the medical management of respiratory failure and timing of interventions.

    NCT04356443
    Conditions
    1. Respiratory Failure
    2. Ventil
    3. Ventilatory Failure
    4. COVID-19
    5. Pneumonia
    6. ARDS, Human
    Interventions
    1. Device: AirGo Respiratory Monitor
    MeSH:Pneumonia Respiratory Insufficiency Respiratory Distress Syndrome, Adult Hypoventilation
    HPO:Hypoventilation Pneumonia

    Primary Outcomes

    Description: Progression of respiratory failure to require endotracheal intubation (and mechanical ventilation)

    Measure: Endotracheal intubation during present hospitalization, recorded through chart review

    Time: Up to three weeks

    Secondary Outcomes

    Description: Maintenance of SpO2 >=90% on no or low flow supplemental oxygen (=< 1 liter by nasal cannula or CPAP, or return of supplemental oxygen to baseline if required supplemental O2 for another indication, prior to onset of COVID-19 infection)

    Measure: Improvement in hypoxemia as indicated by oxygen saturation and requirement for supplemental oxygen, recorded through chart review

    Time: Up to three weeks

    Description: Patient or care provider may request removal of the band for any reason prior to the patient reaching the outcome

    Measure: Premature need for removal of the band, recorded through investigator report

    Time: Up to three weeks

    Description: Death from any cause while in the hospital

    Measure: In-hospital mortality, recorded through chart review

    Time: Up to 24 weeks
    117 COVID-19: A Pilot Study of Adaptive Immunity and Anti-PD1

    This is an open-label, controlled, single-centre pilot study of nivolumab in adult patients with COVID-19. This clinical study aims to evaluate efficacy of anti-PD1 antibody in relation to viral clearance and its safety.

    NCT04356508
    Conditions
    1. COVID-19
    2. SARS-CoV-2
    3. 2019-nCoV
    4. Pneumonia, Viral
    Interventions
    1. Drug: Nivolumab
    MeSH:Pneumonia, Viral Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Viral load changes in NPS based on SARS-CoV-2 RT-PCR

    Measure: Viral clearance kinetics

    Time: From diagnosis to recovery, assessed up to 6 months

    Secondary Outcomes

    Description: Incidence and severity of treatment-related adverse events

    Measure: Treatment-related adverse events of nivolumab (Intervention arm only)

    Time: Up to 1 year after nivolumab dosing

    Description: Changes in lymphocyte counts

    Measure: Lymphocyte kinetics

    Time: On days 1, 4, 6, 8, 10 and 28 from study enrollment

    Description: Changes in cytokine levels (e.g. IL-1B, IL-2, IL-6, TNFa)

    Measure: Cytokine kinetics

    Time: On days 1, 4, 6, 8 and 10 from study enrollment

    Measure: Length of inpatient stay due to COVID-19

    Time: From hospital admission to discharge, assessed up to 6 months
    118 Efficacy of Pulmonary Physiotherapy on Hospitalized Patients With Novel Coronavirus 2019 Pneumonia

    The aim of this study is to evaluate the efficacy of pulmonary physiotherapy on respiratory functions in hospitalized patients with Novel Coronavirus 2019 pneumonia. Patients will be randomized into 1) intervention group: receiving pulmonary physiotherapy technique to improve pulmonary function and walking training or 2) control group: Usual medical care. Patients in both groups will receive therapeutic incentive spirometer. Various outcome measurements of pulmonary functions will be evaluated before and after of interventions. Mortality rate, hospitalization duration and re-admission will be followed until one month after end of intervention. Also, patient's quality of life will be measured after one month.

    NCT04357340
    Conditions
    1. Covid-19
    2. Pneumonia
    3. SARS Pneumonia
    Interventions
    1. Other: Pulmonary Physiotherapy Techniques
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Partial pressure of oxygen in mixed venous blood.

    Measure: Mixed venous O2 pressure (PVO2)

    Time: Baseline

    Description: Partial pressure of oxygen in mixed venous blood.

    Measure: Mixed venous O2 pressure (PVO2)

    Time: Day 3

    Description: Partial pressure of carbon dioxide in mixed venous blood.

    Measure: Mixed venous CO2 pressure (PVCO2)

    Time: Baseline

    Description: Partial pressure of carbon dioxide in mixed venous blood.

    Measure: Mixed venous CO2 pressure (PVCO2)

    Time: Day 3

    Description: Measure of the venous blood acidity or alkalinity

    Measure: PH

    Time: Baseline

    Description: Measure of the venous blood acidity or alkalinity

    Measure: PH

    Time: Day 3

    Description: The amount of bicarbonate ion in the venous blood

    Measure: HCO3

    Time: Baseline

    Description: The amount of bicarbonate ion in the venous blood

    Measure: HCO3

    Time: Day 3

    Description: The amount of oxygen-saturated hemoglobin relative to total hemoglobin (unsaturated + saturated) in the venous blood

    Measure: Oxygen saturation (O2 Sat) from VBG

    Time: Baseline

    Description: The amount of oxygen-saturated hemoglobin relative to total hemoglobin (unsaturated + saturated) in the venous blood

    Measure: Oxygen saturation (O2 Sat) from VBG

    Time: Day 3

    Description: The distance a patient can walk during three minute

    Measure: Three minute walk test

    Time: Baseline

    Description: The distance a patient can walk during three minute

    Measure: Three minute walk test

    Time: Day 3

    Measure: O2 Sat after one minute walking

    Time: Baseline

    Measure: O2 Sat after one minute walking

    Time: Day 3

    Measure: O2 Sat after two minutes use of Partial Rebreather

    Time: Baseline

    Measure: O2 Sat after two minutes use of Partial Rebreather

    Time: Day 3

    Measure: O2 Sat after two minutes free air breathing

    Time: Baseline

    Measure: O2 Sat after two minutes free air breathing

    Time: Day 3

    Measure: O2 sat/ Fio2

    Time: Baseline

    Measure: O2 sat/ Fio2

    Time: Day 3

    Secondary Outcomes

    Description: The number of dead subjects compared to total patients

    Measure: Mortality rate

    Time: until one month

    Description: Patients' hospitalization after discharge due to any reason

    Measure: Number of participants with Rehospitalization

    Time: until one moth

    Description: Using Short-form 36 questionnaire. The minimum score is 0 and the maximum score is 100. Higher scores mean patient's better quality of life.

    Measure: The Health-Related Quality of Life (HRQOL)

    Time: One month after end of intervention

    Description: The amount of shortness of breath using Visual Analogue Scale (VAS). The minimum score is 0 and maximum is 10. The 0 score means no breathlessness and the 10 score is the maximum breathlessness.

    Measure: breathlessness

    Time: Baseline

    Description: The amount of shortness of breath using Visual Analogue Scale (VAS). The minimum score is 0 and maximum is 10. The 0 score means no breathlessness and the 10 score is the maximum breathlessness.

    Measure: breathlessness

    Time: Day 3
    119 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
    120 COVID-19 Epidemic Response Study: A National Observational Longitudinal Non-Interventional Protocol

    A national, observational, longitudinal, non-interventional program aiming to identify prognostic parameters, to investigate the kinetics of the immune response, and to identify predictive biomarkers in SARS-CoV-2 infected patients.

    NCT04357496
    Conditions
    1. Fever
    2. Pneumonia
    3. Cough
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Blood samples drawn from the infected participants will be analysed for prognostic parameters.

    Measure: Identification of prognostic parameters for SARS-CoV-2 infected participants.

    Time: 7 months

    Secondary Outcomes

    Description: Systems from Abbott and Euroimmun will be used for IgG and IgM in SARS-CoV-2.

    Measure: Investigation of the kinetics of immune activation and antibody production against SARS-CoV-2 and correlation with clinical course

    Time: 7 months

    Other Outcomes

    Description: Genomic, proteomic, and transcriptomic analyses will be performed on the blood samples drawn from Covid-19 infected participants over the course of 6 months.

    Measure: Identification of predictive biomarker/s for clinical course in mildly and severely affected Covid-19 patients using genomic, proteomic, and transcriptomic approach.

    Time: 7 months
    121 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
    122 Mortality Prediction Model for the Triage of COVID-19, Pneumonia and Mechanically Ventilated ICU Patients

    The objective of this study is to develop and evaluate an algorithm which accurately predicts mortality in COVID-19, pneumonia and mechanically ventilated ICU patients.

    NCT04358510
    Conditions
    1. COVID-19
    2. Pneumonia
    3. Mechanical Ventilation
    Interventions
    1. Device: COViage
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Deceased or not deceased

    Measure: Mortality outcome in COVID-19 ICU patients

    Time: Through study completion, an average of 2 months

    Description: Deceased or not deceased

    Measure: Mortality outcome in mechanically ventilated ICU patients

    Time: Through study completion, an average of 2 months

    Description: Deceased or not deceased

    Measure: Mortality outcome in pneumonia ICU patients

    Time: Through study completion, an average of 2 months
    123 Expanded Access: Pulsed, Inhaled Nitric Oxide (iNO) for the Treatment of Patients With Mild or Moderate Coronavirus Disease (COVID-19)

    The search for novel therapies to address the ongoing coronavirus (COVID-19) pandemic is ongoing. No proven therapies have been identified to prevent progression of the virus. Preliminary data suggest that inhaled nitric oxide (iNO) could have benefit in preventing viral progression and reducing reliance on supplemental oxygen and ventilator support. Expanded access allows for iNO to be delivered via the portable INOpulse delivery system for the treatment of COVID-19.

    NCT04358588
    Conditions
    1. Coronavirus Infection
    2. COVID-19
    3. Pneumonia, Viral
    Interventions
    1. Drug: iNO (inhaled nitric oxide) delivered via the INOpulse Delivery System
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia, Viral Pneumonia
    HPO:Pneumonia

    124 Baricitinib Therapy in COVID-19: A Pilot Study on Safety and Clinical Impact

    Retrospective study on the efficacy of baricitinib in 12 COVID-19 patients with moderate pneumonia.

    NCT04358614
    Conditions
    1. COVID
    2. Pneumonia
    Interventions
    1. Drug: Baricitinib 4 MG Oral Tablet
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: All adverse event recording

    Measure: To assess the safety of baricitinib combined with antiviral (lopinavir-ritonavir) in terms of serious or non-serious adverse events incidence rate.

    Time: 2 weeks

    Secondary Outcomes

    Description: The percentage of patients improving the clinical and respiratory parameters compared with controls.

    Measure: To evaluate the impact of baricitinib in terms of clinical, laboratory, respiratory parameters.

    Time: 2 weeks

    Description: The percentage of ICU admission in baricitinib group as compared with controls.

    Measure: ICU admission rate

    Time: 2 weeks

    Description: The percentage of discharged in baricitinib group as compared with controls.

    Measure: Discharge rate.

    Time: 2 weeks
    125 Anxiety and Work Resilience Among Tertiary University Hospital Workers During the COVID-19 Outbreak: An Online Survey

    For limiting COVID-19 spreading, the World Health Organisation (WHO) recommended worldwide confinement on 2010. In France, unessential institutions were closed on March 14th and population confinement was decided on March 17th. Quarantine and/or confinement could lead to psychological effects such as confusion, suicide ideation, post-traumatic stress symptoms or anger COVID-19 outbreak highlighted a considerable proportion of health care workers (HCW) with depression, insomnia, anxiety and distress symptoms. In front line, facing the virus with the fear of contracting it and contaminate their closest. During previous outbreaks (H1N1, SARS), HCWs have been shown to experience such negative psychological effects of confinement as well as work avoidance behaviour and physical interaction reduction with infected patients (4-7). In France, Covid 19 outbeak led to increase ICU bed capacity with a full reorganization of the human resources. Some caregivers were reassigned to newly setup units admitting or not Covid-19 patients. In the same time, non-caregivers were also encouraged to work at home whenever possible. Thus, every hospital staff member's private and professional life could be altered by the Covid-19 outbreak. As all these changes in the daily life could induce psychological disturbances, the present study was aimed at assessing the acute anxiety level (main objective) of the staff in our Tertiary University Hospital, (6300 employees). Secondarily, the self-reported insomnia, pain, catastrophism and work avoidance behaviour levels were assessed

    NCT04358640
    Conditions
    1. Critical Illness
    2. Sars-CoV2
    3. SARS Pneumonia
    4. Coronavirus Infection
    5. Stress Disorders, Post-Traumatic
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia Critical Illness Stress Disorders, Post-Traumatic
    HPO:Pneumonia

    Primary Outcomes

    Description: Mesured by STAY Scale

    Measure: Anxiety

    Time: 15 to 45 days after the beginning of the outbreak

    Secondary Outcomes

    Description: Participant suffering of Insomnia

    Measure: Insomnia

    Time: 15 to 45 days after the beginning of the outbreak

    Description: Participant suffering of catastrophism

    Measure: Catastrophism

    Time: 15 to 45 days after the beginning of the outbreak
    126 Phase II, Randomized, Double-blind, Controlled Clinical Trial Evaluating the Efficacy and Safety of Plasma From Patients Cured of COVID-19 Compared to the Best Available Therapy in Subjects With SARS-CoV-2 Pneumonia

    In early December 2019, cases of pneumonia of unknown origin were identified in Wuhan, China. The causative virus was called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The World Health Organization (WHO) has recently declared coronavirus disease 2019 (COVID-19) a public health emergency of international concern. According to the World Health Organization (WHO), the management of COVID-19 has focused primarily on infection prevention, detection and patient monitoring. However, there is no vaccine or specific treatment for SARS-CoV-2 due to the lack of evidence. Treatment options currently include broad-spectrum antiviral drugs but the efficacy and safety of these drugs is still unknown. Convalescent plasma has previously been used to treat various outbreaks of other respiratory infections; however, it has not been shown to be effective in all the diseases studied. Therefore, clinical trials are required to demonstrate its safety and efficacy in patients with VIDOC-19. The present work seeks to determine the mortality from any cause up to 14 days after plasma randomization of patients cured of COVID-19 compared to the Best Available Therapy in subjects with SARS-CoV-2 pneumonia. This is a 2:1 randomized, double-blind, single-center, phase 2, controlled clinical trial (plasma: best available therapy) for the treatment of SARS-CoV-2 pneumonia.

    NCT04358783
    Conditions
    1. Coronavirus Infection
    Interventions
    1. Biological: Plasma
    2. Other: Best Available Therapy
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: any cause mortality during the first 14 days of treatment

    Measure: Early all-cause mortality

    Time: 14 days

    Secondary Outcomes

    Description: (48-hour sampling interval from day 3 of hospitalization to two consecutive negatives).

    Measure: Time in days for SARS-CoV-2 RT-PCR negatives

    Time: 90 days

    Description: In subjects of both arms at day 0, 3, 7, 14 and 90.

    Measure: The serum anti-SARS-CoV-2 antibody titres

    Time: 90 days

    Description: Comparison of anti-SARS-CoV-2 antibody titers

    Measure: Detection of serum antibodies

    Time: days 0, 3, 7, 14 and 90.
    127 Efficacy and Safety of Corticosteroids in Oxygen-dependent Patients With COVID-19 Pneumonia in Grand Ouest Interregion France

    To date, there is no efficient therapeutics to prevent or treat COVID-19 related pulmonary failure. Corticosteroids (CS) could be a helpful therapeutic. Retrospective reports suggested survival improvement in patients with acute respiratory distress syndrome (ARDS). CT scan for COVID19 hospitalized patients showed sometimes unusual aspects of pneumonia, suggestive of an organizing phase of diffuse alveolar damage (DAD). We hypothesize that, in the context of alveolar aggression induced by COVID-19, CT scan could help to individualize patients with a high probability of pulmonary organizing process who could benefit from CS treatment.

    NCT04359511
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Prednisone
    2. Drug: Hydrocortisone
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: The 7-category ordinal scale is as follow: Not hospitalized with resumption of usual activities Not hospitalized, but unable to resume usual activities Hospitalized, not requiring O2 Hospitalized, requiring O2 from 1 to 5 l/min Hospitalized, requiring O2 >6 l/min, nasal high-flow O2, non-invasive mechanical ventilation, or both Hospitalized, requiring ECMO, invasive mechanical ventilation, or both Death.

    Measure: Clinical improvement defined by the improvement of 2 points on a 7-category ordinal scale, at 14 days.

    Time: 14 days

    Secondary Outcomes

    Measure: Proportion of patients free of oxygen at day 14 and 28

    Time: 14 and 28 days

    Measure: Proportion of patients discharged alive from hospital at day 14 and 28

    Time: 14 and 28 days

    Measure: Time to discharge for patients alive

    Time: 28 days

    Measure: Proportion of patients that were hospitalized to ICU or who died at day 14 and 28

    Time: 14 and 28 days

    Measure: 14 and 28 day mortality rate

    Time: 14 and 28 days

    Measure: The time until weaning from oxygen therapy

    Time: 28 days

    Measure: The proportion of patients with clinical degradation of at least 1 point on the ordinal scale to 7 categories on D14 and D28

    Time: 14 and 28 days
    128 Prognostic Value of Serum Interleukin-6 (IL-6) and Soluble Interleukin-6 Receptor (sIL-6R) in Severe Coronavirus Disease (COVID-19) Pneumonia Treated With Tocilizumab - a Prospective Single Center Study (UHID-COVID19)

    This is a single arm, prospective, observational, single center study to assess the role of interleukin-6 (IL-6) and soluble interleukin 6 receptor (sIL-6R) as predictors of efficacy and safety outcomes in patients with severe coronavirus disease (COVID-19) pneumonia treated with tocilizumab. At least 30 patients will be enrolled who are diagnosed with severe COVID-19 pneumonia and meet the entry criteria.

    NCT04359667
    Conditions
    1. COVID-19
    2. Severe Pneumonia
    Interventions
    1. Drug: Tocilizumab 20 MG/ML Intravenous Solution [ACTEMRA]
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: to evaluate the role of laboratory markers as predictors of survival in severe COVID-19 pneumonia patients treated with tocilizumab

    Measure: serum interleukin-6 and soluble interleukin-6 receptor as biomarkers of clinical outcomes in patients with severe coronavirus disease (COVID-19) pneumonia treated with tocilizumab

    Time: baseline

    Description: to evaluate the role of laboratory markers as predictors of survival in severe COVID-19 pneumonia patients treated with tocilizumab

    Measure: serum interleukin-6 and soluble interleukin-6 receptor as biomarkers of clinical outcomes in patients with severe coronavirus disease (COVID-19) pneumonia treated with tocilizumab

    Time: 24 hours post treatment

    Description: to evaluate the role of laboratory markers as predictors of survival in severe COVID-19 pneumonia patients treated with tocilizumab

    Measure: serum interleukin-6 and soluble interleukin-6 receptor as biomarkers of clinical outcomes in patients with severe coronavirus disease (COVID-19) pneumonia treated with tocilizumab

    Time: 48 hours post treatment

    Description: to evaluate the role of laboratory markers as predictors of survival in severe COVID-19 pneumonia patients treated with tocilizumab

    Measure: serum interleukin-6 and soluble interleukin-6 receptor as biomarkers of clinical outcomes in patients with severe coronavirus disease (COVID-19) pneumonia treated with tocilizumab

    Time: on Day 7

    Description: to evaluate the role of laboratory markers as predictors of survival in severe COVID-19 pneumonia patients treated with tocilizumab

    Measure: serum interleukin-6 and soluble interleukin-6 receptor as biomarkers of clinical outcomes in patients with severe coronavirus disease (COVID-19) pneumonia treated with tocilizumab

    Time: on Day 28
    129 Bacterial and Fungal Microbiota of Patients With Severe Viral Pneumonia With SARS-CoV2

    Observational pilot single-center study aiming to determine the microbiota of critically ill patients infected with SARS-CoV-2. COVID-19 patients will be compared to historical critically ill controls with no SARS-CoV-2 infection.

    NCT04359706
    Conditions
    1. Sars-CoV2
    MeSH:Pneumonia, Viral Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: relative abundances and diversity indices

    Measure: Composition of the fecal bacterial and fungal microbiota

    Time: At 28 days

    Secondary Outcomes

    Description: Alterations in fecal microbiota composition (including virose, bacteria and fungi) in COVID-19 patients compared with controls

    Measure: Analysis of the faecal microbiota from rectal swab

    Time: at baseline and every 7 days during 28 days

    Description: Alterations in respiratory microbiota composition (including virose, bacteria and fungi) in COVID-19 patients compared with controls

    Measure: Analysis of the respiratory microbiota from the bronchoalveolar lavage liquid

    Time: at baseline and every 7 days during 28 days

    Description: Changes in blood, c-reactive protein, leucocyte, lymphocyte from baseline

    Measure: Serum inflammatory markers changes

    Time: at 28 days,

    Description: changes in Cytokine/ chemokine from baseline

    Measure: Inflammatory markers changes

    Time: at 28 days,

    Description: death

    Measure: Mortality

    Time: at 28 days,

    Description: Number of days alive without mechanical ventilation

    Measure: mechanical ventilation free days

    Time: at 28 days,
    130 PEEP Incremental and Decremental Alveolar Recruitment of Critically Ill COVID-19 Patients Under Electric Impedance Tomography (EIT)

    COVID-19 originated from Severe Acut Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection leads to critical condition due to hypoxemic respiratory failure with the background of viral pneumonia. Both alevolar recruitment and the subsequent optimal positive end-expiratory pressure (PEEP) adjustment has a pivotal role in the elimination of atelectasis developed by inflammation in the lung parenchyma The gold standard of the follow up of recruitment manoeuvre is the chest computed tomography (CT) examination. However, reduction of intrahospital transport and the exposure with healthcare workers are recommended because of the extremely virulent pathogen spreading easily by droplet infection. In this case bedside investigations have an utmost importance in the management of hygiene regulations. Electric impedance tomography (EIT) is a non-invasive, radiation free functional imaging technique easily applicable at the bedside.

    NCT04360837
    Conditions
    1. COVID-19
    2. Virus; Pneumonia
    3. Atelectasis
    Interventions
    1. Procedure: alveolar recruitment
    MeSH:Pneumonia, Viral Pneumonia Pulmonary Atelectasis
    HPO:Atelectasis Pneumonia

    Primary Outcomes

    Description: Estimation of change in compliance (ml/cmH2O) from the beginning to end of of the incremental/decremental PEEP alveolar recruitment.

    Measure: Changes in lung compliance

    Time: 20 minutes

    Description: Estimation of change in global impedance (%) from the beginning to end of of the incremental/decremental PEEP alveolar recruitment.

    Measure: Change in global impedance

    Time: 20 minutes

    Description: Estimation of change in global impedance (%) on a daily manner.

    Measure: Change in recruitability

    Time: 7 days

    Secondary Outcomes

    Description: Change in arterial partial pressure of oxygen (PaO2) (mmHg) following recruitment

    Measure: Gas exchange

    Time: 20 minutes and 7 days

    Description: Change in plateau pressure (cmH2O) following recruitment

    Measure: Plateau pressure

    Time: 20 minutes and 7 days

    Description: Change in end expiratory lung impedance (%)

    Measure: End expiratory lung impedance (EELI)

    Time: 20 minutes and 7 days

    Description: Change in antero-to-posterior ventilation ratio (%) following intervention

    Measure: Antero-to-posterior ventilation ratio

    Time: 20 minutes and 7 days

    Description: Change in center of ventilation (%) following intervention

    Measure: Center of ventilation

    Time: 20 minutes and 7 days

    Description: Change in global inhomogeneity index (%) following intervention

    Measure: Global inhomogeneity index

    Time: 20 minutes and 7 days
    131 Targeted Steroids for ARDS Due to COVID-19 Pneumonia: A Pilot Randomized Clinical Trial

    This trial will determine the safety and estimate efficacy of targeted corticosteroids in mechanically ventilated patients with the hyper-inflammatory sub phenotype of ARDS due to coronavirus disease 2019 (COVID-19) by implementing a Phase 2A clinical trial.

    NCT04360876
    Conditions
    1. COVID-19
    2. ARDS
    Interventions
    1. Drug: Dexamethasone injection
    2. Drug: Placebos
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Total number of ventilator free days to day 28 of hospitalization. If a patient dies prior to day 28, they will be counted as zero ventilator free days. Follow up will be performed via phone or electronically to determine ventilator free status of those patients discharged prior to day 28.

    Measure: Ventilator Free Days (VFD) at Day 28

    Time: 28 Days

    Secondary Outcomes

    Description: 1. Not hospitalized, no limitations on activities; 2. Not hospitalized, limitation on activities; 3. Hospitalized, not requiring supplemental oxygen; 4. Hospitalized, requiring supplemental oxygen; 5. Hospitalized, on non-invasive ventilation or high flow oxygen devices; 6. Hospitalized, on invasive mechanical ventilation or ECMO; 7. Death.

    Measure: Clinical Status at day 14 as measured by World Health Organization (WHO) 7-point ordinal scale.

    Time: 14 Days

    Measure: Clinical Status at day 28 as measured by WHO 7-point ordinal scale

    Time: 28 Days

    Measure: In-Hospital Mortality at day 28

    Time: 28 Days

    Measure: In-Hospital Mortality at day 90

    Time: 90 Days

    Measure: Time to Mortality to day 28

    Time: 28 Days

    Measure: ICU-free days to day 28

    Time: 28 Days

    Measure: Hospital Length of Stay among survivors to day 90

    Time: 90 Days

    Measure: Severity of ARDS to day 10

    Time: 10 Days

    Measure: Days to resolution of fever

    Time: 28 Days

    Measure: Change in C-Reactive Protein (CRP) level from baseline to day 10

    Time: 10 Days

    Measure: Vasopressor-free days to day 28

    Time: 28 Days

    Measure: Renal replacement-free days to day 28

    Time: 28 Days

    Measure: Duration of mechanical ventilation to day 28

    Time: 28 Days

    Measure: Oxygenation-free days to day 28

    Time: 28 Days

    Measure: Incidence of New Mechanical Ventilation to day 28

    Time: 28 Days

    Measure: Change in sequential organ failure assessment (SOFA) score from baseline to day 10

    Time: 10 Days

    Measure: In-hospital adverse events to day 28

    Time: 28 Days

    Measure: Discontinuation of study drug infusion

    Time: 10 Days
    132 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
    133 Clinical Features and Risk Factors Associated With Worse Outcome in Patients Hospitalized for Covid-19 Pneumonia in France

    The aim of the research is to improve patient management by rapidly identifying, based on the terrain and clinical and biological characteristics, those patients likely to present a severe form of ARDS at risk of leading to intensive care

    NCT04362345
    Conditions
    1. Covid-19
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Measure: Identification of risk factors for severity (death or transfer to resuscitation) of Covid-19 infection

    Time: Files analysed retrospectively from March 1st, 2020 to April 15, 2020 will be examined]
    134 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
    135 Azithromycin With Amoxicillin/Clavulanate Versus Amoxicillin/Clavulanate Alone in COVID-19 Patients With Pneumonia and Hospitalized in a Non-intensive Care Unit Ward (AziA): a Superiority Open-label Randomized Controlled Trial

    The global pandemic of novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began in Wuhan, China, in December 2019, and has since spread worldwide.1 As of April 14, 2020, there have been more than 1.5 million reported cases and 124 000 deaths in more than 200 countries. A recent open-label nonrandomized French study reporte that addition of azithromycin to hydroxychloroquine in 6 patients resulted in numerically superior viral clearance (6/6, 100%) compared with hydroxychloroquine monotherapy (8/14, 57%) or control (2/16, 12.5%). Azithromycin alone has never been tested, whereas azithromycin has immunomodulating and anti-inflammatory properties that could theoretically prevent or limit secondary worsening. Our hypothesis is that azithromycin combined with amoxicillin/clavulanate will be superior to amoxicillin/clavulanate alone to obtain viral clearance at Day 6 in COVID-19 patients with pneumonia and hospitalized in a non-intensive care unit ward.

    NCT04363060
    Conditions
    1. COVID-19 Pneumonia
    Interventions
    1. Combination Product: Azithromycin with amoxicillin/clavulanate
    2. Drug: amoxicillin/clavulanate
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Rate of positive SARS-CoV-2 RT-PCR on nasopharyngeal sample

    Measure: Rate of positive SARS-CoV-2 RT-PCR

    Time: Day 6

    Secondary Outcomes

    Description: Rate of positive SARS-CoV-2 RT-PCR on nasopharyngeal sample

    Measure: Rate of positive SARS-CoV-2 RT-PCR

    Time: Day 10

    Description: Clinical evolution on the WHO Ordinal Scale for Clinical Improvement for COVID-19 score. Scale ranging from 0 to 8 (0:unifected; 8:dead)

    Measure: Clinical evolution on the World Health Organization Ordinal Scale for Clinical Improvement for COVID-19

    Time: day 6, day 10, and day 30

    Description: Total duration of antibiotic treatment during the 30 days following inclusion

    Measure: Total duration of antibiotic treatment during the 30 days following inclusion

    Time: 30 days

    Description: Number of all-cause mortality during the 30 days following inclusion

    Measure: Number of all-cause mortality during the 30 days following inclusion

    Time: 30 days

    Description: Number of in-hospital mortality during the 30 days following inclusion

    Measure: Number of in-hospital mortality during the 30 days following inclusion

    Time: 30 days

    Description: Number of patients transferred to intensive care unit during the 30-day follow-up

    Measure: Number of patients transferred to intensive care unit during the 30-day follow-up

    Time: 30 days

    Description: Number of days without mechanical ventilation during the 30 days following inclusion

    Measure: Number of days without mechanical ventilation during the 30 days following inclusion

    Time: 30 days

    Description: adverse events attributable to antibiotic treatment during the 30 days following inclusion

    Measure: adverse events attributable to antibiotic treatment during the 30 days following inclusion

    Time: 30 days

    Description: Hospital length of stay during the 30 days following inclusion

    Measure: Hospital length of stay during the 30 days following inclusion

    Time: 30 days
    136 Impact of Obstructive Sleep Apnea on Covid-19 Outcomes (OSACOVID-19 Study): A Prospective Observational Cohort Study

    Covid-19 infection is an on-going pandemic with worse diagnosis in adults with comorbid conditions such as hypertension and cardiopulmonary diseases. Obstructive sleep apnea (OSA) is common in those comorbidities and may contribute to worse prognosis for the Covid-19 cases.

    NCT04363333
    Conditions
    1. COVID
    2. Obstructive Sleep Apnea
    3. Pneumonia
    Interventions
    1. Diagnostic Test: Home Sleep Apnea Testing or In-hospital Polysomnography
    MeSH:Apnea Sleep Apnea Syndromes Pneumonia Sleep Apnea, Obstructive
    HPO:Apnea Obstructive sleep apnea Pneumonia Sleep apnea

    Primary Outcomes

    Description: Defined as a decline of 2 categories from admission on a 7-category ordinal scale

    Measure: The rate of clinical improvement

    Time: 7 days

    Description: Defined as a decline of 2 categories from admission on a 7-category ordinal scale

    Measure: The rate of clinical improvement

    Time: 14 days

    Description: Defined as a decline of 2 categories from admission on a 7-category ordinal scale

    Measure: The rate of clinical improvement

    Time: 21 days

    Description: Defined as a decline of 2 categories from admission on a 7-category ordinal scale

    Measure: The rate of clinical improvement

    Time: 28 days

    Secondary Outcomes

    Description: Time to hospital discharge, ICU discharge, weaning from intubation, weaning from supplemental oxygen, incident pneumonia, ARDS, in-hospital mortality

    Measure: Clinical status - improvement

    Time: 7, 14, 21, 28 days

    Description: Defined as an increase in category on a 7-category ordinal scale from admission

    Measure: Clinical status - worsening

    Time: 7, 14, 21, 28 days

    Other Outcomes

    Description: Re-analysis of the correlation of obstructive sleep apnea (objectively verified) severity in terms of apnea-hypopnea index and oxygenation levels with the primary and secondary outcomes as described above (the rate of clinical improvement defined as a decline of 2 categories from admission on a 7-category ordinal scale; time to hospital discharge, ICU discharge, weaning from intubation, weaning from supplemental oxygen, incident pneumonia, ARDS, in-hospital mortality as well as with the lung function, CO-diffusion capacity, cardiac function, CT thorax pathologies, biomarkers (cytokines, polymorphisms) and IgG-antibodies after 4 months.

    Measure: Long-term outcomes

    Time: 4-6 months after the initial hospital admission
    137 A Phase-II, Open-Label, Randomized, Multicenter Study to Investigate the Pharmacodynamics, Pharmacokinetics, Safety, and Efficacy of 8 mg/kg or 4mg/kg Intravenous Tocilizumab in Patients With Moderate to Severe COVID-19 Pneumonia

    This study will assess the pharmacodynamics, pharmacokinetics, safety and efficacy of two different doses of tocilizumab (TCZ) in combination with standard-of-care (SOC) in hospitalized adult participants with moderate to severe COVID-19 pneumonia.

    NCT04363736
    Conditions
    1. COVID-19 Pneumonia
    Interventions
    1. Drug: Tociliuzumab
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Measure: Serum Concentration of interleukin-6 (IL-6) Following Administration of 8 mg/kg IV TCZ

    Time: At pre-defined intervals from first TCZ administration to Day 28

    Measure: Serum Concentration of Soluble Interleukin-6 Receptor (sIL-6R) Following Administration of 8 mg/kg IV TCZ

    Time: At pre-defined intervals from first TCZ administration to Day 28

    Measure: Serum Concentration of Ferritin Following Administration of 8 mg/kg IV TCZ

    Time: At pre-defined intervals from first TCZ administration to Day 28

    Measure: Serum Concentration of C-reactive Protein (CRP) Following Administration of 8 mg/kg IV TCZ

    Time: At pre-defined intervals from first TCZ administration to Day 28

    Measure: Serum Concentration of IL-6 Following Administration of 4 mg/kg IV TCZ

    Time: At pre-defined intervals from first TCZ administration to Day 28

    Measure: Serum Concentration of sIL-6R Following Administration of 4 mg/kg IV TCZ

    Time: At pre-defined intervals from first TCZ administration to Day 28

    Measure: Serum Concentration of Ferritin Following Administration of 4 mg/kg IV TCZ

    Time: At pre-defined intervals from first TCZ administration to Day 28

    Measure: Serum Concentration of CRP Following Administration of 4 mg/kg IV TCZ

    Time: At pre-defined intervals from first TCZ administration to Day 28

    Secondary Outcomes

    Measure: Pecentage of Participants with Adverse Events

    Time: Up to Day 28

    Measure: Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) (COVID-19) Viral Load Over Time

    Time: Up to Day 28

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

    Time: Up to Day 28

    Measure: Proportion of Participants with any Post-Treatment Infection

    Time: Up to Day 28
    138 A Prospective, Open-label, Randomized Pilot Study (Including a Control Group) of BACTEK-R (MV130), Administered Sublingually to Assess the Clinical Impact in Subjects With Mild Pneumonia Due to COVID-19

    The purpose of the study is to confirm if BACTEK-R (MV130) provides clinical benefit in subject with mild pneumonia (CURB-65≤2) by COVID-19 admitted to the Hospital.

    NCT04363814
    Conditions
    1. COVID-19
    Interventions
    1. Biological: Bactek-R
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Number of subjects presenting a improvement in their clinical condition from day 1 to 14 that lead their hospital discharged. Based on the measure of the secondary outcomes.

    Measure: Clinical recovery

    Time: 2 weeks

    Description: Number of subjects presenting a worsening in their clinical condition from day 1 to 14 that leads to their admission to the intensive care unit or their death. Based on the measure of the secondary outcomes.

    Measure: Clinical worsening

    Time: 2 weeks

    Secondary Outcomes

    Description: Symptom (fever, cough, dyspnea, myalgia, diarrhea and so on) will be daily record and classified as mild, moderate, severe.

    Measure: Clinical severity

    Time: 2 weeks

    Description: Time of reduction or disappearance of the symptoms

    Measure: Time to symptoms remission

    Time: 2 weeks

    Description: Record of all the medication administered to the subject

    Measure: Medication Use

    Time: 2 weeks

    Description: Time from the subject's admission to the coronavirus unit until discharge

    Measure: Hospitalization time

    Time: 2 weeks

    Description: Blood routine test will be carried out days 1 and 7

    Measure: Blood routine test

    Time: Days 1 and 7

    Description: Heart rate will be followed everyday during time frame

    Measure: Heart rate

    Time: 2 weeks

    Description: Blood pressure will be followed everyday during time frame

    Measure: Blood pressure

    Time: 2 weeks

    Description: Cardiac auscultation will be recorded everyday during time frame

    Measure: Cardiac auscultation

    Time: 2 weeks

    Description: Blood oxygen saturation will be followed everyday during time frame

    Measure: Oxygen saturation

    Time: 2 weeks

    Description: Adverse events during treatment

    Measure: Adverse events

    Time: 2 weeks
    139 A Phase I/II Study of Human Placental Hematopoietic Stem Cell Derived Natural Killer Cells (CYNK-001) for the Treatment of Adults With COVID-19

    This study is a Phase 1 / 2 trial to determine the safety and efficacy of CYNK-001, an immunotherapy containing Natural Killer (NK) cells derived from human placental CD34+ cells and culture-expanded, in patients with moderate COVID-19 disease.

    NCT04365101
    Conditions
    1. Coronavirus
    2. Coronavirus Infection
    3. Severe Acute Respiratory Syndrome Coronavirus 2
    4. Pneumonia
    5. Pneumonia, Viral
    6. Lung Diseases
    7. Respiratory Tract Disease
    8. Respiratory Tract Infections
    9. Coronaviridae Infections
    10. Nidovirales Infections
    11. RNA Virus Infections
    12. Virus Disease
    13. Immunologic Disease
    14. ARDS
    15. Immunologic Factors
    16. Physiological Effects of Drugs
    17. Antiviral Agents
    18. Anti-infective Agents
    19. Analgesics
    20. Antimetabolites, Antineoplastic
    Interventions
    1. Biological: CYNK-001
    MeSH:Infection Communicable Diseases Respiratory Tract Infections Virus Diseases Coronavirus Infections Severe Acute Respira Severe Acute Respiratory Syndrome Pneumonia, Viral RNA Virus Infections Coronaviridae Infections Nidovirales Infections Pneumonia Lung Diseases Respiratory Tract Diseases Immune System Diseases
    HPO:Abnormal lung morphology Pneumonia Respiratory tract infection

    Primary Outcomes

    Description: Number and severity of adverse events

    Measure: Phase 1: Frequency and Severity of Adverse Events (AE)

    Time: Up to 6 months

    Description: Proportion of subjects with "negative" measurement of COVID-19 by rRT-PCR

    Measure: Phase 1: Rate of clearance of SARS-CoV-2

    Time: Up to 6 months

    Description: Proportion of subjects who improved clinical symptoms related to lower respiratory tract infection, as measured by National Early Warning Score 2 (NEWS2) score.

    Measure: Phase 1: Rate of clinical improvement

    Time: Up to 6 months

    Description: Time from the date of randomization to the clearance of SARS-CoV-2 by rRT-PCR. Negative results will need to be confirmed by a second negative result in the same sample type at least 24 hours after the first negative result.

    Measure: Phase 2: Time to Clearance of SARS-CoV-2

    Time: Up to 28 days

    Description: Time from the date of randomization to the first date of improved clinical symptoms related to lower respiratory tract infection. Improvement as measured by National Early Warning Score 2 (NEWS2) Score.

    Measure: Phase 2: Time to Clinical Improvement by NEWS2 Score

    Time: Up to 28 days

    Secondary Outcomes

    Description: Proportion of subjects with "negative" measurement of COVID-19 by rRT-PCR

    Measure: Rate of Clearance of SARS-CoV-2

    Time: Up to 6 months

    Description: Number and severity of adverse events

    Measure: Phase 2: Frequency and Severity of Adverse Events (AE)

    Time: up to 6 months

    Description: Time to medical discharge as an assessment of overall clinical benefit

    Measure: Overall Clinical Benefit by time to medical discharge

    Time: up to 6 months

    Description: Hospital utilization will be measured as an assessment of overall clinical benefit

    Measure: Overall Clinical Benefit by hospital utilization

    Time: up to 6 months

    Description: Mortality rate will be measured as an assessment of overall clinical benefit

    Measure: Overall Clinical Benefit by measuring mortality rate

    Time: up to 6 months

    Description: Assess the impact of CYNK-001 on changes in sequential organ failure assessment (SOFA) score.

    Measure: Impact of CYNK-001 on sequential organ failure assessment (SOFA) score

    Time: Up to 28 days

    Description: Time from randomization to the date of disappearance of virus from lower respiratory tract infection (LRTI) specimen where it has previously been found (induced sputum, endotracheal aspirate).

    Measure: Time to Pulmonary Clearance

    Time: Up to 28 days

    Description: For ventilatory support subjects, the days with supplemental oxygen-free.

    Measure: Supplemental oxygen-free days

    Time: Up to 28 days

    Description: Proportion of subjects who need invasive or non-invasive ventilation

    Measure: Proportion of subjects requiring ventilation

    Time: Up to 28 days
    140 Protective Effect of Aspirin on COVID-19 Patients

    COVID-19 has a high infection rate and mortality, and serious complications such as heart injury cannot be ignored. Cardiac dysfunction occurred in COVID-19 patients, but the law and mechanism of cardiac dysfunction remains unclear. The occurrence of progressive inflammatory factor storm and coagulation dysfunction in severe and fatal cases of NCP points out a new direction for reducing the incidence of severe and critically ill patients, shortening the length of duration in severe and critically ill patients and reducing the incidence of complications of cardiovascular diseases. Aspirin has the triple effects of inhibiting virus replication, anticoagulant and anti-inflammatory, but it has not received attention in the treatment and prevention of NCP. Although Aspirin is not commonly used in the guidelines for the treatment of NCP, it was widely used in the treatment and prevention of a variety of human diseases after its first synthesis in 1898. Subsequently, aspirin has been confirmed to have antiviral effect on multiple levels. Moreover, one study has confirmed that aspirin can inhibit virus replication by inhibiting prostaglandin E2 (PGE2) in macrophages and upregulation of type I interferon production. Subsequently, pharmacological studies have found that aspirin as an anti-inflammatory and analgesic drug by inhibiting cox-oxidase (COX). Under certain conditions, the platelet is the main contributor of innate immune response, studies have found that in the lung injury model in dynamic neutrophil and platelet aggregation. In summary, the early use of aspirin in covid-19 patients, which has the effects of inhibiting virus replication, anti-platelet aggregation, anti-inflammatory and anti-lung injury, is expected to reduce the incidence of severe and critical patients, shorten the length of hospital duration and reduce the incidence of cardiovascular complications.

    NCT04365309
    Conditions
    1. Novel Coronavirus Pneumonia
    2. Aspirin
    3. Treatment
    Interventions
    1. Drug: Aspirin 100mg
    MeSH:Coronavirus Infections Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: TTCR is defined as the study treatment (oral aspirin enteric-coated tablet) began to fever, breathing rate, blood oxygen saturation recovery, and cough relieving for at least 72 hours.

    Measure: clinical recovery time (TTCR)

    Time: not more than 14 days

    Description: Time of SARS-CoV2 in upper respiratory tract specimens overcasting detected by RT-PCR.

    Measure: the time of SARS-CoV2 overcasting

    Time: not more than 37 days
    141 Effect of Treatments in Patients Hospitalized for Severe COVID-19 Pneumonia: a Multicenter Cohort Study

    Several treatments have been used in during the Covid-19 pandemic of 2020. Using patients' registries from several hospitals in Paris, the investigators retrospectively analyzed associations between specific treatments, including but not limited to hydroxychloroquine, azithromycin, remdesivir, baricitinib, tocilizumab, sarilumab, lopinavir/ritonavir and oseltamivir; and clinical outcomes including, death and mechanical ventilation.

    NCT04365764
    Conditions
    1. Covid-19
    2. ARDS
    3. Pneumonia
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Composite of death and mechanical ventilation (i.e. intubation)

    Measure: Composite of death and mechanical ventilation

    Time: 14-days follow-up

    Secondary Outcomes

    Description: Death

    Measure: Death

    Time: 14-days follow-up

    Description: Enabled by intubation

    Measure: Mechanical ventilation

    Time: 14-days follow-up

    Description: Composite of death and mechanical ventilation

    Measure: Composite of death and mechanical ventilation

    Time: 28-days follow-up

    Description: World Health Organization score

    Measure: World Health Organization score

    Time: 14-days follow-up

    Description: World Health Organization score

    Measure: World Health Organization score

    Time: 28-days follow-up
    142 Oxygen-Ozone as Adjuvant Treatment in Early Control of Disease Progression in Patients With COVID-19 Associated With Modulation of the Gut Microbial Flora

    Italy was the first European country affected by a severe outbreak of the Severe Acute Respiratory Syndrome - CoronaVirus-2 (SARS-CoV-2) epidemic emerged from Wuhan region (China), with a high morbidity and mortality associated with the disease. In light of its pandemic spread and the very limited therapeutic options, COronaVIrus Disease 19 (COVID-19) is considered an unprecedented global health challenge. Therefore, the evaluation of new resources, designed in the first instance for other pathologies but potentially active against COVID-19, represents a priority in clinical research. This is an interventional, non-pharmacological, open, randomized, prospective, non-profit study on the adjuvant use of oxygen ozone therapy plus probiotic supplementation in the early control of disease progression in patients with COVID-19. Contextually, all patients are treated with the current standard of care on the basis of the interim guidelines of the Italian Society of Infectious and Tropical Diseases. The main purpose of the study is to evaluate the effectiveness of an ozone therapy-based intervention (accompanied by supplementation with probiotics) in containing the progression of COVID-19 and in preventing the need for hospitalization in intensive care units.

    NCT04366089
    Conditions
    1. COVID
    2. SARS-CoV 2
    3. Pneumonia, Viral
    4. Coronavirus Infection
    Interventions
    1. Other: Oxygen-ozone therapy, probiotic supplementation and Standard of care
    2. Dietary Supplement: SivoMixx (200 billion)
    3. Drug: Azithromycin
    4. Drug: hydroxychloroquine
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia, Viral Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Comparison between the two groups

    Measure: Delta in the number of patients requiring orotracheal intubation despite treatment

    Time: 21 days

    Secondary Outcomes

    Description: Comparison between the two groups

    Measure: Delta of crude mortality

    Time: 21 days

    Description: Comparison between the two groups

    Measure: Delta of length of stay for patients in hospital

    Time: 90 days

    Description: Comparison between the two groups

    Measure: delta in the value of interleukin (IL)-1

    Time: 21 days

    Description: Comparison between the two groups

    Measure: delta in the value of IL-6

    Time: 21 days

    Description: Comparison between the two groups

    Measure: delta in the value of IL-10

    Time: 21 days

    Description: Comparison between the two groups

    Measure: delta in the value of Tumor Necrosis Factor (TNF)-alpha

    Time: 21 days

    Description: Comparison between the two groups

    Measure: delta in the value of cluster of differentiation (CD)4+ CD38/ Human Leukocyte Antigen-DR isotype (HLA-DR)

    Time: 21 days

    Description: Comparison between the two groups

    Measure: delta in the value of CD8+ CD38/ HLA-DR

    Time: 21 days

    Description: Comparison between the two groups

    Measure: delta in the value of fecal calprotectin

    Time: 21 days

    Description: Comparison between the two groups

    Measure: delta in the value of lipopolysaccharide (LPS)

    Time: 21 days

    Description: Comparison between the two groups

    Measure: delta in the value of zonulin

    Time: 21 days

    Description: Comparison between the two groups

    Measure: delta in the value of alpha1-antitrypsin

    Time: 21 days
    143 Phase I / II Clinical Trial, Multicenter, Randomized and Controlled, to Assess the Safety and Efficacy of Intravenous Administration of Allogeneic Adult Mesenchymal Stem Cells of Expanded Adipose Tissue in Patients With Severe Pneumonia Due to COVID-19

    Phase I/II clinical trial to evaluate the safety and efficacy of Allogenic Adipose Tissue-Derived Mesenchymal Stem Cells Expanded in patients with severe COVID-19 pneumonia

    NCT04366323
    Conditions
    1. Sars-CoV2
    Interventions
    1. Drug: ALLOGENEIC AND EXPANDED ADIPOSE TISSUE-DERIVED MESENCHYMAL STEM CELLS
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Measure: Safety of the administration of allogeneic mesenchymal stem cells derived from adipose tissue assessed by Adverse Event Rate

    Time: 12 months

    Measure: Efficacy of the administration of allogeneic mesenchymal stem cells derived from adipose tissue assessed by Survival Rate

    Time: 28 days
    144 Thrombo Embolic Events in Critical Care Patients With Covid-19 Serious Acute Pneumopathy

    The understanding of haemostasis and inflammation cross-talk has gained considerable knowledge during the past decade in the field of arterial and venous thrombosis. Complex and delicately balanced interaction between coagulation and inflammation involve all cellular and humoral components. Elements of the coagulation system such as activated thrombin, fibrinogen or factor Xa may increase inflammation by promoting the production of pro-inflammatory cytokines, chemokines, growth factors and adhesion molecules that lead to a procoagulant state amplifying the pathological process. Recent evidence supports inflammation as a common pathogenic contributor to both arterial and venous thrombosis, giving rise to the concept of inflammation-induced thrombosis. Patients with infection of COVID-19 and severe pneumoniae seem to have higher risk of thromboembolism. Very few data are available regarding the biological disorders of coagulation in these patients. Th purpose of this project is to analyze hemostasis and coagulation of patients with infection of COVID-19 and severe pneumonia.

    NCT04366752
    Conditions
    1. COVID-19
    2. Pneumonia
    3. ARDS
    4. Hemostasis
    5. Coagulation
    Interventions
    1. Other: venous ultrasound
    2. Other: blood sample
    MeSH:Pneumonia Thromboembolism
    HPO:Pneumonia Thromboembolism

    Primary Outcomes

    Description: The reference range for the thrombin time is usually less than 20 seconds (ie, 15-19 seconds)

    Measure: Variation of thrombin time (in secondes) in Covid-19 patients with pneumonia admitted in ICU.

    Time: up to 6 weeks

    Description: Variation of factor V concentration (U/dL) in Covid-19 patients with pneumonia admitted in ICU.

    Measure: Variation of factor V concentration (U/dL) in Covid-19 patients with pneumonia admitted in ICU.

    Time: up to 6 weeks

    Description: Variation of factor II concentration (U/dL) in Covid-19 patients with pneumonia admitted in ICU.

    Measure: Variation of factor II concentration (U/dL) in Covid-19 patients with pneumonia admitted in ICU.

    Time: up to 6 weeks

    Description: Variation of concentration of fibrin and fibrinogen degradation products (≥ 10 µgm/mL) in Covid-19 patients with pneumonia admitted in ICU.

    Measure: Variation of concentration of fibrin and fibrinogen degradation products (≥ 10 µgm/mL) in Covid-19 patients with pneumonia admitted in ICU.

    Time: up to 6 weeks
    145 The RESCUE 1-19 Trial: Radiation Eliminates Storming Cytokines and Unchecked Edema as a 1-Day Treatment for COVID-19

    This phase I/II trial studies low-dose radiation therapy as a focal anti-inflammatory treatment for patients with pneumonia or SARS associated with COVID-19 infection.

    NCT04366791
    Conditions
    1. Pneumonia
    2. Coronavirus Infection in 2019 (COVID-19)
    3. Severe Acute Respiratory Syndrome (SARS) Pneumonia
    Interventions
    1. Radiation: Low Dose Radiation Therapy
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: The rate will be reported, along with a two-sided 95% exact binomial confidence interval, using the Clopper-Pearson method. The observed extubation rate will be compared to the null rate of 20% using a two-sided binomial test. Statistical significance is assessed at the 0.05 level.

    Measure: Rate of extubation (for intubated patients)

    Time: Screening up to 28 days after radiation therapy

    Secondary Outcomes

    Description: Temperature in degrees (F)

    Measure: Clinical outcome - Temperature

    Time: Screening up to 28 days after radiation therapy

    Description: Heart rate in beats per minutes

    Measure: Clinical outcome - Heart Rate

    Time: Screening up to 28 days after radiation therapy

    Description: Systolic blood pressure in mm Hg

    Measure: Clinical outcome - Systolic blood pressure

    Time: Screening up to 28 days after radiation therapy

    Description: Oxygen saturation in percentage

    Measure: Clinical outcome - Oxygenation

    Time: Screening up to 28 days after radiation therapy

    Description: Respiratory rate in breaths per minute

    Measure: Clinical outcome - Respirations

    Time: Screening up to 28 days after radiation therapy

    Description: FI02 in percentage

    Measure: Clinical outcome - FiO2

    Time: Screening up to 28 days after radiation therapy

    Description: Positive end expiratory pressure (PEEP) in cm H20

    Measure: Clinical outcome - PEEP

    Time: Screening up to 28 days after radiation therapy

    Description: Tidal volume in mL

    Measure: Clinical outcome - Tidal volume

    Time: Screening up to 28 days after radiation therapy

    Description: Extubation/intubation events in percentage

    Measure: Clinical outcome - Intubation/Extubation events

    Time: Screening up to 28 days after radiation therapy

    Description: Survival in percentage

    Measure: Clinical outcome - Overall survival

    Time: Screening up to 28 days after radiation therapy

    Description: Serial chest x-rays categorized using published scale into ordinal ranks 1-5 for SARS.

    Measure: Radiographic outcome - Chest xray

    Time: Screening up to 28 days after radiation therapy

    Description: CT scans with volume of consolidation measured in cubic centimeters.

    Measure: Radiographic outcome - CT can

    Time: Screening up to 28 days after radiation therapy

    Description: White blood cell count in cell count x 10^3/mcL

    Measure: Serologic outcome - WBC

    Time: Screening up to 28 days after radiation therapy

    Description: Hemoglobin in gm/dL

    Measure: Serologic outcome - Hgb

    Time: Screening up to 28 days after radiation therapy

    Description: Procalcitonin in ng/mL

    Measure: Serologic outcome - Procalcitonin

    Time: Screening up to 28 days after radiation therapy

    Description: Absolute neutrophil count in cell count x 10^3/mcL

    Measure: Serologic outcome - ANC

    Time: Screening up to 28 days after radiation therapy

    Description: Creatine kinase in units/L

    Measure: Serologic outcome - Creatine kinase

    Time: Screening up to 28 days after radiation therapy

    Description: Myoglobin in ng/mL

    Measure: Serologic outcome - Myoglobin

    Time: Screening up to 28 days after radiation therapy

    Description: Albumin in gm/dL

    Measure: Serologic outcome - Albumin

    Time: Screening up to 28 days after radiation therapy

    Description: Coagulation pathway time in seconds

    Measure: Serologic outcome - PT/PTT

    Time: Screening up to 28 days after radiation therapy

    Description: D-Dimer in ng/mL

    Measure: Serologic outcome - D-Dimer

    Time: Screening up to 28 days after radiation therapy

    Description: Gamma-glutamyl transferase in units/L

    Measure: Serologic outcome - GGT

    Time: Screening up to 28 days after radiation therapy

    Description: Trygliciericdes in mg/dL

    Measure: Serologic outcome -Triglycerides

    Time: Screening up to 28 days after radiation therapy

    Description: Ferritin in ng/mL

    Measure: Serologic outcome -Ferritin

    Time: Screening up to 28 days after radiation therapy

    Description: Fibrinogen in mg/dL

    Measure: Serologic outcome -Fibrinogen

    Time: Screening up to 28 days after radiation therapy

    Description: Immune marker flow cytometry (refractive index)

    Measure: Serologic Immune markers flow cytometry

    Time: Screening up to 28 days after radiation therapy

    Description: Bilirubin in mg/dL

    Measure: Serologic outcome -Bilirubin

    Time: Screening up to 28 days after radiation therapy

    Description: Lactate Dehydrogenase in units/L

    Measure: Serologic outcome - LDH

    Time: Screening up to 28 days after radiation therapy

    Description: Creatinine in mg/dL

    Measure: Serologic outcome - Creatinine

    Time: Screening up to 28 days after radiation therapy

    Description: Estimated Glomerular Filtration Rate in mL/min/m2

    Measure: Serologic outcome - EGFR

    Time: Screening up to 28 days after radiation therapy

    Description: C-Reactive Protein in mg/L

    Measure: Serologic outcome - CRP

    Time: Screening up to 28 days after radiation therapy

    Description: Alanine Aminotransferase in units/L

    Measure: Serologic outcome - ALT

    Time: Screening up to 28 days after radiation therapy

    Description: Asparatate Aminotransferase in units/L

    Measure: Serologic outcome - AST

    Time: Screening up to 28 days after radiation therapy

    Description: Troponin-I in ng/mL

    Measure: Serologic outcome - Troponin-I

    Time: Screening up to 28 days after radiation therapy

    Description: B-Natriuretic Peptid in pg/mL

    Measure: Serologic outcome - BNP

    Time: Screening up to 28 days after radiation therapy

    Description: pH (no unit)

    Measure: Serologic outcome - Blood Gases pH

    Time: Screening up to 28 days after radiation therapy

    Description: pressure of O2 in mm Hg

    Measure: Serologic outcome - Blood Gases pO2

    Time: Screening up to 28 days after radiation therapy

    Description: pressure of CO2 in mm Hg

    Measure: Serologic outcome - Blood Gases pCO2

    Time: Screening up to 28 days after radiation therapy

    Description: Lactic Acid in mmol/L

    Measure: Serologic outcome - Lactic Acid

    Time: Screening up to 28 days after radiation therapy

    Description: Interleukin-6 in pg/mL

    Measure: Serologic outcome - IL-6

    Time: Screening up to 28 days after radiation therapy

    Description: Potassium in mmol/L

    Measure: Serologic outcome - Potassium

    Time: Screening up to 28 days after radiation therapy
    146 Evaluation of the Impact of Bacteriotherapy in the Treatment of COVID-19

    In light of its high morbidity and mortality, COronaVIrus Disease 19 (COVID-19) pandemic spread is considered an unprecedented global health challenge. Given the very limited therapeutic options available against Severe Acute Respiratory Syndrome - CoronaVirus-2 (SARS-CoV-2) epidemic at this time, the evaluation of new resources, designed in the first instance for other pathologies but potentially active against COVID-19, represents a priority in clinical research. This is an observational, retrospective, non-profit study on the adjuvant use of bacteriotherapy in the early control of disease progression in patients affected by COVID-19 and treated with the current standard of care on the basis of the interim guidelines of the Italian Society of Infectious and Tropical Diseases. The main purpose of the study is to evaluate the effectiveness of bacteriotherapy in reducing the clinical impact of acute diarrhea, containing the progression of COVID-19 and preventing the need for hospitalization in intensive care units.

    NCT04368351
    Conditions
    1. COVID
    2. Pneumonia
    3. Diarrhea
    Interventions
    1. Dietary Supplement: SivoMixx (200 billion)
    2. Drug: Azithromycin
    3. Drug: hydroxychloroquine
    MeSH:Pneumonia Diarrhea
    HPO:Diarrhea Pneumonia

    Primary Outcomes

    Description: Comparison between the two groups. Acute diarrhea was defined as a stool with increased water content, volume, or frequency that lasts less than 14 days.

    Measure: delta of time of disappearance of acute diarrhea

    Time: 21 days

    Secondary Outcomes

    Description: Comparison between the two groups

    Measure: Delta in the number of patients requiring orotracheal intubation despite treatment

    Time: 21 days

    Description: Comparison between the two groups

    Measure: Delta of crude mortality

    Time: 21 days

    Description: Comparison between the two groups

    Measure: Delta of length of stay for patients in hospital

    Time: 21 days
    147 Platelet Inhibition With GP IIb/IIIa Inhibitor in Critically Ill Patients With Coronavirus Disease 2019 (COVID-19). A Compassionate Use Protocol

    This is a compassionate use, proof of concept, phase IIb, prospective, interventional, pilot study in which the investigators will evaluate the effects of compassionate-use treatment with IV tirofiban 25 mcg/kg, associated with acetylsalicylic acid IV, clopidogrel PO and fondaparinux 2.5 mg s/c, in patients affected by severe respiratory failure in Covid-19 associated pneumonia who underwent treatment with continuous positive airway pressure (CPAP).

    NCT04368377
    Conditions
    1. Pneumonia, Viral
    2. Corona Virus Infection
    3. Respiratory Failure
    4. Embolism and Thrombosis
    Interventions
    1. Drug: Tirofiban Injection
    2. Drug: Clopidogrel
    3. Drug: Acetylsalicylic acid
    4. Drug: Fondaparinux
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia, Viral Pneumonia Respiratory Insufficiency Thrombosis Embolism Embolism and Thrombosis
    HPO:Pneumonia Thromboembolism

    Primary Outcomes

    Description: Change in ratio between partial pressure of oxygen in arterial blood, measured by means of arterial blood gas analysis, and inspired oxygen fraction at baseline and after study treatment

    Measure: P/F ratio

    Time: At baseline and 24, 48 and 168 hours after treatment initiation

    Description: Change in partial pressure of oxygen in arterial blood, measured by means of arterial blood gas analysis, at baseline and after study treatment

    Measure: PaO2 difference

    Time: At baseline and 24, 48 and 168 hours after treatment initiation

    Description: Change in alveolar-arterial gradient of oxygen at baseline and after study treatment. Arterial alveolar gradient will be calculated using the following parameters derived from arterial blood gas analysis: partial pressure of oxygen in arterial blood and partial pressure of carbon dioxide in arterial blood.

    Measure: A-a O2 difference

    Time: At baseline and 24, 48 and 168 hours after treatment initiation

    Secondary Outcomes

    Description: Number of days on continuous positive end expiratory pressure (CPAP)

    Measure: CPAP duration

    Time: From the first day of study drugs administration (T0) until day 7 post study drugs administration

    Description: Difference in intensity of the respiratory support (non invasive mechanical ventilation, CPAP, high flow nasal cannula (HFNC), Venturi Mask, nasal cannula, from higher to lower intensity, respectively) employed at baseline and at 72 and 168 hours after study treatment initiation

    Measure: In-hospital change in intensity of the respiratory support

    Time: At baseline and 72 and 168 hours after treatment initiation

    Description: Difference in partial pressure of carbon dioxide in arterial blood, measured by means of arterial blood gas analysis, at baseline and after study treatment

    Measure: PaCO2 difference

    Time: At baseline and 24, 48 and 168 hours after treatment initiation

    Description: Difference in concentration of bicarbonate in arterial blood, measured by means of arterial blood gas analysis, at baseline and after study treatment

    Measure: HCO3- difference

    Time: At baseline and 24, 48 and 168 hours after treatment initiation

    Description: Difference in concentration of lactate in arterial blood, measured by means of arterial blood gas analysis, at baseline and after study treatment

    Measure: Lactate difference

    Time: At baseline and 24, 48 and 168 hours after treatment initiation

    Description: Difference in hemoglobin concentration in blood samples, measured by means of blood chemistry test, at baseline and after study treatment.

    Measure: Hb difference

    Time: At baseline and 24, 48 and 168 hours after treatment initiation

    Description: Difference in platelet concentration in blood samples, measured by means of blood chemistry test, at baseline and after study treatment.

    Measure: Plt difference

    Time: At baseline and 24, 48 and 168 hours after treatment initiation

    Description: Any major or minor adverse effect occuring during and after the administration of the study drug (e.g. bleeding)

    Measure: Adverse effects

    Time: From the first day of study drugs administration until day 30 post study drugs administration
    148 Intelligence-based Remote Pulmonary Rehabilitation and Efficacy Among Discharged COVID-19 Patients

    The noval coronavirus disease 2019 (COVID-19) would cause physical and psychological dysfunctions in infected patients. We expect that an intelligence-based remote pulmonary rehabilitation scheme could improve patients' health status after hospital discharge. The intelligence-based remote pulmonary rehabilitation program is designed in a real-world and prospective manner, aiming to evaluate the efficacy of rehabilitation among 200 patients in the epicenter of China (Wuhan City) according to their varied adherence. An eight-week rehabilitation scheme, including two weeks for physicians and physiotherapists remotely guided training, and six weeks for patient self-management, will be addressed. The primary outcome of current study is six-minute walking distance and lung function, and secondly respiratory muscle strength, physical fitness assessment, symptoms and quality of life, etc. will also be assessed. Recruited patients will be followed up at week 2, 4, 8 after enrollment and at month 1, 3, 6, 12 after the rehabilitation training completed, respectively. The study has been approved by the ethics committee of China-Japan Friendship Hospital and three participating centers in Wuhan City.

    NCT04368793
    Conditions
    1. COVID-2019 Pneumonia
    2. Pulmonary Rehabilitation
    Interventions
    1. Behavioral: Remote pulmonary rehabilitation
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Walking distance within six minutes

    Measure: Six-minute walking distance (6MWD)

    Time: One year

    Description: Forced expiratory volume in one second (FEV1), forced vital capacity (FVC), etc.

    Measure: Pulmonary function

    Time: One year

    Secondary Outcomes

    Description: Maximal inspiratory pressure, maximal expiratory pressure, etc.

    Measure: Respiratory muscle strength

    Time: One year

    Description: Two-minute walking test, short physical performance battery, grip strength of both upper limbs, knee extension strength of both lower limbs, etc.

    Measure: Physical fitness assessment

    Time: One year

    Description: Modified British Medical Research Council (mMRC) dyspnea scale, etc.

    Measure: Symptom

    Time: One year

    Description: Self-training depression scale (SDS) and self-rating anxiety scale (SAS)

    Measure: Psychological evaluation

    Time: One year

    Description: 36-item short-form health survey (SF-36), etc.

    Measure: Quality of life

    Time: One year

    Description: International physical activity questionnaire (IPAQ)

    Measure: Physical activity

    Time: One year

    Description: Proportions of returning to routine work and normal life

    Measure: Proportion of returning to society

    Time: One year
    149 A Phase 3 Open-label, Randomized, Controlled Study to Evaluate the Efficacy and Safety of Intravenously Administered Ravulizumab Compared With Best Supportive Care in Patients With COVID-19 Severe Pneumonia, Acute Lung Injury, or Acute Respiratory Distress Syndrome

    This study will evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of ravulizumab administered in adult patients with Coronavirus Disease 2019 (COVID-19) severe pneumonia, acute lung injury, or acute respiratory distress syndrome. Patients will be randomly assigned to receive ravulizumab in addition to best supportive care (BSC) (2/3 of the patients) or BSC alone (1/3 of the patients). Best supportive care will consist of medical treatment and/or medical interventions per routine hospital practice.

    NCT04369469
    Conditions
    1. COVID-19 Severe Pneumonia
    2. Acute Lung Injury
    3. Acute Respiratory Distress Syndrome
    4. Pneumonia, Viral
    Interventions
    1. Biological: Ravulizumab
    2. Other: Best Supportive Care
    MeSH:Pneumonia, Viral Pneumonia Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Lung Injury Syndrome
    HPO:Pneumonia

    Primary Outcomes

    Measure: Survival (based on all-cause mortality) at Day 29

    Time: Baseline, Day 29

    Secondary Outcomes

    Measure: Number of days free of mechanical ventilation at Day 29

    Time: Baseline, Day 29

    Measure: Duration of intensive care unit stay at Day 29

    Time: Baseline, Day 29

    Measure: Change from baseline in Sequential Organ Failure Assessment at Day 29

    Time: Baseline, Day 29

    Measure: Change from baseline in SpO2/FiO2 at Day 29

    Time: Baseline, Day 29

    Measure: Duration of hospitalization at Day 29

    Time: Baseline, Day 29

    Measure: Survival (based on all-cause mortality) at Day 60 and Day 90

    Time: Baseline, Day 60, Day 90
    150 A Trial of Ozone Auto-hemotherapy in Adults Hospitalized With Covid-19 Pneumonia

    This is a multicenter, randomized, controlled, open-label clinical trial testing the use of ozone auto-hemotherapy in hospitalized patients with Covid-19 pneumonia. Eligible patients will be randomly assigned to receive either ozone auto-hemotherapy plus standard treatment, or standard treatment alone. Patients in the ozone auto-hemotherapy group will receive treatment mixing 100-200ml of blood with ozone at a concentration of 40 μg / mL with a gas volume of 200 ml. Treatment will occur every 12h during 5 days. Standard treatment will be the one used in each hospital participating in the trial. All analyses will be done according to the intention-to-treat principle

    NCT04370223
    Conditions
    1. COVID-19 Pneumonia
    Interventions
    1. Biological: Ozone auto-hemotherapy
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Improved clinical condition defined by an improvement of 2 points in the clinical status, 8 categories, ordinary score of the World Health Organization (WHO)

    Measure: Rate of patients achieving improvement in clinical condition at day 14 after recruitment

    Time: 14 days

    Secondary Outcomes

    Description: mortality

    Measure: Mortality at day 28

    Time: 28 days

    Description: Improved clinical condition defined by an improvement of 2 points in the clinical status, 8 categories, ordinary score of the World Health Organization (WHO)

    Measure: Rate of patients achieving improvement in clinical condition at day 28 after recruitment

    Time: 28 days

    Description: Improved clinical condition defined by an improvement of 2 points in the clinical status, 8 categories, ordinary score of the World Health Organization (WHO)

    Measure: Rate of patients achieving improvement in clinical condition at day 7 after recruitment

    Time: 7 days

    Description: Improved clinical condition defined by an improvement of 2 points in the clinical status, 8 categories, ordinary score of the World Health Organization (WHO)

    Measure: Time to clinical improvement or hospital discharge

    Time: 28 days

    Description: Ventilator-free days from last extubation day until day 28 after recruitment

    Measure: Number of ventilator-free days at 28 days

    Time: 28 days

    Description: Days hospitalized

    Measure: Hospital length of stay

    Time: 28 days

    Description: Number of days until a 2-fold decrease in ferritin (ng/mL)

    Measure: Time to a 2-fold decrease in ferritin

    Time: 14 days

    Description: Number of days until a 2-fold decrease in C-Protein Reactive (mg/L)

    Measure: Time to a 2-fold decrease in C-protein reactive

    Time: 14 days

    Description: Number of days until a 2-fold decrease in Dimer-D (ng/mL)

    Measure: Time to a 2-fold decrease in Dimer-D

    Time: 14 days

    Description: Number of days until a 2-fold decrease in Lactate Dehydrogenase (U/L)

    Measure: Time to a 2-fold decrease in Lactate Dehydrogenase

    Time: 14 days

    Description: Number of days until a 2-fold decrease in Neutrophils to Lymphocytes ratio

    Measure: Time to a 2-fold decrease in Neutrophils to Lymphocytes ratio

    Time: 14 days
    151 Accuracy of Lung Ultrasound in the Diagnosis of covid19 Pneumonia: a Multicenter Study in the Italian Outbreak

    Is Lung Ultrasound really useful in diagnosing COVID19? What can be the usefulness of the Lung Ultrasound in the COVID19 epidemic? In the current state of the art, Sensitivity, Specificity, Positive Predictive Value (PPV) and Negative Predictive Value (NPV) of Lung Ultrasound in the diagnosis of COVID-19 are not yet known. Alveolar-interstitial lung diseases such as viral pneumonia and ARDS seems to have a specific ultrasound pattern that distinguishes them from bacterial pneumonia, preferentially represented by B lines, morphological irregularity of the pleural line, and small subpleural consolidations, but they could share these patterns with other pathologies, reducing specificity. In Italy, the Lung Ultrasound represents a consolidated method for the evaluation and management of all patients who come to the ER, and what we are sure of is its high sensitivity in identifying pathological patterns. Our preliminary data suggest that Lung Ultrasound is highly reliable not to include but to exclude the diagnosis of COVID-19 in patients with respiratory symptoms.

    NCT04370275
    Conditions
    1. COVID-19
    2. Pneumonia, Viral
    MeSH:Pneumonia, Viral Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Lung Ultrasound accuracy in rule-out of patients with respiratory symptoms (fever and / or cough and / or dyspnoea) during the SARS-CoV-2 epidemic compared to nasopharyngeal swab and a composite reference standards

    Measure: Negative Predictive Value of Lung Ultrasound in the diagnosis of COVID-19

    Time: 30 days

    Secondary Outcomes

    Description: Lung Ultrasound accuracy in rule-in of patients with respiratory symptoms (fever and / or cough and / or dyspnoea) during the SARS-CoV-2 epidemic compared to nasopharyngeal swab and a composite reference standards

    Measure: Positive Predictive Value of Lung Ultrasound in the diagnosis of COVID-19

    Time: 30 days

    Measure: Sensitivity and Specificity of Lung Ultrasound in the diagnosis of COVID-19

    Time: 30 days
    152 Tocilizumab in Hospitalized Cancer Patients With Coronavirus 2019 (SARS-CoV-2) and Severe Complications of Coronavirus Disease 19 (COVID-19)

    This phase II expanded access trial will study how well tocilizumab works in reducing the serious symptoms including pneumonitis (severe acute respiratory distress) in patients with cancer and COVID-19. COVID-19 is caused by the SARS-CoV-2 virus. COVID-19 can be associated with an inflammatory response by the immune system which may also cause symptoms of COVID-19 to worsen. This inflammation may be called "cytokine storm," which can cause widespread problems in the body. Tocilizumab is a medicine designed to block the action of a protein called interleukin-6 (IL-6) that is involved with the immune system and is known to be a key factor for problems with excessive inflammation. Tocilizumab is effective in treating "cytokine storm" from a type of cancer immunotherapy and may be effective in reducing the inflammatory response and "cytokine storm" seen in severe COVID-19 disease. Treating the inflammation may help to reduce symptoms, improve the ability to breathe without a breathing machine (ventilator), and prevent patients from having more complications.

    NCT04370834
    Conditions
    1. Hematopoietic and Lymphoid Cell Neoplasm
    2. Malignant Solid Neoplasm
    3. Pneumonia
    4. Pneumonitis
    5. Severe Acute Respiratory Distress Syndrome
    6. Symptomatic COVID-19 Infection Laboratory-Confirmed
    Interventions
    1. Biological: Tocilizumab
    MeSH:Laboratory Infection Neoplasms Pneumonia Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury
    HPO:Neoplasm Pneumonia

    Primary Outcomes

    Measure: Clinical outcome as evaluated by the 7-category Clinical Status Ordinal Scale

    Time: At least 60 days, up to 1 year
    153 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
    154 Safety and Effectiveness of Mesenchymal Stem Cells in the Treatment of Pneumonia of Coronavirus Disease 2019

    The outbreak of coronavirus disease 2019 (COVID-19) at the end of 2019 has seen numerous patients experiencing severe acute lung injury (ALI), which developed into severe respiratory distress syndrome (ARDS). The mortality was as high as 20% -40%. Due to the lack of effective antiviral treatments, supporting treatment is the predominant therapy for COVID-19 pneumonia. Its cure is essentially dependent on the patient's immunity. While the immune system eliminates the virus, numerous inflammatory cytokines are produced and a cytokine storm occurs in severe cases. Mesenchymal stem cells (MSCs) play an important role in injury repair and immune regulation, showing advantageous prospects in the treatment of COVID-19 pneumonia. MSCs prevent cytokine storms by retarding the TNF-α pathway, alleviate sepsis by modulating macrophages, neutrophils, NK cells, DC cells, T lymphocytes and B lymphocytes. After infused, MSCs aggregate in the lungs, improve the lung microenvironment, protect alveolar epithelia, and improve pulmonary fibrosis and pulmonary function.

    NCT04371601
    Conditions
    1. COVID-19 Pneumonia
    Interventions
    1. Drug: Oseltamivir
    2. Drug: hormones
    3. Device: oxygen therapy
    4. Procedure: mesenchymal stem cells
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Improvement of pulmonary function

    Measure: Changes of oxygenation index (PaO2/FiO2) ,blood gas test

    Time: 12 months

    Secondary Outcomes

    Description: Cytokines level

    Measure: Detection of TNF-α levels, IL-10 levels

    Time: 1,3,6,12months

    Description: Immunological status

    Measure: Detection of immune cells that secret cytokines, including CXCR3+, CD4+, CD8+, NK+ cells, and regulatory T cells (CD4 + CD25 + FOXP3 + Treg cells).

    Time: 1,3,6,12months

    Description: Improvement of pulmonary function

    Measure: Changes of oxygenation index (PaO2/FiO2) ,blood gas test

    Time: 1,3,6months

    Description: Infection biomarkers

    Measure: Changes of c-reactive protein and calcitonin

    Time: 1,3,6,12months
    155 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
    156 VALIDATION OF A SEVERITY SCORE TO IDENTIFY PATIENTS ADMITTED FOR COVID-19 PNEUMONIA AT HIGH RISK FOR AN INTENSIVE APPROACH

    The outbreak of the coronavirus disease 2019 (COVID-19), first merged in China in December 2019, is now becoming a Public Health Emergency, recently confirmed as a pandemic disease by the World Health Organization. In particular, since February 2020, a rapidly growing number of cases has been identified in Italy. The clinical picture of ranges from asymptomatic cases, mild upper respiratory tract infections to severe pneumonia with respiratory failure and death. In most severe cases, COVID-19 disease may be complicated by acute respiratory distress syndrome (ARDS), septic shock and multiorgan failure. It results fundamental to early identify those subjects who rapidly may worsen their clinical status, often requiring an intensive care unit (ICU) admission. It has been showed that, mainly in more severe forms of SARS-Cov-2 disease, there is the development of an hyperinflammatory status resembling a cytokine storm syndrome, as already reported in SARS patients. A recent study by Haung et al. reported that patients with COVID-19 infection showed high amounts of IL1B, IFN-gamma, IP10 and MCP1, probably linked to activated T-helper1 (Th1) cell responses. Those requiring ICU admission had higher levels of cytokines than those subjects not requiring ICU admission, thus suggesting that cytokine storm was associated with disease severity. A similarity between cytokine profile of COVID-19 disease and secondary haemophagocytic syndrome (sHLH) has been reported. Therefore, it was suggested to screen all patients with severe COVID-19 infection both for hyperinflammatory markers (like ferritin), and the HScore commonly used to generate a probability for diagnosis of sHLH (8), which includes some laboratory parameters like triglycerides, fibrinogen, ferritin, serum aspartate aminostransferase. Based on our experience on patients affected by pneumonia from Covid19, we have observed that those subjects with a more severe prognosis might have some predictive markers. We intend to verify if these markers can identify those subjects with Covid19 infection who need a more intensive therapy and to find a prognosis score.

    NCT04372199
    Conditions
    1. COVID
    2. Pneumonia
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Measure: To identify the best predictors of critical coronavirus pneumonia and to realize a simple severity score able to early classify high-risk individuals admitted to Internal Medicine Department for COVID-19 disease, needing an intensive approach

    Time: 1 month
    157 Epidemiology and Outcome of Ventilator-associated Pneumonia Among Critically Ill COVID-19 Patients

    The aim of this study is to determine the risk factors for development of ventilator-associated pneumonia (VAP) and to identify the prognostic factors of VAP among Coronavirus Disease 2019 (CoViD-19) patients. We hypothesized that CoViD-19 serves as a high risk factor for the development of VAP and it affects clinical outcome measures negatively.

    NCT04372576
    Conditions
    1. Ventilator Associated Pneumonia
    2. Corona Virus Infection
    Interventions
    1. Diagnostic Test: Assessment of ventilator-associated pneumonia criteria
    MeSH:Pneumonia, Ventilator-Associated Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Measure: 28-day all-cause mortality

    Time: at study completion, anticipated 5 months

    Secondary Outcomes

    Measure: Days of mechanical ventilation

    Time: average time frame expected 2-3 weeks

    Measure: ICU length-of-stay

    Time: average time frame expected 3-4 weeks

    Measure: Antibiotic utilization

    Time: average time frame expected 3-4 weeks (at discharge from ICU)

    Measure: Ventilator-associated pneumonia rate

    Time: at study completion, anticipated 5 months
    158 Antithrombotic Therapy to Ameliorate Complications of COVID-19

    Endothelial injury as a consequence of SARS-CoV-2 infection leads to a dysregulated host inflammatory response and activation of coagulation pathways. Macro- and micro-vascular thrombosis may contribute to morbidity, organ failure, and death. Therapeutic anticoagulation with heparin may improve clinical outcomes in patients with COVID-19 through anti-thrombotic, anti-inflammatory, and anti-viral activities of heparins. This pragmatic, Bayesian adaptive randomized controlled trial will determine whether therapeutic anticoagulation with heparin (subcutaneous low molecular weight heparin or intravenous unfractionated heparin) versus usual care reduces the need for intubation or death in hospitalized patients with COVID-19 not initially requiring invasive mechanical ventilation. The trial uses an adaptive design which was chosen to overcome limitations in available data to inform a priori estimation of event rates and possible effect sizes. The adaptive design also includes response-adaptive randomization based on baseline D-dimer level, probing for differential efficacy across subgroups defined based on initial D-dimer level. This Bayesian adaptive randomized trial will stop at a conclusion 1) when the posterior probability that the proportional odds ratio is greater than 1.0 reaches 99% (definition of benefit); 2) when the posterior probability that the proportional odds ratio is greater than 1.2 is less than 10% (definition of futility) or; 3) when the posterior probability that the proportional odds ratio is less than 1.0 is greater than 90% (definition of harm). The trial will enroll a maximum of 3,000 patients, although in many simulations the trial may require fewer patients. The trial is strategically aligned with the international REMAP-CAP/COVID platform trial to accelerate evidence generation.

    NCT04372589
    Conditions
    1. COVID-19
    2. Pneumonia
    Interventions
    1. Drug: Heparin
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: The primary endpoint is an ordinal endpoint with three possible outcomes based on the worst status of each patient through day 30: no requirement for invasive mechanical ventilation, invasive mechanical ventilation, or death.

    Measure: Intubation and mortality

    Time: 30 days

    Secondary Outcomes

    Measure: All-cause mortality

    Time: 30 days and 90 days

    Description: Invasive mechanical ventilation

    Measure: Intubation

    Time: 30 days

    Description: Days alive outside of the hospital through 30 days following randomization

    Measure: Hospital-free days

    Time: 30 days

    Description: Number of days alive outside of the ICU through 30 days following randomization

    Measure: ICU-free days

    Time: 30 days

    Description: Number of days alive without the use of a ventilator through 30 days following randomization.

    Measure: Ventilator-free days

    Time: 30 days

    Description: The use of non-invasive mechanical ventilation or high flow nasal cannula

    Measure: Non-invasive ventilation

    Time: 30 days

    Description: Number of days alive without the use of vasopressors/inotropes and ventilation (including high flow nasal cannula >30 L/min and FIO2 >40%) through 21 days following randomization, ranked with death at anytime during 21 days as -1

    Measure: Organ support-free

    Time: 21 days

    Measure: Myocardial infarction

    Time: 30 days and 90 days

    Measure: Ischaemic stroke

    Time: 30 days and 90 days

    Measure: Venous thromboembolism

    Time: 30 days and 90 days

    Description: As defined by the International Society on Thrombosis and Haemostasis (ISTH)

    Measure: Major bleeding

    Time: Intervention period (maximum 14 days)

    Description: Laboratory-confirmed

    Measure: Heparin-induced thrombocytopenia (HIT)

    Time: Intervention period (maximum 14 days)
    159 Early Short Course Corticosteroids in Hospitalized Patients With COVID-19

    The investigators intend to study the role of early use of methylprednisolone in the hospitalized patients with a diagnosis of COVID-19 pneumonia.

    NCT04374071
    Conditions
    1. COVID
    2. Pneumonia, Viral
    Interventions
    1. Drug: Methylprednisolone
    MeSH:Pneumonia, Viral Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Number of patients transferred to ICU is each of the groups

    Measure: Transfer to Intensive care unit (ICU)

    Time: 14 days followup for every patient in each group

    Description: Number of patients that needed mechanical ventilation in each of the groups

    Measure: Need for Mechanical Ventilation

    Time: 14 days followup for every patient in each group

    Description: Number of patients who died in each of the groups

    Measure: Mortality

    Time: 14 days followup for every patient in each group

    Secondary Outcomes

    Description: Number of patients who developed ARDS of varying severity per Berlin classification in each of the groups

    Measure: Development and Severity of ARDS

    Time: 14 days followup for every patient in each group

    Description: LOS in each of the groups

    Measure: Length of hospital stay (LOS).

    Time: 14 days followup for every patient in each group
    160 Efficacy and Safety of High-Titer Anti-SARS-CoV-2 (COVID19) Convalescent Plasma for Hospitalized Patients With Infection Due to COVID-19 to Decrease Complications: A Phase II Trial

    This is a single arm phase II trial to assess efficacy and confirm safety of infusions of anti-SARS-CoV-2 convalescent plasma in hospitalized patients with acute respiratory symptoms,with or without confirmed interstitial COVID-19 pneumonia by chest Xray or CT. A total of 29 eligible subjects will be enrolled to receive anti-SARS-CoV-2 plasma.Outcomes will be compared to hospitalized controls with confirmed COVID-19 disease through retrospective chart review.

    NCT04374565
    Conditions
    1. Corona Virus Infection
    2. SARS-CoV 2
    3. SARS Pneumonia
    4. Pneumonia
    Interventions
    1. Drug: High-Titer Anti-SARS-CoV-2 (COVID 19) Convalescent Plasma
    MeSH:Infection Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Will be done by comparing the admission rate to the ICU between patients who received convalescent plasma and a control group who did not enroll in the study, or receive another experimental therapy.

    Measure: Transfer to ICU

    Time: Days 0 - 60

    Description: Will be done by comparing the 28 day mortality rate between enrolled subjects and the control group.

    Measure: 28 day mortality

    Time: Days 0 - 60

    Secondary Outcomes

    Description: Will be collected from time of enrollment until completion of the study. The adverse events will be evaluated by CTCAE V5.0 and MedDRA.

    Measure: Cumulative incidence of serious adverse events

    Time: Days 0 - 60

    Description: Will be done by collecting respiratory tract swabs and testing for SARS-CoV-2 positivity.

    Measure: Rates and duration of SARS-CoV-2

    Time: Days 0, 7, 14, and 21

    Description: Serum or plasma will be collected and analyzed for SARS-CoV-2 antibody.

    Measure: Serum of plasma antibody titer to SARS-CoV-2

    Time: Days 0, 7, 14, and 28

    Description: Blood will be collected and analyzed for cellular and humoral response.

    Measure: Cellular and humoral immune response

    Time: Days 0, 7, 14, 28

    Description: All days where a supplemental oxygen is needed will be recorded as a concomitant medication and will be subtracted from total days the participant is alive and enrolled in the study up to day 28 to determine the supplemental oxygen free days.

    Measure: Supplemental oxygen free days

    Time: Days 0-28

    Description: All days where a ventilator is needed will be recorded as a concomitant procedure and will be subtracted from total days the participant is alive and enrolled in the study up to day 28 to determine the ventilator free days.

    Measure: Ventilator free days

    Time: Days 0 - 28

    Description: All days where the participant is admitted to the ICU will be recorded and subtracted from total days the participant is alive and enrolled in the study up to day 28 to determine the ICU free days.

    Measure: ICU free days

    Time: Days 0 - 28

    Description: The patient will be evaluated throughout their enrollment in the study. The score will be evaluated to see if the score improved or worsened throughout their admission.

    Measure: Sequential organ failure assessment score

    Time: days 0, 1, 4, 7, 14, 21, 28

    Description: Concomitant medications will be recorded throughout the patients participation in the study and vasopressors will be recorded, if they are needed.

    Measure: Need for vasopressors

    Time: Days 0 - 60

    Description: Renal function will be assessed throughout the patients participation in the study. If renal replacement therapy is needed, it will be captured as a concomitant procedure.

    Measure: Need for renal replacement therapy

    Time: Days 0 - 60

    Description: Respiratory function will be assessed throughout the patients participation in the study. If ECMO is needed, it will be captured as a concomitant procedure.

    Measure: Need for extracorporeal membrane oxygenation (ECMO)

    Time: Days 0 - 60

    Description: Will be calculated from the date the patient entered the hospital until they were discharged.

    Measure: Hospital length of stay (LOS)

    Time: Days 0-60

    Description: Will be calculated from the date the patient entered the ICU until they were discharged from the ICU.

    Measure: ICU LOS

    Time: days 0 - 60

    Description: All adverse events will be recorded and evaluated by CTCAE v.5.0. All grade 3 and 4 AEs will be calculated to determine safety of convalescent plasma.

    Measure: Grade 3 or 4 Adverse Events (AEs)

    Time: days 0 - 60
    161 The Role of Sodium Bicarbonate as Adjuvant Treatment of Computed Tomography Identified COVID-19 Pneumonia: A Preliminary Report of Short Term Follow up

    To report the possible role of S.B 8.4% in the treatment of COVID-19pneumonia.

    NCT04374591
    Conditions
    1. Pneumonia
    2. Covid19
    Interventions
    1. Drug: Sodium Bicarbonate
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: defined as return of body temperature and relief of cough for more than 72 hours measured in days

    Measure: Time to clinical recovery

    Time: 7 days

    Secondary Outcomes

    Description: assessed by Chest CT defined as exacerbated, unchanged, moderately improved (with less than 50% pneumonia resolved) and significantly improved (with more than 50% pneumonia resolved).

    Measure: Pulmonary recovery status

    Time: 7 days
    162 Prevalence of Long-term Respiratory Complications of Severe SARS-CoV-2 Pneumonia

    Studies performed after coronavirus epidemics (severe acute respiratory syndrome coronavirus, SARS-CoV and Middle East respiratory syndrome coronavirus, MERS-CoV) have shown a long-term impact on respiratory morbidity, musculoskeletal and psycho-social repercussions. Patients with SARS-CoV pneumonia had fibrotic pulmonary sequelae at 45 days (lower DLCO in 27.3% of cases and radiological lesions in 21.5% of cases). In the MERS-CoV pneumonia study, patients had radiological sequelae in 33% of cases and the 12-month evaluation showed persistence of radiological abnormalities in 23.7% of the cases despite an improvement in respiratory function. Clinical presentation and therapeutic management of severe SARS-CoV-2 infection are in part similar to those induced by SARS-CoV and MERS-CoV. Long-term respiratory complications are therefore expected.

    NCT04376840
    Conditions
    1. Severe SARS-CoV2 Pneumonia
    Interventions
    1. Other: Blood sample and data record
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Interstitial lung disease diagnosed with a thoracic CT-scan

    Measure: medium-term respiratory complications

    Time: 3 months

    Secondary Outcomes

    Description: Interstitial lung disease diagnosed with a thoracic CT-scan

    Measure: long-term respiratory complications

    Time: 12 months
    163 Assessment of Extra Vascular Lung Water and Pulmonary Permeability by Transpulmonary Thermodilution in Critically Ill Patients With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)

    Acute respiratory distress syndrome (ARDS) is a syndromic definition of an acute lung injury with alteration of biomechanics (lower respiratory system compliance) mostly associated with increased lesional edema. Increase in Pulmonary Vascular Permeability Index (PVPI) accompanied with accumulation of excess Extravascular Lung Water (EVLW) is the hallmark of ARDS. In routine clinical practice, the investigators measure the EVLW and PVPI in ARDS patients, as suggested by expert's recommendations, using a transpulmonary thermodilution (TPTD) technique. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a newly recognized illness that has spread rapidly throughout Wuhan (Hubei province) to other provinces in China and around the world. Most critically ill patients with SARS-CoV-2 will present the criteria for the definition of ARDS. However, many of these patients have a particular form of ARDS with severe hypoxemia often associated with near normal respiratory system compliance. This combination is almost never seen in severe ARDS. Thus other mechanisms (including probably vascular mechanisms), that are still poorly described, have to be involved in SARS-CoV-2. EVLW and PVPI have never been assessed in SARS-CoV-2 mechanically ventilated patients. The aim of this study is to evaluate these two parameters in order to best characterize and understand the mechanisms related to SARS-CoV-2. Based on observation of several cases in intensive care units (ICU), the investigators hypothesize that there are following different SARS-CoV-2 patterns: 1. Nearly normal compliance, low lung recruitability, normal EVLW and low PVPI. 2. Low compliance due to increased edema, high lung recruitability, high EVLW and high PVPI.

    NCT04376905
    Conditions
    1. COVID-19
    2. Pneumonia
    3. Acute Respiratory Distress Syndrome
    MeSH:Pneumonia Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Acute Lung Injury Syndrome
    HPO:Pneumonia

    Primary Outcomes

    Description: EVLW (ml/kg) measured by a PiCCO device using TPTD thermodilution

    Measure: Changes of Extra Vascular Lung Water

    Time: Since intubation at day 0 and measured repetitively by 6 hours until day 3

    Secondary Outcomes

    Description: PVPI measured by a PiCCO device using TPTDventilation, duration of ICU length of stay, ICU mortality

    Measure: Changes of Pulmonary Vascular Permeability Index

    Time: Since intubation at day 0 and measured repetitively by 6 hours until day 3

    Description: Changes of pulmonary compliance (ml/mmHg)

    Measure: Changes of pulmonary compliance

    Time: Since intubation at day 0 and measured repetitively by 6 hours until day 3
    164 Pilot Study on the Feasibility of Low Dose Radiotherapy for SARS-Cov-2 Pneumonitis (COVID-19 Low Dose Radiotherapy - COLOR 19)

    Low-dose radiotherapy treatment delivered to both lungs in patients with immune-related pneumonia following COVID-19 infection is backed up by biological and clinical bases that justify its use as a possible therapeutic option in these patients. This is a preliminary exploratory study (non-pharmacological interventional) to evaluate the feasibility and tolerability of low-dose radiotherapy treatment of SARS-Cov-2 immune-mediated pneumonia, for the subsequent implementation of a phase II study.This is a preliminary, monocentric, single-arm, interventional, non-pharmacological exploratory study. All enrolled patients will be treated with low-dose radiotherapy. Participants will undergo irradiation of the lungs, administered in a single fraction at the average prescription dose of 0.7 Gy (further details in the dedicated section).

    NCT04377477
    Conditions
    1. COVID-19
    Interventions
    1. Radiation: Single fraction whole lung radiotherapy
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Evaluation of the feasibility of low-dose radiotherapy treatment of SARS-Cov2 pneumonia, for the purpose of the subsequent implementation of a phase II study; lenght of hospital stay will be recorded

    Measure: Lenght of hospital stay (days)

    Time: Six months

    Description: Evaluation of the feasibility of low-dose radiotherapy treatment of SARS-Cov2 pneumonia; the number of intensive care unit admissions will be recorded

    Measure: Number of Intensive Care Unit admissions

    Time: Six months

    Secondary Outcomes

    Description: Variation of the patient's score according to the Brescia COVID-19 Respiratory Severity Scale (minimum value 0, maximum value 8; higher scores mean a worse outcome) with baseline, assessed at 3, 6 and 10 days after treatment.

    Measure: Variation of the Brescia COVID-19 Respiratory Severity Scale after treatment

    Time: 3, 6 and 10 days

    Description: Evaluation of the safety and tolerance of the low-dose radiotherapy treatment of SARS-Cov2 ( using the CTCAE 5.0 scale)

    Measure: Occurence of CTCAE 5.0 adverse events

    Time: 10 days and 6 months

    Description: Variation of the radiological findings, assessed by chest X-ray (performed 3 and 6 days after treatment) and defined according to the Brixia scoring system (0-18 scale, with 18 meaning the worse outcome)

    Measure: Variation of the chest X-ray radiological findings according to Brixia scoring system

    Time: 3 and 6 days
    165 The Use of Tocilizumab in the Management of Patients Who Have Severe COVID-19 With Suspected Pulmonary Hyperinflammation

    Title: The use of Tocilizumab in the management of patients who have severe COVID-19 with suspected pulmonary hyperinflammation. This is a study designed to assess the therapeutic value of intravenous tocilizumab administered as single 8mg/Kg dose in patients affected by SARS-CoV2 infection with a pulmonary manifestation causing hypoxia. Aim of the study is to test the hypothesis that anti-IL6 treatment can be effective in reducing the virus-induced cytokine storm, blocking deterioration of lung function or even promoting a rapid improvement of clinical conditions, preventing tracheal intubation and/or death. This drug will be administered to those patients entering the ICU with severe acute respiratory failure COVID-19 disease. The endpoints are death and duration of hospitalization. The patients will be assessed with surrogate markers determining the level of the cytokine storm.

    NCT04377750
    Conditions
    1. Covid19 Pneumonia
    Interventions
    1. Drug: Tocilizumab
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: One-month mortality rate .

    Measure: Survival

    Time: One-month
    166 Evaluation of Demographic and Clinical Parameters on Admission and Medications Used for Comorbidities in Patients With Covid-19 Pneumonia: A Single Center Experience in Turkey

    Investigators will recruit patients diagnosed with COVID-19 pneumonia between March 11th, 2020 and April 15th, 2020 in emergency, internal medicine and cardiology outpatient clinics, retrospectively and analyze their clinical and demographic features on admission in regard to their medications used for chronic diseases regularly.

    NCT04379310
    Conditions
    1. Covid-19
    Interventions
    1. Drug: ACE Inhibitors and Calcium Channel Blockers
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: number of segments involved on admission

    Measure: extend of lung involvement

    Time: 1 week

    Description: hypoxia

    Measure: oxygen saturation on admission

    Time: 2 week
    167 Low-dose Computed Tomography in COVID-19 Pneumonia: a Prospective Moscow Study

    Hypothesis: low-dose chest computed tomography, has the same accuracy for the diagnosis of pneumonia compared to the routine protocol. In total, 230 patients are planned to be enrolled in the study. Each patient will have 2 studies (routine chest CT and low-dose chest CT) sequentially during one visit to the computed tomography room.

    NCT04379531
    Conditions
    1. Pneumonia
    2. Coronavirus Infection
    Interventions
    1. Diagnostic Test: Low-dose Chest CT
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: A standardized scale CT1-CT4 will be used. The expected correlation percentage is 90%.

    Measure: Evaluate the correlation between standard CT and low-dose CT scans for the detection of community-acquired pneumonia.

    Time: Upon completion, up to 1 year

    Secondary Outcomes

    Description: Expected threshold - 10 mm.

    Measure: Threshold value of the infiltration zone size detected by low-dose CT scan compared to standard CT scan.

    Time: Upon completion, up to 1 year

    Description: Expected number - more than two zones.

    Measure: Number of infiltration zones of pulmonary parenchyma corresponding to viral pneumonia detected by low-dose CT scan in comparison with standard CT scan.

    Time: Upon completion, up to 1 year
    168 Single-center, Prospective, Open-label, Comparator Study, Blind for Central Accessor to Access the Efficacy, Safety, and Tolerability of Inhalations of Low-doses of Melphalan in Patients With Pneumonia With Confirmed or Suspected COVID-19

    This single-center, prospective, open-label, comparator study, blind for central accessor evaluates the efficacy, safety of inhalations of low-doses of melphalan in patients with pneumonia with confirmed or suspected COVID-19. All patients will receive 0,1 mg of melphalan in 7-10 daily inhalations 1 time per day.

    NCT04380376
    Conditions
    1. COVID-19
    2. Viral Pneumonia
    Interventions
    1. Drug: Melphalan
    2. Other: Standard of care
    MeSH:Pneumonia, Viral Pneumonia Respiratory Aspiration
    HPO:Pneumonia

    Primary Outcomes

    Description: The number of patients with the clinical improvement is defined as an improvement of two points (from the status at baseline) on an ordinal scale of clinical improvement on day 28 or discharge from hospital ( whatever occurs earlier) Death Hospitalized with Invasive mechanical ventilation plus additional organ support - ECMO / pressors / RRT Hospitalized with intubation and mechanical ventilation Hospitalized on non-invasive ventilation or high flow oxygen. Hospitalized on a mask or nasal prongs. Hospitalized no oxygen therapy. Ambulatory, with limitation of activities. Ambulatory, no limitation of activities. I. No clinical or virological evidence of infection.

    Measure: The changes of COVID Ordinal Outcomes Scale

    Time: baseline vs Day 14, day 28

    Description: Percentage of the patients with clinical recovery which is defined as a normalisation of fever, respiratory rate, and oxygen saturation, and improvement of cough, sustained for at least 72 hours, or live hospital discharge, whichever comes first. Normalization and improvement criteria: Fever - <37°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: Percentage of the patients with Clinical Recovery

    Time: baseline vs day 7, day 14, day 28

    Description: The evaluation of changes in modified Borg dyspnea scale. From 0 to 10 units.A lower score means a better clinical result (0 is the absence of dyspnea, and 10 - is maximal dyspnea). Minimal clinically important difference is 1 unit.

    Measure: The changes of the Borg's scale

    Time: Baseline vs day 7, day 14, day 28

    Secondary Outcomes

    Description: Change in C-reactive protein (CRP) level from baseline in mg/ml. A lower level of CRP means a better clinical result.

    Measure: CRP level

    Time: baseline, day 7, Day 14, Day 28

    Description: Change in blood absolute lymphocyte count from baseline. A higher number of lymphocytes means a better clinical result.

    Measure: Lymphocyte count

    Time: baseline, day 7, Day 14, Day 28

    Description: Change in blood D-dimer level from baseline. A lower level of D-dimer means a better clinical result.

    Measure: D-dimer

    Time: baseline, day 7, Day 14, Day 28

    Description: Change in peripheral blood IL-6 level from baseline. A lower level of IL-6 means a better clinical result.

    Measure: IL-6

    Time: baseline, day 7, Day 14, Day 28

    Description: Percentage of patients without artificial lung ventilation during the study. A lower percentage of patients means a better clinical result.

    Measure: Percentage of patients without artificial lung ventilation

    Time: baseline, day 7, Day 14, Day 28
    169 Low Dose Anti-inflammatory Radiotherapy for the Treatment of Pneumonia by COVID-19: Multi-central Prospective Study

    Low radiation doses produce anti-inflammatory effects, which may be useful in the treatment of respiratory complications of COVID-19. This type of treatment is non-invasive and therefore, a priori, it can be used in all types of patients. Main objective: To evaluate the efficacy of low-dose lung irradiation as an adjunctive treatment in interstitial pneumonia in patients with COVID-19 by improving the PAFI O2 by 20% measured 48h after treatment with respect to the pre baseline measurement. -irradiation.

    NCT04380818
    Conditions
    1. Pneumonia, Viral
    Interventions
    1. Radiation: Low-dose radiotherapy
    2. Drug: Hydroxychloroquine Sulfate
    3. Drug: Ritonavir/lopinavir
    4. Drug: Tocilizumab Injection [Actemra]
    5. Drug: Azithromycin
    6. Drug: Corticosteroid
    7. Drug: Low molecular weight heparin
    8. Device: Oxygen supply
    MeSH:Pneumonia, Viral Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: To evaluate the efficacy of low-dose pulmonary irradiation as an adjunctive treatment in interstitial pneumonia in patients with COVID-19 by improving the PAFI O2 by 20% measured 48h after treatment with respect to baseline pre-irradiation measurement. . In cases of impossibility the SaFiO2 will be determined

    Measure: Efficacy of low-dose pulmonary irradiation assessed by change in PAFI O2 by 20%

    Time: Day 2 after interventional radiotherapy

    Secondary Outcomes

    Description: Lung toxicity measured according to CTCAEv5

    Measure: Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

    Time: Day 30 and day 90 after interventional radiotherapy

    Description: Chest CT

    Measure: Change of the radiological image

    Time: Days 7 and day 30 after interventional radiotherapy

    Description: Death of any cause

    Measure: Overall mortality

    Time: Day 15 and Day 30 after interventional radiotherapy

    Description: Interleukins IL-6, IL-10, IL-1, IL-2, IL-8 (pg/ml)

    Measure: Measure of pro-inflammatory interleukins

    Time: Days 1, day 4 and day 7 after interventional radiotherapy

    Description: TGF-β (ng/ml)

    Measure: Measure of trasforming growth factor (TGF-b)

    Time: Days 1, day 4 and day 7 after interventional radiotherapy

    Description: TNF-α (pg/ml)

    Measure: Measure of tumor necrosis factor alpha (TNF-a)

    Time: Days 1, day 4 and day 7 after interventional radiotherapy

    Description: Overexpression of L-, E-, and P-selectin

    Measure: Determining overexpression of pro-inflammatory selectin

    Time: Days 1, day 4 and day 7 after interventional radiotherapy

    Description: Overexpression of ICAM-1, VCAM

    Measure: Determining cell adhesion molecules (CAMs)

    Time: Days 1, day 4 and day 7 after interventional radiotherapy

    Description: PON-1(paraoxonase and arylesterase activity) (IU/ml)

    Measure: Measure of marker of oxidative stress PON-1

    Time: Days 1, day 4 and day 7 after interventional radiotherapy
    170 Inhalation of Ciclesonide for Patients With COVID-19: A Randomised Open Treatment Study (HALT COVID-19)

    Randomized open label clinical trial carried out at study centers in Sweden, including Karolinska University Hospital, S:t Göran Hospital, Danderyd Hospital and Västmanlands Hospital. Patients with COVID-19 who are hospitalized with oxygen therapy are eligible for inclusion. Subjects are randomized to 14 days of inhalation with ciclesonide 360 µg twice daily or to standard of care. Primary outcome is duration of received supplemental oxygen therapy. Key secondary outcome is a composite outcome of death and received invasive mechanical ventilation within 30 days.

    NCT04381364
    Conditions
    1. Covid-19
    2. Pneumonia, Viral
    3. Sars-CoV2
    Interventions
    1. Drug: Ciclesonide Inhalation Aerosol
    MeSH:Pneumonia, Viral Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Time (in days) of received supplemental oxygen therapy (defined as being alive and discharged from hospital to home or at least 48 h of not receiving oxygen therapy during hospitalization).

    Measure: Duration of received supplemental oxygen therapy

    Time: 30 days after study inclusion

    Secondary Outcomes

    Description: Rate of and time to (in days) received invasive mechanical ventilation or all-cause death

    Measure: Invasive mechanical ventilation or all-cause death (key secondary outcome)

    Time: 30 days after study inclusion

    Description: Rate of and time to (in days) death of any cause

    Measure: All cause death

    Time: 30 days after study inclusion

    Description: Rate of and time to (in days) received invasive mechanical ventilation

    Measure: Invasive mechanical ventilation

    Time: 30 days after study inclusion

    Description: Level of remaining dyspnea symptoms according to the Modified Medical Research Council Dyspnea Scale

    Measure: Remaining dyspnea symptoms

    Time: 30-35 days and 5-7 months after inclusion
    171 Efficacy and Safety of Convalescent Plasma vs Human Immunoglobulin for the Treatment of COVID-19 Pneumonia: A Randomized Controlled Trial

    Background: On December 2019, a new human coronavirus infection (COVID-19) was detected in China. Its infectivity and virulence characteristics caused a rapid spread, being declared pandemic on March 2020. The mortality attributed to the infection ranges between 3 and 10%. Main risk factors are age, male sex, and chronic degenerative comorbidities. Due to the absence of therapeutic options, potential alternatives such as human immunoglobulin or plasma from convalescent patients have been administered. Due to the severity of the disease and the associated mortality, it is urgent to find therapeutic alternatives. Objective: To assess the safety and efficacy of the administration of Convalescent plasma vs human immunoglobulin in critically ill patients with COVID-19 infection. Material and methods: Randomized Controlled trial of patients diagnosed with respiratory infection by COVID-19, with severe respiratory failure without indication of mechanical ventilation, or those who due to their severity are intubated upon admission. Randomization will be performed 2:1 to receive plasma from convalescent patients or human immunoglobulin. Outcomes: The primary outcome will be time to discharge from hospital for improvement. The safety outcomes will be: Kirby index (PaO2/FiO2) evolution and dead.

    NCT04381858
    Conditions
    1. COVID-19 Pneumonia
    Interventions
    1. Drug: Plasma from COVID-19 convalescent patient
    2. Drug: Human immunoglobulin
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Mean days from admission as a suspected case of COVID with hospitalization criteria until discharge

    Measure: Mean hospitalization time

    Time: Through study completion, an average of 3 months

    Description: Mean of delta of oxigenation index (PaO2/FiO2)

    Measure: Mean Oxigenation index evolution

    Time: Through study completion, an average of 3 months

    Description: Rate of patients with evolution to severe ARDS (PaO2/FiO2 < 100)

    Measure: Rate of severe ARDS

    Time: Through study completion, an average of 3 months

    Description: Rate of Dead caused by COVID-19 related complications and time to dead caused by COVID-19 complication

    Measure: Rate and time to dead

    Time: Through study completion, an average of 3 months

    Description: Mean time with invasive mechanical ventilation

    Measure: Mean time with invasive mechanical ventilation

    Time: Through study completion, an average of 3 months

    Secondary Outcomes

    Description: Time to negativization of RT-qPCR SARS-CoV-2 test.

    Measure: Time to Viral PCR Negativization

    Time: Through study completion, an average of 3 months.
    172 High Flow Nasal Oxygen Versus Continuous Positive Airway Pressure Helmet Evaluation: A Randomized Crossover Trial in COVID-19 Pneumonia

    The purpose of the COVIDNOCHE trial (HFNO versus CPAP Helmet Evaluation in COVID-19 Pneumonia) is to evaluate the comparative effectiveness of standard care non-invasive respiratory support (helmet CPAP versus HFNO) for acute hypoxemic respiratory failure from COVID-19 pneumonia on ventilator-free days (primary outcome) and other clinical outcomes measured up to 90 days.

    NCT04381923
    Conditions
    1. Severe Acute Respiratory Syndrome Coronavirus 2
    2. Hypoxemic Respiratory Failure
    3. Pneumonia, Viral
    4. COVID
    Interventions
    1. Device: Helmet Continuous Positive Airway Pressure (CPAP)
    2. Device: High Flow Nasal Oxygen (HFNO)
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia, Viral Pneumonia Respiratory Insufficiency
    HPO:Pneumonia

    Primary Outcomes

    Description: VFD is the number of days alive and free of mechanical ventilation in the first 28 days after study enrollment. Death before 28 days will be assigned a VFD equal to 0 to penalize non-survival. In cases of repeated intubation and extubation, periods free from invasive ventilation and lasting at least 24 consecutive hours will be calculated and summed. Timing of intubation and extubation will be captured in hours, and the number of hours a patient received invasive ventilation will be used to calculate duration of ventilation.

    Measure: Ventilator-Free Days (VFD)

    Time: 28 days

    Secondary Outcomes

    Description: Days spent in the ICU and hospital after time of enrollment

    Measure: ICU and Hospital Length of Stay

    Time: 28 days

    Description: Incidence and time to intubation in days after the time of enrollment

    Measure: Intubation

    Time: 28 days

    Description: Incidence of RRT after the time of enrollment

    Measure: Renal Replacement Therapy (RRT)

    Time: 28 days

    Description: Death from any cause during after the time of enrollment

    Measure: Mortality

    Time: 28 days, 90 days
    173 Phase 2, Randomized, Controlled, Open Label Multi-center Study to Assess Efficacy and Safety of DFV890 for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infected Patients With Coronavirus Disease 2019 (COVID-19) Pneumonia and Impaired Respiratory Function

    The study will assess the efficacy and safety of DFV890 for the treatment of SARS-Cov-2 infected patients with COVID-19 pneumonia and impaired respiratory function.

    NCT04382053
    Conditions
    1. COVID 19 Pneumonia, Impaired Respiratory Function
    Interventions
    1. Drug: DFV890
    2. Drug: Standard of Care (SoC)
    MeSH:Pneumonia Respiratory Insufficiency
    HPO:Pneumonia

    Primary Outcomes

    Description: The APACHE II ("Acute Physiology And Chronic Health Evaluation II") is a severity-of-disease classification system. An integer score from 0 to 71 is computed based on several measurements; higher scores correspond to more severe disease and a higher risk of death. Worst case imputation for death will be applied.

    Measure: APACHE II severity of disease score on Day 15 or on the day of discharge (whichever is earlier)

    Time: up to Day 15

    Secondary Outcomes

    Description: C-reactive protein (CRP) is a blood test marker for inflammation in the body. For a standard CRP test, a normal reading is less than 10 milligram per liter (mg/L). It will be analyzed on a log-scale fitting a repeated measures mixed model including treatment group, study day, the three stratification factors and log transformed baseline CRP as a covariate.

    Measure: Serum C-reactive protein (CRP) levels

    Time: up to Day 29

    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 over time

    Time: up to Day 29

    Description: Proportion of participants not requiring mechanical ventilation for survival.

    Measure: Proportion of participants not requiring mechanical ventilation for survival.

    Time: Day 15, Day 29

    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: Proportion of participants with at least one-point improvement from baseline in clinical status

    Time: Baseline, Day 15, Day 29
    174 Treatment of Covid-19 Associated Pneumonia With Allogenic Pooled Olfactory Mucosa-derived Mesenchymal Stem Cells

    Treatment of patients with Covid-19 associated pneumonia using intravenous injection of allogenic pooled olfactory mucosa-derived mesenchymal stem cells

    NCT04382547
    Conditions
    1. COVID
    2. Covid-19
    3. Coronavirus
    4. Pneumonia
    5. Pneumonia, Viral
    6. Pneumonia, Interstitial
    7. Sars-CoV2
    Interventions
    1. Biological: Allogenic pooled olfactory mucosa-derived mesenchymal stem cells
    2. Other: Standard treatment according to the Clinical protocols
    MeSH:Pneumonia, Viral Pneumonia Lung Diseases, Interstitial
    HPO:Interstitial pneumonitis Interstitial pulmonary abnormality Pneumonia

    Primary Outcomes

    Description: Number of patients cured, assessed by PCR in addition to chest CT scan

    Measure: Number of cured patients

    Time: 3 weeks

    Secondary Outcomes

    Description: MSC infusion related adverse events assessed by blood count, liver and function tests

    Measure: Number of patients with treatment-related adverse events

    Time: 3 weeks
    175 Hydroxychloroquine in SARS-CoV-2 (COVID-19) Pneumonia Trial

    Novel coronavirus SARS(Severe Acute Respiratory Syndrome)-CoV-2 was first identified during the outbreak in Wuhan, China in December 2019 with the now resulting pandemic. Aggressive supportive care is the mainstay of treatment currently and rescue with lung protective mechanical ventilation is essential for survival in patients with severe acute respiratory distress syndrome. Despite supportive care, mortality is significant in hospitalized patients in the U.S., especially among patients > 65 years of age. Pharmacologic treatments to decrease disease severity are urgently needed. Hydroxychloroquine is currently widely used for treatment of autoimmune disease including systemic lupus erythematosus and rheumatoid arthritis, and it has been used to prevent and treat malaria. In vitro and in vivo antiviral activity towards SARS-CoV-2 has been reported. Since hydroxychloroquine has been used for decades its properties as a drug are well known. The investigators propose a pragmatic trial of hydroxychloroquine in moderately ill hospitalized adults with SARS-CoV-2 pneumonia with the hypothesis that hydroxychloroquine reduces severity of acute lung injury caused by SARS-CoV-2 infection.

    NCT04382625
    Conditions
    1. SARS-CoV-2 Pneumonia
    2. COVID-19
    Interventions
    1. Drug: Hydroxychloroquine
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: paO2

    Measure: Change from Baseline Oxygenation on Day 1 to Day 5

    Time: Day 1 of treatment to day 5 of treatment

    Description: FIO2

    Measure: Change from Baseline Oxygenation at Day 5

    Time: Day 1 of treatment to day 5 of treatment

    Secondary Outcomes

    Description: Length in hours

    Measure: Intensive Care length of stay

    Time: Day 0 to Day 28

    Description: Length in hours

    Measure: Required Mechanical Ventilation

    Time: Day 0 to Day 28

    Description: Length in hours

    Measure: Required Oxygen supplementation

    Time: Day 0 to Day 28

    Description: Length in hours

    Measure: Hospitalization length of Stay

    Time: Day 0 to Day 28

    Description: Date of Death

    Measure: Mortality

    Time: Day 0 to Day 28

    Description: Cardiologist Diagnostic Documentation

    Measure: Cardiac Arrhythmia - Polymorphic Ventricular Tachycardia

    Time: Day 0 to Day 28

    Description: Cardiologist Diagnostic Documentation

    Measure: Cardiac Arrhythmia - Ventricular Tachycardia

    Time: Day 0 to Day 28

    Description: Cardiologist Diagnostic Documentation

    Measure: Cardiac Arrhythmia - Lengthening QTc

    Time: Day 0 to Day 28
    176 A Phase 2, Randomized, Placebo-controlled, Participant and Investigator Blinded, Multi-center Study to Assess Efficacy and Safety of MAS825 for the Treatment of SARS-CoV-2 Infected Patients With COVID-19 Pneumonia and Impaired Respiratory Function

    The study will assess the efficacy and safety of MAS825 for the treatment of SARS-CoV-2 infected patients with COVID-19 pneumonia and impaired respiratory function

    NCT04382651
    Conditions
    1. COVID-19 Pneumonia, Impaired Respiratory Function
    Interventions
    1. Drug: MAS825
    2. Drug: Matching placebo
    MeSH:Pneumonia Respiratory Insufficiency
    HPO:Pneumonia

    Primary Outcomes

    Description: The APACHE II ("Acute Physiology And Chronic Health Evaluation II") is a severity-of-disease classification system. An integer score from 0 to 71 is computed based on several measurements; higher scores correspond to more severe disease and a higher risk of death. Worst case imputation for death will be applied.

    Measure: APACHE II severity of disease score on Day 15 or on day of discharge (whichever is earlier)

    Time: Up to 15 days

    Secondary Outcomes

    Description: C-reactive protein (CRP) is a blood test marker for inflammation in the body. For a standard CRP test, a normal reading is less than 10 milligram per liter (mg/L). It will be analyzed on a logscale fitting a repeated measures mixed model including treatment group, study day, the three stratification factors and log transformed baseline CRP as a covariate.

    Measure: Serum C-reactive protein (CRP levels)

    Time: Up to 15 days

    Description: Ferritin is a blood test marker for inflammation in the body. For a standard Ferritin test, a normal reading is less than 300 micrograms per liter (μg/L). It will be analyzed on a logscale fitting a repeated measures mixed model including treatment group, study day, the three stratification factors and log transformed baseline Ferritin as a covariate.

    Measure: Ferritin levels

    Time: Up to 15 days

    Description: Proportion of participants without the need for invasive mechanical ventilation for survival.

    Measure: Proportion of participants without the need for invasive mechanical ventilation

    Time: Day 15, Day 29

    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 (noninvasive ventilation or highflow 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: Proportion of participants with at least one level improvement in clinical status

    Time: Day 15, Day 29

    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 (noninvasive ventilation or highflow 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 over time

    Time: Up to 15 days
    177 Effects of Neuromuscular Electrical Stimulation Therapy on Physical Function in Patients With COVID-19 Associated Pneumonia: Study Protocol of a Randomized Controlled Trial

    Neuromuscular electrical stimulation (NMES) has been considered as a promising approach for the early rehabilitation of patients in and/or after the intensive care unit (ICU). Aim of this study is to evaluate the NMES effect on physical function of COVID-19 patients.

    NCT04382729
    Conditions
    1. COVID-19 Pneumonia
    Interventions
    1. Other: Neuromuscular Electrical Stimulation
    2. Other: Physical Therapy Exercise
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: The SPPB score is a composite measure assessing standing balance (ability to stand for up to 10 seconds with feet positioned in three ways: together side-by-side, semi-tandem and tandem), walking speed (time to complete a 4-m walk), and sit-to- stand performance (time to rise from a chair five times). Each task is scored out of 4 points, with the scores from the three tests summed up to give a total, with a maximum of 12 points and a minimum of 0.

    Measure: Short Physical Performance Battery (SPPB) Score

    Time: 1 week after the intervention

    Secondary Outcomes

    Description: The FIM is an 18-item, clinician-reported scale that assesses function in six areas including self-care, continence, mobility, transfers, communication, and cognition. Each of the 18 items is graded on a scale of 1-7 based on level of independence in that item (1 = total assistance required, 7 = complete independence)

    Measure: Functional Independence Measure (FIM) Scale Score

    Time: Before and 1 week after the intervention

    Description: The Fatigue Severity Scale is a 9-item scale which measures the severity of fatigue and its effect on a person's activities and lifestyle

    Measure: Fatigue Severity Scale Score

    Time: Before and 1 week after the intervention

    Description: Handgrip strength is assessed for both sides using a handheld device. Patients are instructed to perform a maximal voluntary isometric contraction by contracting their muscles as forcefully as possible for 4-5 s. The test is repeated three times for each side and the highest value is retained. Lower limb strength is assessed as the sum of knee extension and plantar flexion strength of both sides. Muscle strength is rated using the Medical Research Council (MRC) scale that ranges from 0 (no muscle contraction) to 5 (normal resistance), for a maximum score of 20 points.

    Measure: Muscle Strength

    Time: Before and 1 week after the intervention

    Description: Subjects are required to step out with the dominant leg maximally, then to step out with the other leg maximally, and then to draw and match the first leg to the second leg while maintaining body stability with either supporting leg. The distance between the start line and the tiptoe of the second step foot is measured as the double step length (sum of the first and second steps).

    Measure: Two Step Test Length

    Time: 1 week after the intervention

    Description: The 6 Minute Walk Test is a sub-maximal exercise test used to assess aerobic capacity and endurance. The distance covered over a time of 6 minutes is used as the outcome by which to compare changes in performance capacity.

    Measure: Six Minutes Walking Test Distance

    Time: 1 week after the intervention

    Description: Ultrasound-derived muscle thickness is measured as the distance between the superficial and deep aponeuroses of the rectus femoris muscle (that is measured half-way along the line from the anterior-superior iliac spine to the superior border of the patella). Three consecutive static scans of the rectus femoris of both thighs are acquired in the transverse plane and the mean of six measurements (three measurements per side) is considered.

    Measure: Muscle Thickness

    Time: Before and 1 week after the intervention
    178 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
    179 Predicting Outcomes for Covid-19 Using Sonography

    This study seeks to investigate the role of lung ultrasound in caring for Covid-19 positive patients and whether it can be used to predict patient deterioration. This information will be vital for healthcare workers who seek to identify Covid-19 pneumonia or patients at risk for deterioration early in the disease course.

    NCT04384055
    Conditions
    1. COVID-19
    2. Pneumonia, Viral
    Interventions
    1. Diagnostic Test: Lung Ultrasound
    MeSH:Pneumonia, Viral Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Composite primary outcome of death, ICU admission, mechanical ventilation, or use of high-flow nasal cannula (categorical)

    Measure: Number of Patients Experiencing Death, ICU Admission, Mechanical Ventilation, or Use of High-Flow Nasal Cannula

    Time: 28 days from initial evaluation

    Secondary Outcomes

    Measure: Number of Patients Requiring Mechanical Ventilation

    Time: 28 days from initial evaluation

    Measure: Number of Patients Requiring Supplemental Oxygen Usage

    Time: 28 days from initial evaluation

    Measure: Duration of Supplemental Oxygen Usage

    Time: 28 days from initial evaluation

    Description: Duration of Hospitalization (days)

    Measure: Length of Stay

    Time: 28 days from initial evaluation

    Description: Descriptive analysis of ultrasound findings in Covid-19

    Measure: Characterization of Ultrasound Findings

    Time: 28 days from initial evaluation
    180 Cytokine Adsorption in Patients With Severe COVID-19 Pneumonia Requiring Extracorporeal Membrane Oxygenation - Randomized, Controlled, Open-label Intervention, Multi-center Trial (CYCOV-II-study)

    In December 2019 in the city of Wuhan in China, a series of patients with unclear pneumonia was noticed, some of whom have died of it. In virological analyses of samples from the patients' deep respiratory tract, a novel coronavirus was isolated (SARS-CoV-2). The disease spread rapidly in the city of Wuhan at the beginning of 2020 and soon beyond in China and, in the coming weeks, around the world. Initial studies described numerous severe courses, particularly those associated with increased patient age and previous cardiovascular, metabolic and respiratory diseases. A small number of the particularly severely ill patients required not only highly invasive ventilation therapy but also extracorporeal membrane oxygenation (vv-ECMO) to supply the patient's blood with sufficient oxygen. Even under maximum intensive care treatment, a very high mortality rate of approximately 80-100% was observed in this patient group. In addition, high levels of interleukin-6 (IL-6) could be detected in the blood of these severely ill patients, which in turn were associated with poor outcome. From experience in the therapy of severely ill patients with severe infections and respiratory failure, we know that treatment with a CytoSorb® adsorber can lead to a reduction of the circulating pro- and anti-inflammatory cytokines and thus improve the course of the disease and the outcome of the patients. The aim of the study is to investigate the influence of extracorporeal cytokine adsorption on interleukin-6-levels and time to successful ECMO explantation under controlled conditions in patients with particularly severe COVID-19 disease requiring extracorporeal membrane oxygenation.

    NCT04385771
    Conditions
    1. Coronavirus Infection
    2. COVID
    3. SARS-CoV 2
    4. Respiratory Failure
    5. Cytokine Storm
    6. Extracorporeal Membrane Oxygenation
    Interventions
    1. Device: vv-ECMO + cytokine adsorption (Cytosorb adsorber)
    2. Device: vv-ECMO only (no cytokine adsorption)
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia Respiratory Insufficiency
    HPO:Pneumonia

    Primary Outcomes

    Description: measurement of IL-6 levels in patient blood after 72 hours of cytokine adsorption (in relation to level before initiation of cytokine adsorption)

    Measure: IL-6 reduction by 75% or more after 72 hours as compared to the baseline measurement

    Time: 72 hours

    Description: time to successful ECMO-explantation within 30 days after randomization

    Measure: time to successful ECMO-explantation

    Time: 30 days

    Secondary Outcomes

    Description: Ventilator free days (VFD) in the first 30 days after randomization, where invasive mechanical ventilation (IMV), non-invasive ventilation (NIV) and ECMO are defined as ventilator days. VFD=0, if the patient dies in the first 30 days after randomization

    Measure: Ventilator free days (VFD)

    Time: 30 days

    Description: Time to extubation from ventilation and explantation from ECMO. Death under ventilation and/or ECMO will be analyzed as a competing event. The time will be censored at the time of last visit for surviving patients under ventilation and/or ECMO.

    Measure: Time to extubation from ventilation and explantation from ECMO

    Time: 30 days

    Description: Overall survival time, defined as time from randomization to death. The time will be censored at the time of last visit for surviving patients.

    Measure: Overall survival time

    Time: 30 days

    Description: Days on intensive care unit (ICU)

    Measure: Days on intensive care unit (ICU)

    Time: 30 days

    Description: Vasopressor dosage of adrenaline, noradrenaline, vasopressin, and dobutamine at 24, 48,72 h

    Measure: Vasopressor dosage

    Time: 24, 48, 72 hours

    Description: Total fluid[ml] substitution and fluid balance [ml] at 24, 48, 72 h

    Measure: Fluid substitution and fluid balance

    Time: 24, 48, 72 hours

    Description: Serum lactate at 24, 48, 72 h

    Measure: Serum lactate

    Time: 24, 48, 72 hours

    Description: Urine output at 24, 48, 72 h

    Measure: Urine output

    Time: 24, 48, 72 hours

    Description: Willebrand factor at 24, 48, 72 h

    Measure: Willebrand factor

    Time: 24, 48, 72 hours

    Description: d-dimers at 24, 48, 72 h

    Measure: d-dimers

    Time: 24, 48, 72 hours

    Description: interleukin-6 levels at 24, 48, 72 h

    Measure: interleukin-6 levels

    Time: 24, 48, 72 hours

    Description: Sequential Organ Failure Assessment Score at 24, 48, 72 h (values from 6 to 24, where the higher values explain higher disease severity)

    Measure: SOFA-Score

    Time: 24, 48, 72 hours

    Description: serious complications or malfunctions related to the CytoSorb device

    Measure: serious adverse device effects

    Time: 30 days

    Description: unintended air in the ECMO system during operation of the device

    Measure: adverse event of special interest: air in the ECMO system

    Time: 30 days

    Description: unintended blood-clotting in the ECMO system during operation of the device

    Measure: adverse event of special interest: blood-clotting in the ECMO system

    Time: 30 days

    Description: major bleeding events

    Measure: adverse event of special interest: bleeding complications

    Time: 30 days
    181 Use of High Flow Nasal Cannula Oxygen During Acute Hypoxemic Respiratory Failure Related to Covid-19 and Interest of the Respiratory-oxygenation Index (ROX Index): an Observational Study

    Nasal High Flow oxygen therapy (NHF) is commonly used as first line ventilatory support in patients with acute hypoxemic respiratory failure (AHRF). It's use has been initially limited in Covid-19 patients presenting with AHRF. The aim of the study is to describe the use of NHF in Covid-19-related AHRF and report the changes in the respiratory-oxygenation index (termed ROX index) over time in these patients.

    NCT04385823
    Conditions
    1. Respiratory Syndrome, Acute, Severe
    2. Hypoxic Respiratory Failure
    3. Viral Pneumonia
    Interventions
    1. Device: patients receiving nasal high flow
    MeSH:Pneumonia, Viral Severe Acute Respiratory Syndrome Coronavirus Infections Pneumonia Respiratory Insufficiency
    HPO:Pneumonia

    Primary Outcomes

    Description: values of ROX index during ICU stay

    Measure: Changes in ROX index

    Time: from date of NHF initiation until date of weaning from NHF or date of intubation whichever came first, assessed up to 2 months

    Secondary Outcomes

    Description: percentage of patients requiring intubation

    Measure: NHF failure

    Time: from date of NHF initiation until date of weaning from NHF or date of intubation whichever came first, assessed up to 2 months

    Description: level of flow used with NHF

    Measure: NHF flow

    Time: from date of NHF initiation until date of weaning from NHF or date of intubation whichever came first, assessed up to 2 months

    Description: level of inspired fraction in oxygen used with NHF

    Measure: NHF inspired fraction in oxygen

    Time: from date of NHF initiation until date of weaning from NHF or date of intubation whichever came first, assessed up to 2 months

    Description: level of pulse oxymetry during NHF therapy

    Measure: oxygenation

    Time: from date of NHF initiation until date of weaning from NHF or date of intubation whichever came first, assessed up to 2 months

    Description: respiratory rate during NHF therapy

    Measure: respiratory status

    Time: from date of NHF initiation until date of weaning from NHF or date of intubation whichever came first, assessed up to 2 months

    Description: defining the values of ROX index associated with intubation

    Measure: prediction of intubation

    Time: from date of NHF initiation until date of weaning from NHF or date of intubation whichever came first, assessed up to 2 months

    Description: defining the values of ROX index associated with NHF success (no intubation required)

    Measure: prediction of NHF success

    Time: from date of NHF initiation until date of weaning from NHF or date of intubation whichever came first, assessed up to 2 months
    182 Long Term Functional Outcomes of COVID-19 Patients Treated by Rehabilitation Services viaTelehealth

    This study seeks to assess the impact of physical and pulmonary rehabilitation on patients who have been diagnosed with COVID-19 in the short and long term in hopes of establishing a best practices protocol for treatment of future patients with this disease.

    NCT04385901
    Conditions
    1. SARS-CoV 2
    2. SARS Pneumonia
    Interventions
    1. Behavioral: Therapy Intervention
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Validated test demonstrating functional gait capacity and endurance; measuring change in capacity over time in 6 month increments.

    Measure: Change in 6 Minute Walk Test

    Time: From 6 to 24 months post diagnosis

    Description: Validated questionnaire assessing function and quality of life for patients with pulmonary function issues

    Measure: Change in Short Form 35 (SF-36) Questionnaire

    Time: From 6 to 24 months post diagnosis

    Secondary Outcomes

    Description: Use of grip dynamometer and isokinematic lower extremity testing to determine muscle capacity

    Measure: Change in Strength testing

    Time: From 6 to 24 months post diagnosis

    Description: Measures lung output capacity

    Measure: Change in Peak Flow Meter Test

    Time: From 6 to 24 months post diagnosis
    183 A Phase II, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Safety and Efficacy of MSTT1041A or UTTR1147A in Patients With Severe COVID-19 Pneumonia

    This is a Phase II, randomized, double-blind, placebo-controlled, multicenter study to assess the efficacy and safety of MSTT1041A (astegolimab) compared with placebo and of UTTR1147A compared with placebo, in combination with standard of care (SOC), in patients hospitalized with severe coronavirus disease 2019 (COVID-19) pneumonia.

    NCT04386616
    Conditions
    1. COVID-19 Pneumonia
    Interventions
    1. Drug: MSTT1041A
    2. Drug: MSTT1041A-matched Placebo
    3. Drug: UTTR1147A
    4. Drug: UTTR1147A-matched Placebo
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Measure: Time to Recovery, Defined as the Time to a Score of 1 or 2 on the 7-Category Ordinal Scale (Whichever Occurs First)

    Time: 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: From Baseline up to 28 days

    Measure: Time to Hospital Discharge or "Ready for Discharge"

    Time: Up to 28 days

    Measure: Duration of Supplemental Oxygen

    Time: Up to 28 days

    Measure: Percentage of Participants Alive and Free of Respiratory Failure

    Time: Day 28

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

    Time: Days 14 and 28

    Measure: Incidence of Invasive Mechanical Ventilation or Extracorporeal Membrane Oxygenation (ECMO)

    Time: Up to 28 days

    Measure: Ventilator-Free Days

    Time: Up to 28 days

    Measure: Incidence of Intensive Care Unit (ICU) Stay

    Time: Up to 28 days

    Measure: Duration of ICU Stay

    Time: Up to 28 days

    Measure: Time to Clinical Failure, Defined as the Time to Death, Mechanical Ventilation, ICU Admission, or Withdrawal of Care (Whichever Occurs First)

    Time: Up to 28 days

    Measure: Mortality Rate at Days 14 and 28

    Time: Days 14 and 28

    Measure: Time to Clinical Improvement, Defined as a National Early Warning Score 2 (NEWS2) of ≤2 Maintained for 24 hours

    Time: Up to 28 days

    Measure: Incidence and Severity of Adverse Events, with Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0)

    Time: Up to 60 days

    Measure: Change from Baseline in Respiratory Rate

    Time: From Baseline up to 60 days

    Measure: Change from Baseline in Pulse Rate

    Time: From Baseline up to 60 days

    Measure: Change from Baseline in Systolic Blood Pressure

    Time: From Baseline up to 60 days

    Measure: Change from Baseline in Diastolic Blood Pressure

    Time: From Baseline up to 60 days

    Measure: Change from Baseline in Body Temperature

    Time: From Baseline up to 60 days

    Measure: Change from Baseline in Oxygen Saturation

    Time: From Baseline up to 60 days

    Measure: Change from Baseline in RR, QRS, PR, QT, and QTcF Intervals, as Measured by Electrocardiogram (ECG)

    Time: From Baseline up to 60 days

    Measure: Change from Baseline in Heart Rate, as Measured by Electrocardiogram (ECG)

    Time: From Baseline up to 60 days

    Measure: Number of Participants with Clinical Laboratory Test Abnormalities in Hematology Parameters

    Time: From Baseline up to 60 days

    Measure: Number of Participants with Clinical Laboratory Test Abnormalities in Blood Chemistry Parameters

    Time: From Baseline up to 60 days

    Measure: Serum Concentration of UTTR1147A at Specified Timepoints

    Time: At predefined timepoints from Baseline until Study Completion (up to 60 days)

    Measure: Serum Concentration of MSTT1041A at Specified Timepoints

    Time: At predefined timepoints from Baseline until Study Completion (up to 60 days)

    Measure: Prevalence of Anti-Drug Antibodies (ADAs) at Baseline and Incidence of ADAs During the Study

    Time: From Baseline up to 60 days
    184 Major Determinants of COVID-19 Associated Pneumonia

    Molecular testing (e.g PCR) of respiratory tract samples is the recommended method for the identification and laboratory confirmation of COVID-19 cases. Recent evidence reported that the diagnostic accuracy of many of the available RT-PCR tests for detecting SARS-CoV2 may be lower than optimal. Of course, the economical and clinical implications of diagnostic errors are of foremost significance and in case of infectious outbreaks, namely pandemics, the repercussions are amplified. False positives and false-negative results may jeopardize the health of a single patient and may affect the efficacy of containment of the outbreak and of public health policies. In particular, false-negative results contribute to the ongoing of the infection causing further spread of the virus within the community, masking also other potentially infected people.

    NCT04387799
    Conditions
    1. Pneumonia, Viral
    2. Pneumonia, Bacterial
    3. Coronavirus Infection
    4. Obstructive Lung Disease
    Interventions
    1. Diagnostic Test: Serology for Covid-19
    MeSH:Pneumonia, Bacterial Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia, Viral Pneumonia Lung Diseases Lung Diseases, Obstructive
    HPO:Abnormal lung morphology Pneumonia Pulmonary obstruction

    Primary Outcomes

    Description: assess if inpatients who presented with pneumonia but had a negative test for Covid-19 are positive at the serology for SARS-CoV-2.

    Measure: Serology

    Time: 3 weeks

    Secondary Outcomes

    Description: to find if the combination of CT scan and serology could help us in the identification of those patients who were initially negative at laboratory testing alone.

    Measure: Efficacy of CT scan and Serology

    Time: 3 weeks

    Description: the efficacy of different pharmaceutical treatments against Covid-19

    Measure: Efficacy of different pharmaceutical treatments

    Time: 3 weeks
    185 Study of the Prevalence of Deep Vein Thrombosis in Patients Hospitalized in Intensive Care for Acute Respiratory Failure Linked to Pneumonia Documented With SARS-COV2

    Coronavirus 2 (SARS-CoV2) has been identified as the pathogen responsible for severe acute respiratory syndrome associated with severe inflammatory syndrome and pneumonia (COVID-19). Haemostasis abnormalities have been shown to be associated with a poor prognosis in these patients with this pneumonia. In a Chinese series of 183 patients, the hemostasis balance including thrombin time, fibrinogenemia, fibrin degradation products and antithrombin III were within normal limits. Only the D-Dimer assay was positive in the whole cohort with an average rate of 0.66 µg / mL (normal <50 µg / mL). These hemostasis parameters were abnormal mainly in patients who died during their management; the levels of D-dimers and fibrin degradation products were significantly higher while the antithrombin III was reduced. The findings on the particular elevation of D-dimers in deceased patients as well as the significant increase in thrombin time were also reported in another series. Higher numbers of pulmonary embolisms have been reported in patients with severe form of SARS-COV2 (data in press). This research is based on the hypothesis that the existence of deep vein thrombosis (DVT) could make it possible to screen patients at risk of pulmonary embolism and to set up a curative anticoagulation. The main objective is to describe the prevalence of deep vein thrombosis in patients hospitalized in intensive care for acute respiratory failure linked to documented SARS-COV2 pneumonia, within 24 hours of their admission.

    NCT04388657
    Conditions
    1. COVID
    2. Embolism and Thrombosis
    3. Pneumonia, Viral
    Interventions
    1. Diagnostic Test: Echo-Doppler
    MeSH:Pneumonia, Viral Pneumonia Thrombosis Embolism Embolism and Thrombosis
    HPO:Pneumonia Thromboembolism

    Primary Outcomes

    Description: The primary outcome measure will be the percentage of patients with one or more DVTs from a lower extremity ultrasound scan.

    Measure: percentage of patients with one or more DVTs.

    Time: 28 days
    186 Aerosol Inhalation of the Exosomes Derived From Allogenic COVID-19 T Cell in the Treatment of Early Stage Novel Coronavirus Pneumonia

    Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has caused mass mortality in the last 3 months that necessitates urgent development of new therapeutical agents. So far there is no effective anti-viral drug to reduce viral load that has critical importance to prevent progress into severe viral pneumonia and systemic hyper inflammation state. This project is to offer a biologic agent based on T cell derived exosomes. This is a novel approach using our proprietary protocols for drug development. This clinical trial is to test the safety and efficacy of this new agent following targeted delivery by metered dose inhaler. The project have received proper approvals from the Turkish Ministry of Health and Erciyes University, Kayseri Turkey. Turk-Patent Application Number: PCT/TR2020/050302

    NCT04389385
    Conditions
    1. Corona Virus Infection
    2. Pneumonia
    Interventions
    1. Biological: COVID-19 Specific T Cell derived exosomes (CSTC-Exo)
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Safety Assessment

    Measure: Adverse reaction (AE) and severe AE (SAE)

    Time: 28 days

    Description: Time to Clinical Recovery (TTCR)

    Measure: Efficacy Assessment

    Time: 28 days

    Description: Efficacy Assessment

    Measure: The Rate of Recovery Without Mechanical Ventilator

    Time: 28 days
    187 TOFAcitinib Plus Hydroxycloroquine vs Hydroxycloroquine in Patients With Early Onset SARS-CoV2 (COVID-19) Interstitial Pneumonia:a Multicenter Randomized Controlled Open Label Trial

    Multifocal interstitial pneumonia represents the most common cause of admission in intensive care units and death in SARS-CoV2 infections. In our Hospital, similarly to what reported in literature, up to 25% of admitted patients with pneumonitis requires mechanical ventilation or oro-tracheal intubation within 5-10 days. No established treatment is available for this condition. Preliminary evidence is accumulating about the efficacy of an aggressive treatment of the corona virus-induced inflammation and, in particular, investigators believe that blocking JAK1 is clinically rewarding in down-regulating IL-6 driven inflammation in patients with corona-virus infection. Thus, investigators designed a randomized controlled trial to test the hypothesis that adding Tofacitinib to the standard treatment in the early phase of COVID related pneumonitis could prevent the development of severe respiratory failure needing mechanical ventilation.

    NCT04390061
    Conditions
    1. Pneumonitis, Interstitial
    2. COVID-19
    Interventions
    1. Drug: Tofacitinib
    2. Drug: Hydroxychloroquine
    MeSH:Pneumonia Lung Diseases, Interstitial
    HPO:Interstitial pneumonitis Interstitial pulmonary abnormality Pneumonia

    Primary Outcomes

    Description: Rate of patients needing mechanical ventilation to maintain PaO2/FIO2>150

    Measure: Prevention of severe Respiratory Failure requiring mechanical ventilation

    Time: 14 days

    Secondary Outcomes

    Description: Rate of patients needing admission to the intensive care unit

    Measure: Prevention of need of ICU admission

    Time: 28 days

    Description: Rate of patients who die due to COVID-19 related conditions

    Measure: Prevention of COVID-19 related Deaths

    Time: 28 days

    Description: Role of some clinical and laboratory factors in predicting outcome (Age, sex, smoking status, Body Mass Index (BMI), Comorbidities (Diabetes, number of comorbidities), Respiratory Failure at admission defined as PaO2/FiO2<300, Extension of Ct-scan involvement, basal level of serum IL-6, vW-Factor, Thrombomodulin, KL-6, sACE2 and SP-D )

    Measure: Identification of predictors of outcome

    Time: 14 days

    Description: Rate of severe drug-related adverse events

    Measure: Incidence of Treatment-Emergent Adverse Events

    Time: 28 days
    188 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
    189 What is the Effect of Mesenchymal Stem Cell Therapy on Seriously Ill Patients With Covid 19 in Intensive Care? (Prospective Double Controlled Study)

    This study aims to use the regenerative and repair abilities of stem cells to fight against the harmful effects of the novel coronavirus Covid-19 and therefore develop a treatment strategy. It is known that fatalities from this virus is largely caused by its damage to lungs and other organs. As the disease progresses, these organs fail and lead to mortality. Our hope is that the stem cell transplantation from healthy donors will repair the damage caused by the virus and result in a healthy recovery.

    NCT04392778
    Conditions
    1. Covid19
    2. Pneumonia
    3. Multiple Organ Failure
    4. Corona Virus Infection
    Interventions
    1. Biological: MSC Treatment
    2. Biological: Saline Control
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia Multiple Organ Failure
    HPO:Pneumonia

    Primary Outcomes

    Description: Improvement of clinical symptoms related to Covid-19 infection (fever, pneumonia, shortness of breath)

    Measure: Clinical improvement

    Time: 3 months

    Secondary Outcomes

    Description: Improvement of lungs assessed by CT Scan

    Measure: Lung damage improvement

    Time: 3 months

    Description: Negative, measured by RT-PCR laboratory tests for the virus

    Measure: Sars-Cov-2 viral infection laboratory test

    Time: 3 months

    Description: Cell types and numbers

    Measure: Blood test

    Time: 3 months
    190 BARICIVID-19 STUDY: MultiCentre, Randomised, Phase IIa Clinical Trial Evaluating Efficacy and Tolerability of Baricitinib as add-on Treatment of In-patients With COVID-19 Compared to Standard Therapy

    There is urgent need of an effective therapy for Covid-19. To date, the best treatment of SARS-CoV-2 infection is unknown. Baricitinib has been identified as potential treatment for 2019-nCoV acute respiratory disease, because of its immunomodulating and hypothesized antiviral activity. This is a multicenter randomized clinical trial that aims to evaluate the efficacy and safety of baricitinib in patients with SARS-CoV2 pneumonia. Patients will be randomized to receive or not baricitinib as adjunctive therapy. All patients will continue to receive the ongoing standard therapy: chloroquine/idrossichloroquine and low-molecular weight heparin (LMWH) eventually associated with ritonavir/lopinavir or darunavir/ritonavir will be allowed for all included patients. The primary endpoint measure is the efficacy of baricitinib in reducing the number of patients requiring invasive ventilation after 7 and 14 days of treatment. Secondary endpoints will be mortality rates and toxicity of baricitinib.

    NCT04393051
    Conditions
    1. Covid-19
    2. SARS-CoV 2
    3. SARS Pneumonia
    Interventions
    1. Drug: Baricitinib Oral Tablet
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Reduction of the number of patients requiring invasive ventilation

    Measure: Need of invasive mechanical ventilation

    Time: after 7 and 14 days of treatment

    Secondary Outcomes

    Description: Proportion of any cause deaths

    Measure: Mortality

    Time: 14- and 28-days from randomization

    Description: Days from randomization to invasive mechanical ventilation

    Measure: Time to invasive mechanical ventilation

    Time: 30 days

    Description: Days from randomization to independence from non-invasive mechanical ventilation

    Measure: Time to independence from non-invasive mechanical ventilation

    Time: 30 days

    Description: Days from randomization to independence from oxygen therapy

    Measure: Time to independence from oxygen therapy

    Time: 30 days

    Description: Days from randomization to improvement in oxygenation for at least 48 hours

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

    Time: 30 days

    Description: Days of hospital stay

    Measure: Length of hospital stay

    Time: 30 days

    Description: Days of ICU stay

    Measure: Length of ICU stay

    Time: 30 days

    Description: Changes in pulmonary echography

    Measure: Instrumental response

    Time: 30 days

    Description: Rate of adverse events codified by Common Terminology Criteria for Adverse Events (CTCAE) v. 5.0

    Measure: Proportion of adverse events

    Time: 30 days
    191 Pilot Study of Low-Dose Single or Bilateral Whole Lung Irradiation for SARS-CoV-2 Pneumonia

    In this research study the investigators want to learn more about the potential benefit of radiation to the lung to improve the health of patients who are hospitalized with Coronavirus-19 (COVID-19) due to infection with a virus called SARS-CoV-2. This infection causes inflammation of the lung, which can make it difficult to breathe. As a result, patients may need supplemental oxygen or be placed on a ventilator. The investigators believe that low dose radiation therapy to the lung may reduce this inflammation and increase the likelihood that patients will need less oxygen support such as ventilation or supplemental oxygen, or be discharged from the hospital in fewer days, compared to without radiation therapy. The amount of radiation is much lower than what is typically used to treat other conditions such as cancer, although it is higher than the dose used for routine medical imaging.

    NCT04393948
    Conditions
    1. SARS-CoV 2
    Interventions
    1. Radiation: Phase 1
    2. Radiation: Phase 1
    3. Radiation: Phase 2
    4. Radiation: Phase 2
    5. Radiation: Phase 2
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Subjects will be treated with 100 cGy irradiation to a single (right-sided) lung (dose level 1) or 100 cGy irradiation to both lungs (dose level 2) following a 3 + 3 dose escalation scheme

    Measure: Phase 1: Feasibility and safety of treating hospitalized patients with SARS-CoV-2 pneumonia with single or bilateral whole lung irradiation

    Time: 4 days after randomization

    Description: The ordinal scale is an assessment of the clinical status on a given day. Each day, the worst (lowest) score from the previous day will be recorded as the score for that previous day. 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 low flow supplemental oxygen Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise) Hospitalized, not requiring supplemental oxygen - no longer required ongoing medical care Not hospitalized

    Measure: Phase 2: Proportion with clinical improvement on a 7-point ordinal scale on day 4 after randomization

    Time: 4 days after randomization

    Secondary Outcomes

    Measure: Improvement or worsening on the 7-point ordinal scale over additional intervals

    Time: Up to 30 days after randomization

    Measure: Rate and duration of use of supplemental oxygen

    Time: Up to 30 days after randomization

    Measure: Rate and duration of fever > 38ºC

    Time: Up to 30 days after randomization

    Measure: Rate and duration of invasive mechanical ventilation

    Time: Up to 30 days after randomization

    Measure: Duration of hospitalization

    Time: Up to 30 days after randomization

    Measure: Proportion of participants with overall survival up to 30 days after randomization

    Time: Up to 30 days after randomization

    Measure: Improvement in radiographic findings related to infection/inflammation; comparisons include on study versus baseline scans and irradiated vs. unirradiated lung in subjects randomized to receive single lung irradiation

    Time: Up to 30 days after randomization

    Measure: Treatment-emergent adverse events

    Time: Up to 30 days after randomization
    192 COVID-19 Imaging Features

    The novel coronavirus SARS-CoV2 clinically presents with pneumonia, characterised by fever, cough, dyspnea. The severity of the disease varies widely with evidence of mild disease in the majority of confirmed cases, severe pneumonia-dyspnea, hypoxia or lung involvement at imaging within 24-48 hours- and critical disease with respiratory failure, shock or multi-organ failure in particular patient cohorts. Imaging plays a key role is diagnosis and progression of this disease.

    NCT04394026
    Conditions
    1. Viral Pneumonia
    2. COVID
    MeSH:Pneumonia, Viral Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Evaluate RX imaging aspects at the time of diagnosis and until discharge.

    Measure: Describe qualitative and quantitative variables

    Time: Through study completion, an average of 5 months

    Description: Evaluate CT imaging aspects at the time of diagnosis and until discharge.

    Measure: Describe qualitative and quantitative variables

    Time: Through study completion, an average of 5 months

    Description: Correlate imaging findings to OS

    Measure: Ability of imaging to predict disease progression

    Time: Through study completion, an average of 5 months

    Description: Correlate imaging findings over time

    Measure: Ability of imaging to predict disease evolution

    Time: Through study completion, an average of 5 months

    Secondary Outcomes

    Description: Correlate imaging findings to age and sex

    Measure: Imaging findings and demographic data

    Time: Through study completion, an average of 5 months

    Description: Correlate imaging findings to laboratory values

    Measure: Imaging findings and laboratory exams

    Time: Through study completion, an average of 5 months
    193 Low Doses of Lung Radiation Therapy in Cases of COVID-19 Pneumonia: Prospective Multicentric Study in Radiation Oncology Centers

    The host response against the coronavirus 2 (SARS-CoV-2) appears to be mediated by a 'cytoquine storm' developing a systemic inflammatory mechanism and an acute respiratory distress syndrome (ARDS), in the form of a bilateral pneumonitis, requiring invasive mechanical ventilation (IMV) in an important group of patients. In terms of preventing progression to the critical phase with the consequent need of admission to the intensive care units (ICU), it has been recently proposed that this inflammatory cytoquine-mediated process can be safely treated by a single course of ultra-low radiotherapy (RT) dose < 1 Gy. The main purpose of the study was to analyze the efficacy of ultra low-dose pulmonary RT, as an anti-inflammatory intention in patients with SARS-Cov-2 pneumonia with a poor or no response to standard medical treatment and without IMV.

    NCT04394182
    Conditions
    1. Pneumonia, Viral
    2. Cytokine Storm
    Interventions
    1. Radiation: Ultra-Low-dose radiotherapy
    2. Device: ventilatory support with oxygen therapy
    3. Drug: Lopinavir/ritonavir
    4. Drug: Hydroxychloroquine
    5. Drug: Azithromycin
    6. Drug: Piperacillin/tazobactam
    7. Drug: Low molecular weight heparin
    8. Drug: Corticosteroid injection
    9. Drug: Tocilizumab
    MeSH:Pneumonia, Viral Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: To evaluate the efficacy of ultra low-dose pulmonary RT through clinical evaluation.It was performed by oxygen therapy status assessment after RT treatment. Improvement criteria is considered as an oxygen therapy de-escalation (more to less need for support: Ventimask (VMK) with reservoir >VMK >Nasal Cannula-(NC).)

    Measure: Oxygen Therapy Status at Day 2

    Time: At 2 after RT

    Description: To evaluate the efficacy of ultra low-dose pulmonary RT through clinical evaluation. .It was performed by oxygen saturation (Sat02 %) status assessment after RT treatment. Improvement criteria is considered as a Sat02 with/without oxygen therapy >93% (Pulse oximeter measurement)

    Measure: Oxygen Saturation (Sat02; Pulse oximeter measurement) at Day 2

    Time: At 2 days after RT

    Secondary Outcomes

    Description: Pa02 / Fi02 > 300 mmHg

    Measure: Blood Gas Analysis at Day 2

    Time: At 2 days after RT

    Description: Achievement of normal range value in 1 or more of the inflammatory and immunological parameters (lymphocytes, IL-6, D-dimer, ferritin, LDH, C Reactive Protein (CRP) and fibrinogen)

    Measure: Blood Test at Day 2

    Time: At 2 days after RT

    Description: To evaluate the efficacy of ultra low-dose pulmonary RT through clinical evaluation.It was performed by oxygen therapy status assessment after RT treatment. Improvement criteria is considered as an oxygen therapy de-escalation (more to less need for support: Ventimask (VMK) with reservoir >VMK >Nasal Cannula-(NC).)

    Measure: Oxygen Therapy Status at Day 5

    Time: At 5 after RT

    Description: To evaluate the efficacy of ultra low-dose pulmonary RT through clinical evaluation. .It was performed by oxygen saturation (Sat02 %) status assessment after RT treatment. Improvement criteria is considered as a Sat02 with/without oxygen therapy >93% (Pulse oximeter measurement)

    Measure: Oxygen Saturation (Sat02; Pulse oximeter measurement) at Day 5

    Time: At 5 days after RT

    Description: Achievement of normal range value in 1 or more of the inflammatory and immunological parameters (lymphocytes, IL-6, D-dimer, ferritin, LDH, C Reactive Protein (CRP) and fibrinogen)

    Measure: Blood Test at Day 5

    Time: At 5 days after RT

    Description: To evaluate the efficacy of ultra low-dose pulmonary RT through clinical evaluation.It was performed by oxygen therapy status assessment after RT treatment. Improvement criteria is considered as an oxygen therapy de-escalation (more to less need for support: Ventimask (VMK) with reservoir >VMK >Nasal Cannula-(NC).)

    Measure: Oxygen Therapy Status at Day 7

    Time: At 7 after RT

    Description: To evaluate the efficacy of ultra low-dose pulmonary RT through clinical evaluation. .It was performed by oxygen saturation (Sat02 %) status assessment after RT treatment. Improvement criteria is considered as a Sat02 with/without oxygen therapy >93% (Pulse oximeter measurement)

    Measure: Oxygen Saturation (Sat02; Pulse oximeter measurement) at Day 7

    Time: At 7 days after RT

    Description: Achievement of normal range value in 1 or more of the inflammatory and immunological parameters (lymphocytes, IL-6, D-dimer, ferritin, LDH, C Reactive Protein (CRP) and fibrinogen)

    Measure: Blood Test at Day 7

    Time: At 7 days after RT

    Description: To evaluate the efficacy of ultra low-dose pulmonary RT through radiological evaluation.It was performed by thoracic CT scan after RT treatment . It is considered a radiological improvement the decrease of the Total Severity Score (TSS) from the baseline in > or = 1 point. NOTE: The score values ranged from 0 to 4 according to the sum of the percentage involvement of each of the 5 lung lobes. The total severity score (TSS), was reached by summing the overall involvement in the lung (0-20 points)

    Measure: Change from baseline Total Severity Score (TSS) analyzed in a thoracic CT scan at Day 7

    Time: At 7 days after RT

    Description: Recovery time after RT administration until hospital discharge or death (<48h; 2-7 days; >7 days; clinical worsening or death)

    Measure: Recovery time

    Time: From RT administration until hospital discharge or death

    Description: COVID-19 negativization test

    Measure: COVID-19 status

    Time: At 7 days after RT

    Description: To evaluate the efficacy of ultra low-dose pulmonary RT through radiological evaluation.It was performed by thoracic CT scan after RT treatment . It is considered a radiological improvement the decrease of the Total Severity Score (TSS) from the baseline in > or = 1 point. NOTE: The score values ranged from 0 to 4 according to the sum of the percentage involvement of each of the 5 lung lobes. The total severity score (TSS), was reached by summing the overall involvement in the lung (0-20 points)

    Measure: Change from baseline Total Severity Score (TSS) analyzed in a thoracic CT scan al Month 1

    Time: At 1 month after RT

    Description: Toxicity was assessed and rated according to the NIH Common Terminology Criteria for Adverse Events (CTCAE version 5.0) and RTOG scales.

    Measure: Acute Toxicity

    Time: 1-3 months after RT
    194 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
    195 Low Dose Radiation Therapy for Covid-19 Pneumonia: A Pilot Study

    Radiotherapy in low doses (30 to 100 cGy) was a popular treatment of viral pneumonias until 1940s. Low dose radiation therapy (LDRT) could possibly reduce the inflammation and prevent the cytokine storm thus mitigating the severity of pneumonitis. This is a single arm study designed to assess the feasibility and clinical efficacy of low dose radiation therapy (70 cGy in single fraction) in the patients with COVID-19 pneumonia. A total of 10 eligible patients (as per inclusion criteria) will be recruited and response will be assessed based on the symptomatic improvement or deterioration by using the National Early Warning Score (NEWS). The NEWS score will be recorded on baseline and then on Day 3, Day 7 and Day 14.

    NCT04394793
    Conditions
    1. COVID-19
    2. Pneumonia
    Interventions
    1. Radiation: Low dose radiation therapy
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: NEWS score

    Measure: Symptomatic improvement by National Early warning score (NEWS)

    Time: Day 3

    Description: NEWS score

    Measure: Symptomatic improvement by National Early warning score (NEWS)

    Time: Day 7

    Description: NEWS score

    Measure: Symptomatic improvement by National Early warning score (NEWS)

    Time: Day 14

    Description: Days

    Measure: Length of hospital stay

    Time: 30 days or date of death whichever is earlier

    Description: Number of patients

    Measure: Number of ICU admissions or deaths

    Time: 30 days
    196 Molecular Diagnosis and Prognosis of Severe Pulmonary Infection in Immunosuppressed Hosts

    Serious pneumonia is a serious inflammation of the lungs caused by various pathogens, resulting in severe bacteraemia or toxemia, which in turn causes blood pressure drop, shock, blurred consciousness, restlessness, delirium and coma, etc., and requires intensive care and treatment in intensive care unit (ICU) because of its seriousness. There is an upward trend in the number of clinically immunosuppressed host patients, including long-term use of glucocorticoids for rheumatoid immune diseases and kidney diseases, tumor chemotherapy, organ transplantation, etc. A huge risk for these patients is the diagnosis and treatment of infections, especially lung infections. We have previously observed a significant increase in mortality from severe pneumonia in immunosuppressed patients, and our recent analysis of 204 patients with novel coronavirus pneumonia found that low lymphatic counts, immunosuppression, etc. were independent risk factors for death in patients. Early diagnosis and timely treatment are the main means to reduce the mortality rate of severe pneumonia. CD55 is an important complement regulatory protein that inhibits C3 and C5 activation by blocking the formation and accelerating the decay of new C3 and C5 convertases, both of which mediate the downstream action of all three complement activation pathways, and CD55 protects host cells from complement attack. Our previous study found that CD55 was significantly elevated in patients with severe pneumonia. Therefore, this project proposes "Early diagnosis of severe pneumonia based on combination of biomarkers with new generation pathogenesis and early clinical manifestations". It is proposed to validate the predictive effects of recently discovered markers such as CD55, HBP and CD64 on severe pneumonia through prospective single-center clinical studies, explore the establishment of new predictive models for early diagnosis of severe pneumonia, and optimize the diagnosis and treatment strategy of severe pneumonia, and provide new ideas for accurate treatment of severe pneumonia.

    NCT04395066
    Conditions
    1. Severe Pneumonia
    2. Immunosuppressed Hosts
    3. Diagnosis
    Interventions
    1. Diagnostic Test: CD55
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Measure: Number of patient diagnosed with severe pneumonia within 28 days

    Time: 28 days
    197 A Phase I Study of ResCure™ to Treat COVID-19 Infection

    This is a Phase I open-label interventional study which will test the efficacy of ResCure™ in the treatment of patients with COVID-19 infection.

    NCT04395716
    Conditions
    1. COVID
    2. Covid-19
    3. Corona Virus Infection
    4. Sars-CoV2
    5. Coronavirus-19
    6. SARS Pneumonia
    7. SARS-Associated Coronavirus as Cause of Disease Classified Elsewhere
    Interventions
    1. Biological: ResCure™
    MeSH:Infection Communicable Diseases Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Number of days from COVID-19 diagnosis to recovery via RT-PCR

    Measure: The rate of recovery of mild or moderate COVID-19 in patients using ResCure™

    Time: 12 Weeks

    Description: Reduction and/or progression of symptomatic days, reduction of symptom severity

    Measure: Reduction or progression of symptomatic days

    Time: 12 Weeks

    Description: Pulse from baseline to 12 weeks

    Measure: Assess the safety of ResCure™ via pulse

    Time: 12 Weeks

    Description: Oxygen saturation from baseline to 12 weeks

    Measure: Assess the safety of ResCure™ via oxygen saturation

    Time: 12 Weeks

    Description: EKG from baseline to 12 weeks

    Measure: Assess the safety of ResCure™ via EKG

    Time: 12 Weeks

    Description: Assess Adverse Events and Serious Adverse Events due to ResCure™

    Measure: Assess Tolerability of ResCure™

    Time: 12 Weeks
    198 A Study to Collect Bone Marrow for Process Development and Production of Bone Marrow Mesenchymal Stromal Cells to Treat Severe COVID19 Pneumonitis

    The COVID-19 pandemic, commonly referred to as "coronavirus", first began in the city of Wuhan, China in December 2019. This virus has since spread globally, with infections reported in nearly every country. COVID-19 targets the body's respiratory system, where infections can be found in the nose, throat and lungs. The effect of COVID-19 infection is very variable, where many people might not know that they have been infected and have recovered from COVID-19. However, COVID-19 infection can cause people to have difficulty breathing. This can be severe enough to require hospitalisation and potentially intensive care treatment. While they are being treated in hospital, COVID-19 infected patients can be found to have inflamed tissue in their lungs (referred to medically as "pneumonitis"). This inflammation is thought to be caused by their body's immune systems overacting to the infection rather than the COVID-19 virus itself. By potentially dampening down this overreaction of their immune system, it is hoped that COVID-19 patients with inflamed lungs have better and quicker chance to survive. Mesenchymal stromal cells (MSCs) have been shown to have anti-inflammatory and healing properties on injured tissue. MSCs have been trialled in various diseases but have not yet been tested on patients with COVID-19. In this study, the investigators will obtain bone marrow from healthy volunteers to develop a cell-based treatment for COVID-19-related pneumonitis. The investigators will also determine whether it is feasible to recruit bone marrow donors in a clinically useful timeframe to treat COVID-19 patients. A future trial, COMET20, will use the bone marrow-derived MSCs (BM-MSCs) manufactured in COMET20d to treat COVID-19 patients suffering with pneumonitis, to determine whether the BMMSCs can reduce the likelihood for mechanical ventilation and reduce hospitalisation.

    NCT04397471
    Conditions
    1. Healthy Volunteers for Bone Marrow Donation
    Interventions
    1. Procedure: Bone Marrow Harvest
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Successful identification of healthy volunteers in acceptable timeframe (i.e. within days) to donate bone marrow.

    Measure: Determine feasibility of recruiting healthy volunteers in a clinically useful timeframe.

    Time: 3 or more participants recruited in 1 month

    Description: Successful manufacture of bone marrow-mesenchymal stromal cells suitable for clinical use

    Measure: Manufacture a cell-based product suitable for clinical use

    Time: Successfully opening the next phase of the trial in approx. 2 months

    Secondary Outcomes

    Description: Ability to prepare a dossier acceptable to the MHRA. Success will achieved if the dossier is deemed acceptable.

    Measure: Establishment of a robust process of production

    Time: Successfully opening the next phase of the trial in approx. 2 months

    Description: Successful manufacturing of products will be defined initially as the award of a Manufacturers Specials Licence to the CCTL to allow the manufacture of Bone Marrow-Mesenchymal Stromal Cells for compassionate use.

    Measure: Production of stability data to be used in the MHRA dossier for the COMET clinical trial.

    Time: Successfully opening the next phase of the trial in approx. 2 months

    Description: Successful manufacturing of products will be subsequently defined by production under MA(IMP) licence, allowing for future production under CTIMP and CTA.

    Measure: Production of cell-based products to be administered to COVID-19 patients with severe pneumonitis.

    Time: Successfully opening the next phase of the trial in approx. 2 months

    Description: Successful manufacturing of products, under MA(IMP) licence will be defined as the availability of Bone Marrow-Mesenchymal Stromal Cells to be used in the context of the COMET20 clinical trial.

    Measure: Analysis of cells for understanding production, manufacture and related research.

    Time: Successfully opening the next phase of the trial in approx. 2 months
    199 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
    200 Inhaled NO for the Treatment of COVID-19 Caused by SARS-CoV-2 (US Trial)

    The purpose of this open label, randomized, study is to obtain information on the safety and efficacy of 80 ppm Nitric Oxide given in addition to the standard of care of patients with COVID-19 caused by SARS-CoV-2.

    NCT04397692
    Conditions
    1. Corona Virus Infection
    2. COVID-19
    3. SARS-CoV 2
    4. Nitric Oxide
    5. Respiratory Disease
    6. Pneumonia, Viral
    7. Inhaled Nitric Oxide
    Interventions
    1. Device: Nitric Oxide delivered via LungFit™ system
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia, Viral Pneumonia Respiratory Aspiration Respiration Disord Respiration Disorders Respiratory Tract Diseases
    HPO:Pneumonia

    Primary Outcomes

    Description: Time to deterioration measured by need for NIV, HFNC or intubation

    Measure: Time to deterioration

    Time: 14 Days

    Secondary Outcomes

    Description: Time to non-invasive ventilation

    Measure: Time to NIV

    Time: 14 Days

    Description: Time to high flow nasal cannula

    Measure: Time to HFNC

    Time: 14 Days

    Description: Time to intubation

    Measure: Time to intubation

    Time: 14 days

    Description: Time to patient having stable oxygen saturation (SpO2) of greater than or equal to 93%

    Measure: Time to patient having stable oxygen saturation (SpO2) of greater than or equal to 93%

    Time: 14 days

    Other Outcomes

    Description: Need for supplemental oxygen

    Measure: Need for supplemental oxygen

    Time: 14 days

    Description: Change in viral load

    Measure: Change in viral load

    Time: 30 days

    Description: Duration of the Hospital Length of Stay (LOS)

    Measure: Duration of the Hospital Length of Stay (LOS)

    Time: 14 days

    Description: Mortality rate at Day 30

    Measure: Mortality rate at Day 30

    Time: 30 days
    201 An Open-Label, Controlled, Phase 1, Safety and Exploratory Efficacy Study of Convalescent Plasma for Severely Ill, Hospitalized Participants With COVID-19 Pneumonia Caused by SARS-CoV-2.

    The purpose of this study is to see if this plasma can be safely used in humans with COVID-19 and to see if it improves patients' health as compared to not using it in patients with pneumonia caused by SARS-CoV-2.

    NCT04397757
    Conditions
    1. COVID-19
    Interventions
    1. Biological: COVID-19 Convalescent Plasma
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Cumulative incidence of serious adverse events (SAEs) at Study Day 29.

    Measure: Participants with serious adverse events.

    Time: Up to 29 days from treatment

    Description: Severity is measured by the 8-point ordinal clinical severity scale at D29 where 1 is the best state to be in and 8 is the worst (equals death).

    Measure: Comparison of clinical severity score between patients on the experimental versus control arms;

    Time: Up to 29 days from treatment

    Secondary Outcomes

    Description: Time to recovery, defined by time to levels 1-3 on the ordinal scale

    Measure: Clinical status assessment, using 8-point ordinal scale, of convalescent plasma administration by comparing treatment vs control arms

    Time: Up to 29 days from treatment

    Description: Time to discharge or to a NEWS of ≤ 2 and maintained for 24 hours, whichever occurs first.

    Measure: Clinical status assessment using the National Early Warning Score (NEWS) of convalescent plasma administration by comparing treatment vs control arms

    Time: From enrollment, daily while hospitalized until discharge or death and on Days 15 and 29.

    Description: Oxygen-free days to Day 29.

    Measure: Oxygen-free days of convalescent plasma administration by comparing treatment vs control arms

    Time: From enrollment to Day 29

    Description: Incidence of new oxygenation use up to Day 29.

    Measure: Incidence of new oxygenation use up to Day 29 of convalescent plasma administration by comparing treatment vs control arms

    Time: From enrollment to Day 29.

    Description: Days of new oxygen use up to Day 29.

    Measure: Duration of new oxygen use up to Day 29 of convalescent plasma administration by comparing treatment vs control arms

    Time: From enrollment to Day 29.

    Description: Days of non-invasive ventilation/high flow oxygen up to Day 29

    Measure: Non-invasive ventilation/high flow oxygen days up to Day 29 of convalescent plasma administration by comparing treatment vs control arms

    Time: From enrollment to Day 29.

    Description: Incidence of non-invasive ventilation up to Day 29.

    Measure: Incidence of non-invasive ventilation/high flow oxygen up to Day 29 of convalescent plasma administration by comparing treatment vs control arms

    Time: From enrollment to Day 29.

    Description: Days of non-invasive ventilation/high flow oxygen up to Day 29

    Measure: Duration of non-invasive ventilation/high flow oxygen up to Day 29 of convalescent plasma administration by comparing treatment vs control arms

    Time: From enrollment to Day 29.

    Description: Ventilation/ECMO free days up to Day 29. mechanical ventilation or ECMO use during the study.

    Measure: Ventilator/ECMO free days to Day 29 of convalescent plasma administration by comparing treatment vs control arms

    Time: From enrollment to Day 29.

    Description: Incidence of new mechanical ventilation or ECMO use up to Day 29.

    Measure: Incidence of new mechanical ventilation or ECMO use of convalescent plasma administration by comparing treatment vs control arms

    Time: From enrollment to Day 29.

    Description: Days of new mechanical ventilation or ECMO use up to Day 29.

    Measure: Duration of new mechanical ventilation or ECMO use of convalescent plasma administration by comparing treatment vs control arms

    Time: From enrollment to Day 29.

    Description: Duration of hospitalization.

    Measure: Duration of hospitalization of convalescent plasma administration by comparing treatment vs control arms

    Time: To Day 29

    Description: D14 and D28 mortality.

    Measure: Mortality of convalescent plasma administration by comparing treatment vs control arms

    Time: To Day 28

    Description: Cumulative incidence of SAEs through Day 29.

    Measure: Cumulative incidence of SAEs through Day 29 of convalescent plasma administration by comparing treatment vs control arms

    Time: Through Day 29

    Description: Cumulative incidence of Grade 3 and Grade 4 clinical and/or laboratory adverse events through Day 29.

    Measure: Cumulative incidence of Grade 3 and Grade 4 clinical and/or laboratory adverse events through Day 29 of convalescent plasma administration by comparing treatment vs control arms

    Time: Through Day 29

    Description: Changes in WBC with differential on Days 1, 3, 5, 8, and 11 (while hospitalized); Days 15 and 29 (if attends in person visit or still hospitalized).

    Measure: Changes in WBC with differential through day 29 of convalescent plasma administration by comparing treatment vs control arms

    Time: Through Day 29

    Description: Changes in hemoglobin measurement on Days 1, 3, 5, 8, and 11 (while hospitalized); Days 15 and 29 (if attends in person visit or still hospitalized).

    Measure: Changes in hemoglobin measurement through Day 29 of convalescent plasma administration by comparing treatment vs control arms

    Time: Through Day 29

    Description: Changes in platelets measurement laboratory adverse events on Days 1, 3, 5, 8, and 11 (while hospitalized); Days 15 and 29 (if attends in person visit or still hospitalized).

    Measure: Changes in platelets measurement through Day 29 of convalescent plasma administration by comparing treatment vs control arms

    Time: Through Day 29.

    Description: Changes in creatinine measurement on Days 1, 3, 5, 8, and 11 (while hospitalized); Days 15 and 29 (if attends in person visit or still hospitalized).

    Measure: Changes in creatinine measurement through Day 29 of convalescent plasma administration by comparing treatment vs control arms

    Time: Through Day 29.

    Description: Changes in glucose measurement on Days 1, 3, 5, 8, and 11 (while hospitalized); Days 15 and 29 (if attends in person visit or still hospitalized).

    Measure: Changes in glucose measurement through Day 29 of convalescent plasma administration by comparing treatment vs control arms

    Time: Through Day 29.

    Description: Changes in bilirubin measurement on Days 1, 3, 5, 8, and 11 (while hospitalized); Days 15 and 29 (if attends in person visit or still hospitalized).

    Measure: Changes in bilirubin measurement through Day 29 of convalescent plasma administration by comparing treatment vs control arms

    Time: Through Day 29

    Description: Changes in ALT measurement laboratory adverse events on Days 1, 3, 5, 8, and 11 (while hospitalized); Days 15 and 29 (if attends in person visit or still hospitalized).

    Measure: Changes in ALT measurement laboratory adverse events through Day 29 of convalescent plasma administration by comparing treatment vs control arms

    Time: Through Day 29

    Description: Changes in AST measurement on Days 1, 3, 5, 8, and 11 (while hospitalized); Days 15 and 29 (if attends in person visit or still hospitalized).

    Measure: Changes in AST measurement through Day 29 of convalescent plasma administration by comparing treatment vs control arms

    Time: Through Day 29.

    Description: Changes in PT measurement laboratory adverse events on Days 1, 3, 5, 8, and 11 (while hospitalized); Days 15 and 29 (if attends in person visit or still hospitalized).

    Measure: Changes in PT measurement laboratory adverse events through Day 29 of convalescent plasma administration by comparing treatment vs control arms

    Time: Through Day 29.
    202 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
    203 The Utility of Bedside Lung Ultrasonography on Diagnosis of COVID-19 at Emergency Department

    Novel Coronavirus 2019 Disease (COVID-19) mortality is highly associated with viral pneumonia and its complications. Accurate and prompt diagnosis shown to be effective to improve outcome by providing early treatment strategies. While chest X-ray (CXR) and computerized tomography (CT) are defined as gold standard, given the advantage of being an ionized radiation free, practical technique point of care ultrasound (POCUS) is also reported as a diagnostic tool for COVID-19. There are limited studies regarding the importance of POCUS in diagnosis and review of COVID-19. Therefore the aim of this study is to evaluate the utility of bedside lung ultrasound on diagnosis of COVID-19 for patients admitted to emergency department .

    NCT04399681
    Conditions
    1. COVID
    2. Pneumonia, Viral
    Interventions
    1. Device: Bedside lung ultrasound
    MeSH:Pneumonia, Viral Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Efficacy of POCUS on diagnosis of viral pneumonia caused by COVID 19

    Measure: Presence of viral pneumonia caused by COVID 19

    Time: 3 months
    204 A proof-of Concept Study of the Use of Janus Kinase 1 and 2 Inhibitor, Baricitinib, in the Treatment of COVID-19-related Pneumonia

    The objective of the study is to assess the efficacy and safety of Baricitinib in the treatment of patients with COVID-19 pneumonia. This will be a proof-of-concept trial with an exploratory single-arm proof of concept Phase IIa study to assess the efficacy and safety profile of Baricitinib in a limited number of patients with severe acute respiratory syndrome (SARS)-CoV-2 pneumonia. If the initial proof of concept phase will lead to favourable results, an open-label, Phase II, randomized controlled trial will be then designed and performed to confirm the results obtained in the proof of concept phase. The proof-of-concept phase guarantees that no safety issues arise on a limited number of patients in the use of a drug new to the current condition being treated.

    NCT04399798
    Conditions
    1. Corona Virus Infection
    Interventions
    1. Drug: Baricitinib
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: A patient is consider responder in the absence of either moderate to severe oxygenation impairment according to Berlin criteria - measured as Partial pressure of oxygen/fraction inspired oxygen (PaO2/FiO2)

    Measure: Response to treatment: absence of moderate to severe oxygenation impairment (Berlin criteria)

    Time: 8 days

    Description: Absence of death within 8 days from enrollment

    Measure: Response to treatment: survival

    Time: 8 days

    Secondary Outcomes

    Description: Moderate to severe oxygenation impairment according to Berlin criteria (measured as PaO2/FiO2)

    Measure: To quantify the rate of each of: moderate or severe oxygenation impairment within 8 days

    Time: 8 days

    Description: Moderate to severe oxygenation impairment according to Berlin criteria (measured as PaO2/FiO2)

    Measure: To quantify the rate of each of: moderate or severe oxygenation impairment within 15 days

    Time: 15 days

    Description: To quantify mortality within 8 and 15 days

    Measure: Mortality

    Time: 8 days and 15 days

    Description: SpO2 will be assessed with the median and 25th-75th percentiles

    Measure: Peripheral capillary oxygen saturation (SpO2)

    Time: 8 days; 15 days

    Description: PaO2/FiO2 will be assessed with the median and 25th-75th percentiles

    Measure: Partial pressure of oxygen/fraction inspired oxygen (PaO2/FiO2)

    Time: 8 days; 15 days

    Description: Number of patients over the number of patients enrolled

    Measure: To assess the rate of patients admitted to the intensive care unit

    Time: 8 days; 15 days

    Description: Median number of days and 25th-75th percentiles

    Measure: To measure the length of hospital stay

    Time: 8 days; 15 days

    Description: To quantify 28-day mortality

    Measure: 28-day mortality

    Time: 28 days

    Description: Number of patients readmitted over the number patients enrolled

    Measure: To quantify the rate of re-admission within 28 days

    Time: 28 days

    Description: Number, type, and severity of adverse events

    Measure: To quantify the cumulative incidence and severity of adverse events

    Time: 28 days

    Description: Serial serum assessments from baseline up to 15 days

    Measure: Interleukin (IL)-1; IL-2; IL-10; IL-6; IL-8; IL-17; IL-2 receptor levels;

    Time: 15 days

    Description: Serial serum assessments from baseline up to 15 days

    Measure: TNFalpha; vascular endothelial growth factor (VEGF); interferon gamma (IFNgamma) levels

    Time: 15 days

    Description: Serial assessments from baseline up to 15 days for viral load persistence

    Measure: Viral load analyses

    Time: 15 days
    205 Mavrilimumab to Reduce Progression of Acute Respiratory Failure in Patients With Severe 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.

    NCT04399980
    Conditions
    1. COVID 19
    2. SARS-CoV 2
    3. Pneumonia
    Interventions
    1. Drug: Mavrilimumab
    2. Drug: Placebos
    MeSH:Pneumonia Respiratory Insufficiency Inflammation
    HPO:Pneumonia

    Primary Outcomes

    Description: Number of subjects alive and off of oxygen

    Measure: Proportion of subjects alive and off of oxygen at day 14

    Time: Day 14

    Secondary Outcomes

    Description: Number of subjects that are alive

    Measure: Proportion of subjects alive at 28 days

    Time: Day 28

    Description: Number of subjects alive and without respiratory failure

    Measure: Proportion of subjects alive and without respiratory failure at 28 days

    Time: Day 28
    206 Multiparametric Evaluation of One-year Outcomes in Survivors of the Severe COVID-19 Pneumonia After Intensive Care Unit

    Pneumonia caused by infection at SARS-CoV2 may be complicated by an acute respiratory detress syndrome need to take care in intensive care unit and can lead to mechanical ventilation. COVID-19 is a pandemic disease and lot of patients will survive of severe pneumoniae at SARS-CoV2 treat in ICU. At this time, there is no data about functional prognosis at long term. This aim of this study is to evaluate the recovery of quality of life, respiratory function, neuromuscular function at long term and incidence of post-traumatic stress disorder. Patients will follow during 1year after out of ICU with 3 consultations at 3month, 6month and 12month. At each consultation patients will be evaluated about respiratory function, effort tolerance via 6minutes walking test, psychologic function with IES-R and HAD score and quality of life with SF36. The hypothesis is that patients who survived of ARDS post infection at SARS-CoV2 have persistent functional limitation and alteration of quality of life one year after being discharged from the ICU.

    NCT04401111
    Conditions
    1. COVID
    2. ARDS
    3. Quality of Life
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: The primary outcome is the score SF36 at 3month, 6month, 12 month after discharged of ICU in study population

    Measure: Evaluation of recovery of quality of life in first year after ICU discharged in patients hospitalised for severe pneumonia at SARS-CoV2

    Time: 1 year

    Secondary Outcomes

    Description: Evaluation of functional respiratory exploratory

    Measure: Evaluation of respiratory function during first year after ICU discharged in population studied

    Time: 1 year

    Description: Mesure of the traveled distance in six-min walk test

    Measure: Evaluation at 1 year of evolution of functional exercises capacity in population studied

    Time: 1 year

    Description: Mesure of creatinine clairance and proteinuria

    Measure: Evaluation of evolution of renal function during first year after ICU discharged in population studied

    Time: 1 year

    Description: Sudy of cardiac ultrasonography parameters

    Measure: Evaluation of evolution of right and left myocardic function during first year after ICU discharged in population studied

    Time: 1 year

    Description: Occurence of post-traumatic stress disorder or anxious and depressive disorders in population studied

    Measure: Evaluation at 1 year of incidence of psychiatric pathology

    Time: 1 year

    Description: Rate of return to professional activity

    Measure: Evaluation at 1 year of consequences in professional activity in population studied

    Time: 1 year
    207 Development and Validation of Predictive Models for Intensive Care Admission and Death of COVID-19 Patients in a Secondary Care Hospital in Belgium.

    To build simple and reliable predictive scores for intensive care admissions and deaths in COVID19 patients. These scores adhere to the TRIPOD (transparent reporting of a multivariable prediction model for individual prognosis or diagnosis) reporting guidelines. The outcomes of the study are (i) admission in the Intensive Care Unit admission and (ii) death. All patients admitted in the Emergency Department with a positive reverse transcription-polymerase chain reaction SARS-COV2 test were included in the study. Routine clinical and laboratory data were collected at their admission and during their stay. Chest X-Rays and CT-Scans were performed and analyzed by a senior radiologist. Generalized Linear Models using a binomial distribution with a logit link function (R software version X) were used to develop predictive scores for (i) admission to ICU among emergency ward patients; (ii) death among ICU patients. A first panel of Number Models with the highest AIC (BIC) was preselected. Ten-fold cross-validation was then used to estimate the out-of-sample prediction error among these preselected models. The one with the smallest prediction error was in the end singled out .

    NCT04401228
    Conditions
    1. COVID19
    2. Pneumonia, Viral
    3. Inflammatory Response
    Interventions
    1. Other: predict admission of covid-19 patients to ICU and death with routine and quickly avalaible clinical, biological and radiological variables?
    MeSH:Pneumonia, Viral Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Measure: admission to ICU

    Time: through study completion, an average of 1 year

    Secondary Outcomes

    Measure: death

    Time: through study completion, an average of 1 year
    208 Paediatric Post Pneumococcal Conjugate Vaccine Nasopharyngeal Carriage Study

    The investigators intend to investigate the carriage of pneumococci and other respiratory microbes since the introduction of pneumococcal conjugate vaccines (Prevenar 7 and Prevenar 13). The principal aim is to gain a collection of samples that can be used to help investigate any changes that might occur in the epidemiology of microbes that are carried in the upper respiratory tract and which may cause respiratory disease, sepsis or meningitis after the introduction of Prevenar. Nasopharyngeal and nasal swabs will be taken from up to 2,000 children aged 4 years and under in each year of the study. Swabs will be processed using traditional microbiology and molecular diagnostic techniques and isolated microbes such as S. pneumoniae further characterised using molecular methods. The investigators will also ask parents to complete a short questionnaire requesting: basic demographic data; vaccine history; recent illness; overseas travel and antibiotic usage. The study will contribute to the success of the introduction of pneumococcal conjugate vaccines and will play a central role in maintaining confidence. The study will also help provide information for future vaccine policy as further vaccines are developed against microbes which cause respiratory disease, sepsis and meningitis.

    NCT04401488
    Conditions
    1. S. Pneumoniae
    2. Pneumococcal Conjugate Vaccine
    Interventions
    1. Biological: Prevenar 7 and Prevenar 13
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: To gain a collection of pneumococci and other microbes of related importance that can be used to help investigate any changes that occur in the epidemiology of pneumococcal disease since the introduction of Prevenar 13

    Measure: Collection of pneumococci

    Time: By the end of the study (31/03/2027)

    Secondary Outcomes

    Description: To use all isolated strains to help understand changes in the molecular epidemiology of pneumococci, and other relevant microbe species of the upper respiratory tract.

    Measure: Understand changes in the molecular epidemiology of pneumococci

    Time: By the end of the study (31/03/2027)
    209 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
    210 Safety and Efficacy of Tocilizumab in Moderate to Severe COVID-19 and Increased Inflammatory Markers: a Phase III Randomized Clinical Trial (COVID-19 Coalition Brazil VI) (TOCIBRAS)

    The trial evaluates the efficacy and safety of Tocilizumab, which rapidly reduces the inflammation process through inhibition of IL-6 in patients with moderate to severe COVID-19 with increased inflammatory markers. There will be two arms in the trial, one receiving the best supportive care, and the other receiving it plus tocilizumab. Patients will be followed until Day 29 after randomization.

    NCT04403685
    Conditions
    1. COVID
    2. SARS Pneumonia
    3. Cytokine Release Syndrome
    Interventions
    1. Drug: Tocilizumab
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Evaluation of clinical status of patients on day 15 after randomization, defined by the Ordinal Scale of 7 points (score ranges from 1 to 7, with 7 being the worst score)

    Measure: Evaluation of clinical status

    Time: Day 15 of the trial

    Secondary Outcomes

    Description: All-cause mortality from randomization to day 28

    Measure: All-cause mortality

    Time: 29 days after the randomization

    Description: Deaths that occur during hospital admission.

    Measure: Hospital Mortality

    Time: 29 days after the randomization

    Description: Improvement of SOFA scale of patients at day 8, 15 and 29 after randomization

    Measure: Improvement of Sequential Sepsis-related Organ Failure Assessment (SOFA) scale

    Time: 29 days after the randomization (evaluations at D8 and D15)

    Description: Evaluation of clinical status of patients on the day 8, 22 and 29 after randomization, defined by the Ordinal Scale of 7 points (score ranges from 1 to 7, with 7 being the worst score)

    Measure: Evaluation of clinical status

    Time: 29 days after the randomization (evaluations at D8 and D29)

    Description: Days alive and free from mechanical ventilation since randomization

    Measure: Ventilator free days

    Time: 29 days after the randomization

    Description: Days from randomization to independence of oxygen support

    Measure: Time until oxygen support independence

    Time: 29 days after the randomization

    Description: Number of patients that were not at mechanical ventilation at randomization and that required that support.

    Measure: Need of mechanical ventilation support

    Time: 29 days after the randomization

    Description: Number of days to mechanical ventilation for patients that were not receiving it at randomization. For patients that were not in mechanical ventilation at randomization: number of days until that support was required.

    Measure: Days to mechanical ventilation support.

    Time: 29 days after the randomization

    Description: Lenght of hospitalization stay in survivors (in days)

    Measure: Duration of hospitalization

    Time: 29 days after the randomization

    Description: Incidence of other infections (aside from SARS-CoV 2)

    Measure: Other infections

    Time: 29 days after the randomization

    Description: Incidence of thromboembolic events in patients with COVID-19

    Measure: Incidence of thromboembolic events

    Time: 29 days after the randomization

    Description: Evaluation of adverse events, as well as serious and unexpected adverse events

    Measure: Incidence of adverse events

    Time: 29 days after the randomization (specific evaluations at D8, D15 and D29)

    Other Outcomes

    Description: Correlation of inflammatory tests and cytokines with clinical outcomes: clinical status (ordinal scale), time to oxygen support independence, ventilator free days, need of mechanical ventilation and mortality

    Measure: Correlation of inflammatory tests and cytokines with clinical outcomes

    Time: 29 days after the randomization

    Description: Evaluation the kinetics of hemostasia exams, inflammatory tests, cytokines, flow cytometry of blood cells, CBC, renal and liver exams

    Measure: Exploratory evaluation of laboratory exams during hospitalization

    Time: 29 days after the randomization

    Description: Evaluation of viral clearance of SARS-CoV2 using RT-PCR analysis of nasopharyngeal swab

    Measure: Evaluation of viral clearance of SARS-CoV2

    Time: Day 8 and 15 after randomization
    211 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
    212 Plasma From Covalescent Donors With Covid-19 for the Management of Patients With SARS-COV-2 Fase II and III, a Doble Center Randomized Doble Blind Trial

    The new SARS-CoV-2 coronavirus is an emerging virus originating in Wuhan, China that has spread rapidly throughout the world. As of March 24, 2020, China had reported 81,767 cases with 3,281 deaths, and the World Health Organization (WHO) declared coronavirus 19 (COVID-19) a pandemic. COVID-19 disease is currently a pandemic without specific therapeutic agents and substantial mortality. So it is of utmost importance to find new treatments. Various therapies, such as Remdesivir and Favipiravir, are being investigated but the antiviral efficacy of these drugs is not yet known. The use of convalescent plasma was used as an empirical treatment during the Ebola virus outbreaks in 2014 and in 2015 a protocol was established for the treatment of the Middle East respiratory syndrome coronavirus (MERS) with convalescent plasma. This approach with other viral infections such as SARS-CoV, H5N1 avian influenza and H1N1 influenza suggesting that plasma transfusion from convalescent donors was effective. For this study, plasma from convalescent donors will be collected from those donors who have recovered from SARS-CoV-2 and are between 10 and 14 days after illness. Immunoassays will be carried out to detect total IgM and IgG antibodies against SARS-CoV-2. Patients will receive 1 to 3 convalescent plasma transfusions, depending on the response to treatment. The expected results are: normal body temperature, decrease in viral load or negative between 10-12 days after transfusion of convalescent plasma, which does not progress to ARDS, extubation of mechanical ventilation within two weeks of treatment, recovery of patient.

    NCT04405310
    Conditions
    1. SARS Pneumonia
    Interventions
    1. Biological: Convalescent Plasma of patients with COVID-19
    2. Other: placebo (hartmann plus albumine)
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: any cause

    Measure: Death

    Time: 15 days

    Secondary Outcomes

    Description: Time for discharge from the ICU

    Measure: Lenth of stay ICU

    Time: 15 days

    Description: Number of days with ventilatory support

    Measure: Days of Mechanical Ventilation

    Time: 15 days

    Description: Number of days with need of oxigen suport without Mechanical Ventilation

    Measure: Suplemental Oxigen support

    Time: 15 days

    Description: changes in viral load

    Measure: Viral Load by RT-PCR

    Time: 15 days

    Description: changes in pro- inflamatory and anti-inflamatory biomarkes (IL-6, PCR, Ferritine, D Dimer, IL-8 IL-10

    Measure: Inflamatory biomarkers

    Time: 15 days

    Description: changes in SOFA scale

    Measure: SOFA (sequencial Organ Failure Assesment)

    Time: 15 days
    213 Hydroxychloroquine, Azithromycin in the Treatment of Covid-19 Pneumonia: A Randomized,Open-label,Controlled Clinical Trial

    This study investigates the efficay and tolerance of 5-days course of hydroxychloroquine or hydroxychloroquine and azithromycin of patients with COVID-19 infection. The investigators will undertake a randomized, double-blind, controlled Trial in the region of Sousse Tunisia

    NCT04405921
    Conditions
    1. SARS-CoV-2 Pneumonia
    2. COVID-19
    Interventions
    1. Drug: Hydroxychloroquine 200 Mg Oral Tablet
    2. Drug: Azithromycin 250 MG
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Clinical recovery is defined as a complete resolution clinical signs appeared during the medical history and related to COVID-19.

    Measure: Clinical recovery at day-14, from the start of treatment.

    Time: 14 days

    Secondary Outcomes

    Description: RT-PCR will be realized in same laboratory

    Measure: Viral Clearance via RT-PCR at day 5- 7-10 and day 14

    Time: 5- 7-10 and day 14
    214 Clinical Scores for Outcome Prediction in Patients With Severe COVID-19 Pneumonia Requiring Extracorporeal Membrane Oxygenation - a Retrospective Multi-center Registry Study

    The prognosis of patients with severe COVID-19 disease, whose lungs are so severely diseased that they need to be supported by veno-venous ECMO (extracorporeal membrane oxygenation), is difficult to assess so far. Previously published data from studies, case reports and case series describe a very high mortality in this patient collective. The significance of established clinical prognostic cores in this patient population has not been systematically investigated. This is aggravated by the fact that even at very specialized centers only very few patients from this collective are (can be) treated, so that valid investigations are only possible in a multicenter patient collective. In this registry study, all patients diagnosed with COVID-19 and treated with vv-ECMO in the centers participating in the study should be retrospectively examined. The primary aim of the study is to investigate 30-day survival, secondary objectives include the analysis of different clinical scores at the time of ECMO implantation.

    NCT04405973
    Conditions
    1. COVID-19
    2. SARS-CoV 2
    3. Extracorporeal Membrane Oxygenation
    4. ARDS
    Interventions
    1. Device: vv-ECMO
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: time from ECMO-implantation to death

    Measure: overall survival

    Time: 30 days

    Secondary Outcomes

    Description: time from ECMO-implantation to ECMO-explantation

    Measure: duration of ECMO treatment

    Time: 30 days

    Description: time from ECMO-implantation to extubation

    Measure: duration of ventilation treatment

    Time: 30 days

    Description: time from ECMO-implantation to ICU-discharge

    Measure: duration of initiation of ECMO treatment to ICU discharge

    Time: 30 days
    215 Awake Prone Positioning and Oxygen Therapy in Patients With COVID-19 (APRONOX)

    The prone position strategy for patients with acute respiratory distress syndrome (ARDS) is simple and cost-effective from the first description on its use in patients with acute respiratory failure to improve hypoxemia. Different studies have investigated its safety and efficacy in various clinical settings, demonstrating that its early use in combination with non-invasive mechanical ventilation (NIV) or high-flow oxygen therapy can reduce intubation rate and mortality in ARDS. In the Coronavirus disease 2019 (COVID-19) pandemic, high-value medicine and resource optimization are critical.

    NCT04407468
    Conditions
    1. COVID
    2. ARDS
    3. Pneumonia
    Interventions
    1. Procedure: Prone position
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Relationship between awake prone position and the tracheal intubation

    Measure: To analyze the relationship between the prone position and the need for orotracheal intubation.

    Time: 3 months

    Secondary Outcomes

    Description: See the relationship between the awake prone position and the SaO2/FiO2 INDEX

    Measure: The impact of the prone position on the partial oxygen saturation / inspired oxygen fraction index (SaO2 / FiO2).

    Time: 3 months

    Other Outcomes

    Description: Determine the free hours without the need for orotracheal intubation of patients in the prone position.

    Measure: Determine the free hours without the need for orotracheal intubation of patients in the prone position.

    Time: 3 months
    216 Randomised Controlled Trial Comparing High Versus Low LMWH Dosages in Hospitalized Patients With Severe COVID-19 Pneumonia and Coagulopathy Not Requiring Invasive Mechanical Ventilation

    Randomized, controlled study conducted in hospitalized patients with severe COViD-19 pneumonia and coagulopathy not requiring invasive mechanical ventilation. Aim of this study is to assess whether high doses of Low Molecular Weight Heparin (LMWH) (ie. Enoxaparin 70 IU/kg twice daily) compared to standard prophylactic dose (ie, Enoxaparin 4000 IU once day) are: 1. More effective to prevent clinical worsening, defined as the occurrence of at least one of the following events, whichever comes first, during hospital stay: 1. Death 2. Acute Myocardial Infarction [AMI] 3. Objectively confirmed, symptomatic arterial or venous thromboembolism [TE] 4. Need for either non-invasive - Continuous Positive Airway Pressure (Cpap) or Non-Invasive Ventilation (NIV) - or invasive mechanical ventilation for patients who are in standard oxygen therapy by delivery interfaces at randomisation 5. Need for invasive mechanical ventilation for patients who are in non-invasive mechanical ventilation at randomisation 2. Similar in terms of major bleeding risk during hospital stay

    NCT04408235
    Conditions
    1. COVID
    2. Pneumonia, Viral
    3. Coagulation Disorder
    Interventions
    1. Drug: Enoxaparin
    MeSH:Pneumonia, Viral Pneumonia Hemostatic Disorders Blood Coagulation Disorders
    HPO:Abnormality of coagulation Abnormality of the coagulation cascade Pneumonia

    Primary Outcomes

    Description: Death Acute Myocardial Infarction [AMI] Objectively confirmed, symptomatic arterial or venous thromboembolism [TE] Need for either non-invasive - Continuous Positive Airway Pressure (Cpap) or Non-Invasive Ventilation (NIV) - or invasive mechanical ventilation for patients, who are in standard oxygen therapy by delivery interfaces at randomisation Need for invasive mechanical ventilation for patients, who are in non-invasive mechanical ventilation at randomisation

    Measure: Clinical worsening, defined as the occurrence of at least one of the following events, whichever comes first:

    Time: through study completion, up to 30 days

    Secondary Outcomes

    Description: Death Acute Myocardial Infarction [AMI] Objectively confirmed, symptomatic arterial or venous thromboembolism [TE] Need for either non-invasive - Continuous Positive Airway Pressure (Cpap) or Non-Invasive Ventilation (NIV) - or invasive mechanical ventilation for patients, who are in standard oxygen therapy by delivery interfaces at randomisation Need for invasive mechanical ventilation for patients, who are in non-invasive mechanical ventilation at randomisation Improvement of laboratory parameters of disease severity, including: D-dimer level Plasma fibrinogen levels Mean Platelet Volume Lymphocyte/Neutrophil ratio IL-6 plasma levels

    Measure: Any of the following events occurring within the hospital stay

    Time: through study completion, up to 30 days

    Description: Information about patients' status will be sought in those who are discharged before 30 days on Day 30 from randomisation.

    Measure: Mortality at 30 days

    Time: 30 days
    217 Retrospective Change in the Ratio of Mean Platelet Volume (MPV) to Platellet(PLT) in Covid-19 Pneumonia Patients

    Morbidity, mortality and progress depends on systemic inflammation especially in ARDS patients. Previous studies claims that the proportion of mean platellet volume to platellet which can simply be determined with simple blood tests that are performed at admission, might predict the mortality in ARDS patients. Covid-19 pneumonia has a very similar clinical outlook with ARDS. Therefore we decided to research whether that proportion is legitimate for detecting the progress of Covid-19 pneumonia or not.

    NCT04408378
    Conditions
    1. Coronavirus Infection
    Interventions
    1. Other: observation of covid 19 pneumonia
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: İt has been studied that MPV/PLT ratio can show the cl inical couses of several diseases as well as ARDS. we thought that we can identify the coronavirus pneumonia patients earlier, at admission of hospital by using the hemogrames.

    Measure: estimation of inflammatory changes in Covid 19 pneumonia by using MVP/PLT ratio

    Time: March-May 2020
    218 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
    219 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
    220 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
    221 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 normalization of oxygen saturation (SpO2) (>93% on room air sustained for at least 24 hours)

    Time: Baseline through Day 14 or discharge

    Measure: Duration of supplemental oxygen (O2) requirement

    Time: Baseline through Day 14 or discharge

    Measure: Number of days with fever (temperature >100.4ºF [38.0ºC])

    Time: Baseline through Day 14 or discharge

    Measure: Time to normalization of 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
    222 Phase II Study of Low Dose Pulmonary Irradiation in Patients With COVID-19 Infection of Bad Prognosis

    The administration of low-dose lung irradiation produces anti-inflammatory effects that will decrease the pulmonary inflammatory response. The present study will evaluate the efficacy of treatment with low-dose pulmonary radiotherapy added to standard support therapy, in hospitalized patients with respiratory symptoms due to COVID-19 pneumonia, who do not experience improvement with conventional medical therapy and are not subsidiaries of ICU

    NCT04414293
    Conditions
    1. COVID
    2. Pneumonia, Viral
    Interventions
    1. Radiation: Lung Low Dose Radiation
    MeSH:Pneumonia, Viral Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Clinical improvement of respiratory symptoms due to COVID-19 pneumonia after the treatment, measured as blood oxygen saturation levels

    Measure: blood oxygen saturation level

    Time: 48 hours

    Description: radiological improvement of respiratory symptoms due to COVID-19 pneumonia after the treatment.

    Measure: Torax X-ray

    Time: 48 hours

    Secondary Outcomes

    Description: number of days of hospital stay.

    Measure: Hospitalization

    Time: 2 months

    Description: Number of days free of assisted mechanical respiration.

    Measure: days free of assisted mechanical respiration

    Time: 3 month

    Description: number of deaths

    Measure: Mortality

    Time: 3 months
    223 Echocardiography in Critically-ill Patients With COVID-19 Pneumonia

    Critical care echocardiography (CCE) has been widely used since the 10 last years. Covid outbreak leads that many patients with acute respiratory failure were admitted in the ICU. Many of these patients were ventilated and developed ARDS. Some of them developed deep vein thrombosis and pulmonary embolism. Nothing is already described about the cardiac function and the hemodynamics in these patients (how many RV failure, LV systolic dysfunction,...). The echo group of the cardiodynamix section of European society of intensive care medicien (ESICM) aims to promote CCE and evaluate its interest. The objective is to retrospectively enter in an international database all the echo studies done as usual care in these patients to evaluate (i) incidence of RV failure, (ii) incidence of LV systolic function, (iii) incidence of other patterns. Another objective will be to look for any association between some patterns and respiratory strategy, blood gas analysis, systemic hemodynamics. The echo studies were done and will be reported following one of the recent systematic review published by the same group (Huang S et al. AOIC 2020).

    NCT04414410
    Conditions
    1. COVID
    2. Sars-CoV2
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: LV systolic dysfunction is defined as an ejection fraction < 45%

    Measure: Incidence of Left ventricular systolic dysfunction

    Time: Up to 28 days

    Description: RV failure is defined as RV/LV end-diastolic area > 0.8

    Measure: Incidence of RV failure

    Time: up to 28 days

    Description: Vasoplegia is defined as a normal or supranormal LV ejection fraction without echocarduiographic signs of hypovolemia.

    Measure: Incidence of Vasoplegia

    Time: Up to 28 days

    Description: Hypovolemia is defined as inspiratory collaspe of the superior vena cava in ventilated patients or virtual inferior vena cava in spontaneously breathing patients.

    Measure: Incidence of Hypovolemia

    Time: Up to 28 days

    Secondary Outcomes

    Description: Plateau pressure and RV size

    Measure: Relation between plateau pressure and RV failure

    Time: Up to 28 days

    Description: Tidal volume and RV size

    Measure: Relation between tidal volume and RV failure

    Time: Up to 28 days

    Description: PaO2, PaO2/FiO2, and RV size

    Measure: Relation between PaO2 and RV failure

    Time: Up to 28 days

    Description: PaCO2 and RV size

    Measure: Relation between PaCO2 and RV failure

    Time: Up to 28 days

    Description: PEEP and RV size

    Measure: Relation between PEEP and RV failure

    Time: Up to 28 days
    224 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

    Opaganib, a sphingosine kinase-2 (SphK2) inhibitor, has been broadly tested in Phase I/II studies. Extensive nonclinical data indicates both anti-viral and anti-inflammatory activity via selective SphK2 inhibition which may prove beneficial for treating COVID-19 infection and resulting pneumonia. This proof of concept study will take place in the US and will enroll about 40 hospitalized patients diagnosed with COVID-19 infection who have developed pneumonia and require supplemental oxygen. Half of the patients, i.e. 20 patients, will receive opaganib in addition to standard of care for 14 days. The other 20 will receive matching placebo (capsules that do not contain the medication) in addition to standard of care. Study drug will be administered every day for 14 days, twice each day, 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: Measurement of the oxygen requirement

    Measure: Evaluation of the total oxygen requirement (area under the curve) using daily supplemental oxygen flow (L/min) over 14 days

    Time: Every day from day 1 to day 14 of treatment

    Secondary Outcomes

    Description: Measurement of the oxygen requirement

    Measure: Evaluation of the time to 50% reduction from baseline in supplemental oxygen based on oxygen flow in L/min

    Time: Every day from day 1 to day 14 of treatment

    Measure: Evaluation of the proportion of patients no longer requiring supplemental oxygen for at least 24 hours by Day 14

    Time: From screening phase and every day from day 1 to day 14 of treatment

    Description: Measurement of temperature

    Measure: Evaluation of the proportion of afebrile patients at Day 14

    Time: From screening phase and every day from day 1 to day 14 of treatment

    Description: Nasopharyngeal or oropharyngeal swab for SARS-CoV-2

    Measure: Evaluation of the time to negative swabs for SARS-CoV-2 by PCR

    Time: From screening phase and every day from day 1 to day 14 of treatment and at the end of the 4 weeks follow-up after the end of treatment

    Description: Nasopharyngeal or oropharyngeal swab for SARS-CoV-2

    Measure: Evaluation of the proportion of patients with negative swabs for SARS-CoV-2 by PCR at Day 14

    Time: From screening phase and every day from day 1 to day 14 of treatment and at the end of the 4 weeks follow-up after the end of treatment

    Measure: The percentage of patients who require intubation and mechanical ventilation by Day 14

    Time: From screening phase and every day from day 1 to day 14 of treatment

    Measure: Evaluation of the time to mechanical ventilation

    Time: From screening phase and every day from day 1 to day 14 of treatment

    Description: Evaluation 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

    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

    Measure: Evaluation of mortality 30 days post-baseline

    Time: 30 days after day 1 of treatment

    Other Outcomes

    Measure: To determine the incidence rate of all treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)

    Time: Every day from day 1 to day 14 of treatment and at end of the 4 weeks follow-up after the end of treatment
    225 the Determination of Extracellular Water (ECW) Which is Detected by Bioimpedence Method on Severe and Mild Covid 19 Pneumonia Clinical Course

    According to various studies Covid 19 pneumonia has a very similar clinical course to Acute Respiratory Distress Syndrome (ARDS) which has clarified by Berlin definition. Based on this similarity, extracellular fluid of lungs and diffuse alveolar damage should be observed in covid 19 pneumonia as well. Extracellular water (ECW) can be determine by using whole body bioimpedence system (NİCaS). The aim of this study is to investigate the effect of ECW on the clinical apperence of covid 19 pneumonia clinical course.

    NCT04416009
    Conditions
    1. Extracellular Fluid Alteration
    2. Corona Virus Infection
    Interventions
    1. Device: NİCaS
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Changes of three measurements of extracellular water in both lungs

    Measure: ECW

    Time: three measurements with half an hour intervals
    226 PREEMPTIVE THERAPY WITH COLCHICINE IN PATIENTS OLDER THAN 70 YEARS WITH HIGH RISK OF SEVERE PNEUMONIAE DUE TO CORONAVIRUS SARS-CoV2 (COVID-19)

    This is a phase 3 clinical trial, randomized, single-center, opened, controlled, to evaluate efficacy and safety of early administration of colchicines in patients older than 70 years, with high risk of pulmonary complications due to coronavirus SARS-CoV2 (COVID-19). An approximately number of 1000 subjects meeting all inclusion and none exclusion criteria will be randomized either to receive colchicines or symptomatic treatment with paracetamol during 21 days.

    NCT04416334
    Conditions
    1. SARS-CoV-2 Infection (COVID-19)
    Interventions
    1. Drug: Colchicine plus symptomatic treatment (paracetamol)
    2. Drug: Symptomatic treatment (paracetamol or best symptomatic treatment based on doctor recommendations)
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Measure: Number of participants who die due to COVID-19 infection

    Time: 21 days post-randomization

    Measure: Number of participants who require hospitalization due to COVID-19 infection

    Time: 21 days post-randomization

    Other Outcomes

    Description: not delayed more than 48 hours from initial symptoms

    Measure: A confirmed diagnosis from COVID-19 infection (by positive PCR test) will be mandatory .

    Time: 48 hours
    227 Treatment Effect of Nafamostat Mesylate in Patients With COVID-19 Pneumonia: Open Labelled Randomized Controlled Clinical Trial

    In-vitro studies revealed that nafamostat mesylate has antiviral activity against Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and anti-inflammatory and anti-coagulation effect. However, there is no clinical studies on the efficacy of nafamostat in patients with COVID-19. This study is conducted to evaluate the clinical efficacy of nafamostate mesylate in adult patients hospitalized with COVID-19 pneumonia.

    NCT04418128
    Conditions
    1. Corona Virus Infection
    2. COVID-19
    Interventions
    1. Drug: Nafamostat Mesylate
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Proportion of patients with clinical improvement as defined by live discharge from hospital or a decline of 2 categories on the seven-category ordinal scale of clinical status. * Seven-category ordinal scale of clinical status not hospitalized with resumption of normal activities; not hospitalized, but unable to resume normal activities; hospitalization, not requiring supplemental oxygen; hospitalization, requiring supplemental oxygen; hospitalization, requiring nasal high-flow oxygen therapy and/or noninvasive mechanical ventilation; hospitalization, requiring extracorporeal membrane oxygenation and/or invasive mechanical ventilation; death.

    Measure: Proportion of patients with clinical improvement

    Time: Day 14 & Day 28

    Secondary Outcomes

    Description: Time to clinical improvement (TTCI) was defined as time from randomization to a decline of 2 categories on the seven-category ordinal scale of clinical status or live discharge from the hospital, whichever came first.

    Measure: Time to clinical improvement (TTCI)

    Time: up to 28 days

    Description: * Seven-category ordinal scale of clinical status not hospitalized with resumption of normal activities; not hospitalized, but unable to resume normal activities; hospitalization, not requiring supplemental oxygen; hospitalization, requiring supplemental oxygen; hospitalization, requiring nasal high-flow oxygen therapy and/or noninvasive mechanical ventilation; hospitalization, requiring extracorporeal membrane oxygenation and/or invasive mechanical ventilation; death. Higher scores of Seven-category ordinal scale mean serious clinical status.

    Measure: Clinical status assessed by 7-category ordinal scale

    Time: days 7, 14, and 28

    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 range of NEW score is from zero to 23. Higher scores of NEWS mean the higher risk of poor outcomes. The NEW Score is being used as an efficacy measure.

    Measure: Change in National Early Warning Score (NEWS)

    Time: Day 1 trough Day 28

    Measure: Time to National Early Warning Score (NEWS) of ≤ 2 and maintained for 24 hours

    Time: Day 1 through Day 28

    Measure: Duration of hospitalization

    Time: Day 1 through Day 28

    Measure: Duration of new non-invasive ventilation or high flow oxygen use

    Time: Day 1 through Day 28

    Measure: Incidence of new non-invasive ventilation or high flow oxygen use

    Time: Day 1 through Day 28

    Measure: Duration of new supplement oxygen use

    Time: Day 1 through Day 28

    Measure: Incidence of new supplement oxygen use

    Time: Day 1 through Day 28

    Measure: Duration of new ventilator or extracorporeal membrane oxygenation (ECMO) use

    Time: Day 1 through Day 28

    Measure: Incidence of new ventilator or extracorporeal membrane oxygenation (ECMO) use

    Time: Day 1 through Day 28

    Measure: Mortality at day 28

    Time: Day 1 through Day 28

    Measure: Time (days) from treatment initiation to death

    Time: Day 1 through Day 28

    Measure: Proportions of patients with a negative nasopharyngeal swab and sputum sample for SARS-CoV-2 quantitative RT-PCR

    Time: days 3, 7, 10, 14, and 21

    Measure: Viral load change (log10 viral load) of nasopharyngeal swab and sputum sample for SARS-CoV-2 quantitative RT-PCR

    Time: days 3, 7, 10, 14, and 21

    Measure: Adverse events that occurred during treatment

    Time: Day 1 through Day 28
    228 A Pilot Study to Explore the Efficacy and Safety of Rescue Therapy With Antibodies From Convalescent Patients Obtained With Double-filtration Plasmapheresis (DFPP) and Infused in Patients With Coronavirus Disease 2019 (COVID-19) and Need of Oxygen Support Without Mechanical Ventilation

    The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which originated in Wuhan, China, has become a major concern all over the world. Convalescent plasma or immunoglobulins have been used as a last resort to improve the survival rate of patients with SARS whose condition continued to deteriorate despite treatment with pulsed methylprednisolone. Moreover, several studies showed a shorter hospital stay and lower mortality in patients treated with convalescent plasma than those who were not treated with convalescent plasma. Evidence shows that convalescent plasma from patients who have recovered from viral infections can be used effectively as a treatment of patients with active disease. The use of solutions enriched of antiviral antibodies has several important advantages over the convalescent plasma including the high level of neutralizing antibodies supplied. Moreover, plasma-exchange is expensive and requires large volumes of substitution fluid With either albumin or fresh frozen plasma, increasing the risk of cardiovascular instability in the plasma donor and in the recipient, which can be detrimental in a critically ill patient with COVID 19 pneumonia. The use of plasma as a substitution fluid further increases treatment costs and is associated with risk of infections, allergic reactions and citrate-induced hypocalcemia. Albumin is better tolerated and less expensive, but exchanges using albumin solutions increase the risk of bleeding because of progressive coagulation factor depletion. The aforementioned limitations of plasma therapy can be in part overcome by using selective apheresis methods, such as double-filtration plasmapheresis (DFPP)3. During DFPP, plasma is separated from cellular components by a plasma filter, and is then allowed to pass through a fractionator filter. Depending on the membrane cut-off, the fractionator filter retains larger molecules and returns fluid along with smaller molecules to the circulation. Thus, the selection of a membrane with an appropriate sieving coefficient for IgG allows to efficiently clear autoantibodies in patients with antibody-mediated diseases (e.g., macroglobulinemia, myasthenia gravis and rheumatoid arthritis) with negligible fluid losses and limited removal of albumin and coagulation factors1. In patients with severe membranous nephropathy and high titer of autoreactive, nephritogenic antibodies against the podocyte-expressed M type phospholipase A2 receptor (PLA2R), DFPP accelerated anti PLA2R depletion4. Measurement of the antibody titer in treated patient and recovered fluid showed that antibody removal was extremely effective and that large part of antibodies was removed during the first DFPP procedure. This therapeutic regimen was safe and well tolerated and easy to apply4. In an ongoing pilot study we found that the same methodological approach can be used to remove circulating antibodies from patients who recovered from COVID 19 and to infuse these antibodies in patients with active viral infection. Treatment was well tolerated and preliminary findings are encouraging. Thus, in this novel pilot study we aim to explore whether the infusion of antibodies obtained with one single DFPP procedure from voluntary convalescent donors could offer an effective and safe therapeutic option for patients with earlier stages of coronavirus (COVID-19) pneumonia requiring oxygen supply without mechanical ventilation.

    NCT04418531
    Conditions
    1. Pneumonia, Viral
    2. Corona Virus Infection
    Interventions
    1. Biological: Anti-coronavirus antibodies (immunoglobulins) obtained with DFPP form convalescent patients
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia, Viral Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Measure: Time to weaning of oxygen support

    Time: Through study completion, an average of 3 months

    Secondary Outcomes

    Measure: Chest XR or CT scan evaluation

    Time: Changes during the study up completion, an average of 3 months

    Measure: Survival,

    Time: Through study completion, an average of 3 months

    Measure: Viral titer

    Time: Changes from before Ig administration, one day after Ig administration and every week through study completion, an average of 3 months.

    Measure: Anti COVID 19 IgG antibodies

    Time: Changes from before Ig administration, one day after Ig administration and every week through study completion, an average of 3 months.

    Measure: Anti COVID 19 IgM antibodies

    Time: Changes from before Ig administration, one day after Ig administration and every week through study completion, an average of 3 months.

    Description: Marker of complement activation in plasma.

    Measure: C5a concentration

    Time: Changes from before Ig administration, one day after Ig administration and every week through study completion, an average of 3 months.

    Description: Marker of complement activation in plasma.

    Measure: C3a concentration

    Time: Changes from before Ig administration, one day after Ig administration and every week through study completion, an average of 3 months.

    Description: Marker of complement activation in plasma.

    Measure: Serum C5b-9 concentration Marker of complement activation

    Time: Changes from before Ig administration, one day after Ig administration and every week through study completion, an average of 3 months.

    Description: Marker of complement activation in plasma.

    Measure: Serum IL-6 levels

    Time: Changes from before Ig administration, one day after Ig administration and every week through study completion, an average of 3 months.

    Description: Marker of complement activation in plasma.

    Measure: Serum IL-1b levels

    Time: Changes from before Ig administration, one day after Ig administration and every week through study completion, an average of 3 months.

    Description: Marker of complement activation in plasma.

    Measure: Serum IFNγ levels

    Time: Changes from before Ig administration, one day after Ig administration and every week through study completion, an average of 3 months.

    Description: Marker of complement activation in plasma.

    Measure: Serum MCP-1 levels

    Time: Changes from before Ig administration, one day after Ig administration and every week through study completion, an average of 3 months.

    Description: Marker of complement activation in plasma.

    Measure: Serum TNFα levels

    Time: Changes from before Ig administration, one day after Ig administration and every week through study completion, an average of 3 months.

    Description: Marker of complement activation in plasma.

    Measure: Serum IL-10 levels

    Time: Changes from before Ig administration, one day after Ig administration and every week through study completion, an average of 3 months.

    Description: Marker of complement activation in plasma.

    Measure: Serum IL-2 levels

    Time: Changes from before Ig administration, one day after Ig administration and every week through study completion, an average of 3 months.

    Description: Marker of complement activation in plasma.

    Measure: Serum IL-7 levels

    Time: Changes from before Ig administration, one day after Ig administration and every week through study completion, an average of 3 months.
    229 Multicentric Pragmatic Randomized Controled Trial to Evaluate the Efficacy Chloroquine or Hydroxychloroquine for Five Days in Treating Pneumonia Caused by SARS-Cov-2 - COVID-19

    Facing the challenge of finding an efficient treatment for COVID-19, the viral pneumonia caused by the Coronavirus SARS-Cov-2, this study intended to test if Chloroquine or Hydroxychloroquine, two drugs with strong in-vitro antiviral role proven by numerous studies and with a well defined safety profile established, for efficacy in treating COVID-19 and improving an ordinal primary outcome composed by a 9-levels scale, which was recomended by the World Health Organization.

    NCT04420247
    Conditions
    1. COVID
    2. COVID-19
    3. SARS-CoV 2
    4. Coronavirus
    5. Corona Virus Infection
    Interventions
    1. Drug: Chloroquine
    2. Drug: Hydroxychloroquine
    3. Other: standard care
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Evaluation of the clinical status of patients on the 14th day after randomization defined by the 9-levels ordinal scale, with lower scores meaning better outcomes.

    Measure: World Health Organization (WHO) 9-levels ordinal scale (from 0-8)

    Time: 14 days after randomization

    Secondary Outcomes

    Description: Evaluation of the clinical status of patients on the 5th, 7th, 10th and 28th day after randomization defined by the 9-levels ordinal scale, with lower scores meaning better outcomes.

    Measure: World Health Organization (WHO) 9-levels ordinal scale (from 0-8)

    Time: 5, 7, 10 and 28 days after randomization

    Description: All-cause mortality at 28 days after randomization

    Measure: Mortality

    Time: 28 days after randomization

    Description: Number of days without need of Mechanical Ventilation at 28 days after randomization

    Measure: Ventilation free days

    Time: 28 days after randomization

    Description: ICU Lenght of Stay on survivors at 28 days after randomization

    Measure: ICU Lenght of Stay

    Time: 28 days after randomization

    Description: Hospital Lenght of Stay on survivors at 28 days after randomization

    Measure: Hospital Lenght of Stay

    Time: 28 days after randomization

    Description: Acute Kidney Disease incidence measured by Kidney Disease Improving Global Outcomes (KDIGO) stage 3 sometime until the 28th day after randomization.

    Measure: Acute Kidney Disease incidence

    Time: 28 days after randomization

    Description: Percentage of patients needing dialysis sometime until the 28th day.

    Measure: Percentage of patients needing dialysis

    Time: 28 days after randomization

    Description: Presence of coagulopathy sometime until the 28th day (platelets < 150000 and/or INR >1.5 and/or KPTT > 35 seconds).

    Measure: Coagulopathy incidence

    Time: 28 days after randomization

    Description: Mean of C Reactive Protein Levels on the 5th, 7th, 10th, 14th and 28th day after randomization, during period of hospitalization

    Measure: Mean of C Reactive Protein Levels

    Time: 5, 7, 10, 14 and 28 days after randomization

    Description: Sequential Organ Failure Assessment (SOFA) scores (range, 0-24, with higher scores indicating greater organ dysfunction) on the 5th, 7th, 10th, 14th and 28th day after randomization, during period of hospitalization.

    Measure: Sequential Organ Failure Assessment (SOFA) scores

    Time: 5, 7, 10, 14 and 28 days after randomization

    Description: Neutrophils/lymphocytes ratio on the 5th, 7th, 10th, 14th and 28th day after randomization, during period of hospitalization.

    Measure: Neutrophils/lymphocytes ratio

    Time: 5, 7, 10, 14 and 28 days after randomization

    Other Outcomes

    Description: Safety outcome: Any kind of arrhythmia identified by the attending physician at the time of the intercurrence, confirmed by an electrocardiogram (ECG), sometime until the 28th day

    Measure: Arrhythmia

    Time: 28 days after randomization
    230 Low Dose Radiotherapy as Antinflammatory Treatment for COVID-19 Pneumonitis

    SARS-CoV-2 is causing an unprecedented stress on healthcare systems around the world, due to its high rate of infection and the high morbidity and mortality. The COVID-19 infection triggers an inflammatory cascade with cytokine synthesis, prompting the immune response. Low dose radiotherapy (LD-RT) (≤ 100 cGy) induces an anti-inflammatory response, lowering levels of pro-inflammatory cytokines such as IL-1β or inhibit leukocyte recruitment. LD-RT has been used historically for the pneumonia treatment reporting a rapid clinical improvement (within the first week), as well as a reduced mortality (from around 30% to 10%). Considering these results, LD-RT can potentially afford a therapeutic benefit against SARS-CoV-2. The study purpose is to evaluate prospectively the safety and efficacy of LD-RT for SARS-CoV-2.

    NCT04420390
    Conditions
    1. Covid19
    Interventions
    1. Radiation: Radiotherapy
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Radiological results: Radiological worsening, improvement or without significant changes

    Measure: Radiological response

    Time: 3 days after low dose radiation

    Description: Radiological results: Radiological worsening, improvement or without significant changes

    Measure: Radiological response

    Time: 7 days after low dose radiation

    Secondary Outcomes

    Description: Remission of respiratory symptoms

    Measure: Remission of respiratory symptoms

    Time: up to 6 months

    Description: Time to SPO2>94% or PaO2/FiO2 >350mmHg without oxygen

    Measure: SPO2 and PaO2/FiO2

    Time: 7 days

    Description: Occurrence and grade of CTCAE 5.0 adverse events

    Measure: Adverse events

    Time: 1 year

    Description: Duration of hospitalization

    Measure: Hospitalization

    Time: 3 months

    Description: Overall survival

    Measure: Overall survival

    Time: 1 month

    Description: ferritin value (ng/mL)

    Measure: Ferritin value

    Time: 1 day after low dose radiation

    Description: ferritin value (ng/mL)

    Measure: Ferritin value

    Time: 2 days after low dose radiation

    Description: ferritin value (ng/mL)

    Measure: Ferritin value

    Time: 3 days after low dose radiation

    Description: blood cell count (unit/L)

    Measure: blood cell count

    Time: 1 day after low dose radiation

    Description: blood cell count (unit/L)

    Measure: blood cell count

    Time: 2 days after low dose radiation

    Description: blood cell count (unit/L)

    Measure: blood cell count

    Time: 3 days after low dose radiation

    Description: C-reactive protein (mg/dl)

    Measure: C-reactive protein

    Time: 1 day after low dose radiation

    Description: C-reactive protein (mg/dl)

    Measure: C-reactive protein

    Time: 2 days after low dose radiation

    Description: C-reactive protein (mg/dl)

    Measure: C-reactive protein

    Time: 3 days after low dose radiation

    Description: D-dimer (ng/ml)

    Measure: D-dimer

    Time: 1 day after low dose radiation

    Description: D-dimer (ng/ml)

    Measure: D-dimer

    Time: 2 days after low dose radiation

    Description: D-dimer (ng/ml)

    Measure: D-dimer

    Time: 3 days after low dose radiation

    Description: LDH levels (UI/L)

    Measure: LDH levels

    Time: 1 day after low dose radiation

    Description: LDH levels (UI/L)

    Measure: LDH levels

    Time: 2 days after low dose radiation

    Description: LDH levels (UI/L)

    Measure: LDH levels

    Time: 3 days after low dose radiation
    231 Characterization of Persistent Pulmonary Abnormalities Following COVID-19 Pneumonia

    Severe Acute Respiratory Syndrome SARS-CoV-2, name of the Coronavirus Group of international Committee on taxonomy of viruses, is an emerging virus from the family of coronaviridae, responsible for the COVID-19 pandemic. This infection can progress to viral pneumonia, and in 3% of cases up to acute respiratory distress syndrome (ARDS) which conditions the prognosis of the disease. Due to its unusual clinical presentation with a risk of sudden deterioration on the 8th day as a result of possible hyperinflammatory response, the respiratory impairment of COVID is unique and many questions remain unanswered concerning its evolution once the acute phase has passed. Knowledge of the evolution of pulmonary involvement, particularly in patients requiring hospitalization, can help reduce the morbidity linked to the persistent abnormalities identified by establishing early therapeutic management. It can also provide a better understanding of the mechanisms of pulmonary involvement in the acute phase. Current data regarding the acute phase of COVID-19 suggest that persistent abnormalities remain distant from this infection at all levels of the respiratory system: gas exchange, perfusion, ventilatory mechanics, and interstitial lung disease. The main objective is to characterize persistent gas exchange anomalies 4 months after documented COVID-19 pneumonia, resulting in oxygen desaturation and requiring hospitalization.

    NCT04422613
    Conditions
    1. Pneumonia, Viral
    Interventions
    1. Diagnostic Test: pulmonary anomalies 4 months after documented COVID-19 pneumonia
    MeSH:Pneumonia, Viral Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Alteration of the DLCO test defined by a corrected DLCO value <70% of theoretical and / or desaturation in the 6 Minute Walk Test (loss of 4% or more of SpO2)

    Measure: Alteration of the DLCO

    Time: 4 month

    Secondary Outcomes

    Description: The mechanism of the alteration of gas exchanges will be specified by the analysis of the values obtained during the diffusing CO / NO test, at 4 month after COVID- 19 pneumonia

    Measure: Mechanism of the alteration of gas exchanges

    Time: 4 month

    Description: The mechanism of the alteration of gas exchanges will be specified by the analysis of the other values obtained during the measurement of lung volumes in respiratory function tests at 4 month after COVID- 19 pneumonia

    Measure: Measurement on lung volumes

    Time: 4 month

    Description: The mechanism of the alteration of gas exchanges will be specified by the analysis of the other values obtained during chest CT-scan at 4 month after COVID- 19 pneumonia

    Measure: mechanism of the alteration of gas exchanges by chest scan

    Time: 4 month

    Description: The mechanism of the alteration of gas exchanges identified will be specified by the analysis of the other values obtained during pulmonary scintigraphy, at 4 month after COVID- 19 pneumonia :

    Measure: mechanism of the alteration of gas exchanges by scintigraphy

    Time: 4 month

    Description: the existence of respiratory symptoms, defined by dyspnea, cough, sputum, haemoptysis, chest pain, sign of right ventricular failure, sleep disorders or a 6-minute walk test value <80% of theoretical, at 4 month after COVID- 19 pneumonia

    Measure: Respiratory symptom

    Time: 4 month

    Description: the existence of persistent bronchial or ventilatory anomalies at 4 months, defined on current respiratory function tests (plethysmography, forced oscillometry test, diaphragmatic explorations, measurement of exhaled NO)

    Measure: Bronchial or ventilatory anomalies

    Time: 4 month

    Description: Persistent respiratory anomalies at 4 months will be evaluated at 12 months of the acute episode by an appropriate paraclinical assessment : mechanism of the alteration of gas exchanges, Respiratory symptom and bronchial or ventilatory anomalies will be evaluated

    Measure: Persistent respiratory anomalies

    Time: 12 month
    232 Imatinib for the Treatment of SARS-COV-2 Induced Pneumonia: A Pilot Study

    A randomized controlled pilot study on the safety & efficacy of imatinib for the treatment of patient with moderate to severe SARS-COV-2 induced pneumonia.

    NCT04422678
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Imatinib Mesylate
    2. Drug: Standard of Care
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Proportion of patients with COVID-19 pneumonia progressed to critical illness in need for invasive mechanical ventilation.

    Measure: Primary endpoint: Disease Progression

    Time: 30 Days

    Secondary Outcomes

    Description: Improvement of Hypoxic index( PaO2 / FiO2) calculated daily

    Measure: Improvement in Hypoxic Index

    Time: From inclusion to 30 days follow up

    Description: Hospital Length of stay

    Measure: Hospital Length of Stay

    Time: From inclusion to 30 days follow up

    Description: Days on mechanical ventilation for patients needing intubation & invasive mechanical ventilation

    Measure: Days on invasive mechanical ventilation

    Time: From inclusion to 30 days follow up

    Description: Difference in the median levels of serum IL-6, serum ferritin, CRP at the end of the follow up period between all groups

    Measure: Inflammatory Markers

    Time: From inclusion to 30 days

    Description: Rate of viral clearance as monitored by SARS-COV-2 PCR

    Measure: Viral clearance

    Time: From inclusion to 30 days

    Description: Difference in the overall evaluation of pulmonary infiltrative (improving / deteriorating) as assessed by imaging (Chest X-ray or Non-contrast pulmonary CT)

    Measure: Radiological assessment

    Time: From inclusion to 30 days

    Description: Rate of serious adverse events (SAEs)

    Measure: Safety of Imatinib

    Time: From inclusion to 60 days
    233 Bruk av Ultralyd i Evaluering av Pasienter Med Mistenkt COVID-19 Infeksjon i Norge

    In light of the ongoing COVID-19 epidemic in Norway, it is paramount to develop and utilize clinical tools for assessing and risk stratifying patients with suspected coronary infection in the emergency departments. Diagnostic use of ultrasound in viral pneumonias, including COVID-19 has proved to be very useful. The use of ultrasound will assist in quick detection of lung pathology compatible with increasing severity of the COVID-19 disease. At the same time, the use of ultrasound diagnostics in the emergency department could improve logistics and reduce potential exposure of the corona virus to other health personnel. The purpose of the study is to assess whether ultrasound findings correlates with physical examination, labs, and other imaging diagnostics in patients with suspected or diagnosed COVID-19 disease, as well as assessing whether ultrasound diagnostics can assist in risk stratification. The project is conducted as a prospective multicenter study where ultrasound diagnostics will be performed on patients with suspected coronary infection in the emergency departments. Data collection takes place as part of the daily clinical evaluation of acute patients in the emergency departments. The project is planned to be completed towards the end of 2025.

    NCT04422691
    Conditions
    1. COVID-19
    2. Pneumonia, Viral
    3. Pulmonary Infection
    Interventions
    1. Diagnostic Test: Lung ultrasound
    MeSH:Infection Pneumonia, Viral Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: 30-day mortality

    Measure: Mortality

    Time: up to 30 days

    Description: In-hospital treatment level, e.g. discharge from ED, observational unit, ward, ICU.

    Measure: Level-of-care

    Time: up to 7 days

    Secondary Outcomes

    Description: in days

    Measure: In-hospital length of stay

    Time: Up to 30 days

    Measure: Oxygen usage in the emergency department

    Time: Within 24 hours

    Description: in hours

    Measure: Emergency department length of stay

    Time: Within 24 hours

    Measure: Antibiotics usage

    Time: Within 24 hours

    Other Outcomes

    Description: Clinical correlation between ultrasound findings and vital signs, labs, blood gas and other diagnostic modalities.

    Measure: Clinical correlation

    Time: Within 3 days
    234 Thrombosis Risk Assessment May Predict Clinical Presentation and Length of Hospital Stay in Covid-19 Pneumonia

    Covid-19 mainly affects the respiratory system. Multiple organ dysfunction and a particularly progressive respiratory insufficiency along with a widespread coagulopathy presumed to be due to infection-associated inflammation and the resulting cytokine storm, are strongly associated with high mortality rates. In this study, the association between thrombosis risk and clinical presentation of Covid-19 is investigated.

    NCT04423315
    Conditions
    1. Corona Virus Infection
    2. Thromboembolic Disease
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia Thrombosis Thromboembolism
    HPO:Pneumonia Thromboembolism

    Primary Outcomes

    Description: from admission to discharge expressed in days

    Measure: length of hospital stay

    Time: 2 months
    235 Possibilities of Chest Magnetic Resonance Imaging (MRI) in Diagnostics of COVID-19. The Use of MRI to Assess Lung Damage in Patients With Coronavirus Infection

    Since the onset of the COVID-19 pandemic, the importance of chest computed tomography (CT) in detecting signs of viral pneumonia has become clear from the literature. However, the increased patient flow creates an additional pressure on CT centers. We believe, the use of chest magnetic resonance imaging (MRI) can help to test patients for CОVID-19 when CT scan is not available. Lung MRI may be useful in routing a patient in a difficult epidemiological situation.

    NCT04424355
    Conditions
    1. Coron
    2. Coronavirus Infections
    3. Pneumonia
    Interventions
    1. Diagnostic Test: Chest MRI
    MeSH:Infection Communicable Diseases Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Expected number - more than two zones

    Measure: Number of zones of pulmonary parenchyma corresponding to viral pneumonia detected by chest MRI in comparison with CT scan

    Time: Upon completion, up to 1 year
    236 Prone Positioning on Admission for Hospitalized COVID-19 Pneumonia Protocol

    A pilot study to investigate the effects of the prone positioning (PP) on hospital patients diagnosed with COVID-19 pneumonia. Investigators that early self-proning may prevent intubation and improve mortality in patients with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV-2). Up to 100 participants with a primary diagnosis of confirmed COVID-19 pneumonia will be enrolled to the study. All participants will be screened and those that meet inclusion and exclusion criteria will be enrolled to one of two groups: one with prone positioning (on the belly) and the other with standard supine positioning (on the back). The patient and nursing staff will monitor times spent in various positions. Outcome measures include incidence of intubation, max oxygen requirements, length of hospital stay, ventilator-free days, worsening of oxygenation saturation, and mortality.

    NCT04424797
    Conditions
    1. COVID-19
    Interventions
    1. Other: Prone Positioning
    2. Other: Supine Positioning
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Incidence of intubation

    Measure: Incidence of intubation

    Time: Through study completion, an average of 6 days

    Secondary Outcomes

    Description: Measure of maximum oxygen requirements

    Measure: Maximum oxygen requirement

    Time: Through study completion, an average of 6 days

    Description: Measured in days of hospitalization

    Measure: Length of Stay

    Time: Through study completion, an average of 6 days

    Description: Measured in days not on a ventilator

    Measure: Ventilator-free days

    Time: Through study completion, an average of 6 days

    Description: Whether or not the participant met treatment failure descriptions

    Measure: Treatment failure of prone positioning due to worsening SpO2 status while prone

    Time: Through study completion, an average of 6 days

    Description: Whether or not the participant died while hospitalized

    Measure: Mortality

    Time: Through study completion, an average of 6 days
    237 the Effect of HFNC Treatment on Mortality and Length of ICU Stay in Patient With COVID-19 Pneumonia

    coronavirus disease 2019 related pneumonia is causing acute respiratory failure and this is the most common reason for ICU admission. We have several different way for respiratory support. HFNC is one of the new technics for oxygen support. Our main purpose to observe the effect of HFNC on coronavirus disease 2019 patients' ICU stay and mortality.

    NCT04424836
    Conditions
    1. Coronavirus Infection
    2. Pneumonia, Viral
    3. Acute Respiratory Failure
    Interventions
    1. Device: high flow nasal cannula device
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia, Viral Pneumonia Respiratory Insufficiency
    HPO:Pneumonia

    Primary Outcomes

    Description: the mortality rate of patients

    Measure: short term mortality

    Time: in 28 days.

    Description: means the stay day of patients in intensive care unit

    Measure: icu stay

    Time: up to 28 days

    Secondary Outcomes

    Description: partial oxygen pressure, partial carbon dioxide pressure . both measured in mmhg

    Measure: blood gases

    Time: at the admission time and 24th hour
    238 A Randomized, Open-label Study of the Vascular and Microbiologic Efficacy of Dipyridamole Plus Standard Care vs. Standard Care in Hospitalized COVID19 Patients

    Brief Summary: The goal here is to evaluate dipyridamole in treating respiratory tract infection and circulatory dysfunction due to SARS-CoV-2 coronavirus in hospitalized CVID-19 patients. Infection with SARS-CoV-2 causes human COVID-19 (HCoV-19). The infection is associated with a deleterious inflammatory response and a prothrombotic state in addition to tissue damage from direct viral entry and proliferation. Dipyridamole has anti-platelet and anti-inflammatory effects. The drug was recently demonstrated to have anti-SARS-Cov-2 effect primarily in vitro. The concentration causing anti-viral effect in vitro is within that in the blood of humans taking this drug. As an oral tablet, it has the advantage of easy administration. Anti thrombotic, anti viral and anti inflammatory actions of this drug may be efficacious and safe in hospitalized subjects

    NCT04424901
    Conditions
    1. COVID-19 Pneumonia
    2. Vascular Complications
    Interventions
    1. Drug: Dipyridamole
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: D-dimer and platelet count

    Measure: Coagulation system

    Time: 9 days

    Secondary Outcomes

    Description: Evaluate for a non-detection from nasopharyngeal swab and in stool

    Measure: Viral Detection

    Time: 9 days

    Other Outcomes

    Description: Survival Status Alive

    Measure: Survival

    Time: 9 days

    Description: Change in the markers CRP/Ferritin

    Measure: Inflammatory Markers

    Time: 9 days

    Description: Change in Lymphocyte Count/ Fibrinogen/Cardiac Troponin

    Measure: Blood Markers

    Time: 9 days

    Description: Change in PT, PTT

    Measure: Coagulation Markers

    Time: 9 days

    Description: Change in SpO2/ imaging

    Measure: Pulmonary Status

    Time: 9 days

    Description: Change in fever, cough, sputum

    Measure: Clinical Status

    Time: 9 days
    239 Efficacy and Safety of Darunavir/Cobicistat vs. Lopinavir/Ritonavir in the Management of Patients With COVID-19 Pneumonia in Qatar

    Coronavirus Disease 2019 (COVID-19) is a disease caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus. It was first isolated in Wuhan, China in December 2019 and then rapidly spread to the rest of the world posing a severe threat to global health. Many therapeutics have been investigated for the treatment of this disease with inconclusive outcomes. Protease inhibitors are one of the proposed agents, but their use is limited to their significant drug interactions and side effects. The aim of this study is to compare the efficacy and safety outcomes of Darunavir/Cobicistat versus Lopinavir /Ritonavir in the treatment of patients with COVID-19 pneumonia in Qatar.

    NCT04425382
    Conditions
    1. Coronavirus
    2. COVID
    3. Pneumonia
    Interventions
    1. Drug: Darunavir/Cobicistat
    2. Drug: Lopinavir/Ritonavir
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Clinical Improvement is defined as the time to normalization of fever (defined as temperature <37.8 oC for 72 hours) and/or resolution of baseline sign/symptoms, without the need for symptomatic treatment Virological clearance is defined as the time to two consecutive negative COVID-19 PCR samples

    Measure: Time to Clinical Improvement and/or Virological Clearance (Composite Endpoint)

    Time: Up to 90 days

    Secondary Outcomes

    Description: o Defined as two consecutive negative COVID-19 PCR samples

    Measure: Percentage of Virological Clearance

    Time: At day 14, day 21, and day 28.

    Description: o Defined as the need for respiratory support, vasopressor use, or corticosteroids/immunomodulation therapy

    Measure: Percentage of Clinical Deterioration

    Time: Up to 28 days

    Measure: Incidence of Adverse Events

    Time: Up to 28 days

    Measure: Length of Hospital Stay

    Time: Up to 90 days

    Measure: All-cause Mortality

    Time: At 30 days
    240 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)
    241 A Randomized,Double Blinded, Double Dummy, Parallel Controlled Clinical Trial for Azvudine in the Treatment of Novel Coronavirus Pneumonia (COVID-19)

    To evaluate the efficacy and safety of azvudine in treatment of COVID-19

    NCT04425772
    Conditions
    1. COVID-19
    Interventions
    1. Drug: FNC+Standard of Care
    2. Drug: FNC dummy tablet+Standard of Care
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: (reduction) in viral load from baseline

    Measure: Change (reduction) in viral load from baseline

    Time: On day 7 and 14

    Secondary Outcomes

    Description: proportion of subjects change from mild or moderate type to severe type

    Measure: proportion of subjects change from mild or moderate type to severe type

    Time: up to 21 days

    Description: proportion of subjects change from severe type to critical type

    Measure: proportion of subjects change from severe type to critical type

    Time: up to 21 days

    Description: novel coronavirus nucleic acid conversion rate

    Measure: novel coronavirus nucleic acid conversion rate

    Time: up to 21 days

    Description: Novel coronavirus nucleic acid negative conversion time

    Measure: Novel coronavirus nucleic acid negative conversion time

    Time: up to 21 days

    Description: TIme(Days);Proportion(percent)

    Measure: The time and proportion of improvement in pulmonary imaging

    Time: up to 21 days

    Description: TIme(Days);Proportion(percent)

    Measure: Time and proportion of temperature return to normal

    Time: up to 21 days

    Description: TIme(Days);Proportion(percent)

    Measure: time and rate of improvement of respiratory symptoms and signs (lung rhones, cough, sputum, sore throat, etc.)

    Time: up to 21 days

    Description: TIme(Days);Proportion(percent)

    Measure: time and rate of improvement of diarrhea, myalgia, fatigue and other symptoms

    Time: up to 21 days

    Description: Changes of blood oxygen detection index

    Measure: Changes of blood oxygen detection index

    Time: up to 21 days

    Description: Frequency of requirement for supplemental oxygen or non-invasive ventilation

    Measure: Frequency of requirement for supplemental oxygen or non-invasive ventilation

    Time: up to 21 days

    Description: Frequency of adverse events

    Measure: Frequency of adverse events

    Time: up to 21 days
    242 Evaluation of Ivermectin, Aspirin, Dexamethasone and Enoxaparin as Treatment of covid19

    The associated use of Ivermectin, aspirin, dexamethasone, and enoxaparin (in different combinations and doses) will reduce the impact of COVID infection 19, the need of admission to the intensive care unit, and mortality.

    NCT04425863
    Conditions
    1. Severe Acute Respiratory Syndrome
    2. Ventilation Pneumonitis
    Interventions
    1. Drug: Ivermectin 5 MG/ML oral solution, Aspirin 250 mg tablets
    2. Other: Ivermectin 5 mg/mL oral solution, Dexamethasone 4-mg injection, Aspirin 250 mg tablets
    3. Other: Ivermectin 5 MG/ML oral solution, Dexamethasone 4-mg injection, Enoxaparin injection. Inpatient treatment with mechanical ventilation in ICU.
    MeSH:Severe Acute Respiratory Syndrome Coronavirus Infections Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Number of patients who did not go to a more severe stage of disease or die (i.e. they neither go from mild to moderate or severe, nor go from moderate to severe or die, if they had been already enrolled in a severe condition)

    Measure: Patients Who Improved Their Condition or Did Not Worsen it

    Time: 7 days

    Description: Number of patients needing ICU-treatment including mechanical ventilation after 2-week treatment

    Measure: ICU-treated Patients After 2-week Treatment

    Time: 14 days

    Description: Patients who died within 30 days after enrollment

    Measure: Mortality

    Time: 30 days

    Description: Patients who needed dose adjustment of any of the drugs involved in the treatment protocol

    Measure: Patients Needing Drug Dose Adjustment

    Time: 14 days

    Description: Patient presenting serious adverse events

    Measure: Adverse Events

    Time: 14 days
    243 The Effect of Early Prone Position on Prognosis in Acute Respiratory Failure Due to Coronavirus Disease 2019 Pneumonia

    the purpose of this study to evaluate the effect of early awake PP (prone position)application on oxygenation and intubation requirement in patients with acute respiratory failure due to coronavirus disease 2019 pneumonia.

    NCT04427969
    Conditions
    1. Coronavirus Infection
    2. Acute Respiratory Failure
    Interventions
    1. Behavioral: prone position
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia Respiratory Insufficiency Respiratory Distress Syndrome, Adult
    HPO:Pneumonia

    Primary Outcomes

    Description: the duration of icu stay day

    Measure: intensive care unit stay

    Time: up to 28 days

    Description: mortality percent

    Measure: short term mortality

    Time: up to 28 days

    Secondary Outcomes

    Description: partial oxygen pressure: mmhg , partial carbondiocsit pressure mmhg

    Measure: blood gases

    Time: up to 24 hours
    244 Phase II, Randomized, Double-blind, Controlled Clinical Trial Evaluating the Efficacy and Safety of Chloroquine + Low Dose Losartan Compared to Chloroquine Monotherapy in Subjects With SARS-CoV-2 Pneumonia

    Study design Phase 2, double blinded, single-center, 1:1 randomized clinical trial of Chloroquine vs Chloroquine/losartan for the treatment of SARS-CoV-2 pneumonia in non-critically ill subjects

    NCT04428268
    Conditions
    1. COVID-19 Pneumonia
    Interventions
    1. Drug: Chloroquine Phosphate Tablets
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Determine all-cause mortality up to 28 days after randomization of Chloroquine Phosphate Compared to Chloroquine Phosphate plus Losartan in Non-Critically Ill Patients with SARS-CoV-2 Pneumonia.

    Measure: Overall mortality

    Time: 28 days

    Secondary Outcomes

    Description: Compare the clinical outcome of Chloroquine Phosphate treatment vs Chloroquine Phosphate plus Losartan in the follow-up visit at the end of treatment. Acording to NIH and FDA definitions

    Measure: Clinical outcome assessment

    Time: 28 days

    Description: Assess the adverse events associated to chloroquine and chloroquine plus losartan at 28 days

    Measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

    Time: 28 days

    Description: Time to negative Polymerase chain reaction (PCR) test from baseline: testing every 48hrs until a negative result

    Measure: Time to negative SARS-CoV-2 test

    Time: 28 days
    245 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
    246 Epidemiological and Demographic Data From 150 Patients Diagnosed With Coronavirus Disease 2019 Pneumonia in Intensive Care Unit- a Retrospective, Observational Study in Istanbul, Turkey

    In this study, the investigator examined epidemiological and demographic characteristics, risk factors and 28-day mortality of patients admitted to the intensive care unit with the diagnosis of coronavirus disease 2019 pneumonia.

    NCT04430023
    Conditions
    1. Corona Virus Infection
    2. Pneumonia
    3. Acute Respiratory Failure
    Interventions
    1. Other: epidemiological and demographic characteristics
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia Respiratory Insufficiency
    HPO:Pneumonia

    Primary Outcomes

    Description: mortality rate

    Measure: mortality

    Time: up to 28 days

    Description: Patients' age, gender, BMI, medical history

    Measure: demographic characteristics

    Time: up to 28 days
    247 Treatment of Severe and Critical COVID-19 Pneumonia With Convalescent Plasma

    Open label two arms, non randomized Convalescent Plasma treatment to severe and critical pneumonia COVID-19 hospitlaized patients compared to a historical cohort with matched controls.

    NCT04432103
    Conditions
    1. Covid-19
    Interventions
    1. Biological: Anti SARS-CoV 2 Convalescent Plasma in severe COVID-19 patients
    2. Biological: Anti SARS-CoV 2 Convalescent Plasma in critical COVID-19 patients
    MeSH:Pneumon Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: progression to critical stage

    Measure: INCIDENCE OF CRITICAL PNEUMONIA

    Time: 14 days after convalescent plasma administration

    Description: mortality

    Measure: MORTALITY RATE AMONG CRITICAL PNEUMONIA PATIENTS

    Time: 28 days after convalescent plasma administration

    Secondary Outcomes

    Description: time to need mechanical ventilation

    Measure: INCIDENCE OF MECHANICAL VENTILATION

    Time: 14 days after convalescent plasma treatment

    Description: time of mechanical ventilation needed

    Measure: DAYS OF MECHANICAL VENTILATION

    Time: 28 days after convalescent plasma treatment
    248 Treatment of Severe and Critical COVID-19 Pneumonia With Convalescent Plasma

    Open label two arms, non randomized Convalescent Plasma treatment to severe and critical pneumonia COVID-19 hospitlaized patients compared to a historical cohort with matched controls.

    NCT04432103
    Conditions
    1. Covid-19
    Interventions
    1. Biological: Anti SARS-CoV 2 Convalescent Plasma in severe COVID-19 patients
    2. Biological: Anti SARS-CoV 2 Convalescent Plasma in critical COVID-19 patients
    MeSH:Pneumon Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: progression to critical stage

    Measure: INCIDENCE OF CRITICAL PNEUMONIA

    Time: 14 days after convalescent plasma administration

    Description: mortality

    Measure: MORTALITY RATE AMONG CRITICAL PNEUMONIA PATIENTS

    Time: 28 days after convalescent plasma administration

    Secondary Outcomes

    Description: time to need mechanical ventilation

    Measure: INCIDENCE OF MECHANICAL VENTILATION

    Time: 14 days after convalescent plasma treatment

    Description: time of mechanical ventilation needed

    Measure: DAYS OF MECHANICAL VENTILATION

    Time: 28 days after convalescent plasma treatment
    249 Comparison Between a Pocket Sized and a High End Ultrasound Scanner in the Evaluation of Lung Involvement in Patients With Covid-19 Pneumonia

    Ultrasound imaging of the lung (LUS) and associated tissues has demonstrated clinical utility in COVID-19 patients. The aim of the present study was to evaluate the possibilities of a portable pocket-sized ultrasound scanner in the evaluation of lung involvement in patients with COVID-19 pneumonia, in comparison with a high end ultrasound scanner. Statisical analysis will be performed with Stata for Windows V 16 (Stata corp, Texas College, TX). Power size estimation using Medcalc 19.3.1, (MedCalc Software Ltd, Ostenda, B) showed that hat 34 patients would be required for the comparison of the two methods using the Bland-Altman method assuming a mean difference in total score of 1±1, a false positive rate (α) of 0.05 and a false negative rate of 0.1 (β=0.9).

    NCT04433000
    Conditions
    1. Covid-19 Pneumonia
    Interventions
    1. Diagnostic Test: Butterfly
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: The more widely accepted measure of agreement beteen two instruments. Bland JM, Altman DG (1986) Statistical method for assessing agreement between two methods of clinical measurement. The Lancet i:307-310

    Measure: Bland-Altman estimate of bias and Limits of Agreement (LoA) of patient mean scores obtained with the two instruments

    Time: 1 day
    250 A Randomized, Double-Blind, Parallel Group Study to Assess the Efficacy and Safety of Once Weekly Subcutaneous Injections of Pemziviptadil (PB1046), a Sustained-Release VIP (Vasoactive Intestinal Peptide) ANalogue, in Hospitalized COVID-19 Patients at HiGh Risk for Rapid Clinical Deterioration and ARDS (PB1046 VANGARD Study)

    This is a multicenter, randomized, double-blind, parallel group study to investigate the efficacy of pemziviptadil (PB1046) by improving the clinical outcomes and increasing days alive and free of respiratory failure in hospitalized COVID-19 patients at high risk for rapid clinical deterioration, acute respiratory distress syndrome (ARDS) and death. The study will enroll approximately 210 hospitalized COVID-19 patients who require urgent decision-making and treatment at approximately 20 centers in the United States.

    NCT04433546
    Conditions
    1. Acute Respiratory Distress Syndrome
    2. Coronavirus
    3. Hypoxic Respiratory Failure
    4. Hypoxemic Respiratory Failure
    5. Respiratory Complicati
    6. Respiratory Complication
    7. Respiratory Insufficiency
    8. Cardiac Dysfunction
    9. Pneumonia
    10. Pulmonary Edema
    11. Pulmonary Inflammation
    12. Respiratory Failure
    13. Cytokine Storm
    14. COVID 19
    15. SARS-CoV-2
    16. Cardiac Event
    17. Cardiac Complication
    18. Cardiac Failure
    19. Cardiac Infarct
    Interventions
    1. Drug: Pemziviptadil (PB1046)
    2. Drug: Low Dose (10 mg) Control
    MeSH:Pneumonia Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Respiratory Insufficiency Acute Lung Injury Pulmonary Edema Pulmonary Valve Insufficiency Heart Failure Syndrome Inflammation Clinical Deterioration
    HPO:Abnormal left ventricular function Congestive heart failure Pneumonia Pulmonary edema Pulmonary insufficiency Right ventricular failure

    Primary Outcomes

    Measure: Days alive and free of respiratory failure from initiation of pemziviptadil (PB1046)

    Time: 28 days

    Secondary Outcomes

    Measure: Time to clinical recovery (being well enough for hospital discharge or returning to normal baseline activity level prior to discharge)

    Time: 28 days

    Description: PaO2:FiO2 ratio is the ratio of partial pressure of arterial oxygen to percentage of inspired oxygen

    Measure: Development of ARDS (PaO2:FiO2 ratio < 300 mm Hg) during hospitalization

    Time: Any time point between injection initiation and Day 28

    Measure: All-cause mortality

    Time: 28 days

    Description: Composite of: Total hospital days, Total ICU days, Total days of ventilator use, Total days of ECMO, Total days of invasive hemodynamic monitoring, Total days of mechanical circulatory support, Total days of inotropic or vasopressor therapy

    Measure: Reduction in hospital resource utilization defined as a composite of:total days: in hospital, in ICU, on ventilator, on ECMO, with invasive hemodynamic monitoring, with mechanical circulatory support, and with inotropic or vasopressor therapy

    Time: 28 days

    Measure: Time to clinical improvement as defined by reduction of at least 2 points on an 8-category ordinal scale of clinical improvement or discharge from hospital, whichever comes first.

    Time: Any time point between injection initiation and Day 28

    Measure: Change from baseline in cardiac marker high sensitivity troponin I (hsTnI)

    Time: Any time point between injection initiation and Day 35+7

    Measure: Change from baseline in cardiac marker NT-proBNP

    Time: Any time point between injection initiation and Day 35+7

    Measure: Change from baseline in TNF alpha

    Time: Any time point between injection initiation and Day 35+7

    Measure: Change from baseline in IL-1

    Time: Any time point between injection initiation and Day 35+7

    Measure: Change from baseline in IL-6

    Time: Any time point between injection initiation and Day 35+7

    Measure: Incidence and severity of any treatment emergent adverse events (TEAEs) or serious adverse events (SAEs) as determined by clinical adverse events (AEs) and their relationship to PB1046

    Time: Any time point between injection initiation and Day 35+7

    Measure: Incidence and severity of any treatment emergent adverse events (TEAEs) or serious adverse events (SAEs) as determined by vital signs and their relationship to PB1046

    Time: Any time point between injection initiation and Day 35+7

    Measure: Incidence and severity of any treatment emergent adverse events (TEAEs) or serious adverse events (SAEs) as determined by laboratory results and their relationship to PB1046

    Time: Any time point between injection initiation and Day 35+7

    Measure: Incidence and severity of any treatment emergent adverse events (TEAEs) or serious adverse events (SAEs) as determined by electrocardiogram (ECG) abnormalities and their relationship to PB1046

    Time: Any time point between injection initiation and Day 35+7

    Measure: Incidence and severity of any treatment emergent adverse events (TEAEs) or serious adverse events (SAEs) as determined by incidence of anti-drug antibodies and their relationship to PB1046

    Time: Any time point between injection initiation and Day 35+7

    Other Outcomes

    Measure: Impact on invasive hemodynamic parameters as measured by pulmonary artery pressure if patients require right-heart catherization

    Time: Any time point between injection initiation and Day 35+7

    Measure: Impact on invasive hemodynamic parameters as measured by cardiac output if patients require right-heart catherization

    Time: Any time point between injection initiation and Day 35+7

    Measure: Incidence of multi-system organ failure (MSOF)

    Time: Any time point between injection initiation and Day 35+7

    Measure: Number of multi-system organ failure (MSOF) free days

    Time: Any time point between injection initiation and Day 35+7

    Measure: Number of subjects requiring extracorporeal membrane oxygenation (ECMO)

    Time: Any time point between injection initiation and Day 35+7
    251 Radiation Eliminates Storming Cytokines and Unchecked Edema as a 1-Day Treatment for COVID-19 (RESCUE 1-19): A Randomized Phase III of Best Supportive Care +/- Whole Lung Low-Dose Radiation Therapy in Hospitalized Patients

    This phase III trial compares low dose whole lung radiation therapy to best supportive care plus physicians choice in treating patients with COVID-19 infection. Low dose whole lung radiation therapy may work better than the current best supportive care and physician's choice in improving patients' clinical status, the radiographic appearance of their lungs, or their laboratory blood tests.

    NCT04433949
    Conditions
    1. Pneumonia
    2. Severe Acute Respiratory Syndrome
    3. Symptomatic COVID-19 Infection Laboratory-Confirmed
    Interventions
    1. Other: Best Practice
    2. Radiation: Low Dose Radiation Therapy
    MeSH:Laboratory Infection Severe Acute Respiratory Syndrome Coronavirus Infections Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Will be measured by improvements on oxygenation need prior to intervention compared with after intervention and/or hospital discharge.

    Measure: Time to clinical recovery

    Time: Up to follow-up day 14 after study start

    Secondary Outcomes

    Description: The rates from both cohort will be reported.

    Measure: Freedom from ICU admission

    Time: Up to follow-up day 14 after study start; This may be extended up to 28 days after preplanned interim analysis.

    Description: Temperature in degrees (F)

    Measure: Temperature

    Time: Up to follow-up day 14 after study start

    Description: Heart rate in beats per minutes

    Measure: Heart rate

    Time: Up to follow-up day 14 after study start

    Description: Systolic blood pressure in mm Hg

    Measure: Systolic Blood pressure

    Time: Up to follow-up day 14 after study start

    Description: Oxygen saturation in percentage

    Measure: Oxygen saturation

    Time: Up to follow-up day 14 after study start

    Description: Oxygen saturation in percentage

    Measure: Supplemental oxygenation need

    Time: Up to follow-up day 14 after study start

    Description: Respiratory rate in breaths per minute.

    Measure: Respiratory rate

    Time: Up to follow-up day 14 after study start

    Description: Pre and post intervention; Minimum of 3 (poor) to best (15)

    Measure: Glasgow Comma Scale from minimum of 3 to maximum of 15.

    Time: Up to follow-up day 14 after study start

    Description: Easter Cooperative Oncology Group (ECOG) Performance Status Scale from 0-5; 0 being best; 5 being dead;

    Measure: Performance status

    Time: Up to follow-up day 14 after study start

    Description: Survival in percentage

    Measure: Survival

    Time: Up to follow-up day 14 after study start; This may be extended to 28 days after preplanned interim analysis.

    Description: Serial chest x-rays categorized using published scale into ordinal ranks 1-5 for SARS.

    Measure: Serial chest x-rays severe acute respiratory syndrome (SARS) scoring

    Time: Up to follow-up day 14 after study start;

    Description: CT scans with volume of consolidation measured in cubic centimeters.

    Measure: Changes on computed tomography (CT) scans pre and post RT

    Time: Baseline up to follow-up day 14 after study start

    Description: C-Reactive Protein in mg/L

    Measure: CRP

    Time: Up to follow-up day 14 after study start

    Description: Will be summarized descriptively.

    Measure: Serum chemistry + complete blood cell (CBC) with differential

    Time: Up to follow-up day 14 after study start

    Description: pH (no unit)

    Measure: Blood gases pH(when available)

    Time: Up to follow-up day 14 after study start

    Description: Albumin in gm/dL

    Measure: Albumin

    Time: Up to follow-up day 14 after study start

    Description: Procalcitonin in ng/mL

    Measure: Procalcitonin

    Time: Up to follow-up day 14 after study start

    Description: Asparatate Aminotransferase in units/L

    Measure: Aspartate aminotransferase (AST)

    Time: Up to follow-up day 14 after study start

    Description: Creatinine in mg/dL

    Measure: Creatine kinase

    Time: Up to follow-up day 14 after study start

    Description: Coagulation pathway time in seconds

    Measure: Prothrombin time (PT)/partial thromboplastin time (PTT)

    Time: Up to follow-up day 14 after study start

    Description: Troponin-I in ng/mL

    Measure: Troponin

    Time: Up to follow-up day 14 after study start

    Description: Lactic Acid in mmol/L

    Measure: Lactate

    Time: Up to follow-up day 14 after study start

    Description: B-Natriuretic Peptid in pg/mL

    Measure: NT-pBNP (cardiac injury)

    Time: Up to follow-up day 14 after study start

    Description: Gamma-glutamyl transferase in units/L

    Measure: Gamma-glutamyl transferase (GGT)

    Time: Up to follow-up day 14 after study start

    Description: Trygliciericdes in mg/dL

    Measure: Triglycerides

    Time: Up to follow-up day 14 after study start

    Description: Fibrinogen in mg/dL

    Measure: Fibrinogen

    Time: Up to follow-up day 14 after study start

    Description: Will be summarized descriptively.

    Measure: Changes in CD8 T cells

    Time: Up to follow-up day 14 after study start

    Description: Will be summarized descriptively.

    Measure: Changes in CD4 T cells

    Time: Up to follow-up day 14 after study start

    Description: Will be summarized descriptively.

    Measure: Changes in serum antibodies against COVID-19 epitope

    Time: Up to follow-up day 14 after study start

    Description: Lactate Dehydrogenase in units/L

    Measure: LDH

    Time: Up to follow-up day 14 after study start

    Description: D-Dimer in ng/mL

    Measure: D-Dimer

    Time: Up to follow-up day 14 after study start

    Description: Interleukin-6 in pg/mL

    Measure: IL-6

    Time: Up to follow-up day 14 after study start

    Description: Myoglobin in ng/mL

    Measure: Myoglobin

    Time: Up to follow-up day 14 after study start

    Description: Potassium in mmol/L

    Measure: Potassium

    Time: Up to follow-up day 14 after study start

    Description: Ferritin in ng/mL

    Measure: Ferritin

    Time: Up to follow-up day 14 after study start

    Description: Alanine Aminotransferase in units/L

    Measure: ALT

    Time: Up to follow-up day 14 after study start
    252 Lipid Metabolism in COVID-19 Severe Pneumonia Compared With Severe Pneumonia Caused by Other Pathogen

    SARS-COV 2 infection might be responsible for sever pneumonia. Obesity seems to be a risk factor for severe SARS-COV 2 pneumonia. Lipid metabolism alteration are described with both obesity and sepsis. The aim of the present study was to describe association between lipid metabolism, obesity, sepsis inflammation and clinical outcome in COVID-19 patient with severe pneumonia compared with severe pneumonia caused by other pathogenes.

    NCT04435223
    Conditions
    1. COVID-19 Severe Pneumonia
    2. Severe Pneumonia Due to Other Pathogene
    Interventions
    1. Biological: biological assays in particular on the lipid metabolism
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Measure: Cholesterol concentration

    Time: Within 48 hours following hospital admission

    Secondary Outcomes

    Description: Ventilator free days (28 days)

    Measure: LDL cholesterol / HDL cholesterol/ Lipoprotein size and composition/ Non esterified Fatty acid/ Triglyceridemia/ CETP and PLTP activity/ apolipoprotein canceration/ lipid peroxidation/ Pro and anti inflammatory profile.

    Time: Within 48 hours following hospital admission
    253 SequelaeCov: a Prospective Study on Lung Damage Caused by SARS-CoV-2 Pneumonia

    Pneumonia is a recurrent element of COVID-19 infection, it is often associated with development of respiratory failure and patients frequently need various degrees of oxygen therapy up to non invasive ventilation (NIV-CPAP) and invasive mechanical ventilation (IMV). Main purpose of this study is to evaluate with non invasive clinical instruments (pletysmography, Diffusion lung capacity for carbon monoxide -DLCO-, six minute walking test and dyspnea scores) and radiological tools (chest X-ray and chest CT scan) the development of medium-to-long term pulmonary sequelae caused by SARS-CoV-2 pneumonia.

    NCT04435327
    Conditions
    1. COVID
    2. Pneumonia, Viral
    3. Barotrauma
    4. Interstitial Lung Disease
    5. Bronchiectasis Adult
    6. Emphysema
    MeSH:Pneumonia, Viral Pneumonia Lung Diseases Bronchiectasis Lung Diseases, Interstitial Emphysema Barotrauma
    HPO:Abnormal lung morphology Bronchiectasis Interstitial pneumonitis Interstitial pulmonary abnormality Pneumonia

    Primary Outcomes

    Description: Reduction below 80% of predicted values of DLCO

    Measure: Reduction of Diffusion of Lung CO (DLCO, single breath technique)

    Time: T1 at 6 months from discharge

    Description: Reduction below 80% of predicted values of DLCO

    Measure: Reduction of Diffusion of Lung CO (DLCO, single breath technique)

    Time: T2 at 12 months from discharge

    Secondary Outcomes

    Description: reduction in maximum distance walked

    Measure: Alterations in 6 minute walking test (6MWT)

    Time: T1 at 6 months from discharge

    Description: reduction in maximum distance walked

    Measure: Alterations in 6 minute walking test (6MWT)

    Time: T2 at 12 months from discharge

    Description: reduction in oxygen saturation nadir

    Measure: Alterations in 6 minute walking test (6MWT)

    Time: T1 at 6 months from discharge

    Description: reduction in oxygen saturation nadir

    Measure: Alterations in 6 minute walking test (6MWT)

    Time: T2 at 12 months from discharge

    Description: reduction of Forced Vital Capacity (FVC, %)

    Measure: Alterations of pletismography

    Time: T1 at 6 months from discharge

    Description: reduction of Forced Vital Capacity (FVC, %)

    Measure: Alterations of pletismography

    Time: T2 at 12 months from discharge

    Description: reduction of Forced Vital Capacity (FVC, L)

    Measure: Alterations of pletismography

    Time: T1 at 6 months from discharge

    Description: reduction of Forced Vital Capacity (FVC, L)

    Measure: Alterations of pletismography

    Time: T2 at 12 months from discharge

    Description: reduction of Vital Capacity (VC, %)

    Measure: Alterations of pletismography

    Time: T1 at 6 months from discharge

    Description: reduction of Vital Capacity (VC, %)

    Measure: Alterations of pletismography

    Time: T2 at 12 months from discharge

    Description: reduction of Vital Capacity (VC, L)

    Measure: Alterations of pletismography

    Time: T1 at 6 months from discharge

    Description: reduction of Vital Capacity (VC, L)

    Measure: Alterations of pletismography

    Time: T2 at 12 months from discharge

    Description: reduction of Forced Expiratory Volume in the 1st second (FEV1, L)

    Measure: Alterations of pletismography

    Time: T1 at 6 months from discharge

    Description: reduction of Forced Expiratory Volume in the 1st second (FEV1, %)

    Measure: Alterations of pletismography

    Time: T1 at 6 months from discharge

    Description: reduction of Forced Expiratory Volume in the 1st second (FEV1, L)

    Measure: Alterations of pletismography

    Time: T2 at 12 months from discharge

    Description: reduction of Forced Expiratory Volume in the 1st second (FEV1, L%)

    Measure: Alterations of pletismography

    Time: T2 at 12 months from discharge

    Description: reduction of Total Lung Capacity (TLC, L)

    Measure: Alterations of pletismography

    Time: T1 at 6 months from discharge

    Description: reduction of Total Lung Capacity (TLC, %)

    Measure: Alterations of pletismography

    Time: T1 at 6 months from discharge

    Description: reduction of Total Lung Capacity (TLC, L)

    Measure: Alterations of pletismography

    Time: T2 at 12 months from discharge

    Description: reduction of Total Lung Capacity (TLC, %)

    Measure: Alterations of pletismography

    Time: T2 at 12 months from discharge

    Description: alterations of Residual Volume (RV,%)

    Measure: Alterations of pletismography

    Time: T1 at 6 months from discharge

    Description: alterations of Residual Volume (RV, L)

    Measure: Alterations of pletismography

    Time: T1 at 6 months from discharge

    Description: alterations of Residual Volume (RV, L)

    Measure: Alterations of pletismography

    Time: T2 at 12 months from discharge

    Description: alterations of Residual Volume (RV, %)

    Measure: Alterations of pletismography

    Time: T2 at 12 months from discharge

    Description: increase of Specific Airway Resistance (sRAW) (absolute value)

    Measure: Alterations of pletismography

    Time: T1 at 6 months from discharge

    Description: increase of Specific Airway Resistance (sRAW) (%)

    Measure: Alterations of pletismography

    Time: T1 at 6 months from discharge

    Description: increase of Specific Airway Resistance (sRAW) (absolute value)

    Measure: Alterations of pletismography

    Time: T2 at 12 months from discharge

    Description: increase of Specific Airway Resistance (sRAW) (%)

    Measure: Alterations of pletismography

    Time: T2 at 12 months from discharge

    Description: alterations of Motley Index (VR/CPT)

    Measure: Alterations of pletismography

    Time: T1 at 6 months from discharge

    Description: alterations of Motley Index (VR/CPT)

    Measure: Alterations of pletismography

    Time: T2 at 12 months from discharge

    Description: alterations of Tiffeneau Index (IT)

    Measure: Alterations of pletismography

    Time: T1 at 6 months from discharge

    Description: alterations of Tiffeneau Index (IT)

    Measure: Alterations of pletismography

    Time: T2 at 12 months from discharge

    Description: reduction of PaO2 mmHg

    Measure: Alterations of Arterial Blood Gas Analysis

    Time: T1 at 6 months from discharge

    Description: reduction of PaO2 mmHg

    Measure: Alterations of Arterial Blood Gas Analysis

    Time: T2 at 12 months from discharge

    Description: alteration of PaCO2 mmHg

    Measure: Alterations of Arterial Blood Gas Analysis

    Time: T1 at 6 months from discharge

    Description: alteration of PaCO2 mmHg

    Measure: Alterations of Arterial Blood Gas Analysis

    Time: T2 at 12 months from discharge

    Description: Modified Medical Research Council - mMRC > 0 (minimum 0, maximum 4; higher score means worse outcome)

    Measure: Abnormal Dyspnea Score

    Time: T1 at 6 months from discharge

    Description: Modified Medical Research Council - mMRC > 0(minimum 0, maximum 4; higher score means worse outcome)

    Measure: Abnormal Dyspnea Score

    Time: T2 at 12 months from discharge

    Description: Presence and extension of abnormal pulmonary lung sounds at auscultation

    Measure: Presence and extension of abnormal pulmonary lung sounds at auscultation

    Time: T1 at 6 months from discharge

    Description: Presence and extension of abnormal pulmonary lung sounds at auscultation

    Measure: Presence and extension of abnormal pulmonary lung sounds at auscultation

    Time: T2 at 12 months from discharge

    Description: Presence and extension of radiological alterations at chest X-ray

    Measure: Presence and extension of radiological alterations at chest X-ray

    Time: T1 at 6 months from discharge

    Description: Presence and extension of radiological alterations at chest CT scan

    Measure: Presence and extension of radiological alterations at chest CT scan

    Time: T2 at 12 months from discharge
    254 Uncovering the Cardiac Phenotype of Individuals With SARS-COV-2 and Cardiac Injury

    At the end of December of 2019, a series of patients in Wuhan, China were struck with a mysterious respiratory infection. These isolated events have rapidly grown into a deadly, global pandemic. This pandemic is caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which results in the Coronavirus Disease 2019 (COVID-19). For individuals infected with COVID-19, approximately 30% of the hospitalized cases are associated with cardiovascular complications. Data are emerging that individuals with pre-exiting conditions (like hypertension, diabetes, cancer, or medical issues related to the immune system) are most susceptible to complications related to COVID-19. Furthermore, individuals of certain racial and ethnic backgrounds (e.g. African American and Hispanic) are at a higher risk of death from COVID-19. Despite these emerging observations, it remains unclear who will develop the cardiovascular complications (acute myocardial injury with evidence of a myocarditis-like picture and cardiogenic shock) and what the long term sequelae of this disease will be for survivors of this infection after hospitalization. Thus, the goals of this project are to better understand the epidemiology of cardiac injury in acutely ill COVID-19 patients through deep cardiac phenotyping and identify the molecular profile of individuals most susceptible to cardiac injury from COVID-19.

    NCT04435457
    Conditions
    1. SARS-CoV 2
    2. SARS Pneumonia
    3. COVID-19
    4. SARS-Associated Coronavirus as Cause of Disease Classified Elsewhere
    5. Cardiac Complication
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Patterns of late gadolinium enhancement and T1 and T2 mapping consistent with myocarditis on a post-hospitalization cardiac magnetic resonance imaging examination

    Measure: Prevalence of Myocarditis

    Time: Up to 4 weeks

    Secondary Outcomes

    Description: This includes categorically abnormal structural, mechanical functional, vascular, and metabolic using cardiac magnetic resonance imaging

    Measure: Prevalence of cardiac abnormalities by cardiac magnetic resonance imaging

    Time: Up to 4 weeks

    Description: Presence of cardiac autoantibodies and defects within the immune system as detected by Whole Exome Sequencing making an individual susceptible to subacute cardiac injury during COVID-19 infection

    Measure: Prevalence of molecular and genetic immune system abnormalities

    Time: Up to 4 weeks
    255 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
    256 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

    Time: up to Day 28

    Measure: Time from Randomization to Respiratory Rate ≤ 24 Breaths per Minute on Room Air

    Time: up to Day 28

    Measure: Time from Randomization to Cough Reported as Mild or Absent

    Time: up to Day 28

    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 Fatalities

    Time: up to Day 28

    Measure: Number of Participants with Treatment-Emergent Adverse Events (TEAEs)

    Time: up to Day 28
    257 Assessment of Lung Inflammation With FDG PET/CT in COVID-19

    The aim of the study was to assess the inflammatory status at the presumed peak of the inflammatory phase in non-critically ill patients requiring admission for COVID-19. Patients admitted with COVID-19 from March 27th to May 3rd, 2020 were prospectively enrolled. All patients had an initial chest CT-scan for diagnosis on admission and a second chest CT-scan for follow-up concomitant with a FDG PET/CT between day 6 and day 14 after the onset of symptoms.

    NCT04441489
    Conditions
    1. COVID-19
    2. FDG PET/CT
    3. Inflammation
    MeSH:Pneumonia Inflammation
    HPO:Pneumonia

    Primary Outcomes

    Description: Amount of FDG pathological uptake expressed by maximum signal intensity standardized uptake values (SUVmax)

    Measure: Primary endpoint

    Time: Day 6 to Day 14
    258 Identification of Predictors for the Evolution of COVID-19 Related Interstitial Pneumonia by Transcriptomic and Seroproteomic Techniques

    The investigating group aims at performing an observational, prospective study that involves the evaluation of circulating biomarkers predictive of clinical evolution in patients suffering from COVID-19 disease. In particular, the aim will be to verify whether there are transcripts or cytokines / chemokines in peripheral blood, modulated differently in patients with COVID-19, distinguished on the basis of the evolution towards more severe clinical pictures that require patient intubation or that show signs of cardiovascular damage. The study will be based on the transcriptional analysis of the entire genome and serum protein to evaluate the expression of a broad spectrum of cytokines and chemokines. Genome analysis will allow the genotype to be correlated to the identified gene expression profiles.

    NCT04441502
    Conditions
    1. Covid19
    2. Interstitial Pneumonia
    MeSH:Pneumonia Lung Diseases, Interstitial
    HPO:Interstitial pneumonitis Interstitial pulmonary abnormality Pneumonia

    Primary Outcomes

    Description: Identify circulating transcripts (coding and non-coding for proteins) or cytokines and chemokines which, alone or in combination (COVID19_signature), are predictive of adverse events (death, endotracheal intubation) and the prognostic capacity of COVID19_signature in the prediction of adverse events in additional to the use of standard clinical parameters

    Measure: Circulating markers for COVID-19 signature

    Time: From ICU/ward admission for 8 weeks follow/up

    Secondary Outcomes

    Description: Evaluate the association of COVID19_signature with adverse cardiovascular events. Adverse cardiovascular events are defined: death from cardiovascular causes, acute coronary syndrome, troponin T levels greater than the ninety-ninth percentile of the upper reference limit, stroke, cardiac arrhythmias, development of heart failure, venous thromboembolism

    Measure: COVID-19 signature and adverse cardiovascular events

    Time: From ICU/ward admission for 8 weeks follow/up

    Description: Evaluate, in a subset of 20 patients, the characteristics of the coagulation pattern with specific tests for thrombin generation and fibrinolysis.

    Measure: COVID-19 related coagulation pattern

    Time: From ICU/ward admission for 8 weeks follow/up
    259 Controlled and Randomized Clinical Trial for Evaluating the Effect of a Supplement of Glycine as Adjuvant in the Treatment of COVID-19 Pneumonia in Patients Initiating Mechanical Ventilation

    This study will explore whether a daily supplement of glycine, a substance that has antiinflammatory, cytoprotective, and endothelium-protecting effects, can improve mortality, as well as clinical and biochemical parameters, in patients with severe COVID-19 who initiate mechanical ventilatory support.

    NCT04443673
    Conditions
    1. COVID-19
    2. SARS-CoV Infection
    3. SARS (Severe Acute Respiratory Syndrome)
    4. SARS Pneumonia
    5. ARDS, Human
    6. Pneumonia, Viral
    Interventions
    1. Dietary Supplement: Glycine
    MeSH:Severe Acute Respiratory Syndrome Coronavirus Infections Pneumonia, Viral Pneumonia Respiratory Distress Syndrome, Adult
    HPO:Pneumonia

    Primary Outcomes

    Description: Number of participants who die divided by number of subjects enrolled in the that study group.

    Measure: Mortality

    Time: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.

    Secondary Outcomes

    Description: Number of days spent under mechanical ventilation.

    Measure: Days under mechanical ventilation

    Time: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.

    Description: Arterial pressure of oxygen divided by inspired fraction of oxygen.

    Measure: PaO2/FiO2 ratio

    Time: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.

    Description: Plasma concentration of lactate in arterial blood.

    Measure: Arterial plasma lactate

    Time: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.

    Description: Serum concentration of interleukin 1β.

    Measure: Serum IL-1β

    Time: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.

    Description: Serum concentration of interleukin 2.

    Measure: Serum IL-2

    Time: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.

    Description: Serum concentration of interleukin 4.

    Measure: Serum IL-4

    Time: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.

    Description: Serum concentration of interleukin 5.

    Measure: Serum IL-5

    Time: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.

    Description: Serum concentration of interleukin 6.

    Measure: Serum IL-6

    Time: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.

    Description: Serum concentration of interleukin 7.

    Measure: Serum IL-7

    Time: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.

    Description: Serum concentration of interleukin 8.

    Measure: Serum IL-8

    Time: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.

    Description: Serum concentration of interleukin 10.

    Measure: Serum IL-10

    Time: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.

    Description: Serum concentration of interleukin 12 (p70).

    Measure: Serum IL-12

    Time: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.

    Description: Serum concentration of interleukin 13.

    Measure: Serum IL-13

    Time: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.

    Description: Serum concentration of interleukin 17A.

    Measure: Serum IL-17

    Time: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.

    Description: Serum concentration of granulocyte colony stimulating factor.

    Measure: Serum G-CSF

    Time: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.

    Description: Serum concentration of granulocyte monocyte colony stimulating factor.

    Measure: Serum GM-CSF

    Time: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.

    Description: Serum concentration of interferon gamma.

    Measure: Serum IFN-γ

    Time: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.

    Description: Serum concentration of monocyte chemoattractant protein 1 (MCAF).

    Measure: Serum MCP-1

    Time: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.

    Description: Serum concentration of macrophage inflammatory protein 1β

    Measure: Serum MIP-1β

    Time: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.

    Description: Serum concentration of tumor necrosis factor alpha.

    Measure: Serum TNF-α

    Time: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.

    Description: Serum concentration of creatinine.

    Measure: Serum creatinine

    Time: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.

    Description: Serum concentration of alanine aminotransferase. .

    Measure: Serum alanine aminotransferase

    Time: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.

    Description: Serum concentration of aspartate aminotransferase. .

    Measure: Serum aspartate aminotransferase

    Time: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.

    Description: Serum concentration of alkaline phosphatase.

    Measure: Serum alkaline phosphatase

    Time: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.

    Description: Serum concentration of total bilirubin.

    Measure: Serum total bilirubin

    Time: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.

    Description: Serum concentration of unconjugated bilirubin.

    Measure: Serum unconjugated bilirubin

    Time: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.

    Description: Serum concentration of conjugated bilirubin

    Measure: Serum conjugated bilirubin

    Time: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.

    Description: Serum concentration of C reactive protein.

    Measure: Serum C reactive protein

    Time: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.

    Description: Blood concentration of hemoglobin.

    Measure: Hemoglobin

    Time: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.

    Description: Number of white blood cells per µl blood.

    Measure: Total leukocytes

    Time: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.

    Description: Number of neutrophils per µl blood.

    Measure: Neutrophils

    Time: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.

    Description: Number of lymphocytes per µl blood.

    Measure: Lymphocytes

    Time: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.

    Description: Number of monocytes per µl blood.

    Measure: Monocytes

    Time: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.

    Description: Number of eosinophils per µl blood.

    Measure: Eosinophils

    Time: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.

    Description: Number of basophils per µl blood.

    Measure: Basophils

    Time: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.

    Description: Number of platelets per µl blood.

    Measure: Platelets

    Time: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.

    Description: Time that blood takes to clot.

    Measure: Prothrombin time

    Time: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.

    Description: Serum concentration of plasminogen activator inhibitor 1 (PAI-1).

    Measure: Serum PAI-1

    Time: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.

    Description: Sequence Organ Failure Assessment (SOFA) score, composed by assessment of PaO2/FiO2 ratio, Glasgow coma scale, mean arterial pressure, bilirubin, and platelets.

    Measure: SOFA score

    Time: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.

    Description: Acute Physiology And Chronic Health Evaluation II (APACHE II) score, composed by assessment of AaDO2 or PaO2, temperature, mean arterial pressure, pH arterial, heart rate, respiratory rate, sodium, potassium, creatinine, hematocrit, white blood cell count, Glasgow coma scale.

    Measure: APACHE II score

    Time: From date of enrollment and until the date of weaning from ventilator or death, whichever came first, assessed up to 12 months.
    260 Identification of Factors Associated to Clinical Improvement in Patients With SARS-COV-2 Pneumonia: a Prospective Cohort Study

    The objective is to determine whether the use of ozone autohemotherapy is associated with a decrease in time to clinical improvement

    NCT04444531
    Conditions
    1. COVID-19 Pneumonia
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Measure: Time to clinical improvement

    Time: 28 days

    Secondary Outcomes

    Measure: Clinical improvement at day 14

    Time: 14 days

    Measure: Clinical improvement at day 28

    Time: 28 days

    Measure: Time to a 2-fold decrease of C-protein reactive from baseline

    Time: 28 days

    Measure: Time to a 2-fold decrease of ferritin from baseline

    Time: 28 days

    Measure: Time to a 2-fold decrease of Lactate Dehydrogenase from baseline

    Time: 28 days

    Measure: Time to a 2-fold decrease of D-dimer from baseline

    Time: 28 days
    261 A Multicentre, Open-label Clinical Trial to Evaluate the Effectiveness and Safety of Intravenous Tocilizumab for Treating Patients With COVID-19 Pneumonia: the BREATH-19 Study

    At present, no treatment has been approved for COVID-19. However, in light of the increased interest on using the anti-cytokine therapy targeting IL-6 tocilizumab in COVID-19 infected patients due to its potential benefit, the Spanish Agency for Medicine and Health Products (Agencia Española de Medicamentos y Productos Sanitarios, AEMPS) have initiated the controlled distribution of the drug. Tocilizumab is indeed proposed as a potential treatment for severe COVID-19 in Spain. Based on the positive results of tocilizumab in the treatment of COVID-19 patients and the experience of tocilizumab in inducing rapid reversal of CSS in other pathologies several clinical trials and observational studies are being conducted to assess the effectiveness and safety of tocilizumab in COVID-19 patients. Further studies with a large sample size are required to confirm the effectiveness of tocilizumab in patients with COVID-19 pneumonia. The need for the management of severe COVID-19 disease is imperative, and every effort should be made to collect relevant clinical outcomes. The aim of the present study is to evaluate the effectiveness of IV tocilizumab in treating patients with COVID-19 pneumonia who are currently hospitalized or admitted to ICU by describing improvement of respiratory function and mortality rate. This large real-world cohort therefore provides a unique opportunity to study this potential medicine during the current emergency situation, and support the findings from other ongoing clinical trials and observational studies, such as the Roche-sponsored Phase III study that is planned to start early April.

    NCT04445272
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Tocilizumab
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Calculate the mean time of intubation

    Measure: To calulate the time of intubation

    Time: through study completion, and average of 1 month

    Description: Calculate the mean time with oxygen therapy

    Measure: To calculate the time with oxygen therapy

    Time: through study completion, and average of 1 month

    Description: Calculate the mean time with Non-invasive mechanical ventilation

    Measure: To calculate the time with Non-invasive mechanical ventilation

    Time: through study completion, and average of 1 month

    Description: Number of patients deaths of the total of patients included

    Measure: To evaluate mortality rate

    Time: through study completion, and average of 1 month

    Secondary Outcomes

    Description: To calculate the mean ofPaO2/FiO2

    Measure: To calculate respiratory function parameters

    Time: through study completion, and average of 1 month

    Description: To calculate the mean of levels of oxygen saturation

    Measure: To calculate respiratory function parameters

    Time: through study completion, and average of 1 month

    Description: To calculate the mean of SaO2/FiO2

    Measure: To calculate respiratory function parameters

    Time: through study completion, and average of 1 month

    Description: Evaluate the lung extension of pneumonia

    Measure: To evaluate radiological lung extension

    Time: through study completion, and average of 1 month

    Description: Evaluate the type of lung affection

    Measure: To evaluate radiological evolution

    Time: through study completion, and average of 1 month

    Description: Days of hospitalization in survivors and/or days at ICU throughout the study

    Measure: To describe the duration of hospitalization and ICU use

    Time: through study completion, and average of 1 month

    Description: Percentage of patients with extracorporeal membrane oxygenation

    Measure: To evaluate the requirement of additional organ support

    Time: through study completion, and average of 1 month

    Description: Percentage of patients with molecular adsorbent recirculating system

    Measure: To evaluate the requirement of additional organ support

    Time: through study completion, and average of 1 month

    Description: Percentage of patients with dialysis

    Measure: To evaluate the requirement of additional organ support

    Time: through study completion, and average of 1 month

    Description: Percentage of patients with other support therapy

    Measure: To evaluate the requirement of additional organ support

    Time: through study completion, and average of 1 month

    Description: Analyze the levels of IL-6

    Measure: To evaluate the effect of IV tocilizumab on the serum levels of inflammatory markers

    Time: through study completion, and average of 1 month

    Description: Incidence of adverse events

    Measure: To calculate the number of adverse events in patients with COVID-19 pneumonia treated with Tocilizumab

    Time: through study completion, and average of 1 month

    Description: Incidence of adverse events by dose of Tocilizumab

    Measure: To calculate the number of adverse events in patients with COVID-19 pneumonia treated with Tocilizumab

    Time: through study completion, and average of 1 month

    Description: To evaluate the time to RT-PCR virus negativity

    Measure: To assess time to reverse-transcriptase polymerase chain reaction (RT-PCR) virus negativity

    Time: through study completion, and average of 1 month

    Description: Analyze the levels of CRP

    Measure: To evaluate the effect of IV tocilizumab on the serum levels of inflammatory

    Time: through study completion, and average of 1 month

    Description: Analyze the levels of procalcitonin (PCT)

    Measure: To evaluate the effect of IV tocilizumab on the serum levels of inflammatory

    Time: through study completion, and average of 1 month

    Description: Analyze the levels of ID-dimer

    Measure: To evaluate the effect of IV tocilizumab on the serum levels of inflammatory

    Time: through study completion, and average of 1 month

    Description: Analyze the levels of ferritin

    Measure: To evaluate the effect of IV tocilizumab on the serum levels of inflammatory

    Time: through study completion, and average of 1 month

    Description: Indicende of serious adverse events

    Measure: To calculate the number of serious adverse events in patients with COVID-19 pneumonia treated with Tocilizumab

    Time: through study completion, and average of 1 month

    Description: Indicende of serious adverse events based on dose of Tocilizumab

    Measure: To calculate the number of serious adverse events in patients with COVID-19 pneumonia treated with Tocilizumab

    Time: through study completion, and average of 1 month

    Description: Indicende of adverse events of special interest based on dose of Tocilizumab

    Measure: To calculate the number of adverse events of special interest in patients with COVID-19 pneumonia treated with Tocilizumab

    Time: through study completion, and average of 1 month

    Description: Number of patients deaths of the total of patients included based on dose of Tocilizumab

    Measure: To evaluate mortality rate

    Time: through study completion, and average of 1 month

    Description: Time with intubation, oxygen therapy and Non-invasive mechanical ventilation based on dose of Tocilizumab

    Measure: To evaluate respiratory function

    Time: through study completion, and average of 1 month

    Description: Number of patients deaths of the total of patients included based on severity of disease at the start of the study treatment

    Measure: To evaluate mortality rate

    Time: through study completion, and average of 1 month

    Description: Number of patients deaths of the total of patients included based on presence of cytokine storm syndrome at the start of treatment

    Measure: To evaluate mortality rate

    Time: through study completion, and average of 1 month

    Description: Time with intubation, oxygen therapy and Non-invasive mechanical ventilation based on severity of disease at the start of the study treatment

    Measure: To evaluate respiratory function

    Time: through study completion, and average of 1 month

    Description: Time with intubation, oxygen therapy and Non-invasive mechanical ventilation based on presence of cytokine storm syndrome at the start of treatment

    Measure: To evaluate respiratory function

    Time: through study completion, and average of 1 month
    262 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
    263 Respiratory Mechanics and Gas Exchange in Patients With COVID-19 and Hypoxemic Acute Respiratory Failure: Multicentral Observational Study

    Data on respiratory mechanics and gas exchange in acute respiratory failure in COVID-19 patients is limited. Knowledge of respiratory mechanics and gas exchange in COVID-19 can lead to different selection of mechanical ventilation strategy, reduce ventilator-associated lung injury and improve outcomes. The objective of the study is to evaluate the respiratory mechanics, lung recruitability and gas exchange in COVID-19 -associated acute respiratory failure during the whole course of mechanical ventilation - invasive or non-invasive.

    NCT04445961
    Conditions
    1. SARS Pneumonia
    Interventions
    1. Diagnostic Test: Respiratory mechanics measurement
    2. Diagnostic Test: Gas exchange measurement
    MeSH:Pneumonia Respiratory Insufficiency
    HPO:Pneumonia

    Primary Outcomes

    Description: Positive end-expiratory pressure (PEEP) selection at minimum level with maximum static compliance and the highest peripheral capillary oxygen saturation over fraction of inspired oxygen (SpO2/FiO2)

    Measure: Optimum positive end-expiratory pressure (PEEP) level

    Time: On day 1 during mechanical ventilation

    Description: Positive end-expiratory pressure (PEEP) selection at minimum level with maximum static compliance and the highest peripheral capillary oxygen saturation over fraction of inspired oxygen (SpO2/FiO2)

    Measure: Optimum positive end-expiratory pressure (PEEP) level

    Time: On day 7 during mechanical ventilation

    Description: Peripheral capillary oxygen saturation (SpO2) change from 90% after recruitment maneuver (doubled tidal volume for 15 respiratory cycles) - if peripheral capillary oxygen saturation (SpO2) after recruitment maneuver more than 95%-recruitable

    Measure: Number of patients with recruitable lung

    Time: On day 1 during mechanical ventilation

    Description: Peripheral capillary oxygen saturation (SpO2) change from 90% after recruitment maneuver (doubled tidal volume for 15 respiratory cycles) - if peripheral capillary oxygen saturation (SpO2) after recruitment maneuver more than 95%-recruitable

    Measure: Number of patients with recruitable lung

    Time: On day 7 during mechanical ventilation

    Secondary Outcomes

    Description: Calculation of the alveolar dead space using end-tidal carbon dioxide measurement and arterial carbon dioxide tension measurement

    Measure: Change in alveolar dead space

    Time: On day 1, 3, 5, 7, 10, 14, 21 during mechanical ventilation

    Description: Measurement of plethysmogram variability before and during recruitment maneuver

    Measure: Change in plethysmogram variability during recruitment maneuver

    Time: On day 1, 3, 5, 7, 10, 14, 21 during mechanical ventilation

    Description: Calculation of the arterial partial oxygen tension to inspiratory oxygen fraction (PaO2/FiO2) ratio using arterial oxygen tension measurement

    Measure: Change in arterial partial oxygen tension to inspiratory oxygen fraction (PaO2/FiO2) ratio

    Time: On day 1, 3, 5, 7, 10, 14, 21 during mechanical ventilation

    Description: Positive end-expiratory pressure (PEEP) selection at minimum level with maximum static compliance and the highest peripheral capillary oxygen saturation over fraction of inspired oxygen (SpO2/FiO2)

    Measure: Optimum positive end-expiratory pressure (PEEP) level

    Time: On day 3, 5, 10, 14, 21 during mechanical ventilation

    Description: Driving pressure calculation at different positive end-expiratory pressure (PEEP) levels (8, 10, 12, 14)

    Measure: Change in driving pressure with different positive end-expiratory pressure (PEEP) levels

    Time: On day 1, 3, 5, 7, 10, 14, 21 during mechanical ventilation
    264 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
    265 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
    266 A Multi-center, Open-label, Randomized Parallel Controlled Evaluation on the Efficacy and Safety of BDB-001 Injection in the Treatment of Progressive Severe COVID-19 in Phase II/III

    This multi-center, open, randomized study will evaluate the efficacy and safety of BDB-001 injection in severe COVID-19 with severe pneumonia, or acute lung injury/acute respiratory distress syndrome. Patients will be randomized to two treatment arms (Arm A: Conventional treatment + BDB-001; Arm B: Conventional treatment alone).

    NCT04449588
    Conditions
    1. COVID-19 Pneumonia
    Interventions
    1. Drug: BDB-001 Injection
    2. Other: Conventional treatment
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Measure: Time to recovery of peripheral capillary oxygen saturation (SpO2) from baseline

    Time: Baseline to Day 28

    Measure: 28-day all-cause mortality rate

    Time: Baseline to Day 28

    Secondary Outcomes

    Measure: Percentage of subjects achieving recovery in SpO2

    Time: Baseline to Day 28

    Measure: Mean change of PaO2/FiO2

    Time: Baseline to Day 28

    Measure: Mechanical ventilation time

    Time: Baseline to Day 28

    Measure: Time of oxygen therapy

    Time: Baseline to Day 28

    Measure: Lymphocyte count

    Time: Baseline to Day 28

    Measure: Change in inflammation indicators (CRP or IL-6) from baseline

    Time: Baseline to Day 28

    Measure: Improvement in body temperature

    Time: Baseline to Day 28

    Measure: Mean change from baseline in the clinical improvement based on ordinal scale recommended by the WHO R&D Blueprint during treatment period

    Time: Baseline to Day 28

    Measure: Improvement at Day3, 7, 11 & Day14 based on ordinal scale recommended by the WHO R&D Blueprint during treatment period

    Time: Baseline, Day 3, Day 7, Day 11, Day 14

    Measure: Time to get categories 1 to 4 in the 8-points ordinal scale

    Time: Baseline to Day 28

    Measure: Time to attain an improvement of 1 point on the ordinal scale

    Time: Baseline to Day 28
    267 Early Use of Corticosteroids in Non-critical Patients With COVID-19 Pneumonia (PREDCOVID)

    Steroids has shown benefits in COVID19 patients in observational studies. We hypothesized that early use of corticosteroids, low dose, in mild disease, can decrease progression to respiratory failure and death.

    NCT04451174
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Prednisone
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Measure: Composite Primary End-point: Admission to ICU, Need for Invasive Mechanical Ventilation or All-cause Death by Day 28

    Time: 28 days
    268 Pilot Clinical, Statistical and Epidemiological Study on Efficacy and Safety of Convalescent Plasma for the Management of Patients With COVID-19

    The health contingency established against the Severe Acute Respiratory Syndrome associated type 2 Coronavirus (SARS-CoV-2) has promoted a race against the clock for the search on treatment against the disease related with coronavirus (COVID-19). There are no current approved therapeutic options against the virus, although there is a rush for the development of drugs, vaccines and even the passive immunization through plasma from convalescent patients. This passive immunization is made with the administration of antibodies from patients that went through the infectious state of the disease and progress to clinical remission. SARS-CoV-2, and its predecessor SARS-CoV-1, have great similarities between their genes and proteins; tis allow to hypothesize that the antibodies developed against SARS-CoV1 can recognize the antigens of SARS-CoV-2. In this manner, the transfusion of convalescent plasma to patients with the infection brings the probability on eliminating the infection, in this case SARS-CoV-2. There are evidence of this phenomenon observed in previous pandemics caused by SARS-CoV-1, Influenza AH1N1 and Ebola virus. The objective of the study is to develop a therapeutic strategy based on the administration of plasma from patients with COVID-19 with clinical remission to patients that are coursing with the infection. The expected results hopes to establish an effective treatment and satisfactory recovery of patients with COVID-19. Also, we expect to describe the respective antibodies related against the SARS-CoV-2 infection.

    NCT04452812
    Conditions
    1. COVID-19 Pneumonia
    2. Convalescent Plasma
    Interventions
    1. Biological: Convalescent plasma
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Any cause mortality during the first 30 days of treatment

    Measure: All-cause mortality

    Time: 30 days

    Description: Side effects associated with the administration of convalescent plasma

    Measure: Side effects

    Time: 30 days

    Secondary Outcomes

    Description: Time to discharge from the ICU

    Measure: Length of stay in Intensive Care Unit (ICU)

    Time: 14 days

    Description: Time for discharge from hospital

    Measure: Length of stay in hospitalization

    Time: 21 days

    Description: Number of days with ventilatory support

    Measure: Days of mechanical ventilation

    Time: 14 days

    Description: change in D-dimer (micrograms/L)

    Measure: Inflammatory biomarkers (d-dimer)

    Time: 21 days

    Description: change in C-reactive protein (milligrams/dL)

    Measure: Inflammatory biomarkers (c-reactive protein)

    Time: 21 days

    Description: Change in LDH (UI/L)

    Measure: Inflammatory biomarkers (lactate dehydrogenase)

    Time: 21 days

    Description: Change in ferritin (nanograms/mL)

    Measure: Inflammatory biomarkers (ferritin)

    Time: 21 days
    269 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: If patient is still on oxygen at Day 15 or if the patient is weaned but put back on oxygen then the delay will be censored at 15 days.

    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: b) 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: Evaluation of the National Early Warning Score at Day 15 and difference in NEWS between Day1 and Day15. The NEWS is graded from to 23 with an aggregated score between 0-4 being a low clinical risk and an aggregated score >7 being a hich clinical risk

    Measure: Phase 2b: National Early Warning Score (NEWS)

    Time: Day 1 and Day 15

    Description: Clinical status using the 7-point ordinal scale assessed

    Measure: Phase 2b: clinical status

    Time: Day 3, Day 5, Day 8, Day 11, Day15, and Day 29

    Description: Time to improvement of one category from admission using the 7-point ordinal scale. This scale is rated 0 to 7 with score 0 being the better score (no clinical impact) and 7 being the worst score (death)

    Measure: Phase 2b: Time to improvement

    Time: 29 Days

    Description: d) 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: Duration of oxygen therapy

    Measure: Phase 2b: Oxygen therapy

    Time: 29 Days

    Description: Comparison of oxygen requirement between the two groups

    Measure: Phase 2b: oxygen requirement

    Time: 29 Days

    Description: g) Time to weaning in supplemental oxygen and proportion without O2 requirement at D15, according to baseline (D1) oxygen requirement (≤ 4 L/min or 4 L/min)

    Measure: Phase 2b: Time to weaning

    Time: Day 15

    Description: h) 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: Evaluation of hospital length of stay

    Measure: Phase 2b: Hospital length of stay

    Time: 29 Days

    Description: All cause mortality

    Measure: Phase 2b: mortality

    Time: 29 Days

    Description: 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
    270 Interest of Azithromycin With or Without Hydroxychloroquine for the Treatment of COVID-19 Pneumonia : a Retrospective Observational Study

    During COVID-19 epidemic, hydroxychloroquine was proposed and authorized as a possible key agent in the treatment of COVID-19 hospitalized pneumonia, including in France. Gautret et al. proposed the combination regimen with azithromycin. However only one study reported the interest of azithromycin alone. Retrospective study reporting the impact of the anti-infective agents used during the pandemic in a tertiary care hospital, using azithromycin with or without hydroxychloroquine.

    NCT04453501
    Conditions
    1. COVID
    2. Pn
    3. Pneumonia, Viral
    Interventions
    1. Drug: favorable outcome
    MeSH:Pneumonia, Viral Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: After being admitted, patient was monitored whether he does not required to be transferred in ICU or died because of a severe COVID-19 pneumonia within 7 days. The outcome was purely clinical. If patient was discharged at home after admission and/or was transferred into a rehabilitation center he was considered as a favorable outcome independently of any biological marker.

    Measure: Favorable outcome

    Time: Assessed within 7 days after admission

    Secondary Outcomes

    Description: Studying if biological abnormalities (lymphocyte count or CRP) at admission were associated with an unfavorable outcome

    Measure: Risk factors 1

    Time: Assessed at day 1

    Description: Studying if comorbidities were associated with an unfavorable outcome

    Measure: Risk factors 2

    Time: Assessed at day 1

    Description: Studying whether any regimen was associated with a favorable outcome (including azithromycin)

    Measure: Interest of anti-infective agents

    Time: From date of inclusion until the date of first documented progression to ICU or date of death from any cause, whichever came first, assessed up to 2 months
    271 Impact of the Syndromic PCR System FilmArray on Management of ICU Patients With Severe Pulmonary Disease in the Context of the Covid-19 Pandemic.

    The research aims to determine the impact of a syndromic mutiplex PCR assay (FilmArray) on the management of patients hospitalized in ICU for severe respiratory disease. During the SARS-CoV-2 outbreak, the diagnosis of pneumonia has become considerably more complex as the biological, radiological and clinical criteria of covid-19 interfere with the standard criteria for the diagnosis of severe respiratory diseases. Moreover, patients with COVID-19 are at higher risk of developing other associated infections and thus, patients have therefore often been treated with antibiotics, adequately or not, due to difficulty to quickly identify the etiology of their symptoms with conventional methods. In order to improve their treatment, both diagnostic and therapeutic, we set up a new syndromic molecular test in our laboratories to accelerate and improve the pneumonia management and antibiotic stewardship. This research will include 100 to 150 adult patients hospitalized in ICU during the first half of 2020. It will take place within the Nancy University Hospital and the Reims University Hospital, France.

    NCT04453540
    Conditions
    1. Infectious Disease
    2. Pneumonia
    3. Molecular Diagnosis
    4. Covid-19
    5. Antibiotic Stewardship
    Interventions
    1. Diagnostic Test: FilmArray PCR on respiratory samples
    MeSH:Communicable Diseases Infection Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Antibiotic prescription modification following the FilmArray results as: No prescription No change in antibiotic utilization Antibiotic initiation Antibiotic escalation Antibiotic de-escalation Antibiotic discontinuation

    Measure: Therapeutic decision

    Time: 24 h following the FilmArray results
    272 Inhaled NO for the Treatment of COVID-19 Caused by SARS-CoV-2

    The purpose of this open label, 2-phase, study is to obtain information on the safety of 80 ppm and the safety and efficacy of 150 ppm Nitric Oxide given in addition to the standard of care of patients with COVID-19 caused by SARS-CoV-2.

    NCT04456088
    Conditions
    1. COVID-19
    2. SARS-CoV 2
    3. Respiratory Disease
    4. Pneumonia, Viral
    5. Corona Virus Infection
    Interventions
    1. Combination Product: 150 ppm Nitric Oxide delivered through LungFit Delivery System
    2. Combination Product: 80 ppm Nitric Oxide delivered through LungFit Delivery System
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia, Viral Pneumonia Respiration Disorders Respiratory Tract Diseases
    HPO:Pneumonia

    Primary Outcomes

    Description: Time to deterioration as measured by any one of the following: need for non-invasive ventilation need for high flow nasal cannula (HFNC) or need for intubation Death from any cause

    Measure: Time to deterioration

    Time: up to 14 days

    Secondary Outcomes

    Description: Time to patient having stable oxygen saturation (SpO2) of greater than 92% for longer than 3 hr on room air

    Measure: Time to stable oxygen saturation

    Time: up to 14 days

    Other Outcomes

    Description: Treatment Emergent Adverse Events and SAEs - safety evaluation for 30 days after last inhalation treatment

    Measure: Treatment Emergent Adverse Events and SAEs

    Time: 30 days after last inhalation treatment
    273 Evaluation of the Characteristics of Patients and Healthcare Workers With Suspected or Confirmed of COVID-19 in Villavicencio and Meta State, Colombia

    This observational study aims to collect detailed clinical information on confirmed or suspected patients of COVID-19 treated in hospitals from Meta State, Colombia. The objectives are: 1. To establish the characteristics of patients and healthcare workers treated with COVID-19. 2. To assess previous predisposing morbidity. 3. To detail clinical factors associated with complications. 4. To profile clinical indicators for severity and outcomes.

    NCT04456426
    Conditions
    1. COVID
    2. SARS-CoV 2
    3. SARS Pneumonia
    4. SARS (Disease)
    5. SARS (Severe Acute Respiratory Syndrome)
    MeSH:Severe Acute Respiratory Syndrome Coronavirus Infections Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Death within 30 days of hospital admission

    Measure: Mortality

    Time: 30 days

    Description: Need for intensive care unit admission

    Measure: ICU admission

    Time: 30 days

    Description: Need for intubation and invasive mechanical ventilation

    Measure: Mechanical ventilation

    Time: 30 days

    Secondary Outcomes

    Description: Duration of stay in the intensive care unit

    Measure: ICU length of stay

    Time: 30 days

    Description: Duration of stay in hospitalization

    Measure: Hospital length of stay

    Time: 30 days

    Description: Duration of mechanical ventilation included with intubation or tracheostomy

    Measure: Days of mechanical ventilation

    Time: 30 days
    274 Risk Factors, Personalized Prognoses and 1-year Follow-ups of Patients Admitted to Spanish Intensive Care Units Due to COVID-19

    The latest epidemiological data published from Chine reports that up to 30% of hospital-admitted patients required admission to intensive care units (ICU). The cause for ICU admission for most patients is very severe respiratory failure; 80% of the patients present with severe acute respiratory distress syndrome (SARS) that requires protective mechanical ventilation. Five percent of patients with SARS require extracorporeal circulation (ECMO) techniques. Global mortality data has been thus far reported in different individual publications from China. Without accounting for those patients still admitted to hospital, bona fide information (from a hospital in Wuhan) received by the PI of this project estimates that mortality of hospitalized patients is more than 10%. Evidently, mortality is concentrated in patients admitted to the ICU and those patients who require mechanical ventilation and present with SARS. As data in China was globally reported, risk factors and prognosis of patients with and without SARS who require mechanical ventilation are not definitively known. The efficacy of different treatments administered empirically or based on small, observation studies is also not known. With many still admitted at the time of publication, a recent study in JAMA about 1500 patients admitted to the ICU in the region of Lombardy (Italy) reported a crude mortality rate of 25%. The data published until the current date is merely observational, prospective or retrospective. Data has not been recorded by analysis performed with artificial intelligence (machine learning) in order to report much more personalized results. Furthermore, as it concerns patients admitted to the ICU who survive, respiratory and cardiovascular consequences, as well as quality of living are completely unknown. The study further aims to investigate quality of life and different respiratory and cardiovascular outcomes at 6 months, as well as crude mortality within 1 year after discharge of patients with COVID-19 who survive following ICU admission. Lastly, with the objective to help personalize treatment in accordance with altered biological pathways in each patient, two types of studies will be performed: 1) epigenetics and 2) predictive enrichment of biomarkers in plasma. Hypothesis - A significant percentage of patients (20%) admitted to the hospital with COVID-19 infection is expected to require ICU admission, and need mechanical ventilation (80%) and, in a minor percentage (5%), ECMO. - Patients who survive an acute episode during ICU hospitalization will have a yearly accumulated mortality of 40%. Those who then survive will have respiratory consequences, cardiovascular complications and poor quality of life (6 months).

    NCT04457505
    Conditions
    1. Acute Respiratory Distress Syndrome
    2. Severe Pneumonia
    3. Respiratory Failure
    MeSH:Pneumonia Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Respiratory Insufficiency Acute Lung Injury
    HPO:Pneumonia

    Primary Outcomes

    Description: People who died after one year of follow up

    Measure: One year mortality

    Time: At 12 months of ICU admission

    Description: People who died after one year of follow up

    Measure: Six month mortality

    Time: At 6 month of ICU admission
    275 A Multicenter, Prospective, Randomized, Double-Blind, Placebo-Controlled Phase 2 Study to Assess Safety and Efficacy of ANG- 3777 in Patients Hospitalized With Confirmed COVID-19 Pneumonia

    To assess the clinical efficacy of ANG-3777 relative to the standard of care in reducing the severity and progression of pulmonary and renal dysfunction and mortality in adult patients hospitalized with COVID-19 pneumonia

    NCT04459676
    Conditions
    1. COVID-19
    2. Pneumonia
    Interventions
    1. Drug: Standard of Care (SOC) + ANG-3777
    2. Drug: Standard Of Care (SOC) + Placebo
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Measure: Proportion of patients alive, without the need for mechanical ventilation and free of the need for RRT (on an ongoing basis) at Day 28

    Time: From the time of randomization until (Day 1) until death or until Day28, whichever comes first
    276 A Phase IIa Randomized, Controlled Study of Combination Therapies to Treat COVID-19 Infection

    This study seeks to determine whether dual or quadruple therapy is more effective in treating COVID-19.

    NCT04459702
    Conditions
    1. COVID
    2. COVID-19
    3. Corona Virus Infection
    4. Coronavirus Infection
    5. Coronavirus Sars-Associated as Cause of Disease Classified Elsewhere
    6. Coronavirus-19
    7. SARS-CoV 2
    8. SARS Pneumonia
    Interventions
    1. Drug: hydroxychloroquine
    2. Drug: Azithromycin
    3. Drug: Ritonavir
    4. Drug: Lopinavir
    MeSH:Infection Communicable Diseases Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Time to reduced symptoms in each treatment group as indicated by NEWS scores, which rate patient status based on a zero to three scale for 8 parameters. These values are added up to create the NEWS score. The lower the NEWS score, the better the patient's clinical condition. Zero is the lowest possible score, whereas 7 or greater represents a high degree of clinical risk.

    Measure: Efficacy of Treatment by Reduced Symptoms NEWS (National Early Warning System) scores

    Time: 6 months

    Description: Time to non-infectivity as measured by PCR testing

    Measure: Efficacy of Treatment by Time to Non-Infectivity

    Time: 10 days

    Secondary Outcomes

    Description: Patient symptoms will be recorded using the NEWS system, which rates patient status based on a zero to three scale for 8 parameters. These values are added up to create the NEWS score. The lower the NEWS score, the better the patient's clinical condition. Zero is the lowest possible score, whereas 7 or greater represents a high degree of clinical risk.

    Measure: Safety of Dual Therapy as Measured by Symptoms rated on the NEWS (National Early Warning System) sores

    Time: 6 months

    Description: Patient symptoms will be recorded using the NEWS system, which rates patient status based on a zero to three scale for 8 parameters. These values are added up to create the NEWS score. The lower the NEWS score, the better the patient's clinical condition. Zero is the lowest possible score, whereas 7 or greater represents a high degree of clinical risk.

    Measure: Safety of Quadruple Therapy as Measured by Symptoms rated on the NEWS (National Early Warning System) scores.

    Time: 6 months

    Description: Changes in blood parameters measured in a Complete Blood Count (CBC).

    Measure: Safety of Dual Therapy as Measured by Complete Blood Count

    Time: 6 months

    Description: Changes in blood parameters measured in a Complete Metabolic Panel.

    Measure: Safety of Quadruple Therapy as Measured by Complete Blood Count

    Time: 6 months

    Description: Changes in serum albumin levels

    Measure: Safety of Dual Therapy as Measured by Metabolic Panel -Albumin

    Time: 6 months

    Description: Changes in serum albumin levels

    Measure: Safety of Quadruple Therapy as Measured by Metabolic Panel - Albumin

    Time: 6 months

    Description: Changes in serum albumin/globulin ratio

    Measure: Safety of Quadruple Therapy as Measured by Metabolic Panel - A/G Ratio

    Time: 6 months

    Description: Changes in serum albumin/globulin ratio

    Measure: Safety of Dual Therapy as Measured by Metabolic Panel A/G Ratio

    Time: 6 months

    Description: Changes in serum alkaline phosphatase levels

    Measure: Safety of Quadruple Therapy as Measured by Metabolic Panel - Alkaline Phosphatase

    Time: 6 months

    Description: Changes in serum alkaline phosphatase levels

    Measure: Safety of Dual Therapy as Measured by Metabolic Panel Alkaline Phosphatase

    Time: 6 months

    Description: Changes in serum AST levels

    Measure: Safety of Dual Therapy as Measured by Metabolic Panel - AST

    Time: 6 months

    Description: Changes in serum AST levels

    Measure: Safety of Quadruple Therapy as Measured by Metabolic Panel - AST

    Time: 6 months

    Description: Changes in serum ALT levels

    Measure: Safety of Quadruple Therapy as Measured by Metabolic Panel - ALT

    Time: 6 months

    Description: Changes in serum ALT levels

    Measure: Safety of Dual Therapy as Measured by Metabolic Panel ALT

    Time: 6 months

    Description: Changes in serum BUN/Creatinine Ratio

    Measure: Safety of Dual Therapy as Measured by Metabolic Panel BUN/Creatinine Ratio

    Time: 6 months

    Description: Changes in serum BUN/Creatinine Ratio

    Measure: Safety of Quadruple Therapy as Measured by Metabolic Panel BUN/Creatinine Ratio

    Time: 6 months

    Description: Changes in serum Blood Urea Nitrogen levels

    Measure: Safety of Quadruple Therapy as Measured by Metabolic Panel - BUN

    Time: 6 months

    Description: Changes in serum Blood Urea Nitrogen levels

    Measure: Safety of Dual Therapy as Measured by Metabolic Panel - BUN

    Time: 6 months

    Description: Changes in serum calcium levels

    Measure: Safety of Dual Therapy as Measured by Metabolic Panel - Calcium

    Time: 6 months

    Description: Changes in serum calcium levels

    Measure: Safety of Quadruple Therapy as Measured by Metabolic Panel - Calcium

    Time: 6 months

    Description: Changes in serum carbon dioxide levels

    Measure: Safety of Quadruple Therapy as Measured by Metabolic Panel - Carbon Dioxide

    Time: 6 months

    Description: Changes in serum carbon dioxide levels

    Measure: Safety of Dual Therapy as Measured by Metabolic Panel - Carbon Dioxide

    Time: 6 months

    Description: Changes in serum chloride levels

    Measure: Safety of Dual Therapy as Measured by Metabolic Panel - Chloride

    Time: 6 months

    Description: Changes in serum chloride levels

    Measure: Safety of Quadruple Therapy as Measured by Metabolic Panel - Chloride

    Time: 6 months

    Description: Changes in serum creatinine levels

    Measure: Safety of Quadruple Therapy as Measured by Metabolic Panel - Creatinine

    Time: 6 months

    Description: Changes in serum creatinine levels

    Measure: Safety of Dual Therapy as Measured by Metabolic Panel - Creatinine

    Time: 6 months

    Description: Changes in serum globulin levels

    Measure: Safety of Dual Therapy as Measured by Metabolic Panel - Globulin

    Time: 6 months

    Description: Changes in serum globulin levels

    Measure: Safety of Quadruple Therapy as Measured by Metabolic Panel - Globulin

    Time: 6 months

    Description: Changes in blood glucose levels

    Measure: Safety of Quadruple Therapy as Measured by Metabolic Panel - Glucose

    Time: 6 months

    Description: Changes in blood glucose levels

    Measure: Safety of Dual Therapy as Measured by Metabolic Panel - Glucose

    Time: 6 months

    Description: Changes in blood potassium levels

    Measure: Safety of Dual Therapy as Measured by Metabolic Panel - Potassium

    Time: 6 months

    Description: Changes in blood potassium levels

    Measure: Safety of Quadruple Therapy as Measured by Metabolic Panel - Potassium

    Time: 6 months

    Description: Changes in serum total bilirubin levels

    Measure: Safety of Quadruple Therapy as Measured by Metabolic Panel - Total Bilirubin

    Time: 6 months

    Description: Changes in serum total bilirubin levels

    Measure: Safety of Dual Therapy as Measured by Metabolic Panel - Total Bilirubin

    Time: 6 months

    Description: Changes in serum total protein levels

    Measure: Safety of Dual Therapy as Measured by Metabolic Panel - Total Protein

    Time: 6 months

    Description: Changes in serum total protein levels

    Measure: Safety of Quadruple Therapy as Measured by Metabolic Panel - Total Protein

    Time: 6 months

    Description: Presence or absence of treatment related serious adverse events Grade III or higher

    Measure: Safety of Dual Therapy as Measured by Treatment Related SAE

    Time: 6 months

    Description: Presence or absence of treatment related serious adverse events Grade III or higher

    Measure: Safety of Quadruple Therapy as Measured by Treatment Related SAE

    Time: 6 months
    277 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
    278 Treatment of Coronavirus COVID-19 Pneumonia (Pathogen SARS-CoV-2) With Cryopreserved Allogeneic Multipotent Mesenchymal Stem Cells of the Placenta and Umbilical Cord

    Assessment of the clinical effects of infusions of cryopreserved allogeneic multipotent mesenchymal stem cells of the placenta and umbilical cord for COVID-19 patients with acute respiratory distress syndrome.

    NCT04461925
    Conditions
    1. COVID-19 Pneumonia
    Interventions
    1. Procedure: Placenta-Derived MMSCs; Cryopreserved Placenta-Derived Multipotent Mesenchymal Stromal Cells
    2. Drug: Antibiotics
    3. Drug: Hormones
    4. Drug: Anticoagulant Therapy
    5. Device: Оxygen therapy
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Improvement of pulmonary function. Arterial oxygen tension PaO2 (in mmHg)/fractional inspired oxygen FiO2 (expressed as a fraction, not a percentage), most conveniently the P/F ratio. The normal P/F ratio is ~ 400-500 mmHg (~55-65 kPa). P/F ratio <300mmHg - sign of Acute Respiratory Distress Syndrome (ARDS)

    Measure: Changes of oxygenation index PaO2/FiO2, most conveniently the P/F ratio.

    Time: up to 28 days

    Description: Length of Hospital Stay

    Measure: Changes in length of hospital stay

    Time: up to 28 days

    Description: Marker for efficacy of treatment

    Measure: Changes in mortality rate

    Time: up to 28 days

    Secondary Outcomes

    Description: Infection biomarker. Serum CRP levels can be used for early diagnosis of pneumonia, patients with severe pneumonia had high CRP levels.

    Measure: Changes of С-reactive protein (CRP, mg/L)

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

    Description: CT assessment of pulmonary lesions and lung tissue changes

    Measure: Evaluation of Pneumonia Improvement

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

    Description: Indirect response to lung function

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

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

    Description: Degree of infection

    Measure: Peripheral blood count recovery time

    Time: At baseline, Day 1, Week 1, Week 2, Week 4, Week 8
    279 Mavrilimumab to Reduce Progression of Acute Respiratory Failure in Patients With Severe 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.

    NCT04463004
    Conditions
    1. COVID-19
    2. Sars-CoV2
    3. Pneumonia
    Interventions
    1. Drug: Mavrilimumab
    2. Drug: Placebos
    MeSH:Pneumonia Respiratory Insufficiency Inflammation
    HPO:Pneumonia

    Primary Outcomes

    Description: Number of subjects alive and off of oxygen

    Measure: Proportion of subjects alive and off of oxygen at day 14

    Time: 14 days

    Secondary Outcomes

    Description: Number of subjects alive and without respiratory failure

    Measure: Proportion of subjects alive and without respiratory failure at 28 days

    Time: 28 days
    280 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
    281 Phase II Protocol of Low-Dose Whole Thorax Megavoltage Radiotherapy for Patients With SARS-COV-2 Pneumonia

    Low doses of radiation in the form of chest x-rays has been in the past to treat people with pneumonia. This treatment was thought to reduce inflammation and was found to be effective without side effects. However, it was an expensive treatment and was eventually replaced with less expensive treatment options like penicillin. The COVID-19 virus has emerged recently, causing high rates of pneumonia in people. The authors believe that giving a small dose of radiation to the lungs may reduce inflammation and neutralize the pneumonia caused by COVID-19. For this study, the x-ray given is called radiation therapy. Radiation therapy uses high-energy X-ray beams from a large machine to target the lungs and reduce inflammation. Usually, it is given at much higher doses to treat cancers. The purpose of this study is to find out if adding a single treatment of low-dose x-rays to the lungs might reduce the amount of inflammation in the lungs from COVID-19 infection, which could reduce the need for a ventilator or breathing tube.

    NCT04466683
    Conditions
    1. Covid-19
    2. Sars-CoV2
    3. Pneumonia
    Interventions
    1. Radiation: Low dose radiation 35 cGy
    2. Radiation: High dose radiation 100 cGy
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: The rate of grade 4 toxicity, the rate of mechanical ventilation, the rate of hospital stay greater than 10 days, and the crude all-cause mortality rate will be used to calculate the clinically meaningful event rate (CMER). The rates range would be from 0 to 100% with a lower rate indicating a more favorable dose.

    Measure: Step 1 Dose selection

    Time: At least 2 weeks after the 60th patient enrolled has been evaluated for adverse events. It is estimated that the time frame will be about 1 year to complete enrollment.

    Description: Clinical benefit will have the composite endpoint with the following 3 elements: the rate of mechanical ventilation, the rate of hospital stays of greater than 10 days and the rate of all-cause mortality at 30 from enrollment. A lower rate would indicate a positive clinical benefit and would range from 0 to 100%

    Measure: Clinical benefit of Step 2 Radiation dose

    Time: up to 30 days from the last patient enrollment in Step 2 which is estimated to be about 2 years.

    Secondary Outcomes

    Description: Billing codes will be collected to determine the total cost of hospitalization for each patient at discharge. The cost of hospitalization for the control arm versus experimental radiation arms will be compared.

    Measure: Changes of the cost of care for the control arm versus the radiation arms

    Time: The discharge of the last patient enrolled is estimated to be about 2 years.

    Other Outcomes

    Description: Compare differences within and between arms lymphocyte count in K/ul.

    Measure: Changes in lymphocyte count between control and experimental arms

    Time: Samples are collected pre-dose, 48-72 hours post radiation dose, and 7 days after radiation dose. Control subjects have blood samples collected post randomization, 48-72 hours post randomization, and 7 days post randomization.

    Description: Compare differences within and between arms neutrophil count in K/ul .

    Measure: Changes in neutrophil count between control and experimental arms

    Time: Samples are collected pre-dose, 48-72 hours post radiation dose, and 7 days after radiation dose. Control subjects have blood samples collected post randomization, 48-72 hours post randomization, and 7 days post randomization

    Description: Compare differences within and between arms for the neutrophil to lymphocyte ratio. A decrease in the ratio of neutrophil to lymphocyte count would indicate a more favorable treatment outcome.

    Measure: Changes in neutrophil to lymphocyte ratio between control and experimental arms

    Time: Samples are collected pre-dose, 48-72 hours post radiation dose, and 7 days after radiation dose. Control subjects have blood samples collected post randomization, 48-72 hours post randomization, and 7 days post randomization

    Description: Compare differences within and between arms for the C-reactive protein in mg/L. A decrease in C-reactive protein value would indicate a more favorable treatment outcome.

    Measure: Changes in blood C-reactive protein between control and experimental arms

    Time: Samples are collected pre-dose, 48-72 hours post radiation dose, and 7 days after radiation dose. Control subjects have blood samples collected post randomization, 48-72 hours post randomization, and 7 days post randomization

    Description: Compare differences within and between arms for the IL-6 in pg/ml. A decrease in IL-6 value would indicate a more favorable treatment outcome.

    Measure: Changes in blood IL-6 levels between control and experimental arms

    Time: Samples are collected pre-dose, 48-72 hours post radiation dose, and 7 days after radiation dose. Control subjects have blood samples collected post randomization, 48-72 hours post randomization, and 7 days post randomization

    Description: Compare differences within and between arms for the D-Dimer in mcg/ml. A decrease in D-Dimer value would indicate a more favorable treatment outcome.

    Measure: Changes in blood D-Dimer levels between control and experimental arms

    Time: Samples are collected pre-dose, 48-72 hours post radiation dose, and 7 days after radiation dose. Control subjects have blood samples collected post randomization, 48-72 hours post randomization, and 7 days post randomization

    Description: Compare differences within and between arms for the LDH in U/L. A decrease in LDH value would indicate a more favorable treatment outcome.

    Measure: Changes in blood Lactate dehydrogenase (LDH) levels between control and experimental arms

    Time: Samples are collected pre-dose, 48-72 hours post radiation dose, and 7 days after radiation dose. Control subjects have blood samples collected post randomization, 48-72 hours post randomization, and 7 days post randomization

    Description: Compare differences within and between arms for ferritin in ng/ml. A decrease in Ferritin value would indicate a more favorable treatment outcome.

    Measure: Changes in blood ferritin levels between control and experimental arms

    Time: Samples are collected pre-dose, 48-72 hours post radiation dose, and 7 days after radiation dose. Control subjects have blood samples collected post randomization, 48-72 hours post randomization, and 7 days post randomization
    282 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
    283 Early Cognitive Assessment and Evolutionary Monitoring of Patients With Severe ARDS (Acute Respiratory Distress Syndrome) on SARS-CoV2 Viral Pneumonia Requiring Mechanical Ventilation

    The new coronavirus pandemic responsible for the severe acute respiratory syndrome SARS-CoV2 requires, in its severe forms, the use of invasive ventilation in intensive care. The first patients seen in intensive care presented with neurological symptoms and usually not seen in non-viral ARDS or due to other viral causes. These were mainly restless awakenings, attempts at self-extubation and confusional syndromes. Although the data in the literature do not seem to reveal the presence of SARS-CoV2 in the CSF of these patients, certain elements seem to show parenchymal brain damage with the description of hypometabolism of the frontal regions. In addition, most of these patients present a memory complaint after going into intensive care (personal data not published). We do not know to date what is the cognitive and psychic profile of these patients, nor what will be their future evolution. Some patients may require specific neuro-cognitive rehabilitation. The aim of this study is to assess the cognitive profile of patients infected with COVID-19 who have used invasive ventilation in the intensive care unit of Paris Saint-Joseph hospital since April 2020, in order to be able to compare them between them and follow their evolution in the medium term. This work could make it possible to describe the specific cognitive impairment of SARS-CoV2, by trying to evade other causes of cognitive disorders in patients hospitalized in intensive care for respiratory distress (hypoxia, treatments, metabolic disorders, etc.). The main objective is to follow the medium-term evolution between 3 and 6 months of the cognitive profile of patients with severe form of SARS-CoV2 with the use of ventilatory resuscitation.

    NCT04468035
    Conditions
    1. Covid19
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: This ouctome corresponds to the medium-term evolution between 3 and 6 months of the cognitive profile of patients with severe form of SARS-CoV2 with recourse to ventilatory resuscitation.

    Measure: Medium-term evolution between 3 and 6 months

    Time: Month 6

    Secondary Outcomes

    Description: This outcome corresponds to MMSE orientation score.

    Measure: Cognitive impairment at M3

    Time: Month 3

    Description: This outcome corresponds to MMSE orientation score.

    Measure: Cognitive impairment at M6

    Time: Month 6

    Description: This outcome corresponds to Memory scores.

    Measure: Memory Scores at M3

    Time: Month 3

    Description: This outcome corresponds to Memory scores.

    Measure: Memory Scores at M6

    Time: Month 6
    284 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
    285 Assessment of Lung Recruitablity of Acute Respiratory Distress Syndrome With SARS-CoV-2 Pneumonia by Electrical Impedance Tomography: a Prospective Observational Study

    Novel coronavirus (SARS-CoV-2: severe acute respiratory coronavirus 2) pneumonia often develop the acute respiratory distress syndrome (ARDS). Lung protective ventilation strategy consisting of low tidal volume and high positive end-expiratory pressure (PEEP) is recommended. However, it is not clear whether injured lungs from SARS-CoV-2 pneumonia have the same mechanical properties, especially response to PEEP as common ARDS. Therefore, the investigators propose an observational study to analyze respiratory mechanics and lung recruitablity using EIT (electrical impedance tomography) in patients with ARDS due to SARS-CoV-2 pneumonia.

    NCT04473300
    Conditions
    1. Critical Illness
    2. ARDS
    MeSH:Pneumonia Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Critical Illness
    HPO:Pneumonia

    Primary Outcomes

    Description: The distribution of ventilation measured by EIT at PEEP 5 and 15.

    Measure: The distribution of ventilation

    Time: Through study completion (up to 24 hours)

    Secondary Outcomes

    Description: The changes in dependent and non-dependent silent spaces measured by EIT in PEEP 5 and 15.

    Measure: Silent spaces

    Time: Through study completion (up to 24 hours)

    Description: Respiratory system compliance in PEEP 5 and 15.

    Measure: Respiratory system compliance

    Time: Through study completion (up to 24 hours)

    Description: Oxygenation in PEEP 5 and 15.

    Measure: Oxygenation

    Time: Through study completion (up to 24 hours)

    Description: Dead space ventilation ratio in PEEP 5 and 15.

    Measure: Dead space ventilation ratio

    Time: Through study completion (up to 24 hours)
    286 COVID-19 Convalescent Plasma Treatment in SARS-CoV-2 Infected Patients: Multicenter Interventional Study

    Due to the limitations of COVID-19 treatment and in the absence of licensed antiviral for COVID-19, the historical choice of therapeutic convalescent plasma (CP) is considered especially against RNA viruses .It was known that convalescent plasma does not only neutralize the pathogens but provide passive immunomodulatory properties that allows the recipient to control the exaggerated inflammatory cascade. However, still there is a lack of understanding of the mechanism of action of CCP therapeutic components. Reports from open label trials and case series show that CCP is safe and might be effective in severe cases with COVID-19 . Therefore, the World health organisation (WHO) and Food and Drug Administration (FDA) issued guidelines for the CCP usage and standardised the donor selection , which was further supported by Emergency use Authorisation (EUA) . Therefore, the aim in the current study is to assess the effect of CCP on time to clinical improvement, hospital mortality and to evaluate the changes on oxygen saturation and laboratory markers (lymphocyte counts and C-reactive protein) compared with standard treatment alone in patients with moderate or severe COVID-19 disease.

    NCT04474340
    Conditions
    1. Moderate COVID-19 Pneumonia, Severe COVID-19 Pneumonia
    2. Pneumonia, Viral
    Interventions
    1. Drug: COVID-19 Convalscent Plasma
    MeSH:Pneumonia, Viral Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Time to clinical improvement is defined as a time frame from CCP administration till 30 days or discharge, defined as a 2-grade decrease on an ordinal WHO clinical scale . The WHO clinical scale based on the following 7-grade ordinal levels: 1= ambulatory, independent; 2= ambulatory with assistance; 3=hospitalised, not requiring supplemental oxygen; 4= hospitalised, requiring supplemental oxygen; 5= hospitalised, requiring nasal high-flow oxygen therapy, noninvasive mechanical ventilation, or both; 6= hospitalised, requiring extracorporeal membrane oxygenation, invasive mechanical ventilation, or both; and 7= death.

    Measure: Time to clinical improvement

    Time: 30 days

    Secondary Outcomes

    Measure: All cause mortality

    Time: 30 days
    287 Managed Access Program (MAP) to Provide Access to Canakinumab Treatment of Cytokine Release Syndrome (CRS) in Patients With COVID-19-induced Pneumonia

    This is a global Managed Access Program (MAP) to provide access to canakinumab to patients with cytokine release syndrome resulting from COVID-19 pneumonia

    NCT04476706
    Conditions
    1. Cytokine Release Syndrome in COVID-19-induced Pneumonia
    Interventions
    1. Drug: canakinumab
    MeSH:Pneumonia Syndrome
    HPO:Pneumonia

    288 A Safety Study on the Use of Intermittent Versus Continuous Inhalation of NO in Spontaneous Breathing COVID-19 Patients

    Preliminary data support the effect of Nitric Oxide (NO) on improving the oxygenation in mechanically ventilated patients and spontaneously breathing patients with COVID-19. In vitro studies showed an antiviral effect of NO against SARS-coronavirus. The optimal therapeutic regimen of NO gas in spontaneously breathing hypoxemic patients with COVID-19 is not known. We hypothesize that high concentration inhaled NO with an adjunct of continuous low dose administration between the high concentration treatments can be safely administered in hypoxemic COVID-19 patients compared to the high dose treatment alone. Prolonged administration of NO gas may benefit the patients in terms of the severity of the clinical course and time to recovery. Together with a clinical effect on ventilation-perfusion matching, a prolonged regimen would allow also an increase in antiviral activity (dose and time-dependent).

    NCT04476992
    Conditions
    1. Hypoxemia
    2. Pneumonia, Viral
    3. Coronavirus Infection
    Interventions
    1. Drug: Nitric Oxide-Sessions
    2. Drug: Nitric Oxide-Continuous and Sessions
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia, Viral Pneumonia Hypoxia
    HPO:Hypoxemia Pneumonia

    Primary Outcomes

    Description: The primary outcome will be evaluated with the difference in Methemoglobin levels between the groups at 48 hours after randomization.

    Measure: Change in Methemoglobin level at 48 hours

    Time: 48 hours

    Secondary Outcomes

    Description: The primary outcome will be evaluated with the difference in Methemoglobineamia between the groups at 96 hours after randomization.

    Measure: Change in Methemoglobin level at 96 hours

    Time: 96 hours

    Description: The secondary outcome, "Improve the oxygenation at 48 hours," will be evaluated with the measure of the difference in oxygenation among the groups at 48 hours. Oxygenation will be measured in terms of the SpO2/FiO2 ratio.

    Measure: Improvement in oxygenation between the groups at 48 hours or at discharge if before 48 hours

    Time: 48 hours

    Description: The secondary outcome, "Improve the oxygenation at 96 hours," will be evaluated with the measure of the difference in oxygenation between the groups at 96 hours. Oxygenation will be measured in terms of the SpO2/FiO2 ratio.

    Measure: Improvement in oxygenation between the groups at 96 hours or at discharge if before 96 hours

    Time: 96 hours

    Description: The secondary outcome "difference in the rate of negative RT-PCR for SARS CoV-2" will be evaluated as the rate of negativization of the RT-PCR for SARS-CoV-2 at 5 days after randomization, at discharge and at 28 days after randomization.

    Measure: Rate of positive RT-PCR for SARS-CoV-2 between groups in 5 days, discharge, and 28 days

    Time: 28 days

    Description: The secondary outcome "different time to clinical recovery" will be evaluated as the time between the randomization and the clinical indication to interrupt the administration of oxygen for 24 hours.

    Measure: Time to clinical recovery among groups, defined as time to interruption of oxygen administration for 24 hours or discharge

    Time: 28 days

    Description: The secondary outcome "Different reduction in inflammatory markers" will be evaluated as improvement in the inflammatory markers (IL-6; Ferritin; White Blood Cells; Leucocyte count; CRP; D-Dimer) observed in blood samples collected at day 1, 2, 3, 4, and 7 compared to the Baseline value.

    Measure: Reduction in the inflammatory markers among groups

    Time: 7 days

    Description: The secondary outcome "rate of AKI between groups" will be evaluated as the presence of a comparable rate of AKI during the hospital stay. The AKI will be defined according to the KDIGO classification.

    Measure: Rate of Acute Kidney Disease (AKI) between groups during hospitalization

    Time: 28 days

    Description: The secondary outcome "Difference in Katz score between groups" will be evaluated as the difference in Katz Activities of Daily Living between Baseline and day 28. This questionnaire will coincide with the 28-day phone call to assess health status and survival.

    Measure: Difference in Katz score between groups

    Time: 28 days

    Other Outcomes

    Description: 1. The exploratory outcome "Effect of nitric oxide on heart function in COVID-19 hypoxemic patients" will be evaluated as: the changes observed in heart ultrasound at 48 and 96 hours (or at discharge) compared to the Baseline in all groups. the changes observed in heart ultrasound during the administration of NO comparing pre-treatment, during treatment, and post-treatment.

    Measure: Effect of NO gas treatment on cardiovascular hemodynamics assessed using cardiac ultrasound in COVID-19 hypoxemic patients

    Time: 96 hours

    Description: 2. The secondary outcome "Effect of NO gas on lung function in COVID-19 hypoxemic patients" will be evaluated as: the changes observed in spirometry at 48 and 96 hours (or at discharge) compared to the Baseline in all groups. the changes observed in spirometry during the administration of NO comparing pre-treatment, during treatment, and post-treatment.

    Measure: Effect of NO gas treatment on lung function evaluated with serial spirometry in COVID-19 hypoxemic patients

    Time: 96 hours
    289 Assessment of the Risk of Pulmonary Embolism and Coagulation Profile in Patients With SARS Coronavirus (COV-2) Lung Disease

    The current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is complicated by pneumonia (15 to 20% of cases) requiring hospitalization with oxygen therapy. Almost 20 to 25% of hospitalized patients require intensive care and resuscitation; half die. The main cause of death is acute respiratory distress syndrome (ARDS). However, some deaths have been linked to pulmonary embolism (PE). Recognition of PE is important because there is specific treatment to limit its own mortality. The identification of biological parameters of hemostasis predictive of thromboembolic disease is crucial in these patients. To evaluate the frequency of PE in the patients having to be hospitalized is to practice of a systematic thoracic angiography scanner in the patients having no contra-indication for its realization, as well as during hospitalization in patients deteriorating without any other obvious cause. The thromboembolic events and disturbances of the coagulation system described in patients with SARS-CoV-2 pneumonitis suggest that this viral infection is associated with an increase in the activation of coagulation contributing to the occurrence of thrombosis and especially from PE.

    NCT04479540
    Conditions
    1. Pneumonia, Viral
    Interventions
    1. Radiation: Angiography scanner
    MeSH:Pneumonia, Viral Pneumonia Lung Diseases Pulmonary Embolism Embolism
    HPO:Abnormal lung morphology Pneumonia Pulmonary embolism

    Primary Outcomes

    Description: Rate of patients with pulmonary embolism diagnosed by thoracic angiography scanner

    Measure: Rate of patients with pulmonary embolism

    Time: up to Day 12

    Secondary Outcomes

    Description: Measure of prothrombin level to assess hemostasis parameters of patients with SARS-COV-2pneumonitis during hospitalization

    Measure: Prothrombin level measurement

    Time: up to Day 12

    Description: Measure of activated partial thromboplastin time to assess hemostasis parameters of patients with SARS-COV-2pneumonitis during hospitalization

    Measure: activated partial thromboplastin time measurement

    Time: up to Day 12

    Description: Measure of fibrinogen to assess hemostasis parameters of patients with SARS-COV-2pneumonitis during hospitalization

    Measure: Fibrinogen measurement

    Time: up to Day 12

    Description: Measure of D-dimers to assess hemostasis parameters of patients with SARS-COV-2pneumonitis during hospitalization

    Measure: D-dimers measurement

    Time: up to Day 12

    Description: Measure of Protein C to assess hemostasis parameters of patients with SARS-COV-2pneumonitis during hospitalization

    Measure: Protein C measurement

    Time: up to Day 12

    Description: Measure of Willebrand antigen to assess hemostasis parameters of patients with SARS-COV-2pneumonitis during hospitalization

    Measure: Willebrand antigen measurement

    Time: up to Day 12

    Description: Measure of Soluble tissue factor to assess hemostasis parameters of patients with SARS-COV-2pneumonitis during hospitalization

    Measure: Soluble tissue factor measurement

    Time: up to Day 12

    Description: Measure of soluble thrombomodulin to assess hemostasis parameters of patients with SARS-COV-2pneumonitis during hospitalization

    Measure: Soluble thrombomodulin measurement

    Time: up to Day 12

    Description: Measure of E-selectin to assess hemostasis parameters of patients with SARS-COV-2pneumonitis during hospitalization

    Measure: E-selectin measurement

    Time: up to Day 12

    Description: Measure of thrombin-antithrombin complex to assess hemostasis parameters of patients with SARS-COV-2pneumonitis during hospitalization

    Measure: Thrombin-antithrombin complex measurement

    Time: up to Day 12

    Description: Assessment of clot formation curve by Thrombodynamics® to identify ones predictive of the onset of Pulmonary Embolism or a poor prognosis

    Measure: Assessment of clot formation curve

    Time: Day 1

    Description: Assessment of thrombin generation by Thrombodynamics® to identify ones predictive of the onset of Pulmonary Embolism or a poor prognosis

    Measure: Assessment of thrombin generation

    Time: Day 1

    Description: Assessment of fibrinolysis by Thrombodynamics® to identify ones predictive of the onset of Pulmonary Embolism or a poor prognosis

    Measure: Assessment of fibrinolysis

    Time: Day 1

    Description: Determine patient mortality

    Measure: Mortality

    Time: Day 30
    290 Laparoscopic Bariatric Surgery During Phase 2-3 Covid-19 Pandemic in Italy: a Multicenter, Prospective, Observational Study.

    The first person-to-person Coronavirus disease (COVID-19) transmission in Italy was reported on Feb 21st, 2020, causing one of the most massive outbreak in Europe so far that stopped immediately all elective surgical procedures. Bariatric surgery represents the most effective treatment to obtain an important, long-term weight loss and comorbidities' resolution, including respiratory disorders. A sensitive decrease of epidemic has been observed lately and a gradual and progressive stop of the lockdown (phase 2-3) was planned, when the virus is supposed to be under control and protocols are guiding the restart of the elective bariatric surgery. Several questions are currently open: Laparoscopic bariatric surgery is safe in the phase 2-3? What's the expected complications rate? The actual hospital protocols are effective to minimize the risk of postoperative COVID-19 infection? Aim: to analyse results of bariatric surgery during phase 2-3 COVID-19 pandemic in Italy. Primary end point: 30 days COVID-19 infection, mortality and complications. Secondary end points: readmission rate 30 days, reoperations for any reason related to surgery. Study design: prospective multicenter observational. Setting: Italian National Health Service 8 high-volume bariatric centres. Enrollment criteria: No previous Covid-19 infection; Primary, standard IFSO approved bariatric procedures; No concomitant procedure; No previous major abdominal surgery; >18<60 years old; Compensated comorbidities; Official SICOB's surgical informed consent given, including COVID-19 addendum; Adherence to very restrictive protocols regarding: hospital admission, management of in-hospital patients and after discharge. Follow-up: scheduled outpatient visit 30th postoperative day. Data evaluation: all the cases performed during July/December 2020 will be collected in a prospective database. Patients operated during the period July/December 2019 in the same centers will be considered comparative group (control). Expected results: Transparent information to the patients, and the introduction of the COVID-19 protocol concerning patients and health-professionals protection, should guarantee a safe restart of bariatric surgery in Italy. The network of 8 high-volume centers sharing information and protocols in this "unexplored" period will be a guarantee for patients' safety. Bariatric surgery should induce a postoperative amelioration of the comorbidities reducing the risks in case of a second outbreak.

    NCT04480034
    Conditions
    1. Bariatric Surgery Candidate
    2. Covid19
    3. Complication of Surgical Procedure
    4. Pneumonia, Viral
    5. Viral Infection
    6. Obesity, Morbid
    7. Safety Issues
    8. Readmission
    Interventions
    1. Procedure: Bariatric procedures
    MeSH:Virus Diseases Pneumonia, Viral Pneumonia Obesity Obesity, Morbid
    HPO:Obesity Pneumonia

    Primary Outcomes

    Description: Postbariatric surgery COVID-19 infection, mortality and complications

    Measure: Postoperative COVID-19 infection

    Time: 30 postoperative days

    Secondary Outcomes

    Description: Complications, reoperations for any reason related to bariatric surgery.

    Measure: Complications related to bariatric surgery

    Time: 30 postoperative days
    291 A Randomized, Placebo-controlled Study of the Safety, Tolerability and Pharmacokinetics of Inhaled Nanoparticle Formulation of Remdesivir (GS-5734) and in Combination With NA-831 in Healthy Volunteers

    The clinical study is designed to evaluate the safety, tolerability and pharmacokinetics of inhaled nanoparticle nanoparticle formulation of Remdesivir (GS-5734) alone and in combination with NA-831 in 48 healthy volunteers.

    NCT04480333
    Conditions
    1. Covid19
    2. Corona Virus Infection
    3. Severe Acute Respiratory Syndrome
    4. Severe Acute Respiratory Infection
    5. Severe Acute Respiratory Syndrome (SARS) Pneumonia
    6. Severe Acute Respiratory Syndrome of Upper Respiratory Tract
    7. Neurodegeneration
    8. Neuroinflammatory Response
    Interventions
    1. Drug: Drug: NA-831 - 0.10 mg/kg
    2. Drug: Placebo- 0.10 mg/kg
    3. Drug: Drug: NA-831 - 0.20 mg/kg
    4. Drug: Placebo- 0.20 mg/kg
    5. Drug: Drug: GS-5734 - 1.00 mg/kg
    6. Drug: Placebo- 1.00 mg/kg
    7. Drug: Drug: GS-5734 - 2.00 mg/kg
    8. Drug: Placebo- 2.00 mg/kg
    9. Combination Product: Drugs: NA-831 (0.10 mg/kg) plus GS-5734 (1.00 mg/kg)
    10. Combination Product: Placebo 0.10 mg + 1.00 mg/kg
    11. Combination Product: Drugs: NA-831 (0.20 mg/kg) plus GS-5734 (2.00 mg/kg)
    12. Combination Product: Placebo 0.20 mg + 2.00 mg/kg
    MeSH:Infection Communicable Diseases Respiratory Tract Infections Virus Diseases Severe Acute Respiratory Syndrome Coronavirus Infections Pneumonia Syndrome Nerve Degeneration
    HPO:Neurodegeneration Pneumonia Respiratory tract infection

    Primary Outcomes

    Description: AEs will be assessed using Common Terminology Criteria for Adverse Events (CTCAE) V5.0

    Measure: Proportion of Participants Experiencing any Treatment-Emergent Adverse Events

    Time: First dose date up to Day 30 Follow-up Assessment

    Description: This will be assessed at various time points by clinical laboratory tests and vital signs.

    Measure: Proportion of Participants Experiencing any Treatment-Emergent Graded Laboratory Abnormalities

    Time: First dose date up to Day 30 Follow-up Assessment

    Secondary Outcomes

    Description: Monitoring of the levels of drugs in subject sera at various time points to elucidate the maximum concentration (Cmax) of NA-831 and GS-5734 in human serum.

    Measure: Maximum Concentration (Cmax) - Pharmacokinetic Assessment

    Time: 7 days

    Description: Monitoring of the levels of drugs in subject sera at various time points to elucidate the time to maximum concentration (Tmax) of NA-831 and GS-5734 in human serum

    Measure: Time to Maximum Concentration (Tmax) - Pharmacokinetic Assessment

    Time: 7 days

    Description: Monitoring of the levels of drugs in subject sera at various time points to elucidate the area under the curve from time of administration to the last measurable of NA-831 and GS-5734

    Measure: AUC calculated from time of administration to the last measurable concentration (AUC0-last) - Pharmacokinetic Assessment

    Time: 7 days

    Description: Monitoring of the levels of drugs in subject sera at various time points to elucidate the area under the curve extrapolated to infinity (AUC0-∞) of NA-831 and GS-5734

    Measure: Area Under the Curve Extrapolated to Infinity (AUC0-∞)

    Time: 7 days

    Description: Monitoring of the levels of drugs in subject sera at various time points to elucidate the half-life (t1/2) of NA-831 and GS-5734 in human serum.

    Measure: Half-Life (t1/2) - Pharmacokinetic Assessment

    Time: 7 days

    Description: Monitoring of the levels of drugs in subject sera through various time points to elucidate the volume of distribution (Vd) of NA-831 and GS-5734 in human serum.

    Measure: Volume of Distribution (Vd) - Pharmacokinetic Assessment

    Time: 7 days

    Description: Monitoring of the levels of drugs in subject sera through at various time points to elucidate clearance [CL] of NA-831 and GS-5734 in human serum.

    Measure: Clearance [CL] - Pharmacokinetic Assessment

    Time: 7 days
    292 Evaluation of Clinical Characteristics and Outcome of COVID19 Pneumonia in Assiut

    - Evaluation of the clinical presentation of COVID 19 pneumonia. - Identification the risk factors of severing COVID 19 pneumonia. - Evaluation of the outcome of the disease.

    NCT04481360
    Conditions
    1. Coronavirus
    Interventions
    1. Device: CT of the chest
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Patients assessment using CURB 65|(confusion ,urea level, respiratory rate blood pressure,age above 65 years) score 0 or 1 out patient -2 inpatient observation- 3 or more ICU admission.

    Measure: Clinical evaluation

    Time: through study completion, an average of 1 year
    293 Decitabine for COVID-19 Pneumonia-ARDS Treatment: DART Trial

    This is a a randomized double blind placebo controlled Phase 2 trial with a 12 patient lead-in to evaluate safety, prior to full enrollment to an additional 28 patients (for a total of 40 patients) to assess efficacy of decitabine in the treatment of critically ill patients with COVID-ARDS. The patients will be randomized in a 1:1 ratio to receive standard of care plus Decitabine or standard of care plus saline based placebo. The primary objective is to determine safety and efficacy of decitabine for COVID-19 ARDS based on clinical improvement on a 6-point clinical scale.

    NCT04482621
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Decitabine
    2. Other: Placebo Saline
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Clinical improvement within 10 days since start of treatment, defined as a decrease of at least 1 point within 10 days from baseline on a six-point ordinal scale: Not hospitalized/discharged; Hospitalized, not requiring supplemental oxygen; Hospitalized, requiring supplemental oxygen; Hospitalized, requiring nasal high-flow oxygen therapy, noninvasive mechanical ventilation, or both; Hospitalized, requiring invasive mechanical ventilation, extra-corporeal membrane oxygenation (ECMO), or both; and Death.

    Measure: Change in clinical state as assessed by a 6-point ordinal scale

    Time: Baseline and daily up to day 10

    Secondary Outcomes

    Description: Safety assessments using adverse events will be monitored daily while inpatient and weekly through end of study at week 6 once discharged from hospital. They will be monitored and graded using Common Terminology Criteria Adverse Events version 5.0.

    Measure: Safety as assessed by adverse events

    Time: Up to 6 weeks

    Description: Oxygenation index is used to assess severity of hypoxic respiratory failure. (OI = mean airway pressure (MAP) × Fraction of inspired oxygen (FiO2) × 100÷ partial pressure of oxygen (PaO2). This will be measured daily while subject is on mechanical ventilation up to 6 weeks.

    Measure: Change in oxygenation index

    Time: Daily, up to 6 weeks

    Description: Fraction of inspired oxygen in the oxygen delivery system during hospital stay. Measured at 8 am daily during hospital stay and then weekly until day 29.

    Measure: Change in fraction of inspired oxygen

    Time: Up to day 29

    Description: Number of days for subject that have a reduction by at least 2 point from baseline on a six point ordinal scale: Not hospitalized/discharged; Hospitalized, not requiring supplemental oxygen; Hospitalized, requiring supplemental oxygen; Hospitalized, requiring nasal high-flow oxygen therapy, noninvasive mechanical ventilation, or both; Hospitalized, requiring invasive mechanical ventilation, extra-corporeal membrane oxygenation (ECMO), or both; and Death.

    Measure: Time (days) to clinical improvement

    Time: Up to 6 weeks

    Description: Patients status of alive versus death at completion of study follow up period, i.e. 6 weeks from start.

    Measure: Overall survival

    Time: Up to 6 weeks

    Description: Duration of days from baseline to hospital discharge.

    Measure: Length of stay in hospital

    Time: Till hospital discharge, up to 6 weeks

    Description: For subjects who received mechanical ventilation, total number of days from baseline to end of study at 6 weeks that subject was not on mechanical or non invasive mechanical ventilation.

    Measure: Ventilator free days

    Time: Up to 6 weeks

    Description: If viremic at starting date of decitabine - time from baseline to 1st recorded negative COVID nucleic acid amplification (NAT) based assay, measured in days.

    Measure: Time to Polymerase chain reaction (PCR) negativity

    Time: Up to 6 weeks

    Description: Determines the degree of illness of a patient and prompts critical care intervention. This composite score includes Respiratory Rate, Temperature, oxygen Saturation, Blood Pressure, Oxygen inspired and cognitive status. This will be measured at baseline and weekly while patient is in hospital.

    Measure: Percentage of patients with National Early Warning Score 2 of 3 or more

    Time: Weekly while patient is in hospital, up to 6 weeks
    294 Predicting the Progression to Chronic Fibrosis of Lung Lesions Related to Covid-19 Infection From Chest CT Images

    The main differences observed between SARSCoV-2 pneumonia and other epidemic viral pneumopathies (e.g., seasonal influenza) are the greater infectivity of SARSCoV-2, the clinical severity of the disease, particularly in young patients without co-morbidities, and the observation of radiological images related to significant parenchymal aggression in a large number of patients. The lesions in the acute phase correspond essentially to bilateral ground glass opacity more or less associated with condensations which would be markers of more severe infections. The major scope of the lesions in the acute phase raises the question of whether or not the scanning anomalies are completely resolved over time, and the possible impact on lung function. This risk of sequelae is very important to study given the large number of patients affected by SARSCoV-2, especially since these are often young patients who appear to be "healthy". In the current context of the CoV-2 SARS pandemic, the improved quality and availability of diagnostic scanners provides a wealth of information on the semiology and progression of lung disease with minimal exposure to ionizing radiation. A majority of hospitalized patients with SARSCoV-2 received a CT scan in the early phase of the disease. Indeed, the French Society of Radiology has recommended the performance of a CT scan without injection in thin sections in case of suspicion or for confirmation of the diagnosis in patients presenting initial or secondary clinical signs of severity and justifying hospital management due to the initial lack of reagents for performing biological tests (RT-PCR) and the high sensitivity of the CT scan and its specificity in epidemic periods. The present study aims to study the kinetics of lung involvement in SARS CoV 2, to study the predictive character of the chest CT scan performed at the patient's discharge on the existence of radiological sequelae at 3 months but also at 1 year in order not to misunderstand the constitution of late fibrosis after partial resolution of the CT images. The investigatos will study the correlation between possible radiological abnormalities and the clinical presentation (patient symptoms and lung function). The rigorous follow-up of these patients will allow us to set up, if necessary, early treatment of the detected abnormalities (inhaled corticoids in case of bronchial or bronchiolar damage, study of the place of an anti-fibrosis treatment in case of fibrosis,...).

    NCT04483752
    Conditions
    1. CoV2 SARS Pneumonia
    Interventions
    1. Other: CHEST CT SCAN
    MeSH:Pneumonia Fibrosis
    HPO:Pneumonia

    Primary Outcomes

    Measure: description of the different types of lesions

    Time: 3 months

    Secondary Outcomes

    Measure: quantification of circulating antibodies and correlation between the level of immunization against SARS CoV2, the severity of the initial disease and the existence or not of long-term pulmonary sequelae

    Time: 3 months
    295 Place of Circulating Biomarkers and Respiratory Eicosanoids in the Prognosis of Severe Forms of Covid-19 Pneumonia: BioCovid Study

    The research is a prospective, multicentric (Groupe hospitalier Paris Saint-Joseph, Centre Hospitalier de Versailles André Mignot and Centre Hospitalier Victor Dupouy), non-interventional, prospective study. It aims at measuring eicosanoids at different stages of Covid-19 infection.

    NCT04485364
    Conditions
    1. Coronavirus
    2. Covid19
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: The importance of the inflammatory response in the evolution of respiratory disease during the the patients' hospital care based on criteria such as: The search for systemic biomarkers: the previous work led by the Saint Joseph Hospital Group team has highlighted the potential interest of biomarkers of inflammation in the diagnosis of infectious pathology as well as in the eventual prognosis of these patients. and the study of the production of eicosanoids and their presence in the systemic circulation and in the respiratory tree.

    Measure: Inflammatory response in the evolution of respiratory diseases

    Time: 6 months = the study duration

    Secondary Outcomes

    Description: Evolution of respiratory pathology during mechanical ventilation.

    Measure: Impact of the respiratory disease during mechanical ventilation

    Time: 6 months = the study duration
    296 Efficacy Assessment of Methylprednisolone and Heparin in Patients With COVID-19 Pneumonia: A Randomized, Controlled, 2x2 Factorial Study

    The COVID-19 pandemic has been spreading continuously, and in Brazil, until July 19, 2020, there have been more than 2,000,000 cases with more than 79,000 deaths, with daily increases. The present study proposes to evaluate the efficacy of methylprednisolone and heparin in treatment of patients with COVID-19 pneumonia in a randomized, controlled, 2x2 factorial study.

    NCT04485429
    Conditions
    1. COVID-19
    Interventions
    1. Drug: Methylprednisolone
    2. Drug: Heparin
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Measure: Rate of invasive mechanical ventilation

    Time: 28 days

    Secondary Outcomes

    Description: Severity assessment will be performed using the ordinal severity scale during hospitalization.

    Measure: Severity assessment by ordinal severity scale

    Time: 3 days, 7 days, 14 days, 28 days after randomization

    Description: Severity assessment will be performed using the SOFA score during hospitalization.

    Measure: Severity assessment by SOFA score

    Time: 3 days, 7 days, 14 days, 28 days after randomization

    Measure: Length of hospital stay

    Time: 28 days

    Measure: Length of stay in intensive care

    Time: 28 days

    Measure: Death rate

    Time: 14 days, 28 days, 60 days, 90 days after randomization
    297 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
    298 N-terminal Pro B-type Natriuretic Peptide and Vitamin D Levels as Prognostic Markers in COVID-19 Pneumonia

    This study is designed to assess the difference between level of NT-pro-BNP, and Vitmin D in moderate cases who progressed to severe or critically ill category compared to those who did not. Assessment of any possible correlation between NT-pro-BNP and Vitamin D and the need for mechanical ventilation or mortality in COVID-19 infection.

    NCT04487951
    Conditions
    1. COVID19 Pneumonia
    Interventions
    1. Other: Pro BNP , Vitamin D
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: level of NT-pro-BNP, and Vitamin D

    Measure: NT-pro-BNP and Vitamin D

    Time: 6 month

    Secondary Outcomes

    Description: Assessment of any possible correlation between NT-pro-BNP and Vitamin D and the need for mechanical ventilation or mortality in COVID-19 infection

    Measure: Assessment of any possible correlation between NT-pro-BNP and Vitamin D and the need for mechanical ventilation or mortality in COVID-19 infection

    Time: 6 month
    299 Pathogens Involved in Secondary Infections During Severe Forms of Covid-19 Pneumonia: COVAP Study

    A Respiratory infection with the SARS-CoV2 virus is associated with a major risk of viral pneumonia that can lead to respiratory distress requiring resuscitation. In the most severe forms, it may require mechanical ventilation or even lead to an acute respiratory distress syndrome with a particularly poor prognosis. The SARS-CoV2 is a single-stranded RNA virus of positive polarity and belongs to the beta genus of Coronaviruses. SARS-CoV2 is responsible for the third epidemic in less than twenty years secondary to a Coronavirus (SARS-CoV then MERS-CoV) and if the mortality associated with it is lower than that of previous strains, notably MERS-CoV, its spread is considerably big. As a result, the number of patients developing respiratory distress requiring invasive mechanical ventilation is high, with prolonged ventilation duration in these situations

    NCT04488510
    Conditions
    1. Covid19
    2. Ventilator Associated Pneumonia
    3. Nosocomial Pneumonia
    MeSH:Pneumonia, Ventilator-Associated Healthcare-Associated Pneumonia Coinfection Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Establishing a biobank of the bacterial agents responsible for nosocomial pneumonia acquired under mechanical ventilation in order to: better understand the particularities of the bacteria responsible and obtain the "clinical" strains for in vitro studies that will be carried out secondarily.

    Measure: Research of the bacteria responsible for nosocomial pneumonia

    Time: 6 months

    Secondary Outcomes

    Description: Evaluation of the adhesion properties to the bronchial epithelium (LPS peculiarities of Gram-negative bacteria, the interaction with the virus in in vitro models and the different molecules of interest in the collected bronchial secretions).

    Measure: Additional evaluations to the study

    Time: 6 months
    300 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
    301 The Protocol of Evaluation of Safety and Efficiency of Method of Exosome Inhalation in SARS-CoV-2 Associated Two-Sided Pneumonia

    Coronavirus is an acute viral disease with prevailing upper respiratory tract infections caused by the RNA-containing virus of the genus Betacoronavirus of the Coronaviridae family. Most patients with severe COVID-19 develop pneumonia in the first week of the disease. As the infection progresses, the infiltration increases, and the affected areas increases. Excessive and uncontrolled immune system response with rapidly developing fatal cytokine storm plays the main role in the pathogenesis of acute respiratory distress syndrome (ARDS) due to SARS-CoV-2 infection. According to available data, exosomes can regulate inflammation and regenerative processes due to the change in the concentration of anti-inflammatory cytokines and switch the immune cell to regenerative secretome. Inhalation of exosomes may reduce inflammation and damage to the lung tissue and stimulate the regenerative processes. This protocol has been developed based on the literature, information about the ongoing tests NCT04276987 (A Pilot Clinical Study on Inhalation of Mesenchymal Stem Cells Exosomes Treating Severe Novel Coronavirus Pneumonia) and NCT04384445 (Organicell Flow for Patients With COVID-19), Patent No 271036826 of 2019. "A method for obtaining and concentrating microRNA-containing exosomal multi-potent mesenchymal-stromal cells for use in cosmetic and pharmaceutical products to stimulate regenerative processes and slow down aging.

    NCT04491240
    Conditions
    1. Covid19
    2. SARS-CoV-2 PNEUMONIA
    3. COVID-19
    Interventions
    1. Drug: EXO 1 inhalation
    2. Drug: EXO 2 inhalation
    3. Drug: Placebo inhalation
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Safety assessment such as adverse events will be registered. Adverse events will be monitored during all trial

    Measure: Number of Participants With Non-serious and Serious Adverse Events During Trial

    Time: 30 days after clinic discharge

    Description: Safety assessments such as adverse events during the inhalation procedures will be registered.

    Measure: Number of Participants With Non-serious and Serious Adverse During Inhalation Procedure

    Time: after each inhalation during 10 days

    Secondary Outcomes

    Description: Measure and compare time to clinical recovery compared to placebo. Time to clinical recovery calculated by the number of days the patient has hospitalized.

    Measure: Time to Clinical Recovery (TTCR)

    Time: from first inhalation until discharge from the clinic, up to 30 days

    Description: The concentration of SpO2 by Pulse oximetry device during procedures in the groups. The measure was done before and after each inhalation (total 4 measures per day). The intraday SpO2 data of all patients in groups was calculated as Median with Inter-Quartile Range and presented in the table by days.

    Measure: SpO2 Concentration

    Time: 10 days during inhalation

    Description: Blood biochemistry C reactive protein level in serum.

    Measure: C-reactive Protein

    Time: At the begining of inhalation (day 1) and on next day of last inhalation (day 11)

    Description: Lactic Acid Dehydrogenase (LDH) level in serum

    Measure: Lactic Acid Dehydrogenase (LDH)

    Time: At the beginning of inhalation (day 1) and on next day of last inhalation (day 11)
    302 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
    303 Extracellular Vesicle Infusion Treatment for Severe COVID-19

    To evaluate the safety and efficacy of intravenous administration of bone marrow derived extracellular vesicles, ExoFlo, versus placebo as treatment for moderate-to-severe Acute Respiratory Distress Syndrome (ARDS) in patients with severe COVID-19.

    NCT04493242
    Conditions
    1. Covid19
    2. ARDS
    3. Pneumonia, Viral
    Interventions
    1. Biological: DB-001
    MeSH:Pneumonia, Viral Pneumonia Blister
    HPO:Pneumonia

    Primary Outcomes

    Description: all-cause mortality

    Measure: all-cause mortality

    Time: 28 days

    Description: median days to recovery

    Measure: median days to recovery

    Time: 28 days
    304 Low Dose Whole Lung Radiotherapy for Older Patients With Coronavirus 19 Disease (COVID-19) Pneumonitis: Practical Protocol by the International Geriatric Radiotherapy Group

    Low dose whole lung radiotherapy may improve survival of older patients with COVID-19 pneumonitis

    NCT04493294
    Conditions
    1. COVID-19 Pneumonitis
    Interventions
    1. Radiation: Low dose whole lung radiotherapy for older patients with COVID-19 pneumonitis
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Comparing mortality rate of the whole group of patients treated with low dose whole lung radiotherapy with historical data

    Measure: Mortality rate

    Time: One year

    Secondary Outcomes

    Description: Comparison mortality rate of different ethnic groups treated with whole lung radiotherapy for COVID-19 pneumonia

    Measure: Mortality rate

    Time: One year

    Description: Duration of hospitalization for the whole group and different groups with or without oxygen requirement

    Measure: Duration of hospitalization

    Time: One year

    Description: Ordinal scale at the time of radiotherapy and 28 days later

    Measure: Time to recovery

    Time: One month

    Description: Correlation between oxygen saturation rate and ordinal scale at different times following radiotherapy

    Measure: Oxygen saturation rate

    Time: One year

    Description: Biomarkers for inflammation such as Interleukin 6 will be monitored and correlated with ordinal scale at different times following radiotherapy

    Measure: Patient inflammatory status

    Time: One year
    305 An Open-label Multicenter Randomized Trial to Evaluate the Efficacy of Bioven, Manufactured by Biopharma Plasma, LLC, in Complex Therapy of Patients With Pneumonia Induced by COVID-19 / SARS-CoV-2

    Pneumonia caused by coronavirus infection COVID-19 is characterized by a combination of several dangerous factors that consistently worsen the patient's condition: viral lung damage early in the disease; a sharp increase in inflammation on the background of an unbalanced immune response ("cytokine storm"); joining a bacterial infection. The condition of patients deteriorates significantly mostly at cytokine storm development. The damaging of a large volume of lung tissue leads to develops of respiratory failure, respiratory distress syndrome, or shock. Ventilatory support becomes ineffective and patients die. There are reports of the effectiveness of Human Normal Immunoglobulin for Intravenous Administration (IVIG) high doses when used as part of complex therapy in patients with pneumonia caused by coronavirus COVID-19. In particular, IVIG has a positive effect on survival rates, overall disease course, duration of stay in the intensive care unit, and ventilatory support duration. The probable mechanism of action of high-dose IVIG therapy is considered to be a regulatory effect on the immune system. Similar is the known and confirmed effectiveness of IVIG for autoimmune diseases (Kavasaky disease, Guillain Barre syndrome, Chronic inflammatory demyelinating polyradiculoneuropathy, Multifocal motor neuropathy). This trial to assesses the Efficacy of IVIG (medication trade name - Bioven, manufactured by Biopharma Plasma LLC) in the High Immunomodulatory Dose in Complex Treatment of Severe Pneumonia Caused by COVID-19 / SARS-CoV-2

    NCT04500067
    Conditions
    1. Covid19
    2. Pneumonia
    Interventions
    1. Drug: IVIG
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Number of days post-onset of severe pneumonia to the moment of normalization at least two from following primary outcomes: O2 saturation with self-breathing, respiratory movements rate with self-breathing, body temperature without antipyretics use, lymphocyte count (targeted levels set in the description each of these primary outcomes)

    Measure: Period duration (in days) to clinical improvement

    Time: From date post-onset of severe pneumonia to date of patient discharge or date of death, whichever came first, assessed up to 28 days

    Description: The target level of SPO2 percentage - 95% and above with self-breathing, is used as one of the clinical improvement criteria

    Measure: O2 saturation (SPO2 percentage), with self-breathing

    Time: From date post-onset of severe pneumonia to date of patient discharge or date of death, whichever came first, assessed up to 28 days

    Description: The target level of respiratory movements - 28 per minute or less with self-breathing, is used as one of the clinical improvement criteria

    Measure: Respiratory movements rate (amount per minute), with self-breathing

    Time: From date post-onset of severe pneumonia to date of patient discharge or date of death, whichever came first, assessed up to 28 days

    Description: Measured in degrees Celsius. Fever absence (body temperature no more 37 degrees Celsius) during at least 24 hours without antipyretics, is used as one of the clinical improvement criteria.

    Measure: Body temperature without antipyretics use

    Time: From date post-onset of severe pneumonia to date of patient discharge or date of death, whichever came first, assessed up to 28 days

    Description: The target level 1000 cells / mm3 and above is used as one of the clinical improvement criteria (applicable for patients with lymphocytes count lower 1000 cells / mm3 at screening moment)

    Measure: Lymphocyte count

    Time: From date post-onset of severe pneumonia to date of patient discharge or date of death, whichever came first, assessed up to 28 days

    Secondary Outcomes

    Description: Period duration (in days)

    Measure: Time from the onset of the disease to discharge, in days

    Time: 28 days

    Description: Number of days with ventilatory support

    Measure: Duration of the need for ventilatory support, in days

    Time: 28 days

    Description: Number of days in the intensive care unit

    Measure: Duration of the need for intensive care, in days

    Time: 28 days

    Description: Number of days with necessery of oxygenation support

    Measure: Duration of need for oxygenation in days (SPO2 ≤ 93% with self-breathing)

    Time: 28 days

    Description: Measuring the analyte concentration in plasma (mg/L)

    Measure: The C-reactive protein (CRP) level

    Time: Day 0 (screening), day 5, day 14, day 28

    Description: Measuring the analyte concentration in plasma (pg/mL)

    Measure: The tumor necrozis factor alpha (TNF-α) level

    Time: Day 0 (screening), day 5, day 14, day 28

    Description: Measuring the analyte concentration in plasma (pg/mL)

    Measure: The interleukin-1β (IL-1β) level

    Time: Day 0 (screening), day 5, day 14, day 28

    Description: Measuring the analyte concentration in plasma (pg/mL)

    Measure: The interleukin-6 (IL-6) level

    Time: Day 0 (screening), day 5, day 14, day 28

    Description: Measuring the analyte concentration in plasma (µg FEU/mL)

    Measure: The D-dimer level

    Time: Day 0 (screening), day 5, day 14, day 28

    Description: Measuring the analyte concentration in plasma (g/L)

    Measure: The Complement (C3 component) level

    Time: Day 0 (screening), day 5, day 14, day 28

    Description: Measuring the analyte concentration in plasma (U/mL)

    Measure: The Circulating immune complexes level

    Time: Day 0 (screening), day 5, day 14, day 28

    Description: Analyte concentration in plasma (ng/mL)

    Measure: The ferritin level

    Time: Day 0 (screening), day 5, day 14, day 28

    Description: Analyte concentration in plasma (ng/mL)

    Measure: The procalcitonin level

    Time: Day 0 (screening), day 5, day 14, day 28

    Description: The IgG-subtypes (IgG1-IgG4) concentration in plasma (mg/dL)

    Measure: IgG subtypes

    Time: Day 0 (screening), day 5, day 14, day 28

    Description: Survivealance estimation

    Measure: Survival assessment for a 28-day follow-up period since the onset of severe pneumonia

    Time: 28 days

    Other Outcomes

    Description: Number of participants with adverse reactions related by investigational drug as assessed by CTCАЕ v 4.0

    Measure: Frequency of side effects

    Time: 28 days

    Description: Number of participants with serious adverse reactions related by investigational drug as assessed by CTCАЕ v 4.0

    Measure: Frequency of serious side effects

    Time: 28 days
    306 Phase 2, Multi-center, Randomized, Double-blind, Placebo- Controlled Study to Evaluate the Safety and Efficacy of EC-18 in COVID-19 Infection to Pneumonia

    Prevention of COVID-19 infection to severe pneumonea or ARDS

    NCT04500132
    Conditions
    1. COVID-19
    Interventions
    1. Drug: EC-18
    2. Drug: Placebo EC-18
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Measure: Rate of transition to ARDS

    Time: 14 days after starting IP administration
    307 One-year Cardiac Follow-up of Patients With COVID-19 Pneumonia

    The primary objective of the study is to assess the cardiac status of COVID-19 pneumonia patients during 1 year after discharge

    NCT04501822
    Conditions
    1. Covid19
    2. Cardiac Complication
    Interventions
    1. Diagnostic Test: Evaluation of clinical, instrumental and laboratory diagnostics tests
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Echocardiographic assessment of global strain parameters at 3 and 12 months after discharge

    Measure: Echocardiographic assessment of cardiac function

    Time: up to one year

    Secondary Outcomes

    Description: Major adverse cardiac and cerebrovascular events: cardiac death, myocardial infarction, or stroke at 3 and 12 months after discharge

    Measure: МАССЕ

    Time: up to one year

    Description: Describe the parenchymal lung damage through a quantitative analysis with chest CT at 3 and 12 months after discharge

    Measure: Quantitative analysis of parenchymal lung damage

    Time: up to one year

    Description: Six-min walk test at 3 and 12 months after discharge

    Measure: Functional exercises capacity assessment

    Time: up to one year

    Description: Measure of creatinine clearance at 3 and 12 months after discharge

    Measure: Evaluation of renal function

    Time: up to one year

    Description: Analysis for C-reactive protein at 3 and 12 months after discharge

    Measure: Evaluation of inflammation

    Time: up to one year

    Description: Analysis for activated clotting time at 3 and 12 months

    Measure: Evaluation of coagulation abnormality

    Time: up to one year

    Description: Assessment of the Short Form Health Survey (SF36) at 3 and 12 months after discharge

    Measure: Evaluation of quality of life in first year after discharge

    Time: up to one year
    308 Treatment of COVID-19 With Opaganib in Patients With Pneumonia Requiring Oxygen But Not Mechanical Ventilation

    Patients diagnosed with COVID-19 infection will be offered treatment with Opaganib, 500 mg Q12 hours. Opaganib will be continuously administered for up to 2 weeks, until discharged on room air (if earlier than 2 weeks).

    NCT04502069
    Conditions
    1. COVID-19
    2. Lung Infection
    Interventions
    1. Drug: Opaganib
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: To determine the time to breathing room air (off of supplemental oxygen) after the start of opaganib treatment.

    Measure: Time to breathing room air

    Time: Up to 2 weeks

    Description: All adverse events will be graded according to the revised NCI Common Terminology Criteria for Adverse Events (NCI-CTCAE version 5.0). If an AE is not listed in the NCI-CTCAE v.5.0, then the Investigator will use the terms: mild, moderate, severe, life-threatening, or death to describe the maximum intensity of the AE.

    Measure: Adverse Event Grading and Coding

    Time: Up to 2 weeks
    309 Study of a Possible Respiratory Degradation Prognosis Caused by Biomarkers in Severe Forms of COVID-19 Pneumonia: the LPSARS2 Study

    Respiratory infection with the SARS-CoV2 virus is associated with a major risk of viral pneumonia that can lead to respiratory distress requiring resuscitation. In the most severe forms, it may require a mechanical ventilation or even lead to an acute respiratory distress syndrome with a particularly poor prognosis. The SARS-CoV2 is a single-stranded RNA virus of positive polarity and belongs to the beta genus of Coronaviruses. SARS-CoV2 is responsible for the third epidemic in less than twenty years secondary to a Coronavirus (SARS-CoV then MERS-CoV) and if the mortality associated with it is lower than that of previous strains, particularly MERS-CoV (Middle East Respiratory Syndrome), its spread is considerably bigger. As a result, the number of patients developing respiratory distress that require an invasive mechanical ventilation is high, with prolonged ventilation duration in these situations.

    NCT04505605
    Conditions
    1. Community-acquired Pneumonia
    2. Covid19
    Interventions
    1. Other: Blood samples
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: The study aims at evaluating the interests of the biomarkers dosage: endotoxin (LPS) and circulating cytokines (HMGB1 or RAGE) in the prediction of respiratory degradation through a severe form of COVID-19 acquired pneumonia that requires a hospitalization.

    Measure: Evaluation of the dosage of biomarkers

    Time: 6 months = study duration

    Secondary Outcomes

    Description: The study will be also focusing on the search for a correlation between the biomarkers by blood samples that will be taken on each hospitalized patients.

    Measure: Link between the biomarkers

    Time: 6 months = study duration
    310 Clinical, Laboratory and Imaging Comparison Between COVID-19 Pneumonia Confirmed by PCR Detection on Nasopharyngeal Swab and Negative Swab Pneumonia

    In the late 2019 a new Coronavirus was identified as the cause of a group of atypical interstitial pneumonia cases in Wuhan, a city in the Chinese province of Hubei. In February 2020, the World Health Organization designated COVID-19 disease, which stands for Coronavirus 2019 disease. Following the progressive spread of the infection in other countries of the world, WHO declared the Pandemic on 11 March 2020. Italy was the first European country involved in the spread of the infection and among those with the highest number of victims. The Coronavirus responsible for COVID-19 has, as its main target organ, the respiratory system, being able to determine a serious acute respiratory syndrome similar to that of the cases found during the SARS epidemic of 2003: hence the name of the virus as SARS-CoV-2. The diagnosis of SARS-COV-2 infection is made by direct detection by PCR of viral RNA on different biological materials from patients with suspicious symptoms, and the first level diagnostic test is generally the nasopharyngeal swab. However, even if the specificity of the nasopharyngeal swab is high, its sensitivity can be affected by technical causes (sampling mode), as well as by intrinsic factors related to the method. The purpose of the study is to identify the clinical, laboratory and imaging characteristic which are similar or which can differentiate the hospitalized patients affected by COVID-19 pneumonia (with positive PCR on naso-pharyngeal swab) and patients with pneumonia with negative PCR for COVID-19. To do this, the investigators will compare the clinical, laboratory and imaging characteristics between interstitial pneumonia secondary to SARS-COV-2 infection, confirmed by molecular biology investigations (viral RNA research by PCR on nasopharyngeal swab) and cases of interstitial pneumonia negative to the nasopharyngeal swab.

    NCT04507893
    Conditions
    1. Covid19
    2. Interstitial Pneumonia
    Interventions
    1. Other: Clinical, laboratory and imaging characteristics of pneumonia
    MeSH:Pneumonia Lung Diseases, Interstitial
    HPO:Interstitial pneumonitis Interstitial pulmonary abnormality Pneumonia

    Primary Outcomes

    Description: Accuracy of severity of respiratory insufficiency - evaluated as need of three step "nasal oxygen, oxygen mask, invasive ventilation" - in differentiate COVID-19 infection, classified according to the results of PCR assay for COVID-19 on naso-pharyngeal swab as "COVID-19 patients" and "COVID-19 negative controls"

    Measure: Evaluation of the clinical characteristics of patients with clinical presentation suggestive of COVID-19 infection, classified according to the results of PCR assay as "COVID-19 patients" and "COVID-19 negative controls".

    Time: 75 Days

    Description: Accuracy of the association of 3 haemato-chemical abnormalities (lymphopenia + increased serum transaminases + increased serum LDH) in differentiate COVID-19 infection, classified according to the results of PCR assay for COVID-19 on naso-pharyngeal swab as "COVID-19 patients" and "COVID-19 negative controls".

    Measure: Evaluation of the laboratory characteristics of patients with clinical presentation suggestive of COVID-19 infection, classified according to the results of PCR assay as "COVID-19 patients" and "COVID-19 negative controls".

    Time: 75 Days

    Description: Accuracy of thorax CT scan in differentiate COVID-19 infection, classified according to the results of PCR assay for COVID-19 on naso-pharyngeal swab as "COVID-19 patients" and "COVID-19 negative controls".

    Measure: Evaluation of the imaging characteristics of patients with clinical presentation suggestive of COVID-19 infection, classified according to the results of PCR assay as "COVID-19 patients" and "COVID-19 negative controls".

    Time: 75 Days

    Secondary Outcomes

    Description: Evaluation of mortality in "COVID-19 patients" and "COVID-19 negative controls", hospitalized in the study period.

    Measure: Evaluation of mortality of patients with clinical presentation suggestive of COVID-19 infection, classified according to the results of PCR assay as "COVID-19 patients" and "COVID-19 negative controls".

    Time: 75 Days

    Description: Evaluation of clinical severity in "COVID-19 patients" and "COVID-19 negative controls", hospitalized in the study period.

    Measure: Evaluation of clinical severity of patients with clinical presentation suggestive of COVID-19 infection, classified according to the results of PCR assay as "COVID-19 patients" and "COVID-19 negative controls".

    Time: 75 Days

    Description: Evaluation of hospital stay length in "COVID-19 patients" and "COVID-19 negative controls", hospitalized in the study period.

    Measure: Evaluation of hospital stay length of patients with clinical presentation suggestive of COVID-19 infection, classified according to the results of PCR assay as "COVID-19 patients" and "COVID-19 negative controls".

    Time: 75 Days
    311 Effect of the Use of Anticoagulant Therapy During Hospitalization and Discharge in Patients With COVID-19 Infection

    Viral infections provoke the systemic inflammatory response and cause an imbalance between the procoagulant and anticoagulant homeostatic mechanisms. Multiple pathogenic mechanisms are involved, including endothelial dysfunction, increased von Willebrand factor, Toll receptor activation, and tissue factor pathway activation. D-dimer levels greater than 1000 ng / mL are associated with an 18-fold increased risk of mortality. In this context, many patients may require prophylaxis or antithrombotic treatment with low molecular weight heparins. Currently, there is no validated scheme on the dose and timing of the use of antithrombotic drugs. The study aims to identify the effect of two anticoagulant strategies (prophylactic and therapeutic) on the progression to ventilatory support or death in patients with COVID-19 infection who require hospital care.

    NCT04508439
    Conditions
    1. Covid19
    2. Pneumonia
    3. Coagulation Disorder
    4. Pulmonary Embolism
    Interventions
    1. Drug: Enoxaparin
    MeSH:Pneumonia Pulmonary Embolism Embolism Hemostatic Disorders Blood Coagulation Disorders
    HPO:Abnormality of coagulation Abnormality of the coagulation cascade Pneumonia Pulmonary embolism

    Primary Outcomes

    Description: Identify the benefit of different doses of low molecular weight heparin (enoxaparin) on ventilatory support time in patients requiring hospital care for COVID-19 infection.

    Measure: low molecular weight heparin (enoxaparin) and ventilatory support time

    Time: 30 days

    Description: To compare oral anticoagulation therapy by administering Rivaroxaban 10mg PO every 24 hours on early thrombotic complications

    Measure: thrombotic complications and Rivaroxaban

    Time: 30 days

    Description: Identify the benefit of different doses of low molecular weight heparin (enoxaparin) on the length of hospital stay in patients requiring hospital care for COVID-19 infection.

    Measure: low molecular weight heparin (enoxaparin) and length of hospital stay

    Time: 30 days

    Description: Identify the benefit of different doses of low molecular weight heparin (enoxaparin) over mortality rate in patients requiring hospital care for COVID-19 infection.

    Measure: low molecular weight heparin (enoxaparin) and mortality rate

    Time: 30 days
    312 A Practical, Pilot, Randomized, Controlled Trial of Valproate Alone or in Combination With Quetiapine for Severe COVID-19 Pneumonia With Agitated Delirium

    The primary purpose of this research is to determine whether Valproate alone, and in combination with Quetiapine, lowers confusion and agitation in persons with severe Corona Virus Disease (COVID)19 pneumonia during weaning from the breathing machine (ventilator). Though Valproate and Quetiapine are often given to persons with severe confusion with agitation, the purpose of this small research study is specifically for: a) persons infected with COVID 2019 on a ventilator whose agitation is not responding to the usual medications (like dexmedetomidine), and b) to reduce the time persons are treated with dexmedetomidine, which requires continuous close monitoring in an ICU.

    NCT04513314
    Conditions
    1. Covid19
    2. Hyperactive Delirium
    3. Pneumonia, Viral
    Interventions
    1. Drug: Valproate
    2. Drug: Quetiapine
    3. Other: Standard of Care
    MeSH:Pneumonia, Viral Pneumonia Delirium
    HPO:Pneumonia

    Primary Outcomes

    Description: Richmond Agitation Sedation Scale (RASS) score ranges from +4 (combative) to 0 (alert & calm) to -5 (unarousable).

    Measure: Change from baseline RASS score of +3 or greater

    Time: Baseline, Day 7

    Secondary Outcomes

    Description: Total dose of dexmedetomidine administered will be reported from baseline RASS score of +3 or greater.

    Measure: Total dose of dexmedetomidine administered

    Time: Day 7

    Description: Incidence of Treatment Emergent Adverse Events will include: QTc duration > 470 msecs. Increase in Liver Function Tests to a Grade 3 or higher using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0. Suicidality reported as having a score of moderate or high risk using the Columbia-Suicide Severity Rating Scale Screening (C-SSRS). C-SSRS is a calculated risk assessment tool that scores suicidality from no risk to high risk.

    Measure: Incidence of Treatment Emergent Adverse Events

    Time: Day 7
    313 Prone Position and Respiratory Outcomes in Non-Intubated COVID-19 PatiEnts The "PRONE" Study

    The overall objective of this study is to determine whether a positional maneuver (e.g., prone positioning) decreases the need for escalation of respiratory-related care in patients with coronavirus (COVID-19) pneumonia.

    NCT04517123
    Conditions
    1. Covid19
    2. Pneumonia, Viral
    Interventions
    1. Other: Prone Positioning
    MeSH:Pneumonia, Viral Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Participants will be assessed for the occurrence of an escalation in respiratory related care (Yes or No). Escalation in respiratory related care is clinically defined as any of the following: intubation any increase in flow of supplemental oxygen transition to high flow nasal cannula increase in fraction of inspired oxygen transfer from a lower to a higher level acuity of care (e.g. medical floor to intermediate care unit (IMC) or intensive care unit (ICU); IMC to ICU).

    Measure: Occurrence of an escalation in respiratory related care (yes vs no)

    Time: During hospitalization, up to 30 days

    Secondary Outcomes

    Description: Oxygen Saturation measured in percent oxygen over a 24-hour period.

    Measure: Oxygen Saturation

    Time: Over a consecutive 24-hour period after randomization

    Description: Respiratory effort will be assessed using the respiratory rate (in breaths per minute) over a 24-hour period.

    Measure: Respiratory Effort as assessed by Respiratory Rate

    Time: Over a consecutive 24-hour period after randomization
    314 Toclizumam Versus Dexamethasone in Severe Covid-19 Cases

    randomized controlled trial comparing survival benefit of Tocilizumab therapy with dexamethasone in patients with severe COVID 19

    NCT04519385
    Conditions
    1. Pneumonia, Viral
    Interventions
    1. Drug: Tocilizumab
    2. Drug: Dexamethasone
    MeSH:Pneumonia, Viral Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: survival 14 days from admission date

    Measure: Proportion of participants with Overall Survival at 14 days

    Time: 14 days

    Secondary Outcomes

    Description: Change in Fio2/Pao2

    Measure: Fio2/Pao2

    Time: 2 days
    315 Prospective Hospital Registry of Patients With Suspected or Confirmed Coronavirus Infection (COVID-19) and Community-acquired Pneumonia

    Coronavirus-2019 disease (COVID-19) and community-acquired pneumonia are significant problems of modern medicine. Pneumonia is the most common severe complication of COVID-19. But at the same time, COVID-19 is not the only cause of community-acquired pneumonia. Moreover, pneumonia is only one of the numerous possible severe complications of COVID-19. Medical centers specialized for the hospital treatment of patients with severe COVID-19 and community-acquired pneumonia were organized in different regions of Russia during coronavirus pandemic-2020. The indications for hospitalization to one of these centers based in the National Medical and Surgical Center (NMSC) are: confirmed or suspected severe COVID-19 or community-acquired pneumonia. A prospective medical registry of such patients hospitalized to NMSC, is intended to analyze and compare their clinical and instrumental data, co-morbidity, treatment, short-term and long-term outcomes in real clinical practice. Stage 1. Hospital treatment in NMSC Duration of this stage: from the date of admission to the hospital up to the date of discharge from the hospital / or up to the date of death during the reference hospitalization. The date of admission to the hospital will be the date of enrollment to the study. Evaluation of electronic health record data using the Medical Information System (MIS). Assessment of the outcomes of the hospital phase (discharge from the hospital, death) and significant events (acute respiratory and pulmonary failure, requiring mechanical ventilation; cardiovascular events - myocardial infarction, cerebral stroke, acute heart failure, paroxysmal heart rhythm disturbances, bleedings, thrombosis of large vessels and thromboembolic complications). A survey of patients to clarify data on risk factors, somatic diseases, and drug therapy before hospitalization. COVID-19 was diagnosed when severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was confirmed by Polymerase chain reaction (PCR). Pneumonia was confirmed according to computerized tomography (CT) data. Stage 2. Prospective outpatient follow-up for 24 months Duration of this stage: 24 months after discharge from the hospital This work will be delivered by investigators from the National Medical Research Center for Therapy and Preventive Medicine. Evaluation of long-term outcomes and events among residents of Moscow and the Moscow Region according to a patient survey (contact by phone for 30-60 days, 6 months, 12 and 24 months after discharge from the hospital) and medical records.

    NCT04522076
    Conditions
    1. COVID 19
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Measure: Overall survival

    Time: from admission to discharge or death during reference hospitalization, assessed up to 90 days

    Measure: Time to all-cause mortality or Artificial Pulmonary Ventilation (APV)

    Time: from admission to discharge or death during reference hospitalization, assessed up to 90 days

    Measure: Time to all-cause mortality, nonfatal myocardial infarction, nonfatal cerebral stroke, and coronary or carotid revascularization

    Time: from discharge up to two years after reference hospitalization

    Secondary Outcomes

    Description: Damage area >50% according to the computer tomography data at any time point during hospitalization

    Measure: Proportion of patients with severe pneumonia

    Time: from admission to discharge or death during reference hospitalization, assessed up to 90 days

    Description: SpO2 <90% - at any point during hospitalization

    Measure: Proportion of patients with low oxygen saturation value

    Time: from admission to discharge or death during reference hospitalization, assessed up to 90 days

    Measure: Proportion of patients with Hb <90 g/l (9.0 g/dl) at any point during hospitalization

    Time: from admission to discharge or death during reference hospitalization, assessed up to 90 days

    Measure: Proportion of patients hospitalized or transferred to Intensive Care Unit (ICU)

    Time: from admission to discharge or death during reference hospitalization, assessed up to 90 days

    Measure: Overall survival

    Time: from discharge up to two years after reference hospitalization

    Measure: Time to nonfatal myocardial infarction, nonfatal cerebral stroke, and coronary or carotid revascularization

    Time: from discharge up to two years after reference hospitalization

    Description: In patients with pneumonia during reference hospitalization time to recurrent pneumonia. In patients without pneumonia during reference hospitalization - time to first pneumonia

    Measure: Time to pneumonia/recurrent pneumonia

    Time: from discharge up to two years after reference hospitalization

    Description: In patients without COVID-19 - time to primary diagnosis and in patients with COVID-19 - time to recurrent event

    Measure: Time to primary or recurrent coronavirus infection disease (COVID-19)

    Time: from discharge up to two years after reference hospitalization

    Other Outcomes

    Measure: proportion of patients with nonfatal myocardial infarction

    Time: from admission to discharge or death during reference hospitalization, assessed up to 90 days

    Measure: proportion of patients with nonfatal cerebral stroke

    Time: from admission to discharge or death during reference hospitalization, assessed up to 90 days

    Measure: proportion of patients with bleedings

    Time: from admission to discharge or death during reference hospitalization, assessed up to 90 days

    Description: proportion of patients with thromboembolic events

    Measure: thromboembolic events

    Time: from admission to discharge or death during reference hospitalization, assessed up to 90 days

    Description: the sum of the days when the patients required artificial pulmonary ventilation

    Measure: Duration of Artificial Pulmonary Ventilation

    Time: from admission to discharge or death during reference hospitalization, assessed up to 90 days

    Measure: Minimal value of oxygen blood saturation (SpO2) during the hospital stage.

    Time: from admission to discharge or death during reference hospitalization, assessed up to 90 days

    Measure: Minimal value of hemoglobin (Hb) during the hospital stage

    Time: from admission to discharge or death during reference hospitalization, assessed up to 90 days

    Description: proportion of patients with rehospitalization due to pneumonia, COVID-19, flu and other acute respiratory infections (ARV)

    Measure: Rehospitalization due to pneumonia, COVID-19, flu and other acute respiratory infections (ARV)

    Time: from discharge up to two years after reference hospitalization

    Description: proportion of patients with hospitalization due to cardiovascular disease

    Measure: Hospitalization due to cardiovascular disease (CVD)

    Time: from discharge up to two years after reference hospitalization

    Measure: time to Flu and other ARV (except COVID-19)

    Time: from discharge up to two years after reference hospitalization
    316 An Exploratory Study of ADR-001 in Patients With Severe Pneumonia Caused by SARS-CoV-2 Infection

    Safety and efficacy of ADR-001 are evaluated in Patients with Severe Pneumonia caused by SARS-CoV-2 infection.

    NCT04522986
    Conditions
    1. Severe Acute Respiratory Syndrome Coronavirus 2
    Interventions
    1. Biological: Mesenchymal stem cell
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Adverse events which appear in subjects with ADR-001 treatment are evaluated.

    Measure: Safety: Adverse Event

    Time: 12 weeks
    317 Low-Level Laser Therapy Treatment of Lung Inflammation in COVID-19 Patients

    To determine if a reduction of pneumonic inflammation occurs after treatment with Low-Level Laser Therapy (LLLT) applying red-light technology in the respiratory system of COVID-19 patients suffering from acute viral pneumonia.

    NCT04524715
    Conditions
    1. Covid19
    Interventions
    1. Device: Non-invasive red LLLT treatment to chest of patient.
    2. Device: Sham Device Treatment
    MeSH:Pneumonia Inflammation
    HPO:Pneumonia

    Primary Outcomes

    Description: Change in inflammation of the lungs as measured by O2 saturation levels

    Measure: Inflammation of the lungs - O2

    Time: 10 days

    Description: Change in inflammation of the lungs as measured by C-Reactive Protein (CRP) Test

    Measure: Inflammation of the lungs - CRP

    Time: 10 days

    Description: Change in inflammation of the lungs as measured by IL-6 Levels

    Measure: Inflammation of the lungs - IL6

    Time: 10 days
    318 A Phase I/Ⅱa Trial to Explore the Safety and Efficacy of Allogenic Adipose Tissue-derived Mesenchymal Stem Cell (AstroStem-V) Therapy in Patients With COVID-19 Pneumonia

    This study is an open-label, single-arm study to evaluate the safety and efficacy of Astrostem-V, allogenic adipose tissue derived mesenchymal stem cells (AdMSC), in patients with COVID-19 pneumonia. After each subject completes 12-Weeks visit (Visit 12) and the data management team confirms all individual data have no issue, the individual database will be locked and the blinding will be open for the statistical analysis.

    NCT04527224
    Conditions
    1. Covid19
    Interventions
    1. Drug: AstroStem-V
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Number of subjects with treatment related adverse events as assessed by analysis of adverse events including symptoms.

    Measure: Treatment related adverse events

    Time: From baseline to Week 12

    Description: Number of subjects with treatment related adverse events as assessed by analysis of adverse events including abnormal findings on physical examination, vital signs, ECG, and standard laboratory examination.

    Measure: Number of subjects with treatment related abnormal variation of vital signs, physical examination and laboratory test values

    Time: From baseline to Week 12

    Secondary Outcomes

    Description: Change from baseline in Oxygenation index (PaO2 / FiO2 ratio) at every week

    Measure: Oxygenation index (PaO2 / FiO2 ratio)

    Time: From baseline to Week 12

    Description: Check survival status of the subject at Visit 6, 10(Week 4, 8 and Week 12 if follow-up is possible) and record the status on eCRF.

    Measure: Mortality rate

    Time: Week 4, Week 8, and Week 12

    Description: Check the duration of the ventilator retention, check when the ventilator treatment has been completed after the baseline.

    Measure: Ventilator treatment status

    Time: From Week 1 to Week 12

    Description: Perform chest X-ray or CT every week (W1 - W4) after screening, baseline, and W4 followed by 2 - week intervals (W6, W8). The investigator of each clinical trial organ shall check chest X-ray or CT for bilateral shading and evaluate them.

    Measure: Improvement of pneumonia

    Time: From baseline to Week 12

    Description: Check the SOFA score every week from the baseline to the W4 (W1 - W4) and 2 weeks after the W4 (W6, W8). The Sequential Organ Failure Assessment (SOFA) is a simple and clinically useful indicator that can be used to assess, predict, and monitor long-term failure in patients with multiple organ failure, and therefore increase in SOFA score can be expected to result in multiple organ failure and worse prognosis.

    Measure: SOFA score (Sequential Organ Failure Assessment)

    Time: From baseline to Week 12

    Description: The Real-time PCR (RT-PCR) test for COVID-19 is measured at weekly intervals (W1 - W4) from baseline to baseline to W4 and 2 weeks after W4.

    Measure: 2019 nCOV nucleic acid test

    Time: From baseline to Week 12

    Description: Check hospitalization date, date of admission at intensive care unit, or discharge date and record them in eCRF.

    Measure: Duration of total hospitalization and intensive care unit stay (days)

    Time: From baseline to Week 12
    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 Efficacy and Safety of Using Convalescent Plasma for Treating Patients With COVID-19 Pneumonia Without Indication of Ventilatory Support

    The COVID-19 pandemic has been spreading continuously, and in Brazil, until August 18, 2020, there have been more than 3,359,000 cases with more than 108,536 deaths, with daily increases. The present study proposes to evaluate the efficacy and safety of using convalescent plasma for treating patients with COVID-19 pneumonia without indication of ventilatory support.

    NCT04528368
    Conditions
    1. COVID-19
    Interventions
    1. Biological: Convalescent plasma
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: To evaluate the area under the curve of SARSCoV-2 viral load in nasopharyngeal and or oropharyngeal samples on days 0, 3, 6, 9, 12, 15, 18 and 15 after randomization.

    Measure: Area under the curve of SARS-COV-2 viral load obtained from nasopharyngeal and /or oropharyngeal swabs.

    Time: 0, 3, 6, 9, 12, 15, 18 and 21 days

    Secondary Outcomes

    Description: The seven-point scale is as follows: Death 7 points; Hospital admission for mechanical ventilation plus additional organ support (eg, pressors, RRT, ECMO) = 6 points; Hospital admission for mechanical ventilation = 5 points; Hospital admission for non-invasive ventilation or high-flow oxygen therapy = 4 points; Hospital admission for oxygen therapy (but not requiring high-flow or non-invasive ventilation) = 3 points; Hospital admission but not requiring oxygen therapy = 2 points; Discharged with limitations of activities = 1 point; Discharged with no limitations of activities = 0 point;

    Measure: Assessment of clinical improvement using an Ordinal Severity Scale

    Time: 0, 7, 10, 14, 21 and 28 days

    Measure: Evaluate oxygen saturation

    Time: 0, 3, 6, 9, 12, 15, 18 and 21 days

    Measure: Evaluate oxygen supplementation

    Time: 0, 3, 6, 9, 12, 15, 18 and 21 days

    Measure: Assess respiratory rate

    Time: 0, 3, 6, 9, 12, 15, 18 and 21 days

    Measure: Evaluate the PaO2 / FiO2 ratio (for patients on mechanical mechanisms)

    Time: 0, 3, 6, 9, 12, 15, 18 and 21 days

    Measure: Length of hospital stay

    Time: 21 days

    Measure: Length of stay in intensive care

    Time: 21 days

    Measure: Assess the rate of orotracheal intubation

    Time: 21 days

    Description: Quantification by ELISA the levels of 36 molecules determined simultaneously using the Human Cytokine Array Kit da R&D Systems (C5a, IL-4, IL-32 alpha, CD40 ligand, IL-5, CXCL10 / IP-10, G-CSF, IL-6, CXCL11 / I-TAC, GM-CSF, IL-8, CCL2 / MCP-1, CXCL1 / GRO alpha, IL-10, MIF, CCL1 / I-309, IL-12 p70, CCL3 / MIP-1 alpha, ICAM-1, IL-13, CCL4 / MIP-1 beta, IFN -gamma, IL-16, CCL5 / RANTES, IL-1 alpha, IL-17, CXCL12 / SDF-1, IL-1 beta, IL-17E, Serpin E1 / PAI-1, IL-1ra, IL-23, TNF-alpha, IL-2, IL-27 and TREM-1)

    Measure: Change in the profile of cytokines/chemokines in both groups

    Time: 0, 3, 6, 9, 12, 15, 18 and 21 days

    Measure: Presence of antibodies against SARS-CoV-2 in serum after convalescent plasma administration

    Time: 0, 3, 6, 9, 12, 15, 18 and 21 days

    Measure: Death rate

    Time: 7, 10, 14, 21 and 28 days

    Measure: Rate of transfusion reactions to convalescent plasma infusion

    Time: 21 days
    321 Steroids and Unfractionated Heparin in Critically Ill Patients With Pneumonia From COVID-19 Infection. A Multicenter, Interventional, Randomized, Three Arms Study Design

    SARS-CoV-2 infection seems to induce in most critical cases an excessive and aberrant hyper-inflammatory host immune response that is associated with a so-called "cytokine storm", moreover pro-thrombotic derangements of haemostatic system is another common finding in most severe forms of COVID19 infections, which may be explained by the activation of coagulative cascade primed by inflammatory stimuli, in line with what is observed in many other forms of sepsis. Targeting inflammatory responses exploiting steroids' anti-inflammatory activity along with thrombosis prevention may be a promising therapeutic option to improve patients' outcome. Despite the biological plausibility, no good evidence is available on the efficacy and safety of heparin on sepsis patients, and many issues have to be addressed, regarding the proper timing, dosages and administration schedules of anticoagulant drugs. The primary objective is to assess the hypothesis that an adjunctive therapy with steroids and unfractionated heparin (UFH) or with steroids and low molecular weight heparin (LMWH) are more effective in reducing any-cause mortality in critically-ill patients with pneumonia from COVID- 19 infection compared to low molecular weight heparin (LMWH) alone. Mortality will be measured at 28 days. The study is designed as a multicenter, national, interventional, randomized, investigator sponsored, three arms study. Patients, who satisfy all inclusion criteria and no exclusion criteria, will be randomly assigned in a ratio 1:1:1 to one of the three treatment groups: LMWH group, LMWH+steroids or UFH+steroid group. A possible result showing the efficacy of the composite treatment in reducing the mortality rate among critically ill patients with pneumonia from COVID-19 infection will lead to a revision of the current clinical approach to this disease.

    NCT04528888
    Conditions
    1. Covid19
    2. SARS-CoV Infection
    3. Pneumonia, Viral
    4. Coagulopathy
    Interventions
    1. Drug: Enoxaparin
    2. Drug: Methylprednisolone
    3. Drug: unfractionated heparin
    MeSH:Infection Communicable Diseases Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia, Viral Pneumonia Critical Illness
    HPO:Pneumonia

    Primary Outcomes

    Description: All-cause mortality at day 28, defined as the comparison of proportions of patients death for any cause at day 28 from randomization.

    Measure: All-cause mortality at day 28

    Time: Day 28 from randomization

    Secondary Outcomes

    Description: All-cause mortality at ICU discharge, defined as the comparison of proportions of patients death for any cause at ICU discharge.

    Measure: All-cause mortality at ICU discharge

    Time: from randomization to ICU discharge, censored at day 30

    Description: All-cause mortality at Hospital discharge, defined as the comparison of proportions of patients death for any cause at hospital discharge

    Measure: All-cause mortality at hospital discharge

    Time: from randomization to ICU discharge, censored at day 90

    Description: Occurrence of rescue administration of high-dose steroids or immune-modulatory drugs

    Measure: Need of rescue administration of high-dose steroids or immune-modulatory drugs

    Time: from randomization to ICU discharge, censored at day 28

    Description: Occurrence of new organ dysfunction during ICU stay. Organ dysfunction is defined as a Sequential Organ Failure Assessment (SOFA) score ≥3 for the corresponding organ occurring after randomization.

    Measure: New organ dysfunction during ICU stay

    Time: From randomization to ICU discharge, censored at day 28

    Description: Grade of organ dysfunction during ICU stay, grade of dysfunction is measured with Sequential Organ Failure Assessment (SOFA) score daily from randomization to day 28 or ICU discharge.

    Measure: Grade of organ dysfunction during ICU stay

    Time: From randomization to ICU discharge, censored at day 28

    Description: Total number of days between ICU discharge and day 28. If death occurs during the ICU stay before day 28 the ICU free days calculation will be 0. The ICU readmission before day 28 after randomization will be considered.

    Measure: ICU free days at day 28

    Time: From randomization to day 28

    Description: Occurrence of new infections including bacterial infections, fungal infections by Candida, Aspergillus, and viral reactivations including Adenovirus, Herpes Virus e Cytomegalovirus

    Measure: Occurrence of new infections

    Time: from randomization to day 28

    Description: Total number of days that patient is alive and free of ventilation between randomisation and day 28. Ventilation is considered as positive pressure ventilation, either invasive or non-invasive. Periods of assisted breathing lasting less than 24 hours for surgical procedures will not count against the ventilation free days calculation.

    Measure: Ventilation free days at day 28

    Time: From randomization to day 28, censored at hospital discharge

    Description: Total number of days that patient is alive and free of vasopressors between randomisation and day 28.

    Measure: Vasopressors free-days at day 28

    Time: From randomization to day 28, censored at hospital discharge

    Description: Occurrence of switch from non-invasive to invasive mechanical ventilation

    Measure: Switch from non-invasive to invasive mechanical ventilation

    Time: from randomization to ICU discharge, censored at day 28

    Description: Total number of hours from start of non-invasive to invasive ventilation to switch to invasive ventilation

    Measure: Delay from start of non-invasive ventilation to switch to invasive ventilation

    Time: from randomization to ICU discharge, censored at day 28

    Description: Adverse events occurred from randomization to day 28. Events that are part of the natural history of the primary disease process or expected complications of critical illness will not be reported as adverse events.

    Measure: Occurrence of protocol related adverse events

    Time: From randomization to day 28

    Description: Occurrence of objectively confirmed venous thromboembolism, stroke or myocardial infarction

    Measure: Occurrence of venous thromboembolism, stroke or myocardial infarction

    Time: from randomization to ICU discharge, censored at day 28

    Description: Occurrence of major bleeding defined as transfusion of 2 or more units of packed red blood cells in a day, bleeding that occurs in at least one of the following critical sites [intracranial, intraspinal, intraocular (within the corpus of the eye; thus, a conjunctival bleed is not an intraocular bleed), pericardial, intra-articular, intramuscular with compartment syndrome, or retroperitoneal], bleeding that necessitates surgical intervention and bleeding that is fatal (defined as a bleeding event that was the primary cause of death or contributed directly to death)

    Measure: Occurrence of major bleeding (safety end point)

    Time: from randomization to ICU discharge, censored at day 28

    Description: Occurrence of clinically relevant non-major bleeding defined ad acute clinically overt bleeding that does not meet the criteria for major and consists of any bleeding compromising hemodynamic; spontaneous hematoma larger than 25 cm2, or 100 cm2, intramuscular hematoma documented by ultrasonography, haematuria that was macroscopic and was spontaneous or lasted for more than 24 hours after invasive procedures; haemoptysis, hematemesis or spontaneous rectal bleeding requiring endoscopy or other medical intervention or any other bleeding requiring temporary cessation of a study drug.

    Measure: Occurrence of clinically relevant non-major bleeding (safety end point)

    Time: from randomization to ICU discharge, censored at day 28

    Other Outcomes

    Description: Mean arterial pressure will be measured in millimeters of mercury

    Measure: Mean arterial pressure

    Time: Daily from inclusion until ICU discharge, censored day 28

    Description: hearth rate will be measured in beats per minute

    Measure: hearth rate

    Time: Daily from inclusion until ICU discharge, censored day 28

    Description: respiratory rate will be measured in breaths per minute

    Measure: respiratory rate

    Time: Daily from inclusion until ICU discharge, censored day 28

    Description: diuresis will be measured daily in milliliters of urine output in the previous 24 hours

    Measure: diuresis

    Time: Daily from inclusion until ICU discharge, censored day 28

    Description: systemic body temperature will be measured in celsius degrees

    Measure: systemic body temperature

    Time: Daily from inclusion until ICU discharge, censored day 28

    Description: fluid balance will be measured in milliliters of fluids input and output in the previous 24 hours

    Measure: fluid balance

    Time: Daily from inclusion until ICU discharge, censored day 28

    Description: Haemoglobin will be measured in mg/dl

    Measure: Haemoglobin concentration

    Time: Daily from inclusion to ICU discharge (censored at day 28)

    Description: platelets count will be measured in U 10^3/mm^3

    Measure: platelets count

    Time: Daily from inclusion to ICU discharge (censored at day 28)

    Description: white blood cells count will be measured in U per 10^9/L

    Measure: white blood cells count

    Time: Daily from inclusion to ICU discharge (censored at day 28)

    Description: troponin will be measured in µg/L

    Measure: troponin

    Time: Daily from inclusion to ICU discharge (censored at day 28)

    Description: coagulative function will be measured with parameters INR, PT, aPTT

    Measure: coagulative function

    Time: Daily from inclusion to ICU discharge (censored at day 28)

    Description: D-dimer will be measured in µg/ml

    Measure: D-dimer

    Time: Daily from inclusion to ICU discharge (censored at day 28)

    Description: anti-thrombin will be measured as a percentage

    Measure: anti-thrombin

    Time: Daily from inclusion to ICU discharge (censored at day 28)

    Description: liver function will be assessed through measurement of AST, ALT in U/L

    Measure: Liver function

    Time: Daily from inclusion to ICU discharge (censored at day 28)

    Description: Bilirubin will be measured in mg/dL

    Measure: Bilirubin

    Time: Daily from inclusion to ICU discharge (censored at day 28)

    Description: Creatinine will be measured in mg/dL

    Measure: Creatinine

    Time: Daily from inclusion to ICU discharge (censored at day 28)

    Description: Blood cells count will be measured in Units per x 10^9/L of blood

    Measure: Blood cells count

    Time: daily from inclusion to ICU discharge (censored at day 28)

    Description: C-reactive protein (CRP) will be measured in mg/dl

    Measure: C-reactive protein (CRP)

    Time: daily from inclusion to ICU discharge (censored at day 28)

    Description: procalcitonin(PCT) wiull be measured in ng/ml

    Measure: procalcitonin(PCT)

    Time: daily from inclusion to ICU discharge (censored at day 28)

    Description: interleukin 6 (IL-6) will be measured in pg/ml

    Measure: interleukin 6 (IL-6)

    Time: daily from inclusion to ICU discharge (censored at day 28)

    Description: Ventilation mode will be cathegorized in spontaneous breathing, invasive or non invasive ventilation

    Measure: Ventilation mode

    Time: Daily from inclusion to ICU discharge (censored at day 28)

    Description: inspired oxygen fraction will be measured in percentage of oxygen in inspired air

    Measure: inspired oxygen fraction

    Time: Daily from inclusion to ICU discharge (censored at day 28)

    Description: Gas exchanges will be assessed by measurement of PaO2, PaCO2 in mmHg by arterial blood gas analysis

    Measure: Gas exchanges

    Time: Daily from inclusion to ICU discharge (censored at day 28)

    Description: lactates will be measured in mMol/L

    Measure: lactates

    Time: Daily from inclusion to ICU discharge (censored at day 28)

    Description: pH will be measured in pH scale

    Measure: pH

    Time: Daily from inclusion to ICU discharge (censored at day 28)

    Description: oxygen saturation in blood will be measured in arterial and venous samples in percentage values

    Measure: oxygen saturation in blood

    Time: Daily from inclusion to ICU discharge (censored at day 28)

    Description: New blood, respiratory and urinary-tract infections will be recorded

    Measure: New infections

    Time: From randomization to day 28

    Description: Viral reactivation measured by CMV DNA titres will be recorded.

    Measure: Viral reactivation

    Time: From randomization to day 28

    Description: Need of new renal replacement therapy (intermittent haemodialysis or continuous veno-venous hemofiltration) will be recorded.

    Measure: Need of new renal replacement therapy

    Time: from randomization to day 28

    Description: Adjunctive treatment such as pronation cycles, Nitric Oxide or ECMO will be recorded

    Measure: Adjunctive treatments

    Time: from randomization to ICU discharge (censored at day 28);
    322 Efficacy and Safety Study to Evaluate the Use of Nebulized Heparin in Patients With Severe Acute Respiratory Syndrome Covid-19 (SARS-CoV-2)

    To evaluate the safety and efficacy of the use of inhalational heparin in patients with pulmonary compromise / pneumonia / SARS associated with COVID-19, laboratory with marked inflammation parameters, and prothrombotic state secondary to it (Fibrinogen, Ferritin and / or elevated D-Dimer) , from admission to hospitalization. The combination of inhalation heparin combined with prophylactic doses of LMWH could reduce the progression to severe forms of the disease, and consequently the need for intensive care units and mechanical ventilation.

    NCT04530578
    Conditions
    1. Covid19
    2. Pneumonia
    Interventions
    1. Drug: Heparin sodium
    2. Drug: Enoxaparin
    MeSH:Severe Acute Respiratory Syndrome Coronavirus Infections Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Blood Gas criteria :PaO2 / FiO2 <200 (or the inability to maintain an SpO2 of at least 92% with a reservoir mask). Acute ventilatory failure (pH less than 7.35 with PaCO2 greater than 45 mmHg)

    Measure: Percentage of patients requirement mechanical ventilation

    Time: 15 days

    Secondary Outcomes

    Description: Mean every 48 hours PaO2 to FiO2 ratio

    Measure: Percentage of patients with PaO2 to Fi02 ratio > 300

    Time: 7 days

    Description: To compare the lengths of hospital-stay

    Measure: Lengths of hospital-stay

    Time: Days 60

    Description: All cause mortality

    Measure: Mortality rate

    Time: 30 days
    323 Randomized, Open, Parallel, Single-center, Non-inferiority Clinical Trial, With an Active Control Group, Comparing Two Oral Prednisone Regimens With the Aim of Optimizing the Therapeutic Strategy in Patients With Organizing Pneumonia Post-COVID-19 Infection

    Background: Based on data from the 2003 SARS-COVID pandemic, other serious lung infections, and patients with respiratory distress, it is estimated that 10-30% of patients with severe SARS-COVID-2 pneumonia may present as a sequel an organized pneumonia. The treatment of this complication is not well defined. The use of oral corticosteroids is mandatory to avoid a possible evolution to pulmonary fibrosis, however, the doses to be administered and the duration of treatment are unknown as there is no study specifically aimed at solving this doubt. Many authors advocate high-dose treatment regimens for a minimum of six months, as proposed for cryptogenic organized pneumonia. However, there is a question whether in non-idiopathic cases of organized pneumonia, less intense treatment could resolve the disease. Hypothesis: The use of a less intensive prednisone regimen may be sufficient for therapeutic control in patients with post-COVID-19 organizing pneumonia, in relation to the established standard regimen Simplicity of the procedures: The objective of the NORCOVID study is to identify the optimal treatment regimen with corticosteroids in post-COVID19 patients diagnosed with NO. Specifically, the primary objective of this multicenter randomized trial is to evaluate whether treatment with a less intensive regimen of corticosteroids produces a non-inferior therapeutic effect than the established control regimen. Secondary objectives are to evaluate the effect of treatment on secondary efficacy variables and on safety. DLCO, respiratory function tests, 6MWT test, need for rescue, radiological tests, complications, mortality and the WHO ordinal scale will be evaluated.

    NCT04534478
    Conditions
    1. COVID-19 Pneumonia
    Interventions
    1. Drug: Prednisone
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: The main variable will be the change in pulmonary diffusion, in terms of predicted DLCO (%), between the baseline value and that obtained at 6 months, comparing the two treatment groups, adjusting for the baseline value using a repeated measures model with random effects (mixed model for repeated measurements.

    Measure: Change in pulmonary diffusion.

    Time: Six Months
    324 Randomized Trial, Anti-inflammatory Effect of Low-Dose Whole-Lung Radiation for COVID-19 Pneumonia

    There are several clinical studies that mention the benefits of treatment with low-dose radiation therapy to patients with COVID 19, so this study protocol will be started to determine if there is clinical improvement with treatment and low-dose radiation therapy. to all the lung.

    NCT04534790
    Conditions
    1. COVID-19 Pneumonia
    Interventions
    1. Radiation: Low Dose Radiotherapy
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: improvement of oxygen saturation

    Measure: Clinical improvement

    Time: 7 days

    Secondary Outcomes

    Description: improvement in acute phase reactants and simple tomography

    Measure: improvement of laboratory and imaging parameters

    Time: 7 -14 days
    325 Convalescent Plasma as Potential Therapy for Severe COVID-19 Pneumonia

    To determinate feasibility, safety and outcome with convalescent plasma in patients with severe COVID-19 penumonia

    NCT04535063
    Conditions
    1. Covid19 Pneumonia
    Interventions
    1. Biological: COVID19 convalescent plasma infusion
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: number of subjects surviving at 28 days from plasma infusion

    Measure: 28 days survival

    Time: 28 days

    Secondary Outcomes

    Description: comparison of clinical efficacy according antibodies levels

    Measure: efficacy of plasma infusion according to antibodies levels in the infuse bags

    Time: 28 days

    Description: we will search if clinical efficacy is better when the earlier the infusion is decided

    Measure: clinical efficacy of plasma infusion according to frame time from symptoms onset and hospitalization

    Time: 28 days

    Description: WHO clinical scale is a measure of patient progression through the health-care system with 1 point asymptomatic patient and 10 patient dead

    Measure: change in clinical WHO ordinal scale from 1 to 10 points

    Time: 14 days
    326 A Multicenter, Randomised, Controlled, Open Label Trial on the Efficacy and Safety of Asunercept for Patients With Severe COVID-19 Disease

    This is an open-label, randomized, phase II study with the main objective to investigate the effectiveness and safety of an investigational drug (APG101; International Nonproprietary Name: asunercept) in patients with severe COVID-19 disease. The study aims to decrease overall and SARS-CoV-2 associated pneumonia mortality in patients with COVID-19 as well as to decrease the percentage of patients admitted to Intensive Care Unit (ICU), decrease the need to supply oxygen to patients, reduce the number of days patients are hospitalized in ICU and/or on the ward, decrease the number of days required to obtain a negative result in the PCR (Polymerase Chain Reaction, a laboratory technique that allows the amplification of small fragments of DNA to detect the presence of the virus) test for COVID-19 and decrease the levels of markers that indicate pneumonia.

    NCT04535674
    Conditions
    1. COVID-19 Induced Pneumonia
    2. Covid19
    Interventions
    1. Biological: Asunercept
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: The primary endpoint is time to clinical improvement which is defined as time from randomisation to an (sustained) improvement of at least one category on two consecutive days compared to the status at randomisation measured on a nine-category ordinal scale (proposed by WHO).

    Measure: Time to sustained improvement of one category (i.e. two consecutive days) from randomisation

    Time: Day 1-29

    Secondary Outcomes

    Description: Time to discharge or to a NEWS of ≤2 and maintained for 24 hours, whichever occurs first Change from baseline

    Measure: Efficacy according to the National Early Warning Score (NEWS)

    Time: Day 1-29

    Description: Oxygenation free days until day 29 Incidence and duration of new oxygen use during the trial

    Measure: Oxygenation

    Time: Day 1-29

    Description: Ventilator free days until day 29 Incidence and duration fo new mechanical ventilation use during the trial

    Measure: Ventilation

    Time: Day 1-29

    Description: Duration of hospitalisation Length of ICU stay (in days)

    Measure: Hospitalisation - Length

    Time: Day 1-29

    Description: Proportion of patients admitted to ICU

    Measure: Hospitalisation - Proportion on ICU

    Time: Day 1-29

    Description: 15-day, 29-day all-cause mortality

    Measure: Mortality

    Time: Day 1-29
    327 Utility of Low Doses of Corticosteroids and Cyclosporine Combined With Enoxaparin, in Patients With COVID-19 Pneumonia at the ISSSTE Regional Hospital, Puebla, During the Contingency Period Due to the SARS-Cov2 Pandemic

    Methods: Single-center pilot study included PCR+ SARS-CoV2-patients, hospitalized from April to May 2020 in Puebla, Mexico. Comparative treatment with steroids plus CsA or steroids. Mild, moderate or severe pneumonia was measured by clinical, laboratory tests, lung damage score by computed tomography, and score for clinical improvement. Death rate was evaluated at 28 days.

    NCT04540926
    Conditions
    1. COVID 19 Pneumonia
    Interventions
    1. Drug: Cyclosporin A
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Improvement of patients, defined by the following parameters: lower oxygen requirements (2 liters per minute, or less), absence of fever by three consecutive days, respiratory rate <22, a decrease of 50% or more in the C reactive protein on admission, and length of hospital stay.

    Measure: Number of days to clinical improvement until hospital discharge or death.

    Time: 28 days.
    328 Evaluation of the Safety and Outcomes of Outpatient Management With Mild to Moderate COVID-19 Pneumonia (PneumoCoV-Ambu)

    The purpose of this study is to evaluate the strategy of investigators for outpatients SARS-CoV-2 moderate pneumonia management in terms of efficacy and patient safety. The investigators ultimate goal is to validate first wave management strategy in order to support the investigators future approach in the event of a second wave, and spare the hospital resources by safely keeping at home as many patients as possible.

    NCT04542044
    Conditions
    1. Covid19
    2. Pneumonia
    Interventions
    1. Other: management strategy of outpatient with mild to moderate SARS-CoV-2 pneumonia
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Measure: Secondary hospitalization(s) or death COVID-19 related

    Time: 30 to 60 days from diagnosis

    Secondary Outcomes

    Description: severity of COVID-19 disease on a 7-points ordinal scale (1: not hospitalized, no limitation of activities; 2: not hospitalized, limitation of activities; 3: hospitalized, not requiring supplementary oxygen; 4: hospitalized, requiring supplementary oxygen; 5: hospitalized, on non-invasive mechanical ventilation; 6: hospitalized, on invasive mechanical ventilation or ECMO; 7: death),

    Measure: severity of COVID-19 disease

    Time: 30 to 60 days from diagnosis

    Description: Satisfaction Survey of outpatient management

    Measure: patient satisfaction with management strategies

    Time: 30 to 60 days from diagnosis

    Description: estimation of saved costs compared with a strategy of hospitalization of all COVID-19 related pneumonia cases.

    Measure: Saved costs

    Time: 30 days
    329 A Phase 1/2 Open Label, Multicenter, Single Arm Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of Single Dose Kamada Anti-SARS-CoV-2 in COVID-19 Hospitalized Patients With Pneumonia

    Evaluate the safety pharmacokinetics and pharmacodynamics (PK/PD)of a single dose of Kamada anti-severe acute respiratory syndrome (SARS)- CoV-2 in patients hospitalized with COVID-19 caused pneumonia

    NCT04550325
    Conditions
    1. Covid19
    2. Pneumonia, Viral
    Interventions
    1. Biological: Kamada Anti-SARS-CoV-2
    MeSH:Pneumonia, Viral Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Record adverse events, serious adverse events, and deaths

    Measure: Adverse events, serious adverse events, and deaths

    Time: 14 days

    Description: Record adverse events, serious adverse events, and deaths

    Measure: Adverse events, serious adverse events, and deaths

    Time: 28 days

    Secondary Outcomes

    Description: Measurement of the area under the curve of anti SARS CoV-2 immunoglobulin

    Measure: AUC0-7 of Anti SARS CoV-2 antibodies

    Time: 7 days

    Description: Evaluate virus neutralization activity of patient's plasma

    Measure: Neutralization activity

    Time: 7 days

    Other Outcomes

    Description: Time patient spent in hospital

    Measure: Duration of Hospitalization

    Time: 84 days

    Description: Score on the 6 point ordinate scale

    Measure: Clinical status on the 6 point ordinate scale

    Time: 84 days
    330 Evaluation of a Chest X-Ray AI Neural Network (RadGen SARS-CoV2 Detection System) for the Detection of RT-PCR Confirmed SARS-Cov2 Covid-19 Pneumonia

    This study investigates the diagnostic performance of an AI algorithm in the detection of COVID-19 pneumonia on chest radiographs.

    NCT04561024
    Conditions
    1. Covid19
    Interventions
    1. Diagnostic Test: AI model
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Performance (accuracy, sensitivity, specificity, false-positive rate (FPR), false-negative rate (FNR), and Area Under the Curve (AUC)) of the AI model in detection of COVID-19 pneumonia on their baseline CXR using RT-PCR and historical controls as gold standard in a multi-center / multi-national cohort.

    Measure: Diagnostic Performance of AI model

    Time: 9 months
    331 A Phase 2, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of EG-HPCP-03a Compared to Dexamethasone in Patients With Moderate/Severe (Non-intubated, Non-mechanical Ventilation) COVID-19 Pneumonia

    To study signals of efficacy and safety of a currently available dosage form (IM) of EG-HPCP-03a in reducing the severity of respiratory disease in patients hospitalized with SARS-CoV-2 virus.

    NCT04561180
    Conditions
    1. Pneumonia as One of the Lung Complications Caused by SARS-CoV-2 Infection
    Interventions
    1. Drug: EG-HPCP-03a
    2. Drug: EG-HPCP-03a Placebo
    3. Drug: Standard of Care
    4. Drug: Dexamethasone
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Patients will be assessed for COVID-19 Ordinal Scale for Clinical Improvement scores and respiratory status throughout the study

    Measure: The proportion of patients alive and without respiratory failure

    Time: First dose date to 28 days treatment dosing period
    332 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
    333 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
    334 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
    335 Effectiveness of an Exercise Re-training Program on Dyspnea in Patients After Acute Respiratory Distress Syndrome Secondary to Severe COVID-19 Pneumonia in Post-ICU

    Dyspnea is defined by a subjective sensation of respiratory discomfort, the intensity of which varies according to the terrain, the anamnesis and the cause. Resuscitation is associated with many causes of dyspnea, including initial distress, mechanical ventilation, or after-effects following the pathology and its management. Respiratory distress is the most severe form of impaired lung function. It is the first cause of hospitalization in intensive care. This distress, indicative of the failure of the respiratory system, is always severe and potentially fatal. It therefore constitutes an absolute therapeutic emergency. Dyspnea is often the revealing symptom of the condition and the urgency surrounding its management is an additional factor of concern for the patient. As a result, dyspnea is a pejorative element associated with severity or even death.

    NCT04569266
    Conditions
    1. Dyspnea
    Interventions
    1. Other: specific exercise rehabilitation treatment
    MeSH:Pneumonia Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Dyspnea
    HPO:Dyspnea Pneumonia Respiratory distress

    Primary Outcomes

    Description: Multidimensional Dyspnea Profile (MDP) scale assessment of dyspnea

    Measure: Evaluate the effect of exercise rehabilitation on post-ICU dyspnea

    Time: Day 1

    Description: Multidimensional Dyspnea Profile (MDP) scale assessment of dyspnea

    Measure: Evaluate the effect of exercise rehabilitation on post-ICU dyspnea

    Time: 3 Months

    Secondary Outcomes

    Description: Assessment of dyspnea on the Modified Medical Research Council (mMRC) scale

    Measure: Evaluate the effect of exercise rehabilitation on functional dyspnea

    Time: Day 1

    Description: Assessment of dyspnea on the Modified Medical Research Council (mMRC) scale

    Measure: Evaluate the effect of exercise rehabilitation on functional dyspnea

    Time: 3 Months

    Description: Short-Form Quality of Life Assessment (SF-12)

    Measure: Evaluate the effect of stress rehabilitation on quality of life

    Time: Day 1

    Description: Short-Form Quality of Life Assessment (SF-12)

    Measure: Evaluate the effect of stress rehabilitation on quality of life

    Time: 3 Months
    336 Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) Inhalation to Prevent ARDS in COVID-19 Pneumonia (GI-COVID)

    To assess the safety and tolerability of inhaled molgramostim nebuliser solution in patients with COVID-19 pneumonia.

    NCT04569877
    Conditions
    1. Severe Acute Respiratory Syndrome (SARS) Pneumonia
    2. COVID-19 Pneumonia
    Interventions
    1. Drug: Molgramostim nebuliser solution
    2. Other: Placebo nebuliser solution
    MeSH:Severe Acute Respiratory Syndrome Coronavirus Infections Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Need for mechanical ventilation within 15 days after randomization

    Measure: Mechanical ventilation

    Time: During 15 days

    Secondary Outcomes

    Description: 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 of subject at day 15 and day 29 (on a 7-point ordinal scale):

    Time: At day 15 and day 29

    Description: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] will be measured at day 0 (day before first dose), day 1-9, and day 15

    Measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

    Time: At day 0 (day before first dose), day 1-9, and day 15

    Description: Need for oxygen supply (l/min) to reach peripheral oxygen saturation of 98%

    Measure: Oxygen supply

    Time: At day 0, day 1-7, day 8-9 (24 hours/48 hours post dose) and day 15

    Description: Clinical parameter (4 times daily): temperature (°C degree)

    Measure: Clinical parameter: temperature

    Time: Max. 48 hours before day 0, at day 0, day 1-7, day 8-9 and day 15

    Description: Clinical parameter (4 times daily): blood pressure (mmHg)

    Measure: Clinical parameter: blood pressure

    Time: Max. 48 hours before day 0, at day 0, day 1-7, day 8-9 and day 15

    Description: Clinical parameter (4 times daily): hear beat (beats per minute)

    Measure: Clinical parameter: heart beat

    Time: Max. 48 hours before day 0, at day 0, day 1-7, day 8-9 and day 15

    Description: Clinical parameter (4 times daily): respiratory rate (breaths per minute)

    Measure: Clinical parameter: respiratory rate

    Time: Max. 48 hours before day 0, at day 0, day 1-7, day 8-9 and day 15

    Description: Presence of Severe acute respiratory syndrome coronavirus 2 nucleic acid by PCR test in swabs or tracheal aspirates/bronchoalveolar lavage

    Measure: Severe acute respiratory syndrome coronavirus 2 polymerase chain reaction (PCR)

    Time: Max. 48 hours before day 0 and at day 8-9

    Description: C-reactive protein test measures the amount of C-reactive protein in blood (mg/L)

    Measure: Laboratory: C-reactive protein test

    Time: At day 0, day 1-7, day 8-9 and day 15

    Description: Ferritin test measures the amount of ferritin in the blood (ng/ml)

    Measure: Laboratory: ferritin

    Time: At day 0, day 1-7, day 8-9 and day 15

    Description: Interleukin-6 test (IL-6) measures the amount of IL-6 in the blood (pg/ml)

    Measure: Laboratory: Interleukin-6

    Time: At day 0, day 1-7, day 8-9 and day 15

    Description: Procalcitonin (PCT) test measures the amount of PCT in the blood in (μg/l)

    Measure: Laboratory: procalcitonin

    Time: At day 0, day 1-7, day 8-9 and day 15

    Description: Occurrence of secondary bacterial pneumonia

    Measure: Bacterial pneumonia

    Time: At day 0, day 1-7, day 8-9 and day 15

    Description: Days on vaso-active drugs in a 29-day period

    Measure: Vaso-active drugs

    Time: At day 29

    Description: All-cause mortality

    Measure: Mortality

    Time: At day 29

    Description: GM-CSF levels in serum

    Measure: GM-CSF

    Time: At day 0 and day 1-7
    337 Open Clinical Trial of the Use of Antioxidants and Pentoxifylline as Adjuvant Therapy to Standard Therapy in Patients With and Without Septic Shock Secondary to COVID-19 Severe Pneumonia

    Introduction: SARS-CoV2 infection produces severe pneumonia with pulmonary alveolar collapse. There is no specific treatment to date. In experimental models and humans with septic shock, there is a high production of nitric oxide (NO) and reactive nitrogen species (RNS) and can cause multiple organ failure. The administration of antioxidants such as n-acetylcysteine (NAC), vitamin C, melatonin, and vitamin E participate in increasing the intracellular content of GSH, ROS sequestration, protection of the lipids of cell membranes, cytosol proteins, nuclear DNA, mitochondrial and decrease LPO. Justification: as there is no specific antiviral therapy, the therapeutic options are limited, complications and mortality are high; It is intended to evaluate the effect of antioxidants on the storm outcome of the dysregulation of oxidative stress. Hypothesis: It is postulated that adjuvant therapy with antioxidants and Pentoxifylline reduces the use of ventilators in patients with or without septic shock secondary to severe SARS-COV2 pneumonia as decreases lipoperoxidation, and corrects dysregulation of oxidative stress by increasing the antioxidant capacity. Objectives: To evaluate whether it is possible to avoid intubation or decrease assisted mechanical ventilation days, improve oxidative stress dysregulation in patients with SARS-COV2 infection with severe pneumonia with or without septic shock. Methodology: Quasi-experimental, open analytical, prospective, and longitudinal study (before-after). In patients over 18 years of age who are admitted to the CITIBANAMEX Center with or without septic shock secondary to severe SARS-COV2 pneumonia. There will be two groups: 1) patients without septic shock and 2) patients with septic shock secondary to severe pneumonia due to SARS-COV2. A single antioxidant will be applied following the clinical decision tree (NAC, Vit C, Vit E, melatonin) more Pentoxifylline orally or by orogastric tube for a total of 5 days from the start of the protocol. APACHE II will calculate the risk, SOFA, MEXSOFA, measurements of IL-8, vitamin C, NO3 / NO2, LOP, total antioxidant capacity will be carried out at baseline and 48 hours. SOFA will be calculated for seven days, in addition to days of hospitalization, days of mechanical ventilation. It was evaluated 28 days after discharge by telephone.

    NCT04570254
    Conditions
    1. Pneumonia, Viral
    2. Covid19
    3. ARDS
    4. Oxidative Stress
    Interventions
    1. Drug: Vitamin C
    2. Drug: Vitamin E
    3. Drug: Melatonin
    4. Drug: N-acetyl cysteine
    5. Drug: Pentoxifylline
    MeSH:Pneumonia, Viral Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: It will be evaluated whether secondary to SARS-COV2 pneumonia, the outcome of the patient is dead.

    Measure: Death from any cause

    Time: From admission to discharge, up to 30 days.

    Description: The percentage of patients with SARS-COV2 pneumonia in whom orotracheal intubation was avoided will be evaluated.

    Measure: Percentage of patients who required orotracheal intubation

    Time: From admission to discharge, up to 1 week

    Description: It will be evaluated if it is possible to reduce the days of mechanical ventilation

    Measure: Assisted mechanical ventilation

    Time: From admission to discharge, up to 1 week

    Description: The number of days of stay in the intensive care unit will be evaluated.

    Measure: Stay in an intensive care unit

    Time: From admission to discharge, up to 1 week

    Secondary Outcomes

    Description: For the measurement of lipid peroxidation, 50 µL of CH3-OH with 4% BHT plus a phosphate buffer pH 7.4 was added to 100 µL of plasma. The mixture was vigorously vortexed for 5 seconds and subsequently incubated in a water bath at 37 ° C for 30 minutes. 1.5 mL of 0.8 M tribarbituric acid was added to the sample, which was incubated in a water bath with boiling temperature for one hour. After this time and to stop the reaction, the sample was placed on ice; 1 mL 5% KCl was added to each sample, as was 4 mL of n-butanol; The sample was vortexed for 30 seconds and centrifuged at 4000 rpm at room temperature for 2 min. Subsequently, the butanol phase was extracted, and the absorbance at 532 nm was measured. The calibration curve was obtained using tetra ethoxy propane as a standard.

    Measure: Measure lipoperoxidation in basal and post-therapy samples

    Time: Baseline and 5 days post-dose

    Description: 100 mL of plasma was suspended in 1.5 mL of a reaction mixture prepared as follows: 300 mM of acetate buffer with pH 3.6, 20 mM of ferric chloride hexahydrate, and 10 mM of 2,4,6-Tris-2- Pyridyl-s-triazine dissolved in 40 mM hydrochloric acid in a ratio 10: 1: 1 v / v, respectively. The mixture was vigorously vortexed for 5 seconds. It was incubated at 37 ° C for 15 min in the dark. The absorbance was measured at 593 nm. The calibration curve was obtained using Trolox

    Measure: Evaluation of the total antioxidant capacity

    Time: Baseline and 5 days post-dose

    Description: For the measurement of NO3- / NO2-, 100 µl of plasma were added 100 µL of a 10% solution of ZnSO4, 100 µL of 0.5 N NaOH and 700 µl of tridestated water. It was shaken vigorously and centrifuged at 10,000 rpm for 5 minutes. To the resulting supernatant, Griess reagent (200 µL of 1% sulfanilamide and 200 µL of 1% N- (1-naphthyl) ethylenediamine hydrochloride) was added and incubated for 10 min protected from light at room temperature. The coloration developed after incubation was measured at an analytical wavelength of 540 nm in a double beam UV-Vis spectrometer (DW2000, SLM-Aminco, Urbana, Illinois, USA). The calibration curve was performed with a KNO3 stock solution (Spectrum Quality Products, Inc., Gardena CA) in a concentration range from 0.001 nM to 10 nM.

    Measure: Oxidative and antioxidant stress

    Time: Baseline and 5 days post-dose

    Description: Measurements will be made using the Sequential Organ Failure Assessment (SOFA) every 24 hours. With a minimum score of 0-1 which translates a mortality in initial score and the highest of 0%. The maximum score of more than 14 translates a mortality of 95.2% in the initial evaluation and 89.7% in the highest evaluation.

    Measure: Effect of antioxidant therapy at the level on organ failure secondary to SARS-COV2

    Time: From day 0 to day 7 post antioxidant dose.

    Description: Measurements will be made using the Mexico Sequential Organ Failure Assessment (MEXSOFA) every 24 hours. highest evaluation. Patients with an initial MEXSOFA score of 9 points or less calculated during the first 24 hours after admission to the ICU had a mortality rate of 14.8%, while those with an initial MEXSOFA score of 10 points or more had a mortality rate. 40% mortality rate. The MEXSOFA score at 48 h was also associated with mortality: patients with a score of 9 points or less had a mortality rate of 14.1%, while those with a score of 10 points or more had a rate of 50% mortality.

    Measure: Effect of antioxidant therapy at the level on organ failure secondary to SARS-COV2

    Time: From day 0 to day 7 post antioxidant dose.
    338 Low Dose Lung Radiotherapy to Treat COVID-19 Pneumonia (a Phase I Feasibility Trial)

    The purpose of this study is to document the feasibility and tolerability of low dose thoracic radiotherapy in patients with WHO level 5 COVID 19 infections.

    NCT04572412
    Conditions
    1. Covid19
    Interventions
    1. Radiation: Low dose Radiotherapy
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Feasibility to recruit to the study.

    Measure: Feasibility of Recruitment

    Time: 6 months

    Description: Proportion of patients with no decline in PaO2/FiO2 ratio (P/F Ratio) at 48 hours after each fraction of radiotherapy

    Measure: Tolerability of Low dose Radiotherapy

    Time: 48 hours

    Secondary Outcomes

    Description: The number of patients who withdraw from the study

    Measure: Withdrawal

    Time: 6 months

    Description: The number of Grade 4 or higher CTCAE v5 (apart from asymptomatic lymphopenia) adverse events reported

    Measure: Adverse events

    Time: 1 month

    Description: Ability to perform lymphocyte subset, IL-6, and IL-10 analysis at baseline and 7 days post last fraction of radiotherapy

    Measure: Feasibility of biochemical analysis

    Time: 1 week
    339 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.
    340 Risk Factors, Prognosis and Findings by Computed Tomography in Patients Infected by COVID-19 and Its Association With Severity.

    In the SARS-CoV2 pandemic, imaging studies proved its diagnostic utility to determine the severity of lung involvement. Computed tomography (CT) is a state-of-the-art study proven to be a highly sensitive diagnostic test complemented by RT-PCR testing to determine the disease and the degree of severity. In March 2020, the Dutch Society of Radiology developed a standardized assessment scheme for COVID-19 lung disease, called CO-RADS. This system proposes a level of suspicion of pulmonary involvement of COVID-19, based on the simple chest tomography findings. The level of suspicion ranges from very low (CO-RADS 1) to very high (CO-RADS 5), with two additional categories involving a technically deficient study (CO-RADS 0) and a positive RT-PCR test for SARS -CoV-2 known before tomography (CO-RADS 6). For its part, acute respiratory damage secondary to SARS-COV2 pneumonia causes acute respiratory distress syndrome, which warrants immediate medical attention. During the evaluation and triage of patients with suspected or confirmed SARS-COV2 infection, it is a challenge for health personnel given that the severity and clinical presentation is highly variable. The patient's risk stratification is carried out using previously established and validated risk scales and is a fundamental tool for making clinical decisions. Some of the risk indices and scales have been developed and used in the pandemic epicenters, such as China and Europe. Useful for the clinician is the national early warning scale (NEWS 2), severe disease risk assessment score (COVID-GRAM), the rapid severity index for COVID-19 (qCSI), evaluation score of Modified sequential organ failure (mSOFA), the sepsis-induced coagulopathy score (SIC), the ROX index as a predictor of success to the high-flow nasal cannula. The evaluation of the risk of thrombotic complications such as the Padua risk, of cardiac complications such as QT segment prolongation, through the Tisdale risk score. Risk stratification is essential in the current COVID-19 pandemic situation; upon admission, the clinician will discern if the patient requires in-hospital medical treatment, the risk of severe disease, and progression to assisted mechanical ventilation. This work aims to establish whether the severity of the findings identified by cardiac tomography upon admission and the risk established by the different established prognostic indices.

    NCT04577105
    Conditions
    1. Covid19
    2. ARDS
    3. Pneumonia, Viral
    4. Computed Tomography
    Interventions
    1. Diagnostic Test: Simple chest tomography
    MeSH:Pneumonia, Viral Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: CO-RADS will categorize the level of suspicion of COVID-19. Very low (CO-RADS 1) to very high (CO-RADS 5), with two additional categories involving a technically deficient study (CO-RADS 0) and a positive RT-PCR test for SARS-CoV- 2 known before tomography (CO-RADS 6).

    Measure: Assessment of the level of suspicion of SARS-CoV2 infection

    Time: At hospital admission

    Description: It will be a semi-quantitative assessment of lung lobe lesions' extent considering five lobes (upper right lobes, middle lobe, lower right lobe, upper left lobe, and lower left lobe). Each of these lobes, depending on their condition, is scored from 1 to 5, with 1 <5%, 2 from 5 to 25%, 3> 25 to 50%, 4 from> 50 to 75% and the number 5 greater than 75%. With this, it is grouped into mild affection from 1 to 5 points, moderate from 5 to 15 points, and greater than 15 points as severe affection

    Measure: Evaluate the severity degree of pulmonary affection by chest computed tomography

    Time: At hospital admission

    Description: The requirement for orotracheal intubation and the start of assisted mechanical ventilation after admission will be evaluated

    Measure: Percentage of patients requiring endotracheal intubation

    Time: From admission to discharge, up to 1 week

    Description: Patients who present fatal descent during hospitalization will be evaluated.

    Measure: Death from any cause

    Time: From admission to discharge, up to 1 week

    Secondary Outcomes

    Description: The evaluation of multiple organ failure secondary to sepsis will be carried out using the mSOFA scale, which can predict in-hospital mortality and 30 days, with a minimum score of 0-7 that translates mortality of 0% and a score greater than 11 translates mortality of 58%.

    Measure: Modified Sequential Organ Failure Assessment (mSOFA)

    Time: At hospital admission

    Description: The sepsis-induced coagulopathy score scale (SIC) refers to the diagnosis of coagulopathy when the score is greater than 4 or the INR is greater than or equal to 3.

    Measure: Sepsis-induced coagulopathy (SIC)

    Time: At hospital admission

    Description: A score of 0-4 confers a low risk; on the contrary, a score of more than 7 gives a high risk.

    Measure: National Early Warning Scale (NEWS 2)

    Time: At hospital admission

    Description: It establishes three risk groups: the mild one with a risk of critical illness of less than 1.7% and the high risk of more than 40.4%.

    Measure: COVID-GRAM severe illness risk score

    Time: At hospital admission

    Description: A score less than or equal to 3 gives a low risk with a critical illness risk of 4%, while a score of 10-12 gives a high risk and a critical illness probability of 57%.

    Measure: Rapid Severity Index for COVID-19 (qCSI)

    Time: At hospital admission

    Description: A ratio of 6-8 translates mild physiological stress, while a ratio of more than 18 a severe physiological stress level.

    Measure: Neutrophil-Lymphocyte Ratio (NLR)

    Time: At hospital admission

    Description: The gradient Aa O2 = [(FiO2) × (Atmospheric pressure - Pressure of H2O) - (PaCO2 / 0.8)] - PaO2 of ABG is calculated and a normal gradient with age is estimated with the following formula: Estimate of normal gradient = (Age / 4) + 4. The gradient is increased in conditions such as ARDS, PE, and cardiac failure.

    Measure: Alveolar-arterial gradient of oxygen

    Time: At hospital admission

    Description: Required criteria (must have all three of the following): Timing within 1 week of clinical insult or new/worsening respiratory symptoms, Chest XR shows bilateral opacities not fully explained by effusions, lobar/lung collapse, or nodules Respiratory failure not fully explained by cardiac failure/fluid overload Risk factor (one of the following): Risk factor for ARDS present (e.g. pneumonia, trauma, sepsis, pancreatitis). Objective assessment (Echo) excludes hydrostatic edema. Severity (based on oxygenation, select one of the following): Mild: PaO₂/FiO₂ >200 to ≤300 mmHg with PEEP OR CPAP ≥5 cm H₂O, Moderate: PaO₂/FiO₂ >100 to ≤200 mmHg with PEEP ≥5 cm H₂O and Severe: PaO₂/FiO₂ ≤100 mmHg with PEEP ≥5 cm H₂O

    Measure: Berlin Criteria for Acute Respiratory Distress Syndrome

    Time: At hospital admission
    341 A Phase I/II Dose-escalation Multi Center Study to Evaluate the Safety of Infusion of NatuRal KillEr celLs or MEmory T Cells as Adoptive Therapy in coronaviruS pnEumonia and/or Lymphopenia

    This is a phase I/II clinical trial using adoptive cell therapy with NK cells or memory T cells in patients affected by COVID-19. Severe cases with COVID-19 present a dysregulated immune system with T cell lymphopenia, specially NK cells and memory T cells, and a hyper-inflammatory state. This clinical trial proposes the use of cell therapy for the treatment of patients with worse prognosis due to SARS-CoV-2 infection (those with pneumonia and/or lymphopenia). This is an innovative and a non-pharmacological intervention.

    NCT04578210
    Conditions
    1. Corona Virus Infection
    Interventions
    1. Biological: T memory cells and NK cells
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia Lymphopenia
    HPO:Lymphopenia Pneumonia

    Primary Outcomes

    Description: Any grade 3 or higher toxicity with an attribution of definitely or probably related to the infusion of the cells and any lower grade toxicity that increases to a grade 3 or higher as a direct result of the cell infusion.

    Measure: Occurrence of DLTs in all patients during the study treatment, until 21 days after cell infusion and the MTD

    Time: 3 months
    342 Randomised Multi-arm Trial of Ruxolitinib (RUX) and Fostamatinib (FOS) for COVID-19 Pneumonia

    The Multi-arm trial of Inflammatory Signal Inhibitors for COVID-19 (MATIS) study is a two-stage, open-label, randomised controlled trial assessing the efficacy of ruxolitinib (RUX) and fostamatinib (FOS) individually, compared to standard of care in the treatment of COVID-19 pneumonia. The primary outcome is the proportion of hospitalised patients progressing from mild or moderate to severe COVID-19 pneumonia. Patients are treated for 14 days and will receive follow-up assessment at 7, 14 and 28 days after the first study dose. Patients with mild or moderate COVID-19 pneumonia will be recruited. Initially, n=171 (57 per arm) patients will be recruited in Stage 1. Following interim analysis to assess the efficacy and safety of the treatments, approximately n=285 (95 per arm) will be recruited during Stage 2.

    NCT04581954
    Conditions
    1. Coronavirus
    2. Covid19
    3. Pneumonia
    Interventions
    1. Drug: Ruxolitinib
    2. Drug: Fostamatinib
    3. Other: Standard of care
    MeSH:Coronavirus Infections Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Measure: All-cause mortality

    Time: Day 14

    Measure: Number and proportion of patients requiring invasive ventilation

    Time: Day 14

    Measure: Number and proportion of patients requiring non-invasive ventilation (CPAP and high flow nasal oxygen)

    Time: Day 14

    Secondary Outcomes

    Measure: All-cause mortality

    Time: Day 28

    Measure: Number and proportion of patients requiring invasive ventilation or extracorporeal membrane oxygenation (ECMO)

    Time: Day 14, 28

    Measure: Number and proportion of patients requiring non-invasive ventilation including continuous positive airway pressure (CPAP) or high flow nasal oxygen

    Time: Day 14, 28

    Measure: Number and proportion of patients requiring renal replacement therapy

    Time: Day 14, 28

    Measure: Number and proportion of patients experiencing venous thromboembolism events

    Time: Day 14, 28

    Measure: Length of stay

    Time: Day 14, 28

    Measure: Number and proportion of serious adverse events and discontinuations

    Time: Day 14, 28

    Description: Scale range from 0 (uninfected) to 9 (dead)

    Measure: Absolute change in pneumonia severity on the modified WHO COVID-19 Ordinal Scale

    Time: Day 14, 28
    343 D-dimer Adjusted Versus Therapeutic Dose Low-molecular-weight Heparin in Patients With COVID-19 Pneumonia

    evaluation of the efficacy and safety of D-dimer adjusted heparin versus therapeutic dose heparin in patients with COVID-19 Pneumonia.

    NCT04584580
    Conditions
    1. Coronavirus Disease (COVID)19
    Interventions
    1. Drug: low-molecular-weight heparin
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: All cause mortality

    Measure: mortality

    Time: Until patient is discharged or up to 4 weeks whichever comes first

    Description: clinical signs supported by radiological evidence of arterial thrombosis or venous thromboembolism (e.g. venous or arterial duplex and CT scan of the chest with pulmonary angiography)

    Measure: occurrence of venous and/or arterial thrombosis

    Time: Until patient is discharged or up to 4 weeks whichever comes first

    Secondary Outcomes

    Description: calculation of sepsis induced coagulopathy (SIC) score

    Measure: occurrence of Sepsis-induced coagulopathy

    Time: Until patient is discharged or up to 4 weeks whichever comes first

    Description: Calculation of partial pressure of arterial oxygen/ fraction of inspired oxygen (PaO2/ FIO2) ratio

    Measure: Occurrence of adult respiratory distress syndrome (ARDS)

    Time: Until patient is discharged or up to 4 weeks whichever comes first

    Description: Calculation of sequential organ failure (SOFA) score

    Measure: Occurrence of sepsis

    Time: Until patient is discharged or up to 4 weeks whichever comes first

    Description: occurrence of respiratory failure detected by arterial blood gases analysis

    Measure: ICU admission and need for mechanical ventilation

    Time: Until patient is discharged or up to 4 weeks whichever comes first
    344 Prone Position to Improve Oxygenation in COVID-19 Patients Outside Critical Care (PRONE-COVID Study)

    Prone positioning is known to improve the PaO2/FiO2 ratio and reduce mortality in patients with ARDS managed in the critical care setting. Therefore, it is incorporated into regular clinical practice of managing patients with ARDS in critical care and is being used as such in the COVID-19 outbreak. Given that prone positioning is recommended by the Intensive Care Society in non-ventilated patients with COVID-19, there is an urgent need to better understand the physiological effects of prone positioning in such cases. Furthermore, the translation and applicability of such a low-cost non-invasive intervention in a wider group of patients with pneumonia not specific to covid-19 infection, is an important consideration that merits investigation. This single-centred observational study conducted at Cambridge University Hospitals NHS Foundation Trust aims to improve understanding of physiological effects of prone positioning in non-ventilated patients with COVID-19 and a control group of patients with non-COVID-19 related pneumonia. The study also aims to incorporate a small subset of patients, with an approximately even spread of COVID-19 and non-COVID cases, which allows for an additional exploratory descriptive report on prone positioning over a 24-hour period. This study proposes that prone positioning improves oxygenation in non-ventilated patients with pneumonia (COVID-19 related or not) requiring supplemental oxygen managed outside of the critical care setting.

    NCT04589936
    Conditions
    1. Pneumonia
    2. Covid19
    Interventions
    1. Procedure: Prone positioning
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Oxygenation measured by peripheral saturations in relation to inspired oxygen (FiO2) when patient is prone versus a supine or lateral position using a Masimo device

    Measure: Peripheral Oxygen saturation

    Time: 1 year (June 2021)

    Secondary Outcomes

    Description: To evaluate effects of prone position versus supine or lateral position on derived measures of oxygenation (Pa02:Fi02 ratio calculated from formulae) in relation to inspired oxygen.

    Measure: PaO2 :FiO2 ratio calculated from formulae

    Time: 1 year (June 2021)

    Description: Effects of prone versus supine or lateral position on respiratory rate

    Measure: Respiratory rate measured with Masimo device

    Time: 1 year (June 2021)

    Description: Effects of prone versus supine or lateral position on heart rate

    Measure: Heart rate measured with Masimo device

    Time: 1 year (June 2021)

    Description: Effects of prone versus supine or lateral position on blood pressure

    Measure: Blood pressure measured with Masimo device

    Time: 1 year (June 2021)

    Description: To evaluate whether prone position reduces patient reported severity of breathlessness assessed by visual assessment score.

    Measure: Patient reported severity of breathlessness on a continuous linear scale of 0 to 10cm (10cm being the most severe)

    Time: 1 year (June 2021)

    Description: To evaluate patient tolerability of prone position assessed by visual assessment score.

    Measure: Patient tolerability of prone position on a continuous linear scale of 0 to 10cm (10cm being the most unacceptable)

    Time: 1 year (June 2021)

    Description: To evaluate investigator experience of delivering prone positioning in this study by free text question responses.

    Measure: Investigator experience of delivering prone positioning

    Time: 1 year (June 2021)

    Description: To evaluate the natural position of patients (with the aid of position sensors) who are encouraged to position themselves prone over a 24-hour period (which include sleep) and relationship with oxygenation

    Measure: To assess patient's peripheral oxygen saturation

    Time: 1 year (June 2021)
    345 Myeloid Cells in Patients With Covid-19 Pneumonia

    The purpose of this study is to analyze in depth the relationship of myeloid cell subpopulations during infection by Severe acute respiratory syndrome coronavirus 2 (SARS-Cov2), the virus mediating Covid-19. Myeloid cells include neutrophils, monocytes and dendritic cells, each divided into subpopulations with different functions in immune defense and immune pathologies. The study is based on the following hypotheses: - Infection and the interferon response to infection may induce hyperactive or immunosuppressive differentiation of myeloid cells, that may be treated by specific inhibitors. - Some myeloid cell subpopulations currently identified in our laboratories might be markers for Covid-19 prognosis. - Alternative receptors may be present on myeloid cells, inducing the cytokine storm, a target for therapy. - The expression of Interferon (IFN) receptor and IFN responding genes on myeloid cells and on respiratory epithelial cells may correlate with prognosis and indicate potential treatment targets. - Interferon responses are known to be skewed during Covid-19, but some IFN subtype polymorphisms may correlate with prognosis and these subtypes migt be supplemented or inhibited for therapy.

    NCT04590261
    Conditions
    1. Covid-19; SARS-Cov2
    Interventions
    1. Other: Blood sampling
    2. Other: Nasal Brushing
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Cytometric analysis of surface and intracellular molecules to identify myeloid cell sub-populations and define their function in vivo

    Measure: Myeloid cell sub-population phenotype

    Time: Month zero-month 36

    Secondary Outcomes

    Description: Cell culture and cytometric and analyte analysis of their functions, including IFN production

    Measure: Myeloid cell functions

    Time: Month zero-month 36

    Description: Transcriptomic and proteomic analysis of the functions of myeloid cell subtypes

    Measure: Myeloid cell transcriptomic and proteomic study

    Time: Month zero-month 36

    Description: Single cell RNA sequencing of the nasal brush products

    Measure: Transcriptomic study of nasal epithelial cells

    Time: Month zero-month 36

    Description: High sensitivity detection by state-of-the art ELISA type methods

    Measure: Plasma analyte concentration measurement

    Time: Month zero-month 36
    346 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
    347 Evaluation of Post Infectious Inflammatory Reaction (PIIR) in a Retrospective Study Concerning Children After Streptococcus Pneumoniae, Streptococcus Pyogenes and Neisseria Meningococcus Invasive Infection

    As Covid 19 manifestations that have been recently described, inflammatory manifestation have major impact in infectious disease lesions. Some of them are delayed and provide Post infectious inflammatory reaction (PIIR), they are challenging for diagnosis and for management. Clinician have to avoid unnecessary antibiotic thearapy and in if necessary have to give immunosuppressive therapy. Except for rheumatic disease for group A streptococcus (GAS) infections there are not stanrdized diagnostic criteria and therapeutic protocol, and PIIR have probably a suboptimal management. In this context the investigators aim to explore PIIR in the 3 most frequent bacterial invasive infection in France, by a retrospective monocentric study. The investigators include all children betwwen 2012 and 2018 hospitalized for infections by Streptococcus pneumoniae (SP), Neisseria meningitidis (NM), and GAS invasive infections.

    NCT04594785
    Conditions
    1. Streptococcus Pneumonia
    2. Streptococcus Pyogenes Infection
    3. Neisseria Meningitides Meningiti
    4. Neisseria Meningitides Meningitis
    MeSH:Infection Communicable Diseases Meningococcal Infections Meningitis, Meningococcal Pneumonia Meningitis Inflammation
    HPO:Meningitis Pneumonia

    Primary Outcomes

    Description: Describe the frequency PIIRs following invasive pneumococcal, meningococcal, or group A Streptococcal infection

    Measure: Describe the frequency PIIRs

    Time: 1 day

    Secondary Outcomes

    Description: Describe the characteristics PIIRs following invasive pneumococcal, meningococcal, or group A Streptococcal infection

    Measure: Characteristics PIIRs following invasive pneumococcal, meningococcal, or group A Streptococcal infection

    Time: 1 day

    Other Outcomes

    Description: Identified the predictors of PIIRs in order to find warning symptoms

    Measure: Predictors of PIIRs

    Time: 1 day
    348 Long-term Follow-up Findings of Inpatients for COVID-19 Pneumonia Related to Lung Functions, Radiology and Exercise Capacity

    Coronavirus disease 2019 (COVID-19) is a respiratory tract infection caused by a newly emergent coronavirus (SARS-CoV-2) that can progress to severe multiorgan disease requiring hospitalization. The medium and long-term impact in survivors of COVID-19 on lung function, imaging by thoracic CT, exercise capacity, and health-related quality of life and the relation of these parameters remains to be determined.

    NCT04599998
    Conditions
    1. Covid19
    Interventions
    1. Diagnostic Test: spirometry, thoracic CT, CPET, 6 minute walking test, SF-36 questionnaire
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: in ml

    Measure: Forced vital capacity (FVC)

    Time: at 6-12 months after discharge

    Description: DLCO (%predicted); DLCO/alveolar volume- DLCO/VA (%predicted)

    Measure: Lung diffusion capacity for carbon monoxide (DLCO)

    Time: at 6-12 months after discharge

    Description: m

    Measure: 6-minute walk test distance

    Time: at 6-12 months after discharge

    Description: scores range between 0 and 100 with higher scores indicating a better HRQoL

    Measure: Short-form 36 questionnaire (SF-36)

    Time: at 6-12 months after discharge

    Description: from incremental Cardiopulmonary exercise test (% of predicted)

    Measure: Oxygen uptake at peak exercise

    Time: at 6-12 months after discharge

    Description: from incremental Cardiopulmonary exercise test (L/L)

    Measure: Minute-ventilation/carbon dioxide output during exercise

    Time: at 6-12 months after discharge

    Description: from incremental Cardiopulmonary exercise test (measured with 10-point categorical Borg scale

    Measure: Dyspnea during exercise

    Time: at 6-12 months after discharge

    Description: lung parenchymal abnormalities as percentage of occupied lung

    Measure: Thoracic CT findings

    Time: in hospital and at 6-12 months after discharge

    Description: in ml and %predicted

    Measure: Forced expiratory volume in 1 second

    Time: at 6-12 months after discharge

    Description: in %

    Measure: FEV1/FVC ratio

    Time: at 6-12 months after discharge

    Description: in %

    Measure: Forced vital capacity %predicted (FVC%)

    Time: at 6-12 months after discharge

    Secondary Outcomes

    Description: Recorded separately as present or absent) mortality (recorded as present or absent)

    Measure: Signs and symptoms

    Time: in hospital and at 6-12 months after discharge

    Description: in days

    Measure: Time to hospital discharge

    Time: in hospital

    Description: in days

    Measure: ICU discharge

    Time: in hospital

    Description: in days

    Measure: Weaning from intubation

    Time: in hospital

    Description: in days

    Measure: Weaning from supplemental oxygen

    Time: in hospital

    Description: in days

    Measure: Weaning from noninvasive mechanical ventilation

    Time: in hospital

    Description: recorded as present or absent

    Measure: Mortality

    Time: in hospital and at 6-12 months after discharge
    349 The Extended Protocol of Evaluation of Safety and Efficiency of Method of Exosome Inhalation in COVID-19 Associated Two-Sided Pneumonia

    Coronavirus is an acute viral disease with prevailing upper respiratory tract infections caused by the RNA-containing virus of the genus Betacoronavirus of the Coronaviridae family. Most patients with severe COVID-19 develop pneumonia in the first week of the disease. As the infection progresses, the infiltration increases, and the affected areas increases. Excessive and uncontrolled immune system response with rapidly developing fatal cytokine storm plays the main role in the pathogenesis of acute respiratory distress syndrome (ARDS) due to SARS-CoV-2 infection. According to available data, exosomes can regulate inflammation and regenerative processes due to the change in the concentration of anti-inflammatory cytokines and switch the immune cell to regenerative secretome. Inhalation of exosomes may reduce inflammation and damage to the lung tissue and stimulate the regenerative processes. This protocol has been developed based on the literature, information about the ongoing tests NCT04276987 (A Pilot Clinical Study on Inhalation of Mesenchymal Stem Cells Exosomes Treating Severe Novel Coronavirus Pneumonia) and NCT04384445 (Organicell Flow for Patients With COVID-19), Patent No 271036826 of 2019. "A method for obtaining and concentrating microRNA-containing exosomal multi-potent mesenchymal-stromal cells for use in cosmetic and pharmaceutical products to stimulate regenerative processes and slow down aging.

    NCT04602442
    Conditions
    1. Covid19
    2. SARS-CoV-2 PNEUMONIA
    3. COVID-19
    Interventions
    1. Drug: EXO 1 inhalation
    2. Drug: EXO 2 inhalation
    3. Drug: Placebo inhalation
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Safety assessment such as adverse events will be registered. Adverse events will be monitored during all trial

    Measure: Number of participants with non-serious and serious adverse events during trial

    Time: through study, an average of 2 months

    Description: Safety assessments such as adverse events during the inhalation procedures will be registered.

    Measure: Number of participants with non-serious and serious adverse during inhalation procedure

    Time: 10 days during inhalation procedures

    Secondary Outcomes

    Description: Measure and compare time to clinical recovery and clinical discharge compare to placebo.

    Measure: Time to clinical recovery (TTCR)

    Time: up to 2 months

    Description: Concentration of SpO2 by Pulse oximetry device during procedures and compare to placebo.

    Measure: SpO2 concentration changes

    Time: up to 2 months

    Description: Chest imaging changes for 30 days compared to placebo. Information on the percent of damaged lungs will be analyzed and reported.

    Measure: Chest Imaging Changes

    Time: Three times. At diagnosis, 10-14 days after treatment and 30 days after clinic discharge

    Description: C-reactive protein (CRP, mg/L) concentration in the plasma will be measured. The result will be analyzed and compared in time.

    Measure: Blood biochemistry (CRP)

    Time: Baseline, day 5, 10, 20

    Description: Procalcitonin concentration in plasma (ng/mL) will be measured. The result will be analyzed and compared in time.

    Measure: Procalcitonin concentration

    Time: Baseline, day 5, 10, 20

    Description: Ferritin concentration in plasma (ng/mL) will be measured. The result will be analyzed and compared in time.

    Measure: Ferritin concentration

    Time: Baseline, day 5, 10, 20

    Description: Creatinine concentration (umol/L) in plasma will be measured. The result will be analyzed and compared in time.

    Measure: Creatinine concentration

    Time: Baseline, day 5, 10, 20

    Description: Urea concentration (mmol/L) in plasma will be measured. The result will be analyzed and compared in time.

    Measure: Urea concentration

    Time: Baseline, day 5, 10, 20
    350 Pulmonary Involvement of Novel SARS-COV-2 Infection (COVID-19): Long-term Impact and Predictors of Possible Lasting Damage: Follow the Covid Study

    In December 2019 the first case of human infection by a new coronavirus was identified, currently called SARS-COV-2 (Severe Acute Respiratory Syndrome - Coronavirus - 2), characterized by high contagiousness and the possibility of causing a severe acute respiratory distress syndrome from which its acronym derives and which caused the state of a global pandemic in a few months. The most frequent clinical manifestation of COVID-19 is pneumonia, which in about 20% of cases results in acute respiratory failure. Very few studies have so far addressed the problem of clinical and functional recovery in these patients, most of them just before or after discharge and none specifically focused on patients admitted for ARF. Indeed most of these investigations were limited to a specific field such as symptoms, pulmonary function and radiological changes. There are no guidelines for the follow-up of COVID-19 patients, despite the British Thoracic Society (BTS) has published a guidance for scheduling post-hospitalization assessments. Aim of this study is to describe the long term (6 to 12 months) evolution of lung involvement in patients discharged after an episode of ARF due to COVID-19, identifying possible factor associated to lasting clinical, functional or radiological abnormalities collecting data from hospital stay, 1-month after hospital discharge, 3-months after hospital discharge and 6-to-12-months after hospital discharge.

    NCT04605757
    Conditions
    1. SARS-COV-2 Pneumonia
    Interventions
    1. Other: Clinical, functional and radiological lung involvement evolution
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: For long term clinical evolution of SARS-COV-2 pneumonia Investigators will evaluate the presence or absence of each of the following symptoms (yes/no respectively for presence/absence): dyspnea, fatigue, cough, fever, thoracic pain, nausea, diarrhea, dysgeusia. The presence of each of these symptoms will be collected at the time of the hospital stay due to COVID-19 (H) and at 1-month after hospital discharge followup visit (V1); at 3-months after hospital discharge followup visit (V2); at 6-to-12-months after hospital discharge followup visit (V3). V3 will be performed for study subjects that at V2 show clinical and/or functional and/or radiological abnormalities due to sequelae of COVID-19. Differences in terms of presence and type of each symptoms between H, V1, V2 and V3 will be evaluated.

    Measure: Long term evolution of clinical involvement due to SARS-COV-2 pneumonia / symptoms

    Time: from hospital stay to 6-to-12 months after hospital discharge for SARS-COV-2 pneumonia.

    Description: For long term clinical evolution of SARS-COV-2 pneumonia Investigators will collect respiratory rate (RR, breaths/minute) of study subjects collected during the hospital stay due to COVID-19 (H); at V1, V2and V3. Difference in RR between H, V1, V2 and V3 will be evaluated.

    Measure: Long term evolution of clinical involvement due to SARS-COV-2 pneumonia / respiratory rate

    Time: from hospital stay to 6-to-12 months after hospital discharge for SARS-COV-2 pneumonia.

    Description: Investigators will collect: partial pressure of oxygen [paO2, mmHg], partial pressure of carbon monoxide [paCO2 mmHg], emerged from blood gas exchange analysis performed during H, V1, V2 and V3. For each parameter (paO2, paCO2) the difference between value at H, V1,V2 and V3 will be evaluated.

    Measure: Long term evolution of functional involvement due to SARS-COV-2 pneumonia - blood gas exchange parameters/partial pressure of oxygen and partial pressure of carbon monoxide

    Time: from hospital stay to 6-to-12 months after hospital discharge for SARS-COV-2 pneumonia

    Description: Investigators will collect: - ph [absolute value], emerged from blood gas exchange analysis performed during H, V1, V2 and V3. Difference between pH value at H, V1,V2 and V3 will be evaluated.

    Measure: Long term evolution of functional involvement due to SARS-COV-2 pneumonia - blood gas exchange parameters/ ph

    Time: from hospital stay to 6-to-12 months after hospital discharge for SARS-COV-2 pneumonia

    Description: Investigators will collect: - oxygen saturation [SatO2, in %]), emerged from blood gas exchange analysis performed during H, V1, V2 and V3. Difference between SatO2 value at H, V1,V2 and V3 will be evaluated.

    Measure: Long term evolution of functional involvement due to SARS-COV-2 pneumonia - blood gas exchange parameters/ oxygen saturation

    Time: from hospital stay to 6-to-12 months after hospital discharge for SARS-COV-2 pneumonia

    Description: Investigators will collect: - P/F ratio (ratio between the measured paO2 and fraction of inspired oxygen ratio) expressed in absolute ratio; emerged from blood gas exchange analysis performed during H, V1, V2 and V3. Difference between P/F ratio value at H, V1,V2 and V3 will be evaluated.

    Measure: Long term evolution of functional involvement due to SARS-COV-2 pneumonia - blood gas exchange parameters: P/F ratio

    Time: from hospital stay to 6-to-12 months after hospital discharge for SARS-COV-2 pneumonia

    Description: Investigators will consider the following parameters: forced expiratory volume in the first second [FEV1,expressed in % of predicted value]; forced vital capacity [FVC, expressed in % of predicted value]; total lung capacity [TLC, expressed in % of predicted value]; residual volume [RV, expressed in % of predicted value]; collected through pulmonary function tests performed at V1, V2 and V3. For each parameter (FEV1, FVC, TLC, RV) the difference between value at V1,V2 and V3 will be evaluated.

    Measure: Long term evolution of functional involvement due to SARS-COV-2 pneumonia - pulmonary function tests/ forced expiratory volume in the first second; forced vital capacity; total lung capacity; residual volume

    Time: from 1 month after hospital discharge for SARS-COV-2 pneumonia to 6-to-12 months after hospital discharge

    Description: Investigators will consider the following parameters: FEV1/FVC absolute ratio; RV/TLC absolute ratio; collected through pulmonary function tests performed at V1, V2 and V3. For each parameter (FEV1/FVC, RV/TLC) the difference between value at V1,V2 and V3 will be evaluated.

    Measure: Long term evolution of functional involvement due to SARS-COV-2 pneumonia - pulmonary function tests/ FEV1/FVC ratio and RV/TLC ratio

    Time: from 1 month after hospital discharge for SARS-COV-2 pneumonia to 6-to-12 months after hospital discharge

    Description: Investigators will consider diffusing capacity of carbon monoxide (DLCO), expressed in % of the predicted value collected during V1, V2 and V3. Differences in terms of DLCO values between V1, V2 and V3 will be calculated.

    Measure: Long term evolution of functional involvement due to SARS-COV-2 pneumonia - diffusing capacity of carbon monoxide

    Time: from 1 month after hospital discharge for SARS-COV-2 pneumonia to 6-to-12 months after hospital discharge

    Description: Investigators will consider 6 minute walking test [6MWT] distance, expressed in meters collected during V1, V2 and V3. Differences in terms of 6MWT distance between V1, V2 and V3 will be calculated.

    Measure: Long term evolution of functional involvement due to SARS-COV-2 pneumonia - six minute walking test distance

    Time: from 1 month after hospital discharge for SARS-COV-2 pneumonia to 6-to-12 months after hospital discharge.

    Description: Investigators will consider the presence (yes/no) of desaturation at 6MWT (defined as a difference > 3% between baseline SatO2% and minimum SatO2% during test) collected during V1, V2 and V3. Differences in terms of presence of desaturation at 6MWT between V1, V2 and V3 will be calculated.

    Measure: Long term evolution of functional involvement due to SARS-COV-2 pneumonia - presence of desaturation during six minute walking test

    Time: from 1 month after hospital discharge for SARS-COV-2 pneumonia to 6-to-12 months after hospital discharge.

    Description: For long term radiological evolution of SARS-COV-2 pneumonia Investigators will consider: presence [yes/no] of consolidation and/or ground-glass opacities at chest X-ray and high resolution computed tomography (HRCT) of the lungs, presence/absence [yes/no] of lung abnormalities in lung ultrasound (LUS) evaluation, collected each during H, V1, V2 and V3. Differences between H,V1,V2 and V3 for each characteristics will be described.

    Measure: long term evolution of radiological involvement due to SARS-COV-2 pneumonia

    Time: from hospital stay to 6-to-12 months after hospital discharge for SARS-COV-2 pneumonia.

    Secondary Outcomes

    Description: To identify possible factors associated or correlated to the persistency of clinical and/or functional and/or radiological long term lung involvement due to SARS-COV-2 pneumonia at V1, V2, V3, primary outcome measurements will be stratified according to: the presence [yes/no] of comorbidities (cardiovascular, chronic obstructive pulmonary disease, asthma, immunological disorders, solid cancer, hematological malignancy, diabetes mellitus, immunodepression); age (expressed in years, age≥60 versus age<60 years); sex (male versus female); hospital stay duration (expressed in days); acute respiratory failure duration (expressed in days); of study subjects.

    Measure: identifying possible factors associated to the persistency of clinical, functional and radiological long term lung involvement due to COVID-19

    Time: from hospital stay to 6-to-12 months after hospital discharge for SARS-COV-2 pneumonia.
    351 Clinical Trial on the Safety and Efficacy of Regadenoson for Moderate to Severe COVID-19 Adult Patients

    More than 17 million people have been infected and more than 677K lives have been lost since the COVID-19 pandemic. Unfortunately, there is neither an effective treatment nor is there a vaccination for this deadly virus. The moderate to severe COVID-19 patients suffer acute lung injury and need oxygen therapy, and even ventilators, to help them breathe. When a person gets a viral infection, certain body cells (inflammatory/immune cells) get activated and release a wide range of small molecules, also known as cytokines, to help combat the virus. But it is possible for the body to overreact to the virus and release an overabundance of cytokines, forming what is known as a "cytokine storm". When a cytokine storm is formed, these cytokines cause more damage to their own cells than to the invading COVID-19 that they're trying to fight. Recently, doctors and research scientists are becoming increasingly convinced that, in some cases, this is likely what is happening in the moderate to severe COVID-19 patients. The cytokine storm may be contributing to respiratory failure, which is the leading cause of mortality for severe COVID-19 patients. Therefore, being able to control the formation of cytokine storms will also help alleviate the symptoms and aid in the recovery of severe COVID-19 patients.

    NCT04606069
    Conditions
    1. COVID-19
    2. Lung Inflammation
    Interventions
    1. Drug: Regadenoson
    2. Other: Placebo Control
    MeSH:Pneumonia Inflammation
    HPO:Pneumonia

    Primary Outcomes

    Description: Respiratory failure is defined based on resource utilization requiring at least 1 of the following modalities: 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 or CPAP Whether patient is on ECMO

    Measure: Proportion of patients alive and free of respiratory failure through the 30-day trial.

    Time: 30 Days

    Secondary Outcomes

    Description: We will collect blood samples of the regadenoson and placebo treated patients at the baseline, 30mins, 4 hours during drug infusion and 12 hour post drug infusion. It may also including the daily blood collected on normal standard care base. The inflammatory cytokines, including IL-1 beta, IL-6, IL-4, IL-8, IL-10, IL-12, IL-17, TNF-α, and IFN-γ will be measured using the Luminex™ 100 Multi-analyte System at The UM SOM Cytokine Core Laboratory. The levels of of cytokines will be measure in picogram/milliliter (pg/ml).

    Measure: Change of the levels of the inflammatory cytokines prior, during and post drug infusion.

    Time: 30 days

    Description: The same blood samples used in outcomes 2 will be used to measure the levels of matrix metalloproteinase-2 (MMP-2) and MMP-9 using gelatin zymography as described in our previous publications (Zhao et al, 2010 & 2011). The enzyme levels will be quantified using The Image Lab 5.1 software. The unit will be nanogram/ml (ng/ml).

    Measure: Change of the levels of MMP-2 and MMP-9 prior, during and post drug infusion.

    Time: 30 days
    352 Prospective, Open-label, Randomized, Multi-Center Study for Safety and Efficacy Evaluation of Inhaled Nitric Oxide (NO) Given Intermittently to Adults With Viral Pneumonia

    The purpose of this multi center, open label, randomized, study is to obtain information on the safety and efficacy of 150 ppm Nitric Oxide given in addition to the standard of care of patients with viral pneumonia

    NCT04606407
    Conditions
    1. Viral Pneumonia
    2. Nitric Oxide
    3. Respiratory Disease
    4. Pneumonia, Viral
    5. Inhaled Nitric Oxide
    6. Covid19
    7. SARS-CoV Infection
    Interventions
    1. Device: LungFit™
    MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia, Viral Pneumonia Respiratory Aspiration Respiration Disorders Respiratory Tract Diseases
    HPO:Pneumonia

    Primary Outcomes

    Description: Clinical safety will be assessed by incidence of Serious Adverse Events (SAEs)

    Measure: incidence of Serious Adverse Events

    Time: 30 days

    Secondary Outcomes

    Description: Time to fever resolution

    Measure: fever resolution

    Time: Baseline to 30 days

    Description: Number of patients requiring admission to ICU

    Measure: ICU admission

    Time: Baseline to 30 days

    Description: Time until patient no longer requires supportive oxygen

    Measure: Oxygen support

    Time: Baseline to 30 days

    Description: b.d. Stable room air saturation of 93% and above or returning to baseline saturation, whichever is lower

    Measure: Stable room air saturation

    Time: Baseline to 30 days
    353 Adaptation and Pilot Implementation of a Validated, Electronic Real-Time Clinical Decision Support Tool for Care of Pneumonia Patients in 10 Utah Urgent Care Centers

    We plan to adapt an innovative, validated emergency department (ED) CDS tool based on consensus guidelines for pneumonia care (ePNa) to function in urgent care clinics (Instacares at Intermountain) and combine it seamlessly with Stanford's CheXED artificial intelligence model using an interoperable platform currently under development by Care Transformation Information Services at Intermountain. We will then deploy it to one of two groups of Instacares (randomly selected) using the CFIR framework for Implementation Science best practice.

    NCT04606849
    Conditions
    1. Pneumonia
    Interventions
    1. Other: Physician Survey
    2. Device: ePNa-CheXED
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Frequency of clinicians' disagreement with different ePNa recommendations will be monitored along with a tally of the structured reasons for disagreement entered by clinicians into ePNa.

    Measure: ePNa utilization and impact on the UCC clinical environment

    Time: through study completion, year 3 of the study

    Secondary Outcomes

    Measure: Number of unplanned subsequent ED Visits

    Time: within 7 days of initial encounter

    Measure: Number of unplanned hospitalizations

    Time: within 7 days of initial encounter

    Description: defined by compatible chief complaint (cough, dyspnea, chest pain, fever) plus . 1 pneumonia sign/symptom (temperature . 38.0C or < 36.0C, white blood cell count >10,000/ul or <4000/ul), bandemia >10%, SpO2<90% on room air, respiratory rate >20/minute)19 and radiographic confirmation

    Measure: Accuracy of pneumonia diagnosis given

    Time: through study completion, year 3 of the study

    Description: we want a decrease of . 3% in the ePNa cluster with those transfers replaced by direct hospital admissions or discharge home.

    Measure: The change in the transfer rate of UCC pneumonia patients to an ED

    Time: through study completion, year 3 of the study

    Measure: Use of fewer health care resources

    Time: through study completion, year 3 of the study
    354 Lung Diffusing Capacity for Nitric Oxide and Carbon Monoxide Early After Mild-to-severe COVID-19

    Infection with severe acute respiratory syndrome-CoV-2 (SARS-CoV-2) may be associated with diffuse alveolar damage and pulmonary vasculitis. Thus, it is likely that pulmonary function changes may be seen in COVID-19 survivors. The aim of the present study was to test that simultaneously-determined lung diffusing capacity for nitric oxide and carbon monoxide may be useful to detect post-viral diffusive gas exchange abnormalities early after mild-to-severe COVID-19-related pneumonias.

    NCT04610554
    Conditions
    1. COVID-19 Pneumonia
    MeSH:Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Changes of DLNO after SARS-CoV-2 infection

    Measure: Lung diffusing capacity for nitric oxide (DLNO)

    Time: At a time interval ranging from 15 to 189 days after two nasopharyngeal swabs negative for SARS-CoV-2

    Secondary Outcomes

    Description: Changes of DLco after SARS-CoV-2 infection

    Measure: Lung diffusing capacity for carbon monoxide (DLco)

    Time: At a time interval ranging from 15 to 189 days after two nasopharyngeal swabs negative for SARS-CoV-2
    355 A Phase 2, Multi-Center, Randomized, Placebo-Controlled, Dose-Finding Study Evaluating Efficacy, Safety and Tolerability of Different Doses and Regimens of Allocetra-OTS for the Treatment of Organ Failure in Adult Sepsis Patients

    A phase II, multi-center (approximately 10 sites in Israel), randomized, placebo-controlled, dose- finding study comparing the efficacy, safety and tolerability of different dosing regimens of Allocetra-OTS, in up to 160 adult sepsis patients with organ sysfunction.

    NCT04612413
    Conditions
    1. Sepsis
    2. Community-acquired Pneumonia
    3. Organ Dysfunction Syndrome
    Interventions
    1. Drug: ALLOCETRA-OTS
    2. Other: Placebo
    MeSH:Sepsis Toxemia Pneumonia
    HPO:Pneumonia Sepsis

    Primary Outcomes

    Description: Number and severity of AEs and SAEs throughout 28 days follow up period

    Measure: To compare the safety of different doses and regimens of Allocetra-OTS to that of Placebo in the treatment of organ failure in adult sepsis patients

    Time: 28 days

    Description: Change from baseline in SOFA score throughout 28 days

    Measure: To compare the efficacy of different doses and regimens of Allocetra-OTS to that of Placebo in the treatment of organ failure in adult sepsis patients

    Time: 28 days

    Secondary Outcomes

    Description: Vasopressor-free days over 28 days.

    Measure: compare other clinical manifestations of different doses and regimens of Allocetra-OTS associated with organ failure in sepsis patients

    Time: 28 days

    Description: Ventilator-free days over 28 days

    Measure: compare other clinical manifestations of different doses and regimens of Allocetra-OTS associated with organ failure in sepsis patients.

    Time: 28 days

    Description: Days without renal replacement therapy (dialysis).

    Measure: compare other clinical manifestations of different doses and regimens of Allocetra-OTS associated with organ failure in sepsis patients

    Time: 28 days

    Description: Time in ICU and time in hospital

    Measure: compare other clinical manifestations of different doses and regimens of Allocetra-OTS associated with organ failure in sepsis patients

    Time: 28 days

    Description: Number of days with creatinine ≤ Baseline levels +20%.

    Measure: compare other clinical manifestations of different doses and regimens of Allocetra-OTS associated with organ failure in sepsis patients

    Time: 28 days

    Description: All-cause mortality at Day 28 following first dose

    Measure: compare other clinical manifestations of different doses and regimens of Allocetra-OTS associated with organ failure in sepsis patients

    Time: 28 days

    Description: Changes in CRP levels

    Measure: compare other clinical manifestations of different doses and regimens of Allocetra-OTS associated with organ failure in sepsis patients

    Time: 28 days

    Description: Number and severity of AEs and Serious Adverse Events (SAEs) throughout 12 months follow up period

    Measure: Assess long term safety follow up

    Time: 12 months
    356 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
    357 FX06 to Rescue Acute Respiratory Distress Syndrome During Covid-19 Pneumonia

    Vascular leakage following endothelial injury, responsible for interstitial and alveolar edema, is a major feature of pathogen induced acute lung injury. As acute respiratory distress syndrome (ARDS) due to pandemic Covid-19 is associated with more than 60% mortality, controlling vascular leakage may be a major target to decrease the mortality associated with the spreading of the disease in France. FX06, a drug under clinical development containing fibrin-derived peptide beta15-42, is able to stabilize cell-cell interactions, thereby reducing vascular leak and mortality in several animal models, particularly during lipopolysaccharide-induced and dengue hemorrhagic shock . A phase I study was conducted in humans, with no specific adverse event detected with a dose up to 17.5 mg/kg. In a phase II randomized multicentre double-blinded trial in 234 patients suffering from ST+ acute coronary syndrome, FX06 treated patients exhibited a 58% decrease in the early necrotic core zone. Importantly, adverse events were highly comparable between groups, indicating a high safety profile for the drug . Lastly, the drug was used as a salvage therapy in a patient exhibiting a severe ARDS following EBOLA virus infection . Altogether, those data indicate that FX06 is well tolerated in humans and is a potent regulator of vascular leakage. Our hypothesis here is that FX06 may decrease pulmonary vascular hyperpermeability during ARDS following SARS-CoV-2 infection, thereby improving gas exchanges and the outcome of infected patients.

    NCT04618042
    Conditions
    1. Ards
    2. Covid19
    3. Pneumonia
    Interventions
    1. Drug: FX06
    2. Drug: Placebo of FX06
    MeSH:Pneumonia Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury
    HPO:Pneumonia

    Primary Outcomes

    Description: Assessed by transpulmonary thermodilution Transpulmonary thermodilution systems, part of the standard management in ICU, allow a direct evaluation of vascular hyperpermeability in the lungs using thermodilution technique. EVLWi is a reliable parameter, independently associated with mortality during ARDS

    Measure: Change in extravascular lung water index (EVLWi)

    Time: Between Day 1 and Day 7

    Secondary Outcomes

    Description: measured by transpulmonary thermodilution during 7 days

    Measure: Evolution of daily extravascular lung water index (EVLWi)

    Time: Between Day 1 and Day 7

    Description: measured by transpulmonary thermodilution during 7 days

    Measure: Evolution of daily cardiac index

    Time: Between Day 1 and Day 7

    Description: measured by transpulmonary thermodilution during 7 days

    Measure: Evolution of global end-diastolic volume index

    Time: Between Day 1 and Day 7

    Description: measured by transpulmonary thermodilution during 7 days

    Measure: Evolution of pulmonary vascular permeability index

    Time: Between Day 1 and Day 7

    Measure: Overall survival

    Time: Day 30

    Measure: Mortality rate in ICU and in hospital

    Time: Through study completion an average of 2 months

    Measure: Rate of withdraw or withhold life-sustaining treatments decision

    Time: Day 30

    Measure: Daily weight

    Time: Between Day 1 and Day 7

    Measure: Daily fluid balance

    Time: Between Day 1 and Day 7

    Description: Evolution of blood biological criteria (g/L)

    Measure: Evolution of albuminemia

    Time: Between Day 1 and Day 7

    Measure: Duration of mechanical ventilation

    Time: Day 30

    Measure: Proportion of participants alive and off invasive mechanical ventilation

    Time: Day 30

    Measure: Evolution of Murray ARDS severity score

    Time: Day 1 to day 15

    Description: Scale from 0 to 12 better with higher score indicating more severe radiological pulmonary severity

    Measure: Evolution of radiological Weinberg score

    Time: Day 1 to Day 30

    Description: Scale from 0 to 4 betterwith higher score indicating more severe pulmonary disease

    Measure: Evolution of pulmonary Sequential Organ Failure Assessment) score.

    Time: Day 1 to day 15

    Measure: Rate of rescue therapy with Veino-veinous V-ECMO

    Time: Through study completion an average of 2 months

    Description: Scale from 0 to 24, lower is better.

    Measure: Evolution of SOFA (Sequential Organ Failure Assessment) score

    Time: Day 15

    Description: one or more SOFA sub-score >=3

    Measure: Organ failure free days

    Time: Day 15

    Measure: Renal replacement therapy free days

    Time: Day 30

    Measure: Duration of renal replacement therapy free days

    Time: Day 30

    Measure: Nature and frequency of adverse events

    Time: Through study completion an average of 2 months

    Description: measured at day 1 at time 0 (before FX06 application) and after 5, 15, 30, 60 min

    Measure: Evolution of FX06 concentration

    Time: Day 1

    Description: A test for immunogenicity will be performed on a serum sample at day 7 (2 days after the end of treatment administration) to detect any antibody against FX06. The assay will consist in a three-fold procedure, as recommended by the manufacturer. An initial screening assay will qualitatively measure antibodies to FX06. Samples deemed positive will be subject to a confirmatory assay, which will determine the specificity of the detected antibody against FX06. The third tier of the assay will consist in titre analysis to semi-quantitatively assess the antibody response.

    Measure: Immunogenicity (antibody against FX06) induced by the drug, performed by ELISA according to manufacturer's procedure

    Time: Day 7
    358 Surfactant Protein D Levels in Covid-19 Infection: Case-Control Study

    This study aims to provide some insight into the variation of SD-D protein levels in patients with Covid-19 (-) pneumonia, Covid-19 (+) pneumonia, and CT negative Covid-19 infection in comparison to the normal population through a larger number of cases. Objective of the study is to determine the serum surfactant protein D (SP-D) levels in Covid-19 pneumonia infection.

    NCT04618861
    Conditions
    1. Covid19
    2. Pneumonia
    3. Surfactant Protein Deficiency
    MeSH:Infection Pneumonia Protein Deficiency
    HPO:Pneumonia

    Primary Outcomes

    Description: First primary outcome is determining the serum surfactant protein D level changes in patient who have Covid-19 infection or pneumonia aganist healty controls.

    Measure: Meassuring the serum surfactant protein D levels in patient who have Covid-19 infection or pneumonia.

    Time: 2 months

    Description: Determining the correlation between between serum surfactant protein D levels and demographic datas (age,gender), medical history, vital findings (fever, blood pressure, sPO2), laboratory findings (complete blood count; C-reactive protein (CRP), D-dimer, Ferritin and hsTnT parameters) and radiological findings, time to onset of symptoms, Comorbid diseases, hospitalization location of the patients (service or ICU), clinical scores (PSI and CURB65 scores), CT severity scores .

    Measure: Analyzing the correlations between serum surfactant protein D levels and demographic,laboratory, clinical and radiological datas.

    Time: 2 months
    359 Determination of Biomarkers for the Prediction of Dexamethasone Response in Sars-Cov-2 / COVID-19 Pneumonia

    The primary objective of this study is to demonstrate (at the time of admission) biomarkers of interest (Human Plasma BAK125 panel + interferon panel) for dexamethasone responders versus non-responders in SARS-CoV-2 hypoxemic pneumonia. The secondary objectives are to describe and compare between groups: - The number of days without mechanical ventilation - The need for mechanical ventilation - 28-day mortality - Progression towards acute respiratory distress syndrome (ARDS) - Change in the qSOFA score - Length of hospitalization - The change in the extent of lesions on thoracic computed tomography scan between inclusion and D7 (or the day of discharge from hospital if

    NCT04619693
    Conditions
    1. Pneumonia, Viral
    2. SARS-Cov-2
    MeSH:Pneumonia, Viral Pneumonia
    HPO:Pneumonia

    Primary Outcomes

    Description: Treatment failure is defined as the need to transfer the patient to intensive care for mechanical ventilation.

    Measure: Treatment failure (yes/no)

    Time: Hospital discharge (expected maximum of 28 days)

    Secondary Outcomes

    Description: PeptiQuantTM Plus, Human Plasma BAK 125, Cambridge Isotope Laboratories, Inc

    Measure: Human Plasma BAK-125 proteomics profile

    Time: Baseline (day 0)

    Description: PeptiQuantTM Plus, Human Plasma BAK 125, Cambridge Isotope Laboratories, Inc

    Measure: Human Plasma BAK-125 proteomics profile

    Time: Day 7

    Measure: Circulating blood interferon level

    Time: Baseline (day 0)

    Measure: Circulating blood interferon level

    Time: Day 7

    Description: Measured at least twice per day throughout the initial hospitalization period.

    Measure: A vector of repeated measures of SpO2

    Time: Throughout initial hospitalization (expected maximum of 28 days)

    Description: Measured at least twice per day throughout the initial hospitalization period.

    Measure: A vector of repeated measures of FiO2

    Time: Throughout initial hospitalization (expected maximum of 28 days)

    Description: Measured at least twice per day throughout the initial hospitalization period.

    Measure: A vector of repeated measures of temperature (°C)

    Time: Throughout initial hospitalization (expected maximum of 28 days)

    Description: Measured at least twice per day throughout the initial hospitalization period.

    Measure: A vector of repeated measures of respiratory rate (cycles per minute)

    Time: Throughout initial hospitalization (expected maximum of 28 days)

    Description: Measured at least twice per day throughout the initial hospitalization period.

    Measure: A vector of repeated measures of pulse (bpm)

    Time: Throughout initial hospitalization (expected maximum of 28 days)

    Description: Measured at least twice per day throughout the initial hospitalization period.

    Measure: A vector of repeated measures of systolic blood pressure (mmHg)

    Time: Throughout initial hospitalization (expected maximum of 28 days)

    Description: Measured at least twice per day throughout the initial hospitalization period.

    Measure: A vector of repeated measures of diastolic blood pressure (mmHg)

    Time: Throughout initial hospitalization (expected maximum of 28 days)

    Description: Capillary glycemia will be measured at least twice per day throughout the initial hospitalization period.

    Measure: A vector of repeated measures of capillary glycemia (g/L)

    Time: Throughout initial hospitalization (expected maximum of 28 days)

    Description: The Quick Sequential Organ Failure Assessment (qSOFA) score will be assessed at least twice per day throughout the initial hospitalization period. The quick Sepsis-related organ failure assessment (qSOFA) score ranges from 0 to 3 points, with '3' indicating the worst health state. It uses three criteria, assigning one point for low blood pressure (systolic blood pressure ≤100 mmHg), high respiratory rate (≥22 breaths per min), or altered mentation.

    Measure: A vector of repeated measures of the qSOFA score

    Time: Throughout initial hospitalization (expected maximum of 28 days)

    Measure: Hemoglobin

    Time: Baseline (day 0)

    Measure: Hemoglobin

    Time: Day 2

    Measure: Hemoglobin

    Time: Day 4

    Measure: Hemoglobin

    Time: Day 7 (or day of discharge if before day 7)

    Measure: Platelet count

    Time: Baseline (day 0)

    Measure: Platelet count

    Time: Day 2

    Measure: Platelet count

    Time: Day 4

    Measure: Platelet count

    Time: Day 7 (or day of discharge if before day 7)

    Measure: White blood cell count

    Time: Baseline (day 0)

    Measure: White blood cell count

    Time: Day 2

    Measure: White blood cell count

    Time: Day 4

    Measure: White blood cell count

    Time: Day 7 (or day of discharge if before day 7)

    Measure: Neutrophil percentage

    Time: Baseline (day 0)

    Measure: Neutrophil percentage

    Time: Day 2

    Measure: Neutrophil percentage

    Time: Day 4

    Measure: Neutrophil percentage

    Time: Day 7 (or day of discharge if before day 7)

    Measure: Eosinophil percentage

    Time: Baseline (day 0)

    Measure: Eosinophil percentage

    Time: Day 2

    Measure: Eosinophil percentage

    Time: Day 4

    Measure: Eosinophil percentage

    Time: Day 7 (or day of discharge if before day 7)

    Measure: Basophil percentage

    Time: Baseline (day 0)

    Measure: Basophil percentage

    Time: Day 2

    Measure: Basophil percentage

    Time: Day 4

    Measure: Basophil percentage

    Time: Day 7 (or day of discharge if before day 7)

    Measure: Lymphocyte percentage

    Time: Baseline (day 0)

    Measure: Lymphocyte percentage

    Time: Day 2

    Measure: Lymphocyte percentage

    Time: Day 4

    Measure: Lymphocyte percentage

    Time: Day 7 (or day of discharge if before day 7)

    Measure: Monocyte percentage

    Time: Baseline (day 0)

    Measure: Monocyte percentage

    Time: Day 2

    Measure: Monocyte percentage

    Time: Day 4

    Measure: Monocyte percentage

    Time: Day 7 (or day of discharge if before day 7)

    Measure: Prothrombin rate (%)

    Time: Baseline (day 0)

    Measure: Prothrombin rate (%)

    Time: Day 2

    Measure: Prothrombin rate (%)

    Time: Day 4

    Measure: Prothrombin rate (%)

    Time: Day 7 (or day of discharge if before day 7)

    Measure: Activated partial thromboplastin time ratio

    Time: Baseline (Day 0)

    Measure: Activated partial thromboplastin time ratio

    Time: Day 2

    Measure: Activated partial thromboplastin time ratio

    Time: Day 4

    Measure: Activated partial thromboplastin time ratio

    Time: Day 7 (or day of discharge if before day 7)

    Measure: Fibrinogen (g/L)

    Time: Baseline (Day 0)

    Measure: Fibrinogen (g/L)

    Time: Day 2

    Measure: Fibrinogen (g/L)

    Time: Day 4

    Measure: Fibrinogen (g/L)

    Time: Day 7 (or day of discharge if before day 7)

    Measure: D-Dimers (μg/mL)

    Time: Baseline (Day 0)

    Measure: D-Dimers (μg/mL)

    Time: Day 2

    Measure: D-Dimers (μg/mL)

    Time: Day 4

    Measure: D-Dimers (μg/mL)

    Time: Day 7 (or day of discharge if before day 7)

    Measure: Aspartate aminotransferase (ASAT; UI/L)

    Time: Baseline (Day 0)

    Measure: Aspartate aminotransferase (ASAT; UI/L)

    Time: Day 2

    Measure: Aspartate aminotransferase (ASAT; UI/L)

    Time: Day 4

    Measure: Aspartate aminotransferase (ASAT; UI/L)

    Time: Day 7 (or day of discharge if before day 7)

    Measure: Alanine aminotransferase (ALAT; UI/L)

    Time: Baseline (Day 0)

    Measure: Alanine aminotransferase (ALAT; UI/L)

    Time: Day 2

    Measure: Alanine aminotransferase (ALAT; UI/L)

    Time: Day 4

    Measure: Alanine aminotransferase (ALAT; UI/L)

    Time: Day 7 (or day of discharge if before day 7)

    Measure: Glucose (mmol/L)

    Time: Baseline (Day 0)

    Measure: Glucose (mmol/L)

    Time: Day 2

    Measure: Glucose (mmol/L)

    Time: Day 4

    Measure: Glucose (mmol/L)

    Time: Day 7 (or day of discharge if before day 7)

    Measure: Glycated haemoglobin (HbA1c; %)

    Time: Baseline (Day 0)

    Measure: Glycated haemoglobin (HbA1c; %)

    Time: Day 2

    Measure: Glycated haemoglobin (HbA1c; %)

    Time: Day 4

    Measure: Glycated haemoglobin (HbA1c; %)

    Time: Day 7 (or day of discharge if before day 7)

    Measure: Urea (mmol/L)

    Time: Baseline (Day 0)

    Measure: Urea (mmol/L)

    Time: Day 2

    Measure: Urea (mmol/L)

    Time: Day 4

    Measure: Urea (mmol/L)

    Time: Day 7 (or day of discharge if before day 7)

    Measure: Creatinine (µmol/L)

    Time: Baseline (Day 0)

    Measure: Creatinine (µmol/L)

    Time: Day 2

    Measure: Creatinine (µmol/L)

    Time: Day 4

    Measure: Creatinine (µmol/L)

    Time: Day 7 (or day of discharge if before day 7)

    Measure: Estimated glomerular filtration rate (eGFR, ml/min/1.73m^2)

    Time: Baseline (Day 0)

    Measure: Estimated glomerular filtration rate (eGFR, ml/min/1.73m^2)

    Time: Day 2

    Measure: Estimated glomerular filtration rate (eGFR, ml/min/1.73m^2)

    Time: Day 4

    Measure: Estimated glomerular filtration rate (eGFR, ml/min/1.73m^2)

    Time: Day 7 (or day of discharge if before day 7)

    Measure: Albumin (g/L)

    Time: Baseline (Day 0)

    Measure: Albumin (g/L)

    Time: Day 2

    Measure: Albumin (g/L)

    Time: Day 4

    Measure: Albumin (g/L)

    Time: Day 7 (or day of discharge if before day 7)

    Measure: C reactive protein (CRP, mg/L)

    Time: Baseline (Day 0)

    Measure: C reactive protein (CRP, mg/L)

    Time: Day 2

    Measure: C reactive protein (CRP, mg/L)

    Time: Day 4

    Measure: C reactive protein (CRP, mg/L)

    Time: Day 7 (or day of discharge if before day 7)

    Measure: Lactate dehydrogenase (LDH, UI/L)

    Time: Baseline (Day 0)

    Measure: Lactate dehydrogenase (LDH, UI/L)

    Time: Day 2

    Measure: Lactate dehydrogenase (LDH, UI/L)

    Time: Day 4

    Measure: Lactate dehydrogenase (LDH, UI/L)

    Time: Day 7 (or day of discharge if before day 7)

    Measure: Hypersensitive troponin T (µg/L)

    Time: Baseline (Day 0)

    Measure: Hypersensitive troponin T (µg/L)

    Time: Day 2

    Measure: Hypersensitive troponin T (µg/L)

    Time: Day 4

    Measure: Hypersensitive troponin T (µg/L)

    Time: Day 7 (or day of discharge if before day 7)

    Measure: Ferritin (µg/L)

    Time: Baseline (Day 0)

    Measure: Ferritin (µg/L)

    Time: Day 2

    Measure: Ferritin (µg/L)

    Time: Day 4

    Measure: Ferritin (µg/L)

    Time: Day 7 (or day of discharge if before day 7)

    Description: CD4 refers to cluster of differentiation 4.

    Measure: CD4 cell count

    Time: Baseline (Day 0)

    Description: CD4 refers to cluster of differentiation 4.

    Measure: CD4 cell count

    Time: Day 2

    Description: CD4 refers to cluster of differentiation 4.

    Measure: CD4 cell count

    Time: Day 4

    Description: CD4 refers to cluster of differentiation 4.

    Measure: CD4 cell count

    Time: Day 7 (or day of discharge if before day 7)

    Description: CD8 refers to cluster of differentiation 8.

    Measure: CD8 cell count

    Time: Baseline (Day 0)

    Description: CD8 refers to cluster of differentiation 8.

    Measure: CD8 cell count

    Time: Day 2

    Description: CD8 refers to cluster of differentiation 8.

    Measure: CD8 cell count

    Time: Day 4

    Description: CD8 refers to cluster of differentiation 8.

    Measure: CD8 cell count

    Time: Day 7 (or day of discharge if before day 7)

    Measure: Natural killer cell count

    Time: Baseline (Day 0)

    Measure: Natural killer cell count

    Time: Day 2

    Measure: Natural killer cell count

    Time: Day 4

    Measure: Natural killer cell count

    Time: Day 7 (or day of discharge if before day 7)

    Measure: Activated T cell percentage

    Time: Baseline (Day 0)

    Measure: Activated T cell percentage

    Time: Day 2

    Measure: Activated T cell percentage

    Time: Day 4

    Measure: Activated T cell percentage

    Time: Day 7 (or day of discharge if before day 7)

    Measure: Change in SARS-CoV-2 real-time polymerase chain reaction cycle threshold

    Time: Baseline to day 7 (or day of discharge if before day 7)

    Measure: Change in SARS-CoV-2 IgG serology (% of control signal = PCS)

    Time: Baseline to day 7 (or day of discharge if before day 7)

    Measure: Change in SARS-CoV-2 IgM serology (% of control signal = PCS)

    Time: Baseline to day 7 (or day of discharge if before day 7)

    Measure: Change from positivity at baseline to negativity at Day 7: yes/no for SARS-CoV-2 real time polymerase chain reaction

    Time: Day 7 (or day of discharge if before day 7)

    Measure: Change from positivity at baseline to negativity at Day 7: yes/no for SARS-CoV-2 IgG serology

    Time: Day 7 (or day of discharge if before day 7)

    Measure: Change from positivity at baseline to negativity at Day 7: yes/no for SARS-CoV-2 IgM serology

    Time: Day 7 (or day of discharge if before day 7)

    Description: A reduction in the extent of lesions is defined by a ⩾20% reduction in parenchymal involvement compared to the initial assessment

    Measure: Reduction in the extent of lesions visualized on computed tomography chest scan: yes/no for grand glass opacities

    Time: Day 7 (or day of discharge if before day 7) +- 1 day of leeway for logistics

    Description: A reduction in the extent of lesions is defined by a ⩾20% reduction in parenchymal involvement compared to the initial assessment

    Measure: Reduction in the extent of lesions visualized on computed tomography chest scan: yes/no for consolidation

    Time: Day 7 (or day of discharge if before day 7) +- 1 day of leeway for logistics

    Description: A reduction in the extent of lesions is defined by a ⩾20% reduction in parenchymal involvement compared to the initial assessment

    Measure: Reduction in the extent of lesions visualized on computed tomography chest scan: yes/no for total lesions

    Time: Day 7 (or day of discharge if before day 7) +- 1 day of leeway for logistics

    Measure: Requirement for low flow oxygen therapy during the initial hospitalisation: yes/no

    Time: Day of hospital discharge (expected maximum of 28 days)

    Measure: Requirement for high flow oxygen therapy during the initial hospitalisation: yes/no

    Time: Day of hospital discharge (expected maximum of 28 days)

    Measure: Requirement for non-invasive ventilation during the initial hospitalisation: yes/no

    Time: Day of hospital discharge (expected maximum of 28 days)

    Measure: Requirement for invasive ventilation during the initial hospitalisation: yes/no

    Time: Day of hospital discharge (expected maximum of 28 days)

    Measure: Requirement for dialysis during the initial hospitalisation: yes/no

    Time: Day of hospital discharge (expected maximum of 28 days)

    Measure: Requirement for extracorporeal membrane oxygenation during the initial hospitalisation: yes/no

    Time: Day of hospital discharge (expected maximum of 28 days)

    Measure: Classification of acute respiratory distress syndrome (ARDS) according to the Berlin criteria during initial hospitalization: absent, mild, moderate or severe

    Time: Day of hospital discharge (expected maximum of 28 days)

    Measure: Length of stay (hours) in intensive care

    Time: Day of hospital discharge (expected maximum of 28 days)

    Measure: Length of stay (hours) in hospital

    Time: Day of hospital discharge (expected maximum of 28 days)

    Measure: Days alive and without low flow oxygen therapy

    Time: Day 28

    Measure: Days alive and without high flow oxygen therapy

    Time: Day 28

    Measure: Days alive and without any oxygen therapy

    Time: Day 28

    Measure: Days alive and without non-invasive ventilation

    Time: Day 28

    Measure: Days alive and without invasive ventilation

    Time: Day 28

    Measure: Days alive and without extracorporeal membrane oxygenation

    Time: Day 28

    Measure: Days alive and without intensive care

    Time: Day 28

    Measure: Days alive and without hospitalisation

    Time: Day 28

    Measure: Mortality

    Time: Day of hospital discharge (expected maximum of 28 days)

    Measure: Mortality

    Time: Day 28

    Other Outcomes

    Measure: Presence/absence of incident hyperglycemia during hospitalization

    Time: Day of hospital discharge (expected maximum of 28 days)

    Measure: Presence/absence of secondary infection during hospitalization

    Time: Day of hospital discharge (expected maximum of 28 days)

    Measure: Presence/absence of cardiovascular event (ischemic, stroke, other) during hospitalization

    Time: Day of hospital discharge (expected maximum of 28 days)

    Measure: Presence/absence of digestive hemorrhage during hospitalization

    Time: Day of hospital discharge (expected maximum of 28 days)

    Measure: Presence/absence of neuro-psychiatric event (acute delirium, depressive syndrome, decompensation of an underlying psychiatric pathology) during hospitalization

    Time: Day of hospital discharge (expected maximum of 28 days)

    Measure: Adverse events

    Time: Day of hospital discharge (expected maximum of 28 days)

    Measure: Adverse events

    Time: Day 28

    HPO Nodes


    HP:0002090: Pneumonia
    Genes 272
    TBX20 DCLRE1C ZIC2 HLA-DQA1 GAS8 GRHL3 DNAI2 SFTPC CARD11 DNAJC21 CD81 NODAL PGM3 IL2RG GNPTAB ORC6 SFTPA2 CD247 NTRK1 TNFRSF13C SIX3 ACTA1 MUC5B LAMA3 IL2RG DNMT3B MED25 CHD7 TNFRSF13C EGFR ZBTB24 CACNA1C CYBB RNF125 NFKB1 CITED2 SMARCD2 SLC25A24 BLNK LRBA IRF8 DISP1 GAS1 KIAA0586 FOXH1 SFTPB CFTR KMT2D MAN2B1 LAMC2 P4HTM MASP2 CR2 CREBBP COL11A2 AFF4 ADA ICOS RAG1 FCGR2A CD3D SIX3 PRKCD DLL1 RANBP2 SIX3 TDGF1 PMM2 IL21R GATA4 WAS LTBP3 CFB KCNJ6 FOXH1 SGCG RNU4ATAC CDON TAF1 SLC35C1 LEP CDON EPM2A KDM6A UBB GAS1 FBLN5 ACP5 MCIDAS TBC1D24 CD79B MAN2B1 MTHFD1 TIMM8A SLC35A1 DNAI1 RAG2 ZIC2 BTK IL7R CD3E AFF4 PIK3CD NODAL NBN FOXH1 EFEMP2 NCF1 NFIX OFD1 RNF168 RAG2 SHH RAC1 DISP1 CD19 PANK2 TNFRSF13C FGF8 FANCF GLI2 IGLL1 ALMS1 SBDS EP300 CASP8 BLM ICOS DISP1 TGIF1 CRLF1 ADA UNC119 PIGN FOXP3 FGF8 TDGF1 PTCH1 NCF2 CR2 TDGF1 IL2RG GLI2 FGF8 NIPBL RAG2 WDR1 SHH BTK ZAP70 GLI2 TK2 FGFR1 CREBBP IL2RG GAS1 STAT3 DDR2 TGIF1 DCLRE1C GBA CFAP410 ELANE LAMB3 CDON IL7R MS4A1 NFKB2 STAG2 CD19 EXTL3 PTCH1 SIX3 TCIRG1 TBX20 PAFAH1B1 FOXH1 SAMD9 TNFRSF13B TGIF1 RAG1 ALMS1 NKX2-5 ZIC2 SP110 CD55 CYBA ACTC1 NFKB2 PEPD PNP PKHD1 FGF8 CYBC1 ACP5 TNFRSF11A CSPP1 WDR19 SHH DZIP1L TDGF1 DCLRE1C TLL1 JAK3 DLL1 STAG2 SHH NODAL POLA1 NOS1 TGIF1 PTCH1 ZIC2 ASAH1 TBCD CXCR4 RAC2 FGFR1 GAS1 EFL1 FMO3 HLA-DQB1 RYR1 SRP54 RAG1 BTK ABCA3 ZAP70 CARD11 SETBP1 USB1 SELENON RMRP KNSTRN NADK2 TERT CDON NHLRC1 NKX2-1 PTPRC GATA6 ICOS OSTM1 NODAL GFI1 ACADVL DLL1 PTCH1 TGFB1 TNFRSF13B KPTN TNFSF12 GLI2 ADA JAK3 LIG4 COL11A2 ODAD1 PLOD1 MYH6 DLL1 IFNGR1 SRP54 TNFSF12 IGHM RNU4ATAC SFTPC DOCK8 NBN FOXN1 DISP1 SMC1A
    SNP 0

    HPO

    Alphabetical listing of all HPO terms. Navigate: Correlations   Clinical Trials


    HPO Nodes


    HP:0002090: Pneumonia
    Genes 272
    TBX20 DCLRE1C ZIC2 HLA-DQA1 GAS8 GRHL3 DNAI2 SFTPC CARD11 DNAJC21 CD81 NODAL PGM3 IL2RG GNPTAB ORC6 SFTPA2 CD247 NTRK1 TNFRSF13C SIX3 ACTA1 MUC5B LAMA3 IL2RG DNMT3B MED25 CHD7 TNFRSF13C EGFR ZBTB24 CACNA1C CYBB RNF125 NFKB1 CITED2 SMARCD2 SLC25A24 BLNK LRBA IRF8 DISP1 GAS1 KIAA0586 FOXH1 SFTPB CFTR KMT2D MAN2B1 LAMC2 P4HTM MASP2 CR2 CREBBP COL11A2 AFF4 ADA ICOS RAG1 FCGR2A CD3D SIX3 PRKCD DLL1 RANBP2 SIX3 TDGF1 PMM2 IL21R GATA4 WAS LTBP3 CFB KCNJ6 FOXH1 SGCG RNU4ATAC CDON TAF1 SLC35C1 LEP CDON EPM2A KDM6A UBB GAS1 FBLN5 ACP5 MCIDAS TBC1D24 CD79B MAN2B1 MTHFD1 TIMM8A SLC35A1 DNAI1 RAG2 ZIC2 BTK IL7R CD3E AFF4 PIK3CD NODAL NBN FOXH1 EFEMP2 NCF1 NFIX OFD1 RNF168 RAG2 SHH RAC1 DISP1 CD19 PANK2 TNFRSF13C FGF8 FANCF GLI2 IGLL1 ALMS1 SBDS EP300 CASP8 BLM ICOS DISP1 TGIF1 CRLF1 ADA UNC119 PIGN FOXP3 FGF8 TDGF1 PTCH1 NCF2 CR2 TDGF1 IL2RG GLI2 FGF8 NIPBL RAG2 WDR1 SHH BTK ZAP70 GLI2 TK2 FGFR1 CREBBP IL2RG GAS1 STAT3 DDR2 TGIF1 DCLRE1C GBA CFAP410 ELANE LAMB3 CDON IL7R MS4A1 NFKB2 STAG2 CD19 EXTL3 PTCH1 SIX3 TCIRG1 TBX20 PAFAH1B1 FOXH1 SAMD9 TNFRSF13B TGIF1 RAG1 ALMS1 NKX2-5 ZIC2 SP110 CD55 CYBA ACTC1 NFKB2 PEPD PNP PKHD1 FGF8 CYBC1 ACP5 TNFRSF11A CSPP1 WDR19 SHH DZIP1L TDGF1 DCLRE1C TLL1 JAK3 DLL1 STAG2 SHH NODAL POLA1 NOS1 TGIF1 PTCH1 ZIC2 ASAH1 TBCD CXCR4 RAC2 FGFR1 GAS1 EFL1 FMO3 HLA-DQB1 RYR1 SRP54 RAG1 BTK ABCA3 ZAP70 CARD11 SETBP1 USB1 SELENON RMRP KNSTRN NADK2 TERT CDON NHLRC1 NKX2-1 PTPRC GATA6 ICOS OSTM1 NODAL GFI1 ACADVL DLL1 PTCH1 TGFB1 TNFRSF13B KPTN TNFSF12 GLI2 ADA JAK3 LIG4 COL11A2 ODAD1 PLOD1 MYH6 DLL1 IFNGR1 SRP54 TNFSF12 IGHM RNU4ATAC SFTPC DOCK8 NBN FOXN1 DISP1 SMC1A
    SNP 0

    Reports

    Data processed on September 26, 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.

    Drug Reports   MeSH Reports   HPO Reports  

    Interventions

    4,180 reports on interventions/drugs

    MeSH

    691 reports on MeSH terms

    HPO

    263 reports on HPO terms

    All Terms

    Alphabetical index of all Terms

    Google Colab

    Python example via Google Colab Notebook