CovidResearchTrials by Shray Alag


CovidResearchTrials Covid 19 Research using Clinical Trials (Home Page)


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Clinical Trial MeSH HPO Drug Gene SNP Protein Mutation


Correlated Drug Terms (283)


Name (Synonyms) Correlation
drug591 Hydroxychloroquine Wiki 0.19
drug393 DAS181 Wiki 0.12
drug1073 Presatovir Wiki 0.12
drug280 Camostat Mesilate Wiki 0.12
drug1434 UC-MSCs Wiki 0.12
drug631 Hydroxychloroquine sulfate Wiki 0.11
drug977 PUL-042 Inhalation Solution Wiki 0.11
drug618 Hydroxychloroquine Sulfate Loading Dose Wiki 0.11
drug619 Hydroxychloroquine Sulfate Regular dose Wiki 0.11
drug1403 Tocilizumab (TCZ) Wiki 0.11
drug145 BCG vaccine Wiki 0.11
drug760 Lopinavir/ritonavir Wiki 0.09
drug820 Mesenchymal Stromal Cells Wiki 0.09
drug1330 Suspension of heat killed (autoclaved) Mycobacterium w Wiki 0.09
drug1172 Ruxolitinib Wiki 0.09
drug763 Losartan Wiki 0.09
drug715 Ivermectin Wiki 0.08
drug950 Organicell Flow Wiki 0.08
drug420 Determination of physical activity, quality of life, stress levels of isolated people at home with the danger of coronavirus. Wiki 0.08
drug57 Aerosolized All trans retinoic acid Wiki 0.08
drug240 COPAN swabbing and blood sample collection Wiki 0.08
drug1180 SARS-CoV Wiki 0.08
drug653 Ibrutinib Wiki 0.08
drug87 Anti-SARS-CoV2 Serology Wiki 0.08
drug773 Low-dose chloroquine Wiki 0.08
drug1644 recombinant human interferon Alpha-1b Wiki 0.08
drug996 Peginterferon Lambda-1a Wiki 0.08
drug1354 Tears swab Wiki 0.08
drug150 BM-Allo.MSC Wiki 0.08
drug452 EIDD-2801 Wiki 0.08
drug601 Hydroxychloroquine - Daily dosing Wiki 0.08
drug754 Lopinavir 200Mg/Ritonavir 50Mg Tab Wiki 0.08
drug1136 Recombinant Interferon Alfa-2b Wiki 0.08
drug414 DeltaRex-G Wiki 0.08
drug1408 Tofacitinib Wiki 0.08
drug1121 RT-PCR SARS-Cov2 Wiki 0.08
drug1193 SARS-CoV2 serum antibody testing Wiki 0.08
drug854 NA (no intervention) Wiki 0.08
drug1095 Pyridostigmine Bromide Wiki 0.08
drug720 Ivermectin Oral Product Wiki 0.08
drug533 Galidesivir Wiki 0.08
drug1439 Ulinastatin Wiki 0.08
drug894 Nitric Oxide 0.5 % / Nitrogen 99.5 % Gas for Inhalation Wiki 0.08
drug859 NK Cells Wiki 0.08
drug1522 bacTRL-Spike Wiki 0.08
drug399 Dapagliflozin 10 MG Wiki 0.08
drug658 IgM and IgG diagnostic kits to SARS-CoV-2 Wiki 0.08
drug559 HLCM051 Wiki 0.08
drug1116 REGN3051 Wiki 0.08
drug652 IVERMECTIN (IVER P®) arm will receive IVM 600 µg / kg once daily plus standard care. CONTROL arm will receive standard care. Wiki 0.08
drug16 2019-nCoV PCR Wiki 0.08
drug1238 Serological analyses to be lead on a pre-existing biobank Wiki 0.08
drug711 Isotonic saline 0.9% Wiki 0.08
drug283 Canakinumab Injection 300mg Wiki 0.08
drug1249 Silymarin Wiki 0.08
drug3 - Synthetic anti-malarial drugs Wiki 0.08
drug139 Açaí palm berry extract - natural product Wiki 0.08
drug786 MSCs-derived exosomes Wiki 0.08
drug436 Dociparastat sodium Wiki 0.08
drug322 Clazakizumab 12.5 mg Wiki 0.08
drug918 Normobaric oxygen therapy Wiki 0.08
drug560 HOME-CoV rule implementation Wiki 0.08
drug1289 Standard of care therapies Wiki 0.08
drug1458 VPM1002 Wiki 0.08
drug932 Octagam 10% Wiki 0.08
drug927 Observational Study Wiki 0.08
drug1021 Placebo Administration Wiki 0.08
drug718 Ivermectin + Placebo Wiki 0.08
drug1509 [TIMP-2]*[IGFBP-7] Wiki 0.08
drug1680 vaccine BCG Wiki 0.08
drug761 Lopinavir/ritonavir 400 mg/100 mg Wiki 0.08
drug1495 XCEL-UMC-BETA Wiki 0.08
drug412 Degarelix Wiki 0.08
drug56 Aerosolized 13 cis retinoic acid Wiki 0.08
drug483 Ergoferon Wiki 0.08
drug885 Nicotinamide riboside Wiki 0.08
drug620 Hydroxychloroquine Sulfate Tablets Wiki 0.08
drug632 Hydroxychloroquine sulfate &Azithromycin Wiki 0.08
drug1223 Sars-Cov2 serology Wiki 0.08
drug1003 Personalized health education Wiki 0.08
drug273 CT-V Wiki 0.08
drug1648 risk factors Wiki 0.08
drug1115 REGN3048 Wiki 0.08
drug1521 azoximer bromide Wiki 0.08
drug186 Biological: mRNA-1273: 100 mcg Wiki 0.08
drug1127 Ranitidine Wiki 0.08
drug395 DAS181 OL Wiki 0.08
drug1342 TD-0903 Wiki 0.08
drug284 Canakinumab Injection 600mg Wiki 0.08
drug367 Convalescent SARS COVID-19 plasma Wiki 0.08
drug1462 Vazegepant (BHV-3500) Wiki 0.08
drug1432 Two doses of placebo at the schedule of day 0,28 Wiki 0.08
drug878 NestaCell® Wiki 0.08
drug197 Blood collection Wiki 0.08
drug549 HB-adMSC Wiki 0.08
drug98 ArtemiC Wiki 0.08
drug63 Allogeneic NK transfer Wiki 0.08
drug468 Emtricitabine/Tenofovir Alafenamide 200 MG-25 MG Oral Tablet Wiki 0.08
drug523 Fluvoxamine Wiki 0.08
drug648 IMU-838 Wiki 0.08
drug681 Inhaled sedation Wiki 0.08
drug41 AT-527 Wiki 0.08
drug329 Clinical interview Wiki 0.08
drug790 MVA-MERS-S_DF1 - Low Dose Wiki 0.08
drug126 Ayurvedic Kadha Wiki 0.08
drug135 Azithromycin Capsule Wiki 0.08
drug687 Interferon beta 1a Wiki 0.08
drug1159 Ribavirin Wiki 0.08
drug1393 Thrombin Generation Assay (TGA) Wiki 0.08
drug1161 Rintatolimod Wiki 0.08
drug1101 Quantitative analysis of SARS-CoV-2 antibodies Wiki 0.08
drug971 PLX-PAD Wiki 0.08
drug1061 Povidone-Iodine 0.5% Wiki 0.08
drug924 Observation of patients with known, suspected, or at risk for COVID-19 infection Wiki 0.08
drug1395 Thrombomodulin Modified Thrombin Generation Assay (TGA-TM) Wiki 0.08
drug1368 Telmisartan 40mg Wiki 0.08
drug70 Aluminum hydroxide adjuvant (Alhydrogel®) Wiki 0.08
drug1478 Vitamin Super B-Complex Wiki 0.08
drug530 GLS-1200 Wiki 0.08
drug1345 TJ003234 Wiki 0.08
drug248 COVID-19 IgM/IgG Rapid Testing, mobile device image capture and telemedicine support Wiki 0.08
drug1681 vaccine candidate MVA-MERS-S Wiki 0.08
drug1501 Zanubrutinib Wiki 0.08
drug923 Observation of behavior and COVID-19 infection will be conducted. Wiki 0.08
drug607 Hydroxychloroquine SAR321068 Wiki 0.08
drug1557 favipiravir tablets+chloroquine phosphatetablets tablets Wiki 0.08
drug725 Ketamine Wiki 0.08
drug1409 Tofacitinib 10 mg Wiki 0.08
drug641 Hyperbaric oxygen therapy Wiki 0.08
drug1222 Sarilumab SAR153191 Wiki 0.08
drug540 General health education Wiki 0.08
drug339 ColdZyme® mouth spray Wiki 0.08
drug1321 Sulfonatoporphyrin(TPPS) plus Sunlight exposure. Wiki 0.08
drug1118 RPH-104 80 mg Wiki 0.08
drug164 Baricitinib (janus kinase inhibitor) Wiki 0.08
drug1623 pathogen reduced SARS-CoV-2 convalescent plasma Wiki 0.08
drug69 Aluminum hydroxide Wiki 0.08
drug871 Naltrexone Wiki 0.08
drug678 Inhaled beclomethasone Wiki 0.08
drug133 Azithromycin 500 milligram (mg) oral Tablet Wiki 0.08
drug879 Neutral writing control Wiki 0.08
drug708 Intravenous sedation Wiki 0.08
drug758 Lopinavir/ Ritonavir Oral Tablet Wiki 0.08
drug869 Nafamostat Mesilate Wiki 0.08
drug621 Hydroxychloroquine Sulfate Tablets plus Lopinavir/ Ritonavir Oral Tablets Wiki 0.08
drug579 High-dose chloroquine Wiki 0.08
drug1254 Sirukumab Wiki 0.08
drug463 Electric pad for human external pain therapy Wiki 0.08
drug281 Canakinumab Wiki 0.08
drug1676 thymosin alpha 1 Wiki 0.08
drug1207 Saline Wiki 0.08
drug717 Ivermectin + Doxycycline + Placebo Wiki 0.08
drug1253 Sirolimus 1 MG/ML Wiki 0.08
drug1286 Standard of care (SOC) Wiki 0.08
drug142 BCG Wiki 0.08
drug66 Almitrine Wiki 0.08
drug942 Opaganib Wiki 0.08
drug888 Nintedanib 150 MG Wiki 0.08
drug731 LSALT peptide Wiki 0.08
drug1496 XPro1595 Wiki 0.08
drug536 Garadacimab, Factor XIIa Antagonist Monoclonal Antibody Wiki 0.08
drug1062 Povidone-Iodine 2% Wiki 0.08
drug935 Olokizumab 64 mg Wiki 0.08
drug1412 Tradipitant Wiki 0.08
drug466 Elisa-test for IgM and IgG to SARS-CoV-2 Wiki 0.08
drug722 JNJ-53718678 Wiki 0.08
drug316 Ciclesonide Wiki 0.08
drug892 Nitazoxanide Tablets Wiki 0.08
drug1358 Telehealth monitoring Wiki 0.08
drug151 BM-MSCs Wiki 0.08
drug1503 Zilucoplan® Wiki 0.08
drug1185 SARS-CoV-2 diagnostic rapid test Wiki 0.08
drug782 MRx-4DP0004 Wiki 0.08
drug111 Association of diltiazem and niclosamide Wiki 0.08
drug120 Aviptadil (VIP) Wiki 0.08
drug770 Low nitrite/NDMA meals Wiki 0.08
drug826 Mid-dose chloroquine Wiki 0.08
drug576 High nitrite/NDMA meals Wiki 0.08
drug1006 Phosphate buffered saline Placebo Wiki 0.08
drug1560 gammaCore® Sapphire (non-invasive vagus nerve stimulator) Wiki 0.08
drug1452 Use of virus (Covid-19) genome sequence report to inform infection prevention control procedures Wiki 0.08
drug798 Matched Placebo Hydroxychloroquine Wiki 0.08
drug1112 Quick Defense Wiki 0.08
drug1561 global survey Wiki 0.08
drug980 Pacritinib Wiki 0.08
drug1203 SNDX-6352 Wiki 0.08
drug191 Biospecimen Collection Wiki 0.08
drug43 ATYR1923 1 mg/kg Wiki 0.08
drug1139 Recombinant human alkaline phosphatase Wiki 0.08
drug541 Gimsilumab Wiki 0.08
drug394 DAS181 COVID-19 Wiki 0.08
drug323 Clazakizumab 25 mg Wiki 0.08
drug187 Biological: mRNA-1273: 50 mcg Wiki 0.08
drug230 CD24Fc Wiki 0.08
drug961 Ozanimod Wiki 0.08
drug44 ATYR1923 3 mg/kg Wiki 0.08
drug724 Kerecis Oral and Nasal Spray Wiki 0.08
drug740 Let It Out (LIO)-C Wiki 0.08
drug963 P2Et (Caesalpinia spinosa extract) Wiki 0.08
drug1107 Questionnaire with precaution information Wiki 0.08
drug842 MultiStem Wiki 0.08
drug955 Otilimab Wiki 0.08
drug276 CYNK-001 Wiki 0.08
drug1138 Recombinant S protein SARS vaccine Wiki 0.08
drug344 Combination of Lopinavir /Ritonavir and Interferon beta-1b Wiki 0.08
drug644 IC14 Wiki 0.08
drug1123 Radiation therapy Wiki 0.08
drug233 CERC-002 Wiki 0.08
drug495 Experimental: Questionnaire without precaution information Wiki 0.08
drug1142 Recombinant novel coronavirus vaccine (Adenovirus type 5 vector) Wiki 0.08
drug1122 RTB101 Wiki 0.08
drug30 ABX464 Wiki 0.08
drug556 HCQ+AZT Wiki 0.08
drug177 Biological Sample Collection Wiki 0.08
drug1426 Two doses of low dosage inactivated SARS-CoV-2 vaccine at the schedule of day 0,28 Wiki 0.08
drug513 Favipiravir tablets Wiki 0.08
drug789 MVA-MERS-S_DF1 - High Dose Wiki 0.08
drug730 LB1148 Wiki 0.08
drug1593 meplazumab for injection Wiki 0.08
drug146 BCG-Denmark Wiki 0.08
drug1425 Two doses of high dosage inactivated SARS-CoV-2 vaccine at the schedule of day 0,28 Wiki 0.08
drug1429 Two doses of medium dosage inactivated SARS-CoV-2 vaccine at the schedule of day 0,28 Wiki 0.08
drug129 Azithromycin Wiki 0.07
drug163 Baricitinib Wiki 0.07
drug1146 Remdesivir Wiki 0.06
drug1148 Remestemcel-L Wiki 0.05
drug50 Acalabrutinib Wiki 0.05
drug154 BNT162b1 Wiki 0.05
drug1213 Saliva collection Wiki 0.05
drug802 Mavrilimumab Wiki 0.05
drug321 Clazakizumab Wiki 0.05
drug525 Follow up Wiki 0.05
drug15 200 mg EIDD-2801 Wiki 0.05
drug156 BNT162c2 Wiki 0.05
drug551 HCQ Wiki 0.05
drug531 GLS-5300 Wiki 0.05
drug1137 Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector) Wiki 0.05
drug465 Electronic questionnaire Wiki 0.05
drug401 Data Collection Wiki 0.05
drug596 Hydroxychloroquine + azithromycin Wiki 0.05
drug1233 Selinexor Wiki 0.05
drug884 Niclosamide Wiki 0.05
drug175 Bevacizumab Injection Wiki 0.05
drug313 Chloroquine or Hydroxychloroquine Wiki 0.05
drug1248 Siltuximab Wiki 0.05
drug1367 Telmisartan Wiki 0.05
drug1638 pregnant women with laboratory-confirmed 2019-n-CoV Wiki 0.05
drug728 L-ascorbic acid Wiki 0.05
drug585 Human immunoglobulin Wiki 0.05
drug602 Hydroxychloroquine - Weekly Dosing Wiki 0.05
drug612 Hydroxychloroquine Sulfate 200 MG Wiki 0.05
drug1282 Standard of Care (SOC) Wiki 0.05
drug693 Interleukin-7 Wiki 0.05
drug308 Chloroquine Wiki 0.05
drug153 BNT162a1 Wiki 0.05
drug155 BNT162b2 Wiki 0.05
drug1323 Supportive Care Wiki 0.05
drug1402 Tocilizumab Wiki 0.05
drug1104 Questionnaire Wiki 0.05
drug589 Hydrocortisone Wiki 0.04
drug1359 Telemedicine Wiki 0.04
drug144 BCG Vaccine Wiki 0.04
drug1256 SnPP Protoporphyrin plus Sunlight exposure Wiki 0.04
drug895 Nitric Oxide Gas Wiki 0.04
drug686 Interferon Beta-1B Wiki 0.04
drug442 Doxycycline Wiki 0.04
drug1285 Standard of care Wiki 0.04
drug1042 Placebos Wiki 0.04
drug818 Mepolizumab Wiki 0.04
drug1453 Usual Care Wiki 0.04
drug889 Nitazoxanide Wiki 0.04
drug1530 blood sampling Wiki 0.04
drug1153 Reslizumab Wiki 0.04
drug472 Enoxaparin Wiki 0.03
drug203 Blood sample Wiki 0.03
drug1476 Vitamin D Wiki 0.03
drug1035 Placebo oral tablet Wiki 0.03
drug1220 Sarilumab Wiki 0.03
drug73 Anakinra Wiki 0.03
drug900 No intervention Wiki 0.02
drug608 Hydroxychloroquine Sulfate Wiki 0.02
drug1631 placebo Wiki 0.02
drug505 Favipiravir Wiki 0.02

Correlated MeSH Terms (53)


Name (Synonyms) Correlation
D018352 Coronavirus Infections NIH 0.28
D007239 Infection NIH 0.25
D003141 Communicable Diseases NIH 0.22
D045169 Severe Acute Respiratory Syndrome NIH 0.20
D055371 Acute Lung Injury NIH 0.20
D012128 Respiratory Distress Syndrome, Adult NIH 0.19
D012127 Respiratory Distress Syndrome, Newborn NIH 0.16
D011014 Pneumonia NIH 0.14
D013577 Syndrome NIH 0.13
D055370 Lung Injury NIH 0.12
D012141 Respiratory Tract Infections NIH 0.12
D014777 Virus Diseases NIH 0.11
D009164 Mycobacterium Infections NIH 0.09
D014947 Wounds and Injuries NIH 0.09
D030341 Nidovirales Infections NIH 0.08
D018357 Respiratory Syncytial Virus Infections NIH 0.08
D001171 Arthritis, Juvenile NIH 0.08
D012818 Signs and Symptoms, Respiratory NIH 0.08
D002647 Chilblains NIH 0.08
D016638 Critical Illness NIH 0.06
D003139 Common Cold NIH 0.05
D007154 Immune System Diseases NIH 0.05
D006331 Heart Diseases NIH 0.05
D000257 Adenoviridae Infections NIH 0.05
D003428 Cross Infection NIH 0.05
D058070 Asymptomatic Diseases NIH 0.05
D015004 Yellow Fever NIH 0.05
D018450 Disease Progression NIH 0.05
D001168 Arthritis NIH 0.05
D058186 Acute Kidney Injury NIH 0.05
D007249 Inflammation NIH 0.05
D005334 Fever NIH 0.04
D009369 Neoplasms, NIH 0.04
D001927 Brain Diseases NIH 0.04
D018805 Sepsis NIH 0.04
D003327 Coronary Disease NIH 0.04
D004211 Disseminated Intravascular Coagulation NIH 0.04
D008231 Lymphopenia NIH 0.04
D018184 Paramyxoviridae Infections NIH 0.04
D011024 Pneumonia, Viral NIH 0.04
D029424 Pulmonary Disease, Chronic Obstructive NIH 0.04
D053120 Respiratory Aspiration NIH 0.04
D003333 Coronaviridae Infections NIH 0.04
D001172 Arthritis, Rheumatoid NIH 0.04
D012327 RNA Virus Infections NIH 0.04
D011658 Pulmonary Fibrosis NIH 0.03
D004417 Dyspnea NIH 0.03
D020141 Hemostatic Disorders NIH 0.03
D008173 Lung Diseases, Obstructive NIH 0.03
D001778 Blood Coagulation Disorders NIH 0.03
D007251 Influenza, Human NIH 0.03
D008171 Lung Diseases, NIH 0.03
D012140 Respiratory Tract Diseases NIH 0.02

Correlated HPO Terms (11)


Name (Synonyms) Correlation
HP:0002090 Pneumonia HPO 0.12
HP:0011947 Respiratory tract infection HPO 0.11
HP:0001298 Encephalopathy HPO 0.05
HP:0002664 Neoplasm HPO 0.05
HP:0002206 Pulmonary fibrosis HPO 0.04
HP:0005521 Disseminated intravascular coagulation HPO 0.04
HP:0001945 Fever HPO 0.04
HP:0001928 Abnormality of coagulation HPO 0.04
HP:0002098 Respiratory distress HPO 0.03
HP:0002088 Abnormal lung morphology HPO 0.03
HP:0001919 Acute kidney injury HPO 0.03

There are 166 clinical trials

Clinical Trials


1 Phase I, Double-Blinded, Placebo-Controlled Dosage Escalation Study of the Safety and Immunogenicity of Adjuvanted and Non-Adjuvanted Inactivated SARS Coronavirus (SARS-CoV) Vaccine Administered by the Intramuscular Route

Severe acute respiratory syndrome (SARS) is a viral illness that affects the respiratory (breathing) system. The purpose of this study is to evaluate the safety and protective (immune) responses to different doses of a SARS vaccine given with or without an adjuvant. An adjuvant is a substance that may be added to a vaccine to improve the immune response so that less of the vaccine may need to be given. Study participants will include 72 volunteers, ages 18-40, living in the Houston, Texas area. The study will take place at Baylor College of Medicine. Participants will receive 2 injections of vaccine or placebo (substance made to look like the study vaccine but contains no medication) given 1 month apart. Participants will fill out a memory aid (diary) to document daily temperature and illness signs and symptoms for 7-9 days after each injection. During the 9 study visits, several blood samples will be collected. Participants will be in the study for up to 211 days, including screening.

NCT00533741 Coronavirus (SARS-CoV) Drug: Aluminum hydroxide Drug: Placebo Biological: SARS-CoV
MeSH:Coronavirus Infections

Primary Outcomes

Measure: Frequency and description of serious adverse events (SAEs).

Time: 5 months after receipt of the booster dose of vaccine.

Measure: Frequency of significant increases in serum antibody to CoV S protein in Enzyme Linked Immunosorbent Assay (ELISA) and in neutralization tests, and increases in Geometric Mean Titers (GMT)s in sera.

Time: Screening, 1 and 5 months after the booster dose of vaccine.

Measure: Frequency and severity of solicited injection site and systemic signs and symptoms and unsolicited adverse events (AE) / SAEs.

Time: 1 month after receipt of the first and second doses of vaccine.

Secondary Outcomes

Measure: Frequency of significant serum antibody increases and increases in Geometric Mean Titers (GMT)s, as measured in neutralizing antibody tests and an ELISA against SARS-CoV S protein.

Time: Collected just before the first vaccination and at 1 month (just before booster).

2 Efficacy of Ingesting Gaia Herb's Quick Defense Product in Reducing Acute Respiratory Illness Symptomatology in Women: a 12-Week, Double Blind, Placebo-Controlled Randomized Trial

The primary objective of this study is to evaluate the effectiveness of ingesting an alkylamide-rich echinacea root product (Quick Defense, Gaia Herbs) for 2 days immediately following each onset of acute respiratory illness (ARI) symptomatology during a 12-week period in the winter and early spring in women. Hypothesis: Subjects randomized to Quick Defense compared to placebo over a 12-week period will experience reduced ARI symptomatology, both acutely during each ARI episode and collectively over the entire 12-week study period.

NCT02003651 Acute Respiratory Infections Dietary Supplement: Quick Defense Dietary Supplement: Placebo
MeSH:Respiratory Tract Infections
HPO:Respiratory tract infection

Primary Outcomes

Description: The Wisconsin Upper Respiratory Symptom Survey (WURSS-24) will be used to assess common cold illness severity and symptoms (see attached questionnaire). Subjects will fill in the one-page WURSS-24 at the end of each day during the 12-week monitoring period. This 12-week period will cover the winter and early spring period of 2014. From the responses recorded during the 84-day study, an ARI severity score will be calculated by summing the daily ARI global severity score (0=not sick, 1=very mild ARI to 7=severe). The ARI symptom score for the 84-day period will be calculated by summing all 10 symptom scores for each day's entry (0=do not have this symptom, 1=very mild to 7=severe). In similar fashion, the ARI function ability score for the 84-day period will be calculated by summing all 9 function scores for each day's entry (0=do not have this symptom, 1=very mild to 7=severe). Separate scores will be calculated comparing groups for each illness episode recorded by the subjects.

Measure: Common cold symptoms

Time: 12-weeks

3 A Phase 2b, Randomized, Double-Blind, Placebo-Controlled Multi-Center Study Evaluating Antiviral Effects, Pharmacokinetics, Safety, and Tolerability of GS-5806 in Hematopoietic Cell Transplant (HCT) Recipients With Respiratory Syncytial Virus (RSV) Infection of the Upper Respiratory Tract

The primary objective of this study is to evaluate the effect of presatovir on respiratory syncytial virus (RSV) viral load in autologous or allogeneic hematopoietic cell transplant (HCT) recipients with an acute RSV upper respiratory tract infection (URTI), the effect of presatovir on development of lower respiratory tract complication, being free of any supplemental oxygen progression to respiratory failure, and pharmacokinetics (PK), safety, and tolerability of presatovir.

NCT02254408 Respiratory Syncytial Virus Drug: Presatovir Drug: Placebo
MeSH:Infection

Primary Outcomes

Description: The time-weighted average change, often referred to as the DAVG, provides the average viral burden change from baseline. The mean values presented were calculated using the ANCOVA model and are adjusted for baseline value and stratification factor.

Measure: Time-Weighted Average Change in Nasal Respiratory Syncytial Virus (RSV ) Viral Load From Baseline (Day 1) to Day 9

Time: Baseline; Day 9

Description: A Lower Respiratory Tract Complication (LRTC) was defined as one of the below as determined by the adjudication committee: Primary RSV lower respiratory tract infection (LRTI) Secondary bacterial LRTI LRTI due to unusual pathogens Lower respiratory tract complication of unknown etiology

Measure: Percentage of Participants Who Developed a Lower Respiratory Tract Complication

Time: Up to Day 28

Secondary Outcomes

Description: Participants were considered to have an event if either condition is met: Participant develops a respiratory failure (of any cause) requiring mechanical ventilation (invasive or noninvasive) or; Participant dies prior to or on Day 28

Measure: Percentage of Participants Who Developed Respiratory Failure (of Any Cause) Requiring Mechanical Ventilation (Invasive or Noninvasive) or All-cause Mortality

Time: Up to Day 28

4 A Phase 2b, Randomized, Double-Blind, Placebo-Controlled Multi-Center Study Evaluating Antiviral Effects, Pharmacokinetics, Safety, and Tolerability of GS-5806 in Hematopoietic Cell Transplant (HCT) Recipients With Respiratory Syncytial Virus (RSV) Infection of the Lower Respiratory Tract

The primary objective of this study is to evaluate the effect of presatovir on respiratory syncytial virus (RSV) viral load in autologous or allogeneic hematopoietic cell transplant (HCT) recipients with an acute RSV lower respiratory tract infection (LRTI).

NCT02254421 Respiratory Syncytial Virus Infection Drug: Presatovir Drug: Placebo
MeSH:Infection Communicable Diseases Respiratory Syncytial Virus Infections

Primary Outcomes

Description: The time-weighted average change, often referred to as the DAVG, provides the average viral burden change from baseline. The mean values presented were calculated using the ANCOVA model and are adjusted for baseline value and stratification factors.

Measure: Time-weighted Average Change in Nasal Respiratory Syncytial Viral (RSV) Load From Baseline to Day 9

Time: Baseline to Day 9

Secondary Outcomes

Measure: Number of Supplemental O2-Free Days Through Day 28

Time: Up to Day 28

Measure: Percentage of Participants Developing Respiratory Failure Requiring Mechanical Ventilation Through Day 28

Time: Up to Day 28

Measure: Percentage of All-Cause Mortality Among Participants Through Day 28

Time: Up to Day 28

5 A Randomized Placebo Controlled Trial of Inhaled Beclomethasone After Community-acquired Respiratory Viral Infection in Lung Transplant Recipients

The purpose of this study is to determine if the use of inhaled beclomethasone after a community-acquired respiratory viral infection in a lung transplant recipient decreases the risk of the subsequent development of chronic lung allograft dysfunction.

NCT02351180 Lung Transplant Infection Drug: Inhaled beclomethasone Drug: Placebo
MeSH:Infection Communicable Diseases Virus Diseases

Primary Outcomes

Measure: Freedom from new or progressive chronic lung allograft dysfunction

Time: 180 days

Measure: Death

Time: 180 days

Secondary Outcomes

Measure: Respiratory virus symptom score

Time: 7 days

Measure: Acute rejection

Time: 180 days

Measure: Lymphocytic bronchiolitis

Time: 180 days

Measure: Donor-specific antibodies

Time: 180 days

Measure: Chronic lung allograft dysfunction

Time: 365 days

6 Effects of Low-dose Corticosteroids on Survival of Severe Community-acquired Pneumonia

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

NCT02517489 Community Acquired Pneumonia Drug: Hydrocortisone Drug: Placebo
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Measure: Day 28 all causes mortality

Time: at day 28

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

Measure: Day 21 failure

Time: at day 21

Secondary Outcomes

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

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

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

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

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

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

Measure: Day 28 ventilator-free-days

Time: between 0 and day 28

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

Time: between 0 and day 28

Measure: Day 28 vasopressor-free-days

Time: between 0 and day 28

Measure: ICU and/or intermediate care unit LOS

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

Measure: All-causes mortality at day 90

Time: at day 90

Measure: SF-36 Health Survey at day 90

Time: at day 90

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

Time: at inclusion, day 3 and day 7

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

Time: at inclusion, day 3 and day 7

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

Time: at inclusion, day 3 and day 7

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

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

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

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

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

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

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

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

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

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

Measure: Weight-gain at baseline and day 7

Time: Patients will be followed at baseline and day 7

Other Outcomes

Description: Sub-group of patients included with COVID19

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

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

Description: Sub-group of patients included with COVID19

Measure: Proportion of patients needing endotracheal intubation

Time: at day 21

Description: Sub-group of patients included with COVID19

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

Time: From baseline to day 21

7 Evaluation of ColdZyme® Mouth Spray on Prevention and Alleviation of Induced Rhinovirus Upper Respiratory Tract Infection in Healthy Volunteers. A Double-blind, Randomized, Placebo-controlled Study

This study evaluates the performance of ColdZyme® mouth spray on prevention and alleviation of induced rhinovirus upper respiratory tract infection in healthy volunteers. Half of participants will receive ColdZyme® mouth spray while the other half will receive placebo.

NCT02522949 Common Cold Device: ColdZyme® mouth spray Device: Placebo
MeSH:Common Cold

Primary Outcomes

Description: Reduction in viral load in the URT(Upper Respiratory Tract), after challenge with rhinovirus, in relation to placebo

Measure: Reduction in viral load in the URT

Time: 7 days

Secondary Outcomes

Description: Reduction of number of days having a total symptom severity score of 6 or higher using a 5-graded Jackson scale, in relation to placebo.

Measure: Prevention of symptomatic URTI (Upper Respiratory Tract Infection)

Time: 11 days

Description: Asymptomatic URTI will be assessed by quantification of viral load at peak day (day with highest viral load measured by oropharyngeal swab).

Measure: Prevention of asymptomatic URTI.

Time: 11 days

Description: The number of days with cold is defined as the sum of all days with a total score of ≥ 6 according to the modified method of Jackson.

Measure: Fewer days with symptomatic URTI

Time: 11 days

Description: The number of days with asymptomatic URTI is defined as the sum of all days with a viral load significantly different from the baseline.

Measure: Fewer days with asymptomatic URTI.

Time: 11 days

Description: Nasal samples will be analysed for the quantity of IL-6 (Interleukin 6), IL-8 and IFNα (Interferon alpha).

Measure: Lower level of proinflammatory proteins

Time: 11 days

Measure: Lower daily total symptom score

Time: 11 days

Measure: Lower daily score of individual symptoms

Time: 11 days

8 A Phase 2b, Randomized, Controlled Trial Evaluating GS-5806 in Lung Transplant (LT) Recipients With Respiratory Syncytial Virus (RSV) Infection

The primary objective of this study is to evaluate the effect of presatovir on nasal respiratory syncytial virus (RSV) viral load in RSV-positive lung transplant (LT) recipients with acute respiratory symptoms.

NCT02534350 Respiratory Syncytial Virus (RSV) Drug: Presatovir Drug: Placebo
MeSH:Virus Diseases

Primary Outcomes

Measure: Time-Weighted Average Change in Viral Load From Day 1/Baseline Through Day 7 in Participants in the Full Analysis Set

Time: Up to 7 days

Measure: Time-Weighted Average Change in Viral Load From Day 1/Baseline Through Day 7 in a Subset of Participants in the Full Analysis Set Whose Duration of RSV Symptoms Prior to the First Dose of Study Drug is ≤ Median

Time: Up to 7 days

Secondary Outcomes

Description: The Flu-PRO is a patient-reported outcome questionnaire utilized as a standardized method for evaluating symptoms of influenza. Flu-PRO Score was calculated as the mean of 38 individual scores. Individual scores ranged from 0 (no symptoms) to 4 (worst symptoms) for the 5-point severity scale and 0 (never) to 4 or more times (always) for the 5-point frequency scale. The mean values presented were calculated using the ANCOVA model and are adjusted for baseline value and stratification factor.

Measure: Time-Weighted Average Change in FLU-PRO Score From Day 1/Baseline Through Day 7

Time: Up to 7 days

Description: FEV1 is defined as forced expiratory volume in the first second.

Measure: Percent Change From Study Baseline in FEV1% Predicted Value

Time: Baseline; Day 28

9 MERS-CoV Infection tReated With A Combination of Lopinavir /Ritonavir and Interferon Beta-1b: a Multicenter, Placebo-controlled, Double-blind Randomized Trial

This is a placebo-controlled clinical trial to assess the efficacy and safety of a combination of lopinavir/ritonavir and Interferon beta-1b in hospitalized patients with MERS.

NCT02845843 Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Drug: Combination of Lopinavir /Ritonavir and Interferon beta-1b Drug: Placebo
MeSH:Coronavirus Infections

Primary Outcomes

Measure: 90-day mortality

Time: 90-day

Secondary Outcomes

Measure: Organ support-free days (e.g., supplemental O2, ventilator, extracorporeal membrane oxygenation (ECMO), renal replacement and vasopressors)

Time: 28 days

Measure: RT-PCR cycle threshold value in the lower respiratory samples

Time: At randomization and every 3 days afterwards, until 2 consecutive samples are negative or reaching a maximum of 90 days

Measure: Sequential organ failure assessment (SOFA) scores

Time: Days 0, 3, 7, 14, 21 and 28

Measure: ICU-free days

Time: Number of days in which patients are not being cared for in the ICU during the first 28 days after enrollment

Measure: Length of stay in hospital

Time: Up to one year from enrollment

Measure: Number of Patients with Adverse drug reactions related to the treatment

Time: From enrollment to 28 day

Measure: Karnofsky Performance Scale

Time: 90-day

Measure: ICU mortality

Time: Up to one year from enrollment

Measure: Hospital mortality

Time: Up to one year from enrollment

Measure: 28-day mortality

Time: 28-day

10 International Multicenter Double-blind Placebo-Controlled Parallel-Group Randomized Clinical Trial of Efficacy and Safety of Ergoferon in the Treatment of Acute Respiratory Viral Infections in Children

The international multicenter double-blind placebo-controlled randomized clinical study in parallel groups.The objective of this study is to obtain additional data on the efficacy and safety of Ergoferon in the treatment of acute respiratory viral infections (ARVI) in children aged from 6 months to 6 years old.

NCT03039621 Acute Respiratory Viral Infections Drug: Ergoferon Drug: Placebo
MeSH:Infection Communicable Diseases Virus Diseases

Primary Outcomes

Description: Based on patient diary data. Criteria of alleviation of all ARVI symptoms: oral temperature ≤37.5С for 24 hours (without subsequent increase within the observation period) + absence of ARVI symptoms /presence of ARVI symptoms with ≤3-point of the total score (TS) according to the 4-point scale (0 = no symptom; 1 = mild symptom; 2 = moderate symptom; 3 = severe symptom, for each flu-like nonspecific and respiratory symptom). TS ranges from 0 to 30, and the higher scores mean a worse outcome.

Measure: Time to Alleviation of All ARVI Symptoms.

Time: 14 days of observation.

Secondary Outcomes

Description: Based on patient diary data. Oral temperature ≤37.5С for 24 hours (without subsequent increase within the observation period).

Measure: Time to Normalization of Body Temperature.

Time: 14 days of observation.

Description: Based on patient diary data. Absence of flu-like nonspecific symptoms/presence of one mild flu-like nonspecific symptom.

Measure: Time to Alleviation of Flu-like Nonspecific Symptoms.

Time: 14 days of observation.

Description: Based on patient diary data. Absence of respiratory symptoms/presence of one mild respiratory symptom.

Measure: Time to Alleviation of Respiratory Symptoms.

Time: 14 days of observation.

Description: Based on patient diary data. The total score (TS) ranges from 0 to 30 consisting of 4 flu-like nonspecific (decreased activity/weakness, poor appetite/refusal to eat, sick appearance, sleep disturbance) and 6 respiratory (runny nose, stuffy nose/nasal congestion, sneezing, hoarseness, sore throat, cough) symptoms according to the 4-point scale for each symptom (0 = no symptom; 1 = mild symptom; 2 = moderate symptom; 3 = severe symptom). TS ranges from 0 to 30, and the higher scores mean a worse outcome.

Measure: Flu-like Nonspecific and Respiratory Symptoms Total Score (TS) for Days 2-6.

Time: On days 2-6 of the observation period.

Description: Based on the area under the curve of TS for days 2-6, according to the patient diary. The total score (TS) will be calculated based on the severity of each ARVI symptom (sum of 11 symptoms = body temperature, flu-like nonspecific symptoms (4 symptoms) and respiratory symptoms (6 symptoms) according to the 4-point scale (0 = no symptom; 1 = mild symptom; 2 = moderate symptom; 3 = severe symptom). To calculate TS the absolute oral temperature values, measured in degrees Celsius, will be converted into relative units (or points), given the following gradations: ≤37.5С = 0 point; 37.6-38.1C = 1 point; 38.2-38.8C = 2 points; ≥38.90С = 3 points. For total score minimum and maximum scores are 0 and 33, where higher values represent a worse outcome.

Measure: ARVI Severity.

Time: On days 2-6 of the observation period.

Description: Based on patient diary data. Criteria of recovery/alleviation of all ARVI symptoms: oral temperature ≤37.5С for 24 hours (without subsequent increase within the observation period) + absence of ARVI symptoms /presence of ARVI symptoms with ≤3-point of the total score (TS) according to the 4-point scale for each flu-like nonspecific and respiratory symptom (0 = no symptom; 1 = mild symptom; 2 = moderate symptom; 3 = severe symptom, for each flu-like nonspecific and respiratory symptom).

Measure: Percentage of Recovered Patients.

Time: On days 2-6 of the observation period.

Description: Based on patient diary data. The number of intakes of prescribed antipyretics.

Measure: Rates of Antipyretics Use Per Patient.

Time: On days 1- 5 of the treatment period.

Description: Based on patient diary data. The disease worsening: ARVI complications, including those requiring antibiotics; hospitalization).

Measure: Percentage of Patients With Worsening of Illness.

Time: 14 days of observation peiod.

11 A Phase I Trial to Evaluate the Safety, Tolerability, Pharmacokinetics and Immunogenicity of Co-administered MERS-CoV Antibodies REGN3048 and REGN3051 vs. Placebo in Healthy Adults

This is a Phase 1, first-in-human (FIH), single site, randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability, pharmacokinetics (PK), and immunogenicity of single ascending doses of a co-administered (1:1, w/w) combination of REGN3048 and REGN3051 mAb's, administered IV in healthy adult volunteers. Study duration of approximately 16 months. Approximately 48 evaluable subjects will be enrolled in the study, eight (8) subjects in each one of 6 sequential ascending IV dose cohorts. In each cohort, subjects will be randomized to receive mAb's REGN3048 and REGN3051 (6 subjects) or placebo (2 subjects). Primary Objective: To assess the safety and tolerability of REGN3048 and REGN3051 following co-administration of single, ascending IV doses of 1.5, 5, 15, 25, 50, and 75 mg/kg of each of the two mAb's.

NCT03301090 Corona Virus Infection Other: Placebo Biological: REGN3048 Biological: REGN3051
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome

Primary Outcomes

Measure: Changes from baseline in abbreviated physical examination

Time: Days 1-2

Measure: Changes from baseline in clinical safety laboratory values

Time: From Day 2 up to Day 121

Measure: Changes from baseline in Electrocardiogram (ECG) parameters

Time: 15 mins after infusion

Measure: Changes from baseline in Electrocardiogram (ECG) parameters

Time: 24 hrs after infusion

Measure: Changes from baseline in symptom-directed physical examination

Time: From Day 1 up to Day 121

Measure: Changes from baseline in vital signs

Time: From Day 1 up to Day 121

Measure: The incidence of Adverse Events

Time: From Day 1 up to Day 121

Measure: The incidence of treatment-emergent Serious Adverse Events

Time: From Day 1 up to Day 121

Measure: The severity of Adverse Events assessed by toxicity grading criteria

Time: From Day 1 up to Day 121

Measure: The severity of treatment-emergent Serious Adverse Events assessed by toxicity grading criteria

Time: From Day 1 up to Day 121

Measure: The type of treatment-emergent Serious Adverse Events

Time: From Day 1 up to Day 121

Secondary Outcomes

Measure: AUC for each dose of REGN3048 measured using validated Enzyme Linked Immunosorbent Assays (ELISAs)

Time: From Day 1 up to Day 121

Measure: AUC for each dose of REGN3051 measured using validated Enzyme Linked Immunosorbent Assays (ELISAs)

Time: From Day 1 up to Day 121

Measure: AUC(0-infinity) for each dose of REGN3048 measured using validated Enzyme Linked Immunosorbent Assays (ELISAs)

Time: From Day 1 up to Day 121

Measure: AUC(0-infinity) for each dose of REGN3051 measured using validated Enzyme Linked Immunosorbent Assays (ELISAs)

Time: From Day 1 up to Day 121

Measure: CL for each dose of REGN3048 measured using validated Enzyme Linked Immunosorbent Assays (ELISAs)

Time: From Day 1 up to Day 121

Measure: CL for each dose of REGN3051 measured using validated Enzyme Linked Immunosorbent Assays (ELISAs)

Time: From Day 1 up to Day 121

Measure: CMAX for each dose of REGN3048 measured using validated Enzyme Linked Immunosorbent Assays (ELISAs)

Time: From Day 1 up to Day 121

Measure: CMAX for each dose of REGN3051 measured using validated Enzyme Linked Immunosorbent Assays (ELISAs)

Time: From Day 1 up to Day 121

Measure: K(e) for each dose of REGN3048 measured using validated Enzyme Linked Immunosorbent Assays (ELISAs)

Time: From Day 1 up to Day 121

Measure: K(e) for each dose of REGN3051 measured using validated Enzyme Linked Immunosorbent Assays (ELISAs)

Time: From Day 1 up to Day 121

Measure: t(1/2) for each dose of REGN3048 measured using validated Enzyme Linked Immunosorbent Assays (ELISAs)

Time: From Day 1 up to Day 121

Measure: t(1/2) for each dose of REGN3051 measured using validated Enzyme Linked Immunosorbent Assays (ELISAs)

Time: From Day 1 up to Day 121

Measure: The change from baseline of antibodies against REGN3048 and REGN3051 (anti-drug antibodies, ADA), as measured in serum using validated bridging assays

Time: Day 121

Measure: The change from baseline of antibodies against REGN3048 and REGN3051 (anti-drug antibodies, ADA), as measured in serum using validated bridging assays

Time: Day 57

Measure: TMAX for each dose of REGN3048 measured using validated Enzyme Linked Immunosorbent Assays (ELISAs)

Time: From Day 1 up to Day 121

Measure: TMAX for each dose of REGN3051 measured using validated Enzyme Linked Immunosorbent Assays (ELISAs)

Time: From Day 1 up to Day 121

Measure: V(ss) for each dose of REGN3048 measured using validated Enzyme Linked Immunosorbent Assays (ELISAs)

Time: From Day 1 up to Day 121

Measure: V(ss) for each dose of REGN3051 measured using validated Enzyme Linked Immunosorbent Assays (ELISAs)

Time: From Day 1 up to Day 121

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

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

NCT03808922 Lower Respiratory Tract Infection Parainfluenza Immunocompromised COVID-19 Drug: DAS181 Drug: Placebo Drug: DAS181 COVID-19 Drug: DAS181 OL
MeSH:Infection Communicable Diseases Respiratory Tract Infections Paramyxoviridae Infections
HPO:Respiratory tract infection

Primary Outcomes

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

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

Time: by Day 28

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

Time: Day 14

Secondary Outcomes

Measure: All-cause mortality rate (main study)

Time: at Day 28

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

Time: by Day 21

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

Time: Days 10, 14, 21, 28

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

Time: by Day 28

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

Time: by Days 14, 21, 28 and 35

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

Time: through Day 35

Measure: Total number of inpatient days (main study)

Time: up to Day 35

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

Time: at Day 28

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

Time: at Day 35

Measure: All-cause mortality rate (main study)

Time: at Day 35

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

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

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

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

Measure: Time to RTRA

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

Measure: Time to Clinical stability

Time: Day 14, Day 21, Day 28

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

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

Measure: Time to Clinical deterioration

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

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

Time: Day 14, Day 21, Day 28

Measure: Time to Death (all causes)

Time: Day 14, Day 21, Day 28

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

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

NCT03891420 COVID-19 Yellow Fever Drug: Galidesivir Drug: Placebo
MeSH:Yellow Fever Fever
HPO:Fever

Primary Outcomes

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

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

Measure: number of subjects with change in laboratory parameters

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

Measure: exposure of galidesivir as measured by plasma concentrations

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

Secondary Outcomes

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

Time: change in YFV titer from baseline through Day 21

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

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

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

Time: through Day 21

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

Time: through Day21

Measure: mortality

Time: mortality at Day 56

14 A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Clinical Outcomes, Antiviral Activity, Safety, Tolerability, Pharmacokinetics, and Pharmacokinetics/Pharmacodynamics of JNJ-53718678 in Adult and Adolescent Hematopoietic Stem Cell Transplant Recipients With Respiratory Syncytial Virus Infection of the Upper Respiratory Tract

The purpose of this study is to evaluate the effect of JNJ-53718678 on the development of respiratory syncytial virus (RSV) lower respiratory tract infection (LRTIs) in adult hematopoietic stem cell transplant (HSCT) recipients with RSV upper RTI.

NCT04056611 Respiratory Syncytial Virus Infections Drug: JNJ-53718678 Drug: Placebo
MeSH:Infection Respiratory Syncytial Virus Infections Virus Diseases

Primary Outcomes

Description: The proportion of participants who develop RSV LRTI through Visit Day 28 per the Endpoint Adjudication Committee (EAC) assessment will be reported.

Measure: Proportion of Participants who Develop Respiratory Syncytial Virus (RSV) Lower Respiratory Tract Infection (LRTI)

Time: Up to Day 28

Secondary Outcomes

Description: The proportion of participants who develop RSV-associated LRTC through Visit Day 28 per the EAC's assessment will be reported.

Measure: Proportion of Participants who Develop RSV-associated Lower Respiratory Tract Complication (LRTC)

Time: Up to Day 28

Description: An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.

Measure: Number of Participants with Adverse Events (AEs)

Time: Up to 49 Days

Description: Percentage of participants with abnormal clinical laboratory findings will be reported.

Measure: Percentage of Participants with Abnormal Clinical Laboratory Findings

Time: Up to 49 days

Description: Percentage of participants with abnormal ECGs findings will be reported.

Measure: Percentage of Participants with Abnormal Electrocardiograms (ECGs) Findings

Time: Up to 49 days

Description: Percentage of participants with abnormal vital signs findings will be reported.

Measure: Percentage of Participants with Abnormal Vital Signs Findings

Time: Up to 49 days

Description: The proportion of participants progressing to respiratory failure (of any cause) requiring mechanical ventilation (invasive or noninvasive) and/or death, in participants who develop RSV LRTI or RSV-associated LRTC per the EAC's assessment will be reported.

Measure: Proportion of Participants Progressing to Respiratory Failure (of any Cause) Requiring Mechanical Ventilation (Invasive or Noninvasive) and/or Death, in Participants who Develop RSV LRTI or RSV-associated LRTC per the EAC's Assessment

Time: Up to 49 days

Description: Proportion of participants progressing to respiratory failure (of any cause) requiring mechanical ventilation (invasive or noninvasive) and/or death, (all-cause mortality) will be reported.

Measure: Proportion of Participants Progressing to Respiratory Failure (of any Cause) Requiring Mechanical Ventilation (Invasive or Noninvasive) and/or Death, (all-cause Mortality)

Time: Up to 49 days

Description: Proportion of participants progressing to death (all-cause mortality), in participants who develop RSV LRTI or RSV-associated LRTC per the EAC's assessment will be reported.

Measure: Proportion of Participants Progressing to Death (All-cause Mortality), in Participants who Develop RSV LRTI or RSV-associated LRTC per the EAC's Assessment

Time: Up to 49 days

Description: Proportion of participants progressing to death (all-cause mortality) will be reported.

Measure: Proportion of Participants Progressing to Death (All-cause Mortality)

Time: Up to 49 days

Description: Proportion of participants progressing to respiratory failure (of any cause) requiring mechanical ventilation (invasive or noninvasive), in participants who develop RSV LRTI or RSV-associated LRTC per the EAC's assessment will be reported.

Measure: Proportion of Participants Progressing to Respiratory Failure (of any Cause) Requiring Mechanical Ventilation (Invasive or Noninvasive), in Participants who Develop RSV LRTI or RSV-associated LRTC per the EAC's Assessment

Time: Up to 49 days

Description: Proportion of participants progressing to respiratory failure (of any cause) requiring mechanical ventilation (invasive or noninvasive) will be reported.

Measure: Proportion of Participants Progressing to Respiratory Failure (of any Cause) Requiring Mechanical Ventilation (Invasive or Noninvasive)

Time: Up to 49 days

Description: Number of supplemental O2 free days will be reported.

Measure: Number of Supplemental Oxygen (O2) Free Days Through Day 28

Time: Through Day 28

Description: Incidence of supplemental oxygen requirement in participants will be reported.

Measure: Incidence of Supplemental Oxygen Requirement

Time: Up to 28 days

Description: Duration of supplemental oxygen requirement in participants will be reported.

Measure: Duration of Supplemental Oxygen

Time: Up to 28 days

Description: Change from baseline in respiratory rate as measured by the investigator during scheduled visits will be reported.

Measure: Change from Baseline in Respiratory Rate

Time: Baseline up to 49 days

Description: Change from baseline in heart rate as measured by the investigator during scheduled visits will be reported.

Measure: Change from Baseline in Heart Rate

Time: Baseline up to 49 days

Description: Change from baseline in SpO2 as measured by the investigator during scheduled visits will be reported.

Measure: Change from Baseline in Peripheral Capillary Oxygen Saturation (SpO2)

Time: Baseline up to 49 days

Description: Change from baseline in body temperature as measured by the investigator during scheduled visits will be reported.

Measure: Change from Baseline in Body Temperature

Time: Baseline up to 49 days

Description: Proportion of participants hospitalized (of participants who were not hospitalized at baseline) will be reported.

Measure: Proportion of Participants Hospitalized (of Participants who Were not Hospitalized at Baseline)

Time: Up to 49 days

Description: Proportion of participants re-hospitalized (of participants who were hospitalized at baseline and discharged during the study and of participants who were not hospitalized at baseline, required hospitalization, and were discharged during the study) will be reported.

Measure: Proportion of Participants Re-hospitalized

Time: Up to 49 days

Description: Total length of hospital stay (time in hospital from first dosing) will be reported.

Measure: Total Length of Hospital Stay

Time: Up to 49 days

Description: Total time in the ICU (time in ICU from first dosing) will be reported.

Measure: Total Time in the Intensive Care Unit (ICU)

Time: Up to 49 days

Description: Incidence of Grade 3 and Grade 4 AEs will be assessed by system organ class where Grade 3: Severe and Grade 4: Life-threatening.

Measure: Incidence of Grade 3 and Grade 4 Adverse Events (AEs)

Time: Up to 49 days

Description: Incidence of respiratory AEs will be reported.

Measure: Incidence of Respiratory AEs

Time: Up to 49 days

Description: Incidence of thoracic-related AEs will be reported.

Measure: Incidence of Thoracic-related AEs

Time: Up to 49 days

Description: Incidence of antibiotic use in participants who develop and in those who do not develop RSV LRTI or RSV-associated LRTC per the EAC's assessment will be reported.

Measure: Incidence of Antibiotic use in Participants who Develop and in Those who do not Develop RSV LRTI or RSV-Associated LRTC per the EAC's Assessment

Time: Up to 49 days

Description: Time to resolution of symptoms, assessed through an instrument for participant-reported symptoms (RiiQ Symptom Scale) will be reported.

Measure: Time to Resolution of Symptoms as Assessed by Respiratory Infection Intensity and Impact Questionnaire (RiiQ) Symptom Scale

Time: Up to 49 days

Description: Change from baseline in severity of symptoms reported by participants in the RiiQ symptom scale through Day 28 will be reported.

Measure: Change from Baseline in Severity of Symptoms Reported by Participants in the RiiQ Symptom Scale Through Day 28

Time: Baseline up to Day 28

Description: Time to resolution of respiratory illness, through the PGI-S Scale, will be reported.

Measure: Time to Resolution of Respiratory Illness as Assessed by Patient Global Impression of Severity (PGI-S) Scale

Time: Up to 49 days

Description: Change from baseline in PGI-H scale through Day 28 will be reported.

Measure: Change from Baseline in Patient Global Impression of Health (PGI-H) Scale Through Day 28

Time: Baseline up to Day 28

Description: Change from baseline in PGI-C scale through Day 28 will be reported.

Measure: Change from Baseline in Patient Global Impression of Change (PGI-C) Scale Through Day 28

Time: Baseline up to Day 28

Description: AUC (0-24h) is defined as area under the plasma concentration-time curve from time 0 to 24 hours postdose.

Measure: Area Under the Plasma Concentration-time Curve from Time Zero to 24 Hours Postdose (AUC [0-24]) of JNJ-53718678

Time: Up to 24 hours postdose (on Days 1 and 8)

Description: Ctrough is defined as the observed plasma concentration before dosing or at the end of the dosing interval.

Measure: Trough Plasma Concentration (Ctrough) of JNJ-53718678

Time: Predose on Days 1 and 8

Description: Cmax is defined as the maximum observed plasma concentration of JNJ-53718678 in the dosing interval.

Measure: Maximum Observed Plasma Concentration (Cmax) of JNJ-53718678

Time: Predose; 0.5, 1, 1.5, 2, 4, 8, 24 hours postdose (on Days 1 and 8)

Description: The potential association of plasma concentration-time data of JNJ-53718678 with antiviral activity (RSV viral kinetics) will be analyzed. Association will be analyzed using (non)-linear mixed-effects models in a tabular and/or graphical display.

Measure: Association of Plasma Concentration-time Data of JNJ-53718678 and Antiviral Activity

Time: Up to 49 days

Description: The potential association of plasma concentration-time data of JNJ-53718678 with selected safety (including AEs and laboratory abnormalities) parameters will be analyzed. Association will be analyzed using (non)-linear mixed-effects models in a tabular and/or graphical display.

Measure: Association of Plasma Concentration-time Data of JNJ-53718678 and Safety Parameters

Time: Up to 49 days

Description: The potential association of plasma concentration-time data of JNJ-53718678 with clinical outcomes (proportion of participants developing LRTI) will be analyzed. Association will be analyzed using (non)-linear mixed-effects models in a tabular and/or graphical display.

Measure: Association of Plasma Concentration-time Data of JNJ-53718678 and Clinical Outcomes

Time: Up to 49 days

Description: RSV viral load and change from baseline over time will be measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR) assay in the mid-turbinate nasal swab specimens.

Measure: RSV Viral Load and Change from Baseline Over Time

Time: Baseline up to Day 28

Description: RSV viral load AUC will be determined by quantitative qRT-PCR assay of nasal swabs.

Measure: RSV Viral Load AUC from Immediately Prior to First Dose of Study Drug (Baseline) Through Days 8, 11, 15, 22 and 28

Time: Baseline up to Days 8, 11, 15, 22 and 28

Description: Time to undetectable RSV viral load (per the detection limit of the assay used in the study) will be reported.

Measure: Time to Undetectable RSV Viral Load

Time: Up to 49 days

Description: Proportion of participants with undetectable RSV viral load at each time point throughout the study will be reported.

Measure: Proportion of Participants with Undetectable RSV Viral Load at Each Timepoint

Time: Up to 49 days

Description: Change from baseline for the HRQOL assessment as assessed through the EQ-5D-5L through Day 28 will be reported.

Measure: Change from Baseline for the Health-related Quality of Life (HRQOL) as Assessed by 5-level EuroQol 5-Dimension (EQ-5D-5L) Through Day 28

Time: Baseline up to Day 28

Description: Change from baseline for the HRQOL assessment as assessed through RiiQ impact scales through Day 28 will be reported.

Measure: Change from Baseline for the HRQOL as Assessed by RiiQ Impact Scales Through Day 28

Time: Baseline up to Day 28

Description: Change from baseline in the RSV F gene sequence will be reported.

Measure: Change from Baseline in the RSV F Gene Sequence

Time: Baseline up to 49 days

15 A Two-center, Randomized, Double-blind, Placebo-controlled, Phase Ib Study to Assess the Safety, Tolerability and Immunogenicity of Two Ascending Doses of the Candidate Vaccine MVA-MERS-S_DF-1 in Healthy Study Subjects

The study will be a two center, randomized, double blind, placebo controlled study of the MVA MERS S_DF-1 candidate delivered by i.m. injection. To evaluate the MERS-S-specific antibody responses and safety profile induced by the two dosage levels of MVA-MERS-S_DF-1 the data will be compared to a placebo control group.

NCT04119440 MERS (Middle East Respiratory Syndrome) Biological: MVA-MERS-S_DF1 - Low Dose Biological: MVA-MERS-S_DF1 - High Dose Other: Placebo
MeSH:Coronavirus Infections

Primary Outcomes

Description: Safety and reactogenicity will be assesssed by observation, questionaire and diary. Changes from baseline for safety laboratory measures will be monitored. Occurence of SAE will be collected throughout the entire study duration.

Measure: Frequency of adverse events associated with MVA-MERS-S_DF-1.

Time: day 1, 14, 29, 42, 56, 84, 168, 336, 364

Measure: Frequency and severity of local injection site reactogenicity signs and symptoms

Time: day 1, 14, 29, 42, 84, 336

Secondary Outcomes

Description: Magnitude of MERS-S-specific antibody re-sponses (ELISA and neutralization assays) monitored in a centralized approved laboratory

Measure: Immunogenicity

Time: day 0, 14, 28, 42, 56, 70, 84, 168, 336, 364 (dependent on vaccination scheme)

16 Pharmacodynamic Biomarkers to Support Biosimilar Development: Clinical Study 1: Interleukin-5 Antagonists - Mepolizumab and Reslizumab

This study is designed to assess pharmacokinetics and pharmacodynamics of mepolizumab and reslizumab across an appropriate dose range to inform clinical trial operating characteristics for future clinical pharmacology pharmacodynamics similarity studies. This is a randomized, placebo-controlled, single-dose, parallel arm study in 72 healthy subjects assigned to one of four dose groups (low, intermediate low, intermediate high, and high) of each drug (mepolizumab or reslizumab) or placebo.

NCT04183192 Healthy Subjects Pharmacokinetics Pharmacodynamics Biological: Mepolizumab Biological: Mepolizumab Biological: Mepolizumab Biological: Mepolizumab Biological: Reslizumab Biological: Reslizumab Biological: Reslizumab Biological: Reslizumab Biological: Placebo

Primary Outcomes

Description: 1. The values and variability of standard pharmacodynamic metrics (AUEC and maximal difference at a single time-point) for eosinophils at low, intermediate low, intermediate high, and high doses of mepolizumab and reslizumab

Measure: Area under effect curve and maximum change from baseline for eosinophils for mepolizumab and reslizumab

Time: 63 or 123 days, depending on treatment arm

Secondary Outcomes

Description: 1. The values and variability of pharmacokinetic characteristics (Cmax and area under the curve of free drug concentration) at low, intermediate low, intermediate high, and high doses of mepolizumab and reslizumab.

Measure: Maximum concentration and area under the curve for mepolizumab and reslizumab

Time: 63 or 123 days, depending on treatment arm

Description: 2. Parameters (Emax, and EC50) calculated by the model after combining data from low, intermediate low, intermediate high, and high doses of mepolizumab or reslizumab with placebo data.

Measure: Pharmacodynamic model parameters for mepolizumab and reslizumab

Time: 63 or 123 days, depending on treatment arm

17 Clinical Study of Human Umbilical Cord Mesenchymal Stem Cells in the Treatment of Severe COVID-19

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

NCT04273646 2019 Novel Coronavirus Pneumonia COVID-19 Biological: UC-MSCs Drug: Placebo
MeSH:Coronavirus Infections Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Evaluation of Pneumonia Improvement

Measure: Pneumonia severity index

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

Description: Evaluation of Pneumonia Improvement

Measure: Oxygenation index (PaO2/FiO2)

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

Secondary Outcomes

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

Measure: Side effects in the UC-MSCs treatment group

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

Description: Marker for efficacy of treatment

Measure: 28-days survival

Time: Day 28

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

Measure: Sequential organ failure assessment

Time: Day 28

Description: Markers of Infection

Measure: C-reactive protein

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

Description: Markers of Infection

Measure: Procalcitonin

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

Description: Marker of Immunological function

Measure: Lymphocyte count

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

Description: Marker of Immunological function

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

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

Description: Marker of Immunological function

Measure: CD4+/CD8+ratio

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

18 A Multicenter, Adaptive, Randomized Blinded Controlled Trial of the Safety and Efficacy of Investigational Therapeutics for the Treatment of COVID-19 in Hospitalized Adults

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

NCT04280705 COVID-19 Other: Placebo Drug: Remdesivir

Primary Outcomes

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

Measure: Time to recovery

Time: Day 1 through Day 29

Secondary Outcomes

Measure: Change from baseline in alanine transaminase (ALT)

Time: Day 1 through Day 29

Measure: Change from baseline in aspartate transaminase (AST)

Time: Day 1 through Day 29

Measure: Change from baseline in creatinine

Time: Day 1 through Day 29

Measure: Change from baseline in glucose

Time: Day 1 through Day 29

Measure: Change from baseline in hemoglobin

Time: Day 1 through Day 29

Measure: Change from baseline in platelets

Time: Day 1 through Day 29

Measure: Change from baseline in prothrombin time (PT)

Time: Day 1 through Day 29

Measure: Change from baseline in total bilirubin

Time: Day 1 through Day 29

Measure: Change from baseline in white blood cell count (WBC) with differential

Time: Day 1 through Day 29

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

Measure: Change in National Early Warning Score (NEWS) from baseline

Time: Day 1 through Day 29

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

Measure: Clinical status using ordinal scale

Time: Day 3 through Day 29

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

Measure: Cumulative incidence of Grade 3 and 4 clinical and/or laboratory adverse events (AEs)

Time: Day 1 through Day 29

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

Measure: Cumulative incidence of serious adverse events (SAEs)

Time: Day 1 through Day 29

Description: For any reason.

Measure: Discontinuation or temporary suspension of investigational therapeutics

Time: Day 1 through Day 10

Description: Measured in days.

Measure: Duration of hospitalization

Time: Day 1 through Day 29

Description: Measured in days.

Measure: Duration of new non-invasive ventilation or high flow oxygen use

Time: Day 1 through Day 29

Description: Measured in days.

Measure: Duration of new oxygen use

Time: Day 1 through Day 29

Description: Measured in days.

Measure: Duration of new ventilator or extracorporeal membrane oxygenation (ECMO) use

Time: Day 1 through Day 29

Measure: Incidence of new non-invasive ventilation or high flow oxygen use

Time: Day 1 through Day 29

Measure: Incidence of new oxygen use

Time: Day 1 through Day 29

Measure: Incidence of new ventilator or extracorporeal membrane oxygenation (ECMO) use

Time: Day 1 through Day 29

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

Measure: Mean change in the ordinal scale

Time: Day 1 through Day 29

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

Measure: Percentage of subjects reporting each severity rating on an 8-point ordinal scale

Time: Day 15

Description: Date and cause of death (if applicable).

Measure: Subject 14-day mortality

Time: Day 1 through Day 15

Description: Date and cause of death (if applicable).

Measure: Subject 29-day mortality

Time: Day 1 through Day 29

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

Measure: Time to an improvement of one category using an ordinal scale

Time: Day 1 through Day 29

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

Measure: Time to an improvement of two categories using an ordinal scale

Time: Day 1 through Day 29

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

Measure: Time to discharge or to a National Early Warning Score (NEWS) of Time: Day 1 through Day 29

19 Human Umbilical Cord Mesenchymal Stem Cells Treatment for Pneumonia Patients Infected by 2019 Novel Coronavirus

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

NCT04293692 COVID-19 Biological: UC-MSCs Other: Placebo
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Evaluation of Pneumonia change

Measure: Size of lesion area by chest imaging

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

Description: Evaluation of Pneumonia change

Measure: Blood oxygen saturation

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

Secondary Outcomes

Description: Marker for efficacy of treatment

Measure: Rate of mortality within 28-days

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

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

Measure: Sequential organ failure assessment

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

Description: Number of participants with treatment-related adverse events

Measure: Side effects in the UC-MSCs treatment group

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

Description: Markers of the heart function

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

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

Description: Markers of infection

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

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

Description: Marker of Immunology and inflammation

Measure: CD4+ and CD8+ T cells count

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

Description: Marker of Immunology and inflammation

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

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

Description: Markers of the heart function

Measure: Concentration of the myocardial enzymes

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

20 A Phase IIb Randomized Placebo-Controlled Study to Examine the Efficacy and Safety of DAS181 for the Treatment of Severe Influenza Infection

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

NCT04298060 Influenza Infection SAD-RV Infection and COVID-19 Drug: DAS181 Drug: Placebo
MeSH:Infection Communicable Diseases Influenza, Human

Primary Outcomes

Description: Percent of subjects who have returned to room air

Measure: Percent of subjects who have returned to room air

Time: 7 days

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

Measure: Percent change of subjects return to baseline oxygen requirement

Time: 7 days

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

The study is a double-blind, randomised, placebo-controlled trial that will be conducted in healthcare settings. After obtaining fully informed consent, the investigator will recruit healthcare workers in a healthcare facility delivering direct care to patients with either proven or suspected COVID-19, who can be followed reliably for up to 5 months. 40,000 participants will be recruited and the investigators predict an average of 400-800 participants per site in 50-100 sites. The participant will be randomised in Asia to receive either chloroquine or placebo (1:1 randomisation) or in European and African sites, to receive 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 90 days. If the participant is diagnosed with COVID-19, they will take continue to take the study medication unless advised to stop by their healthcare professional, or 90 days after enrolment, whichever is sooner. Episodes of symptomatic respiratory illness, including symptomatic COVID-19, and clinical outcomes will be recorded in the Case Record Form during the follow-up period.

NCT04303507 COVID19 Coronavirus Acute Respiratory Illnesses Drug: Chloroquine or Hydroxychloroquine Drug: Placebo
MeSH:Coronavirus Infections

Primary Outcomes

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

Measure: Number of symptomatic COVID-19 infections

Time: Approximately 90 days

Secondary Outcomes

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

Measure: Symptoms severity of COVID-19

Time: Approximately 90 days

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

Measure: Number of asymptomatic cases of COVID-19

Time: Approximately 90 days

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

Measure: Number of symptomatic acute respiratory illnesses

Time: Approximately 90 days

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

Measure: Severity of symptomatic acute respiratory illnesses

Time: Approximately 90 days

Other Outcomes

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

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

Time: Approximately 90 days

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

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

Time: Approximately 90 days

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

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

Time: Approximately 90 days

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

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

Time: Approximately 90 days

22 Post-exposure Prophylaxis or Preemptive Therapy for SARS-Coronavirus-2: A Pragmatic Randomized Clinical Trial

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

NCT04308668 Corona Virus Infection Acute Respiratory Distress Syndrome SARS-CoV Infection Coronavirus Coronavirus Infections Drug: Hydroxychloroquine Other: Placebo
MeSH:Infection Co Communicable Diseases Coronavirus Infections Severe Acute Respiratory Syndrome Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury

Primary Outcomes

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

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

Time: 14 days

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

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

Time: 14 days

Secondary Outcomes

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

Measure: Incidence of Hospitalization

Time: 14 days

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

Measure: Incidence of Death

Time: 90 days

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

Measure: Incidence of Confirmed SARS-CoV-2 Detection

Time: 14 days

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

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

Time: 90 days

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

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

Time: 14 days

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

Measure: Overall symptom severity at 5 and 14 days

Time: 5 and 14 days

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

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

Time: 14 days

23 Randomized Controlled Trial of Losartan for Patients With COVID-19 Not Requiring Hospitalization

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

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

Primary Outcomes

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

Measure: Hospital Admission

Time: 15 days

Secondary Outcomes

Description: The PROMIS Dyspnea (shortness of breath) item banks and pools assess self-reported Functional Limitations, Severity, Activity Motivation, Activity Requirements, Airborne Exposure, Assistant Devices Resources, Characteristics, Emotional Response, Task Avoidance and Time Extension as they related to dyspnea. In the 33-item Functional Limitations bank, 33 daily activities are rated in terms of degree of difficulty while engaging in the activity over the past 7 days (0 = no difficulty, 1 = a little difficulty, 2 = some difficulty, 3 = much difficulty). Total scores range from 0 to 99, with higher scores reflecting greater functional limitations.

Measure: Change in PROMIS Dyspnea Functional Limitations

Time: baseline, 10 days

Description: The PROMIS Dyspnea (shortness of breath) item banks and pools assess self-reported Functional Limitations, Severity, Activity Motivation, Activity Requirements, Airborne Exposure, Assistant Devices Resources, Characteristics, Emotional Response, Task Avoidance and Time Extension as they related to dyspnea. The 33-item Severity bank assesses the severity of difficulty breathing during various specific activities (the same 33 activities assessed in Dyspnea Functional Limitations). Each activity is rated in terms of degree of dyspnea (0 = no shortness of breath, 1 = mildly short of breath, 2 = moderately short of breath, 3 = severely short of breath) while engaging in the activity over the past 7 days. Total scores range from 0 to 99 with higher scores reflecting greater levels of dyspnea during daily activity.

Measure: Change in PROMIS Dyspnea Severity

Time: baseline, 10 days

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

Measure: Daily Maximum Temperature

Time: 10 days

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

Measure: Emergency Department/Clinic Presentations

Time: 28 days

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

Measure: Disease Severity Rating Day 7

Time: 7 days

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

Measure: Disease Severity Rating Day 15

Time: 15 days

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

Measure: Disease Severity Rating Day 28

Time: 28 days

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

Measure: Viral Load by Oropharyngeal Swab Day 9

Time: 9 days

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

Measure: Viral Load by Oropharyngeal Swab Day 15

Time: 15 days

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

Measure: Ventilator-Free Days

Time: 28 days

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

Measure: Therapeutic Oxygen-Free Days

Time: 28 days

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

Measure: Need for Hospital Admission at 15 Days

Time: 15 days

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

Measure: Need for Oxygen Therapy at 15 Days

Time: 15 days

24 Randomized Controlled Trial of Losartan for Patients With COVID-19 Requiring Hospitalization

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

NCT04312009 Corona Virus Infection Acute Respiratory Distress Syndrome SARS-CoV Infection Drug: Losartan Other: Placebo
MeSH:Infection Communicable Diseases Coronavirus Infections Severe Acute Respiratory Syndrome Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury

Primary Outcomes

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

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

Time: 7 days

Secondary Outcomes

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

Measure: Daily Hypotensive Episodes

Time: 10 days

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

Measure: Hypotension Requiring Vasopressors

Time: 10 days

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

Measure: Acute Kidney Injury

Time: 10 days

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

Measure: Sequential Organ Failure Assessment (SOFA) Total Score

Time: 10 days

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

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

Time: 10 days

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

Measure: 28-Day Mortality

Time: 28 days

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

Measure: 90-Day Mortality

Time: 90 days

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

Measure: ICU Admission

Time: 10 days

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

Measure: Number of Ventilator-Free Days

Time: 10 days

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

Measure: Number of Therapeutic Oxygen-Free Days

Time: 10 days

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

Measure: Number of Vasopressor-Free Days

Time: 10 days

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

Measure: Length of ICU Stay

Time: 10 days

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

Measure: Length of Hospital Stay

Time: 10 days

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

Measure: Incidence of Respiratory Failure

Time: 10 days

Description: The PROMIS Dyspnea (shortness of breath) item banks and pools assess self-reported Functional Limitations, Severity, Activity Motivation, Activity Requirements, Airborne Exposure, Assistant Devices Resources, Characteristics, Emotional Response, Task Avoidance and Time Extension as they related to dyspnea. In the 33-item Functional Limitations bank, 33 daily activities are rated in terms of degree of difficulty while engaging in the activity over the past 7 days (0 = no difficulty, 1 = a little difficulty, 2 = some difficulty, 3 = much difficulty). Total scores range from 0 to 99, with higher scores reflecting greater functional limitations.

Measure: Change in PROMIS Dyspnea Functional Limitations

Time: 10 days

Description: The PROMIS Dyspnea (shortness of breath) item banks and pools assess self-reported Functional Limitations, Severity, Activity Motivation, Activity Requirements, Airborne Exposure, Assistant Devices Resources, Characteristics, Emotional Response, Task Avoidance and Time Extension as they related to dyspnea. The 33-item Severity bank assesses the severity of difficulty breathing during various specific activities (the same 33 activities assessed in Dyspnea Functional Limitations). Each activity is rated in terms of degree of dyspnea (0 = no shortness of breath, 1 = mildly short of breath, 2 = moderately short of breath, 3 = severely short of breath) while engaging in the activity over the past 7 days. Total scores range from 0 to 99 with higher scores reflecting greater levels of dyspnea during daily activity.

Measure: Change in PROMIS Dyspnea Severity

Time: 10 days

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

Measure: Disease Severity Rating

Time: 10 days

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

Measure: Viral Load by Nasopharyngeal Swab Day 9

Time: 9 days

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

Measure: Viral Load by Nasopharyngeal Swab Day 15

Time: 15 days

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

Measure: Viral Load by Blood Day 9

Time: 9 days

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

Measure: Viral Load by Blood Day 15

Time: 15 days

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

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

NCT04312997 COVID-19 Drug: PUL-042 Inhalation Solution Drug: Placebo
MeSH:Infection Respiratory Aspiration

Primary Outcomes

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

Measure: Severity of COVID-19

Time: 28 days

Secondary Outcomes

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

Measure: SARS-CoV-2 infection

Time: 28 days

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

Measure: Severity of COVID-19 over 14 days

Time: 14 days

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

Measure: Severity of COVID-19 symptoms

Time: 28 days

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

Measure: ICU admission

Time: 28 days

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

Measure: Mechanical Ventilation

Time: 28 days

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

Measure: Mortality

Time: 28 days

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

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

NCT04313023 COVID-19 Drug: PUL-042 Inhalation Solution Drug: Placebo
MeSH:Infection Disease Progression

Primary Outcomes

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

Measure: Severity of COVID-19

Time: 28 days

Secondary Outcomes

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

Measure: Incidence of SARS-CoV-2 infection

Time: 28 days

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

Measure: Incidence of SARS-CoV-2 infection

Time: 14 days

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

Measure: Severity of COVID-19

Time: 14 days

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

Measure: ICU admission

Time: 28 days

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

Measure: Mechanical ventilation

Time: 28 days

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

Measure: Mortality

Time: 28 days

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

Phase 2: The primary objective of the study is to evaluate the clinical efficacy of sarilumab relative to the control arm in adult patients hospitalized with COVID-19 regardless of severity strata. Phase 3: 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 (severe and critical).

NCT04315298 COVID-19 Drug: Sarilumab Drug: Placebo

Primary Outcomes

Description: Phase 2 Only

Measure: Percent change in C-reactive protein (CRP) levels

Time: Day 4

Description: Phase 3 Only 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: Time to improvement (2 points) in clinical status assessment using the 7-point ordinal scale in patients with serum IL-6 levels greater than the upper limit of normal

Time: Up to day 29

Secondary Outcomes

Description: Phase 2 Only

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

Time: Up to day 29

Description: Phase 2 Only

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

Time: Up to day 29

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

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

Time: Up to day 29

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

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

Time: Up to day 29

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

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

Time: Up to day 29

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

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

Time: Up to day 29

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

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

Time: Up to day 29

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

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

Time: Up to day 29

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

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

Time: Up to day 29

Measure: Mean change in the 7-point ordinal scale

Time: Up to day 29

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

Time: Up to day 29

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

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

Time: Up to day 29

Measure: Change from baseline in NEWS2 scoring system

Time: Up to day 29

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

Measure: Number of days with fever

Time: Up to day 29

Measure: Proportion of patients alive, off oxygen

Time: Day 29

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

Time: Up to day 29

Measure: Number of days with hypoxemia

Time: Up to day 29

Measure: Number of days of supplemental oxygen use

Time: Up to day 29

Measure: Time to saturation ≥94% on room air

Time: Up to day 29

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

Time: Baseline to day 29

Measure: Number of patients requiring initiation of mechanical ventilation

Time: Up to day 29

Measure: Number of patients requiring non-invasive ventilation

Time: Up to day 29

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

Time: Up to day 29

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

Time: Up to day 29

Measure: Number of days of hospitalization among survivors

Time: Up to day 29

Measure: Number of deaths due to any cause

Time: Up to day 60

Description: Phase 3 Only

Measure: Change in serum CRP levels

Time: Up to day 29

Measure: Incidence of serious adverse events

Time: Up to Day 29

Measure: Incidence of Grade 4 neutropenia (ANC <500/mm3)

Time: Up to day 29

Measure: Incidence of severe or life-threatening bacterial, invasive fungal, or opportunistic infection

Time: Up to day 29

Measure: Incidence of severe or life-threatening bacterial, invasive fungal, or opportunistic infection in patients with Grade 4 neutropenia

Time: Up to day 29

Measure: Incidence of hypersensitivity reactions

Time: Up to day 29

Measure: Incidence of infusion reactions

Time: Up to day 29

Measure: Incidence of gastrointestinal perforation

Time: Up to day 29

Measure: White blood cell count

Time: Up to day 29 if still hospitalized

Measure: Hemoglobin levels

Time: Up to day 29 if still hospitalized

Measure: Platelet count

Time: Up to day 29 if still hospitalized

Measure: Creatinine levels

Time: Up to day 29 if still hospitalized

Measure: Total bilirubin level

Time: Up to day 29 if still hospitalized

Measure: Alanine aminotransferase (ALT) level

Time: Up to day 29 if still hospitalized

Measure: Aspartate aminotransferase (AST) level

Time: Up to day 29 if still hospitalized

28 Exploratory Clinical Study to Assess the Efficacy of NestaCell® Mesenchymal Stem Cell to Treat Patients With Severe COVID-19 Pneumonia

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

NCT04315987 COVID-19 Pneumonia Biological: NestaCell® Biological: Placebo
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

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

Measure: Change in Clinical Condition

Time: 10 days

Secondary Outcomes

Description: Evaluation of Pneumonia change

Measure: Rate of mortality within 10-days

Time: 10 days

Description: Evaluation of Pneumonia change

Measure: Change of Clinical symptoms - respiratory rate

Time: 10 days

Description: oxygen saturation

Measure: Hypoxia

Time: 10 days

Description: oxygen saturation

Measure: PaO2 / FiO2 ratio

Time: 10 days

Description: Marker of Immunological function

Measure: CD4+ and CD8+ T cell count

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

Description: PaO2 / FiO2 ratio

Measure: Changes of blood oxygen

Time: 10 days

Description: Number of participants with treatment-related adverse events

Measure: Side effects in the treatment group

Time: 10 days

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

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

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

29 A Randomized, Double-blind, Placebo-controlled, Multi-site, Phase III Study to Evaluate the Safety and Efficacy of CD24Fc in COVID-19 Treatment

The study is designed as a randomized, placebo-controlled, double blind, multicenter, Phase III trial to compare two COVID-19 treatment regimens in hospitalized adult subjects who are diagnosed with severe 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 230 subjects will be enrolled and randomized in 1:1 ratio to receive CD24Fc or placebo. All subjects will be treated with the best available treatment. The follow up period is 28 days.

NCT04317040 Severe Coronavirus Disease (COVID-19) Drug: CD24Fc Drug: Placebo
MeSH:Coronavirus Infections

Primary Outcomes

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

Measure: Improvement of COVID-19 disease status

Time: 29 days

Secondary Outcomes

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

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

Time: 29 days

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

Measure: Disease progression of COVID-19

Time: 29 days

Description: All cause of death

Measure: All cause of death

Time: 29 days

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

Measure: Proportion of clinical relapse

Time: 29 days

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

Measure: Conversion rate of clinical status at Day 8

Time: 8 days

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

Measure: Conversion rate of clinical status at Day 15

Time: 15 days

Description: The discharge time, calculated after the randomization.

Measure: Hospital discharge time

Time: 29 days

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

Measure: Duration of mechanical ventilation

Time: 29 days

Description: Duration of pressors (days)

Measure: Duration of pressors

Time: 29 days

Description: Duration of extracorporeal membrane oxygenation (days)

Measure: Duration of ECMO

Time: 29 days

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

Measure: Duration of high flow oxygen therapy

Time: 29 days

Description: Changes of absolute lymphocyte count in peripheral blood

Measure: Absolute lymphocyte count

Time: 29 days

Description: The changes of plasma concentration of D-dimers

Measure: Change of D-dimers

Time: 15 and 29 days

30 Clinical Trial of Favipiravir Tablets Combine With Chloroquine Phosphate in the Treatment of Novel Coronavirus Pneumonia

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

NCT04319900 Novel Coronavirus Pnuemonia Drug: favipiravir tablets+chloroquine phosphatetablets tablets Drug: Favipiravir tablets Drug: Placebo
MeSH:Coronavirus Infections Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Time of improvement or recovery of respiratory symptoms

Measure: Time of Improvement or recovery of respiratory symptoms

Time: 10 days during the intervention period

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

Measure: Number of days virus nucleic acid shedding

Time: 10 days during the intervention period

Description: Frequency of improvement or recovery of respiratory symptoms

Measure: Frequency of Improvement or recovery of respiratory symptoms

Time: 10 days during the intervention period

Secondary Outcomes

Description: Duration of fever after recruitment

Measure: Duration of fever

Time: 10 days during the intervention period

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

Measure: Frequencies of progression to severe illness

Time: 10 days during the intervention period

Description: Time of improvement of pulmonary imaging

Measure: Time of improvement of pulmonary imaging

Time: 10 days during the intervention period

Description: Peripheral blood c-reactive protein concentration

Measure: Peripheral blood c-reactive protein concentration

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

Description: Absolute value of peripheral blood lymphocytes

Measure: Absolute value of peripheral blood lymphocytes

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

Description: percentage of peripheral blood lymphocytes

Measure: percentage of peripheral blood lymphocytes

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

31 A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Safety and Efficacy of Tocilizumab in Patients With Severe COVID-19 Pneumonia

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

NCT04320615 COVID-19 Pneumonia Drug: Tocilizumab (TCZ) Drug: Placebo
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

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

Time: Day 28

Secondary Outcomes

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

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

Time: Up to 60 days

Measure: Incidence of Mechanical Ventilation

Time: Up to 60 days

Measure: Ventilator-Free Days to Day 28

Time: Up to Day 28

Measure: Incidence of Intensive Care Unit (ICU) Stay

Time: Up to 60 days

Measure: Duration of ICU Stay

Time: Up to 60 days

Measure: Time to Clinical Failure

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

Measure: Mortality Rate

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

Measure: Time to Hospital Discharge

Time: Up to 60 days

Measure: Duration of Time on Supplemental Oxygen

Time: Up to 60 days

Measure: Percentage of Participants with Adverse Events

Time: Up to 60 days

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

Time: Up to 60 days

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

Time: Up to 60 days

Measure: Proportion of Participants with Post-Treatment Infection

Time: Up to 60 days

Measure: Serum Concentration of IL-6

Time: Up to 60 days

Measure: Serum Concentration of sIL-6R

Time: Up to 60 days

Measure: Serum Concentration of Ferritin

Time: Up to 60 days

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

Time: Up to 60 days

Measure: Serum Concentration of TCZ

Time: Up to 60 days

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

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

NCT04325893 Coronavirus Drug: Hydroxychloroquine Drug: Placebo
MeSH:Coronavirus Infections

Primary Outcomes

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

Time: Day 14

Secondary Outcomes

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

Time: Day 28

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

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

Time: Day 14

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

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

Time: Day 28

Measure: Number of all-cause mortality at day 14

Time: Day 14

Measure: Number of all-cause mortality at day 28

Time: Day 28

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

Time: Day 5

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

Time: Day 10

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

Time: Day 28

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

Time: day 28

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

Time: day 28

Measure: Rate of severe adverse events at day 28

Time: day 28

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

Time: day 14

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

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

NCT04326426 Coronavirus Infection Drug: Tradipitant Drug: Placebo
MeSH:Infection Co Communicable Diseases Coronavirus Infections Severe Acute Respiratory Syndrome

Primary Outcomes

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

Time: 14 days or discharge

Secondary Outcomes

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

Time: 14 days or discharge

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

Time: 14 days or discharge

Measure: In-hospital mortality

Time: 14 days or discharge

Measure: Mean change in NEWS2 score from baseline

Time: 14 days or discharge

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

Time: 14 days or discharge

Measure: Reduction from baseline of NRS for cough

Time: 14 days or discharge

Measure: Reduction from baseline of NRS for nausea

Time: 14 days or discharge

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

Time: 14 days or discharge

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

Time: 14 days or discharge

34 An Adaptive Phase 3, Randomized, Double-blind, Placebo-controlled Study Assessing Efficacy and Safety of Sarilumab for Hospitalized Patients With COVID19

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

NCT04327388 Corona Virus Infection Drug: Sarilumab SAR153191 Drug: Placebo
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome

Primary Outcomes

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

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

Time: Baseline to Day 29

Secondary Outcomes

Measure: Percent of patients alive at Day 29

Time: Day 29

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

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

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

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

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

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

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

Measure: Time to resolution of fever

Time: Baseline to Day 29

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

Measure: Time to resolution of fever and improvement in oxygenation

Time: Baseline to Day 29

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

Measure: Days with fever

Time: Baseline to Day 29

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

Measure: Time to change in NEWS2 from baseline

Time: Baseline to Day 29

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

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

Time: Baseline to Day 29

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

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

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

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

Measure: Time-to-improvement in oxygenation

Time: Baseline to Day 29

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

Measure: Alive off supplemental oxygen at day 29

Time: Day 29

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

Measure: Days of hypoxemia

Time: Baseline to Day 29

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

Measure: Days of supplemental oxygen use

Time: Baseline to Day 29

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

Time: Baseline to Day 29

Measure: Time to saturation ≥94% on room air

Time: Baseline to Day 29

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

Time: Baseline to Day 29

Description: For those not requiring these interventions at baseline.

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

Time: Baseline to Day 60

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

Time: Baseline to Day 28

Description: For patients are not in ICU at baseline

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

Time: Baseline to Day 60

Measure: Days of hospitalization among survivors

Time: Baseline to Day 60

Measure: Incidence of serious adverse events

Time: Baseline to Day 60

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

Time: Baseline to Day 60

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

Time: Baseline to Day 60

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

Time: Baseline to Day 60

Measure: The number of patients with clinically significant laboratory abnormalities

Time: Baseline to Day 60

35 Reducing Health Care Workers Absenteeism in COVID-19 Pandemic by Enhanced Trained Immune Responses Through Bacillus Calmette-Guérin Vaccination, a Randomized Controlled Trial.

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

NCT04328441 COVID-19 Drug: BCG Vaccine Drug: Placebo

Primary Outcomes

Description: Number of days of unplanned absenteeism for any reason

Measure: Health Care Workers absenteeism

Time: Maximum of 180 days

Secondary Outcomes

Measure: the cumulative incidence of documented COVID-19

Time: Maximum of 180 days

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

Time: Maximum of 180 days

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

Time: Maximum of 180 days

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

Time: Maximum of 180 days

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

Time: Maximum of 180 days

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

Time: Maximum of 180 days

Description: Exploratory

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

Time: Maximum of 180 days

Description: Exploratory

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

Time: Maximum of 180 days

Description: Exploratory

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

Time: Maximum of 180 days

Description: Exploratory

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

Time: Maximum of 180 days

Description: Exploratory

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

Time: Maximum of 180 days

Description: Exploratory

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

Time: Maximum of 180 days

Description: Exploratory

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

Time: Maximum of 180 days

Description: Exploratory

Measure: the cumulative incidence of death for any reason

Time: Maximum of 180 days

Description: Exploratory

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

Time: Maximum of 180 days

Description: Exploratory

Measure: the cumulative incidence of Hospital Admission for any reason

Time: Maximum of 180 days

Description: Exploratory

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

Time: Maximum of 180 days

36 Pre-exposure Prophylaxis for SARS-Coronavirus-2: A Pragmatic Randomized Clinical Trial

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

NCT04328467 COVID-19 Corona Virus Infection ARDS Acute Respiratory Distress Syndrome Drug: Hydroxychloroquine Other: Placebo
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury

Primary Outcomes

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

Measure: COVID-19-free survival

Time: up to 12 weeks

Secondary Outcomes

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

Measure: Incidence of confirmed SARS-CoV-2 detection

Time: up to 12 weeks

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

Measure: Incidence of possible COVID-19 symptoms

Time: up to 12 weeks

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

Measure: Incidence of all-cause study medicine discontinuation

Time: up to 12 weeks

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

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

Time: up to 12 weeks

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

Measure: Incidence of Hospitalization for COVID-19 or death

Time: up to 12 weeks

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

Measure: Incidence of study medication-related side effects

Time: up to 12 weeks

37 A Phase 2 Randomized, Single Blind Study of a Single Dose of Peginterferon Lambda-1a Compared With Placebo in Outpatients With Mild COVID-19

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

NCT04331899 COVID-19 Drug: Peginterferon Lambda-1a Other: Placebo

Primary Outcomes

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

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

Time: 28 days

38 Outcomes Related to COVID-19 Treated With Hydroxychloroquine Among In-patients With Symptomatic Disease

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

NCT04332991 Coronavirus Acute Respiratory Infection SARS-CoV Infection Drug: Hydroxychloroquine Drug: Placebo
MeSH:Infection Communicable Diseases Respiratory Tract Infections Coronavirus Infections Severe Acute Respiratory Syndrome
HPO:Respiratory tract infection

Primary Outcomes

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

Measure: COVID Ordinal Outcomes Scale on Day 15

Time: assessed on study day 15

Secondary Outcomes

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

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

Time: assessed on study day 15

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

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

Time: assessed on study day 29

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

Measure: COVID Ordinal Outcomes Scale on Study Day 3

Time: assessed on study day 3

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

Measure: COVID Ordinal Outcomes Scale on Study Day 8

Time: assessed on study day 8

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

Measure: COVID Ordinal Outcomes Scale on Study Day 29

Time: assessed on study day 29

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

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

Time: Enrollment to Day 28

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

Measure: Oxygen-free days through Day 28

Time: 28 days after randomization

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

Measure: Ventilator-free days through Day 28

Time: 28 days after randomization

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

Measure: Vasopressor-free days through Day 28

Time: 28 days after randomization

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

Measure: ICU-free days to Day 28

Time: 28 days after randomization

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

Measure: Hospital-free days to Day 28

Time: 28 days after randomization

Other Outcomes

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

Measure: Number of patients with seizures to day 28

Time: 28 days after randomization

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

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

Time: 28 days after randomization

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

Measure: Number of patients with cardiac arrest to day 28

Time: 28 days after randomization

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

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

Time: 28 days after randomization

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

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

Time: 28 days after randomization

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

Measure: Number of patients with acute kidney injury to day28

Time: 28 days after randomization

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

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

Time: 28 days after randomization

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

Measure: Number of patients with symptomatic hypoglycemia to day 28

Time: 28 days after randomization

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

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

Time: 28 days after randomization

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

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

Time: 28 days after randomization

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

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

Time: 28 days after randomization

39 A Phase 1b, Randomized, Double-blinded, Placebo-controlled Study of Hydroxychloroquine in Outpatient Adults With COVID-19

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

NCT04333654 Coronavirus Infection Drug: Hydroxychloroquine SAR321068 Drug: Placebo
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome

Primary Outcomes

Description: Viral load assessed by PCR from a nasopharyngeal swab

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

Time: Baseline to Day 3

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

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

Time: Baseline to Day 3

Secondary Outcomes

Description: Viral load assessed by PCR from a nasopharyngeal swab

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

Time: Baseline to Day 5

Description: Viral load assessed by PCR from a nasopharyngeal swab

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

Time: Baseline to end of study (Day14)

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

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

Time: Baseline to end of study (Day14)

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

Measure: Time to resolution of COVID-19 Symptoms

Time: Baseline to end of study (Day14)

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

Measure: Time to resolution of fever

Time: Baseline to end of study (Day14)

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

Measure: Percentage of participants with resolution of fever

Time: Baseline to end of study (Day14)

Measure: Percentage of participants hospitalized

Time: Baseline to end of study (Day14)

Measure: Number of participants with Adverse Events

Time: Baseline to end of study (Day14)

40 An International, Multi-site, Bayesian Platform Adaptive,Randomised, Double-blind, Placebo-controlled Trial Assessing the Effectiveness of Varied Doses of Oral Chloroquine in Preventing or Reducing the Severity of COVID-19 Disease in Healthcare Workers

Healthcare workers are at the frontline of the fight against COVID-19, and as such they are at high risk for infection and possibly for serious infection, linked to the extent of their exposure. The CROWN CORONATION trial prioritizes the protection of healthcare workers as a strategy to prevent collapse of healthcare services.

NCT04333732 COVID 19 Drug: Low-dose chloroquine Drug: Mid-dose chloroquine Drug: High-dose chloroquine Drug: Placebo

Primary Outcomes

Description: To determine the effectiveness (and minimum effective dose schedule) of chloroquine prophylaxis in preventing laboratory-confirmed symptomatic, laboratory test-confirmed COVID-19 (WHO COVID-19 severity scale score >1) in healthcare workers with repeated exposures to SARS-CoV-2.

Measure: Symptomatic COVID-19

Time: 3 months

Description: i) Uninfected - no clinical or virological evidence of infection (Score = 0) ii) Ambulatory - no limitation of activities (score=1) or with limitation (Score=2) iii) Hospitalized - mild no oxygen (Score=3) or with oxygen (Score=4) iv) Hospitalized severe - Scores 5-7* v) Dead * Score 5 is non-invasive ventilation or high flow oxygen; Score 6 is intubation with mechanical ventilation; Score 7 is intubation with additional organ support (e.g. pressors, renal replacement therapy, extra corporeal membrane oxygenation [ECMO]) These outcome definitions are based on WHO R&D Blueprint consensus definitions for COVID-19.

Measure: Peak severity of COVID-19 over the study period

Time: 3 months

41 A Phase 1, Randomized, Observer-Blind, Placebo-Controlled Trial to Evaluate the Safety, Tolerability and Immunogenicity of the bacTRL-Spike Oral Candidate Vaccine for the Prevention of COVID-19 in Healthy Adults

Protocol bacTRL-Spike-1 will be the first-in-human study of bacTRL-Spike, and the first-in-human use of orally delivered bacTRL. Each oral dose of bacTRL-Spike contains bacterial medium with either 1 billion (Group 1A), 3 billion (Group 2A) or 10 billion (Group 3A) colony-forming-units of live Bifidobacterium longum, which has been engineered to deliver plasmids containing synthetic DNA encoding spike protein from SARS-CoV-2. Placebo will consist of bacterial medium without bacteria.

NCT04334980 COVID-19 Biological: bacTRL-Spike Other: Placebo

Primary Outcomes

Description: Adverse events (specifically including incidence of gastrointestinal-associated events) following administration of oral bacTRL-Spike

Measure: Frequency of Adverse Events

Time: Up to12 months post-vaccination

Secondary Outcomes

Description: Antibody against SARS-CoV-2 Spike protein

Measure: SARS-CoV-2 antibodies

Time: Baseline (pre-vaccination), and 1, 3 and 12 months post-vaccination

Description: Incidence and clinical phenotype of confirmed and probable COVID-19 infection among vaccinated participants, based on current public health definitions

Measure: Incidence of COVID-19 infection

Time: Up to 12 months post-vaccination

Description: Isolation of viable bacTRL-Spike from stool post-vaccination

Measure: bacTRL-Spike in stool post-vaccination

Time: Days 7, 14, 21, and 1 and 3 months post-vaccination

Description: Collection of biological samples for future studies to understand immunity against SARS-CoV-2.

Measure: Seroconversion of circulating anti-Spike IgG antibodies & stability of serum IgG titers

Time: Up to 12 months post-vaccination

Description: Collection of biological samples for future studies to understand immunity against SARS-CoV-2.

Measure: Effectiveness of intestinal colonization of the probiotic-based bacTRL-Spike oral vaccine

Time: Up to 12 months post-vaccination

42 CORON-ACT - a Multicenter, Double-blind, Randomized Controlled Phase II Trial on the Efficacy and Safety of Tocilizumab in the Treatment of Coronavirus Induced Disease (COVID-19)

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

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

Primary Outcomes

Measure: Number of patients with ICU admission

Time: 7 days after randomisation

Measure: Number of patients with intubation

Time: 14 days after randomisation

Measure: Number of patients with death

Time: 28 days after randomisation

Secondary Outcomes

Description: Assessed by the 8-point WHO scale

Measure: Illness severity

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

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

Measure: Number of patients with clinical improvement

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

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

Measure: Time to clinical improvement (days)

Time: Up to day 28 after randomisation

Measure: Duration of hospitalization (days)

Time: Up to day 28 after randomisation

Measure: Time to ICU admission (days)

Time: Up to day 28 after randomisation

Measure: Duration of ICU stay

Time: Up to day 28 after randomisation

Measure: Time to intubation

Time: Up to day 28 after randomisation

Measure: Duration of mechanical ventilation (days)

Time: Up to day 28 after randomisation

Other Outcomes

Measure: Number of deaths

Time: Within 28 days after randomisation

Measure: Number of patients with ICU admission

Time: Within 28 days after randomisation

Measure: Number of patients with intubation

Time: Within 28 days after randomisation

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

Measure: Number of patients with events of special interest

Time: Within 28 days after randomisation

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

Time: Within 28 days after randomisation

43 A Multi-center, Randomized, Double-blind, Placebo-controlled, Phase III Clinical Study Evaluating the Efficacy and Safety of Favipiravir in the Treatment of Patients With COVID-19-Moderate Type

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

NCT04336904 COVID-19 Drug: Favipiravir Other: Placebo

Primary Outcomes

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

Measure: Time from randomization to clinical recovery

Time: 90 days

Secondary Outcomes

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

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

Time: 28 days

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

Measure: Incidence of deterioration/aggravation of pneumonia

Time: 28 days

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

Measure: Time from randomization to resolution of pyrexia

Time: 28 days

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

Measure: Time from randomization to relief of cough

Time: 28 days

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

Measure: Time from randomization to relief of dyspnoea

Time: 28 days

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

Measure: Rate of auxiliary oxygen therapy

Time: 28 days

Description: ICU admission rate within 28 days of randomization

Measure: ICU admission rate

Time: 28 days

Description: All-cause mortality within 28 days of randomization

Measure: Mortality

Time: 28 days

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

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

NCT04338802 COVID-19 Nintedanib Safety Effect of Drugs Drug: Nintedanib 150 MG Other: Placebo
MeSH:Pulmonary Fibrosis
HPO:Pulmonary fibrosis

Primary Outcomes

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

Measure: Changes in forced vital capacity (FVC)

Time: 8 weeks

Secondary Outcomes

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

Measure: Changes in carbon monoxide dispersion (DLco%)

Time: 8 weeks

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

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

Time: 8 weeks

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

Measure: Changes in High resolution CT score

Time: 8 weeks

45 Evaluation of the Efficacy and Safety of Camostat Mesilate + Hydroxychloroquine Combination Therapy in Hospitalized Patients With Moderate COVID-19 Infection

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

NCT04338906 COVID Drug: Camostat Mesilate Drug: Placebo Drug: Hydroxychloroquine

Primary Outcomes

Measure: Not hospitalized

Time: day 14 from baseline

Secondary Outcomes

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

Time: day 14

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

Time: day 7 and day 14

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

Time: day 7 and day 14

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

Time: within 14 days

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

Time: within 14 days

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

Time: within 14 days

Measure: Duration of oxygen therapy

Time: within 28 days

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

Time: within 28 days

Measure: Duration of hospitalization

Time: within 28 days

Measure: All cause mortality

Time: day 28

46 Clinical Research of Human Mesenchymal Stem Cells in the Treatment of COVID-19 Pneumonia

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

NCT04339660 COVID-19 Biological: UC-MSCs Other: Placebo
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Improvement and recovery time of inflammatory and immune factors

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

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

Description: Evaluation of Pneumonia change

Measure: Blood oxygen saturation

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

Secondary Outcomes

Description: Marker for efficacy of treatment

Measure: Rate of mortality within 28-days

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

Description: Evaluation of Pneumonia change

Measure: Size of lesion area by chest imaging

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

Description: Marker of Immunology and inflammation

Measure: CD4+ and CD8+ T cells count

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

Description: Degree of infection

Measure: Peripheral blood count recovery time

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

Description: Indirect response to lung function

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

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

Description: Clearance time of COVID-19 in participant

Measure: COVID-19 nucleic acid negative time

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

47 Azithromycin Added to Hydrochloroquine in Patients Admitted to Intensive Care Due to Coronavirus Disease 2019 (COVID-19)- Randomised Controlled Trial

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

NCT04339816 COVID-19 Respiratory Failure Drug: Azithromycin Drug: Hydroxychloroquine Drug: Placebo
MeSH:Respiratory Insufficiency

Primary Outcomes

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

Measure: Proportion of alive patients free off mechanical ventilation

Time: 14 days after enrolment

Secondary Outcomes

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

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

Time: 14 days

Description: Length of stay in intensive care unit

Measure: ICU LOS

Time: 28 days

Description: Proportion of patients who died by day 28

Measure: Mortality28

Time: 28 days

Description: Proportion of patients who died by day 90

Measure: Mortality90

Time: 90 days

48 Hydroxychloroquine for the Treatment of Mild COVID-19 Disease

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

NCT04340544 COVID-19 Drug: Hydroxychloroquine Drug: Placebo

Primary Outcomes

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

Time: 28±2 days

Secondary Outcomes

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

Time: 28±2 days

Measure: All-cause mortality within 28 days

Time: 28±2 days

Other Outcomes

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

Time: 28±2 days

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

Time: 28±2 days

49 A Phase 1b/2, Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study to Evaluate the Safety and Efficacy of TJ003234 in Subjects With Severe Coronavirus Disease 2019 (COVID-19)

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

NCT04341116 Coronavirus Disease 2019 COVID-19 Drug: TJ003234 Drug: Placebo
MeSH:Coronavirus Infections

Primary Outcomes

Description: 8-category ordinal scale

Measure: Proportion (%) of subjects experiencing deterioration in clinical status

Time: Changes from baseline on Day 14

Description: Per CTCAE

Measure: Treatment Emergent Adverse Events

Time: Up to 30 days after drug administration

Secondary Outcomes

Description: 8-category ordinal scale

Measure: Proportion (%) of subjects experiencing deterioration in clinical status

Time: Changes from baseline on Day 7 and Day 30

Description: 8-category ordinal scale: 8, Death; 7, ventilation in addition to extracorporeal membrane oxygen (ECMO), continuous renal replacement therapy (CRRT) or pressors; 6, Intubation and mechanical ventilation; 5, non-invasive mechanical ventilation (NIV) or high-flow oxygen; 4,Oxygen by mask or nasal prongs; 3, Hospitalization without oxygen supplementation; 2, Limitation of activities, discharge from hospital; and 1, No limitation of activities, discharge from hospital

Measure: Clinical status

Time: On Day 7, Day 14 and Day 30

Description: 8-category ordinal scale: 8, Death; 7, ventilation in addition to extracorporeal membrane oxygen (ECMO), continuous renal replacement therapy (CRRT) or pressors; 6, Intubation and mechanical ventilation; 5, non-invasive mechanical ventilation (NIV) or high-flow oxygen; 4,Oxygen by mask or nasal prongs; 3, Hospitalization without oxygen supplementation; 2, Limitation of activities, discharge from hospital; and 1, No limitation of activities, discharge from hospital

Measure: Improvement in clinical status

Time: On Day 7, Day 14 and Day 30

Description: The score is based on six different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems. A higher score predicts a worse clinical outcome.

Measure: Sequential Organ Failure Assessment (SOFA) score

Time: On Day 7 and Day 14

Measure: Change from baseline in PaO2/ FiO2

Time: On Day 7 and Day 14

Description: Defined as SpO2≥94% sustained minimum 24 hours

Measure: Length of time to normalization of oxygen saturation

Time: Up to 30 days after drug administration

Measure: Change from baseline in percentage of subjects requiring mechanical ventilation

Time: On Day 7 and Day 14

Measure: Change from baseline in Glucocorticoid use

Time: On Day 7 and Day 14

Measure: Mortality rate from any cause

Time: Up to 30 days after drug administration

Measure: Length of hospitalization

Time: Up to 30 days after drug administration

Measure: Change from baseline in D-dimer

Time: On Day 7 and Day 14

Measure: Serum concentration of TJ003234

Time: Day 1 predose, Day 1 End of Infusion, Day 7 and Day 14

Measure: Incidence and titer of anti-drug antibodies (ADA)

Time: Day 1 predose, Day 14

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

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

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

Primary Outcomes

Measure: Occurrence of adverse reactions

Time: 0-14 days post vaccination

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

Time: 28 days post vaccination

Measure: Neutralizing antibody response to SARS-CoV-2

Time: 28 days post vaccination

Secondary Outcomes

Measure: Occurrence of adverse events

Time: 0-28 days post vaccination

Measure: Occurrence of serious adverse reaction

Time: 0-6 months post vaccination

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

Time: 0, 14 days and 6 months post vaccination

Measure: Neutralizing antibody response to SARS-CoV-2

Time: 0 and 6 months post vaccination

Measure: Neutralizing antibody response to Ad5-vector

Time: 0, 28 days and 6 months post vaccination

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

Time: 0 and 28 days post vaccination

51 Randomized Controlled Trial of Hydroxychloroquine Versus Placebo for the Treatment of Adult Patients With Acute Coronavirus Disease 2019 - COVID-19

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

NCT04342221 COVID-19, Hydroxychloroquine Sulfate Drug: Hydroxychloroquine Sulfate Drug: Placebo

Primary Outcomes

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

Measure: Effect of HCQ on in vivo viral clearance

Time: 6 months

Other Outcomes

Measure: In-hospital mortality

Time: 60 days

Measure: All-cause mortality

Time: 60 days

Measure: Proportion requiring non-invasive or invasive ventilation

Time: 6 months

Measure: Proportion admitted to ICU

Time: 6 months

Measure: Duration of hospitalization

Time: 6 months

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

Time: 6 months

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

Time: 6 months

52 A Double-blind, Placebo-controlled Clinical Trial of Fluvoxamine for Symptomatic Individuals With COVID-19 Infection

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

NCT04342663 COVID 19 Coronavirus Drug: Fluvoxamine Drug: Placebo
MeSH:Infection Coronavirus Infections

Primary Outcomes

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

Measure: Time to clinical worsening

Time: RCT (approximately 15 days)

Secondary Outcomes

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

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

Time: RCT (approximately 15 days)

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

Measure: clinical deterioration measured by number of days

Time: RCT (approximately 15 days)

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

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

Time: RCT (approximately 15 days)

53 Pyridostigmine in Patients With Severe Acute Respiratory Syndrome Secondary to SARS-CoV-2 Infection

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

NCT04343963 COVID-19 SARS-CoV-2 Drug: Pyridostigmine Bromide Drug: Placebo
MeSH:Infection

Primary Outcomes

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

Measure: Critical condition or death

Time: 28 days

Description: Kinetics of circulating IL-6

Measure: IL-6

Time: 14 days in-hospital, hospital discharge, or death

54 A Randomized Placebo-controlled Safety and Dose-finding Study for the Use of the IL-6 Inhibitor Clazakizumab in Patients With Life-threatening COVID-19 Infection

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

NCT04343989 COVID-19 Drug: Clazakizumab 25 mg Drug: Clazakizumab 12.5 mg Other: Placebo
MeSH:Infection

Primary Outcomes

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

Time: 60 days

Secondary Outcomes

Measure: Cumulative incidence of intubation

Time: 14 days

Measure: Time to extubation

Time: 14 days

Measure: Length of ICU stay

Time: 14 days

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

Time: 14 days

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

Measure: Patient Survival

Time: 28 days

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

Measure: Patient Survival

Time: 60 days

55 Early Infusion of Vitamin C for Treatment of Novel Coronavirus Acute Lung Injury (EVICT-CORONA-ALI)

This study will test to see if a 72-hour intravenous vitamin C infusion protocol (100 mg/kg every 8 hours) in patients with hypoxemia and suspected COVID-19 will reduce the lung injury caused by the SARS-Cov-2.

NCT04344184 COVID-19 Lung Injury, Acute Drug: L-ascorbic acid Other: Placebo
MeSH:Lung Injury Acute Lung Injury Respiratory Distress Syndrome, Adult Wounds and Injuries

Primary Outcomes

Description: Documented days free off mechanical ventilation the first 28 days post enrollment

Measure: Number of ventilator-free days

Time: Up to 28 days

Secondary Outcomes

Description: Mortality at 28-days by all causes

Measure: All-cause-mortality

Time: Up to 28 days

Description: Number of days free of acute inflammation (defined as CRP >= 10 mg/L)

Measure: Acute-inflammation-free days

Time: Up to 28 days

Description: Number of days that the participant is free of organ failure in ALL of the following organ systems: Cardiovascular, Respiratory, Neurological, Liver, Bone marrow organ, Renal

Measure: Organ-failure-free days

Time: Up to 1 year

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

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

NCT04346368 Coronavirus Disease 2019 (COVID-19) Biological: BM-MSCs Biological: Placebo
MeSH:Coronavirus Infections

Primary Outcomes

Description: Evaluation of pneumonia improvement

Measure: Changes of oxygenation index (PaO2/FiO2)

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

Description: Proportion of participants with treatment-related adverse events

Measure: Side effects in the BM-MSCs treatment group

Time: Baseline through 6 months

Secondary Outcomes

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

Measure: Clinical outcome

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

Description: days of the patients in hospital

Measure: Hospital stay

Time: Baseline through 6 months

Description: Evaluation of pneumonia improvement

Measure: CT Scan

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

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

Measure: Changes in viral load

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

Description: Immunological status

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

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

Description: Marker for efficacy

Measure: Rate of mortality within 28-days

Time: From baseline to day 28

Description: Markers of Infection

Measure: Changes of C-reactive protein

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

57 BHV3500-203: Double-Blind, Randomized, Placebo Controlled, Safety and Efficacy Trial of Vazegepant (BHV-3500) Intranasal (IN) for Hospitalized Patients With COVID-19 Requiring Supplemental Oxygen

The purpose of this study is to determine if a CGRP receptor antagonist may potentially blunt the severe inflammatory response at the alveolar level, delaying or reversing the path towards oxygen desaturation, ARDS, requirement for supplemental oxygenation, artificial ventilation or death in patients with COVID-19 on supplemental oxygen.

NCT04346615 COVID-19 Infection Drug: Vazegepant (BHV-3500) Drug: Placebo

Primary Outcomes

Description: Efficacy will be measured by examining the percentage of subjects reported as being in each category of a 6-point, ordinal, severity rating scale 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 evaluate efficacy of vazegepant (BHV-3500) compared with placebo in subjects hospitalized with COVID-19 infection requiring supplemental oxygen, using a 6-point ordinal scale.

Time: Baseline to Day 15

Secondary Outcomes

Measure: The number of unique subjects alive and off of oxygen. These are subjects in categories 5 or 6 of the 6-point ordinal scale being used as the primary endpoint.

Time: Baseline to Day 29

Measure: A subject requiring initiation of invasive mechanical ventilation, non-invasive ventilation, or a high flow nasal cannula is a subject that has any eCRF showing the use of any such device on any day.

Time: Baseline to Day 60

Measure: The number of unique subjects admitted to an ICU verse those not admitted.

Time: Baseline to Day 60

Measure: Subjects are alive and respiratory-failure free if they are categorized as being in categories 3, 4, 5 or 6 of the 6-point ordinal scale being used as the primary endpoint.

Time: Baseline to Day 60

Measure: Subjects are alive and free of either invasive mechanical ventilation or non-invasive ventilation if they are categorized as being in categories 4, 5 or 6 of the 6-point ordinal scale being used as the primary endpoint.

Time: Baseline to Day 60

Measure: Efficacy on Day 29 will be evaluated using the same 6-point severity scales that is used at Day 15.

Time: Baseline at Day 15 and at Day 29

Measure: Time to improvement of one category on the 6-point severity scale will be determined as the number of days from baseline to the first day that an eCRF indicates a one category improvement in the scale.

Time: Baseline to Day 60

Measure: A 48-hour improvement in SpO2/FiO2 ratio consists of two consecutive days where the case report forms show a clinically meaningful increase from baseline.

Time: Baseline to Day 60

Measure: The time to improvement in the in the NEWS2 scale will be determined as the number of days from baseline to the first eCRF that shows an improvement.

Time: Baseline to Day 29

Measure: A score < 2 for 24 hours on the NEWS2 scale consists of a day where all of the reported NEWS2 scores are < 2.

Time: Baseline to Day 29

Measure: The change in NEWS2 scores will be determined as the change from baseline at Day 15 and at Day 29.

Time: Baseline at Day 15 and at Day 29.

Measure: The number of unique subjects alive and off of oxygen.

Time: Baseline to Day 60

Measure: The percentage of subjects discharged to home on supplemental oxygen will determined from the unique number of subjects have eCRF pages indicating they were discharged to home while still on supplemental oxygen.

Time: Baseline to Day 60

Measure: A day with a resting respiratory rate > 24 is a day in which all eCRFs collected for a subject indicate observed respiratory rates > 24 breaths per minute.

Time: Baseline to Day 29

Measure: A day with supplemental oxygen is one in which any case report form collected on that day indicates the use of any amount of supplemental oxygen.

Time: Baseline to Day 29

Measure: Time to saturation greater than or equal to 90% on room air is measured by the number of days from baseline to the first day on which an eCRF indicates saturation greater than or equal to 90% without any supplemental oxygenation.

Time: Baseline to Day 60

Measure: A ventilator free day is a day in which all of the eCRFs collected indicate that the subject was not using a ventilator.

Time: Baseline to Day 29

Measure: SOFA scores will be determined from eCRFs. Values will be determined for subjects at admission to an ICU and for all subjects still in an ICU at the end of the study (Day 29).

Time: Baseline to Day 29

Measure: The number of days of hospitalization will be determined from eCRFs. A hospitalization day is any day that it is shown that a subject spent at least spent part of the day in a hospital.

Time: First day of hospital admission to discharge from hospital (evaluated from Baseline to Day 60)

Measure: Time to fever resolution, without antipyretics, during two contiguous days .

Time: Screening to 48 hours fever free

Measure: The number of deaths, SAEs, severe AEs and Grade 3 or 4 laboratory abnormalities will be tabulated as the number of unique subjects meeting those criteria.

Time: Screening to Day 60

Measure: The incidence of severe or life-threatening bacterial, invasive fungal, or opportunistic infections will be tabulated as the number of unique subjects, reported in eCRFs, as having these conditions at any point in the study

Time: Screening to day 60

Measure: The incidence of intranasal administration reactions will be tabulated, from eCRFs, as the number of unique subjects having such a condition at any point in the study.

Time: Baseline to Day 60

Measure: The percentage of subjects who develop significant renal disease.

Time: Baseline to Day 60

58 Use and Dosage of Hydroxychloroquine and Chloroquine to Convert Real Time Polymerase Chain Reaction (RT-PCR) Positive Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Coronavirus Infectious Disease 2019 (COVID-19) Patients to RT- PCR-Negative as a Means to Reduce Hospitalization Rate

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

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

Primary Outcomes

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

Measure: RT-PCR negative status

Time: 6-7 days

Secondary Outcomes

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

Measure: Progression of symptoms

Time: 7 days

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

Measure: Development of Symptoms

Time: 7 days

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

Measure: Adverse events

Time: 7 days

59 Proof of Concept, Multicentre, Parallel, Randomized, Double-blind Clinical Trial to Assess the Safety and Efficacy of Nitazoxanide 600 mg Compared to Placebo in the Treatment of Hospitalized Patients With COVID-19 in Moderate Condition.

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

NCT04348409 COVID-19 Drug: Nitazoxanide Tablets Drug: Placebo

Primary Outcomes

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

Measure: Viral load

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

Secondary Outcomes

Description: Time to wean off oxygen supplementation

Measure: Evolution of acute respiratory syndrome

Time: 21 days

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

Measure: Change in Clinical Condition

Time: 21 days

Description: Time to be discharged from hospital

Measure: Hospital discharge

Time: 21 days

Description: Evaluation of change in acute respiratory syndrome

Measure: Rate of mortality within 21-days

Time: 21 days

Description: Evaluation of change in acute respiratory syndrome

Measure: Need of mechanical ventilation

Time: 21 days

60 A Phase 2 Randomized Single-Blind Study to Evaluate the Activity and Safety of Low Dose Oral Selinexor (KPT-330) in Patients With Severe COVID-19 Infection

The main purpose of this study is to evaluate the activity of low dose oral selinexor (KPT-330) and to evaluate the clinical recovery, the viral load, length of hospitalization and the rate of morbidity and mortality in participants with severe COVID-19 compared to placebo.

NCT04349098 Coronavirus Infection Drug: Selinexor Other: Placebo
MeSH:Infection Communicable Diseases Coronavirus Infections Severe Acute Respiratory Syndrome

Primary Outcomes

Measure: Percentage of Participants with at Least a 2 Point Improvement in the Ordinal Scale

Time: Baseline to Day 14

Secondary Outcomes

Measure: Time to Clinical Improvement (TTCI)

Time: Up to Day 28

Measure: Overall Death Rate

Time: Day 14, Day 28

Measure: Rate of Mechanical Ventilation

Time: Up to Day 28

Measure: Time to Mechanical Ventilation

Time: Up to Day 28

Measure: Overall Survival

Time: Up to Day 28

Measure: Time to Improvement (2 points) in Clinical Measures Using the Ordinal Scale

Time: Baseline, Day 28

Measure: Time to Intensive Care Unit (ICU) Admission

Time: Up to Day 28

Measure: Rate of Intensive Care Unit (ICU) Admission

Time: Up to Day 28

Measure: Length of Stay in Hospital

Time: Up to Day 28

Measure: Percentage of Participants Discharged from Hospital

Time: Up to Day 28

Measure: Length of Stay in Intensive Care Unit (ICU)

Time: Up to Day 28

Measure: Duration of Oxygen Supplementation

Time: Up to Day 28

Measure: Duration of Mechanical Ventilation

Time: Up to Day 28

Measure: Time to Clinical Improvement in Participants ≤ 70 Years Old

Time: Up to Day 28

Measure: Time to Clinical Improvement in Participants > 70 Years Old

Time: Up to Day 28

Measure: Time to Clinical Improvement in Participants with Pre-existing Diseases

Time: Up to Day 28

Measure: Change in Oxygenation Index

Time: Up to Day 28

Measure: Time to Improvement of One Point Using WHO Ordinal Scale Improvement

Time: Up to Day 28

Measure: Percentage of Participants Experiencing WHO Ordinal Scale Improvement of >1 point

Time: Up to Day 28

Measure: Change from Baseline in C-reactive protein (CRP) Levels

Time: Up to Day 28

Measure: Change from Baseline in Ferritin Levels

Time: Up to Day 28

Measure: Change from Baseline in Lactate Dehydrogenase (LDH) Levels

Time: Up to Day 28

Measure: Changes from Baseline in Blood Plasma Cytokines Levels

Time: Up to Day 28

Measure: Number of Participants with Adverse Events (AE)

Time: From start of study drug administration up to Day 28

61 Value of Early Treatment With Polyvalent Immunoglobulin in the Management of Acute Respiratory Distress Syndrome Associated With SARS-CoV-2 Infections

As of 30/03/2020, 715600 people have been infected with COVID-19 worldwide and 35500 people died, essentially due to respiratory distress syndrome (ARDS) complicated in 25% of the with acute renal failure. No specific pharmacological treatment is available yet. The lung lesions are related to both the viral infection and to an intense inflammatory reaction. Because of it's action, as an immunomodulatory agent that can attenuate the inflammatory reaction and also strengthen the antiviral response, it is proposed to evaluate the effectiveness and safety of intravenous immunoglobulin administration (IGIV) in patients developing ARDS post-SARS-CoV2. IGIV modulates immunity, and this effect results in a decrease of pro-inflammatory activity, key factor in the ARDS related to the COVID-19. It should be noted that IGIV is part of the treatments in various diseases such as autoimmune and inflammatory diffuse interstitial lung diseases. In addition, they have been beneficial in the post-influenza ARDS but also have been in 3 cases of post-SARS-CoV2 ARDS. IGIV is a treatment option because it is well tolerated, especially concerning the kidney. These elements encourage a placebo-controlled trial testing the benefit of IGIV in ARDS post-SARS-CoV2.

NCT04350580 Acute Respiratory Distress Syndrome COVID-19 Drug: Human immunoglobulin Drug: Placebo
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Description: Sum of the days the patient did not receive VM, but if death occurs before D28, the score is zero

Measure: Ventilator-free days

Time: 28 days

Secondary Outcomes

Measure: Mortality

Time: 28 and 90 days

Description: Used to determine the extent of a person's organ function or rate of failure, from 0 to 24, with severity increasing the higher the score

Measure: Sequential Organ Failure Assessment Score

Time: Days 1, 3, 7, 14, 21 and 28

Description: Ratio of arterial oxygen partial pressure (PaO2 in mmHg) to fractional inspired oxygen (FiO2 expressed as a fraction, not a percentage)

Measure: P/F ratio

Time: Days 1, 3, 7, 14, 21 and 28

Measure: Lung compliance

Time: Days 1, 3, 7, 14, 21 and 28

Description: Severity scoring of lung oedema on the chest radiograph

Measure: Radiological score

Time: Days 1, 3, 7, 14, 21 and 28

Description: Concentration in mg/L

Measure: Biological efficacy endpoints - C-reactive protein

Time: Days 1, 3, 7, 14, 21 and 28

Description: Concentration in microgram/L

Measure: Biological efficacy endpoints - Procalcitonin

Time: Days 1, 3, 7, 14, 21 and 28

Description: Number of CD4 HLA-DR+ and CD38+, CD8 lymphocytes

Measure: Immunological profile

Time: Up to 28 days

Description: Use of corticosteroids, antiretroviral, chloroquine

Measure: Number of patients using other treatments for COVID-19 related ARDS

Time: Up to 28 days

Measure: Occurrence of deep vein thrombosis or pulmonary embolism

Time: 28 days

Measure: Total duration of mechanical ventilation, ventilatory weaning and curarisation

Time: 28 days

Description: Divided in 3 stages, with higher severity of kidney injury in higher stages

Measure: Kidney Disease: Improving Global Outcomes (KDIGO) score and need for dialysis

Time: 28 days

Description: Kidney failure, hypersensitivity with cutaneous or hemodynamic manifestations, aseptic meningitis, hemolytic anemia, leuko-neutropenia, transfusion related acute lung injury (TRALI)

Measure: Occurrence of adverse event related to immunoglobulins

Time: 28 days

Description: Medical research council sum score on awakening

Measure: Occurrence of critical illness neuromyopathy

Time: Up to 28 days

Description: Radiological and clinical context associated with a bacteriological sampling in culture of tracheal secretions, bronchiolar-alveolar lavage or a protected distal sampling

Measure: Occurrence of ventilator-acquired pneumonia

Time: Up to 28 days

62 An International, Multicenter, Randomized, Double-blind, Placebo-controlled, Phase III Study Evaluating the Efficacy and Safety of Dapagliflozin in Respiratory Failure in Patients With COVID-19

This is an international, multicenter, parallel-group, randomized, double-blind, placebo controlled, study in hospitalized adult patients with COVID-19 in the US and other countries with high prevalence of COVID-19. The study is evaluating the effect of dapagliflozin 10 mg versus placebo, given once daily for 30 days in addition to background local standard of care therapy, in reducing disease progression, complications, and all-cause mortality.

NCT04350593 COVID-19 Drug: Dapagliflozin 10 MG Drug: Placebo
MeSH:Respiratory Insufficiency

Primary Outcomes

Description: Respiratory decompensation New or worsening congestive HF Requirement for vasopressor therapy and/or inotropic or mechanical circulatory support Ventricular tachycardia or fibrillation lasting at least 30 seconds and/or associated with hemodynamic instability or pulseless electrical activity, or resuscitated cardiac arrest Initiation of renal replacement therapy

Measure: Time to first occurrence of either death from any cause or new/worsened organ dysfunction through 30 days of follow up, defined as at least one of the following:

Time: Randomization through Day 30

Secondary Outcomes

Description: Time to death from any cause Time to new/worsened organ dysfunction (as defined in the primary outcome measure) Clinical status at Day 30 for patients still hospitalized and without any worsening organ dysfunction (using points 3 to 5 of a 7-point ordinal scale) Time to hospital discharge

Measure: Hierarchical composite outcome measures:

Time: Randomization through Day 30

Description: Time to hospital discharge

Measure: Time to hospital discharge

Time: Randomization through Day 30

Description: Total number of days alive, out of hospital, and/or free from mechanical ventilation

Measure: Total number of days alive, out of hospital, and/or free from mechanical ventilation

Time: Randomization through Day 30

Description: Total number of days alive, not in the ICU, and free from mechanical ventilation (as defined in the primary outcome measure)

Measure: Total number of days alive, not in the ICU, and free from mechanical ventilation (as defined in the primary outcome measure)

Time: Randomization through Day 30

Description: Time to death from any cause

Measure: Time to death from any cause

Time: Randomization through Day 30

Description: Time to new/worsened organ dysfunction

Measure: Time to new/worsened organ dysfunction

Time: Randomization through Day 30

Description: Time to acute kidney injury (defined as doubling of s-Creatinine compared to baseline)

Measure: Time to acute kidney injury (defined as doubling of s-Creatinine compared to baseline)

Time: Randomization through Day 30

63 A Phase 1, Double-blind, Randomized, Placebo-controlled, Sponsor-open, SAD and MAD Study in Healthy Subjects to Evaluate the Safety, Tolerability, and PK of Inhaled TD-0903, a Potential Treatment for ALI Associated With COVID-19

This is a phase 1 study in healthy subjects to evaluate the safety, tolerability and pharmacokinetics of single (Part A and B) and multiple (Part B) doses of inhaled TD-0903.

NCT04350736 Acute Lung Injury (ALI) Associated With COVID-19 Inflammatory Lung Conditions Associated With COVID-19 Drug: TD-0903 Drug: Placebo
MeSH:Lung Injury Acute Lung Injury Respiratory Distress Syndrome, Adult

Primary Outcomes

Description: Number and severity of treatment emergent adverse events

Measure: Safety and Tolerability of SAD of TD-0903: Adverse Events

Time: Day 1 to Day 8

Description: Number and severity of treatment emergent adverse events

Measure: Safety and Tolerability of MAD of TD-0903: Adverse Events

Time: Day 1 to Day 14

Secondary Outcomes

Description: Multiple PK variables of TD-0903 will be assessed during SAD and may include, but are not limited to: Area under the plasma concentration-time curve (AUC)

Measure: Pharmacokinetics (PK) of TD-0903 when given as a Single Ascending Dose (SAD): AUC

Time: Day 1 through Day 4

Description: Multiple PK variables of TD-0903 will be assessed during SAD and may include, but are not limited to: Maximum observed concentration (Cmax)

Measure: Pharmacokinetics (PK) of TD-0903 when given as a Single Ascending Dose (SAD): Cmax

Time: Day 1 through Day 4

Description: Multiple PK variables of TD-0903 will be assessed during SAD and may include, but are not limited to: Time to reach maximum observed concentration (Tmax)

Measure: Pharmacokinetics (PK) of TD-0903 when given as a Single Ascending Dose (SAD): Tmax

Time: Day 1 through Day 4

Description: Multiple PK variables of TD-0903 will be assessed during MAD and may include, but are not limited to: Area under the plasma concentration-time curve (AUC)

Measure: Pharmacokinetics (PK) of TD-0903 when given as a Multiple Ascending Dose (MAD): AUC

Time: Day 1 through Day 9

Description: Multiple PK variables of TD-0903 will be assessed during MAD and may include, but are not limited to: Maximum observed concentration (Cmax)

Measure: Pharmacokinetics (PK) of TD-0903 when given as a Multiple Ascending Dose (MAD): Cmax

Time: Day 1 through Day 9

Description: Multiple PK variables of TD-0903 will be assessed during MAD and may include, but are not limited to: Time to reach maximum observed concentration (Tmax)

Measure: Pharmacokinetics (PK) of TD-0903 when given as a Multiple Ascending Dose (MAD): Tmax

Time: Day 1 through Day 9

64 Use and Dosage of Hydroxychloroquine and Chloroquine to Convert Symptomatic RT-PCR Positive Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Coronavirus Infectious Disease 2019 (COVID-19) Patients to RT- PCR-Negative as a Means to Reduce Hospitalization Rate

To treat Pakistani patients with non-life threatening symptomatic SARS-CoV-2 infection with an intent to reduce burden on institutional healthcare services by determining efficacy of different chloroquine and hydroxychloroquine dosing regimens in controlling SARS-CoV-2 infection.

NCT04351191 Sars-CoV2 Symptomatic Condition Covid-19 Drug: Hydroxychloroquine Sulfate Regular dose Drug: Hydroxychloroquine Sulfate Loading Dose Drug: Chloroquine Drug: Placebo

Primary Outcomes

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

Measure: RT-PCR result

Time: 6th and 7th day

Secondary Outcomes

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

Measure: Progression of symptoms

Time: 7 days

Description: Death

Measure: Mortality

Time: 30 days

65 A Multi-Center, Adaptive, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy and Safety of Gimsilumab in Subjects With Lung Injury or Acute Respiratory Distress Syndrome Secondary to COVID-19 (BREATHE).

Study KIN-1901-2001 is a multi-center, adaptive, randomized, double-blind, placebo-controlled study to assess the efficacy and safety of gimsilumab in subjects with lung injury or acute respiratory distress syndrome (ARDS) secondary to COVID-19.

NCT04351243 Lung Injury or Acute Respiratory Distress Syndrome Due to COVID-19 Drug: Gimsilumab Drug: Placebo
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Lung Injury Syndrome Wounds and Injuries

Primary Outcomes

Description: Mortality at Day 43

Measure: Primary endpoint

Time: 43 days

Secondary Outcomes

Description: Subjects who die will be assigned "0" ventilator-free days

Measure: Number of ventilator-free days.

Time: Day 43

Measure: Number of days in the ICU

Time: Day 43

Measure: Number of days of inpatient hospitalization

Time: Day 43

Measure: Incidence of subjects who are alive and not on mechanical ventilation

Time: Days 15, 22, 29, and 43

66 RAndomized Clinical Trial in COvid19 Patients to Assess the Efficacy of the Transmembrane Protease Serine 2 (TMPRSS2) Inhibitor NAfamostat (RACONA Study)

RACONA is a prospective trial that will test the hypothesis that nafamostat can lower lung function deterioration and need for intensive care admission in COVID-19 patients. Design: Adult hospitalized COVID-19 patients will be randomized in a prospective double-blind randomized placebo-controlled study to test the clinical efficacy of nafamostat mesylate (administered intravenously) on top of best standard of care. Primary outcome measures: the time-to-clinical improvement, defined as the time from randomization to an improvement of two points (from the status at randomization) on a seven category ordinal scale or live discharge from the hospital, whichever comes first.

NCT04352400 COVID19 Drug: Nafamostat Mesilate Drug: Placebo

Primary Outcomes

Description: Time-to-clinical improvement (time from randomization to an improvement of two points (from the status at randomization) on a 7 category ordinal scale or live discharge from the hospital, whichever came first.

Measure: Time-to-clinical improvement

Time: day 1 until day 28

Secondary Outcomes

Description: Rate of patients showing improvement of 2 points in 7 category ordinal scale (with 7 points the worst)(PubMed ID: 32187464)

Measure: Responders

Time: day 1 until day 28

Description: Proportion of patients who will progress to critical illness/death

Measure: Critical or dead patients

Time: day 1 until day 28

Description: Change in pO2/FiO2 ratio over time

Measure: pO2/FiO2 ratio

Time: day 1 until day 28

Description: Change Sequential organ failure assessment score (SOFA score) over time. The Score ranges from 0 to 24 (with 24 the worst)(PubMed ID: 11594901)

Measure: SOFA score over time

Time: day 1 until day 28

Description: Duration of hospitalization in survivors (days)

Measure: Hospitalization

Time: day 1 until day 28

Description: Number of patients who require ventilation

Measure: Mechanical ventilation

Time: day 1 until day 28

Description: Duration of ventilation (days)

Measure: Mechanical ventilation duration

Time: day 1 until day 28

Description: Proportion of patients who develop arrhythmia, or myocardial infarction, or other cardiovascular disease not present at the baseline

Measure: Cardiovascular disease

Time: day 1 until day 28

67 A Randomized Phase 2/3 Trial of Hydroxychloroquine In Covid-19 Kinetics

To test if the medication Hydroxychloroquine will decrease the amount of virus(as measured by PCR) , 7 days after initiation of therapy compared to control patients receiving placebo. The study design is a randomized (5 days of medication v. 5 days of placebo) clinical trial initiated immediately after diagnosis in ambulatory health care workers at University of South Alabama Health, or in ambulatory USA patients. At 7 days after enrollment another nasopharyngeal swab will be taken to measure if the virus is still present. At 10 weeks we will measure immunity from Covid-19 using a single blood sample. It is a phase 2/3 clinical trial.

NCT04353271 Covid 19 Corona Virus Infection Drug: Hydroxychloroquine Other: Placebo
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome

Primary Outcomes

Description: Nasopharyngeal swab PCR measurement of viral load expressed as the % of negative PCR swabs

Measure: Percentage of virus free subjects

Time: 7 days after initiation of trial

Description: Participants will self-report disease severity status as one of the following 5 options; no COVID19 illness (score of 1), COVID19 illness with no hospitalization (score of 2), or COVID19 illness with hospitalization (score of 3), or Covid 19 with care requiring hospitalization (score of 4), or Covid 19 with death (Score of 5) .

Measure: Disease severity

Time: 6 days

Secondary Outcomes

Description: Number of subjects in each arm who are hospitalized for Covid 19 infection

Measure: Incidence of hospitalization

Time: 14 days

Description: Number of subjects in each arm who die secondary to Covid-19 infection

Measure: Incidence of Death

Time: 70 Days (10 weeks)

Description: Number of subjects in each arm who have confirmed Covid-19 infection

Measure: Incidence of confirmed SARS-CoV-2 Detection

Time: 14 days

Description: Number of subjects in each arm who discontinue or withdraw medication use for any reason

Measure: Incidence of all-cause study medication discontinuation or withdrawal

Time: 14 days

Description: Blood tests to determine level of immunity in each subject

Measure: Immunity to Covid-19

Time: 70 days (10 weeks)

68 The Effect of Camostat Mesylate on COVID-19 Infection in Ambulatory Patients: An Investigator-Initiated Randomized, Placebo-Controlled, Phase IIa Trial

The rationale of the present clinical trial is that an orally available drug given to outpatients that could reduce the viral burden in the upper respiratory tract could forestall complications of SARS-CoV-2 infection and reduce transmission from one infected individual to another.

NCT04353284 COVID-19 Drug: Camostat Mesilate Other: Placebo

Primary Outcomes

Description: To determine whether camostat mesylate reduces SARS-COV-2 viral load in early COVID-19 disease, change from baseline to day 2 in respiratory (oropharyngeal swab RT-PCR) log10 viral load will be assessed.

Measure: Change in SARS-COV-2 viral load

Time: 2 days

Secondary Outcomes

Description: To determine whether camostat mesylate reduces SARS-COV-2 viral load in early COVID-19 disease, change from baseline to day 7 in respiratory (oropharyngeal swab RT-PCR) log10 viral load will be assessed.

Measure: Change in SARS-COV-2 viral load

Time: 7 days

Description: Change in risk for a positive COVID-19 test at day 6 after enrollment will be assessed by analyzing the proportion of positive cases in each study arm.

Measure: Change in positive COVID-19 status

Time: 7 days

Description: Change of COVID-19 symptom severity from day 0 to day 6 will be assessed with the COVID-19 daily self score tool. Adapted from the FLU-PRO instrument, it consists of 39 items that are answered daily. Items 1-33 are Likert scale questions (rated 0-4) where 0 = not at all and 4 = very much. These items are summed to score the severity of symptoms- where a total score of 132 would indicate the greatest severity of symptoms and a score of 0 would indicate no severity of symptoms. Items 34-38 are also Likert scale questions (rated 0-4) that measure the frequency of specific daily symptoms where 0 = 0 times and 4 = 4 times or more. These items are summed to score the frequency of symptoms- where the highest score for the frequency of symptoms (20) indicates the greatest burden of symptom frequency. The last question (39) asks patients for their highest temperature in Fahrenheit.

Measure: Change in COVID-19 symptom severity

Time: 7 days

Description: Change of COVID-19 symptom severity from day 0 to day 14 will be assessed with the COVID-19 daily self score tool. Adapted from the FLU-PRO instrument, it consists of 39 items that are answered daily. Items 1-33 are Likert scale questions (rated 0-4) where 0 = not at all and 4 = very much. These items are summed to score the severity of symptoms- where a total score of 132 would indicate the greatest severity of symptoms and a score of 0 would indicate no severity of symptoms. Items 34-38 are also Likert scale questions (rated 0-4) that measure the frequency of specific daily symptoms where 0 = 0 times and 4 = 4 times or more. These items are summed to score the frequency of symptoms- where the highest score for the frequency of symptoms (20) indicates the greatest burden of symptom frequency. The last question (39) asks patients for their highest temperature in Fahrenheit.

Measure: Change in COVID-19 symptom severity

Time: 14 days

Description: Change of COVID-19 symptom score from day 0 to day 6 will be assessed with the COVID-19 daily self score tool. Adapted from the FLU-PRO instrument, it consists of 39 items that are answered daily. Items 1-33 are Likert scale questions (rated 0-4) where 0 = not at all and 4 = very much. These items are summed to score the severity of symptoms- where a total score of 132 would indicate the greatest severity of symptoms and a score of 0 would indicate no severity of symptoms. Items 34-38 are also Likert scale questions (rated 0-4) that measure the frequency of specific daily symptoms where 0 = 0 times and 4 = 4 times or more. These items are summed to score the frequency of symptoms- where the highest score for the frequency of symptoms (20) indicates the greatest burden of symptom frequency. The last question (39) asks patients for their highest temperature in Fahrenheit.

Measure: Change in COVID-19 symptom frequency

Time: 7 days

Description: Change of COVID-19 symptom score from day 0 to day 14 will be assessed with the COVID-19 daily self score tool. Adapted from the FLU-PRO instrument, it consists of 39 items that are answered daily. Items 1-33 are Likert scale questions (rated 0-4) where 0 = not at all and 4 = very much. These items are summed to score the severity of symptoms- where a total score of 132 would indicate the greatest severity of symptoms and a score of 0 would indicate no severity of symptoms. Items 34-38 are also Likert scale questions (rated 0-4) that measure the frequency of specific daily symptoms where 0 = 0 times and 4 = 4 times or more. These items are summed to score the frequency of symptoms- where the highest score for the frequency of symptoms (20) indicates the greatest burden of symptom frequency. The last question (39) asks patients for their highest temperature in Fahrenheit.

Measure: Change in COVID-19 symptom frequency

Time: 14 days

Description: Change of COVID-19 symptom score from baseline to day 6 will be assessed with the COVID-19 daily self score tool. Adapted from the FLU-PRO instrument, it consists of 39 items that are answered daily. Items 1-33 are Likert scale questions (rated 0-4) where 0 = not at all and 4 = very much. These items are summed to score the severity of symptoms- where a total score of 132 would indicate the greatest severity of symptoms and a score of 0 would indicate no severity of symptoms. Items 34-38 are also Likert scale questions (rated 0-4) that measure the frequency of specific daily symptoms where 0 = 0 times and 4 = 4 times or more. These items are summed to score the frequency of symptoms- where the highest score for the frequency of symptoms (20) indicates the greatest burden of symptom frequency. The last question (39) asks patients for their highest temperature in Fahrenheit.

Measure: Change in body temperature

Time: 7 days

Description: Change of COVID-19 symptom score from baseline to day 14 will be assessed with the COVID-19 daily self score tool. Adapted from the FLU-PRO instrument, it consists of 39 items that are answered daily. Items 1-33 are Likert scale questions (rated 0-4) where 0 = not at all and 4 = very much. These items are summed to score the severity of symptoms- where a total score of 132 would indicate the greatest severity of symptoms and a score of 0 would indicate no severity of symptoms. Items 34-38 are also Likert scale questions (rated 0-4) that measure the frequency of specific daily symptoms where 0 = 0 times and 4 = 4 times or more. These items are summed to score the frequency of symptoms- where the highest score for the frequency of symptoms (20) indicates the greatest burden of symptom frequency. The last question (39) asks patients for their highest temperature in Fahrenheit.

Measure: Change in body temperature

Time: 14 days

Other Outcomes

Description: As an exploratory endpoint in comparing treatment to placebo groups, time to clinical improvement will be assessed.

Measure: Time to clinical improvement

Time: Up to 1 year

69 A Randomized, Double-blind, Two Arm, Placebo Controlled Clinical Trial to Evaluate the Efficacy and Safety of Mycobacterium w in Preventing COVID-19 in Subjects at Risk of Getting Infected With COVID-19.

This clinical trial is a randomized, blinded, two arms, placebo controlled, clinical trial to evaluate the safety and efficacy of Mycobacterium w in combination with standard care as per hospital practice to prevent COVID 19 in subjects at risk of getting infected with COVID 19.

NCT04353518 COVID-19 Drug: Suspension of heat killed (autoclaved) Mycobacterium w Other: Placebo
MeSH:Mycobacterium Infections

Primary Outcomes

Description: To compare proportion of subjects acquiring COVID-19 infection between two arms over the time till 8 weeks from administration of 1st dose

Measure: Number of subject acquiring COVID-19 infection

Time: From first dosing to week 1, week 2, week 4, week 8 or at any time during the study till 8 week post first dosing..

Secondary Outcomes

Description: Any AE / SAE observed during the study.

Measure: Incidence of Adverse Event and Serious Adverse Event (safety and tolerability)

Time: Till 8 weeks

Description: Whether administration of Mw prevents development of Upper Respiratory Tract Infection (URTI) symptoms in close contacts of COVID-19 patients.

Measure: Number of subject developing Upper Respiratory Tract Infection (URTI) symptoms

Time: From first dosing to week 1, week 2, week 4, week 8 or at any time during the study till 8 week post first dosing.

Description: Whether administration of Mw prevents development of severe COVID-19 infection.

Measure: Number of subject developing severe COVID-19 infection based on ordinal scale

Time: From first dosing to week 1, week 2, week 4, week 8 or at any time during the study till 8 week post first dosing

70 DAS181 for COVID-19: A Phase II/III, Multicenter, Randomized, Placebo-Controlled, Double-Blind Study

It is a multicenter, randomized, placebo-controlled, double-blind study. The study population is defined as subjects diagnosed with lower respiratory tract COVID-19 who require supplemental oxygen ≥2 LPM at the time of randomization.

NCT04354389 COVID-19 Drug: DAS181 Drug: Placebo

Primary Outcomes

Description: Percent of subjects improved (1 to 6 where higher score means worse outcome)

Measure: COVID-19 Clinical Classification (CCC)

Time: Day 14

Description: Percent of subjects return to room air (RTRA)

Measure: Return to room air (RTRA)

Time: Day 14

Secondary Outcomes

Description: time to Improved COVID-19 Clinical Classification 1 to 6 (where higher score means worse outcome)

Measure: Improved COVID-19 Clinical Classification

Time: Day 28

Description: Percent of subjects RTRA

Measure: Return To Room Air (RTRA)

Time: Day 10, 21, 28

Description: Time to

Measure: Death (all cause)

Time: Day 28

Description: Time to

Measure: SARS-CoV-2 RNA undetectable

Time: Day 28

Description: Percent of subjects discharge

Measure: Percent of subjects discharged

Time: Day 14, 21, 28

Description: Time to

Measure: Clinical Deterioration

Time: Day 28

71 Efficacy of Intravenous Almitrine in Reducing the Need for Mechanical Ventilation in Patients With Hypoxemic Acute Respiratory Failure Due to Covid-19-related Pneumonia: a Randomized Controlled Double-blind Study From the Skip-icu Consortium

The COVID-19 outbreak is associated with a surge in ICU bed requirement and substantial mortality (estimated between 0.5% and 3.6%). Admission in the intensive care unit (ICU) and need for mechanical ventilation is reportedly associated with an estimated hospital mortality of more than 30%. Furthermore, the surge in ICU bed requirement is a worldwide-shared issue, leading to sub-optimal ICU management. In acute respiratory failure due to COVID-19-related pneumonia, vasoplegia with vascular enlargement inside the lung lesions and dilation of small vessels seen on chest CT scan largely account for severe hypoxemia whose physiological response is hyperventilation leading to hypocapnia. Almitrine, initially described to reduce intrapulmonary shunt by enhancement of hypoxic pulmonary vasoconstriction in combination with inhaled nitric oxide (iNO), redistributes pulmonary blood flow from shunt areas to lung units with normal ventilation/perfusion (VA/Q) ratio. Low dose of intravenous almitrine (2 µg.kg-1.min-1) alone also improves oxygenation (without combination with iNO) by selective pulmonary vasoconstriction of precapillary pulmonary arteries perfusing lung areas exposed to a hypoxic challenge with a slight increase in mean arterial pulmonary. Therefore, our hypothesis is that 5 days of low dose of almitrine therapy may improve the ventilation-perfusion (VA/Q) ratio at a relatively early stage of this specific lung disease and limit respiratory worsening and subsequent need for mechanical ventilation.

NCT04357457 Covid 19 Hypoxemic Respiratory Failure Drug: Almitrine Drug: Placebo
MeSH:Pneumonia Respiratory Insufficiency
HPO:Pneumonia

Primary Outcomes

Description: Endotracheal intubation within 7 days after randomization Death will be considered as a failure (endotracheal intubation).

Measure: Rate of endotracheal intubation

Time: 7 days

Secondary Outcomes

Measure: 28-day mortality

Time: 28 days

Measure: In-hospital mortality

Time: 28-day

Measure: Number of ventilator-free days

Time: 28 days

Measure: Number of days in the ICU

Time: 28 days

Measure: Number of days in the hospital

Time: 28 days

Description: safety assessment: discontinuation rate of the treatment for arterial lactate more than 4 mmol/L, ALT/AST levels greater than 3 times the upper limit, and diagnosis of pulmonary arterial hypertension or acute cor pulmonale documented by echocardiography.

Measure: Discontinuation rate of the treatment

Time: 28 days

72 Use of a Medical Device, Kerecis Oral and Nasal Spray, for Treating the Symptoms of COVID-19 Via Application to the Naso- and Oropharyngeal Mucosa

Kerecis Oral and Nasal Spray is a Class I CE marked medical device manufactured by Kerecis hf (the "Device"). An 81-patient 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 81 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. 54 patients will be randomized into the Study Device group and 27 patients into the Control group. The Study Device group will be split into two with 27 patients administering the Device to both the oral and nasal passages and 27 patients to the oral only. Patients will administer Study Device or Control for 14 days and will have their symptoms recorded until no further symptoms are reported, up to a maximum of 28 days follow-up.

NCT04357990 COVID-19 Device: Kerecis Oral and Nasal Spray Other: Placebo

Primary Outcomes

Description: The number of days until participants report no symptoms, which they attribute to COVID-19, will be compared between groups. Symptoms include: Fever (38.0°C or higher), chills, dry cough, cough with rise, shortness of breath (rest), shortness of breath (Exercise), dyspnoea, sore throat, runny nose, headache, myalgia/bone pain, anorexia, nausea, vomiting, loss of smell, osteoporosis, abdominal pain, diarrhea, weakness.

Measure: Number of days until complete resolution of symptoms per group

Time: 28 days

Description: The number of participants admitted to hospital due to deterioration of their condition due to COVID-19 will be compared between groups.

Measure: Number of hospital admissions per group

Time: 28 days

Secondary Outcomes

Description: The number of days until participants report a reduction in symptoms, which they attribute to COVID-19, will be compared between groups. Symptoms include: Fever (38.0°C or higher), chills, dry cough, cough with rise, shortness of breath (rest), shortness of breath (Exercise), dyspnoea, sore throat, runny nose, headache, myalgia/bone pain, anorexia, nausea, vomiting, loss of smell, osteoporosis, abdominal pain, diarrhea, weakness.

Measure: Number of days until a reduction in symptoms per group

Time: 28 days

Description: The number of adverse events reported will be compared between groups.

Measure: Number of adverse events per group

Time: 28 days

73 A Multi-center, Randomized, Double-blinded, Placebo-controlled Study to Evaluate the Safety and Efficacy of Hydroxychloroquine Monotherapy and in Combination With Azithromycin in Patients With Moderate and Severe COVID-19 Disease

Two recent studies have suggested that in patients with Covid19, treatment with hydroxychloroquine may shorten the duration of symptoms and improve viral clearance, an effect that appears most pronounce when combined with azithromycin. Hydroxychloroquine treatment may inhibit viral nucleic acid-mediated activation of various innate immune pathways, as well as blockade of lysosomal functions in cell types relevant for viral entry and antigen presentation. The purpose of the study is to determine if oral hydroxychloroquine monotherapy, or in combination with azithromycin results in clinical benefit in patients hospitalized with COVID19 pneumonia.

NCT04358081 Pneumonia Drug: HCQ Drug: HCQ+AZT Drug: Placebo
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: To demonstrate in patients receiving standard of care that the percentage who achieve clinical response with hydroxychloroquine or hydroxychloroquine and azithromycin is superior to placebo at Day 15

Measure: Percentage of participants who achieve clinical response

Time: 15 days

Secondary Outcomes

Description: To demonstrate in patients receiving standard of care that the percentage with viral clearance at Day 15 with hydroxychloroquine or hydroxychloroquine and azithromycin is superior to placebo

Measure: Percentage of Participants with Viral Clearance

Time: 15 Days

Description: To assess in patients receiving standard of care the safety of hydroxychloroquine or hydroxychloroquine and azithromycin compared to placebo

Measure: Number of participants receiving hydroxychloroquine or hydroxychloroquine and azithromycin with adverse events of hydroxychloroquin or hydroxychloroquine and azithromycin compared to placebo

Time: 40 days

74 A Randomized, Double-blind, Two Arm, Controlled Clinical Trial to Compare the Efficacy and Safety of Mycobacterium w (Mw) Administered Along With Standard of Care Versus Placebo Administered Along With Standard of Care, in Adult, COVID 19 Positive Patients Hospitalized But Not Critically Ill.

This is a randomized, double blind, two arms, placebo controlled, clinical trial to study to evaluate the the safety and efficacy of Mycobacterium w in combination with standard of care versus placebo with standard of care for preventing the progression of COVID-19 disease and for reduction in transfer to ICU in COVID-19 infected patients admitted to the hospital.

NCT04358809 COVID-19 Drug: Suspension of heat killed (autoclaved) Mycobacterium w Other: Placebo
MeSH:Mycobacterium Infections Critical Illness

Primary Outcomes

Description: To compare the difference in proportion of patients with increased disease severity

Measure: Number of patients with increased disease severity

Time: From baseline to Day 3, Day 7, Day 14, Day 21, Day 28 or at any time during the study till 28 days post first dosing.

Secondary Outcomes

Description: To evaluate safety of Mw in COVID-19 patients admitted to hospital

Measure: Incidence of adverse events and serious adverse events (Safety)

Time: Till day 28

Description: To compare the proportion of patients discharged from hospital

Measure: Number of COVID-19 patients discharged from hospital

Time: From baseline to Day 3, Day 7, Day 14, Day 21, Day 28 or at any time during the study till 28 days post first dosing.

Description: To compare the proportion of patients transfer to ICU

Measure: Number of COVID-19 patients transfer to ICU

Time: From baseline to Day 3, Day 7, Day 14, Day 21, Day 28 or at any time during the study till 28 days post first dosing.

Description: To compare the proportion of patients with reduction in disease severity by 1 ordinal scale

Measure: Number of COVID-19 patients with reduction in disease severity by 1 ordinal scale

Time: From baseline to Day 3, Day 7, Day 14, Day 21, Day 28 or at any time during the study till 28 days post first dosing.

Description: To compare the proportion of symptom free patients

Measure: Number of of symptom free patients

Time: From baseline to Day 3, Day 7, Day 14, Day 21, Day 28 or at any time during the study till 28 days post first dosing.

75 Comparative Efficacy of Various Doses of Hydroxychloroquine in Pre-Exposure Prophylaxis for COVID 19 in Healthcare Personnel

Hydroxychloroquine has been approved by FDA as one of the treatment options for COVID 19.Healthcare personnel are amongst those at highest risk to contract the disease. Several health authorities are now recommending the use of hydroxychloroquine as pre-exposure prophylaxis is in health care personnel. Several studies are on going in this context. However there is a controversy regarding the dosage regimen. This drug has a half life of 22.4 days. In this study we will be comparing three different doses of Hydroxychloroquine and additionally have a control group in order to determine the efficacy of hydroxychloroquine as pre- exposure prophylaxis in healthcare personnel in various doses.

NCT04359537 COVID 19 Drug: Hydroxychloroquine Sulfate 200 MG Other: Placebo

Primary Outcomes

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

Measure: COVID-19-free survival in experimental arms compared to placebo

Time: 12 weeks

Secondary Outcomes

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

Measure: Incidence of confirmed SARS-COV-2 detection

Time: 12 weeks

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

Measure: Incidence of possible COVID-19 symptoms

Time: 12 weeks

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

Measure: Incidence of all-cause study medicine discontinuation

Time: 12 weeks

Description: Participants will self-report COVID-19 status on an ordinal scale as follows: No illness (score=1), Illness with outpatient observation (score=2), Hospitalization (or post-hospital discharge) (score=3), Hospitalization with ICU stay (score 4),Death from COVID 19(score=5) Possible scores range from 1-5 with higher scores indicating greater disease severity.

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

Time: 12 weeks

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

Measure: Incidence of Hospitalization for COVID-19 or death

Time: 12 weeks

Description: Outcome reported as the percent of participants experiencing any possible adverse events from Hydroxychloroquine

Measure: Incidence of study medication-related adverse events

Time: 12 weeks

76 A Randomized, Double-Blind, Placebo Controlled Trial to Evaluate the Efficacy and Safety of Nitazoxanide (NTZ) for Post Exposure Prophylaxis of COVID-19 and Other Viral Respiratory Illnesses (VRI) in Healthcare Workers

Trial to Evaluate the Efficacy and Safety of Nitazoxanide (NTZ) for Post Exposure Prophylaxis of COVID-19 and Other Viral Respiratory Illnesses (VRI) in Healthcare Workers

NCT04359680 COVID-19 Viral Respiratory Illnesses Drug: Nitazoxanide Drug: Placebo Dietary Supplement: Vitamin Super B-Complex

Primary Outcomes

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

Time: Up to 6 weeks

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

Time: Up to 6 weeks

77 Inhaled Aviptadil for the Treatment of Non-Acute Lung Injury in COVID-19

Brief Summary: SARS-CoV-2 virus infection is known to cause Lung Injury that begins as dyspnea and exercise intolerance, but may rapidly progress to Acute Respiratory Distress Syndrome and the need for mechanical ventilation. Mortality rates as high as 80% have been reported among those who develop ARDS, despite intensive care and mechanical ventilation. Patients with COVID-19 induced non-Acute Lung Injury who have demonstrated reduction in blood oxygenation, dyspnea, and exercise intolerance but do not require endotracheal intubation and mechanical ventilation will be treated with Aviptadil, a synthetic version of Vasoactive Intestinal Polypeptide (VIP) plus Standard of Care vs. placebo + Standard of Care. Patients will be randomized to intravenous Aviptadil will receive inhaled Aviptadil, 100 μg 3x daily vs. placebo 3x daily. The primary outcome will be progression to ARDS over 28 days. Secondary outcomes will include blood oxygenation as measured by pulse oximetry, dyspnea, exercise tolerance, and levels of TNFα IL-6 and other cytokines.

NCT04360096 SARS-CoV 2 COVID ARDS ALI Acute Lung Injury/Acute Respiratory Distress Syndrome (ARDS) Dyspnea Drug: Aviptadil (VIP) Drug: Placebo
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Dyspnea Lung Injury Wounds and Injuries
HPO:Dyspnea Respiratory distress

Primary Outcomes

Description: Progression to ARDS is defined as the need for mechanical ventilation

Measure: Progression to ARDS

Time: 28 days

Secondary Outcomes

Description: Blood PO2 as measured by pulse oximetry

Measure: Blood oxygenation

Time: 28 days

Description: 0 = no shortness of breath at all 0.5 = very, very slight shortness of breath = very mild shortness of breath = mild shortness of breath = moderate shortness of breath or breathing difficulty = somewhat severe shortness of breath = strong or hard breathing 7 = severe shortness of breath or very hard breathing 8 9 = extremely severe shortness of breath 10 = shortness of breath so severe you need to stop the exercise or activity

Measure: RDP Dsypnea Scale

Time: 28 days

Description: Distance walked in six minutes

Measure: Distance walked in six minutes

Time: 28 days

78 Randomized, Double-Blind, Placebo-Controlled Pilot Clinical Trial of the Safety and Efficacy of Telmisartan for the Mitigation of Pulmonary and Cardiac Complications in COVID-19 Patients

This study will enroll 40 symptomatic outpatients tested positive for Coronavirus 2019 (COVID-19). Patients to be randomized 1:1 to Telmisartan (40 mg) vs placebo to be administered orally once daily x 21 days. Daily, the study patients will be asked to keep a record of the severity of their fever, dyspnea and fatigue and take their blood pressure (BP) and temperature. Study visits to occur on day 1 (entry), day 4, day 10 and day 21. Oro-pharyngeal swabs, and approximately 25 cc of blood will be collected at each study visit for safety labs and for the evaluation of the renin-angiotensin system (RAS) system and for various blood biomarkers of inflammation, coagulation and fibrosis.

NCT04360551 COVID-19 Drug: Telmisartan 40mg Drug: Placebo

Primary Outcomes

Description: Based on a modified World Health Organization (WHO) COVID-19 7-point ordinal scale

Measure: Maximum clinical severity of disease

Time: Over the 21 day period of study

Secondary Outcomes

Description: Number of adverse events grade 2 and above utilizing the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0, November 2014

Measure: Incidence of treatment emergent adverse events

Time: Through study completion at day 21 of study

Description: Angiotensin I (AngI), AngII, Ang1-9 and Ang1-7

Measure: Renin angiotensin system peptides

Time: At each study time point (day 4, day 10, day 21)

Description: plasma biomarkers of organ function/coagulation, inflammation, leukocyte chemotaxis, tissue remodeling/fibrosis and immune exhaustion by Luminex multiplexing assays such as TNF-alpha, IL-6, CK-MB, Troponin I, Fractalkine, MCP-1, PD-1, TIMP-1

Measure: Plasma biomarkers

Time: At each study time point (day 4, day 10, day 21)

79 Double Blind, Placebo-controlled, Phase II Trial to Evaluate Safety and Efficacy of Allogenic Mesenchymal Stromal Cells MSV_allo for Treatment of Acute Respiratory Failure in Patients With COVID-19 Pneumonia (COVID_MSV)

Novel coronavirus COVID-19 has become a health emergency around the world. Since first patients were detected in Wuhan China, in December 2019, COVID-19 has spread quickly worldwide, being a severe threat to public health. Fever, dry cough, shortness of breath and breathing distress are the main characteristics of COVID-19 infection. Some patients develop overwhelming lung inflammation and acute respiratory failure, for which there is no specific therapy. Therefore, safe and effective treatment for COVID-19 pneumonia is utterly necessary, mainly in critical cases. Mesenchymal stem cells (MSCs) have been widely used in the immune-mediated inflammatory diseases. MSCs can regulate both innate and adaptive immunity by suppressing the proliferation, differentiation and activation of different cells. These immunomodulatory properties of MSCs support performance of the phase I/II, placebo- controlled, randomized MSCs for treatment of severe COVID-19 pneumonia.

NCT04361942 COVID-19 Pneumonia Biological: Mesenchymal Stromal Cells Other: Placebo
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Index of therapy success to preserve Intensive Care Hospitalization space

Measure: Proportion of patients who have achieved withdrawal of invasive mechanical ventilation

Time: 0-7 days

Description: To measure global success

Measure: Rate of mortality

Time: 28 days

Secondary Outcomes

Description: Index based in the 4 most relevant symptoms and signs: fever, shortness of bread, %Hemoglobin Saturation and PaO2 / FiO2

Measure: Proportion of patients who have achieved clinical response

Time: 0-7days

Description: Evaluation of pneumonia changes

Measure: Proportion of patients who have achieved radiological responses

Time: 0-28 days

Other Outcomes

Description: Haemogram and cell subpopulations

Measure: Blood white cell counts and their subpopulations.

Time: 0-180 days

Description: Lymphocyte profiles, CD3, CD19, CD16+CD56, CD4/CD8, Tregs

Measure: Cellular markers of inflammation

Time: 0-180 days

Description: IL-10, IL-6, IP-10, TNF-alpha

Measure: Cytokines and chemokines in peripheral blood

Time: 0-180 days

80 Performance Evaluation of BCG Vaccination in Healthcare Personnel to Reduce the Severity of SARS-COV-2 Infection in Medellín, Colombia, 2020

Until the first half of April, Colombia has more than 2,800 infected cases and a hundred deaths as a result of COVID-19, with Antioquia being the third department with the highest number of cases. Official records indicate that, in Colombia, the first case was diagnosed on March 6, 2020, corresponding to a patient from Italy. However, in conversations with several infectologists and intensivists from Medellín, it was agreed that clinical cases similar to the clinical presentation that is now recognized as COVID-19 had arisen since the end of 2019 when it was still unknown to everyone. The previous suggests that the virus was already circulating in the country since before March 6, 2020. But at that moment, there were no tools to make a clinical identification, nor to diagnose it from the laboratory's point of view. Considering as real the hypothesis that the infection has been circulating in the country since before the first official diagnosis, the question arises: Why does not the country still has the same healthcare and humanitarian chaos that countries such as Italy and Spain are suffering at this time? To answer this question may be that there are differences in vaccination rates with BCG (Bacille Calmette-Guérin or tuberculosis vaccine), which is significantly higher in Latin America compared to those in Europe. This finding could explain to some extent the situation in the country, since previous studies have shown the influence that this vaccine can have on the immune response against various other pathogens, including viruses. Among the population at risk of infection, health-care workers due to their permanent contact with patients are the population group with the highest risk of contracting SARS-Cov-2 and developing COVID-19 in any of its clinical manifestations, and currently there are no vaccines or proven preventive interventions available to protect them. For this reason, this research study aims to demonstrate whether the centennial vaccine against tuberculosis (BCG), a bacterial disease, can activate the human immune system in a broad way, allowing it to better combat the coronavirus that causes COVID-19 and, perhaps, prevents the complications that lead the patient to the intensive care unit and death. In the future, and if these results are as expected, they may be the basis for undertaking a population vaccination campaign that improves clinical outcomes in the general population.

NCT04362124 COVID-19 Biological: vaccine BCG Other: Placebo
MeSH:Infection

Primary Outcomes

Description: Incidence of COVID-19 cases confirmed or probable in the study population

Measure: Primary outcome

Time: From date of randomization to 360 day of the study

Secondary Outcomes

Description: Incidence of severe or critical infection in COVID-19 cases

Measure: Secondary outcome

Time: From date to diagnosis to 1 month after

Description: Lethality of the infection in both groups

Measure: Secondary outcome

Time: From date to diagnosis to 1 month after

Description: Assess the safety (frequency, seriousness, and severity of adverse events) of BCG vaccination

Measure: Secondary outcome

Time: From date of randomization to 7 day of the study

Description: Prevalence of SARS-Cov-2 infection

Measure: Secondary outcome

Time: At baseline evaluation

81 Phase 3 Randomized, Double-blind, Placebo-controlled Multi-center Study to Assess the Efficacy and Safety of Ruxolitinib in Patients With COVID-19 Associated Cytokine Storm (RUXCOVID)

This is a randomized, double-blind, placebo-controlled, 29-day, multicenter study to assess the efficacy and safety of ruxolitinib + standard-of-care (SoC) therapy, compared with placebo + SoC therapy, in patients aged ≥12 years with COVID-19 pneumonia.

NCT04362137 Covid-19 Drug: Ruxolitinib Drug: Placebo

Primary Outcomes

Description: Efficacy is measured by a composite endpoint of proportion of patients who die, develop respiratory failure [require mechanical ventilation], or require intensive care unit [ICU] care for the treatment of COVID-19.

Measure: Proportion of patients who die, develop respiratory failure [require mechanical ventilation] or require intensive care unit (ICU) care

Time: 29 days

Secondary Outcomes

Description: Clinical status is measured with the 9-point ordinal scale. The scoring is - Uninfected patients have a score 0 (no clinical or virological evidence of infection). - Ambulatory patients (not in hospital or in hospital and ready for discharge) can have a score 1 (no limitation of activities) or 2 (limitation of activities). - Hospitalized patients with mild disease can have score 3 (no oxygen therapy defined as SpO2 ≥ 94% on room air) or 4 (oxygen by mask or nasal prongs). - Hospitalized patients with severe disease can have score 5 (non-invasive ventilation or high-flow oxygen), 6 (intubation and mechanical ventilation) or 7 (ventilation + additional organ support - pressors, RRT (renal replacement therapy), ECMO (extracorporeal membrane oxygenation)). - Patients who die have a score 8.

Measure: Clinical status

Time: Day 15, Day 29

Description: Percentage of patients with at least two points improvement in clinical status on the 9-point ordinal scale.

Measure: Percentage of patients with at least two-point improvement from baseline in clinical status

Time: Baseline, Day 15, Day 29

Description: Percentage of patients with at least one point improvement in clinical status on the 9-point ordinal scale.

Measure: Percentage of patients with at least one-point improvement from baseline in clinical status

Time: Baseline, Day 15, Day 29

Description: Percentage of patients with at least one point deterioration in clinical status on the 9-point ordinal scale.

Measure: Percentage of patients with at least one-point deterioration from baseline in clinical status

Time: Baseline, Day 15, Day 29

Description: Time to improvement from baseline category to one less severe category of the 9-point ordinal scale.

Measure: Time to improvement in clinical status

Time: 29 days

Description: Mean change from baseline in the 9-point ordinal scale.

Measure: Mean change from baseline in the clinical status

Time: Baseline, Day 15, Day 29

Description: Mortality rate at Day 15 and at Day 29

Measure: Mortality rate

Time: Day 15, Day 29

Description: Proportion of patients requiring mechanical ventilation

Measure: Proportion of patients requiring mechanical ventilation

Time: 29 days

Description: Duration of hospitalization

Measure: Duration of hospitalization

Time: 29 days

Description: The time to discharge or to a National Early Warning Score 2 (NEWS2) of ≤2 and maintained for 24 hours whichever comes first. The NEWS2 is based on a simple aggregate scoring system in which a score is allocated to physiological measurements, already recorded in routine practice presentation or when a patient is being monitored in hospital. The score ranges from 0 (best) to 23 (worst).

Measure: Time to discharge or to a NEWS2 score of ≤2

Time: 29 days

Description: The National Early Warning Score 2 (NEWS2) is based on a simple aggregate scoring system in which a score is allocated to physiological measurements, already recorded in routine practice presentation or when a patient is being monitored in hospital. The score ranges from 0 (best) to 23 (worst).

Measure: Change from baseline in NEWS2 score

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

Description: Change from baseline in peripheral oxygen saturation / fraction of inspired oxygen ratio (SpO2/FiO2 ratio)

Measure: Change from baseline in SpO2/FiO2 ratio.

Time: Baseline, Day 15, Day 29

Description: No oxygen therapy is required if oxygen saturation is ≥ 94% on room air.

Measure: Proportion of patients with no oxygen therapy

Time: Day 15, Day 29

82 A Randomized, Controlled Clinical Trial to Test the Safety and Efficacy of Convalescent Donor Plasma to Treat COVID-19 in Hospitalized Adults

The purpose of this study is to test the safety and efficacy of convalescent donor plasma to treat COVID-19 in hospitalized adults in a randomized, placebo-controlled setting. The effect of convalescent plasma will be compared to placebo on clinical outcomes, measured using the COVID Ordinal Outcomes Scale at Day 15, among adults with COVID-19 requiring hospitalization.

NCT04362176 COVID-19 Coronavirus SARS-CoV-2 Biological: pathogen reduced SARS-CoV-2 convalescent plasma Biological: Placebo
MeSH:Coronavirus Infections

Primary Outcomes

Description: Death Hospitalized on invasive mechanical ventilation or ECMO 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:Day 15

Time: Study Day 15

Secondary Outcomes

Description: All-location, all-cause 14-day mortality

Measure: All-location, all-cause 14-day mortality

Time: Baseline to Study Day 14

Description: All-location, all-cause 28-day mortality

Measure: All-location, all-cause 28-day mortality

Time: Baseline to Study Day 28

Description: Death Hospitalized on invasive mechanical ventilation or ECMO 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 Day 3

Time: Baseline to Study Day 3

Description: Death Hospitalized on invasive mechanical ventilation or ECMO 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 Day 8

Time: Study Day 8

Description: Death Hospitalized on invasive mechanical ventilation or ECMO 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 Day 29

Time: Study Day 29

Description: Number of participants that died or received ECMO

Measure: Composite of death or receipt of ECMO through Day 28

Time: Baseline to Day 28

Description: Number of days without use of oxygen

Measure: Oxygen-free days through Day 28

Time: Baseline to Day 28

Description: Number of days without use of vasopressors

Measure: Vasopressor-free days through Day 28

Time: Baseline to Day 28

Description: Number of days without use of a ventilator

Measure: Ventilator-free days through Day 28

Time: Baseline to Day 28

Description: Number of days outside of ICU

Measure: ICU-free days through Day 28

Time: Baseline to Day 28

Description: Number of days outside of the hospital

Measure: Hospital-free days through Day 28

Time: Baseline to Day 28

Other Outcomes

Description: Number of participants with Acute kidney injury

Measure: Acute kidney injury

Time: Baseline to Day 28

Description: Number of participants requiring renal replacement therapy

Measure: Renal replacement therapy

Time: Baseline to Day 28

Description: Number of participants with documented venous thromboembolic disease (DVT or PE)

Measure: Documented venous thromboembolic disease (DVT or PE)

Time: Baseline to Day 28

Description: Number of Participants with myocardial infarction or ischemic stroke

Measure: Documented cardiovascular event (myocardial infarction or ischemic stroke)

Time: Baseline to Day 28

Description: Number of participants with transfusion reaction (fever/rash)

Measure: Transfusion reaction

Time: Baseline to Day 28

Description: Number of participants with transfusion related acute lung injury (TRALI)

Measure: Transfusion related acute lung injury (TRALI)

Time: Baseline to Day 28

Description: Number of participants with transfusion associated circulatory overload (TACO)

Measure: Transfusion associated circulatory overload (TACO)

Time: Baseline to Day 28

Description: Number of participants with transfusion related infection

Measure: Transfusion related infection

Time: Baseline to Day 28

83 A Randomized, Placebo-Controlled, Double-Blind, Single Center, Efficacy and Safety Study of Allogeneic HB-adMSCs for the Treatment of COVID-19

Hope Biosciences is conducting a research study of an investigational product called allogeneic adipose-derived mesenchymal stem cells (abbreviated as HB-adMSCs) as treatment for patients suspected to have COVID-19. The study purpose is to evaluate the safety and efficacy of four IV infusions of either placebo or HB-adMSCs in subjects with COVID-19.

NCT04362189 COVID-19 Drug: HB-adMSC Drug: Placebo

Primary Outcomes

Description: change from baseline in level of D-dimer (ng/mL)

Measure: D-dimer

Time: screening, day 0, 7, 10

Description: change from baseline in interleukin-6

Measure: Interleukin-6

Time: screening, day 0, 7, 10

Description: Change from baseline in C Reactive protein

Measure: C Reactive protein

Time: screening, day 0, 7, 10

Description: change from baseline oxygenation (%)

Measure: Oxygenation

Time: screening, day 0, 7, 10

Description: time to achieve negative PCR test results

Measure: PCR test SARS-CoV-2

Time: Day 0, 3, 7, 10

Secondary Outcomes

Description: Monitoring for changes in qt interval

Measure: EKG qt interval

Time: screening, day 0, 3, 7, 10

Description: change from baseline in leukocyte differential

Measure: Leukocyte differential

Time: screening, day 0, 7, 10

Description: change from baseline in TNF alpha

Measure: TNF alpha

Time: screening, day 0, 7, 10

Description: clinical lab evaluation of level of glucose in the blood (mg/dL)

Measure: Glucose

Time: screening, day 0, 7, 10

Description: clinical lab evaluation of level of calcium in the blood (mg/dL)

Measure: Calcium

Time: screening, day 0, 7, 10

Description: clinical lab evaluation of level of albumin in the blood (g/dL)

Measure: Albumin

Time: screening, day 0, 7, 10

Description: clinical lab evaluation of level of total protein in the blood (g/dL)

Measure: Total protein

Time: screening, day 0, 7, 10

Description: clinical lab evaluation of level of sodium in the blood (mol/L)

Measure: Sodium

Time: screening, day 0, 7, 10

Description: clinical lab evaluation of level of total carbon dioxide in the blood (mmol/L)

Measure: Total carbon dioxide

Time: screening, day 0, 7, 10

Description: clinical lab evaluation of level of potassium in the blood (mmol/L)

Measure: Potassium

Time: screening, day 0, 7, 10

Description: clinical lab evaluation of level of chloride in the blood (mmol/L)

Measure: Chloride

Time: screening, day 0, 7, 10

Description: clinical lab evaluation of level of BUN in the blood (mg/dL)

Measure: BUN

Time: screening, day 0, 7, 10

Description: clinical lab evaluation of level of creatinine in the blood (mg/dL)

Measure: Creatinine

Time: screening, day 0, 7, 10

Description: clinical lab evaluation of level of alkaline phosphatase in the blood (IU/L)

Measure: Alkaline phosphatase

Time: screening, day 0, 7, 10

Description: clinical lab evaluation of level of alanine aminotransferase in the blood (IU/L)

Measure: Alanine aminotransferase

Time: screening, day 0, 7, 10

Description: clinical lab evaluation of level of total bilirubin in the blood (mg/dL)

Measure: Total bilirubin

Time: screening, day 0, 7, 10

Description: clinical lab evaluation of level of white blood cells in the blood (x10^3/uL)

Measure: White blood cells

Time: screening, day 0, 7, 10

Description: clinical lab evaluation of level of red blood cells in the blood (x10^6/uL)

Measure: Red blood cells

Time: screening, day 0, 7, 10

Description: clinical lab evaluation of level of hemoglobin in the blood (g/dL)

Measure: Hemoglobin

Time: screening, day 0, 7, 10

Description: clinical lab evaluation of level of hematocrit in the blood (%)

Measure: Hematocrit

Time: screening, day 0, 7, 10

Description: clinical lab evaluation of level of mean corpuscular volume in the blood (fL)

Measure: Mean corpuscular volume

Time: screening, day 0, 7, 10

Description: clinical lab evaluation of level of mean corpuscular hemoglobin in the blood (pg)

Measure: Mean corpuscular hemoglobin

Time: screening, day 0, 7, 10

Description: clinical lab evaluation of level of mean corpuscular hemoglobin concentration in the blood (g/dL)

Measure: Mean corpuscular hemoglobin concentration

Time: screening, day 0, 7, 10

Description: clinical lab evaluation of level of red cell distribution width in the blood (%)

Measure: Red cell distribution width

Time: screening, day 0, 7, 10

Description: clinical lab evaluation of level of neutrophils in the blood (%)

Measure: Neutrophils

Time: screening, day 0, 7, 10

Description: clinical lab evaluation of level of lymphocytes in the blood (%)

Measure: Lymphs

Time: screening, day 0, 7, 10

Description: clinical lab evaluation of level of monocytes in the blood (%)

Measure: Monocytes

Time: screening, day 0, 7, 10

Description: clinical lab evaluation of level of eosinophils in the blood (%)

Measure: Eosinophils

Time: screening, day 0, 7, 10

Description: clinical lab evaluation of level of basophils in the blood (%)

Measure: Basophils

Time: screening, day 0, 7, 10

Description: clinical lab evaluation of level of absolute neutrophils in the blood (x10^3/uL)

Measure: Absolute neutrophils

Time: screening, day 0, 7, 10

Description: clinical lab evaluation of level of absolute lymphocytes in the blood (x10^3/uL)

Measure: Absolute lymphs

Time: screening, day 0, 7, 10

Description: clinical lab evaluation of level of absolute monocytes in the blood (x10^3/uL)

Measure: Absolute monocytes

Time: screening, day 0, 7, 10

Description: clinical lab evaluation of level of absolute eosinophils in the blood (x10^3/uL)

Measure: Absolute eosinophils

Time: screening, day 0, 7, 10

Description: clinical lab evaluation of level of absolute basophils in the blood (x10^3/uL)

Measure: Absolute basophils

Time: screening, day 0, 7, 10

Description: clinical lab evaluation of level of immature granulocytes in the blood (x10^3/uL)

Measure: Immature granulocytes

Time: screening, day 0, 7, 10

Description: clinical lab evaluation of level of platelets in the blood (x10^3/uL)

Measure: Platelets

Time: screening, day 0, 7, 10

Description: clinical lab evaluation of time for blood to coagulate (seconds)

Measure: Prothrombin time

Time: screening, day 0, 7, 10

Description: clinical lab evaluation of international normalized ratio of blood coagulation (no unit)

Measure: INR

Time: screening, day 0, 7, 10

Description: clinical lab evaluation of percentage of cells CD3- and CD54+ (%)

Measure: NK cell surface antigen (CD3-CD54+)

Time: screening, day 0, 7, 10

Description: clinical lab evaluation of ratio of CD4+ cells to CD8+ cells (no unit)

Measure: CD4+/CD8+ ratio

Time: screening, day 0, 7, 10

Description: clinical lab evaluation of level of IL-10 in the blood (pg/mL)

Measure: IL-10

Time: screening, day 0, 7, 10

Description: clinical lab evaluation of level of VEGF in the blood (pg/mL)

Measure: VEGF

Time: screening, day 0, 7, 10

Description: clinical lab evaluation of level of myoglobin in the blood (ng/mL)

Measure: Myoglobin

Time: screening, day 0, 7, 10

Description: clinical lab evaluation of level of myoglobin in the blood (ng/mL)

Measure: Troponin

Time: screening, day 0, 7, 10

Description: clinical lab evaluation of level of creatinine kinase in the blood (U/L)

Measure: Creatinine kinase

Time: screening, day 0, 7, 10

Description: clinical lab evaluation of level of serum ferritin in the blood (ng/mL)

Measure: Serum ferritin

Time: screening, day 0, 7, 10

Description: incidence of adverse events

Measure: Adverse events

Time: screening through day 28

Description: change from baseline in ordinal scale score

Measure: 7-point ordinal scale

Time: screening, day 0, 3, 7, 10, 28

84 Phase 3 Multicenter, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy and Safety of Canakinumab on Cytokine Release Syndrome in Patients With COVID-19-induced Pneumonia (CAN-COVID)

This is a multicenter, randomized, double-blind, placebo-controlled study to assess the efficacy and safety of canakinumab plus standard-of-care (SOC) compared with placebo plus SOC in adult patients with COVID-19-induced pneumonia and cytokine release syndrome (CRS).

NCT04362813 Covid-19 Drug: Canakinumab Drug: Placebo
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Clinical response is defined as survival without ever requiring invasive mechanical ventilation from Day 3 to Day 29 (both inclusive). A patient will be defined as a non-responder if the worst clinical status at any time from Day 3 to Day 29 is score 6, 7 or 8 on a 9-point ordinal scale ranging from 0 up to 8. Scores 6, 7 and 8 in the 9-point ordinal scale are defined as follows: Hospitalized patients with severe disease have score 6 if they need intubation and mechanical ventilation and score 7 if they need ventilation + additional organ support (pressors, renal replacement therapy, extracorporeal membrane oxygenation). Patients who die have score 8.

Measure: Number of patients with clinical response

Time: Day 3 to Day 29

Secondary Outcomes

Description: COVID-19-related death during the 4-week period after study treatment.

Measure: COVID-19-related death rate during the 4-week period after study treatment

Time: 4 weeks

Description: Clinical chemistry measurement in a blood sample.

Measure: Ratio to baseline in the C-reactive protein (CRP)

Time: Baseline, Day 29

Description: Clinical chemistry measurement in a blood sample.

Measure: Ratio to baseline in the serum ferritin

Time: Baseline, Day 29

Description: Clinical chemistry measurement in a blood sample.

Measure: Ratio to baseline in the D-dimer

Time: Baseline, Day 29

Description: Safety will be monitored from the canakinumab or placebo dose (Day 1) up to 126 days post-dose (Day 127).

Measure: Number of participants with Adverse Event (AE), serious adverse events (SAE), clinically significant changes in laboratory measures, and vital signs

Time: 127 days

85 A Pilot, Multiple Dose Study to Evaluate the Efficacy and Safety of MRx-4DP0004 in Hospitalised Patients With Symptoms of COVID-19 (SARS-CoV-2 Infection)

This is a randomised, double-blind, placebo controlled study to evaluate the efficacy and safety of MRx-4DP0004 in patients with COVID-19. 90 hospitalised patients will be enrolled and randomised (2:1) to receive MRx-4DP0004 or placebo for up to 14 days. MRx-4DP0004 is an immunomodulating Live Biotherapeutic Product (LBP) which is expected to prevent or reduce the hyperinflammatory response to SARS-CoV-2 infection without impairing viral clearance.

NCT04363372 COVID-19 Drug: MRx-4DP0004 Drug: Placebo

Primary Outcomes

Description: Clinical status score will be measured using the WHO Ordinal Scale for Clinical Improvement where patients are scored on a scale of 0-8 with 0 being uninfected and 8 being dead

Measure: Change in mean clinical status score in each treatment arm

Time: Baseline to Day 42

Secondary Outcomes

Description: Safety and tolerability will be determined according to clinically relevant reported adverse events

Measure: Number of adverse events in each treatment arm

Time: Baseline to Day 42

Description: Point changes in clinical status score will be measured using the WHO Ordinal Scale for Clinical Improvement

Measure: Number of patients with an improvement in clinical status score in each treatment arm

Time: Day 1 to Day 42

Description: Point changes in clinical status score will be measured using the WHO Ordinal Scale for Clinical Improvement

Measure: Number of patients with a deterioration in clinical status score in each treatment arm

Time: Day 1 to Day 42

Description: Oxygen saturation will be measured as per local standard procedures

Measure: Number of patients with at least 95% oxygen saturation on room air in each treatment arm

Time: Day 1 to Day 14

Description: Oxygen saturation will be recorded daily during hospitalisation to determine the mean time for each arm to reach at least 95% saturation

Measure: Time to patients with at least 95% oxygen saturation on room air in each treatment arm

Time: Day 1 to Day 14

Description: The NEWS 2 is based on aggregate scoring of physiological measurements including respiration rate, oxygen saturation, systolic blood pressure, pulse rate, level of consciousness and temperature

Measure: Number of patients with an improvement in the National Early Warning Score (NEWS) 2 in each treatment arm

Time: Day 1 to Day 14

Description: The NEWS 2 is based on aggregate scoring of physiological measurements including respiration rate, oxygen saturation, systolic blood pressure, pulse rate, level of consciousness and temperature

Measure: Number of patients with an deterioration in the National Early Warning Score (NEWS) 2 in each treatment arm

Time: Day 1 to Day 14

Description: Details of required respiratory support will be recorded throughout hospitalisation

Measure: Number of patients requiring Continuous Positive Airway Pressure in each treatment arm

Time: Day 1 to Day 14

Description: Details of required respiratory support will be recorded throughout the treatment period

Measure: Number of patients requiring Intermittent Positive Pressure Ventilation in each treatment arm

Time: Day 1 to Day 14

Description: Details of required respiratory support will be recorded throughout the treatment period

Measure: Time to patients requiring Continuous Positive Airway Pressure in each treatment arm

Time: Day 1 to Day 14

Description: Details of required respiratory support will be recorded throughout the treatment period

Measure: Time to patients requiring Intermittent Positive Pressure Ventilation in each treatment arm

Time: Day 1 to Day 14

Description: Length of hospital stay will be compared

Measure: Time to discharge in each treatment arm

Time: Day 1 to Day 42

Description: All cause mortality will be compared

Measure: Number of deaths in each treatment arm

Time: Day 1 to Day 42

86 Hydroxychloroquine as Primary Prophylaxis for COVID-19 in Healthcare Workers (HCQPreP)

This a double-blind, randomized, placebo-controlled clinical trial to determine if primary prophylaxis with hydroxychloroquine in healthcare workers reduces symptomatic COVID-19 infection. Healthcare workers will be randomized at a 1:1 allocation between intervention and placebo arms and followed for 12 weeks. This study will enroll up to 1,700 participates in Lafayette, Louisiana. The primary outcome will number of symptomatic COVID-19 infections. Secondary endpoints included number of days healthcare workers are absent from work and rate of severe infection.

NCT04363450 COVID-19 Corona Virus Infection Wuhan Coronavirus Prophylaxis Healthcare Worker Sars-CoV2 Hydroxychloroquine Drug: Hydroxychloroquine Drug: Placebo
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome

Primary Outcomes

Description: Number of participants who develop symptoms of COVID-19 in the setting of a positive COVID-19 assay

Measure: Incidence of symptomatic COVID-19 infection in healthcare workers

Time: 12 weeks

Secondary Outcomes

Description: Number of days healthcare workers are absent from work due to symptomatic COVID-19 infection

Measure: Absenteeism from work due to COVID-19

Time: 12 weeks

Description: Rate of severe COVID-19 infection in healthcare works (hypoxia in setting of chest imaging >50% lung involvement, respiratory failure, end organ damage or shock)

Measure: Severity of COVID-19 infection

Time: 12 weeks

87 A Randomized-Control Pilot Study to Assess Hydroxychloroquine in Patients Infected With SARS-CoV-2 (COVID-19)

This is a prospective, randomized, participant-blinded, placebo-controlled, pilot study to assess the preliminary efficacy and safety of hydroxychloroquine for the treatment of patients with lower respiratory tract SARS-CoV-2 infection.

NCT04363866 COVID-19 SARS-CoV-2 Drug: Hydroxychloroquine Drug: Placebo

Primary Outcomes

Description: A 6-point ordinal scale ranging from "Death" to "Not hospitalized with full resumption of normal activities" is used to evaluate differences in the clinical status between participants that receive placebo vs hydroxychloroquine

Measure: Clinical Status at Day 5 Assessed by a 6-Point Ordinal Scale

Time: Day 5

Secondary Outcomes

Description: Assess differences in SARS-CoV-2 viral shedding between participants that receive placebo vs hydroxychloroquine

Measure: Number of Participants with Detectable SARS-CoV-2 Virus from Day 0 to Day 28 and at Day 5

Time: Day 0 to Day 28 and at Day 5

Description: Assess by incidence of Grade 3, Grade 4, and Serious Adverse Events (AEs)

Measure: Toxicity of Study Drug Assessed by Incidence of Adverse Events

Time: Day 0 to Day 28

Other Outcomes

Description: Assess length of hospitalization

Measure: Duration of Initial Hospitalization

Time: Day 0 to Day 28

Description: Assess number of deaths during study follow-up

Measure: Mortality During Follow-Up

Time: Day 0 to Day 28

Description: Assess number of deaths in the hospital during initial hospitalization

Measure: Mortality During Initial Hospitalization

Time: Day 0 to Day 28

Description: Assessing utilization of hospital resources

Measure: Incidence of New Hospital Resource Utilization

Time: Day 0 to Day 28

Description: Assessing duration of hospital resource utilization

Measure: Duration of Hospital Resource Utilization

Time: Day 0 to Day 28

Description: Provide preliminary characterization of differences in inflammatory response between participants that receive placebo vs hydroxychloroquine

Measure: Changes in Cytokine Profile

Time: Day 0 to Day 28

88 Study of Immunomodulation Using Naltrexone and Ketamine for COVID-19

Ideal new treatments for Novel Coronavirus-19 (COVID-19) would help halt the progression disease in patients with mild disease prior to the need for artificial respiration (ventilators), and also provide a rescue treatment for patients with severe disease, while also being affordable and available in quantities sufficient to treat large numbers of infected people. Low doses of Naltrexone, a drug approved for treating alcoholism and opiate addiction, as well as Ketamine, a drug approved as an anesthetic, may be able to interrupt the inflammation that causes the worst COVID-19 symptoms and prove an effective new treatment. This study will investigate their effectiveness in a randomized, blinded trial versus standard treatment plus placebo.

NCT04365985 COVID-19 Acute Respiratory Distress Syndrome Severe Acute Respiratory Syndrome (SARS) Coronavirus Infections Drug: Naltrexone Drug: Ketamine Other: Placebo
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Description: Count of participants initially presenting with mild/moderate disease who progress to requiring advanced oxygenation (high flow nasal canula, non-rebreather, continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), or intubation)

Measure: Progression of oxygenation needs

Time: up to 1 month

Secondary Outcomes

Description: Count of participants who develop or experience worsened renal failure as defined by RIFLE criteria, a 5-point scale where the categories are labeled: Risk-Injury-Failure-Loss-End stage renal disease, with Risk being the least severe and End stage renal disease being the most severe. The criteria for determination of stage are factors of serum creatinine and urine output. Numbers of participants worsening one or more RIFLE stages will be reported.

Measure: Renal failure

Time: up to 1 month

Description: Count of participants who develop or experience worsened liver failure as defined by serum transaminases five times normal limits

Measure: Liver failure

Time: up to 1 month

Description: Count of participants who develop cytokine storm as measured by elevated markers of inflammation (elevated D-dimer, hypofibrinogenemia, hyperferritinemia), evidence of acute respiratory distress syndrome (ARDS) measured by imaging findings and mechanical ventilator requirements, and/or continuous fever (≥ 38.1 ° Celsius unremitting)

Measure: Cytokine Storm

Time: up to 1 month

Description: Count of participants who die from COVID-19

Measure: Mortality

Time: up to 1 month post hospital discharge

Description: Length of hospital stay in days

Measure: Length of hospital stay

Time: up to 1 month

Description: Count of patients admitted to the ICU at any time during index hospitalization

Measure: Intensive Care Unit (ICU) admission

Time: up to 1 month

Description: Length of ICU stay in days

Measure: Intensive Care Unit (ICU) duration

Time: up to 1 month

Description: Count of participants requiring intubation

Measure: Intubation

Time: up to 1 month

Description: Length of intubation, measured in days

Measure: Intubation duration

Time: up to 1 month

Description: Time measured in days from hospital admission to determination patient is stable for discharge

Measure: Time until recovery

Time: up to 1 month

89 A Phase 2/3 Study to Assess the Safety and Efficacy of MultiStem® Therapy in Subjects With Acute Respiratory Distress Syndrome (ARDS) Due to Coronavirus Disease (COVID-19)

Multicenter investigation featuring an open-label lead-in followed by a double blinded, randomized, placebo-controlled Phase 2/3 part to evaluate the safety and efficacy of MultiStem therapy in subjects with moderate to severe Acute Respiratory Distress Syndrome (ARDS) due to COVID-19.

NCT04367077 ARDS Biological: MultiStem Biological: Placebo

Primary Outcomes

Measure: Ventilator-Free Days

Time: Day 0 through Day 28.

Measure: Safety and Tolerability as measured by the incidence of treatment-emergent adverse events as assessed by CTCAE v5.0.

Time: Day 28

Secondary Outcomes

Measure: All-cause mortality

Time: Day 60

Measure: Ranked hierarchical composite outcome of alive and ventilator-free

Time: Day 28

Measure: Ventilator-free days

Time: Day 0 through Day 60

90 A PHASE 1/2, PLACEBO-CONTROLLED, RANDOMIZED, OBSERVER-BLIND, DOSE-FINDING STUDY TO DESCRIBE THE SAFETY, TOLERABILITY, IMMUNOGENICITY, AND POTENTIAL EFFICACY OF SARS-COV-2 RNA VACCINE CANDIDATES AGAINST COVID-19 IN HEALTHY ADULTS

This is a Phase 1/2, randomized, placebo-controlled, observer-blind, dose-finding, and vaccine candidate-selection study in healthy adults. The study will evaluate the safety, tolerability, immunogenicity, and potential efficacy of up to 4 different SARS-CoV-2 RNA vaccine candidates against COVID-19: - As a 2-dose or single-dose schedule - At up to 3 different dose levels - In 3 age groups (18 to 55 years of age, 65 to 85 years of age, and 18 to 85 years of age The study consists of 3 stages. Stage 1: to identify preferred vaccine candidate(s), dose level(s), number of doses, and schedule of administration (with the first 15 participants at each dose level of each vaccine candidate comprising a sentinel cohort); Stage 2: an expanded-cohort stage; and Stage 3; a final candidate/dose large-scale stage.

NCT04368728 SARS-CoV-2 Infection COVID-19 Biological: BNT162a1 Biological: BNT162b1 Biological: BNT162b2 Biological: BNT162c2 Other: Placebo

Primary Outcomes

Description: Pain at the injection site, redness, and swelling as self-reported on electronic diaries.

Measure: Percentage of participants reporting local reactions

Time: For 7 days after dose 1 and dose 2

Description: Fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain as self-reported on electronic diaries.

Measure: Percentage of participants reporting systemic events

Time: For 7 days after dose 1 and dose 2

Description: As elicited by investigational site staff

Measure: Percentage of participants reporting adverse events

Time: From dose 1 through 1 month after the last dose

Description: As elicited by investigational site staff

Measure: Percentage of participants reporting serious adverse events

Time: From dose 1 through 6 months after the last dose

Description: As measured at the central laboratory

Measure: Percentage of sentinel cohort participants with abnormal hematology and chemistry laboratory values

Time: 1 day after dose 1

Description: As measured at the central laboratory

Measure: Percentage of sentinel cohort participants with abnormal hematology and chemistry laboratory values

Time: 7 days after dose 1

Description: As measured at the central laboratory

Measure: Percentage of sentinel cohort participants with abnormal hematology and chemistry laboratory values

Time: 7 days after dose 2

Description: As measured at the central laboratory

Measure: Percentage of sentinel cohort participants with grading shifts in hematology and chemistry laboratory assessments

Time: Between baseline and 1 day after dose 1

Description: As measured at the central laboratory

Measure: Percentage of sentinel cohort participants with grading shifts in hematology and chemistry laboratory assessments

Time: Between baseline and 7 days after dose 1

Description: As measured at the central laboratory

Measure: Percentage of sentinel cohort participants with grading shifts in hematology and chemistry laboratory assessments

Time: Between before dose 2 and 7 days after dose 2

Secondary Outcomes

Description: As measured at the central laboratory

Measure: SARS-CoV-2-specific WT serum neutralizing antibody levels, expressed as GMTs

Time: Through 2 years after the final dose

Description: As measured at the central laboratory

Measure: GMFR in SARS-CoV-2-specific WT serum neutralizing titers from before vaccination to each subsequent time point

Time: Through 2 years after the final dose

Description: As measured at the central laboratory

Measure: Proportion of participants achieving a greater than or equal to 4-fold rise from before vaccination in SARS-CoV-2-specific WT serum neutralizing antibody levels

Time: Through 2 years after the final dose

Description: As measured at the central laboratory

Measure: SARS-CoV-2--spike protein-specific binding antibody levels and RBD-specific binding antibody levels, expressed as GMCs

Time: Through 2 years after the final dose

Description: As measured at the central laboratory

Measure: Proportion of participants achieving a greater than or equal to 4-fold rise from before vaccination in SARS-CoV-2--spike protein-specific binding antibody levels and RBD-specific binding antibody levels

Time: Through 2 years after the final dose

Description: As measured at the central laboratory

Measure: GMFR in SARS-CoV-2-spike protein-specific binding antibody levels and RBD-specific binding antibody levels from before vaccination to each subsequent time point

Time: Through 2 years after the final dose

Description: As measured at the central laboratory

Measure: GMR of the geometric mean of SARS-CoV-2-specific WT serum neutralizing titers to the geometric mean of SARS CoV 2 (spike protein and RBD) specific binding antibody levels

Time: Through 2 years after the final dose

Description: Per 1000 person-years of follow-up

Measure: Confirmed COVID-19 incidence

Time: From the last dose of study intervention to the end of the study, up to 2 years

91 A Single-blinded, Randomized, Placebo Controlled Phase II Trial of Prophylactic Treatment With Oral Azithromycin Versus Placebo in Cancer Patients Undergoing Antineoplastic Treatment During the Corona Virus Disease 19 (COVID-19) Pandemic

Prophylactic treatment in cancer patients undergoing antineoplastic therapy during the COVID-19 pandemic.

NCT04369365 COVID Drug: Azithromycin 500 milligram (mg) oral Tablet Drug: Placebo
MeSH:Coronavirus Infections Virus Diseases

Primary Outcomes

Description: assessed by positive polymerase chain reaction (PCR) from routine nasal swabs (performed every 28 days)

Measure: Cumulative number of severe acute respiratory syndrome corona virus 2 (SARS-COV-2) infections

Time: 12 weeks after initiation of therapy

Secondary Outcomes

Description: defined as combined endpoint of hospitalization rate or death

Measure: Number of severe COVID-19 cases

Time: 12 weeks after initiation of therapy

Description: grading as outlined by the world health organization (WHO)

Measure: Severity of COVID-19 cases

Time: 12 weeks after initiation of therapy

Description: significant clinical and laboratory abnormalities according to CTCAE criteria

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

Time: 12 weeks after initiation of therapy

Description: other than COVID-19

Measure: Number of viral and bacterial infections

Time: 12 weeks after initiation of therapy

Description: Development of azithromycin-resistant bacterial strains as assessed by nasal swabs test

Measure: Number of participants with azithromycin-resistant bacterial strains in nasal swabs test

Time: 12 weeks after initiation of therapy

92 A Single Center, Double-blinded, ,Placebo-controlled Phase I Clinical Trial in Healthy Volunteer to Evaluate Tolerance and Pharmacokinetics of Meplazumab of Injection

This is a single center, double-blinded, placebo-controlled phase I clinical trail in healthy volunteer of meplazumab for injection. The primary objective of this phase I trial is to evaluate the safety, tolerability, pharmacokinetic characteristics and occupancy characteristics of peripheral blood cell receptors of meplazumab in healthy volunteer, and provide a reference for the dosage of meplazumab in phase II clinical trial.

NCT04369586 Healthy Volunteers Drug: meplazumab for injection Drug: Placebo

Primary Outcomes

Description: Nature, incidence, and severity of AEs/SAEs, and the relationship to meplazumab treatment.

Measure: Incidence rate of treatment-related adverse events as assessed by CTCAE v5.0

Time: 0-28 days

Secondary Outcomes

Description: AUC0-tn

Measure: Pharmacokinetic assessments of meplazumab- AUC0-tn

Time: 0-28 days

Description: AUC0-∞

Measure: Pharmacokinetic assessments of meplazumab- AUC0-∞

Time: 0-28 days

Measure: Pharmacokinetic assessments of meplazumab-half life time

Time: 0-28 days

Description: Maximum observed plasma concentration of meplazumab (Cmax)

Measure: Pharmacokinetic assessments of meplazumab-Cmax

Time: 0-28 days

93 COVID-19: BCG As Therapeutic Vaccine, Transmission Limitation, and Immunoglobulin Enhancement

To date, there is no vaccine or treatment with proven efficiency against COVID-19, and the transmissibility of the SARS-CoV-2 virus can be inferred by its identification in the oro-nasopharynx. The bacillus Calmette Guérin (BCG) has the potential for cross-protection against viral infections. This study evaluates the impact of previous (priming effect, from the titer of anti-BCG interferon-gamma) or current BCG exposure (boost with intradermal vaccine) on 1) clinical evolution of COVID-19; 2) elimination of SARS-CoV-2 at different times and disease phenotypes; and 3) seroconversion rate and titration (anti-SARS-CoV-2 IgA, IgM, and IgG).

NCT04369794 COVID-19 Therapeutic Vaccine BCG SARS-CoV 2 Transmission Biological: BCG Biological: Placebo

Primary Outcomes

Description: Classified as mild, moderate and severe

Measure: Clinical evolution of COVID-19

Time: 45 days of symptoms onset or diagnosis

Description: Virus detection by PCR

Measure: SARS-CoV-2 elimination

Time: 7 days of symptoms onset or diagnosis

Description: Titration of anti SARS-CoV-2 IgA, IgM and IgG

Measure: Seroconversion rate and titration

Time: 7 days of symptoms onset or diagnosis

Secondary Outcomes

Description: Classified according to type and severity

Measure: Local and systemic adverse events to BCG vaccination

Time: 3 months

Other Outcomes

Description: Virus detection by PCR

Measure: SARS-CoV-2 elimination

Time: 21 days of symptoms onset or diagnosis

Description: Titration of anti SARS-CoV-2 IgA, IgM and IgG

Measure: Seroconversion rate

Time: 21 days of symptoms onset or diagnosis

Description: Virus detection by PCR

Measure: SARS-CoV-2 elimination

Time: 45 days of symptoms onset or diagnosis

Description: Titration of anti SARS-CoV-2 IgA, IgM and IgG

Measure: Seroconversion rate and titration

Time: 45 days of symptoms onset or diagnosis

94 A Multicenter, Double-Blind, Randomized, Placebo-Controlled Trial of XPro1595 in the Treatment of Participants With Pulmonary Complications From Coronavirus Disease (COVID-19)

The purpose of this study is to determine whether XPro1595 can prevent the progression of respiratory complications in COVID19 patients.

NCT04370236 COVID-19 Drug: XPro1595 Drug: Placebo

Primary Outcomes

Description: Disease progression is defined by the development of need for mechanical ventilation or death. Mechanical ventilation includes CPAP, BIPAP or mechanical ventilation requiring intubation.

Measure: Proportion of participants with disease progression from randomization to 28 days post-randomization

Time: 28 days

Secondary Outcomes

Measure: Proportion of participants with all-cause mortality

Time: 28 days

Measure: Proportion of participants who transfer to ICU level care by Day 28 (ICU level care is defined as a hospital setting where patient to nurse ratio is < 4);

Time: 28 days

Measure: Proportion of participants with a new onset of neurologic disease (requiring medical intervention), including stroke by Day 28;

Time: 28 days

Measure: Proportion of participants with evidence of new CHF or new MI requiring medical intervention by Day 28;

Time: 28 days

Measure: Proportion of participants with a new onset embolus or thrombus by Day 28;

Time: 28 days

Measure: Proportion of participants who develop a need for renal replacement therapy (defined as need for any type of dialysis including intermittent or continuous peritoneal or hemodialysis) by Day 28;

Time: 28 days

Measure: Proportion of participants with an increase in the WHO Ordinal Scale of Clinical Improvement score at any time during the study;

Time: 28 days

Measure: Length of hospital stay defined as the number of days in hospital from time of randomization to time of discharge or death, whichever occurs first;

Time: 28 days

Measure: Change from baseline in inflammation markers over time.

Time: 28 days

Other Outcomes

Measure: Incidence of adverse events and serious adverse events not due to underlying disease

Time: 28 days

Measure: Incidence of abnormal findings in clinical safety laboratory parameters, vital signs, and ECGs.

Time: 28 days

95 Mesenchymal Stem Cells for the Treatment of Moderate to Severe COVID-19 Acute Respiratory Distress Syndrome

The mortality rate in SARS-CoV-2-related severe ARDS is high despite treatment with antivirals, glucocorticoids, immunoglobulins, and ventilation. Preclinical and clinical evidence indicate that MSCs migrate to the lung and respond to the pro-inflammatory lung environment by releasing anti-inflammatory factors reducing the proliferation of pro-inflammatory cytokines while modulating regulatory T cells and macrophages to promote resolution of inflammation. Therefore, MSCs may have the potential to increase survival in management of COVID-19 induced ARDS. The primary objective of this phase 3 trial is to evaluate the efficacy and safety of the addition of the mesenchymal stromal cell (MSC) remestemcel-L plus standard of care compared to placebo plus standard of care in patients with acute respiratory distress syndrome (ARDS) due to SARS-CoV-2. The secondary objective is to assess the impact of MSCs on inflammatory biomarkers.

NCT04371393 Mesenchymal Stromal Cells Remestemcel-L Acute Respiratory Distress Syndrome COVID Biological: Remestemcel-L Drug: Placebo
MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Description: Number of all-cause mortality within 30 days of randomization.

Measure: Number of all-cause mortality

Time: 30 days

Secondary Outcomes

Description: Number of days alive off mechanical ventilatory support calculated as the number of days, within the 60 days window, that patients were alive and free of mechanical ventilatory support.

Measure: Number of days alive off mechanical ventilatory support

Time: 60 days

Description: Safety analyses will be assessed by adverse event rates calculated as the ratio of the total number of events over 30 days divided by total patient-time at risk for the specific event from randomization.

Measure: Number of adverse events

Time: 30 days

Measure: Number of participants alive at day 7

Time: 7 days

Measure: Number of participants alive at day 14

Time: 14 days

Measure: Number of participants alive at day 60

Time: 60 days

Measure: Number of participants alive at day 90

Time: 90 days

Description: The number and percent of patients with resolution and/or improvement of ARDS at day 7

Measure: Number of participants with resolution and/or improvement of ARDS

Time: 7 days

Description: The number and percent of patients with resolution and/or improvement of ARDS at day 14

Measure: Number of participants with resolution and/or improvement of ARDS

Time: 14 days

Description: The number and percent of patients with resolution and/or improvement of ARDS at day 21

Measure: Number of participants with resolution and/or improvement of ARDS

Time: 21 days

Description: The number and percent of patients with resolution and/or improvement of ARDS at day 30

Measure: Number of participants with resolution and/or improvement of ARDS

Time: 30 days

Description: Change from baseline of the 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: Change from baseline of the severity of ARDS

Time: baseline and 7 days

Description: Change from baseline of the 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: Change from baseline of the severity of ARDS

Time: baseline and 14 days

Description: Change from baseline of the 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: Change from baseline of the severity of ARDS

Time: baseline and 21 days

Description: Change from baseline of the 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: Change from baseline of the severity of ARDS

Time: baseline and 30 days

Description: Hospital length of stay

Measure: Length of stay

Time: 12 months

Description: Change from baseline in Clinical Improvement Scale at day 7. Clinical Improvement Scale full scale from 1 to 7, with higher score indicating more clinical improvement.

Measure: Clinical Improvement Scale

Time: 7 days

Description: Change from baseline in Clinical Improvement Scale at day 14. Full scale from 1 to 7, with higher score indicating more clinical improvement.

Measure: Clinical Improvement Scale

Time: 14 days

Description: Change from baseline in Clinical Improvement Scale at day 21. Clinical Improvement Scale full scale from 1 to 7, with higher score indicating more clinical improvement.

Measure: Clinical Improvement Scale

Time: 21 days

Description: Change from baseline in Clinical Improvement Scale at day 30. Clinical Improvement Scale full scale from 1 to 7, with higher score indicating more clinical improvement.

Measure: Clinical Improvement Scale

Time: 30 days

Description: Changes from baseline in serum hs-CRP concentration at days 7

Measure: Change in serum hs-CRP concentration

Time: baseline and 7 days

Description: Changes from baseline in serum hs-CRP concentration at days 14

Measure: Change in serum hs-CRP concentration

Time: baseline and 14 days

Description: Changes from baseline in serum hs-CRP concentration at days 21

Measure: Change in serum hs-CRP concentration

Time: baseline and 21 days

Description: Changes from baseline in serum hs-CRP concentration at days 30

Measure: Change in serum hs-CRP concentration

Time: baseline and 30 days

Description: Changes from baseline in IL-6 inflammatory marker level at 7 days

Measure: Change in IL-6 inflammatory marker level

Time: baseline and 7 days

Description: Changes from baseline in IL-6 inflammatory marker level at 14 days

Measure: Change in IL-6 inflammatory marker level

Time: baseline and 14 days

Description: Changes from baseline in IL-6 inflammatory marker level at 21 days

Measure: Change in IL-6 inflammatory marker level

Time: baseline and 21 days

Description: Changes from baseline in IL-6 inflammatory marker level at 30 days

Measure: Change in IL-6 inflammatory marker level

Time: baseline and 30 days

Description: Changes from baseline in IL-6 inflammatory marker level at 7 days

Measure: Change in IL-8 inflammatory marker level

Time: baseline and 7 days

Description: Changes from baseline in IL-6 inflammatory marker level at 14 days

Measure: Change in IL-8 inflammatory marker level

Time: baseline and 14 days

Description: Changes from baseline in IL-6 inflammatory marker level at 21 days

Measure: Change in IL-8 inflammatory marker level

Time: baseline and 21 days

Description: Changes from baseline in IL-6 inflammatory marker level at 30 days

Measure: Change in IL-8 inflammatory marker level

Time: baseline and 30 days

Description: Changes from baseline in TNF-alpha inflammatory marker level at 7 days

Measure: Change in TNF-alpha inflammatory marker level

Time: baseline and 7 days

Description: Changes from baseline in TNF-alpha inflammatory marker level at 14 days

Measure: Change in TNF-alpha inflammatory marker level

Time: baseline and 14 days

Description: Changes from baseline in TNF-alpha inflammatory marker level at 21 days

Measure: Change in TNF-alpha inflammatory marker level

Time: baseline and 21 days

Description: Changes from baseline in TNF-alpha inflammatory marker level at 30 days

Measure: Change in TNF-alpha inflammatory marker level

Time: baseline and 30 days

96 A Randomized, Double-Blinded, Placebo-Controlled Trial Evaluating the Virological Efficacy, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Sirolimus Adjuvant Therapy in Patients With Coronavirus Disease (COVID-19)

This is a double-blinded, two-arm, randomized, placebo controlled study comparing the virological efficacy of add-on sirolimus with standard care to placebo and standard care. Virological efficacy is defined as the change from baseline to day 7 in SARS-CoV-2 viral burden measured by quantitative real-time polymerase chain reaction.

NCT04371640 SARS-CoV-2 Covid-19 Drug: Sirolimus 1 MG/ML Drug: Placebo

Primary Outcomes

Description: SARS-CoV-2 viral burden will be quantified for both arms using a qRT-PCR

Measure: Change in SARS-CoV-2 viral burden from baseline to day 7 of treatment

Time: Baseline, and days 1, 2, 3, 4, 5, 6, & 7 post-dose for all patients

Secondary Outcomes

Description: SARS-CoV-2 viral burden will be quantified for both arms using a qRT-PCR

Measure: Change in SARS-CoV-2 viral burden at days 1-6

Time: Days 1, 2, 3, 4, 5, and 6 post-dose for all patients

Description: Safety and tolerability of sirolimus in patients with COVID-19

Measure: Rate of treatment emergent adverse events

Time: Days 1, 2, 3, 4, 5, and 6 post-dose for all patients

97 Doxycycline Versus Placebo in COVID-19 + Patients Without Hospitalization Criteria: Prospective, Multicenter, Randomized, Double-blind Study

The aim of the study is to compare a treatment with doxycycline vs a placebo as soon as the patient is confirmed COVID-19 + and before the onset of oxygen dependence with the aim of reducing or even abolishing the cytokine explosion and thus the evolution towards a serious form of the disease which can lead to death. Three criteria support the rational use of tetrcycline in COVI-19 (1) The coronaviruses is known to bind to metalloproteases (MMPs) of the host, in particular to ensure viral survival. Tetracyclines are known to chelate zinc from MMPs. Their chelating activity may help inhibit COVID19 infection by limiting its ability to replicate in the host. (2) Tetracyclines may also be able to inhibit the replication of positive-polarity single-stranded RNA viruses, such as COVID19 (demonstrated on the dengue virus). (3) In addition, tetracyclines are modulators of innate immunity (anti-inflammatory activity), a property used in the treatment of inflammatory skin diseases for many years. These modulating effects are noted on several targets of innate immunity: They can decrease the expression of NFKB, the release of inflammatory cytokines such as TNF-α, IL-1β and IL-6, inhibit granulomas inflammatory and free radical release. Tetracyclines could therefore participate in limiting the cytokine release induced by COVID19. Their lipophilic nature and their strong pulmonary penetration could allow them to inhibit viral replication.

NCT04371952 COVID19 Drug: Doxycycline Drug: Placebo

Primary Outcomes

Description: Percentage of patients with clinical worsening (SaO2 ≤ 93%) after at least 48 hours of treatment

Measure: Percentage of Patients with Clinical Respiratory Aggravation

Time: after at least 48 hours of treatment

Description: Percentage of patients hospitalized after at least 48 hours of experimental treatment

Measure: Percentage of patients hospitalized

Time: after at least 48 hours of experimental treatment

Description: Percentage of patients requiring ventilatory assistance

Measure: Percentage of patients requiring ventilatory assistance

Time: Day 0 to Day 28

Secondary Outcomes

Description: Number of positive SARS-CoV-2 PCR tests on D-1 / D0 and D7 (+/- 2 days)

Measure: Positive SARS-CoV-2 PCR Test

Time: Day -1 or day 0 AND Day 7

Description: Duration of symptoms (fever, painful symptoms: headache, sore throat, dyspnea)

Measure: Duration of symptoms

Time: Day 0 to Day 28

Description: Total duration of hospitalization

Measure: Duration of hospitalization

Time: From day 0 until to the end of hospitalization or date of death for any cause, whichever came first, assessed up to 3 months after Day0

Description: Duration of hospitalization in intensive care or reanimation

Measure: Hospitalization intensive care or reanimation

Time: From day 0 until to the end of hospitalization or date of death for any cause, whichever came first, assessed up to 3 months after Day0

Description: Duration of mechanical ventilatory assistance

Measure: Duration of mechanical ventilatory assistance

Time: to the end of mechanical ventilatory assistance if any, assessed up to 3 months after Day0

Description: Percentage of deaths related to SARS-CoV-2 infection

Measure: Percentage of deaths related to SARS-CoV-2

Time: Day 28, or end of hospitalization if any (assessed up to 3 months after Day0)

Description: Number of AE / SAE in both arms

Measure: AE / SAE in both arms

Time: Day 28, or end of hospitalization if any (assessed up to 3 months after Day0)

98 Trial of Early Therapies During Non-hospitalized Outpatient Window (TREAT NOW) for COVID-18

Blinded, multicenter, placebo-controlled, randomized clinical trial evaluating hydroxychloroquine vs lopinavir/ritonavir vs placebo in early outpatient treatment of adults with COVID-19

NCT04372628 COVID-19 Drug: Hydroxychloroquine Drug: Lopinavir/ritonavir 400 mg/100 mg Other: Placebo

Primary Outcomes

Description: Death Hospitalized on mechanical ventilation or extracorporeal membrane oxygenator (ECMO) Hospitalized on supplemental oxygen Hospitalized not on supplemental oxygen Not hospitalized with symptoms and limitation in activity Not hospitalized with symptoms but with no limitation in activity Not hospitalized without symptoms nor limitation in activity symptoms at the milder end of the scale for this outpatient trial

Measure: Modified COVID Ordinal Outcomes Scale: Study Day 15

Time: Day 15

Secondary Outcomes

Description: Death Hospitalized on mechanical ventilation or ECMO Hospitalized on supplemental oxygen Hospitalized not on supplemental oxygen Not hospitalized with symptoms and limitation in activity Not hospitalized with symptoms but with no limitation in activity Not hospitalized without symptoms nor limitation in activity

Measure: Modified COVID Ordinal Outcome Scale: Study Day 8

Time: Day 8

Description: Death Hospitalized on mechanical ventilation or ECMO Hospitalized on supplemental oxygen Hospitalized not on supplemental oxygen Not hospitalized with symptoms and limitation in activity Not hospitalized with symptoms but with no limitation in activity Not hospitalized without symptoms nor limitation in activity Ordinal Scale

Measure: Modified COVID Ordinal Outcome Scale: Study Day 29

Time: Day 29

Description: Proportion hospitalized

Measure: Proportion of patients hospitalized: Day 1 to 29

Time: Day 1 to Day 29

Description: Number of days from enrollment to hospitalization

Measure: Time to hospitalization Day 1 to Day 29

Time: Day 1 to Day 29

Description: Number of days from enrollment to resolution of COVID-19 symptoms

Measure: Time to symptom resolution: Day 1 to Day 29

Time: Day 1 to Day 29

Description: Survival status

Measure: All-cause, all-location mortality: Day 1 to Day 29

Time: Day 1 to Day 29

Description: Number of Days without oxygen

Measure: Oxygen-free days: Day 1 to Day 29

Time: Day 1 to Day 29

Description: Number of days without fever

Measure: Fever-free days: Day 1 to Day 29

Time: Day 1 to Day 29

Description: Number of days without ventilator use

Measure: Ventilator-free days: Day 1 to Day 29

Time: Day 1 to Day 29

Description: Number of days outside the ICU

Measure: ICU-free days: Day 1 to Day 29

Time: Day 1 to Day 29

Description: Number of days outside the hospital

Measure: Hospital-free days: Day 1 to Day 29

Time: Day 1 to Day 29

99 RCT in Asymptomatic Volunteers With COVID-19 Comparing Azithromycin and Hydroxychloroquine vs. Hydroxychloroquine Alone vs Standard of Care Without Antibiotics

The coronavirus disease-2019 (COVID-19) is spreading throughout the United States. While there are no known therapies to treat those who have become sick, there have been some reports that a medication currently used to treat rheumatoid arthritis, lupus, and malaria (Hydroxychloroquine sulfate, also known as Plaquenil) may help to lessen the chance or severity of illness, especially if combined with a medicine that treats other kinds of infections (Azithromycin, also known as Zithromax or Zmax or Zpak). There are some people who test positive for the virus but who are otherwise not ill. Current standard of care is to advise these people to self-monitor but no treatment is offered. It is not known how many of these individuals will remain symptom free, and how many will become sick or how severe those symptoms will be. This study will randomize those people who do not have symptoms into one of three treatment plans 1) Hydroxycholoquine and Azithromycin, or 2) no active medication (placebo). All participants will be followed for 2 months. The study will determine if there is any benefit to those who are asymptomatic to taking taking Hydroxychloroquine sulfate in combination with Azithromycin, or if there is no benefit from taking these medications.

NCT04374552 SARS-CoV-2 Infection Drug: Hydroxychloroquine sulfate &Azithromycin Drug: Placebo

Primary Outcomes

Description: Change in SARS-CoV-2 viral from baseline to day 6

Measure: The primary outcome is the rate of decline in viral load over the 10 days after randomization

Time: 10 days

100 IbrutiNib in SARS CoV-2 Induced Pulmonary Injury and Respiratory Failure (iNSPIRE)

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Lung failure is the main cause of death related to COVID-19 infection. The main objective of this study is to evaluate if Ibrutinib is safe and can reduce respiratory failure in participants with COVID-19 infection. Ibrutinib is an investigational drug being developed for the treatment of COVID-19. Participants are assigned 1 of 2 groups, called treatment arms. Each group receives a different treatment. There is a 1 in 2 chance that participants will be assigned to placebo. Around 46 adult participants with a diagnosis of COVID-19 will be enrolled at multiple sites in Unites States. Participants will receive oral doses of Ibrutinib or placebo capsules once daily for 4 weeks along with standard care. There will be higher treatment burden for participants in this trial compared to their standard of care. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects.

NCT04375397 CoronaVirus Induced Disease-2019 (COVID-19) Drug: Ibrutinib Drug: Placebo
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Respiratory Insufficiency Lung Injury

Primary Outcomes

Description: Respiratory failure is defined by clinical diagnosis of respiratory failure and initiation of 1 of the following therapies: Endotracheal intubation and mechanical ventilation OR Extracorporeal membrane oxygenation OR high-flow nasal cannula oxygen delivery OR non-invasive positive pressure ventilation OR clinical diagnosis of respiratory failure with initiation of none of these measures only when clinical decision-making driven is driven solely by resource limitation.

Measure: Percentage of Participants Alive and Without Respiratory Failure

Time: Day 28

Secondary Outcomes

Description: WHO-8 is an 8 point ordinal scale for clinical improvement with scores ranging from 0 (uninfected) through 8 (Death).

Measure: Change in the World Health Organization (WHO)-8 Point Ordinal Scale From Baseline

Time: Day 14

Description: Time on supplemental oxygen imputed to the maximum number of days on study drug (28) for all points following the death of a participant.

Measure: Median Reduction in Days Spent on Supplemental Oxygen

Time: Up to Day 28

Description: Percentage of participants with mortality from any cause.

Measure: All-Cause Mortality

Time: Up to Day 28

Description: Respiratory failure is defined by clinical diagnosis of respiratory failure and initiation of 1 of the following therapies: Endotracheal intubation and mechanical ventilation OR Extracorporeal membrane oxygenation OR high-flow nasal cannula oxygen delivery OR non-invasive positive pressure ventilation OR clinical diagnosis of respiratory failure with initiation of none of these measures only when clinical decision-making driven is driven solely by resource limitation.

Measure: Percentage of Participants Experiencing Respiratory Failure or Death

Time: Up to Day 28

Description: Percentage of participants alive and not requiring mechanical ventilation.

Measure: Mechanical Ventilation-Free Survival

Time: Up to Day 56

Description: Defined as number of days from the first day of using mechanical ventilation to the last day of using mechanical ventilation.

Measure: Days on Mechanical Ventilation

Time: Up to Day 56

Description: The duration of hospitalization is defined as the time in days from the first day of hospitalized to the date of discharge or death.

Measure: Duration of hospitalization

Time: Up to Day 56

Description: Time to discharge is defined as the time in days from the first day of hospitalized to the date of discharge.

Measure: Time to Discharge

Time: Up to Day 56

Description: PaO2:FiO2 ratio is an index of respiratory distress.

Measure: Partial Pressure of Oxygen in Arterial Blood (PaO2) to Fraction of Inspired Oxygen (FiO2) Ratio

Time: Up to Day 56

Description: Oxygenation Index is a parameter of pulmonary function of participants.

Measure: Oxygenation Index

Time: Up to Day 56

Description: An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent adverse events (TEAEs) are defined as any event that began or worsened in severity on or after the first dose of study drug.

Measure: Number of Participants With Adverse Events

Time: Up to Day 56

Description: Laboratory abnormalities will be analyzed according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

Measure: Number of Participants With Abnormal Laboratory Findings

Time: Up to Day 56

101 A Randomized, Double-blind, Placebo-controlled, Study Evaluating the Efficacy and Safety of Otilimab IV in Patients With Severe Pulmonary COVID-19 Related Disease

This 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-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 patients with severe COVID-19 related pulmonary disease. The study population will consist of hospitalized participants with new onset hypoxia requiring significant oxygen support or requiring early invasive mechanical ventilation (less than or equal to [<=] 48 hours before dosing). Participants will be randomized to receive a single intravenous (IV) infusion of otilimab or placebo, in addition to standard of care.

NCT04376684 Severe Acute Respiratory Syndrome Biological: Otilimab Biological: Placebo Drug: Standard of care
MeSH:Severe Acute Respiratory Syndrome Coronavirus Infections

Primary Outcomes

Description: Participants are alive and free of respiratory failure if they are in category 1, 2, 3 or 4 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale is as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized, limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, high-flow oxygen (≥15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death.

Measure: Proportion of participants alive and free of respiratory failure at Day 28

Time: Day 28

Secondary Outcomes

Description: Number of deaths due to all causes will be assessed.

Measure: Number of deaths due to all causes at Day 60

Time: Day 60

Description: Time to death due to all causes will be assessed.

Measure: Time to number of deaths due to all causes at Day 60

Time: Day 60

Description: Participants alive and free of respiratory failure if they are in category 1, 2, 3 or 4 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale is as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized, limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, high-flow oxygen (≥15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death.

Measure: Proportion of participants alive and free of respiratory failure at Day 7

Time: Day 7

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 14

Time: Day 14

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 42

Time: Day 42

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 60

Time: Day 60

Description: Time will be recorded from dosing to recovery from respiratory failure. Participants are in respiratory failure if they are in category 5 or above from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale is as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized, limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, high-flow oxygen (≥15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death.

Measure: Time to recovery from respiratory failure

Time: Day 28

Description: Participants are independent of supplementary oxygen if they are in category 1, 2 or 3 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale is as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized, limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, high-flow oxygen (≥15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death.

Measure: Proportion of participants alive and independent of supplementary oxygen at Day 7

Time: Day 7

Description: Participants are independent of supplementary oxygen if they are in category 1, 2 or 3 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale is as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized, limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, high-flow oxygen (≥15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death.

Measure: Proportion of participants alive and independent of supplementary oxygen at Day 14

Time: Day 14

Description: Participants are independent of supplementary oxygen if they are in category 1, 2 or 3 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale is as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized, limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, high-flow oxygen (≥15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death.

Measure: Proportion of participants alive and independent of supplementary oxygen at Day 28

Time: Day 28

Description: Participants are independent of supplementary oxygen if they are in category 1, 2 or 3 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale is as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized, limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, high-flow oxygen (≥15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death.

Measure: Proportion of participants alive and independent of supplementary oxygen at Day 42

Time: Day 42

Description: Participants are independent of supplementary oxygen if they are in category 1, 2 or 3 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale is as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized, limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, high-flow oxygen (≥15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death.

Measure: Proportion of participants alive and independent of supplementary oxygen at Day 60

Time: Day 60

Description: Time will be recorded from dosing to last dependence on supplementary oxygen. Participants are dependent on supplementary oxygen if they are in category 4 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 last dependence on supplementary oxygen

Time: Day 28

Description: For participants not in ICU at time of dosing, the proportion of participants admitted to the ICU prior to Day 28.

Measure: Proportion of participants admitted to Intensive Care Unit (ICU)

Time: Day 28

Description: Defined as the time from dosing to when the participant is discharged from the ICU.

Measure: Time to final Intensive Care Unit (ICU) discharge

Time: Day 28

Description: Time from dosing to when a participant is discharged from the hospital.

Measure: Time to final hospital discharge

Time: Day 28

Description: An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence, that at any dose results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, congenital anomaly/birth defect or any other important medical event that may jeopardize the participant or may require medical or surgical treatment to prevent one of the other outcomes listed before.

Measure: Number of participants with Adverse events (AEs) and Serious adverse events (SAEs)

Time: Up to Day 60

102 A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Assess the Efficacy and Safety of Ruxolitinib in Participants With COVID-19-Associated ARDS Who Require Mechanical Ventilation (RUXCOVID-DEVENT)

The purpose of this study is to evaluate the efficacy and safety of ruxolitinib in the treatment of participants with COVID-19-associated Acute Respiratory Distress Syndrome (ARDS) who require mechanical ventilation.

NCT04377620 COVID-19 Drug: Placebo Drug: Ruxolitinib

Primary Outcomes

Description: To evaluate the 28-day mortality rate of ruxolitinib 5 mg BID + SoC therapy and ruxolitinib 15 mg BID + SoC compared with placebo + SoC therapy, in participants with COVID-19-associated ARDS who require mechanical ventilation.

Measure: Proportion of participants who have died due to any cause

Time: Up to Day 29

Secondary Outcomes

Description: Number of days participant did not require mechanical ventilation

Measure: Number of Ventilator free days

Time: Day 29

Description: Number of days participant is out of the ICU

Measure: Number of ICU free days

Time: Day 29

Description: Number of days participant did not receive supplemental oxygen

Measure: Oxygen free days

Time: Day 29

Description: Number of days without use of vasopressor therapy

Measure: Vasopressor free days

Time: Day 29

Description: Number of days Partcipant is out of the hospital

Measure: Hospital free days

Time: Day 29

Description: Clinical status of participant at Day 15 and 29 based on participant state. The scale ranges from 0-8 with 0 being no clinical or virological evidence of infection and 8 being dead

Measure: Improvement in the COVID-19 ordinal scale

Time: Day 15 and 29

Description: SOFA score is a scoring system to determine the extent of a person's organ function or rate of failure. The score is based on 6 different scores, 1 each for the respiratory, cardiovascular, hepatic, coagulation, renal, and neurological systems.

Measure: Change in SOFA Score

Time: from baseline to Days 3, 5, 8, 11, 15, and 29

Description: Adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug/treatment.

Measure: Number of treatment-related adverse events

Time: Day 29

103 A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety and Efficacy of Ciclesonide Metered-Dose Inhaler in Non-hospitalized Patients 12 Years of Age and Older With Symptomatic COVID-19 Infection

The purpose of this study is to assess the safety and efficacy of Alvesco (ciclesonide) Inhalation Aerosol in non hospitalized patients with symptomatic COVID-19 infection in a multicenter, randomized, double-blind, placebo controlled study

NCT04377711 COVID-19 Drug: Ciclesonide Drug: Placebo

Primary Outcomes

Measure: Percentage of patients hospital admission or death by day 30

Time: Day 30

Secondary Outcomes

Measure: All-cause mortality by day 30

Time: Day 30

Measure: COVID-19-related mortality by day 30

Time: Day 30

Measure: Percentage of patients with subsequent emergency department visit or hospital admission for reasons attributable to COVID 19 by day 30

Time: Day 30

Measure: Time to hospital admission or death

Time: Day 30

Measure: Time to alleviation of COVID-19-related symptoms of cough, dyspnea, chills, and feeling feverish, defined as symptom-free for a continuous period of more than 24 hours (ie, > 3 AM/PM assessments)

Time: Day 30

Measure: Change from baseline in oxygen saturation levels

Time: Day 30

Measure: Change from baseline in COVID-19 viral load in nasopharyngel sample nasal secretions at day 30

Time: Day 30

Measure: Safety will be assessed based on adverse events.

Time: Day 60

104 A Prospective, Multi-Center, Randomized, Placebo-Controlled, Double-Blinded Study to Evaluate the Efficacy, Safety and Tolerability of IMU-838 as Addition to Investigator's Choice of Standard of Care Therapy, in Patients With Coronavirus Disease 19

At present there is no approved drug treatment for Covid-19. In this study we plan to investigate if an experimental drug called IMU-838 (vidofludimus calcium) can improve your symptoms, prevent worsening that would initiate further treatments such as ventilation, and can lower your virus number if given in addition to your doctor's choice of standard therapy. We will also test if IMU-838 has any side effects and measure the level of IMU 838 in your blood. Experimental drug means that it is not yet authorized for marketing in your country. To date approximately 600 individuals have received IMU-838 (or a drug similar to IMU-838 that contains the same active substance as IMU-838) in research studies.

NCT04379271 COVID-19 Drug: IMU-838 Other: Placebo
MeSH:Coronavirus Infections

Primary Outcomes

Description: Clinical

Measure: Proportion of patients without any need* for INV until end-of-study (EoS)

Time: Throughout the Study (Day 0 to Day 28)

Secondary Outcomes

Description: Key Secondary

Measure: Duration of ICU treatment until EoS

Time: Throughout the Study (Day 0 to Day 28 )

Description: Key Secondary

Measure: 28-day all-cause mortality

Time: Throughout the Study (Day 0 to Day 28 )

Description: Efficacy: defined as the time from first dose of investigational medicinal product (IMP) to an improvement of at least 2 points on the WHO 9 category ordinal scale , or live discharge from hospital without oxygen supplementation, whichever comes first

Measure: Time to clinical improvement

Time: Throughout the Study (Day 0 to Day 28 )

Description: Efficacy: Duration of hospitalization (for US sites only: or treatment in special outpatient setting in lieu of hospitalization due to resource restraints)

Measure: Duration of hospitalization

Time: Throughout the Study (Day 0 to Day 28 )

Description: Efficacy

Measure: Proportion of patients both for all patients and surviving patients free of renal-replacement therapy (RRT)* until EoS

Time: Throughout the Study (Day 0 to Day 28 )

Description: Efficacy

Measure: Proportion of patients both for all patients and surviving patients free from extracorporeal membrane oxygenation (ECMO)* until EoS

Time: Throughout the Study (Day 0 to Day 28 )

Description: Efficacy

Measure: Proportion of patients free of INV until Days 6 and 14*

Time: Throughout the Study (Day 0 to Day 28 )

Description: Efficacy

Measure: Proportion of patients free of RRT until Days 6 and 14*

Time: Day 0 to Days 6 and 14

Description: Efficacy

Measure: Proportion of patients free ECMO until Days 6 and 14*

Time: Day 0 to Days 6 and 14

Description: Efficacy

Measure: Proportion of patients with improvement of at least 2 points (from randomization) on the 9-category WHO ordinal scale1 on Days 6, 14, and 28

Time: on Days 6, 14, and 28

Description: Efficacy

Measure: Proportion of patients with auxiliary oxygen therapy (including all types of oxygen therapy) on Days 6, 14, and 28

Time: on Days 6, 14, and 28

Description: Efficacy

Measure: Proportion of patients with clinical recovery: Axillary temperature ≤36.6 ℃, or oral temperature ≤37.2 ℃, or rectal or tympanic temperature ≤37.8 ℃;

Time: Throughout the Study (Day 0 to Day 28 )

Description: Efficacy

Measure: Proportion of patients with clinical recovery: Respiratory frequency ≤24 times/min without oxygen inhalation; and

Time: Throughout the Study (Day 0 to Day 28 )

Description: Efficacy

Measure: Proportion of patients with clinical recovery: Oxygen saturation ≥98% without oxygen inhalation

Time: Throughout the Study (Day 0 to Day 28 )

Description: Efficacy

Measure: Proportion of patients with clinical improvement, defined as the time from first dose of IMP to an improvement of at least 2 points on the WHO 9 category ordinal scale, or live discharge from hospital without oxygen supplementation, whichever comes first

Time: Throughout the Study (Day 0 to Day 28 )

Description: Efficacy

Measure: Clinical patient status on the 9-category WHO ordinal scale1 on Days 6, 14, and 28

Time: on Days 6, 14, and 28

Description: Efficacy

Measure: Duration of INV

Time: Throughout the Study (Day 0 to Day 28 )

Description: Efficacy

Measure: Duration of ECMO

Time: Throughout the Study (Day 0 to Day 28)

Description: Efficacy

Measure: Duration of RRT

Time: Throughout the Study (Day 0 to Day 28)

Description: Efficacy

Measure: Duration of auxiliary oxygen therapy (including all types of oxygen therapy)

Time: Throughout the Study (Day 0 to Day 28)

Description: Efficacy

Measure: Duration of hospitalization for survivors

Time: Throughout the Study (Day 0 to Day 28)

Description: Efficacy

Measure: The rate of ICU* admission on Days 6, 14, and 28

Time: on Days 6, 14, and 28

Description: Efficacy

Measure: Hospital-free days

Time: Throughout the Study (Day 0 to Day 28)

Description: Efficacy

Measure: Time from IMP treatment initiation to death

Time: Throughout the Study (Day 0 to Day 28)

Description: Efficacy

Measure: Time to first prescription of INV

Time: Throughout the Study (Day 0 to Day 28)

Description: Efficacy

Measure: Time to first prescription of RRT

Time: Throughout the Study (Day 0 to Day 28)

Description: Efficacy

Measure: Time to first prescription of ECMO

Time: Throughout the Study (Day 0 to Day 28)

Description: Efficacy

Measure: Time to first prescription of INV, RRT, and ECMO

Time: Throughout the Study (Day 0 to Day 28)

Description: Efficacy

Measure: Time to ICU admission

Time: Throughout the Study (Day 0 to Day 28)

Description: Efficacy

Measure: Cumulative dose of vasoactive therapies and days with vasoactive therapies (daily until Day 14)

Time: Day 0 to day 14

Description: Efficacy

Measure: Time to clinical recovery

Time: Throughout the Study (Day 0 to Day 28)

Description: Pharmacokinetics

Measure: Morning trough plasma levels of IMU-838 on Days 0, 1, 2, 3, 6, 14, and 28

Time: on Days 0, 1, 2, 3, 6, 14, and 28

Description: Pharmacokinetics

Measure: Correlation of trough levels (quartiles) to selected clinical outcomes (Clinical improvement accoding to WHO criteria)

Time: on Days 0, 1, 2, 3, 6, 14, and 28

Description: Safety

Measure: Adverse events (AEs) and serious AEs

Time: Throughout the Study (Day 0 to Day 28)

Description: Safety Height in centimeters will be recorded without shoes. Changes in vital signs judged by the investigator as clinically significant will be reported as an AE.

Measure: Vital signs: height

Time: only at Screening

Description: Safety Weight in kilograms will be recorded without shoes. Changes in vital signs judged by the investigator as clinically significant will be reported as an AE.

Measure: Vital signs: weight

Time: Throughout the Study (Day 0 to Day 28)

Description: Safety Body temperature can be measured axillary, oral, rectal or tympanic, but should be always measured by the same method for a patient. Changes in vital signs judged by the investigator as clinically significant will be reported as an AE.

Measure: Vital signs: body temperature (ºC)

Time: Throughout the Study (Day 0 to Day 28)

Description: Safety Pulse must be measured with the patient in a seated position (if possible), after at least 5 minutes at rest. Changes in vital signs judged by the investigator as clinically significant will be reported as an AE.

Measure: Vital signs: pulse rates,

Time: Throughout the Study (Day 0 to Day 28)

Description: Safety Blood pressure (systolic and diastolic) must be measured with the patient in a seated position (if possible), after at least 5 minutes at rest. Changes in vital signs judged by the investigator as clinically significant will be reported as an AE.

Measure: Vital signs: systolic and diastolic blood pressures

Time: Throughout the Study (Day 0 to Day 28)

Description: Safety

Measure: Clinical laboratory parameters: blood chemistry

Time: Throughout the Study (Day 0 to Day 28)

Description: Safety

Measure: Clinical laboratory parameters: hematology

Time: Throughout the Study (Day 0 to Day 28)

Description: Safety

Measure: Clinical laboratory parameters: urinalysis

Time: Throughout the Study (Day 0 to Day 28)

Description: Safety

Measure: 12-lead electrocardiogram: heart rate

Time: Day 0 to Day 6 and Day 28

Description: Safety

Measure: 12-lead electrocardiogram: PQ-interval

Time: Day 0 to Day 6 and Day 28

Description: Safety

Measure: 12-lead electrocardiogram: QRS-interval

Time: Day 0 to Day 6 and Day 28

Description: Safety

Measure: 12-lead electrocardiogram: QT interval

Time: Day 0 to Day 6 and Day 28

Description: Safety

Measure: 12-lead electrocardiogram: the heart rate-corrected QTc interval (according to Bazett's formula)

Time: Day 0 to Day 6 and Day 28

Description: Safety

Measure: Temperature

Time: Throughout the Study (Day 0 to Day 28)

Description: Disease markers

Measure: D-dimer

Time: Throughout the Study (Day 0 to Day 28)

Description: Disease markers

Measure: Lactate dehydrogenase (LDH)

Time: Throughout the Study (Day 0 to Day 28)

Description: Disease markers

Measure: C-reactive protein

Time: Throughout the Study (Day 0 to Day 28)

Description: Disease markers

Measure: Troponin I

Time: Throughout the Study (Day 0 to Day 28)

Description: Disease markers

Measure: Procalcitonin

Time: Throughout the Study (Day 0 to Day 28)

Description: Disease markers

Measure: Correlation of disease markers to selected clinical outcomes (Clinical improvement accoding to WHO criteria)

Time: Throughout the Study (Day 0 to Day 28)

Description: Virologic markers

Measure: Severe Acute Respiratory Syndrome Coronavirus Virus (SARS-CoV-2) mean viral load - log10 copies in spontaneous sputum and nasopharyngeal swab samples: Decrease of SARS-CoV-2 viral load

Time: Throughout the Study (Day 0 to Day 28)

Description: Virologic markers

Measure: Severe Acute Respiratory Syndrome Coronavirus Virus (SARS-CoV-2) mean viral load - log10 copies in spontaneous sputum and nasopharyngeal swab samples: Time course of SARS-CoV-2 viral load

Time: Throughout the Study (Day 0 to Day 28)

Description: Virologic markers

Measure: Qualitative virologic clearance in spontaneous sputum and nasopharyngeal swab samples (= 2 consecutive negative SARS-CoV-2 reverse transcriptase polymerase chain reaction tests at least 24 hours apart)

Time: Throughout the Study (Day 0 to Day 28)

Description: Virologic markers

Measure: Rate of conversion to a negative SARS-CoV-2 (qualitative) test on Days 6, 14 and 28

Time: on Days 6, 14 and 28

Description: Virologic markers

Measure: Time to conversion to a negative SARS-CoV-2 (qualitative) test

Time: Throughout the Study (Day 0 to Day 28)

Description: Biomarkers

Measure: Interleukin (IL)-17

Time: Day 0, 6, 14 and Day 28

Description: Biomarkers

Measure: Interleukin (IL)-1ß

Time: Day 0, 6, 14 and Day 28

Description: Biomarkers

Measure: Interleukin (IL)-6

Time: Day 0, 6, 14 and 28

Description: Biomarkers

Measure: interferon gamma (IFNγ)

Time: Day 0, 6, 14 and 28

Description: Biomarkers

Measure: tumor necrosis factor alpha

Time: Day 0, 6, 14 and 28

Description: Serologic markers

Measure: Immunoglobulin (Ig)A and IgG antibodies against SARS-CoV-2: • Time to appearance of IgA and/or IgG antibodies

Time: Day 0, 6, 14 and 28

Description: Serologic markers

Measure: Immunoglobulin (Ig)A and IgG antibodies against SARS-CoV-2: • Proportion of patients with IgA and/or IgG antibodies on Days 6, 14, and 28

Time: Day 0, 6, 14 and 28

105 Single-center, Phase II, Randomized Double-blind, Placebo-controlled Study of Hydroxychloroquine Compared to Placebo as Treatment for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection

This study is being done to see if hydroxychloroquine is an effective treatment for COVID-19.

NCT04379492 COVID-19 COVID19 Sars-CoV2 SARS-Cov-2 Drug: Hydroxychloroquine Other: Placebo

Primary Outcomes

Description: Clinical improvement is defined as a composite endpoint of a two-point clinical improvement on the Ordinal Scale for Clinical Improvement (OSCI). The OSCI is an ordinal scale of 9 severity levels (from 0 to 8) for COVID-19

Measure: Clinical improvement on the Ordinal Scale for Clinical Improvement (OSCI)

Time: 14 days

Description: Clinical improvement is defined as no mechanical ventilation for respiratory failure attributed to SARS-CoV-2 within 14 days of randomization.

Measure: Number of participants requiring mechanical ventilation for respiratory failure

Time: 14 days

106 An International, Multicenter, Randomized, Double-blind, Adaptive Placebo-controlled Study of the Efficacy and Safety of a Single Administration of Olokizumab and RPH-104 With Standard Therapy in Patients With Severe SARS-CoV-2 Infection (COVID-19)

The primary objective of the study is to evaluate the efficacy and safety of a single dose of RPH-104 (80 mg) or OKZ (64 mg) compared to placebo in addition to standard therapy in patients with severe SARS-CoV-2 infection (COVID-19) at Day 15 of the study

NCT04380519 COVID-19 Biological: RPH-104 80 mg Drug: Olokizumab 64 mg Drug: Placebo
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome

Primary Outcomes

Description: Proportion of patients, responded to the study therapy, in each of the treatment groups. The patient can be considered as the therapy responder, in case tocilizumab or sarilumab were not administered and there is an improvement of a clinical status at least by 1 point on a 6-points COVID-19 scale, where 1 point means most favorable outcome, 6 points means most undesirable outcome.

Measure: Proportion of patients, responded to the study therapy, in each of the treatment groups

Time: Day 15

Secondary Outcomes

Description: Changes of patients' clinical status on a 6 points ordinal scale over time

Measure: Changes of patients' clinical status on a 6 points ordinal scale over time

Time: from Day 2 until Day 15, Day 29

Description: Mortality rate over the follow-up period

Measure: Mortality rate over the follow-up period

Time: from Day 1 until Day 29

Description: Improvement of the patient's clinical status by at least 2 points on a 6-point ordinal scale in the absence of tocilizumab or sarilumab administration.

Measure: Improvement of the patient's clinical status by at least 2 points on a 6-point ordinal scale in the absence of tocilizumab or sarilumab administration.

Time: on screening and then from Day 1 until Day 29

Description: Proportion of patients received tocilizumab or sarilumab due to COVID-19

Measure: Proportion of patients received tocilizumab or sarilumab due to COVID-19

Time: from Day 1 until the Day 29

Other Outcomes

Description: Proportion of patients having National Early Warning Score 2 (NEWS2) of ≤ 4 maintained for 2 consecutive days

Measure: Proportion of patients having National Early Warning Score 2 of ≤ 4 maintained for 2 consecutive days

Time: from day 3 until day 15

Description: Time to a NEWS2 of ≤ 2 maintained for two consecutive days

Measure: Time to a NEWS2 of ≤ 2 maintained for two consecutive days

Time: from day 1 until day 15

Description: Changes from baseline of cytokine storm surrogate markers: white blood counts, lymphocyte counts, neutrophils counts, CRP, ferritin (if applicable), D-dimer (if applicable)

Measure: Changes from baseline of cytokine storm surrogate markers: white blood counts, lymphocyte counts, neutrophils counts, C-Reactive protein (CRP), ferritin (if applicable), D-dimer (if applicable)

Time: Day 2, Day 3, Day5, Day 7, Day 15

Description: Mortality during an ICU stay, on days 7, 15, 29 of the study

Measure: Mortality during an ICU stay, on days 7, 15, 29 of the study

Time: On Day 7, Day 15, Day 29

Description: Time to increase of oxygen saturation SpO2 ≥ 94% n the absence of oxygen support maintained for two consecutive days

Measure: Time to increase of oxygen saturation SpO2 ≥ 94% n the absence of oxygen support maintained for two consecutive days

Time: from Day 2 until Day 15

Description: Changes of oxygenation index PaO2/FiO2 from baseline (if applicable) during hospitalization period

Measure: Changes of oxygenation index PaO2/FiO2 from baseline (if applicable) during hospitalization period

Time: On Day 1 and from Day 2 until Day 15

Description: Duration of ICU stay measured in days

Measure: Duration of ICU stay measured in days

Time: from Day 2 until Day 15

Description: Changes from baseline (if applicable) in severity of ARDS according to WHO criteria

Measure: Changes from baseline (if applicable) in severity of Acute Respiratory Distress Syndrome (ARDS) according to World Health Organization (WHO) criteria

Time: from Day 1 until Day 15

Description: Duration of mechanical ventilation and EMO (if applicable) measured in days

Measure: Duration of mechanical ventilation and Extracorporeal Membrane Oxygenation (EMO) (if applicable) measured in days

Time: from Day 2 until Day 15

Description: Duration of oxygen support (if applicable) measured in days

Measure: Duration of oxygen support (if applicable) measured in days

Time: from Day 1 until Day 15

Description: Proportion of patients having National Early Warning Score 2 of ≤ 2 maintained for 2 consecutive days

Measure: Proportion of patients having National Early Warning Score 2 of ≤ 2 maintained for 2 consecutive days

Time: from day 3 until day 15

Description: Time to a NEWS2 of ≤ 4 maintained for two consecutive days

Measure: Time to a NEWS2 of ≤ 4 maintained for two consecutive days

Time: from day 1 until day 15

Description: Time to improvement in severity of ARDS according to WHO criteria in one category changing from baseline (if applicable)

Measure: Time to improvement in severity of ARDS according to WHO criteria in one category changing from baseline (if applicable)

Time: On Day 1 and from Day 2 until Day 15

Description: Time to fever resolution i.e. setting of axillary body temperature <38 °C without antipyretics when measured for 2 consecutive days (if applicable)

Measure: Time to fever resolution i.e. setting of axillary body temperature <38 °C without antipyretics when measured for 2 consecutive days (if applicable)

Time: from day 1 until day 15

Description: Time to improvement of clinical status by 1 point on a 6-points COVID-19 scale

Measure: Time to improvement of clinical status by 1 point on a 6-points COVID-19 scale

Time: from day 1 until day 29

Description: Time to improvement of clinical status by 2 points on a 6-points COVID-19 scale

Measure: Time to improvement of clinical status by 2 points on a 6-points COVID-19 scale

Time: from day 1 until day 29

Description: Proportion of patients with the deterioration of clinical status by 1 point on a 6-points COVID-19 scale during the study

Measure: Proportion of patients with the deterioration of clinical status by 1 point on a 6-points COVID-19 scale during the study

Time: from Day 1 until Day 29

Description: Proportion of patients with the deterioration of clinical status by 1 point on a 6-points COVID-19 scale during the study, excluding the patients moved to the category 6, if applicable

Measure: Proportion of patients with the deterioration of clinical status by 1 point on a 6-points COVID-19 scale during the study, excluding the patients moved to the category 6, if applicable

Time: from Day 1 until Day 29

Description: Time to the deterioration of clinical status by 1 point on a 6-points COVID-19 scale during the study (if applicable)

Measure: Time to the deterioration of clinical status by 1 point on a 6-points COVID-19 scale during the study (if applicable)

Time: from Day 1 until Day 29

107 Phase 2, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Sirukumab in Confirmed Severe or Critical COVID-19 Disease

The purpose of this study is to evaluate the clinical response of sirukumab (administered as a single intravenous dose) plus standard of care (SOC) compared to placebo plus SOC in COVID-19.

NCT04380961 Severe or Critical Confirmed Coronavirus Disease (COVID)-19 Drug: Sirukumab Drug: Placebo Other: Standard of Care (SOC)
MeSH:Coronavirus Infections

Primary Outcomes

Description: Time to improvement is defined as an improvement of at least 2 categories relative to baseline on the 6-point ordinal clinical recovery scale. The 6-point ordinal clinical recovery scale provides 6 mutually exclusive conditions ordered from best to worst, and the score reflects the participant's worst situation on the day assessed. The ordinal clinical recovery scale categories are : not hospitalized (category 1); Hospitalization; not requiring supplemental oxygen (category 2); hospitalized, requiring low flow supplemental oxygen (category 3); hospitalized, on non-invasive pressure ventilation or high flow oxygen devices (category 4); hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO (category 5); death (category 6).

Measure: Time to Improvement of at Least 2 Categories Relative to Baseline on the 6-Point Ordinal Clinical Recovery Scale

Time: Up to Day 28

Secondary Outcomes

Description: Percentage of participants with an improvement of at Least 2 categories relative to baseline on the 6-point ordinal clinical recovery scale on Day 28 will be reported.

Measure: Percentage of Participants with an Improvement of at Least 2 Categories Relative to Baseline on the 6-Point Ordinal Clinical Recovery Scale on Day 28

Time: Day 28

Description: A SAE is any adverse event (AE) that results in: death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect and is a suspected transmission of any infectious agent via a medicinal product, is medically important.

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

Time: Up to Day 28

Description: An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product.

Measure: Percentage of Participants with Related Adverse Events

Time: Up to Day 28

Description: Percentage of participants with severe or life-threatening, bacterial, invasive fungal, viral or opportunistic infections (other than severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) will be reported.

Measure: Percentage of Participants with Severe or Life Threatening Bacterial, Invasive Fungal, Viral or Opportunistic Infections

Time: Up to Day 28

Description: Percentage of participants with grade 3 (severe) or 4 (life-threatening) neutropenia will be reported.

Measure: Percentage of Participants with Grade 3 and 4 Neutropenia

Time: Up to Day 28

Description: Percentage of participants with grade 3 (severe) or 4 (life-threatening) lymphocytopenia will be reported.

Measure: Percentage of Participants with Grade 3 and 4 Lymphocytopenia

Time: Up to Day 28

Description: Percentage of participants with increased ALT >=3 times ULN combined with increased bilirubin >2 times ULN (up to Day 28) will be reported.

Measure: Percentage of Participants with Increased Alanine Aminotransferase (ALT) Greater than or equal to 3 Times Upper Limit of Normal (ULN) Combined with Increased Bilirubin > 2 Times ULN

Time: Up to Day 28

Description: Time to improvement of at least 1 category relative to baseline on the 6-point ordinal clinical recovery scale will be reported.

Measure: Time to Improvement of at least 1 Category Relative to Baseline on the 6-Point Ordinal Clinical Recovery Scale

Time: Up to Day 28

Description: Percentage of participants with an improvement of at Least 1 category relative to baseline on the 6-point ordinal clinical recovery scale on Day 28 will be reported.

Measure: Percentage of Participants with an Improvement of at Least 1 Category Relative to Baseline on the 6-Point Ordinal Clinical Recovery Scale on Day 28

Time: Day 28

Description: Time from study intervention to end of oxygen supplementation is defined as achieving category 1 or 2 on the 6-point ordinal clinical recovery scale.

Measure: Time from Study Intervention to end of Oxygen Supplementation

Time: Up to Day 28

Description: Time from study intervention to hospital discharge among the surviving participants will be reported.

Measure: Time from Study Intervention to Hospital Discharge Among the Surviving Participants

Time: Up to Day 28

Description: Total length of hospitalization (days from admission to hospital discharge) among the surviving participants will be reported.

Measure: Total Length of Hospitalization

Time: Up to Day 28

Description: Percentage of participants with all-cause mortality will be reported.

Measure: Percentage of Participants with All-cause Mortality

Time: Up to Day 28

Description: Number of Ventilation free Days will be reported.

Measure: Number of Ventilation Free Days

Time: Up to Day 28

Description: Participant's clinical status at Day 7, 14, 21, 28 will be assessed by 6-point ordinal clinical recovery scale.

Measure: Participant's Clinical Status at Day 7, 14, 21, 28 as Assessed by 6-Point Ordinal Clinical Recovery Scale

Time: Day 7, 14, 21, 28

Description: Total time on invasive mechanical ventilation will be reported.

Measure: Total Time on Invasive Mechanical Ventilation

Time: Up to Day 28

Description: Percentage of participants with a worse category relative to baseline on the 6-point ordinal clinical recovery scale over time 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: Up to Day 28

Description: Percentage participants on ECMO over time will be reported.

Measure: Percentage of Participants on Extracorporeal Membrane Oxygenation (ECMO) Over Time

Time: Up to Day 28

Description: Total time on ECMO will be reported.

Measure: Total Time on ECMO

Time: Up to Day 28

Description: Percentage of alive participants at Day 28, Week 8 and Week 16 will be reported.

Measure: Percentage of Alive Participants at Day 28, Week 8 and Week 16

Time: Day 28, Week 8 and Week 16

Description: Percentage of alive participants that required readmission (if previously discharged) at Week 8 and Week 16 will be reported.

Measure: Percentage of Alive Participants that Required Readmission at Week 8 and Week 16

Time: Week 8 and Week 16

Description: A SAE is any adverse event (AE) that results in: death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect and is a suspected transmission of any infectious agent via a medicinal product, is medically important.

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

Time: Up to Week 16

108 A Randomized Placebo-Controlled Safety and Dose-Finding Study for the Use of the IL-6 Inhibitor Clazakizumab in Patients With Life-threatening COVID-19 Infection

In this study, the investigators propose to administer clazakizumab to patients with life-threatening Coronavirus Disease 2019 (COVID-19) infection manifest by pulmonary failure and a clinical picture consistent with a cytokine storm syndrome. This is a single-center randomized, double-blind, placebo-controlled trial in which 30 patients will be enrolled and randomly assigned in a 1:1 ratio to two study arms and receive clazakizumab at a dose of 25 mg or placebo.

NCT04381052 COVID-19 Drug: Clazakizumab Other: Placebo
MeSH:Infection

Primary Outcomes

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

Time: 60 days

Secondary Outcomes

Measure: Cumulative Incidence of Intubation

Time: 14 days

Measure: Time to Extubation

Time: 14 days

Measure: Length of Intensive Care Unit (ICU) stay

Time: 14 days

Measure: Number of Patients who Present a Decrease in C-reactive protein (CRP)

Time: 14 days

Measure: Number of Patients with Acute Kidney Injury (AKI)

Time: 14 days

Measure: Number of Patients with a Need for Renal Replacement Therapy (RRT)

Time: 14 days

Measure: Duration of Renal Replacement Therapy (RRT)

Time: 60 days

Description: Number of participants alive at day 28.

Measure: Patient Survival

Time: 28 days

Description: Number of participants alive at day 60, end of study.

Measure: Patient Survival

Time: 60 days

Measure: Number of Patients with Hemodialysis

Time: 60 days

Measure: Number of Patients with Continuous Renal Replacement Therapies (CRRT)

Time: 60 days

Measure: Number of Patients with Peritoneal Dialysis

Time: 60 days

109 A Multi-centre, Adaptive, Randomized, Double-blind, Placebo-controlled Comparative Clinical Study of the Safety and Efficacy of Polyoxidonium®, Lyophilizate for Solution for Injections and Topical Application, 6 mg (NPO Petrovax Pharm LLC, Russia) in Patients With Coronavirus Disease (COVID-19).

The purpose of this study is to demonstrate the superiority of Polyoxidonium®, lyophilizate for solution for injections and topical application, 6 mg over placebo in hospitalized patients with coronavirus disease (COVID-19). This is a multicentre prospective, randomized, double-blind, placebo-controlled, parallel-group phase IIb\IIIa clinical trial.

NCT04381377 Infections, Coronavirus Drug: azoximer bromide Other: Placebo
MeSH:Coronavirus Infections

Primary Outcomes

Description: The primary efficacy outcome will be defined based on the blinded analysis of data of the first 100 patients in the 1st part of the study. There is uncertainty about the clinical course and potential different trajectories according to baseline disease severity, so the day of the primary endpoint may be modified based on a blinded evaluation of the primary efficacy outcome in various days.

Measure: Clinical status of the patient (according to 7-point ordinal scale)

Time: Day 15

Secondary Outcomes

Description: Time to improvement by one category from admission on the ordinal scale. Clinical status of the patient. Average change in the ordinal scale from baseline.

Measure: Clinical status of the patient (according to 7-point ordinal scale)

Time: Clinical status of the patient and the average change in the ordinal scale from baseline, both on days 3, 5, 8, 11, 29.

Description: The time to discharge or to a NEWS of ≤ 2 and maintained for 24 hours, whichever occurs first. Change in NEWS from baseline.

Measure: NEWS

Time: Change in NEWS from baseline on days 3, 5, 8, 11, 15, 29.

Description: Oxygenation free days. Incidence and duration of new oxygen use.

Measure: Oxygenation

Time: Oxygenation free days in the first 28 days (to day 29). Incidence and duration of new oxygen use during the study.

Description: Ventilator free days. Incidence and duration of new mechanical ventilation use.

Measure: Mechanical Ventilation

Time: Ventilator free days in the first 28 days (to day 29). Incidence and duration of new mechanical ventilation use during the trial.

Measure: Mortality

Time: 28-day mortality

110 A Phase II Randomized Double-Blind Placebo-Controlled Clinical Trial Of Hydroxychloroquine For Prophylaxis Against Covid-19 In Patients Receiving Radiotherapy (COVID)

The researchers are doing this study to find out whether the study drug hydroxychloroquine can prevent infection with the COVID-19 virus, compared with placebo, in people who are receiving radiation therapy for their cancer. The placebo used in this study is a tablet that looks the same as the study drug and is taken in the same way, but it does not contain any active ingredients.

NCT04381988 COVID-19 Cancer Drug: Hydroxychloroquine Other: Placebo Radiation: Radiation therapy

Primary Outcomes

Description: Any patients who are enrolled and subsequently test positive for SARS-CoV-2 by RT-PCR (outside RT-PCR test results allowed) at any point during the 9 weeks following enrollment will be an event that is considered in the 9-week SARS-CoV-2 infection rate primary endpoint.

Measure: cumulative incidence of SARS-CoV-2 infection

Time: within 9 weeks from randomization

Secondary Outcomes

Description: Patients who are positive for SARS-CoV-2 (as defined above) who develop a new oxygen requirement attributable to COVID-19, tachypnea (RR > 20), or those who require hospitalization due to COVID-19 will be considered to have severe COVID-19.

Measure: cumulative incidence of severe COVID-19 or death

Time: within 12 weeks of randomization

111 A Phase II, Controlled Clinical Study Designed to Evaluate the Effect of ArtemiC in Patients Diagnosed With COVID-19

Agent Name and Study Duration ArtemiC is a medical spray comprised of Artemisinin (6 mg/ml), Curcumin (20 mg/ml), Frankincense (=Boswellia) (15 mg/ml) and vitamin C (60 mg/ml) in micellar formulation for spray administration. Patients will receive up to 6 mg Artemisinin, 20 mg Curcumin, 15 mg Frankincense and 60 mg vitamin C given daily as an add-on therapy (in addition to standard care) in two divided doses, on Days 1 and 2. Patients will be randomized in a manner of 2:1 for study drug (ArteminC) and Standard of Care to Placebo and Standard of Care. Patient follow-up will last 2 weeks. During this time, patients will be monitored for adverse events. Additional time will be required for follow up (until hospital discharge) in order to check side effects and study drug efficacy. Placebo, composed of the same solvent but without active ingredients, will be given in the placebo group as add-on therapy, 2 times a day, on Days 1 and 2. Overall rationale A preparation of ArtemiC, comprising Artemisinin, Curcumin, Boswellia, and Vitamin C in a nanoparticular formulation, is proposed as a treatment for the disease associated with the novel corona virus SARS-CoV-2. It is readily available in light of its status as a food supplement. This initiative is presented under the urgent circumstances of the fulminant pandemic caused by this lethal disease, which is known as COVID-19 and has spread across the globe causing death and disrupting the normal function of modern society. The grounds for the proposal are rooted in existing knowledge on the components and pharmacological features of this formulation and their relevance to the current understanding of the disease process being addressed. Leading among these considerations are well established immuno-modulatory activities of the active ingredients as established in vitro and in vivo and published over the years. These activities as apparent, for example, in diminishing activity of TNF alpha and IL-6 levels are acknowledged to be relevant to the pathophysiology processes involved in the progressive form of COVID-19. The active agents have in addition prominent anti-oxidant, anti-inflammatory as well as anti-aggregant and anti-microbial activities. Based on these activities and observations in animal models, together with clinical experience of the separate ingredients and in various combinations in other contexts it is proposed to evaluate their effect in the context of COVID-19. Study Purpose This study is designed to evaluate the safety and efficacy of ArtemiC on patients diagnosed with COVID-19. Methodology 50 adult patients who suffer from COVID-19 infection studied in parallel groups treated with active agent or placebo as add on to standard care. Safety will be assessed through collection and analysis of adverse events, blood and urine laboratory assessments and vital signs.

NCT04382040 COVID-19 Corona Virus Infection SARS-CoV 2 Coronavirus Coronavirus Infection Drug: ArtemiC Drug: Placebo
MeSH:Infection Communicable Diseases Coronavirus Infections Severe Acute Respiratory Syndrome

Primary Outcomes

Description: patient will be assessed using a scoring table for changes in clinical signs

Measure: Time to clinical improvement, defined as a national Early Warning Score 2 (NEWS2) of Time: 24 hours

Description: Adverse events caused by the study drug will be assessed

Measure: Percentage of participants with definite or probable drug related adverse events

Time: 14 days

Secondary Outcomes

Measure: Time to negative COVID-19 PCR

Time: 14 days

Measure: Proportion of participants with normalization of fever and oxygen saturation through day 14 since onset of symptoms

Time: 14 days

Measure: COVID-19 related survival

Time: 14 days

Measure: Incidence and duration of mechanical ventilation

Time: 14 days

Measure: Incidence of Intensive Care Init (ICU) stay

Time: 14 days

Measure: Duration of ICU stay

Time: 14 days

Measure: Duration of time on supplemental oxygen

Time: 14 days

112 A Phase 2, Randomized, Double Blind, Placebo-Controlled Study of Zanubrutinib Treatment in Patients Hospitalized for COVID-19 Infection and Pulmonary Distress

The primary objective of this study is to evaluate if the addition of zanubrutinib to supportive care increases the respiratory failure-free survival rate at Day 28 in participants hospitalized for Corona Virus Disease 2019 (COVID-19) and pulmonary distress.

NCT04382586 COVID-19 Pulmonary Complications COVID-19 Drug: Zanubrutinib Drug: Supportive Care Drug: Placebo
MeSH:Infection

Primary Outcomes

Description: Respiratory failure-free survival rate 28 is defined as the proportion of patients who have not had respiratory failure nor died <= 28 days from randomization.

Measure: Respiratory failure-free survival rate at day 28

Time: 28 Days

Secondary Outcomes

Measure: Median reduction in days spent on supplemental oxygen

Time: Up to 28 Days

Measure: All-cause mortality

Time: Up to 28 Days

Measure: Proportion of participants experiencing respiratory failure or death

Time: Up to 28 Days

Measure: Mechanical ventilation-free survival

Time: Up to 28 Days

Measure: Days on mechanical ventilation

Time: Up to 28 Days

Measure: Duration of hospitalization

Time: Up to 28 Days

Measure: Time to discharge

Time: Up to 28 Days

Measure: PaO2:FiO2 and/or oxygenation index

Time: Up to 28 Days

Description: This scale evaluates the safety and efficacy of investigational therapeutic agents in combination with care for the treatment of hospitalized participants suffering from COVID-19 infections on a scale of scores from 0 to 8, with higher scores indicating higher level of severity of the disease. (0 = No clinical or virological evidence of disease, and 8 = Death)

Measure: Change from Baseline to Day 14 in WHO - 8 Point Ordinal Scale

Time: Up to 28 Days

113 A Prospective, Randomized, Open-label, Interventional Study to Investigate the Efficacy of Complement C5 Inhibition With Zilucoplan® in Improving Oxygenation and short-and Long-term Outcome of COVID-19 Patients With Acute Hypoxic Respiratory Failure

The study is a randomized controlled, open-label trial comparing subcutaneous Zilucoplan® with standard of care to standard of care alone. In the active group, Zilucoplan® will be administered subcutaneously once daily for 14 days or till discharge from the hospital, whichever comes first. The hypothesis of the proposed intervention is that Zilucoplan® (complement C5 inhibitor) has profound effects on inhibiting acute lung injury post COVID-19, and can promote lung repair mechanisms, that lead to a 25% improvement in lung oxygenation parameters. This hypothesis is based on experiments performed in mice showing that C5a blockade can prevent mortality and prevent ARDS in mice with post-viral acute lung injury. Eligible patients include patients with confirmed COVID-19 infection suffering from hypoxic respiratory failure defined as O2 saturation below 93% on minimal 2l/min O2 therapy and/or ratio PaO2/FiO2 below 350.

NCT04382755 COVID-19 Drug: Zilucoplan® Drug: Placebo
MeSH:Respiratory Insufficiency

Primary Outcomes

Description: defined by Pa02/FiO2 ratio while breathing room air, P(Aa)O2 gradient and a/A pO2 ratio

Measure: Mean change in oxygenation

Time: at predose, day 6 and day 15 (or at discharge, whichever comes first)

Description: defined by Pa02/FiO2 ratio while breathing room air, P(Aa)O2 gradient and a/A pO2 ratio

Measure: Median change in oxygenation

Time: at predose, day 6 and day 15 (or at discharge, whichever comes first)

Secondary Outcomes

Measure: number of AE's (Adverse Events)

Time: during hospital admission (up to 28 days)

Measure: number of SAE's (Serious Adverse Events)

Time: during hospital admission (up to 28 days)]

Description: 6-point ordinal scale defined as Death Hospitalized, on invasive mechanical ventilation or ECMO; Hospitalized, on non-invasive ventilation Hospitalized, requiring supplemental oxygen Hospitalized, not requiring supplemental oxygen Not hospitalized

Measure: mean change in 6-point ordinal scale change

Time: between day 1 and respectively day 6, day 15 (or discharge, whichever comes first) and day 28 (by phone call).

Description: defined as independence from supplemental oxygen

Measure: Time since randomization until improvement in oxygenation

Time: during hospital admission (up to 28 days)

Description: defined as SpO2 < 93% breathing room air or the dependence on supplemental oxygen

Measure: Number of days with hypoxia

Time: during hospital admission (up to 28 days)

Measure: Number of days of supplemental oxygen use

Time: during hospital admission (up to 28 days)

Measure: Time to absence of fever (defined as 37.1°C or more) for more than 48h without antipyretic

Time: during hospital admission (up to 28 days)

Description: defined as 37.1°C or more

Measure: Number of days with fever

Time: during hospital admission (up to 28 days)

Measure: Time to halving of CRP levels to peak value during trial

Time: during hospital admission (up to 28 days)

Measure: Time to halving of ferritin levels compared to peak value during trial

Time: during hospital admission (up to 28 days)

Measure: Incidence of AE's

Time: during hospital admission (up to 28 days)

Measure: Incidence of SAE's

Time: at 10-20 weeks follow-up

Measure: Incidence of SUSAR's (Suspected Unexpected Serious Adverse Reaction)

Time: during hospital admission (up to 28 days)

Measure: Incidence of SAR's (Serious Adverse Reaction)

Time: during hospital admission (up to 28 days)

Measure: Duration of hospital stay

Time: during hospital admission (up to 28 days)

Measure: Duration of hospital stay in survivors

Time: during hospital admission (up to 28 days)

Description: Clinical sign score: 0( best) - 18 (worse)

Measure: Mean change in clinical sign score between day 1 and day 6

Time: day 1, day 6 or on discharge, whichever is first

Description: Clinical sign score: 0( best) - 18 (worse)

Measure: Mean change in clinical sign score between day 1and day 15 (or on discharge, whichever is first)

Time: day 1, day 15 or on discharge, whichever is first

Description: Clinical sign score: 0( best) - 18 (worse)

Measure: Mean change in clinical sign score between day 1 and day 28 (or on discharge, whichever is first)

Time: day 1, day 28 or on discharge, whichever is first

Description: SOFA score: 0 (best) - 24 (worse)

Measure: Mean change of SOFA score between day 1 and day 6 (or on discharge, whichever is first)

Time: day 1, day 6 or on discharge, whichever is first

Description: SOFA score: 0 (best) - 24 (worse)

Measure: Mean change of SOFA score between day 1 and day 15 or on discharge, whichever is first)

Time: day 1, day 15 or on discharge, whichever is first

Description: NEWS2 score: 0 (best) - 24 (worse)

Measure: Mean change NEWS2 (National Early Warning) score between day 1 and day 6

Time: day 1, day 6 or on discharge, whichever is first

Description: NEWS2 score: 0 (best) - 24 (worse)

Measure: Mean change NEWS2 (National Early Warning) score between day 1 and day 15

Time: day 1, day 15 or on discharge, whichever is first

Description: 6-point ordinal scale: Death Hospitalized, on invasive mechanical ventilation or ECMO; Hospitalized, on non-invasive ventilation or high flow oxygen devices; Hospitalized, requiring supplemental oxygen Hospitalized, not requiring supplemental oxygen Not hospitalized

Measure: Percentage of patients reporting each severity rating on a 6-point ordinal scale at randomization, day 6 and 15 (or discharge, whichever comes first) and day 28 (phone call)

Time: day 1, day 6, day 15 (or discharge, whichever comes first)

Description: 6-point ordinal scale: Death Hospitalized, on invasive mechanical ventilation or ECMO; Hospitalized, on non-invasive ventilation or high flow oxygen devices; Hospitalized, requiring supplemental oxygen Hospitalized, not requiring supplemental oxygen Not hospitalized

Measure: 6-point Ordinal Scale at 6 and 15 days (or discharge whichever comes first) and day 28 (phone call), in relation to serum D-dimers and complement C5a levels at randomization

Time: day 1, day 6, day 15 (or discharge, whichever comes first)

Measure: Incidence of nosocomial bacterial or invasive fungal infection for 28 days (phone call) after enrolment in trial

Time: day 28

Description: defined by Hs (Hemophagocytic Syndrome) score

Measure: incidence of secondary haemophagocytic lymphohistiocytosis in relation to serum D-dimers and complement C5a at randomization

Time: day 1, day 6, day 15 (or discharge, whichever comes first)

Measure: Time since randomization until first use of high-flow oxygen devices in non-ventilated patients

Time: during hospital admission (up to 28 days)

Measure: Time since randomization until first use of non-invasive mechanical ventilation in non-ventilated patients

Time: during hospital admission (up to 28 days)

Measure: Time since randomization until first use of invasive mechanical ventilation in non-ventilated patients

Time: during hospital admission (up to 28 days)

Measure: Time since to first use of salvage systemic steroids in ventilated patients

Time: during hospital admission (up to 28 days)

Measure: Number of ventilator-free days

Time: day 1, day 28 or discharge whichever comes first

Measure: Duration of invasive and non-invasive mechanical ventilation in ventilated patients

Time: during hospital admission (up to 28 days)

Measure: Duration of ICU stay in patients that enrolled in trial on invasive or non-invasive mechanical ventilation for less than 24h prior to or after randomization

Time: during hospital admission (up to 28 days)

Description: criteria-defined ARDS (according to the American-European Consensus Conference (AECC) diagnostic criteria for ARDS: acute onset; ratio of partial pressure of arterial oxygen to fraction of inspired oxygen (PaO2/FiO2) of 200mmHg or less, regardless of positive end-expiratory pressure; bilateral infiltrates seen on frontal chest radiograph; and pulmonary artery wedge pressure of 18 mm Hg or less when measured, or no clinical evidence of left atrial hypertension)

Measure: Time since randomization to progression to ARDS (Acute Respiratory Distress Syndrome) in ventilated patients

Time: during hospital admission (up to 28 days)

Measure: Time to progression to ARDS in ventilated patients according to D-dimers at randomization

Time: during hospital admission (up to 28 days)

Measure: Time to progression to ARDS in ventilated patients according to complement C5a at randomization

Time: during hospital admission (up to 28 days)

Measure: All-cause mortality rate (excluding group that entered during ventilation)

Time: at day 28

Measure: All-cause mortality rate (including group that entered during ventilation)

Time: at day 28

Measure: Percentage of patients in clinical status on 6-point Ordinal Scale

Time: at 12-22 weeks follow-up

Description: Clinical sign score: 0( best) - 18 (worse)

Measure: Mean change in clinical sign score between day 1 and follow up 12-22 weeks

Time: day 1, follow-up 12-22 weeks

Measure: Incidence of lung function abnormalities at follow

Time: at 12-22 weeks follow-up

Measure: Incidence of lung fibrosis on chest CT scan

Time: at 12-22 weeks follow-up

Measure: All cause mortality for the entire study population

Time: at follow up 12-22 weeks

114 Randomized, Double-blind, Placebo-controlled Clinical Trial of Convalescent Plasma for the Treatment of COVID-19 Pneumonia With Severity Criteria

A multicenter randomized, double-blind, placebo-controlled clinical trial of Convalescent SARS COVID-19 plasma versus Placebo to evaluate the effect between arms on an ordinal score of six mutually exclusive categories of clinical status at day 30 after study initiation.

NCT04383535 SARS Virus SARS-CoV-2 COVID-19 Other: Convalescent SARS COVID-19 plasma Other: Placebo
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Ordinal outcome with six mutually exclusive categories to describe the patient's clinical status during follow-up. The six categories are: (1) death; (2) in intensive care; (3) hospitalised but requiring supplemental oxygen; (4) hospitalised and not requiring supplemental oxygen; (5) discharged but unable to resume normal activities; or (6) discharged with full resumption of normal activities.

Measure: Clinical status during follow-up at 30th day

Time: 30th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)

Secondary Outcomes

Description: Ordinal outcome with six mutually exclusive categories to describe the patient's clinical status during follow-up. The six categories are: (1) death; (2) in intensive care; (3) hospitalised but requiring supplemental oxygen; (4) hospitalised and not requiring supplemental oxygen; (5) discharged but unable to resume normal activities; or (6) discharged with full resumption of normal activities.

Measure: Clinical status during follow-up at 7th day

Time: 7th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)

Description: Ordinal outcome with six mutually exclusive categories to describe the patient's clinical status during follow-up. The six categories are: (1) death; (2) in intensive care; (3) hospitalised but requiring supplemental oxygen; (4) hospitalised and not requiring supplemental oxygen; (5) discharged but unable to resume normal activities; or (6) discharged with full resumption of normal activities.

Measure: Clinical status during follow-up at 14th day

Time: 14th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)

Description: Hospital discharge or intrahospital death

Measure: Time until hospital discharge (days).

Time: Whenever the patient is discharge from the hospital or die without discharge, through study completion, an average of 14 days from admission

Description: ICU discharge or ICU death

Measure: Time until discharge from ICU (days)

Time: Whenever the patient is discharge from ICU or die in ICU, through study completion, an average of 10 days from admission

Description: Death and time to death

Measure: Time to death

Time: In a 30 days follow up period

Description: Time until complete functional recovery (according to basal status).

Measure: Time until complete functional recovery

Time: Whenever the patient returns to basal functional status until 1 month from discharge

Description: Percentage of participants with adverse events / serious adverse events

Measure: Percentage of participants with adverse events / serious adverse events

Time: In a 30 days follow up period

Description: Percentage of patients with negative SARS-CoV-3 PCR

Measure: Percentage of patients with negative SARS-CoV-3 PCR at Day 14th

Time: 14th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)

Description: D Dimer plasma concentration

Measure: D Dimer plasma concentration at Day 14th

Time: 14th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)

Description: Ferritin plasma concentration

Measure: Ferritin plasma concentration at Day 13th

Time: 13th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)

Description: Plasma concentration of neutralizing antibodies

Measure: Plasma concentration of neutralizing antibodies at Day 2nd

Time: 2nd Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)

Description: Plasma concentration of neutralizing antibodies

Measure: Plasma concentration of neutralizing antibodies at Day 7th

Time: 7th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)

Description: Post-transfusion adverse reactions between study groups

Measure: Post-transfusion adverse reactions

Time: In a 30 days follow up period

115 A Phase I/II Randomized, Double Blinded, Placebo Trial to Evaluate the Safety and Potential Efficacy of Intravenous Infusion of Organicell Flow for the Treatment of Moderate to SARS Related to COVID-19 Infection vs Placebo

The purpose of this research study is to evaluate the safety and potential efficacy of Intravenous Infusion of Organicell Flow for treatment of moderate to severe Acute Respiratory Syndrome (SARS) related to COVID-19 infection vs Placebo.

NCT04384445 Corona Virus Infection COVID-19 SARS Acute Respiratory Distress Syndrome Biological: Organicell Flow Other: Placebo
MeSH:Infection Coronavi Coronavirus Infections Severe Acute Respiratory Syndrome Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury

Primary Outcomes

Description: Safety will be defined by the incidence of any infusion associated adverse events as assessed by treating physician

Measure: Incidence of any infusion associated adverse events

Time: 60 Days

Description: Safety will be defined by the incidence of severe adverse events as assessed by treating physician

Measure: Incidence of Severe Adverse Events

Time: 60 Days

Secondary Outcomes

Description: Measured at day 60 or at hospital discharge, whichever comes first.

Measure: All Cause Mortality

Time: 60 Days

Description: Number of participants that are alive at 60 days post first infusion follow up

Measure: Survival Rate

Time: 60 Days

Description: Measure IL-6, IL-2, TNF-alpha from serum of blood samples

Measure: Cytokine Levels

Time: Day 0, Day 4, Day 8, Day14, Day 21, Day 28

Description: D-dimer from serum of blood samples methodology using blood samples or nose / throat swab

Measure: D-dimer Levels

Time: Day 0, Day 4, Day 8, Day14, Day 21, Day 28

Description: CRP from serum of blood samples

Measure: C-reactive protein Levels

Time: Day 0, Day 4, Day 8, Day14, Day 21, Day 28

Description: Viral load by real time RT methodology using blood samples or nose / throat swab

Measure: Quantification of the COVID-19

Time: Day 0, Day 4, Day 8

Description: Improved organ failure within 30 days, including cardiovascular system, coagulation system, liver, kidney and other extra-pulmonary organs using Sequential Organ Failure Assessment (SOFA) score.

Measure: Improved Organ Failure

Time: Day 30

Description: Chest imaging changes for 30 days compare to placebo: 1) Ground-glass opacity, - 2) Local patchy shadowing, 3) Bilateral patchy shadowing, and 4) Interstitial abnormalities.

Measure: Chest Imaging Changes

Time: Day o, Day 30

116 A Randomised Double-blind Placebo-controlled Trial to Determine the Safety and Efficacy of Inhaled SNG001 (IFN-β1a for Nebulisation) for the Treatment of Patients With Confirmed SARS-CoV-2 Infection

SNG001 is an inhaled drug that contains a antiviral protein called interferon beta (IFN-β). IFN-β in produced in the lungs during viral lung infections. It has been shown that older people and people with some chronic diseases have an IFN-β deficiency. Many viruses inhibit IFN-β as part of their strategy to evade the immune system. Addition of IFN-β in vitro protects lung cells from viral infection. IFN-β protects cells against the MERS and SARS coronaviruses (close relatives of SARS-CoV-2, the virus that causes COVID-19). SNG001 is an inhaled formulation of interferon beta-1a it is currently in Phase II clinical trials for COPD patients. Synairgen has conducted randomised placebo controlled clinical trials of SNG001 involving >200 asthma and COPD patients. These trials have shown that SNG001 has: - been well tolerated during virus infections - enhanced antiviral activity in the lungs (measured in sputum and blood samples) - provided significant lung function benefit over placebo in asthma in two Phase II trials. Synairgen believes SNG001 could help prevent worsening or accelerate recovery of severe lower respiratory tract illness in COVID-19 patients. Patients who are in hospital or non-hospitalised but are a high risk groups (e.g. elderly or diabetics) will be invited to take part in the trial. The patient would receive either SNG001 or placebo once daily for 14 days. The severity of the patients condition would be recorded on a scale developed by the World Health Organisation and the patient would be asked questions about their breathlessness, cough and sputum every day, as well as assess their general medical condition and safety. If SNG001 proves to be beneficial it would be a major breakthrough for the treatment of COVID-19.

NCT04385095 SARS-CoV-2 Drug: Interferon beta 1a Drug: Placebo
MeSH:Infe Infection

Primary Outcomes

Description: Change in condition measured using the Ordinal Scale for Clinical Improvement during the dosing period - minimum of 0 (patient is well) to a maximum of 8 (death)

Measure: Ordinal Scale for Clinical Improvement

Time: Day 1 to day 28

Secondary Outcomes

Description: Progression to pneumonia as diagnosed by chest x-ray, if no pneumonia is present at time of enrolment

Measure: Progression to pneumonia

Time: Day 2 to day 28

Description: Evolution of pneumonia, as diagnosed by chest x-ray, if pneumonia is present at time of enrolment

Measure: Progression to pneumonia

Time: Day 1 to day 28

Description: Time to clinical improvement

Measure: Time to clinical improvement

Time: Time to hospital discharge OR Time to NEWS2 of ≤ 2 maintained for 24 hours

Description: NEWS2 assessment of acute-illness severity on a scale of 0 ( being well) up to 24 (requiring emergency response)

Measure: National Early Warning Score 2 (NEWS2) assessment of acute-illness severity

Time: Day 1 to day 28

Description: Changes in daily breathlessness, cough and sputum scale (BCSS) on a scale of 0 (no symptoms) up to 4 (severe symptoms)

Measure: Changes in daily breathlessness, cough and sputum scale (BCSS)

Time: Day 1 to day 28

Description: Looking at blood pressure measured in mmHg

Measure: Safety and tolerability - blood pressure II. Viral load

Time: Day 1 to day 28

Description: Looking at heart rate measured in beats per minute

Measure: Safety and tolerability - heart rate II. Viral load

Time: Day 1 to day 28

Description: Looking at temperature measured in degrees Celsius

Measure: Safety and tolerability - temperature II. Viral load

Time: Day 1 to day 28

Description: Looking at respiratory rate measure in breaths per minute

Measure: Safety and tolerability - respiratory rate II. Viral load

Time: Day 1 to day 28

Description: Looking at oxygen levels measured in a %

Measure: Safety and tolerability - oxygen saturation II. Viral load

Time: Day 1 to day 28

Description: Looking at adverse events (numbers and terms)

Measure: Safety and tolerability - adverse events II. Viral load

Time: Day 1 to day 28

Description: Looking at concomitant medications given during treatment

Measure: Safety and tolerability - concomitant medications II. Viral load

Time: Day 1 to day 28

117 A Phase III, Double-blind, Randomized, Placebo-controlled Multicentre Clinical Trial to Assess the Efficacy and Safety of VPM1002 in Reducing Healthcare Professionals' Absenteeism in the SARS-CoV-2 Pandemic by Modulating the Immune System

The aim of this study is to investigate whether vaccination of healthcare professionals with VPM1002 could reduce the number of days absent from work due to respiratory disease (with or without documented SARS-CoV-2 infection). VPM1002 is a vaccine that is a further development of the old Bacillus Calmette-Guérin (BCG) vaccine, which has been used successfully as a vaccine against tuberculosis for about 100 years, especially in developing countries. VPM1002 has been shown in various clinical studies to be significantly safer than the BCG vaccine. VPM1002 strengthens the body's immune defence and vaccination with BCG reduces the frequency of respiratory diseases. It is therefore assumed that a VPM1002 vaccination could also provide (partial) protection against COVID-19 disease caused by the new corona virus "SARS-CoV 2". A total of 1200 health care professionals (doctors, nurses and paramedical staff) with high expected exposure to SARSCoV-2 infected patients will receive a single dose of either VPM1002 or Placebo. All subjects will be requested to enter data regarding absenteeism, adverse events / serious adverse events, hospitalizations, intensive care unit admissions into an online questionnaire.

NCT04387409 Infection, Respiratory Tract Biological: VPM1002 Biological: Placebo
MeSH:Respiratory Tract Infections
HPO:Respiratory tract infection

Primary Outcomes

Measure: Number of days absent from work due to respiratory disease (with or without documented SARS-CoV-2 infection)

Time: From day 0 to day 240

Secondary Outcomes

Measure: Cumulative incidence of documented SARS-CoV-2 infection

Time: From day 0 to day 240

Measure: Number of days absent from work due to documented SARS-CoV-2 infection

Time: From day 0 to day 240

Measure: Number of days absent from work due to exposure to person with documented SARS-CoV-2 infection

Time: From day 0 to day 240

Measure: Number of days absent from work due to symptoms of respiratory disease, documented SARS-CoV-2 infection, or fever (≥ 38 °C)

Time: From day 0 to day 240

Measure: Number of days of self-reported fever (≥ 38 °C)

Time: From day 0 to day 240

Measure: Number of days of self-reported acute respiratory symptoms

Time: From day 0 to day 240

Measure: Cumulative incidence of self-reported acute respiratory symptoms

Time: From day 0 to day 240

Measure: Cumulative incidence of death for any reason

Time: From day 0 to day 240

Measure: Cumulative incidence of death due to documented SARS-CoV-2 infection

Time: From day 0 to day 240

Measure: Cumulative incidence of ICU admission for any reason

Time: From day 0 to day 240

Measure: Cumulative incidence of ICU admission due to documented SARS-CoV-2 infection

Time: From day 0 to day 240

Measure: Cumulative incidence of hospital admission for any reason

Time: From day 0 to day 240

Measure: Cumulative incidence of hospital admission due to documented SARS-CoV-2 infection

Time: From day 0 to day 240

118 A Randomized, Double-Blind, Placebo-Controlled, Multicenter, Parallel-Group Phase II Study to Evaluate the Efficacy and Safety of Intramuscular Injections of PLX PAD for the Treatment of Severe COVID-19

This clinical trial will examine if a new treatment of Mesenchymal Stems Cells (called PLX-PAD) can help patients intubated and mechanically ventilated due to COVID-19 to recover more quickly with less complications.

NCT04389450 COVID ARDS Biological: PLX-PAD Biological: Placebo

Primary Outcomes

Measure: Number of ventilator free days

Time: 28 days

Secondary Outcomes

Measure: All-cause mortality

Time: 28 days

Measure: Duration of mechanical ventilation

Time: 8 weeks

119 A Phase 2/3 Study to Evaluate the Safety and Efficacy of Dociparstat Sodium for the Treatment of Severe COVID-19 in Adults at High Risk of Respiratory Failure

A randomized, double-blind, placebo-controlled Phase 2/3 study to evaluate the safety and efficacy of DSTAT in patients with Acute Lung Injury (ALI) due to COVID-19. This study is designed to determine if DSTAT can accelerate recovery and prevent progression to mechanical ventilation in patients severely affected by COVID-19.

NCT04389840 COVID-19 Acute Lung Injury SARS-CoV-2 Drug: Dociparastat sodium Drug: Placebo
MeSH:Respiratory Insufficiency Lung Injury Acute Lung Injury Respiratory Distress Syndrome, Adult

Primary Outcomes

Description: Alive and free of invasive mechanical ventilation

Measure: Proportion of participants who are alive and free of invasive mechanical ventilation

Time: Through Day 28

Secondary Outcomes

Description: Time to all-cause mortality

Measure: All-cause mortality

Time: Through Day 28

120 Pilot Study to Evaluate the Potential of Ivermectin to Reduce COVID-19 Transmission

SAINT is a double-blind, randomized controlled trial with two parallel groups that evaluates the efficacy of ivermectin in reducing nasal viral carriage at seven days after treatment in SARS-CoV-2 infected patients who are at low risk of progression to severe disease. The trial is currently planned at a single center in Navarra.

NCT04390022 Covid-19 Coronavirus Infection SARS-CoV-2 Infection Drug: Ivermectin Drug: Placebo
MeSH:Infection Communicable Diseases Coronavirus Infections Severe Acute Respiratory Syndrome

Primary Outcomes

Description: Proportion of patients with a positive SARS-CoV-2 PCR from a nasopharyngeal swab at day 7 post-treatment

Measure: Proportion of patients with a positive SARS-CoV-2 PCR

Time: 7 days post-treatment

Secondary Outcomes

Description: Change from baseline quantitative and semi-quantitative PCR in nasopharyngeal swab

Measure: Mean viral load

Time: Baseline and on days 4, 7, 14 and 21

Description: Proportion of patients with fever and cough at days 4, 7, 14 and 21 as well as proportion of patients progressing to severe disease or death during the trial

Measure: Fever and cough progression

Time: Up to and including day 21

Description: Proportion of participants with positive IgG at day 21

Measure: Seroconversion at day 21

Time: Up to and including day 21

Description: Proportion of drug-related adverse events

Measure: Proportion of drug-related adverse events

Time: 7 days post treatment

Description: Levels in median fluorescence intensity (MFI) of IgG, IgM and IgA against the receptor-binding domain of the spike glycoprotein of SARS-CoV-2 in plasma, measured by a Luminex assay

Measure: Levels of IgG, IgM and IgA

Time: Up to and including day 28

Description: Frequency (% over total PBMC) of innate immune cells (myeloid and plasmacytoid dendritic cells, NK cell, classical, intermediate and pro-inflammatory macrophages) measured in cryopreserved PBMC by flow cytometry

Measure: Frequency of innate immune cells

Time: Up to and including day 7

Description: Frequency of CD4+ T and CD8+ T cells (% over total CD4+T and CD8+ T) expressing any functional marker upon in vitro stimulation of PBMC with SARS-CoV-2 peptides, measured by flow cytometry

Measure: Frequency SARS-CoV-2-specific CD4+ T and and CD8+ T cells

Time: Up to and including day 7

Description: Concentration (all in pg/mL) of epidermal growth factor (EGF), fibroblast growth factor (FGF), granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), tumour necrosis factor (TNF), interferon (IFN)-α, IFN-γ, interleukin (IL)-1RA, IL-1β, IL-2, IL-2R, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12(p40/p70), IL-13, IL-15, IL-17, IFN-γ induced protein (IP-10), monocyte chemoattractant protein (MCP-1), monokine induced by IFN-γ (MIG), macrophage inflammatory protein (MIP)-1α, MIP-1β in plasma measured by a Luminex assay using a commercially available kit (Cytokine Human Magnetic 30-Plex Panel from ThermoFisher)

Measure: Results from cytokine Human Magnetic 30-Plex Panel

Time: Up to and including day 28

121 A Prospective, Double-blind, Randomized, Parallel, Placebo-controlled Pilot Clinical Trial for the Evaluation of the Efficacy and Safety of Two Doses of WJ-MSC in Patients With Acute Respiratory Distress Syndrome Secondary to Infection by COVID-19

Randomized, double-blind, parallel, two-arms clinical trial to assess the efficacy and safety of 2 infusions of Wharton-Jelly mesenchymal stromal cells (day 1 and day 3, endovenously at 1E6cells/Kg per dose) in patients with moderate acute respiratory distress syndrome (ARDS) secondary to SARS-CoV-2 infection. Follow-up will be established on days 3, 5, 7, 14, 21, and 28. Long term follow-up will be performed at 3, 6 and 12 months.

NCT04390139 COVID-19 SARS-CoV 2 Adult Respiratory Distress Syndrome Drug: XCEL-UMC-BETA Other: Placebo
MeSH:Respiratory Distress Syndrome, Newborn Respi Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

Primary Outcomes

Description: Number of patients who died, by treatment group

Measure: All-cause mortality at day 28

Time: Day 28

Secondary Outcomes

Description: Number of patients with treatment-emergent adverse events, by treatment group

Measure: Safety of WJ-MSC

Time: Day 28

Description: Number of patients who, after the start of treatment, required rescue medication, by treatment group

Measure: Need for treatment with rescue medication

Time: Day 28

Description: Number of days that the patient requires invasive mechanical ventilation from the start of treatment to day +28, by treatment group

Measure: Need and duration of mechanical ventilation

Time: Day 28

Description: Days after treatment in which the patient remains alive and free of invasive mechanical ventilation, per treatment group.

Measure: Ventilator free days

Time: Day 28

Description: Variation of the oxygenation index (PaO2 / FiO2) with respect to the baseline value, by treatment group.

Measure: Evolution of PaO2 / FiO2 ratio

Time: Day 28

Description: Variation of the score of the Sequential Organ Failure Assessment (SOFA) Index with respect to the baseline value, by treatment group.

Measure: Evolution of the SOFA index

Time: Day 28

Description: Variation of Acute Physiology and Chronic Health disease Classification System II (APACHE II) score, by treatment group.

Measure: Evolution of the APACHE II score

Time: Day 28

Description: Days of stay in the ICU from the day of admission until discharge to day 28, or date of death if earlier, by treatment group.

Measure: Duration of hospitalization

Time: Day 28

Description: Variation in the count and percentage of leukocytes and neutrophils, by treatment group.

Measure: Evolution of markers of immune response (leucocyte count, neutrophils)

Time: Day 28

Description: Feasibility will be evaluated by the time elapsed from the request of the treatment by the hospital center until the delivery date

Measure: Feasibility of WJ-MSC administration

Time: Day 28

Description: Feasibility will be evaluated by the number of patients treated within 2 days of the request for treatment.

Measure: Feasibility of WJ-MSC administration

Time: Day 28

Description: Variation in the values of the biomarker, by treatment group.

Measure: Evolution of disease biomarker: polymerase chain reaction (RT-PCR)

Time: Day 28

Description: Variation in the values of the biomarker, by treatment group.

Measure: Evolution of disease biomarker: lactate dehydrogenase (LDH)

Time: Day 28

Description: Variation in the values of the biomarker, by treatment group.

Measure: Evolution of disease biomarker: D-dimer

Time: Day 28

Description: Variation in the values of the biomarker, by treatment group.

Measure: Evolution of disease biomarker: Ferritin

Time: Day 28

Other Outcomes

Description: Blood sample analysis

Measure: Analysis of subpopulations of lymphocytes and immunoglobulins

Time: Day 28

Description: In vitro response will be assessed using commercial viral antigens (Miltenyi Biotech)

Measure: Evaluation of the in vitro response of the receptor lymphocytes

Time: Day 28

Description: Reactivity will be assessed using ELISPOT

Measure: Study of reactivity against SARS-CoV-2 peptides

Time: Day 28

Description: Blood sample analysis

Measure: Immunophenotypic study of memory cells in response to SARS-CoV-2 peptides

Time: Day 28

Description: Blood sample analysis for the patient's genomic sequencing

Measure: Genetic variability of patient's genotype in response to treatment

Time: Day 28

Description: Genomic sequencing of the SARS-CoV-2 in a nasopharyngeal sample

Measure: Genetic variability of the SARS-CoV-2 genotype in response to treatment

Time: Day 28

122 A Phase 2 Study to Evaluate LB1148 for the Treatment of Pulmonary Dysfunction Associated With COVID-19 Pneumonia

This is a Phase 2, proof of concept, randomized, placebo-controlled, multicenter study to evaluate the ability of LB1148 to attenuate pulmonary dysfunction associated with COVID-19 pneumonia. The primary objective of this study is to determine if enteral administration of LB1148 will effect disease progression in hospitalized patients with moderate to severe COVID-19 via measurement of the proportion of subjects alive and free of respiratory failure at Day 28.

NCT04390217 COVID-19 Coronavirus Disease 2019 Covid19 COVID-19 Pneumonia Drug: LB1148 Drug: Placebo
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: The proportion of subjects alive and free of respiratory failure at Day 28.

Measure: Effect of LB1148 on disease progression via measurement of the proportion of patients who are alive and free of respiratory failure.

Time: 28 Days

Secondary Outcomes

Description: Number and proportion of patients with improved clinical status as assessed by a 9-point ordinal scale of disease severity at fixed timepoints (Days 3, 5, 7, 8, 10, 14, 28)

Measure: Clinical status at fixed time points

Time: Measured at 3, 5, 7, 8, 10, 14 and 28 Days

Description: Length of hospital stay (live discharge)

Measure: Duration of hospital stay

Time: 28 Days

Description: Number and proportion of patients requiring admission to the intensive care unit

Measure: Measurement of the number and proportion of patients requiring admission to the intensive care unit (ICU) during hospitalization

Time: 28 Days

Description: Length of ICU stay

Measure: Duration of ICU stay

Time: 28 Days

Description: Number and proportion of patients requiring invasive mechanical ventilation

Measure: Invasive mechanical ventilation requirements

Time: 28 Days

Description: Length of time patients require invasive mechanical ventilation

Measure: Duration of invasive mechanical ventilation

Time: 28 Days

Description: The number and proportion of patients deceased at Day 28

Measure: All-cause 28-day mortality

Time: 28 Days

Description: The incidence and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs)

Measure: Safety and tolerability of LB1148

Time: 28 Days

123 Efficacy and Safety of Hydroxychloroquine and Ivermectin in Hospitalized no Critical Patients Secondary to COVID-19 Infection: Randomized Controlled Trial

Background: In December 2019, patients with pneumonia secondary to a new subtype of Coronavirus (COVID-19) were identified in China. In a few weeks the virus spread and cases started practically all over the world. In February 2020, the WHO declared a pandemic. Severe symptoms have been found in patients mainly with comorbidities and over 50 years of age. At this time there is no proven therapeutic alternative. In vitro studies and observational experiences showed that antimalarial drugs (Chloroquine and hydroxychloroquine) had antiviral activity and increased viral clearance. Ivermectin, on the other hand, has been shown in vitro to reduce viral replication and in an observational cohort, greater viral clearance with promising clinical results. So far there is no standard of treatment and clinical trials are needed to find effective treatment alternatives. Objective: To evaluate the safety and efficacy of treatment with hydroxychloroquine and ivermectin for serious COVID-19 infections in no critical hospitalized patients. Material and methods: Randomized controlled trial of patients diagnosed with respiratory infection by COVID-19, who present criteria for hospitalization. Randomization will be performed to receive hydroxychloroquine at a dose of 400 mg every 12 hours for one day and then 200 mg every 12 hours, to complete a 5-day treatment schedule. Group 2: Ivermectin 12 mg every 24 hours for one day (less than 80 kg) or Ivermectin 18 mg every 24 hours for one day (greater than 80 kg) + placebo until the fifth day. Group 3: Placebo. Prior to randomization, the risk of cardiovascular complications determined by corrected QT interval, related to hydroxychloroquine intake will be assessed. If the patient is at high risk, the allocation will be to ivermectin only or to placebo in an independent randomization, if the risk is low, any of the three groups could be assigned. Outcomes: The primary outcome will be discharge from hospital for improvement. The safety outcomes will be requirement of mechanical intubation, septic shock or death. Viral clearance will also be evaluated by means of PCR, which will be taken on the 5th day after admission, day 14 and 21.

NCT04391127 COVID-19 Drug: Hydroxychloroquine Drug: Ivermectin Drug: Placebo
MeSH:Infection

Primary Outcomes

Description: Days from admission as a suspected case of COVID with hospitalization criteria until discharge

Measure: Mean days of hospital stay

Time: Three months

Description: Respiratory deterioration defined by respiratory rate > 25 per minute, requirement of high oxygen supply (FiO2 > 80% ) to maintain oxygen saturation > 90 %, invasive mechanical ventilation or dead.

Measure: Rate of Respiratory deterioration, requirement of invasive mechanical ventilation or dead

Time: Three months

Description: Daily delta of oxygenation index during the hospitalization

Measure: Mean of oxygenation index delta

Time: Three months

Secondary Outcomes

Description: Mean time to viral negativization of RT-qPCR SARS-CoV-2. Pre Specified time: 5, 14, 21 and 28 days after the first positive PCR.

Measure: Mean time to viral PCR negativization

Time: 5, 14, 21 and 28 days after the first positive PCR

124 Phase 2, Randomized, Double-Blind, Placebo-Controlled Study of the Effect of Anti-CD14 Treatment in Patients With SARS-CoV-2 (COVID-19)

This is a multicenter, randomized, double-blind, placebo-controlled phase 2 study of IC14, an antibody to CD14, in reducing the severity of respiratory disease in hospitalized COVID-19 patients.

NCT04391309 Sars-CoV2 Biological: IC14 Other: Placebo

Primary Outcomes

Description: Days alive and free of any episodes of acute respiratory failure through Day 22 defined by need for high-flow nasal cannula, noninvasive positive-pressure ventilation, endotracheal intubation and mechanical ventilation, and extracorporeal membrane oxygenation

Measure: Acute respiratory failure

Time: Day 1-22

Secondary Outcomes

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

Measure: Time to clinical improvement

Time: Day 1-29

Description: Proportion of patients alive and free of any episode of acute respiratory failure through Days 8, 15, 22, and 29

Measure: Acute respiratory failure

Time: Days 1-8, 1-15, 1-22, 1-29

Description: Proportion of patients alive and free of invasive mechanical ventilation through Days 8, 15, 22, and 29

Measure: Invasive mechanical ventilation

Time: Days 1-8, 1-15, 1-22, 1-29

Description: Days alive and free of acute respiratory failure through Days 15 and 29

Measure: Acute respiratory failure

Time: Days 1-15 and 1-29

Description: Days alive and free of invasive mechanical ventilation through Days 15, 22, and 29

Measure: Invasive mechanical ventilation

Time: Days 1-15, 1-22, 1-29

Description: Days alive and hospitalized through Day 29

Measure: Hospitalization

Time: Days 1-29

Description: Change in Sequential Organ Failure Assessment (SOFA) score (range 0 [best] to 24 [worst]) from baseline to Day 8, Day 15, and Day 22

Measure: Sequential Organ Failure Assessment

Time: Days 1-8, 1-15, 1-22

Description: Worst SOFA score from baseline to Day 22

Measure: Sequential Organ Failure Assessment

Time: Days 1-22

Description: Proportion of patients alive and discharged from the hospital at Days 15 and 29.

Measure: Hospitalization

Time: Days 1-15, 1-29

Description: Mean change in the eight-point ordinal scale (1 [worst] to 8 [best]) through Day 29

Measure: Ordinal Scale

Time: Days 1-29

Description: Time to improvement in one category from baseline using an eight-point ordinal scale (1 [worst] to 8 [best]) through Day 29.

Measure: Time to clinical improvement

Time: Days 1-29

Description: Time to improvement in two categories from baseline using an eight-point ordinal scale (1 [worst] to 8 [best]) through Day 29.

Measure: Time to clinical improvment

Time: Days 1-29

Description: Time to recovery through Day 29. Day of recovery is defined as the first day on which the subject satisfies one of categories 6-8 from the ordinal scale.

Measure: Time to recovery

Time: Days 1-29

Description: Change in C-reactive protein in blood on Days 4 and 8 compared to baseline (from normal < 10 mg/L [normal] to >10 mg/L [worse])

Measure: Change in C-reactive protein

Time: Day 4 compared to baseline; Day 8 compared to baseline

Description: Cumulative incidence of Grade 3 and 4 clinical and/or laboratory adverse events

Measure: Adverse events

Time: Days 1-60

Description: Cumulative incidence of serious adverse events

Measure: Serious adverse events

Time: Days 1-60

125 A Randomized, Double-Blind, Placebo-Controlled, First-in-Human Study Designed to Evaluate the Safety, Tolerability, and Pharmacokinetics of EIDD-2801 Following Oral Administration to Healthy Volunteers

This is a First In Human study designed to assess the safety, tolerability and pharmacokinetics of EIDD-2801 in healthy human volunteers.

NCT04392219 Coronavirus Drug: EIDD-2801 Drug: Placebo
MeSH:Coronavirus Infections

Primary Outcomes

Description: Number and severity of treatment emergent adverse events

Measure: Safety and Tolerability of Single Ascending Dose (SAD) of EIDD-2801 (Part 1): Adverse Events

Time: From screening through study completion, up to 15 days

Description: Number and severity of treatment emergent adverse events

Measure: Safety and Tolerability of Multiple Ascending Dose (MAD) of EIDD-2801 (Part 3): Adverse Events

Time: From screening through study completion, up to 20 days

Description: Multiple pharmacokinetic variables of EIDD-2801 will be assessed and may include, but are not limited to: Maximum observed concentration Cmax

Measure: Pharmacokinetics (PK) of EIDD-2801 when given as Single Doses (Part 2): Maximum observed concentration Cmax

Time: Day 1 through Day 18

Secondary Outcomes

Description: Multiple PK variables of EIDD-2801 will be assessed and may include, but are not limited to: Maximum observed concentration Cmax

Measure: Pharmacokinetics (PK) of EIDD-2801 when given as Single Ascending Dose (SAD) (Part 1): Maximum observed concentration Cmax

Time: Day 1 up to Day 4

Description: Multiple PK variables of EIDD-2801 will be assessed and may include, but are not limited to: Maximum observed concentration Cmax

Measure: Pharmacokinetics (PK) of EIDD-2801 when given as Multiple Ascending Dose (MAD) (Part 3): Maximum observed concentration Cmax

Time: Day 1 up to Day 14

Description: Number and severity of treatment emergent adverse events

Measure: Safety and Tolerability of Single Doses of EIDD-2801 (Part 2): Adverse Events

Time: From screening through study completion, up to 30 days

126 A Phase 2/3, Randomized, Double Blind, Placebo-controlled Study to Evaluate the Efficacy and the Safety of ABX464 in Treating Inflammation and Preventing COVID-19 Associated Acute Respiratory Failure in Patients Aged ≥ 65 and Patients Aged ≥18 With at Least One Additional Risk Factor Who Are Infected With SARS-CoV-2.

A phase 2/3, randomized, double blind, placebo-controlled study to evaluate the efficacy and the safety of ABX464 in treating inflammation and preventing acute respiratory failure in patients aged ≥65 and patients aged ≥18 with at least one additional risk factor who are infected with SARS-CoV-2 (the MiR-AGE study).

NCT04393038 COVID-19 Drug: ABX464 Drug: Placebo
MeSH:Respiratory Insufficiency Inflammation

Primary Outcomes

Measure: Rate of patients with no invasive or non-invasive mechanical ventilation (IMV and NIV, respectively), but excluding simple nasal/mask oxygen supplementation, and who are alive

Time: at the end of the 28-day treatment period

Secondary Outcomes

Measure: Rate of patients hospitalized

Time: 28-day treatment period

Description: 7-point ordinal scale is defined as Not hospitalized, no limitations on activities; Not hospitalized, limitation on activities; Hospitalized, not requiring supplemental oxygen; Hospitalized, requiring supplemental oxygen; Hospitalized, on non-invasive ventilation or high flow oxygen devices; Hospitalized, on invasive mechanical ventilation or ECMO; Death

Measure: Percentage of patients reporting each severity rating on a 7-point ordinal scale

Time: 28-day treatment period

Measure: Change from enrolment in inflammatory markers in plasma and in immune phenotype and assessment of cell-activation markers in PBMCs

Time: at each study visit during the 28-day treatment period

Measure: Rate of patients requiring oxygen supplementation

Time: 28-day treatment period

Measure: Time to hospitalization

Time: 28-day treatment period

Measure: Time to assisted ventilation and oxygen supplementation

Time: 28-day treatment period

Measure: Change from baseline in microRNA-124 levels

Time: at each study visit during the 28-day treatment period

Measure: Change from baseline in CRP, Troponin I & T and D-dimer

Time: at each study visit during the 28-day treatment period

Description: Nasopharyngeal sample and/or in blood

Measure: SARS-CoV-2 viral load

Time: at each study visit during the 28-day treatment period

Measure: Number and rates of participants with Treatment Emergent Adverse Event

Time: 28-day treatment period

127 A Multi-Center, Randomized, Double-Blind, Placebo Controlled Study of the Safety and Efficacy of Ulinastatin for the Treatment of COVID-19 in Hospitalized Patients

The primary objective of this study is to evaluate the safety and efficacy of intravenous (IV) infusion of ulinastatin compared to placebo with respect to time to recovery, disease severity, need for ventilator support, and mortality in patients with COVID 19.

NCT04393311 COVID-19 Drug: Ulinastatin Drug: Placebo

Primary Outcomes

Description: Time to recovery, defined as attaining a score of 6, 7, or 8 on the COVID-19 disease severity scale, an 8 point ordinal scale used in the NIH Adaptive COVID-19 Treatment Trial (ACTT; NCT04280705). = Death; = Hospitalized and on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); = Hospitalized and on non-invasive ventilation or high-flow oxygen devices; = Hospitalized and requiring supplemental oxygen; = Hospitalized and not requiring supplemental oxygen but requiring ongoing medical care (COVID-19-related or otherwise); = Hospitalized and not requiring supplemental oxygen and no longer requiring ongoing medical care; = Not hospitalized, limitation on activities and/or requiring home oxygen; = Not hospitalized, no limitation on activities

Measure: Time to recovery

Time: Up to 29 days

Secondary Outcomes

Description: COVID-19 disease severity scale (range; 1-8, higher scores correspond to better health state).

Measure: COVID-19 disease severity scale score on Day 8

Time: Day 8

Description: COVID-19 disease severity scale (range; 1-8, higher scores correspond to better health state).

Measure: COVID-19 disease severity scale score on Day 15

Time: Day 15

Description: COVID-19 disease severity scale (range; 1-8, higher scores correspond to better health state).

Measure: COVID-19 disease severity scale score on Day 22

Time: Day 22

Description: COVID-19 disease severity scale (range; 1-8, higher scores correspond to better health state).

Measure: COVID-19 disease severity scale score on Day 29

Time: Day 29

Measure: Incidence of mortality at Day 29

Time: 29 days

Measure: Incidence of in-hospital mortality

Time: Up to 29 days

Measure: Number of days alive and not on mechanical ventilator or ECMO in the 28 days following first dose

Time: Up to 29 days

Measure: Number of patients with resolution of symptoms defined as score of 8 on the 8-point ordinal scale at Day 29

Time: Day 29

Measure: Number of patients alive and free of respiratory failure defined as score of 4, 5, 6, 7, or 8 on the 8-point ordinal scale at Day 29

Time: Day 29

Description: For patients requiring mechanical ventilation.

Measure: Duration of mechanical ventilation

Time: Up to 29 days

Description: For patients requiring mechanical ECMO.

Measure: Duration of ECMO

Time: Up to 29 days

Description: For patients requiring non-invasive ventilation

Measure: Duration of noninvasive ventilation

Time: Up to 29 days

Description: For patients admitted to ICU

Measure: Duration of ICU stay

Time: Up to 29 days

Measure: Duration of hospital stay

Time: Up to 29 days

Measure: Change in oxygen saturation

Time: Between screening and 24 hours after last dose (up to 11 days)

128 Trial of Silymarin in Adults With COVID-19 Pneumonia

A randomized placebo controlled trial to assess the clinical outcome in COVID-19 Pneumonia following administration of Silymarin owing to its role as a p38 MAPK pathway inhibitor and its antiviral, anti-inflammatory and anti-oxidant effects

NCT04394208 COVID-19 Viral Pneumonia Human Coronavirus Drug: Silymarin Drug: Placebo
MeSH:Pneumonia, Viral Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Defined as the time from randomization to an improvement of two points (from the status of randomization) on seven category ordinal scale or live discharge from the hospital, whichever comes first.

Measure: Time to clinical improvement

Time: 7-28 days

Secondary Outcomes

Description: Clinical status as assessed with the seven-category ordinal scale on days 7 and 14

Measure: Clinical outcome

Time: 7-14 days

Description: Time in days patient was intubated

Measure: Duration of Mechanical Ventilation

Time: Randomization till hospital discharge or death whichever came first, assessed up to 28 days

Description: Total days of hospitalization

Measure: Hospitalization

Time: Randomization till hospital discharge or death whichever came first, assessed up to 28 days

Description: number of days patient remained with positive RT-PCR SARS-CoV-2 swab

Measure: Virologic Response

Time: Randomization till discharge, up to 28 days

Description: Any adverse events whether related to medication or not

Measure: Adverse events

Time: Randomization till hospital discharge, up to 28 days

129 Combination With Inhibitor of Neutrophil Elastase (All-trans Retinoic Acid ) and Isotretinoin May Enhances Neutralizing Antibodies in COVID -19 Infected Patients Better Than COVID-19 Inactivated Vaccines

Unfortunately, All of the vaccinated monkeys treated with the Oxford vaccine known as ChAdOx1 nCoV-19, is undergoing trials in Britain.became infected when challenged as judged by recovery of virus RNA from nasal secretions," said Dr William Haseltine, a former Harvard Medical School professor who had a role in the development of early Aids treatments. and in general future COVID-19 vaccination which depends on inactivated viral vaccine will be restricted to healthy people with strong immunity and It will not be given to patients with History of contact with COVID-19 infection. In addition to the COVID-19 antigens with hyper mutation lead to (ADE) phenomenon in which IgG antibodies facilitate viral entry and fusion with infected cell through uptake of the virus-IgG complex via the Fc receptors and later viral fusion with antigen presenting cells like macrophages and B cells via FcR , through the neonatal FcR instead of antibodies induced viral agglutination and this is known as antibody dependent enhancement (ADE)(2) There are various hypotheses on how ADE happens and there is a likelihood that more than one mechanism exists. In one such pathway, some cells of the immune system lack the usual receptors on their surfaces that the virus uses to gain entry, but they have Fc R that bind to one end of antibodies. The virus binds to the antigen-binding site at the other end, and in this way gains entry to and infects the immune cell. Dengue virus can use this mechanism to infect human macrophages.(3) An ongoing question in the COVID-19 pandemic is whether—and if so, to what extent—COVID-19 receives ADE from prior infection with other COVID-19. ADE can hamper vaccine development, as a vaccine may cause the production of antibodies which, via ADE, worsen the disease the vaccine is designed to protect against. Vaccine candidates for Dengue virus and feline infectious peritonitis virus had to be stopped because they elicited ADE.(4) ADE in COVID-19 infection can be caused by high mutation rate of the gene that encodes spike (S) protein. A thorough analysis of amino acid variability in COVID-19 virus proteins, that included the S-protein, revealed that least conservative amino acids are in most exposed fragments of S-protein including receptor binding domain (RBD).(5) A study reported that Inhibitors of NET stimulate murine B lymphocyte differentiation into IgG- and IgA-producing cells via immunoglobulin class switching . A study demonstrated that depletion of NET improves the production of mucosal IgA and IgG after sublingual immunization with Bacillus anthracis edema toxin as adjuvant and also, another study demonstrated that extracellular traps (NETs)—may contribute to organ damage and mortality in COVID-19 and also reported that there is aberrant linking between NET formation and pulmonary diseases, thrombosis, mucous secretions in the airways, and cytokine production. If our hypothesis is correct, targeting NETs directly and/or indirectly with existing drugs may reduce the clinical severity of COVID-19. So,the principal investigator expects that High NETs in covid-19 infection may be the reason of delayed antibody response and severe complications.Currently, only limited information is available on the host innate immune status of COVID-19 infected patients. In one report where 99 cases in Wuhan were investigated, increased total NETs (38%), reduced total lymphocytes (35%) and increased serum IL-6 (52%) .25 In a separate report also from Wuhan, it revealed that in 41 patients, increased total NETs, decreased total lymphocytes in patients of ICU vs. non-ICU care were found to be statistically different. Increased NETs and decreased lymphocytes also correlate with disease severity .(10) B cells/plasma cells produce COVID-19 specific Abs that may help neutralize viruses.(11) Humoral immune response, especially production of neutralizing antibody, plays a protective role by limiting infection at later phase and prevents reinfection in the future. In Covid-19, both T and B cell epitopes were extensively mapped for the structural proteins, S, N, M and E protein.(12) ,(14) Delayed antibodies response and secretion after covid -19 symptoms onset may be responsible for antibody dependent enhancement (ADE) Because this immune response takes a while to show up, antibody tests will be negative for those newly infected with COVID-19, which is why they're not used for diagnosis. "If it's the beginning of the infection, you don't pick it up, it's something that only develops later," Dr. Melanie Ott, a virologist at the Gladstone Institutes Finally, according to this protocol the investigator will treat with potent inhibitor of NET elastase plus Isotretinoin and the mechanism of action will be discussed in Detailed Description

NCT04396067 COVID -19 Drug: Aerosolized 13 cis retinoic acid Drug: Aerosolized All trans retinoic acid Other: Placebo

Primary Outcomes

Description: Proportion of lung injury score decreased or increased after treatment

Measure: lung injury score

Time: at 7 days

Secondary Outcomes

Description: Serum levels of CRP, ESR ,IL-1,IL-6,TNF and Type I interferon

Measure: Serum levels of CRP, ESR ,IL-1,IL-6,TNF and Type I interferon

Time: at day 7 and 14 after randimization

Description: Serum level of COVID19 RNA

Measure: Serum level of COVID19 RNA

Time: at day 7 and 14

Description: less than 250 ng/mL, or less than 0.4 mcg/mL of blood sample

Measure: d-dimers

Time: within 14 days

Description: lymphocyte counts

Measure: Absolute lymphocyte counts

Time: at day 7 and 14 after randimization

Description: To determine the immune correlates of viral clearance (Antibody Titres sufficient for viral clearance and neutralizing ) against future exposure to SARS-CoV-2

Measure: The immune correlates of protection against future exposure to SARS-CoV-2

Time: within 14 days

Description: Number of CD4 HLA-DR+ and CD38+, CD8 lymphocytes

Measure: Immunological profile

Time: within 14 days

Measure: Total duration of mechanical ventilation, ventilatory weaning and curarisation

Time: at day 7 and 14

Description: Kidney failure, hypersensitivity with cutaneous or hemodynamic manifestations, aseptic meningitis, hemolytic anemia, leuko-neutropenia, transfusion related acute lung injury (TRALI)

Measure: Occurrence of adverse event related to immunoglobulins

Time: at day 14

Description: serum levels of IgG and IgM against COVID-19

Measure: IgG, IgA and IgM against COVID-19

Time: at day 7 and 14

Description: ACE2 expression in patients with COVID-19 infection

Measure: ACE2 expression in patients with COVID-19 infection

Time: at day 7 and 14

Measure: All cause mortality rate [

Time: at day 7 and 14

Measure: Ventilation free days

Time: at 14 days

Measure: ICU free days

Time: at 14 days

130 A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of AT-527 in Subjects With Moderate COVID-19

The objectives of this study are to evaluate the safety, tolerability and efficacy of AT-527 in older subjects (ages 45-80 years) with moderate COVID-19 and risk factors for poor outcomes (such as obesity (BMI>30), hypertension, diabetes or asthma). Eligible subjects will be randomized to blinded AT-527 (nucleotide analog) tablets or matching placebo tablets to be administered orally for 10 days. Local supportive standard of care (SOC) will be allowed for all subjects. Efficacy and safety observations will be compared for treatment with active AT-527 tablets + SOC vs. placebo tablets + SOC.

NCT04396106 COVID-19 Drug: AT-527 Other: Placebo

Primary Outcomes

Description: Respiratory failure defined as requirement for intubated mechanical ventilation.

Measure: Proportions (active vs. placebo) of subjects who progress to respiratory failure

Time: Day 14 and Follow-up Day 14

Measure: Proportions (active vs. placebo) of subjects experiencing treatment-emergent adverse events

Time: Day 14 and Follow-up Day 14

Secondary Outcomes

Description: Clinical recovery defined as time from start of treatment until normal body temperature and respiratory rate (<20 breaths per minute), with sufficient alleviation of other signs and symptoms to support discharge

Measure: Time to clinical recovery

Time: Day 14

131 Safety and Efficacy of Post-exposure Prophylaxis With Hydroxychloroquine (HCQ) for the Prevention of COVID-19 in High-risk Older Individuals in Long-term and Specialized Care: A Double-blind Randomized Control Trial

Older adults are at the highest risk of complications and severe illness for 2019-nCoV infections. Hydroxychloroquine (HCQ), an emerging chemoprophylaxis, which holds clinical and mechanistic plausibility, will help to reduce disease incidence and mitigate disease severity across in-patient settings. This study is designed to assess the safety and efficacy of post-exposure prophylaxis with hydroxychloroquine (HCQ) for the prevention of Coronavirus Infectious Disease-19 (COVID-19) in high-risk older individuals in long-term and specialized care.

NCT04397328 COVID-19 Drug: Hydroxychloroquine Drug: Placebo

Primary Outcomes

Measure: Incidence of symptomatic fever >37.8, dry cough, or shortness of breath (resident/patient report or nurse observation) respiratory infection with confirmed PCR+ result for SARS-CoV-2.

Time: baseline through day 90

Secondary Outcomes

Measure: Requirement for admission to acute care hospital and/or ICU admission or death

Time: baseline through day 90

Measure: Asymptomatic PCR+ SARS-CoV-2 test result

Time: baseline, days 2, 5, 12, and 19

Measure: Time to clinical recovery (TTCR).

Time: baseline through day 90

132 Clinical Study to Investigate the Urinary Excretion of N-nitrosodimethylamine (NDMA) After Ranitidine Administration

Ranitidine is an over-the-counter and prescription drug, which decreases the amount of acid secreted by the stomach. Some ranitidine medicines contain an impurity called N-nitrosodimethylamine (NDMA) at low levels. NDMA is classified as a probable human carcinogen (a substance that could cause cancer) based on results from laboratory tests. NDMA is a known environmental contaminant and found in water and foods, including meats, dairy products, and vegetables. The US Food and Drug Administration (FDA) has found levels of NDMA in some ranitidine products similar to the levels you would expect to be exposed to if you ate common foods like grilled or smoked meats. The ranitidine that will be used in this study has been tested twice (months apart) and shown to have stable NDMA levels well below the acceptable daily limit. Of note, the risk of NDMA with ranitidine is only relevant with prolonged chronic administration as at the acceptable limit, there is approximately a 1 in 100,000 chance of cancer after 70 years of exposure to that level. FDA has also conducted tests that simulate the potential formation of NDMA from ranitidine after it has been exposed to acid in the stomach with a normal diet. Results of these tests indicate that NDMA is not formed in typical stomach conditions. Similarly, if ranitidine is exposed to a simulated small intestinal fluid, NDMA is not formed. Other laboratory experiments suggest a combination of nitrites, such as found in processed meats, and an acidic environment may increase NDMA formation, however the levels of nitrites tested were very high. Separately, a previous study in 10 healthy volunteers showed that volunteers who received ranitidine had an increase in urinary NDMA excreted over 24 h. The level of increase was greater than would be expected from laboratory testing. This clinical study is being performed to determine if and how much NDMA is produced from ranitidine in the human body and whether nitrite-containing foods may increase formation of NDMA. The study will use a prescription dose of ranitidine (300 mg) to test whether there is increased urinary NDMA excretion levels over 24-hours after ranitidine administration in comparison to placebo when participants are administered low nitrite/NDMA meals and when subjects are administered high nitrite/NDMA meals. On 4 different days, each participant will receive ranitidine or placebo with high nitrite/NDMA meals and ranitidine or placebo with low nitrite/NDMA meals.

NCT04397445 Ranitidine Adverse Reaction Pharmacokinetics Food-drug Interaction Drug: Ranitidine Other: Low nitrite/NDMA meals Drug: Placebo Other: High nitrite/NDMA meals

Primary Outcomes

Description: Determined by calculating cumulative amount excreted during specified intervals, and summarizing totals over a 24-h period.

Measure: 24-hour Urinary NDMA Excretion

Time: 24 hours

Other Outcomes

Description: Determined for each subject using non-compartmental methods. All parameters will be reported with standard descriptive statistics including the geometric mean and coefficient of variation. Calculation of pharmacokinetic parameters will be performed using actual sampling times over a 24-h period.

Measure: Area under the curve from time zero to infinity (AUC(0-inf)) of plasma ranitidine

Time: 24 hours

Description: Determined for each subject using non-compartmental methods. All parameters will be reported with standard descriptive statistics including the geometric mean and coefficient of variation. Calculation of pharmacokinetic parameters will be performed using actual sampling times over a 24-h period.

Measure: AUC(0-inf) of plasma NDMA

Time: 24 hours

Description: Determined for each subject using non-compartmental methods. All parameters will be reported with standard descriptive statistics including the geometric mean and coefficient of variation. Calculation of pharmacokinetic parameters will be performed using actual sampling times over a 24-h period.

Measure: AUC(0-inf) of plasma dimethylamine (DMA)

Time: 24 hours

Description: Determined by calculating cumulative amount excreted during specified intervals, and summarizing totals over a 24-h period.

Measure: Cumulative ranitidine amount excreted in urine over 24 hours after drug administration

Time: 24 hours

Description: Determined by calculating cumulative amount excreted during specified intervals, and summarizing totals over a 24-h period.

Measure: Cumulative DMA amount excreted in urine over 24 hours after drug administration

Time: 24 hours

133 A Randomized, Double Blind, Placebo-controlled Trial of Mavrilimumab for Acute Respiratory Failure Due to COVID-19 Pneumonia With Hyper-inflammation (the COMBAT-19 Trial)

This study is a prospective, phase II, multi-center, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of mavrilimumab in hospitalized patients with acute respiratory failure requiring oxygen supplementation in COVID- 19 pneumonia and a hyper-inflammatory status. The study will randomize patients to mavrilimumab or placebo, in addition to standard of care per local practice. The total trial duration will be 12 weeks after single mavrilimumab or placebo dose.

NCT04397497 Covid-19 Acute Respiratory Failure ARDS, Human Sars-CoV2 Viral Pneumonia Drug: Mavrilimumab Drug: Placebo
MeSH:Pneumonia, Viral Pneumonia Respiratory Insufficiency Respiratory Distress Syndrome, Adult Inflammation
HPO:Pneumonia

Primary Outcomes

Description: Time to the absence of need for oxygen supplementation (time to first period of 24 hrs with a SpO2 of 94%) within day 14 of treatment, stated as Kaplan- Mayer estimates of the proportion of patients on room air at day 14 and median time to room air attainment in each arm

Measure: Reduction in the dependency on oxygen supplementation

Time: within day 14 of treatment

Secondary Outcomes

Description: Response is defined as a 7-point ordinal scale of 3 or less, i.e. no supplemental oxygen

Measure: Proportion of responders (using the WHO 7-point ordinal scale)

Time: Day 7, 14, and 28

Description: Time from date of randomization to the date with a 7-point ordinal scale of 3 or less, i.e. no supplemental oxygen

Measure: Time to response (using the WHO 7-point ordinal scale)

Time: Within day 28 of intervention

Description: Proportion of patients with at least two-point improvement in clinical status

Measure: Proportion of improving patients (using the WHO 7-point ordinal scale)

Time: At day 7, 14, and 28

Description: Time to resolution of fever (for at least 48 hours) in absence of antipyretics, or discharge, whichever is sooner

Measure: Time to resolution of fever

Time: Within day 28 of intervention

Description: COVID-19-related death

Measure: Reduction in case fatality

Time: Within day 28 of intervention

Description: Proportion of hospitalized patients who died or required mechanical ventilation (WHO Categories 6 or 7)

Measure: Proportion of patient requiring mechanical ventilation/deaths

Time: Within day 14 of intervention

Description: Change of the following serological markers over follow-up (C-reactive protein; Ferritin; D-Dimer)

Measure: Change in biochemical markers

Time: Within day 28 of intervention or discharge -whatever comes first

Description: Median changes of NEWS2 score from baseline

Measure: Median changes in the National Early Warning Score 2 (NEWS2)

Time: At day 7, 14, and 28

Description: Time to clinical improvement (as defined as a NEWS2 score of 2 or less maintained for at least 24 hours or discharge, whichever comes first)

Measure: Time to clinical improvement as evaluated with the National Early Warning Score 2 (NEWS2)

Time: Within day 28 of intervention or discharge -whatever comes first

Description: Variations from baseline to subsequent timepoints (when available) in terms of percentage of lung involvement, modifications in the normal parenchyma, ground glass opacities (GGO), crazy paving pattern,parenchymal consolidations, and evolution towards fibrosis.

Measure: Variations in radiological findings

Time: Within day 28 of intervention or discharge -whatever comes first

Description: Number of patients with treatment- related side effects (as assessed by Common Terminology Criteria for Adverse Event (CTCAE) v.5.0), serious adverse events, adverse events of special interest, clinically significant changes in laboratory measurements and vital signs

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

Time: By day 84

Other Outcomes

Description: To evaluate the primary and secondary endpoints in different subgroups of patients: mild respiratory failure: PaO2/FiO2 ≤ 300 and > 200 mmHg; moderate respiratory failure: PaO2/FiO2 ≤ 200 and > 100 mmHg

Measure: Clinical efficacy of mavrilimumab compared to the control arm by clinical severity

Time: Within day 28 of intervention

Description: Median changes in serum IL-6

Measure: Changes in serum IL-6 (exploratory biomarker)

Time: By day 84

Description: Median changes in serum IL-1 receptor antagonist

Measure: Changes in serum IL-1RA (exploratory biomarker)

Time: By day 84

Description: Median changes in serum TNF-alpha

Measure: Changes in serum TNF-alpha (exploratory biomarker)

Time: By day 84

Description: Median variations in haemoglobin and leucocyte counts

Measure: Changes in CBC + differential (exploratory biomarker)

Time: By day 84

Description: Median titres od anti-SARS-CoV2 antibodies

Measure: Level of anti-SARS-CoV2 antibodies (exploratory biomarker)

Time: By day 84

Description: Proportion of patients with a positive swab for SARS-CoV2 by PCR

Measure: Virus eradication (exploratory biomarker)

Time: By day 84

Description: Proportion of patients who developed anti-drug antibodies

Measure: Anti-drug antibodies (exploratory biomarker)

Time: By day 84

134 Phase 1b Randomized, Double-Blind, Placebo-Controlled Study Of The Safety Of Therapeutic Treatment With Immunomodulatory Mesenchymal Stem Cells In Adults With COVID-19 Infection Requiring Mechanical Ventilation

This is a phase 1b randomized, double-blind, placebo-controlled study in adult subjects with Coronavirus Disease 2019 (COVID-19). This clinical trial will evaluate the preliminary safety and efficacy of BM-Allo.MSC vs placebo in treating subjects with severe disease requiring ventilator support during COVID 19 infection.

NCT04397796 COVID Biological: BM-Allo.MSC Biological: Placebo
MeSH:Infection

Primary Outcomes

Description: Incidence of AEs within 30 days of randomization.

Measure: Incidence of AEs

Time: 30 days

Description: Mortality within 30 days of randomization.

Measure: Mortality

Time: 30 days

Description: Cause of death within 30 days of randomization

Measure: Death

Time: 30 days

Description: Number of ventilator-free days within 60 days of randomization.

Measure: Number of ventilator-free days

Time: 60 days

Secondary Outcomes

Description: Time from randomization to an improvement of one category using the ordinal scale. The ordinal scale is as follows: Death Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) Hospitalized, on non-invasive ventilation or high flow oxygen devices Hospitalized, requiring supplemental oxygen Hospitalized, not requiring supplemental oxygen Not hospitalized, limitation on activities Not hospitalized, no limitations on activities

Measure: Improvement of one category

Time: 30 days

Description: Change in the 7-point ordinal scale from baseline. The ordinal scale is as follows: Death Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) Hospitalized, on non-invasive ventilation or high flow oxygen devices Hospitalized, requiring supplemental oxygen Hospitalized, not requiring supplemental oxygen Not hospitalized, limitation on activities Not hospitalized, no limitations on activities

Measure: 7-point ordinal scale

Time: 30 days

Description: Change in NEWS from baseline. The following 7 clinical parameters will be assessed: Respiration rate Oxygen saturation Any supplemental oxygen Temperature Systolic blood pressure Heart rate Level of consciousness Measurements within normal ranges are assigned a 0. If the measurement in each category is substantially above or below the normal range, it is given a +1, +2, or +3. The more far off than normal, the bigger the number (in each category). A higher number indicates worse outcome. Each category can be 0-3, except for supplemental oxygen which is only 0-2. The highest value a patient can get is 20.

Measure: NEWS

Time: 30 days

Description: Time from randomization to discharge or to a NEWS of ≤ 2 maintained for 24 hours, whichever occurs first.

Measure: NEWS of ≤ 2

Time: 30 days

Description: Change from baseline in Sequential Organ Failure Assessment (SOFA) score on days 8, 15, 22, and 29. System Score for each category is 0-4 with 28 is the maximum score for worst outcome. The following categories are: Respiration Coagulation Liver Cardiovascular Central Nervous System Renal

Measure: Sequential Organ Failure Assessment (SOFA)

Time: days 8, 15, 22, and 29

Description: Number of days requiring oxygen.

Measure: Oxygen

Time: 30 days

Description: Duration of hospitalization from randomization.

Measure: Hospitalization

Time: 30 days

Description: Incidence of SAEs within 30 days of randomization

Measure: Incidence of SAEs

Time: 30 days

135 A Randomized, Observer-Blind, Dose-escalation Phase I/II Clinical Trial of Ad5-nCoV Vaccine in Healthy Adults From 18 to <85 Years of Age in Canada

This study is a phase I /II adaptive clinical trial to evaluate the safety, tolerability and the Immunogenicity of Ad5-nCoV in healthy adults from 18 to <55 and 65 to <85 years of age,with the randomized, observer-blind, dose-escalation design

NCT04398147 COVID-19 Biological: Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector) Biological: Placebo

Primary Outcomes

Description: The occurrence of Solicited AE in all groups within 0-6 days after each vaccination;

Measure: Incidence of the Solicited AE in all groups

Time: 0-6 days after each vaccination

Description: The occurrence of Unsolicited AE in all groups within 0-28 days after each vaccination.

Measure: Incidence of Unsolicited AE in all groups

Time: 0-28 days after each vaccination

Description: The occurrence of Serious adverse events (SAE) in all groups within 6 months after the final vaccination.

Measure: Incidence of Serious adverse events (SAE) in all groups

Time: 6 months after the final vaccination

Secondary Outcomes

Description: Geometric mean titer (GMT) of the IgG antibody against SARS-CoV-2 measured on Day 0, Day 14, Day 28, Day 84 and Day 168 after vaccination in the one dose group and Day 0, 14, 28, 56, 70, 84, and 224 in the two dose group (ELISA method);

Measure: Geometric mean titer (GMT) of the IgG antibody against SARS-CoV-2 (ELISA method);

Time: Day 0, Day 14, Day 28, Day 84 and Day 168 after vaccination in the one dose group and Day 0, 14, 28, 56, 70, 84, and 224 in the two dose group

Description: Seroconversion rate (%of subjects with 4-fold or greater increase in antibody level) of the IgG antibody against SARS-CoV-2 measured on Day 14, Day 28, Day 84 and Day 168 after vaccination in the one dose group and Day 14, 28, 56, 70, 84, and 224 in the two dose group (ELISA method );

Measure: Seroconversion rate of the IgG antibody against SARS-CoV-2(ELISA method )

Time: Day 14, Day 28, Day 84 and Day 168 after vaccination in the one dose group and Day 14, 28, 56, 70, 84, and 224 in the two dose group

Description: Geometric Mean Increase Ratio (GMI) of the specific antibody against SARS-CoV-2 measured on Day 14, Day 28, Day 84 and Day 168 after vaccination in the one dose group and Day 14, 28, 56, 70, 84, and 224 in the two dose group (ELISA method);

Measure: Geometric Mean Increase Ratio (GMI) of the specific antibody against SARS-CoV-2(ELISA method);

Time: Day 14, Day 28, Day 84 and Day 168 after vaccination in the one dose group and Day 14, 28, 56, 70, 84, and 224 in the two dose group

Description: Geometric mean titer (GMT) of the neutralizing antibody against SARS-CoV-2 measured on Day 0, Day 14, Day 28 and Day 168 after vaccination in the one dose group and Day 0, 14, 28, 56, 70, 84, and 224 in the two dose group (Pseudo-viral neutralization assay)

Measure: Geometric mean titer (GMT) of the neutralizing antibody against SARS-CoV-2(Pseudo-viral neutralization assay)

Time: Day 0, Day 14, Day 28 and Day 168 after vaccination in the one dose group and Day 0, 14, 28, 56, 70, 84, and 224 in the two dose group

Description: Seroconversion rate of the neutralizing antibody against SARS-CoV-2 measured on Day 14, Day 28 and Day 168 after vaccination in the one dose group and Day 14, 28, 56, 70, 84, and 224 in the two dose group(Pseudo-viral neutralization assay);

Measure: Seroconversion rate of the neutralizing antibody against SARS-CoV-2(Pseudo-viral neutralization assay)

Time: Day 14, Day 28 and Day 168 after vaccination in the one dose group and Day 14, 28, 56, 70, 84, and 224 in the two dose group

Description: Geometric mean increase ratio (GMI) of neutralizing antibody against SARS-CoV-2 measured on Day 14, Day 28 and Day 168 after vaccination in the one dose group and Day 14, 28, 56, 70, 84, and 224 in the two dose group (Pseudo-viral neutralization assay)

Measure: Geometric mean increase ratio (GMI) of neutralizing antibody against SARS-CoV-2 (Pseudo-viral neutralization assay)

Time: Day 14, Day 28 and Day 168 after vaccination in the one dose group and Day 14, 28, 56, 70, 84, and 224 in the two dose group

Description: Geometric Mean Titer (GMT) of the neutralizing antibody against adenovirus type 5 vector measured on Day 0, Day 14, Day 28, Day 84 and Day 168 after vaccination in the one dose group and Day 0, 14, 28, 56, 70, 84, and 224 in the two dose group;

Measure: Geometric Mean Titer (GMT) of the neutralizing antibody against adenovirus type 5 vector

Time: Day 0, Day 14, Day 28, Day 84 and Day 168 after vaccination in the one dose group and Day 0, 14, 28, 56, 70, 84, and 224 in the two dose group

Description: Geometric mean increase ratio (GMI) of the neutralizing antibody against adenovirus type 5 vector measured on Day 14, Day 28, Day 84 and Day 168 after vaccination in the one dose group and Day 14, 28, 56, 70, 84, and 224 in the two dose group

Measure: Geometric mean increase ratio (GMI) of the neutralizing antibody against adenovirus type 5 vector

Time: Day 14, Day 28, Day 84 and Day 168 after vaccination in the one dose group and Day 14, 28, 56, 70, 84, and 224 in the two dose group

Description: The positive rate of IFN-γ stimulated by S protein overlapping peptide library detected by ELISpot

Measure: cellular immune response by ELISpot

Time: on Day 0, Day 14, Day 28 and Day 168 in the one dose group and Day 0, 14, 28, 56, 70, 84, and 224 in the two dose group

Description: The positive rate of IFN-γ, TNF-α, and IL-2 expressed by CD4+ and CD8+ T lymphocytes stimulated by S protein overlapping peptide library detected by Intracellular Cytokine Staining (ICS);

Measure: cellular immune response by ICS

Time: Day 0, Day 14, Day 28 and Day 168 in the one dose group and Day 0, 14, 28, 56, 70, 84, and 224 in the two dose group

136 Niclosamide for Patients With Mild to Moderate Disease From Novel Coronavirus (COVID-19)

This study will evaluate the antihelmintic drug, Niclosamide, as a potential treatment for mild to moderate coronavirus disease 2019 (COVID-19).

NCT04399356 COVID (SARS-CoV-2) Drug: Niclosamide Drug: Placebo Other: Telehealth monitoring

Primary Outcomes

Description: Oropharangeal swab

Measure: Change in respiratory viral clearance (by PCR)

Time: Day 3 and 10

Secondary Outcomes

Description: Fecal swab

Measure: Fecal viral clearance (by PCR)

Time: Day 14

Description: Oropharngeal swab

Measure: Reduction (change) in viral shedding (by PCR)

Time: Days 1,3,7,10,14

137 EFFICACY AND SAFETY OF OCTAGAM 10% THERAPY IN COVID-19 PATIENTS WITH SEVERE DISEASE PROGRESSION

This is a randomized, double-blind, placebo-controlled, multicenter, Phase 3 study to evaluate if high-dose Octagam 10% therapy can stabilize or improve clinical status in patients with severe Coronavirus disease

NCT04400058 Covid-19 Biological: Octagam 10% Other: Placebo
MeSH:Disease Progression

Primary Outcomes

Description: The primary endpoint is stabilization or improvement in clinical status defined as maintenance or improvement by one category on a 6-category clinical status scale on Day 7. Clinical status categories will be defined as: Hospital discharge or meet discharge criteria (discharge criteria are defined as clinical recovery, i.e. fever, respiratory rate, oxygen saturation return to normal, and cough relief). Hospitalization, not requiring supplemental oxygen. Hospitalization, requiring supplemental oxygen (but not NIV/HFNC). ICU/hospitalization, requiring NIV/HFNC therapy. ICU, requiring Extracorporeal Membrane Oxygenation (ECMO) and/or IMV. Death.

Measure: Stabilization or Improvement in Clinical Status

Time: 7 days

Secondary Outcomes

Description: Change from baseline in oxygen saturation

Measure: Oxygen saturation

Time: Up to 33 days

Description: Change from baseline in Modified Borg Dyspnea scale

Measure: Modified Borg Dyspnea scale

Time: Up to 33 days

Description: Change from baseline in Quality of Life

Measure: Quality of Life (McGill Quality of Life Single-Item Scale)

Time: Up to 33 daya

Description: Time to intubation

Measure: Time to intubation

Time: Up to 33 days

Description: Time to extubation

Measure: Time to extubation

Time: Up to 33 days

Description: Time to mechanical ventilation

Measure: Time to mechanical ventilation

Time: Up to 33 days

Description: Time to cessation of mechanical ventilation

Measure: Time to cessation of mechanical ventilation

Time: Up to 33 days

Description: Time to change of modality for oxygenation

Measure: Time to change of modality for oxygenation

Time: Up to 33 days

Description: Time to death

Measure: Time to death

Time: Up to 33 days

Description: Imaging findings (chest CT/chest X-ray)

Measure: Imaging findings (chest CT/chest X-ray)

Time: Up to 7 days

Description: Change from baseline in blood glucose

Measure: Blood glucose

Time: Up to 33 daya

Description: Change from baseline in blood calcium

Measure: Blood calcium

Time: Up to 33 days

Description: Change from baseline in sodium

Measure: Sodium

Time: Up to 33 days

Description: Change from baseline in potassium

Measure: Potassium

Time: Up to 33 days

Description: Change from baseline in carbon dioxide

Measure: Carbon dioxide

Time: Up to 33 days

Description: Change from baseline in chloride

Measure: Chloride

Time: Up to 33 days

Description: Change from baseline in albumin

Measure: Albumin

Time: Up to 33 days

Description: Change from baseline in total protein

Measure: Total protein

Time: Up to 33 days

Description: Change from baseline in alkaline phosphatase

Measure: Alkaline phosphatase

Time: Up to 33 days

Description: Change from baseline in alanine transaminase

Measure: Alanine transaminase

Time: Up to 33 days

Description: Change from baseline in aspartate aminotransferase

Measure: Aspartate aminotransferase

Time: Up to 33 days

Description: Change from baseline in bilirubin

Measure: Bilirubin

Time: Up to 33 days

Description: Change from baseline in blood urea nitrogen

Measure: Blood urea nitrogen

Time: Up to 33 days

Description: Change from baseline in D-dimer

Measure: D-dimer

Time: Up to 33 days

Description: Change from baseline in fibrinogen

Measure: Fibrinogen

Time: Up to 33 days

Description: Change from baseline in PT

Measure: PT

Time: Up to 33 days

Description: Change from baseline in PTT

Measure: PTT

Time: Up to 33 days

Description: Change from baseline in INR

Measure: INR

Time: Up to 33 days

Description: Change from baseline in hsCRP

Measure: hsCRP

Time: Up to 33 days

Description: Change from baseline in ferritin

Measure: Ferritin

Time: Up to 33 days

Description: Change from baseline in LDH

Measure: LDH

Time: Up to 33 days

Description: Change from baseline in IgG

Measure: IgG

Time: Up to 33 days

Description: Change from baseline in IgM

Measure: IgM

Time: Up to 33 days

Description: Change from baseline in IgA

Measure: IgA

Time: Up to 33 days

Description: Change from baseline in IFE

Measure: IFE

Time: Up to 33 days

Description: Change from baseline in troponin

Measure: Troponin

Time: Up to 33 days

Description: Change from baseline in red blood cell count

Measure: Red blood cell count

Time: Up to 33 days

Description: Change from baseline in hemoglobjn

Measure: Hemoglobin

Time: Up to 33 days

Description: Change from baseline in hematocrit

Measure: Hematocrit

Time: Up to 33 days

Description: Change from baseline in mean corpuscular volume

Measure: Mean corpuscular volume

Time: Up to 33 days

Description: Change from baseline in mean corpuscular hemoglobin

Measure: Mean corpuscular hemoglobin

Time: Up to 33 days

Description: Change from baseline in mean corpuscular hemoglobin concentration

Measure: Mean corpuscular hemoglobin concentration

Time: Up to 33 days

Description: Change from baseline in red cell distribution width

Measure: Red cell distribution width

Time: Up to 33 days

Description: Change from baseline in white blood cell count

Measure: White blood cell count

Time: Up to 33 days

Description: Change from baseline in white blood cell differential

Measure: White blood cell differential

Time: Up to 33 days

Description: Change from baseline in platelet count

Measure: Platelet count

Time: Up to 33 days

Description: Change from baseline in mean platelet volume

Measure: Mean platelet volume

Time: Up to 33 days

Description: Change from baseline in platelet distribution width

Measure: Platelet distribution width

Time: Up to 33 days

Description: Frequency of adverse events

Measure: Frequency of adverse events

Time: 33 days

Description: Frequency of serious adverse events

Measure: Frequency of serious adverse events

Time: 33 days

138 A Multicenter, Adaptive, Randomized Blinded Controlled Trial of the Safety and Efficacy of Investigational Therapeutics for the Treatment of COVID-19 in Hospitalized Adults (ACTT-II)

ACTT-II will evaluate the combination of baricitinib and remdesivir compared to remdesivir alone. Subjects will be assessed daily while hospitalized. If the subjects are discharged from the hospital, they will have a study visit at Days 15, 22, and 29. For discharged subjects, it is preferred that the Day 15 and 29 visits are in person to obtain safety laboratory tests and oropharyngeal (OP) swab and blood (serum only) samples for secondary research as well as clinical outcome data. However, infection control or other restrictions may limit the ability of the subject to return to the clinic. In this case, these visits may be conducted by phone, and only clinical data will be obtained. The Day 22 visit does not have laboratory tests or collection of samples and is conducted by phone. The primary outcome is time to recovery by Day 29.

NCT04401579 COVID-19 Other: Placebo Drug: Remdesivir Drug: Baricitinib

Primary Outcomes

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

Measure: Time to recovery

Time: Day 1 through Day 29

Secondary Outcomes

Measure: Change from baseline in alanine transaminase (ALT)

Time: Day 1 through Day 29

Measure: Change from baseline in aspartate transaminase (AST)

Time: Day 1 through Day 29

Measure: Change from baseline in creatinine

Time: Day 1 through Day 29

Measure: Change from baseline in glucose

Time: Day 1 through Day 29

Measure: Change from baseline in hemoglobin

Time: Day 1 through Day 29

Measure: Change from baseline in platelets

Time: Day 1 through Day 29

Description: PT reported as international normalized ratio (INR).

Measure: Change from baseline in prothrombin time (PT)

Time: Day 1 through Day 29

Measure: Change from baseline in total bilirubin

Time: Day 1 through Day 29

Measure: Change from baseline in white blood cell count (WBC) with differential

Time: Day 1 through Day 29

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

Measure: Change in National Early Warning Score (NEWS) from baseline

Time: Day 1 through Day 29

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

Measure: Cumulative incidence of Grade 3 and 4 clinical and/or laboratory adverse events (AEs)

Time: Day 1 through Day 29

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

Measure: Cumulative incidence of serious adverse events (SAEs)

Time: Day 1 through Day 29

Description: Measured in days.

Measure: Duration of hospitalization

Time: Day 1 through Day 29

Description: Measured in days.

Measure: Duration of new non-invasive ventilation or high flow oxygen use

Time: Day 1 through Day 29

Description: Measured in days.

Measure: Duration of new oxygen use

Time: Day 1 through Day 29

Description: Measured in days.

Measure: Duration of new ventilator or extracorporeal membrane oxygenation (ECMO) use

Time: Day 1 through Day 29

Description: Measured in days

Measure: Duration of oxygen use

Time: Day 1 through Day 29

Description: For any reason.

Measure: Incidence of discontinuation or temporary suspension of investigational therapeutics

Time: Day 1 through Day 10

Measure: Incidence of new non-invasive ventilation or high flow oxygen use

Time: Day 1 through Day 29

Measure: Incidence of new oxygen use

Time: Day 1 through Day 29

Measure: Incidence of new ventilator or extracorporeal membrane oxygenation (ECMO) use

Time: Day 1 through Day 29

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

Measure: Mean change in the ordinal scale

Time: Day 1 through Day 29

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

Measure: Participant's clinical status at Day 15 by ordinal scale

Time: Day 15

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

Measure: Percentage of subjects reporting each severity rating on an 8 point ordinal scale

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

Description: Date and cause of death (if applicable).

Measure: Subject 14-day mortality

Time: Day 1 through Day 15

Description: Date and cause of death (if applicable).

Measure: Subject 28-day mortality

Time: Day 1 through Day 29

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

Measure: Time to an improvement of one category using an ordinal scale

Time: Day 1 through Day 29

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

Measure: Time to an improvement of two categories using an ordinal scale

Time: Day 1 through Day 29

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

Measure: Time to discharge or to a National Early Warning Score (NEWS) of Time: Day 1 through Day 29

139 Multicenter, Randomized, Double-Blind, Placebo-Controlled, Proof of Concept Trial of LSALT Peptide as Prevention of Acute Respiratory Distress Syndrome (ARDS) and Other Organ Injuries in Patients Infected With SARS-CoV-2 (COVID-19)

To evaluate the efficacy of intravenous LSALT peptide plus standard of care to prevent the progression of COVID-19 to mild, moderate or severe ARDS, acute kidney injury, cardiomyopathy, acute liver injury, coagulopathy, or death in patients infected with SARS-CoV-2 compared with placebo plus standard of care.

NCT04402957 COVID Severe Acute Respiratory Syndrome Sars-CoV2 Drug: LSALT peptide Drug: Placebo
MeSH:Severe Acute Respiratory Syndrome Coronavirus Infections Syndrome

Primary Outcomes

Description: To evaluate the efficacy of intravenous LSALT peptide plus standard of care to prevent the progression of COVID-19 to mild, moderate or severe ARDS, acute kidney injury, cardiomyopathy, acute liver injury, coagulopathy, or death in patients infected with SARS-CoV-2 compared with placebo plus standard of care.

Measure: Development of Acute Respiratory Distress Syndrome (ARDS) and Other Organ Injuries

Time: 28 days

Secondary Outcomes

Description: High-frequency oscillatory ventilation, with its rapid delivery of low tidal volumes and a respiratory rate in the range of 60 to 900 breaths/minute, has also been utilized in ARDS patients.

Measure: Ventilation-free days

Time: 28 days

Description: Oxygen therapy provided as non-invasive therapy for ARDS patients.

Measure: Time on nasal cannula or oxygen masks

Time: 28 days

Description: 28 day mortality - all cause and attributable

Measure: 28 day mortality - all cause and attributable

Time: 28 days

Description: ICU and hospitalization length of stay (days)

Measure: ICU and hospitalization length of stay (days)

Time: 28 days

Description: Swab (nasopharyngeal, nasal, throat, sputum, or lower respiratory tract) at baseline (Day 1) and every 3 days thereafter until eradication → virologic clearance rate

Measure: SARS-CoV2 testing

Time: 28 days

Description: Extracorporeal membrane oxygenation (ECMO) is often used for severe ARDS to allow lung healing/repair and reverse respiratory failure.

Measure: Need and duration for extracorporeal membrane oxygenation (ECMO)

Time: 28 days

Description: Vasopressor free days

Measure: Vasopressor free days

Time: 28 days

Description: Chest X-rays performed at Baseline, Day 3, at clinical improvement, and end-of-treatment (EOT) and study (EOS) to determine presence of bilateral opacities.

Measure: Radiographic pulmonary assessments

Time: 28 days

Description: Change in daily mMRC dyspnea and SOFA scores (0 to 4) with 4 being the most severe outcome

Measure: Change in modified Medical Research Council (mMRC) dyspnea and Sequential Organ Failure Assessment (SOFA) scores

Time: 28 days

Description: Incidence of other organ (non-lung) disorders

Measure: Incidence of non-lung disorders

Time: 28 days

Description: Change in liver function tests (ALT and AST) from baseline

Measure: Measures of liver dysfunction

Time: 28 days

Description: Change in SCr and eGFR from baseline

Measure: Measures of kidney dysfunction

Time: 28 days

Description: Change in highly-sensitive troponin (hs-troponin) from baseline

Measure: Measures of cardiac dysfunction

Time: 28 days

Description: Change in baseline immunoglobulins (IgG, IgM) at EOS.

Measure: Changes in immunogenic responses

Time: 28 days

Description: Changes in total healthcare costs from admission to discharge between treatment groups.

Measure: Healthcare outcomes

Time: 28 days

Description: Change in serum cytokines including IL-1α, IL-1ß, IL-1ra, IL-5, IL-6, IL-8, IL-12, TNFα, CXCL10/IP10, MCP-3, and ferritin drawn at the same time as LSALT peptide levels

Measure: Molecular changes in pro-inflammatory pathways

Time: 28 days

Description: Pharmacokinetics of LSALT peptide over the study period.

Measure: Pharmacokinetics of LSALT peptide

Time: 28 days

140 Hydroxychloroquine and Lopinavir/ Ritonavir for Hospitalization and Mortality Reduction in Patients With COVID-19 and Mild Disease Symptoms: "The Hope Coalition"

The COVID-19 pandemic has been characterized by high morbidity and mortality, especially in certain subgroups of patients. To date, no treatment has been shown to be effective in controlling this disease in hospitalized patients with moderate and / or severe cases of this disease. Hydroxychloroquine and lopinavir / ritonavir have been shown to inhibit SARS-CoV viral replication in experimental severe acute respiratory symptoms models and have similar activity against SARS-CoV2. Although widely used in studies of critically ill patients, to date, no study has demonstrated its role on the treatment of high-risk, newly diagnosed patients with COVID-19 and mild symptoms.

NCT04403100 COVID-19 Coronavirus Infection Virus Disease Acute Respiratory Infection SARS-CoV Infection Drug: Hydroxychloroquine Sulfate Tablets Drug: Lopinavir/ Ritonavir Oral Tablet Drug: Hydroxychloroquine Sulfate Tablets plus Lopinavir/ Ritonavir Oral Tablets Drug: Placebo
MeSH:Infection Communicable Diseases Respiratory Tract Infections Coronavirus Infections Severe Acute Respiratory Syndrome Virus Diseases
HPO:Respiratory tract infection

Primary Outcomes

Description: Hospitalization is defined as at least 24 hours of acute care in a hospital or similar acute care facility (emergency settings, temporary emergency facilities created for acute care of COVID-19 pandemic)

Measure: Proportion of participants who were hospitalized for progression of COVID-19 disease

Time: Measuring during 28-day period since randomization (Intention to treat analysis)

Measure: Proportion of participants who died due to COVID-19 progression and/ or complications

Time: Measuring during 28-day period since randomization (Intention to treat analysis)

Secondary Outcomes

Description: Viral load change on 03, 07, 10 and 14 after randomization (200 patients per arm)

Measure: Proportion of participants with viral load change on 03, 07, 10 and 14 after randomization

Time: Measuring during 14-day period since randomization

Description: Proportion of participants with clinical improvement, defined as normalization of temperature, Respiratory rate, SaO2, and cough relief (> 50% compared to baseline measured on a visual analog scale) in the last 72 hours.

Measure: Time to clinical improvement

Time: Measuring during 28-day period since randomization

Description: Proportion of participants with clinical improvement, defined as as time to need for hospitalization due to dyspnea, death, need for mechanical ventilation, shock and need for vasoactive amines;

Measure: Time to clinical failure

Time: Measuring during 28-day period since randomization

Description: Proportion of participants with hospitalization for any cause

Measure: Hospitalization for any cause

Time: Measuring during 28-day period since randomization

Measure: Proportion of participants who died due to pulmonary complications

Time: Measuring during 28-day period since randomization

Measure: Proportion of participants who died due to cardiovascular complications

Time: Measuring during 28-day period since randomization

Description: Evaluation of adverse events evaluated as associated to any of study arms

Measure: Proportion of participants who presented with adverse events

Time: Measuring during 28-day period since randomization

Description: Proportion of participants who presented sustained improvement on respiratory scale defined as at least 48 hours of improvement.

Measure: Time to improvement on respiratory scale symptoms

Time: Measuring during 28-day period since randomization

Measure: proportion of non-adherent participants to any of study drugs

Time: Measuring during 10-day period since randomization

141 Randomized Clinical Trial of Açaí Palm Berry Extract as an Intervention in Patients Diagnosed With COVID-19

The Açaí trial will be testing if the açaí berry extract, a safe natural product with anti-inflammatory properties, can be used as a treatment option in adult patients with COVID-19 in the community.

NCT04404218 COVID Dietary Supplement: Açaí palm berry extract - natural product Other: Placebo

Primary Outcomes

Description: Symptom comparison between patients from the treatment vs control group, using an ordinal symptom scale based on the WHO scale. Patients who were hospitalized will be classified according to their worst score over 30 days and non-hospitalized patients according to their score at 30 days.

Measure: 7-point ordinal symptom scale

Time: 30 days

Secondary Outcomes

Description: First occurrence of all-cause mortality or need for mechanical ventilation

Measure: The composite of all-cause mortality and need for mechanical ventilation

Time: 30 days

Description: First occurrence of all-cause mortality or hospitalization

Measure: The composite of all-cause mortality and hospitalization

Time: 30 days

Description: All-cause mortality

Measure: All-cause mortality

Time: 30 days

Description: Need for mechanical ventilation

Measure: Need for mechanical ventilation

Time: 30 days

Description: Need for hospitalization

Measure: Need for hospitalization

Time: 30 days

142 A Phase 3 Randomized, Double-blind, Placebo-controlled, Multicenter Study of Pacritinib Plus Standard of Care Versus Placebo and Standard of Care in Hospitalized Patients With Severe COVID-19 With or Without Cancer

This is a Phase 3 randomized, double-blind, placebo-controlled, multicenter study to evaluate the efficacy and safety of pacritinib in hospitalized patients with severe COVID-19 with or without cancer.

NCT04404361 COVID Drug: Pacritinib Drug: Placebo

Primary Outcomes

Description: The proportion is calculated as the number of patients who progress divided by the total number of patients in the ITT population.

Measure: Proportion of patients who progress to IMV and/or ECMO or death during the 28 days following randomization

Time: 28 days

143 A Phase 2a, Randomized, Observer-Blind, Placebo Controlled, Dose-Confirmation Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of mRNA-1273 SARS-COV-2 Vaccine in Adults Aged 18 Years and Older

This clinical study will assess the safety, reactogenicity, and immunogenicity of 2 dose levels of mRNA-1273 SARS-COV-2 vaccine in adults 18 years of age or older.

NCT04405076 SARS-CoV-2 Biological: Biological: mRNA-1273: 50 mcg Other: Placebo Biological: Biological: mRNA-1273: 100 mcg

Primary Outcomes

Measure: Solicited local and systemic adverse reactions (ARs)

Time: 7 days post-vaccination

Measure: Unsolicited adverse events (AEs)

Time: 28 days post-vaccination

Measure: Medically-attended adverse events (MAAEs)

Time: Month 0 through Month 13

Measure: Serious adverse events (SAEs)

Time: Month 0 through Month 13

Measure: Change in the measure of clinical safety laboratory values in Cohort 2 from baseline

Time: Through 1 month after last vaccination

Measure: The number and percentage of participants with abnormalities in blood pressure, temperature, HR or respiratory rate will be assessed.

Time: Through 1 year after last vaccination

Measure: The number and percentage of participants with abnormalities in physical examinations will be assessed

Time: Through 1 year after last vaccination

Measure: Evaluate immunogenicity of mRNA-1273 by titer of SARS-CoV-2-specific binding antibody (bAb) measured by enzyme-linked immunosorbent assay (ELISA)

Time: Through 1 year after the final dose

Secondary Outcomes

Measure: Titer of SARS-CoV-2-specific neutralizing antibody (nAb)

Time: Through 1 year post last vaccination

Description: Seroconversion as measured by an increase of SARS-CoV-2-specific neutralizing antibody (nAb) titer either from below the limit of detection (LOD) or lower limit of quantification (LLOQ) to equal to or above LOD or LLOQ, or a 4-times higher titer in participants with pre-existing nAb titers.

Measure: Seroconversion as measured by an increase of SARS-CoV-2-specific neutralizing antibody (nAb) titer

Time: Through 1 year post last vaccination

144 Randomized, Double-blind, Placebo-controlled Trial of TAF/FTC for Pre-exposure Prophylaxis of COVID-19 in Healthcare Workers (CoviPrep Study)

A randomized parallel double-blinded placebo-controlled clinical trial to evaluate the effect of Emtricitabine/Tenofovir alafenamide (FTC/TAF) compared with placebo on the risk of developing SARS-CoV-2 disease (COVID-19) in healthcare workers with high transmission risk in addition to currently recommended control measures.

NCT04405271 Healthcare Workers COVID-19 SARS-CoV 2 Drug: Emtricitabine/Tenofovir Alafenamide 200 MG-25 MG Oral Tablet Drug: Placebo

Primary Outcomes

Description: SARS-CoV-2 disease (COVID-19) with or without symptoms at week 12 of treatment as defined by the presence of specific antibodies against the virus. Positive cases will be confirmed by PCR

Measure: COVID-19 incident cases

Time: During treatment (12 weeks)

Secondary Outcomes

Description: Number of asymptomatic SARS-CoV-2 (Covid-19) infections confirmed by serology

Measure: Number of asymptomatic SARS-CoV-2 (Covid-19) infections confirmed by serology

Time: During treatment (12 weeks)

Description: Severity of symptomatic SARS-CoV-2 (Covid-19) infections as defined by the following categories: Mild symptoms: malaise, fever, cough, arthralgia myalgias, Moderate symptoms: same as above plus shortness of breath Severe symptoms: clinical status requiring admission in Intensive care unit

Measure: Severity of symptomatic COVID-19

Time: During treatment (12 weeks)

Description: Respiratory symptom duration in days

Measure: Respiratory symptom duration in days

Time: During treatment (12 weeks)

Description: Relation between treatments and symptoms duration

Measure: Relation between treatments and symptoms duration

Time: During treatment (12 weeks)

Description: Time course of specific IgM/IgG seroconversion

Measure: Time course of specific IgM/IgG seroconversion

Time: During treatment (12 weeks)

145 A Phase IIa Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Safety, Tolerability and Efficacy of EIDD-2801 to Eliminate Infectious Virus Detection in Persons With COVID-19

This is a phase IIa, double-blind, placebo-controlled, randomized trial, designed to compare the safety, tolerability, and antiviral activity of EIDD-2801 versus placebo as measured by infectious virus detection in symptomatic adult outpatients with COVID-19

NCT04405570 SARS-CoV 2 Drug: 200 mg EIDD-2801 Drug: Placebo
MeSH:Communicable Diseases Infection

Primary Outcomes

Description: The distribution of days until first non-detectable SARS-CoV-2 in nasopharyngeal (NP) swabs will be estimated for each randomized arm (drug versus placebo), using Kaplan-Meier methods with a corresponding stratified log-rank test (to account for the "early" versus "late" time from symptom onset randomization strata)

Measure: Virologic Efficacy

Time: 28 days

Description: Measure the safety and tolerability of EIDD-2801 by estimating in the randomization arm the probability of 1) any adverse events (AEs) leading to early discontinuation of blinded treatment (active or placebo), 2) study drug-related discontinuation of treatment, 3) new grade 3 or higher AE (not already present at baseline), and 4) study drug-related new grade 3 or higher AE. The cumulative probability of each safety and each tolerability endpoint (4 endpoints) by using the Kaplan-Meier approach and stratified log-rank test.

Measure: Number of Participants with any Adverse Events (AEs) as Assessed by Kaplan Meier Approach

Time: 28 days

Secondary Outcomes

Description: Measure the safety and tolerability of EIDD-2801 by estimating the occurrence of Grade 2 or higher AE and drug related AEs by using the Kaplan-Meier approach and stratified log-rank test.

Measure: Number of Participants With any Adverse Events (AEs), Grade 2 or higher as Assessed by Kaplan Meier Approach

Time: 28 days

146 Randomized, Placebo Controlled, Double Blind Clinical Trial to Evaluate the Efficacy of Molecule D11AX22 in Adults Patients From Cali, Colombia With Early Stages of SARS COV2 / COVID-19

Double blind, placebo controlled, randomized clinical trial to evaluate the efficacy of ivermectin in preventing progression of disease in adult patients with early stages of COVID-19

NCT04405843 COVID-19 Drug: Ivermectin Oral Product Drug: Placebo

Primary Outcomes

Description: Time until deterioration of 2 or more points in an ordinal 7 points scale.

Measure: Time to event

Time: 21 days

Secondary Outcomes

Description: Clinical condition in an ordinal scale of 7 points, on day 2. Higher scores indicate worse outcomes

Measure: Clinical condition on day 2

Time: On day 2 (± 1 day) after randomization

Description: Clinical condition in an ordinal scale of 7 points, on day 5. Higher scores indicate worse outcomes

Measure: Clinical condition on day 5

Time: On day 5 (± 1 day) after randomization

Description: Clinical condition in an ordinal scale of 7 points, on day 8. Higher scores indicate worse outcomes

Measure: Clinical condition on day 8

Time: On day 8 (± 1 day) after randomization

Description: Clinical condition in an ordinal scale of 7 points, on day 11. Higher scores indicate worse outcomes

Measure: Clinical condition on day 11

Time: On day 11 (± 1 day) after randomization

Description: Clinical condition in an ordinal scale of 7 points, on day 15. Higher scores indicate worse outcomes

Measure: Clinical condition on day 15

Time: On day 15 (± 1 day) after randomization

Description: Clinical condition in an ordinal scale of 7 points, on day 21. Higher scores indicate worse outcomes

Measure: Clinical condition on day 21

Time: On day 21 (± 1 day) after randomization

Description: Proportion of subjects who require hospitalization, use of supplementary oxygen for >24 hours or ICU admission

Measure: Proportion of subjects with additional care

Time: 21 days

Description: Proportion of subjects who die

Measure: Proportion of subjects who die

Time: From randomization up to 28 days

Description: Duration of supplementary oxygen, hospitalization, ICU stay

Measure: Duration of additional care

Time: 21 days

Description: Proportion of subjects who develop solicited adverse events

Measure: Adverse events

Time: 21 days

Description: Proportion of subjects who required discontinuation of the trial due to adverse events

Measure: Proportion of subjects who discontinue intervention

Time: 21 days

147 Ivermectin and Doxycycline in Combination or Ivermectin Alone for the Treatment of Adult Bangladeshi Patients Hospitalized for COVID-19: a Randomised, Double-blind, Placebo-controlled Trial.

Burden: Initial outbreak of corona virus disease 2019 (COVID-19) was reported from Wuhan, China in early December 2019 Presently known to be caused by a novel beta-corona virus, named as Severe acute respiratory syndrome corona virus 2 ( SARS-CoV-2) World Health Organization (WHO) declared a pandemic on March The clinical characteristics of COVID-19 include respiratory symptoms, fever, cough, dyspnoea and pneumonia Infected individuals exhibit: 1. Mostly mild illness (80% +) recover without any treatment (~80%) 2. Moderate illness that needs hospitalization and recovers after standard 3. supportive treatment (~14%) 4. Critical illness (~5%) needs ICU support 5. Death (1-2% ) COVID-19 has now spread >210 countries and territories globally SARS-CoV-2 is a respiratory virus which spreads primarily through droplets generalized when an infected person coughs or sneezes or through droplets of saliva or discharge from the nose Symptomatic management remains the mainstay of treatment strategy Mortality appears to be more common in older individuals and those with co-morbidities, such as chronic lung disease, cardiovascular disease and diabetes Young people with no comorbidities also appear to be at risk for critical illness including multi-organ failure and death. Seen more in Bangladesh between 21-40 yrs of age Knowledge Gap: There is no specific treatment against this new virus that WHO has officially declared until now There are many pharmacologic therapies that are being used or considered for treatment of COVID-19 National Guidelines on Clinical Management of Corona virus Disease 2019 (Covid-19): V 5.0 date 9th April 2020) CDC, DGHS, GoB Thus an RCT is urgently needed in Bangladesh: Based on recent literatures on Rx studies in COVID-19 patients from other countries as well as its availability & affordability of those repurposed medicines

NCT04407130 COVID-19 Patients Drug: Ivermectin + Doxycycline + Placebo Drug: Ivermectin + Placebo Drug: Placebo

Primary Outcomes

Description: • Presence of virus will be negative on Day 7 detected by RT PCR

Measure: Virological clearance

Time: within 7 days after enrollment

Description: • Body temperature will be between 36.1 to 37.2 C by day 7 detected by Infrared thermometer

Measure: Remission of fever

Time: within 7 days after enrollment

Description: • Remission of cough: No signs of cough showing respiratory rate within 12-20/ min, on day7

Measure: Remission of cough

Time: within 7 days after enrollment

Secondary Outcomes

Description: Detected SPO2 level <94% on Day 7or before by pulse oxymeter

Measure: Patients requiring oxygen

Time: within 7 days after enrollment

Description: Patients who fail to maintain pulse oxymeter detected SpO2 level>88% despite O2 supplementation of 2-6L/min, on Day 7 or before

Measure: Patients failing to maintain SpO2 >88% despite oxygenation

Time: within 7 days after enrollment

Description: Any number of days on oxygen support on Day 7 or before recorded in CRF

Measure: Number of days on oxygen support

Time: within 7 days after enrollment

Description: CXR showing decreases lung opacity or consolidation on day 7 compared with enrollment day

Measure: Chest X-ray improvement

Time: within 7 days after enrollment

Description: Hospital stay ≥7days to ≤14 days as per CRF records

Measure: Duration of hospitalization

Time: within 14 days after enrollment

Description: Death any time during 14 days of study period from any cause recorded in CRF and Hospital death certificate

Measure: All causes of mortality

Time: within 14 days after enrollment

148 Effects of Nicotinamide Riboside on the Clinical Outcome of Covid-19 in the Elderly. A Randomized Double-blind, Placebo-controlled Trial of Nicotinamide Riboside NR-COVID19

The purpose of this study is to investigate whether nicotinamide riboside supplementation can attenuate the severity of SARS-CoV-2 infections in elderly patients. A major event in aging is the loss of the central metabolite nicotinamide adenine dinucleotide (NAD+) that appear to be important in the proinflammatory environment that occur during aging. Notably, recent work from our and other groups suggest that aging can be ameliorated by even a short-term treatment of the NAD+ precursor nicotinamide riboside. Nicotinamide riboside has recently been shown to be able to return aging tissues to a younger state even after short term treatment. This vitamin B3- analog is naturally occurring, is readily taken up through oral administration and has been tested in human trials with few side effects. In this randomized double blinded case-control trial, the investigators will treat elderly (>70 year old) COVID19 patients with 1 g of nicotinamide riboside (NR-E) or placebo for 2 weeks and investigate if this affects the clinical course of the disease.

NCT04407390 COVID Dietary Supplement: Nicotinamide riboside Dietary Supplement: Placebo

Primary Outcomes

Description: Hypoxic respiratory failure as defined by need for oxygen therapy

Measure: Hypoxic respiratory failure

Time: Day 1

Description: Hypoxic respiratory failure as defined by need for oxygen therapy

Measure: Hypoxic respiratory failure

Time: Day 7

Description: Hypoxic respiratory failure as defined by need for oxygen therapy

Measure: Hypoxic respiratory failure

Time: Day 14

Description: Hypoxic respiratory failure as defined by need for oxygen therapy

Measure: Hypoxic respiratory failure

Time: Day 90

Secondary Outcomes

Description: Overall mortality

Measure: Mortality

Time: Day 1

Description: Overall mortality

Measure: Mortality

Time: Day 7

Description: Overall mortality

Measure: Mortality

Time: Day 14

Description: Overall mortality

Measure: Mortality

Time: Day 90

Description: Sepsis

Measure: Sepsis

Time: Day 1

Description: Sepsis

Measure: Sepsis

Time: Day 7

Description: Sepsis

Measure: Sepsis

Time: Day 14

Description: Sepsis

Measure: Sepsis

Time: Day 90

Description: Circulatory failure as defined by a need for interventions to support the circulatory system.

Measure: Circulatory failure

Time: Day 1

Description: Circulatory failure as defined by a need for interventions to support the circulatory system.

Measure: Circulatory failure

Time: Day 7

Description: Circulatory failure as defined by a need for interventions to support the circulatory system.

Measure: Circulatory failure

Time: Day 14

Description: Circulatory failure as defined by a need for interventions to support the circulatory system.

Measure: Circulatory failure

Time: Day 90

Description: Days in hospital

Measure: Days in hospital

Time: Day 1

Description: Days in hospital

Measure: Days in hospital

Time: Day 7

Description: Days in hospital

Measure: Days in hospital

Time: Day 14

Description: Days in hospital

Measure: Days in hospital

Time: Day 90

Description: Measurements of NAD+ and related metabolite levels by mass spectrometry in whole blood.

Measure: NAD levels

Time: Day 1

Description: Measurements of NAD+ and related metabolite levels by mass spectrometry in whole blood.

Measure: NAD levels

Time: Day 7

Description: Measurements of NAD+ and related metabolite levels by mass spectrometry in whole blood.

Measure: NAD levels

Time: Day 14

Description: Measurements of NAD+ and related metabolite levels by mass spectrometry in whole blood.

Measure: NAD levels

Time: Day 90

149 Multicenter, Double-blind, Randomized, Placebo-controlled Study to Assess the Efficacy, Safety and Tolerability of Ivermectin in Mild Virus-positive Subjects (SARS-CoV)-2 With or Without Symptoms

This study aims to evaluate the efficacy, safety and tolerability of Ivermectin in patients with mild SARS-CoV-2 infection, in the rate of progression to severe 2019 novel coronavirus disease (COVID-19). The primary efficacy endpoint is the proportion of participants with a disease control status defined as no progression of severe disease Hypothesis (H0): There is no difference between group A (ivermectin + paracetamol) and group B (ivermectin + paracetamol) in terms of the primary endpoint on day 14.

NCT04407507 COVID-19 Drug: Ivermectin Drug: Placebo

Primary Outcomes

Description: The subject is considered to have progressed to severe illness when one or more of the following criteria are present: Breathing difficulty (≥30 breaths per minute); Resting oxygen saturation ≤93%; Severe complications such as: respiratory failure, need for mechanical ventilation, septic shock, non-respiratory organic failure.

Measure: Participants with a disease control status defined as no disease progression to severe.

Time: 14 days

150 A Multicenter, Randomized, Double-blinded Placebo-controlled Study of Recombinant Interleukin-7 (CYT107) for Immune Restoration of Hospitalized Lymphopenic Patients With Coronavirus COVID-19 Infection in France and Belgium

Comparison of the effects of CYT107 vs Placebo administered IM at 10μg/ kg twice a week for two weeks on immune reconstitution of lymphopenic COVID-19 patients.

NCT04407689 COVID-19 Lymphocytopenia Drug: Interleukin-7 Drug: Placebo
MeSH:Lymphopenia
HPO:Lymphopenia

Primary Outcomes

Description: A statistically significant increase of the absolute lymphocyte count (ALC) from randomization to day 30 or Hospital Discharge

Measure: Improvement of the absolute lymphocyte count (ALC) of lymphopenic (ALC≤1000/mm3) COVID-19 infected participants out to approximately 30 days following initial Study drug administration or Hospital discharge (HD), whichever occurs first

Time: 1 month

Secondary Outcomes

Description: The time to clinical improvement to determine if CYT107 will improve the clinical status of hospitalized COVID-19 patients as measured by clinical improvement score

Measure: "clinical improvement" as defined by a 2 points improvement in a 7-point ordinal scale for Clinical Assessment, through day 30 or HD.

Time: 1 month

Description: The decrease of SARS-CoV-2 viral load from measurements at baseline and days of treatment dose 4 and dose 5, Day 21 and Day 30 or HD (whichever occurs first)

Measure: a significant decline of SARS-CoV-2 viral load through day 30 or HD

Time: 1 month or HD (whichever occurs first)

Description: Incidence of secondary infections based on pre-specified criteria as adjudicated by the Secondary Infections Committee (SIC) through Day 45

Measure: frequency of secondary infections through day 45 compared tp placebo arm

Time: 45 days

Description: Number of days of hospitalization during index hospitalization (defined as time from initial Study drug treatment through HD)

Measure: length of hospitalization compared to placebo arm

Time: 45 days

Description: Number of days in ICU during index hospitalization

Measure: length of stay in ICU compared to placebo arm

Time: 45 days

Description: Readmissions to ICU through Day 45

Measure: number of readmissions to ICU compared to placebo arm

Time: 45 days

Description: Organ support free days (OSFDs) during index hospitalization (This includes ventilator assistance free days)

Measure: organ support free days compared to placebo arm

Time: 45 days

Description: Number of readmissions to the hospital through Day 45

Measure: Frequency of re-hospitalization through day 45 compared to placebo arm

Time: 45 days

Description: All-cause mortality through Day 45

Measure: All-cause mortality through day 45 compared to placebo arm

Time: 45 days

Description: Absolute numbers of CD4+ and CD8+ T-cell counts at timepoints indicated on the Schedule of Activities (SoA) through Day 30 or HD

Measure: CD4+ and CD8+ T cell counts compared to placebo arm

Time: 30 days

Description: Track and evaluate other known biomarkers of inflammation, Ferritin, from baseline to day 30

Measure: level of other known biomarkers of inflammation: Ferritin compared to placebo arm

Time: 30 days

Description: Track and evaluate other known biomarkers of inflammation, CRP from baseline to day 30

Measure: Level of other known biomarkers of inflammation: CRP compared to placebo arm

Time: 30 days

Description: Track and evaluate other known biomarkers of inflammation, D-dimer from baseline to day 30

Measure: Level of other known biomarkers of inflammation: D-dimer compared to placebo arm

Time: 30 days

Description: Evaluate improvement of the NEWS2 score value. Score form 0 to 4: NO Risk Score of 7 or more: High risk

Measure: Physiological status through NEWS2 evaluation compared to Placebo arm

Time: 30 days

Other Outcomes

Description: Incidence and scoring of all grade 3-4 adverse events through Day 45 (using CTCAE Version 5.0 to assess severity)

Measure: Safety assessment through incidence and scoring of grade 3-4 adverse events

Time: 45 days

151 Efficacy, Safety, and Tolerability of GLS-1200 Topical Nasal Spray in the Prevention of Incident Confirmed, Symptomatic SARS-CoV-2 Infection in Healthcare Personnel

This clinical trial will evaluate the safety, tolerability and effectiveness of topical GLS-1200 nasal spray to reduce the incidence of confirmed, symptomatic SARS-CoV-2 infection.

NCT04408183 SARS-CoV 2 Infection Drug: GLS-1200 Drug: Placebo
MeSH:Infection Communicable Diseases

Primary Outcomes

Measure: Evaluate the number of GLS-1200 topical nasal spray adverse events as assessed by CTCAE v5.0

Time: 4 weeks of treatment

Measure: Incidence of SARS-CoV-2 infection, confirmed by PCR relative to treatment group

Time: 4 weeks of treatment

Secondary Outcomes

Measure: Symptom score of documented SARS-CoV-2 infection relative to treatment group with a higher score being a worse outcome.

Time: 4 weeks of treatment

152 A Phase III, Randomized, Double-Blind, Multicenter Study to Evaluate the Efficacy and Safety of Remdesivir Plus Tocilizumab Compared With Remdesivir Plus Placebo in Hospitalized Patients With Severe COVID-19 Pneumonia

This study will evaluate the efficacy and safety of combination therapy with remdesivir plus tocilizumab compared with remdesivir plus placebo in hospitalized patients with COVID-19 pneumonia.

NCT04409262 COVID-19 Pneumonia Drug: Remdesivir Drug: Tocilizumab Drug: Placebo
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Measure: Clinical Status as Assessed by the Investigator Using a 7-Category Ordinal Scale of Clinical Status on Day 28

Time: Day 28

Secondary Outcomes

Measure: Time to Clinical Improvement (TTCI) Defined as Time from Randomization to National Early Warning Score 2 (NEWS2) Score of Time: Up to Day 28

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

Time: Up to Day 28

Measure: Clinical Status as Assessed by the Investigator Using a 7-Category Ordinal Scale of Clinical Status on Days 7, 14, and 21

Time: Days 7, 14, and 21

Measure: Proportion of Participants Requiring Initiation of Mechanical Ventilation Post-baseline

Time: Up to Day 28

Measure: Ventilator-Free Days from Randomization to Day 28

Time: Up to Day 28

Measure: Proportion of Participants Requiring Initiation of Intensive Care Unit (ICU) Care Post-baseline

Time: Up to Day 28

Measure: Duration of ICU Stay in Days

Time: Up to Day 28

Description: For participants entering the study already in ICU or on mechanical ventilation, clinical failure is defined as a one-category worsening on the ordinal scale, withdrawal or death.

Measure: Time to Clinical Failure, Defined as the Time from Randomization to the First Occurrence of Death, Mechanical Ventilation, ICU Admission, or Withdrawal (whichever occurs first)

Time: Up to Day 28

Measure: Mortality Rate on Days 7, 14, 21, 28, and 60

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

Measure: Time to Recovery, Defined as Time from Randomization to the Time when a Category of 2, Non-ICU Hospital Ward (or "Ready for Hospital Ward") not Requiring Supplemental Oxygen, or Better is Observed

Time: Up to Day 28

Measure: Time from Randomization to Hospital Discharge or "Ready for Discharge" (as Evidenced by Normal Body Temperature and Respiratory Rate, and Stable Oxygen Saturation on Ambient Air or Time: Up to Day 28

Measure: Duration of Supplemental Oxygen Use

Time: Up to Day 28

Other Outcomes

Measure: Percentage of Participants with Adverse Events (AEs)

Time: Up to Day 28

Measure: Proportion of Participants with any Post-Treatment Infection

Time: Up to Day 28

Measure: Plasma Concentration of Remdesivir

Time: Up to Day 28

153 Randomized Double Blind Placebo-Controlled Study to Determine if Prophylaxis With RTB101 Compared to Placebo Reduces Severity of Lab Confirmed COVID19 in Adults ≥65 Years in a Nursing Home in Which ≥1 Person(s) Have Lab Confirmed COVID19

The purpose of this study is to determine if prophylaxis with RTB101 decreases the severity of laboratory-confirmed COVID-19 among adults ≥ 65 years who reside in a nursing homes in which one or more residents or staff have laboratory-confirmed COVID-19

NCT04409327 COVID19 Drug: RTB101 Drug: Placebo

Primary Outcomes

Measure: The percentage of subjects who develop laboratory-confirmed COVID-19: - with protocol-defined progressive symptoms OR - are hospitalized OR - die

Time: Through Week 4

Secondary Outcomes

Measure: The percentage of subjects who develop symptomatic laboratory-confirmed COVID-19 infection

Time: Through Week 4

Measure: Mortality rate in subjects who develop laboratory-confirmed COVID19

Time: Through Week 8

Measure: Percent of subjects who are hospitalized due to having one or more predefined COVID-19 symptoms and laboratory-confirmed SARS-CoV-2

Time: Through Week 4

Measure: Percent of subjects who require mechanical ventilation, noninvasive ventilation, high flow nasal canula oxygen delivery or ICU admission during the hospitalization for COVID19

Time: Through Week 8

Measure: Safety and tolerability will be assessed by report of AE/SAEs

Time: Through Week 5 and 8

154 A Phase 2, Multicenter, Double Blind, Randomized, Placebo-Controlled Study to Evaluate CSL312 in Coronavirus Disease 2019 (COVID 19)

This is a prospective, phase 2, multicenter, randomized, double blind, placebo controlled, parallel group study to assess the safety and efficacy of CSL312 administered intravenously, in combination with standard of care (SOC) treatment, in patients with Coronavirus disease 2019 (COVID 19)

NCT04409509 Coronavirus Disease 2019 (COVID‑19) Biological: Garadacimab, Factor XIIa Antagonist Monoclonal Antibody Drug: Placebo
MeSH:Coronavirus Infections

Primary Outcomes

Measure: The incidence of tracheal intubation or death prior to tracheal intubation

Time: From randomization to Day 28

Secondary Outcomes

Measure: Proportion of subjects with death from all causes

Time: From randomization to Day 28

Measure: Proportion of subjects intubated

Time: From randomization to Day 28

Measure: Number and proportion of subjects with ≥ 2‑point improvement on National Institute of Allergy and Infectious Diseases (NIAID) Ordinal scale

Time: From randomization to Day 28

Measure: Number and proportion of subjects within each of the categories of the NIAID

Time: From randomization to Day 28

Measure: Proportion of subjects requiring continuous positive airway pressure (CPAP)

Time: From randomization to Day 28

Measure: Proportion of subjects requiring bilevel positive airway pressure (BiPAP)

Time: From randomization to Day 28

Measure: Proportion of subjects requiring high‑flow nasal cannula (HFNC)

Time: From randomization to Day 28

Measure: Proportion of subjects requiring extracorporeal membrane oxygenation (ECMO)

Time: From randomization to Day 28

Measure: Maximum change from baseline in Sequential Organ Failure Assessment (SOFA) score

Time: From randomization to Day 28

Measure: Average SOFA score over the subject's duration of the study

Time: From randomization to Day 28

Measure: Length of hospital stay

Time: From randomization to Day 28

Measure: Number and proportion of subjects experiencing Adverse Events (AEs)

Time: Up to 28 days after CSL312 or placebo administration

Measure: Number and proportion of subjects experiencing serious adverse events (SAEs)

Time: Up to 28 days after CSL312 or placebo administration

Measure: Number and proportion of subjects with adverse events of special interest (AESIs)

Time: Up to 28 days after CSL312 or placebo administration

Measure: Number and proportion of subjects with CSL312 induced anti‑CSL312 antibodies

Time: Up to 28 days after CSL312 or placebo administration

Measure: Maximum plasma concentration (Cmax) of CSL312

Time: Up to 28 days after CSL312 administration

Measure: Time to maximum plasma concentration (Tmax) of CSL312

Time: Up to 28 days after CSL312 administration

Measure: Area under the plasma concentration‑time curve (AUC) of CSL312

Time: Up to 28 days after CSL312 administration

155 Study of the P2Et Extract Obtained From Caesalpinia Spinosa in the Symptomatic Treatment of Subjects With COVID-19 at the Hospital Universitario San Ignacio, Colombia.

Antioxidants, and particularly polyphenols, have shown protection in respiratory pathologies, which is related to the decrease in the severity of the clinical picture and suppression of inflammation. This suppression of inflammation may be related to the inhibition of NF-kB polyphenols, where its activation is related to the stimulation of 150 stimuli including cytokines (IL-1β, IL-6, THF-α, GM-CSF, MCP-1), TLRs, among others. There may be other additional mechanisms that can help control virus-induced respiratory pathologies, among which are the regulation of reactive oxygen species (ROS) associated with tissue destruction caused by the virus and a selective antiviral action can be reported. direct. The standardized P2Et extract obtained from C. spinosa, by the Immunobiology Group of the Pontificia Universidad Javeriana, is highly antioxidant, decreases lipid peroxidation and tissue damage and induces complete autophagy in stressed or tumor cells. The induction of a full autophagic flow could inhibit the replication of beta-coronaviruses like SARS-CoV-2. Furthermore, P2Et can decrease the factors involved in tissue damage by reducing IL-6 and decrease ILC2 cells of the lung in animals with lung metastases (unpublished data). These antecedents suggest that the supplementation of patients with COVID-19 with the extract P2Et, could improve their general condition and decrease the inflammatory mediators and the viral load.

NCT04410510 COVID Coronavirus Infection SARS-CoV 2 COVID19 Drug: P2Et (Caesalpinia spinosa extract) Other: Placebo
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome

Primary Outcomes

Description: Proportion of patients who reduce the time in the hospital

Measure: Evaluate the efficacy of P2Et in reducing the length of hospital stay of patients with clinical suspicion or confirmed case of COVID-19

Time: 30 days

Secondary Outcomes

Description: Efficacy of P2Et in reducing the time to clinically significant improvement in patients with clinical suspicion or confirmed case of COVID-19

Measure: Efficacy of P2Et in reducing the time to clinically significant improvement in patients with clinical suspicion or confirmed case of COVID-19

Time: 30 days

Description: Evaluate the efficacy of P2Et in increasing the proportion of patients with clinical suspicion or confirmed case of COVID-19, who achieve clinical improvement after 14 days of treatment

Measure: Proportion of patients with clinical suspicion or confirmed case of COVID-19, who achieve clinical improvement after 14 days of treatment

Time: 30 days

Description: Evaluate the efficacy of P2Et in increasing the proportion of patients with clinical suspicion or confirmed case of COVID-19, who achieve clinical improvement after 28 days of treatment

Measure: Proportion of patients with clinical suspicion or confirmed case of COVID-19, who achieve clinical improvement after 28 days of treatment

Time: 30 days

Description: Assess the efficacy of P2Et in reducing the proportion of hospitalized patients with clinical suspicion or confirmed case of COVID-19 who require admission to the ICU due to worsening clinical symptoms.

Measure: Efficacy of P2Et in reducing the proportion of hospitalized patients with clinical suspicion or confirmed case of COVID-19 who require admission to the ICU due to worsening clinical symptoms.

Time: 30 days

Description: Evaluate the efficacy of P2Et in reducing the proportion of patients with clinical suspicion or confirmed case of COVID-19 who die from the disease.

Measure: Efficacy of P2Et in reducing the proportion of patients with clinical suspicion or confirmed case of COVID-19 who die from the disease.

Time: 30 days

Description: Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) of the P2Et in patients with COVID-19

Measure: Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) of the P2Et in patients with COVID-19

Time: 30 days

156 Hydroxychloroquine Efficacy and Safety in Preventing SARS-CoV-2 Infection and COVID-19 Disease Severity During Pregnancy

It still unclear how SARS-CoV-2 affects pregnant women and their offspring, as well as which factors may influence obstetrical disease and outcomes, including the timing of maternal viral exposure by gestational age, the effects of parity, age, host immune responses, coexisting medical and obstetrical conditions and the effects of treatment regimens. While further information is gathered, based on the existing evidence from other infections causing pneumonia, pregnant women should be considered to be at high risk for developing severe infection during the current COVID-19 epidemic. Results from clinical trials with HCQ in nonpregnant adults may not be directly extrapolated to pregnant women given the special features of the pregnancy status. Thus, clinical research is urgently needed to improve the care and reduce the risk of poor pregnancy outcomes of women in this and in future epidemics.

NCT04410562 Pregnancy Related COVID Covid-19 Drug: Hydroxychloroquine Drug: Placebo
MeSH:Infection

Primary Outcomes

Description: Number of PCR-confirmed infected pregnant women assessed from collected nasopharyngeal and oropharyngeal swabs at day 21 after treatment start

Measure: Number of PCR confirmed cases among pregnant women

Time: 21 days after intervention

Secondary Outcomes

Measure: Incidence of COVID-19 disease during pregnancy

Time: through study completion, an average of 1 year

Measure: Incidence of COVID-19-related admissions

Time: through study completion, an average of 1 year

Measure: Incidence of all-cause admissions

Time: through study completion, an average of 1 year

Measure: Incidence of all-cause outpatient attendances

Time: through study completion, an average of 1 year

Measure: Mean duration of symptoms-signs of COVID-19

Time: through study completion, an average of 1 year

Measure: Frequency and severity of adverse events

Time: through study completion, an average of 1 year

Measure: Incidence of preeclampsia

Time: through study completion, an average of 1 year

Measure: Incidence of gestational diabetes

Time: through study completion, an average of 1 year

Measure: Incidence of SARS-CoV-2 infections during pregnancy

Time: through study completion, an average of 1 year

Measure: Prevalence of intrauterine growth restriction

Time: through study completion, an average of 1 year

Measure: Maternal mortality rate

Time: through study completion, an average of 1 year

Measure: Proportion of neonates with SARS-CoV-2- intrauterine infection by PCR-confirmed SARS-CoV-2-infection in nasopharyngeal aspirate.

Time: through study completion, an average of 1 year

Measure: Proportion of neonates with clinical signs/symptoms of COVID-19

Time: through study completion, an average of 1 year

Measure: Prevalence of low birth weight (<10th centile according to local standards)

Time: through study completion, an average of 1 year

Measure: Prevalence of preterm birth (<37 weeks of gestational age)

Time: through study completion, an average of 1 year

Measure: Prevalence of embryo and foetal losses (miscarriages and stillbirths)

Time: through study completion, an average of 1 year

Measure: Frequency of congenital malformations

Time: through study completion, an average of 1 year

Measure: Proportion of adverse perinatal outcome

Time: through study completion, an average of 1 year

Measure: Neonatal morbidity

Time: through study completion, an average of 1 year

Measure: Neonatal mortality rate

Time: through study completion, an average of 1 year

157 Randomized Controlled Trial of High Dose of Vitamin D as Compared With Placebo to Prevent Complications Among COVID-19 Patients

The recent inception of the coronavirus SARS-CoV-2, responsible for the coronavirus disease (COVID-19), has caused thousands of deaths globally. The most frequently reported complications among COVID-19 patients are from respiratory involvement. Vitamin D has immunomodulatory effects that could protect against COVID-19 infection. Indeed, there is good evidence from randomized clinical trials suggesting that high doses of vitamin D administered during cold seasons prevent viral respiratory infections in at risk individual, and more recently, observational studies suggested that the mortality rate from COVID-19 is inversely correlated with levels of serum 25(OH)vitamin D. The hypothesis of the study is that a high dose of vitamin D given orally to patients admitted to the hospital for COVID-19 will prevent the occurrence of respiratory deragement and other adverse clinical events. To evaluate the aforementioned hypothesis, a randomized, controlled, double-blind, clinical trial comparing a 500.000 UI dose of vitamin D versus placebo among COVID-19 patients at moderate risk, requiring hospitalization but without requirements of critical care at admission was designed. The intervention will be one dose of 500.000 UI given orally or matching placebo. The trial has a sequential design with two steps: - The first step, projected to include 200 patients, will assess the effects of the intervention on the respiratory SOFA; and - If there is a detectable effects, the second step, projected to include 1265 patients, will assess the effects on a combined event that includes need of high dose of oxygen or mechanical ventilation. All study outcomes will be measured during the index hospitalization.

NCT04411446 COVID Drug: Vitamin D Drug: Placebo

Primary Outcomes

Description: Is the respiratory component of the sequential organ failure assessment score (SOFA score). It is a 4 points scale, each point indicate a deeper respiratory impairment. The score is based on the relationship between the arterial pressure of oxygen (PaO2) and inspired fraction of oxygen (FiO2), as the ratio of both (PaFi). In the cases were arterial blood gas are not measured, the pulse oximetry will be used instead. The respiratory SOFA is as follows: 1: PaO2/FiO2 >=300; 2: PaO2/FiO2 >=200 and <300; 3: PaO2/FiO2 >=100 and <200; 4: PaO2/FiO2 <300. The minimum respiratory SOFA score will be record on daily basis during first week or to death or discharge, whichever occur first. This outcome is the primary outcome of the first study phase.

Measure: Respiratory SOFA.

Time: One week

Description: The start of oxygen supplementation at FiO2 >40% or the initiation of invasive through orotracheal intubation) or non-invasive ventilation (Continuous positive airway pressure or Bilevel positive airway ventilation). This outcome will be recorded during hospitalization to 30 days, the death or discharge, whichever occur first. This is the primary outcome of the second study phase.

Measure: Need of a high dose of oxygen or mechanical ventilation.

Time: 30 days

Secondary Outcomes

Description: Difference between the oxygen saturation at study entry and the lowest oxygen saturation measured during the first week, the death or discharge, whichever occur first. The oxygen saturation will be measured by pulse oximetry using commercially available devices.

Measure: Change in oxygen saturation.

Time: One week

Description: Oxygen saturation equal or less than 90% in any moment during the hospitalization. This outcome will be measured by pulse oximetry using commercially available devices. The outcome will be measured during the first week, the death or hospital discharge, whichever occur first.

Measure: Oxygen desaturation.

Time: One week

Description: The difference between the Quick SOFA score at study entry and the highest value recorded during the hospitalization. The outcome will be measured during the hospitalization until 30 days, the death or discharge whichever occur first.

Measure: Change in Quick SOFA score.

Time: 30 days.

Description: Myocardial infarction is defined as suspicious symptoms with new Q waves in the EKG and enzymatic elevations compatible with the Fourth MI Definition. The outcome will be measured during the hospitalization until 30 days, the death or discharge whichever occur first.

Measure: Myocardial infarction.

Time: 30 days

Description: Stroke is defined as a focal neurological loss lasting >24 hs as reported by treating physician. The outcome will be measured during the hospitalization until 30 days, the death or discharge whichever occur first.

Measure: Stroke.

Time: 30 days

Description: Acute kidney injury is defined as an increase of at least 50% in serum creatinine levels (as compared with any previous value during the hospitalization). The outcome will be measured during the hospitalization until 30 days, the death or discharge whichever occur first.

Measure: Acute kidney injury.

Time: 30 days

Description: Pulmonary thromboembolism is defined as the presence of suspicious symptoms (i.e. dyspnea) confirmed with objective evidence of a thrombus in the pulmonary tree by CT or MRI or Pulmonary Angiography. The outcome will be measured during the hospitalization until 30 days, the death or discharge whichever occur first.

Measure: Pulmonary thromboembolism.

Time: 30 days

Description: Combined outcome of the aforementioned events, Stroke is defined as a focal neurological loss lasting >24 hs as reported by treating physician. Myocardial infarction is defined as suspicious symptoms with new Q waves in the EKG and enzymatic elevations compatible with the Fourth MI Definition. Pulmonary thromboembolism is defined as the presence of suspicious symptoms (i.e. dyspnea) confirmed with objective evidence of a thrombus in the pulmonary tree by CT or MRI or Pulmonary Angiography. Acute kidney injury is defined as an increase of at least 50% in serum creatinine levels (as compared with any previous value during the hospitalization). The outcome will be measured during the hospitalization until 30 days, the death or discharge whichever occur first.

Measure: Combined endpoint (stroke, myocardial infarction, acute kidney injury and pulmonary thromboembolism.

Time: 30 days

Description: Admission to Intensive Care Unit due to clinical deterioration as judged by the treating physician. The outcome will be measured during the hospitalization until 30 days, the death or discharge whichever occur first.

Measure: Admission to ICU.

Time: 30 days

Description: The start of mechanical ventilation invasive during the hospitalization until 30 days, the death or discharge whichever occur first.

Measure: Invasive Mechanical Ventilation.

Time: 30 days

Description: Total duration of initial hospital stay in days. The outcome will be measured during the hospitalization until 30 days, the death or discharge whichever occur first. In the cases with hospital stays longer than 30 days, it will considered as 30 days.

Measure: Hospital Length of Stay.

Time: 30 days.

Description: Total duration of initial ICU stay in days. The outcome will be measured during the hospitalization until 30 days, the death or discharge whichever occur first. In the cases with ICU stays longer than 30 days, it will considered as 30 days.

Measure: ICU length of stay.

Time: 30 days

Description: Death of any cause during the hospitalization until 30 days or discharge whichever occur first.

Measure: Death

Time: 30 days.

158 A DB, Placebo-Controlled, Two-Arm Parallel-Group, Phase 3 RCT to Investigate the Efficacy and Safety of Recombinant Human Alkaline Phosphatase for Treatment of Patients With SA-AKI

Clinical phase 3 study to investigate the effect of recAP on 28 day mortality in patients admitted to the ICU with acute kidney injury that is caused by sepsis. 1400 patients will be included in the study that is conducted in approx. 100 ICU's in Europe and North America There are two arms in the study, one with active treatment and one with an inactive compound (placebo). Treatment is by 1 hour intravenous infusion, for three days. Patients are followed up for 28 days to see if there is an improvement on mortality, and followed for 90 and 180 days for mortality and other outcomes e.g. long-term kidney function and quality of life.

NCT04411472 Acute Kidney Injury Due to Sepsis Biological: Recombinant human alkaline phosphatase Other: Placebo
MeSH:Sepsis Acute Kidney Injury
HPO:Acute kidney injury Sepsis

Primary Outcomes

Description: To demonstrate an effect of recAP on 28 day all cause mortality

Measure: 28-day all-cause mortality

Time: 28 days

Secondary Outcomes

Description: MAKE 90: dead or on RRT or ≥25% decline in estimated glomerular filtration rate (eGFR) on Day 90 relative to the known or assumed pre-AKI reference level.

Measure: To investigate the effect of recAP on long-term Major Adverse Kidney Events (MAKE).

Time: 90 Days

Description: Days alive and free of organ support through Day 28, i.e., days alive with no MV, RRT, vasopressors or inotropes (with death within 28 days counting as zero days).

Measure: To investigate the effect of recAP on use of organ support, i.e., mechanical ventilation (MV), Renal Replacement Therapy (RRT), vasopressors or inotropes.

Time: 28 days

Description: Days alive and out of the ICU through Day 28 (with death within 28 days counting as zero days).

Measure: To investigate the effect of recAP on length of stay (LOS) in ICU.

Time: 28 days

Description: Time to death through Day 90.

Measure: To investigate the effect of recAP on 90-day allcause mortality

Time: 90 days

159 A Randomized, Double-blind, Placebo-controlled, Multicenter, Phase 2 Clinical Trial to Evaluate the Efficacy and Safety of CERC-002 in Adults With COVID 19 Pneumonia and Acute Lung Injury

The study is a prospective, randomized, placebo-controlled, single-blind phase 2 clinical study of the efficacy and safety of CERC-002, a potent inhibitor of LIGHT, for the treatment of patients with COVID-19 pneumonia who have mild to moderate ARDS. LIGHT is a cytokine in the TNF super family (TNFSF14) which drives inflammation and induces many other cytokines including IL-1, IL-6 and GM-CSF. LIGHT levels have been shown to be elevated in COVID-19 infected patients and inhibiting LIGHT is hypothesized to ameliorate the cytokine storm which has shown to be a major factor in progression of ARDS. The study will assess the efficacy and safety of CERC-002 in patients with severe COVID-19 over a 28 day period as single dose on top of standard of care.

NCT04412057 COVID-19 Pneumonia Acute Lung Injury ARDS Drug: CERC-002 Drug: Placebo
MeSH:Pneumonia Lung Injury Acute Lung Injury Respiratory Distress Syndrome, Adult Wounds and Injuries
HPO:Pneumonia

Primary Outcomes

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

Measure: Proportion of patient alive and free of respiratory failure

Time: Baseline to Day 28

Secondary Outcomes

Description: 1-month mortality

Measure: Proportion of subjects who are alive

Time: Baseline to Day 28

160 A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study Assessing the Safety and Efficacy of Tofacitinib in Hospitalized Participants With COVID-19 Pneumonia Who Are Receiving Standard of Care Therapy

The study is designed as a multicenter, randomized, double-blind, placebo-controlled, parallel group study of the safety and efficacy of tofacitinib in hospitalized adult participants with COVID-19 pneumonia who are receiving SoC therapy and who are not on HFNC, noninvasive ventilation, invasive mechanical ventilation, or ECMO on Day 1 at the time of randomization. Participants with laboratory confirmed SARS-CoV-2 infection as determined by a positive PCR or other commercially available or public health assay, who have agreed to participate will be screened within 48 hours after hospitalization to determine eligibility. This should be completed within 48 hours prior to Day 1. Eligible participants will be randomized on Day 1 in a 1:1 ratio to the tofacitinib treatment group or the placebo treatment group and will receive treatment for up to 14 days, or until discharge from the hospital, whichever is earlier. If a participant requires intubation prior to the end of the 14-day treatment period, they will continue to receive tofacitinib or matching placebo until Day 14 (or until discharge from the hospital, if earlier than Day 14), if clinically appropriate. Participants will be assessed daily (up to Day 28) while hospitalized for clinical, safety, and laboratory parameters. Follow-up visits will occur on Day 28, 28 to 35 days after the ET/ED/EOT visit, and on Day 60. An independent, external DSMB will be convened to oversee the safety of participants and make recommendations regarding the conduct of the trial in accordance with the Charter.

NCT04412252 COVID-19 Drug: Tofacitinib Other: Placebo
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Death or respiratory failure (1, 2, or 3, on an 8-point ordinal scale of disease severity) at Day 28. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.

Measure: Clinical status using ordinal scale

Time: Day 28

Secondary Outcomes

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

Measure: Clinical status using ordinal scale

Time: Day 14

Description: Category 3 to 8 on an ordinal scale of disease severity. The scale is as follows: 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.

Measure: Status of alive and not using mechanical ventilation or extracorporeal membrane oxygenation (ECMO)

Time: Day 14 and Day 28

Description: Category 5 to 8 on an ordinal scale of disease severity. The scale is as follows: 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.

Measure: Status of discharged or not requiring supplemental oxygen

Time: Day 28

Description: Category 1 on an ordinal scale of disease severity. The scale is as follows: 1) Death.

Measure: Mortality

Time: Day 60

161 A Randomized Double-blind Placebo-controlled Study to Evaluate the Safety and Efficacy of ATYR1923 In Adult Patients With Severe Pneumonia Related to SARS-CoV-2 Infection (COVID-19)

A Phase 2 study to evaluate the safety and preliminary efficacy of ATYR1923, compared to placebo, in hospitalized patients with SARS-CoV-2 (COVID-19) severe pneumonia not requiring mechanical ventilation

NCT04412668 SARS-CoV-2 (COVID-19) Severe Pneumonia Drug: ATYR1923 1 mg/kg Drug: ATYR1923 3 mg/kg Drug: Placebo
MeSH:Pneumonia
HPO:Pneumonia

Primary Outcomes

Measure: Incidence of treatment-emergent adverse events (TEAEs)

Time: Baseline through Day 60

Secondary Outcomes

Measure: Time to normalization of oxygen saturation (SpO2) (>93% on room air sustained for at least 24 hours)

Time: Baseline through Day 14 or discharge

Measure: Duration of supplemental oxygen (O2) requirement

Time: Baseline through Day 14 or discharge

Measure: Number of days with fever (temperature >100.4ºF [38.0ºC])

Time: Baseline through Day 14 or discharge

Measure: Time to normalization of temperature (≤100.4ºF [38.0ºC])

Time: Baseline through Day 14 or discharge

Measure: Change from baseline in World Health Organization (WHO) Ordinal Scale score on Days 5, 7, 14, 28, and 60

Time: Baseline through Day 60

Measure: Time to improvement from inpatient hospital admission based on at least a 1 point reduction in WHO Ordinal Scale score

Time: Baseline through Day 60

162 A Randomized Clinical Trial for Enhanced Trained Immune Responses Through Bacillus Calmette-Guérin Vaccination to Prevent Infections by COVID-19: The ACTIVATE II Trial

Based on findings of the interim analysis of the ACTIVATE study showing 53% decrease of the incidence of all new infections with BCG vaccination, a new trial is designed aiming to validate if BCG can protect against COVID-19 (Corona Virus Disease-19).The aim of the study is to demonstrate in a double-blind, placebo-controlled approach if vaccination of participants susceptible to COVID-19 with BCG vaccine may modulate their disease susceptibility for COVID-19. This will be validated using both clinical and immunological criteria.

NCT04414267 COVID-19 Virus Diseases Corona Virus Infection Coronary Heart Disease Chronic Obstructive Pulmonary Disease Biological: BCG vaccine Biological: Placebo
MeSH:Infection Coronavirus Infections Severe Acute Respiratory Syndrome Lung Diseases, Obstructive Pulmonary Disease, Chronic Obstructive Heart Diseases Coronary Disease Virus Diseases
HPO:Chronic obstructive pulmonary disease Obstructive lung disease

Primary Outcomes

Description: This is set on visit 3 (90 ± 5 days from the date of visit 1). The two groups of vaccination are compared for the primary endpoints which is composite. Patients who meet any of the following will be considered to meet the primary endpoint: Positive for the respiratory questionnaire endpoint when at least one of the following combination is met either at visit 2 and/or at visit 3: One situation definitively related to COVID-19 All four questions of symptoms possibly related to COVID-19 At least two questions of symptoms possibly related to COVID-19 as well as need for admission at the emergency department of any hospital and/or need for intake of antibiotics At least four questions of symptoms probably related to COVID-19 one of which is "need for admission at the emergency department of any hospital and/or need for intake of antibiotics" Positive IgG or IgM antibodies against SARS-CoV-2

Measure: Positive for the respiratory questionnaire consisted of questions concerning the appearance of symptoms possibly, probably and/or definitively related to COVID-19 on visit 3.

Time: Visit 3 (90 +/- 5 days)

Secondary Outcomes

Description: The two groups of vaccination are compared for the primary endpoints which is composite (as defined at primary study endpoint) and meet a positive respiratory questionnaire endpoint on visit 4

Measure: Positive respiratory questionnaire endpoint consisted of questions concerning the appearance of symptoms possibly, probably and/or definitively related to COVID-19 on visit 4

Time: Visit 4 (135 +/- 5 days)

Description: The two groups of vaccination are compared for the primary endpoints which is composite (as defined at primary study endpoint) and meet a positive respiratory questionnaire endpoint (as defined at primary study endpoint) on visit 5

Measure: Positive respiratory questionnaire endpoint consisted of questions concerning the appearance of symptoms possibly, probably and/or definitively related to COVID-19 on visit 5

Time: Visit 5 (180 +/- 5 days)

Description: Prevalence of IgG/IgM against SARS-CoV-2 will be measured among the patients who failed the eligibility procedure and the patients that were eligible and were enrolled

Measure: Prevalence of IgG/IgM against SARS-CoV-2

Time: Screening Visit and Visit 3 (90 +/- 5 days)

Description: Itemized analysis of each of the components of the respiratory questionnaire on each study visit

Measure: Analysis of each of the components of the respiratory questionnaire consisted of questions concerning the appearance of symptoms possibly, probably and/or definitively related to COVID-19.

Time: Visit 2 (45 +/- 5 days), Visit 3 (90 +/- 5 days), Visit 4 (135 +/- 5 days), Visit 5 (180 +/- 5 days)

163 Opaganib, a Sphingosine Kinase-2 (SK2) Inhibitor in COVID-19 Pneumonia: a Randomized, Double-blind, Placebo-Controlled Phase 2a Study, in Adult Subjects Hospitalized With SARS-CoV-2 Positive Pneumonia

Opaganib, a sphingosine kinase-2 (SphK2) inhibitor, has been broadly tested in Phase I/II studies. Extensive nonclinical data indicates both anti-viral and anti-inflammatory activity via selective SphK2 inhibition which may prove beneficial for treating COVID-19 infection and resulting pneumonia. This proof of concept study will take place in the US and will enroll about 40 hospitalized patients diagnosed with COVID-19 infection who have developed pneumonia and require supplemental oxygen. Half of the patients, i.e. 20 patients, will receive opaganib in addition to standard of care for 14 days. The other 20 will receive matching placebo (capsules that do not contain the medication) in addition to standard of care. Study drug will be administered every day for 14 days, twice each day, unless the patient has been discharged from the hospital without requiring supplemental oxygen, in which case study drug will only be administered for 10 days. All participants will be followed up for 4 weeks after their last dose of study drug.

NCT04414618 Coronavirus Infections Drug: Opaganib Drug: Placebo
MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia
HPO:Pneumonia

Primary Outcomes

Description: Measurement of the oxygen requirement

Measure: Evaluation of the total oxygen requirement (area under the curve) using daily supplemental oxygen flow (L/min) over 14 days

Time: Every day from day 1 to day 14 of treatment

Secondary Outcomes

Description: Measurement of the oxygen requirement

Measure: Evaluation of the time to 50% reduction from baseline in supplemental oxygen based on oxygen flow in L/min

Time: Every day from day 1 to day 14 of treatment

Measure: Evaluation of the proportion of patients no longer requiring supplemental oxygen for at least 24 hours by Day 14

Time: From screening phase and every day from day 1 to day 14 of treatment

Description: Measurement of temperature

Measure: Evaluation of the proportion of afebrile patients at Day 14

Time: From screening phase and every day from day 1 to day 14 of treatment

Description: Nasopharyngeal or oropharyngeal swab for SARS-CoV-2

Measure: Evaluation of the time to negative swabs for SARS-CoV-2 by PCR

Time: From screening phase and every day from day 1 to day 14 of treatment and at the end of the 4 weeks follow-up after the end of treatment

Description: Nasopharyngeal or oropharyngeal swab for SARS-CoV-2

Measure: Evaluation of the proportion of patients with negative swabs for SARS-CoV-2 by PCR at Day 14

Time: From screening phase and every day from day 1 to day 14 of treatment and at the end of the 4 weeks follow-up after the end of treatment

Measure: The percentage of patients who require intubation and mechanical ventilation by Day 14

Time: From screening phase and every day from day 1 to day 14 of treatment

Measure: Evaluation of the time to mechanical ventilation

Time: From screening phase and every day from day 1 to day 14 of treatment

Description: Evaluation the proportion of patients, with at least one measurement of fever at baseline (defined as temperature >38.0 C[100.4 F]), who are afebrile (defined as temperature <37.2C [99 F]) at Day 14

Measure: Evaluation the proportion of patients, with at least one measurement of fever at baseline who are afebrile at Day 14

Time: From screening phase and every day from day 1 to day 14 of treatment

Measure: Evaluation of mortality 30 days post-baseline

Time: 30 days after day 1 of treatment

Other Outcomes

Measure: To determine the incidence rate of all treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)

Time: Every day from day 1 to day 14 of treatment and at end of the 4 weeks follow-up after the end of treatment

164 A Phase 2, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Axatilimab for the Treatment of Hospitalized Patients With Respiratory Signs and Symptoms Secondary to Novel Coronavirus Disease (COVID-19)

This is a randomized, double-blind, placebo-controlled, 29-day study to assess the efficacy and safety of axatilimab plus standard of care, compared with placebo plus standard of care, in patients with respiratory signs and symptoms secondary to novel coronavirus disease (COVID-19).

NCT04415073 Coronavirus COVID ARDS Cytokine Storm Cytokine Release Syndrome Drug: SNDX-6352 Drug: Placebo
MeSH:Coronavirus Infections

Primary Outcomes

Description: Respiratory failure as defined by need for mechanical ventilation, extracorporeal membrane oxygenation (ECMO), non-invasive ventilation >6L oxygen/minute, or clinical diagnosis of respiratory failure with initiation of none of these measures only when clinical decision-making is driven solely by resource limitation

Measure: Proportion of subjects alive and free of respiratory failure

Time: 29 Days

Secondary Outcomes

Description: Proportion of subjects achieving a ≥ 2 category improvement on 7-point ordinal score relative to the baseline on Day 28 as collected on Day 29

Measure: Secondary clinical improvement outcomes

Time: 29 Days

Description: National early warning score (NEWS) of ≤2 maintained for 24 hours

Measure: Time to clinical improvement (TTCI)

Time: 29 Days

Description: Change from baseline to Day 29 or hospital discharge or death, if sooner, in the ratio of peripheral hemoglobin oxygen saturation to fraction of inspired oxygen (SpO2/FiO2)

Measure: To evaluate improvement in oxygenation in hospitalized adults with respiratory signs and symptoms secondary to COVID 19 treated with axatilimab

Time: 29 Days

Description: Serum concentrations of IL 6 and c-reactive protein (CRP) change from baseline to Day 15 or hospital discharge or death

Measure: To evaluate changes in biomarkers following treatment with axatilimab

Time: 15 Days

Description: Frequency and severity of AEs and SAEs

Measure: To evaluate the safety and tolerability of axatilimab in the same population

Time: 29 Days

Description: Proportion of subjects who require initiation of mechanical ventilation after study entry

Measure: Ventilation outcomes

Time: 29 Days

Description: Proportion of subjects who are SARS CoV-2 virus free by Day 15 or hospital discharge, whichever is sooner

Measure: To evaluate antiviral effect of axatilimab in hospitalized adults with recently diagnosed SARS CoV-2 infection

Time: Day 15

Description: Serum concentration of axatilimab and presence of anti-drug antibody

Measure: To characterize exposure to axatilimab

Time: 29 Day

165 Investigation of Tofacitinib to Mitigate the Impact of COVID-19 (I-TOMIC) in Moderate SARS-CoV-2 (MODERATE I-TOMIC)

The purpose of this randomized, double blinded, placebo controlled study is to assess the efficacy and safety of tofacitinib in hospitalized adult (18-65 years old) patients with SARS-CoV-2 and pneumonia who require supplemental oxygen and have serologic markers of inflammation but do not need mechanical ventilation.

NCT04415151 COVID-19 Drug: Tofacitinib 10 mg Drug: Placebo

Primary Outcomes

Description: The primary objective of this study is to determine whether tofacitinib improves the clinical outcomes of patients with moderate SARS-CoV-2 infection as determined by the primary outcome measure: Proportion of subjects alive and not needing any form of mechanical ventilation, high flow oxygen, or ECMO by day 14.

Measure: Disease Severity

Time: 14 days

Secondary Outcomes

Description: Clinical improvement as measured by NIAID 8-point ordinal scale (i.e., 1 = death and 8 = Not hospitalized, no limitations on activities) at day 14. The scale is as follows: Death Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) Hospitalized, on non-invasive ventilation or high flow oxygen devices Hospitalized, requiring supplemental oxygen Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care Not hospitalized, limitation on activities and/or requiring home oxygen Not hospitalized, no limitations on activities.

Measure: Clinical improvement

Time: 14 days

Description: Clinical improvement as measured by NIAID 8-point ordinal scale (i.e., 1 = death and 8 = Not hospitalized, no limitations on activities) (days 3 through day 14): The scale is as follows: Death Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) Hospitalized, on non-invasive ventilation or high flow oxygen devices Hospitalized, requiring supplemental oxygen Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care Not hospitalized, limitation on activities and/or requiring home oxygen Not hospitalized, no limitations on activities.

Measure: Clinical improvement

Time: Up to 14 days

Description: Time to recovery [ Time Frame: Day 1 through Day 14] (Day of recovery is defined as the first day on which the subject satisfies one of the following three categories from the ordinal scale: Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care Not hospitalized, limitation on activities and/or requiring home oxygen Not hospitalized, no limitations on activities)

Measure: Time to recovery

Time: Up to 14 days

Description: Time to clinical improvement (defined as a 2-point increase on the NIAID 8-point ordinal scale (i.e., 1 = death and 8 = Not hospitalized, no limitations on activities). The scale is as follows: Death Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) Hospitalized, on non-invasive ventilation or high flow oxygen devices Hospitalized, requiring supplemental oxygen Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care Not hospitalized, limitation on activities and/or requiring home oxygen Not hospitalized, no limitations on activities.

Measure: Time to clinical improvement

Time: 30 days

Description: Clinical status on the NIAID 8-point ordinal scale at day 30 The scale is as follows: Death Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) Hospitalized, on non-invasive ventilation or high flow oxygen devices Hospitalized, requiring supplemental oxygen Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care Not hospitalized, limitation on activities and/or requiring home oxygen Not hospitalized, no limitations on activities.

Measure: Clinical status

Time: 30 Days

Description: Clinical status on the NIAID 8-point ordinal scale at day 60 The scale is as follows: Death Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) Hospitalized, on non-invasive ventilation or high flow oxygen devices Hospitalized, requiring supplemental oxygen Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care Not hospitalized, limitation on activities and/or requiring home oxygen Not hospitalized, no limitations on activities.

Measure: Clinical status

Time: 60 Days

Description: Clinical status on the NIAID 8-point ordinal scale at day 90 The scale is as follows: Death Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) Hospitalized, on non-invasive ventilation or high flow oxygen devices Hospitalized, requiring supplemental oxygen Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care Not hospitalized, limitation on activities and/or requiring home oxygen Not hospitalized, no limitations on activities.

Measure: Clinical status

Time: 90 Days

Description: Mortality rate at day 30

Measure: Mortality

Time: 30 Days

Description: Mortality rate at day 60

Measure: Mortality

Time: 60 Days

Description: Mortality rate at day 90

Measure: Mortality

Time: 90 Days

Description: Proportion of patients requiring mechanical ventilatory support.

Measure: Mechanical Ventilatory Support

Time: Up to 14 Days

Description: Duration of invasive mechanical ventilation (days).

Measure: Mechanical Ventilatory Support Duration

Time: Up to 14 Days

Description: Invasive mechanical ventilation free days.

Measure: Freedom from mechanical ventilation

Time: Up to 14 Days

Description: Adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug/treatment.

Measure: Adverse events

Time: Up to 14 days

Description: Did the patient receive an intervention with additional immunomodulatory agent (i.e. IL-6 targeting therapy)? (y/n)

Measure: Additional intervention

Time: Up to 14 days

Description: Change in SARS-CoV-2 viral titers during intervention.

Measure: Viral titer

Time: Up to 14 days

166 Reducing Hospital Admission of Elderly in SARS-CoV-2 Pandemic Via the Induction of Trained Immunity by Bacillus Calmette-Guérin Vaccination, a Randomized Controlled Trial

Bacillus Calmette-Guérin (BCG) vaccine not only protects against tuberculosis, but has also been shown to induce protection against various infections with a viral aetiology, leading to significant reductions in morbidity and mortality. We hypothesize that BCG vaccination might be a potent preventive measure against SARS-CoV-2 infection and/or may reduce disease severity in elderly people, who are known to be at increased risk of illness and death from SARS-CoV-2 infection. Therefore, we will in this placebo-controlled adaptive multi-centre randomized controlled trial evaluate the ability of BCG to reduce hospital admission and its efficacy to improve the clinical course of SARS-CoV-2 infection in elderly people((≥ 60 years of age).

NCT04417335 COVID-19 Biological: BCG vaccine Biological: Placebo

Primary Outcomes

Measure: SARS-CoV-2 related hospital admission

Time: Maximum of 1 year

Secondary Outcomes

Measure: the duration of hospital admission due to documented COVID-19

Time: Maximum of 1 year

Measure: the cumulative incidence of documented SARS-CoV-2 infection

Time: Maximum of 1 year

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

Time: Maximum of 1 year

Measure: the cumulative incidence of death due to documented SARS-CoV-2 infection

Time: 1 year

Measure: the cumulative incidence of hospital admission for any reason

Time: Maximum of 1 year

Measure: the cumulative incidence of Intensive Care Admission due to documented SARS-CoV-2 infection

Time: Maximum of 1 year


Related HPO nodes (Using clinical trials)


HP:0002094: Dyspnea
Genes 456
IFT52 CCDC103 COL2A1 GATA6 KCNA1 SRP54 DNAAF2 TET2 TGFB2 CPT2 VCL OPTN RRM2B SCN4A EDN1 SPINK1 DISC1 VPS33A LRRC56 FOXF1 DPM1 STN1 GYG1 LAMC2 NKX2-1 DNAH11 FOXP3 TRPV6 CAV1 ORC1 SETBP1 IRAK1 PPARGC1A GBA HYDIN SLC2A10 SCN1B DNAH9 SQSTM1 CYB5R3 DNASE1L3 COX10 DNAH5 GNAS LRP4 TRNK PRRT2 MRPL3 DNAH1 ALDH7A1 DNAI1 ORC6 CSPP1 COL1A2 SLC5A7 RSPH3 CLCNKB LOX TGFBR2 FASTKD2 CTRC FAM13A SFTPC EFEMP2 UBQLN2 SLC52A3 CCDC39 MAPT SDCCAG8 FUS ACADM OTX2 FGFR2 FBP1 DNAJC21 MATR3 ND3 RAPSN FBN1 NKX2-1 SFTPA2 COX6B1 SMPD1 NDUFB11 CHRNA1 FGFR2 NDUFB8 COX7B COX8A EIF2AK4 FIG4 HLA-DRB1 FBLN5 ARMC4 CHMP2B TSC1 MMAA STAT3 SSR4 LYRM4 CYB5A POLG2 TSC1 ZIC3 STT3B C1R MYL3 FBP1 MPC1 LDLRAP1 HLA-DRB1 SLC25A4 ATXN2 CHRNE ACVRL1 GLA ABCG8 TRMU GNAS LAMB2 CFTR CCDC151 USP9X LAMA3 IRF2BP2 ND1 VCP IL1RN FGFR2 ND6 BCOR ETFA ND2 POMT1 TERT CHRND ALAS2 BMPER CDC6 SCO2 DRC1 WAS STK36 TRMT5 GBA LIFR SH2B3 FAM20C TRNS1 RPGR NDUFS2 VCP TGFB3 DNAL1 CFAP298 RPS28 TET2 ZBTB16 NUMA1 DCTN1 DNAAF1 CSF2RB SMAD4 TRNE TAF15 ACADVL GAS2L2 AGRN SNAP25 CSF2RA FGFR2 STAT5B DNAAF5 GBA C1QA PON1 TTC25 SLC25A1 DNAAF3 PMM2 MMUT MEGF10 CCR6 FLNC SLC35A1 CCN2 DYNC2LI1 PRPH EPHB4 MMUT HLA-DRB1 STAT5B TRNV DMPK SLC18A3 SOX9 SBDS COX14 KCNJ6 NABP1 TREM2 CHRNB1 SMAD3 GTPBP3 MUSK WIPF1 DSC2 DOK7 TRNN PFN1 MCIDAS RARA C9ORF72 HLCS CCDC40 PET100 EP300 NKX2-5 SCN4A SCN4A ENG CHAT CHRNB1 SOD1 GLT8D1 CRELD1 DNAJB13 TRNW SCNN1B ANG GLE1 NEK1 PIGT SCNN1A COL2A1 APOB ZFPM2 RSPH4A NGLY1 COLQ FOXE3 TRAK1 ATRX CCNO NPM1 VAMP1 LGI4 PLCB4 MYBPC3 NR2F2 CNTNAP1 NDUFAF3 ELN SCN5A COPA TK2 SLC25A3 CHAT SLC12A3 CYB5R3 ETFDH AIMP2 PRKAR1A CRLF1 COA8 GAA SCO2 TBX4 FIP1L1 UBE3B DNAI2 ND4 LAMB3 TACO1 SPAG1 CHRNE TWNK PML SFTPC XYLT1 TBL1XR1 SFTPA2 JAK2 TARDBP ISCU MARS1 MYH11 RPS26 STX16 COX20 GATA6 RTEL1 TERT ERF SCNN1G PNKD TERC SFTPB SERPING1 DPM2 GNAS PRKCSH DNA2 SURF1 MAPT NME8 DNAAF4 FGFR1 EFTUD2 UNC13A CHRND NOD2 TBK1 ADAMTS13 PARN PRRX1 CFAP410 BMPER RSPH1 VAPB ARX DBH CCNF TRPM4 CCDC114 GNAI3 TUBB4A ATP11A CAV1 COQ7 TBC1D24 GATA4 TSC2 NAGS DPP9 ITGA3 PRSS1 BMPR2 CFAP300 ERBB4 ADNP MFAP5 EPOR MYO9A TRNL1 ORC6 AGRN SPEF2 PRRX1 CDC45 MAT2A RUNX2 MYH11 SFTPA1 LDLR POLG TRIP11 OFD1 PRKAR1A FOXJ1 MYL2 ZMYND10 CHRNE PLEC SFTPC MGME1 MYLK NEB USP9X COA8 TRIP11 HBB GMNN TSC2 CASR ORC4 ND5 DSP STAT4 NUP214 TRNE HLA-B MGME1 DNAAF3 DNA2 RSPH9 ABCA3 BTNL2 NEFH IFT81 COL2A1 LTBP3 IKZF1 KAT6A KLHL7 DAO SCN5A RNU4ATAC SCO1 PUF60 DNAJB6 ATP6 HCCS TNNC1 PON3 BTNL2 ADCY6 DMPK CFAP221 COL13A1 DNAAF6 AK9 STT3B PGM1 ACTA2 CHCHD10 PRKG1 TTN TGFBR1 MUC5B SERPINA1 IRF5 ABCA3 HNRNPA1 COL13A1 NPPA SIK1 GATA6 SPP1 CHRNA1 CSF2RB ORC1 NAGS EPHA4 EDA LRRC6 MUC5B PON2 COL2A1 GAS8 MMAB SYT2 EOMES SLC25A1 JPH2 PCSK9 ANXA11 AIFM1 VPS33A DPM2 ABCG5 CDT1 CREBBP ETFB TRNK CCDC65
Protein Mutations 0
SNP 0
HP:0001945: Fever
Genes 344
TRNF MEFV SCNN1B TNFAIP3 LPIN2 IL2RG CD247 WT1 TH TLR3 SCNN1A IL2RG NLRP3 TET2 ERCC4 SPINK1 HLA-DRB1 MLX LIPA NGLY1 TCF4 PTS ATP1A3 LPIN2 HAVCR2 KLRC4 DCLRE1C NPM1 NOTCH3 KIF1B H19 NOD2 SPINK1 IL12A CTRC TRNL1 LPIN1 RYR1 LRRC8A PRKAR1A BCL10 CRLF1 GAA NKX2-1 NLRP3 CHD7 FIP1L1 ND4 SLC29A3 PTPN3 LACC1 KRT8 CASK IRAK1 SCYL1 RNASEH2B SPTB MST1 PML MALT1 AQP2 TBL1XR1 IL12A-AS1 ERAP1 SH3KBP1 CD79B LBR SRP54 SLC12A1 IL7R TP53 SPTA1 SLCO1B1 EIF2B4 TRNK FOXP1 IL7R SLC19A3 TRIM28 UNC93B1 ND1 NLRP3 SCNN1G ELP1 RYR1 RANBP2 IFIH1 NAB2 NGF JAK2 WT1 COX2 NCF2 MVK CTRC BCL2 STAT6 ANK1 KRT18 IRF8 ELANE COG6 CYP11B2 CD79A NOD2 CFH RNASEH2A QDPR ADAMTS13 BCR CACNA1A ERCC3 IGH BLNK PSMB9 ND3 HMGCL RMRP TCF3 EIF2B2 SLC29A3 BRCA2 GYPC IGH CACNA1S HLA-B TRNQ CACNA1S HLA-DPB1 SPTB ERCC2 ADAR ADA NCF4 CPT2 TMEM165 MEFV POMP C4A ABL1 STX11 CD27 UBAC2 GALC CALR PTPN22 IRF8 ZFHX2 NTRK1 NLRP3 HLA-DRB1 TSC2 TRNS1 NCF1 TRIP13 TP53 IL23R F5 STAT3 STAT3 RAG2 NLRC4 PRSS1 IBA57 CHEK2 TSC1 ELANE ADA2 BTK EPB41 C1R GFI1 BCAP31 TRNL1 COL1A1 FBP1 POU6F2 TET2 SLC4A1 PRNP PIK3R1 GLA LIFR SLC12A3 CFTR EIF2B3 PRKAR1A AVPR2 DDB2 CYTB TLR4 BIRC3 PEX6 HAVCR2 IRF2BP2 HLA-DPA1 ACAT1 ND1 SPTA1 STAT4 TRAF3 DIS3L2 IL10 EIF2B5 GCH1 ATM TNFRSF1A IGH RB1 RAG1 ND6 XIAP HBB EIF2B1 BCOR ND2 MPL KCNJ1 ND5 TRIM28 STAT4 PSMB8 HLA-B WAS EPB42 NLRP12 AK2 TRNW COX3 HTR1A POLR3A LIFR HMGCL P4HTM TNFRSF1A RNASEH2C STIM1 MYD88 BTNL2 SH2B3 TRNH COX1 CYBA PSMB4 IKZF1 KLHL7 GATA2 JAK2 NLRP1 REST CFHR1 ZBTB16 CALR NLRC4 NUMA1 LIG4 GPR35 AVPR2 ND5 ATP6 RAG1 ND4 SLC11A1 BCL6 TREX1 XPA TRNS2 IL36RN PTPN22 ALPL STAT5B C1QA LYST SAMHD1 ERCC5 RAB27A RAG2 CFHR3 PMM2 AVP XPC NLRP3 NLRP3 CYBB JAK2 TCIRG1 CYP11B2 RYR1 MPL ATP1A2 MEFV IL12B FAS CCR1 MYD88 PSTPIP1 RUNX1 CD3E ABCC2 HLA-DRB1 ORAI1 SPP1 TBK1 TRNV AQP2 COL1A1 CYP21A2 PMP22 TICAM1 HLA-DRB1 EDA STING1 RNF168 GPC3 NABP1 ATP13A2 TREX1 DST PRSS2 UNC13D IFNGR1 CD3D WIPF1 NLRP3 CFTR IGHM CYBC1 STXBP2 ND6 CTLA4 PRTN3 RARA IGLL1 MEFV IL6 NLRC4 CCND1 HLA-B NLRC4 PRSS1 SLCO1B3 G6PD MIF TRNW
HP:0011947: Respiratory tract infection
Genes 645
CCDC103 GATA6 IL2RG COL13A1 NCF4 DNAI1 EPG5 CSPP1 RYR1 ABCA12 CACNA1B IL2RG POLR3A DNAAF2 TRAIP CLCA4 JAK3 SOX11 OFD1 IL17RC SLC12A6 IGHM TCTN3 NECTIN1 INSR IER3IP1 GAS8 DCLRE1C BCR NOTCH3 CLEC7A PSAP VPS33A LRRC56 PWRN1 ATM TGFB1 BCL10 RAG2 CCDC39 CD8A NKX2-1 OCRL DNAH11 CHD7 TINF2 FOXP3 RANBP2 CR2 RNU4ATAC SETBP1 CD3D MALT1 PLP1 HYDIN SPAG1 TAP2 AGA IRAK4 DNAH9 NELFA IL7R TNFSF12 RUNX2 DNAAF4 IL17RA ADA DNAI2 DNAH5 GRHL3 FOXP1 ATP6V0A2 DNAH1 LCK DNAI1 SMARCA4 ORC6 ELP1 MASP2 DCLRE1C SLC5A7 RSPH3 MTHFD1 NIPAL4 G6PC3 CCNO IRF8 CHAMP1 SLC52A3 CCDC39 PIK3CD SDCCAG8 NHP2 EPM2A SCNN1A MYSM1 CD81 TNFSF12 UNC119 CCDC65 ARMC4 RAG1 ARID2 LRBA NCF2 SMN1 CDCA7 FLNA DCLRE1C RMRP TBC1D23 TPM3 NFKB2 DSG1 NKX2-1 SFTPA2 SMPD1 UBE2A RAG2 FAT4 SNORD116-1 IPW MYO5A WAS CFTR KDM6A ICOS RYR1 SLC25A22 NFKB1 DNAH11 RPGR RAG1 SOX4 NCF1 ARSB NME8 ALMS1 ARMC4 DCLRE1C TSC1 STAT3 STAT3 CR2 TSC1 RAB3GAP2 GFI1 ARID1A TAF1 HACD1 ALB RNF125 ADAMTS3 UMPS LAMTOR2 LEPR SMARCB1 IDUA CARD11 LAMB2 CFTR CCDC151 USP9X LEP TECPR2 DNMT3B RSPH4A COL6A1 TNFSF11 BIRC3 RYR1 PRKDC GLB1 TYK2 PEPD HLA-DPA1 TCIRG1 LRRC56 CFTR FBLN5 SNORD115-1 TNFRSF13B SCNN1G GNPTAB CORO1A CXCR4 DNAAF6 IDUA SNX10 MED25 CFAP410 FCGR3A BTK GMNN ABCA12 RAC1 ACP5 EDARADD CD19 POLE GBA LAMA2 STAT1 LIPN NFKB2 DRC1 VPS13A WAS NFKB1 NFKB2 STK36 AK2 MGP GBA CCDC22 SLC1A4 RNF113A DNAJB13 SULT2B1 BLM TAP1 INPPL1 TNFRSF1A CFAP298 ZBTB24 PIK3R1 RPGR DNAH5 DNAL1 CFAP298 GATA2 BTK SMPD1 ICOS DCTN4 DKC1 FUCA1 DNAAF1 LIG4 CSF2RB ACADVL PRPS1 RAG1 GAS2L2 AGRN RIPK1