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Adaptive COVID-19 Treatment Trial 3 (ACTT-3)

Primary Purpose

COVID-19

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Interferon beta-1a

Placebo

Remdesivir

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 respiratory specimen or saliva, as documented by either of the following:
- PCR or other assay positive in sample collected < 72 hours prior to randomization; OR
- PCR or other assay positive in sample collected >/= 72 hours but < 7 days prior to randomization AND progressive disease suggestive of ongoing SARS-CoV-2 infection.
Note: if written documentation of the positive test result is not available at enrollment (e.g., report from other institution), the subject may be enrolled but the PCR should be repeated at the time of enrollment.
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.
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 (both pharmacologic and other types of interventions) for the treatment of COVID-19 through Day 29.

Exclusion Criteria:

Anticipated discharge from the hospital or transfer to another hospital which is not a study site within 72 hours.
Subject meets criteria for ordinal scale category 6 or 7 at the time of screening.
Subject has a positive test for influenza virus during this current hospital admission.
Subjects with an estimated glomerular filtration rate (eGFR) < 30 mL/min are excluded unless in the opinion of the PI, the potential benefit of receiving remdesivir outweighs the potential risk of study participation.
Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 5 times the upper limits of normal.
Total white cell blood cell count (WBC) <1500 cells/microliter.
Platelet count <50,000/microliter.
History of chronic liver disease (e.g., jaundice, ascites, hepatic encephalopathy, history of bleeding esophageal or gastric varices). No laboratory testing is needed.
Pregnancy or breast feeding (lactating women who agree to discard breast milk from Day 1 until three weeks after the last study product is given are not excluded).
Allergy to any study medication including history of hypersensitivity to natural or recombinant interferon beta or human albumin.
Patient has a chronic or acute medical condition or is taking a medication that cannot be discontinued at enrollment, that in the judgement of the PI, places them at unacceptable risk for a poor clinical outcome if they were to participate in the study.
Received three or more doses of remdesivir, including the loading dose, outside of the study for COVID-19.
Received convalescent plasma or intravenous immunoglobulin [IVIg] for the treatment of COVID-19.
Received any interferon product within two weeks of screening, either for the treatment of COVID-19 or for a chronic medical condition (e.g., multiple sclerosis, HCV infection).
Received any of the following in the two weeks prior to screening as treatment of COVID-19:
- Small molecule tyrosine kinase inhibitors (e.g. baricitinib, imatinib, gefitinib, acalabrutinib, etc.);
- Monoclonal antibodies targeting cytokines (e.g., TNF inhibitors, anti-interleukin-1 [IL-1], anti-IL-6 [tocilizumab or sarilumab], etc.);
- Monoclonal antibodies targeting T-cells or B-cells as treatment for COVID-19.
Prior enrollment in ACTT-3.

Sites / Locations

University of Alabama at Birmingham School of Medicine - Infectious Disease
UCSF Fresno Center for Medical Education and Research - Clinical Research Center
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 HIV, ID, and Global Medicine
Cedars Sinai Medical Center
Eastern Colorado Health Care System
Denver Health Division of Hospital Medicine - Main Campus
University of Florida Health - Shands Hospital - Division of Infectious Diseases and Global Medicine
University of Florida Health - Jacksonville - Department of Emergency Medicine
University of Miami Miller School of Medicine - Infectious Diseases
Emory Vaccine Center - The Hope Clinic
Atlanta VA Medical Center - Infectious Diseases Clinic
Tripler Army Medical Center (TAMC)
Northwestern Hospital - Infectious Disease
University of Illinois at Chicago Division of Infectious Diseases
University of Iowa Hospitals & Clinics - Department of Internal Medicine
Ochsner Medical Center - Kenner - Department of Infectious Diseases
Southeast Louisiana Veterans Health Care System - 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
Hospital of the University of Pennsylvania - 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
Methodist Hospital - Houston
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
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 Enfermedades Respiratorias (INER) - Ismael Cosío Villegas
Instituto Nacional de Ciencias Medicas y Nutrición Salvador Zubirán - Departamento de Infectologia
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

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Remdesivir plus Interferon Beta-1a

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 44 mcg of interferon beta-1a administered by a 0.5 mL subcutaneous injection on Days 1, 3, 5, and 7 while hospitalized for a total of 4 doses.

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 a 0.5 mL placebo injection administered subcutaneously on Days 1, 3, 5, and 7 while hospitalized for a total of 4 doses.

Outcomes

Primary Outcome Measures

Time to Recovery for Participants With Baseline Ordinal Score 4, 5 and 6

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, but new or increased limitation on activities and/or new or increased requirement for home oxygen; 3) Hospitalized, not requiring supplemental oxygen and no longer requires ongoing medical care.

Time to Recovery for Participants With Baseline Ordinal Score 4, 5 and 6 by Race

Time to Recovery for Participants With Baseline Ordinal Score 4, 5 and 6 by Ethnicity

Time to Recovery for Participants With Baseline Ordinal Score 4, 5 and 6 by Sex

Secondary Outcome Measures

Change From Baseline in Alanine Aminotransferase (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. The measure was assessed by baseline ordinal scale category (categories 4 and 5 versus category 6).

Change From Baseline in Aspartate Aminotransferase (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. The measure was assessed by baseline ordinal scale category (categories 4 and 5 versus category 6).

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. The measure was assessed by baseline ordinal scale category (categories 4 and 5 versus category 6).

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. The measure was assessed by baseline ordinal scale category (categories 4 and 5 versus category 6).

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.

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. The outcome was assessed by baseline ordinal scale category (categories 4 and 5 versus category 6).

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. The outcome was assessed by baseline ordinal scale category (categories 4 and 5 versus category 6).

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. The outcome was assessed overall and by baseline ordinal scale category (categories 4 and 5 versus category 6).

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. The outcome was assessed by baseline ordinal scale category (categories 4 and 5 versus category 6).

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. The outcome was assessed by baseline ordinal scale category (categories 4 and 5 versus category 6).

Change From Baseline in Neutrophils

Blood to evaluate neutrophils was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge. The outcome was assessed by baseline ordinal scale category (categories 4 and 5 versus category 6).

Change From Baseline in Lymphoctyes

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. The outcome was assessed by baseline ordinal scale category (categories 4 and 5 versus category 6).

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. The outcome was assessed by baseline ordinal scale category (categories 4 and 5 versus category 6).

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. The outcome was assessed by baseline ordinal scale category (categories 4 and 5 versus category 6).

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. The outcome was assessed by baseline ordinal scale category (categories 4 and 5 versus category 6).

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 Invasive Mechanical Ventilation

Duration of invasive ventilation was measured in days among participants who required invasive ventilation, 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 Non Invasive Ventilation or High Flow Oxygen Use

Duration of non invasive ventilation or high flow oxygen use was measured in days, 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.

Number of Participants With Discontinuation or Temporary Suspension of Study Product Administration

Discontinuation or temporary suspension of study product administration, including participants who died or were discharged, was evaluated by baseline ordinal scale category (categories 4 and 5 versus category 6).

Proportion of Participants With New Non-invasive Ventilation or High Flow Oxygen Use

Proportion of participants with new non-invasive ventilation or high flow oxygen use was assessed as for participants in Ordinal Score 4 and 5.

Proportion of Participants With New Oxygen Use

Incidence of new oxygen use was assessed as for participants in Ordinal Score 4 and 5 who were not on oxygen at baseline.

Proportion of Participants With New Ventilator or Extracorporeal Membrane Oxygenation (ECMO) Use

Incidence of new ventilator or extracorporeal membrane oxygenation (ECMO) use was assessed among participants not on ventilator or extracorporeal membrane oxygenation (ECMO) use at baseline.

Mean Change From Baseline 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: 1) Not hospitalized, no limitations on activities; 2) Not hospitalized, but new or increased limitation on activities and/or new or increased requirement for home oxygen; 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 5) Hospitalized, requiring supplemental oxygen; 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 8) Death. A positive change indicates a worsening and a negative change is an improvement.

Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 15 for Participants With Baseline Ordinal Score 4 and 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. 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 Reporting Each Severity Rating on an 8 Point Ordinal Scale at Day 1

Percentage of Participants Reporting Each Severity Rating on an 8 Point Ordinal Scale at Day 3

Percentage of Participants Reporting Each Severity Rating on an 8 Point Ordinal Scale at Day 5

Percentage of Participants Reporting Each Severity Rating on an 8 Point Ordinal Scale at Day 8

Percentage of Participants Reporting Each Severity Rating on an 8 Point Ordinal Scale at Day 11

Percentage of Participants Reporting Each Severity Rating on an 8 Point Ordinal Scale at Day 15

Percentage of Participants Reporting Each Severity Rating on an 8 Point Ordinal Scale at Day 22

Percentage of Participants Reporting Each Severity Rating on an 8 Point 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 National Early Warning Score (NEWS) of </= 2 and Maintained for 24 Hours, Whichever Occurs First

Time to Recovery for Patients With a Baseline Ordinal Score of 4 and 5

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.

Full Information

NCT ID

NCT04492475

First Posted

July 28, 2020

Last Updated

March 9, 2022

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

1. Study Identification

Unique Protocol Identification Number

NCT04492475

Brief Title

Adaptive COVID-19 Treatment Trial 3 (ACTT-3)

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-3)

Study Type

Interventional

2. Study Status

Record Verification Date

November 2020

Overall Recruitment Status

Completed

Study Start Date

August 5, 2020 (Actual)

Primary Completion Date

December 21, 2020 (Actual)

Study Completion Date

December 21, 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-3 will evaluate the combination of interferon beta-1a and remdesivir compared to remdesivir alone. Subjects will be assessed daily while hospitalized. If the subjects are discharged from the hospital, they will have a study visit at Days 15, 22, and 29. For discharged subjects, it is preferred that the Day 15 and 29 visits are in person to obtain safety laboratory tests and oropharyngeal (OP) swab and blood (serum only) samples for secondary research as well as clinical outcome data. However, infection control or other restrictions may limit the ability of the subject to return to the clinic. In this case, these visits may be conducted by phone, and only clinical data will be obtained. The Day 22 visit does not have laboratory tests or collection of samples and is conducted by phone. The primary outcome is time to recovery by Day 29.

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-3 will evaluate the combination of interferon beta-1a and remdesivir compared to remdesivir alone. Subjects will be assessed daily while hospitalized. If the subjects are discharged from the hospital, they will have a study visit at Days 15, 22, and 29. For discharged subjects, it is preferred that the Day 15 and 29 visits are in person to obtain safety laboratory tests and oropharyngeal (OP) swab and blood (serum only) samples for secondary research as well as clinical outcome data. However, infection control or other restrictions may limit the ability of the subject to return to the clinic. In this case, these visits may be conducted by phone, and only clinical data will be obtained. The Day 22 visit does not have laboratory tests or collection of samples and is conducted by phone. 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 for patients with baseline ordinal score 4, 5 and 6. 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

969 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Remdesivir plus Interferon Beta-1a

Arm Type

Experimental

Arm Description

Arm Title

Remdesivir plus Placebo

Arm Type

Placebo Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Interferon beta-1a

Intervention Description

Rebif (R) is a purified 166 amino acid human interferon beta glycoprotein with an amino acid sequence identical to natural fibroblast derived human interferon beta. Each 0.5 mL prefilled syringe contains 44 mcg of interferon beta-1a, 4 mg human albumin, USP; 27.3 mg mannitol, USP; 0.4 mg sodium acetate; and water for injection, USP.

Intervention Type

Other

Intervention Name(s)

Placebo

Intervention Description

The interferon beta-1a placebo contains either 0.5 mL 0.9% normal saline or 0.5 mL sterile water for injection.

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.

Primary Outcome Measure Information:

Title

Time to Recovery for Participants With Baseline Ordinal Score 4, 5 and 6

Description

Time Frame

Day 1 through Day 29

Title

Time to Recovery for Participants With Baseline Ordinal Score 4, 5 and 6 by Race

Description

Time Frame

Day 1 through Day 29

Title

Time to Recovery for Participants With Baseline Ordinal Score 4, 5 and 6 by Ethnicity

Description

Time Frame

Day 1 through Day 29

Title

Time to Recovery for Participants With Baseline Ordinal Score 4, 5 and 6 by Sex

Description

Time Frame

Day 1 through Day 29

Secondary Outcome Measure Information:

Title

Change From Baseline in Alanine Aminotransferase (ALT)

Description

Time Frame

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

Title

Change From Baseline in Aspartate Aminotransferase (AST)

Description

Time Frame

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

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

Title

Change From Baseline in Hemoglobin

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 Platelets

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 Lymphoctyes

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 Invasive Mechanical Ventilation

Description

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 Non Invasive Ventilation or High Flow Oxygen Use

Description

Time Frame

Day 1 through Day 29

Title

Duration of Oxygen Use

Description

Time Frame

Day 1 through Day 29

Title

Number of Participants With Discontinuation or Temporary Suspension of Study Product Administration

Description

Time Frame

Day 1 through Day 10

Title

Proportion of Participants With New Non-invasive Ventilation or High Flow Oxygen Use

Description

Proportion of participants with new non-invasive ventilation or high flow oxygen use was assessed as for participants in Ordinal Score 4 and 5.

Time Frame

Day 1 through Day 29

Title

Proportion of Participants With New Oxygen Use

Description

Incidence of new oxygen use was assessed as for participants in Ordinal Score 4 and 5 who were not on oxygen at baseline.

Time Frame

Day 1 through Day 29

Title

Proportion of Participants With New Ventilator or Extracorporeal Membrane Oxygenation (ECMO) Use

Description

Incidence of new ventilator or extracorporeal membrane oxygenation (ECMO) use was assessed among participants not on ventilator or extracorporeal membrane oxygenation (ECMO) use at baseline.

Time Frame

Day 1 through Day 29

Title

Mean Change From Baseline 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 for Participants With Baseline Ordinal Score 4 and 5

Description

Time Frame

Day 15

Title

Percentage of Participants Reporting Each Severity Rating on an 8 Point Ordinal Scale at Day 1

Description

Time Frame

Day 1

Title

Percentage of Participants Reporting Each Severity Rating on an 8 Point Ordinal Scale at Day 3

Description

Time Frame

Day 3

Title

Percentage of Participants Reporting Each Severity Rating on an 8 Point Ordinal Scale at Day 5

Description

Time Frame

Day 5

Title

Percentage of Participants Reporting Each Severity Rating on an 8 Point Ordinal Scale at Day 8

Description

Time Frame

Day 8

Title

Percentage of Participants Reporting Each Severity Rating on an 8 Point Ordinal Scale at Day 11

Description

Time Frame

Day 11

Title

Percentage of Participants Reporting Each Severity Rating on an 8 Point Ordinal Scale at Day 15

Description

Time Frame

Day 15

Title

Percentage of Participants Reporting Each Severity Rating on an 8 Point Ordinal Scale at Day 22

Description

Time Frame

Day 22

Title

Percentage of Participants Reporting Each Severity Rating on an 8 Point 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 National Early Warning Score (NEWS) of </= 2 and Maintained for 24 Hours, Whichever Occurs First

Description

Time Frame

Day 1 through Day 29

Title

Time to Recovery for Patients With a Baseline Ordinal Score of 4 and 5

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

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 respiratory specimen or saliva, as documented by either of the following: PCR or other assay positive in sample collected < 72 hours prior to randomization; OR PCR or other assay positive in sample collected >/= 72 hours but < 7 days prior to randomization AND progressive disease suggestive of ongoing SARS-CoV-2 infection. Note: if written documentation of the positive test result is not available at enrollment (e.g., report from other institution), the subject may be enrolled but the PCR should be repeated at the time of enrollment. 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. 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 (both pharmacologic and other types of interventions) for the treatment of COVID-19 through Day 29. Exclusion Criteria: Anticipated discharge from the hospital or transfer to another hospital which is not a study site within 72 hours. Subject meets criteria for ordinal scale category 6 or 7 at the time of screening. Subject has a positive test for influenza virus during this current hospital admission. Subjects with an estimated glomerular filtration rate (eGFR) < 30 mL/min are excluded unless in the opinion of the PI, the potential benefit of receiving remdesivir outweighs the potential risk of study participation. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 5 times the upper limits of normal. Total white cell blood cell count (WBC) <1500 cells/microliter. Platelet count <50,000/microliter. History of chronic liver disease (e.g., jaundice, ascites, hepatic encephalopathy, history of bleeding esophageal or gastric varices). No laboratory testing is needed. Pregnancy or breast feeding (lactating women who agree to discard breast milk from Day 1 until three weeks after the last study product is given are not excluded). Allergy to any study medication including history of hypersensitivity to natural or recombinant interferon beta or human albumin. Patient has a chronic or acute medical condition or is taking a medication that cannot be discontinued at enrollment, that in the judgement of the PI, places them at unacceptable risk for a poor clinical outcome if they were to participate in the study. Received three or more doses of remdesivir, including the loading dose, outside of the study for COVID-19. Received convalescent plasma or intravenous immunoglobulin [IVIg] for the treatment of COVID-19. Received any interferon product within two weeks of screening, either for the treatment of COVID-19 or for a chronic medical condition (e.g., multiple sclerosis, HCV infection). Received any of the following in the two weeks prior to screening as treatment of COVID-19: Small molecule tyrosine kinase inhibitors (e.g. baricitinib, imatinib, gefitinib, acalabrutinib, etc.); Monoclonal antibodies targeting cytokines (e.g., TNF inhibitors, anti-interleukin-1 [IL-1], anti-IL-6 [tocilizumab or sarilumab], etc.); Monoclonal antibodies targeting T-cells or B-cells as treatment for COVID-19. Prior enrollment in ACTT-3.

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

UCSF Fresno Center for Medical Education and Research - Clinical Research Center

City

Fresno

State/Province

California

ZIP/Postal Code

93701

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 HIV, ID, 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

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 Florida Health - Jacksonville - Department of Emergency Medicine

City

Jacksonville

State/Province

Florida

ZIP/Postal Code

32209

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

Tripler Army Medical Center (TAMC)

City

Honolulu

State/Province

Hawaii

ZIP/Postal Code

96859

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 Division of Infectious Diseases

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60612

Country

United States

Facility Name

University of Iowa Hospitals & Clinics - Department of Internal Medicine

City

Iowa City

State/Province

Iowa

ZIP/Postal Code

52242

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 - 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

55455-0356

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

10016-6402

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

Hospital of the University of Pennsylvania - Infectious Diseases

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19104-4238

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

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

Methodist Hospital - Houston

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

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

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

Seongnam

State/Province

Gyeonggi-do

Country

Korea, Republic of

Facility Name

Seoul National University Hospital

City

Seoul

State/Province

Jongno-gu

ZIP/Postal Code

03080

Country

Korea, Republic of

Facility Name

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

City

Mexico City

ZIP/Postal Code

14080

Country

Mexico

Facility Name

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

City

Mexico City

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

Country

Singapore

12. IPD Sharing Statement

Citations:

PubMed Identifier

34672949

Citation

Kalil AC, Mehta AK, Patterson TF, Erdmann N, Gomez CA, Jain MK, Wolfe CR, Ruiz-Palacios GM, Kline S, Regalado Pineda J, Luetkemeyer AF, Harkins MS, Jackson PEH, Iovine NM, Tapson VF, Oh MD, Whitaker JA, Mularski RA, Paules CI, Ince D, Takasaki J, Sweeney DA, Sandkovsky U, Wyles DL, Hohmann E, Grimes KA, Grossberg R, Laguio-Vila M, Lambert AA, Lopez de Castilla D, Kim E, Larson L, Wan CR, Traenkner JJ, Ponce PO, Patterson JE, Goepfert PA, Sofarelli TA, Mocherla S, Ko ER, Ponce de Leon A, Doernberg SB, Atmar RL, Maves RC, Dangond F, Ferreira J, Green M, Makowski M, Bonnett T, Beresnev T, Ghazaryan V, Dempsey W, Nayak SU, Dodd L, Tomashek KM, Beigel JH; ACTT-3 study group members. Efficacy of interferon beta-1a plus remdesivir compared with remdesivir alone in hospitalised adults with COVID-19: a double-bind, randomised, placebo-controlled, phase 3 trial. Lancet Respir Med. 2021 Dec;9(12):1365-1376. doi: 10.1016/S2213-2600(21)00384-2. Epub 2021 Oct 18.

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

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 3 (ACTT-3)

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