Brief Summary
This 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 Coronavirus Disease 2019 (COVID-19). Big Effect Trial (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 70 domestic sites and 5 international sites. 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 200 (100 treatment and 100 shared placebo) 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.
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 200 (100 treatment and 100 shared placebo) 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.
Brief Title
ACTIV-5 / Big Effect Trial (BET-B) for the Treatment of COVID-19
Detailed Description
This 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 Coronavirus Disease 2019 (COVID-19). Big Effect Trial (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 70 domestic sites and 5 international sites. 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 200 (100 treatment and 100 shared placebo) 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. Subjects will be assessed daily while hospitalized. Once subjects are discharged from the hospital, they will have a study visit at Days 8, 15, 22, 29, and 60 as an outpatient. The Day 8, Day 22 and Day 60 visits do not have laboratory tests or collection of samples and may be conducted by phone. All subjects will undergo a series of efficacy and safety laboratory assessments. Safety laboratory tests and blood (serum and plasma) research samples and oropharyngeal (OP) swabs will be obtained on Day 1 (prior to study product administration) and Days 3, 5, 8, and 11 while hospitalized. OP swabs (oropharyngeal swabs are preferred, but if these are not obtainable, saliva or nasopharyngeal or nasal swabs may be substituted) and blood research samples plus safety laboratory tests will be collected on Day 15 and 29 if the subject attends an in-person visit or is still hospitalized. However, if infection control considerations or other restrictions prevent the subject from returning to the clinic, Day 15 and 29 visits may be conducted by phone and only clinical data will be obtained.
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. The key secondary objectives are to 1) evaluate the clinical efficacy of different investigational therapeutics as assessed by time to recovery compared to the control arm, and 2) to evaluate the proportion of subjects alive and without respiratory failure through Day 29.
Contacts:
20-0013 Central Contact
Telephone: 1 (301) 7617948
Email: DMIDClinicalTrials@niaid.nih.gov
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 200 (100 treatment and 100 shared placebo) 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. Subjects will be assessed daily while hospitalized. Once subjects are discharged from the hospital, they will have a study visit at Days 8, 15, 22, 29, and 60 as an outpatient. The Day 8, Day 22 and Day 60 visits do not have laboratory tests or collection of samples and may be conducted by phone. All subjects will undergo a series of efficacy and safety laboratory assessments. Safety laboratory tests and blood (serum and plasma) research samples and oropharyngeal (OP) swabs will be obtained on Day 1 (prior to study product administration) and Days 3, 5, 8, and 11 while hospitalized. OP swabs (oropharyngeal swabs are preferred, but if these are not obtainable, saliva or nasopharyngeal or nasal swabs may be substituted) and blood research samples plus safety laboratory tests will be collected on Day 15 and 29 if the subject attends an in-person visit or is still hospitalized. However, if infection control considerations or other restrictions prevent the subject from returning to the clinic, Day 15 and 29 visits may be conducted by phone and only clinical data will be obtained.
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. The key secondary objectives are to 1) evaluate the clinical efficacy of different investigational therapeutics as assessed by time to recovery compared to the control arm, and 2) to evaluate the proportion of subjects alive and without respiratory failure through Day 29.
Contacts:
20-0013 Central Contact
Telephone: 1 (301) 7617948
Email: DMIDClinicalTrials@niaid.nih.gov
Categories
Completion Date
Completion Date Type
Actual
Conditions
COVID-19
Eligibility Criteria
Inclusion Criteria:
1. Admitted to a hospital with symptoms suggestive of Coronavirus Disease 2019 (COVID-19) and requires ongoing medical care.
2. Subject (or legally authorized representative) provides informed consent prior to initiation of any study procedures.
3. Subject (or legally authorized representative) understands and agrees to comply with planned study procedures.
4. Male or non-pregnant female adult \>/= 18 years of age at time of enrollment.
5. Illness of any duration and has laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection as determined by polymerase chain reaction (PCR) or other commercial or public health assay (e.g., Nucleic Acid Amplification Test \[NAAT\], antigen test) in any respiratory specimen, or saliva \</=14 days prior to randomization.
6. Illness of any duration, and requiring, just prior to randomization, supplemental oxygen (any flow), mechanical ventilation or Extracorporeal Membrane Oxygenation (ECMO) (ordinal score 5, 6, or 7).
7. Women of childbearing potential must agree to either abstinence or use at least one acceptable method of contraception\* from the time of screening through 5 months post study intraperitoneal (IP) dosing.
\* Acceptable methods include barrier contraceptives (condoms or diaphragm) with spermicide, intrauterine devices (IUDs), hormonal contraceptives, oral contraceptive pills, and surgical sterilization.
8. Agrees not to participate in another blinded clinical trial (both pharmacologic and other types of interventions) for the treatment of COVID-19 through Day 29.
Exclusion Criteria:
1. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 5 times the upper limit of normal.
2. Subjects with a low glomerular filtration rate (eGFR), specifically:
1. Subjects with a glomerular filtration rate (eGFR) 20-30 mL/min are excluded unless in the opinion of the principal investigator (PI), the potential benefit of participation outweighs the potential risk of study participation.
2. All subjects with a glomerular filtration rate (eGFR) \<20 mL/min (including hemodialysis and hemofiltration) are excluded.
3. Pregnancy or breast feeding.
4. Anticipated discharge from the hospital or transfer to another hospital which is not a study site within 72 hours of enrollment.
5. Allergy to any study medication.
6. Received five or more doses of remdesivir prior to screening.
7. Received small molecule tyrosine kinase inhibitors, including Janus kinase (JAK) inhibitors (e.g., baricitinib, ibrutinib, acalabrutinib, imatinib, gefitinib), in the 4 weeks prior to screening.
8. Received monoclonal antibodies targeting cytokines (e.g., tumor necrosis factor (TNF) inhibitors, anti-IL-1 \[e.g., anakinra, canakinumab\], anti-IL-6 \[e.g., tocilizumab, sarilumab, sitlukimab\]), or T-cells (e.g., abatacept) in the 4 weeks prior to screening.
9. Received monoclonal antibodies targeting B-cells (e.g., rituximab, and including any targeting multiple cell lines including B-cells) in the 3 months prior to screening.
10. Received granulocyte-macrophage colony-stimulating factor (GM-CSF) agents (e.g., sargramostim) within 2 months prior to screening.
11. Received other immunosuppressants in the 4 weeks prior to screening and in the judgement of the investigator, the risk of immunosuppression with lenzilumab is larger than the risk of Coronavirus Disease 2019 (COVID-19).
12. Received any live vaccine in the 4 weeks prior to screening.
13. Known active tuberculosis.
14. Known history of Human Immunodeficiency Virus (HIV), Hepatitis B (HBV) or untreated hepatitis C (HCV) infection.
15. History of pulmonary alveolar proteinosis (PAP).
16. Has a malignancy currently receiving immunosuppressive chemotherapy, immunodeficiency, uncontrolled opportunistic infection, or uncontrolled cirrhosis.
17. Has a medical condition that could, in the judgment of the investigator, limit the interpretation and generalizability of trial results.
18. Positive test for influenza virus during the current illness (influenza testing is not required by protocol).
19. Previous participation in an ACTIV-5/Big Effect Trial (BET).
1. Admitted to a hospital with symptoms suggestive of Coronavirus Disease 2019 (COVID-19) and requires ongoing medical care.
2. Subject (or legally authorized representative) provides informed consent prior to initiation of any study procedures.
3. Subject (or legally authorized representative) understands and agrees to comply with planned study procedures.
4. Male or non-pregnant female adult \>/= 18 years of age at time of enrollment.
5. Illness of any duration and has laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection as determined by polymerase chain reaction (PCR) or other commercial or public health assay (e.g., Nucleic Acid Amplification Test \[NAAT\], antigen test) in any respiratory specimen, or saliva \</=14 days prior to randomization.
6. Illness of any duration, and requiring, just prior to randomization, supplemental oxygen (any flow), mechanical ventilation or Extracorporeal Membrane Oxygenation (ECMO) (ordinal score 5, 6, or 7).
7. Women of childbearing potential must agree to either abstinence or use at least one acceptable method of contraception\* from the time of screening through 5 months post study intraperitoneal (IP) dosing.
\* Acceptable methods include barrier contraceptives (condoms or diaphragm) with spermicide, intrauterine devices (IUDs), hormonal contraceptives, oral contraceptive pills, and surgical sterilization.
8. Agrees not to participate in another blinded clinical trial (both pharmacologic and other types of interventions) for the treatment of COVID-19 through Day 29.
Exclusion Criteria:
1. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 5 times the upper limit of normal.
2. Subjects with a low glomerular filtration rate (eGFR), specifically:
1. Subjects with a glomerular filtration rate (eGFR) 20-30 mL/min are excluded unless in the opinion of the principal investigator (PI), the potential benefit of participation outweighs the potential risk of study participation.
2. All subjects with a glomerular filtration rate (eGFR) \<20 mL/min (including hemodialysis and hemofiltration) are excluded.
3. Pregnancy or breast feeding.
4. Anticipated discharge from the hospital or transfer to another hospital which is not a study site within 72 hours of enrollment.
5. Allergy to any study medication.
6. Received five or more doses of remdesivir prior to screening.
7. Received small molecule tyrosine kinase inhibitors, including Janus kinase (JAK) inhibitors (e.g., baricitinib, ibrutinib, acalabrutinib, imatinib, gefitinib), in the 4 weeks prior to screening.
8. Received monoclonal antibodies targeting cytokines (e.g., tumor necrosis factor (TNF) inhibitors, anti-IL-1 \[e.g., anakinra, canakinumab\], anti-IL-6 \[e.g., tocilizumab, sarilumab, sitlukimab\]), or T-cells (e.g., abatacept) in the 4 weeks prior to screening.
9. Received monoclonal antibodies targeting B-cells (e.g., rituximab, and including any targeting multiple cell lines including B-cells) in the 3 months prior to screening.
10. Received granulocyte-macrophage colony-stimulating factor (GM-CSF) agents (e.g., sargramostim) within 2 months prior to screening.
11. Received other immunosuppressants in the 4 weeks prior to screening and in the judgement of the investigator, the risk of immunosuppression with lenzilumab is larger than the risk of Coronavirus Disease 2019 (COVID-19).
12. Received any live vaccine in the 4 weeks prior to screening.
13. Known active tuberculosis.
14. Known history of Human Immunodeficiency Virus (HIV), Hepatitis B (HBV) or untreated hepatitis C (HCV) infection.
15. History of pulmonary alveolar proteinosis (PAP).
16. Has a malignancy currently receiving immunosuppressive chemotherapy, immunodeficiency, uncontrolled opportunistic infection, or uncontrolled cirrhosis.
17. Has a medical condition that could, in the judgment of the investigator, limit the interpretation and generalizability of trial results.
18. Positive test for influenza virus during the current illness (influenza testing is not required by protocol).
19. Previous participation in an ACTIV-5/Big Effect Trial (BET).
Inclusion Criteria
Inclusion Criteria:
1. Admitted to a hospital with symptoms suggestive of Coronavirus Disease 2019 (COVID-19) and requires ongoing medical care.
2. Subject (or legally authorized representative) provides informed consent prior to initiation of any study procedures.
3. Subject (or legally authorized representative) understands and agrees to comply with planned study procedures.
4. Male or non-pregnant female adult \>/= 18 years of age at time of enrollment.
5. Illness of any duration and has laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection as determined by polymerase chain reaction (PCR) or other commercial or public health assay (e.g., Nucleic Acid Amplification Test \[NAAT\], antigen test) in any respiratory specimen, or saliva \</=14 days prior to randomization.
6. Illness of any duration, and requiring, just prior to randomization, supplemental oxygen (any flow), mechanical ventilation or Extracorporeal Membrane Oxygenation (ECMO) (ordinal score 5, 6, or 7).
7. Women of childbearing potential must agree to either abstinence or use at least one acceptable method of contraception\* from the time of screening through 5 months post study intraperitoneal (IP) dosing.
\* Acceptable methods include barrier contraceptives (condoms or diaphragm) with spermicide, intrauterine devices (IUDs), hormonal contraceptives, oral contraceptive pills, and surgical sterilization.
8. Agrees not to participate in another blinded clinical trial (both pharmacologic and other types of interventions) for the treatment of COVID-19 through Day 29.
1. Admitted to a hospital with symptoms suggestive of Coronavirus Disease 2019 (COVID-19) and requires ongoing medical care.
2. Subject (or legally authorized representative) provides informed consent prior to initiation of any study procedures.
3. Subject (or legally authorized representative) understands and agrees to comply with planned study procedures.
4. Male or non-pregnant female adult \>/= 18 years of age at time of enrollment.
5. Illness of any duration and has laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection as determined by polymerase chain reaction (PCR) or other commercial or public health assay (e.g., Nucleic Acid Amplification Test \[NAAT\], antigen test) in any respiratory specimen, or saliva \</=14 days prior to randomization.
6. Illness of any duration, and requiring, just prior to randomization, supplemental oxygen (any flow), mechanical ventilation or Extracorporeal Membrane Oxygenation (ECMO) (ordinal score 5, 6, or 7).
7. Women of childbearing potential must agree to either abstinence or use at least one acceptable method of contraception\* from the time of screening through 5 months post study intraperitoneal (IP) dosing.
\* Acceptable methods include barrier contraceptives (condoms or diaphragm) with spermicide, intrauterine devices (IUDs), hormonal contraceptives, oral contraceptive pills, and surgical sterilization.
8. Agrees not to participate in another blinded clinical trial (both pharmacologic and other types of interventions) for the treatment of COVID-19 through Day 29.
Gender
All
Gender Based
false
Keywords
Adults
COVID-19
Multicenter
Putative
Therapeutics
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
99 Years
Minimum Age
18 Years
NCT Id
NCT04583969
Org Class
Nih
Org Full Name
National Institute of Allergy and Infectious Diseases (NIAID)
Org Study Id
20-0013B
Overall Status
Completed
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Multicenter Platform Trial of Putative Therapeutics for the Treatment of COVID-19 in Hospitalized Adults
Primary Outcomes
Outcome Description
Ordinal scale categories include 7) Hospitalized, on Invasive Mechanical Ventilation or Extracorporeal Membrane Oxygenation (ECMO) and 8) Death. Mechanical ventilation-free survival was assessed through Day 29, defined as the proportion of participants who had not died nor were hospitalized on invasive mechanical ventilation or ECMO from Day 1 through Day 29. Estimates for the proportions are estimated from a logistic regression model adjusted for baseline dexamethasone, baseline ordinal score, age (continuous), and baseline CRP.
Outcome Measure
Proportion of Participants Alive and Without Mechanical Ventilation Through Day 29 in Participants With Baseline Ordinal Score of 5 or 6, C-reactive Protein (CRP)<150mg/L and Age <85 Years
Outcome Time Frame
Day 1 through Day 29
Secondary Outcomes
Outcome Description
Mechanical ventilation-free survival was assessed through Day 29, defined as the proportion of participants who had not died nor were hospitalized on invasive mechanical ventilation or ECMO from Day 1 through Day 29. Estimates for the proportions are estimated from a logistic regression model adjusted for baseline dexamethasone, baseline ordinal score, age (continuous), and baseline CRP.
Outcome Time Frame
Day 1 through Day 29
Outcome Measure
Proportion of Participants Alive and Without Mechanical Ventilation Through Day 29 in Participants With Any Baseline Ordinal Score
Outcome Description
Day of sustained recovery is defined as the first day on which the participant satisfies 1 of the following 3 categories from the clinical status ordinal scale (and does not return to a score of = 4 up to and including Study Day 60): 1) Not hospitalized, no new or increased limitations on activities; 2) Not hospitalized, but new or increased limitation on activities and/or requiring new or increased home oxygen, Continuous Positive Airway Pressure (CPAP), or Bilevel Positive Airway Pressure (BiPAP); 3) Hospitalized, not requiring new or increased supplemental oxygen - no longer requires ongoing medical care.
Outcome Time Frame
Day 1 through Day 60
Outcome Measure
Time to Sustained Recovery in Participants With a Baseline Ordinal Score of 5 or 6, CRP<150mg/L and Age <85 Years
Outcome Description
Day of sustained recovery is defined as the first day on which the participant satisfies 1 of the following 3 categories from the clinical status ordinal scale (and does not return to a score of = 4 up to and including Study Day 60): 1) Not hospitalized, no new or increased limitations on activities; 2) Not hospitalized, but new or increased limitation on activities and/or requiring new or increased home oxygen, CPAP, or BiPAP; 3) Hospitalized, not requiring new or increased supplemental oxygen - no longer requires ongoing medical care.
Outcome Time Frame
Day 1 through Day 60
Outcome Measure
Time to Sustained Recovery in Participants With Any Baseline Ordinal Score
Outcome Description
The ordinal scale categories are defined as: 1) Not hospitalized, no new or increased limitations on activities; 2) Not hospitalized, but new or increased limitation on activities and/or requiring new or increased home oxygen, CPAP, or BiPAP; 3) Hospitalized, not requiring new or increased supplemental oxygen - no longer requires ongoing medical care; 4) Hospitalized, not requiring new or increased supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 5) Hospitalized, requiring new or increased supplemental oxygen; 6) Hospitalized, requiring new or increased non-invasive ventilation or highflow oxygen devices; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 8) Death
Outcome Time Frame
Day 8
Outcome Measure
Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 8
Outcome Description
Blood 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. Lower results are better, so a higher negative change from baseline indicates a more favorable outcome.
Outcome Time Frame
Days 1, 3, 5, 8, 11, 15, 29
Outcome Measure
Change From Baseline in C-Reactive Protein (CRP)
Outcome Description
Blood 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. Lower results are better, so a higher negative change from baseline indicates a more favorable outcome.
Outcome Time Frame
Days 1, 3, 5, 8, 11, 15, 29
Outcome Measure
Change From Baseline in D-dimer
Outcome Description
Blood 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. Lower results are better, so a higher negative change from baseline indicates a more favorable outcome.
Outcome Time Frame
Days 1, 3, 5, 8, 11, 15, 29
Outcome Measure
Change From Baseline in Ferritin
Outcome Description
Blood 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. Higher results are better, so a higher positive change from baseline indicates a more favorable outcome.
Outcome Time Frame
Days 1, 3, 5, 8, 11, 15, 29
Outcome Measure
Change From Baseline in Fibrinogen
Outcome Description
Blood 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. Lower results are better, so a higher negative change from baseline indicates a more favorable outcome.
Outcome Time Frame
Days 1, 3, 5, 8, 11, 15, 29
Outcome Measure
Change From Baseline in Alanine Aminotransferase (ALT)
Outcome Description
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. Lower results are better, so a higher negative change from baseline indicates a more favorable outcome.
Outcome Time Frame
Days 1, 3, 5, 8, 11, 15, 29
Outcome Measure
Change From Baseline in Aspartate Transaminase (AST)
Outcome Description
Blood 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. Lower results are better, so a higher negative change from baseline indicates a more favorable outcome.
Outcome Time Frame
Days 1, 3, 5, 8, 11, 15, 29
Outcome Measure
Change From Baseline in Creatinine
Outcome Description
Blood 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. Lower results are better, so a higher negative change from baseline indicates a more favorable outcome.
Outcome Time Frame
Days 1, 3, 5, 8, 11, 15, 29
Outcome Measure
Change From Baseline in International Normalized Ratio (INR)
Outcome Description
Blood 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. Higher results are better, so a higher positive change from baseline indicates a more favorable outcome.
Outcome Time Frame
Days 1, 3, 5, 8, 11, 15, 29
Outcome Measure
Change From Baseline in Hemoglobin
Outcome Description
Blood 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. Higher results are better, so a higher positive change from baseline indicates a more favorable outcome.
Outcome Time Frame
Days 1, 3, 5, 8, 11, 15, 29
Outcome Measure
Change From Baseline in Platelets Count
Outcome Description
Blood 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. Lower results are better, so a higher negative change from baseline indicates a more favorable outcome.
Outcome Time Frame
Days 1, 3, 5, 8, 11, 15, 29
Outcome Measure
Change From Baseline in Total Bilirubin
Outcome Description
Blood 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. Higher results are better, so a higher positive change from baseline indicates a more favorable outcome.
Outcome Time Frame
Days 1, 3, 5, 8, 11, 15, 29
Outcome Measure
Change From Baseline in White Blood Cell (WBC) Count
Outcome Description
Blood 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. Higher results are better, so a higher positive change from baseline indicates a more favorable outcome.
Outcome Time Frame
Days 1, 3, 5, 8, 11, 15, 29
Outcome Measure
Change From Baseline in Neutrophils
Outcome Description
Blood 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. Lower results are better, so a higher negative change from baseline indicates a more favorable outcome.
Outcome Time Frame
Days 1, 3, 5, 8, 11, 15, 29
Outcome Measure
Change From Baseline in Eosinophils
Outcome Description
Blood 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. Lower results are better, so a higher negative change from baseline indicates a more favorable outcome.
Outcome Time Frame
Days 1, 3, 5, 8, 11, 15, 29
Outcome Measure
Change From Baseline in Basophils
Outcome Description
Blood 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. Higher results are better, so a higher positive change from baseline indicates a more favorable outcome.
Outcome Time Frame
Days 1, 3, 5, 8, 11, 15, 29
Outcome Measure
Change From Baseline in Lymphocytes
Outcome Description
Blood 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. Lower results are better, so a higher negative change from baseline indicates a more favorable outcome.
Outcome Time Frame
Days 1, 3, 5, 8, 11, 15, 29
Outcome Measure
Change From Baseline in Monocytes
Outcome Description
Grade 3 AEs are defined as events that interrupt usual activities of daily living, or significantly affects clinical status, or may require intensive therapeutic intervention. Severe events are usually incapacitating. Grade 4 AEs are defined as events that are potentially life threatening while Grade 5 AEs are those that are fatal. Laboratory results were considered AEs if they were grade 3 or above according to the thresholds in the Division of AIDS (DAIDS) Table for Grading the Severity of Adverse Events.
Outcome Time Frame
Day 1 through Day 60
Outcome Measure
Number of Participants Reporting Grade 3, 4, or 5 Clinical and/or Laboratory Adverse Events (AEs)
Outcome Description
An SAE is defined as an AE or suspected adverse reaction that 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.
Outcome Time Frame
Day 1 through Day 60
Outcome Measure
Number of Participants Reporting Serious Adverse Events (SAEs)
Outcome Description
Discontinuation or temporary suspension of study product is defined as any episode of early discontinuation or interruption of study product administration.
Outcome Time Frame
Day 1 through Day 29
Outcome Measure
Number of Participants Who Discontinued or Temporarily Suspended Study Treatment
Outcome Description
Duration of hospitalization is defined first as the total number of days hospitalized for COVID-19, including readmissions for COVID-19-related reasons. It is also calculated as the total number of days hospitalized, including any readmissions for any reason.
Outcome Time Frame
Day 1 through Day 29
Outcome Measure
Duration of Hospitalization
Outcome Description
Duration of invasive ventilation/ECMO was measured in days among participants who required invasive ventilation or died.
Outcome Time Frame
Day 1 through Day 29
Outcome Measure
Days of Invasive Mechanical Ventilation/Extracorporeal Membrane Oxygenation (ECMO) Use
Outcome Description
Duration of new invasive mechanical ventilation/ECMO use was measured in days among participants not on invasive ventilation/ECMO at baseline who progressed to invasive ventilation/ECMO or died.
Outcome Time Frame
Day 1 through Day 29
Outcome Measure
Days of New Mechanical Ventilation or Extracorporeal Membrane Oxygenation (ECMO) Use
Outcome Description
Duration of non-invasive ventilation or high flow oxygen use was measured in days among participants who required non-invasive ventilation/high flow oxygen, invasive ventilation/ECMO or died.
Outcome Time Frame
Day 1 through Day 29
Outcome Measure
Days of Non-invasive Ventilation/High Flow Oxygen Use
Outcome Description
Duration of new non-invasive ventilation or high flow oxygen use was measured in days among participants not on non-invasive ventilation/high flow oxygen at baseline who progressed to non-invasive ventilation/high flow oxygen, invasive ventilation/ECMO or died.
Outcome Time Frame
Day 1 through Day 29
Outcome Measure
Days of New Non-invasive Ventilation/High Flow Oxygen Use
Outcome Description
Duration of supplemental oxygen use was measured in days among participants who required any supplemental oxygen, non-invasive ventilation/high flow oxygen, invasive ventilation/ECMO or died.
Outcome Time Frame
Day 1 through Day 29
Outcome Measure
Days of Supplemental Oxygen Use
Outcome Description
New Invasive Mechanical Ventilation / Extracorporeal Membrane Oxygenation (ECMO) Use is defined as participants not on invasive ventilation/ECMO at baseline who progressed to invasive ventilation/ECMO or died during the study.
Outcome Time Frame
Day 1 through Day 29
Outcome Measure
Number of Participants With New Invasive Mechanical Ventilation / Extracorporeal Membrane Oxygenation (ECMO) Use
Outcome Description
New Non-invasive Ventilation/High Flow Oxygen Use is defined as participants in the hospitalized requiring new or increased supplemental oxygen ordinal scale or below at baseline who progressed to noninvasive ventilation/high flow oxygen, invasive ventilation/ECMO or died during the study.
Outcome Time Frame
Day 1 through Day 29
Outcome Measure
Number of Participants With New Non-invasive Ventilation/High Flow Oxygen Use
Outcome Description
The ordinal scale categories are defined as: 1) Not hospitalized, no new or increased limitations on activities;2) Not hospitalized, but new or increased limitation on activities and/or requiring new or increased home oxygen, CPAP, or BiPAP; 3) Hospitalized, not requiring new or increased supplemental oxygen - no longer requires ongoing medical care; 4) Hospitalized, not requiring new or increased supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 5) Hospitalized, requiring new or increased supplemental oxygen; 6) Hospitalized, requiring new or increased non-invasive ventilation or highflow oxygen devices; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 8) Death. A positive change indicates a worsening and a negative change is an improvement.
Outcome Time Frame
Days 1, 3, 5, 8, 11, 15, 22, 29
Outcome Measure
Mean Change in Ordinal Scale
Outcome Description
The mortality rate was determined as the proportion of participants who died by study Day 15. The proportions reported are Kaplan-Meier estimates.
Outcome Time Frame
Day 1 through Day 15
Outcome Measure
14-day Participant Mortality
Outcome Description
The mortality rate was determined as the proportion of participants who died by study Day 29. The proportions reported are Kaplan-Meier estimates.
Outcome Time Frame
Day 1 through Day 29
Outcome Measure
28-day Participant Mortality
Outcome Description
The mortality rate was determined as the proportion of participants who died by study Day 60. The proportions reported are Kaplan-Meier estimates.
Outcome Time Frame
Day 1 through Day 60
Outcome Measure
59-day Participant Mortality
Outcome Description
Ordinal scale categories include 7) Hospitalized, on Invasive Mechanical Ventilation or Extracorporeal Membrane Oxygenation (ECMO) and 8) Death. Defined as the proportion of participants who were alive and were not hospitalized on invasive mechanical ventilation or ECMO at the Day 29 visit.
Outcome Time Frame
Day 29
Outcome Measure
Proportion of Participants Not Meeting Criteria for One of Two Ordinal Scale Categories at Day 29
Outcome Description
The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Not hospitalized, no new or increased limitations on activities; 2) Not hospitalized, but new or increased limitation on activities and/or requiring new or increased home oxygen, CPAP, or BiPAP; 3) Hospitalized, not requiring new or increased supplemental oxygen - no longer requires ongoing medical care; 4) Hospitalized, not requiring new or increased supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 5) Hospitalized, requiring new or increased supplemental oxygen; 6) Hospitalized, requiring new or increased noninvasive ventilation or high-flow oxygen devices; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 8) Death.
Outcome Time Frame
Day 1 through Day 60
Outcome Measure
Time to an Improvement of One Category From Baseline Using an Ordinal Scale
Outcome Description
The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Not hospitalized, no new or increased limitations on activities; 2) Not hospitalized, but new or increased limitation on activities and/or requiring new or increased home oxygen, CPAP, or BiPAP; 3) Hospitalized, not requiring new or increased supplemental oxygen - no longer requires ongoing medical care; 4) Hospitalized, not requiring new or increased supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 5) Hospitalized, requiring new or increased supplemental oxygen; 6) Hospitalized, requiring new or increased noninvasive ventilation or high-flow oxygen devices; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 8) Death.
Outcome Time Frame
Day 1 through Day 60
Outcome Measure
Time to an Improvement of Two Categories From Baseline Using an Ordinal Scale
Outcome Description
The time to death from study Day 1 to study Day 29, measured in days. The times reported are Kaplan-Meier estimates.
Outcome Time Frame
Day 1 through Day 29
Outcome Measure
Time to Death
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
99
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Robert Grossberg
Investigator Email
rgrossbe@montefiore.org
Investigator Phone
718-920-5276
Categories Mesh Debug
COVID-19 --- COVID-19
COVID-19 --- PNEUMONIA, VIRAL
COVID-19 --- PNEUMONIA
Lung --- PNEUMONIA
COVID-19 --- RESPIRATORY TRACT INFECTIONS
Lung --- RESPIRATORY TRACT INFECTIONS
COVID-19 --- INFECTIONS
Infectious Disease --- INFECTIONS
COVID-19 --- VIRUS DISEASES
Hepatitis --- VIRUS DISEASES
Infectious Disease --- VIRUS DISEASES
COVID-19 --- CORONAVIRUS INFECTIONS
COVID-19 --- CORONAVIRIDAE INFECTIONS
COVID-19 --- NIDOVIRALES INFECTIONS
COVID-19 --- RNA VIRUS INFECTIONS
Infectious Disease --- RNA VIRUS INFECTIONS
Lung & Chest Cancers --- LUNG DISEASES
COVID-19 --- LUNG DISEASES
Lung --- LUNG DISEASES
Asthma and Other Respiratory Diseases --- RESPIRATORY TRACT DISEASES
Lung & Chest Cancers --- RESPIRATORY TRACT DISEASES
COVID-19 --- RESPIRATORY TRACT DISEASES
Lung --- RESPIRATORY TRACT DISEASES
MeSH Terms
COVID-19
PNEUMONIA, VIRAL
PNEUMONIA
RESPIRATORY TRACT INFECTIONS
INFECTIONS
VIRUS DISEASES
CORONAVIRUS INFECTIONS
CORONAVIRIDAE INFECTIONS
NIDOVIRALES INFECTIONS
RNA VIRUS INFECTIONS
LUNG DISEASES
RESPIRATORY TRACT DISEASES
LENZILUMAB
COUNTERFEIT DRUGS
REMDESIVIR
SUBSTANDARD DRUGS
PHARMACEUTICAL PREPARATIONS