Adaptive COVID-19 Treatment Trial 2 (ACTT-2)
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
Overall Status
Completed
CT.gov ID
NCT04401579
Collaborator
(none)
1,033
71
2
2.8
14.5
5.3
Study Details
Study Description
Brief Summary
ACTT-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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
This study is an adaptive randomized double-blind placebo-controlled trial to evaluate the safety and efficacy of novel therapeutic agents in hospitalized adults diagnosed with COVID-19. The study is a multicenter trial that will be conducted in up to approximately 100 sites globally. The study will compare different investigational therapeutic agents to a control arm. New arms can be introduced according to scientific and public health needs. There will be interim monitoring to 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. This adaptive platform is used to rapidly evaluate different therapeutics in a population of those hospitalized with moderate to severe COVID-19. The platform will provide a common framework sharing a similar population, design, endpoints, and safety oversight. New stages with new therapeutics can be introduced. One independent Data and Safety Monitoring Board (DSMB) will actively monitor interim data in all stages to make recommendations about early study closure or changes to study arms.
ACTT-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.
All subjects will undergo a series of efficacy, safety, and laboratory assessments. Safety laboratory tests and blood (serum and plasma) research samples and oropharyngeal (OP) swabs will be obtained on Days 1 (prior to infusion) and Days 3, 5, 8, and 11 (while hospitalized). OP swabs and blood (serum only) plus safety laboratory tests will be collected on Day 15 and 29 (if the subject attends an in-person visit or are still hospitalized).
The primary outcome is time to recovery by Day 29. A key secondary outcome evaluates treatment-related improvements in the 8-point ordinal scale at Day 15. Each stage may prioritize different secondary endpoints for the purpose of multiple comparison analyses.
Contacts:
20-0006 Central Contact
Telephone: 1 (301) 7617948
Email: DMIDClinicalTrials@niaid.nih.gov
Study Design
Study Type:
Interventional
Actual Enrollment
:
1033 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Multicenter, Adaptive, Randomized Blinded Controlled Trial of the Safety and Efficacy of Investigational Therapeutics for the Treatment of COVID-19 in Hospitalized Adults (ACTT-2)
Actual Study Start Date
:
May 8, 2020
Actual Primary Completion Date
:
Jul 31, 2020
Actual Study Completion Date
:
Jul 31, 2020
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Remdesivir plus Baricitinib 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. |
Drug: Remdesivir
Drug Remdesivir is a single diastereomer monophosphoramidate prodrug designed for the intracellular delivery of a modified adenine nucleoside analog GS-441524. In addition to the active ingredient, the lyophilized formulation of Remdesivir contains the following inactive ingredients: water for injection, sulfobutylether beta-cyclodextrin sodium (SBECD), and hydrochloric acid and/or sodium hydroxide.
Drug: Baricitinib
Baricitinib is a Janus kinase (JAK) inhibitor with the chemical name [1-(ethylsulfonyl)-3-(4-(7Hpyrrolo(2,3-d)pyrimidin-4-yl)-1H-pyrazol-1-yl)azetidin-3-yl]acetonitrile Each tablet contains 2 mg of baricitinib and the following inactive ingredients: croscarmellose sodium, magnesium stearate, mannitol, microcrystalline cellulose, ferric oxide, lecithin (soya), polyethylene glycol, polyvinyl alcohol, talc and titanium dioxide.
|
| Placebo Comparator: Remdesivir plus Placebo 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. |
Other: Placebo
The matching Baricitinib placebo contains lactose monohydrate, microcrystalline cellulose, croscarmellose sodium, and magnesium stearate. The coating for the placebo tablet is identical to that of the corresponding active tablet.
Drug: Remdesivir
Drug Remdesivir is a single diastereomer monophosphoramidate prodrug designed for the intracellular delivery of a modified adenine nucleoside analog GS-441524. In addition to the active ingredient, the lyophilized formulation of Remdesivir contains the following inactive ingredients: water for injection, sulfobutylether beta-cyclodextrin sodium (SBECD), and hydrochloric acid and/or sodium hydroxide.
|
Outcome Measures
Primary Outcome Measures
- Time to Recovery [Day 1 through Day 29]
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.
- Time to Recovery by Race [Day 1 through Day 29]
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.
- Time to Recovery by Ethnicity [Day 1 through Day 29]
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.
- Time to Recovery by Sex [Day 1 through Day 29]
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.
Secondary Outcome Measures
- Change From Baseline in Alanine Transaminase (ALT) [Days 1, 3, 5, 8, 11, 15 and 29]
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.
- Change From Baseline in Aspartate Transaminase (AST) [Days 1, 3, 5, 8, 11, 15 and 29]
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.
- Change From Baseline in Creatinine [Days 1, 3, 5, 8, 11, 15 and 29]
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.
- Change From Baseline in Glucose [Days 1, 3, 5, 8, 11, 15 and 29]
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.
- Change From Baseline in Hemoglobin [Days 1, 3, 5, 8, 11, 15 and 29]
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.
- Change From Baseline in Platelets [Days 1, 3, 5, 8, 11, 15 and 29]
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.
- Change From Baseline in Prothrombin International Normalized Ratio (INR) [Days 1, 3, 5, 8, 11, 15 and 29]
Blood to evaluate INR 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.
- Change From Baseline in Total Bilirubin [Days 1, 3, 5, 8, 11, 15 and 29]
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.
- Change From Baseline in White Blood Cell Count (WBC) [Days 1, 3, 5, 8, 11, 15 and 29]
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.
- Change From Baseline in Neutrophils [Days 1, 3, 5, 8, 11, 15 and 29]
BBlood 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.
- Change From Baseline in Lymphocytes [Days 1, 3, 5, 8, 11, 15 and 29]
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.
- Change From Baseline in Monocytes [Days 1, 3, 5, 8, 11, 15 and 29]
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.
- Change From Baseline in Basophils [Days 1, 3, 5, 8, 11, 15 and 29]
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.
- Change From Baseline in Eosinophils [Days 1, 3, 5, 8, 11, 15 and 29]
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.
- Change in National Early Warning Score (NEWS) From Baseline [Days 1, 3, 5, 8, 11, 15, 22, and 29]
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.
- Percentage of Participants Reporting Grade 3 and 4 Clinical and/or Laboratory Adverse Events (AEs) [Day 1 through Day 29]
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.
- Percentage of Participants Reporting Serious Adverse Events (SAEs) [Day 1 through Day 29]
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.
- Duration of Hospitalization [Day 1 through Day 29]
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.
- Duration of New Non-invasive Ventilation or High Flow Oxygen Use [Day 1 through Day 29]
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
- Duration of New Oxygen Use [Day 1 through Day 29]
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
- Duration of New Ventilator or Extracorporeal Membrane Oxygenation (ECMO) Use [Day 1 through Day 29]
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
- Duration of Oxygen Use [Day 1 through Day 29]
Duration of oxygen use was measured in days among participants who were on oxygen in based, calculated in two ways. The first includes imputations for participants who died. The second method is restricted to participants who did not die.
- Percentage of Participants Discontinued or Temporarily Suspended From Investigational Therapeutics [Day 1 through Day 14]
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 of Remdesivir, or in the 14 doses of Baricitinib/placebo.
- Percentage of Participants Requiring New Ventilator or Extracorporeal Membrane Oxygenation (ECMO) Use [Day 1 through Day 29]
The percentage of participants requiring new ventilator or ECMO use was determined as the percentage not on a ventilator or ECMO at baseline
- Percentage of Participants Requiring New Oxygen Use [Day 1 through Day 29]
The percentage of participants requiring new oxygen use was determined as the percentage of participants not requiring oxygen at baseline
- Mean Change in the Ordinal Scale [Day 1, 3, 5, 8, 11, 15, 22, and 29]
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.
- Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 15 [Day 15]
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. Data was imputed using last observation carried forward or worst possible score based on hospitalization status (2 if not hospitalized, 7 if hospitalized) when there was a change in hospitalization status since last score. Deaths were imputed as an 8.
- Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 1 [Day 1]
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.
- Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 3 [Day 3]
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.
- Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 5 [Day 5]
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.
- Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 8 [Day 8]
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.
- Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 11 [Day 11]
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.
- Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 22 [Day 22]
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.
- Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 29 [Day 29]
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.
- 14-day Participant Mortality [Day 1 through Day 15]
The mortality rate was determined as the proportion of participants who died by study Day 15. The proportions reported are Kaplan-Meier estimates.
- 28-day Participant Mortality [Day 1 through Day 29]
The mortality rate was determined as the proportion of participants who died by study Day 29. The proportions reported are Kaplan-Meier estimates.
- Time to an Improvement of One Category Using an Ordinal Scale [Day 1 through Day 29]
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
- Time to an Improvement of Two Categories Using an Ordinal Scale [Day 1 through Day 29]
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
- Time to Discharge or to a NEWS of 2 or Less and Maintained for 24 Hours, Whichever Occurs First [Day 1 through Day 29]
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.
- Change From Baseline in C-reactive Protein (CRP) [Days 1, 3, 5, 8, 11, 15 and 29]
Blood to evaluate CRP 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.
- Change From Baseline in D-dimer Concentration [Days 1, 3, 5, 8, 11, 15 and 29]
Blood to evaluate d-dimer concentration 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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 99 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Admitted to a hospital with symptoms suggestive of COVID-19.
-
Subject (or legally authorized representative) provides informed consent prior to initiation of any study procedures.
-
Subject (or legally authorized representative) understands and agrees to comply with planned study procedures.
-
Male or non-pregnant female adult > / = 18 years of age at time of enrollment.
-
Has laboratory-confirmed SARS-CoV-2 infection as determined by polymerase chain reaction (PCR) or other commercial or public health assay in any specimen, as documented by either of the following:
-
PCR positive in sample collected < 72 hours prior to randomization; OR
-
PCR positive in sample collected >/= 72 hours prior to randomization, documented inability to obtain a repeat sample (e.g. due to lack of testing supplies, limited testing capacity, results taking >24 hours, etc.) AND progressive disease suggestive of ongoing SARS-CoV-2 infection.
- Illness of any duration, and at least one of the following:
-
Radiographic infiltrates by imaging (chest x-ray, CT scan, etc.), OR
-
SpO2 < / = 94% on room air, OR
-
Requiring supplemental oxygen, OR
-
Requiring mechanical ventilation or extracorporeal membrane oxygenation (ECMO).
-
Women of childbearing potential must agree to either abstinence or use at least one primary form of contraception not including hormonal contraception from the time of screening through Day 29.
-
Agrees to not participate in another clinical trial for the treatment of COVID-19 through Day 29.
Exclusion Criteria:
-
Alanine Transaminase (ALT) or Aspartate Transaminase (AST) > 5 times the upper limit of normal.
-
Estimated glomerular filtration rate (eGFR) < 30 ml/min or patient is receiving hemodialysis or hemofiltration at time of screening.
-
Neutropenia (absolute neutrophil count <1000 cells/microliter) (<1.0 x 103/microliter or <1.0 GI/L).
-
Lymphopenia (absolute lymphocyte count <200 cells/microliter) (<0.20 x 103/microliter or <0.20 GI/L)
-
Pregnancy or breast feeding.
-
Anticipated discharge from the hospital or transfer to another hospital which is not a study site within 72 hours.
-
Allergy to any study medication.
-
Received three or more doses of remdesivir, including the loading dose, outside of the study under the EUA (or similar mechanism) for COVID-19.
-
Received convalescent plasma or intravenous immunoglobulin [IVIg]) for COVID-19, the current illness for which they are being enrolled.
-
Received small molecule tyrosine kinase inhibitors (e.g. baricitinib, imatibib, genfinitib), in the 1 week prior to screening
-
Received monoclonal antibodies targeting cytokines (e.g., TNF inhibitors, anti-interleukin-1 [IL-1], anti-IL-6 [tocilizumab or sarilumab]), or T-cells (e.g., abatacept) in the 4 weeks prior to screening.
-
Received monoclonal antibodies targeting B-cell (e.g., rituximab, and including any targeting multiple cell lines including B-cells) in the 3 months prior to screening.
-
Received other immunosuppressants in the 4 weeks prior to screening and in the judgement of the investigator, the risk of immunosuppression with baricitinib is larger than the risk of COVID-19.
-
Received >/= 20 mg/day of prednisone or equivalent for >/=14 consecutive days in the 4 weeks prior to screening.
-
Use of probenecid that cannot be discontinued at study enrollment.
-
Have diagnosis of current active tuberculosis (TB) or, if known, latent TB treated for less than 4 weeks with appropriate anti-tuberculosis therapy per local guidelines (by history only, no screening required).
-
Suspected serious, active bacterial, fungal, viral, or other infection (besides COVID-19) that in the opinion of the investigator could constitute a risk when taking investigational product.
-
Have received any live vaccine (that is, live attenuated) within 4 weeks before screening, or intend to receive a live vaccine (or live attenuated) during the study. Note: Use of non-live (inactivated) vaccinations is allowed for all subjects.
-
Have a history of VTE (deep vein thrombosis [DVT] or pulmonary embolism [PE]) within 12 weeks prior to screening or have a history of recurrent (>1) VTE (DVT/PE).
-
Immunocompromised patients, patients with a chronic medical condition, or those taking a medication that cannot be discontinued at enrollment, who, in the judgment of PI, are at increased risk for serious infections or other safety concerns given the study products.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Alabama at Birmingham School of Medicine - Infectious Disease | Birmingham | Alabama | United States | 35233 |
| 2 | University of California San Diego Health - Jacobs Medical Center | La Jolla | California | United States | 29037 |
| 3 | University of California Los Angeles Medical Center - Westwood Clinic | Los Angeles | California | United States | 90095 |
| 4 | University of California Irvine Medical Center - Infectious Disease | Orange | California | United States | 92868-3298 |
| 5 | VA Palo Alto Health Care System - Infectious Diseases | Palo Alto | California | United States | 94304-1207 |
| 6 | Stanford University - Stanford Hospital and Clinics - Pediatrics - Infectious Diseases | Palo Alto | California | United States | 94304-1503 |
| 7 | University of California Davis Medical Center - Internal Medicine - Infectious Disease | Sacramento | California | United States | 95817-1460 |
| 8 | Naval Medical Center San Diego - Infectious Disease Clinic | San Diego | California | United States | 92314 |
| 9 | University of California San Francisco - Zuckerberg San Francisco General Hospital - Division of Human Immunodeficiency Virus, Infectious Disease, and Global Medicine | San Francisco | California | United States | 94110-2859 |
| 10 | Cedars Sinai Medical Center | West Hollywood | California | United States | 90048-1804 |
| 11 | Eastern Colorado Health Care System | Aurora | Colorado | United States | 80045 |
| 12 | Denver Health Division of Hospital Medicine - Main Campus | Denver | Colorado | United States | 80204 |
| 13 | Georgetown University Medical Center - Division of Infectious Diseases | Washington | District of Columbia | United States | 20007 |
| 14 | University of Florida Health - Shands Hospital - Division of Infectious Diseases and Global Medicine | Gainesville | Florida | United States | 32610 |
| 15 | University of Miami Miller School of Medicine - Infectious Diseases | Miami | Florida | United States | 33136 |
| 16 | Emory Vaccine Center - The Hope Clinic | Decatur | Georgia | United States | 30030-1705 |
| 17 | Atlanta VA Medical Center - Infectious Diseases Clinic | Decatur | Georgia | United States | 30033 |
| 18 | Northwestern Hospital - Infectious Disease | Chicago | Illinois | United States | 60611-2908 |
| 19 | University of Illinois at Chicago College of Medicine - Division of Infectious Diseases | Chicago | Illinois | United States | 60612 |
| 20 | Indiana University School of Medicine - Infectious Diseases | Indianapolis | Indiana | United States | 46202 |
| 21 | Ochsner Medical Center - Kenner - Department of Infectious Diseases | Kenner | Louisiana | United States | 70065 |
| 22 | Southeast Louisiana Veterans Health Care System (SLVHCS) - Section of Infectious Diseases | New Orleans | Louisiana | United States | 70119 |
| 23 | University of Maryland School of Medicine - Center for Vaccine Development - Baltimore | Baltimore | Maryland | United States | 21201 |
| 24 | Johns Hopkins Hospital - Medicine - Infectious Diseases | Baltimore | Maryland | United States | 21287-0005 |
| 25 | Walter Reed National Military Medical Center | Bethesda | Maryland | United States | 20889 |
| 26 | National Institutes of Health - Clinical Center, National Institute of Allergy and Infectious Diseases Laboratory Of Immunoregulation, Clinical Research Section | Bethesda | Maryland | United States | 20892-1504 |
| 27 | Massachusetts General Hospital - Infectious Diseases | Boston | Massachusetts | United States | 02114-2621 |
| 28 | University of Massachusetts Medical School - Infectious Diseases and Immunology | Worcester | Massachusetts | United States | 01655-0002 |
| 29 | University of Minnesota Medical Center, Fairview - Infectious Diseases and International Medicine | Minneapolis | Minnesota | United States | 55455-0341 |
| 30 | Saint Louis University - Center for Vaccine Development | Saint Louis | Missouri | United States | 63104-1015 |
| 31 | University of Nebraska Medical Center - Infectious Diseases | Omaha | Nebraska | United States | 68198-5400 |
| 32 | University of New Mexico Clinical and Translational Science Center | Albuquerque | New Mexico | United States | 87106 |
| 33 | Montefiore Medical Center - Infectious Diseases | Bronx | New York | United States | 10467-2401 |
| 34 | New York University School of Medicine - Langone Medical Center - Microbiology - Parasitology | New York | New York | United States | 10016 |
| 35 | University of Rochester Medical Center - Vaccine Research Unit | Rochester | New York | United States | 14642-0001 |
| 36 | Duke Human Vaccine Institute - Duke Vaccine and Trials Unit | Durham | North Carolina | United States | 27704 |
| 37 | Womack Army Medical Center - Pulmonary and Respiratory Services | Fort Bragg | North Carolina | United States | 28310 |
| 38 | Kaiser Permanente Northwest - Center for Health Research | Portland | Oregon | United States | 97227 |
| 39 | Penn State Health Milton S. Hershey Medical Center - Division of Infectious Diseases | Hershey | Pennsylvania | United States | 17033 |
| 40 | University of Pennsylvania Perelman School of Medicine - Penn Institute for Immunology | Philadelphia | Pennsylvania | United States | 19104-4863 |
| 41 | Vanderbilt University Medical Center - Infectious Diseases | Nashville | Tennessee | United States | 37232-0011 |
| 42 | Baylor Scott & White Health - Baylor University Medical Center - North Texas Infectious Disease Consultants | Dallas | Texas | United States | 75246 |
| 43 | University of Texas Southwestern Medical Center - Internal Medicine - Infectious Diseases | Dallas | Texas | United States | 75390-8884 |
| 44 | Brooke Army Medical Center | Fort Sam Houston | Texas | United States | 78234 |
| 45 | University of Texas Medical Branch - Division of Infectious Disease | Galveston | Texas | United States | 77555-0435 |
| 46 | Baylor College of Medicine - Molecular Virology and Microbiology | Houston | Texas | United States | 77030-3411 |
| 47 | University of Texas Health Science Center at San Antonio - Infectious Diseases | San Antonio | Texas | United States | 78229-3901 |
| 48 | University of Utah - Infectious Diseases | Salt Lake City | Utah | United States | 84132 |
| 49 | University of Virginia - Acute Care Surgery | Charlottesville | Virginia | United States | 22908-0816 |
| 50 | Naval Medical Center Portsmouth - Infectious Disease Division | Portsmouth | Virginia | United States | 23708 |
| 51 | EvergreenHealth Infectious Disease Service | Kirkland | Washington | United States | 98034 |
| 52 | Providence Sacred Heart Medical Center | Spokane | Washington | United States | 99204 |
| 53 | Madigan Army Medical Center - Infectious Disease Clinic | Tacoma | Washington | United States | 98431 |
| 54 | University of Copenhagen - Centre of Excellence for Health, Immunity and Infections (CHIP) - Department of Infectious Diseases | Copenhagen | Denmark | 2100 | |
| 55 | National Center for Global Health and Medicine Hospital - Disease Control and Prevention Center | Tokyo | Japan | 162-8655 | |
| 56 | Seoul National University Bundang Hospital - Division of Infectious Diseases | Bundang-gu Seongnam-si | Korea, Republic of | 13620 | |
| 57 | Seoul National University Hospital | Seoul | Korea, Republic of | 03080 | |
| 58 | Instituto Nacional de Ciencias Medicas y Nutrición Salvador Zubirán - Departamento de Infectologia | Mexico City | Mexico | 14080 | |
| 59 | Instituto Nacional de Enfermedades Respiratorias (INER) - Ismael CosÃo Villegas | Mexico City | Mexico | 14080 | |
| 60 | National University Health System - Division of Infectious Diseases | Singapore | Singapore | 119228 | |
| 61 | National Centre for Infectious Diseases (NCID) | Singapore | Singapore | 308442 | |
| 62 | Changi General Hospital - Clinical Trials and Research Unit (CTRU) | Singapore | Singapore | 529889 | |
| 63 | Ng Teng Fong General Hospital - Infectious Disease Service | Singapore | Singapore | 609606 | |
| 64 | Hospital Clinic Barcelona, Servicio de Salud Internacional | Barcelona | Cataluña | Spain | 08036 |
| 65 | Hospital Germans Trias i Pujol - Servei Malalties Infeccioses | Barcelona | Cataluña | Spain | 08916 |
| 66 | Hospital Clinico San Carlos - Enfermedades Infecciosas | Madrid | Spain | 28040 | |
| 67 | Royal Sussex County Hospital - Department of Intensive Care Medicine | Brighton | United Kingdom | ||
| 68 | Saint Thomas' Hospital - Directorate of Infection | City Of London | United Kingdom | ||
| 69 | St. James's University Hospital - Infectious Diseases | Leeds | United Kingdom | ||
| 70 | Royal Victoria Infirmary - Department of Infectious Diseases | Newcastle Upon Tyne | United Kingdom | ||
| 71 | John Radcliffe Hospital | Oxford | United Kingdom |
Sponsors and Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
None specified.Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT04401579
Other Study ID Numbers:
- 20-0006 ACTT-2
First Posted:
May 26, 2020
Last Update Posted:
Mar 14, 2022
Last Verified:
Apr 1, 2020
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Product Manufactured in and Exported from the U.S.:
No
Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID)
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Participants were recruited at the participating sites from those admitted with symptoms of COVID-19 confirmed by PCR. Enrollment occurred between 08May2020 and 01Jul2020. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Remdesivir Plus Baricitinib | Remdesivir Plus Placebo |
|---|---|---|
| Arm/Group Description | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. Remdesivir: Drug Remdesivir is a single diastereomer monophosphoramidate prodrug designed for the intracellular delivery of a modified adenine nucleoside analog GS-441524. In addition to the active ingredient, the lyophilized formulation of Remdesivir contains the following inactive ingredients: water for injection, sulfobutylether beta-cyclodextrin sodium (SBECD), and hydrochloric acid and/or sodium hydroxide. Baricitinib: Baricitinib is a Janus kinase (JAK) inhibitor with the chemical name [1-(ethylsulfonyl)-3-(4-(7Hpyrrolo(2,3-d)pyrimidin-4-yl)-1H-pyrazol-1-yl)azetidin-3-yl]acetonitrile Each tablet contains 2 mg of baricitinib and the following inactive ingredients: croscarmellose sodium, magnesium stearate, mannitol, microcrystalline cellulose, ferric oxide, lecithin (soya), polyethylene glycol, polyvinyl alcohol, talc and titanium dioxide. | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. Remdesivir: Drug Remdesivir is a single diastereomer monophosphoramidate prodrug designed for the intracellular delivery of a modified adenine nucleoside analog GS-441524. In addition to the active ingredient, the lyophilized formulation of Remdesivir contains the following inactive ingredients: water for injection, sulfobutylether beta-cyclodextrin sodium (SBECD), and hydrochloric acid and/or sodium hydroxide. Placebo: The matching Baricitinib placebo contains lactose monohydrate, microcrystalline cellulose, croscarmellose sodium, and magnesium stearate. The coating for the placebo tablet is identical to that of the corresponding active tablet |
| Period Title: Overall Study | ||
| STARTED | 515 | 518 |
| Treated | 507 | 509 |
| COMPLETED | 431 | 408 |
| NOT COMPLETED | 84 | 110 |
Baseline Characteristics
| Arm/Group Title | Remdesivir Plus Baricitinib | Remdesivir Plus Placebo | Total |
|---|---|---|---|
| Arm/Group Description | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. | Total of all reporting groups |
| Overall Participants | 515 | 518 | 1033 |
| Age (Count of Participants) | |||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
368
71.5%
|
360
69.5%
|
728
70.5%
|
| >=65 years |
147
28.5%
|
158
30.5%
|
305
29.5%
|
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
55.0
(15.4)
|
55.8
(16.0)
|
55.4
(15.7)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
196
38.1%
|
185
35.7%
|
381
36.9%
|
| Male |
319
61.9%
|
333
64.3%
|
652
63.1%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||
| Hispanic or Latino |
263
51.1%
|
268
51.7%
|
531
51.4%
|
| Not Hispanic or Latino |
246
47.8%
|
240
46.3%
|
486
47%
|
| Unknown or Not Reported |
6
1.2%
|
10
1.9%
|
16
1.5%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
2
0.4%
|
8
1.5%
|
10
1%
|
| Asian |
49
9.5%
|
52
10%
|
101
9.8%
|
| Native Hawaiian or Other Pacific Islander |
4
0.8%
|
7
1.4%
|
11
1.1%
|
| Black or African American |
77
15%
|
79
15.3%
|
156
15.1%
|
| White |
251
48.7%
|
245
47.3%
|
496
48%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
132
25.6%
|
127
24.5%
|
259
25.1%
|
| Region of Enrollment (Count of Participants) | |||
| South Korea |
11
2.1%
|
11
2.1%
|
22
2.1%
|
| Singapore |
22
4.3%
|
22
4.2%
|
44
4.3%
|
| United States |
441
85.6%
|
444
85.7%
|
885
85.7%
|
| Japan |
0
0%
|
1
0.2%
|
1
0.1%
|
| Denmark |
4
0.8%
|
5
1%
|
9
0.9%
|
| Mexico |
35
6.8%
|
33
6.4%
|
68
6.6%
|
| United Kingdom |
0
0%
|
1
0.2%
|
1
0.1%
|
| Spain |
2
0.4%
|
1
0.2%
|
3
0.3%
|
| Disease severity (Count of Participants) | |||
| Severe Disease Severity |
176
34.2%
|
191
36.9%
|
367
35.5%
|
| Moderate Disease Severity |
339
65.8%
|
327
63.1%
|
666
64.5%
|
Outcome Measures
| Title | Time to Recovery |
|---|---|
| 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. |
| Time Frame | Day 1 through Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intent-to-treat (ITT) population includes all participants who were randomized |
| Arm/Group Title | Remdesivir Plus Baricitinib | Remdesivir Plus Placebo |
|---|---|---|
| Arm/Group Description | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. |
| Measure Participants | 515 | 518 |
| Median (95% Confidence Interval) [Days] |
7.0
|
8.0
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Remdesivir Plus Baricitinib, Remdesivir Plus Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.047 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Cox Proportional Hazard |
| Estimated Value | 1.15 | |
| Confidence Interval |
(2-Sided) 95% 1.00 to 1.31 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline in Alanine Transaminase (ALT) |
|---|---|
| Description | 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. |
| Time Frame | Days 1, 3, 5, 8, 11, 15 and 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety population includes all treated participants with available data at baseline and the post baseline assessment point, analyzed as treated. |
| Arm/Group Title | Remdesivir Plus Baricitinib | Remdesivir Plus Placebo |
|---|---|---|
| Arm/Group Description | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. |
| Measure Participants | 491 | 491 |
| Day 3 |
3.3
(37.1)
|
2.0
(30.1)
|
| Day 5 |
16.8
(104.4)
|
8.8
(40.9)
|
| Day 8 |
7.9
(45.2)
|
7.8
(46.9)
|
| Day 11 |
0.0
(37.5)
|
7.3
(70.2)
|
| Day 15 |
5.0
(61.5)
|
3.9
(55.1)
|
| Day 29 |
-5.4
(43.0)
|
2.3
(116.1)
|
| Title | Change From Baseline in Aspartate Transaminase (AST) |
|---|---|
| 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. |
| Time Frame | Days 1, 3, 5, 8, 11, 15 and 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety population includes all treated participants with available data at baseline and the post baseline assessment point, analyzed as treated. |
| Arm/Group Title | Remdesivir Plus Baricitinib | Remdesivir Plus Placebo |
|---|---|---|
| Arm/Group Description | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. |
| Measure Participants | 486 | 487 |
| Day 3 |
3.1
(72.4)
|
2.4
(126.4)
|
| Day 5 |
27.4
(413.1)
|
2.8
(48.3)
|
| Day 8 |
-5.6
(38.4)
|
-4.3
(42.3)
|
| Day 11 |
-10.6
(46.4)
|
6.4
(208.3)
|
| Day 15 |
-6.0
(110.1)
|
-3.9
(91.0)
|
| Day 29 |
-17.1
(46.7)
|
2.4
(291.1)
|
| Title | Change From Baseline in Creatinine |
|---|---|
| Description | 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. |
| Time Frame | Days 1, 3, 5, 8, 11, 15 and 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety population includes all treated participants with available data at baseline and the post baseline assessment point, analyzed as treated. |
| Arm/Group Title | Remdesivir Plus Baricitinib | Remdesivir Plus Placebo |
|---|---|---|
| Arm/Group Description | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. |
| Measure Participants | 494 | 495 |
| Day 3 |
-0.036
(0.465)
|
-0.019
(0.362)
|
| Day 5 |
-0.078
(0.475)
|
0.001
(0.556)
|
| Day 8 |
-0.082
(0.570)
|
0.129
(0.958)
|
| Day 11 |
-0.055
(0.798)
|
0.194
(1.037)
|
| Day 15 |
-0.042
(0.714)
|
0.094
(0.662)
|
| Day 29 |
-0.034
(0.678)
|
0.033
(0.511)
|
| Title | Change From Baseline in Glucose |
|---|---|
| Description | 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. |
| Time Frame | Days 1, 3, 5, 8, 11, 15 and 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety population includes all treated participants with available data at baseline and the post baseline assessment point, analyzed as treated. |
| Arm/Group Title | Remdesivir Plus Baricitinib | Remdesivir Plus Placebo |
|---|---|---|
| Arm/Group Description | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. |
| Measure Participants | 493 | 493 |
| Day 3 |
-17.1
(56.4)
|
-6.0
(54.0)
|
| Day 5 |
-15.9
(59.7)
|
-1.6
(58.4)
|
| Day 8 |
-16.8
(78.9)
|
5.0
(73.7)
|
| Day 11 |
-8.1
(72.3)
|
1.2
(66.2)
|
| Day 15 |
-11.1
(69.8)
|
0.8
(68.3)
|
| Day 29 |
-4.6
(66.5)
|
-2.2
(60.3)
|
| Title | Change From Baseline in Hemoglobin |
|---|---|
| Description | 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. |
| Time Frame | Days 1, 3, 5, 8, 11, 15 and 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety population includes all treated participants with available data at baseline and the post baseline assessment point, analyzed as treated. |
| Arm/Group Title | Remdesivir Plus Baricitinib | Remdesivir Plus Placebo |
|---|---|---|
| Arm/Group Description | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. |
| Measure Participants | 493 | 494 |
| Day 3 |
-0.46
(1.05)
|
-0.34
(1.51)
|
| Day 5 |
-0.62
(1.23)
|
-0.64
(1.13)
|
| Day 8 |
-0.93
(1.61)
|
-1.08
(1.47)
|
| Day 11 |
-1.29
(1.85)
|
-1.62
(1.88)
|
| Day 15 |
-0.96
(1.87)
|
-1.12
(2.38)
|
| Day 29 |
-0.54
(1.87)
|
-0.77
(2.25)
|
| Title | Change From Baseline in Platelets |
|---|---|
| Description | 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. |
| Time Frame | Days 1, 3, 5, 8, 11, 15 and 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety population includes all treated participants with available data at baseline and the post baseline assessment point, analyzed as treated. |
| Arm/Group Title | Remdesivir Plus Baricitinib | Remdesivir Plus Placebo |
|---|---|---|
| Arm/Group Description | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. |
| Measure Participants | 493 | 494 |
| Day 3 |
55.9
(54.0)
|
52.6
(51.6)
|
| Day 5 |
116.6
(87.8)
|
106.1
(86.9)
|
| Day 8 |
197.9
(137.4)
|
158.9
(128.5)
|
| Day 11 |
229.9
(156.0)
|
145.7
(146.4)
|
| Day 15 |
175.9
(158.8)
|
111.6
(134.9)
|
| Day 29 |
16.5
(95.8)
|
36.9
(107.9)
|
| Title | Change From Baseline in Prothrombin International Normalized Ratio (INR) |
|---|---|
| Description | Blood to evaluate INR 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. |
| Time Frame | Days 1, 3, 5, 8, 11, 15 and 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety population includes all treated participants with available data at baseline and the post baseline assessment point, analyzed as treated. |
| Arm/Group Title | Remdesivir Plus Baricitinib | Remdesivir Plus Placebo |
|---|---|---|
| Arm/Group Description | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. |
| Measure Participants | 447 | 439 |
| Day 3 |
-0.03
(1.13)
|
0.05
(0.59)
|
| Day 5 |
0.02
(1.25)
|
0.08
(0.65)
|
| Day 8 |
0.01
(0.96)
|
0.08
(0.98)
|
| Day 11 |
0.04
(0.65)
|
0.03
(1.04)
|
| Day 15 |
-0.04
(0.25)
|
-0.08
(0.91)
|
| Day 29 |
-0.12
(0.55)
|
-0.03
(0.99)
|
| Title | Change From Baseline in Total Bilirubin |
|---|---|
| Description | 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. |
| Time Frame | Days 1, 3, 5, 8, 11, 15 and 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety population includes all treated participants with available data at baseline and the post baseline assessment point, analyzed as treated. |
| Arm/Group Title | Remdesivir Plus Baricitinib | Remdesivir Plus Placebo |
|---|---|---|
| Arm/Group Description | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. |
| Measure Participants | 490 | 491 |
| Day 3 |
-0.06
(0.32)
|
-0.01
(0.43)
|
| Day 5 |
-0.04
(0.37)
|
0.01
(0.42)
|
| Day 8 |
-0.06
(0.41)
|
0.01
(0.66)
|
| Day 11 |
-0.08
(0.43)
|
0.08
(1.19)
|
| Day 15 |
-0.10
(0.37)
|
0.08
(1.20)
|
| Day 29 |
-0.10
(0.36)
|
0.01
(0.91)
|
| Title | Change From Baseline in White Blood Cell Count (WBC) |
|---|---|
| Description | 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. |
| Time Frame | Days 1, 3, 5, 8, 11, 15 and 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety population includes all treated participants with available data at baseline and the post baseline assessment point, analyzed as treated. |
| Arm/Group Title | Remdesivir Plus Baricitinib | Remdesivir Plus Placebo |
|---|---|---|
| Arm/Group Description | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. |
| Measure Participants | 493 | 494 |
| Day 3 |
-0.831
(3.020)
|
-0.037
(2.588)
|
| Day 5 |
-0.276
(3.399)
|
0.392
(3.238)
|
| Day 8 |
0.663
(4.006)
|
1.606
(4.536)
|
| Day 11 |
1.869
(5.683)
|
2.938
(5.419)
|
| Day 15 |
0.694
(5.125)
|
2.162
(5.741)
|
| Day 29 |
-0.364
(4.532)
|
0.712
(4.176)
|
| Title | Change From Baseline in Neutrophils |
|---|---|
| Description | BBlood 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. |
| Time Frame | Days 1, 3, 5, 8, 11, 15 and 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety population includes all treated participants with available data at baseline and the post baseline assessment point, analyzed as treated. |
| Arm/Group Title | Remdesivir Plus Baricitinib | Remdesivir Plus Placebo |
|---|---|---|
| Arm/Group Description | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. |
| Measure Participants | 488 | 493 |
| Day 3 |
-1.925
(6.234)
|
-0.333
(2.787)
|
| Day 5 |
-1.334
(8.092)
|
-0.204
(3.630)
|
| Day 8 |
-0.813
(9.695)
|
1.139
(6.665)
|
| Day 11 |
-0.046
(8.881)
|
1.847
(5.152)
|
| Day 15 |
-1.192
(7.844)
|
1.414
(7.995)
|
| Day 29 |
-1.708
(6.735)
|
-0.656
(4.205)
|
| Title | Change From Baseline in Lymphocytes |
|---|---|
| Description | 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. |
| Time Frame | Days 1, 3, 5, 8, 11, 15 and 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety population includes all treated participants with available data at baseline and the post baseline assessment point, analyzed as treated. |
| Arm/Group Title | Remdesivir Plus Baricitinib | Remdesivir Plus Placebo |
|---|---|---|
| Arm/Group Description | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. |
| Measure Participants | 488 | 493 |
| Day 3 |
0.503
(2.290)
|
0.074
(3.844)
|
| Day 5 |
0.620
(2.540)
|
0.205
(3.838)
|
| Day 8 |
0.515
(2.094)
|
0.304
(1.366)
|
| Day 11 |
0.541
(1.204)
|
0.409
(0.709)
|
| Day 15 |
0.687
(1.579)
|
0.718
(1.684)
|
| Day 29 |
0.653
(1.293)
|
0.927
(1.996)
|
| Title | Change From Baseline in Monocytes |
|---|---|
| Description | 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. |
| Time Frame | Days 1, 3, 5, 8, 11, 15 and 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety population includes all treated participants with available data at baseline and the post baseline assessment point, analyzed as treated. |
| Arm/Group Title | Remdesivir Plus Baricitinib | Remdesivir Plus Placebo |
|---|---|---|
| Arm/Group Description | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. |
| Measure Participants | 487 | 493 |
| Day 3 |
0.004
(0.810)
|
0.062
(0.750)
|
| Day 5 |
0.094
(1.053)
|
0.153
(1.013)
|
| Day 8 |
0.105
(0.948)
|
0.279
(0.758)
|
| Day 11 |
0.210
(0.439)
|
0.378
(0.512)
|
| Day 15 |
0.256
(0.591)
|
0.329
(0.606)
|
| Day 29 |
0.108
(0.434)
|
0.212
(0.745)
|
| Title | Change From Baseline in Basophils |
|---|---|
| Description | 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. |
| Time Frame | Days 1, 3, 5, 8, 11, 15 and 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety population includes all treated participants with available data at baseline and the post baseline assessment point, analyzed as treated. |
| Arm/Group Title | Remdesivir Plus Baricitinib | Remdesivir Plus Placebo |
|---|---|---|
| Arm/Group Description | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. |
| Measure Participants | 483 | 492 |
| Day 3 |
0.000
(0.039)
|
0.001
(0.050)
|
| Day 5 |
0.007
(0.070)
|
0.006
(0.044)
|
| Day 8 |
0.011
(0.055)
|
0.017
(0.075)
|
| Day 11 |
0.014
(0.063)
|
0.022
(0.063)
|
| Day 15 |
0.026
(0.085)
|
0.037
(0.104)
|
| Day 29 |
0.022
(0.045)
|
0.036
(0.092)
|
| Title | Change From Baseline in Eosinophils |
|---|---|
| Description | 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. |
| Time Frame | Days 1, 3, 5, 8, 11, 15 and 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety population includes all treated participants with available data at baseline and the post baseline assessment point, analyzed as treated. |
| Arm/Group Title | Remdesivir Plus Baricitinib | Remdesivir Plus Placebo |
|---|---|---|
| Arm/Group Description | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. |
| Measure Participants | 484 | 492 |
| Day 3 |
0.050
(0.135)
|
0.039
(0.201)
|
| Day 5 |
0.104
(0.402)
|
0.075
(0.257)
|
| Day 8 |
0.088
(0.126)
|
0.086
(0.232)
|
| Day 11 |
0.078
(0.119)
|
0.115
(0.299)
|
| Day 15 |
0.121
(0.231)
|
0.109
(0.163)
|
| Day 29 |
0.192
(0.171)
|
0.205
(0.267)
|
| Title | Change in National Early Warning Score (NEWS) From Baseline |
|---|---|
| Description | The NEW score has demonstrated an ability to discriminate patients at risk of poor outcomes. This score is based on 7 clinical parameters (respiration rate, oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate, level of consciousness). The NEW Score is being used as an efficacy measure. The minimum score is 0, representing the better outcome, and the maximum value is 19, representing the worse outcome. |
| Time Frame | Days 1, 3, 5, 8, 11, 15, 22, and 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intent-to-treat (ITT) population includes all participants who were randomized with data at baseline and at each timepoint. Missing values were imputed using Last Observation Carried Forward. |
| Arm/Group Title | Remdesivir Plus Baricitinib | Remdesivir Plus Placebo |
|---|---|---|
| Arm/Group Description | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. |
| Measure Participants | 515 | 518 |
| Day 3 |
-0.5
(2.5)
|
-0.1
(2.6)
|
| Day 5 |
-0.9
(2.8)
|
-0.4
(2.8)
|
| Day 8 |
-1.5
(2.9)
|
-0.8
(3.3)
|
| Day 11 |
-1.8
(3.2)
|
-1.1
(3.5)
|
| Day 15 |
-2.1
(3.3)
|
-1.2
(3.9)
|
| Day 22 |
-2.0
(3.8)
|
-1.2
(4.6)
|
| Day 29 |
-2.2
(4.3)
|
-1.4
(5.0)
|
| Title | Percentage of Participants Reporting Grade 3 and 4 Clinical and/or Laboratory Adverse Events (AEs) |
|---|---|
| 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. |
| Time Frame | Day 1 through Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety population includes all participants with available data post baseline, analyzed as treated. |
| Arm/Group Title | Remdesivir Plus Baricitinib | Remdesivir Plus Placebo |
|---|---|---|
| Arm/Group Description | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. |
| Measure Participants | 507 | 509 |
| Number (95% Confidence Interval) [percentage of participants] |
40.8
7.9%
|
46.8
9%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Remdesivir Plus Baricitinib, Remdesivir Plus Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Difference (RD) |
| Estimated Value | -6 | |
| Confidence Interval |
(2-Sided) 95% -12 to 0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Participants Reporting Serious Adverse Events (SAEs) |
|---|---|
| Description | An SAE is defined as an AE or suspected adverse reaction is considered serious if, in the view of either the investigator or the sponsor, it results in death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect. |
| Time Frame | Day 1 through Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety population includes all participants with available data post baseline, analyzed as treated. |
| Arm/Group Title | Remdesivir Plus Baricitinib | Remdesivir Plus Placebo |
|---|---|---|
| Arm/Group Description | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. |
| Measure Participants | 507 | 509 |
| Number (95% Confidence Interval) [percentage of participants] |
16.0
3.1%
|
21.0
4.1%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Remdesivir Plus Baricitinib, Remdesivir Plus Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Risk Difference (RD) |
| Estimated Value | -5 | |
| Confidence Interval |
(2-Sided) 95% -10 to 0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Duration of Hospitalization |
|---|---|
| Description | 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. |
| Time Frame | Day 1 through Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intent-to-treat (ITT) population includes all participants who were randomized |
| Arm/Group Title | Remdesivir Plus Baricitinib | Remdesivir Plus Placebo |
|---|---|---|
| Arm/Group Description | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. |
| Measure Participants | 515 | 518 |
| Including imputation for participants who died |
8
|
8
|
| Restricted to participants who did not die |
8
|
8
|
| Title | Duration of New Non-invasive Ventilation or High Flow Oxygen Use |
|---|---|
| Description | 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 |
| Time Frame | Day 1 through Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population is restricted to randomized participants who were not on non-invasive ventilation or high-flow oxygen at baseline but who subsequently required non-invasive or high-flow oxygen. |
| Arm/Group Title | Remdesivir Plus Baricitinib | Remdesivir Plus Placebo |
|---|---|---|
| Arm/Group Description | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. |
| Measure Participants | 70 | 82 |
| Including imputations for participants who died |
6
|
4.5
|
| Among participants who did not die |
5
|
4
|
| Title | Duration of New Oxygen Use |
|---|---|
| Description | 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 |
| Time Frame | Day 1 through Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population is restricted to randomized participants who were not on oxygen at baseline but who subsequently required oxygen. |
| Arm/Group Title | Remdesivir Plus Baricitinib | Remdesivir Plus Placebo |
|---|---|---|
| Arm/Group Description | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. |
| Measure Participants | 16 | 29 |
| Including imputations for participants who died |
3
|
3
|
| Among participants who did not die |
3
|
3
|
| Title | Duration of New Ventilator or Extracorporeal Membrane Oxygenation (ECMO) Use |
|---|---|
| Description | 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 |
| Time Frame | Day 1 through Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population is restricted to randomized participants not on a ventilator or ECMO at baseline but who subsequently required a ventilator or ECMO. |
| Arm/Group Title | Remdesivir Plus Baricitinib | Remdesivir Plus Placebo |
|---|---|---|
| Arm/Group Description | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. |
| Measure Participants | 46 | 70 |
| Including imputations for participants who died |
16
|
27
|
| Among participants who did not die |
13
|
20
|
| Title | Duration of Oxygen Use |
|---|---|
| Description | Duration of oxygen use was measured in days among participants who were on oxygen in based, calculated in two ways. The first includes imputations for participants who died. The second method is restricted to participants who did not die. |
| Time Frame | Day 1 through Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population is restricted to randomized participants who were on oxygen at baseline. |
| Arm/Group Title | Remdesivir Plus Baricitinib | Remdesivir Plus Placebo |
|---|---|---|
| Arm/Group Description | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. |
| Measure Participants | 445 | 446 |
| Including imputations for participants who died |
10
|
12
|
| Among participants who did not die |
9
|
10
|
| Title | Percentage of Participants Discontinued or Temporarily Suspended From Investigational Therapeutics |
|---|---|
| Description | 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 of Remdesivir, or in the 14 doses of Baricitinib/placebo. |
| Time Frame | Day 1 through Day 14 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intent-to-treat (ITT) population includes all participants who were randomized |
| Arm/Group Title | Remdesivir Plus Baricitinib | Remdesivir Plus Placebo |
|---|---|---|
| Arm/Group Description | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. |
| Measure Participants | 515 | 518 |
| Received less than 10 Infusions of Remdesivir due to Discharge |
55
10.7%
|
51
9.8%
|
| Received less than 10 Infusions of Remdesivir due to Death |
0
0%
|
1
0.2%
|
| Received less than 14 doses of Baricitinib/Placebo due to Discharge |
66
12.8%
|
59
11.4%
|
| Received less than 14 doses of Baricitinib/Placebo due to Death |
0
0%
|
1
0.2%
|
| Had Any Infusions of Remdesivir Halted or Slowed |
2
0.4%
|
2
0.4%
|
| Had Any Oral Doses of Baricitinib/Placebo Modified |
16
3.1%
|
18
3.5%
|
| Missed Any Maintenance Dose of Remdesivir |
23
4.5%
|
27
5.2%
|
| Missed Any Oral Dose of Baricitinib/Placebo |
30
5.8%
|
34
6.6%
|
| Terminated Early Prior to Completing 10 Infusions of Remdesivir |
3
0.6%
|
4
0.8%
|
| Terminated Early Prior to Completing 14 doses of Baricitinib/Placebo |
4
0.8%
|
5
1%
|
| Title | Percentage of Participants Requiring New Ventilator or Extracorporeal Membrane Oxygenation (ECMO) Use |
|---|---|
| Description | The percentage of participants requiring new ventilator or ECMO use was determined as the percentage not on a ventilator or ECMO at baseline |
| Time Frame | Day 1 through Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population is restricted to randomized participants not on a ventilator or ECMO at baseline. |
| Arm/Group Title | Remdesivir Plus Baricitinib | Remdesivir Plus Placebo |
|---|---|---|
| Arm/Group Description | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. |
| Measure Participants | 461 | 461 |
| Number (95% Confidence Interval) [percentage of participants] |
10
1.9%
|
15
2.9%
|
| Title | Percentage of Participants Requiring New Oxygen Use |
|---|---|
| Description | The percentage of participants requiring new oxygen use was determined as the percentage of participants not requiring oxygen at baseline |
| Time Frame | Day 1 through Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population is restricted to randomized participants not requiring oxygen at baseline. |
| Arm/Group Title | Remdesivir Plus Baricitinib | Remdesivir Plus Placebo |
|---|---|---|
| Arm/Group Description | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. |
| Measure Participants | 70 | 72 |
| Number (95% Confidence Interval) [percentage of participants] |
23
4.5%
|
40
7.7%
|
| Title | Mean Change in the Ordinal Scale |
|---|---|
| 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: 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. |
| Time Frame | Day 1, 3, 5, 8, 11, 15, 22, and 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intent-to-treat (ITT) population includes all participants who were randomized reporting a clinical score. Missing values were imputed using Last Observation Carried Forward. |
| Arm/Group Title | Remdesivir Plus Baricitinib | Remdesivir Plus Placebo |
|---|---|---|
| Arm/Group Description | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. |
| Measure Participants | 515 | 518 |
| Day 3 |
0.1
(0.5)
|
0.1
(0.6)
|
| Day 5 |
0.0
(0.7)
|
0.0
(0.7)
|
| Day 8 |
-0.3
(0.9)
|
-0.1
(0.9)
|
| Day 11 |
-0.4
(1.0)
|
-0.2
(1.0)
|
| Day 15 |
-2.3
(1.9)
|
-1.9
(2.0)
|
| Day 22 |
-2.7
(1.9)
|
-2.3
(2.1)
|
| Day 29 |
-2.9
(1.9)
|
-2.5
(2.1)
|
| Title | Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 15 |
|---|---|
| Description | The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 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. Data was imputed using last observation carried forward or worst possible score based on hospitalization status (2 if not hospitalized, 7 if hospitalized) when there was a change in hospitalization status since last score. Deaths were imputed as an 8. |
| Time Frame | Day 15 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intent-to-treat (ITT) population includes all participants who were randomized. |
| Arm/Group Title | Remdesivir Plus Baricitinib | Remdesivir Plus Placebo |
|---|---|---|
| Arm/Group Description | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. |
| Measure Participants | 515 | 518 |
| Death at or before study visit |
2
0.4%
|
3
0.6%
|
| Hospitalized, on invasive mech. vent. or ECMO |
9
1.7%
|
16
3.1%
|
| Hospitalized, on non-invasive vent./high flow O2 |
4
0.8%
|
4
0.8%
|
| Hospitalized, requiring supplemental oxygen |
8
1.6%
|
10
1.9%
|
| Hospitalized, not on O2, requiring ongoing care |
6
1.2%
|
3
0.6%
|
| Hospitalized, not requiring O2, no longer req care |
2
0.4%
|
1
0.2%
|
| Not hospitalized, limit on activities/req home O2 |
34
6.6%
|
31
6%
|
| Not hospitalized, no limitations on activities |
34
6.6%
|
32
6.2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Remdesivir Plus Baricitinib, Remdesivir Plus Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.44 |
| Comments | ||
| Method | Regression, Logistic | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.26 | |
| Confidence Interval |
(2-Sided) 95% 1.01 to 1.57 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 1 |
|---|---|
| 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: 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 Frame | Day 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intent-to-treat (ITT) population includes all participants who were randomized |
| Arm/Group Title | Remdesivir Plus Baricitinib | Remdesivir Plus Placebo |
|---|---|---|
| Arm/Group Description | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. |
| Measure Participants | 515 | 518 |
| Death at or before study Visit |
0
0%
|
0
0%
|
| Hospitalized, on invasive mech. vent. or ECMO |
10
1.9%
|
11
2.1%
|
| Hospitalized, on non-invasive vent./high flow O2 |
20
3.9%
|
22
4.2%
|
| Hospitalized, requiring supplemental oxygen |
56
10.9%
|
53
10.2%
|
| Hospitalized, not on O2, requiring ongoing care |
14
2.7%
|
14
2.7%
|
| Hospitalized, not requiring O2, no longer req care |
0
0%
|
0
0%
|
| Not hospitalized, limit on activities/req home O2 |
0
0%
|
0
0%
|
| Not hospitalized, no limitations on activities |
0
0%
|
0
0%
|
| No clinical status score reported - Hospitalized |
0
0%
|
0
0%
|
| No clinical status score reported - Discharged |
0
0%
|
0
0%
|
| No clinical status score reported - Discontinued |
0
0%
|
0
0%
|
| Title | Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 3 |
|---|---|
| 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: 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 Frame | Day 3 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intent-to-treat (ITT) population includes all participants who were randomized |
| Arm/Group Title | Remdesivir Plus Baricitinib | Remdesivir Plus Placebo |
|---|---|---|
| Arm/Group Description | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. |
| Measure Participants | 515 | 518 |
| Death at or before study Visit |
0.4
0.1%
|
0
0%
|
| Hospitalized, on invasive mech. vent. or ECMO |
15
2.9%
|
16
3.1%
|
| Hospitalized, on non-invasive vent./high flow O2 |
22
4.3%
|
22
4.2%
|
| Hospitalized, requiring supplemental oxygen |
45
8.7%
|
44
8.5%
|
| Hospitalized, not on O2, requiring ongoing care |
16
3.1%
|
14
2.7%
|
| Hospitalized, not requiring O2, no longer req care |
0.2
0%
|
1
0.2%
|
| Not hospitalized, limit on activities/req home O2 |
0
0%
|
0
0%
|
| Not hospitalized, no limitations on activities |
0
0%
|
0
0%
|
| No clinical status score reported - Hospitalized |
0
0%
|
0
0%
|
| No clinical status score reported - Discharged |
0.2
0%
|
0.4
0.1%
|
| No clinical status score reported - Discontinued |
1
0.2%
|
2
0.4%
|
| Title | Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 5 |
|---|---|
| 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: 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 Frame | Day 5 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intent-to-treat (ITT) population includes all participants who were randomized |
| Arm/Group Title | Remdesivir Plus Baricitinib | Remdesivir Plus Placebo |
|---|---|---|
| Arm/Group Description | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. |
| Measure Participants | 515 | 518 |
| Death at or before study Visit |
1
0.2%
|
0
0%
|
| Hospitalized, on invasive mech. vent. or ECMO |
15
2.9%
|
18
3.5%
|
| Hospitalized, on non-invasive vent./high flow O2 |
17
3.3%
|
18
3.5%
|
| Hospitalized, requiring supplemental oxygen |
35
6.8%
|
33
6.4%
|
| Hospitalized, not on O2, requiring ongoing care |
19
3.7%
|
15
2.9%
|
| Hospitalized, not requiring O2, no longer req care |
1
0.2%
|
1
0.2%
|
| Not hospitalized, limit on activities/req home O2 |
0.2
0%
|
0
0%
|
| Not hospitalized, no limitations on activities |
0.2
0%
|
0
0%
|
| No clinical status score reported - Hospitalized |
0
0%
|
0.2
0%
|
| No clinical status score reported - Discharged |
10
1.9%
|
13
2.5%
|
| No clinical status score reported - Discontinued |
2
0.4%
|
3
0.6%
|
| Title | Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 8 |
|---|---|
| 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: 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 Frame | Day 8 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intent-to-treat (ITT) population includes all participants who were randomized |
| Arm/Group Title | Remdesivir Plus Baricitinib | Remdesivir Plus Placebo |
|---|---|---|
| Arm/Group Description | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. |
| Measure Participants | 515 | 518 |
| Death at or before study Visit |
1
0.2%
|
1
0.2%
|
| Hospitalized, on invasive mech. vent. or ECMO |
13
2.5%
|
18
3.5%
|
| Hospitalized, on non-invasive vent./high flow O2 |
11
2.1%
|
12
2.3%
|
| Hospitalized, requiring supplemental oxygen |
18
3.5%
|
18
3.5%
|
| Hospitalized, not on O2, requiring ongoing care |
12
2.3%
|
10
1.9%
|
| Hospitalized, not requiring O2, no longer req care |
1
0.2%
|
1
0.2%
|
| Not hospitalized, limit on activities/req home O2 |
0.2
0%
|
0
0%
|
| Not hospitalized, no limitations on activities |
0.4
0.1%
|
0
0%
|
| No clinical status score reported - Hospitalized |
0
0%
|
0.4
0.1%
|
| No clinical status score reported - Discharged |
40
7.8%
|
36
6.9%
|
| No clinical status score reported - Discontinued |
3
0.6%
|
4
0.8%
|
| Title | Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 11 |
|---|---|
| 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: 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 Frame | Day 11 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intent-to-treat (ITT) population includes all participants who were randomized |
| Arm/Group Title | Remdesivir Plus Baricitinib | Remdesivir Plus Placebo |
|---|---|---|
| Arm/Group Description | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. |
| Measure Participants | 515 | 518 |
| Death at or before study Visit |
1
0.2%
|
2
0.4%
|
| Hospitalized, on invasive mech. vent. or ECMO |
11
2.1%
|
16
3.1%
|
| Hospitalized, on non-invasive vent./high flow O2 |
6
1.2%
|
7
1.4%
|
| Hospitalized, requiring supplemental oxygen |
12
2.3%
|
10
1.9%
|
| Hospitalized, not on O2, requiring ongoing care |
9
1.7%
|
7
1.4%
|
| Hospitalized, not requiring O2, no longer req care |
1
0.2%
|
1
0.2%
|
| Not hospitalized, limit on activities/req home O2 |
0
0%
|
0
0%
|
| Not hospitalized, no limitations on activities |
0.2
0%
|
0.2
0%
|
| No clinical status score reported - Hospitalized |
0
0%
|
1
0.2%
|
| No clinical status score reported - Discharged |
56
10.9%
|
52
10%
|
| No clinical status score reported - Discontinued |
3
0.6%
|
4
0.8%
|
| Title | Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 22 |
|---|---|
| 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: 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 Frame | Day 22 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intent-to-treat (ITT) population includes all participants who were randomized |
| Arm/Group Title | Remdesivir Plus Baricitinib | Remdesivir Plus Placebo |
|---|---|---|
| Arm/Group Description | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. |
| Measure Participants | 515 | 518 |
| Death at or before study Visit |
4
0.8%
|
6
1.2%
|
| Hospitalized, on invasive mech. vent. or ECMO |
6
1.2%
|
9
1.7%
|
| Hospitalized, on non-invasive vent./high flow O2 |
3
0.6%
|
1
0.2%
|
| Hospitalized, requiring supplemental oxygen |
3
0.6%
|
5
1%
|
| Hospitalized, not on O2, requiring ongoing care |
2
0.4%
|
3
0.6%
|
| Hospitalized, not requiring O2, no longer req care |
1
0.2%
|
0.4
0.1%
|
| Not hospitalized, limit on activities/req home O2 |
24
4.7%
|
25
4.8%
|
| Not hospitalized, no limitations on activities |
44
8.5%
|
37
7.1%
|
| No clinical status score reported - Hospitalized |
0
0%
|
0
0%
|
| No clinical status score reported - Discharged |
4
0.8%
|
3
0.6%
|
| No clinical status score reported - Discontinued |
9
1.7%
|
10
1.9%
|
| Title | Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 29 |
|---|---|
| Description | The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 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 Frame | Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intent-to-treat (ITT) population includes all participants who were randomized |
| Arm/Group Title | Remdesivir Plus Baricitinib | Remdesivir Plus Placebo |
|---|---|---|
| Arm/Group Description | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. |
| Measure Participants | 515 | 518 |
| Death at or before study Visit |
5
1%
|
7
1.4%
|
| Hospitalized, on invasive mech. vent. or ECMO |
3
0.6%
|
7
1.4%
|
| Hospitalized, on non-invasive vent./high flow O2 |
2
0.4%
|
1
0.2%
|
| Hospitalized, requiring supplemental oxygen |
2
0.4%
|
3
0.6%
|
| Hospitalized, not on O2, requiring ongoing care |
3
0.6%
|
1
0.2%
|
| Hospitalized, not requiring O2, no longer req care |
1
0.2%
|
0.2
0%
|
| Not hospitalized, limit on activities/req home O2 |
23
4.5%
|
23
4.4%
|
| Not hospitalized, no limitations on activities |
49
9.5%
|
43
8.3%
|
| No clinical status score reported - Hospitalized |
0
0%
|
0
0%
|
| No clinical status score reported - Discharged |
0.4
0.1%
|
1
0.2%
|
| No clinical status score reported - Discontinued |
12
2.3%
|
13
2.5%
|
| No clinical status, completed study without reporting score |
0.2
0%
|
0.2
0%
|
| Title | 14-day Participant Mortality |
|---|---|
| Description | The mortality rate was determined as the proportion of participants who died by study Day 15. The proportions reported are Kaplan-Meier estimates. |
| Time Frame | Day 1 through Day 15 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The ITT population consists of all participants as randomized. |
| Arm/Group Title | Remdesivir Plus Baricitinib | Remdesivir Plus Placebo |
|---|---|---|
| Arm/Group Description | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. |
| Measure Participants | 515 | 518 |
| Number (95% Confidence Interval) [proportion of participants] |
0.02
0%
|
0.03
0%
|
| Title | 28-day Participant Mortality |
|---|---|
| Description | The mortality rate was determined as the proportion of participants who died by study Day 29. The proportions reported are Kaplan-Meier estimates. |
| Time Frame | Day 1 through Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The ITT population includes all participants as randomized. |
| Arm/Group Title | Remdesivir Plus Baricitinib | Remdesivir Plus Placebo |
|---|---|---|
| Arm/Group Description | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. |
| Measure Participants | 515 | 518 |
| Number (95% Confidence Interval) [proportion of participants] |
0.05
0%
|
0.08
0%
|
| Title | Time to an Improvement of One Category Using an Ordinal Scale |
|---|---|
| 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: 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 |
| Time Frame | Day 1 through Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The ITT population includes all participants as randomized |
| Arm/Group Title | Remdesivir Plus Baricitinib | Remdesivir Plus Placebo |
|---|---|---|
| Arm/Group Description | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. |
| Measure Participants | 515 | 518 |
| Median (95% Confidence Interval) [Days] |
6.0
|
8.0
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Remdesivir Plus Baricitinib, Remdesivir Plus Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.002 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Cox Proportional Hazard |
| Estimated Value | 1.21 | |
| Confidence Interval |
(2-Sided) 95% 1.06 to 1.39 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Time to an Improvement of Two Categories Using an Ordinal Scale |
|---|---|
| Description | The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities. Time to improvement by at least two categories was determined for each participant |
| Time Frame | Day 1 through Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The ITT population includes all participants as randomized |
| Arm/Group Title | Remdesivir Plus Baricitinib | Remdesivir Plus Placebo |
|---|---|---|
| Arm/Group Description | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. |
| Measure Participants | 515 | 518 |
| Median (95% Confidence Interval) [Days] |
12.0
|
13.0
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Remdesivir Plus Baricitinib, Remdesivir Plus Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.005 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Cox Proportional Hazard |
| Estimated Value | 1.20 | |
| Confidence Interval |
(2-Sided) 95% 1.05 to 1.38 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Time to Discharge or to a NEWS of 2 or Less and Maintained for 24 Hours, Whichever Occurs First |
|---|---|
| Description | The NEW score has demonstrated an ability to discriminate patients at risk of poor outcomes. This score is based on 7 clinical parameters (respiration rate, oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate, level of consciousness). The NEW Score is being used as an efficacy measure. 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. |
| Time Frame | Day 1 through Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The ITT population includes participants as randomized, and restricted to those with a baseline NEWS score of 2 or greater. |
| Arm/Group Title | Remdesivir Plus Baricitinib | Remdesivir Plus Placebo |
|---|---|---|
| Arm/Group Description | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. |
| Measure Participants | 361 | 334 |
| Median (95% Confidence Interval) [Days] |
6.0
|
7.0
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Remdesivir Plus Baricitinib, Remdesivir Plus Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.003 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Cox Proportional Hazard |
| Estimated Value | 1.24 | |
| Confidence Interval |
(2-Sided) 95% 1.07 to 1.44 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline in C-reactive Protein (CRP) |
|---|---|
| Description | Blood to evaluate CRP 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. |
| Time Frame | Days 1, 3, 5, 8, 11, 15 and 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety population includes all treated participants with available data at baseline and the post baseline assessment point, analyzed as treated. |
| Arm/Group Title | Remdesivir Plus Baricitinib | Remdesivir Plus Placebo |
|---|---|---|
| Arm/Group Description | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. |
| Measure Participants | 446 | 455 |
| Day 3 |
-23.035
(169.442)
|
-18.671
(102.661)
|
| Day 5 |
-58.935
(110.364)
|
-30.908
(150.076)
|
| Day 8 |
-78.411
(104.943)
|
-62.038
(125.254)
|
| Day 11 |
-103.789
(124.751)
|
-88.881
(159.184)
|
| Day 15 |
-122.339
(110.502)
|
-112.588
(155.762)
|
| Day 29 |
-131.333
(115.243)
|
-122.342
(268.733)
|
| Title | Change From Baseline in D-dimer Concentration |
|---|---|
| Description | Blood to evaluate d-dimer concentration 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. |
| Time Frame | Days 1, 3, 5, 8, 11, 15 and 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety population includes all treated participants with available data at baseline and the post baseline assessment point, analyzed as treated. |
| Arm/Group Title | Remdesivir Plus Baricitinib | Remdesivir Plus Placebo |
|---|---|---|
| Arm/Group Description | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. |
| Measure Participants | 436 | 432 |
| Day 3 |
-0.374
(7.062)
|
0.384
(5.663)
|
| Day 5 |
0.053
(10.968)
|
-0.149
(5.978)
|
| Day 8 |
-0.271
(9.994)
|
0.351
(5.387)
|
| Day 11 |
0.622
(12.779)
|
0.309
(7.283)
|
| Day 15 |
-0.988
(11.352)
|
-0.422
(6.579)
|
| Day 29 |
0.774
(27.229)
|
-0.219
(10.386)
|
| Title | Time to Recovery by Race |
|---|---|
| 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. |
| Time Frame | Day 1 through Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intent-to-treat (ITT) population includes all participants who were randomized |
| Arm/Group Title | Remdesivir Plus Baricitinib | Remdesivir Plus Placebo |
|---|---|---|
| Arm/Group Description | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. |
| Measure Participants | 515 | 518 |
| Asian |
10
|
10.0
|
| Black or African American |
7.0
|
6.0
|
| White |
7.0
|
7.0
|
| Other |
7.0
|
8.0
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Remdesivir Plus Baricitinib, Remdesivir Plus Placebo |
|---|---|---|
| Comments | This analysis is for Asian participants. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Cox Proportional Hazard |
| Estimated Value | 1.11 | |
| Confidence Interval |
(2-Sided) 95% 0.73 to 1.68 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Remdesivir Plus Baricitinib, Remdesivir Plus Placebo |
|---|---|---|
| Comments | This analysis is for Black or African American participants. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Cox Proportional Hazard |
| Estimated Value | 1.06 | |
| Confidence Interval |
(2-Sided) 95% 0.75 to 1.50 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Remdesivir Plus Baricitinib, Remdesivir Plus Placebo |
|---|---|---|
| Comments | This analysis is for White participants. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Cox Proportional Hazard |
| Estimated Value | 1.13 | |
| Confidence Interval |
(2-Sided) 95% 0.93 to 1.37 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Remdesivir Plus Baricitinib, Remdesivir Plus Placebo |
|---|---|---|
| Comments | This analysis is for Race of Other participants. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Cox Proportional Hazard |
| Estimated Value | 1.34 | |
| Confidence Interval |
(2-Sided) 95% 1.03 to 1.74 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Time to Recovery by Ethnicity |
|---|---|
| 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. |
| Time Frame | Day 1 through Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intent-to-treat (ITT) population includes all participants who were randomized and for whom ethnicity was reported |
| Arm/Group Title | Remdesivir Plus Baricitinib | Remdesivir Plus Placebo |
|---|---|---|
| Arm/Group Description | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. |
| Measure Participants | 509 | 508 |
| Not Hispanic or Latino |
7.0
|
9.0
|
| Hispanic or Latino |
7.0
|
7.0
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Remdesivir Plus Baricitinib, Remdesivir Plus Placebo |
|---|---|---|
| Comments | This analysis is for Not Hispanic or Latino participants | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Cox Proportional Hazard |
| Estimated Value | 1.31 | |
| Confidence Interval |
(2-Sided) 95% 1.08 to 1.60 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Remdesivir Plus Baricitinib, Remdesivir Plus Placebo |
|---|---|---|
| Comments | This analysis is for Hispanic or Latino participants. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Cox Proportional Hazard |
| Estimated Value | 1.08 | |
| Confidence Interval |
(2-Sided) 95% 0.89 to 1.31 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Time to Recovery by Sex |
|---|---|
| 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. |
| Time Frame | Day 1 through Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intent-to-treat (ITT) population includes all participants who were randomized |
| Arm/Group Title | Remdesivir Plus Baricitinib | Remdesivir Plus Placebo |
|---|---|---|
| Arm/Group Description | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. |
| Measure Participants | 515 | 518 |
| Male |
7.0
|
9.0
|
| Female |
7.0
|
7.0
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Remdesivir Plus Baricitinib, Remdesivir Plus Placebo |
|---|---|---|
| Comments | This analysis is for Male participants. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Cox Proportional Hazard |
| Estimated Value | 1.23 | |
| Confidence Interval |
(2-Sided) 95% 1.04 to 1.46 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Remdesivir Plus Baricitinib, Remdesivir Plus Placebo |
|---|---|---|
| Comments | This analysis is for Female participants. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Cox Proportional Hazard |
| Estimated Value | 1.06 | |
| Confidence Interval |
(2-Sided) 95% 0.85 to 1.32 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Adverse Events
| Time Frame | Serious and Grade 3 and 4 non-serious adverse events were collected for 29 days after the first dose. Laboratory values were systematically assessed at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29. Treatment emergent and fatal AEs are reported. | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | Given the severity of underlying illness, participants were expected to have many symptoms and abnormalities in vital signs and laboratory values. All Grade 3 and 4 AEs were captured as AEs in this trial. Grade 2 or higher, suspected drug-related hypersensitivity reaction or deep vein thrombosis of any grade was reported as an AE in this trial. All cause mortality was calculated for the ITT population, while SAEs and AEs reflect the as treated population. | |||
| Arm/Group Title | Remdesivir Plus Baricitinib | Remdesivir Plus Placebo | ||
| Arm/Group Description | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib administered orally daily for the duration of the hospitalization up to a 14-day total course. | 200 mg of Remdesivir administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir while hospitalized for up to a 10-day total course and 4 mg (2 tablets of 2 mg) of Baricitinib Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course. | ||
All Cause Mortality |
||||
| Remdesivir Plus Baricitinib | Remdesivir Plus Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 24/515 (4.7%) | 37/518 (7.1%) | ||
Serious Adverse Events |
||||
| Remdesivir Plus Baricitinib | Remdesivir Plus Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 88/507 (17.4%) | 109/509 (21.4%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 1/507 (0.2%) | 1 | 2/509 (0.4%) | 2 |
| Leukopenia | 1/507 (0.2%) | 1 | 0/509 (0%) | 0 |
| Sickle cell anaemia with crisis | 1/507 (0.2%) | 1 | 0/509 (0%) | 0 |
| Lymphopenia | 0/507 (0%) | 0 | 1/509 (0.2%) | 1 |
| Cardiac disorders | ||||
| Cardiac arrest | 2/507 (0.4%) | 2 | 3/509 (0.6%) | 3 |
| Pulseless electrical activity | 2/507 (0.4%) | 2 | 1/509 (0.2%) | 1 |
| Cardio-respiratory arrest | 1/507 (0.2%) | 1 | 1/509 (0.2%) | 1 |
| Cardiac failure | 1/507 (0.2%) | 1 | 0/509 (0%) | 0 |
| Sinus tachycardia | 1/507 (0.2%) | 1 | 0/509 (0%) | 0 |
| Aortic valve stenosis | 0/507 (0%) | 0 | 1/509 (0.2%) | 1 |
| Arrhythmia | 0/507 (0%) | 0 | 1/509 (0.2%) | 1 |
| Atrial fibrillation | 0/507 (0%) | 0 | 1/509 (0.2%) | 1 |
| Atrioventricular block | 0/507 (0%) | 0 | 1/509 (0.2%) | 1 |
| Bradycardia | 0/507 (0%) | 0 | 1/509 (0.2%) | 1 |
| Left ventricular failure | 0/507 (0%) | 0 | 1/509 (0.2%) | 1 |
| Right ventricular dysfunction | 0/507 (0%) | 0 | 1/509 (0.2%) | 1 |
| Eye disorders | ||||
| Visual impairment | 1/507 (0.2%) | 1 | 0/509 (0%) | 0 |
| Gastrointestinal disorders | ||||
| Gastrointestinal haemorrhage | 1/507 (0.2%) | 1 | 0/509 (0%) | 0 |
| Abdominal pain | 0/507 (0%) | 0 | 1/509 (0.2%) | 1 |
| General disorders | ||||
| Multiple organ dysfunction syndrome | 2/507 (0.4%) | 2 | 6/509 (1.2%) | 6 |
| Chest pain | 2/507 (0.4%) | 2 | 0/509 (0%) | 0 |
| Asthenia | 1/507 (0.2%) | 1 | 0/509 (0%) | 0 |
| Non-cardiac chest pain | 1/507 (0.2%) | 1 | 0/509 (0%) | 0 |
| Injection site induration | 0/507 (0%) | 0 | 1/509 (0.2%) | 1 |
| Oedema peripheral | 0/507 (0%) | 0 | 1/509 (0.2%) | 1 |
| Hepatobiliary disorders | ||||
| Hepatic haemorrhage | 0/507 (0%) | 0 | 1/509 (0.2%) | 1 |
| Hepatitis | 0/507 (0%) | 0 | 1/509 (0.2%) | 1 |
| Immune system disorders | ||||
| Hypersensitivity | 0/507 (0%) | 0 | 1/509 (0.2%) | 1 |
| Infections and infestations | ||||
| Septic shock | 4/507 (0.8%) | 4 | 8/509 (1.6%) | 8 |
| Pneumonia | 2/507 (0.4%) | 2 | 8/509 (1.6%) | 8 |
| Sepsis | 2/507 (0.4%) | 2 | 5/509 (1%) | 5 |
| Intervertebral discitis | 1/507 (0.2%) | 1 | 0/509 (0%) | 0 |
| Lower respiratory tract infection | 1/507 (0.2%) | 1 | 0/509 (0%) | 0 |
| Prostatic abscess | 1/507 (0.2%) | 1 | 0/509 (0%) | 0 |
| Urinary tract infection | 1/507 (0.2%) | 1 | 0/509 (0%) | 0 |
| Aspergillus infection | 0/507 (0%) | 0 | 1/509 (0.2%) | 1 |
| Lung abscess | 0/507 (0%) | 0 | 1/509 (0.2%) | 1 |
| Urosepsis | 0/507 (0%) | 0 | 1/509 (0.2%) | 1 |
| Injury, poisoning and procedural complications | ||||
| Procedural hypotension | 1/507 (0.2%) | 1 | 0/509 (0%) | 0 |
| Endotracheal intubation complication | 0/507 (0%) | 0 | 1/509 (0.2%) | 2 |
| Fall | 0/507 (0%) | 0 | 1/509 (0.2%) | 1 |
| Overdose | 0/507 (0%) | 0 | 1/509 (0.2%) | 1 |
| Subdural haematoma | 0/507 (0%) | 0 | 1/509 (0.2%) | 1 |
| Investigations | ||||
| Alanine aminotransferase increased | 0/507 (0%) | 0 | 3/509 (0.6%) | 3 |
| Aspartate aminotransferase increased | 0/507 (0%) | 0 | 2/509 (0.4%) | 2 |
| Lymphocyte count decreased | 1/507 (0.2%) | 1 | 0/509 (0%) | 0 |
| Blood creatinine increased | 0/507 (0%) | 0 | 1/509 (0.2%) | 1 |
| Blood glucose decreased | 0/507 (0%) | 0 | 1/509 (0.2%) | 1 |
| Haemoglobin decreased | 0/507 (0%) | 0 | 1/509 (0.2%) | 1 |
| Troponin increased | 0/507 (0%) | 0 | 1/509 (0.2%) | 1 |
| Metabolism and nutrition disorders | ||||
| Dehydration | 1/507 (0.2%) | 1 | 0/509 (0%) | 0 |
| Acidosis | 0/507 (0%) | 0 | 1/509 (0.2%) | 1 |
| Diabetic ketoacidosis | 0/507 (0%) | 0 | 1/509 (0.2%) | 1 |
| Hyperkalaemia | 0/507 (0%) | 0 | 1/509 (0.2%) | 1 |
| Hypoglycaemia | 0/507 (0%) | 0 | 1/509 (0.2%) | 1 |
| Metabolic acidosis | 0/507 (0%) | 0 | 1/509 (0.2%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||
| Haematoma muscle | 0/507 (0%) | 0 | 1/509 (0.2%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Lipoma | 1/507 (0.2%) | 1 | 0/509 (0%) | 0 |
| Nervous system disorders | ||||
| Cerebrovascular accident | 1/507 (0.2%) | 1 | 2/509 (0.4%) | 2 |
| Encephalopathy | 1/507 (0.2%) | 1 | 2/509 (0.4%) | 2 |
| Guillain-Barre syndrome | 1/507 (0.2%) | 1 | 0/509 (0%) | 0 |
| Nervous system disorder | 1/507 (0.2%) | 1 | 0/509 (0%) | 0 |
| Haemorrhage intracranial | 0/507 (0%) | 0 | 1/509 (0.2%) | 1 |
| Presyncope | 0/507 (0%) | 0 | 1/509 (0.2%) | 1 |
| Renal and urinary disorders | ||||
| Acute kidney injury | 5/507 (1%) | 5 | 11/509 (2.2%) | 11 |
| Renal failure | 0/507 (0%) | 0 | 5/509 (1%) | 5 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Respiratory failure | 29/507 (5.7%) | 30 | 37/509 (7.3%) | 38 |
| Acute respiratory failure | 18/507 (3.6%) | 18 | 16/509 (3.1%) | 16 |
| Acute respiratory distress syndrome | 4/507 (0.8%) | 4 | 10/509 (2%) | 10 |
| Respiratory distress | 7/507 (1.4%) | 8 | 7/509 (1.4%) | 7 |
| Pulmonary embolism | 5/507 (1%) | 5 | 1/509 (0.2%) | 1 |
| Hypoxia | 3/507 (0.6%) | 3 | 3/509 (0.6%) | 4 |
| Dyspnoea | 2/507 (0.4%) | 2 | 4/509 (0.8%) | 4 |
| Pneumothorax | 1/507 (0.2%) | 1 | 4/509 (0.8%) | 4 |
| Respiratory arrest | 1/507 (0.2%) | 1 | 1/509 (0.2%) | 1 |
| Pneumonia aspiration | 1/507 (0.2%) | 1 | 0/509 (0%) | 0 |
| Pneumomediastinum | 0/507 (0%) | 0 | 1/509 (0.2%) | 1 |
| Tachypnoea | 0/507 (0%) | 0 | 2/509 (0.4%) | 2 |
| Vascular disorders | ||||
| Hypotension | 6/507 (1.2%) | 6 | 5/509 (1%) | 5 |
| Shock | 2/507 (0.4%) | 2 | 4/509 (0.8%) | 4 |
| Deep vein thrombosis | 1/507 (0.2%) | 1 | 1/509 (0.2%) | 1 |
| Distributive shock | 1/507 (0.2%) | 1 | 0/509 (0%) | 0 |
| Thrombophlebitis | 1/507 (0.2%) | 1 | 0/509 (0%) | 0 |
| Embolism venous | 0/507 (0%) | 0 | 1/509 (0.2%) | 1 |
Other (Not Including Serious) Adverse Events |
||||
| Remdesivir Plus Baricitinib | Remdesivir Plus Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 147/507 (29%) | 164/509 (32.2%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 25/507 (4.9%) | 28 | 31/509 (6.1%) | 40 |
| Investigations | ||||
| Glomerular filtration rate decreased | 50/507 (9.9%) | 52 | 45/509 (8.8%) | 46 |
| Haemoglobin decreased | 30/507 (5.9%) | 32 | 31/509 (6.1%) | 32 |
| Lymphocyte count decreased | 25/507 (4.9%) | 28 | 36/509 (7.1%) | 36 |
| Blood glucose increased | 26/507 (5.1%) | 26 | 28/509 (5.5%) | 28 |
| Metabolism and nutrition disorders | ||||
| Hyperglycaemia | 29/507 (5.7%) | 34 | 40/509 (7.9%) | 47 |
| Renal and urinary disorders | ||||
| Acute kidney injury | 16/507 (3.2%) | 17 | 27/509 (5.3%) | 28 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
| Name/Title | John Beigel, MD |
|---|---|
| Organization | NIAID |
| Phone | 3014519881 |
| jbeigel@niaid.nih.gov |
Responsible Party:
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT04401579
Other Study ID Numbers:
- 20-0006 ACTT-2
First Posted:
May 26, 2020
Last Update Posted:
Mar 14, 2022
Last Verified:
Apr 1, 2020