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Adaptive COVID-19 Treatment Trial 2 (ACTT-2)

Primary Purpose

COVID-19

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Placebo

Remdesivir

Baricitinib

About this trial

This is an interventional treatment trial for COVID-19 focused on measuring Adaptive, COVID-19, Efficacy, Multicenter, novel coronavirus, Safety

Eligibility Criteria

18 Years - 99 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

University of Alabama at Birmingham School of Medicine - Infectious Disease
University of California San Diego Health - Jacobs Medical Center
University of California Los Angeles Medical Center - Westwood Clinic
University of California Irvine Medical Center - Infectious Disease
VA Palo Alto Health Care System - Infectious Diseases
Stanford University - Stanford Hospital and Clinics - Pediatrics - Infectious Diseases
University of California Davis Medical Center - Internal Medicine - Infectious Disease
Naval Medical Center San Diego - Infectious Disease Clinic
University of California San Francisco - Zuckerberg San Francisco General Hospital - Division of Human Immunodeficiency Virus, Infectious Disease, and Global Medicine
Cedars Sinai Medical Center
Eastern Colorado Health Care System
Denver Health Division of Hospital Medicine - Main Campus
Georgetown University Medical Center - Division of Infectious Diseases
University of Florida Health - Shands Hospital - Division of Infectious Diseases and Global Medicine
University of Miami Miller School of Medicine - Infectious Diseases
Emory Vaccine Center - The Hope Clinic
Atlanta VA Medical Center - Infectious Diseases Clinic
Northwestern Hospital - Infectious Disease
University of Illinois at Chicago College of Medicine - Division of Infectious Diseases
Indiana University School of Medicine - Infectious Diseases
Ochsner Medical Center - Kenner - Department of Infectious Diseases
Southeast Louisiana Veterans Health Care System (SLVHCS) - Section of Infectious Diseases
University of Maryland School of Medicine - Center for Vaccine Development - Baltimore
Johns Hopkins Hospital - Medicine - Infectious Diseases
Walter Reed National Military Medical Center
National Institutes of Health - Clinical Center, National Institute of Allergy and Infectious Diseases Laboratory Of Immunoregulation, Clinical Research Section
Massachusetts General Hospital - Infectious Diseases
University of Massachusetts Medical School - Infectious Diseases and Immunology
University of Minnesota Medical Center, Fairview - Infectious Diseases and International Medicine
Saint Louis University - Center for Vaccine Development
University of Nebraska Medical Center - Infectious Diseases
University of New Mexico Clinical and Translational Science Center
Montefiore Medical Center - Infectious Diseases
New York University School of Medicine - Langone Medical Center - Microbiology - Parasitology
University of Rochester Medical Center - Vaccine Research Unit
Duke Human Vaccine Institute - Duke Vaccine and Trials Unit
Womack Army Medical Center - Pulmonary and Respiratory Services
Kaiser Permanente Northwest - Center for Health Research
Penn State Health Milton S. Hershey Medical Center - Division of Infectious Diseases
University of Pennsylvania Perelman School of Medicine - Penn Institute for Immunology
Vanderbilt University Medical Center - Infectious Diseases
Baylor Scott & White Health - Baylor University Medical Center - North Texas Infectious Disease Consultants
University of Texas Southwestern Medical Center - Internal Medicine - Infectious Diseases
Brooke Army Medical Center
University of Texas Medical Branch - Division of Infectious Disease
Baylor College of Medicine - Molecular Virology and Microbiology
University of Texas Health Science Center at San Antonio - Infectious Diseases
University of Utah - Infectious Diseases
University of Virginia - Acute Care Surgery
Naval Medical Center Portsmouth - Infectious Disease Division
EvergreenHealth Infectious Disease Service
Providence Sacred Heart Medical Center
Madigan Army Medical Center - Infectious Disease Clinic
University of Copenhagen - Centre of Excellence for Health, Immunity and Infections (CHIP) - Department of Infectious Diseases
National Center for Global Health and Medicine Hospital - Disease Control and Prevention Center
Seoul National University Bundang Hospital - Division of Infectious Diseases
Seoul National University Hospital
Instituto Nacional de Ciencias Medicas y Nutrición Salvador Zubirán - Departamento de Infectologia
Instituto Nacional de Enfermedades Respiratorias (INER) - Ismael Cosío Villegas
National University Health System - Division of Infectious Diseases
National Centre for Infectious Diseases (NCID)
Changi General Hospital - Clinical Trials and Research Unit (CTRU)
Ng Teng Fong General Hospital - Infectious Disease Service
Hospital Clinic Barcelona, Servicio de Salud Internacional
Hospital Germans Trias i Pujol - Servei Malalties Infeccioses
Hospital Clinico San Carlos - Enfermedades Infecciosas
Royal Sussex County Hospital - Department of Intensive Care Medicine
Saint Thomas' Hospital - Directorate of Infection
St. James's University Hospital - Infectious Diseases
Royal Victoria Infirmary - Department of Infectious Diseases
John Radcliffe Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Remdesivir plus Baricitinib

Remdesivir plus Placebo

Arm 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.

Outcomes

Primary Outcome Measures

Time to Recovery

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

Time to Recovery by Ethnicity

Time to Recovery by Sex

Secondary Outcome Measures

Change From Baseline in Alanine Transaminase (ALT)

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)

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

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

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

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

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)

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

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)

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

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

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

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

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

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

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)

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)

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

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

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

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

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

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

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

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

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

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

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

Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 3

Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 5

Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 8

Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 11

Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 22

Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 29

14-day Participant Mortality

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

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

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

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

Change From Baseline in C-reactive Protein (CRP)

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

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.

Full Information

NCT ID

NCT04401579

First Posted

May 22, 2020

Last Updated

March 9, 2022

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

1. Study Identification

Unique Protocol Identification Number

NCT04401579

Brief Title

Adaptive COVID-19 Treatment Trial 2 (ACTT-2)

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)

Study Type

Interventional

2. Study Status

Record Verification Date

April 2020

Overall Recruitment Status

Completed

Study Start Date

May 8, 2020 (Actual)

Primary Completion Date

July 31, 2020 (Actual)

Study Completion Date

July 31, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

5. 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.

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

COVID-19

Keywords

Adaptive, COVID-19, Efficacy, Multicenter, novel coronavirus, Safety

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

1033 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Remdesivir plus Baricitinib

Arm Type

Experimental

Arm Description

Arm Title

Remdesivir plus Placebo

Arm Type

Placebo Comparator

Arm 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 Placebo administered orally daily for the duration of the hospitalization up to a 14-day total course.

Intervention Type

Other

Intervention Name(s)

Placebo

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Remdesivir

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Baricitinib

Intervention Description

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.

Primary Outcome Measure Information:

Title

Time to Recovery

Description

Time Frame

Day 1 through Day 29

Title

Time to Recovery by Race

Description

Time Frame

Day 1 through Day 29

Title

Time to Recovery by Ethnicity

Description

Time Frame

Day 1 through Day 29

Title

Time to Recovery by Sex

Description

Time Frame

Day 1 through Day 29

Secondary Outcome Measure Information:

Title

Change From Baseline in Alanine Transaminase (ALT)

Description

Time Frame

Days 1, 3, 5, 8, 11, 15 and 29

Title

Change From Baseline in Aspartate Transaminase (AST)

Description

Time Frame

Days 1, 3, 5, 8, 11, 15 and 29

Title

Change From Baseline in Creatinine

Description

Time Frame

Days 1, 3, 5, 8, 11, 15 and 29

Title

Change From Baseline in Glucose

Description

Time Frame

Days 1, 3, 5, 8, 11, 15 and 29

Title

Change From Baseline in Hemoglobin

Description

Time Frame

Days 1, 3, 5, 8, 11, 15 and 29

Title

Change From Baseline in Platelets

Description

Time Frame

Days 1, 3, 5, 8, 11, 15 and 29

Title

Change From Baseline in Prothrombin International Normalized Ratio (INR)

Description

Time Frame

Days 1, 3, 5, 8, 11, 15 and 29

Title

Change From Baseline in Total Bilirubin

Description

Time Frame

Days 1, 3, 5, 8, 11, 15 and 29

Title

Change From Baseline in White Blood Cell Count (WBC)

Description

Time Frame

Days 1, 3, 5, 8, 11, 15 and 29

Title

Change From Baseline in Neutrophils

Description

Time Frame

Days 1, 3, 5, 8, 11, 15 and 29

Title

Change From Baseline in Lymphocytes

Description

Time Frame

Days 1, 3, 5, 8, 11, 15 and 29

Title

Change From Baseline in Monocytes

Description

Time Frame

Days 1, 3, 5, 8, 11, 15 and 29

Title

Change From Baseline in Basophils

Description

Time Frame

Days 1, 3, 5, 8, 11, 15 and 29

Title

Change From Baseline in Eosinophils

Description

Time Frame

Days 1, 3, 5, 8, 11, 15 and 29

Title

Change in National Early Warning Score (NEWS) From Baseline

Description

Time Frame

Days 1, 3, 5, 8, 11, 15, 22, and 29

Title

Percentage of Participants Reporting Grade 3 and 4 Clinical and/or Laboratory Adverse Events (AEs)

Description

Time Frame

Day 1 through Day 29

Title

Percentage of Participants Reporting Serious Adverse Events (SAEs)

Description

Time Frame

Day 1 through Day 29

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

Title

Duration of New Non-invasive Ventilation or High Flow Oxygen Use

Description

Time Frame

Day 1 through Day 29

Title

Duration of New Oxygen Use

Description

Time Frame

Day 1 through Day 29

Title

Duration of New Ventilator or Extracorporeal Membrane Oxygenation (ECMO) Use

Description

Time Frame

Day 1 through Day 29

Title

Duration of Oxygen Use

Description

Time Frame

Day 1 through Day 29

Title

Percentage of Participants Discontinued or Temporarily Suspended From Investigational Therapeutics

Description

Time Frame

Day 1 through Day 14

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

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

Title

Mean Change in the Ordinal Scale

Description

Time Frame

Day 1, 3, 5, 8, 11, 15, 22, and 29

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

Title

Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 1

Description

Time Frame

Day 1

Title

Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 3

Description

Time Frame

Day 3

Title

Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 5

Description

Time Frame

Day 5

Title

Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 8

Description

Time Frame

Day 8

Title

Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 11

Description

Time Frame

Day 11

Title

Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 22

Description

Time Frame

Day 22

Title

Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 29

Description

Time Frame

Day 29

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

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

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

Title

Time to an Improvement of Two Categories Using an Ordinal Scale

Description

Time Frame

Day 1 through Day 29

Title

Time to Discharge or to a NEWS of 2 or Less and Maintained for 24 Hours, Whichever Occurs First

Description

Time Frame

Day 1 through Day 29

Title

Change From Baseline in C-reactive Protein (CRP)

Description

Time Frame

Days 1, 3, 5, 8, 11, 15 and 29

Title

Change From Baseline in D-dimer Concentration

Description

Time Frame

Days 1, 3, 5, 8, 11, 15 and 29

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

99 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Facility Information:

Facility Name

University of Alabama at Birmingham School of Medicine - Infectious Disease

City

Birmingham

State/Province

Alabama

ZIP/Postal Code

35233

Country

United States

Facility Name

University of California San Diego Health - Jacobs Medical Center

City

La Jolla

State/Province

California

ZIP/Postal Code

29037

Country

United States

Facility Name

University of California Los Angeles Medical Center - Westwood Clinic

City

Los Angeles

State/Province

California

ZIP/Postal Code

90095

Country

United States

Facility Name

University of California Irvine Medical Center - Infectious Disease

City

Orange

State/Province

California

ZIP/Postal Code

92868-3298

Country

United States

Facility Name

VA Palo Alto Health Care System - Infectious Diseases

City

Palo Alto

State/Province

California

ZIP/Postal Code

94304-1207

Country

United States

Facility Name

Stanford University - Stanford Hospital and Clinics - Pediatrics - Infectious Diseases

City

Palo Alto

State/Province

California

ZIP/Postal Code

94304-1503

Country

United States

Facility Name

University of California Davis Medical Center - Internal Medicine - Infectious Disease

City

Sacramento

State/Province

California

ZIP/Postal Code

95817-1460

Country

United States

Facility Name

Naval Medical Center San Diego - Infectious Disease Clinic

City

San Diego

State/Province

California

ZIP/Postal Code

92314

Country

United States

Facility Name

University of California San Francisco - Zuckerberg San Francisco General Hospital - Division of Human Immunodeficiency Virus, Infectious Disease, and Global Medicine

City

San Francisco

State/Province

California

ZIP/Postal Code

94110-2859

Country

United States

Facility Name

Cedars Sinai Medical Center

City

West Hollywood

State/Province

California

ZIP/Postal Code

90048-1804

Country

United States

Facility Name

Eastern Colorado Health Care System

City

Aurora

State/Province

Colorado

ZIP/Postal Code

80045

Country

United States

Facility Name

Denver Health Division of Hospital Medicine - Main Campus

City

Denver

State/Province

Colorado

ZIP/Postal Code

80204

Country

United States

Facility Name

Georgetown University Medical Center - Division of Infectious Diseases

City

Washington

State/Province

District of Columbia

ZIP/Postal Code

20007

Country

United States

Facility Name

University of Florida Health - Shands Hospital - Division of Infectious Diseases and Global Medicine

City

Gainesville

State/Province

Florida

ZIP/Postal Code

32610

Country

United States

Facility Name

University of Miami Miller School of Medicine - Infectious Diseases

City

Miami

State/Province

Florida

ZIP/Postal Code

33136

Country

United States

Facility Name

Emory Vaccine Center - The Hope Clinic

City

Decatur

State/Province

Georgia

ZIP/Postal Code

30030-1705

Country

United States

Facility Name

Atlanta VA Medical Center - Infectious Diseases Clinic

City

Decatur

State/Province

Georgia

ZIP/Postal Code

30033

Country

United States

Facility Name

Northwestern Hospital - Infectious Disease

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60611-2908

Country

United States

Facility Name

University of Illinois at Chicago College of Medicine - Division of Infectious Diseases

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60612

Country

United States

Facility Name

Indiana University School of Medicine - Infectious Diseases

City

Indianapolis

State/Province

Indiana

ZIP/Postal Code

46202

Country

United States

Facility Name

Ochsner Medical Center - Kenner - Department of Infectious Diseases

City

Kenner

State/Province

Louisiana

ZIP/Postal Code

70065

Country

United States

Facility Name

Southeast Louisiana Veterans Health Care System (SLVHCS) - Section of Infectious Diseases

City

New Orleans

State/Province

Louisiana

ZIP/Postal Code

70119

Country

United States

Facility Name

University of Maryland School of Medicine - Center for Vaccine Development - Baltimore

City

Baltimore

State/Province

Maryland

ZIP/Postal Code

21201

Country

United States

Facility Name

Johns Hopkins Hospital - Medicine - Infectious Diseases

City

Baltimore

State/Province

Maryland

ZIP/Postal Code

21287-0005

Country

United States

Facility Name

Walter Reed National Military Medical Center

City

Bethesda

State/Province

Maryland

ZIP/Postal Code

20889

Country

United States

Facility Name

National Institutes of Health - Clinical Center, National Institute of Allergy and Infectious Diseases Laboratory Of Immunoregulation, Clinical Research Section

City

Bethesda

State/Province

Maryland

ZIP/Postal Code

20892-1504

Country

United States

Facility Name

Massachusetts General Hospital - Infectious Diseases

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02114-2621

Country

United States

Facility Name

University of Massachusetts Medical School - Infectious Diseases and Immunology

City

Worcester

State/Province

Massachusetts

ZIP/Postal Code

01655-0002

Country

United States

Facility Name

University of Minnesota Medical Center, Fairview - Infectious Diseases and International Medicine

City

Minneapolis

State/Province

Minnesota

ZIP/Postal Code

55455-0341

Country

United States

Facility Name

Saint Louis University - Center for Vaccine Development

City

Saint Louis

State/Province

Missouri

ZIP/Postal Code

63104-1015

Country

United States

Facility Name

University of Nebraska Medical Center - Infectious Diseases

City

Omaha

State/Province

Nebraska

ZIP/Postal Code

68198-5400

Country

United States

Facility Name

University of New Mexico Clinical and Translational Science Center

City

Albuquerque

State/Province

New Mexico

ZIP/Postal Code

87106

Country

United States

Facility Name

Montefiore Medical Center - Infectious Diseases

City

Bronx

State/Province

New York

ZIP/Postal Code

10467-2401

Country

United States

Facility Name

New York University School of Medicine - Langone Medical Center - Microbiology - Parasitology

City

New York

State/Province

New York

ZIP/Postal Code

10016

Country

United States

Facility Name

University of Rochester Medical Center - Vaccine Research Unit

City

Rochester

State/Province

New York

ZIP/Postal Code

14642-0001

Country

United States

Facility Name

Duke Human Vaccine Institute - Duke Vaccine and Trials Unit

City

Durham

State/Province

North Carolina

ZIP/Postal Code

27704

Country

United States

Facility Name

Womack Army Medical Center - Pulmonary and Respiratory Services

City

Fort Bragg

State/Province

North Carolina

ZIP/Postal Code

28310

Country

United States

Facility Name

Kaiser Permanente Northwest - Center for Health Research

City

Portland

State/Province

Oregon

ZIP/Postal Code

97227

Country

United States

Facility Name

Penn State Health Milton S. Hershey Medical Center - Division of Infectious Diseases

City

Hershey

State/Province

Pennsylvania

ZIP/Postal Code

17033

Country

United States

Facility Name

University of Pennsylvania Perelman School of Medicine - Penn Institute for Immunology

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19104-4863

Country

United States

Facility Name

Vanderbilt University Medical Center - Infectious Diseases

City

Nashville

State/Province

Tennessee

ZIP/Postal Code

37232-0011

Country

United States

Facility Name

Baylor Scott & White Health - Baylor University Medical Center - North Texas Infectious Disease Consultants

City

Dallas

State/Province

Texas

ZIP/Postal Code

75246

Country

United States

Facility Name

University of Texas Southwestern Medical Center - Internal Medicine - Infectious Diseases

City

Dallas

State/Province

Texas

ZIP/Postal Code

75390-8884

Country

United States

Facility Name

Brooke Army Medical Center

City

Fort Sam Houston

State/Province

Texas

ZIP/Postal Code

78234

Country

United States

Facility Name

University of Texas Medical Branch - Division of Infectious Disease

City

Galveston

State/Province

Texas

ZIP/Postal Code

77555-0435

Country

United States

Facility Name

Baylor College of Medicine - Molecular Virology and Microbiology

City

Houston

State/Province

Texas

ZIP/Postal Code

77030-3411

Country

United States

Facility Name

University of Texas Health Science Center at San Antonio - Infectious Diseases

City

San Antonio

State/Province

Texas

ZIP/Postal Code

78229-3901

Country

United States

Facility Name

University of Utah - Infectious Diseases

City

Salt Lake City

State/Province

Utah

ZIP/Postal Code

84132

Country

United States

Facility Name

University of Virginia - Acute Care Surgery

City

Charlottesville

State/Province

Virginia

ZIP/Postal Code

22908-0816

Country

United States

Facility Name

Naval Medical Center Portsmouth - Infectious Disease Division

City

Portsmouth

State/Province

Virginia

ZIP/Postal Code

23708

Country

United States

Facility Name

EvergreenHealth Infectious Disease Service

City

Kirkland

State/Province

Washington

ZIP/Postal Code

98034

Country

United States

Facility Name

Providence Sacred Heart Medical Center

City

Spokane

State/Province

Washington

ZIP/Postal Code

99204

Country

United States

Facility Name

Madigan Army Medical Center - Infectious Disease Clinic

City

Tacoma

State/Province

Washington

ZIP/Postal Code

98431

Country

United States

Facility Name

University of Copenhagen - Centre of Excellence for Health, Immunity and Infections (CHIP) - Department of Infectious Diseases

City

Copenhagen

ZIP/Postal Code

2100

Country

Denmark

Facility Name

National Center for Global Health and Medicine Hospital - Disease Control and Prevention Center

City

Tokyo

ZIP/Postal Code

162-8655

Country

Japan

Facility Name

Seoul National University Bundang Hospital - Division of Infectious Diseases

City

Bundang-gu Seongnam-si

ZIP/Postal Code

13620

Country

Korea, Republic of

Facility Name

Seoul National University Hospital

City

Seoul

ZIP/Postal Code

03080

Country

Korea, Republic of

Facility Name

Instituto Nacional de Ciencias Medicas y Nutrición Salvador Zubirán - Departamento de Infectologia

City

Mexico City

ZIP/Postal Code

14080

Country

Mexico

Facility Name

Instituto Nacional de Enfermedades Respiratorias (INER) - Ismael Cosío Villegas

City

Mexico City

ZIP/Postal Code

14080

Country

Mexico

Facility Name

National University Health System - Division of Infectious Diseases

City

Singapore

ZIP/Postal Code

119228

Country

Singapore

Facility Name

National Centre for Infectious Diseases (NCID)

City

Singapore

ZIP/Postal Code

308442

Country

Singapore

Facility Name

Changi General Hospital - Clinical Trials and Research Unit (CTRU)

City

Singapore

ZIP/Postal Code

529889

Country

Singapore

Facility Name

Ng Teng Fong General Hospital - Infectious Disease Service

City

Singapore

ZIP/Postal Code

609606

Country

Singapore

Facility Name

Hospital Clinic Barcelona, Servicio de Salud Internacional

City

Barcelona

State/Province

Cataluña

ZIP/Postal Code

08036

Country

Spain

Facility Name

Hospital Germans Trias i Pujol - Servei Malalties Infeccioses

City

Barcelona

State/Province

Cataluña

ZIP/Postal Code

08916

Country

Spain

Facility Name

Hospital Clinico San Carlos - Enfermedades Infecciosas

City

Madrid

ZIP/Postal Code

28040

Country

Spain

Facility Name

Royal Sussex County Hospital - Department of Intensive Care Medicine

City

Brighton

Country

United Kingdom

Facility Name

Saint Thomas' Hospital - Directorate of Infection

City

City Of London

Country

United Kingdom

Facility Name

St. James's University Hospital - Infectious Diseases

City

Leeds

Country

United Kingdom

Facility Name

Royal Victoria Infirmary - Department of Infectious Diseases

City

Newcastle Upon Tyne

Country

United Kingdom

Facility Name

John Radcliffe Hospital

City

Oxford

Country

United Kingdom

12. IPD Sharing Statement

Citations:

PubMed Identifier

35695334

Citation

Kramer A, Prinz C, Fichtner F, Fischer AL, Thieme V, Grundeis F, Spagl M, Seeber C, Piechotta V, Metzendorf MI, Golinski M, Moerer O, Stephani C, Mikolajewska A, Kluge S, Stegemann M, Laudi S, Skoetz N. Janus kinase inhibitors for the treatment of COVID-19. Cochrane Database Syst Rev. 2022 Jun 13;6(6):CD015209. doi: 10.1002/14651858.CD015209.

Results Reference

derived

PubMed Identifier

34473343

Citation

Kreuzberger N, Hirsch C, Chai KL, Tomlinson E, Khosravi Z, Popp M, Neidhardt M, Piechotta V, Salomon S, Valk SJ, Monsef I, Schmaderer C, Wood EM, So-Osman C, Roberts DJ, McQuilten Z, Estcourt LJ, Skoetz N. SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19. Cochrane Database Syst Rev. 2021 Sep 2;9(9):CD013825. doi: 10.1002/14651858.CD013825.pub2.

Results Reference

derived

PubMed Identifier

33306283

Citation

Kalil AC, Patterson TF, Mehta AK, Tomashek KM, Wolfe CR, Ghazaryan V, Marconi VC, Ruiz-Palacios GM, Hsieh L, Kline S, Tapson V, Iovine NM, Jain MK, Sweeney DA, El Sahly HM, Branche AR, Regalado Pineda J, Lye DC, Sandkovsky U, Luetkemeyer AF, Cohen SH, Finberg RW, Jackson PEH, Taiwo B, Paules CI, Arguinchona H, Erdmann N, Ahuja N, Frank M, Oh MD, Kim ES, Tan SY, Mularski RA, Nielsen H, Ponce PO, Taylor BS, Larson L, Rouphael NG, Saklawi Y, Cantos VD, Ko ER, Engemann JJ, Amin AN, Watanabe M, Billings J, Elie MC, Davey RT, Burgess TH, Ferreira J, Green M, Makowski M, Cardoso A, de Bono S, Bonnett T, Proschan M, Deye GA, Dempsey W, Nayak SU, Dodd LE, Beigel JH; ACTT-2 Study Group Members. Baricitinib plus Remdesivir for Hospitalized Adults with Covid-19. N Engl J Med. 2021 Mar 4;384(9):795-807. doi: 10.1056/NEJMoa2031994. Epub 2020 Dec 11.

Results Reference

derived

PubMed Identifier

33148977

Citation

Azzi Y, Bartash R, Scalea J, Loarte-Campos P, Akalin E. COVID-19 and Solid Organ Transplantation: A Review Article. Transplantation. 2021 Jan 1;105(1):37-55. doi: 10.1097/TP.0000000000003523.

Results Reference

derived

Learn more about this trial

Adaptive COVID-19 Treatment Trial 2 (ACTT-2)

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