Developed by Shray Alag, The Harker School
Sections: Correlations,
Clinical Trials, and HPO
Navigate: Clinical Trials and HPO
Name (Synonyms) | Correlation | |
---|---|---|
drug3321 | Remdesivir placebo Wiki | 0.27 |
drug4401 | blood donation SMS Wiki | 0.22 |
drug3 | (Standard of Care) SoC Wiki | 0.19 |
Name (Synonyms) | Correlation | |
---|---|---|
drug228 | Aerolized Hydroxychloroquine Sulfate Wiki | 0.19 |
drug1819 | Hydroxychloroquine, Azithromycin Wiki | 0.19 |
drug3561 | Self-help guided by a lay provider Wiki | 0.19 |
drug3863 | TAK-788 Wiki | 0.19 |
drug1820 | Hydroxychloroquine, Clindamycin Wiki | 0.19 |
drug1879 | Icatibant Wiki | 0.19 |
drug549 | Best available care Wiki | 0.19 |
drug2752 | PCL COV05 - COVID 19 Ag Rapid FIA test (Rapid Antigen Test) Wiki | 0.19 |
drug392 | Attention Control Group Wiki | 0.19 |
drug868 | Cenicriviroc Wiki | 0.19 |
drug803 | CT-V Wiki | 0.19 |
drug2376 | Midazolam injection Wiki | 0.19 |
drug3771 | Standardized crisis management and coping protocol plan toward Coronavirus disease 2019 (COVID-19) Wiki | 0.19 |
drug500 | BVRS-GamVac Wiki | 0.19 |
drug2069 | Ketamine Injectable Product Wiki | 0.19 |
drug2340 | Merimepodib Wiki | 0.19 |
drug1660 | Group Lifestyle Balance™ Wiki | 0.19 |
drug2233 | MELT-100 Wiki | 0.19 |
drug76 | 80 ppm Nitric Oxide delivered through LungFit Delivery System Wiki | 0.19 |
drug2295 | Matching Placebo Wiki | 0.19 |
drug1821 | Hydroxychloroquine, Clindamycin, Primaquine - high dose. Wiki | 0.19 |
drug1835 | Hyperimmune immunoglobulin to SARS-CoV-2 (hIVIG) Wiki | 0.19 |
drug1964 | Interferon-Alpha2B Wiki | 0.19 |
drug2348 | Mesenchymal stem cell therapy Wiki | 0.19 |
drug1453 | Experimental drug Wiki | 0.19 |
drug579 | Biomarkers expression Wiki | 0.19 |
drug1233 | Diphenhydramine Wiki | 0.19 |
drug1057 | Convalescent Serum Wiki | 0.19 |
drug2746 | Oxytocin Wiki | 0.19 |
drug30 | 150 ppm Nitric Oxide delivered through LungFit Delivery System Wiki | 0.19 |
drug1822 | Hydroxychloroquine, Clindamycin, Primaquine - low dose. Wiki | 0.19 |
drug1823 | Hydroxychloroquine, Doxycycline Wiki | 0.19 |
drug4065 | Transcranial Electrical Stimulation Wiki | 0.19 |
drug3276 | Razuprotafib Wiki | 0.19 |
drug4016 | Tigerase® and best available care Wiki | 0.19 |
drug4197 | Valsartan (Diovan) Wiki | 0.19 |
drug3988 | Therapeutic Plasma exchange Wiki | 0.19 |
drug4282 | Waiting list where participants wait for delayed treatment Wiki | 0.19 |
drug4419 | cenicriviroc Wiki | 0.19 |
drug3734 | Standard of Care (SoC) Wiki | 0.13 |
drug2040 | Ivermectin Oral Product Wiki | 0.13 |
drug1928 | Infliximab Wiki | 0.13 |
drug3373 | Risankizumab Wiki | 0.13 |
drug911 | Chloroquine or hydroxychloroquine Wiki | 0.13 |
drug3728 | Standard of Care Wiki | 0.12 |
drug179 | Abatacept Wiki | 0.11 |
drug2117 | Lenzilumab Wiki | 0.11 |
drug3323 | Remestemcel-L Wiki | 0.11 |
drug455 | BCG vaccine Wiki | 0.11 |
drug340 | Apremilast Wiki | 0.11 |
drug1962 | Interferon beta-1a Wiki | 0.09 |
drug163 | AZD1222 Wiki | 0.09 |
drug1771 | Hydrocortisone Wiki | 0.09 |
drug1959 | Interferon Beta-1A Wiki | 0.09 |
drug4025 | Tocilizumab Wiki | 0.09 |
drug2916 | Placebo Wiki | 0.08 |
drug2093 | LY3819253 Wiki | 0.08 |
drug514 | Baricitinib Wiki | 0.07 |
drug2176 | Losartan Wiki | 0.06 |
drug2174 | Lopinavir/ritonavir Wiki | 0.06 |
drug2365 | Methylprednisolone Wiki | 0.05 |
drug4650 | placebo Wiki | 0.05 |
drug1511 | Favipiravir Wiki | 0.04 |
drug1775 | Hydroxychloroquine Wiki | 0.04 |
drug3738 | Standard of care Wiki | 0.04 |
drug1047 | Convalescent Plasma Wiki | 0.04 |
drug2981 | Placebo oral tablet Wiki | 0.03 |
Name (Synonyms) | Correlation | |
---|---|---|
D018352 | Coronavirus Infections NIH | 0.13 |
D045169 | Severe Acute Respiratory Syndrome NIH | 0.10 |
D014029 | Tobacco Use Disorder NIH | 0.09 |
Name (Synonyms) | Correlation | |
---|---|---|
D000066553 | Problem Behavior NIH | 0.07 |
D000070642 | Brain Injuries, Traumatic NIH | 0.06 |
D001930 | Brain Injuries, NIH | 0.05 |
D013577 | Syndrome NIH | 0.05 |
D016638 | Critical Illness NIH | 0.05 |
D012120 | Respiration Disorders NIH | 0.04 |
D014777 | Virus Diseases NIH | 0.04 |
D012140 | Respiratory Tract Diseases NIH | 0.04 |
D007239 | Infection NIH | 0.04 |
D002318 | Cardiovascular Diseases NIH | 0.03 |
D014947 | Wounds and Injuries NIH | 0.03 |
D012127 | Respiratory Distress Syndrome, Newborn NIH | 0.03 |
D055371 | Acute Lung Injury NIH | 0.03 |
D011014 | Pneumonia NIH | 0.03 |
D012128 | Respiratory Distress Syndrome, Adult NIH | 0.03 |
D001008 | Anxiety Disorders NIH | 0.03 |
D011024 | Pneumonia, Viral NIH | 0.02 |
D003141 | Communicable Diseases NIH | 0.01 |
Name (Synonyms) | Correlation | |
---|---|---|
HP:0000708 | Behavioral abnormality HPO | 0.07 |
HP:0001626 | Abnormality of the cardiovascular system HPO | 0.03 |
HP:0002090 | Pneumonia HPO | 0.03 |
Navigate: Correlations HPO
There are 28 clinical trials
In December 2019, Wuhan, in Hubei province, China, became the center of an outbreak of pneumonia of unknown cause. In a short time, Chinese scientists had shared the genome information of a novel coronavirus (SARS-CoV-2) from these pneumonia patients and developed a real-time reverse transcription PCR (real-time RT-PCR) diagnostic assay. Given no specific antiviral therapy for COVID-19 and the availability of remdesvir as a potential antiviral agent based on pre-clinical studies in SARS-CoV and MERS-CoV infections, this randomized, controlled, double blind trial will evaluate the efficacy and safety of remdesivir in patients hospitalized with mild or moderate COVID-19.
Description: TTCR is defined as the time (in hours) from initiation of study treatment (active or placebo) until normalisation of fever, respiratory rate, and oxygen saturation, and alleviation of cough, sustained for at least 72 hours, or live hospital discharge, whichever comes first. Normalisation and alleviation criteria: Fever - <37°C, Respiratory rate - ≤24/minute on room air, Oxygen saturation - >94% on room air, Cough - mild or absent on a patient reported scale of severe, moderate, mild, absent.
Measure: Time to Clinical recoveryTime to Clinical Recovery (TTCR) Time: up to 28 daysDescription: baseline SpO2 during screening, PaO2/FiO2 <300mmHg or a respiratory rate ≥ 24 breaths per min without supplemental oxygen
Measure: All cause mortality Time: up to 28 daysDescription: Defined as SPO2≤ 94% on room air or PaO2/FiO2 <300mmHg and requirement for supplemental oxygen or more advanced ventilator support.
Measure: Frequency of respiratory progression Time: up to 28 daysIn December 2019, Wuhan, in Hubei province, China, became the center of an outbreak of pneumonia of unknown cause. In a short time, Chinese scientists had shared the genome information of a novel coronavirus (SARS-CoV-2) from these pneumonia patients and developed a real-time reverse transcription PCR (real-time RT-PCR) diagnostic assay. Given no specific antiviral therapy for COVID-19 and the ready availability of remdesvir as a potential antiviral agent, based on pre-clinical studies in SARS-CoV and MERS-CoV infections, this randomized, controlled, double blind trial will evaluate the efficacy and safety of remdesivir in patients hospitalized with severe COVID-19.
Description: The primary endpoint is time to clinical improvement (censored at Day 28), defined as the time (in days) from randomization of study treatment (remdesivir or placebo) until a decline of two categories on a six-category ordinal scale of clinical status (1 ꞊ discharged; 6 ꞊ death) or live discharge from hospital. Six-category ordinal scale: 6. Death; 5. ICU, requiring ECMO and/or IMV; 4. ICU/hospitalization, requiring NIV/ HFNC therapy; 3. Hospitalization, requiring supplemental oxygen (but not NIV/ HFNC); 2. Hospitalization, not requiring supplemental oxygen; 1. Hospital discharge or meet discharge criteria (discharge criteria are defined as clinical recovery, i.e. fever, respiratory rate, oxygen saturation return to normal, and cough relief). Abbreviation: IMV, invasive mechanical ventilation; NIV, non-invasive mechanical ventilation; HFNC, High-flow nasal cannula.
Measure: Time to Clinical Improvement (TTCI) [Censored at Day 28] Time: up to 28 daysDescription: Clinical status, assessed by the ordinal scale at fixed time points (days 7, 14, 21, and 28).
Measure: Clinical status Time: days 7, 14, 21, and 28Description: Time to Hospital Discharge OR NEWS2 (National Early Warning Score 2) of ≤ 2 maintained for 24 hours.
Measure: Time to Hospital Discharge OR NEWS2 (National Early Warning Score 2) of ≤ 2 maintained for 24 hours. Time: up to 28 daysThis study is an adaptive, randomized, double-blind, placebo-controlled trial to evaluate the safety and efficacy of novel therapeutic agents in hospitalized adults diagnosed with COVID-19. The study is a multicenter trial that will be conducted in up to approximately 100 sites globally. The study will compare different investigational therapeutic agents to a control arm. There will be interim monitoring to introduce new arms and allow early stopping for futility, efficacy, or safety. If one therapy proves to be efficacious, then this treatment may become the control arm for comparison(s) with new experimental treatment(s). Any such change would be accompanied by an updated sample size. Because background standards of supportive care may evolve/improve over time as more is learned about successful management of COVID-19, comparisons of safety and efficacy will be based on data from concurrently randomized subjects. An independent Data and Safety Monitoring Board (DSMB) will actively monitor interim data to make recommendations about early study closure or changes to study arms. To evaluate the clinical efficacy, as assessed by time to recovery, of different investigational therapeutics as compared to the control arm.
Description: Day of recovery is defined as the first day on which the subject satisfies one of the following three categories from the ordinal scale: 1) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Not hospitalized, no limitations on activities.
Measure: Time to Recovery Time: Day 1 through Day 29Description: Blood to evaluate ALT was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.
Measure: Change From Baseline in Alanine Transaminase (ALT) Time: Days 1, 3, 5, 8, 11, 15 and 29Description: Blood to evaluate AST was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.
Measure: Change From Baseline in Aspartate Transaminase (AST) Time: Days 1, 3, 5, 8, 11, 15 and 29Description: Blood to evaluate serum creatinine was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.
Measure: Change From Baseline in Creatinine Time: Days 1, 3, 5, 8, 11, 15 and 29Description: Blood to evaluate serum glucose was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.
Measure: Change From Baseline in Glucose Time: Days 1, 3, 5, 8, 11, 15 and 29Description: Blood to evaluate hemoglobin was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.
Measure: Change From Baseline in Hemoglobin Time: Days 1, 3, 5, 8, 11, 15 and 29Description: Blood to evaluate platelets was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.
Measure: Change From Baseline in Platelets Time: Days 1, 3, 5, 8, 11, 15 and 29Description: Blood to evaluate PT was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.
Measure: Change From Baseline in Prothrombin Time (PT) Time: Days 1, 3, 5, 8, 11, 15 and 29Description: Blood to evaluate total bilirubin was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.
Measure: Change From Baseline in Total Bilirubin Time: Days 1, 3, 5, 8, 11, 15 and 29Description: Blood to evaluate WBC was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.
Measure: Change From Baseline in White Blood Cell Count (WBC) Time: Days 1, 3, 5, 8, 11, 15 and 29Description: Blood to evaluate neutrophils was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.
Measure: Change From Baseline in Neutrophils Time: Days 1, 3, 5, 8, 11, 15 and 29Description: Blood to evaluate lymphocytes was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.
Measure: Change From Baseline in Lymphocytes Time: Days 1, 3, 5, 8, 11, 15 and 29Description: Blood to evaluate monocytes was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.
Measure: Change From Baseline in Monocytes Time: Days 1, 3, 5, 8, 11, 15 and 29Description: Blood to evaluate basophils was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.
Measure: Change From Baseline in Basophils Time: Days 1, 3, 5, 8, 11, 15 and 29Description: Blood to evaluate eosinophils was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.
Measure: Change From Baseline in Eosinophils Time: Days 1, 3, 5, 8, 11, 15 and 29Description: The NEW score has demonstrated an ability to discriminate patients at risk of poor outcomes. This score is based on 7 clinical parameters (respiration rate, oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate, level of consciousness). The NEW Score is being used as an efficacy measure. The minimum score is 0, representing the better outcome, and the maximum value is 19, representing the worse outcome.
Measure: Change in National Early Warning Score (NEWS) From Baseline Time: Days 1, 3, 5, 8, 11, 15, 22, and 29Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.
Measure: Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 1 Time: Day 1Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.
Measure: Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 3 Time: Day 3Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.
Measure: Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 5 Time: Day 5Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.
Measure: Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 8 Time: Day 8Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.
Measure: Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 11 Time: Day 11Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.
Measure: Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 15 Time: Day 15Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.
Measure: Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 22 Time: Day 22Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.
Measure: Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 29 Time: Day 29Description: Grade 3 AEs are defined as events that interrupt usual activities of daily living, or significantly affects clinical status, or may require intensive therapeutic intervention. Severe events are usually incapacitating. Grade 4 AEs are defined as events that are potentially life threatening.
Measure: Percentage of Participants Reporting Grade 3 and 4 Clinical and/or Laboratory Adverse Events (AEs) Time: Day 1 through Day 29Description: An SAE is defined as an AE or suspected adverse reaction is considered serious if, in the view of either the investigator or the sponsor, it results in death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect.
Measure: Percentage of Participants Reporting Serious Adverse Events (SAEs) Time: Day 1 through Day 29Description: Participants may have been discontinued from investigational therapeutics due to discharge or death. The halting or slowing of the infusion for any reason was collected, as was missed doses in the series of 10 doses.
Measure: Percentage of Participants Discontinued or Temporarily Suspended From Investigational Therapeutics Time: Day 1 through Day 10Description: Duration of hospitalization was determined two ways. The first includes imputations for participants who died. The second method is restricted to participants who did not die.
Measure: Duration of Hospitalization Time: Day 1 through Day 29Description: Duration of new non-invasive ventilation or high flow oxygen use was measured in days among participants who were not on non-invasive ventilation or high-flow oxygen use at baseline, determined two ways. The first includes imputations for participants who died. The second method is restricted to participants who did not die
Measure: Duration of New Non-invasive Ventilation or High Flow Oxygen Use Time: Day 1 through Day 29Description: Duration of new oxygen use was measured in days among participants who were not on oxygen at baseline, determined two ways. The first includes imputations for participants who died. The second method is restricted to participants who did not die .
Measure: Duration of New Oxygen Use Time: Day 1 through Day 29Description: Duration of new ventilator or ECMO use was measured in days among participants who were not on a ventilator or ECMO at baseline, determined two ways. The first includes imputations for participants who died. The second method is restricted to participants who did not die
Measure: Duration of New Ventilator or Extracorporeal Membrane Oxygenation (ECMO) Use Time: Day 1 through Day 29Description: New non-invasive ventilation or high-flow oxygen use was determined as the percentage of subject not on non-invasive ventilation or high-flow oxygen at baseline.
Measure: Percentage of Participants Requiring New Non-invasive Ventilation or High-flow Oxygen Use Time: Day 1 through Day 29Description: The percentage of participants requiring new oxygen use was determined as the percentage of participants not requiring oxygen at baseline
Measure: Percentage of Participants Requiring New Oxygen Use Time: Day 1 through Day 29Description: The percentage of participants requiring new ventilator or ECMO use was determined as the percentage not on a ventilator or ECMO at baseline
Measure: Percentage of Participants Requiring New Ventilator or Extracorporeal Membrane Oxygenation (ECMO) Use Time: Day 1 through Day 29Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities. A positive change indicates a worsening and a negative change is an improvement.
Measure: Mean Change in the Ordinal Scale Time: Day 1, 3, 5, 8, 11, 15, 22, and 29Description: The mortality rate was determined as the proportion of participants who died by study Day 15.
Measure: 14-day Participant Mortality Time: Day 1 through Day 15Description: The mortality rate was determined as the proportion of participants who died by study Day 29.
Measure: 29-day Participant Mortality Time: Day 1 through Day 29Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities. Time to improvement by at least one category was determined for each participant
Measure: Time to an Improvement by at Least One Category Using an Ordinal Scale Time: Day 1 through Day 29Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities. Time to improvement by at least two categories was determined for each participant
Measure: Time to an Improvement of at Least Two Categories Using an Ordinal Scale Time: Day 1 through Day 29Description: The NEW score has demonstrated an ability to discriminate patients at risk of poor outcomes. This score is based on 7 clinical parameters (respiration rate, oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate, level of consciousness). The NEW Score is being used as an efficacy measure. The minimum score is 0, representing the better outcome, and the maximum value is 19, representing the worse outcome. The time to discharge or a NEWS of less than or equal to 2 was determined for each participant.
Measure: Time to Discharge or to a NEWS of 2 or Less and Maintained for 24 Hours, Whichever Occurs First Time: Day 1 through Day 29The primary objective of this study is to evaluate the efficacy of 2 remdesivir (RDV) regimens compared to standard of care (SOC), with respect to clinical status assessed by a 7-point ordinal scale on Day 11.
Description: The odds ratio represents the odds of improvement in the ordinal scale between the treatment groups. The ordinal scale is an assessment of the clinical status at a given day. Each day, the worst score from the previous day will be recorded. 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 low flow supplemental oxygen 5. Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (coronavirus (COVID-19) related or otherwise) 6. Hospitalized, not requiring supplemental oxygen - no longer required ongoing medical care (other than per protocol Remdesivir administration 7. Not hospitalized.
Measure: The Odds of Ratio for Improvement on a 7-point Ordinal Scale on Day 11 Time: Day 11The primary objective of this study is to evaluate the efficacy of 2 remdesivir (RDV) regimens with respect to clinical status assessed by a 7-point ordinal scale on Day 14.
Description: The odds ratio represents the odds of improvement in the ordinal scale between the treatment groups. The ordinal scale is an assessment of the clinical status at a given day. Each day, the worst score from the previous day will be recorded. 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 low flow supplemental oxygen 5. Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (coronavirus (COVID-19) related or otherwise) 6. Hospitalized, not requiring supplemental oxygen - no longer required ongoing medical care (other than per protocol Remdesivir administration 7. Not hospitalized.
Measure: The Odds of Ratio for Improvement on a 7-point Ordinal Scale on Day 14 Time: Day 14Disease caused by 2019 Novel Coronavirus also known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
This study is a multi-centre, adaptive, randomized, open clinical trial of the safety and efficacy of treatments for COVID-19 in hospitalized adults. The study is a multi-centre/country trial that will be conducted in various sites in Europe with Inserm as sponsor. Adults (≥18 year-old) hospitalized for COVID-19 with SpO2 ≤ 94% on room air OR acute respiratory failure requiring supplemental oxygen or ventilatory support will be randomized between 4 treatment arms, each to be given in addition to the usual standard of care (SoC) in the participating hospital: SoC alone versus SoC + Remdesivir versus SoC + Lopinavir/Ritonavir versus SoC (this treatment arm has been ceased since June 29, 2020) + Lopinavir/Ritonavir plus interferon ß-1a versus SoC (this treatment arm has been ceased since June 29, 2020) + Hydroxychloroquine (this treatment arm has been ceased since May 24, 2020). Randomization will be stratified by European region and severity of illness at enrollment (moderate disease: patients NOT requiring non-invasive ventilation NOR high flow oxygen devices NOR invasive mechanical ventilation NOR ECMO and severe disease: patients requiring non-invasive ventilation OR high flow oxygen devices OR invasive mechanical ventilation OR ECMO). The interim trial results will be monitored by a Data Monitoring Committee, and if at any stage evidence emerges that any one treatment arm is definitely inferior then it will be centrally decided that that arm will be discontinued. Conversely, if good evidence emerges while the trial is continuing that some other treatment(s) should also be being evaluated then it will be centrally decided that one or more extra arms will be added while the trial is in progress. The primary objective of the study is to evaluate the clinical efficacy and safety of different investigational therapeutics relative to the control arm in patients hospitalized with COVID-19, the primary endpoint is the subject clinical status (on a 7-point ordinal scale) at day 15.
Description: Not hospitalized, no limitations on activities Not hospitalized, limitation on activities; Hospitalized, not requiring supplemental oxygen; Hospitalized, requiring supplemental oxygen; Hospitalized, on non-invasive ventilation or high flow oxygen devices; Hospitalized, on invasive mechanical ventilation or ECMO; Death.
Measure: Percentage of subjects reporting each severity rating on a 7-point ordinal scale Time: Day 15Description: Time to an improvement of one category from admission on an ordinal scale. Time to an improvement of two categories from admission on an ordinal scale. Time to discharge (categories 1 or 2 of ordinal scale) from admission. Subject clinical status on an ordinal scale at days 3, 5, 8, 11, and 29. Mean change in the ranking on an ordinal scale from baseline to days 3, 5, 8, 11, 15 and 29 from baseline.
Measure: Percentage of subjects reporting each severity rating on a 7-point on an ordinal scale Time: Days 3, 5, 8, 11, 15 and 29Description: • Change from baseline to days 3, 5, 8, 11, 15, and 29 in NEWS.
Measure: The time to discharge or to a NEWS of ≤ 2 and maintained for 24 hours, whichever occurs first. Time: Days 3, 5, 8, 11, 15 and 29Description: • Duration of hospitalization (days).
Measure: Hospitalization Time: 29 daysDescription: Rate of mortality
Measure: Mortality Time: In hospital, Day 28, Day 90Description: On Day 1, plasma concentration 4 hours after the first administration (peak), and before the second administration (trough at H12) On Days 3, 5, 8 and 11, trough plasma concentration (before dose administration) while hospitalized
Measure: Plasma concentration of lopinavir Time: Days 1, 3, 5, 8 and 11Description: On Day 1, plasma concentration 4 hours after the first administration (peak), and before the second administration (trough at H12) On Days 3, 5, 8 and 11, trough plasma concentration (before dose administration) while hospitalized
Measure: Plasma concentration of hydroxychloroquine Time: Days 1, 3, 5, 8 and 11The (World Health Organization) WHO NOR- (Coronavirus infectious disease) COVID 19 study is a multi-centre, adaptive, randomized, open clinical trial to evaluate the safety and efficacy of hydroxychloroquine, remdesivir and standard of care in hospitalized adult patients diagnosed with COVID-19. This trial will follow the core WHO protocol but has additional efficacy, safety and explorative endpoints.
Description: All cause in-hospital mortality
Measure: In-hospital mortality Time: 3 weeksThe primary objective of this study is to provide expanded access of remdesivir (RDV) for the treatment of severe acute respiratory syndrome coronavirus (SARS-CoV2) infection.
COVID 19 treatment using Chloroquine, Remedesvir.
Description: the estimated number of patients with improvement or mortality
Measure: Number of patients with improvement or mortality Time: 6 monthsDiagnostic determination of disease and treatment responses has been limited to qualitative imaging, measurement of serum markers of disease, and sampling of tissue. In each of these instances, there is a built in error either due to sensitivity and specificity issues, clinician interpretation of results, or acceptance of the use of an indirect marker (blood test) of what is happening elsewhere in the body - at the tissue level. The Fleming Method for Tissue and Vascular Differentiation and Metabolism (FMTVDM) using same state single or sequential quantification comparisons [1] provides the first and only patented test (#9566037) - along with the associated submitted patent applications ruled to be covered under #9566037 - that quantitatively measures changes in tissue resulting from inter alia a disease process. This includes inter alia coronary artery disease (CAD), cancer and infectious/inflammatory processes including CoVid-19 pneumonia (CVP) resulting from the metabolic and regional blood flow differences (RBFDs) caused by these diseases. The purpose of this paper is to make clinicians and researchers aware of this proposed method for investigating the prevalence and severity of CVP - in addition to providing rapid determination of treatment response in each patient, directing treatment decisions; thereby reducing the loss of time, money, resources and patient lives.
Description: Measured improvement in tissue as measured using FMTVDM
Measure: Improvement in FMTVDM Measurement with nuclear imaging. Time: 72 hoursDescription: Extubation
Measure: Ventilator status Time: 7 daysDescription: Self explanatory
Measure: Survival status Time: 30 daysThis study is a retrospective cohort trial to assess the efficacy of remdesivir in hospitalized adult patients diagnosed with COVID-19. The study is a multicenter trial which will be carried out on different sites in France. This trial is retrospective and will analyze the data collected during treatment.
Description: Study the prognostic factors of the clinical course of patients on Day 15 under treatment with remdesivir. Clinical progress will be categorized using a 7-point ordinal scale.
Measure: Clinical course on Day 15. Time: 15 daysDescription: Explore the prognostic factors of the clinical course of patients on Day 3
Measure: Clinical course on Day 3. Time: 3 daysDescription: Explore the prognostic factors of the clinical course of patients on Day 8
Measure: Clinical course on Day 8 Time: 8 daysDescription: Explore the prognostic factors of the clinical course of patients on Day11
Measure: Clinical course on Day 11. Time: 11 daysDescription: Explore the prognostic factors of the clinical course of patients on D29.
Measure: Clinical course on Day 29. Time: 29 daysDescription: Duration of treatment with remdesivir
Measure: Duration of treatment Time: 29 daysDescription: PaO2 / FiO2 and artificial ventilation; platelets; bilirubin; average blood pressure and use of vasoactive drugs; Glasgow score; creatinine.
Measure: Sepsis-related Organ Failure Assessment score Time: Day 3, 8, 11, 15 and 29Description: Duration without mechanical ventilation within 29 days of initiation of treatment with remdesivir
Measure: Duration without mechanical ventilation Time: 29 daysDescription: Mortality at 29 days after initiation of treatment with remdesivir.
Measure: Mortality Time: 29 daysDescription: Evaluate the safety of the treatment with cumulative incidence of grade 3 and 4 adverse events (AEs).
Measure: cumulative incidence of grade 3 and 4 adverse events (AEs). Time: 29 daysACTT-2 will evaluate the combination of baricitinib and remdesivir compared to remdesivir alone. Subjects will be assessed daily while hospitalized. If the subjects are discharged from the hospital, they will have a study visit at Days 15, 22, and 29. For discharged subjects, it is preferred that the Day 15 and 29 visits are in person to obtain safety laboratory tests and oropharyngeal (OP) swab and blood (serum only) samples for secondary research as well as clinical outcome data. However, infection control or other restrictions may limit the ability of the subject to return to the clinic. In this case, these visits may be conducted by phone, and only clinical data will be obtained. The Day 22 visit does not have laboratory tests or collection of samples and is conducted by phone. The primary outcome is time to recovery by Day 29.
Description: Day of recovery is defined as the first day on which the subject satisfies one of the following three categories from the ordinal scale: 1) Not hospitalized, no limitations on activities; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Hospitalized, not requiring supplemental oxygen and no longer requires ongoing medical care.
Measure: Time to recovery Time: Day 1 through Day 29Description: PT reported as international normalized ratio (INR).
Measure: Change from baseline in prothrombin time (PT) 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: 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: 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: Measured in days
Measure: Duration of oxygen use Time: Day 1 through Day 29Description: For any reason.
Measure: Incidence of discontinuation or temporary suspension of investigational therapeutics Time: Day 1 through Day 10Description: 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: Participant's clinical status at Day 15 by ordinal scale Time: Day 15Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.
Measure: Percentage of subjects reporting each severity rating on an 8 point ordinal scale Time: Days 3, 5, 8, 11, 22, and 29Description: 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 28-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 29This study will evaluate the efficacy and safety of combination therapy with remdesivir plus tocilizumab compared with remdesivir plus placebo in hospitalized patients with COVID-19 pneumonia.
Description: For participants entering the study already in ICU or on mechanical ventilation, clinical failure is defined as a one-category worsening on the ordinal scale, withdrawal or death.
Measure: Time to Clinical Failure, Defined as the Time from Randomization to the First Occurrence of Death, Mechanical Ventilation, ICU Admission, or Withdrawal (whichever occurs first) Time: Up to Day 60The purpose of this study is to assess the safety and efficacy of merimepodib (MMPD) oral solution when administered in combination with remdesivir in adult patients with advanced COVID-19.
Description: Proportion of subjects alive at Day 28 who are not hospitalized or if hospitalized are free of respiratory failure
Measure: Number of subjects not hospitalized or, if hospitalized, free of respiratory failure Time: Day 0 to Day 28Description: Number of Adverse Events (AEs) and number & percentage of subjects experiencing AEs after administration of the first dose of study drug
Measure: Adverse Events Time: Day 0 to Day 56Description: Change in NIAID 8-point ordinal scale, where 1=Death and 8=Not hospitalized, no limitations on activities
Measure: National Institute of Allergy and Infectious Disease (NIAID) 8-Point Ordinal Scale Time: Day 0 to Day 28Description: Duration of fever
Measure: Temperature Time: Day 0 to Day 37Description: Number of deaths
Measure: Death Time: Day 0 to Day 56Description: Need and duration of mechanical ventilation
Measure: Mechanical ventilation Time: Day 0 to Day 56Description: Duration of vasopressor support
Measure: Vasopressor Support Time: Day 0 to Day 56Description: Duration of oxygen therapy via mechanical ventilation, face mask or nasal cannula
Measure: Oxygen Therapy Time: Day 0 to Day 37Description: Time to cessation of viral shedding based on absence of SARS-CoV-2 in a PCR based COVID-19 test
Measure: Cessation of Viral Shedding Time: Day 0 to Day 37Description: Change in SpO2/FiO2
Measure: Change in Oxygen Saturation/Fraction of Inspired Oxygen Time: Day 0 to Day 37The primary objectives of this study are to evaluate the safety, tolerability, and pharmacokinetics (PK) of remdesivir (RDV) in participants with laboratory-confirmed coronavirus disease 2019 (COVID-19) aged 0 days to < 18 years.
Description: Plasma concentrations will be drawn as follows: (1) for cohorts 1-4 on Day 2, and Day 3, Day 5 is optional; (2) for cohorts 5-7 on Day 2 or Day 3.
Measure: Plasma Concentrations of Remdesivir (RDV) and Metabolites Time: Day 2: end of infusion and 4 hours post end of infusion, Day 3: pre-infusion and 2 hours post end of infusion, and Day 5: middle of infusion and 6 hours post end of infusion; infusion duration: 30 minutes to 2 hoursDescription: The ordinal scale is an assessment of the clinical status at a given day. Each day, the worst score from the previous day will be recorded. 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 low flow supplemental oxygen 5.) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (coronavirus (COVID-19) related or otherwise) 6.) Hospitalized, not requiring supplemental oxygen - no longer required ongoing medical care (other than per protocol Remdesivir administration) 7.) Not hospitalized.
Measure: Clinical Improvement on a 7-point Ordinal Scale Time: First dose date up to 10 daysDescription: Confirmed negative PCR is defined by 2 consecutive negative PCR results.
Measure: Days to First Confirmed Negative Polymerase Chain Reaction (PCR) Result Time: First dose date up to 10 daysDescription: The PEWS is measured by 3 components, including 1.) behavior, 2.) perfusion assessed by capillary refill and heart rate, and 3.) respiratory status assessed by respiratory rate, effort, and oxygen requirement. The score ranges between zero to 9 point, with 9 point representing the highest severity level.
Measure: Clinical Improvement Based on Scoring Using the Pediatric Early Warning Score (PEWS) Improvement Scale Time: First dose date up to 10 daysDescription: Plasma concentrations will be drawn as follows: (1) for cohorts 1-4 on Day 2, and Day 3, Day 5 is optional; (2) for cohorts 5-7 on Day 2 or Day 3.
Measure: Plasma Concentrations of Sulfobutylether β-cyclodextrin Sodium (SBECD) Time: Day 2: end of infusion and 4 hours post end of infusion, Day 3: pre-infusion and 2 hours post end of infusion, and Day 5: middle of infusion and 6 hours post end of infusion; infusion duration: 30 minutes to 2 hoursThe goal of this project is to rapidly screen promising agents, in the setting of an adaptive platform trial, for treatment of critically ill COVID-19 patients. In this phase 2 platform design, agents will be identified with a signal suggesting a big impact on reducing mortality and the need for, as well as duration, of mechanical ventilation.
Description: Time to achieve durable change in COVID-19 to ordinal level 4 or less for at least 48 hours
Measure: Identify agents that will result in substantial improvements to the clinical condition of participants with COVID-19 Time: Up to 28 daysDescription: % of COVID-19 level 5 who never progress to COVID-19 level 6/7
Measure: Improvement in disease severity Time: Up to 60 daysDescription: Ventilator-free Days
Measure: Health care utilization Time: Up to 60 daysDescription: Total grade 3 or higher AEs by arm and total number of patients with grade 3 or higher AEs by arm. ● Total grade 3 or higher AEs of special interest by arm and total number of patients with grade 3 or higher AEs of special interest by arms (based upon lab assessments)
Measure: Frequency of serious AEs Time: Up to 60 daysDescription: Mortality at 28 days after study enrollment
Measure: Mortality Time: Up to 28 daysACTT-3 will evaluate the combination of interferon beta-1a and remdesivir compared to remdesivir alone. Subjects will be assessed daily while hospitalized. If the subjects are discharged from the hospital, they will have a study visit at Days 15, 22, and 29. For discharged subjects, it is preferred that the Day 15 and 29 visits are in person to obtain safety laboratory tests and oropharyngeal (OP) swab and blood (serum only) samples for secondary research as well as clinical outcome data. However, infection control or other restrictions may limit the ability of the subject to return to the clinic. In this case, these visits may be conducted by phone, and only clinical data will be obtained. The Day 22 visit does not have laboratory tests or collection of samples and is conducted by phone. The primary outcome is time to recovery by Day 29.
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 and 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: 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: Measured in days.
Measure: Duration of hospitalization Time: Day 1 through Day 29Description: Measured in days.
Measure: Duration of invasive mechanical ventilation 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: Measured in days.
Measure: Duration of non invasive ventilation/high flow oxygen use Time: Day 1 through Day 29Description: Measured in days
Measure: Duration of oxygen use Time: Day 1 through Day 29Description: For any reason.
Measure: Incidence of discontinuation or temporary suspension of investigational therapeutics Time: Day 1 through Day 10Description: 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: Participant's clinical status at Day 15 by ordinal scale Time: Day 15Description: The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.
Measure: Percentage of subjects reporting each severity rating on an 8 point ordinal scale Time: Days 3, 5, 8, 11, 22, and 29Description: 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 28-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 29Description: 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 and 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 for participants not on mechanical ventilation (baseline ordinal score of 4, 5, or 6) Time: Day 1 through Day 29Beyond supportive care, there are currently no proven treatment options for coronavirus disease (COVID-19) and related pneumonia, caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).Investigators have seen recently from experience in Western countries with best health care systems that pandemics cannot be managed in hospitals. Investigators have seen ICUs crowded to capacity, healthcare workers being exposed and going to quarantine or dying after exposure to large doses of viral inoculums. Investigators recommend that institutions should register for Clinical trials and consider emergency use of TPE. In Pandemics, time is of essence to avoid mortality by intervening early with available evidence, preferably as part of clinical trial.Since the outbreak of corona virus disease (COVID-19), main treatment modalities have been antivirals, interferons, glucocorticoids, anti-coagulants and supportive treatment in addition to traditional Chinese medicine. There are also clinical trials exploring hydroxyquinoline / chloroquine sulphate, azithromycin, immunoglobulins, Vitamin-C, washed microbiota, nebulized interferon, teicoplanin as well as Mesenchymal stem cells. However, most of these trials were small and remain in the experimental phase with currently no effective / specific antiviral with robust scientific evidence as regards the mortality reduction in COVID-19.In an attempt to treat COVID-19, investigator will use different investigational treatment either alone or in combination to see mortality and morbidity benefit on the basis of limitted evidence available so far. These investigational modalities include Therapeutic plasma exchange (TPE), Convalescent Plasma (CP), Remdesivir, Tocilizumab and Mesenchymal stem cell (MSC) therapy in addition to standard supportive treatment.
Description: death or recovery
Measure: survival Time: 28 daysDescription: duration in days
Measure: duration of hospitalization Time: 28 daysDescription: duration in days to normalize symptoms and laboratory parameters
Measure: Time to resolution of cytokine release storm Time: 28 daysDescription: Time in days to turn PCR negative
Measure: Time of viral clearance Time: 45 daysDescription: incidence of Post Covid lung fibrosis
Measure: Complications Time: 90 daysThis study looks at the safety and effectiveness of different drugs in treating COVID-19 in people who have been hospitalized with the infection. Participants in the study will be treated with either a study drug plus current standard of care (SOC), or with placebo plus current SOC.
Description: Oxygen requirements measured by 7 categories (1 = least severe, 7 = most severe). The participant's highest (i.e. most severe) observed score is used.
Measure: Pulmonary ordinal outcome (Stage 1) Time: Day 5Description: Extrapulmonary complications and respiratory dysfunction measured by 7 categories (1= least severe, 7 = most severe). The participant's highest (i.e. most severe) observed score is used.
Measure: Pulmonary+ ordinal outcome (Stage 1) Time: Day 5Description: Sustained recovery defined as being discharged from the index hospitalization, followed by being alive and home for 14 consecutive days prior to Day 90.
Measure: Time from randomization to sustained recovery (Stage 2) Time: Up to Day 90Description: Oxygen requirements measured by 7 categories (1 = least severe, 7 = most severe). The participant's highest (i.e. most severe) observed score is used.
Measure: Pulmonary ordinal outcome Time: Days 1-7, 14 and 28Description: Extrapulmonary complications and respiratory dysfunction measured by 7 categories (1= least severe, 7 = most severe). The participant's highest (i.e. most severe) observed score is used.
Measure: Pulmonary+ ordinal outcome Time: Days 1-7Description: Total of: Respiratory rate (breaths per minute) scored from 0 to +3; Oxygen saturation (%) scored from 0 to +3; Any supplemental oxygen scored from 0 to +2; Temperature scored from 0 to +3; Systolic BP scored from 0 to +3; Heart rate (beats per minute) scored from 0 to +3.; and AVPU (alert, voice, pain, unresponsive) scored from 0 to +3. A higher score denotes a worse outcome.
Measure: Change in New Early Warning (NEW) Score Time: Baseline to Day 5This protocol will serve as a platform for assessing treatments for adult patients hospitalized for medical management of COVID-19 without related serious end-organ failure. Trials will involve sites around the world strategically chosen to ensure rapid enrollment. This trial will compare hyperimmune intravenous immunoglobulin (hIVIG) with matched placebo, when added to standard of care (SOC), for preventing further disease progression and mortality related to COVID-19. SOC will include remdesivir unless it is contraindicated for an individual patient.
Description: The primary objective is to compare the clinical status of patients in each group on day 7 of follow-up using the primary ordinal outcome with 7 mutually exclusive categories: 7. Death 6. End-organ failure 5. Life-threatening end-organ dysfunction 4. Serious end-organ dysfunction 3. Moderate end-organ dysfunction 2. Limiting symptoms due to COVID-19 1. No limiting symptoms due to COVID-19 Outcome is reported as the percent of participants in each of 7 categories.
Measure: Ordinal Outcome Scale - Day 7 Time: 7 daysDescription: Outcome reported as the percent of participants who expire for any reason by day 28 post treatment.
Measure: All-cause mortality through Day 28 Time: 28 daysDescription: A secondary outcome is to compare the clinical status of patients in each group on day 3, 5, 14, and 28 of follow-up using the primary ordinal outcome. Outcome is reported as the percent of participants in each of 7 categories.
Measure: Ordinal Outcome Scale Time: 3 days, 5 days, 14 days, and 28 daysDescription: The National Early Warning Score (NEWS) is used to determine the degree of illness of a patient and prompt critical care intervention. The score takes into account respiratory rate, oxygen saturation, use of respiratory support, body temperature, blood pressure, and heart rate. These data are entered into a program to calculate a NEW score. Scores range from -3 to +3 with scores closer to zero representing a lower degree of illness. Scores will be collected at baseline and day 7 and the change in score at these 2 time points will be reported.
Measure: Change in National Early Warning Score (NEWS) Time: 7 daysDescription: Time to worsening is defined as the 3 least favorable categories on the primary ordinal scale. Outcome is reported as the percent of participants in each arm who are characterized as categories 5, 6, and 7 on the primary ordinal scale at 7, 14, and 28 days post treatment.
Measure: Time to Worsening Time: 7 days, 14 days, and 28 daysDescription: Outcome is reported as the percent of participants in each arm who are alive and discharged from the hospital to home or rehabilitation at days 7, 14, and 28 post treatment.
Measure: Discharge Status Time: 7 days, 14 days, and 28 daysDescription: Outcome is reported as the mean number of days alive and outside the hospital from study entry to Day 28 for participants in each arm.
Measure: Days Alive Outside the Hospital Time: 28 daysDescription: A secondary outcome is to compare the clinical status of patients in each group on day 3, 5, 7, 14, and 28 post treatment limited to using the pulmonary elements of the primary ordinal outcome (e.g., requirement for invasive ventilation). Outcome is reported as the percent of participants in each arm who fall into each of the 7 categories of the primary ordinal outcome with regard to their pulmonary dysfunction only.
Measure: Pulmonary-only Components of the Primary Ordinal Outcome Time: 3 days, 5 days, 7 days, 14 days, and 28 daysDescription: A secondary outcome is to compare the clinical status of patients in each group on day 3, 5, 7, 14, and 28 post treatment limited to using the thrombotic conditions (e.g., arterial thrombosis) in the primary ordinal outcome. Outcome is reported as the percent of participants in each arm who fall in each of the 7 categories of the primary ordinal outcome with regard to thrombotic conditions only.
Measure: Thrombotic Components of the Primary Ordinal Outcome Time: 3 days, 5 days, 7 days, 14 days, and 28 daysDescription: Time to recovery is defined as the 2 most favorable categories on the primary ordinal scale. Outcome is reported as the percent of participants in each arm who are characterized as categories 1 or 2 at 7, 14, and 28 days post treatment.
Measure: Time to recovery Time: 7 days, 14 days, and 28 daysDescription: Clinical organ dysfunction is defined by new onset of any one or more of the following. Outcome is reported as the percent of participants in each arm who meet any 1 of the following criteria by day 28 post treatment. A) Respiratory dysfunction B) Cardiac and vascular dysfunction C) Renal dysfunction D) Hepatic dysfunction E) Neurological dysfunction F) Haematological dysfunction G) Serious infection
Measure: Clinical Organ Dysfunction Time: 28 daysDescription: Outcome is reported as the percent of participants in each arm who experience a new grade 3 or 4 event, a serious adverse event (SAE), or death through day 7 (primary safety endpoint) post treatment.
Measure: Safety and Tolerability - Adverse Events Time: 7 daysDescription: Outcome is reported as the percent of participants in each arm for who had any grade of reaction during the infusion or within 2 hours afterwards, for whom the infusion is interrupted prior to completion, or for whom the infusion is stopped prior to completion.
Measure: Safety and Tolerability - Infusion Reactions, Interruptions, or Cessation Time: approximately 2 hoursDescription: Outcome is reported as the percent of participants in each arm who experience a serious adverse event (SAE) or death through day 28 post treatment.
Measure: Safety and Tolerability - Serious Adverse Events Time: 28 daysDescription: Outcome is reported as the percent of participants in each arm who experience an adverse event (AE) of any grade present (new or continuing) on days 1, 3, 7, and 28 post treatment.
Measure: Safety and Tolerability - Prevalence of Adverse Events Time: 1 day, 3 days, 7 days, and 28 daysDescription: Outcome reported as the change in anti-SARS-CoV-2 IgG antibody level in blood from baseline to 1, 3, 7, and 28 days post treatment. Outcome is reported in units of antibody titer.
Measure: Change in Neutralizing Antibody Level Time: 1 day, 3 days, 7 days, and 28 daysRemdesivir is a monophosphoramidate prodrug of an adenosine analogue and it has a broad-spectrum antiviral activity against paramyxoviruses, falviviruses and coronaviruses. It showed in vitro activity on human airway epithelial cells against SARS-CoV-2. It is an investigational drug and granted an Emergency Use Authorization by Food and Drug Administration FDA, so it is under clinical trial. The potent mechanism of action of this drug is still unclear but it effects through several processes. It can interfere with nsp12 polymerase even when exoribonuclease proofreading is intact. It can also produce nucleoside triphosphate NTP that acts pharmacologically active alternate substrate of RNA-chain terminator, as a result NTP can constrain active triphosphates into viral RNA of coronaviruses. There is evidence of high genetic barrier to develop resistance against Remdesivir in coronavirus as a result of which is maintains its effectiveness in antiviral therapies against these viruses. Effectiveness of Remdesivir has been reported against different groups of coronaviruses including Alphacoronavirus NL63 and several SARS/MERS-CoV coronaviruses.
Description: Clinical improvement of COVID-19 patients by Remdesivir.
Measure: Clinical response after administration Time: 10 daysDescription: Overall survival of COVID-19 patients after drug administration.
Measure: Clinical response to treatment Time: 15 daysDescription: Number of days of hospital admission either in ICU or HDUs till date of discharge
Measure: Duration of hospitalization Time: 15 daysDescription: Duration of increased supplemental oxygen requirement from baseline
Measure: Supplemental Oxygen Requirement from Baseline Time: 15 daysThis study is an adaptive, randomized, open-label, controlled clinical trial, performed worldwide in collaboration with WHO and INSERM.
Description: WHO 7-point ordinal scale: Not hospitalized, no limitations on activities; Not hospitalized, limitation on activities; Hospitalized, not requiring supplemental oxygen; Hospitalized, requiring supplemental oxygen; Hospitalized, on non-invasive ventilation or high flow oxygen devices; Hospitalized, on invasive mechanical ventilation or ECMO; Death
Measure: Improvement of clinical status on the ordinal 7-point severity-scale at day 15. Time: at day 15The purpose of this study is to describe the pharmacokinetic (PK) properties and safety of remdesivir (GS-5734TM) (RDV) administered to pregnant and non-pregnant women with COVID-19. It is a Phase I, prospective, open label, non-randomized opportunistic PK study in pregnant and non-pregnant women of childbearing potential hospitalized and receiving RDV for treatment of COVID-19. RDV will not be provided as part of the study.
Description: For Arm 1 only; Calculated using non-compartmental methods
Measure: PK Outcome: Area under the plasma concentration-time curve (AUC) of RDV Time: Through Day 5 of infusionsDescription: For Arm 1 only; Calculated using non-compartmental methods
Measure: PK Outcome: Half-life (t1/2) of RDV Time: Through Day 5 of infusionsDescription: For Arm 1 only; Calculated using non-compartmental methods
Measure: PK Outcome: Trough concentration (Ctrough) of GS-441524 Time: Through Day 5 of infusionsDescription: For Arm 1 only; Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017
Measure: Safety Outcome: Maternal renal adverse event (AE) of any grade Time: Through 7 Days post-last infusionDescription: For Arm 1 only; Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017
Measure: Safety Outcome: Maternal hepatic AE of any grade Time: Through 7 Days post-last infusionDescription: For Arm 1 only; Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017
Measure: Safety Outcome: Maternal hematologic AE of any grade Time: Through 7 Days post-last infusionDescription: For Arm 1 only; Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017
Measure: Safety Outcome: Maternal Grade 3 or higher AE Time: Through 4 Weeks post-last infusion and DeliveryDescription: For Arm 1 only; Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017
Measure: Safety Outcome: Serious AE Time: Through 4 Weeks post-last infusion and DeliveryDescription: For Arm 1 only; Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017
Measure: Safety Outcome: Maternal Grade 3 or higher AE assessed as related to RDV by the Clinical Management Committee (CMC) Time: Through 4 Weeks post-last infusion and DeliveryDescription: For Arm 1 only
Measure: Safety Outcome: Pregnancy loss Time: DeliveryDescription: For Arm 1 only
Measure: Safety Outcome: Congenital anomalies Time: DeliveryDescription: For Arm 1 only
Measure: Safety Outcome: Preterm birth, defined as < 37 weeks Time: DeliveryDescription: For Arm 1 only
Measure: Safety Outcome: Preterm birth, defined as < 34 weeks Time: DeliveryDescription: For Arm 1 only
Measure: Safety Outcome: Small for gestational age, defined as < 10th percentile Time: DeliveryDescription: For Arm 1 only
Measure: Safety Outcome: Newborn birth weight Time: DeliveryDescription: For Arm 1 only
Measure: Safety Outcome: Newborn length Time: DeliveryDescription: For Arm 1 only
Measure: Safety Outcome: Newborn head circumference Time: DeliveryDescription: For Arm 2 only; Calculated using non-compartmental methods
Measure: PK Outcome: AUC of RDV Time: Through Day 5 of infusionsDescription: For Arm 2 only; Calculated using non-compartmental methods
Measure: PK Outcome: t1/2 of RDV Time: Through Day 5 of infusionsDescription: For Arm 2 only; Calculated using non-compartmental methods
Measure: PK Outcome: Ctrough of GS-441524 Time: Through Day 5 of infusionsDescription: For Arm 2 only; Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017
Measure: Safety Outcome: Renal AE of any grade Time: Through 7 Days post-last infusionDescription: For Arm 2 only; Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017
Measure: Safety Outcome: Hepatic AE of any grade Time: Through 7 Days post-last infusionDescription: For Arm 2 only; Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017
Measure: Safety Outcome: Hematologic AE of any grade Time: Through 7 Days post-last infusionDescription: For Arm 2 only; Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017
Measure: Safety Outcome: Grade 3 or higher AE Time: Through 4 Weeks post-last infusionDescription: For Arm 2 only; Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017
Measure: Safety Outcome: Serious AE Time: Through 4 Weeks post-last infusionDescription: For Arm 2 only; Graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, dated July 2017
Measure: Safety Outcome: Grade 3 or higher AE assessed as related to RDV by the CMC Time: Through 4 Weeks post-last infusionDescription: For women in Arm 1 who received RDV within 5 days of delivery only
Measure: PK Outcome: Ratio of cord blood/maternal plasma RDV concentrations Time: DeliveryDescription: For women in Arm 1 who received RDV within 5 days of delivery only
Measure: PK Outcome: Ratio of cord blood/maternal plasma GS-441524 concentrations Time: DeliveryThis is a platform trial to conduct a series of randomized, double-blind, placebo-controlled trials using common assessments and endpoints in hospitalized adults diagnosed with COVID-19. BET is a proof-of-concept study with the intent of identifying promising treatments to enter a more definitive study. The study will be conducted in up to 40 sites throughout the US. The study will compare different investigational therapeutic agents to a common control arm and determine which have relatively large effects. In order to maintain the double blind, each intervention will have a matched placebo. However, the control arm will be shared between interventions and may include participants receiving the matched placebo for a different intervention. The goal is not to determine clear statistical significance for an intervention, but rather to determine which products have clinical data suggestive of efficacy and should be moved quickly into larger studies. Estimates produced from BET will provide an improved basis for designing the larger trial, in terms of sample size and endpoint selection. Products with little indication of efficacy will be dropped on the basis of interim evaluations. In addition, some interventions may be discontinued on the basis of interim futility or efficacy analyses. One or more interventions may be started at any time. The number of interventions enrolling are programmatic decisions and will be based on the number of sites and the pace of enrollment. At the time of enrollment, subjects will be randomized to receive any one of the active arms they are eligible for or placebo. Approximately 100 subjects will be assigned to each arm entering the platform and a given site will generally have no more than 3 interventions at once. The BET-A stage will evaluate the combination of remdesivir with risankizumab vs remdesivir with a risankizumab placebo. The primary objective is to evaluate the clinical efficacy of different investigational therapeutics relative to the control arm in adults hospitalized with COVID-19 according to clinical status (8-point ordinal scale) at Day 8.
Description: Clinical status assessed using ordinal scale: 1) Not hospitalized, no limitations on activities; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Hospitalized, not requiring supplemental oxygen and no longer requires ongoing medical care; 4) Hospitalized, not requiring supplemental oxygen but requiring ongoing medical care (COVID-19 related or otherwise); 5) Hospitalized, requiring supplemental oxygen; 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 8) Death.
Measure: Clinical efficacy in adults hospitalized with COVID-19 according to clinical status on an 8-point ordinal scale. Time: Day 8Description: 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: Day of recovery is defined as the first day on which the subject satisfies one of the following three categories from the ordinal scale: 1) Not hospitalized, no limitations on activities; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care.
Measure: Clinical efficacy, as assessed by time to recovery Time: Day 1 through Day 29Description: For any reason.
Measure: Discontinuation or temporary suspension of study product administration Time: Day 1 through Day 29Description: Measured in days.
Measure: Duration of hospitalization Time: Day 1 through Day 29Description: Measured in days.
Measure: Duration of new mechanical ventilation or extracorporeal membrane oxygenation (ECMO) use Time: Day 1 through Day 29Description: Measured in days.
Measure: Duration of new non-invasive ventilation or high flow oxygen use during the study Time: Day 1 through Day 29Description: Measured in days; supplemental oxygen concentration or flow rate will be measured.
Measure: Duration of new oxygen use Time: Day 1 through Day 29Description: Measured in days.
Measure: Duration of non-invasive ventilation/high flow oxygen use Time: Day 1 through Day 29Description: Supplemental oxygen concentration or flow rate will be measured.
Measure: Incidence of new oxygen use Time: Day 1 through Day 29Description: Clinical outcome assessed using ordinal scale: 1) Not hospitalized, no limitations on activities; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Hospitalized, not requiring supplemental oxygen and no longer requires ongoing medical care; 4) Hospitalized, not requiring supplemental oxygen but requiring ongoing medical care (COVID-19 related or otherwise); 5) Hospitalized, requiring supplemental oxygen; 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 8) Death.
Measure: Mean change in the ordinal scale Time: Day 1 through Day 29Description: Measured in days; supplemental oxygen concentration or flow rate will be measured.
Measure: Oxygenation use Time: Day 1 through Day 29Description: A subject who is "alive and without respiratory failure" is defined as meeting any one of the following five categories from the ordinal scale: 1) Not hospitalized, no limitations on activities; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3)Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 5) Hospitalized, requiring supplemental oxygen.
Measure: Proportion of subjects alive and without respiratory failure Time: Day 1 to Day 29Description: 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: Clinical outcome assessed using ordinal scale: 1) Not hospitalized, no limitations on activities; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Hospitalized, not requiring supplemental oxygen and no longer requires ongoing medical care; 4) Hospitalized, not requiring supplemental oxygen but requiring ongoing medical care (COVID-19 related or otherwise); 5) Hospitalized, requiring supplemental oxygen; 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 8) Death.
Measure: Time to an improvement of one category using an ordinal scale Time: Day 1 through Day 29Description: Clinical outcome assessed using ordinal scale: 1) Not hospitalized, no limitations on activities; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Hospitalized, not requiring supplemental oxygen and no longer requires ongoing medical care; 4) Hospitalized, not requiring supplemental oxygen but requiring ongoing medical care (COVID-19 related or otherwise); 5) Hospitalized, requiring supplemental oxygen; 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 8) Death.
Measure: Time to an improvement of two categories using an ordinal scale Time: Day 1 through Day 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 29Description: Measured in days.
Measure: Ventilator/ extracorporeal membrane oxygenation (ECMO) use Time: Day 1 through Day 29This is a platform trial to conduct a series of randomized, double-blind, placebo-controlled trials using common assessments and endpoints in hospitalized adults diagnosed with COVID-19. BET is a proof-of-concept study with the intent of identifying promising treatments to enter a more definitive study. The study will be conducted in up to 40 sites throughout the US. The study will compare different investigational therapeutic agents to a common control arm and determine which have relatively large effects. In order to maintain the double blind, each intervention will have a matched placebo. However, the control arm will be shared between interventions and may include participants receiving the matched placebo for a different intervention. The goal is not to determine clear statistical significance for an intervention, but rather to determine which products have clinical data suggestive of efficacy and should be moved quickly into larger studies. Estimates produced from BET will provide an improved basis for designing the larger trial, in terms of sample size and endpoint selection. Products with little indication of efficacy will be dropped on the basis of interim evaluations. In addition, some interventions may be discontinued on the basis of interim futility or efficacy analyses. One or more interventions may be started at any time. The number of interventions enrolling are programmatic decisions and will be based on the number of sites and the pace of enrollment. At the time of enrollment, subjects will be randomized to receive any one of the active arms they are eligible for or placebo. Approximately 100 subjects will be assigned to each arm entering the platform and a given site will generally have no more than 3 interventions at once. The BET-B stage will evaluate the combination of remdesivir with lenzilumab vs remdesivir with a lenzilumab placebo. The primary objective is to evaluate the clinical efficacy of different investigational therapeutics relative to the control arm in adults hospitalized with COVID-19 according to clinical status (8-point ordinal scale) at Day 8.
Description: Clinical status assessed using ordinal scale: 1) Not hospitalized, no limitations on activities; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Hospitalized, not requiring supplemental oxygen and no longer requires ongoing medical care; 4) Hospitalized, not requiring supplemental oxygen but requiring ongoing medical care (COVID-19 related or otherwise); 5) Hospitalized, requiring supplemental oxygen; 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 8) Death.
Measure: Clinical efficacy in adults hospitalized with COVID-19 according to clinical status on an 8-point ordinal scale Time: Day 8Description: 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: Day of recovery is defined as the first day on which the subject satisfies one of the following three categories from the ordinal scale: 1) Not hospitalized, no limitations on activities; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care.
Measure: Clinical efficacy, as assessed by time to recovery Time: Day 1 through Day 29Description: For any reason.
Measure: Discontinuation or temporary suspension of study product administration Time: Day 1 through Day 29Description: Measured in days.
Measure: Duration of hospitalization Time: Day 1 through Day 29Description: Measured in days.
Measure: Duration of new mechanical ventilation or extracorporeal membrane oxygenation (ECMO) use Time: Day 1 through Day 29Description: Measured in days.
Measure: Duration of new non-invasive ventilation or high flow oxygen use during the study Time: Day 1 through Day 29Description: Measured in days; supplemental oxygen concentration or flow rate will be measured.
Measure: Duration of new oxygen use Time: Day 1 through Day 29Description: Measured in days.
Measure: Duration of non-invasive ventilation/high flow oxygen use Time: Day 1 through Day 29Description: Supplemental oxygen concentration or flow rate will be measured.
Measure: Incidence of new oxygen use Time: Day 1 through Day 29Description: Measured in days.
Measure: Incidence of ventilator/ extracorporeal membrane oxygenation (ECMO) use Time: Day 1 through Day 29Description: Clinical outcome assessed using ordinal scale: 1) Not hospitalized, no limitations on activities; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Hospitalized, not requiring supplemental oxygen and no longer requires ongoing medical care; 4) Hospitalized, not requiring supplemental oxygen but requiring ongoing medical care (COVID-19 related or otherwise); 5) Hospitalized, requiring supplemental oxygen; 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 8) Death.
Measure: Mean change in the ordinal scale Time: Day 1 through Day 29Description: Measured in days; supplemental oxygen concentration or flow rate will be measured.
Measure: Oxygenation use Time: Day 1 through Day 29Description: A subject who is "alive and without respiratory failure" is defined as meeting any one of the following five categories from the ordinal scale: 1) Not hospitalized, no limitations on activities; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3)Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 5) Hospitalized, requiring supplemental oxygen.
Measure: Proportion of subjects alive and without respiratory failure Time: Day 1 through Day 29Description: 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: Clinical outcome assessed using ordinal scale: 1) Not hospitalized, no limitations on activities; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Hospitalized, not requiring supplemental oxygen and no longer requires ongoing medical care; 4) Hospitalized, not requiring supplemental oxygen but requiring ongoing medical care (COVID-19 related or otherwise); 5) Hospitalized, requiring supplemental oxygen; 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 8) Death.
Measure: Time to an improvement of one category using an ordinal scale Time: Day 1 through Day 29Description: Clinical outcome assessed using ordinal scale: 1) Not hospitalized, no limitations on activities; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Hospitalized, not requiring supplemental oxygen and no longer requires ongoing medical care; 4) Hospitalized, not requiring supplemental oxygen but requiring ongoing medical care (COVID-19 related or otherwise); 5) Hospitalized, requiring supplemental oxygen; 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 8) Death.
Measure: Time to an improvement of two categories using an ordinal scale Time: Day 1 through Day 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 29ACTIV-1 IM is a master protocol designed to evaluate multiple investigational agents for the treatment of moderately or severely ill patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The research objectives are to evaluate each agent with respect to speed of recovery, mortality, illness severity, and hospital resource utilization. Each agent will be evaluated as add-on therapy to the standard of care (SoC) in use at the local clinics, including remdesivir (provided). The SoC may change during the course of the study based on other research findings. Comparisons of the agents among themselves is not a research objective. The study population corresponds to moderately and severely ill patients infected with the coronavirus disease 2019 (COVID-19) virus. Recruitment will target patients already hospitalized for treatment of COVID-19 infection as well as patients being treated for COVID-19 infection in Emergency Departments while waiting to be admitted to the hospital. Patients both in and out of the ICU are included in the study population.
Description: time to recovery by Day 29
Measure: Number of patients that recovered from COVID-19 Time: days 1-29Description: Number of patients hospitalized on invasive mechanical ventilation
Measure: Change in number of patients hospitalized on invasive mechanical ventilation Time: Days 15 and 29Description: 8-point ordinal clinical scale assessed
Measure: number of patients that improved clinically Time: Days 3, 5, 8, 11, 15, 29, and 60Description: mortality rate
Measure: Number of patient deaths Time: Day 14Description: compared to baseline the amount of supplementation oxygen
Measure: Number of patients with decreased supplemental oxygenation needed Time: Day 29Description: assessment of non-invasive ventilation/ high flow oxygen up to day 29
Measure: Change in number of patients needing non-invasive ventilation/ high flow oxygen Time: Day 29Description: number of days in the hospital
Measure: Number of days patients are in the hospital Time: Days 3, 5, 8, 11, 15, 22, and 29Description: Cumulative incidence of SAEs and AEs of grade 3 and 4
Measure: Number of SAEs and AEs of grade 3 and 4 Time: Days 3, 5, 8, 11, 15, 22, and 29Description: Number of patients with changes in abnormal WBC counts
Measure: Number of patients with changes in abnormal WBC counts Time: Days 3, 5, 8, 11, 15, and 29Description: time to discharge or to a NEWS of <=2 and maintained for 24 hours
Measure: Number of patients with National Early Warning Scores (NEWS) <=2 Time: Days 3, 5, 8, 11, 15, and 29Background - A novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first identified in December 2019 as the cause of a respiratory illness COVID-19 in Wuhan City, China. WHO declared a public health emergency outbreak of this virus on 30 January 2020 and declared COVID-19 a global pandemic on 11 March, 2020. Bangladesh reported its first case on March 8, 2020 and first fatality on April 1, 2020. Bangladesh had shown a staggered course of COVID-19 transmission initially but a surge in cases was observed from April, 2020. Remdesivir remains as the only potential therapy for the treatment of COVID-19 till date. Based on several pre-clinical studies in SARS-CoV and MERS-CoV infections, Animal trials in COVID-19 and data from human trials, this randomized, controlled, open label trial will evaluate the antiviral activity and safety of Remdesivir in Bangladeshi hospitalized patients with severe COVID-19. This study finding will provide knowledge if Remdesivir is effective enough to treat Bangladeshi COVID-19 hospitalized patients with adequate safety and tolerability. The result of this study will help the key opinion leaders regarding the matter, to take appropriate decision regarding usage of Remdesivir for the treatment of COVID-19 in Bangladesh. Study Procedure - All patients will receive the standard medical care for COVID-19+ve at the respective hospitals. Vital signs will be recorded every 24 hrs for 1st 5 days then once in 2 days till discharge or as per the discretion of the attending physicians. After screening the COVID-19 confirmed patients will be randomized into 2 treatment arms. Patient's safety assessment e. g. blood parameters (CBC, Creatinine, SGPT, RBS, Creatinine, Creatinine Clearance) will be done on screening, day 5 and day 14 or discharge; Chest X-ray and ECG on screening and day 14 or discharge. SARS-CoV-2 (viral load) will be looked in on day 5, day 10 and day 14 or at the time of discharge. In case any study patient deteriorates during the study period will be managed as per the guideline of that particular hospital and if needed will be shifted to ICU. Patients who will recover will be discharged as per the national guideline for the COVID-19 hospitalized patients. Patients will be contacted at 28 days either over phone or in person to get their health status since discharge.
Description: Time to clinical improvement (censored at Day 28), defined as the time (in days) from randomization of study treatment until a decline of two categories on a six-category ordinal scale of clinical status (1 ꞊ discharged; 6 ꞊ death) or live discharge from hospital. Six-category ordinal scale: Hospital discharge or meet discharge criteria Hospitalization, not requiring supplemental oxygen; Hospitalization, requiring supplemental oxygen (but not NIV/ HFNC); ICU/hospitalization, requiring NIV/ HFNC therapy; ICU, requiring ECMO and/or IMV; Death;
Measure: Time to Clinical Improvement (TTCI) Time: 28 DaysAlphabetical listing of all HPO terms. Navigate: Correlations Clinical Trials
Data processed on September 26, 2020.
An HTML report was created for each of the unique drugs, MeSH, and HPO terms associated with COVID-19 clinical trials. Each report contains a list of either the drug, the MeSH terms, or the HPO terms. All of the terms in a category are displayed on the left-hand side of the report to enable easy navigation, and the reports contain a list of correlated drugs, MeSH, and HPO terms. Further, all reports contain the details of the clinical trials in which the term is referenced. Every clinical trial report shows the mapped HPO and MeSH terms, which are also hyperlinked. Related HPO terms, with their associated genes, protein mutations, and SNPs are also referenced in the report.
Drug Reports MeSH Reports HPO Reports