Developed by Shray Alag, The Harker School
Sections: Correlations,
Clinical Trials, and HPO
Navigate: Clinical Trials and HPO
Name (Synonyms) | Correlation | |
---|---|---|
drug2153 | Nitazoxanide Wiki | 0.13 |
drug1750 | LY3819253 Wiki | 0.11 |
drug1472 | Hydroxychloroquine Wiki | 0.11 |
Name (Synonyms) | Correlation | |
---|---|---|
drug1705 | Ivermectin Wiki | 0.11 |
drug2782 | Remdesivir Wiki | 0.10 |
drug152 | Ad26.COV2.S Wiki | 0.09 |
drug3226 | Suspension of heat killed (autoclaved) Mycobacterium w Wiki | 0.08 |
drug127 | AZD7442 Wiki | 0.08 |
drug2141 | Niclosamide Wiki | 0.08 |
drug1566 | Ibrutinib Wiki | 0.08 |
drug3581 | Vitamin Super B-Complex Wiki | 0.08 |
drug3519 | VPM1002 Wiki | 0.08 |
drug1824 | Losartan Wiki | 0.08 |
drug2834 | Rivaroxaban Wiki | 0.08 |
drug759 | Clazakizumab Wiki | 0.08 |
drug377 | BNT162b2 Wiki | 0.07 |
drug359 | BCG vaccine Wiki | 0.07 |
drug136 | Acalabrutinib Wiki | 0.07 |
drug2718 | REGN10933+REGN10987 combination therapy Wiki | 0.07 |
drug333 | Azithromycin Wiki | 0.07 |
drug1262 | Favipiravir Wiki | 0.07 |
drug1741 | L-ascorbic acid Wiki | 0.07 |
drug1751 | LY3832479 Wiki | 0.07 |
drug119 | AVIGAN 200 MG Film Tablets Wiki | 0.07 |
drug664 | CVnCoV Vaccine Wiki | 0.07 |
drug1299 | Fluvoxamine Wiki | 0.07 |
drug1118 | Ebselen Wiki | 0.07 |
drug2358 | PUL-042 Inhalation Solution Wiki | 0.07 |
drug259 | Apixaban 2.5 MG Wiki | 0.07 |
drug2142 | Niclosamide Oral Tablet Wiki | 0.07 |
drug3387 | Tofacitinib 10 mg Wiki | 0.07 |
drug2260 | Olokizumab 64 mg Wiki | 0.07 |
drug3253 | TD-0903 Wiki | 0.07 |
drug1504 | Hydroxychloroquine Sulfate Tablets Wiki | 0.07 |
drug3376 | Tocilizumab (TCZ) Wiki | 0.07 |
drug2039 | Molnupiravir Wiki | 0.07 |
drug1503 | Hydroxychloroquine Sulfate Regular dose Wiki | 0.07 |
drug224 | Angiotensin-(1-7) Wiki | 0.07 |
drug2912 | SCTA01 Wiki | 0.07 |
drug667 | CYT107 Wiki | 0.07 |
drug1285 | Fisetin Wiki | 0.07 |
drug1717 | Ivermectin Pill Wiki | 0.07 |
drug1502 | Hydroxychloroquine Sulfate Loading Dose Wiki | 0.07 |
drug2731 | RTB101 Wiki | 0.07 |
drug675 | Canakinumab Wiki | 0.07 |
drug1045 | Disulfiram Wiki | 0.07 |
drug1082 | Duvelisib Wiki | 0.07 |
drug1142 | Electronic questionnaire Wiki | 0.07 |
drug165 | Aeonose Wiki | 0.07 |
drug391 | Baricitinib Wiki | 0.07 |
drug2885 | SARS-CoV-2 rS/Matrix-M1 Adjuvant Wiki | 0.07 |
drug3469 | UC-MSCs Wiki | 0.06 |
drug3121 | Standard Medical Treatment Wiki | 0.06 |
drug2760 | Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector) Wiki | 0.06 |
drug281 | Aspirin Wiki | 0.06 |
drug672 | Camostat Mesilate Wiki | 0.06 |
drug3375 | Tocilizumab Wiki | 0.06 |
drug944 | DAS181 Wiki | 0.06 |
drug3862 | mRNA-1273 Wiki | 0.05 |
drug1607 | Inactivated SARS-CoV-2 Vaccine (Vero cell) Wiki | 0.05 |
drug376 | BNT162b1 Wiki | 0.05 |
drug744 | Chloroquine or Hydroxychloroquine Wiki | 0.05 |
drug2786 | Remestemcel-L Wiki | 0.05 |
drug1982 | Mesenchymal stromal cells Wiki | 0.05 |
drug1640 | Interferon beta-1a Wiki | 0.05 |
drug125 | AZD1222 Wiki | 0.05 |
drug954 | DWRX2003 Wiki | 0.05 |
drug1334 | Gam-COVID-Vac Wiki | 0.05 |
drug879 | Convalescent plasma Wiki | 0.05 |
drug3639 | Zinc Wiki | 0.05 |
drug381 | BRII-198 Wiki | 0.05 |
drug2959 | Sample Collection/Performance Evaluation (B) Wiki | 0.05 |
drug761 | Clazakizumab 25 mg Wiki | 0.05 |
drug539 | CAP-1002 Wiki | 0.05 |
drug469 | Blood for research purposes Wiki | 0.05 |
drug1376 | HB-adMSC Wiki | 0.05 |
drug1803 | Longeveron Mesenchymal Stem Cells (LMSCs) Wiki | 0.05 |
drug3434 | Triazavirin (Riamilovir) Wiki | 0.05 |
drug2333 | PF-06650833 Wiki | 0.05 |
drug3687 | azoximer bromide Wiki | 0.05 |
drug282 | Aspirin 100mg Wiki | 0.05 |
drug4067 | vaccine BCG Wiki | 0.05 |
drug1333 | Galidesivir Wiki | 0.05 |
drug2137 | New QIAstat-Dx fully automatic multiple PCR detection platform Wiki | 0.05 |
drug175 | Aerosolized All trans retinoic acid Wiki | 0.05 |
drug2095 | NaCl 0.9% Wiki | 0.05 |
drug682 | Cannabidiol, pharmaceutically produced with < 5 ppm THC Wiki | 0.05 |
drug3390 | Toremifene Wiki | 0.05 |
drug215 | Analysis of cytokine response, innate and adaptive immune response, complement activation, and serum neurofilaments as a marker of neurological damage. Wiki | 0.05 |
drug1203 | Exercise Group Wiki | 0.05 |
drug2939 | Saline Control Wiki | 0.05 |
drug364 | BGB DXP593 Wiki | 0.05 |
drug2854 | SAR443122 Wiki | 0.05 |
drug1388 | HLX71 Wiki | 0.05 |
drug2490 | Placebo comparator: DW-NI Wiki | 0.05 |
drug2601 | Probiotics Wiki | 0.05 |
drug3510 | V590 Wiki | 0.05 |
drug1753 | LYT-100 Wiki | 0.05 |
drug1848 | Low-Concentration Essential Oil Wiki | 0.05 |
drug257 | Apilimod Dimesylate Capsule Wiki | 0.05 |
drug3257 | TJ003234 Wiki | 0.05 |
drug2199 | Non-enhanced CT scan of the chest Wiki | 0.05 |
drug2764 | Recombinant human plasma gelsolin (Rhu-pGSN) Wiki | 0.05 |
drug1832 | Low Dose of KBP-COVID-19 Wiki | 0.05 |
drug760 | Clazakizumab 12.5 mg Wiki | 0.05 |
drug2128 | Neonatal resuscitation without PPE for the prevention of SARS-Cov-2 infection Wiki | 0.05 |
drug3579 | Vitamin D3 or Placebo Wiki | 0.05 |
drug2335 | PH94B Wiki | 0.05 |
drug1742 | L-citrulline Wiki | 0.05 |
drug2581 | Predictors adverse evolution Wiki | 0.05 |
drug2235 | OP-101 Wiki | 0.05 |
drug3395 | Tradipitant Wiki | 0.05 |
drug2972 | Sarilumab SAR153191 Wiki | 0.05 |
drug1878 | MF59 adjuvanted SARS-CoV-2 Sclamp vaccine 15mcg Wiki | 0.05 |
drug897 | CoronaVac Wiki | 0.05 |
drug3648 | Zinc Sulfate 220 MG Wiki | 0.05 |
drug225 | Angiotensin-Converting Enzyme Inhibitors (ACE-I) and Angiotensin II Receptor Blockers (ARB) Wiki | 0.05 |
drug3784 | fostamatinib Wiki | 0.05 |
drug1012 | Diagnostic Test: serology test for COVID-19 Wiki | 0.05 |
drug1759 | Lactobaciltus rhamnosus GG Placebo Wiki | 0.05 |
drug234 | Anti-SARS-CoV-2 equine immunoglobulin fragments (INOSARS) Wiki | 0.05 |
drug1951 | Meditation app usage Wiki | 0.05 |
drug2624 | Propofol Wiki | 0.05 |
drug2228 | Nutrition support Wiki | 0.05 |
drug167 | Aerobic Exercises Wiki | 0.05 |
drug1732 | Ketamine Wiki | 0.05 |
drug1804 | Lopinavir Wiki | 0.05 |
drug2116 | Nasopharyngeal, oropharyngeal, or saliva swab Wiki | 0.05 |
drug1568 | Ibuprofen Wiki | 0.05 |
drug2269 | Omnibiotic AAD Wiki | 0.05 |
drug2752 | Rayaldee 30Mcg Extended-Release (ER) Capsule Wiki | 0.05 |
drug1556 | INM005 Wiki | 0.05 |
drug3187 | Storage of operating waste Wiki | 0.05 |
drug2083 | NK Cells Wiki | 0.05 |
drug103 | ARDSNet Wiki | 0.05 |
drug1821 | Lopinavir/Ritonavir 400 mg/100 mg Wiki | 0.05 |
drug1447 | Home-based exercise training Wiki | 0.05 |
drug3621 | XC221 Wiki | 0.05 |
drug2243 | Observational Wiki | 0.05 |
drug2620 | Prone position ventilation Wiki | 0.05 |
drug2691 | Questionnaire completion Wiki | 0.05 |
drug3637 | Zavegepant (BHV-3500) Wiki | 0.05 |
drug268 | Arbidol Hydrochloride Granules Wiki | 0.05 |
drug2716 | REGN10933 + REGN10987 Wiki | 0.05 |
drug255 | Antroquinonol Wiki | 0.05 |
drug2152 | Nintedanib 150 MG [Ofev] Wiki | 0.05 |
drug592 | COVID-19 IgG / IgM rapid test (whole blood, serum, plasma) Wiki | 0.05 |
drug31 | 1: Usual practice Wiki | 0.05 |
drug526 | Budesonide Wiki | 0.05 |
drug4006 | semen analysis Wiki | 0.05 |
drug533 | C21 Wiki | 0.05 |
drug409 | Bempegaldesleukin Wiki | 0.05 |
drug3204 | Support treatment Wiki | 0.05 |
drug1894 | MSC Treatment Wiki | 0.05 |
drug155 | AdCOVID Wiki | 0.05 |
drug832 | Complex diagnostic panel Wiki | 0.05 |
drug3014 | Serological analyses to be lead on a pre-existing biobank Wiki | 0.05 |
drug3912 | not applicable (observational study) Wiki | 0.05 |
drug260 | Apixaban 5MG Wiki | 0.05 |
drug1077 | DuACT Wiki | 0.05 |
drug3391 | Tracheal intubation and cardiopulmonary resuscitation Wiki | 0.05 |
drug2476 | Placebo Group Wiki | 0.05 |
drug1710 | Ivermectin 3mg Tab Wiki | 0.05 |
drug116 | AV-COVID-19 Wiki | 0.05 |
drug1357 | Group 2: control group with enoxaparin 40mg/d Wiki | 0.05 |
drug3511 | V591 Wiki | 0.05 |
drug1879 | MF59 adjuvanted SARS-CoV-2 Sclamp vaccine 45mcg Wiki | 0.05 |
drug1429 | High-Titer Anti-SARS-CoV-2 (COVID 19) Convalescent Plasma Wiki | 0.05 |
drug3270 | Taste and olfactory function evaluation Wiki | 0.05 |
drug2633 | Prospective study with two measurement points investigating the impact of viral mitigation protocols on parental burnout Wiki | 0.05 |
drug3809 | hydrocortisone Wiki | 0.05 |
drug3477 | Ulinastatin Wiki | 0.05 |
drug171 | Aerosol-reducing Mask Wiki | 0.05 |
drug2164 | Nitric Oxide-Continuous and Sessions Wiki | 0.05 |
drug1554 | INB03 Wiki | 0.05 |
drug1491 | Hydroxychloroquine SAR321068 Wiki | 0.05 |
drug520 | Bromhexine Hydrochloride Tablets Wiki | 0.05 |
drug1647 | Interleukin 6 (IL6) Antagonist Wiki | 0.05 |
drug2802 | Respiratory Mechanics Wiki | 0.05 |
drug3126 | Standard Public Health measures Wiki | 0.05 |
drug1977 | Mesenchymal cells Wiki | 0.05 |
drug3678 | anti-SARS-CoV-2 plasma Wiki | 0.05 |
drug3564 | Virtual Reality Wiki | 0.05 |
drug2125 | Nebulized administration of RLF-100 or Placebo Wiki | 0.05 |
drug1387 | HLX70 Wiki | 0.05 |
drug2151 | Nintedanib 150 MG Wiki | 0.05 |
drug564 | COR-101 Wiki | 0.05 |
drug1764 | Late dexamethazone Wiki | 0.05 |
drug709 | Cenicriviroc (CVC) Wiki | 0.05 |
drug3182 | Sterile normal saline (0.9%) Wiki | 0.05 |
drug3263 | TXA127 Wiki | 0.05 |
drug2565 | Povidone-Iodine 0.4% NI Wiki | 0.05 |
drug3230 | Symptom Survey Wiki | 0.05 |
drug1778 | Levilimab Wiki | 0.05 |
drug156 | Additional and minimal collection of products of the human body carried out during a sample for standard of care Wiki | 0.05 |
drug2364 | Paracetamol Wiki | 0.05 |
drug3057 | Single high dose vitamin D Wiki | 0.05 |
drug3122 | Standard Of Care (SOC) Wiki | 0.05 |
drug2954 | Saliva specimen Wiki | 0.05 |
drug2149 | Nil intervention Wiki | 0.05 |
drug3653 | Zotatifin Wiki | 0.05 |
drug346 | BACMUNE (MV130) Wiki | 0.05 |
drug1505 | Hydroxychloroquine Sulfate Tablets plus Lopinavir/ Ritonavir Oral Tablets Wiki | 0.05 |
drug1267 | Favipiravir + Currently used therapy Wiki | 0.05 |
drug3714 | captopril 25mg Wiki | 0.05 |
drug2493 | Placebo control + best supportive care Wiki | 0.05 |
drug1182 | Enzalutamide Pill Wiki | 0.05 |
drug1558 | INOpulse Wiki | 0.05 |
drug3048 | Silymarin Wiki | 0.05 |
drug192 | Almitrine Wiki | 0.05 |
drug3266 | Tafenoquine Oral Tablet Wiki | 0.05 |
drug2908 | SCB-2019 with AS03 adjuvant Wiki | 0.05 |
drug2567 | Povidone-Iodine 0.5% NI Wiki | 0.05 |
drug1095 | EIT-Group Wiki | 0.05 |
drug2593 | Previfenon® Wiki | 0.05 |
drug356 | BCG Wiki | 0.05 |
drug1269 | Favipiravir Combined With Tocilizumab Wiki | 0.05 |
drug660 | CVnCoV Wiki | 0.05 |
drug3737 | conjunctival RT PCR Wiki | 0.05 |
drug3869 | melatonin Wiki | 0.05 |
drug3190 | Study Arm Wiki | 0.05 |
drug3198 | Sudarshan Kriya Yoga (SKY) Wiki | 0.05 |
drug4010 | serum NGAL and cystatin c Wiki | 0.05 |
drug3833 | insurance navigation Wiki | 0.05 |
drug768 | Clinical diagnosis of COVID-19 by a health care professional Wiki | 0.05 |
drug1382 | HCQ+AZT Wiki | 0.05 |
drug1769 | Lenalidomide as a 5 mg capsule PO daily, days 1, 3, and 5. Wiki | 0.05 |
drug373 | BM-MSCs Wiki | 0.05 |
drug97 | ARCT-021 Dose 4 Wiki | 0.05 |
drug3782 | feces samples (COVI-BIOME ancillary study) Wiki | 0.05 |
drug3201 | Sulodexide Wiki | 0.05 |
drug3657 | a specifically designed self-administered questionnaire Wiki | 0.05 |
drug1962 | MenACWY Wiki | 0.05 |
drug2548 | Plitidepsin 2.0 mg/day Wiki | 0.05 |
drug2397 | Pegylated Interferon-α2b Wiki | 0.05 |
drug647 | CSL324 Wiki | 0.05 |
drug2361 | Pacritinib Wiki | 0.05 |
drug3638 | Zilucoplan® Wiki | 0.05 |
drug372 | BM-Allo.MSC Wiki | 0.05 |
drug1709 | Ivermectin + Placebo Wiki | 0.05 |
drug2909 | SCB-2019 with CpG 1018 adjuvant plus Alum adjuvant Wiki | 0.05 |
drug1781 | Licensed seasonal influenza vaccine Wiki | 0.05 |
drug1920 | Maraviroc+Favipiravir+CT Wiki | 0.05 |
drug683 | Cannabis, Medical Wiki | 0.05 |
drug3426 | Treatment and prophylaxis Wiki | 0.05 |
drug98 | ARCT-021 Dose Regimen 1 Wiki | 0.05 |
drug2569 | Povidone-Iodine 0.6% NI Wiki | 0.05 |
drug2717 | REGN10933+REGN10987 Wiki | 0.05 |
drug1895 | MSCT Wiki | 0.05 |
drug3807 | human cord tissue mesenchymal stromal cells Wiki | 0.05 |
drug2079 | NGM621 Wiki | 0.05 |
drug2626 | Proprietary extract of Nerium oleander Wiki | 0.05 |
drug347 | BAT Wiki | 0.05 |
drug271 | ArtemiC Wiki | 0.05 |
drug1794 | Liquid Alpha1-Proteinase Inhibitor (Human) Wiki | 0.05 |
drug2783 | Remdesivir (RDV) Wiki | 0.05 |
drug1888 | MRG-001 Wiki | 0.05 |
drug265 | Aprepitant injectable emulsion Wiki | 0.05 |
drug3061 | Sirukumab Wiki | 0.05 |
drug3865 | mavrilimumab Wiki | 0.05 |
drug1881 | MFS Wiki | 0.05 |
drug2166 | Nitric Oxide-Sessions Wiki | 0.05 |
drug1322 | GC4419 Wiki | 0.05 |
drug2347 | PRO-SERO-COV Wiki | 0.05 |
drug3247 | TAK-919 Wiki | 0.05 |
drug2743 | Rapamycin Wiki | 0.05 |
drug2549 | Plitidepsin 2.5 mg/day Wiki | 0.05 |
drug3531 | Valsartan (Diovan) Wiki | 0.05 |
drug1963 | MenACWY boost Wiki | 0.05 |
drug1507 | Hydroxychloroquine and azithromycin treatment Wiki | 0.05 |
drug2914 | SELF-BREATHE Wiki | 0.05 |
drug3007 | Serelogy testing, RT PCR Wiki | 0.05 |
drug3312 | Tested for SARS-CoV-2 (regardless of the result) Wiki | 0.05 |
drug1515 | Hydroxychloroquine sulfate &Azithromycin Wiki | 0.05 |
drug335 | Azithromycin / Ivermectin / Ribaroxaban / Paracetamol Wiki | 0.05 |
drug336 | Azithromycin / Ribaroxaban / Paracetamol Wiki | 0.05 |
drug952 | DUR-928 Wiki | 0.05 |
drug3736 | congenital malformation Wiki | 0.05 |
drug3578 | Vitamin D3 (cholecalciferol) Wiki | 0.05 |
drug1046 | Dociparastat sodium Wiki | 0.05 |
drug172 | Aerosolized 13 cis retinoic acid Wiki | 0.05 |
drug1239 | FAVIRA 200 MG Film Tablet Wiki | 0.05 |
drug2323 | P2Et (Caesalpinia spinosa extract) Wiki | 0.05 |
drug3642 | Zinc (zinc gluconate) & Vitamin D (cholecalciferol) Wiki | 0.05 |
drug1392 | Health Enhancement Program Wiki | 0.05 |
drug2127 | Neonatal resuscitation with PPE for the prevention of SARS-Cov-2 infection Wiki | 0.05 |
drug3866 | measurement of circulating sFlt1 concentration Wiki | 0.05 |
drug2551 | Point-of-Care Ultrasonography (POCUS) Wiki | 0.05 |
drug2360 | Pacebo: Calcium citrate Wiki | 0.05 |
drug1731 | Kaplan Meier analysis Wiki | 0.05 |
drug2177 | No intervention - quality of life measure Wiki | 0.05 |
drug1327 | GLS-5310 Wiki | 0.05 |
drug509 | Brexanolone Wiki | 0.05 |
drug3487 | Umbilical cord derived mesenchymal stem cells Wiki | 0.05 |
drug2163 | Nitric Oxide lozenges, 30 mg Wiki | 0.05 |
drug2205 | Non-invasive ventilatory support Wiki | 0.05 |
drug3440 | Two COVID-19 vaccine candidate (TMV-083) administrations - Low dose Wiki | 0.05 |
drug55 | 5-ALA-Phosphate + SFC (5-ALA + SFC) Wiki | 0.05 |
drug2899 | SARS-CoV2 Autoantibody detection Wiki | 0.05 |
drug3907 | none - observational Wiki | 0.05 |
drug3573 | Vitamin C tablets Wiki | 0.05 |
drug382 | BTL-TML-COVID Wiki | 0.05 |
drug1117 | Eating habits Wiki | 0.05 |
drug3790 | glenzocimab Wiki | 0.05 |
drug339 | Azithromycin 500 milligram (mg) oral Tablet Wiki | 0.05 |
drug2597 | PrimePro Wiki | 0.05 |
drug580 | COVID positive via testing Wiki | 0.05 |
drug517 | Brief informational infographic Wiki | 0.05 |
drug1383 | HFB30132A Wiki | 0.05 |
drug493 | Botulinum Neurotoxin Wiki | 0.05 |
drug3305 | Tenecteplase Wiki | 0.05 |
drug2740 | Ramipril 2.5 MG Oral Capsule Wiki | 0.05 |
drug3000 | Sending thorax ct video images via smartphone applications Wiki | 0.05 |
drug946 | DAS181 OL Wiki | 0.05 |
drug2708 | RAPA-501-Allo off-the-shelf Therapy of COVID-19 Wiki | 0.05 |
drug2310 | Ovotransferrin Wiki | 0.05 |
drug3425 | Treamid Wiki | 0.05 |
drug931 | Curently used therapy for COVID-19 non-critical patients Wiki | 0.05 |
drug3651 | Zofin Wiki | 0.05 |
drug2150 | Nintedanib Wiki | 0.05 |
drug1255 | Facial mask Wiki | 0.05 |
drug2874 | SARS-CoV-2 inactivated vaccine Wiki | 0.05 |
drug3060 | Sirolimus 1 MG/ML Wiki | 0.05 |
drug2193 | Non-Interventional Wiki | 0.05 |
drug1823 | Lopinavir/ritonavir treatment Wiki | 0.05 |
drug1748 | LSALT peptide Wiki | 0.05 |
drug945 | DAS181 COVID-19 Wiki | 0.05 |
drug3044 | Sildenafil Wiki | 0.05 |
drug2661 | Pyronaridine-Artesunate Wiki | 0.05 |
drug3773 | exercise brochure Wiki | 0.05 |
drug1860 | Lower-dose prophylactic anticoagulation Wiki | 0.05 |
drug1241 | FFP2 Wiki | 0.05 |
drug812 | Combined ART/hydroxychloroquine Wiki | 0.05 |
drug1006 | Dexmedetomidine Injectable Product Wiki | 0.05 |
drug115 | ATYR1923 3 mg/kg Wiki | 0.05 |
drug348 | BAT + Calcifediol Wiki | 0.05 |
drug1214 | Experimental Group Wiki | 0.05 |
drug43 | 2: Usual practice + SYMBICORT RAPIHALER Wiki | 0.05 |
drug3563 | Virtual Peer Support Platform Wiki | 0.05 |
drug1892 | MRx-4DP0004 Wiki | 0.05 |
drug1080 | Dutasteride Wiki | 0.05 |
drug2965 | Sampling of tissue Wiki | 0.05 |
drug953 | DWJ1248 Wiki | 0.05 |
drug1643 | Interferon-Beta Wiki | 0.05 |
drug3160 | Standard therapy Wiki | 0.05 |
drug1886 | MR or M-M-R II ® vaccine Wiki | 0.05 |
drug2636 | Proxalutamide Wiki | 0.05 |
drug94 | ARCT-021 Dose 1 Wiki | 0.05 |
drug1197 | Ex vivo expanded Wharton's Jelly Mesenchymal Stem Cells Wiki | 0.05 |
drug1428 | High-Concentration Essential Oil Wiki | 0.05 |
drug2767 | Recombinant novel coronavirus vaccine (Adenovirus type 5 vector) Wiki | 0.05 |
drug1672 | Interview by psychologists Wiki | 0.05 |
drug326 | Awake Prone Positioning Wiki | 0.05 |
drug2958 | Sample Collection/Performance Evaluation (A) Wiki | 0.05 |
drug331 | Ayurvedic Kadha Wiki | 0.05 |
drug1514 | Hydroxychloroquine sulfate Wiki | 0.05 |
drug1880 | MF59 adjuvanted SARS-CoV-2 Sclamp vaccine 5mcg Wiki | 0.05 |
drug3470 | UCMSCs Wiki | 0.05 |
drug2568 | Povidone-Iodine 0.5% NS Wiki | 0.05 |
drug2577 | Prasugrel Hydrochloride 10 MG Oral Tablet Wiki | 0.05 |
drug854 | Control Period Wiki | 0.05 |
drug3433 | TriCor® 145mg tablets Wiki | 0.05 |
drug1326 | GLS-1200 Wiki | 0.05 |
drug2574 | Povidone-iodine Wiki | 0.05 |
drug2879 | SARS-CoV-2 rS/Matrix M1-Adjuvant Wiki | 0.05 |
drug1918 | Maraviroc + Currently used therapy Wiki | 0.05 |
drug3428 | Treatment as usual vitamin D Wiki | 0.05 |
drug433 | Biological collection (patients co infected HIV Sras-CoV-2) Wiki | 0.05 |
drug1574 | IgG Wiki | 0.05 |
drug3185 | Stool collection or fecal swab Wiki | 0.05 |
drug3670 | allogeneic mesenchymal stem cell Wiki | 0.05 |
drug964 | Dapagliflozin 10 MG Wiki | 0.05 |
drug3708 | blood test for SARS-COV2 serology Wiki | 0.05 |
drug2675 | Quantitative analysis of anti-SARS-CoV-2-antibodies Wiki | 0.05 |
drug3130 | Standard Ventilation Strategy Wiki | 0.05 |
drug1936 | Mavrilimumab Wiki | 0.05 |
drug477 | Blood sample for whole genome sequencing Wiki | 0.05 |
drug3717 | care as usual Wiki | 0.05 |
drug1379 | HCQ Wiki | 0.05 |
drug2186 | No research related technology based social interactions Wiki | 0.05 |
drug3726 | chloroquine Wiki | 0.05 |
drug787 | Cognitive behavior therapy (CBT), specifically using the Facing Your Fears (FYF) curriculum Wiki | 0.05 |
drug1916 | Manremyc Wiki | 0.05 |
drug3933 | pathogen reduced SARS-CoV-2 convalescent plasma Wiki | 0.05 |
drug2432 | Physical and Cognitive Activity Wiki | 0.05 |
drug2679 | Quercetin Wiki | 0.05 |
drug1779 | Lianhua Qingwen Wiki | 0.05 |
drug367 | BIO 300 Oral Suspension Wiki | 0.05 |
drug3439 | Two COVID-19 vaccine candidate (TMV-083) administrations - High dose Wiki | 0.05 |
drug556 | CM4620-IE (Injectable Emulsion) Wiki | 0.05 |
drug1749 | LY3127804 Wiki | 0.05 |
drug1571 | Icosapent ethyl (IPE) Wiki | 0.05 |
drug232 | Anti-SARS-CoV-2 IgT seropositivity Wiki | 0.05 |
drug1539 | IC14 Wiki | 0.05 |
drug396 | Base therapy Wiki | 0.05 |
drug1959 | Melatonin 2mg Wiki | 0.05 |
drug3195 | Study of immune-mediated mechanisms in patients tested positive for SARS-CoV-2 Wiki | 0.05 |
drug2668 | Qualitative interviews (in 40 patients : 20 with COVID-19 and 20 without COVID-19) Wiki | 0.05 |
drug198 | Alvelestat Wiki | 0.05 |
drug2684 | Questionaire Wiki | 0.05 |
drug2440 | Piclidenoson Wiki | 0.05 |
drug3939 | phone call Wiki | 0.05 |
drug81 | AK119 Wiki | 0.05 |
drug2419 | Phage Therapy Wiki | 0.05 |
drug3567 | Viruxal Oral and Nasal Spray Wiki | 0.05 |
drug446 | Biological: mRNA-1273: 100 mcg Wiki | 0.05 |
drug2080 | NHANES smell and taste tests Wiki | 0.05 |
drug1532 | Hyperimmune immunoglobulin to SARS-CoV-2 (hIVIG) Wiki | 0.05 |
drug3589 | WEB embolization Wiki | 0.05 |
drug541 | CAStem Wiki | 0.05 |
drug2641 | Psychoeducational intervention Wiki | 0.05 |
drug2271 | One COVID-19 vaccine candidate (TMV-083) administration - High dose Wiki | 0.05 |
drug117 | AVICOD 200 MG Film Tablet Wiki | 0.05 |
drug3575 | Vitamin D 1000 IU Wiki | 0.05 |
drug919 | Covidfree@home Wiki | 0.05 |
drug93 | ARBs and/or ACE inhibitors Wiki | 0.05 |
drug2935 | STI-5656 Wiki | 0.05 |
drug365 | BGB-DXP593 Wiki | 0.05 |
drug3677 | anti-SARS-CoV-2 human convalescent plasma Wiki | 0.05 |
drug2221 | Novel laser inferometry test for CORONA virus Wiki | 0.05 |
drug1725 | Janus Kinase Inhibitor (ruxolitinib) Wiki | 0.05 |
drug881 | Convalescent plasma transfusion Wiki | 0.05 |
drug2599 | Probiorinse Wiki | 0.05 |
drug3641 | Zinc (zinc gluconate) Wiki | 0.05 |
drug366 | BI 764198 Wiki | 0.05 |
drug2811 | Respiratory rehabilitation program (RR). Wiki | 0.05 |
drug2868 | SARS-CoV-2 antibody immunoassays Wiki | 0.05 |
drug1460 | Human Ezrin Peptide 1 (HEP1) Wiki | 0.05 |
drug758 | Clarithromycin 500mg Wiki | 0.05 |
drug891 | Coping strategies video Wiki | 0.05 |
drug2308 | Otilimab Wiki | 0.05 |
drug1763 | Lanadelumab Wiki | 0.05 |
drug2891 | SARS-CoV-2 vaccine (inactivated) Wiki | 0.05 |
drug286 | Assessing antibody responses, neutralizing capacity and memory B-cell function Wiki | 0.05 |
drug1811 | Lopinavir 200Mg/Ritonavir 50Mg Tab Wiki | 0.05 |
drug2587 | Premier Biotech COVID-19 IgG/IgM Rapid test Cassette Wiki | 0.05 |
drug126 | AZD1656 Wiki | 0.05 |
drug3301 | Telmisartan 40mg Wiki | 0.05 |
drug169 | Aerolized Hydroxychloroquine Sulfate Wiki | 0.05 |
drug2255 | Octagam 10% Wiki | 0.05 |
drug1847 | Low or upper respiratory tract sample Wiki | 0.05 |
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drug350 | BBV152 Wiki | 0.05 |
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drug544 | CD24Fc Wiki | 0.05 |
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drug425 | Bicalutamide 150 Mg Oral Tablet Wiki | 0.03 |
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drug1902 | MW33 injection Wiki | 0.03 |
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drug143 | Acebilustat Wiki | 0.03 |
drug1115 | Early-Dexamethasone Wiki | 0.03 |
drug1090 | EDP1815 Wiki | 0.03 |
drug2147 | Nigella Sativa / Black Cumin Wiki | 0.03 |
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drug1297 | Fluoxetine Wiki | 0.03 |
drug2849 | Ruxolitinib Oral Tablet Wiki | 0.03 |
drug4078 | vv-ECMO + cytokine adsorption (Cytosorb adsorber) Wiki | 0.03 |
drug1259 | Famotidine 20 MG Wiki | 0.03 |
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Name (Synonyms) | Correlation | |
---|---|---|
D018352 | Coronavirus Infections NIH | 0.38 |
D045169 | Severe Acute Respiratory Syndrome NIH | 0.31 |
D007239 | Infection NIH | 0.21 |
Name (Synonyms) | Correlation | |
---|---|---|
D012128 | Respiratory Distress Syndrome, Adult NIH | 0.18 |
D055371 | Acute Lung Injury NIH | 0.18 |
D003141 | Communicable Diseases NIH | 0.17 |
D011014 | Pneumonia NIH | 0.17 |
D012127 | Respiratory Distress Syndrome, Newborn NIH | 0.17 |
D013577 | Syndrome NIH | 0.14 |
D055370 | Lung Injury NIH | 0.10 |
D000077062 | Burnout, Psychological NIH | 0.09 |
D012141 | Respiratory Tract Infections NIH | 0.08 |
D011658 | Pulmonary Fibrosis NIH | 0.07 |
D009164 | Mycobacterium Infections NIH | 0.07 |
D000755 | Anemia, Sickle Cell NIH | 0.07 |
D000690 | Amyotrophic Lateral Sclerosis NIH | 0.07 |
D016472 | Motor Neuron Disease NIH | 0.07 |
D058345 | Asymptomatic Infections NIH | 0.07 |
D000370 | Ageusia NIH | 0.07 |
D011024 | Pneumonia, Viral NIH | 0.06 |
D007249 | Inflammation NIH | 0.06 |
D014947 | Wounds and Injuries NIH | 0.06 |
D018450 | Disease Progression NIH | 0.06 |
D012140 | Respiratory Tract Diseases NIH | 0.06 |
D014777 | Virus Diseases NIH | 0.05 |
D001987 | Bronchiectasis NIH | 0.05 |
D001321 | Autistic Disorder NIH | 0.05 |
D008231 | Lymphopenia NIH | 0.05 |
D008171 | Lung Diseases, NIH | 0.05 |
D019973 | Alcohol-Related Disorders NIH | 0.05 |
D000544 | Alzheimer Disease NIH | 0.05 |
D000532 | Altitude Sickness NIH | 0.05 |
D008569 | Memory Disorders NIH | 0.05 |
D000067877 | Autism Spectrum Disorder NIH | 0.05 |
D009877 | Endophthalmitis NIH | 0.05 |
D000071074 | Neonatal Sepsis NIH | 0.05 |
D000070627 | Chronic Traumatic Encephalopathy NIH | 0.05 |
D002481 | Cellulitis NIH | 0.05 |
D006948 | Hyperkinesis NIH | 0.05 |
D058070 | Asymptomatic Diseases NIH | 0.05 |
D011470 | Prostatic Hyperplasia NIH | 0.05 |
D002532 | Intracranial Aneurysm NIH | 0.05 |
D015817 | Eye Infections NIH | 0.05 |
D054517 | Orbital Cellulitis NIH | 0.05 |
D000783 | Aneurysm, NIH | 0.05 |
D050197 | Atherosclerosis NIH | 0.05 |
D000741 | Anemia, Aplastic NIH | 0.05 |
D015004 | Yellow Fever NIH | 0.05 |
D006965 | Hyperplasia NIH | 0.05 |
D010265 | Paraproteinemias NIH | 0.05 |
D011552 | Pseudomonas Infections NIH | 0.05 |
D018184 | Paramyxoviridae Infections NIH | 0.05 |
D001469 | Barotrauma NIH | 0.05 |
D011645 | Puerperal Infection NIH | 0.05 |
D056660 | Hereditary Autoinflammatory Diseases NIH | 0.05 |
D008998 | Monoclonal Gammopathy of Undetermined Significance NIH | 0.05 |
D066087 | Perinatal Death NIH | 0.05 |
D005879 | Tourette Syndrome NIH | 0.05 |
D004646 | Emphysema NIH | 0.05 |
D000275 | Adjustment Disorders NIH | 0.05 |
D017093 | Liver Failure NIH | 0.05 |
D008218 | Lymphocytosis NIH | 0.05 |
D010505 | Familial Mediterranean Fever NIH | 0.05 |
D002006 | Brucellosis NIH | 0.05 |
D003424 | Crohn Disease NIH | 0.05 |
D016739 | Behavior, Addictive NIH | 0.05 |
D008258 | Waldenstrom Macroglobulinemia NIH | 0.05 |
D007010 | Hyponatremia NIH | 0.05 |
D019896 | Alpha 1-Antitrypsin Deficiency NIH | 0.05 |
D063130 | Maternal Death NIH | 0.05 |
D000071257 | Emergence Delirium NIH | 0.05 |
D012120 | Respiration Disorders NIH | 0.04 |
D000073397 | Occupational Stress NIH | 0.04 |
D007676 | Kidney Failure, Chronic NIH | 0.04 |
D003333 | Coronaviridae Infections NIH | 0.04 |
D014115 | Toxemia NIH | 0.04 |
D016638 | Critical Illness NIH | 0.04 |
D005355 | Fibrosis NIH | 0.04 |
D002318 | Cardiovascular Diseases NIH | 0.04 |
D029424 | Pulmonary Disease, Chronic Obstructive NIH | 0.04 |
D001008 | Anxiety Disorders NIH | 0.04 |
D017563 | Lung Diseases, Interstitial NIH | 0.04 |
D013927 | Thrombosis NIH | 0.04 |
D000860 | Hypoxia NIH | 0.04 |
D008173 | Lung Diseases, Obstructive NIH | 0.04 |
D030341 | Nidovirales Infections NIH | 0.03 |
D005356 | Fibromyalgia NIH | 0.03 |
D005334 | Fever NIH | 0.03 |
D007945 | Leukemia, Lymphoid NIH | 0.03 |
D012598 | Scoliosi NIH | 0.03 |
D000505 | Alopecia NIH | 0.03 |
D000070642 | Brain Injuries, Traumatic NIH | 0.03 |
D018805 | Sepsis NIH | 0.03 |
D012640 | Seizures NIH | 0.03 |
D009190 | Myelodysplastic Syndromes NIH | 0.03 |
D002659 | Child Development Disorders, Pervasive NIH | 0.03 |
D020522 | Lymphoma, Mantle-Cell NIH | 0.03 |
D016470 | Bacteremia NIH | 0.03 |
D003231 | Conjunctivitis NIH | 0.03 |
D001528 | Behcet Syndrome NIH | 0.03 |
D000068376 | Compassion Fatigue NIH | 0.03 |
D000067073 | Psychological Trauma NIH | 0.03 |
D012327 | RNA Virus Infections NIH | 0.03 |
D006526 | Hepatitis C NIH | 0.03 |
D000428 | Alcohol Drinking NIH | 0.03 |
D044882 | Glucose Metabolism Disorders NIH | 0.03 |
D001714 | Bipolar Disorder NIH | 0.03 |
D000857 | Olfaction Disorders NIH | 0.03 |
D059350 | Chronic Pain NIH | 0.03 |
D058186 | Acute Kidney Injury NIH | 0.03 |
D004417 | Dyspnea NIH | 0.03 |
D014808 | Vitamin D Deficiency NIH | 0.03 |
D011251 | Pregnancy Complications, Infectious NIH | 0.03 |
D007319 | Sleep Initiation and Maintenance Disorders NIH | 0.03 |
D008659 | Metabolic Diseases NIH | 0.03 |
D001249 | Asthma NIH | 0.03 |
D001289 | Attention Deficit Disorder with Hyperactivity NIH | 0.03 |
D045888 | Ganglion Cysts NIH | 0.03 |
D000257 | Adenoviridae Infections NIH | 0.03 |
D015451 | Leukemia, Lymphocytic, Chronic, B-Cell NIH | 0.03 |
D003550 | Cystic Fibrosis NIH | 0.03 |
D053120 | Respiratory Aspiration NIH | 0.03 |
D013315 | Stress, Psychological NIH | 0.03 |
D019966 | Substance-Related Disorders NIH | 0.02 |
D007938 | Leukemia, NIH | 0.02 |
D003643 | Death, NIH | 0.02 |
D003327 | Coronary Disease NIH | 0.02 |
D003324 | Coronary Artery Disease NIH | 0.02 |
D016769 | Embolism and Thrombosis NIH | 0.02 |
D003863 | Depression, NIH | 0.02 |
D007154 | Immune System Diseases NIH | 0.02 |
D001930 | Brain Injuries, NIH | 0.02 |
D001927 | Brain Diseases NIH | 0.02 |
D003693 | Delirium NIH | 0.02 |
D009102 | Multiple Organ Failure NIH | 0.02 |
D001327 | Autoimmune Diseases NIH | 0.02 |
D007674 | Kidney Diseases NIH | 0.02 |
D007153 | Immunologic Deficiency Syndromes NIH | 0.02 |
D010300 | Parkinsonian NIH | 0.02 |
D008223 | Lymphoma, NIH | 0.02 |
D004194 | Disease NIH | 0.02 |
D040921 | Stress Disorders, Traumatic NIH | 0.02 |
D003920 | Diabetes Mellitus, NIH | 0.02 |
D009103 | Multiple Sclerosis NIH | 0.02 |
D011665 | Pulmonary Valve Insufficiency NIH | 0.02 |
D006331 | Heart Diseases NIH | 0.02 |
D003289 | Convalescence NIH | 0.02 |
D015212 | Inflammatory Bowel Diseases NIH | 0.02 |
D013313 | Stress Disorders, Post-Traumatic NIH | 0.02 |
D009369 | Neoplasms, NIH | 0.02 |
D006333 | Heart Failure NIH | 0.02 |
D054556 | Venous Thromboembolism NIH | 0.02 |
D060825 | Cognitive Dysfunction NIH | 0.02 |
D007251 | Influenza, Human NIH | 0.01 |
D020246 | Venous Thrombosis NIH | 0.01 |
D001172 | Arthritis, Rheumatoid NIH | 0.01 |
D003924 | Diabetes Mellitus, Type 2 NIH | 0.01 |
D020521 | Stroke NIH | 0.01 |
D001168 | Arthritis NIH | 0.01 |
D011655 | Pulmonary Embolism NIH | 0.01 |
D004617 | Embolism NIH | 0.01 |
D006973 | Hypertension NIH | 0.01 |
D013923 | Thromboembolism NIH | 0.01 |
D003866 | Depressive Disorder NIH | 0.01 |
D004630 | Emergencies NIH | 0.01 |
Name (Synonyms) | Correlation | |
---|---|---|
HP:0002090 | Pneumonia HPO | 0.17 |
HP:0011947 | Respiratory tract infection HPO | 0.08 |
HP:0002206 | Pulmonary fibrosis HPO | 0.07 |
Name (Synonyms) | Correlation | |
---|---|---|
HP:0006802 | Abnormal anterior horn cell morphology HPO | 0.07 |
HP:0000224 | Hypogeusia HPO | 0.07 |
HP:0007354 | Amyotrophic lateral sclerosis HPO | 0.07 |
HP:0002110 | Bronchiectasis HPO | 0.05 |
HP:0001888 | Lymphopenia HPO | 0.05 |
HP:0002088 | Abnormal lung morphology HPO | 0.05 |
HP:0003811 | Neonatal death HPO | 0.05 |
HP:0002487 | Hyperkinetic movements HPO | 0.05 |
HP:0002354 | Memory impairment HPO | 0.05 |
HP:0002617 | Vascular dilatation HPO | 0.05 |
HP:0008711 | Benign prostatic hyperplasia HPO | 0.05 |
HP:0100827 | Lymphocytosis HPO | 0.05 |
HP:0012133 | Erythroid hypoplasia HPO | 0.05 |
HP:0002863 | Myelodysplasia HPO | 0.05 |
HP:0002902 | Hyponatremia HPO | 0.05 |
HP:0004944 | Dilatation of the cerebral artery HPO | 0.05 |
HP:0002511 | Alzheimer disease HPO | 0.05 |
HP:0040187 | Neonatal sepsis HPO | 0.05 |
HP:0100658 | Cellulitis HPO | 0.05 |
HP:0100280 | Crohn's disease HPO | 0.05 |
HP:0002621 | Atherosclerosis HPO | 0.05 |
HP:0001399 | Hepatic failure HPO | 0.05 |
HP:0030858 | Addictive behavior HPO | 0.05 |
HP:0005508 | Monoclonal immunoglobulin M proteinemia HPO | 0.05 |
HP:0001626 | Abnormality of the cardiovascular system HPO | 0.04 |
HP:0006510 | Chronic pulmonary obstruction HPO | 0.04 |
HP:0006515 | Interstitial pneumonitis HPO | 0.04 |
HP:0006536 | Pulmonary obstruction HPO | 0.04 |
HP:0012418 | Hypoxemia HPO | 0.04 |
HP:0100806 | Sepsis HPO | 0.03 |
HP:0000717 | Autism HPO | 0.03 |
HP:0001945 | Fever HPO | 0.03 |
HP:0005526 | Lymphoid leukemia HPO | 0.03 |
HP:0005550 | Chronic lymphatic leukemia HPO | 0.03 |
HP:0100754 | Mania HPO | 0.03 |
HP:0002293 | Alopecia of scalp HPO | 0.03 |
HP:0000509 | Conjunctivitis HPO | 0.03 |
HP:0000458 | Anosmia HPO | 0.03 |
HP:0012532 | Chronic pain HPO | 0.03 |
HP:0001919 | Acute kidney injury HPO | 0.03 |
HP:0100512 | Low levels of vitamin D HPO | 0.03 |
HP:0002098 | Respiratory distress HPO | 0.03 |
HP:0001250 | Seizure HPO | 0.03 |
HP:0002099 | Asthma HPO | 0.03 |
HP:0007018 | Attention deficit hyperactivity disorder HPO | 0.03 |
HP:0000729 | Autistic behavior HPO | 0.03 |
HP:0100785 | Insomnia HPO | 0.03 |
HP:0001677 | Coronary artery atherosclerosis HPO | 0.02 |
HP:0000077 | Abnormality of the kidney HPO | 0.02 |
HP:0002960 | Autoimmunity HPO | 0.02 |
HP:0002665 | Lymphoma HPO | 0.02 |
HP:0001298 | Encephalopathy HPO | 0.02 |
HP:0002721 | Immunodeficiency HPO | 0.02 |
HP:0000819 | Diabetes mellitus HPO | 0.02 |
HP:0002037 | Inflammation of the large intestine HPO | 0.02 |
HP:0010444 | Pulmonary insufficiency HPO | 0.02 |
HP:0002664 | Neoplasm HPO | 0.02 |
HP:0001635 | Congestive heart failure HPO | 0.02 |
HP:0001268 | Mental deterioration HPO | 0.02 |
HP:0001370 | Rheumatoid arthritis HPO | 0.01 |
HP:0001909 | Leukemia HPO | 0.01 |
HP:0002625 | Deep venous thrombosis HPO | 0.01 |
HP:0005978 | Type II diabetes mellitus HPO | 0.01 |
HP:0001297 | Stroke HPO | 0.01 |
HP:0001369 | Arthritis HPO | 0.01 |
HP:0002204 | Pulmonary embolism HPO | 0.01 |
HP:0000822 | Hypertension HPO | 0.01 |
HP:0001907 | Thromboembolism HPO | 0.01 |
HP:0000716 | Depressivity HPO | 0.01 |
Navigate: Correlations HPO
There are 459 clinical trials
This study will seek to enroll immunocompromised patients with Lower Tract parainfluenza infection. It also contains a sub-study to enroll patients with severe COVID-19.
Description: Removal of all oxygen support (with stable SpO2)
Measure: Percent of subjects who Return to Room Air (RTRA) (main study) Time: by Day 28Maternal and neonatal infections are among the most frequent causes of maternal and neonatal deaths, and current antibiotic strategies have not been effective in preventing many of these deaths. Recently, a randomized clinical trial conducted in a single site in The Gambia showed that treatment with oral dose of 2 g azithromycin vs. placebo for all women in labor reduced selected maternal and neonatal infections. However, it is unknown if this therapy reduces maternal and neonatal sepsis and mortality. The A-PLUS trial includes two primary hypotheses, a maternal hypothesis and a neonatal hypothesis. First, a single, prophylactic intrapartum oral dose of 2 g azithromycin given to women in labor will reduce maternal death or sepsis. Second, a single, prophylactic intrapartum oral dose of 2 g azithromycin given to women in labor will reduce intrapartum/neonatal death or sepsis.
Description: Incidence of maternal death or sepsis within 6 weeks (42 days) post-delivery in intervention vs. placebo group.
Measure: Maternal: Incidence of maternal death or sepsis within 6 weeks (42 days) post-delivery in intervention vs. placebo group. Time: within 6 weeks (42 days)Description: Incidence of intrapartum/neonatal death or sepsis within 4 weeks (28 days) post-delivery in intervention vs. placebo group
Measure: Neonatal: Incidence of intrapartum/neonatal death or sepsis within 4 weeks (28 days) post-delivery in intervention vs. placebo group Time: 4 weeks (28 days) post-deliveryDescription: Fever (>100.4°F/38°C) in addition to one or more of the following: fetal tachycardia ≥160 bpm, maternal tachycardia >100 bpm, tender uterus between contractions, or purulent/foul smelling discharge from uterus prior to delivery.
Measure: Incidence of chorioamnionitis Time: prior to deliveryDescription: Fever (>100.4°F/38°C) in addition to one or more of maternal tachycardia >100 bpm, tender uterine fundus, or purulent/foul smelling discharge from uterus after delivery.
Measure: Incidence of endometritis Time: within 42 days post-deliveryDescription: Wound infection (Purulent infection of a perineal or Cesarean wound with or without fever. In the absence of purulence, requires presence of fever >100.4°F/38°C and at least one of the following signs of local infection: pain or tenderness, swelling, heat, or redness around the incision/laceration); Abdominopelvic abscess (Evidence of pus in the abdomen or pelvis noted during open surgery, interventional aspiration or imaging); Pneumonia (Fever >100.4°F/38°C and clinical symptoms suggestive of lung infection including cough and/or tachypnea >24 breaths/min or radiological confirmation); Pyelonephritis (Fever >100.4°F/38°C and one or more of the following: urinalysis/dip suggestive of infection, costovertebral angle tenderness, or confirmatory urine culture); Mastitis/breast abscess or infection (Fever >100.4°F/38°C and one or more of the following: breast pain, swelling, warmth, redness, or purulent drainage).
Measure: Incidence of other infections Time: within 42 days post-deliveryDescription: Use of subsequent maternal antibiotic therapy after randomization to 42 days postpartum for any reason.
Measure: Incidence of use of subsequent maternal antibiotic therapy Time: after randomization to 42 days post-deliveryDescription: Time from drug administration until initial discharge after delivery (time may vary by site).
Measure: Maternal initial hospital length of stay Time: within 42 days post-deliveryDescription: Maternal readmissions within 42 days of delivery
Measure: Incidence of maternal readmissions Time: within 42 days post-deliveryDescription: Maternal admission to special care units
Measure: Incidence of maternal admission to special care units Time: within 42 days post-deliveryDescription: Maternal unscheduled visit for care
Measure: Incidence of maternal unscheduled visit for care Time: within 42 days post-deliveryDescription: Maternal GI symptoms including nausea, vomiting, and diarrhea and other reported side effects.
Measure: Incidence of maternal GI symptoms Time: within 42 days post-deliveryDescription: Maternal death due to sepsis using the Global Network algorithm for cause of death
Measure: Incidence of maternal death due to sepsis Time: within 42 days post-deliveryDescription: Incidence of other neonatal infections.
Measure: Incidence of other neonatal infections (e.g. eye infection, skin infection) Time: within 42 days post-deliveryDescription: Neonatal initial hospital length of stay, defined as time of delivery until initial discharge (time may vary by site).
Measure: Neonatal initial hospital length of stay Time: within 28 days of deliveryDescription: Neonatal readmissions within 42 days of delivery
Measure: Incidence of neonatal readmissions Time: within 42 days of deliveryDescription: Neonatal admission to special care units
Measure: Incidence of neonatal admission to special care units Time: within 28 days of deliveryDescription: Neonatal unscheduled visit for care
Measure: Incidence of neonatal unscheduled visit for care Time: within 42 days post-deliveryDescription: Neonatal death due to sepsis using the Global Network algorithm for causes of death
Measure: Incidence of neonatal death due to sepsis Time: within 28 days of deliveryDescription: Pyloric stenosis within 42 days of delivery, defined as clinical suspicion based on severe vomiting leading to death, surgical intervention (pyloromyotomy) as verified from medical records, or radiological confirmation.
Measure: Incidence of pyloric stenosis within 42 days of delivery Time: within 42 days of deliveryThis is a placebo-controlled, randomized, double-blind study to evaluate the pharmacokinetics, safety and antiviral activity of galidesivir in subjects with yellow fever (YF) or COVID-19.
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.
Description: Evaluation of Pneumonia Improvement
Measure: Pneumonia severity index Time: From Baseline (0W) to 12 week after treatmentDescription: Evaluation of Pneumonia Improvement
Measure: Oxygenation index (PaO2/FiO2) Time: From Baseline (0W) to 12 week after treatmentDescription: 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 treatmentDescription: Marker for efficacy of treatment
Measure: 28-days survival Time: Day 28Description: 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 28Description: Markers of Infection
Measure: C-reactive protein Time: From Baseline (0W) to 12 week after treatmentDescription: Markers of Infection
Measure: Procalcitonin Time: From Baseline (0W) to 12 week after treatmentDescription: Marker of Immunological function
Measure: Lymphocyte count Time: From Baseline (0W) to 12 week after treatmentDescription: Marker of Immunological function
Measure: CD3+, CD4+ and CD8+ T celll count Time: From Baseline (0W) to 12 week after treatmentDescription: Marker of Immunological function
Measure: CD4+/CD8+ratio Time: From Baseline (0W) to 12 week after treatmentAccording to previous studies, viral pneumonia can develop into pulmonary fibrosis, which can affect patients'lung function and even life health.This study aims to observe the efficacy and safety of Fuzheng Huayu Tablets in the treatment of pulmonary fibrosis after COVID-19.
Description: Evaluation of pulmonary fibrosis Improvement. pulmonary fibrosis judged by HRCT score.HRCT images are divided into four grades according to the score, and a reduction of one grade is an improvement.
Measure: The improvement proportion of pulmonary fibrosis Time: Week 24Description: Evaluation of Lung Function Improvement
Measure: Blood oxygen saturation Time: Week 24Description: Discomfort symptoms include dyspnea, cough, exhausted, fatigue, insomnia, sweating, poor appetite, diarrhea, etc., which are common manifestations of patients with COVID-19
Measure: Clinical symptom score Time: Week 24Description: This scale can reflect the quality of life of patients to some extent.
Measure: Quality of Life-BREF (QOL-BREF) Time: Week 24Description: This scale can reflect the quality of life of patients to some extent.
Measure: Patient Health Questionnaire-9(PHQ-9) Time: Week 24Description: This scale can reflect the quality of life of patients to some extent.
Measure: Generalized anxiety disorder-7(GAD-7) Time: Week 24Description: Evaluation of Lung Function Improvement
Measure: The 6-minute walk distance Time: Week 24This study is an adaptive, randomized, double-blind, placebo-controlled trial to evaluate the safety and efficacy of novel therapeutic agents in hospitalized adults diagnosed with COVID-19. The study is a multicenter trial that will be conducted in up to approximately 100 sites globally. The study will compare different investigational therapeutic agents to a control arm. There will be interim monitoring to introduce new arms and allow early stopping for futility, efficacy, or safety. If one therapy proves to be efficacious, then this treatment may become the control arm for comparison(s) with new experimental treatment(s). Any such change would be accompanied by an updated sample size. Because background standards of supportive care may evolve/improve over time as more is learned about successful management of COVID-19, comparisons of safety and efficacy will be based on data from concurrently randomized subjects. An independent Data and Safety Monitoring Board (DSMB) will actively monitor interim data to make recommendations about early study closure or changes to study arms. To evaluate the clinical efficacy, as assessed by time to recovery, of different investigational therapeutics as compared to the control arm.
Description: Day of recovery is defined as the first day on which the subject satisfies one of the following three categories from the ordinal scale: 1) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Not hospitalized, no limitations on activities.
Measure: Time to Recovery Time: Day 1 through Day 29Description: Blood to evaluate ALT was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.
Measure: Change From Baseline in Alanine Transaminase (ALT) Time: Days 1, 3, 5, 8, 11, 15 and 29Description: Blood to evaluate AST was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.
Measure: Change From Baseline in Aspartate Transaminase (AST) Time: Days 1, 3, 5, 8, 11, 15 and 29Description: Blood to evaluate serum creatinine was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.
Measure: Change From Baseline in Creatinine Time: Days 1, 3, 5, 8, 11, 15 and 29Description: Blood to evaluate serum glucose was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.
Measure: Change From Baseline in Glucose Time: Days 1, 3, 5, 8, 11, 15 and 29Description: Blood to evaluate hemoglobin was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.
Measure: Change From Baseline in Hemoglobin Time: Days 1, 3, 5, 8, 11, 15 and 29Description: Blood to evaluate platelets was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.
Measure: Change From Baseline in Platelets Time: Days 1, 3, 5, 8, 11, 15 and 29Description: Blood to evaluate PT was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.
Measure: Change From Baseline in Prothrombin Time (PT) Time: Days 1, 3, 5, 8, 11, 15 and 29Description: Blood to evaluate total bilirubin was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.
Measure: Change From Baseline in Total Bilirubin Time: Days 1, 3, 5, 8, 11, 15 and 29Description: Blood to evaluate WBC was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.
Measure: Change From Baseline in White Blood Cell Count (WBC) Time: Days 1, 3, 5, 8, 11, 15 and 29Description: Blood to evaluate neutrophils was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.
Measure: Change From Baseline in Neutrophils Time: Days 1, 3, 5, 8, 11, 15 and 29Description: Blood to evaluate lymphocytes was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.
Measure: Change From Baseline in Lymphocytes Time: Days 1, 3, 5, 8, 11, 15 and 29Description: Blood to evaluate monocytes was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.
Measure: Change From Baseline in Monocytes Time: Days 1, 3, 5, 8, 11, 15 and 29Description: Blood to evaluate basophils was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.
Measure: Change From Baseline in Basophils Time: Days 1, 3, 5, 8, 11, 15 and 29Description: Blood to evaluate eosinophils was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.
Measure: Change From Baseline in Eosinophils Time: Days 1, 3, 5, 8, 11, 15 and 29Description: The NEW score has demonstrated an ability to discriminate patients at risk of poor outcomes. This score is based on 7 clinical parameters (respiration rate, oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate, level of consciousness). The NEW Score is being used as an efficacy measure. The minimum score is 0, representing the better outcome, and the maximum value is 19, representing the worse outcome.
Measure: Change in National Early Warning Score (NEWS) From Baseline Time: Days 1, 3, 5, 8, 11, 15, 22, and 29Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.
Measure: Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 1 Time: Day 1Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.
Measure: Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 3 Time: Day 3Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.
Measure: Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 5 Time: Day 5Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.
Measure: Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 8 Time: Day 8Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.
Measure: Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 11 Time: Day 11Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.
Measure: Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 15 Time: Day 15Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.
Measure: Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 22 Time: Day 22Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.
Measure: Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 29 Time: Day 29Description: Grade 3 AEs are defined as events that interrupt usual activities of daily living, or significantly affects clinical status, or may require intensive therapeutic intervention. Severe events are usually incapacitating. Grade 4 AEs are defined as events that are potentially life threatening.
Measure: Percentage of Participants Reporting Grade 3 and 4 Clinical and/or Laboratory Adverse Events (AEs) Time: Day 1 through Day 29Description: An SAE is defined as an AE or suspected adverse reaction is considered serious if, in the view of either the investigator or the sponsor, it results in death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect.
Measure: Percentage of Participants Reporting Serious Adverse Events (SAEs) Time: Day 1 through Day 29Description: Participants may have been discontinued from investigational therapeutics due to discharge or death. The halting or slowing of the infusion for any reason was collected, as was missed doses in the series of 10 doses.
Measure: Percentage of Participants Discontinued or Temporarily Suspended From Investigational Therapeutics Time: Day 1 through Day 10Description: Duration of hospitalization was determined two ways. The first includes imputations for participants who died. The second method is restricted to participants who did not die.
Measure: Duration of Hospitalization Time: Day 1 through Day 29Description: Duration of new non-invasive ventilation or high flow oxygen use was measured in days among participants who were not on non-invasive ventilation or high-flow oxygen use at baseline, determined two ways. The first includes imputations for participants who died. The second method is restricted to participants who did not die
Measure: Duration of New Non-invasive Ventilation or High Flow Oxygen Use Time: Day 1 through Day 29Description: Duration of new oxygen use was measured in days among participants who were not on oxygen at baseline, determined two ways. The first includes imputations for participants who died. The second method is restricted to participants who did not die .
Measure: Duration of New Oxygen Use Time: Day 1 through Day 29Description: Duration of new ventilator or ECMO use was measured in days among participants who were not on a ventilator or ECMO at baseline, determined two ways. The first includes imputations for participants who died. The second method is restricted to participants who did not die
Measure: Duration of New Ventilator or Extracorporeal Membrane Oxygenation (ECMO) Use Time: Day 1 through Day 29Description: New non-invasive ventilation or high-flow oxygen use was determined as the percentage of subject not on non-invasive ventilation or high-flow oxygen at baseline.
Measure: Percentage of Participants Requiring New Non-invasive Ventilation or High-flow Oxygen Use Time: Day 1 through Day 29Description: The percentage of participants requiring new oxygen use was determined as the percentage of participants not requiring oxygen at baseline
Measure: Percentage of Participants Requiring New Oxygen Use Time: Day 1 through Day 29Description: The percentage of participants requiring new ventilator or ECMO use was determined as the percentage not on a ventilator or ECMO at baseline
Measure: Percentage of Participants Requiring New Ventilator or Extracorporeal Membrane Oxygenation (ECMO) Use Time: Day 1 through Day 29Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities. A positive change indicates a worsening and a negative change is an improvement.
Measure: Mean Change in the Ordinal Scale Time: Day 1, 3, 5, 8, 11, 15, 22, and 29Description: The mortality rate was determined as the proportion of participants who died by study Day 15.
Measure: 14-day Participant Mortality Time: Day 1 through Day 15Description: The mortality rate was determined as the proportion of participants who died by study Day 29.
Measure: 29-day Participant Mortality Time: Day 1 through Day 29Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities. Time to improvement by at least one category was determined for each participant
Measure: Time to an Improvement by at Least One Category Using an Ordinal Scale Time: Day 1 through Day 29Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities. Time to improvement by at least two categories was determined for each participant
Measure: Time to an Improvement of at Least Two Categories Using an Ordinal Scale Time: Day 1 through Day 29Description: The NEW score has demonstrated an ability to discriminate patients at risk of poor outcomes. This score is based on 7 clinical parameters (respiration rate, oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate, level of consciousness). The NEW Score is being used as an efficacy measure. The minimum score is 0, representing the better outcome, and the maximum value is 19, representing the worse outcome. The time to discharge or a NEWS of less than or equal to 2 was determined for each participant.
Measure: Time to Discharge or to a NEWS of 2 or Less and Maintained for 24 Hours, Whichever Occurs First Time: Day 1 through Day 29The 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.
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 8Description: Evaluation of Pneumonia change
Measure: Blood oxygen saturation Time: At baseline, Day 1, Week 1, Week 2, Week 4, Week 8Description: Marker for efficacy of treatment
Measure: Rate of mortality within 28-days Time: At baseline, Day 1, Week 1, Week 2, Week 4, Week 8Description: 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 8Description: 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 8Description: 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 8Description: 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 8Description: Marker of Immunology and inflammation
Measure: CD4+ and CD8+ T cells count Time: At baseline, Day 1, Week 1, Week 2, Week 4, Week 8Description: 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 8Description: Markers of the heart function
Measure: Concentration of the myocardial enzymes Time: At baseline, Day 1, Week 1, Week 2, Week 4, Week 8This is a Phase IIb study consisting of two cohorts to evaluate efficacy, safety and pharmacokinetics of DAS181 in IFV infection. An approximate total of 280 subjects will be enrolled into this study.
Description: Percent of subjects who have returned to room air
Measure: Percent of subjects who have returned to room air Time: 7 daysDescription: Percent change of subjects return to baseline oxygen requirement by Day 7 compared to Day 1
Measure: Percent change of subjects return to baseline oxygen requirement Time: 7 daysThe study is a double-blind, randomised, placebo-controlled trial that will be conducted in healthcare settings and other facilities directly involved in COVID-19 case management. We will recruit healthcare workers and other staff working in a facility where there are cases of either proven, or suspected, COVID-19, who can be followed reliably for 5 months. 40,000 participants will be recruited and we predict an average of 400-800 participants per site in 50-100 sites. The participant will be randomised to receive either chloroquine or placebo (1:1 randomisation), or to hydroxychloroquine or placebo (1:1 randomisation). A loading dose of 10mg base/kg (four 155mg tablets for a 60kg subject), followed by 155 mg daily (250mg chloroquine phosphate salt/ 200mg hydroxychloroquine sulphate) will be taken for 3 months. If the participant is diagnosed with COVID-19, they will take continue to take the study medication until: - 90 days after enrolment (i.e., completion of kit) - hospitalised due to COVID-19 disease (i.e., not for quarantine purposes) in which case they will stop, or - advised to stop by their healthcare professional for other reasons Episodes of symptomatic respiratory illness, including symptomatic COVID-19, and clinical outcomes will be recorded in the Case Record Form during the follow-up period.
Description: Number of symptomatic COVID-19 infections will be compared between the chloroquine or hydroxychloroquine and placebo groups
Measure: Number of symptomatic COVID-19 infections Time: Approximately 90 daysDescription: Symptoms severity of COVID-19 will be compared between the two groups using a respiratory severity score.
Measure: Symptoms severity of COVID-19 Time: Approximately 90 daysDescription: Number of asymptomatic cases of COVID-19 will be determined by comparing serology in all participants at time of enrolment and at the end of follow up.
Measure: Number of asymptomatic cases of COVID-19 Time: Approximately 90 daysDescription: Number of symptomatic acute respiratory illnesses will be compared between the chloroquine or hydroxychloroquine and placebo groups.
Measure: Number of symptomatic acute respiratory illnesses Time: Approximately 90 daysDescription: Severity of symptomatic acute respiratory illnesses will be compared between the chloroquine or hydroxychloroquine and placebo groups.
Measure: Severity of symptomatic acute respiratory illnesses Time: Approximately 90 daysDescription: Genetic loci and levels of biochemical components will be correlated with frequency of COVID-19, Acute Respiratory Infection and disease severity.
Measure: Genetic loci and levels of biochemical components will be correlated with frequency of COVID-19, ARI and disease severity. Time: Approximately 90 daysDescription: Number of days lost to work in relation to the treatment arm
Measure: Assess the impact of chloroquine or hydroxychloroquine prophylaxis on number of days lost to work during the pandemic. Time: Approximately 90 daysDescription: The trial will collect data on monetary costs associated with the use of healthcare resources and determine the effects between treatment groups.
Measure: Assess the impact of chloroquine or hydroxychloroquine prophylaxis on healthcare costs Time: Approximately 90 daysDescription: The trial will collect data on health-related quality of life using the quality of life questionnaire (EQ-5D-3L) to determine the effects between treatment groups.
Measure: Assess the impact of chloroquine or hydroxychloroquine prophylaxis on quality of life measures using the quality of life questionnaire (EQ-5D-3L) Time: Approximately 90 daysStudy Objective: 1. To test if post-exposure prophylaxis with hydroxychloroquine can prevent symptomatic COVID-19 disease after known exposure to the SARS-CoV-2 coronavirus. 2. To test if early preemptive hydroxychloroquine therapy can prevent disease progression in persons with known symptomatic COVID-19 disease, decreasing hospitalizations and symptom severity.
Description: Number of participants at 14 days post enrollment with active COVID19 disease.
Measure: Incidence of COVID19 Disease among those who are asymptomatic at baseline Time: 14 daysDescription: Repeated Measure mixed regression model of change in: Visual Analog Scale 0-10 score of rating overall symptom severity (0 = no symptoms; 10 = most severe)
Measure: Overall change in disease severity over 14 days among those who are symptomatic at baseline Time: 14 daysDescription: Outcome reported as the number of participants in each arm who require hospitalization for COVID19-related disease.
Measure: Incidence of Hospitalization Time: 14 daysDescription: Outcome reported as the number of participants in each arm who expire due to COVID-19-related disease.
Measure: Incidence of Death Time: 90 daysDescription: Outcome reported as the number of participants in each arm who have confirmed SARS-CoV-2 infection.
Measure: Incidence of Confirmed SARS-CoV-2 Detection Time: 14 daysDescription: Outcome reported as the number of participants in each arm who self-report symptoms compatible with COVID19 infection.
Measure: Incidence of Symptoms Compatible with COVID19 (possible disease) Time: 90 daysDescription: Outcome reported as the number of participants in each arm who discontinue or withdraw medication use for any reason.
Measure: Incidence of All-Cause Study Medicine Discontinuation or Withdrawal Time: 14 daysDescription: Visual Analog Scale 0-10 score of rating overall symptom severity (0 = no symptoms; 10 = most severe)
Measure: Overall symptom severity at 5 and 14 days Time: 5 and 14 daysDescription: Participants will self-report disease severity status as one of the following 3 options; no COVID19 illness (score of 1), COVID19 illness with no hospitalization (score of 2), or COVID19 illness with hospitalization or death (score of 3). Increased scale score indicates greater disease severity. Outcome is reported as the percent of participants who fall into each category per arm.
Measure: Ordinal Scale of COVID19 Disease Severity at 14 days among those who are symptomatic at trial entry Time: 14 daysThis is a multi-center, double-blinded study of COVID-19 infected patients randomized 1:1 to daily losartan or placebo for 10 days or treatment failure (hospital admission).
Description: Outcome reported as the number of participants per arm admitted to inpatient hospital care due to COVID-19-related disease within 15 days of randomization. Currently, there is a pre-planned pooled analysis with a national trial network under development.
Measure: Hospital Admission Time: 15 daysDescription: The PROMIS Dyspnea (shortness of breath) item banks and pools assess self-reported shortness of breath in general, intensity, frequency and duration on a 0-10 scale, with 0 being no symptoms and 10 being the most severe. Finally, the patient answers the question "I've been short of breath" using a 0-4 scale, 0 being none and the most severe. There is no validated, unified single score and each item is evaluated individually.
Measure: Change in PROMIS Dyspnea scale Time: 10 daysDescription: The SF-12 is a self-reported validated outcome measure assessing the impact of health on an individual's everyday life. Patients fill out a 12 question survey which is then scored by a clinician or researcher. Physical score is computed using the scores of twelve questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health. The 33-item Severity bank assesses the severity of difficulty breathing during various specific activities (the same 33 activities assessed in Dyspnea Functional Limitations). Each activity is rated in terms of degree of dyspnea (0 = no shortness of breath, 1 = mildly short of breath, 2 = moderately short of breath, 3 = severely short of breath) while engaging in the activity over the past 7 days. Total scores range from 0 to 99 with higher scores reflecting greater levels of dyspnea during daily activity.
Measure: Change in SF-12 Physical Composite Score Time: 10 daysDescription: The SF-12 is a self-reported validated outcome measure assessing the impact of health on an individual's everyday life. Patients fill out a 12 question survey which is then scored by a clinician or researcher. Mental composite score is computed using the scores of twelve questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health.
Measure: Change in SF-12 Mental Composite Score Time: 10 daysDescription: Participants will report their maximum daily oral temperature to the study team. Outcome is reported as the mean maximum daily body temperature (in degrees Celsius) over 10 days.
Measure: Daily Maximum Temperature Time: 10 daysDescription: Outcome is reported as the mean number of emergency department and clinic presentations combined per participant in each arm.
Measure: Emergency Department/Clinic Presentations Time: 28 daysDescription: Outcome reported as the number of participants in each arm who fall into each of 7 categories. Lower scores indicate greater condition severity. The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen; 6) Not hospitalized, limitation on activities; 7) Not hospitalized, no limitations on activities.
Measure: Disease Severity Rating Day 7 Time: 7 daysDescription: Outcome reported as the number of participants in each arm who fall into each of 7 categories. Lower scores indicate greater condition severity. The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen; 6) Not hospitalized, limitation on activities; 7) Not hospitalized, no limitations on activities.
Measure: Disease Severity Rating Day 15 Time: 15 daysDescription: Outcome reported as the number of participants in each arm who fall into each of 7 categories. Lower scores indicate greater condition severity. The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen; 6) Not hospitalized, limitation on activities; 7) Not hospitalized, no limitations on activities.
Measure: Disease Severity Rating Day 28 Time: 28 daysDescription: Participants will collect oropharyngeal swabs every third day for the duration of study participation. Viral load is measured as number of viral genetic copies per mL.
Measure: Viral Load by Oropharyngeal Swab Day 9 Time: 9 daysDescription: Participants will collect oropharyngeal swabs every third day for the duration of study participation. Viral load is measured as number of viral genetic copies per mL.
Measure: Viral Load by Oropharyngeal Swab Day 15 Time: 15 daysDescription: Outcome reported as the mean number of days participants in each arm did not require ventilator use.
Measure: Ventilator-Free Days Time: 28 daysDescription: Outcome reported as the mean number of days participants in each arm did not require therapeutic oxygen use.
Measure: Therapeutic Oxygen-Free Days Time: 28 daysDescription: Outcome reported as the percent of participants in each arm who require hospital admission by day 15 following randomization.
Measure: Need for Hospital Admission at 15 Days Time: 15 daysDescription: Outcome reported as the percent of participants in each arm who require oxygen therapy by day 15 following randomization.
Measure: Need for Oxygen Therapy at 15 Days Time: 15 daysThis is a multi-center, double-blinded study of COVID-19 infected patients requiring inpatient hospital admission randomized 1:1 to daily Losartan or placebo for 7 days or hospital discharge.
Description: Outcome calculated from the partial pressure of oxygen or peripheral saturation of oxygen by pulse oximetry divided by the fraction of inspired oxygen (PaO2 or SaO2 : FiO2 ratio). PaO2 is preferentially used if available. A correction is applied for endotracheal intubation and/or positive end-expiratory pressure. Patients discharged prior to day 7 will have a home pulse oximeter send home for measurement of the day 7 value, and will be adjusted for home O2 use, if applicable. Patients who died will be applied a penalty with a P/F ratio of 0.
Measure: Difference in Estimated (PEEP adjusted) P/F Ratio at 7 days Time: 7 daysDescription: Outcome reported as the mean number of daily hypotensive episodes (MAP < 65 mmHg) prompting intervention (indicated by a fluid bolus >=500 mL) per participant in each arm.
Measure: Daily Hypotensive Episodes Time: 10 daysDescription: Outcome reported as the number of participants in each arm requiring the use of vasopressors for hypotension.
Measure: Hypotension Requiring Vasopressors Time: 10 daysDescription: Outcome reported as the number of participants in each arm who experience acute kidney injury as defined by the Kidney Disease Improving Global Outcomes (KDIGO) guidelines: Increase in serum creatinine by 0.3mg/dL or more within 48 hours OR Increase in serum creatinine to 1.5 times baseline or more within the last 7 days OR Urine output less than 0.5 mL/kg/h for 6 hours.
Measure: Acute Kidney Injury Time: 10 daysDescription: The SOFA assessment is used to track a person's risk status during stay in the Intensive Care Unit (ICU). The score is based on six different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal, and neurological systems. Each organ system is assigned a point value from 0 (normal) to 4 (high degree of dysfunction/failure). Total score is calculated by entering patient data into a SOFA calculator, a widely-available software. Total scores range from 0-24, with higher scores indicating greater chance of mortality.
Measure: Sequential Organ Failure Assessment (SOFA) Total Score Time: 10 daysDescription: Oxygen saturation (percent) is measured by pulse oximeter. Fraction of inspired oxygen (FiO2) (unitless) is the volumetric fraction of oxygen to other gases in respiratory support. The F/S ratio is unitless.
Measure: Oxygen Saturation / Fractional Inhaled Oxygen (F/S) Time: 10 daysDescription: Outcome reported as the number of participants who have expired at 28 days post enrollment.
Measure: 28-Day Mortality Time: 28 daysDescription: Outcome reported as the number of participants who have expired at 90 days post enrollment.
Measure: 90-Day Mortality Time: 90 daysDescription: Outcome reported as the number of participants in each arm who require admission to the Intensive Care Unit (ICU).
Measure: ICU Admission Time: 10 daysDescription: Outcome reported as the mean number of days participants in each arm did not require mechanical ventilation during an in-patient hospital admission.
Measure: Number of Ventilator-Free Days Time: 10 daysDescription: Outcome reported as the mean number of days participants in each arm did not require therapeutic oxygen usage during an in-patient hospital admission.
Measure: Number of Therapeutic Oxygen-Free Days Time: 10 daysDescription: Outcome reported as the mean number of days participants in each arm did not require vasopressor usage during an in-patient hospital admission.
Measure: Number of Vasopressor-Free Days Time: 10 daysDescription: Outcome reported as the mean length of stay (in days) in the Intensive Care Unit (ICU) for participants in each arm.
Measure: Length of ICU Stay Time: 10 daysDescription: Outcome reported as the mean length of in-patient hospital stay (in days) for participants in each arm.
Measure: Length of Hospital Stay Time: 10 daysDescription: Outcome reported as the number of participants requiring BiPAP OR high flow nasal cannula OR mechanical ventilation OR extracorporeal membranous oxygenation (ECMO) utilization during in-patient hospital care in each arm.
Measure: Incidence of Respiratory Failure Time: 10 daysDescription: The PROMIS Dyspnea (shortness of breath) item banks and pools assess self-reported shortness of breath in general, intensity, frequency and duration on a 0-10 scale, with 0 being no symptoms and 10 being the most severe. Finally, the patient answers the question "I've been short of breath" using a 0-4 scale, 0 being none and the most severe. There is no validated, unified single score and each item is evaluated individually.
Measure: Change in PROMIS Dyspnea scale Time: 10 daysDescription: The SF-12 is a self-reported validated outcome measure assessing the impact of health on an individual's everyday life. Patients fill out a 12 question survey which is then scored by a clinician or researcher. Physical score is computed using the scores of twelve questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health.
Measure: Change in SF-12 Physical Composite Score Time: 10 daysDescription: The SF-12 is a self-reported validated outcome measure assessing the impact of health on an individual's everyday life. Patients fill out a 12 question survey which is then scored by a clinician or researcher. Mental composite score is computed using the scores of twelve questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health.
Measure: Change in SF-12 Mental Composite Score Time: 10 daysDescription: Outcome reported as the number of participants in each arm who fall into each of 7 categories. Lower scores indicate greater condition severity. The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen; 6) Not hospitalized, limitation on activities; 7) Not hospitalized, no limitations on activities.
Measure: Disease Severity Rating Time: 10 daysDescription: Nasopharyngeal swabs will be collected every third day for the duration of study participation. Viral load is measured as number of viral genetic copies per mL.
Measure: Viral Load by Nasopharyngeal Swab Day 9 Time: 9 daysDescription: Nasopharyngeal swabs will be collected every third day for the duration of study participation. Viral load is measured as number of viral genetic copies per mL.
Measure: Viral Load by Nasopharyngeal Swab Day 15 Time: 15 daysDescription: Blood will be collected every third day for viral load assessment for the duration of study participation. Viral load is measured as number of viral genetic copies per mL.
Measure: Viral Load by Blood Day 9 Time: 9 daysDescription: Blood will be collected every third day for viral load assessment for the duration of study participation. Viral load is measured as number of viral genetic copies per mL.
Measure: Viral Load by Blood Day 15 Time: 15 daysAdults who have tested positive for SARS-CoV-2 infection and who do not require supplemental oxygen will receive PUL-042 Inhalation Solution or placebo 3 times over a one week period in addition to their normal care. Subjects will be be followed and assessed for their clinical status over 28 days to see if PUL-042 Inhalation Solution improves the clinical outcome
Description: To determine the efficacy of PUL-042 Inhalation Solution in decreasing the severity of COVID-19 in subjects: 1) who have documented SARS-CoV-2 infection and, 2) who do not require supplemental oxygen (Ordinal Scale for Clinical Improvement 3 or less) at the time of enrollment. The primary endpoint is the difference in the proportion of patients with clinically meaningful worsening of COVID-19 within 28 days from the start of experimental therapy, as indicated by an increase of at least 2 points on the Ordinal Scale for Clinical Improvement. The Ordinal Scale for Clinical Improvement is a nine point scale (0-8) with 0 being no clinical or virological evidence of infection and 8 being death.
Measure: Severity of COVID-19 Time: 28 daysDescription: SARS-Co-V-2 positivity up to 28 days from the start of experimental therapy
Measure: SARS-CoV-2 infection Time: 28 daysDescription: To determine the difference in the proportion of COVID-19 patients with clinically meaningful worsening of COVID-19 within 14 days from the start of experimental therapy, as indicated by an increase of at least 2 points on the Ordinal Scale for Clinical Improvement. The Ordinal Scale for Clinical Improvement is a nine point scale (0-8) with 0 being no clinical or virological evidence of infection and 8 being death.
Measure: Severity of COVID-19 over 14 days Time: 14 daysDescription: To assess the progression of COVID-19 severity during the study as measured by the SARS-CoV-2 Symptom Score. The SARS-CoV-2 Symptom Score measures 3 elements on a 0-3 scale (cough, shortness of breath or difficulty breathing, and muscle aches or fatigue) ranging from 0 for none to 3 for severe. The fourth element is fever and it is rated on a 0-4 scale with 0 being no fever and 4 being life-threatening.
Measure: Severity of COVID-19 symptoms Time: 28 daysDescription: The requirement for ICU admission within 28 days from the start of the experimental therapy.
Measure: ICU admission Time: 28 daysDescription: The requirement for mechanical ventilation within 28 days from the start of the experimental therapy.
Measure: Mechanical Ventilation Time: 28 daysDescription: All cause mortality at 28 days from the start of experimental therapy
Measure: Mortality Time: 28 daysSubjects who have documented exposure to SARS-CoV-2 (COVID-19) will receive 4 doses of PUL-042 Inhalation Solution or 4 doses of a placebo solution by inhalation over 10 days. Subjects will be followed for the incidence and severity of COVID-19 over 28 days. Subjects will be tested for infection with SARS-CoV-2 at the beginning, middle and end of the study.
Description: To determine the efficacy of PUL-042 Inhalation Solution in the prevention of viral infection with SARS-CoV-2 and progression to COVID-19 in subjects: 1) who have repeated exposure to individuals with SARS-CoV-2 infection and, 2) are asymptomatic at enrollment. The primary endpoint is the severity of COVID-19 as measured by the maximum difference from the baseline value in the Ordinal Scale for Symptom Improvement within 28 days from the start of experimental therapy.
Measure: Severity of COVID-19 Time: 28 daysDescription: Positive test for SARS-CoV-2 infection 28 days from the start of experimental therapy in subjects who test negative for SARS-CoV-2 at the pre-treatment visit
Measure: Incidence of SARS-CoV-2 infection Time: 28 daysDescription: Positive test for SARS-CoV-2 infection 14 days from the start of experimental therapy in subjects who test negative for SARS-CoV-2 at the pre-treatment visit
Measure: Incidence of SARS-CoV-2 infection Time: 14 daysDescription: The severity of COVID-19 as measured by the maximum difference from the baseline value in the Ordinal Scale for Symptom Improvement within 14 days from the start of experimental therapy.
Measure: Severity of COVID-19 Time: 14 daysDescription: The requirement for ICU admission within 28 days from the start of experimental therapy.
Measure: ICU admission Time: 28 daysDescription: The requirement for mechanical ventilation within 28 days from the start of experimental therapy.
Measure: Mechanical ventilation Time: 28 daysDescription: All cause mortality at 28 days from the start of experimental therapy.
Measure: Mortality Time: 28 daysPhase 2: The primary objective of the study is to evaluate the clinical efficacy of sarilumab relative to the control arm in adult patients hospitalized with COVID-19 regardless of disease severity strata. Phase 3 Cohort 1: The primary objective of the study is to evaluate the clinical efficacy of sarilumab relative to the control arm in adult patients hospitalized with critical COVID-19 receiving mechanical ventilation at baseline. Phase 3 Cohort 2: The primary objective of the study is to evaluate the clinical efficacy of sarilumab relative to the control arm in adult patients hospitalized with COVID-19 receiving mechanical ventilation at baseline.
Description: Phase 2
Measure: Percent change in C-reactive protein (CRP) levels in patients with serum IL-6 level greater than the upper limit of normal Time: Day 4Description: Phase 3 Cohort 1 7-point Ordinal Scale: Death; Hospitalized, requiring invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); Hospitalized, requiring non-invasive ventilation or high flow oxygen devices; Hospitalized, requiring supplemental oxygen; Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care Not hospitalized
Measure: Proportion of patients with at least 1-point improvement in clinical status using the 7-point ordinal scale in patients with critical COVID-19 receiving mechanical ventilation at baseline Time: Up to day 22Description: Phase 3 Cohort 2
Measure: Proportion of patients with at least 1-point improvement in clinical status using the 7-point ordinal scale in patients with COVID-19 receiving mechanical ventilation at baseline Time: Up to day 22Description: Phase 2
Measure: Time to improvement (2 points) in clinical status assessment on the 7-point ordinal scale in severe or critical patients with serum IL-6 levels greater than the upper limit of normal Time: Up to day 29Description: Phase 2
Measure: Time to improvement (2 points) in clinical status assessment on the 7-point ordinal scale reporting in severe or critical patients with all IL-6 levels Time: Up to day 29Description: Phase 2 Resolution of fever defined as postbaseline body temperature <37.2°C (oral), or <37.6°C (rectal or tympanic) or <36.8°C (temporal or axillary) Documented fever defined as ≥38°C (oral), ≥38.4°C (rectal or tympanic), or ≥37.6°C (temporal or axillary)
Measure: Time to resolution of fever for at least 48 hours without antipyretics in patients with documented fever Time: Up to day 29Description: Phase 2 Defined as postbaseline body temperature <37.2°C (oral), or <37.6°C (rectal or tympanic) or <36.8°C (temporal or axillary)
Measure: Time to resolution of fever for at least 48 hours without antipyretics by clinical severity Time: Up to day 29Description: Phase 2 Defined as postbaseline body temperature <37.2°C (oral), or <37.6°C (rectal or tympanic) or <36.8°C (temporal or axillary)
Measure: Time to resolution of fever for at least 48 hours without antipyretics by baseline IL-6 levels Time: Up to day 29Description: Phase 2 Improvement in oxygenation defined as increase in SpO2/FiO2 of 50 or greater compared to the nadir SpO2/FiO2
Measure: Time to improvement in oxygenation for at least 48 hours Time: Up to day 29Description: Phase 2 Defined as increase in SpO2/FiO2 of 50 or greater compared to the nadir SpO2/FiO2
Measure: Time to improvement in oxygenation for at least 48 hours by clinical severity Time: Up to day 29Description: Phase 2 Defined as increase in SpO2/FiO2 of 50 or greater compared to the nadir SpO2/FiO2
Measure: Time to improvement in oxygenation for at least 48 hours by baseline IL-6 levels Time: Up to day 29Description: Phase 2 Resolution of fever defined as postbaseline body temperature <37.2°C (oral), or <37.6°C (rectal or tympanic) or <36.8°C (temporal or axillary) Improvement in oxygenation defined as increase in SpO2/FiO2 of 50 or greater compared to the nadir SpO2/FiO2
Measure: Time to resolution of fever and improvement in oxygenation for at least 48 hours Time: Up to day 29Description: Phase 2
Measure: Mean change in the 7-point ordinal scale Time: Up to day 29Description: Phase 2
Measure: Percentage of patients in each clinical status category using the 7-point ordinal scale Time: Up to day 29Description: Phase 2 NEWS2 consists of: Physiological Parameters: Respiration rate (per minute), SpO2 Scale 1 (%), SpO2 Scale 2 (%), Use of Air or oxygen, Systolic blood pressure (mmHg), Pulse (per minute), Consciousness, Temperature (°C)
Measure: Time to discharge or to a National Early Warning Score 2 (NEWS2) of ≤2 and maintained for 24 hours Time: Up to day 29Description: Phase 2
Measure: Change from baseline in NEWS2 scoring system Time: Up to day 29Description: Phase 2 Defined as ≥38°C (oral), ≥38.4°C (rectal or tympanic) or ≥37.6°C (temporal or axillary)
Measure: Number of days with fever Time: Up to day 29Description: Phase 2
Measure: Proportion of patients alive, off oxygen Time: At day 29Description: Phase 2
Measure: Number of days of resting respiratory rate >24 breaths/min Time: Up to day 29Description: Phase 2
Measure: Number of days with hypoxemia Time: Up to day 29Description: Phase 2
Measure: Number of days of supplemental oxygen use Time: Up to day 29Description: Phase 2
Measure: Time to saturation ≥94% on room air Time: Up to day 29Description: Phase 2
Measure: Number of ventilator free days in the first 28 days Time: Baseline to day 29Description: Phase 2
Measure: Number of patients requiring initiation of mechanical ventilation Time: Up to day 29Description: Phase 2
Measure: Number of patients requiring non-invasive ventilation Time: Up to day 29Description: Phase 2
Measure: Number of patients requiring the use of high flow nasal cannula Time: Up to day 29Description: Phase 2
Measure: Number of patients admitted into an intensive care unit (ICU) Time: Up to day 29Description: Phase 2
Measure: Number of days of hospitalization among survivors Time: Up to day 29Description: Phase 2
Measure: Number of deaths due to any cause Time: Up to day 60Description: Phase 3
Measure: Proportion of patients with at least 1-point improvement in clinical status using the 7-point ordinal scale Time: Up to day 22Description: Phase 3 Defined as discharged, or alive without supplemental oxygen use or at pre-COVID oxygen use
Measure: Proportion of patients who recover Time: Up to day 22Description: Phase 3
Measure: Proportion of deaths Time: Through day 29Description: Phase 3
Measure: Proportion of patients alive not receiving mechanical ventilation Time: At day 22Description: Phase 3
Measure: Proportion of patients alive not requiring extracorporeal membrane oxygenation (ECMO) Time: At day 22Description: Phase 3
Measure: Proportion of patients with a 2-point improvement in clinical status on the 7-point ordinal scale Time: Up to day 22Description: Phase 3
Measure: Time to at least 1-point improvement in clinical status assessment on the 7-point ordinal scale Time: Up to day 29Description: Phase 3
Measure: Time to at least 2-point improvement in clinical status assessment on the 7-point ordinal scale Time: Up to day 29Description: Phase 3
Measure: Proportion of patients receiving mechanical ventilation Time: Up to day 22Description: Phase 3
Measure: Proportion of patients receiving ECMO Time: Up to day 22Description: Phase 3
Measure: Proportion of patients discharged and alive Time: At day 22Description: Phase 3 Defined as discharged or alive without supplemental oxygen use or at pre-COVID oxygen use
Measure: Time to recovery Time: Up to day 29Description: Phase 3
Measure: Proportion of deaths Time: Through day 60Description: Phase 3
Measure: Time to death due to any cause Time: Through day 60Description: Phase 3
Measure: Number of ventilator free days Time: Up to day 29Description: Phase 3
Measure: Number of days of hospitalization among survivors Time: Up to day 29Description: Phase 2 and Phase 3
Measure: Proportion of patients with serious adverse events Time: Up to Day 29Description: Phase 2 and Phase 3
Measure: Proportion of patients with Grade 4 neutropenia (ANC <500/mm3) Time: Up to day 29Description: Phase 2 and Phase 3
Measure: Proportion of patients with severe or life-threatening bacterial, invasive fungal, or opportunistic infection Time: Up to day 29Description: Phase 2 and Phase 3
Measure: Proportion of patients with severe or life-threatening bacterial, invasive fungal, or opportunistic infection in patients with Grade 4 neutropenia (ANC <500/mm3) Time: Up to day 29Description: Phase 2 and Phase 3
Measure: Proportion of patients with hypersensitivity reactions Time: Up to day 29Description: Phase 2 and Phase 3
Measure: Proportion of patients with infusion reactions Time: Up to day 29Description: Phase 2 and Phase 3
Measure: Proportion of patients with gastrointestinal perforation Time: Up to day 29Description: Phase 2 and Phase 3
Measure: White blood cell count Time: Up to day 29 if still hospitalizedDescription: Phase 2 and Phase 3
Measure: Hemoglobin levels Time: Up to day 29 if still hospitalizedDescription: Phase 2 and Phase 3
Measure: Platelet count Time: Up to day 29 if still hospitalizedDescription: Phase 2 and Phase 3
Measure: Creatinine levels Time: Up to day 29 if still hospitalizedDescription: Phase 2 and Phase 3
Measure: Total bilirubin level Time: Up to day 29 if still hospitalizedDescription: Phase 2 and Phase 3
Measure: Alanine aminotransferase (ALT) level Time: Up to day 29 if still hospitalizedDescription: Phase 2 and Phase 3
Measure: Aspartate aminotransferase (AST) level Time: Up to day 29 if still hospitalizedThis is phase II study to assess the efficacy of NestaCell® (mesenchymal stem cell) to treat severe COVID-19 pneumonia.
Description: Ordinal scale (WHO ordinal scale that measures illness severity over time)
Measure: Change in Clinical Condition Time: 10 daysDescription: Evaluation of Pneumonia change
Measure: Rate of mortality within 10-days Time: 10 daysDescription: Evaluation of Pneumonia change
Measure: Change of Clinical symptoms - respiratory rate Time: 10 daysDescription: oxygen saturation
Measure: Hypoxia Time: 10 daysDescription: oxygen saturation
Measure: PaO2 / FiO2 ratio Time: 10 daysDescription: 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 daysDescription: Number of participants with treatment-related adverse events
Measure: Side effects in the treatment group Time: 10 daysDescription: 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.The study is designed as a randomized, placebo-controlled, double blind, multicenter, Phase III trial to compare two COVID-19 treatment regimens in hospitalized adult subjects who are diagnosed with severe and critical COVID 19. Arm A: CD24Fc/Best Available Treatment; Arm B: placebo/ Best Available Treatment. CD24Fc will be administered as single dose of 480 mg via IV infusion on Day 1. Total of 270 subjects will be enrolled and randomized in 1:1 ratio to receive CD24Fc or placebo. All subjects will be treated with the best available treatment. The follow up period is 28 days.
Description: Time to improve in clinical status: the time (days) required from the start of treatment to the improvement of clinical status "severe" to "moderate/mild"; or improvement from "scale 2, 3, or 4" to "scale 5 or higher" based on NIAID ordinal scales.
Measure: Improvement of COVID-19 disease status Time: 29 daysDescription: Proportion of patients who died or had respiratory failure, defined as the need for mechanical ventilation, ECMO, non-invasive ventilation, or high flow oxygen devices, at Day 29
Measure: Proportion of patients who died or had respiratory failure. Time: 29 daysDescription: Time for disease progression from NIAID scale 3 or 4 to need to be on invasive mechanical ventilation, or ESMO, or death, or from NIAID scale 2 to death.
Measure: Disease progression of COVID-19 Time: 29 daysDescription: All cause of death
Measure: All cause of death Time: 15 days and 29 daysDescription: Proportion of clinical relapse, as defined by rate of return to oxygen support for more than 1 day within 29 days from randomization after initial recovery
Measure: Proportion of clinical relapse Time: 29 daysDescription: Conversion rate of clinical status on days 8 (proportion of subjects who changed from NIAID ordinal "scale 3 or 4" to "scale 5 or higher")
Measure: Conversion rate of clinical status at Day 8 Time: 8 daysDescription: Conversion rate of clinical status on days 15 (proportion of subjects who changed from NIAID ordinal "scale 3 or 4" to "scale 5 or higher")
Measure: Conversion rate of clinical status at Day 15 Time: 15 daysDescription: The discharge time, calculated after the randomization.
Measure: Hospital discharge time Time: 29 daysDescription: Duration of mechanical ventilation (IMV, NIV) (days)
Measure: Duration of mechanical ventilation Time: 29 daysDescription: Duration of pressors (days)
Measure: Duration of pressors Time: 29 daysDescription: Duration of extracorporeal membrane oxygenation (days)
Measure: Duration of ECMO Time: 29 daysDescription: Duration of oxygen therapy (oxygen inhalation by high flow nasal cannula or mask) (days)
Measure: Duration of high flow oxygen therapy Time: 29 daysDescription: Changes of absolute lymphocyte count in peripheral blood
Measure: Absolute lymphocyte count Time: 29 daysDescription: The changes of plasma concentration of D-dimers
Measure: Change of D-dimers Time: 15 and 29 daysThis 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.
A new human coronavirus responsible for pneumonia, SARS-CoV-2, emerged in China in December 2019 and has spread rapidly. COVID-19, the disease caused by this virus, has a very polymorphous clinical presentation, which ranges from upper respiratory tract infections to acute respiratory distress syndrome. It may appear serious straightaway or may evolve in two stages, with a worsening 7 to 10 days after the first clinical signs, potentially linked to a cytokine storm and accompanied by a high risk of thrombosis. The global mortality rate of COVID-19 is between 3% and 4%, with severe forms being more frequent among older patients. Management is symptomatic as no antiviral treatment has demonstrated any clinical benefit in this condition. Hydroxychloroquine is a derivative of chloroquine commonly used in some autoimmune diseases, such as systemic lupus erythematosus. It is active in vitro in cellular models of infection by many viruses such as HIV, hepatitis C or SARS-CoV. However, its interest in viral infections in humans has not been demonstrated. Very recently, a preliminary uncontrolled study evaluated the effect of hydroxychloroquine on viral shedding in subjects with COVID-19. Among 20 patients treated with hydroxychloroquine at a dose of 600 mg per day, the percentage of patients with detectable SARS-CoV-2 RNA in the nasopharynx decreased from 100% at inclusion (start of treatment) to 43% six days later. In comparison, 15 of 16 untreated patients had a positive RT-PCR six days after inclusion. Furthermore, hydroxychloroquine has immunomodulating and anti-inflammatory properties, which could theoretically prevent or limit secondary worsening. The research hypothesis is that treatment with hydroxychloroquine improves prognosis and reduces the risk of death or use for invasive ventilation in patients with COVID-19.
Description: WHO Ordinal Scale for Clinical Improvement ranges from 0 to 8, higher score meaning poorer outcome
Measure: Clinical evolution on the WHO Ordinal Scale for Clinical Improvement for COVID-19 between day 0 and day 14 Time: Day 14Description: WHO Ordinal Scale for Clinical Improvement ranges from 0 to 8, higher score meaning poorer outcome
Measure: Clinical evolution on the WHO Ordinal Scale for Clinical Improvement for COVID-19 between day 0 and day 28. Time: Day 28This is a randomized, double-blind placebo-controlled trial to investigate the efficacy and safety of tradipitant 85 mg orally given twice daily to treat inflammatory lung injury associated with severe or critical COVID-19 infection. On evaluation for enrollment, participant will need to meet all inclusion and exclusion criteria. If participant consents, they will be randomized 1:1 to treatment with either tradipitant 85 mg PO BID or placebo in addition to standard of care for COVID-19 infection as per the protocol at the treating hospital. NEWS 2 will be assessed at screening and daily following randomization. Inflammatory lab markers as detailed should be collected once per day in the morning, preferably at the same time every morning. All enrolled participants will have whole blood collected for whole genome sequencing.
Primary Objective: To evaluate the clinical efficacy of sarilumab relative to the control arm in adult patients hospitalized with severe or critical COVID-19 Secondary Objectives: - Evaluate the 28-day survival rate - Evaluate the clinical efficacy of sarilumab compared to the control arm by clinical severity - Evaluate changes in the National Early Warning Score 2 (NEWS2) - Evaluate the duration of predefined symptoms and signs (if applicable) - Evaluate the duration of supplemental oxygen dependency (if applicable) - Evaluate the incidence of new mechanical ventilation use during the study - Evaluate the duration of new mechanical ventilation use during the Study - Evaluate the proportion of patients requiring rescue medication during the 28-day period - Evaluate need for admission into intensive care unit (ICU) - Evaluate duration of hospitalization (days) - The secondary safety objectives of the study are to evaluate the safety of sarilumab through hospitalization (up to day 29 if patient is still hospitalized) compared to the control arm as assessed by incidence of: - Serious adverse events (SAEs) - Major or opportunistic bacterial or fungal infections in patients with grade 4 neutropenia - Grade ≥2 infusion related reactions - Grade ≥2 hypersensitivity reactions - Increase in alanine transaminase (ALT) ≥3X upper limit of normal (ULN) (for patients with normal baseline) or >3X ULN AND at least 2-fold increase from baseline value (for patients with abnormal baseline) - Major or opportunistic bacterial or fungal infections
Description: The ordinal scale is an assessment of the clinical status. Score ranges 1-7. Lower score is worse.
Measure: Time to improvement of 2 points in clinical status assessment from baseline using the 7-point ordinal scale Time: Baseline to Day 29Description: The ordinal scale is an assessment of the clinical status. Score ranges 1-7. Lower score is worse.
Measure: Proportion of patients with one point improvement from baseline in clinical status assessment at days 4, 7, 15, 21, 29 using the 7-point ordinal scale Time: Baseline to Days 4, 7, 15, 21, 29Description: The ordinal scale is an assessment of the clinical status. Score ranges 1-7. Lower score is worse.
Measure: Mean change in the 7-point ordinal scale from baseline to Days 4, 7, 15, 21, and 29 (or until discharge) Time: Baseline to Days 4, 7, 15, 21, 29 (or until discharge)Description: Defined as body temperature (≤36.6°C [axilla], or ≤37.2 °C [oral], or ≤37.8°C [rectal or tympanic]) for at least 48 hours without antipyretics or until discharge, whichever is sooner.
Measure: Time to resolution of fever Time: Baseline to Day 29Description: Resolution of both fever and improvement in oxygenation. Resolution of fever is defined as body temperature (≤36.6°C [axilla], or ≤37.2 °C [oral], or ≤37.8°C [rectal or tympanic]) for at least 48 hours without antipyretics or until discharge, whichever is sooner. Improvement in oxygenation is defined as SpO2/FiO2 of 50 or greater compared to the nadir SpO2/FiO2 for at least 48 hours, or until discharge, whichever is sooner.
Measure: Time to resolution of fever and improvement in oxygenation Time: Baseline to Day 29Description: Fever is defined as >37.4°C (axilla), or >38.0 °C (oral), or >38.4°C (rectal or tympanic) based on maximum value observed during a 24-hour period.
Measure: Days with fever Time: Baseline to Day 29Description: The National Early Warning Score (NEWS2) is used to standardize the assessment of acute-illness severity, track the clinical condition of patients, and to alert clinical teams to patient deterioration. Score ranges from 0-20. A higher score is worse.
Measure: Time to change in NEWS2 from baseline Time: Baseline to Day 29Description: The NEWS2 is used to standardize the assessment of acute-illness severity, track the clinical condition of patients, and to alert clinical teams to patient deterioration. Score ranges from 0-20. A higher score is worse.
Measure: Time to NEWS2 of <2 and maintained for 24 hours Time: Baseline to Day 29Description: The NEWS2 is used to standardize the assessment of acute-illness severity, track the clinical condition of patients, and to alert clinical teams to patient deterioration. Score ranges from 0-20. A higher score is worse.
Measure: Mean change from baseline to days 4, 7, 15, 21, and 29 in NEWS2 Time: Baseline to days 4, 7, 15, 21, and 29Description: SpO2/FiO2 of 50 or greater compared to the nadir for at least 48 hours, or until discharge, whichever is sooner. SpO2 is oxygen saturation and FiO2 is the fraction of inspired oxygen.
Measure: Time-to-improvement in oxygenation Time: Baseline to Day 29Description: Supplemental oxygen is defined as oxygen administration by nasal cannula, simple face mask, or other similar oxygen delivery device.
Measure: Alive off supplemental oxygen at day 29 Time: Day 29Description: Hypoxemia is defined as SpO2 <93% on room air, or requiring supplemental oxygen, or mechanical ventilatory support.
Measure: Days of hypoxemia Time: Baseline to Day 29Description: Supplemental oxygen is defined as oxygen administration by nasal cannula, simple face mask, or other similar oxygen delivery device.
Measure: Days of supplemental oxygen use Time: Baseline to Day 29Description: For those not requiring these interventions at baseline.
Measure: The number of patients with Initiation of mechanical ventilation, non-invasive ventilation, or use of high flow nasal cannula Time: Baseline to Day 60Description: For patients are not in ICU at baseline
Measure: The number of patients transferred to the ICU or the need to transfer to the ICU (if the ICU is not available) Time: Baseline to Day 60Rationale: Covid-19 spreads rapidly throughout the world. A large epidemic in the Netherlands would seriously challenge the available hospital capacity, and this would be augmented by absenteeism of healthcare workers (HCW). Strategies to prevent absenteeism of HCW are, therefore, desperately needed to safeguard continuous patient care. Bacille Calmette-Guérin (BCG) is a vaccine against tuberculosis, with protective non-specific effects against other respiratory tract infections in in vitro and in vivo studies, and reported significant reductions in morbidity and mortality. The hypothesis is that BCG vaccination can reduce HCW absenteeism during the epidemic phase of Covid-19. Objective: Primary objective: To reduce absenteeism among HCW with direct patient contacts during the epidemic phase of Covid-19. Secondary objective: To reduce hospital admission, ICU admission or death in HCW with direct patient contacts during the epidemic phase of Covid-19. Study design: A placebo-controlled adaptive multi-centre randomized controlled trial. Study population: HCW with direct patient contacts among which nurses and physicians working at emergency rooms and wards where Covid-19-infected patients are treated. Intervention: Participants will be randomized between intracutaneous administration of BCG vaccine or placebo in a 1:1 ratio. Main study parameters/endpoints: Primary endpoint: number of days of (unplanned) absenteeism for any reason. Secondary endpoints include the number of days of (unplanned) absenteeism because of documented Covid-19 infection, and the cumulative incidence of hospital admission, Intensive Care Admission, and death. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Based on previous experience and randomized controlled trials in adult and elderly individuals, the risks of BCG vaccination are considered low. The objective of this trial is to evaluate the beneficial effects of BCG vaccination through a lower work absenteeism rate of HCW and/or a mitigated clinical course of Covid-19 infection. The primary endpoint and the adaptive design with frequent interim analyses facilitate maximum efficiency of the trial, so that results can inform policy making during the ongoing epidemic.
Description: Number of days of unplanned absenteeism for any reason
Measure: Health Care Workers absenteeism Time: Maximum of 365 daysDescription: Exploratory
Measure: the number of days of absenteeism, because of imposed quarantine as a result of exposure to COVID-19 Time: Maximum of 365 daysDescription: Exploratory
Measure: the number of days of absenteeism, because of imposed quarantine as a result of having acute respiratory symptoms, fever or documented COVID-19 Time: Maximum of 365 daysDescription: Exploratory
Measure: the number of days of unplanned absenteeism because of self-reported acute respiratory symptoms Time: Maximum of 365 daysDescription: Exploratory
Measure: the number of days of self-reported fever (≥38 gr C) Time: Maximum of 365 daysDescription: Exploratory
Measure: the cumulative incidence of self-reported fever (≥38 gr C) Time: Maximum of 365 daysDescription: Exploratory
Measure: the number of days of self-reported acute respiratory symptoms Time: Maximum of 365 daysDescription: Exploratory
Measure: the cumulative incidence of self-reported acute respiratory symptoms Time: Maximum of 365 daysDescription: Exploratory
Measure: the cumulative incidence of death for any reason Time: Maximum of 365 daysDescription: Exploratory
Measure: the cumulative incidence of Intensive Care Admission for any reason Time: Maximum of 365 daysDescription: Exploratory
Measure: the cumulative incidence of Hospital Admission for any reason Time: Maximum of 365 daysDescription: Exploratory
Measure: the cumulative incidence and magnitude of plasma/serum antibodies (IgA,M,G) and SARS-CoV-2-specific antibodies at 12 weeks after vaccination and at the end of the study period Time: Maximum of 365 daysDescription: Exploratory
Measure: the cumulative incidence and magnitude of plasma/serum antibodies (IgA,M,G) and SARS-CoV-2-specific antibodies at 12 weeks after vaccination and at the end of the study period Time: 3-6 months after inclusionObjective: To determine if pre-exposure prophylaxis with hydroxychloroquine is effective for the prevention of COVID-19 disease.
Description: Outcome reported as the percent of participants in each arm who are COVID-19-free at the end of study treatment.
Measure: COVID-19-free survival Time: up to 12 weeksDescription: Outcome reported as the percent of participants in each arm who have a confirmed SARS-CoV-2 infection during study treatment.
Measure: Incidence of confirmed SARS-CoV-2 detection Time: up to 12 weeksDescription: Outcome reported as the percent of participants in each arm who report COVID-19-related symptoms during study treatment.
Measure: Incidence of possible COVID-19 symptoms Time: up to 12 weeksDescription: Outcome reported as the percent of participants in each arm who discontinue study medication use for any reason during treatment.
Measure: Incidence of all-cause study medicine discontinuation Time: up to 12 weeksDescription: Participants will self-report COVID-19 status on an ordinal scale as follows: No illness (score=1), Illness with outpatient observation (score=2), Hospitalization (or post-hospital discharge) (score=3), or Hospitalization with ICU stay or death (score=4). Possible scores range from 1-4 with higher scores indicating greater disease severity.
Measure: Ordinal Scale of COVID-19 Disease maximum severity if COVID-19 diagnosed at study end Time: up to 12 weeksDescription: Outcome reported as the percent of participants in each arm who are hospitalized or expire due to COVID-19 during study treatment.
Measure: Incidence of Hospitalization for COVID-19 or death Time: up to 12 weeksDescription: Outcome reported as the percent of participants in each arm who experience medication-related side effects during study treatment.
Measure: Incidence of study medication-related side effects Time: up to 12 weeksTo evaluate the efficacy of a single dose of subcutaneous injections of 180 ug of Peginterferon Lambda-1a, compared with placebo in reducing the duration of viral shedding of SARS-CoV-2 virus in patients with uncomplicated COVID-19 disease.
Description: Time to first of two consecutive negative respiratory secretions obtained by oropharyngeal and/or anterior nare swabs for SARS-CoV-2 by qRT-PCR.
Measure: Duration of Viral shedding of SARS-CoV-2 by qRT-PCR Time: 28 daysDescription: Sars-CoV-2 RNA level in oropharyngeal and/or anterior nare swabs collected daily.
Measure: Sars-CoV-2 viral load Time: 28 daysDescription: Area under the curve of SARSCoV-2 viral load in oropharyngeal and/or anterior nare swabs collected daily.
Measure: Area under the curve of SARS-COV-2 viral load Time: 28 daysDescription: Time to alleviation of all symptoms (fever, chills, cough, nasal congestion, muscle pains), defined as the time from initiation of treatment until all symptoms are rated as absent or mild in symptomatic patients.
Measure: Time to alleviation of all symptoms Time to alleviation of all symptoms Time: 28 daysORCHID is a multicenter, blinded, placebo-controlled, randomized clinical trial evaluating hydroxychloroquine for the treatment of adults hospitalized with COVID-19. Patients, treating clinicians, and study personnel will all be blinded to study group assignment.
Description: We will determine the COVID Ordinal Scale for all patients on study day 15 COVID Ordinal Scale defined as: Death Hospitalized on invasive mechanical ventilation or ECMO ( extracorporeal membrane oxygenation) Hospitalized on non-invasive ventilation or high flow nasal cannula Hospitalized on supplemental oxygen Hospitalized not on supplemental oxygen Not hospitalized with limitation in activity (continued symptoms) Not hospitalized without limitation in activity (no symptoms)
Measure: COVID Ordinal Outcomes Scale on Day 15 Time: assessed on study day 15Description: Vital status of the patient on day 15 will be determined using any of the following methods: medical record review, phone calls to patient or proxy
Measure: all-location, all-cause mortality assessed on day 15 Time: assessed on study day 15Description: Vital status of the patient at day 28 will be determined using any of the following methods: medical record review, phone calls to patient or proxy
Measure: all-location, all-cause mortality assessed on day 29 Time: assessed on study day 29Description: We will determine the COVID Ordinal Scale for all patients on study day 3
Measure: COVID Ordinal Outcomes Scale on Study Day 3 Time: assessed on study day 3Description: We will determine the COVID Ordinal Scale on study day 8
Measure: COVID Ordinal Outcomes Scale on Study Day 8 Time: assessed on study day 8Description: We will determine the COVID Ordinal Scale on study day 29
Measure: COVID Ordinal Outcomes Scale on Study Day 29 Time: assessed on study day 29Description: We will determine the number of patients who are either dead or on ECMO ( extracorporeal membrane oxygenation) between enrollment and day 28
Measure: Number of patients dead or with receipt of ECMO between enrollment and Day 28 Time: Enrollment to Day 28Description: The number of calendar days between randomization and 28 days later that the patient is alive and without the use of oxygen therapy. Patients who die prior to day 28 are assigned zero oxygen free days.
Measure: Oxygen-free days through Day 28 Time: 28 days after randomizationDescription: Ventilator-free days is defined to be 28 days minus the duration of mechanical ventilation through day 28. Participants who do not survive to day 28 are assigned zero ventilator-free days.
Measure: Ventilator-free days through Day 28 Time: 28 days after randomizationDescription: The number of calendar days between randomization and 28 days later that the patient is alive and without the use of vasopressor therapy. Patients who die prior to day 28 are assigned zero vasopressor free days.
Measure: Vasopressor-free days through Day 28 Time: 28 days after randomizationDescription: The number of days spent out of the ICU to day 28.
Measure: ICU-free days to Day 28 Time: 28 days after randomizationDescription: Defined as 28 days minus the number of days from randomization to discharge home.If a patient has not been discharged home prior to day 28 or dies prior to day 28, hospital free days will be zero.
Measure: Hospital-free days to Day 28 Time: 28 days after randomizationDescription: We will determine the number of patients that experience seizure between randomization and day 28
Measure: Number of patients with seizures to day 28 Time: 28 days after randomizationDescription: We will determine the number of patients that experience ventricular arrhythmia between randomization and day 28
Measure: Number of patients with atrial or ventricular arrhythmia to day 28 Time: 28 days after randomizationDescription: We will determine the number of patients that experience cardiac arrest between randomization and day 28
Measure: Number of patients with cardiac arrest to day 28 Time: 28 days after randomizationDescription: We will determine the number of patients that experience elevation in aspartate aminotransferase or alanine aminotransferase to twice the local upper limit of normal between randomization and day 28
Measure: Number of patients with elevation in aspartate aminotransferase or alanine aminotransferase to twice the local upper limit of normal to day 28 Time: 28 days after randomizationDescription: We will determine the number of patients that experience acute pancreatitis between randomization and day 28
Measure: Number of patients with acute pancreatitis arrest to day 28 Time: 28 days after randomizationDescription: We will determine the number of patients that experience acute kidney injury between randomization and day 28
Measure: Number of patients with acute kidney injury to day28 Time: 28 days after randomizationDescription: We will determine the number of patients that experience renal replacement therapy between randomization and day 28
Measure: Number of patients with receipt of renal replacement therapy to day 28 Time: 28 days after randomizationDescription: We will determine the number of patients that experience symptomatic hypoglycemia between randomization and day 28
Measure: Number of patients with symptomatic hypoglycemia to day 28 Time: 28 days after randomizationDescription: We will determine the number of patients that experience neutropenia, lymphopenia, anemia, or thrombocytopenia between randomization and day 28
Measure: Number of patients with neutropenia, lymphopenia, anemia, or thrombocytopenia to day 28 Time: 28 days after randomizationDescription: We will determine the number of patients that experience severe dermatologic reaction between randomization and day 28
Measure: Number of patients with severe dermatologic reaction to day 28 Time: 28 days after randomizationDescription: Time to recovery, defined as time to reaching level 5, 6, or 7 on the COVID Outcomes Scale, which is the time to the earlier of final liberation from supplemental oxygen or hospital discharge
Measure: Time to recovery, defined as time to reaching level 5, 6, or 7 on the COVID Outcomes Scale, which is the time to the earlier of final liberation from supplemental oxygen or hospital discharge Time: 28 days after randomizationPatients with documented moderate COVID-19 infection will be randomized 1:1 to receive piclidenoson 2 mg Q12H orally with standard supportive care (SSC - intervention arm) or placebo orally with SSC (control arm) for up to 28 days.
Description: Proportion of subjects alive and free of respiratory failure (defined as need for non-invasive or invasive mechanical ventilation, high-flow oxygen, or extracorporeal membrane oxygenation) at Day 29
Measure: Proportion of subjects alive and free of respiratory failure Time: 29 daysDescription: Proportion of subjects alive and discharged to home without need for supplemental oxygen at Day 29
Measure: Proportion of subjects discharged home alive Time: 29 daysDescription: Proportion of patients experiencing AEs
Measure: Treatment-emergent adverse events (AEs) Time: 29 daysDescription: • Clinical status at Day 29 on NIAID 8-point ordinal scale (NIH 2020): Not hospitalized, no limitations Not hospitalized, with limitations Hospitalized, no active medical problems Hospitalized, not on oxygen Hospitalized, on oxygen Hospitalized, on high-flow oxygen or noninvasive mechanical ventilation Hospitalized, on mechanical ventilation or ECMO Death
Measure: Clinical status Time: 29 daysDescription: Time (days) to improvement of 2 points on 7-point ordinal clinical scale
Measure: Time to improvement Time: 29 daysDescription: Proportion of patients who require mechanical ventilation
Measure: Incidence of mechanical ventilation Time: 29 daysDescription: Ventilator-free days to Day 29
Measure: Ventilator-free days Time: 29 daysDescription: Proportion of patients who require ICU admission
Measure: Incidence of Intensive Care Unit (ICU) admission Time: 29 daysDescription: Duration (days) of ICU stay
Measure: Duration of ICU stay Time: 29 daysDescription: Time (days) to hospital discharge
Measure: Time to hospital discharge Time: 29 daysDescription: Duration (days) of need for supplemental oxygen
Measure: Duration of need for supplemental oxygen Time: 29 daysDescription: Time (days) to virus negativity by RT-PCR, defined as absence of SARS CoV 2 on 2 consecutive days of sampling
Measure: Time to virus negativity Time: 29 daysDescription: SARS-CoV-2 viral load (number of copies) by quantitative RT-PCR
Measure: SARS-CoV-2 viral load Time: 29 daysDescription: Proportion of patients experiencing AEs leading to early discontinuation of trial treatment
Measure: AEs leading to withdrawal Time: 29 daysDescription: Proportion of patients experiencing SAEs
Measure: Treatment-emergent serious AEs (SAEs) Time: 29 daysDescription: Proportion of patients experiencing treatment-emergent changes in clinical laboratory parameters or ECGs
Measure: Treatment-emergent abnormalities in clinical laboratory parameters or electrocardiograms (ECGs) Time: 29 daysDescription: Proportion of patients who meet study safety-related stopping rules
Measure: Incidence of meeting safety-related stopping rules Time: 29 daysDescription: Plasma concentrations over time of piclidenoson
Measure: Pharmacokinetics of piclidenoson in this patient population Time: 5 daysDescription: Change from baseline in serum concentrations of cytokines
Measure: Serum cytokine levels Time: 29 daysPrimary Objective: To assess the effect of hydroxychloroquine versus placebo on nasopharyngeal SARS-CoV-2 viral load in outpatient adults with COVID-19 Secondary Objectives: - To assess the effect of hydroxychloroquine versus placebo on clinical signs and symptoms and progression of disease in outpatient adults with COVID-19 - To assess the safety and tolerability of hydroxychloroquine in outpatient adults with COVID-19
Description: Viral load assessed by PCR from a nasopharyngeal swab
Measure: Change from baseline to Day 3 in nasopharyngeal SARS-CoV-2 viral load (if quantitative PCR is available) Time: Baseline to Day 3Description: Viral load assessed by PCR from a nasopharyngeal swab - 2. Viral load assessed by PCR from a nasopharyngeal swab
Measure: Number of participants by PCR result status (positive or negative) (if quantitative PCR is not available) Time: Baseline to Day 3Description: Viral load assessed by PCR from a nasopharyngeal swab
Measure: Change from baseline to Day 5 in nasopharyngeal SARS-CoV-2 viral load Time: Baseline to Day 5Description: Viral load assessed by PCR from a nasopharyngeal swab
Measure: Number of participants by PCR result status (positive or negative) Time: Baseline to end of study (Day14)Description: COVID-19 symptoms (feverishness, sore throat, cough, shortness of breath, myalgias) will be scored by the participant on a 4-point scale ( 0 =none; 1 = mild; 2 = moderate; 3 = severe)
Measure: Number of participants with COVID-19 symptoms by severity Time: Baseline to end of study (Day14)Description: COVID-19 symptoms (feverishness, sore throat, cough, shortness of breath, myalgias) will be scored by the participant on a 4-point scale ( 0 =none; 1 = mild; 2 = moderate; 3 = severe). Resolution of a symptom is defined as when a symptom previously scored ≥ 1 on the scale is scored as 0
Measure: Time to resolution of COVID-19 Symptoms Time: Baseline to end of study (Day14)Description: Resolution of fever defined as the first day of 2 consecutive daily temperatures < 37.7 C
Measure: Time to resolution of fever Time: Baseline to end of study (Day14)Description: Resolution of fever defined as the first day of 2 consecutive daily temperatures < 37.7 C
Measure: Percentage of participants with resolution of fever Time: Baseline to end of study (Day14)The objective of CROWN CORONATION is the prevention of symptomatic COVID-19 by using combinations of approved and safe repurposed interventions, with complementary mechanisms of action.
Description: To determine the incidence of the trial intervention(s) in preventing laboratory test-confirmed, symptomatic COVID19 (i.e. any of the following: cough, shortness of breath or difficulty breathing, fever, chills, muscle pain, sore throat, new loss of taste or smell, nausea, vomiting, or diarrhea), in healthcare workers with repeated exposures to SARS-CoV-2 by day 60 after enrollment.
Measure: Symptomatic COVID-19 Time: 60 daysDescription: Severity of COVID-19 will be graded on a simplified version of the ordinal World Health Organization COVID-19 severity scale (WHO COVID-19 severity scale).
Measure: Severity of COVID-19 over the study period Time: 60 daysDescription: SARS-CoV-2 infection (by serology) over up to 5 months of follow-up
Measure: Effectiveness of preventing/reducing SARS-CoV-2 infection Time: 5 monthsThis is an double-blind, randomized, placebo controlled phase III study in hospitalized subjects with confirmed SARS-CoV-2.
Description: Time to treatment failure during the 28-day treatment period. Treatment failure is defined as additional or alternative treatment required, or intubation and invasive ventilation, or transfer to intensive care unit, or death.
Measure: Evaluation of EPA-FFA efficacy compared to placebo Time: 28 daysDescription: To determine whether EPA-FFA gastro-resistant capsules decreases the time to and amount of clinical improvement as determined by the WHO 9-point ordinal scale during the study.
Measure: Time to and amount of clinical improvement Time: 28 daysDescription: To determine whether EPA-FFA gastro-resistant capsules increases the number of subjects alive and discharged home without supplemental oxygen therapy.
Measure: Change in recovery and survival rate Time: 28 daysDescription: To determine whether EPA-FFA gastro-resistant capsules decreases CRP and IL-6 during the study.
Measure: Reduction of CRP and IL-6 Time: 28 daysDescription: To determine whether EPA-FFA gastro-resistant capsules increases IFN-γ during the study
Measure: Increase in IFN-γ Time: 28 daysDescription: To determine whether EPA-FFA gastro-resistant capsules decreases other proinflammatory chemokines and cytokines.
Measure: Reduction in proinflammatory chemokines and cytokines. Time: 28 daysDescription: To evaluate the safety of EPA-FFA gastro-resistant capsules in the treatment of COVID-19 (SARS-CoV-2) by assessing subjects clinical lab parameters and vital signs, and the number and proportion of subjects with AEs.
Measure: Safety - Vitals, AEs and Clinical lab parameters Time: throughout the study, about 3 monthsThe mortality rate of the disease caused by the corona virus induced disease (COVID-19) has been estimated to be 3.7% (WHO), which is more than 10-fold higher than the mortality of influenza. Patients with certain risk factors seem to die by an overwhelming reaction of the immune system to the virus, causing a cytokine storm with features of Cytokine-Release Syndrome (CRS) and Macrophage Activation Syndrome (MAS) and resulting in Acute Respiratory Distress Syndrome (ARDS). Several pro-inflammatory cytokines are elevated in the plasma of patients and features of MAS in COVID-19, include elevated levels of ferritin, d-dimer, and low platelets. There is increasing data that cytokine-targeted biological therapies can improve outcomes in CRS or MAS and even in sepsis. Tocilizumab (TCZ), an anti-IL-6R biological therapy, has been approved for the treatment of CRS and is used in patients with MAS. Based on these data, it is hypothesized that TCZ can reduce mortality in patients with severe COVID-19 prone to CRS and ARDS. The overall purpose of this study is to evaluate whether treatment with TCZ reduces the severity and mortality in patients with COVID-19.
Description: Assessed by the 8-point WHO scale
Measure: Illness severity Time: At days 2, 7, 14, 28 after randomisationDescription: Clinical improvement is defined as a ≥ 2-point improvement in the 8-point WHO scale
Measure: Number of patients with clinical improvement Time: At days 2, 7, 14, 28 after randomisationDescription: Clinical improvement is defined as a ≥ 2-point improvement in the 8-point WHO scale
Measure: Time to clinical improvement (days) Time: Up to day 28 after randomisationDescription: Events of special interest are defined as secondary infections, acute kidney failure, hepatic, and cardiac failure
Measure: Number of patients with events of special interest Time: Within 28 days after randomisationThis study evaluates treatment with Favipiravir combined with supportive care for adult patients with COVID-19-moderate type.
Description: The duration from start of treatment (Favipiravir or placebo) to normalization of pyrexia, respiratory rate and SPO2 and relief of cough (where there are relevant abnormal symptoms at enrolment) that is maintained for at least 72 hours.
Measure: Time from randomization to clinical recovery Time: 90 daysDescription: 1. Time from randomization to negativity in RT-PCR nucleic acid test for 2019-nCov within 28 days of randomization;
Measure: Time from randomization to negativity in RT-PCR nucleic acid test Time: 28 daysDescription: Incidence of deterioration/aggravation of pneumonia (defined as SPO2≤93% or PaO2/FiO2 ≤300 mmHg or distressed RR≥30/min without oxygen inhalation and requiring oxygen therapy or more advanced breath support) within 28 days of randomization;
Measure: Incidence of deterioration/aggravation of pneumonia Time: 28 daysDescription: Time from randomization to resolution of pyrexia (defined the same as for the primary efficacy variable; applicable to subjects with pyrexia at enrolment) within 28 days of randomization;
Measure: Time from randomization to resolution of pyrexia Time: 28 daysDescription: Time from randomization to relief of cough (defined the same as for the primary efficacy variable; applicable to subjects with cough at enrolment) within 28 days of randomization; It is recommended that the severity of cough be graded as per NCI-CTCAE v5.0: Mild: Requires non-prescription treatment; Moderate: Requires medication treatment; limits instrumental activities of daily living; Severe: Limits self-care activities of daily living
Measure: Time from randomization to relief of cough Time: 28 daysDescription: Time from randomization to relief of dyspnoea (defined as subject-perceived improvement or resolution of dyspnoea; applicable to subjects with dyspnoea at enrolment) within 28 days of randomization;
Measure: Time from randomization to relief of dyspnoea Time: 28 daysDescription: 6. Rate of auxiliary oxygen therapy or non-invasive ventilation within 28 days of randomization
Measure: Rate of auxiliary oxygen therapy Time: 28 daysDescription: ICU admission rate within 28 days of randomization
Measure: ICU admission rate Time: 28 daysDescription: All-cause mortality within 28 days of randomization
Measure: Mortality Time: 28 daysThis center intends to conduct a single-center, randomized, placebo-controlled study to evaluate the effectiveness and safety of Nintedanib ethanesulfonate soft capsule in the treatment of pulmonary fibrosis in patients with moderate to severe COVID-19.
Description: Changes in forced vital capacity (FVC) after treatment compared to baseline.
Measure: Changes in forced vital capacity (FVC) Time: 8 weeksDescription: Changes incarbon monoxide dispersion (DLco%) after treatment compared to baseline.
Measure: Changes in carbon monoxide dispersion (DLco%) Time: 8 weeksDescription: Changes in the six-minute walk test (6MWT) after treatment compared to baseline.
Measure: Changes in the six-minute walk test (6MWT) Time: 8 weeksDescription: Changes in High resolution CT score after treatment compared to baseline.The minimum and maximum values are 0 and 25 , and higher scores mean a worse outcome. As for the score, it is the expected value and will be determined according to the actual result
Measure: Changes in High resolution CT score Time: 8 weeksEvaluation of the efficacy and safety of hydroxychloroquine - camostat combination therapy in hospitalized patients with moderate COVID-19 infection, CLOCC-Trial Primary Objectives: The primary objective of this study is to demonstrate, that a combination therapy of hydroxychloroquine and camostat (Foipan®) is superior to hydroxychloroquine + placebo in participants with moderate COVID-19.
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.
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 weeksDescription: Evaluation of Pneumonia change
Measure: Blood oxygen saturation Time: Monitor blood oxygen saturation of the participants within 4 weeksDescription: 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 4Description: 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 4Description: 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 4Description: Degree of infection
Measure: Peripheral blood count recovery time Time: At baseline, Day 1, Day 2, Day 7, Week 2, Week 3, Week 4Description: 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 4Description: 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 4Trial design: Prospective, multi-centre, randomised, pragmatic, double blind trial Methods: Participants: Adult (>18 years) within 24 hours of admission to intensive care unit with proven or suspected COVID-19 infection, whether or not mechanically ventilated. Exclusion criteria: symptoms of febrile disease for ≥1 week, treatment limitations in place or moribund patients, allergy or intolerance of any study treatment, incl. long QT syndromes, participation in another outcome-based interventional trial within last 30 days, patients taking Hydrochloroquine for other indication than COVID-19, pregnancy. Interventions: Patients will be randomised in 1:1:1 ratio to receive Hydrochloroquine 800mg orally in two doses followed by 400mg daily in two doses and Azithromycin 500 mg orally in one dose followed by 250 mg in one dose for a total of 5 days (HC-A group) or Hydrochloroquine+ placebo (HC group) or placebo + placebo (C-group) in addition to best standard of care, which may evolve during the trial period but will not differ between groups. Objective: To test the hypothesis that early administration of combination therapy slows disease progression and improves mechanical-ventilation free survival. Outcomes: Primary outcome: Composite percentage of patients alive and not on end-of-life pathway who are free of mechanical ventilation at day 14. Secondary outcomes: Composite percentage of patients alive and not on end-of-life pathway who are free of mechanical ventilation at day 14 in the subgroup of patients without the need of mechanical ventilation at baseline. ICU-LOS D28 and D 90 mortality (in hospital) Tertiary (exploratory) outcomes: Viral load at D7 of study enrolment (No of viral RNA copies/ml of blood), proportion of patients alive and rtPCR negative from nasal swab at D14, Difference of FiO2 requirement and respiratory system compliance between day 0 and 7. Randomization: In 1:1:1 ratio and stratified according to study centre and patients age (cut-off 70 years) Blinding (masking): Patients, treating clinicians, outcome assessors and data analyst will be blinded to study treatment allocation. Unblinded study pharmacist or research nurse will prepare investigational products.
Description: Composite percentage of patients alive and not on end-of-life pathway who are free of mechanical ventilation at day 14.
Measure: Proportion of alive patients free off mechanical ventilation Time: 14 days after enrolmentDescription: Composite percentage of patients alive and not on end-of-life pathway who are free of mechanical ventilation at day 14 in the subgroup of patients without the need of mechanical ventilation at baseline.
Measure: Proportion of patients who avoided the need of mechanical ventilation Time: 14 daysDescription: Length of stay in intensive care unit
Measure: ICU LOS Time: 28 daysDescription: Proportion of patients who died by day 28
Measure: Mortality28 Time: 28 daysDescription: Proportion of patients who died by day 90
Measure: Mortality90 Time: 90 daysThe current outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) is a global health emergency with a case fatality rate so far approximately 4% and a growing number of confirmed cases (>57.000) in Germany. There is no data available on the efficacy of antiviral agents for the treatment of COVID-19. In-vitro data show that hydroxychloroquine can inhibit SARS-CoV-2 [1] replication and anecdotal reports from Chinese COVID-19 patients [2, 3] suggest that chloroquine is a good candidate for treatment. No data have been published and reported evidence is based on non-controlled use of hydroxychloroquine. The aim of this placebo-controlled trial is to assess the effect of hydroxychloroquine on duration of symptoms in mild COVID-19 patients and time of virus shedding as an important tool to reduce the risk of further community transmissions. This data will inform practice for the design of larger trials on clinical efficacy of hydroxychloroquine in the treatment and post- and preexposure prophylaxis of COVID-19 and as a tool for reduction of community transmission.
This is a randomized, double-blind, placebo-controlled, multi-center trial to evaluate the safety and efficacy of TJ003234 administered as an intravenous (IV) infusion in subjects with severe COVID-19 under supportive care, and to assess the effect of TJ003234 on the levels of cytokines.
This is a phase II, randomised, double-blinded and placebo-controlled clinical trial in healthy adults above 18 years of age. This clinical trial is designed to evaluate the immunogenicity and safety of Ad5-nCoV which encodes for a full-length spike (S) protein of SARS-CoV-2.
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.
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 daysDescription: Progression to a higher level of care, e.g. ICU
Measure: Proportion of patients who require escalation in care Time: 14 daysDescription: 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 daysDescription: Survival to hospital discharge
Measure: Proportion of patients surviving to hospital discharge Time: daysDescription: Incidence and type of adverse events
Measure: Drug safety profile Time: 14 daysDescription: Number of days spent on advanced respiratory support measures
Measure: Duration of advanced respiratory support Time: daysDescription: Length of hospitalization (in patients who survive to discharge)
Measure: Duration of hospital stay Time: daysDescription: 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: daysDescription: Time (in days) to resolution of fever
Measure: Time to resolution of fever Time: 14 daysDescription: 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 daysThe current outbreak of COVID-19 caused by SARS-CoV-2 is a global health emergency with a case fatality rate so far approximately 4% and a growing number of confirmed cases (>9500) in Germany. There is no data available on the efficacy of antiviral agents for the treatment of COVID-19. In vitro data show that hydroxychloroquine can inhibit SARS-CoV-2 replication and anecdotal reports from COVID-19 patients in China and France suggest that chloroquine or hydroxychloroquine is a good candidate for treatment. In the French study a favourable effect was seen when hydroxychloroquine was used together with azithromycin in a small series of COVID-19 patients. However, so far all published evidence is based on non-controlled use of hydroxychloroquine. We propose to conduct a placebo-controlled trial in COVID-19 patients with mild to moderate disease in Germany to assess virological efficacy, tolerability and safety of hydroxychloroquine in the treatment of COVID-19. The objective of this trial is to identify an effect of hydroxychloroquine on viral clearance in vivo. This data will inform practice for the design of larger trials on clinical efficacy of hydroxychloroquine in the treatment and post-exposure prophylaxis of COVID-19.
Description: Viral clearance defined as time to sustained SARS-CoV-2-specific RNA copy number ≤100, measured by real time reverse-transcription polymerase chain reaction RT-PCR in throat swabs.
Measure: Effect of HCQ on in vivo viral clearance Time: 6 monthsThe purpose of this research study is to determine if a drug called fluvoxamine can be used early in the course of the COVID-19 infection to prevent more serious complications like shortness of breath. Fluvoxamine is an anti-depressant drug approved by the FDA for the treatment of obsessive-compulsive disorder. The use of fluvoxamine for the treatment of COVID-19 is considered investigational, which means the US Food and Drug Administration has not approved it for this use. This study is fully-remote, which means that there is no face-to-face contact; study materials including study drug will be shipped to participants' houses. Only residents of Missouri and Illinois may participate.
Description: Clinical worsening is defined meeting both of the following: (1) presence of dyspnea and/or hospitalization for shortness of breath or pneumonia, plus (2) decrease in O2 saturation (<92%) on room air and/or supplemental oxygen requirement in order to keep O2 saturation >92%.
Measure: Time to clinical worsening Time: RCT (approximately 15 days)Description: (1) moderate severity of illness as defined by O2 saturation <92% but no supplemental oxygen requirement; (2) O2 saturation plus supplemental oxygen requirement; (3) O2 saturation <92% plus hospitalization (related to dyspnea/hypoxia); (4) the above, plus ventilator support requirement; (5) the above, plus ventilator support for at least 3 days; (6) death.
Measure: clinical deterioration on a Likert-type scale (1-6) Time: RCT (approximately 15 days)Description: (1) requiring supplemental oxygen; (2) requiring hospitalization; (3) requiring ventilator support.
Measure: clinical deterioration measured by number of days Time: RCT (approximately 15 days)Description: Outcomes will be collected daily, with symptomatic data collected approximately twice daily. The most severe symptom at baseline will be the focus.
Measure: Symptomatic severity on a likert scale (0-10 where 0= none and 10=very severe) Time: RCT (approximately 15 days)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.
Description: Number of days on which a participant breathes without assistance
Measure: Number of Ventilator Free Days Time: Day 1 to Day 28Description: 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 28Description: Survival without Respiratory Failure
Measure: Percentage of Participants who are Alive and Respiratory Failure Free Time: Day 1 to Day 28Description: Mortality
Measure: Mortality Time: Day 1 to Day 28Description: Days of Hospitalization
Measure: Length of Hospitalization Time: Day 1 to Day 28Description: Number of Participants with any Serious Adverse Event (SAE)
Measure: Number of Participants with any Serious Adverse Event (SAE) Time: Day 1 to Day 28Description: 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 28Trial to evaluate the efficacy and safety of NTZ for post-exposure prophylaxis of COVID-19 and other VRIs in elderly LTCF residents.
Description: The proportion of subjects with symptomatic laboratory-confirmed COVID-19 identified after start of treatment and before the end of the 6-week treatment period.
Measure: Symptomatic laboratory-confirmed COVID-19 Time: up to 6 weeksDescription: The proportion of subjects with symptomatic laboratory-confirmed VRI identified after the start of treatment and before the end of the 6-week treatment period.
Measure: Symptomatic laboratory-confirmed VRI Time: up to 6 weeksWe will evaluate low-dose pyridostigmine as add-on therapy to best medical care in patients with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and its related Coronavirus Disease 2019 (COVID-19) who require hospitalization. Our hypothesis is that, in comparison to the placebo, pyridostigmine will reduce in at least 10% a composite outcome [death; mechanical ventilation; >2 point-increase in the SOFA score) by day 28. We will also evaluate interleukin (IL)-6 kinetics during the first 14 days of in-hospital stay. It is estimated that 25-33% of patients hospitalized for COVID-19 are admitted to intensive care units (ICU) for severe hypoxemia. The reported mortality in those with severe disease ranges between 38% and 49%. So far, there is no pharmacological therapeutic (or else) strategy known to reduce morbidity and mortality in these patients. Mortality in COVID-19 appears to be mediated not necessarily by the direct effect of the infection, but by the disproportionate inflammatory response of the host. Pyridostigmine is an old drug that, by inhibiting acetylcholine-esterase, the enzymatic machinery that degrades acetylcholine (ACh), results in increased ACh bioavailability. ACh, in turn, ligates to nicotinic-alpha7 receptors in macrophages and T cells, resulting in reduced overactivation of these immune cells. In experimental murine sepsis, this family of drugs has resulted in reduced inflammation and mortality. Human evidence is scarce for severe inflammatory conditions. However, recent evidence from our group and others indicates that pyridostigmine has an immunomodulatory effect in people living with HIV, resulting in elevation of CD4+ T cell counts, decreased immune activation, and reduction in inflammatory mediators. Altogether, this suggests that ACh-esterase inhibitors may act as immunomodulators during viral infections, potentially reducing the inflammatory cascade (the so-called "cytokine storm") observed in critically ill COVID-19 patients. At the proposed dose (60mg/d), the rate of minor adverse events is less than 5% with no reported serious adverse effects. From that perspective, we consider that pyridostigmine can function as an immuno-modulator and reduce morbidity and mortality in COVID-19-stricken patients, with the added value of a safe pharmacological profile. Moreover, as an old drug, re-purposing it for a novel indication may be a simpler, more efficient approach than developing a novel one from the ground up.
Description: Composite of death, Need for mechanical ventilation, or an increase of 2 or more points in the SOFA score
Measure: Critical condition or death Time: 28 daysDescription: Kinetics of circulating IL-6
Measure: IL-6 Time: 14 days in-hospital, hospital discharge, or deathIn this study invetigators propose to administer clazakizumab to patients with life-threatening COVID-19 infection manifest by pulmonary failure and a clinical picture consistent with a cytokine storm syndrome. This is a single-center randomized, double-blind, placebo-controlled trial in which 80 patients will be enrolled and randomly assigned in a 1:1:1 ratio to three study arms and received clazakizumab at a dose of 12.5 mg, 25 mg or placebo. Based on interim analysis, the remaining 10 subjects at NYU will be randomly assigned to a 1:1 ratio to two arms that will receive clazakizumab at a dose of 25 mg or placebo. The NYU site will serve as the central data management site for other centers who undertake this protocol. Other sites will enroll patients based on the two arm 1:1 randomization. 60 patients at outside sites are expected to enroll.
Description: Number of patients who remain alive at time point.
Measure: Patient Survival Time: 28 daysDescription: Number of patients who remain alive at end of study.
Measure: Patient Survival Time: 60 daysThis study will the safety of a 96-hour intravenous vitamin C infusion protocol (50 mg/kg every 6 hours) in patients with hypoxemia and suspected COVID-19.
Description: COVID disease status will be measured by the 9-point (from 0 to 8) World Health Organization (WHO) ordinal scale for disease improvement at 28 days.
Measure: Change in COVID disease status Time: Baseline to 28, 60 and 90 daysDescription: Change in serum oxalate levels
Measure: Renal safety biomarkers - serum oxalate Time: On days 5,7 and 14Description: Microscopic analysis of urine for presence of oxalate stones
Measure: Renal safety biomarkers - urine oxalate stones Time: On days 5,7 and 14Description: 24-hour urine oxalate levels
Measure: Renal safety biomarkers - 24-hour urine oxalate levels Time: On days 5,7 and 14Description: Renal-failure free days, with AKI defined by the KDIGO criteria
Measure: Acute Kidney Injury-free days Time: On day 28, 90Description: Mortality by all causes
Measure: Number of deaths Time: On day 28, 60 and 90 daysDescription: Difference in plasma ferritin levels in ng/mL, compared to baseline levels
Measure: Change in plasma ferritin levels Time: Days 1-7 compared with baselineDescription: Difference in D-dimer levels in mcg/mL, compared to baseline levels
Measure: Change in plasma D-dimer levels Time: Days 1-7 compared with baselineDescription: Difference in lactate dehydrogenase (LDH) levels in units/L, compared to baseline levels
Measure: Change in serum lactate dehydrogenase (LDH) levels Time: Days 1-7 compared with baselineDescription: Difference in plasma IL-6 levels in pg/mL, compared to baseline levels
Measure: Change in plasma IL-6 levels Time: Days 1-7 compared with baselineDescription: Respiratory failure defined as resource utilization requiring at least 1 of the following: Endotracheal intubation and mechanical ventilation, Oxygen delivered by high-flow nasal cannula (heated, humidified, oxygen delivered via reinforced nasal cannula at flow rates >20L/min with fraction of delivered oxygen ≥0.5), noninvasive positive pressure ventilation, extracorporeal membrane oxygenation
Measure: Proportion of patients alive and free of respiratory failure Time: At 28-daysDescription: Percentage of patients alive and not requiring invasive mechanical ventilation
Measure: Proportion of patients alive and free of invasive mechanical ventilation Time: At 28-daysPart 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.
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 30Description: 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 30Description: Concentration measured using a validated assay
Measure: CM4620-IE serum concentration Time: enrollment through 72 hoursCoronavirus Disease 2019 (COVID-19) is spreading worldwide and has become a public health emergency of major international concern. Currently, no specific drugs or vaccines are available. For severe cases, it was found that aberrant pathogenic T cells and inflammatory monocytes are rapidly activated and then producing a large number of cytokines and inducing an inflammatory storm.Mesenchymal stem cells (MSCs) have been shown to possess a comprehensive powerful immunomodulatory function. This study aims to investigate the safety and efficacy of intravenous infusion of mesenchymal stem cells in severe patients with COVID-19.
Description: Evaluation of pneumonia improvement
Measure: Changes of oxygenation index (PaO2/FiO2) Time: At baseline, 6 hour, Day 1, Day 3,Week 1, Week 2, Week 4, Month 6.Description: Proportion of participants with treatment-related adverse events
Measure: Side effects in the BM-MSCs treatment group Time: Baseline through 6 monthsDescription: Improvement of clinical symptoms including duration of fever, respiratory destress, pneumonia, cough, sneezing, diarrhea.
Measure: Clinical outcome Time: At baseline, 6 hour, Day 1, Day 3,Week 1, Week 2, Week 4, Month 6.Description: days of the patients in hospital
Measure: Hospital stay Time: Baseline through 6 monthsDescription: Evaluation of pneumonia improvement
Measure: CT Scan Time: At baseline, 6 hour, Day 1, Day 3,Week 1, Week 2, Week 4, Month 6.Description: (deep sputum / pharyngeal swab / nasal swab / anal swab / tear fluid / stomach fluid / feces / blood or alveolar lavage fluid)
Measure: Changes in viral load Time: At baseline, 6 hour, Day 1, Day 3,Week 1, Week 2, Week 4, Month 6.Description: Immunological status
Measure: Changes of CD4+, CD8+ cells count and concentration of cytokines Time: At baseline, 6 hour, Day 1, Day 3,Week 1, Week 2, Week 4, Month 6.Description: Marker for efficacy
Measure: Rate of mortality within 28-days Time: From baseline to day 28Description: Markers of Infection
Measure: Changes of C-reactive protein Time: At baseline, 6 hour, Day 1, Day 3,Week 1, Week 2, Week 4, Month 6.The purpose of this study is to determine if a CGRP receptor antagonist may potentially blunt the severe inflammatory response at the alveolar level, delaying or reversing the path towards oxygen desaturation, ARDS, requirement for supplemental oxygenation, artificial ventilation or death in patients with COVID-19 on supplemental oxygen. * BHV-3500, formerly "vazegepant", is now referred to as "zavegepant" (za ve' je pant). The World Health Organization (WHO) International Nonproprietary Names (INN) Expert Committee revised the name to "zavegepant" which was accepted by the United States Adopted Names (USAN ) Council for use in the U.S. and is pending formal adoption by the INN for international use.
Description: a. Efficacy will be measured by the difference between groups in the meah 6-point severity rating at Day 15. The severity ratings are: Death Hospitalized, on invasive mechanical ventilation or ECMO Hospitalized, on non-invasive ventilation or high flow oxygen devices Hospitalized, requiring supplemental oxygen Hospitalized, not requiring supplemental oxygen Not hospitalized
Measure: To compare the efficacy of zavegepant (BHV-3500) to placebo in subjects hospitalized with COVID-19 infection requiring supplemental oxygen, using a six-point rating scale at Day 15. . Time: Baseline to Day 15The objective of this study is to evaluate the efficacy of oral favipiravir plus standard of care treatment (SOC) compared with placebo plus SOC in reducing the duration of shedding of SARS-CoV2 virus in patients with mild or asymptomatic COVID-19.
Description: Time in days from randomization to the first two negative results of nasal and/or oropharyngeal swab.
Measure: Time until cessation of oral shedding of SARS-CoV-2 virus Time: Up to 28 daysDescription: Viral load (nucleic acid) will be assessed by RT-PCR over time.
Measure: Sars-CoV-2 viral load Time: Up to 28 daysDescription: Clinical worsening will be determined by clinician assessment.
Measure: Count of participants with clinical worsening of COVID-19 disease Time: Up to 28 daysDescription: This outcome will be assessed in patient who are asymptomatic of COVID-19 infection at the time of enrollment
Measure: Count of participant with absence of development of any symptoms Time: Up to 28 daysDescription: Cmax is a pharmacokinetic parameter that measures the maximum concentration of drug in plasma.
Measure: Cmax of favipiravir Time: Days 1 and 10 (samples taken 30 minutes prior to and 1 hour following favipiravir administration)Description: Cmin is a pharmacokinetic parameter that measures the minimum concentration of drug in plasma.
Measure: Cmin of favipiravir Time: Days 1 and 10 (samples taken 30 minutes prior to and 1 hour following favipiravir administration)To create a protocol for treatment of Pakistani patients with SARS-CoV-2 infection with an intent to reduce burden on institutional healthcare services by determining efficacy of different quinone drug dosing regimens in controlling SARS-CoV-2 infection for asymptomatic patients.
Description: Percentage of patients who become RT-PCR negative with two RT-PCR tests performed at day 6 and day 7
Measure: RT-PCR negative status Time: 6-7 daysDescription: Time to progression to next stage of SARS-CoV-2 disease severity index
Measure: Progression of symptoms Time: 7 daysDescription: Time to onset of fever (temperature greater than 100 degree F), cough, or shortness of breath (respiratory rate >22 per minute).
Measure: Development of Symptoms Time: 7 daysDescription: Drug related adverse events as determined by data safety and monitoring board (DSMB)
Measure: Adverse events Time: 7 daysThe trial is randomized, blinded, two arms, active comparator controlled, clinical trial to evaluate the safety and efficacy of Mycobacterium w in combination with standard care as per hospital practice versus standard care alone in critically ill adult patients suffering from COVID-19 infection.
Description: To study the effect of Mw on recovery of organ function as assessed by Ordinal scale
Measure: 7-category ordinal scale that ranges from 1 (not hospitalized with resumption of normal activities) to 7 (death) Time: Change in Ordinal scale from baseline to day 3, day 7, day 14, day 21 and day 28 and day of transfer from ICU, if discharged earlier than 28 days post-randomization.Description: 28 day mortality
Measure: 28 day mortality Time: Till day 28, post-randomization or death or discharge, whichever is earlier.Description: Any AE / SAE or event of clinical significance observed during the study.
Measure: Incidence of AE / SAE or event of clinical significance Time: Till day 28Description: Percent of subjects with SARS-CoV-2 detectable in nasal or oropharyngeal (OP) sample.
Measure: SARS-CoV-2 detectable in nasal or oropharyngeal (OP) sample Time: At days 3, 7, 14, 21, and 28Description: ICU length of stay
Measure: ICU length of stay Time: Till day 28Description: Duration of mechanical ventilation
Measure: Duration of mechanical ventilation Time: Till day 28Description: Duration of hospitalization
Measure: Duration of hospitalization Time: Till day 28Description: Percentage of subjects having clinical improvement defined as two-point improvement on a seven category ordinal scale.
Measure: Clinical improvement Time: From baseline to day 14 & Day 28Description: Time (in days) from treatment initiation to death.
Measure: Time (in days) from treatment initiation to death Time: Till day 28Description: To study the effect of Mw on recovery of organ function as assessed by Sequential Organ Failure Assessment (SOFA) which is based on six different scores, one for each of the respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems each scored from 0 to 4 with an increasing score reflecting worsening organ dysfunction
Measure: Sequential Organ Failure Assessment (SOFA) scores Time: Change in SOFA score from baseline to day 3, day 7, day 14, day 21 and day 28 and day of transfer from ICU, if discharged earlier than 28 days post-randomization.The purpose of this clinical trial is to assess the safety and efficacy of Clevudine 120 mg versus placebo once daily administration with standard of care therapy for 14 days (maximum up to 21 days) in patients with moderate COVID-19.
Description: The primary efficacy endpoint for this clinical trial is the rate of patients with negative SARS-Coronavirus-2 (SARS-CoV-2) in a two-day continuous Real-Time-RT-PCR test from baseline to before the 15th day.
Measure: The rate of subjects tested as negative SARS-Coronavirus-2 (SARS-CoV-2) Time: within 15daysThis is a proof of concept study to evaluate the efficacy of nitazoxanide (600 mg BID) to treat hospitalized patients with moderate COVID-19.
Description: PCR will be done to evaluate the change in viral load
Measure: Viral load Time: day 1, 4, 7, 14 and 21Description: Time to wean off oxygen supplementation
Measure: Evolution of acute respiratory syndrome Time: 21 daysDescription: WHO Ordinal Scale for Clinical Improvement that measures illness severity over time (0=uninfected; ambulatory, no limitation of activities=1; ambulatory, limitation of activities=2, hospitalized no oxygen therapy=3; hospitalized oxygen by mask or nasal prongs=4; hospitalized non invasive ventilation or high-flow oxygen=5; hospitalized intubation or mechanical ventilation=6; hospitalized ventilation + additional organ support=7; death=8)
Measure: Change in Clinical Condition Time: 21 daysDescription: Time to be discharged from hospital
Measure: Hospital discharge Time: 21 daysDescription: Evaluation of change in acute respiratory syndrome
Measure: Rate of mortality within 21-days Time: 21 daysDescription: Evaluation of change in acute respiratory syndrome
Measure: Need of mechanical ventilation Time: 21 daysThis study is a phase II, parallel, prospective, randomized, double-blind, placebo controlled trial. The present study will aim to address the efficacy and safety of acute administration of triiodothyronine on ICU patients diagnosed with pulmonary infection due to COVID-19 and require mechanical respiratory support or ECMO.
Description: The primary objective of the study is to determine whether the administration of intravenous triiodothyronine in ICU patients diagnosed with pulmonary infection due to COVID-19 facilitates weaning from cardiorespiratory support compared to placebo. Successful weaning is defined as no requirement for ventilatory support after extubation (mechanical support) or support from ECMO for 48 hours. The primary objective will be measured as percentage of patients successfully weaned after 30 days of follow-up.
Measure: Assessment of weaning from cardiorespiratory support Time: 30 daysDescription: Hemodynamic status will be assessed by continuous blood pressure measurements (systolic BP in mmHg)
Measure: Assessment of hemodynamic status Time: 30 daysDescription: Hemodynamic status will be assessed by continuous blood pressure measurements (diastolic BP in mmHg)
Measure: Assessment of hemodynamic status Time: 30 daysDescription: Hemodynamic status will be assessed by continuous blood pressure measurements (mean BP in mmHg)
Measure: Assessment of hemodynamic status Time: 30 daysDescription: Hemodynamic status will be assessed by the number of participants with use of inotropic and vasoactive drugs
Measure: Assessment of hemodynamic status Time: 30 daysDescription: Pulmonary function will be assessed by arterial measurement of blood gases (arterial partial pressure of oxygen in mmHg)
Measure: Assessment of pulmonary function Time: 30 daysDescription: Pulmonary function will be assessed by arterial measurement of blood gases (arterial partial pressure of carbon dioxide in mmHg)
Measure: Assessment of pulmonary function Time: 30 daysDescription: Pulmonary function will be assessed by arterial measurement of lactate levels (in mmol/L)
Measure: Assessment of pulmonary function Time: 30 daysDescription: Hepatic function will be assessed by laboratory measurements in blood. Changes in aspartate aminotransferase (AST in IU/L) will be measured.
Measure: Assessment of hepatic function Time: 30 daysDescription: Hepatic function will be assessed by laboratory measurements in blood. Changes in alanine aminotransferase (ALT in IU/L) will be measured.
Measure: Assessment of hepatic function Time: 30 daysDescription: Hepatic function will be assessed by laboratory measurements in blood. Changes in gamma-glutamyl transpeptidase (γ-GT in IU/L) will be measured.
Measure: Assessment of hepatic function Time: 30 daysDescription: Hepatic function will be assessed by laboratory measurements in blood. Changes in bilirubin in mg/dL will be measured.
Measure: Assessment of hepatic function Time: 30 daysDescription: Hepatic function will be assessed by laboratory measurements in blood. Changes in fibrinogen in mg/dL will be measured.
Measure: Assessment of hepatic function Time: 30 daysDescription: Hepatic function will be assessed by laboratory measurements in blood. Changes in d-dimers in ng/ml will be measured.
Measure: Assessment of hepatic function Time: 30 daysDescription: Urine volume during 24 hours (in ml) will be recorded.
Measure: Assessment of renal function Time: 30 daysDescription: Changes in urea (in mg/dL) will be recorded.
Measure: Assessment of renal function Time: 30 daysDescription: Changes in uric acid (in mg/dL) will be recorded.
Measure: Assessment of renal function Time: 30 daysDescription: Changes in creatinine (in mg/dL) will be recorded.
Measure: Assessment of renal function Time: 30 daysDescription: Echocardiographic assessment of cardiac left ventricular ejection fraction (LVEF, %)
Measure: Assessment of cardiac function Time: 30 daysDescription: Measurements of cardiac troponin I (in μg/L) will be used to assess myocardial injury
Measure: Assessment of cardiac injury Time: 30 daysDescription: COVID-19 infection will be assessed by inflammatory indices in blood (white blood cells in number per μL)
Measure: Assessment of the course of COVID-19 infection Time: 30 daysDescription: COVID-19 infection will be assessed by inflammatory indices in blood (CRP in mg/L)
Measure: Assessment of the course of COVID-19 infection Time: 30 daysDescription: COVID-19 infection will be assessed by inflammatory indices in blood (erythrocyte sedimentation rate in mm/hr)
Measure: Assessment of the course of COVID-19 infection Time: 30 daysDescription: COVID-19 infection will be assessed by temperature monitoring (in degrees Celsius)
Measure: Assessment of the course of COVID-19 infection Time: 30 daysDescription: COVID-19 infection will be assessed by time needed (in days) for the patient to become negative in COVID-19
Measure: Assessment of the course of COVID-19 infection Time: 30 daysDescription: Number of participants with major (death, cardiac Arrest, electromechanical dissociation, pulmonary embolism, new myocardial infarction, stroke, pulmonary edema, cardiogenic shock and hypotension, septic shock, pulmonary embolism, serious bleeding) events be recorded during the follow up period
Measure: Assessment of clinical outcome and safety Time: 30 daysDescription: Number of participants with minor (myocarditis, Venous Thromboembolism, left Ventricular mural thrombus, renal failure, hepatic failure, stress ulcers, minor bleeding, paroxysmal supraventricular tachycardia and atrial fibrillation, rhythm disturbances) events will be recorded during the follow up period
Measure: Assessment of clinical outcome and safety Time: 30 daysThe main purpose of this study is to evaluate the activity of low dose oral selinexor (KPT-330) and to evaluate the clinical recovery, the viral load, length of hospitalization and the rate of morbidity and mortality in participants with severe COVID-19 compared to placebo.
As of 30/03/2020, 715600 people have been infected with COVID-19 worldwide and 35500 people died, essentially due to respiratory distress syndrome (ARDS) complicated in 25% of the with acute renal failure. No specific pharmacological treatment is available yet. The lung lesions are related to both the viral infection and to an intense inflammatory reaction. Because of it's action, as an immunomodulatory agent that can attenuate the inflammatory reaction and also strengthen the antiviral response, it is proposed to evaluate the effectiveness and safety of intravenous immunoglobulin administration (IGIV) in patients developing ARDS post-SARS-CoV2. IGIV modulates immunity, and this effect results in a decrease of pro-inflammatory activity, key factor in the ARDS related to the COVID-19. It should be noted that IGIV is part of the treatments in various diseases such as autoimmune and inflammatory diffuse interstitial lung diseases. In addition, they have been beneficial in the post-influenza ARDS but also have been in 3 cases of post-SARS-CoV2 ARDS. IGIV is a treatment option because it is well tolerated, especially concerning the kidney. These elements encourage a placebo-controlled trial testing the benefit of IGIV in ARDS post-SARS-CoV2.
Description: Sum of the days the patient did not receive VM, but if death occurs before D28, the score is zero
Measure: Ventilator-free days Time: 28 daysDescription: Vital status at 28 and 90 days
Measure: Mortality Time: 28 and 90 daysDescription: Used to determine the extent of a person's organ function or rate of failure, from 0 to 24, with severity increasing the higher the score
Measure: Sequential Organ Failure Assessment Score Time: Days 1, 3, 7, 14, 21 and 28Description: Ratio of arterial oxygen partial pressure (PaO2 in mmHg) to fractional inspired oxygen (FiO2 expressed as a fraction, not a percentage)
Measure: P/F ratio Time: Days 1, 3, 7, 14, 21 and 28Description: Measure of lung compliance
Measure: Lung compliance Time: Days 1, 3, 7, 14, 21 and 28Description: Severity scoring of lung oedema on the chest radiograph
Measure: Radiological score Time: Days 1, 3, 7, 14, 21 and 28Description: Concentration in mg/L
Measure: Biological efficacy endpoints - C-reactive protein Time: Days 1, 3, 7, 14, 21 and 28Description: Concentration in microgram/L
Measure: Biological efficacy endpoints - Procalcitonin Time: Days 1, 3, 7, 14, 21 and 28Description: Number of CD4 HLA-DR+ and CD38+, CD8 lymphocytes
Measure: Immunological profile Time: Up to 28 daysDescription: Use of corticosteroids, antiretroviral, chloroquine
Measure: Number of patients using other treatments for COVID-19 related ARDS Time: Up to 28 daysDescription: Diagnosis of deep vein thrombosis or pulmonary embolism through imaging exam (eg ultrasound and CT scan)
Measure: Occurrence of deep vein thrombosis or pulmonary embolism Time: 28 daysDescription: Total time of mechanical ventilation, weaning and use of neuromuscular blockade
Measure: Total duration of mechanical ventilation, ventilatory weaning and curarisation Time: 28 daysDescription: Divided in 3 stages, with higher severity of kidney injury in higher stages
Measure: Kidney Disease: Improving Global Outcomes (KDIGO) score and need for dialysis Time: 28 daysDescription: Kidney failure, hypersensitivity with cutaneous or hemodynamic manifestations, aseptic meningitis, hemolytic anemia, leuko-neutropenia, transfusion related acute lung injury (TRALI)
Measure: Occurrence of adverse event related to immunoglobulins Time: 28 daysDescription: Medical research council sum score on awakening
Measure: Occurrence of critical illness neuromyopathy Time: Up to 28 daysDescription: Radiological and clinical context associated with a bacteriological sampling in culture of tracheal secretions, bronchiolar-alveolar lavage or a protected distal sampling
Measure: Occurrence of ventilator-acquired pneumonia Time: Up to 28 daysThis is an international, multicenter, parallel-group, randomized, double-blind, placebo controlled, study in hospitalized adult patients with COVID-19 in the US and other countries with high prevalence of COVID-19. The study is evaluating the effect of dapagliflozin 10 mg versus placebo, given once daily for 30 days in addition to background local standard of care therapy, in reducing disease progression, complications, and all-cause mortality.
Description: Respiratory decompensation (e.g., invasive or non-invasive mechanical ventilation) New or worsening congestive HF Requirement for vasopressor therapy and/or inotropic or mechanical circulatory support Ventricular tachycardia or fibrillation lasting at least 30 seconds and/or associated with hemodynamic instability or pulseless electrical activity, or resuscitated cardiac arrest Initiation of renal replacement therapy
Measure: Time to first occurrence of either death from any cause or new/worsened organ dysfunction through 30 days of follow up, defined as at least one of the following: Time: Randomization through Day 30Description: Time to death from any cause Time to new/worsened organ dysfunction (as defined in the primary outcome measure) Clinical status at Day 30 for patients still hospitalized and without any worsening organ dysfunction (using points 3 to 5 of a 7-point ordinal scale) Time to hospital discharge
Measure: Hierarchical composite outcome measures including time to death from any cause, time to new/worsened organ dysfunction, clinical status at day 30 and time to hospital discharge Time: Randomization through Day 30Description: Time to hospital discharge
Measure: Time to hospital discharge Time: Randomization through Day 30Description: Total number of days alive, out of hospital, and/or free from mechanical ventilation
Measure: Total number of days alive, out of hospital, and/or free from mechanical ventilation Time: Randomization through Day 30Description: Total number of days alive, not in the ICU, and free from mechanical ventilation (as defined in the primary outcome measure)
Measure: Total number of days alive, not in the ICU, and free from mechanical ventilation (as defined in the primary outcome measure) Time: Randomization through Day 30Description: Time to death from any cause
Measure: Time to death from any cause Time: Randomization through Day 30Description: Time to new/worsened organ dysfunction
Measure: Time to new/worsened organ dysfunction Time: Randomization through Day 30Description: Time to acute kidney injury (defined as doubling of s-Creatinine compared to baseline)
Measure: Time to acute kidney injury (defined as doubling of s-Creatinine compared to baseline) Time: Randomization through Day 30This is a phase 1 study in healthy subjects to evaluate the safety, tolerability and pharmacokinetics of single (Part A and B) and multiple (Part B) doses of inhaled TD-0903.
Description: Number and severity of treatment emergent adverse events
Measure: Safety and Tolerability of SAD of TD-0903: Adverse Events Time: Day 1 to Day 8Description: Number and severity of treatment emergent adverse events
Measure: Safety and Tolerability of MAD of TD-0903: Adverse Events Time: Day 1 to Day 14Description: Multiple PK variables of TD-0903 will be assessed during SAD and may include, but are not limited to: Area under the plasma concentration-time curve (AUC)
Measure: Pharmacokinetics (PK) of TD-0903 when given as a Single Ascending Dose (SAD): AUC Time: Day 1 through Day 4Description: Multiple PK variables of TD-0903 will be assessed during SAD and may include, but are not limited to: Maximum observed concentration (Cmax)
Measure: Pharmacokinetics (PK) of TD-0903 when given as a Single Ascending Dose (SAD): Cmax Time: Day 1 through Day 4Description: Multiple PK variables of TD-0903 will be assessed during SAD and may include, but are not limited to: Time to reach maximum observed concentration (Tmax)
Measure: Pharmacokinetics (PK) of TD-0903 when given as a Single Ascending Dose (SAD): Tmax Time: Day 1 through Day 4Description: Multiple PK variables of TD-0903 will be assessed during MAD and may include, but are not limited to: Area under the plasma concentration-time curve (AUC)
Measure: Pharmacokinetics (PK) of TD-0903 when given as a Multiple Ascending Dose (MAD): AUC Time: Day 1 through Day 9Description: Multiple PK variables of TD-0903 will be assessed during MAD and may include, but are not limited to: Maximum observed concentration (Cmax)
Measure: Pharmacokinetics (PK) of TD-0903 when given as a Multiple Ascending Dose (MAD): Cmax Time: Day 1 through Day 9Description: Multiple PK variables of TD-0903 will be assessed during MAD and may include, but are not limited to: Time to reach maximum observed concentration (Tmax)
Measure: Pharmacokinetics (PK) of TD-0903 when given as a Multiple Ascending Dose (MAD): Tmax Time: Day 1 through Day 9To treat Pakistani patients with non-life threatening symptomatic SARS-CoV-2 infection with an intent to reduce burden on institutional healthcare services by determining efficacy of different chloroquine and hydroxychloroquine dosing regimens in controlling SARS-CoV-2 infection.
Description: Percentage of patients who become RT-PCR negative with two RT-PCR tests performed at day 6 and day 7
Measure: RT-PCR result Time: 6th and 7th dayDescription: Time to progression to next stage of SARS-CoV-2 disease severity index
Measure: Progression of symptoms Time: 7 daysDescription: Death
Measure: Mortality Time: 30 daysStudy KIN-1901-2001 is a multi-center, adaptive, randomized, double-blind, placebo-controlled study to assess the efficacy and safety of gimsilumab in subjects with lung injury or acute respiratory distress syndrome (ARDS) secondary to COVID-19.
Description: Subjects who die will be assigned "0" ventilator-free days
Measure: Number of ventilator-free days Time: Baseline to Day 29Patients over equal or older than 65 yearswill be treated with a hydroxychloroquine versus placebo reduced loading dose of 600mg on the first day followed with 400mg/day divided in 2x200mg for 6 more days resulting in a total duration of therapy of 7 days. Measurement of Hydroxychloroquine-levels will be performed on day 7, . A follow-up by video or telephone conference will be performed to observe drug intake and collect adverse events during treatment phase on a daily base on working days and once during the weekend (i.e. 6 out of 7 days). After treatment phase follow-up by telephone calls will be done on day 10, 30, 60 (+/- 2 days).
RACONA is a prospective trial that will test the hypothesis that nafamostat can lower lung function deterioration and need for intensive care admission in COVID-19 patients. Design: Adult hospitalized COVID-19 patients will be randomized in a prospective double-blind randomized placebo-controlled study to test the clinical efficacy of nafamostat mesylate (administered intravenously) on top of best standard of care. Primary outcome measures: the time-to-clinical improvement, defined as the time from randomization to an improvement of two points (from the status at randomization) on a seven category ordinal scale or live discharge from the hospital, whichever comes first.
Description: Time-to-clinical improvement (time from randomization to an improvement of two points (from the status at randomization) on a 7 category ordinal scale or live discharge from the hospital, whichever came first.
Measure: Time-to-clinical improvement Time: day 1 until day 28Description: Rate of patients showing improvement of 2 points in 7 category ordinal scale (with 7 points the worst)(PubMed ID: 32187464)
Measure: Responders Time: day 1 until day 28Description: Proportion of patients who will progress to critical illness/death
Measure: Critical or dead patients Time: day 1 until day 28Description: Change in pO2/FiO2 ratio over time
Measure: pO2/FiO2 ratio Time: day 1 until day 28Description: Change Sequential organ failure assessment score (SOFA score) over time. The Score ranges from 0 to 24 (with 24 the worst)(PubMed ID: 11594901)
Measure: SOFA score over time Time: day 1 until day 28Description: Duration of hospitalization in survivors (days)
Measure: Hospitalization Time: day 1 until day 28Description: Number of patients who require ventilation
Measure: Mechanical ventilation Time: day 1 until day 28Description: Duration of ventilation (days)
Measure: Mechanical ventilation duration Time: day 1 until day 28Description: Proportion of patients who develop arrhythmia, or myocardial infarction, or other cardiovascular disease not present at the baseline
Measure: Cardiovascular disease Time: day 1 until day 28To test if the medication Hydroxychloroquine will decrease the amount of virus(as measured by PCR) , 7 days after initiation of therapy compared to control patients receiving placebo. The study design is a randomized (5 days of medication v. 5 days of placebo) clinical trial initiated immediately after diagnosis in ambulatory health care workers at University of South Alabama Health, or in ambulatory USA patients. At 7 days after enrollment another nasopharyngeal swab will be taken to measure if the virus is still present. At 10 weeks we will measure immunity from Covid-19 using a single blood sample. It is a phase 2/3 clinical trial.
Description: Nasopharyngeal swab PCR measurement of viral load expressed as the % of negative PCR swabs
Measure: Percentage of virus free subjects Time: 7 days after initiation of trialDescription: Participants will self-report disease severity status as one of the following 5 options; no COVID19 illness (score of 1), COVID19 illness with no hospitalization (score of 2), or COVID19 illness with hospitalization (score of 3), or Covid 19 with care requiring hospitalization (score of 4), or Covid 19 with death (Score of 5) .
Measure: Disease severity Time: 6 daysDescription: Number of subjects in each arm who are hospitalized for Covid 19 infection
Measure: Incidence of hospitalization Time: 14 daysDescription: Number of subjects in each arm who die secondary to Covid-19 infection
Measure: Incidence of Death Time: 70 Days (10 weeks)Description: Number of subjects in each arm who have confirmed Covid-19 infection
Measure: Incidence of confirmed SARS-CoV-2 Detection Time: 14 daysDescription: Number of subjects in each arm who discontinue or withdraw medication use for any reason
Measure: Incidence of all-cause study medication discontinuation or withdrawal Time: 14 daysDescription: Blood tests to determine level of immunity in each subject
Measure: Immunity to Covid-19 Time: 70 days (10 weeks)The rationale of the present clinical trial is that an orally available drug given to outpatients that could reduce the viral burden in the upper respiratory tract could forestall complications of SARS-CoV-2 infection and reduce transmission from one infected individual to another.
Description: To determine whether camostat mesylate reduces SARS-COV-2 viral load in early COVID-19 disease, change from day 0 to day 4 in respiratory (oropharyngeal swab RT-PCR) log10 viral load will be assessed.
Measure: Change in SARS-COV-2 viral load Time: 5 daysDescription: To determine whether camostat mesylate reduces SARS-COV-2 viral load in early COVID-19 disease, change from day 0 to day 2 in respiratory (oropharyngeal swab RT-PCR) log10 viral load will be assessed.
Measure: Change in SARS-COV-2 viral load Time: 3 daysDescription: To determine whether camostat mesylate reduces SARS-COV-2 viral load in early COVID-19 disease, change from day 0 to day 6 in respiratory (oropharyngeal swab RT-PCR) log10 viral load will be assessed.
Measure: Change in SARS-COV-2 viral load Time: 7 daysDescription: Change in risk for a positive COVID-19 test at day 6 after enrollment (day 0) will be assessed by analyzing the proportion of positive cases in each study arm.
Measure: Change in positive COVID-19 status Time: 7 daysDescription: Change in risk for a positive COVID-19 test at day 13 after enrollment (day 0) will be assessed by analyzing the proportion of positive cases in each study arm.
Measure: Change in positive COVID-19 status Time: 14 daysDescription: Change in risk for a positive COVID-19 test at day 27 after enrollment (day 0) will be assessed by analyzing the proportion of positive cases in each study arm.
Measure: Change in positive COVID-19 status Time: 28 daysDescription: Change of COVID-19 symptom severity from day 0 to day 6 will be assessed with the COVID-19 daily self score tool. Adapted from the FLU-PRO instrument, it consists of 39 items that are answered daily. Items 1-33 are Likert scale questions (rated 0-4) where 0 = not at all and 4 = very much. These items are summed to score the severity of symptoms- where a total score of 132 would indicate the greatest severity of symptoms and a score of 0 would indicate no severity of symptoms. Items 34-38 are also Likert scale questions (rated 0-4) that measure the frequency of specific daily symptoms where 0 = 0 times and 4 = 4 times or more. These items are summed to score the frequency of symptoms- where the highest score for the frequency of symptoms (20) indicates the greatest burden of symptom frequency. The last question (39) asks patients for their highest temperature in Fahrenheit.
Measure: Change in COVID-19 symptom severity Time: 7 daysDescription: Change of COVID-19 symptom severity from day 0 to day 14 will be assessed with the COVID-19 daily self score tool. Adapted from the FLU-PRO instrument, it consists of 39 items that are answered daily. Items 1-33 are Likert scale questions (rated 0-4) where 0 = not at all and 4 = very much. These items are summed to score the severity of symptoms- where a total score of 132 would indicate the greatest severity of symptoms and a score of 0 would indicate no severity of symptoms. Items 34-38 are also Likert scale questions (rated 0-4) that measure the frequency of specific daily symptoms where 0 = 0 times and 4 = 4 times or more. These items are summed to score the frequency of symptoms- where the highest score for the frequency of symptoms (20) indicates the greatest burden of symptom frequency. The last question (39) asks patients for their highest temperature in Fahrenheit.
Measure: Change in COVID-19 symptom severity Time: 14 daysDescription: Change of COVID-19 symptom score from day 0 to day 6 will be assessed with the COVID-19 daily self score tool. Adapted from the FLU-PRO instrument, it consists of 39 items that are answered daily. Items 1-33 are Likert scale questions (rated 0-4) where 0 = not at all and 4 = very much. These items are summed to score the severity of symptoms- where a total score of 132 would indicate the greatest severity of symptoms and a score of 0 would indicate no severity of symptoms. Items 34-38 are also Likert scale questions (rated 0-4) that measure the frequency of specific daily symptoms where 0 = 0 times and 4 = 4 times or more. These items are summed to score the frequency of symptoms- where the highest score for the frequency of symptoms (20) indicates the greatest burden of symptom frequency. The last question (39) asks patients for their highest temperature in Fahrenheit.
Measure: Change in COVID-19 symptom frequency Time: 7 daysDescription: Change of COVID-19 symptom score from day 0 to day 14 will be assessed with the COVID-19 daily self score tool. Adapted from the FLU-PRO instrument, it consists of 39 items that are answered daily. Items 1-33 are Likert scale questions (rated 0-4) where 0 = not at all and 4 = very much. These items are summed to score the severity of symptoms- where a total score of 132 would indicate the greatest severity of symptoms and a score of 0 would indicate no severity of symptoms. Items 34-38 are also Likert scale questions (rated 0-4) that measure the frequency of specific daily symptoms where 0 = 0 times and 4 = 4 times or more. These items are summed to score the frequency of symptoms- where the highest score for the frequency of symptoms (20) indicates the greatest burden of symptom frequency. The last question (39) asks patients for their highest temperature in Fahrenheit.
Measure: Change in COVID-19 symptom frequency Time: 14 daysDescription: Change of COVID-19 symptom score from baseline to day 6 will be assessed with the COVID-19 daily self score tool. Adapted from the FLU-PRO instrument, it consists of 39 items that are answered daily. Items 1-33 are Likert scale questions (rated 0-4) where 0 = not at all and 4 = very much. These items are summed to score the severity of symptoms- where a total score of 132 would indicate the greatest severity of symptoms and a score of 0 would indicate no severity of symptoms. Items 34-38 are also Likert scale questions (rated 0-4) that measure the frequency of specific daily symptoms where 0 = 0 times and 4 = 4 times or more. These items are summed to score the frequency of symptoms- where the highest score for the frequency of symptoms (20) indicates the greatest burden of symptom frequency. The last question (39) asks patients for their highest temperature in Fahrenheit.
Measure: Change in body temperature Time: 7 daysDescription: Change of COVID-19 symptom score from baseline to day 14 will be assessed with the COVID-19 daily self score tool. Adapted from the FLU-PRO instrument, it consists of 39 items that are answered daily. Items 1-33 are Likert scale questions (rated 0-4) where 0 = not at all and 4 = very much. These items are summed to score the severity of symptoms- where a total score of 132 would indicate the greatest severity of symptoms and a score of 0 would indicate no severity of symptoms. Items 34-38 are also Likert scale questions (rated 0-4) that measure the frequency of specific daily symptoms where 0 = 0 times and 4 = 4 times or more. These items are summed to score the frequency of symptoms- where the highest score for the frequency of symptoms (20) indicates the greatest burden of symptom frequency. The last question (39) asks patients for their highest temperature in Fahrenheit.
Measure: Change in body temperature Time: 14 daysThis clinical trial is a randomized, blinded, two arms, placebo controlled, clinical trial to evaluate the safety and efficacy of Mycobacterium w in combination with standard care as per hospital practice to prevent COVID 19 in subjects at risk of getting infected with COVID 19.
Description: To compare proportion of subjects acquiring COVID-19 infection between two arms over the time till 8 weeks from administration of 1st dose
Measure: Number of subject acquiring COVID-19 infection Time: From first dosing to week 1, week 2, week 4, week 8 or at any time during the study till 8 week post first dosing..Description: Any AE / SAE observed during the study.
Measure: Incidence of Adverse Event and Serious Adverse Event (safety and tolerability) Time: Till 8 weeksDescription: Whether administration of Mw prevents development of Upper Respiratory Tract Infection (URTI) symptoms in close contacts of COVID-19 patients.
Measure: Number of subject developing Upper Respiratory Tract Infection (URTI) symptoms Time: From first dosing to week 1, week 2, week 4, week 8 or at any time during the study till 8 week post first dosing.Description: Whether administration of Mw prevents development of severe COVID-19 infection.
Measure: Number of subject developing severe COVID-19 infection based on ordinal scale Time: From first dosing to week 1, week 2, week 4, week 8 or at any time during the study till 8 week post first dosingIt is a multicenter, randomized, placebo-controlled, double-blind study. The study population is defined as subjects diagnosed with lower respiratory tract COVID-19 who require supplemental oxygen ≥2 LPM at the time of randomization.
Description: Percent of subjects who reach level 1 of COVID-19 Clinical Classification (discharged or return to normal activity)
Measure: Percent of subjects who have recovered Time: Day 5, 10, 14, 21, 28Description: time to Improved COVID-19 Clinical Classification 1 to 6 (where higher score means worse outcome)
Measure: Improved COVID-19 Clinical Classification Time: Day 28Description: Percent of subjects RTRA
Measure: Return To Room Air (RTRA) Time: Day 10, 21, 28Description: Time to
Measure: SARS-CoV-2 RNA undetectable Time: Day 28Description: Time to
Measure: Clinical Deterioration Time: Day 28Description: Percent of subjects discharge
Measure: Percent of subjects discharged Time: Day 14, 21, 28Description: Time to
Measure: Death (all cause) Time: Day 28The 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.
Description: Endotracheal intubation within 7 days after randomization Death will be considered as a failure (endotracheal intubation).
Measure: Rate of endotracheal intubation Time: 7 daysDescription: 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 daysViruxal Oral and Nasal Spray is a Class I CE marked medical device manufactured by Kerecis hf (the "Device"). A double blind clinical trial will be conducted to evaluate the Device against placebo in COVID-19 positive, symptomatic patients in Iceland. Immediate access to COVID-19 patients is available through a well-organized COVID-19 outpatient follow-up clinic. Up to 128 patients with mild to moderate symptoms of COVID-19 will be recruited (so called "higher end of the low risk group"). These patients will be positive for COVID-19, be symptomatic with upper respiratory symptoms, but without involvement of the entire respiratory system. The patients will be randomized to receive treatment with the Study Device or to receive placebo. 64 patients will be randomized into the Study Device group and 64 patients into the Control group. Patients will administer Study Device or Control for 14 days and will have their symptoms recorded until no further symptoms are reported, up to a maximum of 28 days follow-up.
Description: The number of days until participants report no symptoms, which they attribute to COVID-19, will be compared between groups. Symptoms include: Fever (38.0°C or higher), chills, dry cough, cough with rise, shortness of breath (rest), shortness of breath (Exercise), dyspnoea, sore throat, runny nose, headache, myalgia/bone pain, anorexia, nausea, vomiting, loss of smell, osteoporosis, abdominal pain, diarrhea, weakness.
Measure: Number of days until complete resolution of symptoms per group Time: 28 daysDescription: The number of participants admitted to hospital due to deterioration of their condition due to COVID-19 will be compared between groups.
Measure: Number of hospital admissions per group Time: 28 daysDescription: The number of days until participants report a reduction in symptoms, which they attribute to COVID-19, will be compared between groups. Symptoms include: Fever (38.0°C or higher), chills, dry cough, cough with rise, shortness of breath (rest), shortness of breath (Exercise), dyspnoea, sore throat, runny nose, headache, myalgia/bone pain, anorexia, nausea, vomiting, loss of smell, osteoporosis, abdominal pain, diarrhea, weakness.
Measure: Number of days until a reduction in symptoms per group Time: 28 daysDescription: The number of adverse events reported will be compared between groups.
Measure: Number of adverse events per group Time: 28 daysTwo recent studies have suggested that in patients with Covid19, treatment with hydroxychloroquine may shorten the duration of symptoms and improve viral clearance, an effect that appears most pronounce when combined with azithromycin. Hydroxychloroquine treatment may inhibit viral nucleic acid-mediated activation of various innate immune pathways, as well as blockade of lysosomal functions in cell types relevant for viral entry and antigen presentation. The purpose of the study is to determine if oral hydroxychloroquine monotherapy, or in combination with azithromycin results in clinical benefit in patients hospitalized with COVID19 pneumonia.
Description: To demonstrate in patients receiving standard of care that the percentage who achieve clinical response with hydroxychloroquine or hydroxychloroquine and azithromycin is superior to placebo at Day 15
Measure: Percentage of participants who achieve clinical response Time: 15 daysDescription: To demonstrate in patients receiving standard of care that the percentage with viral clearance at Day 15 with hydroxychloroquine or hydroxychloroquine and azithromycin is superior to placebo
Measure: Percentage of Participants with Viral Clearance Time: 15 DaysDescription: To assess in patients receiving standard of care the safety of hydroxychloroquine or hydroxychloroquine and azithromycin compared to placebo
Measure: Number of participants receiving hydroxychloroquine or hydroxychloroquine and azithromycin with adverse events of hydroxychloroquin or hydroxychloroquine and azithromycin compared to placebo Time: 40 daysStudy 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
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 14Description: 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 28Description: 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 14Description: 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 90Description: 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 90Description: 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 28Description: 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 28Description: Proportion of subjects readmitted to the hospital
Measure: Efficacy: Proportion of subjects readmitted to the hospital Time: Up to 90 daysDescription: 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 28Description: 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 28Description: Proportion of subjects with rhu-pGSN antibodies
Measure: Immunogenicity: Proportion of subjects with rhu-pGSN antibodies Time: Days 1, 28, and 90Description: 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 3Description: 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 3Description: 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 3Description: 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 3Description: 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 3This is a randomized, double blind, two arms, placebo controlled, clinical trial to study to evaluate the the safety and efficacy of Mycobacterium w in combination with standard of care versus placebo with standard of care for preventing the progression of COVID-19 disease and for reduction in transfer to ICU in COVID-19 infected patients admitted to the hospital.
Description: To compare the difference in proportion of patients with increased disease severity
Measure: Number of patients with increased disease severity Time: From baseline to Day 3, Day 7, Day 14, Day 21, Day 28 or at any time during the study till 28 days post first dosing.Description: To evaluate safety of Mw in COVID-19 patients admitted to hospital
Measure: Incidence of adverse events and serious adverse events (Safety) Time: Till day 28Description: To compare the proportion of patients discharged from hospital
Measure: Number of COVID-19 patients discharged from hospital Time: From baseline to Day 3, Day 7, Day 14, Day 21, Day 28 or at any time during the study till 28 days post first dosing.Description: To compare the proportion of patients transfer to ICU
Measure: Number of COVID-19 patients transfer to ICU Time: From baseline to Day 3, Day 7, Day 14, Day 21, Day 28 or at any time during the study till 28 days post first dosing.Description: To compare the proportion of patients with reduction in disease severity by 1 ordinal scale
Measure: Number of COVID-19 patients with reduction in disease severity by 1 ordinal scale Time: From baseline to Day 3, Day 7, Day 14, Day 21, Day 28 or at any time during the study till 28 days post first dosing.Description: To compare the proportion of symptom free patients
Measure: Number of of symptom free patients Time: From baseline to Day 3, Day 7, Day 14, Day 21, Day 28 or at any time during the study till 28 days post first dosing.Hydroxychloroquine has been approved by FDA as one of the treatment options for COVID 19.Healthcare personnel are amongst those at highest risk to contract the disease. Several health authorities are now recommending the use of hydroxychloroquine as pre-exposure prophylaxis is in health care personnel. Several studies are on going in this context. However there is a controversy regarding the dosage regimen. This drug has a half life of 22.4 days. In this study we will be comparing three different doses of Hydroxychloroquine and additionally have a control group in order to determine the efficacy of hydroxychloroquine as pre- exposure prophylaxis in healthcare personnel in various doses.
Description: Outcome reported as the percentage of participants in each arm who are COVID-19-free at the end of study treatment
Measure: COVID-19-free survival in experimental arms compared to placebo Time: 12 weeksDescription: Outcome reported as the percent of participants in each arm who have a confirmed SARS-CoV-2 infection during study treatment.
Measure: Incidence of confirmed SARS-COV-2 detection Time: 12 weeksDescription: Outcome reported as the percent of participants in each arm who report COVID-19-related symptoms during study treatment
Measure: Incidence of possible COVID-19 symptoms Time: 12 weeksDescription: Outcome reported as the percent of participants in each arm who discontinue study medication use for any reason during treatment.
Measure: Incidence of all-cause study medicine discontinuation Time: 12 weeksDescription: Participants will self-report COVID-19 status on an ordinal scale as follows: No illness (score=1), Illness with outpatient observation (score=2), Hospitalization (or post-hospital discharge) (score=3), Hospitalization with ICU stay (score 4),Death from COVID 19(score=5) Possible scores range from 1-5 with higher scores indicating greater disease severity.
Measure: Ordinal Scale of COVID-19 Disease maximum severity if COVID-19 diagnosed at study end Time: 12 weeksDescription: Outcome reported as the percent of participants in each arm who are hospitalized or expire due to COVID-19 during study treatment.
Measure: Incidence of Hospitalization for COVID-19 or death Time: 12 weeksDescription: Outcome reported as the percent of participants experiencing any possible adverse events from Hydroxychloroquine
Measure: Incidence of study medication-related adverse events Time: 12 weeksTrial to Evaluate the Efficacy and Safety of Nitazoxanide (NTZ) for Pre- and Post Exposure Prophylaxis of COVID-19 and Other Viral Respiratory Illnesses (VRI) in Healthcare Workers and Others at Increased Risk of SARS-CoV-2 Infection
Brief Summary: SARS-CoV-2 virus infection is known to cause Lung Injury that begins as dyspnea and exercise intolerance, but may rapidly progress to Critical COVID-19 with Respiratory Failure and the need for noninvasive or mechanical ventilation. Mortality rates as high as 80% have been reported among those who require mechanical ventilation, despite best available intensive care. Patients with moderate and severe COVID-19 by FDA definition who have not developed respiratory failure be treated with nebulized RLF-100 (aviptadil, a synthetic version of Vasoactive Intestinal Polypeptide (VIP)) 100 μg 3x daily plus Standard of Care vs. placebo + Standard of Care using an FDA 501(k) cleared mesh nebulizer. The primary outcome will be progression to in severity of COVID-19 (i.e. moderate progressing to to severe or critical OR severe progressing to critical) over 28 days. Secondary outcomes will include blood oxygenation as measured by pulse oximetry, dyspnea, exercise tolerance, and levels of TNFα IL-6 and other cytokines.
Description: Progression to ARDS is defined as the need for mechanical ventilation
Measure: Progression to ARDS Time: 28 daysDescription: Blood PO2 as measured by pulse oximetry
Measure: Blood oxygenation Time: 28 daysDescription: 0 = no shortness of breath at all 0.5 = very, very slight shortness of breath = very mild shortness of breath = mild shortness of breath = moderate shortness of breath or breathing difficulty = somewhat severe shortness of breath = strong or hard breathing 7 = severe shortness of breath or very hard breathing 8 9 = extremely severe shortness of breath 10 = shortness of breath so severe you need to stop the exercise or activity
Measure: RDP Dsypnea Scale Time: 28 daysDescription: Distance walked in six minutes
Measure: Distance walked in six minutes Time: 28 daysThis study will enroll 40 symptomatic outpatients tested positive for Coronavirus 2019 (COVID-19). Patients to be randomized 1:1 to Telmisartan (40 mg) vs placebo to be administered orally once daily x 21 days. Daily, the study patients will be asked to keep a record of the severity of their fever, dyspnea and fatigue and take their blood pressure (BP) and temperature. Study visits to occur on day 1 (entry), day 4, day 10 and day 21. Oro-pharyngeal swabs, and approximately 25 cc of blood will be collected at each study visit for safety labs and for the evaluation of the renin-angiotensin system (RAS) system and for various blood biomarkers of inflammation, coagulation and fibrosis.
Description: Based on a modified World Health Organization (WHO) COVID-19 7-point ordinal scale
Measure: Maximum clinical severity of disease Time: Over the 21 day period of studyDescription: Number of adverse events grade 2 and above utilizing the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0, November 2014
Measure: Incidence of treatment emergent adverse events Time: Through study completion at day 21 of studyDescription: Angiotensin I (AngI), AngII, Ang1-9 and Ang1-7
Measure: Renin angiotensin system peptides Time: At each study time point (day 4, day 10, day 21)Description: plasma biomarkers of organ function/coagulation, inflammation, leukocyte chemotaxis, tissue remodeling/fibrosis and immune exhaustion by Luminex multiplexing assays such as TNF-alpha, IL-6, CK-MB, Troponin I, Fractalkine, MCP-1, PD-1, TIMP-1
Measure: Plasma biomarkers Time: At each study time point (day 4, day 10, day 21)Double-blind randomized controlled clinical trial (RCT) of low-dose lenalidomide in the treatment of elderly patients (> 60 years of age) with mild to moderate clinical signs of COVID-19 disease from the Hospital Universitario of Getafe. The study will include patients of both sexes (> 60 years of age) with mild to moderate clinical presentation of COVID-19 (ROX index > 10). Subjects will be randomly assigned to the experimental arm with lenalidomide (5 mg/24h, day 1, 3 and 5) or to the controlled arm. Other concomitant medication for the treatment of COVID-19 will be also considered.
Description: Days to clinical recovery or days until discharge
Measure: Clinical improvement Time: 30 daysDescription: o Improvement of the neutrophil-to-lymphocyte ratio (NLR)
Measure: Immune-inflammatory improvement Time: 30 daysDescription: All-cause mortality at 30 days after enrollment
Measure: Mortality Time: 30 daysNovel 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.
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 daysDescription: To measure global success
Measure: Rate of mortality Time: 28 daysDescription: 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: 0-7daysDescription: Evaluation of pneumonia changes
Measure: Proportion of patients who have achieved radiological responses Time: 0-28 daysDescription: Haemogram and cell subpopulations
Measure: Blood white cell counts and their subpopulations. Time: 0-180 daysDescription: Lymphocyte profiles, CD3, CD19, CD16+CD56, CD4/CD8, Tregs
Measure: Cellular markers of inflammation Time: 0-180 daysDescription: IL-10, IL-6, IP-10, TNF-alpha
Measure: Cytokines and chemokines in peripheral blood Time: 0-180 daysUntil the first half of April, Colombia has more than 2,800 infected cases and a hundred deaths as a result of COVID-19, with Antioquia being the third department with the highest number of cases. Official records indicate that, in Colombia, the first case was diagnosed on March 6, 2020, corresponding to a patient from Italy. However, in conversations with several infectologists and intensivists from Medellín, it was agreed that clinical cases similar to the clinical presentation that is now recognized as COVID-19 had arisen since the end of 2019 when it was still unknown to everyone. The previous suggests that the virus was already circulating in the country since before March 6, 2020. But at that moment, there were no tools to make a clinical identification, nor to diagnose it from the laboratory's point of view. Considering as real the hypothesis that the infection has been circulating in the country since before the first official diagnosis, the question arises: Why does not the country still has the same healthcare and humanitarian chaos that countries such as Italy and Spain are suffering at this time? To answer this question may be that there are differences in vaccination rates with BCG (Bacille Calmette-Guérin or tuberculosis vaccine), which is significantly higher in Latin America compared to those in Europe. This finding could explain to some extent the situation in the country, since previous studies have shown the influence that this vaccine can have on the immune response against various other pathogens, including viruses. Among the population at risk of infection, health-care workers due to their permanent contact with patients are the population group with the highest risk of contracting SARS-Cov-2 and developing COVID-19 in any of its clinical manifestations, and currently there are no vaccines or proven preventive interventions available to protect them. For this reason, this research study aims to demonstrate whether the centennial vaccine against tuberculosis (BCG), a bacterial disease, can activate the human immune system in a broad way, allowing it to better combat the coronavirus that causes COVID-19 and, perhaps, prevents the complications that lead the patient to the intensive care unit and death. In the future, and if these results are as expected, they may be the basis for undertaking a population vaccination campaign that improves clinical outcomes in the general population.
Description: Incidence of COVID-19 cases confirmed or probable in the study population
Measure: Primary outcome Time: From date of randomization to 360 day of the studyDescription: Incidence of severe or critical infection in COVID-19 cases
Measure: Secondary outcome Time: From date to diagnosis to 1 month afterDescription: Lethality of the infection in both groups
Measure: Secondary outcome Time: From date to diagnosis to 1 month afterDescription: Assess the safety (frequency, seriousness, and severity of adverse events) of BCG vaccination
Measure: Secondary outcome Time: From date of randomization to 7 day of the studyDescription: Prevalence of SARS-Cov-2 infection
Measure: Secondary outcome Time: At baseline evaluationThis is a randomized, double-blind, placebo-controlled, 29-day, multicenter study to assess the efficacy and safety of ruxolitinib + standard-of-care (SoC) therapy, compared with placebo + SoC therapy, in patients aged ≥12 years with COVID-19 pneumonia.
Description: Efficacy is measured by a composite endpoint of proportion of patients who die, develop respiratory failure [require mechanical ventilation], or require intensive care unit [ICU] care for the treatment of COVID-19.
Measure: Proportion of patients who die, develop respiratory failure [require mechanical ventilation] or require intensive care unit (ICU) care Time: 29 daysDescription: Clinical status is measured with the 9-point ordinal scale. The scoring is - Uninfected patients have a score 0 (no clinical or virological evidence of infection). - Ambulatory patients (not in hospital or in hospital and ready for discharge) can have a score 1 (no limitation of activities) or 2 (limitation of activities). - Hospitalized patients with mild disease can have score 3 (no oxygen therapy defined as SpO2 ≥ 94% on room air) or 4 (oxygen by mask or nasal prongs). - Hospitalized patients with severe disease can have score 5 (non-invasive ventilation or high-flow oxygen), 6 (intubation and mechanical ventilation) or 7 (ventilation + additional organ support - pressors, RRT (renal replacement therapy), ECMO (extracorporeal membrane oxygenation)). - Patients who die have a score 8.
Measure: Clinical status Time: Day 15, Day 29Description: Percentage of patients with at least two points improvement in clinical status on the 9-point ordinal scale.
Measure: Percentage of patients with at least two-point improvement from baseline in clinical status Time: Baseline, Day 15, Day 29Description: Percentage of patients with at least one point improvement in clinical status on the 9-point ordinal scale.
Measure: Percentage of patients with at least one-point improvement from baseline in clinical status Time: Baseline, Day 15, Day 29Description: Percentage of patients with at least one point deterioration in clinical status on the 9-point ordinal scale.
Measure: Percentage of patients with at least one-point deterioration from baseline in clinical status Time: Baseline, Day 15, Day 29Description: Time to improvement from baseline category to one less severe category of the 9-point ordinal scale.
Measure: Time to improvement in clinical status Time: 29 daysDescription: Mean change from baseline in the 9-point ordinal scale.
Measure: Mean change from baseline in the clinical status Time: Baseline, Day 15, Day 29Description: Mortality rate at Day 15 and at Day 29
Measure: Mortality rate Time: Day 15, Day 29Description: Proportion of patients requiring mechanical ventilation
Measure: Proportion of patients requiring mechanical ventilation Time: 29 daysDescription: Duration of hospitalization
Measure: Duration of hospitalization Time: 29 daysDescription: The time to discharge or to a National Early Warning Score 2 (NEWS2) of ≤2 and maintained for 24 hours whichever comes first. The NEWS2 is based on a simple aggregate scoring system in which a score is allocated to physiological measurements, already recorded in routine practice presentation or when a patient is being monitored in hospital. The score ranges from 0 (best) to 23 (worst).
Measure: Time to discharge or to a NEWS2 score of ≤2 Time: 29 daysDescription: The National Early Warning Score 2 (NEWS2) is based on a simple aggregate scoring system in which a score is allocated to physiological measurements, already recorded in routine practice presentation or when a patient is being monitored in hospital. The score ranges from 0 (best) to 23 (worst).
Measure: Change from baseline in NEWS2 score Time: Baseline, Days 3, 5, 8, 11, 15, and 29Description: Change from baseline in peripheral oxygen saturation / fraction of inspired oxygen ratio (SpO2/FiO2 ratio)
Measure: Change from baseline in SpO2/FiO2 ratio. Time: Baseline, Day 15, Day 29Description: No oxygen therapy is required if oxygen saturation is ≥ 94% on room air.
Measure: Proportion of patients with no oxygen therapy Time: Day 15, Day 29The purpose of this study is to test the safety and efficacy of convalescent donor plasma to treat COVID-19 in hospitalized adults in a randomized, placebo-controlled setting. The effect of convalescent plasma will be compared to placebo on clinical outcomes, measured using the COVID-19 7-point Ordinal Clinical Progression Outcomes Scale at Day 15, among adults with COVID-19 requiring hospitalization.
Description: Not hospitalized with resumption of normal activities. Not hospitalized, but unable to resume normal activities. Hospitalized, not on supplemental oxygen. Hospitalized, on supplemental oxygen. Hospitalized, on nasal high-flow oxygen therapy, noninvasive mechanical ventilation, or both Hospitalized, on ECMO, invasive mechanical ventilation, or both. Death
Measure: COVID-19 7-point Ordinal Clinical Progression Outcomes Scale Time: Study Day 15Description: All-location, all-cause 14-day mortality
Measure: All-location, all-cause 14-day mortality Time: Baseline to Study Day 14 (assessed on Study Day 15)Description: All-location, all-cause 28-day mortality
Measure: All-location, all-cause 28-day mortality Time: Baseline to Study Day 28 (assessed on Study Day 29)Description: Number of participants that survived to Day 28
Measure: Survival through 28 days Time: Baseline to Day 28 (assessed on Study Day 29)Description: Number days from admission to discharge thru Day 28
Measure: Time to hospital discharge through 28 days Time: Admission to discharge (assessed on Study Day 29)Description: Not hospitalized with resumption of normal activities. Not hospitalized, but unable to resume normal activities. Hospitalized, not on supplemental oxygen. Hospitalized, on supplemental oxygen. Hospitalized, on nasal high-flow oxygen therapy, noninvasive mechanical ventilation, or both Hospitalized, on ECMO, invasive mechanical ventilation, or both. Death
Measure: COVID-19 7-point Ordinal Clinical Progression Outcomes Scale on Study Day 3 Time: Baseline to Study Day 3Description: Not hospitalized with resumption of normal activities. Not hospitalized, but unable to resume normal activities. Hospitalized, not on supplemental oxygen. Hospitalized, on supplemental oxygen. Hospitalized, on nasal high-flow oxygen therapy, noninvasive mechanical ventilation, or both Hospitalized, on ECMO, invasive mechanical ventilation, or both. Death
Measure: COVID-19 7-point Ordinal Clinical Progression Outcomes Scale on Study Day 8 Time: Study Day 8Description: Not hospitalized with resumption of normal activities. Not hospitalized, but unable to resume normal activities. Hospitalized, not on supplemental oxygen. Hospitalized, on supplemental oxygen. Hospitalized, on nasal high-flow oxygen therapy, noninvasive mechanical ventilation, or both Hospitalized, on ECMO, invasive mechanical ventilation, or both. Death
Measure: COVID-19 7-point Ordinal Clinical Progression Outcomes Scale on Study Day 29 Time: Study Day 29Description: Number of days without use of oxygen
Measure: Oxygen-free days through Day 28 Time: Baseline to Day 28Description: Number of days without use of a ventilator
Measure: Ventilator-free days through Day 28 Time: Baseline to Day 28Description: Number of days without use of vasopressors
Measure: Vasopressor-free days through Day 28 Time: Baseline to Day 28Description: Number of days outside of ICU
Measure: ICU-free days through Day 28 Time: Baseline to Day 28Description: Number of days outside of the hospital
Measure: Hospital-free days through Day 28 Time: Baseline to Day 28Description: Number of participants with Acute kidney injury
Measure: Acute kidney injury Time: Baseline to Day 28Description: Number of participants requiring renal replacement therapy
Measure: Renal replacement therapy Time: Baseline to Day 28Description: Number of participants with documented venous thromboembolic disease (DVT or PE)
Measure: Documented venous thromboembolic disease (DVT or PE) Time: Baseline to Day 28Description: Number of Participants with myocardial infarction or ischemic stroke
Measure: Documented cardiovascular event (myocardial infarction or ischemic stroke) Time: Baseline to Day 28Description: Number of participants with transfusion reaction (fever/rash)
Measure: Transfusion reaction Time: Baseline to Day 28Description: Number of participants with transfusion related acute lung injury (TRALI)
Measure: Transfusion related acute lung injury (TRALI) Time: Baseline to Day 28Description: Number of participants with transfusion associated circulatory overload (TACO)
Measure: Transfusion associated circulatory overload (TACO) Time: Baseline to Day 28Description: Number of participants with transfusion related infection
Measure: Transfusion related infection Time: Baseline to Day 28Hope Biosciences is conducting a research study of an investigational product called allogeneic adipose-derived mesenchymal stem cells (abbreviated as HB-adMSCs) as treatment for patients suspected to have COVID-19. The study purpose is to evaluate the safety and efficacy of four IV infusions of either placebo or HB-adMSCs in subjects with COVID-19.
Description: change from baseline in interleukin-6
Measure: Interleukin-6 Time: screening, day 0, 7, 10Description: Change from baseline in C Reactive protein
Measure: C Reactive protein Time: screening, day 0, 7, 10Description: change from baseline oxygenation (%)
Measure: Oxygenation Time: screening, day 0, 7, 10Description: change from baseline in TNF alpha
Measure: TNF alpha Time: screening, day 0, 7, 10Description: change from baseline level of IL-10 in the blood (pg/mL)
Measure: IL-10 Time: screening, day 0, 7. 10Description: Time to return to room air
Measure: Return to room air (RTRA) Time: Day 0, 3, 7, 10, 28Description: Monitoring for changes in qt interval
Measure: EKG qt interval Time: screening, day 0, 3, 7, 10Description: change from baseline in leukocyte differential
Measure: Leukocyte differential Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of glucose in the blood (mg/dL)
Measure: Glucose Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of calcium in the blood (mg/dL)
Measure: Calcium Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of albumin in the blood (g/dL)
Measure: Albumin Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of total protein in the blood (g/dL)
Measure: Total protein Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of sodium in the blood (mol/L)
Measure: Sodium Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of total carbon dioxide in the blood (mmol/L)
Measure: Total carbon dioxide Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of potassium in the blood (mmol/L)
Measure: Potassium Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of chloride in the blood (mmol/L)
Measure: Chloride Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of BUN in the blood (mg/dL)
Measure: BUN Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of creatinine in the blood (mg/dL)
Measure: Creatinine Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of alkaline phosphatase in the blood (IU/L)
Measure: Alkaline phosphatase Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of alanine aminotransferase in the blood (IU/L)
Measure: Alanine aminotransferase Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of total bilirubin in the blood (mg/dL)
Measure: Total bilirubin Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of white blood cells in the blood (x10^3/uL)
Measure: White blood cells Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of red blood cells in the blood (x10^6/uL)
Measure: Red blood cells Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of hemoglobin in the blood (g/dL)
Measure: Hemoglobin Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of hematocrit in the blood (%)
Measure: Hematocrit Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of mean corpuscular volume in the blood (fL)
Measure: Mean corpuscular volume Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of mean corpuscular hemoglobin in the blood (pg)
Measure: Mean corpuscular hemoglobin Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of mean corpuscular hemoglobin concentration in the blood (g/dL)
Measure: Mean corpuscular hemoglobin concentration Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of red cell distribution width in the blood (%)
Measure: Red cell distribution width Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of neutrophils in the blood (%)
Measure: Neutrophils Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of lymphocytes in the blood (%)
Measure: Lymphs Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of monocytes in the blood (%)
Measure: Monocytes Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of eosinophils in the blood (%)
Measure: Eosinophils Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of basophils in the blood (%)
Measure: Basophils Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of absolute neutrophils in the blood (x10^3/uL)
Measure: Absolute neutrophils Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of absolute lymphocytes in the blood (x10^3/uL)
Measure: Absolute lymphs Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of absolute monocytes in the blood (x10^3/uL)
Measure: Absolute monocytes Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of absolute eosinophils in the blood (x10^3/uL)
Measure: Absolute eosinophils Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of absolute basophils in the blood (x10^3/uL)
Measure: Absolute basophils Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of immature granulocytes in the blood (x10^3/uL)
Measure: Immature granulocytes Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of platelets in the blood (x10^3/uL)
Measure: Platelets Time: screening, day 0, 7, 10Description: clinical lab evaluation of time for blood to coagulate (seconds)
Measure: Prothrombin time Time: screening, day 0, 7, 10Description: clinical lab evaluation of international normalized ratio of blood coagulation (no unit)
Measure: INR Time: screening, day 0, 7, 10Description: clinical lab evaluation of percentage of cells CD3- and CD54+ (%)
Measure: NK cell surface antigen (CD3-CD54+) Time: screening, day 0, 7, 10Description: clinical lab evaluation of ratio of CD4+ cells to CD8+ cells (no unit)
Measure: CD4+/CD8+ ratio Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of myoglobin in the blood (ng/mL)
Measure: Myoglobin Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of myoglobin in the blood (ng/mL)
Measure: Troponin Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of creatinine kinase in the blood (U/L)
Measure: Creatinine kinase MB Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of serum ferritin in the blood (ng/mL)
Measure: Serum ferritin Time: screening, day 0, 7, 10Description: incidence of adverse events
Measure: Adverse events Time: screening through day 28Description: change from baseline in ordinal scale score; scale of 1-7; a score of 1 indicates death and 7 indicates subject is not hospitalized and has no limitations on activities.
Measure: 7-point ordinal scale Time: screening, day 0, 3, 7, 10, 28Description: change from baseline in D-dimer
Measure: D-dimer Time: screening, day 0, 7, 10Description: change from baseline chest x-ray result
Measure: Chest X-ray Time: Day 0, Day 28Description: change from baseline CT scan result
Measure: CT scan Time: Day 0, Day 28Description: time to achieve negative PCR test results
Measure: PCR test for SARS-CoV-2 Time: day 0, 3, 7, 10This 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).
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 29Description: 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 weeksDescription: Clinical chemistry measurement in a blood sample.
Measure: Ratio to baseline in the C-reactive protein (CRP) Time: Baseline, Day 29Description: Clinical chemistry measurement in a blood sample.
Measure: Ratio to baseline in the serum ferritin Time: Baseline, Day 29Description: Clinical chemistry measurement in a blood sample.
Measure: Ratio to baseline in the D-dimer Time: Baseline, Day 29Description: 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 daysThis is a randomised, double-blind, placebo controlled study to evaluate the efficacy and safety of MRx-4DP0004 in patients with COVID-19. 90 hospitalised patients will be enrolled and randomised (2:1) to receive MRx-4DP0004 or placebo for up to 14 days. MRx-4DP0004 is an immunomodulating Live Biotherapeutic Product (LBP) which is expected to prevent or reduce the hyperinflammatory response to SARS-CoV-2 infection without impairing viral clearance.
Description: Clinical status score will be measured using the WHO Ordinal Scale for Clinical Improvement where patients are scored on a scale of 0-8 with 0 being uninfected and 8 being dead
Measure: Change in mean clinical status score in each treatment arm Time: Baseline to Day 42Description: Safety and tolerability will be determined according to clinically relevant reported adverse events
Measure: Number of adverse events in each treatment arm Time: Baseline to Day 42Description: Point changes in clinical status score will be measured using the WHO Ordinal Scale for Clinical Improvement
Measure: Number of patients with an improvement in clinical status score in each treatment arm Time: Day 1 to Day 42Description: Point changes in clinical status score will be measured using the WHO Ordinal Scale for Clinical Improvement
Measure: Number of patients with a deterioration in clinical status score in each treatment arm Time: Day 1 to Day 42Description: Oxygen saturation will be measured as per local standard procedures
Measure: Number of patients with at least 95% oxygen saturation on room air in each treatment arm Time: Day 1 to Day 14Description: Oxygen saturation will be recorded daily during hospitalisation to determine the mean time for each arm to reach at least 95% saturation
Measure: Time to patients with at least 95% oxygen saturation on room air in each treatment arm Time: Day 1 to Day 14Description: The NEWS 2 is based on aggregate scoring of physiological measurements including respiration rate, oxygen saturation, systolic blood pressure, pulse rate, level of consciousness and temperature
Measure: Number of patients with an improvement in the National Early Warning Score (NEWS) 2 in each treatment arm Time: Day 1 to Day 14Description: The NEWS 2 is based on aggregate scoring of physiological measurements including respiration rate, oxygen saturation, systolic blood pressure, pulse rate, level of consciousness and temperature
Measure: Number of patients with an deterioration in the National Early Warning Score (NEWS) 2 in each treatment arm Time: Day 1 to Day 14Description: Details of required respiratory support will be recorded throughout hospitalisation
Measure: Number of patients requiring Continuous Positive Airway Pressure in each treatment arm Time: Day 1 to Day 14Description: Details of required respiratory support will be recorded throughout the treatment period
Measure: Number of patients requiring Intermittent Positive Pressure Ventilation in each treatment arm Time: Day 1 to Day 14Description: Details of required respiratory support will be recorded throughout the treatment period
Measure: Time to patients requiring Continuous Positive Airway Pressure in each treatment arm Time: Day 1 to Day 14Description: Details of required respiratory support will be recorded throughout the treatment period
Measure: Time to patients requiring Intermittent Positive Pressure Ventilation in each treatment arm Time: Day 1 to Day 14Description: Length of hospital stay will be compared
Measure: Time to discharge in each treatment arm Time: Day 1 to Day 42Description: All cause mortality will be compared
Measure: Number of deaths in each treatment arm Time: Day 1 to Day 42This a double-blind, randomized, placebo-controlled clinical trial to determine if primary prophylaxis with hydroxychloroquine in healthcare workers reduces symptomatic COVID-19 infection. Healthcare workers will be randomized at a 1:1 allocation between intervention and placebo arms and followed for 12 weeks. This study will enroll up to 1,700 participates in Lafayette, Louisiana. The primary outcome will number of symptomatic COVID-19 infections. Secondary endpoints included number of days healthcare workers are absent from work and rate of severe infection.
Description: Number of participants who develop symptoms of COVID-19 in the setting of a positive COVID-19 assay
Measure: Incidence of symptomatic COVID-19 infection in healthcare workers Time: 12 weeksDescription: Number of days healthcare workers are absent from work due to symptomatic COVID-19 infection
Measure: Absenteeism from work due to COVID-19 Time: 12 weeksDescription: Rate of severe COVID-19 infection in healthcare works (hypoxia in setting of chest imaging >50% lung involvement, respiratory failure, end organ damage or shock)
Measure: Severity of COVID-19 infection Time: 12 weeksIn this study Investigators propose to administer clazakizumab to patients with life-threatening COVID-19 infection manifest by pulmonary failure and a clinical picture consistent with a cytokine storm syndrome. This is a single-center randomized, double-blind, placebo-controlled trial in which 30 patients will be enrolled and randomly assigned in a 1:1 ratio to two study arms that will receive clazakizumab at a dose of 25 mg or placebo.
Description: Serum CRP (measured in mg/dl) will be evaluated at baseline and on days 1 and 2 following clazakizumab or placebo administration to assess response
Measure: Change in C-reactive protein (CRP) level Time: Up to 3 daysThis is a prospective, randomized, double-blinded, placebo-controlled, pilot study to assess the preliminary efficacy and safety of hydroxychloroquine for the treatment of patients with lower respiratory tract SARS-CoV-2 infection.
Description: A 6-point ordinal scale ranging from "Death" to "Not hospitalized with full resumption of normal activities" is used to evaluate differences in the clinical status between participants that receive placebo vs hydroxychloroquine
Measure: Clinical Status at Day 5 Assessed by a 6-Point Ordinal Scale Time: Day 5Description: Assess differences in SARS-CoV-2 viral shedding between participants that receive placebo vs hydroxychloroquine
Measure: Number of Participants with Detectable SARS-CoV-2 Virus from Day 0 to Day 28 and at Day 5 Time: Day 0 to Day 28 and at Day 5Description: Assess by incidence of Grade 3, Grade 4, and Serious Adverse Events (AEs)
Measure: Toxicity of Study Drug Assessed by Incidence of Adverse Events Time: Day 0 to Day 28Description: Assess length of hospitalization
Measure: Duration of Initial Hospitalization Time: Day 0 to Day 28Description: Assess number of deaths during study follow-up
Measure: Mortality During Follow-Up Time: Day 0 to Day 28Description: Assess number of deaths in the hospital during initial hospitalization
Measure: Mortality During Initial Hospitalization Time: Day 0 to Day 28Description: Assessing utilization of hospital resources
Measure: Incidence of New Hospital Resource Utilization Time: Day 0 to Day 28Description: Assessing duration of hospital resource utilization
Measure: Duration of Hospital Resource Utilization Time: Day 0 to Day 28Description: Provide preliminary characterization of differences in inflammatory response between participants that receive placebo vs hydroxychloroquine
Measure: Changes in Cytokine Profile Time: Day 0 to Day 28Ideal new treatments for Novel Coronavirus-19 (COVID-19) would help halt the progression disease in patients with mild disease prior to the need for artificial respiration (ventilators), and also provide a rescue treatment for patients with severe disease, while also being affordable and available in quantities sufficient to treat large numbers of infected people. Low doses of Naltrexone, a drug approved for treating alcoholism and opiate addiction, as well as Ketamine, a drug approved as an anesthetic, may be able to interrupt the inflammation that causes the worst COVID-19 symptoms and prove an effective new treatment. This study will investigate their effectiveness in a randomized, blinded trial versus standard treatment plus placebo.
Description: Count of participants initially presenting with mild/moderate disease who progress to requiring advanced oxygenation (high flow nasal canula, non-rebreather, continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), or intubation)
Measure: Progression of oxygenation needs Time: up to 1 monthDescription: Count of participants who develop or experience worsened renal failure as defined by RIFLE criteria, a 5-point scale where the categories are labeled: Risk-Injury-Failure-Loss-End stage renal disease, with Risk being the least severe and End stage renal disease being the most severe. The criteria for determination of stage are factors of serum creatinine and urine output. Numbers of participants worsening one or more RIFLE stages will be reported.
Measure: Renal failure Time: up to 1 monthDescription: Count of participants who develop or experience worsened liver failure as defined by serum transaminases five times normal limits
Measure: Liver failure Time: up to 1 monthDescription: Count of participants who develop cytokine storm as measured by elevated markers of inflammation (elevated D-dimer, hypofibrinogenemia, hyperferritinemia), evidence of acute respiratory distress syndrome (ARDS) measured by imaging findings and mechanical ventilator requirements, and/or continuous fever (≥ 38.1 ° Celsius unremitting)
Measure: Cytokine Storm Time: up to 1 monthDescription: Count of participants who die from COVID-19
Measure: Mortality Time: up to 1 month post hospital dischargeDescription: Length of hospital stay in days
Measure: Length of hospital stay Time: up to 1 monthDescription: Count of patients admitted to the ICU at any time during index hospitalization
Measure: Intensive Care Unit (ICU) admission Time: up to 1 monthDescription: Length of ICU stay in days
Measure: Intensive Care Unit (ICU) duration Time: up to 1 monthDescription: Count of participants requiring intubation
Measure: Intubation Time: up to 1 monthDescription: Length of intubation, measured in days
Measure: Intubation duration Time: up to 1 monthDescription: Time measured in days from hospital admission to determination patient is stable for discharge
Measure: Time until recovery Time: up to 1 monthThis is a randomized, double-blind, placebo-controlled, single-ascending dose study of AVM0703 administered as a single intravenous (IV) infusion to patients with COVID-19. The study is designed to evaluate the safety, tolerability, and pharmacokinetics of single-ascending dosing of AVM0703 in patients with COVID-19.
Description: The primary endpoint of the Phase 1 portion of the study is to evaluate the safety of AVM0703 in subjects with severe or life-threatening COVID-19 infection, and to identify the RP2D.
Measure: Dose-Limiting Toxicities Time: 0-12 monthsDescription: The primary endpoint of the Phase 1/2 portion of the study is to evaluate the efficacy of AVM0703 in subjects with severe or life-threatening COVID-19 infection.
Measure: 28 day all-cause mortality will be a primary end point for Phase 1 and 2 Time: 0-12 monthsMulticenter investigation featuring an open-label lead-in followed by a double blinded, randomized, placebo-controlled Phase 2/3 part to evaluate the safety and efficacy of MultiStem therapy in subjects with moderate to severe Acute Respiratory Distress Syndrome (ARDS) due to COVID-19.
This is a Phase 1/2/3, randomized, placebo-controlled, observer-blind, dose-finding, vaccine candidate-selection, and efficacy study in healthy individuals. The study consists of 2 parts: Phase 1: to identify preferred vaccine candidate(s) and dose level(s); Phase 2/3: an expanded cohort and efficacy part. The study will evaluate the safety, tolerability, and immunogenicity of 2 different SARS CoV 2 RNA vaccine candidates against COVID 19 and the efficacy of 1 candidate: - As a 2-dose (separated by 21 days) schedule; - At various different dose levels in Phase 1; - In 3 age groups (Phase 1: 18 to 55 years of age, 65 to 85 years of age; Phase 2/3: ≥12 years of age [stratified as 12-15, 16-55 or >55 years of age]). The candidate selected for evaluation in Phase 2/3 is BNT162b2 (mid-dose).
Description: Pain at the injection site, redness, and swelling as self-reported on electronic diaries.
Measure: Percentage of participants in Phase 1 reporting local reactions Time: For 7 days after dose 1 and dose 2Description: Fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain as self-reported on electronic diaries.
Measure: Percentage of participants in Phase 1 reporting systemic events Time: For 7 days after dose 1 and dose 2Description: As elicited by investigational site staff
Measure: Percentage of participants in Phase 1 reporting adverse events Time: From dose 1 through 1 month after the last doseDescription: As elicited by investigational site staff
Measure: Percentage of participants in Phase 1 reporting serious adverse events Time: From dose 1 through 6 months after the last doseDescription: As measured at the central laboratory
Measure: Percentage of Phase 1 participants with abnormal hematology and chemistry laboratory values Time: 1 day after dose 1Description: As measured at the central laboratory
Measure: Percentage of Phase 1 participants with abnormal hematology and chemistry laboratory values Time: 7 days after dose 1Description: As measured at the central laboratory
Measure: Percentage of Phase 1 participants with abnormal hematology and chemistry laboratory values Time: 7 days after dose 2Description: As measured at the central laboratory
Measure: Percentage of Phase 1 participants with grading shifts in hematology and chemistry laboratory assessments Time: Between baseline and 1 day after dose 1Description: As measured at the central laboratory
Measure: Percentage of Phase 1 participants with grading shifts in hematology and chemistry laboratory assessments Time: Between baseline and 7 days after dose 1Description: As measured at the central laboratory
Measure: Percentage of Phase 1 participants with grading shifts in hematology and chemistry laboratory assessments Time: Between before dose 2 and 7 days after dose 2Description: Pain at the injection site, redness, and swelling as self-reported on electronic diaries.
Measure: In the first 360 participants randomized into Phase 2/3, percentage of participants reporting local reactions Time: For 7 days after dose 1 and dose 2Description: Fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain as self-reported on electronic diaries.
Measure: In the first 360 participants randomized into Phase 2/3, percentage of participants reporting systemic events Time: For 7 days after dose 1 and dose 2Description: As elicited by investigational site staff
Measure: In the first 360 participants randomized into Phase 2/3, percentage of participants reporting adverse events Time: From dose 1 through 1 month after the last doseDescription: As elicited by investigational site staff
Measure: In the first 360 participants randomized into Phase 2/3, percentage of participants reporting serious adverse events Time: From dose 1 through 6 months after the last doseDescription: Pain at the injection site, redness, and swelling as self-reported on electronic diaries.
Measure: In a subset of at least 6000 participants randomized in Phase 2/3, percentage of participants reporting local reactions Time: For 7 days after dose 1 and dose 2Description: Fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain as self-reported on electronic diaries.
Measure: In a subset of at least 6000 participants randomized in Phase 2/3, percentage of participants reporting systemic events Time: For 7 days after dose 1 and dose 2Description: As elicited by investigational site staff
Measure: Percentage of participants in Phase 2/3 reporting adverse events Time: From dose 1 through 1 month after the last doseDescription: As elicited by investigational site staff
Measure: Percentage of participants in Phase 2/3 reporting serious adverse events Time: From dose 1 through 6 months after the last doseDescription: Per 1000 person-years of follow-up
Measure: Confirmed COVID-19 in Phase 2/3 participants without evidence of infection before vaccination Time: From 7 days after the second dose of study intervention to the end of the study, up to 2 yearsDescription: Per 1000 person-years of follow-up
Measure: Confirmed COVID-19 in Phase 2/3 participants with and without evidence of infection before vaccination Time: From 7 days after the second dose of study intervention to the end of the study, up to 2 yearsDescription: As elicited by investigational site staff
Measure: Percentage of participants 12-15 years of age in Phase 3 reporting adverse events Time: From dose 1 through 1 month after the last doseDescription: As elicited by investigational site staff
Measure: Percentage of participants 12-15 years of age in Phase 3 reporting adverse events Time: From dose 1 through 6 months after the last doseDescription: Pain at the injection site, redness, and swelling as self-reported on electronic diaries.
Measure: In participants 12-15 years of age randomized in Phase 3, percentage of participants reporting local reactions Time: For 7 days after dose 1 and dose 2Description: Fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain as self-reported on electronic diaries.
Measure: In participants 12-15 years of age randomized in Phase 3, percentage of participants reporting systemic events Time: For 7 days after dose 1 and dose 2Description: As measured at the central laboratory
Measure: In Phase 1 participants, SARS-CoV-2 serum neutralizing antibody levels, expressed as GMTs Time: Through 2 years after the final doseDescription: As measured at the central laboratory
Measure: In Phase 1 participants, GMFR in SARS-CoV-2 serum neutralizing titers from before vaccination to each subsequent time point Time: Through 2 years after the final doseDescription: As measured at the central laboratory
Measure: Proportion of participants in Phase 1 achieving a greater than or equal to 4-fold rise from before vaccination in SARS-CoV-2 serum neutralizing antibody levels Time: Through 2 years after the final doseDescription: As measured at the central laboratory
Measure: In Phase 1 participants, SARS-CoV-2 anti-S1 binding antibody levels and anti-RBD binding antibody levels, expressed as GMCs Time: Through 2 years after the final doseDescription: As measured at the central laboratory
Measure: Proportion of participants in Phase 1 achieving a greater than or equal to 4-fold rise from before vaccination in SARS-CoV-2 anti-S1 binding antibody levels and anti-RBD binding antibody levels Time: Through 2 years after the final doseDescription: As measured at the central laboratory
Measure: In Phase 1 participants, GMFR in SARS-CoV-2 anti-S1 binding antibody levels and anti-RBD binding antibody levels from before vaccination to each subsequent time point Time: Through 2 years after the final doseDescription: As measured at the central laboratory
Measure: In Phase 1 participants, GMR of the geometric mean of SARS-CoV-2 serum neutralizing titers to the geometric mean of SARS CoV 2 (anti-S1 and anti-RBD) binding antibody levels Time: Through 2 years after the final doseDescription: Per 1000 person-years of follow-up
Measure: Confirmed COVID-19 in Phase 2/3 participants without evidence of infection before vaccination Time: From 14 days after the second dose of study intervention to the end of the study, up to 2 yearsDescription: Per 1000 person-years of follow-up
Measure: Confirmed COVID-19 in Phase 2/3 participants with and without evidence of infection before vaccination Time: From 14 days after the second dose of study intervention to the end of the study, up to 2 yearsDescription: Per 1000 person-years of follow-up
Measure: Confirmed severe COVID-19 in Phase 2/3 participants without evidence of infection before vaccination Time: From 7 days after the second dose of study intervention to the end of the study, up to 2 yearsDescription: Per 1000 person-years of follow-up
Measure: Confirmed severe COVID-19 in Phase 2/3 participants without evidence of infection before vaccination Time: From 14 days after the second dose of study intervention to the end of the study, up to 2 yearsDescription: Per 1000 person-years of follow-up
Measure: Confirmed severe COVID-19 in Phase 2/3 participants with and without evidence of infection before vaccination Time: From 7 days after the second dose of study intervention to the end of the study, up to 2 yearsDescription: Per 1000 person-years of follow-up
Measure: Confirmed severe COVID-19 in Phase 2/3 participants with and without evidence of infection before vaccination Time: From 14 days after the second dose of study intervention to the end of the study, up to 2 yearsDescription: Per 1000 person-years of follow-up
Measure: Confirmed COVID-19 (according to the CDC-defined symptoms) in Phase 2/3 participants without evidence of infection before vaccination Time: From 7 days after the second dose of study intervention to the end of the study, up to 2 yearsDescription: Per 1000 person-years of follow-up
Measure: Confirmed COVID-19 (according to the CDC-defined symptoms) in Phase 2/3 participants without evidence of infection before vaccination Time: From 14 days after the second dose of study intervention to the end of the study, up to 2 yearsDescription: Per 1000 person-years of follow-up
Measure: Confirmed COVID-19 (according to the CDC-defined symptoms) in Phase 2/3 participants with and without evidence of infection before vaccination Time: From 7 days after the second dose of study intervention to the end of the study, up to 2 yearsDescription: Per 1000 person-years of follow-up
Measure: Confirmed COVID-19 (according to the CDC-defined symptoms) in Phase 2/3 participants with and without evidence of infection before vaccination Time: From 14 days after the second dose of study intervention to the end of the study, up to 2 yearsDescription: As measured at the central laboratory
Measure: GMR of SARS CoV 2 neutralizing titers in the 2 age groups (12-15 years of age to 16-25 years of age) Time: 1 month after the second doseProphylactic treatment in cancer patients undergoing antineoplastic therapy during the COVID-19 pandemic.
Description: assessed by positive polymerase chain reaction (PCR) from routine nasal swabs (performed every 28 days)
Measure: Cumulative number of severe acute respiratory syndrome corona virus 2 (SARS-COV-2) infections Time: 12 weeks after initiation of therapyDescription: defined as combined endpoint of hospitalization rate or death
Measure: Number of severe COVID-19 cases Time: 12 weeks after initiation of therapyDescription: grading as outlined by the world health organization (WHO)
Measure: Severity of COVID-19 cases Time: 12 weeks after initiation of therapyDescription: significant clinical and laboratory abnormalities according to CTCAE criteria
Measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] Time: 12 weeks after initiation of therapyDescription: other than COVID-19
Measure: Number of viral and bacterial infections Time: 12 weeks after initiation of therapyDescription: Development of azithromycin-resistant bacterial strains as assessed by nasal swabs test
Measure: Number of participants with azithromycin-resistant bacterial strains in nasal swabs test Time: 12 weeks after initiation of therapyTo date, there is no vaccine or treatment with proven efficiency against COVID-19, and the transmissibility of the SARS-CoV-2 virus can be inferred by its identification in the oro-nasopharynx. The bacillus Calmette Guérin (BCG) has the potential for cross-protection against viral infections. This study evaluates the impact of previous (priming effect, from the titer of anti-BCG interferon-gamma) or current BCG exposure (boost with intradermal vaccine) on 1) clinical evolution of COVID-19; 2) elimination of SARS-CoV-2 at different times and disease phenotypes; and 3) seroconversion rate and titration (anti-SARS-CoV-2 IgA, IgM, and IgG).
Description: Classified as mild, moderate and severe
Measure: Clinical evolution of COVID-19 Time: 45 days of symptoms onset or diagnosisDescription: Virus detection by PCR
Measure: SARS-CoV-2 elimination Time: 7 days of symptoms onset or diagnosisDescription: Titration of anti SARS-CoV-2 IgA, IgM and IgG
Measure: Seroconversion rate and titration Time: 7 days of symptoms onset or diagnosisDescription: Classified according to type and severity
Measure: Local and systemic adverse events to BCG vaccination Time: 3 monthsDescription: Virus detection by PCR
Measure: SARS-CoV-2 elimination Time: 21 days of symptoms onset or diagnosisDescription: Titration of anti SARS-CoV-2 IgA, IgM and IgG
Measure: Seroconversion rate Time: 21 days of symptoms onset or diagnosisDescription: Virus detection by PCR
Measure: SARS-CoV-2 elimination Time: 45 days of symptoms onset or diagnosisDescription: Titration of anti SARS-CoV-2 IgA, IgM and IgG
Measure: Seroconversion rate and titration Time: 45 days of symptoms onset or diagnosisThe purpose of this study is to determine whether XPro1595 can prevent the progression of respiratory complications in COVID19 patients.
Description: Disease progression is defined by the development of need for mechanical ventilation or death. Mechanical ventilation includes CPAP, BIPAP or mechanical ventilation requiring intubation.
Measure: Proportion of participants with disease progression from randomization to 28 days post-randomization Time: 28 daysThe 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).
Description: improvement of WHO ordinal scale
Measure: Clinical improvement using WHO ordinal scale Time: day 28Description: 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 28The mortality rate in SARS-CoV-2-related severe ARDS is high despite treatment with antivirals, glucocorticoids, immunoglobulins, and ventilation. Preclinical and clinical evidence indicate that MSCs migrate to the lung and respond to the pro-inflammatory lung environment by releasing anti-inflammatory factors reducing the proliferation of pro-inflammatory cytokines while modulating regulatory T cells and macrophages to promote resolution of inflammation. Therefore, MSCs may have the potential to increase survival in management of COVID-19 induced ARDS. The primary objective of this phase 3 trial is to evaluate the efficacy and safety of the addition of the mesenchymal stromal cell (MSC) remestemcel-L plus standard of care compared to placebo plus standard of care in patients with acute respiratory distress syndrome (ARDS) due to SARS-CoV-2. The secondary objective is to assess the impact of MSCs on inflammatory biomarkers.
Description: Number of all-cause mortality within 30 days of randomization.
Measure: Number of all-cause mortality Time: 30 daysDescription: Number of days alive off mechanical ventilatory support calculated as the number of days, within the 60 days window, that patients were alive and free of mechanical ventilatory support.
Measure: Number of days alive off mechanical ventilatory support Time: 60 daysDescription: Safety analyses will be assessed by adverse event rates calculated as the ratio of the total number of events over 30 days divided by total patient-time at risk for the specific event from randomization.
Measure: Number of adverse events Time: 30 daysDescription: The number and percent of patients with resolution and/or improvement of ARDS at day 7
Measure: Number of participants with resolution and/or improvement of ARDS Time: 7 daysDescription: The number and percent of patients with resolution and/or improvement of ARDS at day 14
Measure: Number of participants with resolution and/or improvement of ARDS Time: 14 daysDescription: The number and percent of patients with resolution and/or improvement of ARDS at day 21
Measure: Number of participants with resolution and/or improvement of ARDS Time: 21 daysDescription: The number and percent of patients with resolution and/or improvement of ARDS at day 30
Measure: Number of participants with resolution and/or improvement of ARDS Time: 30 daysDescription: severity of ARDS according to Berlin Criteria at days 7 post-randomization Change from baseline of the severity of ARDS according to Berlin Criteria at days 7, 14, 21 and 30 post-randomization will be compared between treatment groups using a Cochran-Mantel-Haenszel test stratified by baseline severity.
Measure: Severity of ARDS Time: baseline and 7 daysDescription: severity of ARDS according to Berlin Criteria at days 14 post-randomization Change from baseline of the severity of ARDS according to Berlin Criteria at days 7, 14, 21 and 30 post-randomization will be compared between treatment groups using a Cochran-Mantel-Haenszel test stratified by baseline severity.
Measure: Severity of ARDS Time: baseline and 14 daysDescription: severity of ARDS according to Berlin Criteria at days 21 post-randomization Change from baseline of the severity of ARDS according to Berlin Criteria at days 7, 14, 21 and 30 post-randomization will be compared between treatment groups using a Cochran-Mantel-Haenszel test stratified by baseline severity.
Measure: Severity of ARDS Time: baseline and 21 daysDescription: severity of ARDS according to Berlin Criteria at days 30 post-randomization Change from baseline of the severity of ARDS according to Berlin Criteria at days 7, 14, 21 and 30 post-randomization will be compared between treatment groups using a Cochran-Mantel-Haenszel test stratified by baseline severity.
Measure: Severity of ARDS Time: baseline and 30 daysDescription: Hospital length of stay
Measure: Length of stay Time: 12 monthsDescription: number of readmission
Measure: Readmissions Time: 12 monthsDescription: Change from baseline in Clinical Improvement Scale at day 7. Clinical Improvement Scale full scale from 1 to 7, with higher score indicating more clinical improvement.
Measure: Clinical Improvement Scale Time: 7 daysDescription: Change from baseline in Clinical Improvement Scale at day 14. Full scale from 1 to 7, with higher score indicating more clinical improvement.
Measure: Clinical Improvement Scale Time: 14 daysDescription: Change from baseline in Clinical Improvement Scale at day 21. Clinical Improvement Scale full scale from 1 to 7, with higher score indicating more clinical improvement.
Measure: Clinical Improvement Scale Time: 21 daysDescription: Change from baseline in Clinical Improvement Scale at day 30. Clinical Improvement Scale full scale from 1 to 7, with higher score indicating more clinical improvement.
Measure: Clinical Improvement Scale Time: 30 daysDescription: Changes from baseline in plasma hs-CRP concentration at days 7
Measure: Change in plasma hs-CRP concentration Time: baseline and 7 daysDescription: Changes from baseline in plasma hs-CRP concentration at days 14
Measure: Change in plasma hs-CRP concentration Time: baseline and 14 daysDescription: Changes from baseline in plasma hs-CRP concentration at days 21
Measure: Change in plasma hs-CRP concentration Time: baseline and 21 daysDescription: Changes from baseline in serum hs-CRP concentration at days 30
Measure: Change in serum hs-CRP concentration Time: baseline and 30 daysDescription: Changes from baseline in IL-6 inflammatory marker level at 7 days
Measure: Change in IL-6 inflammatory marker level Time: baseline and 7 daysDescription: Changes from baseline in IL-6 inflammatory marker level at 14 days
Measure: Change in IL-6 inflammatory marker level Time: baseline and 14 daysDescription: Changes from baseline in IL-6 inflammatory marker level at 21 days
Measure: Change in IL-6 inflammatory marker level Time: baseline and 21 daysDescription: Changes from baseline in IL-6 inflammatory marker level at 30 days
Measure: Change in IL-6 inflammatory marker level Time: baseline and 30 daysDescription: Changes from baseline in IL-6 inflammatory marker level at 7 days
Measure: Change in IL-8 inflammatory marker level Time: baseline and 7 daysDescription: Changes from baseline in IL-6 inflammatory marker level at 21 days
Measure: Change in IL-8 inflammatory marker level Time: baseline and 21 daysDescription: Changes from baseline in IL-6 inflammatory marker level at 14 days
Measure: Change in IL-8 inflammatory marker level Time: baseline and 14 daysDescription: Changes from baseline in IL-6 inflammatory marker level at 30 days
Measure: Change in IL-8 inflammatory marker level Time: baseline and 30 daysDescription: Changes from baseline in TNF-alpha inflammatory marker level at 7 days
Measure: Change in TNF-alpha inflammatory marker level Time: baseline and 7 daysDescription: Changes from baseline in TNF-alpha inflammatory marker level at 14 days
Measure: Change in TNF-alpha inflammatory marker level Time: baseline and 14 daysDescription: Changes from baseline in TNF-alpha inflammatory marker level at 21 days
Measure: Change in TNF-alpha inflammatory marker level Time: baseline and 21 daysDescription: Changes from baseline in TNF-alpha inflammatory marker level at 30 days
Measure: Change in TNF-alpha inflammatory marker level Time: baseline and 30 daysDescription: including the presence of emphysema, COPD, asthma, pulmonary fibrosis, other pulmonary disease, and the need for respiratory support will be reported by randomization
Measure: Pulmonary symptoms Time: 6 monthsDescription: including the presence of emphysema, COPD, asthma, pulmonary fibrosis, other pulmonary disease, and the need for respiratory support will be reported by randomization
Measure: Pulmonary symptoms Time: 12 monthsThis is a double-blinded, two-arm, randomized, placebo controlled study comparing the virological efficacy of add-on sirolimus with standard care to placebo and standard care. Virological efficacy is defined as the change from baseline to day 7 in SARS-CoV-2 viral burden measured by quantitative real-time polymerase chain reaction.
Description: SARS-CoV-2 viral burden will be quantified for both arms using a qRT-PCR
Measure: Change in SARS-CoV-2 viral burden from baseline to day 7 of treatment Time: Baseline, and days 1, 2, 3, 4, 5, 6, & 7 post-dose for all patientsDescription: SARS-CoV-2 viral burden will be quantified for both arms using a qRT-PCR
Measure: Change in SARS-CoV-2 viral burden at days 1-6 Time: Days 1, 2, 3, 4, 5, and 6 post-dose for all patientsDescription: Safety and tolerability of sirolimus in patients with COVID-19
Measure: Rate of treatment emergent adverse events Time: Days 1, 2, 3, 4, 5, and 6 post-dose for all patientsThe aim of the study is to compare a treatment with doxycycline vs a placebo as soon as the patient is confirmed COVID-19 + and before the onset of oxygen dependence with the aim of reducing or even abolishing the cytokine explosion and thus the evolution towards a serious form of the disease which can lead to death. Three criteria support the rational use of tetrcycline in COVI-19 (1) The coronaviruses is known to bind to metalloproteases (MMPs) of the host, in particular to ensure viral survival. Tetracyclines are known to chelate zinc from MMPs. Their chelating activity may help inhibit COVID19 infection by limiting its ability to replicate in the host. (2) Tetracyclines may also be able to inhibit the replication of positive-polarity single-stranded RNA viruses, such as COVID19 (demonstrated on the dengue virus). (3) In addition, tetracyclines are modulators of innate immunity (anti-inflammatory activity), a property used in the treatment of inflammatory skin diseases for many years. These modulating effects are noted on several targets of innate immunity: They can decrease the expression of NFKB, the release of inflammatory cytokines such as TNF-α, IL-1β and IL-6, inhibit granulomas inflammatory and free radical release. Tetracyclines could therefore participate in limiting the cytokine release induced by COVID19. Their lipophilic nature and their strong pulmonary penetration could allow them to inhibit viral replication.
Description: Percentage of patients with clinical worsening (SaO2 ≤ 93%) after at least 48 hours of treatment
Measure: Percentage of Patients with Clinical Respiratory Aggravation Time: after at least 48 hours of treatmentDescription: Percentage of patients hospitalized after at least 48 hours of experimental treatment
Measure: Percentage of patients hospitalized Time: after at least 48 hours of experimental treatmentDescription: Percentage of patients requiring ventilatory assistance
Measure: Percentage of patients requiring ventilatory assistance Time: Day 0 to Day 28Description: Number of positive SARS-CoV-2 PCR tests on D-1 / D0 and D7 (+/- 2 days)
Measure: Positive SARS-CoV-2 PCR Test Time: Day -1 or day 0 AND Day 7Description: Duration of symptoms (fever, painful symptoms: headache, sore throat, dyspnea)
Measure: Duration of symptoms Time: Day 0 to Day 28Description: Total duration of hospitalization
Measure: Duration of hospitalization Time: From day 0 until to the end of hospitalization or date of death for any cause, whichever came first, assessed up to 3 months after Day0Description: Duration of hospitalization in intensive care or reanimation
Measure: Hospitalization intensive care or reanimation Time: From day 0 until to the end of hospitalization or date of death for any cause, whichever came first, assessed up to 3 months after Day0Description: Duration of mechanical ventilatory assistance
Measure: Duration of mechanical ventilatory assistance Time: to the end of mechanical ventilatory assistance if any, assessed up to 3 months after Day0Description: Percentage of deaths related to SARS-CoV-2 infection
Measure: Percentage of deaths related to SARS-CoV-2 Time: Day 28, or end of hospitalization if any (assessed up to 3 months after Day0)Description: Number of AE / SAE in both arms
Measure: AE / SAE in both arms Time: Day 28, or end of hospitalization if any (assessed up to 3 months after Day0)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.
The exceedingly high mortality rates of severe and critical COVID-19 warrant the identification and evaluation of novel therapies that could potentially mitigate the advanced disease manifestations. Based on preclinical data from this institution and others, the investigators hypothesize that PI3K inhibition with duvelisib could potentially quell aberrant hyperactivtation of the innate immune system, preferentially polarize macrophages, reduce pulmonary inflammation, and limit viral persistence, thereby improving patient outcomes.
Description: -For those on a ventilator at the time of randomization
Measure: Duration of ventilator use Time: Through completion of follow-up (estimated to be 7 months)Description: -Defined as increase in viral load of >0.5 log on two consecutive days, or >1 log increase in one day, not in keeping with any baseline trend of rising viral loads during the pre-treatment viral testing
Measure: Viral kinetics as measured by virologic failure Time: Through completion of follow-up (estimated to be 7 months)Blinded, multicenter, placebo-controlled, randomized clinical trial evaluating lopinavir/ritonavir vs placebo in early outpatient treatment of adults with COVID-19
Description: Death Hospitalized on mechanical ventilation or extracorporeal membrane oxygenator (ECMO) Hospitalized on supplemental oxygen Hospitalized not on supplemental oxygen Not hospitalized with symptoms and limitation in activity Not hospitalized with symptoms but with no limitation in activity Not hospitalized without symptoms nor limitation in activity symptoms at the milder end of the scale for this outpatient trial
Measure: Modified COVID Ordinal Outcomes Scale: Study Day 15 Time: Day 15Description: Death Hospitalized on mechanical ventilation or ECMO Hospitalized on supplemental oxygen Hospitalized not on supplemental oxygen Not hospitalized with symptoms and limitation in activity Not hospitalized with symptoms but with no limitation in activity Not hospitalized without symptoms nor limitation in activity
Measure: Modified COVID Ordinal Outcome Scale: Study Day 8 Time: Day 8Description: Death Hospitalized on mechanical ventilation or ECMO Hospitalized on supplemental oxygen Hospitalized not on supplemental oxygen Not hospitalized with symptoms and limitation in activity Not hospitalized with symptoms but with no limitation in activity Not hospitalized without symptoms nor limitation in activity Ordinal Scale
Measure: Modified COVID Ordinal Outcome Scale: Study Day 29 Time: Day 29Description: Proportion hospitalized
Measure: Proportion of patients hospitalized: Day 1 to 29 Time: Day 1 to Day 29Description: Number of days from enrollment to hospitalization
Measure: Time to hospitalization Day 1 to Day 29 Time: Day 1 to Day 29Description: Number of days from enrollment to resolution of COVID-19 symptoms
Measure: Time to symptom resolution: Day 1 to Day 29 Time: Day 1 to Day 29Description: Survival status
Measure: All-cause, all-location mortality: Day 1 to Day 29 Time: Day 1 to Day 29Description: Number of Days without oxygen
Measure: Oxygen-free days: Day 1 to Day 29 Time: Day 1 to Day 29Description: Number of days without fever
Measure: Fever-free days: Day 1 to Day 29 Time: Day 1 to Day 29Description: Number of days without ventilator use
Measure: Ventilator-free days: Day 1 to Day 29 Time: Day 1 to Day 29Description: Number of days outside the ICU
Measure: ICU-free days: Day 1 to Day 29 Time: Day 1 to Day 29Description: Number of days outside the hospital
Measure: Hospital-free days: Day 1 to Day 29 Time: Day 1 to Day 29The coronavirus disease-2019 (COVID-19) is spreading throughout the United States. While there are no known therapies to treat those who have become sick, there have been some reports that a medication currently used to treat rheumatoid arthritis, lupus, and malaria (Hydroxychloroquine sulfate, also known as Plaquenil) may help to lessen the chance or severity of illness, especially if combined with a medicine that treats other kinds of infections (Azithromycin, also known as Zithromax or Zmax or Zpak). There are some people who test positive for the virus but who are otherwise not ill. Current standard of care is to advise these people to self-monitor but no treatment is offered. It is not known how many of these individuals will remain symptom free, and how many will become sick or how severe those symptoms will be. This study will randomize those people who do not have symptoms into one of three treatment plans 1) Hydroxycholoquine and Azithromycin, or 2) no active medication (placebo). All participants will be followed for 2 months. The study will determine if there is any benefit to those who are asymptomatic to taking taking Hydroxychloroquine sulfate in combination with Azithromycin, or if there is no benefit from taking these medications.
Description: Change in SARS-CoV-2 viral from baseline to day 6
Measure: The primary outcome is the rate of decline in viral load over the 10 days after randomization Time: 10 daysCoronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Lung failure is the main cause of death related to COVID-19 infection. The main objective of this study is to evaluate if Ibrutinib is safe and can reduce respiratory failure in participants with COVID-19 infection. Ibrutinib is an investigational drug being developed for the treatment of COVID-19. Participants are assigned 1 of 2 groups, called treatment arms. Each group receives a different treatment. There is a 1 in 2 chance that participants will be assigned to placebo. Around 46 adult participants with a diagnosis of COVID-19 will be enrolled at multiple sites in Unites States. Participants will receive oral doses of Ibrutinib or placebo capsules once daily for 4 weeks along with standard care. There may be higher treatment burden for participants in this trial compared to their standard of care. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects.
Description: Respiratory failure is defined by clinical diagnosis of respiratory failure and initiation of 1 of the following therapies: Endotracheal intubation and mechanical ventilation OR Extracorporeal membrane oxygenation OR high-flow nasal cannula oxygen delivery OR non-invasive positive pressure ventilation OR clinical diagnosis of respiratory failure with initiation of none of these measures only when clinical decision-making driven is driven solely by resource limitation.
Measure: Percentage of Participants Alive and Without Respiratory Failure Time: Day 28Description: WHO-8 is an 8 point ordinal scale for clinical improvement with scores ranging from 0 (uninfected) through 8 (Death).
Measure: Change in the World Health Organization (WHO)-8 Point Ordinal Scale From Baseline Time: Day 14Description: Time on supplemental oxygen imputed to the maximum number of days on study drug (28) for all points following the death of a participant.
Measure: Median Reduction in Days Spent on Supplemental Oxygen Time: Up to Day 28Description: Percentage of participants with mortality from any cause.
Measure: All-Cause Mortality Time: Up to Day 28Description: Respiratory failure is defined by clinical diagnosis of respiratory failure and initiation of 1 of the following therapies: Endotracheal intubation and mechanical ventilation OR Extracorporeal membrane oxygenation OR high-flow nasal cannula oxygen delivery OR non-invasive positive pressure ventilation OR clinical diagnosis of respiratory failure with initiation of none of these measures only when clinical decision-making driven is driven solely by resource limitation.
Measure: Percentage of Participants Experiencing Respiratory Failure or Death Time: Up to Day 28Description: Percentage of participants alive and not requiring mechanical ventilation.
Measure: Mechanical Ventilation-Free Survival Time: Up to Day 56Description: Defined as number of days from the first day of using mechanical ventilation to the last day of using mechanical ventilation.
Measure: Days on Mechanical Ventilation Time: Up to Day 56Description: The duration of hospitalization is defined as the time in days from the first day of hospitalized to the date of discharge or death.
Measure: Duration of hospitalization Time: Up to Day 56Description: Time to discharge is defined as the time in days from the first day of hospitalized to the date of discharge.
Measure: Time to Discharge Time: Up to Day 56Description: PaO2:FiO2 ratio is an index of respiratory distress.
Measure: Partial Pressure of Oxygen in Arterial Blood (PaO2) to Fraction of Inspired Oxygen (FiO2) Ratio Time: Up to Day 56Description: Oxygenation Index is a parameter of pulmonary function of participants.
Measure: Oxygenation Index Time: Up to Day 56Description: An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent adverse events (TEAEs) are defined as any event that began or worsened in severity on or after the first dose of study drug.
Measure: Number of Participants With Adverse Events Time: Up to Day 56Description: Laboratory abnormalities will be analyzed according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Measure: Number of Participants With Abnormal Laboratory Findings Time: Up to Day 56OSCAR (Otilimab in Severe COVID-19 Related Disease) is a multi-center, double-blind, randomized, placebo-controlled trial to assess the efficacy and safety of otilimab for the treatment of severe pulmonary COVID-19 related disease. Otilimab is a human monoclonal anti-granulocyte macrophage colony stimulating factor (GM-CSF) antibody that has not previously been tested in participants with severe pulmonary COVID-19 related disease. The aim of this study is to evaluate the benefit-risk of a single infusion of otilimab in the treatment of participants with severe COVID-19 related pulmonary disease. The study population will consist of hospitalized participants with new onset hypoxia requiring significant oxygen support or requiring early invasive mechanical ventilation (less than or equal to [<=] 48 hours before dosing). Participants will be randomized to receive a single intravenous (IV) infusion of otilimab or placebo, in addition to standard of care.
Description: Participants are alive and free of respiratory failure if they are in category 1, 2, 3 or 4 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale is as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized, limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, high-flow oxygen (≥15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death.
Measure: Proportion of participants alive and free of respiratory failure at Day 28 Time: Day 28Description: Number of deaths due to all causes will be assessed.
Measure: Number of deaths due to all causes at Day 60 Time: Day 60Description: Time to death due to all causes will be assessed.
Measure: Time to number of deaths due to all causes up to Day 60 Time: Up to Day 60Description: Participants alive and free of respiratory failure if they are in category 1, 2, 3 or 4 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale is as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized, limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, high-flow oxygen (≥15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death.
Measure: Proportion of participants alive and free of respiratory failure at Days 7, 14, 42 and 60 Time: Days 7, 14, 42, and 60Description: Time will be recorded from dosing to recovery from respiratory failure. Participants are in respiratory failure if they are in category 5 or above from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale is as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized, limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, high-flow oxygen (≥15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death.
Measure: Time to recovery from respiratory failure Time: Up to Day 28Description: Participants are independent of supplementary oxygen if they are in category 1, 2 or 3 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale is as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized, limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, high-flow oxygen (≥15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death.
Measure: Proportion of participants alive and independent of supplementary oxygen at Days 7, 14, 28, 42, and 60 Time: Days 7, 14, 28, 42, and 60Description: Participants are independent of supplementary oxygen if they are in category 1, 2 or 3 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale is as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized, limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, high-flow oxygen (≥15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death.
Measure: Time to last dependence on supplementary oxygen Time: Up to Day 28Description: For participants not in ICU at time of dosing, the proportion of participants admitted to the ICU prior to Day 28.
Measure: Proportion of participants admitted to Intensive Care Unit (ICU) Time: Up to Day 28Description: Defined as the time from dosing to when the participant is discharged from the ICU.
Measure: Time to final ICU discharge Time: Up to Day 28Description: Time from dosing to when a participant is discharged from the hospital.
Measure: Time to final hospital discharge Time: Up to Day 28Description: AEs and SAEs will be collected.
Measure: Number of participants with Adverse events (AEs) and Serious adverse events (SAEs) Time: Up to Day 60The purpose of this study is to evaluate the efficacy and safety of ruxolitinib in the treatment of participants with COVID-19-associated Acute Respiratory Distress Syndrome (ARDS) who require mechanical ventilation.
Description: To evaluate the 28-day mortality rate of ruxolitinib 5 mg BID + SoC therapy and ruxolitinib 15 mg BID + SoC compared with placebo + SoC therapy, in participants with COVID-19-associated ARDS who require mechanical ventilation.
Measure: Proportion of participants who have died due to any cause Time: Up to Day 29Description: Number of days participant did not require mechanical ventilation
Measure: Number of Ventilator free days Time: Day 29Description: Number of days participant is out of the ICU
Measure: Number of ICU free days Time: Day 29Description: Number of days participant did not receive supplemental oxygen
Measure: Oxygen free days Time: Day 29Description: Number of days without use of vasopressor therapy
Measure: Vasopressor free days Time: Day 29Description: Number of days Partcipant is out of the hospital
Measure: Hospital free days Time: Day 29Description: Clinical status of participant at Day 15 and 29 based on participant state. The scale ranges from 0-8 with 0 being no clinical or virological evidence of infection and 8 being dead
Measure: Improvement in the COVID-19 ordinal scale Time: Day 15 and 29Description: SOFA score is a scoring system to determine the extent of a person's organ function or rate of failure. The score is based on 6 different scores, 1 each for the respiratory, cardiovascular, hepatic, coagulation, renal, and neurological systems.
Measure: Change in SOFA Score Time: from baseline to Days 3, 5, 8, 11, 15, and 29Description: Adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug/treatment.
Measure: Number of treatment-related adverse events Time: Day 29The purpose of this study is to assess the safety and efficacy of Alvesco (ciclesonide) Inhalation Aerosol in non hospitalized patients with symptomatic COVID-19 infection in a multicenter, randomized, double-blind, placebo controlled study
At present there is no approved drug treatment for Covid-19. In this study we plan to investigate if an experimental drug called IMU-838 (vidofludimus calcium) can improve your symptoms, prevent worsening that would initiate further treatments such as ventilation, and can lower your virus number if given in addition to your doctor's choice of standard therapy. We will also test if IMU-838 has any side effects and measure the level of IMU 838 in your blood. Experimental drug means that it is not yet authorized for marketing in your country. To date approximately 600 individuals have received IMU-838 (or a drug similar to IMU-838 that contains the same active substance as IMU-838) in research studies.
Description: Clinical
Measure: Proportion of patients without any need* for INV until end-of-study (EoS) Time: Throughout the Study (Day 0 to Day 28)Description: Key Secondary
Measure: Duration of ICU treatment until EoS Time: Throughout the Study (Day 0 to Day 28 )Description: Key Secondary
Measure: 28-day all-cause mortality Time: Throughout the Study (Day 0 to Day 28 )Description: Efficacy: defined as the time from first dose of investigational medicinal product (IMP) to an improvement of at least 2 points on the WHO 9 category ordinal scale , or live discharge from hospital without oxygen supplementation, whichever comes first
Measure: Time to clinical improvement Time: Throughout the Study (Day 0 to Day 28 )Description: Efficacy: Duration of hospitalization (for US sites only: or treatment in special outpatient setting in lieu of hospitalization due to resource restraints)
Measure: Duration of hospitalization Time: Throughout the Study (Day 0 to Day 28 )Description: Efficacy
Measure: Proportion of patients both for all patients and surviving patients free of renal-replacement therapy (RRT)* until EoS Time: Throughout the Study (Day 0 to Day 28 )Description: Efficacy
Measure: Proportion of patients both for all patients and surviving patients free from extracorporeal membrane oxygenation (ECMO)* until EoS Time: Throughout the Study (Day 0 to Day 28 )Description: Efficacy
Measure: Proportion of patients free of INV until Days 6 and 14* Time: Throughout the Study (Day 0 to Day 28 )Description: Efficacy
Measure: Proportion of patients free of RRT until Days 6 and 14* Time: Day 0 to Days 6 and 14Description: Efficacy
Measure: Proportion of patients free ECMO until Days 6 and 14* Time: Day 0 to Days 6 and 14Description: Efficacy
Measure: Proportion of patients with improvement of at least 2 points (from randomization) on the 9-category WHO ordinal scale1 on Days 6, 14, and 28 Time: on Days 6, 14, and 28Description: Efficacy
Measure: Proportion of patients with auxiliary oxygen therapy (including all types of oxygen therapy) on Days 6, 14, and 28 Time: on Days 6, 14, and 28Description: Efficacy
Measure: Proportion of patients with clinical recovery: Axillary temperature ≤36.6 ℃, or oral temperature ≤37.2 ℃, or rectal or tympanic temperature ≤37.8 ℃; Time: Throughout the Study (Day 0 to Day 28 )Description: Efficacy
Measure: Proportion of patients with clinical recovery: Respiratory frequency ≤24 times/min without oxygen inhalation; and Time: Throughout the Study (Day 0 to Day 28 )Description: Efficacy
Measure: Proportion of patients with clinical recovery: Oxygen saturation ≥98% without oxygen inhalation Time: Throughout the Study (Day 0 to Day 28 )Description: Efficacy
Measure: Proportion of patients with clinical improvement, defined as the time from first dose of IMP to an improvement of at least 2 points on the WHO 9 category ordinal scale, or live discharge from hospital without oxygen supplementation, whichever comes first Time: Throughout the Study (Day 0 to Day 28 )Description: Efficacy
Measure: Clinical patient status on the 9-category WHO ordinal scale1 on Days 6, 14, and 28 Time: on Days 6, 14, and 28Description: Efficacy
Measure: Duration of INV Time: Throughout the Study (Day 0 to Day 28 )Description: Efficacy
Measure: Duration of ECMO Time: Throughout the Study (Day 0 to Day 28)Description: Efficacy
Measure: Duration of RRT Time: Throughout the Study (Day 0 to Day 28)Description: Efficacy
Measure: Duration of auxiliary oxygen therapy (including all types of oxygen therapy) Time: Throughout the Study (Day 0 to Day 28)Description: Efficacy
Measure: Duration of hospitalization for survivors Time: Throughout the Study (Day 0 to Day 28)Description: Efficacy
Measure: The rate of ICU* admission on Days 6, 14, and 28 Time: on Days 6, 14, and 28Description: Efficacy
Measure: Hospital-free days Time: Throughout the Study (Day 0 to Day 28)Description: Efficacy
Measure: Time from IMP treatment initiation to death Time: Throughout the Study (Day 0 to Day 28)Description: Efficacy
Measure: Time to first prescription of INV Time: Throughout the Study (Day 0 to Day 28)Description: Efficacy
Measure: Time to first prescription of RRT Time: Throughout the Study (Day 0 to Day 28)Description: Efficacy
Measure: Time to first prescription of ECMO Time: Throughout the Study (Day 0 to Day 28)Description: Efficacy
Measure: Time to first prescription of INV, RRT, and ECMO Time: Throughout the Study (Day 0 to Day 28)Description: Efficacy
Measure: Time to ICU admission Time: Throughout the Study (Day 0 to Day 28)Description: Efficacy
Measure: Cumulative dose of vasoactive therapies and days with vasoactive therapies (daily until Day 14) Time: Day 0 to day 14Description: Efficacy
Measure: Time to clinical recovery Time: Throughout the Study (Day 0 to Day 28)Description: Pharmacokinetics
Measure: Morning trough plasma levels of IMU-838 on Days 0, 1, 2, 3, 6, 14, and 28 Time: on Days 0, 1, 2, 3, 6, 14, and 28Description: Pharmacokinetics
Measure: Correlation of trough levels (quartiles) to selected clinical outcomes (Clinical improvement accoding to WHO criteria) Time: on Days 0, 1, 2, 3, 6, 14, and 28Description: Safety
Measure: Adverse events (AEs) and serious AEs Time: Throughout the Study (Day 0 to Day 28)Description: Safety Height in centimeters will be recorded without shoes. Changes in vital signs judged by the investigator as clinically significant will be reported as an AE.
Measure: Vital signs: height Time: only at ScreeningDescription: Safety Weight in kilograms will be recorded without shoes. Changes in vital signs judged by the investigator as clinically significant will be reported as an AE.
Measure: Vital signs: weight Time: Throughout the Study (Day 0 to Day 28)Description: Safety Body temperature can be measured axillary, oral, rectal or tympanic, but should be always measured by the same method for a patient. Changes in vital signs judged by the investigator as clinically significant will be reported as an AE.
Measure: Vital signs: body temperature (ºC) Time: Throughout the Study (Day 0 to Day 28)Description: Safety Pulse must be measured with the patient in a seated position (if possible), after at least 5 minutes at rest. Changes in vital signs judged by the investigator as clinically significant will be reported as an AE.
Measure: Vital signs: pulse rates, Time: Throughout the Study (Day 0 to Day 28)Description: Safety Blood pressure (systolic and diastolic) must be measured with the patient in a seated position (if possible), after at least 5 minutes at rest. Changes in vital signs judged by the investigator as clinically significant will be reported as an AE.
Measure: Vital signs: systolic and diastolic blood pressures Time: Throughout the Study (Day 0 to Day 28)Description: Safety
Measure: Clinical laboratory parameters: blood chemistry Time: Throughout the Study (Day 0 to Day 28)Description: Safety
Measure: Clinical laboratory parameters: hematology Time: Throughout the Study (Day 0 to Day 28)Description: Safety
Measure: Clinical laboratory parameters: urinalysis Time: Throughout the Study (Day 0 to Day 28)Description: Safety
Measure: 12-lead electrocardiogram: heart rate Time: Day 0 to Day 6 and Day 28Description: Safety
Measure: 12-lead electrocardiogram: PQ-interval Time: Day 0 to Day 6 and Day 28Description: Safety
Measure: 12-lead electrocardiogram: QRS-interval Time: Day 0 to Day 6 and Day 28Description: Safety
Measure: 12-lead electrocardiogram: QT interval Time: Day 0 to Day 6 and Day 28Description: Safety
Measure: 12-lead electrocardiogram: the heart rate-corrected QTc interval (according to Bazett's formula) Time: Day 0 to Day 6 and Day 28Description: Safety
Measure: Temperature Time: Throughout the Study (Day 0 to Day 28)Description: Disease markers
Measure: D-dimer Time: Throughout the Study (Day 0 to Day 28)Description: Disease markers
Measure: Lactate dehydrogenase (LDH) Time: Throughout the Study (Day 0 to Day 28)Description: Disease markers
Measure: C-reactive protein Time: Throughout the Study (Day 0 to Day 28)Description: Disease markers
Measure: Troponin I Time: Throughout the Study (Day 0 to Day 28)Description: Disease markers
Measure: Procalcitonin Time: Throughout the Study (Day 0 to Day 28)Description: Disease markers
Measure: Correlation of disease markers to selected clinical outcomes (Clinical improvement accoding to WHO criteria) Time: Throughout the Study (Day 0 to Day 28)Description: Virologic markers
Measure: Severe Acute Respiratory Syndrome Coronavirus Virus (SARS-CoV-2) mean viral load - log10 copies in spontaneous sputum and nasopharyngeal swab samples: Decrease of SARS-CoV-2 viral load Time: Throughout the Study (Day 0 to Day 28)Description: Virologic markers
Measure: Severe Acute Respiratory Syndrome Coronavirus Virus (SARS-CoV-2) mean viral load - log10 copies in spontaneous sputum and nasopharyngeal swab samples: Time course of SARS-CoV-2 viral load Time: Throughout the Study (Day 0 to Day 28)Description: Virologic markers
Measure: Qualitative virologic clearance in spontaneous sputum and nasopharyngeal swab samples (= 2 consecutive negative SARS-CoV-2 reverse transcriptase polymerase chain reaction tests at least 24 hours apart) Time: Throughout the Study (Day 0 to Day 28)Description: Virologic markers
Measure: Rate of conversion to a negative SARS-CoV-2 (qualitative) test on Days 6, 14 and 28 Time: on Days 6, 14 and 28Description: Virologic markers
Measure: Time to conversion to a negative SARS-CoV-2 (qualitative) test Time: Throughout the Study (Day 0 to Day 28)Description: Biomarkers
Measure: Interleukin (IL)-17 Time: Day 0, 6, 14 and Day 28Description: Biomarkers
Measure: Interleukin (IL)-1ß Time: Day 0, 6, 14 and Day 28Description: Biomarkers
Measure: Interleukin (IL)-6 Time: Day 0, 6, 14 and 28Description: Biomarkers
Measure: interferon gamma (IFNγ) Time: Day 0, 6, 14 and 28Description: Biomarkers
Measure: tumor necrosis factor alpha Time: Day 0, 6, 14 and 28Description: Serologic markers
Measure: Immunoglobulin (Ig)A and IgG antibodies against SARS-CoV-2: • Time to appearance of IgA and/or IgG antibodies Time: Day 0, 6, 14 and 28Description: Serologic markers
Measure: Immunoglobulin (Ig)A and IgG antibodies against SARS-CoV-2: • Proportion of patients with IgA and/or IgG antibodies on Days 6, 14, and 28 Time: Day 0, 6, 14 and 28This study is being done to see if hydroxychloroquine is an effective treatment for COVID-19.
Description: Clinical improvement is defined as a composite endpoint of a two-point clinical improvement on the Ordinal Scale for Clinical Improvement (OSCI). The OSCI is an ordinal scale of 9 severity levels (from 0 to 8) for COVID-19
Measure: Clinical improvement on the Ordinal Scale for Clinical Improvement (OSCI) Time: 14 daysDescription: Clinical improvement is defined as no mechanical ventilation for respiratory failure attributed to SARS-CoV-2 within 14 days of randomization.
Measure: Number of participants requiring mechanical ventilation for respiratory failure Time: 14 daysThe primary objective of the study is to evaluate the efficacy and safety of a single dose of RPH-104 (80 mg) or OKZ (64 mg) compared to placebo in addition to standard therapy in patients with severe SARS-CoV-2 infection (COVID-19) at Day 15 of the study
Description: Proportion of patients, responded to the study therapy, in each of the treatment groups. The patient can be considered as the therapy responder, in case tocilizumab or sarilumab were not administered and there is an improvement of a clinical status at least by 1 point on a 6-points COVID-19 scale, where 1 point means most favorable outcome, 6 points means most undesirable outcome.
Measure: Proportion of patients, responded to the study therapy, in each of the treatment groups Time: Day 15Description: Changes of patients' clinical status on a 6 points ordinal scale over time
Measure: Changes of patients' clinical status on a 6 points ordinal scale over time Time: from Day 2 until Day 15, Day 29Description: Mortality rate over the follow-up period
Measure: Mortality rate over the follow-up period Time: from Day 1 until Day 29Description: Improvement of the patient's clinical status by at least 2 points on a 6-point ordinal scale in the absence of tocilizumab or sarilumab administration.
Measure: Improvement of the patient's clinical status by at least 2 points on a 6-point ordinal scale in the absence of tocilizumab or sarilumab administration. Time: on screening and then from Day 1 until Day 29Description: Proportion of patients received tocilizumab or sarilumab due to COVID-19
Measure: Proportion of patients received tocilizumab or sarilumab due to COVID-19 Time: from Day 1 until the Day 29Description: Proportion of patients having National Early Warning Score 2 (NEWS2) of ≤ 4 maintained for 2 consecutive days
Measure: Proportion of patients having National Early Warning Score 2 of ≤ 4 maintained for 2 consecutive days Time: from day 3 until day 15Description: Time to a NEWS2 of ≤ 2 maintained for two consecutive days
Measure: Time to a NEWS2 of ≤ 2 maintained for two consecutive days Time: from day 1 until day 15Description: Changes from baseline of cytokine storm surrogate markers: white blood counts, lymphocyte counts, neutrophils counts, CRP, ferritin (if applicable), D-dimer (if applicable)
Measure: Changes from baseline of cytokine storm surrogate markers: white blood counts, lymphocyte counts, neutrophils counts, C-Reactive protein (CRP), ferritin (if applicable), D-dimer (if applicable) Time: Day 2, Day 3, Day5, Day 7, Day 15Description: Mortality during an ICU stay, on days 7, 15, 29 of the study
Measure: Mortality during an ICU stay, on days 7, 15, 29 of the study Time: On Day 7, Day 15, Day 29Description: Time to increase of oxygen saturation SpO2 ≥ 94% n the absence of oxygen support maintained for two consecutive days
Measure: Time to increase of oxygen saturation SpO2 ≥ 94% n the absence of oxygen support maintained for two consecutive days Time: from Day 2 until Day 15Description: Changes of oxygenation index PaO2/FiO2 from baseline (if applicable) during hospitalization period
Measure: Changes of oxygenation index PaO2/FiO2 from baseline (if applicable) during hospitalization period Time: On Day 1 and from Day 2 until Day 15Description: Duration of ICU stay measured in days
Measure: Duration of ICU stay measured in days Time: from Day 2 until Day 15Description: Changes from baseline (if applicable) in severity of ARDS according to WHO criteria
Measure: Changes from baseline (if applicable) in severity of Acute Respiratory Distress Syndrome (ARDS) according to World Health Organization (WHO) criteria Time: from Day 1 until Day 15Description: Duration of mechanical ventilation and EMO (if applicable) measured in days
Measure: Duration of mechanical ventilation and Extracorporeal Membrane Oxygenation (EMO) (if applicable) measured in days Time: from Day 2 until Day 15Description: Duration of oxygen support (if applicable) measured in days
Measure: Duration of oxygen support (if applicable) measured in days Time: from Day 1 until Day 15Description: Proportion of patients having National Early Warning Score 2 of ≤ 2 maintained for 2 consecutive days
Measure: Proportion of patients having National Early Warning Score 2 of ≤ 2 maintained for 2 consecutive days Time: from day 3 until day 15Description: Time to a NEWS2 of ≤ 4 maintained for two consecutive days
Measure: Time to a NEWS2 of ≤ 4 maintained for two consecutive days Time: from day 1 until day 15Description: Time to improvement in severity of ARDS according to WHO criteria in one category changing from baseline (if applicable)
Measure: Time to improvement in severity of ARDS according to WHO criteria in one category changing from baseline (if applicable) Time: On Day 1 and from Day 2 until Day 15Description: Time to fever resolution i.e. setting of axillary body temperature <38 °C without antipyretics when measured for 2 consecutive days (if applicable)
Measure: Time to fever resolution i.e. setting of axillary body temperature <38 °C without antipyretics when measured for 2 consecutive days (if applicable) Time: from day 1 until day 15Description: Time to improvement of clinical status by 1 point on a 6-points COVID-19 scale
Measure: Time to improvement of clinical status by 1 point on a 6-points COVID-19 scale Time: from day 1 until day 29Description: Time to improvement of clinical status by 2 points on a 6-points COVID-19 scale
Measure: Time to improvement of clinical status by 2 points on a 6-points COVID-19 scale Time: from day 1 until day 29Description: Proportion of patients with the deterioration of clinical status by 1 point on a 6-points COVID-19 scale during the study
Measure: Proportion of patients with the deterioration of clinical status by 1 point on a 6-points COVID-19 scale during the study Time: from Day 1 until Day 29Description: Proportion of patients with the deterioration of clinical status by 1 point on a 6-points COVID-19 scale during the study, excluding the patients moved to the category 6, if applicable
Measure: Proportion of patients with the deterioration of clinical status by 1 point on a 6-points COVID-19 scale during the study, excluding the patients moved to the category 6, if applicable Time: from Day 1 until Day 29Description: Time to the deterioration of clinical status by 1 point on a 6-points COVID-19 scale during the study (if applicable)
Measure: Time to the deterioration of clinical status by 1 point on a 6-points COVID-19 scale during the study (if applicable) Time: from Day 1 until Day 29The purpose of this study is to evaluate the clinical response of sirukumab (administered as a single intravenous dose) plus standard of care (SOC) compared to placebo plus SOC in COVID-19.
Description: Time to improvement is defined as an improvement of at least 2 categories relative to baseline on the 6-point ordinal clinical recovery scale. The 6-point ordinal clinical recovery scale provides 6 mutually exclusive conditions ordered from best to worst, and the score reflects the participant's worst situation on the day assessed. The ordinal clinical recovery scale categories are : not hospitalized (category 1); Hospitalization; not requiring supplemental oxygen (category 2); hospitalized, requiring low flow supplemental oxygen (category 3); hospitalized, on non-invasive pressure ventilation or high flow oxygen devices (category 4); hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO (category 5); death (category 6).
Measure: Time to Improvement of at Least 2 Categories Relative to Baseline on the 6-Point Ordinal Clinical Recovery Scale Time: Up to Day 28Description: Percentage of participants with an improvement of at Least 2 categories relative to baseline on the 6-point ordinal clinical recovery scale on Day 28 will be reported.
Measure: Percentage of Participants with an Improvement of at Least 2 Categories Relative to Baseline on the 6-Point Ordinal Clinical Recovery Scale on Day 28 Time: Day 28Description: Percentage of participants with all-cause mortality will be reported.
Measure: Percentage of Participants with All-cause Mortality Time: Up to Day 28Description: A SAE is any adverse event (AE) that results in: death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect and is a suspected transmission of any infectious agent via a medicinal product, is medically important.
Measure: Percentage of Participants with Serious Adverse Events (SAEs) Time: Up to Day 28Description: An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product.
Measure: Percentage of Participants with Related Adverse Events Time: Up to Day 28Description: Percentage of participants with severe or life-threatening, bacterial, invasive fungal, viral or opportunistic infections (other than severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) will be reported.
Measure: Percentage of Participants with Severe or Life Threatening Bacterial, Invasive Fungal, Viral or Opportunistic Infections Time: Up to Day 28Description: Percentage of participants with grade 3 (severe) or 4 (life-threatening) neutropenia will be reported.
Measure: Percentage of Participants with Grade 3 and 4 Neutropenia Time: Up to Day 28Description: Percentage of participants with grade 3 (severe) or 4 (life-threatening) lymphocytopenia will be reported.
Measure: Percentage of Participants with Grade 3 and 4 Lymphocytopenia Time: Up to Day 28Description: Percentage of participants with increased ALT >=3 times ULN combined with increased bilirubin >2 times ULN (up to Day 28) will be reported.
Measure: Percentage of Participants with Increased Alanine Aminotransferase (ALT) Greater than or equal to 3 Times Upper Limit of Normal (ULN) Combined with Increased Bilirubin > 2 Times ULN Time: Up to Day 28Description: Time to improvement of at least 1 category relative to baseline on the 6-point ordinal clinical recovery scale will be reported.
Measure: Time to Improvement of at least 1 Category Relative to Baseline on the 6-Point Ordinal Clinical Recovery Scale Time: Up to Day 28Description: Percentage of participants with an improvement of at Least 1 category relative to baseline on the 6-point ordinal clinical recovery scale on Day 28 will be reported.
Measure: Percentage of Participants with an Improvement of at Least 1 Category Relative to Baseline on the 6-Point Ordinal Clinical Recovery Scale on Day 28 Time: Day 28Description: Time from study intervention to end of oxygen supplementation is defined as achieving category 1 or 2 on the 6-point ordinal clinical recovery scale.
Measure: Time from Study Intervention to end of Oxygen Supplementation Time: Up to Day 28Description: Time from study intervention to hospital discharge among the surviving participants will be reported.
Measure: Time from Study Intervention to Hospital Discharge Among the Surviving Participants Time: Up to Day 28Description: Total length of hospitalization (days from admission to hospital discharge) among the surviving participants will be reported.
Measure: Total Length of Hospitalization Time: Up to Day 28Description: Number of Ventilation free Days will be reported.
Measure: Number of Ventilation Free Days Time: Up to Day 28Description: Participant's clinical status at Day 7, 14, 21, 28 will be assessed by 6-point ordinal clinical recovery scale.
Measure: Participant's Clinical Status at Day 7, 14, 21, 28 as Assessed by 6-Point Ordinal Clinical Recovery Scale Time: Day 7, 14, 21, 28Description: Total time on invasive mechanical ventilation will be reported.
Measure: Total Time on Invasive Mechanical Ventilation Time: Up to Day 28Description: Percentage of participants with a worsening of at least 1 category on the 6-point ordinal clinical recovery scale over time (between Day 5 and Day 28) will be reported.
Measure: Percentage of Participants with a Worse Category Relative to Baseline on the 6-Point Ordinal Clinical Recovery Scale over Time Time: From Day 5 up to Day 28Description: Percentage participants on ECMO over time will be reported.
Measure: Percentage of Participants on Extracorporeal Membrane Oxygenation (ECMO) Over Time Time: Up to Day 28Description: Total time on ECMO will be reported.
Measure: Total Time on ECMO Time: Up to Day 28Description: Percentage of alive participants at Day 28, Week 8 and Week 16 will be reported.
Measure: Percentage of Alive Participants at Day 28, Week 8 and Week 16 Time: Day 28, Week 8 and Week 16Description: Percentage of alive participants that required readmission (if previously discharged) at Week 8 and Week 16 will be reported.
Measure: Percentage of Alive Participants that Required Readmission at Week 8 and Week 16 Time: Week 8 and Week 16Description: A SAE is any adverse event (AE) that results in: death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect and is a suspected transmission of any infectious agent via a medicinal product, is medically important.
Measure: Percentage of Participants with Serious Adverse Events (SAEs) Time: Up to Week 16In this study, the investigators propose to administer clazakizumab to patients with life-threatening Coronavirus Disease 2019 (COVID-19) infection manifest by pulmonary failure and a clinical picture consistent with a cytokine storm syndrome. This is a single-center randomized, double-blind, placebo-controlled trial in which 30 patients will be enrolled and randomly assigned in a 1:1 ratio to two study arms and receive clazakizumab at a dose of 25 mg or placebo.
Description: Number of participants alive at day 28.
Measure: Patient Survival Time: 28 daysDescription: Number of participants alive at day 60, end of study.
Measure: Patient Survival Time: 60 daysThe purpose of this study is to demonstrate the superiority of Polyoxidonium®, lyophilizate for solution for injections and topical application, 6 mg over placebo in hospitalized patients with coronavirus disease (COVID-19). This is a multicentre prospective, randomized, double-blind, placebo-controlled, parallel-group phase IIb\IIIa clinical trial.
Description: The primary efficacy outcome will be defined based on the blinded analysis of data of the first 100 patients in the 1st part of the study. There is uncertainty about the clinical course and potential different trajectories according to baseline disease severity, so the day of the primary endpoint may be modified based on a blinded evaluation of the primary efficacy outcome in various days.
Measure: Clinical status of the patient (according to 7-point ordinal scale) Time: Day 15Description: Time to improvement by one category from admission on the ordinal scale. Clinical status of the patient. Average change in the ordinal scale from baseline.
Measure: Clinical status of the patient (according to 7-point ordinal scale) Time: Clinical status of the patient and the average change in the ordinal scale from baseline, both on days 3, 5, 8, 11, 29.Description: The time to discharge or to a NEWS of ≤ 2 and maintained for 24 hours, whichever occurs first. Change in NEWS from baseline.
Measure: NEWS Time: Change in NEWS from baseline on days 3, 5, 8, 11, 15, 29.Description: Oxygenation free days. Incidence and duration of new oxygen use.
Measure: Oxygenation Time: Oxygenation free days in the first 28 days (to day 29). Incidence and duration of new oxygen use during the study.Description: Ventilator free days. Incidence and duration of new mechanical ventilation use.
Measure: Mechanical Ventilation Time: Ventilator free days in the first 28 days (to day 29). Incidence and duration of new mechanical ventilation use during the trial.The researchers are doing this study to find out whether the study drug hydroxychloroquine can prevent infection with the COVID-19 virus, compared with placebo, in people who are receiving radiation therapy for their cancer. The placebo used in this study is a tablet that looks the same as the study drug and is taken in the same way, but it does not contain any active ingredients.
Description: Any patients who are enrolled and subsequently test positive for SARS-CoV-2 by RT-PCR (outside RT-PCR test results allowed) at any point during the 9 weeks following enrollment will be an event that is considered in the 9-week SARS-CoV-2 infection rate primary endpoint.
Measure: cumulative incidence of SARS-CoV-2 infection Time: within 9 weeks from randomizationDescription: Patients who are positive for SARS-CoV-2 (as defined above) who develop a new oxygen requirement attributable to COVID-19, tachypnea (RR > 20), or those who require hospitalization due to COVID-19 will be considered to have severe COVID-19.
Measure: cumulative incidence of severe COVID-19 or death Time: within 12 weeks of randomizationAgent Name and Study Duration ArtemiC is a medical spray comprised of Artemisinin (6 mg/ml), Curcumin (20 mg/ml), Frankincense (=Boswellia) (15 mg/ml) and vitamin C (60 mg/ml) in micellar formulation for spray administration. Patients will receive up to 6 mg Artemisinin, 20 mg Curcumin, 15 mg Frankincense and 60 mg vitamin C given daily as an add-on therapy (in addition to standard care) in two divided doses, on Days 1 and 2. Patients will be randomized in a manner of 2:1 for study drug (ArteminC) and Standard of Care to Placebo and Standard of Care. Patient follow-up will last 2 weeks. During this time, patients will be monitored for adverse events. Additional time will be required for follow up (until hospital discharge) in order to check side effects and study drug efficacy. Placebo, composed of the same solvent but without active ingredients, will be given in the placebo group as add-on therapy, 2 times a day, on Days 1 and 2. Overall rationale A preparation of ArtemiC, comprising Artemisinin, Curcumin, Boswellia, and Vitamin C in a nanoparticular formulation, is proposed as a treatment for the disease associated with the novel corona virus SARS-CoV-2. It is readily available in light of its status as a food supplement. This initiative is presented under the urgent circumstances of the fulminant pandemic caused by this lethal disease, which is known as COVID-19 and has spread across the globe causing death and disrupting the normal function of modern society. The grounds for the proposal are rooted in existing knowledge on the components and pharmacological features of this formulation and their relevance to the current understanding of the disease process being addressed. Leading among these considerations are well established immuno-modulatory activities of the active ingredients as established in vitro and in vivo and published over the years. These activities as apparent, for example, in diminishing activity of TNF alpha and IL-6 levels are acknowledged to be relevant to the pathophysiology processes involved in the progressive form of COVID-19. The active agents have in addition prominent anti-oxidant, anti-inflammatory as well as anti-aggregant and anti-microbial activities. Based on these activities and observations in animal models, together with clinical experience of the separate ingredients and in various combinations in other contexts it is proposed to evaluate their effect in the context of COVID-19. Study Purpose This study is designed to evaluate the safety and efficacy of ArtemiC on patients diagnosed with COVID-19. Methodology 50 adult patients who suffer from COVID-19 infection studied in parallel groups treated with active agent or placebo as add on to standard care. Safety will be assessed through collection and analysis of adverse events, blood and urine laboratory assessments and vital signs.
Description: patient will be assessed using a scoring table for changes in clinical signs
Measure: Time to clinical improvement, defined as a national Early Warning Score 2 (NEWS2) of = 2 Maintained for 24 Hours in comparison to routine treatment Time: 24 hoursDescription: Adverse events caused by the study drug will be assessed
Measure: Percentage of participants with definite or probable drug related adverse events Time: 14 daysThe primary objective of this study is to evaluate if the addition of zanubrutinib to supportive care increases the respiratory failure-free survival rate at Day 28 in participants hospitalized for Corona Virus Disease 2019 (COVID-19) and pulmonary distress.
Description: Respiratory failure-free survival rate 28 is defined as the proportion of patients who have not had respiratory failure nor died <= 28 days from randomization.
Measure: Respiratory failure-free survival rate at day 28 Time: 28 DaysDescription: This scale evaluates the safety and efficacy of investigational therapeutic agents in combination with care for the treatment of hospitalized participants suffering from COVID-19 infections on a scale of scores from 0 to 8, with higher scores indicating higher level of severity of the disease. (0 = No clinical or virological evidence of disease, and 8 = Death)
Measure: Change from Baseline to Day 14 in WHO - 8 Point Ordinal Scale Time: Up to 28 DaysThe study is a randomized controlled, open-label trial comparing subcutaneous Zilucoplan® with standard of care to standard of care alone. In the active group, Zilucoplan® will be administered subcutaneously once daily for 14 days or till discharge from the hospital, whichever comes first. The hypothesis of the proposed intervention is that Zilucoplan® (complement C5 inhibitor) has profound effects on inhibiting acute lung injury post COVID-19, and can promote lung repair mechanisms, that lead to a 25% improvement in lung oxygenation parameters. This hypothesis is based on experiments performed in mice showing that C5a blockade can prevent mortality and prevent ARDS in mice with post-viral acute lung injury. Eligible patients include patients with confirmed COVID-19 infection suffering from hypoxic respiratory failure defined as O2 saturation below 93% on minimal 2l/min O2 therapy and/or ratio PaO2/FiO2 below 350.
Description: defined by Pa02/FiO2 ratio while breathing room air, P(Aa)O2 gradient and a/A pO2 ratio
Measure: Mean change in oxygenation Time: at predose, day 6 and day 15 (or at discharge, whichever comes first)Description: defined by Pa02/FiO2 ratio while breathing room air, P(Aa)O2 gradient and a/A pO2 ratio
Measure: Median change in oxygenation Time: at predose, day 6 and day 15 (or at discharge, whichever comes first)Description: 6-point ordinal scale defined as Death Hospitalized, on invasive mechanical ventilation or ECMO; Hospitalized, on non-invasive ventilation Hospitalized, requiring supplemental oxygen Hospitalized, not requiring supplemental oxygen Not hospitalized
Measure: mean change in 6-point ordinal scale change Time: between day 1 and respectively day 6, day 15 (or discharge, whichever comes first) and day 28 (by phone call).Description: defined as independence from supplemental oxygen
Measure: Time since randomization until improvement in oxygenation Time: during hospital admission (up to 28 days)Description: defined as SpO2 < 93% breathing room air or the dependence on supplemental oxygen
Measure: Number of days with hypoxia Time: during hospital admission (up to 28 days)Description: defined as 37.1°C or more
Measure: Number of days with fever Time: during hospital admission (up to 28 days)Description: SOFA score: 0 (best) - 24 (worse)
Measure: Mean change of SOFA score between day 1 and day 6 (or on discharge, whichever is first) Time: day 1, day 6 or on discharge, whichever is firstDescription: SOFA score: 0 (best) - 24 (worse)
Measure: Mean change of SOFA score between day 1 and day 15 or on discharge, whichever is first) Time: day 1, day 15 or on discharge, whichever is firstDescription: 6-point ordinal scale: Death Hospitalized, on invasive mechanical ventilation or ECMO; Hospitalized, on non-invasive ventilation or high flow oxygen devices; Hospitalized, requiring supplemental oxygen Hospitalized, not requiring supplemental oxygen Not hospitalized
Measure: Percentage of patients reporting each severity rating on a 6-point ordinal scale at randomization, day 6 and 15 (or discharge, whichever comes first) and day 28 (phone call) Time: day 1, day 6, day 15 (or discharge, whichever comes first)Description: 6-point ordinal scale: Death Hospitalized, on invasive mechanical ventilation or ECMO; Hospitalized, on non-invasive ventilation or high flow oxygen devices; Hospitalized, requiring supplemental oxygen Hospitalized, not requiring supplemental oxygen Not hospitalized
Measure: 6-point Ordinal Scale at 6 and 15 days (or discharge whichever comes first) and day 28 (phone call), in relation to serum D-dimers and complement C5a levels at randomization Time: day 1, day 6, day 15 (or discharge, whichever comes first)Description: criteria-defined ARDS criteria-defined ARDS according to the adapted Berlin criteria as follow: within 1 week of a known Clinical insult or new or worsening respiratory symptoms bilateral infiltrates not supposed to be of cardiac origin or fluid overload PaO2/FiO2 < 300 mmHg
Measure: Time since randomization to progression to ARDS (Acute Respiratory Distress Syndrome) Time: during hospital admission (up to 28 days)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.
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)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 admissionDescription: 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 admissionDescription: Death and time to death
Measure: Time to death Time: In a 30 days follow up periodDescription: 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 dischargeDescription: 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 periodDescription: 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 periodThe purpose of this research study is to evaluate the safety and potential efficacy of Intravenous Infusion of Zofin for treatment of moderate to severe Acute Respiratory Syndrome (SARS) related to COVID-19 infection vs Placebo.
Description: Safety will be defined by the incidence of any infusion associated adverse events as assessed by treating physician
Measure: Incidence of any infusion associated adverse events Time: 60 DaysDescription: Safety will be defined by the incidence of severe adverse events as assessed by treating physician
Measure: Incidence of Severe Adverse Events Time: 60 DaysDescription: Measured at day 60 or at hospital discharge, whichever comes first.
Measure: All Cause Mortality Time: 60 DaysDescription: Number of participants that are alive at 60 days post first infusion follow up
Measure: Survival Rate Time: 60 DaysDescription: Measure IL-6, TNF-alpha from serum of blood samples
Measure: Cytokine Levels Time: Day 0, Day 4, Day 8, Day14, Day 21, Day 28Description: D-dimer from serum of blood samples methodology using blood samples or nose / throat swab
Measure: D-dimer Levels Time: Day 0, Day 4, Day 8, Day14, Day 21, Day 28Description: CRP from serum of blood samples
Measure: C-reactive protein Levels Time: Day 0, Day 4, Day 8, Day14, Day 21, Day 28Description: Viral load by real time RT methodology using blood samples or nose / throat swab
Measure: Quantification of the COVID-19 Time: Day 0, Day 4, Day 8Description: Improved organ failure within 30 days, including cardiovascular system, coagulation system, liver, kidney and other extra-pulmonary organs using Sequential Organ Failure Assessment (SOFA) score.
Measure: Improved Organ Failure Time: Day 30Description: Chest imaging changes for 30 days compare to placebo: 1) Ground-glass opacity, - 2) Local patchy shadowing, 3) Bilateral patchy shadowing, and 4) Interstitial abnormalities.
Measure: Chest Imaging Changes Time: Day o, Day 30SNG001 is an inhaled drug that contains a antiviral protein called interferon beta (IFN-β). IFN-β in produced in the lungs during viral lung infections. It has been shown that older people and people with some chronic diseases have an IFN-β deficiency. Many viruses inhibit IFN-β as part of their strategy to evade the immune system. Addition of IFN-β in vitro protects lung cells from viral infection. IFN-β protects cells against the MERS and SARS coronaviruses (close relatives of SARS-CoV-2, the virus that causes COVID-19). SNG001 is an inhaled formulation of interferon beta-1a it is currently in Phase II clinical trials for COPD patients. Synairgen has conducted randomised placebo controlled clinical trials of SNG001 involving >200 asthma and COPD patients. These trials have shown that SNG001 has: - been well tolerated during virus infections - enhanced antiviral activity in the lungs (measured in sputum and blood samples) - provided significant lung function benefit over placebo in asthma in two Phase II trials. Synairgen believes SNG001 could help prevent worsening or accelerate recovery of severe lower respiratory tract illness in COVID-19 patients. Patients who are in hospital or non-hospitalised but are a high risk groups (e.g. elderly or diabetics) will be invited to take part in the trial. The patient would receive either SNG001 or placebo once daily for 14 days. The severity of the patients condition would be recorded on a scale developed by the World Health Organisation and the patient would be asked questions about their breathlessness, cough and sputum every day, as well as assess their general medical condition and safety. The study will start as a Pilot phase where 100 patients will be randomised in the hospital setting and a 120 patients randomised in the home setting. Once each of the Pilot phases are complete, a Pivotal phase will be conducted. It is estimated that the size of each of the Pivotal phases (hospital and home) will be around 100 to 300 patients per arm. The actual number will be determined after the data review at the end of each of the Pilot phases. If SNG001 proves to be beneficial it would be a major breakthrough for the treatment of COVID-19.
Description: Change in condition measured using the Ordinal Scale for Clinical Improvement during the dosing period - minimum of 0 (patient is well) to a maximum of 8 (death)
Measure: Ordinal Scale for Clinical Improvement Time: Day 1 to Days 15 and 28Description: Progression to pneumonia as diagnosed by chest x-ray, if no pneumonia is present at time of enrolment
Measure: Progression to pneumonia (hospital setting only) Time: Day 2 to Day 28Description: Evolution of pneumonia, as diagnosed by chest x-ray, if pneumonia is present at time of enrolment
Measure: Progression to pneumonia (hospital setting only) Time: Day 1 to Day 28Description: Time to clinical improvement
Measure: Time to clinical improvement (hospital setting only) Time: Time to hospital discharge OR Time to NEWS2 of ≤ 2 maintained for 24 hoursDescription: NEWS2 assessment of acute-illness severity on a scale of 0 ( being well) up to 24 (requiring emergency response)
Measure: National Early Warning Score 2 (NEWS2) assessment of acute-illness severity (hospital setting only) Time: Day 1 to Day 28Description: Changes in daily breathlessness, cough and sputum scale (BCSS) on a scale of 0 (no symptoms) up to 4 (severe symptoms)
Measure: Changes in daily breathlessness, cough and sputum scale (BCSS) Time: Day 1 to Day 28Description: Looking at blood pressure measured in mmHg
Measure: Safety and tolerability - blood pressure II. Viral load Time: Day 1 to Day 28Description: Looking at heart rate measured in beats per minute
Measure: Safety and tolerability - heart rate II. Viral load Time: Day 1 to Day 28Description: Looking at temperature measured in degrees Celsius
Measure: Safety and tolerability - temperature II. Viral load Time: Day 1 to Day 28Description: Looking at respiratory rate measure in breaths per minute
Measure: Safety and tolerability - respiratory rate II. Viral load Time: Day 1 to Day 28Description: Looking at oxygen levels measured in a %
Measure: Safety and tolerability - oxygen saturation II. Viral load Time: Day 1 to Day 28Description: Looking at adverse events (numbers and terms)
Measure: Safety and tolerability - adverse events II. Viral load Time: Day 1 to Day 28Description: Looking at concomitant medications given during treatment
Measure: Safety and tolerability - concomitant medications II. Viral load Time: Day 1 to Day 28Description: Temperature ≤37.8 °C AND COVID-19 symptoms (breathing, cough, sputum, muscle aches, headache, fatigue, sore throat, loss or change to sense of smell and taste, rhinorrhoea and anorexia) all rated as absent or mild
Measure: Time to clinical improvement (home setting only) Time: Day 1 to Day 28Description: Time to improvement of COVID-19 symptoms (fever, breathing, cough, sputum, muscle aches, headache, fatigue, sore throat, loss or change to sense of smell and/or taste, rhinorrhoea and anorexia)
Measure: Time to improvement of COVID-19 symptoms (home setting only). Time: Day 1 to Day 28Description: Time to self-reported recover
Measure: Time to self-reported recovery (home setting only) Time: Day 2 to Day 16Description: Self-reported daily rating of overall feeling of wellness
Measure: Self-reported daily rating of overall feeling of wellness (home setting only). Time: Day 1 to Day 28Description: Quality of life measured using EQ-5D-5L
Measure: Quality of life measured using EQ-5D-5L (home setting only). Time: Day 1 to Day 28Description: Time to virus clearance and viral load
Measure: Virus clearance/load (if samples are available) Time: Day 1 to Day 28Description: Blood and sputum biomarkers
Measure: Blood and sputum biomarkers (if samples are available). Time: Day 1 to Day 28Description: Contact with health services
Measure: Contact with health services (home setting only Time: Day 1 to Day 28Description: Consumption of antibiotics
Measure: Consumption of antibiotics (home setting only Time: Day 1 to Day 28The aim of this study is to investigate whether vaccination of healthcare professionals with VPM1002 could reduce the number of days absent from work due to respiratory disease (with or without documented SARS-CoV-2 infection). VPM1002 is a vaccine that is a further development of the old Bacillus Calmette-Guérin (BCG) vaccine, which has been used successfully as a vaccine against tuberculosis for about 100 years, especially in developing countries. VPM1002 has been shown in various clinical studies to be significantly safer than the BCG vaccine. VPM1002 strengthens the body's immune defence and vaccination with BCG reduces the frequency of respiratory diseases. It is therefore assumed that a VPM1002 vaccination could also provide (partial) protection against COVID-19 disease caused by the new corona virus "SARS-CoV 2". A total of 1200 health care professionals (doctors, nurses and paramedical staff) with high expected exposure to SARSCoV-2 infected patients will receive a single dose of either VPM1002 or Placebo. All subjects will be requested to enter data regarding absenteeism, adverse events / serious adverse events, hospitalizations, intensive care unit admissions into an online questionnaire.
This clinical trial will examine if a new treatment of Mesenchymal-like Adherent stromal Cells (called PLX-PAD) can help patients intubated and mechanically ventilated due to COVID-19 to recover more quickly with less complications.
A randomized, double-blind, placebo-controlled Phase 2/3 study to evaluate the safety and efficacy of DSTAT in patients with Acute Lung Injury (ALI) due to COVID-19. This study is designed to determine if DSTAT can accelerate recovery and prevent progression to mechanical ventilation in patients severely affected by COVID-19.
Description: Alive and free of invasive mechanical ventilation
Measure: Proportion of participants who are alive and free of invasive mechanical ventilation Time: Through Day 28Description: Time to all-cause mortality
Measure: All-cause mortality Time: Through Day 28SAINT is a double-blind, randomized controlled trial with two parallel groups that evaluates the efficacy of ivermectin in reducing nasal viral carriage at seven days after treatment in SARS-CoV-2 infected patients who are at low risk of progression to severe disease. The trial is currently planned at a single center in Navarra.
Description: Proportion of patients with a positive SARS-CoV-2 PCR from a nasopharyngeal swab at day 7 post-treatment. PCRs were performed using two target genes (E and N).
Measure: Proportion of Patients With a Positive SARS-CoV-2 PCR Time: 7 days post-treatmentDescription: Quantitative and semi-quantitative PCR in nasopharyngeal swab. PCRs were performed using two target genes (E and N).
Measure: Median Viral Load Time: Baseline and on days 4, 7, 14 and 21Description: Proportion of patients with fever and cough
Measure: Fever and Cough Progression Time: Days 4, 7, 14 and 21Description: Proportion of participants with positive IgG at day 21
Measure: Seroconversion at Day 21 Time: Up to and including day 21Description: Proportion of drug-related adverse events
Measure: Proportion of Drug-related Adverse Events Time: 7 days post treatmentDescription: Levels in median fluorescence intensity (MFI) of IgG, IgM and IgA against the receptor-binding domain of the spike glycoprotein of SARS-CoV-2 in plasma, measured by a Luminex assay. [Results not yet available]
Measure: Levels of IgG, IgM and IgA Time: Up to and including day 28Description: Frequency (% over total PBMC) of innate immune cells (myeloid a