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Adaptive COVID-19 Treatment Trial (ACTT)

Primary Purpose

COVID-19

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Placebo
Remdesivir
Sponsored by
National Institute of Allergy and Infectious Diseases (NIAID)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

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

Eligibility Criteria

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

Inclusion Criteria:

  1. Admitted to a hospital with symptoms suggestive of COVID-19 infection.
  2. Subject (or legally authorized representative) provides informed consent prior to initiation of any study procedures.
  3. Subject (or legally authorized representative) understands and agrees to comply with planned study procedures.
  4. Male or non-pregnant female adult > / = 18 years of age at time of enrollment.

  5. 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 or the following:

    1. PCR positive in sample collected < 72 hours prior to randomization; OR

      Exclusion Criteria:

    2. 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.

  6. Illness of any duration, and at least one of the following:

    1. Radiographic infiltrates by imaging (chest x-ray, CT scan, etc.), OR
    2. SpO2 < / = 94% on room air, OR
    3. Requiring supplemental oxygen, OR
    4. Requiring mechanical ventilation.
  7. 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.
  8. Agrees to not participate in another clinical trial for the treatment of COVID-19 or SARS-CoV-2 through Day 29.

Exclusion Criteria:

  1. Alanine Transaminase (ALT) or Aspartate Transaminase (AST) > 5 times the upper limit of normal.
  2. Estimated glomerular filtration rate (eGFR) < 30 ml/min (including patients receiving hemodialysis or hemofiltration).
  3. Pregnancy or breast feeding.
  4. Anticipated discharge from the hospital or transfer to another hospital which is not a study site within 72 hours.
  5. Allergy to any study medication.

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
  • 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
  • Stanford University - Stanford Hospital and Clinics - Pediatrics - Infectious Diseases
  • Cedars Sinai Medical Center
  • Denver Health Division of Hospital Medicine - Main Campus
  • Emory Vaccine Center - The Hope Clinic
  • Northwestern Hospital - Infectious Disease
  • University of Illinois at Chicago College of Medicine - Division 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
  • 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
  • Penn State Health Milton S. Hershey Medical Center - Division of Infectious Diseases
  • Hospital of the University of Pennsylvania - Infectious Diseases
  • Vanderbilt University Medical Center - 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 Virginia - Acute Care Surgery
  • Naval Medical Center Portsmouth - Infectious Disease Division
  • EvergreenHealth Infectious Disease Service
  • The University of Washington - Virology Research Clinic
  • 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
  • Universitatsklinikum Bonn, Medizinische Klinik I - Bereich Infektiologie/HIV der Medizinischen Klinik
  • Universitatsklinikum Koeln Klinik I fur Innere Medizin Klinisches Studienzentrum fur Infektiologie I
  • Universitätsklinikum Frankfurt -Medizinische Klinik II - Infektiologie
  • AHEPA University Hospital - 1st Department of Internal Medicine
  • Medical School of Athens University - Evangelismos Hospital - Department of Critical Care and Pulmonary Services
  • 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 Centre for Infectious Diseases
  • Hospital Clinic Barcelona, Servicio de Salud Internacional
  • Hospital Germans Trias i Pujol - Servei Malalties Infeccioses
  • Royal Sussex County Hospital - Department of Intensive Care Medicine
  • Saint Thomas' Hospital - Directorate of Infection
  • Royal Victoria Infirmary - Department of Infectious Diseases
  • St. James's University Hospital - Infectious Diseases
  • John Radcliffe Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Placebo

Remdesivir

Arm Description

200 mg of Remdesivir placebo administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir placebo while hospitalized for up to a 10 days total course. n=286.

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 days total course. n=286.

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) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Not hospitalized, no limitations on activities.
Time to Recovery by Race
Day of recovery is defined as the first day on which the subject satisfies one of the following three categories from the ordinal scale: 1) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Not hospitalized, no limitations on activities.
Time to Recovery by Ethnicity
Day of recovery is defined as the first day on which the subject satisfies one of the following three categories from the ordinal scale: 1) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Not hospitalized, no limitations on activities.
Time to Recovery by Sex
Day of recovery is defined as the first day on which the subject satisfies one of the following three categories from the ordinal scale: 1) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Not hospitalized, no limitations on activities.

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 Time (PT)
Blood to evaluate PT was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.
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
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.
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 at Each Clinical Status Using Ordinal Scale at Day 1
The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.
Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 3
The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.
Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 5
The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.
Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 8
The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.
Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 11
The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.
Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 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.
Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 22
The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.
Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 29
The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.
Percentage of Participants 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.
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.
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
Percentage of Participants Requiring New Non-invasive Ventilation or High-flow Oxygen Use
New non-invasive ventilation or high-flow oxygen use was determined as the percentage of subject not on non-invasive ventilation or high-flow oxygen at baseline.
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
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
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.
14-day Participant Mortality
The mortality rate was determined as the proportion of participants who died by study Day 15.
29-day Participant Mortality
The mortality rate was determined as the proportion of participants who died by study Day 29.
Time to an Improvement by at Least 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 at Least 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
The NEW score has demonstrated an ability to discriminate patients at risk of poor outcomes. This score is based on 7 clinical parameters (respiration rate, oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate, level of consciousness). The NEW Score is being used as an efficacy measure. The minimum score is 0, representing the better outcome, and the maximum value is 19, representing the worse outcome. The time to discharge or a NEWS of less than or equal to 2 was determined for each participant.

Full Information

First Posted
February 20, 2020
Last Updated
March 9, 2022
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
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1. Study Identification

Unique Protocol Identification Number
NCT04280705
Brief Title
Adaptive COVID-19 Treatment Trial (ACTT)
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
Study Type
Interventional

2. Study Status

Record Verification Date
April 2020
Overall Recruitment Status
Completed
Study Start Date
February 21, 2020 (Actual)
Primary Completion Date
May 21, 2020 (Actual)
Study Completion Date
May 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
No
Product Manufactured in and Exported from the U.S.
No

5. Study Description

Brief Summary
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. There will be interim monitoring to introduce new arms and allow early stopping for futility, efficacy, or safety. If one therapy proves to be efficacious, then this treatment may become the control arm for comparison(s) with new experimental treatment(s). Any such change would be accompanied by an updated sample size. Because background standards of supportive care may evolve/improve over time as more is learned about successful management of COVID-19, comparisons of safety and efficacy will be based on data from concurrently randomized subjects. An independent Data and Safety Monitoring Board (DSMB) will actively monitor interim data to make recommendations about early study closure or changes to study arms. To evaluate the clinical efficacy, as assessed by time to recovery, of different investigational therapeutics as compared to the control arm.
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. There will be interim monitoring to introduce new arms and allow early stopping for futility, efficacy, or safety. If one therapy proves to be efficacious, then this treatment may become the control arm for comparison(s) with new experimental treatment(s). Any such change would be accompanied by an updated sample size. Because background standards of supportive care may evolve/improve over time as more is learned about successful management of COVID-19, comparisons of safety and efficacy will be based on data from concurrently randomized subjects. An independent Data and Safety Monitoring Board (DSMB) will actively monitor interim data to make recommendations about early study closure or changes to study arms. The initial sample size is projected to be 572 subjects to achieve 400 subjects with a "recovered" status (per the primary objective). The primary analysis will be based on those subjects enrolled in order to 400 recoveries. An additional analysis of the moderate severity subgroup (those with baseline status of "Hospitalized, requiring supplemental oxygen" or "Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care") is also of public health importance. Hence, enrollment will be permitted until the date of April 20, 2020 to ensure 400 recoveries and provide additional data about this important subgroup. With recent enrollment rates, the total sample size may be 600 to over 800. 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 as an outpatient. For discharged subjects, it is preferred that the Day 15 and 29 visits are in person to obtain safety laboratory tests and 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, Day 15 and 29 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 may also be 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. As little is known about the clinical course of COVID-19, a pilot study will be used for a blinded sample size reassessment. 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, ACTT

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
1062 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
200 mg of Remdesivir placebo administered intravenously on Day 1, followed by a 100 mg once-daily maintenance dose of Remdesivir placebo while hospitalized for up to a 10 days total course. n=286.
Arm Title
Remdesivir
Arm Type
Experimental
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 days total course. n=286.
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
The supplied placebo lyophilized formulation is identical in physical appearance to the active lyophilized formulation and contains the same inactive ingredients. Alternatively, a placebo of normal saline of equal volume may be given if there are limitations on matching placebo supplies.
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
Description
Day of recovery is defined as the first day on which the subject satisfies one of the following three categories from the ordinal scale: 1) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Not hospitalized, no limitations on activities.
Time Frame
Day 1 through Day 29
Title
Time to Recovery by Race
Description
Day of recovery is defined as the first day on which the subject satisfies one of the following three categories from the ordinal scale: 1) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Not hospitalized, no limitations on activities.
Time Frame
Day 1 through Day 29
Title
Time to Recovery by Ethnicity
Description
Day of recovery is defined as the first day on which the subject satisfies one of the following three categories from the ordinal scale: 1) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Not hospitalized, no limitations on activities.
Time Frame
Day 1 through Day 29
Title
Time to Recovery by Sex
Description
Day of recovery is defined as the first day on which the subject satisfies one of the following three categories from the ordinal scale: 1) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Not hospitalized, no limitations on activities.
Time Frame
Day 1 through Day 29
Secondary Outcome Measure Information:
Title
Change From Baseline in Alanine Transaminase (ALT)
Description
Blood to evaluate ALT was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.
Time Frame
Days 1, 3, 5, 8, 11, 15 and 29
Title
Change From Baseline in Aspartate Transaminase (AST)
Description
Blood to evaluate AST was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.
Time Frame
Days 1, 3, 5, 8, 11, 15 and 29
Title
Change From Baseline in Creatinine
Description
Blood to evaluate serum creatinine was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.
Time Frame
Days 1, 3, 5, 8, 11, 15 and 29
Title
Change From Baseline in Glucose
Description
Blood to evaluate serum glucose was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.
Time Frame
Days 1, 3, 5, 8, 11, 15 and 29
Title
Change From Baseline in Hemoglobin
Description
Blood to evaluate hemoglobin was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.
Time Frame
Days 1, 3, 5, 8, 11, 15 and 29
Title
Change From Baseline in Platelets
Description
Blood to evaluate platelets was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.
Time Frame
Days 1, 3, 5, 8, 11, 15 and 29
Title
Change From Baseline in Prothrombin Time (PT)
Description
Blood to evaluate PT was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.
Time Frame
Days 1, 3, 5, 8, 11, 15 and 29
Title
Change From Baseline in Total Bilirubin
Description
Blood to evaluate total bilirubin was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.
Time Frame
Days 1, 3, 5, 8, 11, 15 and 29
Title
Change From Baseline in White Blood Cell Count (WBC)
Description
Blood to evaluate WBC was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.
Time Frame
Days 1, 3, 5, 8, 11, 15 and 29
Title
Change From Baseline in Neutrophils
Description
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.
Time Frame
Days 1, 3, 5, 8, 11, 15 and 29
Title
Change From Baseline in Lymphocytes
Description
Blood to evaluate lymphocytes was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.
Time Frame
Days 1, 3, 5, 8, 11, 15 and 29
Title
Change From Baseline in Monocytes
Description
Blood to evaluate monocytes was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.
Time Frame
Days 1, 3, 5, 8, 11, 15 and 29
Title
Change From Baseline in Basophils
Description
Blood to evaluate basophils was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.
Time Frame
Days 1, 3, 5, 8, 11, 15 and 29
Title
Change From Baseline in Eosinophils
Description
Blood to evaluate eosinophils was collected at Days 1, 3, 5, 8, and 11 while participants were inpatient, and at Days 15 and 29, with the Day 1 assessment serving as baseline. Participants who had been discharged had blood collected if infection control measures allowed for in-person visits after discharge.
Time Frame
Days 1, 3, 5, 8, 11, 15 and 29
Title
Change in National Early Warning Score (NEWS) From Baseline
Description
The NEW score has demonstrated an ability to discriminate patients at risk of poor outcomes. This score is based on 7 clinical parameters (respiration rate, oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate, level of consciousness). The NEW Score is being used as an efficacy measure. The minimum score is 0, representing the better outcome, and the maximum value is 19, representing the worse outcome.
Time Frame
Days 1, 3, 5, 8, 11, 15, 22, and 29
Title
Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 1
Description
The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.
Time Frame
Day 1
Title
Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 3
Description
The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.
Time Frame
Day 3
Title
Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 5
Description
The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.
Time Frame
Day 5
Title
Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 8
Description
The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.
Time Frame
Day 8
Title
Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 11
Description
The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.
Time Frame
Day 11
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.
Time Frame
Day 15
Title
Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 22
Description
The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.
Time Frame
Day 22
Title
Percentage of Participants at Each Clinical Status Using Ordinal Scale at Day 29
Description
The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities.
Time Frame
Day 29
Title
Percentage of Participants Reporting Grade 3 and 4 Clinical and/or Laboratory Adverse Events (AEs)
Description
Grade 3 AEs are defined as events that interrupt usual activities of daily living, or significantly affects clinical status, or may require intensive therapeutic intervention. Severe events are usually incapacitating. Grade 4 AEs are defined as events that are potentially life threatening.
Time Frame
Day 1 through Day 29
Title
Percentage of Participants Reporting Serious Adverse Events (SAEs)
Description
An SAE is defined as an AE or suspected adverse reaction is considered serious if, in the view of either the investigator or the sponsor, it results in death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect.
Time Frame
Day 1 through Day 29
Title
Percentage of Participants Discontinued or Temporarily Suspended From Investigational Therapeutics
Description
Participants may have been discontinued from investigational therapeutics due to discharge or death. The halting or slowing of the infusion for any reason was collected, as was missed doses in the series of 10 doses.
Time Frame
Day 1 through Day 10
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
Duration of new non-invasive ventilation or high flow oxygen use was measured in days among participants who were not on non-invasive ventilation or high-flow oxygen use at baseline, determined two ways. The first includes imputations for participants who died. The second method is restricted to participants who did not die
Time Frame
Day 1 through Day 29
Title
Duration of New Oxygen Use
Description
Duration of new oxygen use was measured in days among participants who were not on oxygen at baseline, determined two ways. The first includes imputations for participants who died. The second method is restricted to participants who did not die .
Time Frame
Day 1 through Day 29
Title
Duration of New Ventilator or Extracorporeal Membrane Oxygenation (ECMO) Use
Description
Duration of new ventilator or ECMO use was measured in days among participants who were not on a ventilator or ECMO at baseline, determined two ways. The first includes imputations for participants who died. The second method is restricted to participants who did not die
Time Frame
Day 1 through Day 29
Title
Percentage of Participants Requiring New Non-invasive Ventilation or High-flow Oxygen Use
Description
New non-invasive ventilation or high-flow oxygen use was determined as the percentage of subject not on non-invasive ventilation or high-flow oxygen at baseline.
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
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
Mean Change in the Ordinal Scale
Description
The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 8) Death; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5) Hospitalized, requiring supplemental oxygen; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 1) Not hospitalized, no limitations on activities. A positive change indicates a worsening and a negative change is an improvement.
Time Frame
Day 1, 3, 5, 8, 11, 15, 22, and 29
Title
14-day Participant Mortality
Description
The mortality rate was determined as the proportion of participants who died by study Day 15.
Time Frame
Day 1 through Day 15
Title
29-day Participant Mortality
Description
The mortality rate was determined as the proportion of participants who died by study Day 29.
Time Frame
Day 1 through Day 29
Title
Time to an Improvement by at Least 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 at Least Two Categories Using an Ordinal Scale
Description
The ordinal scale is an assessment of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities. Time to improvement by at least two categories was determined for each participant
Time Frame
Day 1 through Day 29
Title
Time to Discharge or to a NEWS of 2 or Less and Maintained for 24 Hours, Whichever Occurs First
Description
The NEW score has demonstrated an ability to discriminate patients at risk of poor outcomes. This score is based on 7 clinical parameters (respiration rate, oxygen saturation, any supplemental oxygen, temperature, systolic blood pressure, heart rate, level of consciousness). The NEW Score is being used as an efficacy measure. The minimum score is 0, representing the better outcome, and the maximum value is 19, representing the worse outcome. The time to discharge or a NEWS of less than or equal to 2 was determined for each participant.
Time Frame
Day 1 through Day 29

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Admitted to a hospital with symptoms suggestive of COVID-19 infection. 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 or the following: PCR positive in sample collected < 72 hours prior to randomization; OR Exclusion Criteria: 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. 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 or SARS-CoV-2 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 (including patients receiving hemodialysis or hemofiltration). 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.
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
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
Stanford University - Stanford Hospital and Clinics - Pediatrics - Infectious Diseases
City
Stanford
State/Province
California
ZIP/Postal Code
94305-2200
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
Denver Health Division of Hospital Medicine - Main Campus
City
Denver
State/Province
Colorado
ZIP/Postal Code
80204
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
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
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
21201-1509
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
68105
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
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
Vanderbilt University Medical Center - Infectious Diseases
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232-0011
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 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
The University of Washington - Virology Research Clinic
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
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
Universitatsklinikum Bonn, Medizinische Klinik I - Bereich Infektiologie/HIV der Medizinischen Klinik
City
Bonn
State/Province
Nordrhein-Westfalen
ZIP/Postal Code
53127
Country
Germany
Facility Name
Universitatsklinikum Koeln Klinik I fur Innere Medizin Klinisches Studienzentrum fur Infektiologie I
City
Cologne
ZIP/Postal Code
50937
Country
Germany
Facility Name
Universitätsklinikum Frankfurt -Medizinische Klinik II - Infektiologie
City
Frankfurt
ZIP/Postal Code
60590
Country
Germany
Facility Name
AHEPA University Hospital - 1st Department of Internal Medicine
City
Thessaloniki
State/Province
Central Macedonia
ZIP/Postal Code
P.O. 54636
Country
Greece
Facility Name
Medical School of Athens University - Evangelismos Hospital - Department of Critical Care and Pulmonary Services
City
Athens
ZIP/Postal Code
GR-10675
Country
Greece
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
State/Province
Gyeonggi-do
ZIP/Postal Code
13620
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 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 Centre for Infectious Diseases
City
Singapore
ZIP/Postal Code
308442
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
Royal Sussex County Hospital - Department of Intensive Care Medicine
City
East Sussex
State/Province
Brighton
ZIP/Postal Code
BN2 5BE
Country
United Kingdom
Facility Name
Saint Thomas' Hospital - Directorate of Infection
City
London
State/Province
London, City Of
ZIP/Postal Code
SE1 7EH
Country
United Kingdom
Facility Name
Royal Victoria Infirmary - Department of Infectious Diseases
City
Level 6, Ward 19
State/Province
Newcastle Upon Tyne
ZIP/Postal Code
NE1 4LP
Country
United Kingdom
Facility Name
St. James's University Hospital - Infectious Diseases
City
Leeds
State/Province
West Yorkshire
ZIP/Postal Code
LS9 7TK
Country
United Kingdom
Facility Name
John Radcliffe Hospital
City
Headington, Oxford
ZIP/Postal Code
OX3 9DU
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
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Adaptive COVID-19 Treatment Trial (ACTT)

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