Name (Synonyms) | Correlation | |
---|---|---|
drug505 | Hydroxychloroquine Wiki | 0.22 |
drug898 | Presatovir Wiki | 0.17 |
drug650 | Losartan Wiki | 0.13 |
drug1196 | UC-MSCs Wiki | 0.13 |
drug336 | DAS181 Wiki | 0.13 |
drug379 | Doxycycline Wiki | 0.12 |
drug532 | Hydroxychloroquine Sulfate Loading Dose Wiki | 0.12 |
drug1169 | Tocilizumab (TCZ) Wiki | 0.12 |
drug820 | PUL-042 Inhalation Solution Wiki | 0.12 |
drug533 | Hydroxychloroquine Sulfate Regular dose Wiki | 0.12 |
drug1108 | Suspension of heat killed (autoclaved) Mycobacterium w Wiki | 0.10 |
drug977 | Ruxolitinib Wiki | 0.10 |
drug108 | Azithromycin Wiki | 0.10 |
drug934 | REGN3051 Wiki | 0.09 |
drug942 | Ranitidine Wiki | 0.09 |
drug56 | Alvelestat (MPH996) Plus Aerosolized 13 cis retinoic acid Wiki | 0.09 |
drug754 | Nitazoxanide Tablets Wiki | 0.09 |
drug311 | Convalescent Plasma 1 Unit Wiki | 0.09 |
drug342 | Dapagliflozin Wiki | 0.09 |
drug435 | Favipiravir tablets Wiki | 0.09 |
drug948 | Recombinant Human Interferon α2b Spray Wiki | 0.09 |
drug452 | Galidesivir Wiki | 0.09 |
drug616 | JNJ-53718678 Wiki | 0.09 |
drug1119 | TD-0903 Wiki | 0.09 |
drug607 | Intravenous sedation Wiki | 0.09 |
drug916 | Pyridostigmine Bromide Wiki | 0.09 |
drug993 | SARS-CoV-2-test Wiki | 0.09 |
drug476 | HOME-CoV rule implementation Wiki | 0.09 |
drug1254 | Zilucoplan® Wiki | 0.09 |
drug879 | Platelet count, platelet, mean platelet volume and platelet distribution Width in COVID-19 Wiki | 0.09 |
drug57 | Ambrisentan Wiki | 0.09 |
drug628 | Let It Out (LIO)-C Wiki | 0.09 |
drug557 | IMU-838 Wiki | 0.09 |
drug655 | Low nitrite/NDMA meals Wiki | 0.09 |
drug815 | PLX-PAD Wiki | 0.09 |
drug1252 | Zanubrutinib Wiki | 0.09 |
drug648 | Lopinavir/ritonavir 400 mg/100 mg Wiki | 0.09 |
drug81 | ArtemiC Wiki | 0.09 |
drug617 | Kerecis Oral and Nasal Spray Wiki | 0.09 |
drug933 | REGN3048 Wiki | 0.09 |
drug101 | Aviptadil (VIP) Wiki | 0.09 |
drug709 | Montelukast 10mg Wiki | 0.09 |
drug444 | Fluvoxamine Wiki | 0.09 |
drug224 | COVID-19 swap test PCR Wiki | 0.09 |
drug700 | Mid-dose chloroquine Wiki | 0.09 |
drug914 | Pulmonary and Motor Rehabilitation Wiki | 0.09 |
drug751 | Nintedanib 150 MG Wiki | 0.09 |
drug78 | Apple Watch Series 5 Wiki | 0.09 |
drug388 | EDP1815 Wiki | 0.09 |
drug80 | Arbidol Hydrochloride Granules Wiki | 0.09 |
drug275 | Clazakizumab 12.5 mg Wiki | 0.09 |
drug931 | Quick Defense Wiki | 0.09 |
drug24 | ABX464 Wiki | 0.09 |
drug1166 | To assess for development of IgG antibodies against SARS-CoV2 Wiki | 0.09 |
drug543 | Hydroxychloroquine sulfate &Azithromycin Wiki | 0.09 |
drug1136 | Telmisartan 40mg Wiki | 0.09 |
drug1127 | Teleconsultation either by phone or by computer consultation Wiki | 0.09 |
drug787 | Octagam 10% Wiki | 0.09 |
drug380 | Drug Isotretinoin (13 cis retinoic acid ) capsules+standard treatment Wiki | 0.09 |
drug127 | BM-Allo.MSC Wiki | 0.09 |
drug745 | New QIAstat-Dx fully automatic multiple PCR detection platform Wiki | 0.09 |
drug312 | Convalescent Plasma 2 Units Wiki | 0.09 |
drug188 | Bromhexine Hydrochloride Tablets Wiki | 0.09 |
drug337 | DAS181 COVID-19 Wiki | 0.09 |
drug294 | Combination of Lopinavir /Ritonavir and Interferon beta-1b Wiki | 0.09 |
drug938 | Radiation therapy Wiki | 0.09 |
drug355 | Degarelix Wiki | 0.09 |
drug329 | Covid-19 + patients Wiki | 0.09 |
drug123 | BCG-Denmark Wiki | 0.09 |
drug196 | CD24Fc Wiki | 0.09 |
drug1271 | azoximer bromide Wiki | 0.09 |
drug712 | MultiStem Wiki | 0.09 |
drug1174 | Tradipitant Wiki | 0.09 |
drug582 | Inhaled sedation Wiki | 0.09 |
drug158 | Biological sampling Wiki | 0.09 |
drug1400 | standard operating procedures Wiki | 0.09 |
drug1245 | Whole Exome Sequencing Wiki | 0.09 |
drug124 | BIOMARKERS IN THE LONG TERM IMPACT OF CORONAVIRUS INFECTION IN THE CARDIORRESPIRATORY SYSTEM Wiki | 0.09 |
drug1263 | all treatment about COVID-2019 Wiki | 0.09 |
drug622 | LB1148 Wiki | 0.09 |
drug1216 | VPM1002 Wiki | 0.09 |
drug834 | Peginterferon Lambda-1a Wiki | 0.09 |
drug169 | Blood and derivatives. Wiki | 0.09 |
drug276 | Clazakizumab 25 mg Wiki | 0.09 |
drug493 | High-dose chloroquine Wiki | 0.09 |
drug854 | Placebo Administration Wiki | 0.09 |
drug240 | Canakinumab Wiki | 0.09 |
drug1366 | oxygen treatment Wiki | 0.09 |
drug1418 | vaccine BCG Wiki | 0.09 |
drug468 | HCQ Wiki | 0.09 |
drug289 | ColdZyme® mouth spray Wiki | 0.09 |
drug671 | MVA-MERS-S_DF1 - High Dose Wiki | 0.09 |
drug389 | EIDD-2801 Wiki | 0.09 |
drug466 | HB-adMSC Wiki | 0.09 |
drug107 | Azinc Wiki | 0.09 |
drug579 | Inhaled beclomethasone Wiki | 0.09 |
drug128 | BM-MSCs Wiki | 0.09 |
drug1330 | lopinavir/ritonavir Wiki | 0.09 |
drug1305 | favipiravir tablets+chloroquine phosphatetablets tablets Wiki | 0.09 |
drug399 | Electric pad for human external pain therapy Wiki | 0.09 |
drug384 | Duvelisib Wiki | 0.09 |
drug588 | Interferon beta 1a Wiki | 0.09 |
drug1247 | XCEL-UMC-BETA Wiki | 0.09 |
drug611 | Isotretinoin(Aerosolized 13 cis retinoic acid) +standard treatment Wiki | 0.09 |
drug1034 | Silymarin Wiki | 0.09 |
drug737 | Naltrexone Wiki | 0.09 |
drug54 | Aluminum hydroxide Wiki | 0.09 |
drug990 | SARS-CoV-2 questionnaire survey Wiki | 0.09 |
drug1128 | Telehealth monitoring Wiki | 0.09 |
drug1038 | Sirolimus 1 MG/ML Wiki | 0.09 |
drug899 | Presatovir placebo Wiki | 0.09 |
drug777 | Nutrition support Wiki | 0.09 |
drug736 | Nafamostat Mesilate Wiki | 0.09 |
drug1201 | Ulinastatin Wiki | 0.09 |
drug458 | Gimsilumab Wiki | 0.09 |
drug375 | Dociparastat sodium Wiki | 0.09 |
drug323 | Coping strategies video Wiki | 0.09 |
drug94 | Atorvastatin Wiki | 0.09 |
drug315 | Convalescent SARS COVID-19 plasma Wiki | 0.09 |
drug1039 | Sirukumab Wiki | 0.09 |
drug518 | Hydroxychloroquine Only Product in Oral Dose Form Wiki | 0.09 |
drug613 | Ivermectin 6 MG Oral Tablet (2 tablets) Wiki | 0.09 |
drug51 | Almitrine Wiki | 0.09 |
drug1272 | bacTRL-Spike Wiki | 0.09 |
drug235 | CYNK-001 Wiki | 0.09 |
drug343 | Dapagliflozin 10 MG Wiki | 0.09 |
drug954 | Recombinant novel coronavirus vaccine (Adenovirus type 5 vector) Wiki | 0.09 |
drug1220 | Vazegepant (BHV-3500) Wiki | 0.09 |
drug421 | Exercise brochure Wiki | 0.09 |
drug936 | RPH-104 80 mg Wiki | 0.09 |
drug561 | Ibrutinib Wiki | 0.09 |
drug1122 | TJ003234 Wiki | 0.09 |
drug804 | Otilimab Wiki | 0.09 |
drug618 | Ketamine Wiki | 0.09 |
drug338 | DAS181 OL Wiki | 0.09 |
drug1359 | non-contact magnetically-controlled capsule endoscopy Wiki | 0.09 |
drug800 | Organicell Flow Wiki | 0.09 |
drug658 | Low-dose chloroquine Wiki | 0.09 |
drug1282 | care modalities Wiki | 0.09 |
drug239 | Camostat Mesilate Wiki | 0.09 |
drug1340 | meplazumab for injection Wiki | 0.09 |
drug790 | Olokizumab 64 mg Wiki | 0.09 |
drug521 | Hydroxychloroquine SAR321068 Wiki | 0.09 |
drug984 | SARS-CoV Wiki | 0.09 |
drug490 | High nitrite/NDMA meals Wiki | 0.09 |
drug76 | Any drug used to treat Covid-19 Wiki | 0.09 |
drug744 | Neutral writing control Wiki | 0.09 |
drug1003 | Saline Wiki | 0.09 |
drug554 | IC14 Wiki | 0.09 |
drug31 | AT-527 Wiki | 0.09 |
drug664 | MRx-4DP0004 Wiki | 0.09 |
drug1368 | pathogen reduced SARS-CoV-2 convalescent plasma Wiki | 0.09 |
drug433 | Favipiravir Combined With Tocilizumab Wiki | 0.09 |
drug1354 | no intervention Wiki | 0.09 |
drug136 | BVRS-GamVac-Combi Wiki | 0.09 |
drug473 | HCQ+AZT Wiki | 0.09 |
drug270 | Ciclesonide Wiki | 0.09 |
drug672 | MVA-MERS-S_DF1 - Low Dose Wiki | 0.09 |
drug120 | BCG Wiki | 0.09 |
drug1014 | Sarilumab SAR153191 Wiki | 0.09 |
drug415 | Ergoferon Wiki | 0.09 |
drug112 | Azithromycin 500 milligram (mg) oral Tablet Wiki | 0.09 |
drug522 | Hydroxychloroquine Sulfate Wiki | 0.08 |
drug647 | Lopinavir/ritonavir Wiki | 0.08 |
drug1067 | Standard of care Wiki | 0.08 |
drug612 | Ivermectin Wiki | 0.07 |
drug262 | Chloroquine Wiki | 0.07 |
drug1102 | Supportive Care Wiki | 0.06 |
drug393 | Echocardiography Wiki | 0.06 |
drug749 | Niclosamide Wiki | 0.06 |
drug499 | Human immunoglobulin Wiki | 0.06 |
drug526 | Hydroxychloroquine Sulfate 200 MG Wiki | 0.06 |
drug542 | Hydroxychloroquine sulfate Wiki | 0.06 |
drug839 | Peripheral blood draw Wiki | 0.06 |
drug450 | GLS-5300 Wiki | 0.06 |
drug534 | Hydroxychloroquine and Azithromycin Wiki | 0.06 |
drug1064 | Standard of Care (SOC) Wiki | 0.06 |
drug131 | BNT162b1 Wiki | 0.06 |
drug683 | Mavrilimumab Wiki | 0.06 |
drug267 | Chloroquine or Hydroxychloroquine Wiki | 0.06 |
drug274 | Clazakizumab Wiki | 0.06 |
drug959 | Remestemcel-L Wiki | 0.06 |
drug133 | BNT162c2 Wiki | 0.06 |
drug950 | Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector) Wiki | 0.06 |
drug621 | L-ascorbic acid Wiki | 0.06 |
drug1258 | Zinc Sulfate Wiki | 0.06 |
drug1379 | pregnant women with laboratory-confirmed 2019-n-CoV Wiki | 0.06 |
drug1020 | Selinexor Wiki | 0.06 |
drug130 | BNT162a1 Wiki | 0.06 |
drug132 | BNT162b2 Wiki | 0.06 |
drug1033 | Siltuximab Wiki | 0.06 |
drug1168 | Tocilizumab Wiki | 0.06 |
drug431 | Favipiravir Wiki | 0.05 |
drug865 | Placebo oral tablet Wiki | 0.05 |
drug957 | Remdesivir Wiki | 0.05 |
drug1062 | Standard of Care Wiki | 0.05 |
drug122 | BCG Vaccine Wiki | 0.05 |
drug503 | Hydrocortisone Wiki | 0.05 |
drug527 | Hydroxychloroquine Sulfate 200 MG [Plaquenil] Wiki | 0.05 |
drug586 | Interferon Beta-1A Wiki | 0.05 |
drug1291 | convalescent plasma Wiki | 0.05 |
drug1082 | Standard treatment Wiki | 0.05 |
drug694 | Mesenchymal Stromal Cells Wiki | 0.05 |
drug1133 | Telerehabilitation Wiki | 0.04 |
drug872 | Placebos Wiki | 0.04 |
drug1211 | Usual Care Wiki | 0.04 |
drug140 | Baricitinib Wiki | 0.04 |
drug1012 | Sarilumab Wiki | 0.04 |
drug60 | Anakinra Wiki | 0.03 |
drug1373 | placebo Wiki | 0.03 |
drug923 | Questionnaire Wiki | 0.03 |
Name (Synonyms) | Correlation | |
---|---|---|
D007239 | Infection NIH | 0.27 |
D018352 | Coronavirus Infections NIH | 0.27 |
D003141 | Communicable Diseases NIH | 0.26 |
D014777 | Virus Diseases NIH | 0.19 |
D055371 | Acute Lung Injury NIH | 0.18 |
D045169 | Severe Acute Respiratory Syndrome NIH | 0.18 |
D012128 | Respiratory Distress Syndrome, Adult NIH | 0.17 |
D012127 | Respiratory Distress Syndrome, Newborn NIH | 0.14 |
D055370 | Lung Injury NIH | 0.13 |
D018357 | Respiratory Syncytial Virus Infections NIH | 0.13 |
D012327 | RNA Virus Infections NIH | 0.13 |
D058070 | Asymptomatic Diseases NIH | 0.12 |
D011014 | Pneumonia NIH | 0.12 |
D003333 | Coronaviridae Infections NIH | 0.10 |
D009164 | Mycobacterium Infections NIH | 0.10 |
D012141 | Respiratory Tract Infections NIH | 0.10 |
D004066 | Digestive System Diseases NIH | 0.09 |
D030341 | Nidovirales Infections NIH | 0.09 |
D005767 | Gastrointestinal Diseases NIH | 0.09 |
D020196 | Trauma, Nervous System NIH | 0.09 |
D009422 | Nervous System Diseases NIH | 0.09 |
D012640 | Seizures NIH | 0.09 |
D015817 | Eye Infections NIH | 0.09 |
D003072 | Cognition Disorders NIH | 0.09 |
D004827 | Epilepsy NIH | 0.09 |
D007049 | Iatrogenic Disease NIH | 0.09 |
D007249 | Inflammation NIH | 0.08 |
D014947 | Wounds and Injuries NIH | 0.08 |
D013577 | Syndrome NIH | 0.08 |
D016638 | Critical Illness NIH | 0.07 |
D007251 | Influenza, Human NIH | 0.07 |
D003139 | Common Cold NIH | 0.06 |
D007154 | Immune System Diseases NIH | 0.06 |
D001927 | Brain Diseases NIH | 0.06 |
D003231 | Conjunctivitis NIH | 0.06 |
D003693 | Delirium NIH | 0.06 |
D000257 | Adenoviridae Infections NIH | 0.06 |
D060825 | Cognitive Dysfunction NIH | 0.06 |
D015004 | Yellow Fever NIH | 0.06 |
D018450 | Disease Progression NIH | 0.06 |
D005334 | Fever NIH | 0.05 |
D000077062 | Burnout, Psychological NIH | 0.05 |
D011658 | Pulmonary Fibrosis NIH | 0.05 |
D018184 | Paramyxoviridae Infections NIH | 0.05 |
D020521 | Stroke NIH | 0.04 |
D053120 | Respiratory Aspiration NIH | 0.04 |
D004417 | Dyspnea NIH | 0.04 |
D011024 | Pneumonia, Viral NIH | 0.04 |
D008171 | Lung Diseases, NIH | 0.04 |
D058186 | Acute Kidney Injury NIH | 0.04 |
D012140 | Respiratory Tract Diseases NIH | 0.03 |
Name (Synonyms) | Correlation | |
---|---|---|
HP:0002090 | Pneumonia HPO | 0.12 |
HP:0011947 | Respiratory tract infection HPO | 0.10 |
HP:0000509 | Conjunctivitis HPO | 0.06 |
HP:0001268 | Mental deterioration HPO | 0.06 |
HP:0001250 | Seizure HPO | 0.06 |
HP:0011024 | Abnormality of the gastrointestinal tract HPO | 0.06 |
HP:0001298 | Encephalopathy HPO | 0.06 |
HP:0002206 | Pulmonary fibrosis HPO | 0.05 |
HP:0001945 | Fever HPO | 0.05 |
HP:0001297 | Stroke HPO | 0.04 |
HP:0002098 | Respiratory distress HPO | 0.04 |
HP:0002088 | Abnormal lung morphology HPO | 0.04 |
HP:0001919 | Acute kidney injury HPO | 0.04 |
There are 133 clinical trials
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.
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.
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-weeksThe 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.
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 9Description: 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 28Description: 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 28The 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).
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 9The 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.
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.
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 21Description: 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-stayDescription: Sub-group of patients included with COVID19
Measure: Proportion of patients needing endotracheal intubation Time: at day 21Description: Sub-group of patients included with COVID19
Measure: Proportion of patients experiencing secondary infection during their ICU-stay Time: From baseline to day 21This 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.
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 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysThe 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.
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 daysDescription: FEV1 is defined as forced expiratory volume in the first second.
Measure: Percent Change From Study Baseline in FEV1% Predicted Value Time: Baseline; Day 28This 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.
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.
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.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.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.
This study will seek to enroll immunocompromised patients with Lower Tract parainfluenza infection. It also contains a sub-study to enroll patients with severe COVID-19.
Description: Removal of all oxygen support (with stable SpO2)
Measure: Percent of subjects who Return to Room Air (RTRA) (main study) Time: by Day 28This is a placebo-controlled, randomized, double-blind study to evaluate the pharmacokinetics, safety and antiviral activity of galidesivir in subjects with yellow fever (YF) or COVID-19.
The 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.
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 28Description: 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 28Description: 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 DaysDescription: Percentage of participants with abnormal clinical laboratory findings will be reported.
Measure: Percentage of Participants with Abnormal Clinical Laboratory Findings Time: Up to 49 daysDescription: Percentage of participants with abnormal ECGs findings will be reported.
Measure: Percentage of Participants with Abnormal Electrocardiograms (ECGs) Findings Time: Up to 49 daysDescription: Percentage of participants with abnormal vital signs findings will be reported.
Measure: Percentage of Participants with Abnormal Vital Signs Findings Time: Up to 49 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: Number of supplemental O2 free days will be reported.
Measure: Number of Supplemental Oxygen (O2) Free Days Through Day 28 Time: Through Day 28Description: Incidence of supplemental oxygen requirement in participants will be reported.
Measure: Incidence of Supplemental Oxygen Requirement Time: Up to 28 daysDescription: Duration of supplemental oxygen requirement in participants will be reported.
Measure: Duration of Supplemental Oxygen Time: Up to 28 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: Total length of hospital stay (time in hospital from first dosing) will be reported.
Measure: Total Length of Hospital Stay Time: Up to 49 daysDescription: 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 daysDescription: 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 daysDescription: Incidence of respiratory AEs will be reported.
Measure: Incidence of Respiratory AEs Time: Up to 49 daysDescription: Incidence of thoracic-related AEs will be reported.
Measure: Incidence of Thoracic-related AEs Time: Up to 49 daysDescription: 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 daysDescription: 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 daysDescription: 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 28Description: 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 daysDescription: 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 28Description: 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 28Description: 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 8Description: 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 daysDescription: 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 daysDescription: 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 daysDescription: 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 28Description: 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 28Description: 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 daysDescription: 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 daysDescription: 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 28Description: 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 28Description: 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 daysThe 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.
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, 364Description: 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)The novel coronavirus pneumonia is a kind of new emerging respiratory infectious disease, characterized by fever, dry cough, and chest tightness, and caused by the infection of the 2019 novel coronavirus (2019-nCoV). In severe cases, there will be rapid respiratory system failure. The novel coronavirus pneumonia is extremely contagious and the disease progresses rapidly. It has become a urgent and serious public health event that threatens human life and health globally. Among them, severe pneumonia caused by novel coronavirus is characterized by extensive acute inflammation of the lungs and the patient is critically ill. At present, there is no effective treatment in clinical practice.Most of them should receive supportive care to help relieve symptoms. For severe cases, treatment should include care to support vital organ functions. This clinical trial is to inspect the safety and efficiency of Human Umbilical Cord Mesenchymal Stem Cells (UC-MSCs) therapy for severe pneumonia patients infected with 2019-nCoV.
Description: Evaluation of Pneumonia Improvement
Measure: Pneumonia severity index Time: From Baseline (0W) to 12 week after treatmentDescription: Evaluation of Pneumonia Improvement
Measure: Oxygenation index (PaO2/FiO2) Time: From Baseline (0W) to 12 week after treatmentDescription: Incidence of acute and chronic treatment-related adverse events in patients with novel coronavirus severe pneumonia receiving UC-MSCs infusion as assessed.
Measure: Side effects in the UC-MSCs treatment group Time: From Baseline (0W) to 96 week after treatmentDescription: Marker for efficacy of treatment
Measure: 28-days survival Time: Day 28Description: Markers of organ function(Score each criterion on a scale of 0 to 4, and the higher the score, the worse the prognosis.)
Measure: Sequential organ failure assessment Time: Day 28Description: Markers of Infection
Measure: C-reactive protein Time: From Baseline (0W) to 12 week after treatmentDescription: Markers of Infection
Measure: Procalcitonin Time: From Baseline (0W) to 12 week after treatmentDescription: Marker of Immunological function
Measure: Lymphocyte count Time: From Baseline (0W) to 12 week after treatmentDescription: Marker of Immunological function
Measure: CD3+, CD4+ and CD8+ T celll count Time: From Baseline (0W) to 12 week after treatmentDescription: Marker of Immunological function
Measure: CD4+/CD8+ratio Time: From Baseline (0W) to 12 week after treatmentThis study is an adaptive, randomized, double-blind, placebo-controlled trial to evaluate the safety and efficacy of novel therapeutic agents in hospitalized adults diagnosed with COVID-19. The study is a multicenter trial that will be conducted in up to approximately 100 sites globally. The study will compare different investigational therapeutic agents to a control arm. There will be interim monitoring to introduce new arms and allow early stopping for futility, efficacy, or safety. If one therapy proves to be efficacious, then this treatment may become the control arm for comparison(s) with new experimental treatment(s). Any such change would be accompanied by an updated sample size. Because background standards of supportive care may evolve/improve over time as more is learned about successful management of COVID-19, comparisons of safety and efficacy will be based on data from concurrently randomized subjects. An independent Data and Safety Monitoring Board (DSMB) will actively monitor interim data to make recommendations about early study closure or changes to study arms. To evaluate the clinical efficacy, as assessed by time to recovery, of different investigational therapeutics as compared to the control arm.
Description: Day of recovery is defined as the first day on which the subject satisfies one of the following three categories from the ordinal scale: 1) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Not hospitalized, no limitations on activities.
Measure: Time to recovery Time: Day 1 through Day 29Description: 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 29Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.
Measure: Clinical status using ordinal scale Time: Day 3 through Day 29Description: Grade 3 AEs are defined as events that interrupt usual activities of daily living, or significantly affects clinical status, or may require intensive therapeutic intervention. Severe events are usually incapacitating. Grade 4 AEs are defined as events that are potentially life threatening.
Measure: Cumulative incidence of Grade 3 and 4 clinical and/or laboratory adverse events (AEs) Time: Day 1 through Day 29Description: An SAE is defined as an AE or suspected adverse reaction is considered serious if, in the view of either the investigator or the sponsor, it results in death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect.
Measure: Cumulative incidence of serious adverse events (SAEs) Time: Day 1 through Day 29Description: For any reason.
Measure: Discontinuation or temporary suspension of investigational therapeutics Time: Day 1 through Day 10Description: Measured in days.
Measure: Duration of hospitalization Time: Day 1 through Day 29Description: Measured in days.
Measure: Duration of new non-invasive ventilation or high flow oxygen use Time: Day 1 through Day 29Description: Measured in days.
Measure: Duration of new oxygen use Time: Day 1 through Day 29Description: Measured in days.
Measure: Duration of new ventilator or extracorporeal membrane oxygenation (ECMO) use Time: Day 1 through Day 29Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 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 29Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.
Measure: Percentage of subjects reporting each severity rating on an 8-point ordinal scale Time: Day 15Description: Date and cause of death (if applicable).
Measure: Subject 14-day mortality Time: Day 1 through Day 15Description: Date and cause of death (if applicable).
Measure: Subject 29-day mortality Time: Day 1 through Day 29Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 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 29Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.
Measure: Time to an improvement of two categories using an ordinal scale Time: Day 1 through Day 29Description: The NEW score has demonstrated an ability to discriminate patients at risk of poor outcomes. This score is based on 7 clinical parameters (respiration rate, oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate, level of consciousness). The NEW Score is being used as an efficacy measure.
Measure: Time to discharge or to a National Early Warning Score (NEWS) of = 2 and maintained for 24 hours, whichever occurs first Time: Day 1 through Day 29The 2019 novel coronavirus pneumonia outbroken in Wuhan, China, which spread quickly to 26 countries worldwide and presented a serious threat to public health. It is mainly characterized by fever, dry cough, shortness of breath and breathing difficulties. Some patients may develop into rapid and deadly respiratory system injury with overwhelming inflammation in the lung. Currently, there is no effective treatment in clinical practice. The present clinical trial is to explore the safety and efficacy of Human Umbilical Cord Mesenchymal Stem Cells (UC-MSCs) therapy for novel coronavirus pneumonia patients.
Description: Evaluation of Pneumonia change
Measure: Size of lesion area by chest imaging Time: At baseline, Day 1, Week 1, Week 2, Week 4, Week 8Description: Evaluation of Pneumonia change
Measure: Blood oxygen saturation Time: At baseline, Day 1, Week 1, Week 2, Week 4, Week 8Description: Marker for efficacy of treatment
Measure: Rate of mortality within 28-days Time: At baseline, Day 1, Week 1, Week 2, Week 4, Week 8Description: 0-4 score, the higher the score is, the poor of the prognosis will be.
Measure: Sequential organ failure assessment Time: At baseline, Day 1, Week 1, Week 2, Week 4, Week 8Description: Number of participants with treatment-related adverse events
Measure: Side effects in the UC-MSCs treatment group Time: At baseline, Day 1, Week 1, Week 2, Week 4, Week 8Description: Markers of the heart function
Measure: Electrocardiogram, the changes of ST-T interval mostly Time: At baseline, Day 1, Week 1, Week 2, Week 4, Week 8Description: Markers of infection
Measure: Concentration of C-reactive protein C-reactive protein, immunoglobulin Time: At baseline, Day 1, Week 1, Week 2, Week 4, Week 8Description: Marker of Immunology and inflammation
Measure: CD4+ and CD8+ T cells count Time: At baseline, Day 1, Week 1, Week 2, Week 4, Week 8Description: Marker of Immunology and inflammation
Measure: Concentration of the blood cytokine (IL-1β, IL-6, IL-8,IL-10,TNF-α) Time: At baseline, Day 1, Week 1, Week 2, Week 4, Week 8Description: Markers of the heart function
Measure: Concentration of the myocardial enzymes Time: At baseline, Day 1, Week 1, Week 2, Week 4, Week 8This is a Phase IIb study consisting of two cohorts to evaluate efficacy, safety and pharmacokinetics of DAS181 in IFV infection. An approximate total of 280 subjects will be enrolled into this study.
Description: Percent of subjects who have returned to room air
Measure: Percent of subjects who have returned to room air Time: 7 daysDescription: Percent change of subjects return to baseline oxygen requirement by Day 7 compared to Day 1
Measure: Percent change of subjects return to baseline oxygen requirement Time: 7 daysThe study is a double-blind, randomised, placebo-controlled trial that will be conducted in healthcare settings. 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.
Description: Number of symptomatic COVID-19 infections will be compared between the chloroquine or hydroxychloroquine and placebo groups
Measure: Number of symptomatic COVID-19 infections Time: Approximately 90 daysDescription: Symptoms severity of COVID-19 will be compared between the two groups using a respiratory severity score.
Measure: Symptoms severity of COVID-19 Time: Approximately 90 daysDescription: Number of asymptomatic cases of COVID-19 will be determined by comparing serology in all participants at time of enrolment and at the end of follow up.
Measure: Number of asymptomatic cases of COVID-19 Time: Approximately 90 daysDescription: Number of symptomatic acute respiratory illnesses will be compared between the chloroquine or hydroxychloroquine and placebo groups.
Measure: Number of symptomatic acute respiratory illnesses Time: Approximately 90 daysDescription: Severity of symptomatic acute respiratory illnesses will be compared between the chloroquine or hydroxychloroquine and placebo groups.
Measure: Severity of symptomatic acute respiratory illnesses Time: Approximately 90 daysDescription: Genetic loci and levels of biochemical components will be correlated with frequency of COVID-19, Acute Respiratory Infection and disease severity.
Measure: Genetic loci and levels of biochemical components will be correlated with frequency of COVID-19, ARI and disease severity. Time: Approximately 90 daysDescription: Number of days lost to work in relation to the treatment arm
Measure: Assess the impact of chloroquine or hydroxychloroquine prophylaxis on number of days lost to work during the pandemic. Time: Approximately 90 daysDescription: The trial will collect data on monetary costs associated with the use of healthcare resources and determine the effects between treatment groups.
Measure: Assess the impact of chloroquine or hydroxychloroquine prophylaxis on healthcare costs Time: Approximately 90 daysDescription: The trial will collect data on health-related quality of life using the quality of life questionnaire (EQ-5D-3L) to determine the effects between treatment groups.
Measure: Assess the impact of chloroquine or hydroxychloroquine prophylaxis on quality of life measures using the quality of life questionnaire (EQ-5D-3L) Time: Approximately 90 daysStudy Objective: 1. To test if post-exposure prophylaxis with hydroxychloroquine can prevent symptomatic COVID-19 disease after known exposure to the SARS-CoV-2 coronavirus. 2. To test if early preemptive hydroxychloroquine therapy can prevent disease progression in persons with known symptomatic COVID-19 disease, decreasing hospitalizations and symptom severity.
Description: Number of participants at 14 days post enrollment with active COVID19 disease.
Measure: Incidence of COVID19 Disease among those who are asymptomatic at baseline Time: 14 daysDescription: Repeated Measure mixed regression model of change in: Visual Analog Scale 0-10 score of rating overall symptom severity (0 = no symptoms; 10 = most severe)
Measure: Overall change in disease severity over 14 days among those who are symptomatic at baseline Time: 14 daysDescription: Outcome reported as the number of participants in each arm who require hospitalization for COVID19-related disease.
Measure: Incidence of Hospitalization Time: 14 daysDescription: Outcome reported as the number of participants in each arm who expire due to COVID-19-related disease.
Measure: Incidence of Death Time: 90 daysDescription: Outcome reported as the number of participants in each arm who have confirmed SARS-CoV-2 infection.
Measure: Incidence of Confirmed SARS-CoV-2 Detection Time: 14 daysDescription: Outcome reported as the number of participants in each arm who self-report symptoms compatible with COVID19 infection.
Measure: Incidence of Symptoms Compatible with COVID19 (possible disease) Time: 90 daysDescription: Outcome reported as the number of participants in each arm who discontinue or withdraw medication use for any reason.
Measure: Incidence of All-Cause Study Medicine Discontinuation or Withdrawal Time: 14 daysDescription: Visual Analog Scale 0-10 score of rating overall symptom severity (0 = no symptoms; 10 = most severe)
Measure: Overall symptom severity at 5 and 14 days Time: 5 and 14 daysDescription: Participants will self-report disease severity status as one of the following 3 options; no COVID19 illness (score of 1), COVID19 illness with no hospitalization (score of 2), or COVID19 illness with hospitalization or death (score of 3). Increased scale score indicates greater disease severity. Outcome is reported as the percent of participants who fall into each category per arm.
Measure: Ordinal Scale of COVID19 Disease Severity at 14 days among those who are symptomatic at trial entry Time: 14 daysThis is a multi-center, double-blinded study of COVID-19 infected patients randomized 1:1 to daily losartan or placebo for 10 days or treatment failure (hospital admission).
Description: Outcome reported as the number of participants per arm admitted to inpatient hospital care due to COVID-19-related disease within 15 days of randomization. Currently, there is a pre-planned pooled analysis with a national trial network under development.
Measure: Hospital Admission Time: 15 daysDescription: The PROMIS Dyspnea (shortness of breath) item banks and pools assess self-reported 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 daysDescription: 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 daysDescription: Participants will report their maximum daily oral temperature to the study team. Outcome is reported as the mean maximum daily body temperature (in degrees Celsius) over 10 days.
Measure: Daily Maximum Temperature Time: 10 daysDescription: Outcome is reported as the mean number of emergency department and clinic presentations combined per participant in each arm.
Measure: Emergency Department/Clinic Presentations Time: 28 daysDescription: Outcome reported as the number of participants in each arm who fall into each of 7 categories. Lower scores indicate greater condition severity. The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen; 6) Not hospitalized, limitation on activities; 7) Not hospitalized, no limitations on activities.
Measure: Disease Severity Rating Day 7 Time: 7 daysDescription: Outcome reported as the number of participants in each arm who fall into each of 7 categories. Lower scores indicate greater condition severity. The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen; 6) Not hospitalized, limitation on activities; 7) Not hospitalized, no limitations on activities.
Measure: Disease Severity Rating Day 15 Time: 15 daysDescription: Outcome reported as the number of participants in each arm who fall into each of 7 categories. Lower scores indicate greater condition severity. The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen; 6) Not hospitalized, limitation on activities; 7) Not hospitalized, no limitations on activities.
Measure: Disease Severity Rating Day 28 Time: 28 daysDescription: Participants will collect oropharyngeal swabs every third day for the duration of study participation. Viral load is measured as number of viral genetic copies per mL.
Measure: Viral Load by Oropharyngeal Swab Day 9 Time: 9 daysDescription: Participants will collect oropharyngeal swabs every third day for the duration of study participation. Viral load is measured as number of viral genetic copies per mL.
Measure: Viral Load by Oropharyngeal Swab Day 15 Time: 15 daysDescription: Outcome reported as the mean number of days participants in each arm did not require ventilator use.
Measure: Ventilator-Free Days Time: 28 daysDescription: Outcome reported as the mean number of days participants in each arm did not require therapeutic oxygen use.
Measure: Therapeutic Oxygen-Free Days Time: 28 daysDescription: Outcome reported as the percent of participants in each arm who require hospital admission by day 15 following randomization.
Measure: Need for Hospital Admission at 15 Days Time: 15 daysDescription: Outcome reported as the percent of participants in each arm who require oxygen therapy by day 15 following randomization.
Measure: Need for Oxygen Therapy at 15 Days Time: 15 daysThis is a multi-center, double-blinded study of COVID-19 infected patients requiring inpatient hospital admission randomized 1:1 to daily Losartan or placebo for 7 days or hospital discharge.
Description: Outcome calculated from the partial pressure of oxygen or peripheral saturation of oxygen by pulse oximetry divided by the fraction of inspired oxygen (PaO2 or SaO2 : FiO2 ratio). PaO2 is preferentially used if available. A correction is applied for endotracheal intubation and/or positive end-expiratory pressure. Patients discharged prior to day 7 will have a home pulse oximeter send home for measurement of the day 7 value, and will be adjusted for home O2 use, if applicable. Patients who died will be applied a penalty with a P/F ratio of 0.
Measure: Difference in Estimated (PEEP adjusted) P/F Ratio at 7 days Time: 7 daysDescription: Outcome reported as the mean number of daily hypotensive episodes (MAP < 65 mmHg) prompting intervention (indicated by a fluid bolus >=500 mL) per participant in each arm.
Measure: Daily Hypotensive Episodes Time: 10 daysDescription: Outcome reported as the number of participants in each arm requiring the use of vasopressors for hypotension.
Measure: Hypotension Requiring Vasopressors Time: 10 daysDescription: Outcome reported as the number of participants in each arm who experience acute kidney injury as defined by the Kidney Disease Improving Global Outcomes (KDIGO) guidelines: Increase in serum creatinine by 0.3mg/dL or more within 48 hours OR Increase in serum creatinine to 1.5 times baseline or more within the last 7 days OR Urine output less than 0.5 mL/kg/h for 6 hours.
Measure: Acute Kidney Injury Time: 10 daysDescription: The SOFA assessment is used to track a person's risk status during stay in the Intensive Care Unit (ICU). The score is based on six different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal, and neurological systems. Each organ system is assigned a point value from 0 (normal) to 4 (high degree of dysfunction/failure). Total score is calculated by entering patient data into a SOFA calculator, a widely-available software. Total scores range from 0-24, with higher scores indicating greater chance of mortality.
Measure: Sequential Organ Failure Assessment (SOFA) Total Score Time: 10 daysDescription: Oxygen saturation (percent) is measured by pulse oximeter. Fraction of inspired oxygen (FiO2) (unitless) is the volumetric fraction of oxygen to other gases in respiratory support. The F/S ratio is unitless.
Measure: Oxygen Saturation / Fractional Inhaled Oxygen (F/S) Time: 10 daysDescription: Outcome reported as the number of participants who have expired at 28 days post enrollment.
Measure: 28-Day Mortality Time: 28 daysDescription: Outcome reported as the number of participants who have expired at 90 days post enrollment.
Measure: 90-Day Mortality Time: 90 daysDescription: Outcome reported as the number of participants in each arm who require admission to the Intensive Care Unit (ICU).
Measure: ICU Admission Time: 10 daysDescription: Outcome reported as the mean number of days participants in each arm did not require mechanical ventilation during an in-patient hospital admission.
Measure: Number of Ventilator-Free Days Time: 10 daysDescription: Outcome reported as the mean number of days participants in each arm did not require therapeutic oxygen usage during an in-patient hospital admission.
Measure: Number of Therapeutic Oxygen-Free Days Time: 10 daysDescription: Outcome reported as the mean number of days participants in each arm did not require vasopressor usage during an in-patient hospital admission.
Measure: Number of Vasopressor-Free Days Time: 10 daysDescription: Outcome reported as the mean length of stay (in days) in the Intensive Care Unit (ICU) for participants in each arm.
Measure: Length of ICU Stay Time: 10 daysDescription: Outcome reported as the mean length of in-patient hospital stay (in days) for participants in each arm.
Measure: Length of Hospital Stay Time: 10 daysDescription: Outcome reported as the number of participants requiring BiPAP OR high flow nasal cannula OR mechanical ventilation OR extracorporeal membranous oxygenation (ECMO) utilization during in-patient hospital care in each arm.
Measure: Incidence of Respiratory Failure Time: 10 daysDescription: The PROMIS Dyspnea (shortness of breath) item banks and pools assess self-reported 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 daysDescription: 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 daysDescription: Outcome reported as the number of participants in each arm who fall into each of 7 categories. Lower scores indicate greater condition severity. The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen; 6) Not hospitalized, limitation on activities; 7) Not hospitalized, no limitations on activities.
Measure: Disease Severity Rating Time: 10 daysDescription: Nasopharyngeal swabs will be collected every third day for the duration of study participation. Viral load is measured as number of viral genetic copies per mL.
Measure: Viral Load by Nasopharyngeal Swab Day 9 Time: 9 daysDescription: Nasopharyngeal swabs will be collected every third day for the duration of study participation. Viral load is measured as number of viral genetic copies per mL.
Measure: Viral Load by Nasopharyngeal Swab Day 15 Time: 15 daysDescription: Blood will be collected every third day for viral load assessment for the duration of study participation. Viral load is measured as number of viral genetic copies per mL.
Measure: Viral Load by Blood Day 9 Time: 9 daysDescription: Blood will be collected every third day for viral load assessment for the duration of study participation. Viral load is measured as number of viral genetic copies per mL.
Measure: Viral Load by Blood Day 15 Time: 15 daysAdults who have tested positive for SARS-CoV-2 infection and who do not require supplemental oxygen will receive PUL-042 Inhalation Solution or placebo 3 times over a one week period in addition to their normal care. Subjects will be be followed and assessed for their clinical status over 28 days to see if PUL-042 Inhalation Solution improves the clinical outcome
Description: To determine the efficacy of PUL-042 Inhalation Solution in decreasing the severity of COVID-19 in subjects: 1) who have documented SARS-CoV-2 infection and, 2) who do not require supplemental oxygen (Ordinal Scale for Clinical Improvement 3 or less) at the time of enrollment. The primary endpoint is the difference in the proportion of patients with clinically meaningful worsening of COVID-19 within 28 days from the start of experimental therapy, as indicated by an increase of at least 2 points on the Ordinal Scale for Clinical Improvement. The Ordinal Scale for Clinical Improvement is a nine point scale (0-8) with 0 being no clinical or virological evidence of infection and 8 being death.
Measure: Severity of COVID-19 Time: 28 daysDescription: SARS-Co-V-2 positivity up to 28 days from the start of experimental therapy
Measure: SARS-CoV-2 infection Time: 28 daysDescription: To determine the difference in the proportion of COVID-19 patients with clinically meaningful worsening of COVID-19 within 14 days from the start of experimental therapy, as indicated by an increase of at least 2 points on the Ordinal Scale for Clinical Improvement. The Ordinal Scale for Clinical Improvement is a nine point scale (0-8) with 0 being no clinical or virological evidence of infection and 8 being death.
Measure: Severity of COVID-19 over 14 days Time: 14 daysDescription: To assess the progression of COVID-19 severity during the study as measured by the SARS-CoV-2 Symptom Score. The SARS-CoV-2 Symptom Score measures 3 elements on a 0-3 scale (cough, shortness of breath or difficulty breathing, and muscle aches or fatigue) ranging from 0 for none to 3 for severe. The fourth element is fever and it is rated on a 0-4 scale with 0 being no fever and 4 being life-threatening.
Measure: Severity of COVID-19 symptoms Time: 28 daysDescription: The requirement for ICU admission within 28 days from the start of the experimental therapy.
Measure: ICU admission Time: 28 daysDescription: The requirement for mechanical ventilation within 28 days from the start of the experimental therapy.
Measure: Mechanical Ventilation Time: 28 daysDescription: All cause mortality at 28 days from the start of experimental therapy
Measure: Mortality Time: 28 daysSubjects who have documented exposure to SARS-CoV-2 (COVID-19) will receive 4 doses of PUL-042 Inhalation Solution or 4 doses of a placebo solution by inhalation over 10 days. Subjects will be followed for the incidence and severity of COVID-19 over 28 days. Subjects will be tested for infection with SARS-CoV-2 at the beginning, middle and end of the study.
Description: To determine the efficacy of PUL-042 Inhalation Solution in the prevention of viral infection with SARS-CoV-2 and progression to COVID-19 in subjects: 1) who have repeated exposure to individuals with SARS-CoV-2 infection and, 2) are asymptomatic at enrollment. The primary endpoint is the severity of COVID-19 as measured by the maximum difference from the baseline value in the Ordinal Scale for Symptom Improvement within 28 days from the start of experimental therapy.
Measure: Severity of COVID-19 Time: 28 daysDescription: Positive test for SARS-CoV-2 infection 28 days from the start of experimental therapy in subjects who test negative for SARS-CoV-2 at the pre-treatment visit
Measure: Incidence of SARS-CoV-2 infection Time: 28 daysDescription: Positive test for SARS-CoV-2 infection 14 days from the start of experimental therapy in subjects who test negative for SARS-CoV-2 at the pre-treatment visit
Measure: Incidence of SARS-CoV-2 infection Time: 14 daysDescription: The severity of COVID-19 as measured by the maximum difference from the baseline value in the Ordinal Scale for Symptom Improvement within 14 days from the start of experimental therapy.
Measure: Severity of COVID-19 Time: 14 daysDescription: The requirement for ICU admission within 28 days from the start of experimental therapy.
Measure: ICU admission Time: 28 daysDescription: The requirement for mechanical ventilation within 28 days from the start of experimental therapy.
Measure: Mechanical ventilation Time: 28 daysDescription: All cause mortality at 28 days from the start of experimental therapy.
Measure: Mortality Time: 28 daysPhase 2: The primary objective of the study is to evaluate the clinical efficacy of sarilumab relative to the control arm in adult patients hospitalized with COVID-19 regardless of 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).
Description: Phase 2 Only
Measure: Percent change in C-reactive protein (CRP) levels Time: Day 4Description: 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 29Description: 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 29Description: 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 29Description: Resolution of fever defined as postbaseline body temperature <37.2°C (oral), or <37.6°C (rectal or tympanic) or <36.8°C (temporal or axillary) Documented fever defined as ≥38°C (oral), ≥38.4°C (rectal or tympanic), or ≥37.6°C (temporal or axillary)
Measure: Time to resolution of fever for at least 48 hours without antipyretics in patients with documented fever Time: Up to day 29Description: Defined as postbaseline body temperature <37.2°C (oral), or <37.6°C (rectal or tympanic) or <36.8°C (temporal or axillary)
Measure: Time to resolution of fever for at least 48 hours without antipyretics by clinical severity Time: Up to day 29Description: Defined as postbaseline body temperature <37.2°C (oral), or <37.6°C (rectal or tympanic) or <36.8°C (temporal or axillary)
Measure: Time to resolution of fever for at least 48 hours without antipyretics by baseline IL-6 levels Time: Up to day 29Description: Improvement in oxygenation defined as increase in SpO2/FiO2 of 50 or greater compared to the nadir SpO2/FiO2
Measure: Time to improvement in oxygenation for at least 48 hours Time: Up to day 29Description: Defined as increase in SpO2/FiO2 of 50 or greater compared to the nadir SpO2/FiO2
Measure: Time to improvement in oxygenation for at least 48 hours by clinical severity Time: Up to day 29Description: Defined as increase in SpO2/FiO2 of 50 or greater compared to the nadir SpO2/FiO2
Measure: Time to improvement in oxygenation for at least 48 hours by baseline IL-6 levels Time: Up to day 29Description: Resolution of fever defined as postbaseline body temperature <37.2°C (oral), or <37.6°C (rectal or tympanic) or <36.8°C (temporal or axillary) Improvement in oxygenation defined as increase in SpO2/FiO2 of 50 or greater compared to the nadir SpO2/FiO2
Measure: Time to resolution of fever and improvement in oxygenation for at least 48 hours Time: Up to day 29Description: NEWS2 consists of: Physiological Parameters: Respiration rate (per minute), SpO2 Scale 1 (%), SpO2 Scale 2 (%), Use of Air or oxygen, Systolic blood pressure (mmHg), Pulse (per minute), Consciousness, Temperature (°C)
Measure: Time to discharge or to a National Early Warning Score 2 (NEWS2) of ≤2 and maintained for 24 hours Time: Up to day 29Description: Defined as ≥38°C (oral), ≥38.4°C (rectal or tympanic) or ≥37.6°C (temporal or axillary)
Measure: Number of days with fever Time: Up to day 29Description: Phase 3 Only
Measure: Change in serum CRP levels Time: Up to day 29The 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.
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: 14 daysDescription: Time for disease progression from NIAID scale 3 or 4 to scale 2 or 1, and patients need to be on invasive mechanical ventilation, or ESMO, or death.
Measure: Disease progression of COVID-19 Time: 28 daysDescription: All cause of death
Measure: All cause of death Time: 28 daysDescription: Conversion rate of clinical status on days 8 (proportion of subjects who changed from "severe" to "moderate or mild", or the improvement from "scale 3 or 4" to "scale 5 or higher" on NIAID ordinal scale)
Measure: Conversion rate of clinical status at Day 8 Time: 7 daysDescription: Conversion rate of clinical status on days 15 (proportion of subjects who changed from "severe" to "moderate or mild", or the improvement from "scale 3 or 4" to "scale 5 or higher" on NIAID ordinal scale)
Measure: Conversion rate of clinical status at Day 15 Time: 14 daysDescription: The discharge time or NEWS2 (National Early Warning Score 2) of ≤2 is maintained for 24 hours
Measure: Hospital discharge time Time: 28 daysDescription: Duration of mechanical ventilation (IMV, NIV) (days)
Measure: Duration of mechanical ventilation Time: 28 daysDescription: Duration of pressors (days)
Measure: Duration of pressors Time: 28 daysDescription: Duration of extracorporeal membrane oxygenation (days)
Measure: Duration of ECMO Time: 28 daysDescription: Duration of oxygen therapy (oxygen inhalation by nasal cannula or mask) (days)
Measure: Duration of oxygen therapy Time: 28 daysDescription: Length of hospital stay (days)
Measure: Length of hospital stay Time: 28 daysDescription: Changes of absolute lymphocyte count in peripheral blood
Measure: Absolute lymphocyte count Time: 28 daysThis 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.
Description: Time of improvement or recovery of respiratory symptoms
Measure: Time of Improvement or recovery of respiratory symptoms Time: 10 days during the intervention periodDescription: 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 periodDescription: Frequency of improvement or recovery of respiratory symptoms
Measure: Frequency of Improvement or recovery of respiratory symptoms Time: 10 days during the intervention periodDescription: Duration of fever after recruitment
Measure: Duration of fever Time: 10 days during the intervention periodDescription: 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 periodDescription: Time of improvement of pulmonary imaging
Measure: Time of improvement of pulmonary imaging Time: 10 days during the intervention periodDescription: Peripheral blood c-reactive protein concentration
Measure: Peripheral blood c-reactive protein concentration Time: day-1,3,7,14 after the intervention periodDescription: Absolute value of peripheral blood lymphocytes
Measure: Absolute value of peripheral blood lymphocytes Time: day-1,3,7,14 after the intervention periodDescription: percentage of peripheral blood lymphocytes
Measure: percentage of peripheral blood lymphocytes Time: day-1,3,7,14 after the intervention periodThis study will evaluate the efficacy, safety, pharmacodynamics, and pharmacokinetics of tocilizumab (TCZ) compared with a matching placebo in combination with standard of care (SOC) in hospitalized patients with severe COVID-19 pneumonia.
A new human coronavirus responsible for pneumonia, SARS-CoV-2, emerged in China in December 2019 and has spread rapidly. COVID-19, the disease caused by this virus, has a very polymorphous clinical presentation, which ranges from upper respiratory tract infections to acute respiratory distress syndrome. It may appear serious straightaway or may evolve in two stages, with a worsening 7 to 10 days after the first clinical signs, potentially linked to a cytokine storm and accompanied by a high risk of thrombosis. The global mortality rate of COVID-19 is between 3% and 4%, with severe forms being more frequent among older patients. Management is symptomatic as no antiviral treatment has demonstrated any clinical benefit in this condition. Hydroxychloroquine is a derivative of chloroquine commonly used in some autoimmune diseases, such as systemic lupus erythematosus. It is active in vitro in cellular models of infection by many viruses such as HIV, hepatitis C or SARS-CoV. However, its interest in viral infections in humans has not been demonstrated. Very recently, a preliminary uncontrolled study evaluated the effect of hydroxychloroquine on viral shedding in subjects with COVID-19. Among 20 patients treated with hydroxychloroquine at a dose of 600 mg per day, the percentage of patients with detectable SARS-CoV-2 RNA in the nasopharynx decreased from 100% at inclusion (start of treatment) to 43% six days later. In comparison, 15 of 16 untreated patients had a positive RT-PCR six days after inclusion. Furthermore, hydroxychloroquine has immunomodulating and anti-inflammatory properties, which could theoretically prevent or limit secondary worsening. The research hypothesis is that treatment with hydroxychloroquine improves prognosis and reduces the risk of death or use for invasive ventilation in patients with COVID-19.
Description: WHO Ordinal Scale for Clinical Improvement ranges from 0 to 8, higher score meaning poorer outcome
Measure: Clinical evolution on the WHO Ordinal Scale for Clinical Improvement for COVID-19 between day 0 and day 14 Time: Day 14Description: WHO Ordinal Scale for Clinical Improvement ranges from 0 to 8, higher score meaning poorer outcome
Measure: Clinical evolution on the WHO Ordinal Scale for Clinical Improvement for COVID-19 between day 0 and day 28. Time: Day 28This is a randomized, double-blind placebo-controlled trial to investigate the efficacy and safety of tradipitant 85 mg orally given twice daily to treat inflammatory lung injury associated with severe or critical COVID-19 infection. On evaluation for enrollment, participant will need to meet all inclusion and exclusion criteria. If participant consents, they will be randomized 1:1 to treatment with either tradipitant 85 mg PO BID or placebo in addition to standard of care for COVID-19 infection as per the protocol at the treating hospital. NEWS 2 will be assessed at screening and daily following randomization. Inflammatory lab markers as detailed should be collected once per day in the morning, preferably at the same time every morning. All enrolled participants will have whole blood collected for whole genome sequencing.
Primary Objective: To evaluate the clinical efficacy of sarilumab relative to the control arm in adult patients hospitalized with severe or critical COVID-19 Secondary Objectives: - Evaluate the 28-day survival rate - Evaluate the clinical efficacy of sarilumab compared to the control arm by clinical severity - Evaluate changes in the National Early Warning Score 2 (NEWS2) - Evaluate the duration of predefined symptoms and signs (if applicable) - Evaluate the duration of supplemental oxygen dependency (if applicable) - Evaluate the incidence of new mechanical ventilation use during the study - Evaluate the duration of new mechanical ventilation use during the Study - Evaluate the proportion of patients requiring rescue medication during the 28-day period - Evaluate need for admission into intensive care unit (ICU) - Evaluate duration of hospitalization (days) - The secondary safety objectives of the study are to evaluate the safety of sarilumab through hospitalization (up to day 29 if patient is still hospitalized) compared to the control arm as assessed by incidence of: - Serious adverse events (SAEs) - Major or opportunistic bacterial or fungal infections in patients with grade 4 neutropenia - Grade ≥2 infusion related reactions - Grade ≥2 hypersensitivity reactions - Increase in alanine transaminase (ALT) ≥3X upper limit of normal (ULN) (for patients with normal baseline) or >3X ULN AND at least 2-fold increase from baseline value (for patients with abnormal baseline) - Major or opportunistic bacterial or fungal infections
Description: The ordinal scale is an assessment of the clinical status. Score ranges 1-7. Lower score is worse.
Measure: Time to improvement of 2 points in clinical status assessment from baseline using the 7-point ordinal scale Time: Baseline to Day 29Description: The ordinal scale is an assessment of the clinical status. Score ranges 1-7. Lower score is worse.
Measure: Proportion of patients with one point improvement from baseline in clinical status assessment at days 4, 7, 15, 21, 29 using the 7-point ordinal scale Time: Baseline to Days 4, 7, 15, 21, 29Description: The ordinal scale is an assessment of the clinical status. Score ranges 1-7. Lower score is worse.
Measure: Mean change in the 7-point ordinal scale from baseline to Days 4, 7, 15, 21, and 29 (or until discharge) Time: Baseline to Days 4, 7, 15, 21, 29 (or until discharge)Description: Defined as body temperature (≤36.6°C [axilla], or ≤37.2 °C [oral], or ≤37.8°C [rectal or tympanic]) for at least 48 hours without antipyretics or until discharge, whichever is sooner.
Measure: Time to resolution of fever Time: Baseline to Day 29Description: Resolution of both fever and improvement in oxygenation. Resolution of fever is defined as body temperature (≤36.6°C [axilla], or ≤37.2 °C [oral], or ≤37.8°C [rectal or tympanic]) for at least 48 hours without antipyretics or until discharge, whichever is sooner. Improvement in oxygenation is defined as SpO2/FiO2 of 50 or greater compared to the nadir SpO2/FiO2 for at least 48 hours, or until discharge, whichever is sooner.
Measure: Time to resolution of fever and improvement in oxygenation Time: Baseline to Day 29Description: Fever is defined as >37.4°C (axilla), or >38.0 °C (oral), or >38.4°C (rectal or tympanic) based on maximum value observed during a 24-hour period.
Measure: Days with fever Time: Baseline to Day 29Description: The National Early Warning Score (NEWS2) is used to standardize the assessment of acute-illness severity, track the clinical condition of patients, and to alert clinical teams to patient deterioration. Score ranges from 0-20. A higher score is worse.
Measure: Time to change in NEWS2 from baseline Time: Baseline to Day 29Description: The NEWS2 is used to standardize the assessment of acute-illness severity, track the clinical condition of patients, and to alert clinical teams to patient deterioration. Score ranges from 0-20. A higher score is worse.
Measure: Time to NEWS2 of <2 and maintained for 24 hours Time: Baseline to Day 29Description: The NEWS2 is used to standardize the assessment of acute-illness severity, track the clinical condition of patients, and to alert clinical teams to patient deterioration. Score ranges from 0-20. A higher score is worse.
Measure: Mean change from baseline to days 4, 7, 15, 21, and 29 in NEWS2 Time: Baseline to days 4, 7, 15, 21, and 29Description: SpO2/FiO2 of 50 or greater compared to the nadir for at least 48 hours, or until discharge, whichever is sooner. SpO2 is oxygen saturation and FiO2 is the fraction of inspired oxygen.
Measure: Time-to-improvement in oxygenation Time: Baseline to Day 29Description: Supplemental oxygen is defined as oxygen administration by nasal cannula, simple face mask, or other similar oxygen delivery device.
Measure: Alive off supplemental oxygen at day 29 Time: Day 29Description: Hypoxemia is defined as SpO2 <93% on room air, or requiring supplemental oxygen, or mechanical ventilatory support.
Measure: Days of hypoxemia Time: Baseline to Day 29Description: Supplemental oxygen is defined as oxygen administration by nasal cannula, simple face mask, or other similar oxygen delivery device.
Measure: Days of supplemental oxygen use Time: Baseline to Day 29Description: For those not requiring these interventions at baseline.
Measure: The number of patients with Initiation of mechanical ventilation, non-invasive ventilation, or use of high flow nasal cannula Time: Baseline to Day 60Description: For patients are not in ICU at baseline
Measure: The number of patients transferred to the ICU or the need to transfer to the ICU (if the ICU is not available) Time: Baseline to Day 60Rationale: Covid-19 spreads rapidly throughout the world. A large epidemic in the Netherlands would seriously challenge the available hospital capacity, and this would be augmented by absenteeism of healthcare workers (HCW). Strategies to prevent absenteeism of HCW are, therefore, desperately needed to safeguard continuous patient care. Bacille Calmette-Guérin (BCG) is a vaccine against tuberculosis, with protective non-specific effects against other respiratory tract infections in in vitro and in vivo studies, and reported significant reductions in morbidity and mortality. The hypothesis is that BCG vaccination can reduce HCW absenteeism during the epidemic phase of Covid-19. Objective: Primary objective: To reduce absenteeism among HCW with direct patient contacts during the epidemic phase of Covid-19. Secondary objective: To reduce hospital admission, ICU admission or death in HCW with direct patient contacts during the epidemic phase of Covid-19. Study design: A placebo-controlled adaptive multi-centre randomized controlled trial. Study population: HCW with direct patient contacts among which nurses and physicians working at emergency rooms and wards where Covid-19-infected patients are treated. Intervention: Participants will be randomized between intracutaneous administration of BCG vaccine or placebo in a 1:1 ratio. Main study parameters/endpoints: Primary endpoint: number of days of (unplanned) absenteeism for any reason. Secondary endpoints include the number of days of (unplanned) absenteeism because of documented Covid-19 infection, and the cumulative incidence of hospital admission, Intensive Care Admission, and death. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Based on previous experience and randomized controlled trials in adult and elderly individuals, the risks of BCG vaccination are considered low. The objective of this trial is to evaluate the beneficial effects of BCG vaccination through a lower work absenteeism rate of HCW and/or a mitigated clinical course of Covid-19 infection. The primary endpoint and the adaptive design with frequent interim analyses facilitate maximum efficiency of the trial, so that results can inform policy making during the ongoing epidemic.
Description: Number of days of unplanned absenteeism for any reason
Measure: Health Care Workers absenteeism Time: Maximum of 180 daysDescription: Exploratory
Measure: the number of days of absenteeism, because of imposed quarantine as a result of exposure to COVID-19 Time: Maximum of 180 daysDescription: Exploratory
Measure: the number of days of absenteeism, because of imposed quarantine as a result of having acute respiratory symptoms, fever or documented COVID-19 Time: Maximum of 180 daysDescription: Exploratory
Measure: the number of days of unplanned absenteeism because of self-reported acute respiratory symptoms Time: Maximum of 180 daysDescription: Exploratory
Measure: the number of days of self-reported fever (≥38 gr C) Time: Maximum of 180 daysDescription: Exploratory
Measure: the cumulative incidence of self-reported fever (≥38 gr C) Time: Maximum of 180 daysDescription: Exploratory
Measure: the number of days of self-reported acute respiratory symptoms Time: Maximum of 180 daysDescription: Exploratory
Measure: the cumulative incidence of self-reported acute respiratory symptoms Time: Maximum of 180 daysDescription: Exploratory
Measure: the cumulative incidence of death for any reason Time: Maximum of 180 daysDescription: Exploratory
Measure: the cumulative incidence of Intensive Care Admission for any reason Time: Maximum of 180 daysDescription: Exploratory
Measure: the cumulative incidence of Hospital Admission for any reason Time: Maximum of 180 daysDescription: Exploratory
Measure: • the cumulative incidence and magnitude of plasma/serum antibodies (IgA,M,G) and SARS-CoV-2-specific antibodies at 12 weeks after vaccination and at the end of the study period Time: Maximum of 180 daysObjective: To determine if pre-exposure prophylaxis with hydroxychloroquine is effective for the prevention of COVID-19 disease.
Description: Outcome reported as the percent of participants in each arm who are COVID-19-free at the end of study treatment.
Measure: COVID-19-free survival Time: up to 12 weeksDescription: Outcome reported as the percent of participants in each arm who have a confirmed SARS-CoV-2 infection during study treatment.
Measure: Incidence of confirmed SARS-CoV-2 detection Time: up to 12 weeksDescription: Outcome reported as the percent of participants in each arm who report COVID-19-related symptoms during study treatment.
Measure: Incidence of possible COVID-19 symptoms Time: up to 12 weeksDescription: Outcome reported as the percent of participants in each arm who discontinue study medication use for any reason during treatment.
Measure: Incidence of all-cause study medicine discontinuation Time: up to 12 weeksDescription: Participants will self-report COVID-19 status on an ordinal scale as follows: No illness (score=1), Illness with outpatient observation (score=2), Hospitalization (or post-hospital discharge) (score=3), or Hospitalization with ICU stay or death (score=4). Possible scores range from 1-4 with higher scores indicating greater disease severity.
Measure: Ordinal Scale of COVID-19 Disease maximum severity if COVID-19 diagnosed at study end Time: up to 12 weeksDescription: Outcome reported as the percent of participants in each arm who are hospitalized or expire due to COVID-19 during study treatment.
Measure: Incidence of Hospitalization for COVID-19 or death Time: up to 12 weeksDescription: Outcome reported as the percent of participants in each arm who experience medication-related side effects during study treatment.
Measure: Incidence of study medication-related side effects Time: up to 12 weeksTo evaluate the efficacy of a single dose of subcutaneous injections of 180 ug of Peginterferon Lambda-1a, compared with placebo in reducing the duration of viral shedding of SARS-CoV-2 virus in patients with uncomplicated COVID-19 disease.
Description: Time to first of two consecutive negative respiratory secretions obtained by 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 daysORCHID is a multicenter, blinded, placebo-controlled, randomized clinical trial evaluating hydroxychloroquine for the treatment of adults hospitalized with COVID-19. Patients, treating clinicians, and study personnel will all be blinded to study group assignment.
Description: We will determine the COVID Ordinal Scale for all patients on study day 15 COVID Ordinal Scale defined as: Death Hospitalized on invasive mechanical ventilation or ECMO ( extracorporeal membrane oxygenation) Hospitalized on non-invasive ventilation or high flow nasal cannula Hospitalized on supplemental oxygen Hospitalized not on supplemental oxygen Not hospitalized with limitation in activity (continued symptoms) Not hospitalized without limitation in activity (no symptoms)
Measure: COVID Ordinal Outcomes Scale on Day 15 Time: assessed on study day 15Description: Vital status of the patient on day 15 will be determined using any of the following methods: medical record review, phone calls to patient or proxy
Measure: all-location, all-cause mortality assessed on day 15 Time: assessed on study day 15Description: Vital status of the patient at day 28 will be determined using any of the following methods: medical record review, phone calls to patient or proxy
Measure: all-location, all-cause mortality assessed on day 29 Time: assessed on study day 29Description: We will determine the COVID Ordinal Scale for all patients on study day 3
Measure: COVID Ordinal Outcomes Scale on Study Day 3 Time: assessed on study day 3Description: We will determine the COVID Ordinal Scale on study day 8
Measure: COVID Ordinal Outcomes Scale on Study Day 8 Time: assessed on study day 8Description: We will determine the COVID Ordinal Scale on study day 29
Measure: COVID Ordinal Outcomes Scale on Study Day 29 Time: assessed on study day 29Description: We will determine the number of patients who are either dead or on ECMO ( extracorporeal membrane oxygenation) between enrollment and day 28
Measure: Number of patients dead or with receipt of ECMO between enrollment and Day 28 Time: Enrollment to Day 28Description: The number of calendar days between randomization and 28 days later that the patient is alive and without the use of oxygen therapy. Patients who die prior to day 28 are assigned zero oxygen free days.
Measure: Oxygen-free days through Day 28 Time: 28 days after randomizationDescription: Ventilator-free days is defined to be 28 days minus the duration of mechanical ventilation through day 28. Participants who do not survive to day 28 are assigned zero ventilator-free days.
Measure: Ventilator-free days through Day 28 Time: 28 days after randomizationDescription: The number of calendar days between randomization and 28 days later that the patient is alive and without the use of vasopressor therapy. Patients who die prior to day 28 are assigned zero vasopressor free days.
Measure: Vasopressor-free days through Day 28 Time: 28 days after randomizationDescription: The number of days spent out of the ICU to day 28.
Measure: ICU-free days to Day 28 Time: 28 days after randomizationDescription: Defined as 28 days minus the number of days from randomization to discharge home.If a patient has not been discharged home prior to day 28 or dies prior to day 28, hospital free days will be zero.
Measure: Hospital-free days to Day 28 Time: 28 days after randomizationDescription: We will determine the number of patients that experience seizure between randomization and day 28
Measure: Number of patients with seizures to day 28 Time: 28 days after randomizationDescription: We will determine the number of patients that experience ventricular arrhythmia between randomization and day 28
Measure: Number of patients with atrial or ventricular arrhythmia to day 28 Time: 28 days after randomizationDescription: We will determine the number of patients that experience cardiac arrest between randomization and day 28
Measure: Number of patients with cardiac arrest to day 28 Time: 28 days after randomizationDescription: We will determine the number of patients that experience elevation in aspartate aminotransferase or alanine aminotransferase to twice the local upper limit of normal between randomization and day 28
Measure: Number of patients with elevation in aspartate aminotransferase or alanine aminotransferase to twice the local upper limit of normal to day 28 Time: 28 days after randomizationDescription: We will determine the number of patients that experience acute pancreatitis between randomization and day 28
Measure: Number of patients with acute pancreatitis arrest to day 28 Time: 28 days after randomizationDescription: We will determine the number of patients that experience acute kidney injury between randomization and day 28
Measure: Number of patients with acute kidney injury to day28 Time: 28 days after randomizationDescription: We will determine the number of patients that experience renal replacement therapy between randomization and day 28
Measure: Number of patients with receipt of renal replacement therapy to day 28 Time: 28 days after randomizationDescription: We will determine the number of patients that experience symptomatic hypoglycemia between randomization and day 28
Measure: Number of patients with symptomatic hypoglycemia to day 28 Time: 28 days after randomizationDescription: We will determine the number of patients that experience neutropenia, lymphopenia, anemia, or thrombocytopenia between randomization and day 28
Measure: Number of patients with neutropenia, lymphopenia, anemia, or thrombocytopenia to day 28 Time: 28 days after randomizationDescription: We will determine the number of patients that experience severe dermatologic reaction between randomization and day 28
Measure: Number of patients with severe dermatologic reaction to day 28 Time: 28 days after randomizationPrimary Objective: To assess the effect of hydroxychloroquine versus placebo on nasopharyngeal SARS-CoV-2 viral load in outpatient adults with COVID-19 Secondary Objectives: - To assess the effect of hydroxychloroquine versus placebo on clinical signs and symptoms and progression of disease in outpatient adults with COVID-19 - To assess the safety and tolerability of hydroxychloroquine in outpatient adults with COVID-19
Description: Viral load assessed by PCR from a nasopharyngeal swab
Measure: Change from baseline to Day 3 in nasopharyngeal SARS-CoV-2 viral load (if quantitative PCR is available) Time: Baseline to Day 3Description: Viral load assessed by PCR from a nasopharyngeal swab - 2. Viral load assessed by PCR from a nasopharyngeal swab
Measure: Number of participants by PCR result status (positive or negative) (if quantitative PCR is not available) Time: Baseline to Day 3Description: Viral load assessed by PCR from a nasopharyngeal swab
Measure: Change from baseline to Day 5 in nasopharyngeal SARS-CoV-2 viral load Time: Baseline to Day 5Description: Viral load assessed by PCR from a nasopharyngeal swab
Measure: Number of participants by PCR result status (positive or negative) Time: Baseline to end of study (Day14)Description: COVID-19 symptoms (feverishness, sore throat, cough, shortness of breath, myalgias) will be scored by the participant on a 4-point scale ( 0 =none; 1 = mild; 2 = moderate; 3 = severe)
Measure: Number of participants with COVID-19 symptoms by severity Time: Baseline to end of study (Day14)Description: COVID-19 symptoms (feverishness, sore throat, cough, shortness of breath, myalgias) will be scored by the participant on a 4-point scale ( 0 =none; 1 = mild; 2 = moderate; 3 = severe). Resolution of a symptom is defined as when a symptom previously scored ≥ 1 on the scale is scored as 0
Measure: Time to resolution of COVID-19 Symptoms Time: Baseline to end of study (Day14)Description: Resolution of fever defined as the first day of 2 consecutive daily temperatures < 37.7 C
Measure: Time to resolution of fever Time: Baseline to end of study (Day14)Description: Resolution of fever defined as the first day of 2 consecutive daily temperatures < 37.7 C
Measure: Percentage of participants with resolution of fever Time: Baseline to end of study (Day14)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.
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 monthsDescription: 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 monthsProtocol 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.
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-vaccinationDescription: Antibody against SARS-CoV-2 Spike protein
Measure: SARS-CoV-2 antibodies Time: Baseline (pre-vaccination), and 1, 3 and 12 months post-vaccinationDescription: 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-vaccinationDescription: 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-vaccinationDescription: 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-vaccinationDescription: 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-vaccinationThe mortality rate of the disease caused by the corona virus induced disease (COVID-19) has been estimated to be 3.7% (WHO), which is more than 10-fold higher than the mortality of influenza. Patients with certain risk factors seem to die by an overwhelming reaction of the immune system to the virus, causing a cytokine storm with features of Cytokine-Release Syndrome (CRS) and Macrophage Activation Syndrome (MAS) and resulting in Acute Respiratory Distress Syndrome (ARDS). Several pro-inflammatory cytokines are elevated in the plasma of patients and features of MAS in COVID-19, include elevated levels of ferritin, d-dimer, and low platelets. There is increasing data that cytokine-targeted biological therapies can improve outcomes in CRS or MAS and even in sepsis. Tocilizumab (TCZ), an anti-IL-6R biological therapy, has been approved for the treatment of CRS and is used in patients with MAS. Based on these data, it is hypothesized that TCZ can reduce mortality in patients with severe COVID-19 prone to CRS and ARDS. The overall purpose of this study is to evaluate whether treatment with TCZ reduces the severity and mortality in patients with COVID-19.
Description: Assessed by the 8-point WHO scale
Measure: Illness severity Time: At days 2, 7, 14, 28 after randomisationDescription: Clinical improvement is defined as a ≥ 2-point improvement in the 8-point WHO scale
Measure: Number of patients with clinical improvement Time: At days 2, 7, 14, 28 after randomisationDescription: Clinical improvement is defined as a ≥ 2-point improvement in the 8-point WHO scale
Measure: Time to clinical improvement (days) Time: Up to day 28 after randomisationDescription: Events of special interest are defined as secondary infections, acute kidney failure, hepatic, and cardiac failure
Measure: Number of patients with events of special interest Time: Within 28 days after randomisationThis study evaluates treatment with Favipiravir combined with supportive care for adult patients with COVID-19-moderate type.
Description: The duration from start of treatment (Favipiravir or placebo) to normalization of pyrexia, respiratory rate and SPO2 and relief of cough (where there are relevant abnormal symptoms at enrolment) that is maintained for at least 72 hours.
Measure: Time from randomization to clinical recovery Time: 90 daysDescription: 1. Time from randomization to negativity in RT-PCR nucleic acid test for 2019-nCov within 28 days of randomization;
Measure: Time from randomization to negativity in RT-PCR nucleic acid test Time: 28 daysDescription: Incidence of deterioration/aggravation of pneumonia (defined as SPO2≤93% or PaO2/FiO2 ≤300 mmHg or distressed RR≥30/min without oxygen inhalation and requiring oxygen therapy or more advanced breath support) within 28 days of randomization;
Measure: Incidence of deterioration/aggravation of pneumonia Time: 28 daysDescription: Time from randomization to resolution of pyrexia (defined the same as for the primary efficacy variable; applicable to subjects with pyrexia at enrolment) within 28 days of randomization;
Measure: Time from randomization to resolution of pyrexia Time: 28 daysDescription: Time from randomization to relief of cough (defined the same as for the primary efficacy variable; applicable to subjects with cough at enrolment) within 28 days of randomization; It is recommended that the severity of cough be graded as per NCI-CTCAE v5.0: Mild: Requires non-prescription treatment; Moderate: Requires medication treatment; limits instrumental activities of daily living; Severe: Limits self-care activities of daily living
Measure: Time from randomization to relief of cough Time: 28 daysDescription: Time from randomization to relief of dyspnoea (defined as subject-perceived improvement or resolution of dyspnoea; applicable to subjects with dyspnoea at enrolment) within 28 days of randomization;
Measure: Time from randomization to relief of dyspnoea Time: 28 daysDescription: 6. Rate of auxiliary oxygen therapy or non-invasive ventilation within 28 days of randomization
Measure: Rate of auxiliary oxygen therapy Time: 28 daysDescription: ICU admission rate within 28 days of randomization
Measure: ICU admission rate Time: 28 daysDescription: All-cause mortality within 28 days of randomization
Measure: Mortality Time: 28 daysThis center intends to conduct a single-center, randomized, placebo-controlled study to evaluate the effectiveness and safety of Nintedanib ethanesulfonate soft capsule in the treatment of pulmonary fibrosis in patients with moderate to severe COVID-19.
Description: Changes in forced vital capacity (FVC) after treatment compared to baseline.
Measure: Changes in forced vital capacity (FVC) Time: 8 weeksDescription: Changes incarbon monoxide dispersion (DLco%) after treatment compared to baseline.
Measure: Changes in carbon monoxide dispersion (DLco%) Time: 8 weeksDescription: Changes in the six-minute walk test (6MWT) after treatment compared to baseline.
Measure: Changes in the six-minute walk test (6MWT) Time: 8 weeksDescription: Changes in High resolution CT score after treatment compared to baseline.The minimum and maximum values are 0 and 25 , and higher scores mean a worse outcome. As for the score, it is the expected value and will be determined according to the actual result
Measure: Changes in High resolution CT score Time: 8 weeksEvaluation of the efficacy and safety of hydroxychloroquine - camostat combination therapy in hospitalized patients with moderate COVID-19 infection, CLOCC-Trial Primary Objectives: The primary objective of this study is to demonstrate, that a combination therapy of hydroxychloroquine and camostat (Foipan®) is superior to hydroxychloroquine + placebo in participants with moderate COVID-19.
The COVID-19 pneumonia has grown to be a global public health emergency since patients were first detected in Wuhan, China, in December 2019, which spread quickly to worldwide and presented a serious threat to public health. It is mainly characterized by fever, dry cough, shortness of breath and breathing difficulties. Some patients may develop into rapid and deadly respiratory system injury with overwhelming inflammation in the lung. Currently, no specific drugs or vaccines are available to cure the patients with COVID-19 pneumonia. Hence, there is a large unmet need for a safe and effective treatment for COVID-19 pneumonia patients, especially the critically ill cases. The significant clinical outcome and well tolerance was observed by the adoptive transfer of allogenic MSCs. We proposed that the adoptive transfer therapy of MSCs might be an ideal choice to be used. We expect to provide new options for the treatment of critically ill COVID-19 pneumonia patients and contribute to improving the quality of life of critically ill patients.
Description: Improvement and recovery time of inflammatory and immune factors
Measure: The immune function (TNF-α 、IL-1β、IL-6、TGF-β、IL-8、PCT、CRP) Time: Observe the immune function of the participants within 4 weeksDescription: Evaluation of Pneumonia change
Measure: Blood oxygen saturation Time: Monitor blood oxygen saturation of the participants within 4 weeksDescription: Marker for efficacy of treatment
Measure: Rate of mortality within 28-days Time: At baseline, Day 1, Day 2, Day 7, Week 2, Week 3, Week 4Description: Evaluation of Pneumonia change
Measure: Size of lesion area by chest imaging Time: At baseline, Day 1, Day 2, Day 7, Week 2, Week 3, Week 4Description: Marker of Immunology and inflammation
Measure: CD4+ and CD8+ T cells count Time: At baseline, Day 1, Day 2, Day 7, Week 2, Week 3, Week 4Description: Degree of infection
Measure: Peripheral blood count recovery time Time: At baseline, Day 1, Day 2, Day 7, Week 2, Week 3, Week 4Description: Indirect response to lung function
Measure: Duration of respiratory symptoms (fever, dry cough, difficulty breathing, etc.) Time: At baseline, Day 1, Day 2, Day 7, Week 2, Week 3, Week 4Description: Clearance time of COVID-19 in participant
Measure: COVID-19 nucleic acid negative time Time: At baseline, Day 1, Day 2, Day 7, Week 2, Week 3, Week 4Trial design: Prospective, multi-centre, randomised, pragmatic, double blind trial Methods: Participants: Adult (>18 years) within 24 hours of admission to intensive care unit with proven or suspected COVID-19 infection, whether or not mechanically ventilated. Exclusion criteria: symptoms of febrile disease for ≥1 week, treatment limitations in place or moribund patients, allergy or intolerance of any study treatment, incl. long QT syndromes, participation in another outcome-based interventional trial within last 30 days, patients taking Hydrochloroquine for other indication than COVID-19, pregnancy. Interventions: Patients will be randomised in 1:1:1 ratio to receive Hydrochloroquine 800mg orally in two doses followed by 400mg daily in two doses and Azithromycin 500 mg orally in one dose followed by 250 mg in one dose for a total of 5 days (HC-A group) or Hydrochloroquine+ placebo (HC group) or placebo + placebo (C-group) in addition to best standard of care, which may evolve during the trial period but will not differ between groups. Objective: To test the hypothesis that early administration of combination therapy slows disease progression and improves mechanical-ventilation free survival. Outcomes: Primary outcome: Composite percentage of patients alive and not on end-of-life pathway who are free of mechanical ventilation at day 14. Secondary outcomes: Composite percentage of patients alive and not on end-of-life pathway who are free of mechanical ventilation at day 14 in the subgroup of patients without the need of mechanical ventilation at baseline. ICU-LOS D28 and D 90 mortality (in hospital) Tertiary (exploratory) outcomes: Viral load at D7 of study enrolment (No of viral RNA copies/ml of blood), proportion of patients alive and rtPCR negative from nasal swab at D14, Difference of FiO2 requirement and respiratory system compliance between day 0 and 7. Randomization: In 1:1:1 ratio and stratified according to study centre and patients age (cut-off 70 years) Blinding (masking): Patients, treating clinicians, outcome assessors and data analyst will be blinded to study treatment allocation. Unblinded study pharmacist or research nurse will prepare investigational products.
Description: Composite percentage of patients alive and not on end-of-life pathway who are free of mechanical ventilation at day 14.
Measure: Proportion of alive patients free off mechanical ventilation Time: 14 days after enrolmentDescription: Composite percentage of patients alive and not on end-of-life pathway who are free of mechanical ventilation at day 14 in the subgroup of patients without the need of mechanical ventilation at baseline.
Measure: Proportion of patients who avoided the need of mechanical ventilation Time: 14 daysDescription: Length of stay in intensive care unit
Measure: ICU LOS Time: 28 daysDescription: Proportion of patients who died by day 28
Measure: Mortality28 Time: 28 daysDescription: Proportion of patients who died by day 90
Measure: Mortality90 Time: 90 daysThe current outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) is a global health emergency with a case fatality rate so far approximately 4% and a growing number of confirmed cases (>57.000) in Germany. There is no data available on the efficacy of antiviral agents for the treatment of COVID-19. In-vitro data show that hydroxychloroquine can inhibit SARS-CoV-2 [1] replication and anecdotal reports from Chinese COVID-19 patients [2, 3] suggest that chloroquine is a good candidate for treatment. No data have been published and reported evidence is based on non-controlled use of hydroxychloroquine. The aim of this placebo-controlled trial is to assess the effect of hydroxychloroquine on duration of symptoms in mild COVID-19 patients and time of virus shedding as an important tool to reduce the risk of further community transmissions. This data will inform practice for the design of larger trials on clinical efficacy of hydroxychloroquine in the treatment and post- and preexposure prophylaxis of COVID-19 and as a tool for reduction of community transmission.
This is a randomized, double-blind, placebo-controlled, multi-center trial to evaluate the safety and efficacy of TJ003234 administered as an intravenous (IV) infusion in subjects with severe COVID-19 under supportive care, and to assess the effect of TJ003234 on the levels of cytokines.
Description: 8-category ordinal scale
Measure: Proportion (%) of subjects experiencing deterioration in clinical status Time: Changes from baseline on Day 14Description: Per CTCAE
Measure: Treatment Emergent Adverse Events Time: Up to 30 days after drug administrationDescription: 8-category ordinal scale
Measure: Proportion (%) of subjects experiencing deterioration in clinical status Time: Changes from baseline on Day 7 and Day 30Description: 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 30Description: 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 30Description: 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 14Description: Defined as SpO2≥94% sustained minimum 24 hours
Measure: Length of time to normalization of oxygen saturation Time: Up to 30 days after drug administrationThis is a phase II, randomised, double-blinded and placebo-controlled clinical trial in healthy adults above 18 years of age. This clinical trial is designed to evaluate the immunogenicity and safety of Ad5-nCoV which encodes for a full-length spike (S) protein of SARS-CoV-2.
The current outbreak of COVID-19 caused by SARS-CoV-2 is a global health emergency with a case fatality rate so far approximately 4% and a growing number of confirmed cases (>9500) in Germany. There is no data available on the efficacy of antiviral agents for the treatment of COVID-19. In vitro data show that hydroxychloroquine can inhibit SARS-CoV-2 replication and anecdotal reports from COVID-19 patients in China and France suggest that chloroquine or hydroxychloroquine is a good candidate for treatment. In the French study a favourable effect was seen when hydroxychloroquine was used together with azithromycin in a small series of COVID-19 patients. However, so far all published evidence is based on non-controlled use of hydroxychloroquine. We propose to conduct a placebo-controlled trial in COVID-19 patients with mild to moderate disease in Germany to assess virological efficacy, tolerability and safety of hydroxychloroquine in the treatment of COVID-19. The objective of this trial is to identify an effect of hydroxychloroquine on viral clearance in vivo. This data will inform practice for the design of larger trials on clinical efficacy of hydroxychloroquine in the treatment and post-exposure prophylaxis of COVID-19.
Description: Viral clearance defined as time to sustained SARS-CoV-2-specific RNA copy number ≤100, measured by real time reverse-transcription polymerase chain reaction RT-PCR in throat swabs.
Measure: Effect of HCQ on in vivo viral clearance Time: 6 monthsThe purpose of this research study is to determine if a drug called fluvoxamine can be used early in the course of the COVID-19 infection to prevent more serious complications like shortness of breath. Fluvoxamine is an anti-depressant drug approved by the FDA for the treatment of obsessive-compulsive disorder. The use of fluvoxamine for the treatment of COVID-19 is considered investigational, which means the US Food and Drug Administration has not approved it for this use. This study is fully-remote, which means that there is no face-to-face contact; study materials including study drug will be shipped to participants' houses. Only residents of Missouri and Illinois may participate.
Description: Clinical worsening is defined meeting both of the following: (1) presence of dyspnea and/or hospitalization for shortness of breath or pneumonia, plus (2) decrease in O2 saturation (<92%) on room air and/or supplemental oxygen requirement in order to keep O2 saturation >92%.
Measure: Time to clinical worsening Time: RCT (approximately 15 days)Description: (1) moderate severity of illness as defined by O2 saturation <92% but no supplemental oxygen requirement; (2) O2 saturation plus supplemental oxygen requirement; (3) O2 saturation <92% plus hospitalization (related to dyspnea/hypoxia); (4) the above, plus ventilator support requirement; (5) the above, plus ventilator support for at least 3 days; (6) death.
Measure: clinical deterioration on a Likert-type scale (1-6) Time: RCT (approximately 15 days)Description: (1) requiring supplemental oxygen; (2) requiring hospitalization; (3) requiring ventilator support.
Measure: clinical deterioration measured by number of days Time: RCT (approximately 15 days)Description: Outcomes will be collected daily, with symptomatic data collected approximately twice daily. The most severe symptom at baseline will be the focus.
Measure: Symptomatic severity on a likert scale (0-10 where 0= none and 10=very severe) Time: RCT (approximately 15 days)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.
Description: Composite of death, Need for mechanical ventilation, or an increase of 2 or more points in the SOFA score
Measure: Critical condition or death Time: 28 daysDescription: Kinetics of circulating IL-6
Measure: IL-6 Time: 14 days in-hospital, hospital discharge, or deathIn this study invetigators propose to administer clazakizumab to patients with life-threatening COVID-19 infection manifest by pulmonary failure and a clinical picture consistent with a cytokine storm syndrome. This is a single-center randomized, double-blind, placebo-controlled trial in which 80 patients will be enrolled and randomly assigned in a 1:1:1 ratio to three study arms and received clazakizumab at a dose of 12.5 mg, 25 mg or placebo. Based on interim analysis, the remaining 10 subjects at NYU will be randomly assigned to a 1:1 ratio to two arms that will receive clazakizumab at a dose of 25 mg or placebo. The NYU site will serve as the central data management site for other centers who undertake this protocol. Other sites will enroll patients based on the two arm 1:1 randomization. 60 patients at outside sites are expected to enroll.
Description: Number of patients who remain alive at time point.
Measure: Patient Survival Time: 28 daysDescription: Number of patients who remain alive at end of study.
Measure: Patient Survival Time: 60 daysThis study will 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.
Description: Documented days free off mechanical ventilation the first 28 days post enrollment
Measure: Number of ventilator-free days Time: Up to 28 daysDescription: Mortality at 28-days by all causes
Measure: All-cause-mortality Time: Up to 28 daysDescription: Number of days free of acute inflammation (defined as CRP >= 10 mg/L)
Measure: Acute-inflammation-free days Time: Up to 28 daysDescription: 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 yearCoronavirus Disease 2019 (COVID-19) is spreading worldwide and has become a public health emergency of major international concern. Currently, no specific drugs or vaccines are available. For severe cases, it was found that aberrant pathogenic T cells and inflammatory monocytes are rapidly activated and then producing a large number of cytokines and inducing an inflammatory storm.Mesenchymal stem cells (MSCs) have been shown to possess a comprehensive powerful immunomodulatory function. This study aims to investigate the safety and efficacy of intravenous infusion of mesenchymal stem cells in severe patients with COVID-19.
Description: Evaluation of pneumonia improvement
Measure: Changes of oxygenation index (PaO2/FiO2) Time: At baseline, 6 hour, Day 1, Day 3,Week 1, Week 2, Week 4, Month 6.Description: Proportion of participants with treatment-related adverse events
Measure: Side effects in the BM-MSCs treatment group Time: Baseline through 6 monthsDescription: Improvement of clinical symptoms including duration of fever, respiratory destress, pneumonia, cough, sneezing, diarrhea.
Measure: Clinical outcome Time: At baseline, 6 hour, Day 1, Day 3,Week 1, Week 2, Week 4, Month 6.Description: days of the patients in hospital
Measure: Hospital stay Time: Baseline through 6 monthsDescription: Evaluation of pneumonia improvement
Measure: CT Scan Time: At baseline, 6 hour, Day 1, Day 3,Week 1, Week 2, Week 4, Month 6.Description: (deep sputum / pharyngeal swab / nasal swab / anal swab / tear fluid / stomach fluid / feces / blood or alveolar lavage fluid)
Measure: Changes in viral load Time: At baseline, 6 hour, Day 1, Day 3,Week 1, Week 2, Week 4, Month 6.Description: Immunological status
Measure: Changes of CD4+, CD8+ cells count and concentration of cytokines Time: At baseline, 6 hour, Day 1, Day 3,Week 1, Week 2, Week 4, Month 6.Description: Marker for efficacy
Measure: Rate of mortality within 28-days Time: From baseline to day 28Description: Markers of Infection
Measure: Changes of C-reactive protein Time: At baseline, 6 hour, Day 1, Day 3,Week 1, Week 2, Week 4, Month 6.The purpose of this study is to determine if a CGRP receptor antagonist may potentially blunt the severe inflammatory response at the alveolar level, delaying or reversing the path towards oxygen desaturation, ARDS, requirement for supplemental oxygenation, artificial ventilation or death in patients with COVID-19 on supplemental oxygen.
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 15To create a protocol for treatment of Pakistani patients with SARS-CoV-2 infection with an intent to reduce burden on institutional healthcare services by determining efficacy of different quinone drug dosing regimens in controlling SARS-CoV-2 infection for asymptomatic patients.
Description: Percentage of patients who become RT-PCR negative with two RT-PCR tests performed at day 6 and day 7
Measure: RT-PCR negative status Time: 6-7 daysDescription: Time to progression to next stage of SARS-CoV-2 disease severity index
Measure: Progression of symptoms Time: 7 daysDescription: Time to onset of fever (temperature greater than 100 degree F), cough, or shortness of breath (respiratory rate >22 per minute).
Measure: Development of Symptoms Time: 7 daysDescription: Drug related adverse events as determined by data safety and monitoring board (DSMB)
Measure: Adverse events Time: 7 daysThis is a proof of concept study to evaluate the efficacy of nitazoxanide (600 mg BID) to treat hospitalized patients with moderate COVID-19.
Description: PCR will be done to evaluate the change in viral load
Measure: Viral load Time: day 1, 4, 7, 14 and 21Description: Time to wean off oxygen supplementation
Measure: Evolution of acute respiratory syndrome Time: 21 daysDescription: WHO Ordinal Scale for Clinical Improvement that measures illness severity over time (0=uninfected; ambulatory, no limitation of activities=1; ambulatory, limitation of activities=2, hospitalized no oxygen therapy=3; hospitalized oxygen by mask or nasal prongs=4; hospitalized non invasive ventilation or high-flow oxygen=5; hospitalized intubation or mechanical ventilation=6; hospitalized ventilation + additional organ support=7; death=8)
Measure: Change in Clinical Condition Time: 21 daysDescription: Time to be discharged from hospital
Measure: Hospital discharge Time: 21 daysDescription: Evaluation of change in acute respiratory syndrome
Measure: Rate of mortality within 21-days Time: 21 daysDescription: Evaluation of change in acute respiratory syndrome
Measure: Need of mechanical ventilation Time: 21 daysThe main purpose of this study is to evaluate the activity of low dose oral selinexor (KPT-330) and to evaluate the clinical recovery, the viral load, length of hospitalization and the rate of morbidity and mortality in participants with severe COVID-19 compared to placebo.
As of 30/03/2020, 715600 people have been infected with COVID-19 worldwide and 35500 people died, essentially due to respiratory distress syndrome (ARDS) complicated in 25% of the with acute renal failure. No specific pharmacological treatment is available yet. The lung lesions are related to both the viral infection and to an intense inflammatory reaction. Because of it's action, as an immunomodulatory agent that can attenuate the inflammatory reaction and also strengthen the antiviral response, it is proposed to evaluate the effectiveness and safety of intravenous immunoglobulin administration (IGIV) in patients developing ARDS post-SARS-CoV2. IGIV modulates immunity, and this effect results in a decrease of pro-inflammatory activity, key factor in the ARDS related to the COVID-19. It should be noted that IGIV is part of the treatments in various diseases such as autoimmune and inflammatory diffuse interstitial lung diseases. In addition, they have been beneficial in the post-influenza ARDS but also have been in 3 cases of post-SARS-CoV2 ARDS. IGIV is a treatment option because it is well tolerated, especially concerning the kidney. These elements encourage a placebo-controlled trial testing the benefit of IGIV in ARDS post-SARS-CoV2.
Description: Sum of the days the patient did not receive VM, but if death occurs before D28, the score is zero
Measure: Ventilator-free days Time: 28 daysDescription: Used to determine the extent of a person's organ function or rate of failure, from 0 to 24, with severity increasing the higher the score
Measure: Sequential Organ Failure Assessment Score Time: Days 1, 3, 7, 14, 21 and 28Description: Ratio of arterial oxygen partial pressure (PaO2 in mmHg) to fractional inspired oxygen (FiO2 expressed as a fraction, not a percentage)
Measure: P/F ratio Time: Days 1, 3, 7, 14, 21 and 28Description: Severity scoring of lung oedema on the chest radiograph
Measure: Radiological score Time: Days 1, 3, 7, 14, 21 and 28Description: Concentration in mg/L
Measure: Biological efficacy endpoints - C-reactive protein Time: Days 1, 3, 7, 14, 21 and 28Description: Concentration in microgram/L
Measure: Biological efficacy endpoints - Procalcitonin Time: Days 1, 3, 7, 14, 21 and 28Description: Number of CD4 HLA-DR+ and CD38+, CD8 lymphocytes
Measure: Immunological profile Time: Up to 28 daysDescription: Use of corticosteroids, antiretroviral, chloroquine
Measure: Number of patients using other treatments for COVID-19 related ARDS Time: Up to 28 daysDescription: Divided in 3 stages, with higher severity of kidney injury in higher stages
Measure: Kidney Disease: Improving Global Outcomes (KDIGO) score and need for dialysis Time: 28 daysDescription: Kidney failure, hypersensitivity with cutaneous or hemodynamic manifestations, aseptic meningitis, hemolytic anemia, leuko-neutropenia, transfusion related acute lung injury (TRALI)
Measure: Occurrence of adverse event related to immunoglobulins Time: 28 daysDescription: Medical research council sum score on awakening
Measure: Occurrence of critical illness neuromyopathy Time: Up to 28 daysDescription: Radiological and clinical context associated with a bacteriological sampling in culture of tracheal secretions, bronchiolar-alveolar lavage or a protected distal sampling
Measure: Occurrence of ventilator-acquired pneumonia Time: Up to 28 daysThis is an international, multicenter, parallel-group, randomized, double-blind, placebo controlled, study in hospitalized adult patients with COVID-19 in the US and other countries with high prevalence of COVID-19. The study is evaluating the effect of dapagliflozin 10 mg versus placebo, given once daily for 30 days in addition to background local standard of care therapy, in reducing disease progression, complications, and all-cause mortality.
Description: Respiratory decompensation New or worsening congestive HF Requirement for vasopressor therapy and/or inotropic or mechanical circulatory support Ventricular tachycardia or fibrillation lasting at least 30 seconds and/or associated with hemodynamic instability or pulseless electrical activity, or resuscitated cardiac arrest Initiation of renal replacement therapy
Measure: Time to first occurrence of either death from any cause or new/worsened organ dysfunction through 30 days of follow up, defined as at least one of the following: Time: Randomization through Day 30Description: Time to death from any cause Time to new/worsened organ dysfunction (as defined in the primary outcome measure) Clinical status at Day 30 for patients still hospitalized and without any worsening organ dysfunction (using points 3 to 5 of a 7-point ordinal scale) Time to hospital discharge
Measure: Hierarchical composite outcome measures: Time: Randomization through Day 30Description: Time to hospital discharge
Measure: Time to hospital discharge Time: Randomization through Day 30Description: Total number of days alive, out of hospital, and/or free from mechanical ventilation
Measure: Total number of days alive, out of hospital, and/or free from mechanical ventilation Time: Randomization through Day 30Description: Total number of days alive, not in the ICU, and free from mechanical ventilation (as defined in the primary outcome measure)
Measure: Total number of days alive, not in the ICU, and free from mechanical ventilation (as defined in the primary outcome measure) Time: Randomization through Day 30Description: Time to death from any cause
Measure: Time to death from any cause Time: Randomization through Day 30Description: Time to new/worsened organ dysfunction
Measure: Time to new/worsened organ dysfunction Time: Randomization through Day 30Description: Time to acute kidney injury (defined as doubling of s-Creatinine compared to baseline)
Measure: Time to acute kidney injury (defined as doubling of s-Creatinine compared to baseline) Time: Randomization through Day 30This is a phase 1 study in healthy subjects to evaluate the safety, tolerability and pharmacokinetics of single (Part A and B) and multiple (Part B) doses of inhaled TD-0903.
Description: Number and severity of treatment emergent adverse events
Measure: Safety and Tolerability of SAD of TD-0903: Adverse Events Time: Day 1 to Day 8Description: Number and severity of treatment emergent adverse events
Measure: Safety and Tolerability of MAD of TD-0903: Adverse Events Time: Day 1 to Day 14Description: Multiple PK variables of TD-0903 will be assessed during SAD and may include, but are not limited to: Area under the plasma concentration-time curve (AUC)
Measure: Pharmacokinetics (PK) of TD-0903 when given as a Single Ascending Dose (SAD): AUC Time: Day 1 through Day 4Description: Multiple PK variables of TD-0903 will be assessed during SAD and may include, but are not limited to: Maximum observed concentration (Cmax)
Measure: Pharmacokinetics (PK) of TD-0903 when given as a Single Ascending Dose (SAD): Cmax Time: Day 1 through Day 4Description: Multiple PK variables of TD-0903 will be assessed during SAD and may include, but are not limited to: Time to reach maximum observed concentration (Tmax)
Measure: Pharmacokinetics (PK) of TD-0903 when given as a Single Ascending Dose (SAD): Tmax Time: Day 1 through Day 4Description: Multiple PK variables of TD-0903 will be assessed during MAD and may include, but are not limited to: Area under the plasma concentration-time curve (AUC)
Measure: Pharmacokinetics (PK) of TD-0903 when given as a Multiple Ascending Dose (MAD): AUC Time: Day 1 through Day 9Description: Multiple PK variables of TD-0903 will be assessed during MAD and may include, but are not limited to: Maximum observed concentration (Cmax)
Measure: Pharmacokinetics (PK) of TD-0903 when given as a Multiple Ascending Dose (MAD): Cmax Time: Day 1 through Day 9Description: Multiple PK variables of TD-0903 will be assessed during MAD and may include, but are not limited to: Time to reach maximum observed concentration (Tmax)
Measure: Pharmacokinetics (PK) of TD-0903 when given as a Multiple Ascending Dose (MAD): Tmax Time: Day 1 through Day 9To treat Pakistani patients with non-life threatening symptomatic SARS-CoV-2 infection with an intent to reduce burden on institutional healthcare services by determining efficacy of different chloroquine and hydroxychloroquine dosing regimens in controlling SARS-CoV-2 infection.
Description: Percentage of patients who become RT-PCR negative with two RT-PCR tests performed at day 6 and day 7
Measure: RT-PCR result Time: 6th and 7th dayDescription: Time to progression to next stage of SARS-CoV-2 disease severity index
Measure: Progression of symptoms Time: 7 daysDescription: Death
Measure: Mortality Time: 30 daysStudy KIN-1901-2001 is a multi-center, adaptive, randomized, double-blind, placebo-controlled study to assess the efficacy and safety of gimsilumab in subjects with lung injury or acute respiratory distress syndrome (ARDS) secondary to COVID-19.
Description: Mortality at Day 43
Measure: Primary endpoint Time: 43 daysDescription: Subjects who die will be assigned "0" ventilator-free days
Measure: Number of ventilator-free days. Time: Day 43RACONA is a prospective trial that will test the hypothesis that nafamostat can lower lung function deterioration and need for intensive care admission in COVID-19 patients. Design: Adult hospitalized COVID-19 patients will be randomized in a prospective double-blind randomized placebo-controlled study to test the clinical efficacy of nafamostat mesylate (administered intravenously) on top of best standard of care. Primary outcome measures: the time-to-clinical improvement, defined as the time from randomization to an improvement of two points (from the status at randomization) on a seven category ordinal scale or live discharge from the hospital, whichever comes first.
Description: Time-to-clinical improvement (time from randomization to an improvement of two points (from the status at randomization) on a 7 category ordinal scale or live discharge from the hospital, whichever came first.
Measure: Time-to-clinical improvement Time: day 1 until day 28Description: Rate of patients showing improvement of 2 points in 7 category ordinal scale (with 7 points the worst)(PubMed ID: 32187464)
Measure: Responders Time: day 1 until day 28Description: Proportion of patients who will progress to critical illness/death
Measure: Critical or dead patients Time: day 1 until day 28Description: Change in pO2/FiO2 ratio over time
Measure: pO2/FiO2 ratio Time: day 1 until day 28Description: Change Sequential organ failure assessment score (SOFA score) over time. The Score ranges from 0 to 24 (with 24 the worst)(PubMed ID: 11594901)
Measure: SOFA score over time Time: day 1 until day 28Description: Duration of hospitalization in survivors (days)
Measure: Hospitalization Time: day 1 until day 28Description: Number of patients who require ventilation
Measure: Mechanical ventilation Time: day 1 until day 28Description: Duration of ventilation (days)
Measure: Mechanical ventilation duration Time: day 1 until day 28Description: Proportion of patients who develop arrhythmia, or myocardial infarction, or other cardiovascular disease not present at the baseline
Measure: Cardiovascular disease Time: day 1 until day 28To test if the medication Hydroxychloroquine will decrease the amount of virus(as measured by PCR) , 7 days after initiation of therapy compared to control patients receiving placebo. The study design is a randomized (5 days of medication v. 5 days of placebo) clinical trial initiated immediately after diagnosis in ambulatory health care workers at University of South Alabama Health, or in ambulatory USA patients. At 7 days after enrollment another nasopharyngeal swab will be taken to measure if the virus is still present. At 10 weeks we will measure immunity from Covid-19 using a single blood sample. It is a phase 2/3 clinical trial.
Description: Nasopharyngeal swab PCR measurement of viral load expressed as the % of negative PCR swabs
Measure: Percentage of virus free subjects Time: 7 days after initiation of trialDescription: Participants will self-report disease severity status as one of the following 5 options; no COVID19 illness (score of 1), COVID19 illness with no hospitalization (score of 2), or COVID19 illness with hospitalization (score of 3), or Covid 19 with care requiring hospitalization (score of 4), or Covid 19 with death (Score of 5) .
Measure: Disease severity Time: 6 daysDescription: Number of subjects in each arm who are hospitalized for Covid 19 infection
Measure: Incidence of hospitalization Time: 14 daysDescription: Number of subjects in each arm who die secondary to Covid-19 infection
Measure: Incidence of Death Time: 70 Days (10 weeks)Description: Number of subjects in each arm who have confirmed Covid-19 infection
Measure: Incidence of confirmed SARS-CoV-2 Detection Time: 14 daysDescription: Number of subjects in each arm who discontinue or withdraw medication use for any reason
Measure: Incidence of all-cause study medication discontinuation or withdrawal Time: 14 daysDescription: Blood tests to determine level of immunity in each subject
Measure: Immunity to Covid-19 Time: 70 days (10 weeks)The rationale of the present clinical trial is that an orally available drug given to outpatients that could reduce the viral burden in the upper respiratory tract could forestall complications of SARS-CoV-2 infection and reduce transmission from one infected individual to another.
Description: To determine whether camostat mesylate reduces SARS-COV-2 viral load in early COVID-19 disease, change from 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 daysDescription: 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 daysDescription: 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 daysDescription: Change of COVID-19 symptom severity from day 0 to day 6 will be assessed with the COVID-19 daily self score tool. Adapted from the FLU-PRO instrument, it consists of 39 items that are answered daily. Items 1-33 are Likert scale questions (rated 0-4) where 0 = not at all and 4 = very much. These items are summed to score the severity of symptoms- where a total score of 132 would indicate the greatest severity of symptoms and a score of 0 would indicate no severity of symptoms. Items 34-38 are also Likert scale questions (rated 0-4) that measure the frequency of specific daily symptoms where 0 = 0 times and 4 = 4 times or more. These items are summed to score the frequency of symptoms- where the highest score for the frequency of symptoms (20) indicates the greatest burden of symptom frequency. The last question (39) asks patients for their highest temperature in Fahrenheit.
Measure: Change in COVID-19 symptom severity Time: 7 daysDescription: Change of COVID-19 symptom severity from day 0 to day 14 will be assessed with the COVID-19 daily self score tool. Adapted from the FLU-PRO instrument, it consists of 39 items that are answered daily. Items 1-33 are Likert scale questions (rated 0-4) where 0 = not at all and 4 = very much. These items are summed to score the severity of symptoms- where a total score of 132 would indicate the greatest severity of symptoms and a score of 0 would indicate no severity of symptoms. Items 34-38 are also Likert scale questions (rated 0-4) that measure the frequency of specific daily symptoms where 0 = 0 times and 4 = 4 times or more. These items are summed to score the frequency of symptoms- where the highest score for the frequency of symptoms (20) indicates the greatest burden of symptom frequency. The last question (39) asks patients for their highest temperature in Fahrenheit.
Measure: Change in COVID-19 symptom severity Time: 14 daysDescription: Change of COVID-19 symptom score from day 0 to day 6 will be assessed with the COVID-19 daily self score tool. Adapted from the FLU-PRO instrument, it consists of 39 items that are answered daily. Items 1-33 are Likert scale questions (rated 0-4) where 0 = not at all and 4 = very much. These items are summed to score the severity of symptoms- where a total score of 132 would indicate the greatest severity of symptoms and a score of 0 would indicate no severity of symptoms. Items 34-38 are also Likert scale questions (rated 0-4) that measure the frequency of specific daily symptoms where 0 = 0 times and 4 = 4 times or more. These items are summed to score the frequency of symptoms- where the highest score for the frequency of symptoms (20) indicates the greatest burden of symptom frequency. The last question (39) asks patients for their highest temperature in Fahrenheit.
Measure: Change in COVID-19 symptom frequency Time: 7 daysDescription: Change of COVID-19 symptom score from day 0 to day 14 will be assessed with the COVID-19 daily self score tool. Adapted from the FLU-PRO instrument, it consists of 39 items that are answered daily. Items 1-33 are Likert scale questions (rated 0-4) where 0 = not at all and 4 = very much. These items are summed to score the severity of symptoms- where a total score of 132 would indicate the greatest severity of symptoms and a score of 0 would indicate no severity of symptoms. Items 34-38 are also Likert scale questions (rated 0-4) that measure the frequency of specific daily symptoms where 0 = 0 times and 4 = 4 times or more. These items are summed to score the frequency of symptoms- where the highest score for the frequency of symptoms (20) indicates the greatest burden of symptom frequency. The last question (39) asks patients for their highest temperature in Fahrenheit.
Measure: Change in COVID-19 symptom frequency Time: 14 daysDescription: Change of COVID-19 symptom score from baseline to day 6 will be assessed with the COVID-19 daily self score tool. Adapted from the FLU-PRO instrument, it consists of 39 items that are answered daily. Items 1-33 are Likert scale questions (rated 0-4) where 0 = not at all and 4 = very much. These items are summed to score the severity of symptoms- where a total score of 132 would indicate the greatest severity of symptoms and a score of 0 would indicate no severity of symptoms. Items 34-38 are also Likert scale questions (rated 0-4) that measure the frequency of specific daily symptoms where 0 = 0 times and 4 = 4 times or more. These items are summed to score the frequency of symptoms- where the highest score for the frequency of symptoms (20) indicates the greatest burden of symptom frequency. The last question (39) asks patients for their highest temperature in Fahrenheit.
Measure: Change in body temperature Time: 7 daysDescription: Change of COVID-19 symptom score from baseline to day 14 will be assessed with the COVID-19 daily self score tool. Adapted from the FLU-PRO instrument, it consists of 39 items that are answered daily. Items 1-33 are Likert scale questions (rated 0-4) where 0 = not at all and 4 = very much. These items are summed to score the severity of symptoms- where a total score of 132 would indicate the greatest severity of symptoms and a score of 0 would indicate no severity of symptoms. Items 34-38 are also Likert scale questions (rated 0-4) that measure the frequency of specific daily symptoms where 0 = 0 times and 4 = 4 times or more. These items are summed to score the frequency of symptoms- where the highest score for the frequency of symptoms (20) indicates the greatest burden of symptom frequency. The last question (39) asks patients for their highest temperature in Fahrenheit.
Measure: Change in body temperature Time: 14 daysDescription: 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 yearThis clinical trial is a randomized, blinded, two arms, placebo controlled, clinical trial to evaluate the safety and efficacy of Mycobacterium w in combination with standard care as per hospital practice to prevent COVID 19 in subjects at risk of getting infected with COVID 19.
Description: To compare proportion of subjects acquiring COVID-19 infection between two arms over the time till 8 weeks from administration of 1st dose
Measure: Number of subject acquiring COVID-19 infection Time: From first dosing to week 1, week 2, week 4, week 8 or at any time during the study till 8 week post first dosing..Description: Any AE / SAE observed during the study.
Measure: Incidence of Adverse Event and Serious Adverse Event (safety and tolerability) Time: Till 8 weeksDescription: Whether administration of Mw prevents development of Upper Respiratory Tract Infection (URTI) symptoms in close contacts of COVID-19 patients.
Measure: Number of subject developing Upper Respiratory Tract Infection (URTI) symptoms Time: From first dosing to week 1, week 2, week 4, week 8 or at any time during the study till 8 week post first dosing.Description: Whether administration of Mw prevents development of severe COVID-19 infection.
Measure: Number of subject developing severe COVID-19 infection based on ordinal scale Time: From first dosing to week 1, week 2, week 4, week 8 or at any time during the study till 8 week post first dosingIt is a multicenter, randomized, placebo-controlled, double-blind study. The study population is defined as subjects diagnosed with lower respiratory tract COVID-19 who require supplemental oxygen ≥2 LPM at the time of randomization.
Description: Percent of subjects improved (1 to 6 where higher score means worse outcome)
Measure: COVID-19 Clinical Classification (CCC) Time: Day 14Description: Percent of subjects return to room air (RTRA)
Measure: Return to room air (RTRA) Time: Day 14Description: time to Improved COVID-19 Clinical Classification 1 to 6 (where higher score means worse outcome)
Measure: Improved COVID-19 Clinical Classification Time: Day 28Description: Percent of subjects RTRA
Measure: Return To Room Air (RTRA) Time: Day 10, 21, 28Description: Time to
Measure: Death (all cause) Time: Day 28Description: Time to
Measure: SARS-CoV-2 RNA undetectable Time: Day 28Description: Percent of subjects discharge
Measure: Percent of subjects discharged Time: Day 14, 21, 28Description: Time to
Measure: Clinical Deterioration Time: Day 28The COVID-19 outbreak is associated with a surge in ICU bed requirement and substantial mortality (estimated between 0.5% and 3.6%). Admission in the intensive care unit (ICU) and need for mechanical ventilation is reportedly associated with an estimated hospital mortality of more than 30%. Furthermore, the surge in ICU bed requirement is a worldwide-shared issue, leading to sub-optimal ICU management. In acute respiratory failure due to COVID-19-related pneumonia, vasoplegia with vascular enlargement inside the lung lesions and dilation of small vessels seen on chest CT scan largely account for severe hypoxemia whose physiological response is hyperventilation leading to hypocapnia. Almitrine, initially described to reduce intrapulmonary shunt by enhancement of hypoxic pulmonary vasoconstriction in combination with inhaled nitric oxide (iNO), redistributes pulmonary blood flow from shunt areas to lung units with normal ventilation/perfusion (VA/Q) ratio. Low dose of intravenous almitrine (2 µg.kg-1.min-1) alone also improves oxygenation (without combination with iNO) by selective pulmonary vasoconstriction of precapillary pulmonary arteries perfusing lung areas exposed to a hypoxic challenge with a slight increase in mean arterial pulmonary. Therefore, our hypothesis is that 5 days of low dose of almitrine therapy may improve the ventilation-perfusion (VA/Q) ratio at a relatively early stage of this specific lung disease and limit respiratory worsening and subsequent need for mechanical ventilation.
Description: Endotracheal intubation within 7 days after randomization Death will be considered as a failure (endotracheal intubation).
Measure: Rate of endotracheal intubation Time: 7 daysDescription: safety assessment: discontinuation rate of the treatment for arterial lactate more than 4 mmol/L, ALT/AST levels greater than 3 times the upper limit, and diagnosis of pulmonary arterial hypertension or acute cor pulmonale documented by echocardiography.
Measure: Discontinuation rate of the treatment Time: 28 daysKerecis 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.
Description: The number of days until participants report no symptoms, which they attribute to COVID-19, will be compared between groups. Symptoms include: Fever (38.0°C or higher), chills, dry cough, cough with rise, shortness of breath (rest), shortness of breath (Exercise), dyspnoea, sore throat, runny nose, headache, myalgia/bone pain, anorexia, nausea, vomiting, loss of smell, osteoporosis, abdominal pain, diarrhea, weakness.
Measure: Number of days until complete resolution of symptoms per group Time: 28 daysDescription: The number of participants admitted to hospital due to deterioration of their condition due to COVID-19 will be compared between groups.
Measure: Number of hospital admissions per group Time: 28 daysDescription: The number of days until participants report a reduction in symptoms, which they attribute to COVID-19, will be compared between groups. Symptoms include: Fever (38.0°C or higher), chills, dry cough, cough with rise, shortness of breath (rest), shortness of breath (Exercise), dyspnoea, sore throat, runny nose, headache, myalgia/bone pain, anorexia, nausea, vomiting, loss of smell, osteoporosis, abdominal pain, diarrhea, weakness.
Measure: Number of days until a reduction in symptoms per group Time: 28 daysDescription: The number of adverse events reported will be compared between groups.
Measure: Number of adverse events per group Time: 28 daysTwo recent studies have suggested that in patients with Covid19, treatment with hydroxychloroquine may shorten the duration of symptoms and improve viral clearance, an effect that appears most pronounce when combined with azithromycin. Hydroxychloroquine treatment may inhibit viral nucleic acid-mediated activation of various innate immune pathways, as well as blockade of lysosomal functions in cell types relevant for viral entry and antigen presentation. The purpose of the study is to determine if oral hydroxychloroquine monotherapy, or in combination with azithromycin results in clinical benefit in patients hospitalized with COVID19 pneumonia.
Description: To demonstrate in patients receiving standard of care that the percentage who achieve clinical response with hydroxychloroquine or hydroxychloroquine and azithromycin is superior to placebo at Day 15
Measure: Percentage of participants who achieve clinical response Time: 15 daysDescription: To demonstrate in patients receiving standard of care that the percentage with viral clearance at Day 15 with hydroxychloroquine or hydroxychloroquine and azithromycin is superior to placebo
Measure: Percentage of Participants with Viral Clearance Time: 15 DaysDescription: To assess in patients receiving standard of care the safety of hydroxychloroquine or hydroxychloroquine and azithromycin compared to placebo
Measure: Number of participants receiving hydroxychloroquine or hydroxychloroquine and azithromycin with adverse events of hydroxychloroquin or hydroxychloroquine and azithromycin compared to placebo Time: 40 daysThis is a randomized, double blind, two arms, placebo controlled, clinical trial to study to evaluate the the safety and efficacy of Mycobacterium w in combination with standard of care versus placebo with standard of care for preventing the progression of COVID-19 disease and for reduction in transfer to ICU in COVID-19 infected patients admitted to the hospital.
Description: To compare the difference in proportion of patients with increased disease severity
Measure: Number of patients with increased disease severity Time: From baseline to Day 3, Day 7, Day 14, Day 21, Day 28 or at any time during the study till 28 days post first dosing.Description: To evaluate safety of Mw in COVID-19 patients admitted to hospital
Measure: Incidence of adverse events and serious adverse events (Safety) Time: Till day 28Description: To compare the proportion of patients discharged from hospital
Measure: Number of COVID-19 patients discharged from hospital Time: From baseline to Day 3, Day 7, Day 14, Day 21, Day 28 or at any time during the study till 28 days post first dosing.Description: To compare the proportion of patients transfer to ICU
Measure: Number of COVID-19 patients transfer to ICU Time: From baseline to Day 3, Day 7, Day 14, Day 21, Day 28 or at any time during the study till 28 days post first dosing.Description: To compare the proportion of patients with reduction in disease severity by 1 ordinal scale
Measure: Number of COVID-19 patients with reduction in disease severity by 1 ordinal scale Time: From baseline to Day 3, Day 7, Day 14, Day 21, Day 28 or at any time during the study till 28 days post first dosing.Description: To compare the proportion of symptom free patients
Measure: Number of of symptom free patients Time: From baseline to Day 3, Day 7, Day 14, Day 21, Day 28 or at any time during the study till 28 days post first dosing.Hydroxychloroquine has been approved by FDA as one of the treatment options for COVID 19.Healthcare personnel are amongst those at highest risk to contract the disease. Several health authorities are now recommending the use of hydroxychloroquine as pre-exposure prophylaxis is in health care personnel. Several studies are on going in this context. However there is a controversy regarding the dosage regimen. This drug has a half life of 22.4 days. In this study we will be comparing three different doses of Hydroxychloroquine and additionally have a control group in order to determine the efficacy of hydroxychloroquine as pre- exposure prophylaxis in healthcare personnel in various doses.
Description: Outcome reported as the percentage of participants in each arm who are COVID-19-free at the end of study treatment
Measure: COVID-19-free survival in experimental arms compared to placebo Time: 12 weeksDescription: Outcome reported as the percent of participants in each arm who have a confirmed SARS-CoV-2 infection during study treatment.
Measure: Incidence of confirmed SARS-COV-2 detection Time: 12 weeksDescription: Outcome reported as the percent of participants in each arm who report COVID-19-related symptoms during study treatment
Measure: Incidence of possible COVID-19 symptoms Time: 12 weeksDescription: Outcome reported as the percent of participants in each arm who discontinue study medication use for any reason during treatment.
Measure: Incidence of all-cause study medicine discontinuation Time: 12 weeksDescription: Participants will self-report COVID-19 status on an ordinal scale as follows: No illness (score=1), Illness with outpatient observation (score=2), Hospitalization (or post-hospital discharge) (score=3), Hospitalization with ICU stay (score 4),Death from COVID 19(score=5) Possible scores range from 1-5 with higher scores indicating greater disease severity.
Measure: Ordinal Scale of COVID-19 Disease maximum severity if COVID-19 diagnosed at study end Time: 12 weeksDescription: Outcome reported as the percent of participants in each arm who are hospitalized or expire due to COVID-19 during study treatment.
Measure: Incidence of Hospitalization for COVID-19 or death Time: 12 weeksDescription: Outcome reported as the percent of participants experiencing any possible adverse events from Hydroxychloroquine
Measure: Incidence of study medication-related adverse events Time: 12 weeksBrief 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.
Description: Progression to ARDS is defined as the need for mechanical ventilation
Measure: Progression to ARDS Time: 28 daysDescription: Blood PO2 as measured by pulse oximetry
Measure: Blood oxygenation Time: 28 daysDescription: 0 = no shortness of breath at all 0.5 = very, very slight shortness of breath = very mild shortness of breath = mild shortness of breath = moderate shortness of breath or breathing difficulty = somewhat severe shortness of breath = strong or hard breathing 7 = severe shortness of breath or very hard breathing 8 9 = extremely severe shortness of breath 10 = shortness of breath so severe you need to stop the exercise or activity
Measure: RDP Dsypnea Scale Time: 28 daysDescription: Distance walked in six minutes
Measure: Distance walked in six minutes Time: 28 daysThis study will enroll 40 symptomatic outpatients tested positive for Coronavirus 2019 (COVID-19). Patients to be randomized 1:1 to Telmisartan (40 mg) vs placebo to be administered orally once daily x 21 days. Daily, the study patients will be asked to keep a record of the severity of their fever, dyspnea and fatigue and take their blood pressure (BP) and temperature. Study visits to occur on day 1 (entry), day 4, day 10 and day 21. Oro-pharyngeal swabs, and approximately 25 cc of blood will be collected at each study visit for safety labs and for the evaluation of the renin-angiotensin system (RAS) system and for various blood biomarkers of inflammation, coagulation and fibrosis.
Description: Based on a modified World Health Organization (WHO) COVID-19 7-point ordinal scale
Measure: Maximum clinical severity of disease Time: Over the 21 day period of studyDescription: Number of adverse events grade 2 and above utilizing the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0, November 2014
Measure: Incidence of treatment emergent adverse events Time: Through study completion at day 21 of studyDescription: Angiotensin I (AngI), AngII, Ang1-9 and Ang1-7
Measure: Renin angiotensin system peptides Time: At each study time point (day 4, day 10, day 21)Description: plasma biomarkers of organ function/coagulation, inflammation, leukocyte chemotaxis, tissue remodeling/fibrosis and immune exhaustion by Luminex multiplexing assays such as TNF-alpha, IL-6, CK-MB, Troponin I, Fractalkine, MCP-1, PD-1, TIMP-1
Measure: Plasma biomarkers Time: At each study time point (day 4, day 10, day 21)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.
Description: Index of therapy success to preserve Intensive Care Hospitalization space
Measure: Proportion of patients who have achieved withdrawal of invasive mechanical ventilation Time: 0-7 daysDescription: To measure global success
Measure: Rate of mortality Time: 28 daysDescription: Index based in the 4 most relevant symptoms and signs: fever, shortness of bread, %Hemoglobin Saturation and PaO2 / FiO2
Measure: Proportion of patients who have achieved clinical response Time: 0-7daysDescription: Evaluation of pneumonia changes
Measure: Proportion of patients who have achieved radiological responses Time: 0-28 daysDescription: Haemogram and cell subpopulations
Measure: Blood white cell counts and their subpopulations. Time: 0-180 daysDescription: Lymphocyte profiles, CD3, CD19, CD16+CD56, CD4/CD8, Tregs
Measure: Cellular markers of inflammation Time: 0-180 daysDescription: IL-10, IL-6, IP-10, TNF-alpha
Measure: Cytokines and chemokines in peripheral blood Time: 0-180 daysUntil the first half of April, Colombia has more than 2,800 infected cases and a hundred deaths as a result of COVID-19, with Antioquia being the third department with the highest number of cases. Official records indicate that, in Colombia, the first case was diagnosed on March 6, 2020, corresponding to a patient from Italy. However, in conversations with several infectologists and intensivists from Medellín, it was agreed that clinical cases similar to the clinical presentation that is now recognized as COVID-19 had arisen since the end of 2019 when it was still unknown to everyone. The previous suggests that the virus was already circulating in the country since before March 6, 2020. But at that moment, there were no tools to make a clinical identification, nor to diagnose it from the laboratory's point of view. Considering as real the hypothesis that the infection has been circulating in the country since before the first official diagnosis, the question arises: Why does not the country still has the same healthcare and humanitarian chaos that countries such as Italy and Spain are suffering at this time? To answer this question may be that there are differences in vaccination rates with BCG (Bacille Calmette-Guérin or tuberculosis vaccine), which is significantly higher in Latin America compared to those in Europe. This finding could explain to some extent the situation in the country, since previous studies have shown the influence that this vaccine can have on the immune response against various other pathogens, including viruses. Among the population at risk of infection, health-care workers due to their permanent contact with patients are the population group with the highest risk of contracting SARS-Cov-2 and developing COVID-19 in any of its clinical manifestations, and currently there are no vaccines or proven preventive interventions available to protect them. For this reason, this research study aims to demonstrate whether the centennial vaccine against tuberculosis (BCG), a bacterial disease, can activate the human immune system in a broad way, allowing it to better combat the coronavirus that causes COVID-19 and, perhaps, prevents the complications that lead the patient to the intensive care unit and death. In the future, and if these results are as expected, they may be the basis for undertaking a population vaccination campaign that improves clinical outcomes in the general population.
Description: Incidence of COVID-19 cases confirmed or probable in the study population
Measure: Primary outcome Time: From date of randomization to 360 day of the studyDescription: Incidence of severe or critical infection in COVID-19 cases
Measure: Secondary outcome Time: From date to diagnosis to 1 month afterDescription: Lethality of the infection in both groups
Measure: Secondary outcome Time: From date to diagnosis to 1 month afterDescription: Assess the safety (frequency, seriousness, and severity of adverse events) of BCG vaccination
Measure: Secondary outcome Time: From date of randomization to 7 day of the studyDescription: Prevalence of SARS-Cov-2 infection
Measure: Secondary outcome Time: At baseline evaluationThis is a randomized, double-blind, placebo-controlled, 29-day, multicenter study to assess the efficacy and safety of ruxolitinib + standard-of-care (SoC) therapy, compared with placebo + SoC therapy, in patients aged ≥12 years with COVID-19 pneumonia.
Description: Efficacy is measured by a composite endpoint of proportion of patients who die, develop respiratory failure [require mechanical ventilation], or require intensive care unit [ICU] care for the treatment of COVID-19.
Measure: Proportion of patients who die, develop respiratory failure [require mechanical ventilation] or require intensive care unit (ICU) care Time: 29 daysDescription: Clinical status is measured with the 9-point ordinal scale. The scoring is - Uninfected patients have a score 0 (no clinical or virological evidence of infection). - Ambulatory patients (not in hospital or in hospital and ready for discharge) can have a score 1 (no limitation of activities) or 2 (limitation of activities). - Hospitalized patients with mild disease can have score 3 (no oxygen therapy defined as SpO2 ≥ 94% on room air) or 4 (oxygen by mask or nasal prongs). - Hospitalized patients with severe disease can have score 5 (non-invasive ventilation or high-flow oxygen), 6 (intubation and mechanical ventilation) or 7 (ventilation + additional organ support - pressors, RRT (renal replacement therapy), ECMO (extracorporeal membrane oxygenation)). - Patients who die have a score 8.
Measure: Clinical status Time: Day 15, Day 29Description: Percentage of patients with at least two points improvement in clinical status on the 9-point ordinal scale.
Measure: Percentage of patients with at least two-point improvement from baseline in clinical status Time: Baseline, Day 15, Day 29Description: Percentage of patients with at least one point improvement in clinical status on the 9-point ordinal scale.
Measure: Percentage of patients with at least one-point improvement from baseline in clinical status Time: Baseline, Day 15, Day 29Description: Percentage of patients with at least one point deterioration in clinical status on the 9-point ordinal scale.
Measure: Percentage of patients with at least one-point deterioration from baseline in clinical status Time: Baseline, Day 15, Day 29Description: Time to improvement from baseline category to one less severe category of the 9-point ordinal scale.
Measure: Time to improvement in clinical status Time: 29 daysDescription: Mean change from baseline in the 9-point ordinal scale.
Measure: Mean change from baseline in the clinical status Time: Baseline, Day 15, Day 29Description: Mortality rate at Day 15 and at Day 29
Measure: Mortality rate Time: Day 15, Day 29Description: Proportion of patients requiring mechanical ventilation
Measure: Proportion of patients requiring mechanical ventilation Time: 29 daysDescription: Duration of hospitalization
Measure: Duration of hospitalization Time: 29 daysDescription: The time to discharge or to a National Early Warning Score 2 (NEWS2) of ≤2 and maintained for 24 hours whichever comes first. The NEWS2 is based on a simple aggregate scoring system in which a score is allocated to physiological measurements, already recorded in routine practice presentation or when a patient is being monitored in hospital. The score ranges from 0 (best) to 23 (worst).
Measure: Time to discharge or to a NEWS2 score of ≤2 Time: 29 daysDescription: The National Early Warning Score 2 (NEWS2) is based on a simple aggregate scoring system in which a score is allocated to physiological measurements, already recorded in routine practice presentation or when a patient is being monitored in hospital. The score ranges from 0 (best) to 23 (worst).
Measure: Change from baseline in NEWS2 score Time: Baseline, Days 3, 5, 8, 11, 15, and 29Description: Change from baseline in peripheral oxygen saturation / fraction of inspired oxygen ratio (SpO2/FiO2 ratio)
Measure: Change from baseline in SpO2/FiO2 ratio. Time: Baseline, Day 15, Day 29Description: No oxygen therapy is required if oxygen saturation is ≥ 94% on room air.
Measure: Proportion of patients with no oxygen therapy Time: Day 15, Day 29The purpose of this study is to test the safety and efficacy of convalescent donor plasma to treat COVID-19 in hospitalized adults in a randomized, placebo-controlled setting. The effect of convalescent plasma will be compared to placebo on clinical outcomes, measured using the COVID Ordinal Outcomes Scale at Day 15, among adults with COVID-19 requiring hospitalization.
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 15Description: All-location, all-cause 14-day mortality
Measure: All-location, all-cause 14-day mortality Time: Baseline to Study Day 14Description: All-location, all-cause 28-day mortality
Measure: All-location, all-cause 28-day mortality Time: Baseline to Study Day 28Description: 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 3Description: 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 8Description: 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 29Description: Number of participants that died or received ECMO
Measure: Composite of death or receipt of ECMO through Day 28 Time: Baseline to Day 28Description: Number of days without use of oxygen
Measure: Oxygen-free days through Day 28 Time: Baseline to Day 28Description: Number of days without use of vasopressors
Measure: Vasopressor-free days through Day 28 Time: Baseline to Day 28Description: Number of days without use of a ventilator
Measure: Ventilator-free days through Day 28 Time: Baseline to Day 28Description: Number of days outside of ICU
Measure: ICU-free days through Day 28 Time: Baseline to Day 28Description: Number of days outside of the hospital
Measure: Hospital-free days through Day 28 Time: Baseline to Day 28Description: Number of participants with Acute kidney injury
Measure: Acute kidney injury Time: Baseline to Day 28Description: Number of participants requiring renal replacement therapy
Measure: Renal replacement therapy Time: Baseline to Day 28Description: Number of participants with documented venous thromboembolic disease (DVT or PE)
Measure: Documented venous thromboembolic disease (DVT or PE) Time: Baseline to Day 28Description: Number of Participants with myocardial infarction or ischemic stroke
Measure: Documented cardiovascular event (myocardial infarction or ischemic stroke) Time: Baseline to Day 28Description: Number of participants with transfusion reaction (fever/rash)
Measure: Transfusion reaction Time: Baseline to Day 28Description: Number of participants with transfusion related acute lung injury (TRALI)
Measure: Transfusion related acute lung injury (TRALI) Time: Baseline to Day 28Description: Number of participants with transfusion associated circulatory overload (TACO)
Measure: Transfusion associated circulatory overload (TACO) Time: Baseline to Day 28Description: Number of participants with transfusion related infection
Measure: Transfusion related infection Time: Baseline to Day 28Hope Biosciences is conducting a research study of an investigational product called allogeneic adipose-derived mesenchymal stem cells (abbreviated as HB-adMSCs) as treatment for patients suspected to have COVID-19. The study purpose is to evaluate the safety and efficacy of four IV infusions of either placebo or HB-adMSCs in subjects with COVID-19.
Description: change from baseline in level of D-dimer (ng/mL)
Measure: D-dimer Time: screening, day 0, 7, 10Description: change from baseline in interleukin-6
Measure: Interleukin-6 Time: screening, day 0, 7, 10Description: Change from baseline in C Reactive protein
Measure: C Reactive protein Time: screening, day 0, 7, 10Description: change from baseline oxygenation (%)
Measure: Oxygenation Time: screening, day 0, 7, 10Description: time to achieve negative PCR test results
Measure: PCR test SARS-CoV-2 Time: Day 0, 3, 7, 10Description: Monitoring for changes in qt interval
Measure: EKG qt interval Time: screening, day 0, 3, 7, 10Description: change from baseline in leukocyte differential
Measure: Leukocyte differential Time: screening, day 0, 7, 10Description: change from baseline in TNF alpha
Measure: TNF alpha Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of glucose in the blood (mg/dL)
Measure: Glucose Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of calcium in the blood (mg/dL)
Measure: Calcium Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of albumin in the blood (g/dL)
Measure: Albumin Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of total protein in the blood (g/dL)
Measure: Total protein Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of sodium in the blood (mol/L)
Measure: Sodium Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of total carbon dioxide in the blood (mmol/L)
Measure: Total carbon dioxide Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of potassium in the blood (mmol/L)
Measure: Potassium Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of chloride in the blood (mmol/L)
Measure: Chloride Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of BUN in the blood (mg/dL)
Measure: BUN Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of creatinine in the blood (mg/dL)
Measure: Creatinine Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of alkaline phosphatase in the blood (IU/L)
Measure: Alkaline phosphatase Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of alanine aminotransferase in the blood (IU/L)
Measure: Alanine aminotransferase Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of total bilirubin in the blood (mg/dL)
Measure: Total bilirubin Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of white blood cells in the blood (x10^3/uL)
Measure: White blood cells Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of red blood cells in the blood (x10^6/uL)
Measure: Red blood cells Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of hemoglobin in the blood (g/dL)
Measure: Hemoglobin Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of hematocrit in the blood (%)
Measure: Hematocrit Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of mean corpuscular volume in the blood (fL)
Measure: Mean corpuscular volume Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of mean corpuscular hemoglobin in the blood (pg)
Measure: Mean corpuscular hemoglobin Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of mean corpuscular hemoglobin concentration in the blood (g/dL)
Measure: Mean corpuscular hemoglobin concentration Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of red cell distribution width in the blood (%)
Measure: Red cell distribution width Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of neutrophils in the blood (%)
Measure: Neutrophils Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of lymphocytes in the blood (%)
Measure: Lymphs Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of monocytes in the blood (%)
Measure: Monocytes Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of eosinophils in the blood (%)
Measure: Eosinophils Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of basophils in the blood (%)
Measure: Basophils Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of absolute neutrophils in the blood (x10^3/uL)
Measure: Absolute neutrophils Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of absolute lymphocytes in the blood (x10^3/uL)
Measure: Absolute lymphs Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of absolute monocytes in the blood (x10^3/uL)
Measure: Absolute monocytes Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of absolute eosinophils in the blood (x10^3/uL)
Measure: Absolute eosinophils Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of absolute basophils in the blood (x10^3/uL)
Measure: Absolute basophils Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of immature granulocytes in the blood (x10^3/uL)
Measure: Immature granulocytes Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of platelets in the blood (x10^3/uL)
Measure: Platelets Time: screening, day 0, 7, 10Description: clinical lab evaluation of time for blood to coagulate (seconds)
Measure: Prothrombin time Time: screening, day 0, 7, 10Description: clinical lab evaluation of international normalized ratio of blood coagulation (no unit)
Measure: INR Time: screening, day 0, 7, 10Description: clinical lab evaluation of percentage of cells CD3- and CD54+ (%)
Measure: NK cell surface antigen (CD3-CD54+) Time: screening, day 0, 7, 10Description: clinical lab evaluation of ratio of CD4+ cells to CD8+ cells (no unit)
Measure: CD4+/CD8+ ratio Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of IL-10 in the blood (pg/mL)
Measure: IL-10 Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of VEGF in the blood (pg/mL)
Measure: VEGF Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of myoglobin in the blood (ng/mL)
Measure: Myoglobin Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of myoglobin in the blood (ng/mL)
Measure: Troponin Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of creatinine kinase in the blood (U/L)
Measure: Creatinine kinase Time: screening, day 0, 7, 10Description: clinical lab evaluation of level of serum ferritin in the blood (ng/mL)
Measure: Serum ferritin Time: screening, day 0, 7, 10Description: incidence of adverse events
Measure: Adverse events Time: screening through day 28Description: change from baseline in ordinal scale score
Measure: 7-point ordinal scale Time: screening, day 0, 3, 7, 10, 28This 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).
Description: Clinical response is defined as survival without ever requiring invasive mechanical ventilation from Day 3 to Day 29 (both inclusive). A patient will be defined as a non-responder if the worst clinical status at any time from Day 3 to Day 29 is score 6, 7 or 8 on a 9-point ordinal scale ranging from 0 up to 8. Scores 6, 7 and 8 in the 9-point ordinal scale are defined as follows: Hospitalized patients with severe disease have score 6 if they need intubation and mechanical ventilation and score 7 if they need ventilation + additional organ support (pressors, renal replacement therapy, extracorporeal membrane oxygenation). Patients who die have score 8.
Measure: Number of patients with clinical response Time: Day 3 to Day 29Description: COVID-19-related death during the 4-week period after study treatment.
Measure: COVID-19-related death rate during the 4-week period after study treatment Time: 4 weeksDescription: Clinical chemistry measurement in a blood sample.
Measure: Ratio to baseline in the C-reactive protein (CRP) Time: Baseline, Day 29Description: Clinical chemistry measurement in a blood sample.
Measure: Ratio to baseline in the serum ferritin Time: Baseline, Day 29Description: Clinical chemistry measurement in a blood sample.
Measure: Ratio to baseline in the D-dimer Time: Baseline, Day 29Description: Safety will be monitored from the canakinumab or placebo dose (Day 1) up to 126 days post-dose (Day 127).
Measure: Number of participants with Adverse Event (AE), serious adverse events (SAE), clinically significant changes in laboratory measures, and vital signs Time: 127 daysThis is a randomised, double-blind, placebo controlled study to evaluate the efficacy and safety of MRx-4DP0004 in patients with COVID-19. 90 hospitalised patients will be enrolled and randomised (2:1) to receive MRx-4DP0004 or placebo for up to 14 days. MRx-4DP0004 is an immunomodulating Live Biotherapeutic Product (LBP) which is expected to prevent or reduce the hyperinflammatory response to SARS-CoV-2 infection without impairing viral clearance.
Description: Clinical status score will be measured using the WHO Ordinal Scale for Clinical Improvement where patients are scored on a scale of 0-8 with 0 being uninfected and 8 being dead
Measure: Change in mean clinical status score in each treatment arm Time: Baseline to Day 42Description: Safety and tolerability will be determined according to clinically relevant reported adverse events
Measure: Number of adverse events in each treatment arm Time: Baseline to Day 42Description: Point changes in clinical status score will be measured using the WHO Ordinal Scale for Clinical Improvement
Measure: Number of patients with an improvement in clinical status score in each treatment arm Time: Day 1 to Day 42Description: Point changes in clinical status score will be measured using the WHO Ordinal Scale for Clinical Improvement
Measure: Number of patients with a deterioration in clinical status score in each treatment arm Time: Day 1 to Day 42Description: Oxygen saturation will be measured as per local standard procedures
Measure: Number of patients with at least 95% oxygen saturation on room air in each treatment arm Time: Day 1 to Day 14Description: Oxygen saturation will be recorded daily during hospitalisation to determine the mean time for each arm to reach at least 95% saturation
Measure: Time to patients with at least 95% oxygen saturation on room air in each treatment arm Time: Day 1 to Day 14Description: The NEWS 2 is based on aggregate scoring of physiological measurements including respiration rate, oxygen saturation, systolic blood pressure, pulse rate, level of consciousness and temperature
Measure: Number of patients with an improvement in the National Early Warning Score (NEWS) 2 in each treatment arm Time: Day 1 to Day 14Description: The NEWS 2 is based on aggregate scoring of physiological measurements including respiration rate, oxygen saturation, systolic blood pressure, pulse rate, level of consciousness and temperature
Measure: Number of patients with an deterioration in the National Early Warning Score (NEWS) 2 in each treatment arm Time: Day 1 to Day 14Description: Details of required respiratory support will be recorded throughout hospitalisation
Measure: Number of patients requiring Continuous Positive Airway Pressure in each treatment arm Time: Day 1 to Day 14Description: Details of required respiratory support will be recorded throughout the treatment period
Measure: Number of patients requiring Intermittent Positive Pressure Ventilation in each treatment arm Time: Day 1 to Day 14Description: Details of required respiratory support will be recorded throughout the treatment period
Measure: Time to patients requiring Continuous Positive Airway Pressure in each treatment arm Time: Day 1 to Day 14Description: Details of required respiratory support will be recorded throughout the treatment period
Measure: Time to patients requiring Intermittent Positive Pressure Ventilation in each treatment arm Time: Day 1 to Day 14Description: Length of hospital stay will be compared
Measure: Time to discharge in each treatment arm Time: Day 1 to Day 42Description: All cause mortality will be compared
Measure: Number of deaths in each treatment arm Time: Day 1 to Day 42This a double-blind, randomized, placebo-controlled clinical trial to determine if primary prophylaxis with hydroxychloroquine in healthcare workers reduces symptomatic COVID-19 infection. Healthcare workers will be randomized at a 1:1 allocation between intervention and placebo arms and followed for 12 weeks. This study will enroll up to 1,700 participates in Lafayette, Louisiana. The primary outcome will number of symptomatic COVID-19 infections. Secondary endpoints included number of days healthcare workers are absent from work and rate of severe infection.
Description: Number of participants who develop symptoms of COVID-19 in the setting of a positive COVID-19 assay
Measure: Incidence of symptomatic COVID-19 infection in healthcare workers Time: 12 weeksDescription: Number of days healthcare workers are absent from work due to symptomatic COVID-19 infection
Measure: Absenteeism from work due to COVID-19 Time: 12 weeksDescription: Rate of severe COVID-19 infection in healthcare works (hypoxia in setting of chest imaging >50% lung involvement, respiratory failure, end organ damage or shock)
Measure: Severity of COVID-19 infection Time: 12 weeksThis 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.
Description: A 6-point ordinal scale ranging from "Death" to "Not hospitalized with full resumption of normal activities" is used to evaluate differences in the clinical status between participants that receive placebo vs hydroxychloroquine
Measure: Clinical Status at Day 5 Assessed by a 6-Point Ordinal Scale Time: Day 5Description: Assess differences in SARS-CoV-2 viral shedding between participants that receive placebo vs hydroxychloroquine
Measure: Number of Participants with Detectable SARS-CoV-2 Virus from Day 0 to Day 28 and at Day 5 Time: Day 0 to Day 28 and at Day 5Description: Assess by incidence of Grade 3, Grade 4, and Serious Adverse Events (AEs)
Measure: Toxicity of Study Drug Assessed by Incidence of Adverse Events Time: Day 0 to Day 28Description: Assess length of hospitalization
Measure: Duration of Initial Hospitalization Time: Day 0 to Day 28Description: Assess number of deaths during study follow-up
Measure: Mortality During Follow-Up Time: Day 0 to Day 28Description: Assess number of deaths in the hospital during initial hospitalization
Measure: Mortality During Initial Hospitalization Time: Day 0 to Day 28Description: Assessing utilization of hospital resources
Measure: Incidence of New Hospital Resource Utilization Time: Day 0 to Day 28Description: Assessing duration of hospital resource utilization
Measure: Duration of Hospital Resource Utilization Time: Day 0 to Day 28Description: Provide preliminary characterization of differences in inflammatory response between participants that receive placebo vs hydroxychloroquine
Measure: Changes in Cytokine Profile Time: Day 0 to Day 28Ideal new treatments for Novel Coronavirus-19 (COVID-19) would help halt the progression disease in patients with mild disease prior to the need for artificial respiration (ventilators), and also provide a rescue treatment for patients with severe disease, while also being affordable and available in quantities sufficient to treat large numbers of infected people. Low doses of Naltrexone, a drug approved for treating alcoholism and opiate addiction, as well as Ketamine, a drug approved as an anesthetic, may be able to interrupt the inflammation that causes the worst COVID-19 symptoms and prove an effective new treatment. This study will investigate their effectiveness in a randomized, blinded trial versus standard treatment plus placebo.
Description: Count of participants initially presenting with mild/moderate disease who progress to requiring advanced oxygenation (high flow nasal canula, non-rebreather, continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), or intubation)
Measure: Progression of oxygenation needs Time: up to 1 monthDescription: Count of participants who develop or experience worsened renal failure as defined by RIFLE criteria, a 5-point scale where the categories are labeled: Risk-Injury-Failure-Loss-End stage renal disease, with Risk being the least severe and End stage renal disease being the most severe. The criteria for determination of stage are factors of serum creatinine and urine output. Numbers of participants worsening one or more RIFLE stages will be reported.
Measure: Renal failure Time: up to 1 monthDescription: Count of participants who develop or experience worsened liver failure as defined by serum transaminases five times normal limits
Measure: Liver failure Time: up to 1 monthDescription: Count of participants who develop cytokine storm as measured by elevated markers of inflammation (elevated D-dimer, hypofibrinogenemia, hyperferritinemia), evidence of acute respiratory distress syndrome (ARDS) measured by imaging findings and mechanical ventilator requirements, and/or continuous fever (≥ 38.1 ° Celsius unremitting)
Measure: Cytokine Storm Time: up to 1 monthDescription: Count of participants who die from COVID-19
Measure: Mortality Time: up to 1 month post hospital dischargeDescription: Length of hospital stay in days
Measure: Length of hospital stay Time: up to 1 monthDescription: Count of patients admitted to the ICU at any time during index hospitalization
Measure: Intensive Care Unit (ICU) admission Time: up to 1 monthDescription: Length of ICU stay in days
Measure: Intensive Care Unit (ICU) duration Time: up to 1 monthDescription: Count of participants requiring intubation
Measure: Intubation Time: up to 1 monthDescription: Length of intubation, measured in days
Measure: Intubation duration Time: up to 1 monthDescription: Time measured in days from hospital admission to determination patient is stable for discharge
Measure: Time until recovery Time: up to 1 monthMulticenter investigation featuring an open-label lead-in followed by a double blinded, randomized, placebo-controlled Phase 2/3 part to evaluate the safety and efficacy of MultiStem therapy in subjects with moderate to severe Acute Respiratory Distress Syndrome (ARDS) due to COVID-19.
This is a Phase 1/2, 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.
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 2Description: Fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain as self-reported on electronic diaries.
Measure: Percentage of participants reporting systemic events Time: For 7 days after dose 1 and dose 2Description: As elicited by investigational site staff
Measure: Percentage of participants reporting adverse events Time: From dose 1 through 1 month after the last doseDescription: As elicited by investigational site staff
Measure: Percentage of participants reporting serious adverse events Time: From dose 1 through 6 months after the last doseDescription: As measured at the central laboratory
Measure: Percentage of sentinel cohort participants with abnormal hematology and chemistry laboratory values Time: 1 day after dose 1Description: As measured at the central laboratory
Measure: Percentage of sentinel cohort participants with abnormal hematology and chemistry laboratory values Time: 7 days after dose 1Description: As measured at the central laboratory
Measure: Percentage of sentinel cohort participants with abnormal hematology and chemistry laboratory values Time: 7 days after dose 2Description: 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 1Description: 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 1Description: 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 2Description: 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 doseDescription: 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 doseDescription: 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 doseDescription: 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 doseDescription: 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 doseDescription: 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 doseDescription: 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 doseDescription: 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 yearsProphylactic treatment in cancer patients undergoing antineoplastic therapy during the COVID-19 pandemic.
Description: assessed by positive polymerase chain reaction (PCR) from routine nasal swabs (performed every 28 days)
Measure: Cumulative number of severe acute respiratory syndrome corona virus 2 (SARS-COV-2) infections Time: 12 weeks after initiation of therapyDescription: defined as combined endpoint of hospitalization rate or death
Measure: Number of severe COVID-19 cases Time: 12 weeks after initiation of therapyDescription: grading as outlined by the world health organization (WHO)
Measure: Severity of COVID-19 cases Time: 12 weeks after initiation of therapyDescription: significant clinical and laboratory abnormalities according to CTCAE criteria
Measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] Time: 12 weeks after initiation of therapyDescription: other than COVID-19
Measure: Number of viral and bacterial infections Time: 12 weeks after initiation of therapyDescription: Development of azithromycin-resistant bacterial strains as assessed by nasal swabs test
Measure: Number of participants with azithromycin-resistant bacterial strains in nasal swabs test Time: 12 weeks after initiation of therapyThis 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.
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 daysDescription: AUC0-tn
Measure: Pharmacokinetic assessments of meplazumab- AUC0-tn Time: 0-28 daysDescription: AUC0-∞
Measure: Pharmacokinetic assessments of meplazumab- AUC0-∞ Time: 0-28 daysDescription: Maximum observed plasma concentration of meplazumab (Cmax)
Measure: Pharmacokinetic assessments of meplazumab-Cmax Time: 0-28 daysTo date, there is no vaccine or treatment with proven efficiency against COVID-19, and the transmissibility of the SARS-CoV-2 virus can be inferred by its identification in the oro-nasopharynx. The bacillus Calmette Guérin (BCG) has the potential for cross-protection against viral infections. This study evaluates the impact of previous (priming effect, from the titer of anti-BCG interferon-gamma) or current BCG exposure (boost with intradermal vaccine) on 1) clinical evolution of COVID-19; 2) elimination of SARS-CoV-2 at different times and disease phenotypes; and 3) seroconversion rate and titration (anti-SARS-CoV-2 IgA, IgM, and IgG).
Description: Classified as mild, moderate and severe
Measure: Clinical evolution of COVID-19 Time: 45 days of symptoms onset or diagnosisDescription: Virus detection by PCR
Measure: SARS-CoV-2 elimination Time: 7 days of symptoms onset or diagnosisDescription: Titration of anti SARS-CoV-2 IgA, IgM and IgG
Measure: Seroconversion rate and titration Time: 7 days of symptoms onset or diagnosisDescription: Classified according to type and severity
Measure: Local and systemic adverse events to BCG vaccination Time: 3 monthsDescription: Virus detection by PCR
Measure: SARS-CoV-2 elimination Time: 21 days of symptoms onset or diagnosisDescription: Titration of anti SARS-CoV-2 IgA, IgM and IgG
Measure: Seroconversion rate Time: 21 days of symptoms onset or diagnosisDescription: Virus detection by PCR
Measure: SARS-CoV-2 elimination Time: 45 days of symptoms onset or diagnosisDescription: Titration of anti SARS-CoV-2 IgA, IgM and IgG
Measure: Seroconversion rate and titration Time: 45 days of symptoms onset or diagnosisThe mortality rate in SARS-CoV-2-related severe ARDS is high despite treatment with antivirals, glucocorticoids, immunoglobulins, and ventilation. Preclinical and clinical evidence indicate that MSCs migrate to the lung and respond to the pro-inflammatory lung environment by releasing anti-inflammatory factors reducing the proliferation of pro-inflammatory cytokines while modulating regulatory T cells and macrophages to promote resolution of inflammation. Therefore, MSCs may have the potential to increase survival in management of COVID-19 induced ARDS. The primary objective of this phase 3 trial is to evaluate the efficacy and safety of the addition of the mesenchymal stromal cell (MSC) remestemcel-L plus standard of care compared to placebo plus standard of care in patients with acute respiratory distress syndrome (ARDS) due to SARS-CoV-2. The secondary objective is to assess the impact of MSCs on inflammatory biomarkers.
Description: Number of all-cause mortality within 30 days of randomization.
Measure: Number of all-cause mortality Time: 30 daysDescription: Number of days alive off mechanical ventilatory support calculated as the number of days, within the 60 days window, that patients were alive and free of mechanical ventilatory support.
Measure: Number of days alive off mechanical ventilatory support Time: 60 daysDescription: Safety analyses will be assessed by adverse event rates calculated as the ratio of the total number of events over 30 days divided by total patient-time at risk for the specific event from randomization.
Measure: Number of adverse events Time: 30 daysDescription: The number and percent of patients with resolution and/or improvement of ARDS at day 7
Measure: Number of participants with resolution and/or improvement of ARDS Time: 7 daysDescription: The number and percent of patients with resolution and/or improvement of ARDS at day 14
Measure: Number of participants with resolution and/or improvement of ARDS Time: 14 daysDescription: The number and percent of patients with resolution and/or improvement of ARDS at day 21
Measure: Number of participants with resolution and/or improvement of ARDS Time: 21 daysDescription: The number and percent of patients with resolution and/or improvement of ARDS at day 30
Measure: Number of participants with resolution and/or improvement of ARDS Time: 30 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: Hospital length of stay
Measure: Length of stay Time: 12 monthsDescription: Change from baseline in Clinical Improvement Scale at day 7. Clinical Improvement Scale full scale from 1 to 7, with higher score indicating more clinical improvement.
Measure: Clinical Improvement Scale Time: 7 daysDescription: Change from baseline in Clinical Improvement Scale at day 14. Full scale from 1 to 7, with higher score indicating more clinical improvement.
Measure: Clinical Improvement Scale Time: 14 daysDescription: Change from baseline in Clinical Improvement Scale at day 21. Clinical Improvement Scale full scale from 1 to 7, with higher score indicating more clinical improvement.
Measure: Clinical Improvement Scale Time: 21 daysDescription: Change from baseline in Clinical Improvement Scale at day 30. Clinical Improvement Scale full scale from 1 to 7, with higher score indicating more clinical improvement.
Measure: Clinical Improvement Scale Time: 30 daysDescription: Changes from baseline in serum hs-CRP concentration at days 7
Measure: Change in serum hs-CRP concentration Time: baseline and 7 daysDescription: Changes from baseline in serum hs-CRP concentration at days 14
Measure: Change in serum hs-CRP concentration Time: baseline and 14 daysDescription: Changes from baseline in serum hs-CRP concentration at days 21
Measure: Change in serum hs-CRP concentration Time: baseline and 21 daysDescription: Changes from baseline in serum hs-CRP concentration at days 30
Measure: Change in serum hs-CRP concentration Time: baseline and 30 daysDescription: Changes from baseline in IL-6 inflammatory marker level at 7 days
Measure: Change in IL-6 inflammatory marker level Time: baseline and 7 daysDescription: Changes from baseline in IL-6 inflammatory marker level at 14 days
Measure: Change in IL-6 inflammatory marker level Time: baseline and 14 daysDescription: Changes from baseline in IL-6 inflammatory marker level at 21 days
Measure: Change in IL-6 inflammatory marker level Time: baseline and 21 daysDescription: Changes from baseline in IL-6 inflammatory marker level at 30 days
Measure: Change in IL-6 inflammatory marker level Time: baseline and 30 daysDescription: Changes from baseline in IL-6 inflammatory marker level at 7 days
Measure: Change in IL-8 inflammatory marker level Time: baseline and 7 daysDescription: Changes from baseline in IL-6 inflammatory marker level at 14 days
Measure: Change in IL-8 inflammatory marker level Time: baseline and 14 daysDescription: Changes from baseline in IL-6 inflammatory marker level at 21 days
Measure: Change in IL-8 inflammatory marker level Time: baseline and 21 daysDescription: Changes from baseline in IL-6 inflammatory marker level at 30 days
Measure: Change in IL-8 inflammatory marker level Time: baseline and 30 daysDescription: Changes from baseline in TNF-alpha inflammatory marker level at 7 days
Measure: Change in TNF-alpha inflammatory marker level Time: baseline and 7 daysDescription: Changes from baseline in TNF-alpha inflammatory marker level at 14 days
Measure: Change in TNF-alpha inflammatory marker level Time: baseline and 14 daysDescription: Changes from baseline in TNF-alpha inflammatory marker level at 21 days
Measure: Change in TNF-alpha inflammatory marker level Time: baseline and 21 daysDescription: Changes from baseline in TNF-alpha inflammatory marker level at 30 days
Measure: Change in TNF-alpha inflammatory marker level Time: baseline and 30 daysThis is a double-blinded, two-arm, randomized, placebo controlled study comparing the virological efficacy of add-on sirolimus with standard care to placebo and standard care. Virological efficacy is defined as the change from baseline to day 7 in SARS-CoV-2 viral burden measured by quantitative real-time polymerase chain reaction.
Description: SARS-CoV-2 viral burden will be quantified for both arms using a qRT-PCR
Measure: Change in SARS-CoV-2 viral burden from baseline to day 7 of treatment Time: Baseline, and days 1, 2, 3, 4, 5, 6, & 7 post-dose for all patientsDescription: SARS-CoV-2 viral burden will be quantified for both arms using a qRT-PCR
Measure: Change in SARS-CoV-2 viral burden at days 1-6 Time: Days 1, 2, 3, 4, 5, and 6 post-dose for all patientsDescription: Safety and tolerability of sirolimus in patients with COVID-19
Measure: Rate of treatment emergent adverse events Time: Days 1, 2, 3, 4, 5, and 6 post-dose for all patientsThe aim of the study is to compare a treatment with doxycycline vs a placebo as soon as the patient is confirmed COVID-19 + and before the onset of oxygen dependence with the aim of reducing or even abolishing the cytokine explosion and thus the evolution towards a serious form of the disease which can lead to death. Three criteria support the rational use of tetrcycline in COVI-19 (1) The coronaviruses is known to bind to metalloproteases (MMPs) of the host, in particular to ensure viral survival. Tetracyclines are known to chelate zinc from MMPs. Their chelating activity may help inhibit COVID19 infection by limiting its ability to replicate in the host. (2) Tetracyclines may also be able to inhibit the replication of positive-polarity single-stranded RNA viruses, such as COVID19 (demonstrated on the dengue virus). (3) In addition, tetracyclines are modulators of innate immunity (anti-inflammatory activity), a property used in the treatment of inflammatory skin diseases for many years. These modulating effects are noted on several targets of innate immunity: They can decrease the expression of NFKB, the release of inflammatory cytokines such as TNF-α, IL-1β and IL-6, inhibit granulomas inflammatory and free radical release. Tetracyclines could therefore participate in limiting the cytokine release induced by COVID19. Their lipophilic nature and their strong pulmonary penetration could allow them to inhibit viral replication.
Description: Percentage of patients with clinical worsening (SaO2 ≤ 93%) after at least 48 hours of treatment
Measure: Percentage of Patients with Clinical Respiratory Aggravation Time: after at least 48 hours of treatmentDescription: Percentage of patients hospitalized after at least 48 hours of experimental treatment
Measure: Percentage of patients hospitalized Time: after at least 48 hours of experimental treatmentDescription: Percentage of patients requiring ventilatory assistance
Measure: Percentage of patients requiring ventilatory assistance Time: Day 0 to Day 28Description: Number of positive SARS-CoV-2 PCR tests on D-1 / D0 and D7 (+/- 2 days)
Measure: Positive SARS-CoV-2 PCR Test Time: Day -1 or day 0 AND Day 7Description: Duration of symptoms (fever, painful symptoms: headache, sore throat, dyspnea)
Measure: Duration of symptoms Time: Day 0 to Day 28Description: Total duration of hospitalization
Measure: Duration of hospitalization Time: From day 0 until to the end of hospitalization or date of death for any cause, whichever came first, assessed up to 3 months after Day0Description: Duration of hospitalization in intensive care or reanimation
Measure: Hospitalization intensive care or reanimation Time: From day 0 until to the end of hospitalization or date of death for any cause, whichever came first, assessed up to 3 months after Day0Description: Duration of mechanical ventilatory assistance
Measure: Duration of mechanical ventilatory assistance Time: to the end of mechanical ventilatory assistance if any, assessed up to 3 months after Day0Description: Percentage of deaths related to SARS-CoV-2 infection
Measure: Percentage of deaths related to SARS-CoV-2 Time: Day 28, or end of hospitalization if any (assessed up to 3 months after Day0)Description: Number of AE / SAE in both arms
Measure: AE / SAE in both arms Time: Day 28, or end of hospitalization if any (assessed up to 3 months after Day0)Blinded, multicenter, placebo-controlled, randomized clinical trial evaluating hydroxychloroquine vs lopinavir/ritonavir vs placebo in early outpatient treatment of adults with COVID-19
Description: Death Hospitalized on mechanical ventilation or extracorporeal membrane oxygenator (ECMO) Hospitalized on supplemental oxygen Hospitalized not on supplemental oxygen Not hospitalized with symptoms and limitation in activity Not hospitalized with symptoms but with no limitation in activity Not hospitalized without symptoms nor limitation in activity symptoms at the milder end of the scale for this outpatient trial
Measure: Modified COVID Ordinal Outcomes Scale: Study Day 15 Time: Day 15Description: Death Hospitalized on mechanical ventilation or ECMO Hospitalized on supplemental oxygen Hospitalized not on supplemental oxygen Not hospitalized with symptoms and limitation in activity Not hospitalized with symptoms but with no limitation in activity Not hospitalized without symptoms nor limitation in activity
Measure: Modified COVID Ordinal Outcome Scale: Study Day 8 Time: Day 8Description: Death Hospitalized on mechanical ventilation or ECMO Hospitalized on supplemental oxygen Hospitalized not on supplemental oxygen Not hospitalized with symptoms and limitation in activity Not hospitalized with symptoms but with no limitation in activity Not hospitalized without symptoms nor limitation in activity Ordinal Scale
Measure: Modified COVID Ordinal Outcome Scale: Study Day 29 Time: Day 29Description: Proportion hospitalized
Measure: Proportion of patients hospitalized: Day 1 to 29 Time: Day 1 to Day 29Description: Number of days from enrollment to hospitalization
Measure: Time to hospitalization Day 1 to Day 29 Time: Day 1 to Day 29Description: Number of days from enrollment to resolution of COVID-19 symptoms
Measure: Time to symptom resolution: Day 1 to Day 29 Time: Day 1 to Day 29Description: Survival status
Measure: All-cause, all-location mortality: Day 1 to Day 29 Time: Day 1 to Day 29Description: Number of Days without oxygen
Measure: Oxygen-free days: Day 1 to Day 29 Time: Day 1 to Day 29Description: Number of days without fever
Measure: Fever-free days: Day 1 to Day 29 Time: Day 1 to Day 29Description: Number of days without ventilator use
Measure: Ventilator-free days: Day 1 to Day 29 Time: Day 1 to Day 29Description: Number of days outside the ICU
Measure: ICU-free days: Day 1 to Day 29 Time: Day 1 to Day 29Description: Number of days outside the hospital
Measure: Hospital-free days: Day 1 to Day 29 Time: Day 1 to Day 29The coronavirus disease-2019 (COVID-19) is spreading throughout the United States. While there are no known therapies to treat those who have become sick, there have been some reports that a medication currently used to treat rheumatoid arthritis, lupus, and malaria (Hydroxychloroquine sulfate, also known as Plaquenil) may help to lessen the chance or severity of illness, especially if combined with a medicine that treats other kinds of infections (Azithromycin, also known as Zithromax or Zmax or Zpak). There are some people who test positive for the virus but who are otherwise not ill. Current standard of care is to advise these people to self-monitor but no treatment is offered. It is not known how many of these individuals will remain symptom free, and how many will become sick or how severe those symptoms will be. This study will randomize those people who do not have symptoms into one of three treatment plans 1) Hydroxycholoquine and Azithromycin, or 2) no active medication (placebo). All participants will be followed for 2 months. The study will determine if there is any benefit to those who are asymptomatic to taking taking Hydroxychloroquine sulfate in combination with Azithromycin, or if there is no benefit from taking these medications.
Description: Change in SARS-CoV-2 viral from baseline to day 6
Measure: The primary outcome is the rate of decline in viral load over the 10 days after randomization Time: 10 daysCoronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Lung failure is the main cause of death related to COVID-19 infection. The main objective of this study is to evaluate if Ibrutinib is safe and can reduce respiratory failure in participants with COVID-19 infection. Ibrutinib is an investigational drug being developed for the treatment of COVID-19. Participants are assigned 1 of 2 groups, called treatment arms. Each group receives a different treatment. There is a 1 in 2 chance that participants will be assigned to placebo. Around 46 adult participants with a diagnosis of COVID-19 will be enrolled at multiple sites in Unites States. Participants will receive oral doses of Ibrutinib or placebo capsules once daily for 4 weeks along with standard care. There 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.
Description: Respiratory failure is defined by clinical diagnosis of respiratory failure and initiation of 1 of the following therapies: Endotracheal intubation and mechanical ventilation OR Extracorporeal membrane oxygenation OR high-flow nasal cannula oxygen delivery OR non-invasive positive pressure ventilation OR clinical diagnosis of respiratory failure with initiation of none of these measures only when clinical decision-making driven is driven solely by resource limitation.
Measure: Percentage of Participants Alive and Without Respiratory Failure Time: Day 28Description: WHO-8 is an 8 point ordinal scale for clinical improvement with scores ranging from 0 (uninfected) through 8 (Death).
Measure: Change in the World Health Organization (WHO)-8 Point Ordinal Scale From Baseline Time: Day 14Description: Time on supplemental oxygen imputed to the maximum number of days on study drug (28) for all points following the death of a participant.
Measure: Median Reduction in Days Spent on Supplemental Oxygen Time: Up to Day 28Description: Percentage of participants with mortality from any cause.
Measure: All-Cause Mortality Time: Up to Day 28Description: Respiratory failure is defined by clinical diagnosis of respiratory failure and initiation of 1 of the following therapies: Endotracheal intubation and mechanical ventilation OR Extracorporeal membrane oxygenation OR high-flow nasal cannula oxygen delivery OR non-invasive positive pressure ventilation OR clinical diagnosis of respiratory failure with initiation of none of these measures only when clinical decision-making driven is driven solely by resource limitation.
Measure: Percentage of Participants Experiencing Respiratory Failure or Death Time: Up to Day 28Description: Percentage of participants alive and not requiring mechanical ventilation.
Measure: Mechanical Ventilation-Free Survival Time: Up to Day 56Description: Defined as number of days from the first day of using mechanical ventilation to the last day of using mechanical ventilation.
Measure: Days on Mechanical Ventilation Time: Up to Day 56Description: The duration of hospitalization is defined as the time in days from the first day of hospitalized to the date of discharge or death.
Measure: Duration of hospitalization Time: Up to Day 56Description: Time to discharge is defined as the time in days from the first day of hospitalized to the date of discharge.
Measure: Time to Discharge Time: Up to Day 56Description: PaO2:FiO2 ratio is an index of respiratory distress.
Measure: Partial Pressure of Oxygen in Arterial Blood (PaO2) to Fraction of Inspired Oxygen (FiO2) Ratio Time: Up to Day 56Description: Oxygenation Index is a parameter of pulmonary function of participants.
Measure: Oxygenation Index Time: Up to Day 56Description: An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent adverse events (TEAEs) are defined as any event that began or worsened in severity on or after the first dose of study drug.
Measure: Number of Participants With Adverse Events Time: Up to Day 56Description: Laboratory abnormalities will be analyzed according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Measure: Number of Participants With Abnormal Laboratory Findings Time: Up to Day 56This 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.
Description: Participants are alive and free of respiratory failure if they are in category 1, 2, 3 or 4 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale is as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized, limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, high-flow oxygen (≥15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death.
Measure: Proportion of participants alive and free of respiratory failure at Day 28 Time: Day 28Description: Number of deaths due to all causes will be assessed.
Measure: Number of deaths due to all causes at Day 60 Time: Day 60Description: Time to death due to all causes will be assessed.
Measure: Time to number of deaths due to all causes at Day 60 Time: Day 60Description: Participants alive and free of respiratory failure if they are in category 1, 2, 3 or 4 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale is as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized, limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, high-flow oxygen (≥15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death.
Measure: Proportion of participants alive and free of respiratory failure at Day 7 Time: Day 7Description: 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 14Description: 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 42Description: 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 60Description: Time will be recorded from dosing to recovery from respiratory failure. Participants are in respiratory failure if they are in category 5 or above from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale is as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized, limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, high-flow oxygen (≥15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death.
Measure: Time to recovery from respiratory failure Time: Day 28Description: Participants are independent of supplementary oxygen if they are in category 1, 2 or 3 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale is as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized, limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, high-flow oxygen (≥15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death.
Measure: Proportion of participants alive and independent of supplementary oxygen at Day 7 Time: Day 7Description: 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 14Description: 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 28Description: Participants are independent of supplementary oxygen if they are in category 1, 2 or 3 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale is as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized, limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, high-flow oxygen (≥15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death.
Measure: Proportion of participants alive and independent of supplementary oxygen at Day 42 Time: Day 42Description: 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 60Description: 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 28Description: For participants not in ICU at time of dosing, the proportion of participants admitted to the ICU prior to Day 28.
Measure: Proportion of participants admitted to Intensive Care Unit (ICU) Time: Day 28Description: 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 28Description: Time from dosing to when a participant is discharged from the hospital.
Measure: Time to final hospital discharge Time: Day 28Description: 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 60The purpose of this study is to evaluate the efficacy and safety of ruxolitinib in the treatment of participants with COVID-19-associated Acute Respiratory Distress Syndrome (ARDS) who require mechanical ventilation.
Description: To evaluate the 28-day mortality rate of ruxolitinib 5 mg BID + SoC therapy and ruxolitinib 15 mg BID + SoC compared with placebo + SoC therapy, in participants with COVID-19-associated ARDS who require mechanical ventilation.
Measure: Proportion of participants who have died due to any cause Time: Up to Day 29Description: Number of days participant did not require mechanical ventilation
Measure: Number of Ventilator free days Time: Day 29Description: Number of days participant is out of the ICU
Measure: Number of ICU free days Time: Day 29Description: Number of days participant did not receive supplemental oxygen
Measure: Oxygen free days Time: Day 29Description: Number of days without use of vasopressor therapy
Measure: Vasopressor free days Time: Day 29Description: Number of days Partcipant is out of the hospital
Measure: Hospital free days Time: Day 29Description: Clinical status of participant at Day 15 and 29 based on participant state. The scale ranges from 0-8 with 0 being no clinical or virological evidence of infection and 8 being dead
Measure: Improvement in the COVID-19 ordinal scale Time: Day 15 and 29Description: SOFA score is a scoring system to determine the extent of a person's organ function or rate of failure. The score is based on 6 different scores, 1 each for the respiratory, cardiovascular, hepatic, coagulation, renal, and neurological systems.
Measure: Change in SOFA Score Time: from baseline to Days 3, 5, 8, 11, 15, and 29Description: Adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug/treatment.
Measure: Number of treatment-related adverse events Time: Day 29The purpose of this study is to assess the safety and efficacy of Alvesco (ciclesonide) Inhalation Aerosol in non hospitalized patients with symptomatic COVID-19 infection in a multicenter, randomized, double-blind, placebo controlled study
At present there is no approved drug treatment for Covid-19. In this study we plan to investigate if an experimental drug called IMU-838 (vidofludimus calcium) can improve your symptoms, prevent worsening that would initiate further treatments such as ventilation, and can lower your virus number if given in addition to your doctor's choice of standard therapy. We will also test if IMU-838 has any side effects and measure the level of IMU 838 in your blood. Experimental drug means that it is not yet authorized for marketing in your country. To date approximately 600 individuals have received IMU-838 (or a drug similar to IMU-838 that contains the same active substance as IMU-838) in research studies.
Description: Clinical
Measure: Proportion of patients without any need* for INV until end-of-study (EoS) Time: Throughout the Study (Day 0 to Day 28)Description: Key Secondary
Measure: Duration of ICU treatment until EoS Time: Throughout the Study (Day 0 to Day 28 )Description: Key Secondary
Measure: 28-day all-cause mortality Time: Throughout the Study (Day 0 to Day 28 )Description: Efficacy: defined as the time from first dose of investigational medicinal product (IMP) to an improvement of at least 2 points on the WHO 9 category ordinal scale , or live discharge from hospital without oxygen supplementation, whichever comes first
Measure: Time to clinical improvement Time: Throughout the Study (Day 0 to Day 28 )Description: Efficacy: Duration of hospitalization (for US sites only: or treatment in special outpatient setting in lieu of hospitalization due to resource restraints)
Measure: Duration of hospitalization Time: Throughout the Study (Day 0 to Day 28 )Description: Efficacy
Measure: Proportion of patients both for all patients and surviving patients free of renal-replacement therapy (RRT)* until EoS Time: Throughout the Study (Day 0 to Day 28 )Description: Efficacy
Measure: Proportion of patients both for all patients and surviving patients free from extracorporeal membrane oxygenation (ECMO)* until EoS Time: Throughout the Study (Day 0 to Day 28 )Description: Efficacy
Measure: Proportion of patients free of INV until Days 6 and 14* Time: Throughout the Study (Day 0 to Day 28 )Description: Efficacy
Measure: Proportion of patients free of RRT until Days 6 and 14* Time: Day 0 to Days 6 and 14Description: Efficacy
Measure: Proportion of patients free ECMO until Days 6 and 14* Time: Day 0 to Days 6 and 14Description: Efficacy
Measure: Proportion of patients with improvement of at least 2 points (from randomization) on the 9-category WHO ordinal scale1 on Days 6, 14, and 28 Time: on Days 6, 14, and 28Description: Efficacy
Measure: Proportion of patients with auxiliary oxygen therapy (including all types of oxygen therapy) on Days 6, 14, and 28 Time: on Days 6, 14, and 28Description: Efficacy
Measure: Proportion of patients with clinical recovery: Axillary temperature ≤36.6 ℃, or oral temperature ≤37.2 ℃, or rectal or tympanic temperature ≤37.8 ℃; Time: Throughout the Study (Day 0 to Day 28 )Description: Efficacy
Measure: Proportion of patients with clinical recovery: Respiratory frequency ≤24 times/min without oxygen inhalation; and Time: Throughout the Study (Day 0 to Day 28 )Description: Efficacy
Measure: Proportion of patients with clinical recovery: Oxygen saturation ≥98% without oxygen inhalation Time: Throughout the Study (Day 0 to Day 28 )Description: Efficacy
Measure: Proportion of patients with clinical improvement, defined as the time from first dose of IMP to an improvement of at least 2 points on the WHO 9 category ordinal scale, or live discharge from hospital without oxygen supplementation, whichever comes first Time: Throughout the Study (Day 0 to Day 28 )Description: Efficacy
Measure: Clinical patient status on the 9-category WHO ordinal scale1 on Days 6, 14, and 28 Time: on Days 6, 14, and 28Description: Efficacy
Measure: Duration of INV Time: Throughout the Study (Day 0 to Day 28 )Description: Efficacy
Measure: Duration of ECMO Time: Throughout the Study (Day 0 to Day 28)Description: Efficacy
Measure: Duration of RRT Time: Throughout the Study (Day 0 to Day 28)Description: Efficacy
Measure: Duration of auxiliary oxygen therapy (including all types of oxygen therapy) Time: Throughout the Study (Day 0 to Day 28)Description: Efficacy
Measure: Duration of hospitalization for survivors Time: Throughout the Study (Day 0 to Day 28)Description: Efficacy
Measure: The rate of ICU* admission on Days 6, 14, and 28 Time: on Days 6, 14, and 28Description: Efficacy
Measure: Hospital-free days Time: Throughout the Study (Day 0 to Day 28)Description: Efficacy
Measure: Time from IMP treatment initiation to death Time: Throughout the Study (Day 0 to Day 28)Description: Efficacy
Measure: Time to first prescription of INV Time: Throughout the Study (Day 0 to Day 28)Description: Efficacy
Measure: Time to first prescription of RRT Time: Throughout the Study (Day 0 to Day 28)Description: Efficacy
Measure: Time to first prescription of ECMO Time: Throughout the Study (Day 0 to Day 28)Description: Efficacy
Measure: Time to first prescription of INV, RRT, and ECMO Time: Throughout the Study (Day 0 to Day 28)Description: Efficacy
Measure: Time to ICU admission Time: Throughout the Study (Day 0 to Day 28)Description: Efficacy
Measure: Cumulative dose of vasoactive therapies and days with vasoactive therapies (daily until Day 14) Time: Day 0 to day 14Description: Efficacy
Measure: Time to clinical recovery Time: Throughout the Study (Day 0 to Day 28)Description: Pharmacokinetics
Measure: Morning trough plasma levels of IMU-838 on Days 0, 1, 2, 3, 6, 14, and 28 Time: on Days 0, 1, 2, 3, 6, 14, and 28Description: Pharmacokinetics
Measure: Correlation of trough levels (quartiles) to selected clinical outcomes (Clinical improvement accoding to WHO criteria) Time: on Days 0, 1, 2, 3, 6, 14, and 28Description: Safety
Measure: Adverse events (AEs) and serious AEs Time: Throughout the Study (Day 0 to Day 28)Description: Safety Height in centimeters will be recorded without shoes. Changes in vital signs judged by the investigator as clinically significant will be reported as an AE.
Measure: Vital signs: height Time: only at ScreeningDescription: Safety Weight in kilograms will be recorded without shoes. Changes in vital signs judged by the investigator as clinically significant will be reported as an AE.
Measure: Vital signs: weight Time: Throughout the Study (Day 0 to Day 28)Description: Safety Body temperature can be measured axillary, oral, rectal or tympanic, but should be always measured by the same method for a patient. Changes in vital signs judged by the investigator as clinically significant will be reported as an AE.
Measure: Vital signs: body temperature (ºC) Time: Throughout the Study (Day 0 to Day 28)Description: Safety Pulse must be measured with the patient in a seated position (if possible), after at least 5 minutes at rest. Changes in vital signs judged by the investigator as clinically significant will be reported as an AE.
Measure: Vital signs: pulse rates, Time: Throughout the Study (Day 0 to Day 28)Description: Safety Blood pressure (systolic and diastolic) must be measured with the patient in a seated position (if possible), after at least 5 minutes at rest. Changes in vital signs judged by the investigator as clinically significant will be reported as an AE.
Measure: Vital signs: systolic and diastolic blood pressures Time: Throughout the Study (Day 0 to Day 28)Description: Safety
Measure: Clinical laboratory parameters: blood chemistry Time: Throughout the Study (Day 0 to Day 28)Description: Safety
Measure: Clinical laboratory parameters: hematology Time: Throughout the Study (Day 0 to Day 28)Description: Safety
Measure: Clinical laboratory parameters: urinalysis Time: Throughout the Study (Day 0 to Day 28)Description: Safety
Measure: 12-lead electrocardiogram: heart rate Time: Day 0 to Day 6 and Day 28Description: Safety
Measure: 12-lead electrocardiogram: PQ-interval Time: Day 0 to Day 6 and Day 28Description: Safety
Measure: 12-lead electrocardiogram: QRS-interval Time: Day 0 to Day 6 and Day 28Description: Safety
Measure: 12-lead electrocardiogram: QT interval Time: Day 0 to Day 6 and Day 28Description: Safety
Measure: 12-lead electrocardiogram: the heart rate-corrected QTc interval (according to Bazett's formula) Time: Day 0 to Day 6 and Day 28Description: Safety
Measure: Temperature Time: Throughout the Study (Day 0 to Day 28)Description: Disease markers
Measure: D-dimer Time: Throughout the Study (Day 0 to Day 28)Description: Disease markers
Measure: Lactate dehydrogenase (LDH) Time: Throughout the Study (Day 0 to Day 28)Description: Disease markers
Measure: C-reactive protein Time: Throughout the Study (Day 0 to Day 28)Description: Disease markers
Measure: Troponin I Time: Throughout the Study (Day 0 to Day 28)Description: Disease markers
Measure: Procalcitonin Time: Throughout the Study (Day 0 to Day 28)Description: Disease markers
Measure: Correlation of disease markers to selected clinical outcomes (Clinical improvement accoding to WHO criteria) Time: Throughout the Study (Day 0 to Day 28)Description: Virologic markers
Measure: Severe Acute Respiratory Syndrome Coronavirus Virus (SARS-CoV-2) mean viral load - log10 copies in spontaneous sputum and nasopharyngeal swab samples: Decrease of SARS-CoV-2 viral load Time: Throughout the Study (Day 0 to Day 28)Description: Virologic markers
Measure: Severe Acute Respiratory Syndrome Coronavirus Virus (SARS-CoV-2) mean viral load - log10 copies in spontaneous sputum and nasopharyngeal swab samples: Time course of SARS-CoV-2 viral load Time: Throughout the Study (Day 0 to Day 28)Description: Virologic markers
Measure: Qualitative virologic clearance in spontaneous sputum and nasopharyngeal swab samples (= 2 consecutive negative SARS-CoV-2 reverse transcriptase polymerase chain reaction tests at least 24 hours apart) Time: Throughout the Study (Day 0 to Day 28)Description: Virologic markers
Measure: Rate of conversion to a negative SARS-CoV-2 (qualitative) test on Days 6, 14 and 28 Time: on Days 6, 14 and 28Description: Virologic markers
Measure: Time to conversion to a negative SARS-CoV-2 (qualitative) test Time: Throughout the Study (Day 0 to Day 28)Description: Biomarkers
Measure: Interleukin (IL)-17 Time: Day 0, 6, 14 and Day 28Description: Biomarkers
Measure: Interleukin (IL)-1ß Time: Day 0, 6, 14 and Day 28Description: Biomarkers
Measure: Interleukin (IL)-6 Time: Day 0, 6, 14 and 28Description: Biomarkers
Measure: interferon gamma (IFNγ) Time: Day 0, 6, 14 and 28Description: Biomarkers
Measure: tumor necrosis factor alpha Time: Day 0, 6, 14 and 28Description: Serologic markers
Measure: Immunoglobulin (Ig)A and IgG antibodies against SARS-CoV-2: • Time to appearance of IgA and/or IgG antibodies Time: Day 0, 6, 14 and 28Description: Serologic markers
Measure: Immunoglobulin (Ig)A and IgG antibodies against SARS-CoV-2: • Proportion of patients with IgA and/or IgG antibodies on Days 6, 14, and 28 Time: Day 0, 6, 14 and 28This study is being done to see if hydroxychloroquine is an effective treatment for COVID-19.
Description: Clinical improvement is defined as a composite endpoint of a two-point clinical improvement on the Ordinal Scale for Clinical Improvement (OSCI). The OSCI is an ordinal scale of 9 severity levels (from 0 to 8) for COVID-19
Measure: Clinical improvement on the Ordinal Scale for Clinical Improvement (OSCI) Time: 14 daysDescription: Clinical improvement is defined as no mechanical ventilation for respiratory failure attributed to SARS-CoV-2 within 14 days of randomization.
Measure: Number of participants requiring mechanical ventilation for respiratory failure Time: 14 daysThe primary objective of the study is to evaluate the efficacy and safety of a single dose of RPH-104 (80 mg) or OKZ (64 mg) compared to placebo in addition to standard therapy in patients with severe SARS-CoV-2 infection (COVID-19) at Day 15 of the study
Description: Proportion of patients, responded to the study therapy, in each of the treatment groups. The patient can be considered as the therapy responder, in case tocilizumab or sarilumab were not administered and there is an improvement of a clinical status at least by 1 point on a 6-points COVID-19 scale, where 1 point means most favorable outcome, 6 points means most undesirable outcome.
Measure: Proportion of patients, responded to the study therapy, in each of the treatment groups Time: Day 15Description: Changes of patients' clinical status on a 6 points ordinal scale over time
Measure: Changes of patients' clinical status on a 6 points ordinal scale over time Time: from Day 2 until Day 15, Day 29Description: Mortality rate over the follow-up period
Measure: Mortality rate over the follow-up period Time: from Day 1 until Day 29Description: Improvement of the patient's clinical status by at least 2 points on a 6-point ordinal scale in the absence of tocilizumab or sarilumab administration.
Measure: Improvement of the patient's clinical status by at least 2 points on a 6-point ordinal scale in the absence of tocilizumab or sarilumab administration. Time: on screening and then from Day 1 until Day 29Description: Proportion of patients received tocilizumab or sarilumab due to COVID-19
Measure: Proportion of patients received tocilizumab or sarilumab due to COVID-19 Time: from Day 1 until the Day 29Description: Proportion of patients having National Early Warning Score 2 (NEWS2) of ≤ 4 maintained for 2 consecutive days
Measure: Proportion of patients having National Early Warning Score 2 of ≤ 4 maintained for 2 consecutive days Time: from day 3 until day 15Description: Time to a NEWS2 of ≤ 2 maintained for two consecutive days
Measure: Time to a NEWS2 of ≤ 2 maintained for two consecutive days Time: from day 1 until day 15Description: Changes from baseline of cytokine storm surrogate markers: white blood counts, lymphocyte counts, neutrophils counts, CRP, ferritin (if applicable), D-dimer (if applicable)
Measure: Changes from baseline of cytokine storm surrogate markers: white blood counts, lymphocyte counts, neutrophils counts, C-Reactive protein (CRP), ferritin (if applicable), D-dimer (if applicable) Time: Day 2, Day 3, Day5, Day 7, Day 15Description: Mortality during an ICU stay, on days 7, 15, 29 of the study
Measure: Mortality during an ICU stay, on days 7, 15, 29 of the study Time: On Day 7, Day 15, Day 29Description: Time to increase of oxygen saturation SpO2 ≥ 94% n the absence of oxygen support maintained for two consecutive days
Measure: Time to increase of oxygen saturation SpO2 ≥ 94% n the absence of oxygen support maintained for two consecutive days Time: from Day 2 until Day 15Description: Changes of oxygenation index PaO2/FiO2 from baseline (if applicable) during hospitalization period
Measure: Changes of oxygenation index PaO2/FiO2 from baseline (if applicable) during hospitalization period Time: On Day 1 and from Day 2 until Day 15Description: Duration of ICU stay measured in days
Measure: Duration of ICU stay measured in days Time: from Day 2 until Day 15Description: Changes from baseline (if applicable) in severity of ARDS according to WHO criteria
Measure: Changes from baseline (if applicable) in severity of Acute Respiratory Distress Syndrome (ARDS) according to World Health Organization (WHO) criteria Time: from Day 1 until Day 15Description: Duration of mechanical ventilation and EMO (if applicable) measured in days
Measure: Duration of mechanical ventilation and Extracorporeal Membrane Oxygenation (EMO) (if applicable) measured in days Time: from Day 2 until Day 15Description: Duration of oxygen support (if applicable) measured in days
Measure: Duration of oxygen support (if applicable) measured in days Time: from Day 1 until Day 15Description: Proportion of patients having National Early Warning Score 2 of ≤ 2 maintained for 2 consecutive days
Measure: Proportion of patients having National Early Warning Score 2 of ≤ 2 maintained for 2 consecutive days Time: from day 3 until day 15Description: Time to a NEWS2 of ≤ 4 maintained for two consecutive days
Measure: Time to a NEWS2 of ≤ 4 maintained for two consecutive days Time: from day 1 until day 15Description: Time to improvement in severity of ARDS according to WHO criteria in one category changing from baseline (if applicable)
Measure: Time to improvement in severity of ARDS according to WHO criteria in one category changing from baseline (if applicable) Time: On Day 1 and from Day 2 until Day 15Description: Time to fever resolution i.e. setting of axillary body temperature <38 °C without antipyretics when measured for 2 consecutive days (if applicable)
Measure: Time to fever resolution i.e. setting of axillary body temperature <38 °C without antipyretics when measured for 2 consecutive days (if applicable) Time: from day 1 until day 15Description: Time to improvement of clinical status by 1 point on a 6-points COVID-19 scale
Measure: Time to improvement of clinical status by 1 point on a 6-points COVID-19 scale Time: from day 1 until day 29Description: Time to improvement of clinical status by 2 points on a 6-points COVID-19 scale
Measure: Time to improvement of clinical status by 2 points on a 6-points COVID-19 scale Time: from day 1 until day 29Description: Proportion of patients with the deterioration of clinical status by 1 point on a 6-points COVID-19 scale during the study
Measure: Proportion of patients with the deterioration of clinical status by 1 point on a 6-points COVID-19 scale during the study Time: from Day 1 until Day 29Description: Proportion of patients with the deterioration of clinical status by 1 point on a 6-points COVID-19 scale during the study, excluding the patients moved to the category 6, if applicable
Measure: Proportion of patients with the deterioration of clinical status by 1 point on a 6-points COVID-19 scale during the study, excluding the patients moved to the category 6, if applicable Time: from Day 1 until Day 29Description: Time to the deterioration of clinical status by 1 point on a 6-points COVID-19 scale during the study (if applicable)
Measure: Time to the deterioration of clinical status by 1 point on a 6-points COVID-19 scale during the study (if applicable) Time: from Day 1 until Day 29The purpose of this study is to evaluate the clinical response of sirukumab (administered as a single intravenous dose) plus standard of care (SOC) compared to placebo plus SOC in COVID-19.
Description: Time to improvement is defined as an improvement of at least 2 categories relative to baseline on the 6-point ordinal clinical recovery scale. The 6-point ordinal clinical recovery scale provides 6 mutually exclusive conditions ordered from best to worst, and the score reflects the participant's worst situation on the day assessed. The ordinal clinical recovery scale categories are : not hospitalized (category 1); Hospitalization; not requiring supplemental oxygen (category 2); hospitalized, requiring low flow supplemental oxygen (category 3); hospitalized, on non-invasive pressure ventilation or high flow oxygen devices (category 4); hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO (category 5); death (category 6).
Measure: Time to Improvement of at Least 2 Categories Relative to Baseline on the 6-Point Ordinal Clinical Recovery Scale Time: Up to Day 28Description: Percentage of participants with an improvement of at Least 2 categories relative to baseline on the 6-point ordinal clinical recovery scale on Day 28 will be reported.
Measure: Percentage of Participants with an Improvement of at Least 2 Categories Relative to Baseline on the 6-Point Ordinal Clinical Recovery Scale on Day 28 Time: Day 28Description: A SAE is any adverse event (AE) that results in: death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect and is a suspected transmission of any infectious agent via a medicinal product, is medically important.
Measure: Percentage of Participants with Serious Adverse Events (SAEs) Time: Up to Day 28Description: An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product.
Measure: Percentage of Participants with Related Adverse Events Time: Up to Day 28Description: Percentage of participants with severe or life-threatening, bacterial, invasive fungal, viral or opportunistic infections (other than severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) will be reported.
Measure: Percentage of Participants with Severe or Life Threatening Bacterial, Invasive Fungal, Viral or Opportunistic Infections Time: Up to Day 28Description: Percentage of participants with grade 3 (severe) or 4 (life-threatening) neutropenia will be reported.
Measure: Percentage of Participants with Grade 3 and 4 Neutropenia Time: Up to Day 28Description: Percentage of participants with grade 3 (severe) or 4 (life-threatening) lymphocytopenia will be reported.
Measure: Percentage of Participants with Grade 3 and 4 Lymphocytopenia Time: Up to Day 28Description: Percentage of participants with increased ALT >=3 times ULN combined with increased bilirubin >2 times ULN (up to Day 28) will be reported.
Measure: Percentage of Participants with Increased Alanine Aminotransferase (ALT) Greater than or equal to 3 Times Upper Limit of Normal (ULN) Combined with Increased Bilirubin > 2 Times ULN Time: Up to Day 28Description: Time to improvement of at least 1 category relative to baseline on the 6-point ordinal clinical recovery scale will be reported.
Measure: Time to Improvement of at least 1 Category Relative to Baseline on the 6-Point Ordinal Clinical Recovery Scale Time: Up to Day 28Description: Percentage of participants with an improvement of at Least 1 category relative to baseline on the 6-point ordinal clinical recovery scale on Day 28 will be reported.
Measure: Percentage of Participants with an Improvement of at Least 1 Category Relative to Baseline on the 6-Point Ordinal Clinical Recovery Scale on Day 28 Time: Day 28Description: Time from study intervention to end of oxygen supplementation is defined as achieving category 1 or 2 on the 6-point ordinal clinical recovery scale.
Measure: Time from Study Intervention to end of Oxygen Supplementation Time: Up to Day 28Description: Time from study intervention to hospital discharge among the surviving participants will be reported.
Measure: Time from Study Intervention to Hospital Discharge Among the Surviving Participants Time: Up to Day 28Description: Total length of hospitalization (days from admission to hospital discharge) among the surviving participants will be reported.
Measure: Total Length of Hospitalization Time: Up to Day 28Description: Percentage of participants with all-cause mortality will be reported.
Measure: Percentage of Participants with All-cause Mortality Time: Up to Day 28Description: Number of Ventilation free Days will be reported.
Measure: Number of Ventilation Free Days Time: Up to Day 28Description: Participant's clinical status at Day 7, 14, 21, 28 will be assessed by 6-point ordinal clinical recovery scale.
Measure: Participant's Clinical Status at Day 7, 14, 21, 28 as Assessed by 6-Point Ordinal Clinical Recovery Scale Time: Day 7, 14, 21, 28Description: Total time on invasive mechanical ventilation will be reported.
Measure: Total Time on Invasive Mechanical Ventilation Time: Up to Day 28Description: Percentage of participants with a 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 28Description: Percentage participants on ECMO over time will be reported.
Measure: Percentage of Participants on Extracorporeal Membrane Oxygenation (ECMO) Over Time Time: Up to Day 28Description: Total time on ECMO will be reported.
Measure: Total Time on ECMO Time: Up to Day 28Description: Percentage of alive participants at Day 28, Week 8 and Week 16 will be reported.
Measure: Percentage of Alive Participants at Day 28, Week 8 and Week 16 Time: Day 28, Week 8 and Week 16Description: Percentage of alive participants that required readmission (if previously discharged) at Week 8 and Week 16 will be reported.
Measure: Percentage of Alive Participants that Required Readmission at Week 8 and Week 16 Time: Week 8 and Week 16Description: A SAE is any adverse event (AE) that results in: death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect and is a suspected transmission of any infectious agent via a medicinal product, is medically important.
Measure: Percentage of Participants with Serious Adverse Events (SAEs) Time: Up to Week 16In this study, the investigators propose to administer clazakizumab to patients with life-threatening Coronavirus Disease 2019 (COVID-19) infection manifest by pulmonary failure and a clinical picture consistent with a cytokine storm syndrome. This is a single-center randomized, double-blind, placebo-controlled trial in which 30 patients will be enrolled and randomly assigned in a 1:1 ratio to two study arms and receive clazakizumab at a dose of 25 mg or placebo.
Description: Number of participants alive at day 28.
Measure: Patient Survival Time: 28 daysDescription: Number of participants alive at day 60, end of study.
Measure: Patient Survival Time: 60 daysThe purpose of this study is to demonstrate the superiority of Polyoxidonium®, lyophilizate for solution for injections and topical application, 6 mg over placebo in hospitalized patients with coronavirus disease (COVID-19). This is a multicentre prospective, randomized, double-blind, placebo-controlled, parallel-group phase IIb\IIIa clinical trial.
Description: The primary efficacy outcome will be defined based on the blinded analysis of data of the first 100 patients in the 1st part of the study. There is uncertainty about the clinical course and potential different trajectories according to baseline disease severity, so the day of the primary endpoint may be modified based on a blinded evaluation of the primary efficacy outcome in various days.
Measure: Clinical status of the patient (according to 7-point ordinal scale) Time: Day 15Description: Time to improvement by one category from admission on the ordinal scale. Clinical status of the patient. Average change in the ordinal scale from baseline.
Measure: Clinical status of the patient (according to 7-point ordinal scale) Time: Clinical status of the patient and the average change in the ordinal scale from baseline, both on days 3, 5, 8, 11, 29.Description: The time to discharge or to a NEWS of ≤ 2 and maintained for 24 hours, whichever occurs first. Change in NEWS from baseline.
Measure: NEWS Time: Change in NEWS from baseline on days 3, 5, 8, 11, 15, 29.Description: Oxygenation free days. Incidence and duration of new oxygen use.
Measure: Oxygenation Time: Oxygenation free days in the first 28 days (to day 29). Incidence and duration of new oxygen use during the study.Description: Ventilator free days. Incidence and duration of new mechanical ventilation use.
Measure: Mechanical Ventilation Time: Ventilator free days in the first 28 days (to day 29). Incidence and duration of new mechanical ventilation use during the trial.The researchers are doing this study to find out whether the study drug hydroxychloroquine can prevent infection with the COVID-19 virus, compared with placebo, in people who are receiving radiation therapy for their cancer. The placebo used in this study is a tablet that looks the same as the study drug and is taken in the same way, but it does not contain any active ingredients.
Description: Any patients who are enrolled and subsequently test positive for SARS-CoV-2 by RT-PCR (outside RT-PCR test results allowed) at any point during the 9 weeks following enrollment will be an event that is considered in the 9-week SARS-CoV-2 infection rate primary endpoint.
Measure: cumulative incidence of SARS-CoV-2 infection Time: within 9 weeks from randomizationDescription: Patients who are positive for SARS-CoV-2 (as defined above) who develop a new oxygen requirement attributable to COVID-19, tachypnea (RR > 20), or those who require hospitalization due to COVID-19 will be considered to have severe COVID-19.
Measure: cumulative incidence of severe COVID-19 or death Time: within 12 weeks of randomizationAgent Name and Study Duration ArtemiC is a medical spray comprised of Artemisinin (6 mg/ml), Curcumin (20 mg/ml), Frankincense (=Boswellia) (15 mg/ml) and vitamin C (60 mg/ml) in micellar formulation for spray administration. Patients will receive up to 6 mg Artemisinin, 20 mg Curcumin, 15 mg Frankincense and 60 mg vitamin C given daily as an add-on therapy (in addition to standard care) in two divided doses, on Days 1 and 2. Patients will be randomized in a manner of 2:1 for study drug (ArteminC) and Standard of Care to Placebo and Standard of Care. Patient follow-up will last 2 weeks. During this time, patients will be monitored for adverse events. Additional time will be required for follow up (until hospital discharge) in order to check side effects and study drug efficacy. Placebo, composed of the same solvent but without active ingredients, will be given in the placebo group as add-on therapy, 2 times a day, on Days 1 and 2. Overall rationale A preparation of ArtemiC, comprising Artemisinin, Curcumin, Boswellia, and Vitamin C in a nanoparticular formulation, is proposed as a treatment for the disease associated with the novel corona virus SARS-CoV-2. It is readily available in light of its status as a food supplement. This initiative is presented under the urgent circumstances of the fulminant pandemic caused by this lethal disease, which is known as COVID-19 and has spread across the globe causing death and disrupting the normal function of modern society. The grounds for the proposal are rooted in existing knowledge on the components and pharmacological features of this formulation and their relevance to the current understanding of the disease process being addressed. Leading among these considerations are well established immuno-modulatory activities of the active ingredients as established in vitro and in vivo and published over the years. These activities as apparent, for example, in diminishing activity of TNF alpha and IL-6 levels are acknowledged to be relevant to the pathophysiology processes involved in the progressive form of COVID-19. The active agents have in addition prominent anti-oxidant, anti-inflammatory as well as anti-aggregant and anti-microbial activities. Based on these activities and observations in animal models, together with clinical experience of the separate ingredients and in various combinations in other contexts it is proposed to evaluate their effect in the context of COVID-19. Study Purpose This study is designed to evaluate the safety and efficacy of ArtemiC on patients diagnosed with COVID-19. Methodology 50 adult patients who suffer from COVID-19 infection studied in parallel groups treated with active agent or placebo as add on to standard care. Safety will be assessed through collection and analysis of adverse events, blood and urine laboratory assessments and vital signs.
Description: patient will be assessed using a scoring table for changes in clinical signs
Measure: Time to clinical improvement, defined as a national Early Warning Score 2 (NEWS2) of = 2 Maintained for 24 Hours in comparison to routine treatment Time: 24 hoursDescription: Adverse events caused by the study drug will be assessed
Measure: Percentage of participants with definite or probable drug related adverse events Time: 14 daysThe primary objective of this study is to evaluate if the addition of zanubrutinib to supportive care increases the respiratory failure-free survival rate at Day 28 in participants hospitalized for Corona Virus Disease 2019 (COVID-19) and pulmonary distress.
Description: Respiratory failure-free survival rate 28 is defined as the proportion of patients who have not had respiratory failure nor died <= 28 days from randomization.
Measure: Respiratory failure-free survival rate at day 28 Time: 28 DaysDescription: This scale evaluates the safety and efficacy of investigational therapeutic agents in combination with care for the treatment of hospitalized participants suffering from COVID-19 infections on a scale of scores from 0 to 8, with higher scores indicating higher level of severity of the disease. (0 = No clinical or virological evidence of disease, and 8 = Death)
Measure: Change from Baseline to Day 14 in WHO - 8 Point Ordinal Scale Time: Up to 28 DaysThe study is a randomized controlled, open-label trial comparing subcutaneous Zilucoplan® with standard of care to standard of care alone. In the active group, Zilucoplan® will be administered subcutaneously once daily for 14 days or till discharge from the hospital, whichever comes first. The hypothesis of the proposed intervention is that Zilucoplan® (complement C5 inhibitor) has profound effects on inhibiting acute lung injury post COVID-19, and can promote lung repair mechanisms, that lead to a 25% improvement in lung oxygenation parameters. This hypothesis is based on experiments performed in mice showing that C5a blockade can prevent mortality and prevent ARDS in mice with post-viral acute lung injury. Eligible patients include patients with confirmed COVID-19 infection suffering from hypoxic respiratory failure defined as O2 saturation below 93% on minimal 2l/min O2 therapy and/or ratio PaO2/FiO2 below 350.
Description: defined by Pa02/FiO2 ratio while breathing room air, P(Aa)O2 gradient and a/A pO2 ratio
Measure: Mean change in oxygenation Time: at predose, day 6 and day 15 (or at discharge, whichever comes first)Description: defined by Pa02/FiO2 ratio while breathing room air, P(Aa)O2 gradient and a/A pO2 ratio
Measure: Median change in oxygenation Time: at predose, day 6 and day 15 (or at discharge, whichever comes first)Description: 6-point ordinal scale defined as Death Hospitalized, on invasive mechanical ventilation or ECMO; Hospitalized, on non-invasive ventilation Hospitalized, requiring supplemental oxygen Hospitalized, not requiring supplemental oxygen Not hospitalized
Measure: mean change in 6-point ordinal scale change Time: between day 1 and respectively day 6, day 15 (or discharge, whichever comes first) and day 28 (by phone call).Description: defined as independence from supplemental oxygen
Measure: Time since randomization until improvement in oxygenation Time: during hospital admission (up to 28 days)Description: defined as SpO2 < 93% breathing room air or the dependence on supplemental oxygen
Measure: Number of days with hypoxia Time: during hospital admission (up to 28 days)Description: defined as 37.1°C or more
Measure: Number of days with fever Time: during hospital admission (up to 28 days)Description: 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 firstDescription: 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 firstDescription: 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 firstDescription: SOFA score: 0 (best) - 24 (worse)
Measure: Mean change of SOFA score between day 1 and day 6 (or on discharge, whichever is first) Time: day 1, day 6 or on discharge, whichever is firstDescription: SOFA score: 0 (best) - 24 (worse)
Measure: Mean change of SOFA score between day 1 and day 15 or on discharge, whichever is first) Time: day 1, day 15 or on discharge, whichever is firstDescription: 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 firstDescription: 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 firstDescription: 6-point ordinal scale: Death Hospitalized, on invasive mechanical ventilation or ECMO; Hospitalized, on non-invasive ventilation or high flow oxygen devices; Hospitalized, requiring supplemental oxygen Hospitalized, not requiring supplemental oxygen Not hospitalized
Measure: Percentage of patients reporting each severity rating on a 6-point ordinal scale at randomization, day 6 and 15 (or discharge, whichever comes first) and day 28 (phone call) Time: day 1, day 6, day 15 (or discharge, whichever comes first)Description: 6-point ordinal scale: Death Hospitalized, on invasive mechanical ventilation or ECMO; Hospitalized, on non-invasive ventilation or high flow oxygen devices; Hospitalized, requiring supplemental oxygen Hospitalized, not requiring supplemental oxygen Not hospitalized
Measure: 6-point Ordinal Scale at 6 and 15 days (or discharge whichever comes first) and day 28 (phone call), in relation to serum D-dimers and complement C5a levels at randomization Time: day 1, day 6, day 15 (or discharge, whichever comes first)Description: 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)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)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 weeksA multicenter randomized, double-blind, placebo-controlled clinical trial of Convalescent SARS COVID-19 plasma versus Placebo to evaluate the effect between arms on an ordinal score of six mutually exclusive categories of clinical status at day 30 after study initiation.
Description: Ordinal outcome with six mutually exclusive categories to describe the patient's clinical status during follow-up. The six categories are: (1) death; (2) in intensive care; (3) hospitalised but requiring supplemental oxygen; (4) hospitalised and not requiring supplemental oxygen; (5) discharged but unable to resume normal activities; or (6) discharged with full resumption of normal activities.
Measure: Clinical status during follow-up at 30th day Time: 30th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)Description: Ordinal outcome with six mutually exclusive categories to describe the patient's clinical status during follow-up. The six categories are: (1) death; (2) in intensive care; (3) hospitalised but requiring supplemental oxygen; (4) hospitalised and not requiring supplemental oxygen; (5) discharged but unable to resume normal activities; or (6) discharged with full resumption of normal activities.
Measure: Clinical status during follow-up at 7th day Time: 7th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)Description: Ordinal outcome with six mutually exclusive categories to describe the patient's clinical status during follow-up. The six categories are: (1) death; (2) in intensive care; (3) hospitalised but requiring supplemental oxygen; (4) hospitalised and not requiring supplemental oxygen; (5) discharged but unable to resume normal activities; or (6) discharged with full resumption of normal activities.
Measure: Clinical status during follow-up at 14th day Time: 14th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)Description: Hospital discharge or intrahospital death
Measure: Time until hospital discharge (days). Time: Whenever the patient is discharge from the hospital or die without discharge, through study completion, an average of 14 days from admissionDescription: ICU discharge or ICU death
Measure: Time until discharge from ICU (days) Time: Whenever the patient is discharge from ICU or die in ICU, through study completion, an average of 10 days from admissionDescription: Death and time to death
Measure: Time to death Time: In a 30 days follow up periodDescription: Time until complete functional recovery (according to basal status).
Measure: Time until complete functional recovery Time: Whenever the patient returns to basal functional status until 1 month from dischargeDescription: Percentage of participants with adverse events / serious adverse events
Measure: Percentage of participants with adverse events / serious adverse events Time: In a 30 days follow up periodDescription: Percentage of patients with negative SARS-CoV-3 PCR
Measure: Percentage of patients with negative SARS-CoV-3 PCR at Day 14th Time: 14th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)Description: D Dimer plasma concentration
Measure: D Dimer plasma concentration at Day 14th Time: 14th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)Description: Ferritin plasma concentration
Measure: Ferritin plasma concentration at Day 13th Time: 13th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)Description: Plasma concentration of neutralizing antibodies
Measure: Plasma concentration of neutralizing antibodies at Day 2nd Time: 2nd Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)Description: Plasma concentration of neutralizing antibodies
Measure: Plasma concentration of neutralizing antibodies at Day 7th Time: 7th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)Description: Post-transfusion adverse reactions between study groups
Measure: Post-transfusion adverse reactions Time: In a 30 days follow up periodThe purpose of this research study is to evaluate the safety and potential efficacy of Intravenous Infusion of Organicell Flow for treatment of moderate to severe Acute Respiratory Syndrome (SARS) related to COVID-19 infection vs Placebo.
Description: Safety will be defined by the incidence of any infusion associated adverse events as assessed by treating physician
Measure: Incidence of any infusion associated adverse events Time: 60 DaysDescription: Safety will be defined by the incidence of severe adverse events as assessed by treating physician
Measure: Incidence of Severe Adverse Events Time: 60 DaysDescription: Measured at day 60 or at hospital discharge, whichever comes first.
Measure: All Cause Mortality Time: 60 DaysDescription: Number of participants that are alive at 60 days post first infusion follow up
Measure: Survival Rate Time: 60 DaysDescription: Measure IL-6, IL-2, TNF-alpha from serum of blood samples
Measure: Cytokine Levels Time: Day 0, Day 4, Day 8, Day14, Day 21, Day 28Description: D-dimer from serum of blood samples methodology using blood samples or nose / throat swab
Measure: D-dimer Levels Time: Day 0, Day 4, Day 8, Day14, Day 21, Day 28Description: CRP from serum of blood samples
Measure: C-reactive protein Levels Time: Day 0, Day 4, Day 8, Day14, Day 21, Day 28Description: Viral load by real time RT methodology using blood samples or nose / throat swab
Measure: Quantification of the COVID-19 Time: Day 0, Day 4, Day 8Description: Improved organ failure within 30 days, including cardiovascular system, coagulation system, liver, kidney and other extra-pulmonary organs using Sequential Organ Failure Assessment (SOFA) score.
Measure: Improved Organ Failure Time: Day 30Description: Chest imaging changes for 30 days compare to placebo: 1) Ground-glass opacity, - 2) Local patchy shadowing, 3) Bilateral patchy shadowing, and 4) Interstitial abnormalities.
Measure: Chest Imaging Changes Time: Day o, Day 30SNG001 is an inhaled drug that contains a antiviral protein called interferon beta (IFN-β). IFN-β in produced in the lungs during viral lung infections. It has been shown that older people and people with some chronic diseases have an IFN-β deficiency. Many viruses inhibit IFN-β as part of their strategy to evade the immune system. Addition of IFN-β in vitro protects lung cells from viral infection. IFN-β protects cells against the MERS and SARS coronaviruses (close relatives of SARS-CoV-2, the virus that causes COVID-19). SNG001 is an inhaled formulation of interferon beta-1a it is currently in Phase II clinical trials for COPD patients. Synairgen has conducted randomised placebo controlled clinical trials of SNG001 involving >200 asthma and COPD patients. These trials have shown that SNG001 has: - been well tolerated during virus infections - enhanced antiviral activity in the lungs (measured in sputum and blood samples) - provided significant lung function benefit over placebo in asthma in two Phase II trials. Synairgen believes SNG001 could help prevent worsening or accelerate recovery of severe lower respiratory tract illness in COVID-19 patients. Patients who are in hospital or non-hospitalised but are a high risk groups (e.g. elderly or diabetics) will be invited to take part in the trial. The patient would receive either SNG001 or placebo once daily for 14 days. The severity of the patients condition would be recorded on a scale developed by the World Health Organisation and the patient would be asked questions about their breathlessness, cough and sputum every day, as well as assess their general medical condition and safety. If SNG001 proves to be beneficial it would be a major breakthrough for the treatment of COVID-19.
Description: Change in condition measured using the Ordinal Scale for Clinical Improvement during the dosing period - minimum of 0 (patient is well) to a maximum of 8 (death)
Measure: Ordinal Scale for Clinical Improvement Time: Day 1 to day 28Description: 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 28Description: 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 28Description: Time to clinical improvement
Measure: Time to clinical improvement Time: Time to hospital discharge OR Time to NEWS2 of ≤ 2 maintained for 24 hoursDescription: NEWS2 assessment of acute-illness severity on a scale of 0 ( being well) up to 24 (requiring emergency response)
Measure: National Early Warning Score 2 (NEWS2) assessment of acute-illness severity Time: Day 1 to day 28Description: Changes in daily breathlessness, cough and sputum scale (BCSS) on a scale of 0 (no symptoms) up to 4 (severe symptoms)
Measure: Changes in daily breathlessness, cough and sputum scale (BCSS) Time: Day 1 to day 28Description: Looking at blood pressure measured in mmHg
Measure: Safety and tolerability - blood pressure II. Viral load Time: Day 1 to day 28Description: Looking at heart rate measured in beats per minute
Measure: Safety and tolerability - heart rate II. Viral load Time: Day 1 to day 28Description: Looking at temperature measured in degrees Celsius
Measure: Safety and tolerability - temperature II. Viral load Time: Day 1 to day 28Description: Looking at respiratory rate measure in breaths per minute
Measure: Safety and tolerability - respiratory rate II. Viral load Time: Day 1 to day 28Description: Looking at oxygen levels measured in a %
Measure: Safety and tolerability - oxygen saturation II. Viral load Time: Day 1 to day 28Description: Looking at adverse events (numbers and terms)
Measure: Safety and tolerability - adverse events II. Viral load Time: Day 1 to day 28Description: Looking at concomitant medications given during treatment
Measure: Safety and tolerability - concomitant medications II. Viral load Time: Day 1 to day 28The aim of this study is to investigate whether vaccination of healthcare professionals with VPM1002 could reduce the number of days absent from work due to respiratory disease (with or without documented SARS-CoV-2 infection). VPM1002 is a vaccine that is a further development of the old Bacillus Calmette-Guérin (BCG) vaccine, which has been used successfully as a vaccine against tuberculosis for about 100 years, especially in developing countries. VPM1002 has been shown in various clinical studies to be significantly safer than the BCG vaccine. VPM1002 strengthens the body's immune defence and vaccination with BCG reduces the frequency of respiratory diseases. It is therefore assumed that a VPM1002 vaccination could also provide (partial) protection against COVID-19 disease caused by the new corona virus "SARS-CoV 2". A total of 1200 health care professionals (doctors, nurses and paramedical staff) with high expected exposure to SARSCoV-2 infected patients will receive a single dose of either VPM1002 or Placebo. All subjects will be requested to enter data regarding absenteeism, adverse events / serious adverse events, hospitalizations, intensive care unit admissions into an online questionnaire.
This clinical trial will examine if a new treatment of Mesenchymal Stems Cells (called PLX-PAD) can help patients intubated and mechanically ventilated due to COVID-19 to recover more quickly with less complications.
A randomized, double-blind, placebo-controlled Phase 2/3 study to evaluate the safety and efficacy of DSTAT in patients with Acute Lung Injury (ALI) due to COVID-19. This study is designed to determine if DSTAT can accelerate recovery and prevent progression to mechanical ventilation in patients severely affected by COVID-19.
Description: Alive and free of invasive mechanical ventilation
Measure: Proportion of participants who are alive and free of invasive mechanical ventilation Time: Through Day 28Description: Time to all-cause mortality
Measure: All-cause mortality Time: Through Day 28SAINT is a double-blind, randomized controlled trial with two parallel groups that evaluates the efficacy of ivermectin in reducing nasal viral carriage at seven days after treatment in SARS-CoV-2 infected patients who are at low risk of progression to severe disease. The trial is currently planned at a single center in Navarra.
Description: Proportion of patients with a positive SARS-CoV-2 PCR from a nasopharyngeal swab at day 7 post-treatment
Measure: Proportion of patients with a positive SARS-CoV-2 PCR Time: 7 days post-treatmentDescription: Change from baseline quantitative and semi-quantitative PCR in nasopharyngeal swab
Measure: Mean viral load Time: Baseline and on days 4, 7, 14 and 21Description: 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 21Description: Proportion of participants with positive IgG at day 21
Measure: Seroconversion at day 21 Time: Up to and including day 21Description: Proportion of drug-related adverse events
Measure: Proportion of drug-related adverse events Time: 7 days post treatmentDescription: Levels in median fluorescence intensity (MFI) of IgG, IgM and IgA against the receptor-binding domain of the spike glycoprotein of SARS-CoV-2 in plasma, measured by a Luminex assay
Measure: Levels of IgG, IgM and IgA Time: Up to and including day 28Description: 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 7Description: 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 7Description: 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 28Randomized, 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.
Description: Number of patients who died, by treatment group
Measure: All-cause mortality at day 28 Time: Day 28Description: Number of patients with treatment-emergent adverse events, by treatment group
Measure: Safety of WJ-MSC Time: Day 28Description: Number of patients who, after the start of treatment, required rescue medication, by treatment group
Measure: Need for treatment with rescue medication Time: Day 28Description: 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 28Description: Days after treatment in which the patient remains alive and free of invasive mechanical ventilation, per treatment group.
Measure: Ventilator free days Time: Day 28Description: Variation of the oxygenation index (PaO2 / FiO2) with respect to the baseline value, by treatment group.
Measure: Evolution of PaO2 / FiO2 ratio Time: Day 28Description: 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 28Description: 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 28Description: 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 28Description: 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 28Description: 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 28Description: 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 28Description: Variation in the values of the biomarker, by treatment group.
Measure: Evolution of disease biomarker: polymerase chain reaction (RT-PCR) Time: Day 28Description: Variation in the values of the biomarker, by treatment group.
Measure: Evolution of disease biomarker: lactate dehydrogenase (LDH) Time: Day 28Description: Variation in the values of the biomarker, by treatment group.
Measure: Evolution of disease biomarker: D-dimer Time: Day 28Description: Variation in the values of the biomarker, by treatment group.
Measure: Evolution of disease biomarker: Ferritin Time: Day 28Description: Blood sample analysis
Measure: Analysis of subpopulations of lymphocytes and immunoglobulins Time: Day 28Description: 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 28Description: Reactivity will be assessed using ELISPOT
Measure: Study of reactivity against SARS-CoV-2 peptides Time: Day 28Description: Blood sample analysis
Measure: Immunophenotypic study of memory cells in response to SARS-CoV-2 peptides Time: Day 28Description: Blood sample analysis for the patient's genomic sequencing
Measure: Genetic variability of patient's genotype in response to treatment Time: Day 28Description: 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 28This 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.
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 DaysDescription: 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 DaysDescription: Length of hospital stay (live discharge)
Measure: Duration of hospital stay Time: 28 DaysDescription: 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 DaysDescription: Length of ICU stay
Measure: Duration of ICU stay Time: 28 DaysDescription: Number and proportion of patients requiring invasive mechanical ventilation
Measure: Invasive mechanical ventilation requirements Time: 28 DaysDescription: Length of time patients require invasive mechanical ventilation
Measure: Duration of invasive mechanical ventilation Time: 28 DaysDescription: The number and proportion of patients deceased at Day 28
Measure: All-cause 28-day mortality Time: 28 DaysDescription: The incidence and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs)
Measure: Safety and tolerability of LB1148 Time: 28 DaysBackground: 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.
Description: Days from admission as a suspected case of COVID with hospitalization criteria until discharge
Measure: Mean days of hospital stay Time: Three monthsDescription: 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 monthsDescription: Daily delta of oxygenation index during the hospitalization
Measure: Mean of oxygenation index delta Time: Three monthsDescription: 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: One monthThis 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.
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 1-22Description: 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 1-29Description: 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, 1-29Description: 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, 1-29Description: Days alive and free of acute respiratory failure through Days 15 and 29
Measure: Acute respiratory failure Time: Days 1-15 and 1-29Description: Days alive and free of invasive mechanical ventilation through Days 15, 22, and 29
Measure: Invasive mechanical ventilation Time: Days 1-15, 1-22, 1-29Description: Days alive and hospitalized through Day 29
Measure: Hospitalization Time: Days 1-29Description: 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, 1-22Description: Worst SOFA score from baseline to Day 22
Measure: Sequential Organ Failure Assessment Time: Days 1-22Description: Proportion of patients alive and discharged from the hospital at Days 15 and 29.
Measure: Hospitalization Time: Days 1-15, 1-29Description: Mean change in the eight-point ordinal scale (1 [worst] to 8 [best]) through Day 29
Measure: Ordinal Scale Time: Days 1-29Description: 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 1-29Description: 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 1-29Description: 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 1-29Description: 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 baselineDescription: Cumulative incidence of Grade 3 and 4 clinical and/or laboratory adverse events
Measure: Adverse events Time: Days 1-60Description: Cumulative incidence of serious adverse events
Measure: Serious adverse events Time: Days 1-60This is a First In Human study designed to assess the safety, tolerability and pharmacokinetics of EIDD-2801 in healthy human volunteers.
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 daysDescription: 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 daysDescription: 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 18Description: 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 4Description: 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 14Description: 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 daysA 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).
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 periodDescription: Nasopharyngeal sample and/or in blood
Measure: SARS-CoV-2 viral load Time: at each study visit during the 28-day treatment periodThe 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.
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 daysDescription: 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 8Description: 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 15Description: 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 22Description: 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 29Description: For patients requiring mechanical ventilation.
Measure: Duration of mechanical ventilation Time: Up to 29 daysDescription: For patients requiring mechanical ECMO.
Measure: Duration of ECMO Time: Up to 29 daysDescription: For patients requiring non-invasive ventilation
Measure: Duration of noninvasive ventilation Time: Up to 29 daysDescription: For patients admitted to ICU
Measure: Duration of ICU stay Time: Up to 29 daysA 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
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 daysDescription: Clinical status as assessed with the seven-category ordinal scale on days 7 and 14
Measure: Clinical outcome Time: 7-14 daysDescription: 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 daysDescription: Total days of hospitalization
Measure: Hospitalization Time: Randomization till hospital discharge or death whichever came first, assessed up to 28 daysDescription: number of days patient remained with positive RT-PCR SARS-CoV-2 swab
Measure: Virologic Response Time: Randomization till discharge, up to 28 daysDescription: Any adverse events whether related to medication or not
Measure: Adverse events Time: Randomization till hospital discharge, up to 28 daysUnfortunately, COVID-19 vaccination will be restricted to healthy people with strong immunity and It will not be given to patients with History of contact with a SARS-CoV-2 infection (positive in nucleic acid test). In addition to the COVID-19 viral antigens lead to stimulate antibodies formation of IgM in acute phase and IgG type in chronic phase which is facilitate viral entry and fusion with infected cell through uptake of the virus-IgG complex via the Fc family of receptors and later viral fusion with antigen presenting cells like macrophages, B cells, monocytes via FcR family, and vascular endothelium through the neonatal Fc receptor (nFcR) 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 receptors 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, if there was a preceding infection with a different strain of the virus, causing a normally mild viral infection to become life-threatening.(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 coronaviruses. 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 (a cat coronavirus) had to be stopped because they elicited ADE.(4) ADE in coronavirus infection can be caused by high mutation rate of the gene that encodes spike (S) protein. A thorough analysis of amino acid variability in SARS-CoV-2 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) High neutrophils 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 SARS-CoV-2 infected patients. In one report where 99 cases in Wuhan were investigated, increased total neutrophils (38%), reduced total lymphocytes (35%),increased serum IL-6 (52%) and increased c-reactive protein (84%) were observed.25 In a separate report also from Wuhan, it revealed that in 41 patients, increased total neutrophils, decreased total lymphocytes in patients of ICU vs. non-ICU care were found to be statistically different. Increased neutrophils and decreased lymphocytes also correlate with disease severity and death.(10) B cells/plasma cells produce SARS-CoV-2 specific antibodies 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 SARS-CoV, both T and B cell epitopes were extensively mapped for the structural proteins, S, N, M and E protein.(12) Whether the kinetic/titer of specific antibody correlates with disease severity remains to be investigated.(14)Delayed antibodies response and secretion after covid -19 symptoms onset is responsible for antibody dependent enhancement (ADE) A study shows the first seroconversion day of IgA was 2 days after onset of initial symptoms, and the first seroconversion day of IgM and IgG was 5 days after onset. The positive rate of antibodies in the 183 samples was 98.9%, 93.4% and 95.1%, for IgA, IgM and IgG, respectively. The seroconversion rate for IgA, IgM or IgG was 100% 32 days after symptom onset. According to the cumulative seroconversion curve, the median conversion time for IgA, IgM and IgG was 13, 14 and 14 days, respectively. (6) 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 and immunologist at the Gladstone Institutes So, the principal investigator expects that delayed antibodies response and delayed immunoglobulin class switching are the main reason for antibodies inactivity and non-specificity in the highly mutated COVID-19 infection. Finally, according to this protocol the principal investigator will treat with two potent antibody and immunity inducing drug and the mechanism of action will be discussed in Detailed Description
Description: To evaluate the effect of alvelestat (MPH996) administered twice daily (bid) for 12 weeks on blood markers of neutrophil elastase activity, within-individual % change in plasma desmosine/isodesmosine will be measured.
Measure: Within-individual % change in plasma desmosine/isodesmosine Time: baseline, week 2Description: To evaluate the safety and tolerability of alvelestat (MPH996) administered twice daily (bid) for 2 weeks treatment numbers and % of subjects who experience at least 1 treatment-emergent adverse event will be measured.
Measure: Numbers and % of subjects who experience at least 1 treatment-emergent adverse event Time: baseline, week 2Description: Proportion of lung injury score decreased or increased after treatment
Measure: lung injury score Time: at 7and 14 daysDescription: 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 randimizationDescription: Serum level of COVID19 RNA
Measure: Serum level of COVID19 RNA Time: at day 7 and 14Description: less than 250 ng/mL, or less than 0.4 mcg/mL of blood sample
Measure: d-dimers Time: within 14 daysDescription: lymphocyte counts
Measure: Absolute lymphocyte counts Time: at day 7 and 14 after randimizationDescription: 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 daysDescription: Number of CD4 HLA-DR+ and CD38+, CD8 lymphocytes
Measure: Immunological profile Time: within 14 daysDescription: Kidney failure, hypersensitivity with cutaneous or hemodynamic manifestations, aseptic meningitis, hemolytic anemia, leuko-neutropenia, transfusion related acute lung injury (TRALI)
Measure: Occurrence of adverse event related to immunoglobulins Time: at day 14Description: serum levels of IgG and IgM against COVID-19
Measure: IgG, IgA and IgM against COVID-19 Time: at day 7 and 14Description: ACE2 expression in patients with COVID-19 infection
Measure: ACE2 expression in patients with COVID-19 infection Time: at day 7 and 14The 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.
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 14Description: 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 14Older 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.
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.
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 hoursDescription: 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 hoursDescription: 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 hoursDescription: 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 hoursDescription: 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 hoursDescription: 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 hoursThis 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.
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 treatmentDescription: 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 28Description: 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 interventionDescription: 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 28Description: 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 interventionDescription: COVID-19-related death
Measure: Reduction in case fatality Time: Within day 28 of interventionDescription: 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 interventionDescription: 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 firstDescription: Median changes of NEWS2 score from baseline
Measure: Median changes in the National Early Warning Score 2 (NEWS2) Time: At day 7, 14, and 28Description: 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 firstDescription: 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 firstDescription: 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: Safety of mavrilimumab in patients with severe COVID-19-pneumonia Time: By day 84Description: 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 interventionDescription: Changes in exploratory biomarkers: Inflammatory biomarkers (i.e. IL-6, IL-1RA, TNF-alpha, CBC and differential) Levels of antibodies to SARS- CoV-2 / SARS-Cov-2 positivity by PCR Levels of anti-drug antibiodies (ADA)
Measure: Changes in exploratory biomarkers Time: By day 84This 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.
Description: Incidence of AEs within 30 days of randomization.
Measure: Incidence of AEs Time: 30 daysDescription: Mortality within 30 days of randomization.
Measure: Mortality Time: 30 daysDescription: Cause of death within 30 days of randomization
Measure: Death Time: 30 daysDescription: Number of ventilator-free days within 60 days of randomization.
Measure: Number of ventilator-free days Time: 60 daysDescription: 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 daysDescription: 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 daysDescription: 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 daysDescription: Time from randomization to discharge or to a NEWS of ≤ 2 maintained for 24 hours, whichever occurs first.
Measure: NEWS of ≤ 2 Time: 30 daysDescription: 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 29Description: Number of days requiring oxygen.
Measure: Oxygen Time: 30 daysDescription: Duration of hospitalization from randomization.
Measure: Hospitalization Time: 30 daysDescription: Incidence of SAEs within 30 days of randomization
Measure: Incidence of SAEs Time: 30 daysThis 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
Description: Solicited AE in all groups within 0-6 days after each vaccination;
Measure: Solicited AE in all groups Time: 0-6 days after each vaccinationDescription: Unsolicited AE in all groups within 0-28 days after each vaccination.
Measure: Unsolicited AE in all groups Time: 0-28 days after each vaccinationDescription: Serious adverse events (SAE) in all groups within 6 months after the final vaccination.
Measure: Serious adverse events (SAE) in all groups Time: 6 months after the final vaccinationDescription: 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 groupDescription: 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 groupDescription: 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 groupDescription: 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 groupDescription: 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 groupDescription: 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 groupDescription: 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 groupDescription: 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 groupDescription: 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 groupDescription: 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 groupThis study will evaluate the antihelmintic drug, Niclosamide, as a potential treatment for mild to moderate coronavirus disease 2019 (COVID-19).
Description: Oropharangeal swab
Measure: Change in respiratory viral clearance (by PCR) Time: Day 3 and 10Description: Fecal swab
Measure: Fecal viral clearance (by PCR) Time: Day 14Description: Oropharngeal swab
Measure: Reduction (change) in viral shedding (by PCR) Time: Days 1,3,7,10,14This 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
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 daysDescription: Change from baseline in oxygen saturation
Measure: Oxygen saturation Time: Up to 33 daysDescription: Change from baseline in Modified Borg Dyspnea scale
Measure: Modified Borg Dyspnea scale Time: Up to 33 daysDescription: Change from baseline in Quality of Life
Measure: Quality of Life (McGill Quality of Life Single-Item Scale) Time: Up to 33 dayaDescription: Time to intubation
Measure: Time to intubation Time: Up to 33 daysDescription: Time to extubation
Measure: Time to extubation Time: Up to 33 daysDescription: Time to mechanical ventilation
Measure: Time to mechanical ventilation Time: Up to 33 daysDescription: Time to cessation of mechanical ventilation
Measure: Time to cessation of mechanical ventilation Time: Up to 33 daysDescription: Time to change of modality for oxygenation
Measure: Time to change of modality for oxygenation Time: Up to 33 daysDescription: Time to death
Measure: Time to death Time: Up to 33 daysDescription: Imaging findings (chest CT/chest X-ray)
Measure: Imaging findings (chest CT/chest X-ray) Time: Up to 7 daysDescription: Change from baseline in blood glucose
Measure: Blood glucose Time: Up to 33 dayaDescription: Change from baseline in blood calcium
Measure: Blood calcium Time: Up to 33 daysDescription: Change from baseline in sodium
Measure: Sodium Time: Up to 33 daysDescription: Change from baseline in potassium
Measure: Potassium Time: Up to 33 daysDescription: Change from baseline in carbon dioxide
Measure: Carbon dioxide Time: Up to 33 daysDescription: Change from baseline in chloride
Measure: Chloride Time: Up to 33 daysDescription: Change from baseline in albumin
Measure: Albumin Time: Up to 33 daysDescription: Change from baseline in total protein
Measure: Total protein Time: Up to 33 daysDescription: Change from baseline in alkaline phosphatase
Measure: Alkaline phosphatase Time: Up to 33 daysDescription: Change from baseline in alanine transaminase
Measure: Alanine transaminase Time: Up to 33 daysDescription: Change from baseline in aspartate aminotransferase
Measure: Aspartate aminotransferase Time: Up to 33 daysDescription: Change from baseline in bilirubin
Measure: Bilirubin Time: Up to 33 daysDescription: Change from baseline in blood urea nitrogen
Measure: Blood urea nitrogen Time: Up to 33 daysDescription: Change from baseline in D-dimer
Measure: D-dimer Time: Up to 33 daysDescription: Change from baseline in fibrinogen
Measure: Fibrinogen Time: Up to 33 daysDescription: Change from baseline in PT
Measure: PT Time: Up to 33 daysDescription: Change from baseline in PTT
Measure: PTT Time: Up to 33 daysDescription: Change from baseline in INR
Measure: INR Time: Up to 33 daysDescription: Change from baseline in hsCRP
Measure: hsCRP Time: Up to 33 daysDescription: Change from baseline in ferritin
Measure: Ferritin Time: Up to 33 daysDescription: Change from baseline in LDH
Measure: LDH Time: Up to 33 daysDescription: Change from baseline in IgG
Measure: IgG Time: Up to 33 daysDescription: Change from baseline in IgM
Measure: IgM Time: Up to 33 daysDescription: Change from baseline in IgA
Measure: IgA Time: Up to 33 daysDescription: Change from baseline in IFE
Measure: IFE Time: Up to 33 daysDescription: Change from baseline in troponin
Measure: Troponin Time: Up to 33 daysDescription: Change from baseline in red blood cell count
Measure: Red blood cell count Time: Up to 33 daysDescription: Change from baseline in hemoglobjn
Measure: Hemoglobin Time: Up to 33 daysDescription: Change from baseline in hematocrit
Measure: Hematocrit Time: Up to 33 daysDescription: Change from baseline in mean corpuscular volume
Measure: Mean corpuscular volume Time: Up to 33 daysDescription: Change from baseline in mean corpuscular hemoglobin
Measure: Mean corpuscular hemoglobin Time: Up to 33 daysDescription: Change from baseline in mean corpuscular hemoglobin concentration
Measure: Mean corpuscular hemoglobin concentration Time: Up to 33 daysDescription: Change from baseline in red cell distribution width
Measure: Red cell distribution width Time: Up to 33 daysDescription: Change from baseline in white blood cell count
Measure: White blood cell count Time: Up to 33 daysDescription: Change from baseline in white blood cell differential
Measure: White blood cell differential Time: Up to 33 daysDescription: Change from baseline in platelet count
Measure: Platelet count Time: Up to 33 daysDescription: Change from baseline in mean platelet volume
Measure: Mean platelet volume Time: Up to 33 daysDescription: Change from baseline in platelet distribution width
Measure: Platelet distribution width Time: Up to 33 daysDescription: Frequency of adverse events
Measure: Frequency of adverse events Time: 33 daysDescription: Frequency of serious adverse events
Measure: Frequency of serious adverse events Time: 33 days