Adaptive COVID-19 Treatment Trial (ACTT)

NCT04280705 | Completed Phase 3 Results FDA Drug

• 1 other identifier: 20-0006
• Study Type: interventional
• Target: 1,062
• Locations: 10 countries
• Sites: 60

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.

Conditions

COVID-19

Keywords

Adaptive; COVID-19; Efficacy; Multicenter; novel coronavirus; Safety; ACTT

Outcome Measures

Primary Outcomes (4)

• 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.

  Day 1 through Day 29

• 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.

  Day 1 through Day 29

• 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.

  Day 1 through Day 29

• 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.

  Day 1 through Day 29

Secondary Outcomes (39)

• Change From Baseline in Alanine Transaminase (ALT)

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

• Change From Baseline in Aspartate Transaminase (AST)

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

• Change From Baseline in Creatinine

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

• Change From Baseline in Glucose

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

• Change From Baseline in Hemoglobin

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

Study Arms (2)

Placebo

PLACEBO COMPARATOR

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.

Other: Placebo

Remdesivir

EXPERIMENTAL

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.

Drug: Remdesivir

Interventions

Placebo OTHER

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.

Placebo

Remdesivir DRUG

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.

Remdesivir

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (60)

University of Alabama at Birmingham School of Medicine - Infectious Disease

Birmingham, Alabama, 35233, United States

Location

University of California San Diego Health - Jacobs Medical Center

La Jolla, California, 29037, United States

Location

University of California Los Angeles Medical Center - Westwood Clinic

Los Angeles, California, 90095, United States

Location

University of California Irvine Medical Center - Infectious Disease

Orange, California, 92868-3298, United States

Location

VA Palo Alto Health Care System - Infectious Diseases

Palo Alto, California, 94304-1207, United States

Location

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

Sacramento, California, 95817-1460, United States

Location

Naval Medical Center San Diego - Infectious Disease Clinic

San Diego, California, 92314, United States

Location

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

San Francisco, California, 94110-2859, United States

Location

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

Stanford, California, 94305-2200, United States

Location

Cedars Sinai Medical Center

West Hollywood, California, 90048-1804, United States

Location

Denver Health Division of Hospital Medicine - Main Campus

Denver, Colorado, 80204, United States

Location

Emory Vaccine Center - The Hope Clinic

Decatur, Georgia, 30030-1705, United States

Location

Northwestern Hospital - Infectious Disease

Chicago, Illinois, 60611-2908, United States

Location

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

Chicago, Illinois, 60612, United States

Location

Southeast Louisiana Veterans Health Care System - Section of Infectious Diseases

New Orleans, Louisiana, 70119, United States

Location

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

Baltimore, Maryland, 21201-1509, United States

Location

Johns Hopkins Hospital - Medicine - Infectious Diseases

Baltimore, Maryland, 21287-0005, United States

Location

Walter Reed National Military Medical Center

Bethesda, Maryland, 20889, United States

Location

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

Bethesda, Maryland, 20892-1504, United States

Location

Massachusetts General Hospital - Infectious Diseases

Boston, Massachusetts, 02114-2621, United States

Location

University of Massachusetts Medical School - Infectious Diseases and Immunology

Worcester, Massachusetts, 01655-0002, United States

Location

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

Minneapolis, Minnesota, 55455-0341, United States

Location

Saint Louis University - Center for Vaccine Development

St Louis, Missouri, 63104-1015, United States

Location

University of Nebraska Medical Center - Infectious Diseases

Omaha, Nebraska, 68105, United States

Location

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

New York, New York, 10016-6402, United States

Location

University of Rochester Medical Center - Vaccine Research Unit

Rochester, New York, 14642-0001, United States

Location

Montefiore Medical Center - Infectious Diseases

The Bronx, New York, 10467-2401, United States

Location

Duke Human Vaccine Institute - Duke Vaccine and Trials Unit

Durham, North Carolina, 27704, United States

Location

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

Hershey, Pennsylvania, 17033, United States

Location

Hospital of the University of Pennsylvania - Infectious Diseases

Philadelphia, Pennsylvania, 19104-4238, United States

Location

Vanderbilt University Medical Center - Infectious Diseases

Nashville, Tennessee, 37232-0011, United States

Location

Brooke Army Medical Center

Fort Sam Houston, Texas, 78234, United States

Location

University of Texas Medical Branch - Division of Infectious Disease

Galveston, Texas, 77555-0435, United States

Location

Baylor College of Medicine - Molecular Virology and Microbiology

Houston, Texas, 77030-3411, United States

Location

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

San Antonio, Texas, 78229-3901, United States

Location

University of Virginia - Acute Care Surgery

Charlottesville, Virginia, 22908-0816, United States

Location

Naval Medical Center Portsmouth - Infectious Disease Division

Portsmouth, Virginia, 23708, United States

Location

EvergreenHealth Infectious Disease Service

Kirkland, Washington, 98034, United States

Location

The University of Washington - Virology Research Clinic

Seattle, Washington, 98104, United States

Location

Providence Sacred Heart Medical Center

Spokane, Washington, 99204, United States

Location

Madigan Army Medical Center - Infectious Disease Clinic

Tacoma, Washington, 98431, United States

Location

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

Copenhagen, 2100, Denmark

Location

Universitatsklinikum Bonn, Medizinische Klinik I - Bereich Infektiologie/HIV der Medizinischen Klinik

Bonn, North Rhine-Westphalia, 53127, Germany

Location

Universitatsklinikum Koeln Klinik I fur Innere Medizin Klinisches Studienzentrum fur Infektiologie I

Cologne, 50937, Germany

Location

Universitätsklinikum Frankfurt -Medizinische Klinik II - Infektiologie

Frankfurt, 60590, Germany

Location

AHEPA University Hospital - 1st Department of Internal Medicine

Thessaloniki, Central Macedonia, P.O. 54636, Greece

Location

Medical School of Athens University - Evangelismos Hospital - Department of Critical Care and Pulmonary Services

Athens, GR-10675, Greece

Location

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

Tokyo, 162-8655, Japan

Location

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

Mexico City, 14080, Mexico

Location

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

Mexico City, 14080, Mexico

Location

National Centre for Infectious Diseases

Singapore, 308442, Singapore

Location

Seoul National University Bundang Hospital - Division of Infectious Diseases

Bundang-gu Seongnam-si, Gyeonggi-do, 13620, South Korea

Location

Seoul National University Hospital

Seoul, Jongno-gu, 03080, South Korea

Location

Hospital Clinic Barcelona, Servicio de Salud Internacional

Barcelona, Catalonia, 08036, Spain

Location

Hospital Germans Trias i Pujol - Servei Malalties Infeccioses

Barcelona, Catalonia, 08916, Spain

Location

Royal Sussex County Hospital - Department of Intensive Care Medicine

East Sussex, Brighton, BN2 5BE, United Kingdom

Location

Saint Thomas' Hospital - Directorate of Infection

London, London, City of, SE1 7EH, United Kingdom

Location

Royal Victoria Infirmary - Department of Infectious Diseases

Level 6, Ward 19, Newcastle Upon Tyne, NE1 4LP, United Kingdom

Location

St. James's University Hospital - Infectious Diseases

Leeds, West Yorkshire, LS9 7TK, United Kingdom

Location

John Radcliffe Hospital

Headington, Oxford, OX3 9DU, United Kingdom

Location

Related Publications (9)

• Singh K, Rubenstein K, Callier V, Shaw-Saliba K, Rupert A, Dewar R, Laverdure S, Highbarger H, Lallemand P, Huang ML, Jerome KR, Sampoleo R, Mills MG, Greninger AL, Juneja K, Porter D, Benson CA, Dempsey W, El Sahly HM, Focht C, Jilg N, Paules CI, Rapaka RR, Uyeki TM, Clifford Lane H, Beigel J, Dodd LE; Adaptive COVID-19 Treatment Trial (ACTT-1) Study Group Members. SARS-CoV-2 RNA and Nucleocapsid Antigen Are Blood Biomarkers Associated With Severe Disease Outcomes That Improve in Response to Remdesivir. J Infect Dis. 2024 Sep 23;230(3):624-634. doi: 10.1093/infdis/jiae198.

  PMID: 38657001 DERIVED

• Hedskog C, Rodriguez L, Roychoudhury P, Huang ML, Jerome KR, Hao L, Ireton RC, Li J, Perry JK, Han D, Camus G, Greninger AL, Gale M Jr, Porter DP. Viral Resistance Analyses From the Remdesivir Phase 3 Adaptive COVID-19 Treatment Trial-1 (ACTT-1). J Infect Dis. 2023 Nov 2;228(9):1263-1273. doi: 10.1093/infdis/jiad270.

  PMID: 37466213 DERIVED

• Grundeis F, Ansems K, Dahms K, Thieme V, Metzendorf MI, Skoetz N, Benstoem C, Mikolajewska A, Griesel M, Fichtner F, Stegemann M. Remdesivir for the treatment of COVID-19. Cochrane Database Syst Rev. 2023 Jan 25;1(1):CD014962. doi: 10.1002/14651858.CD014962.pub2.

  PMID: 36695483 DERIVED

• Potter GE, Bonnett T, Rubenstein K, Lindholm DA, Rapaka RR, Doernberg SB, Lye DC, Mularski RA, Hynes NA, Kline S, Paules CI, Wolfe CR, Frank MG, Rouphael NG, Deye GA, Sweeney DA, Colombo RE, Davey RT Jr, Mehta AK, Whitaker JA, Castro JG, Amin AN, Colombo CJ, Levine CB, Jain MK, Maves RC, Marconi VC, Grossberg R, Hozayen S, Burgess TH, Atmar RL, Ganesan A, Gomez CA, Benson CA, Lopez de Castilla D, Ahuja N, George SL, Nayak SU, Cohen SH, Lalani T, Short WR, Erdmann N, Tomashek KM, Tebas P. Temporal Improvements in COVID-19 Outcomes for Hospitalized Adults: A Post Hoc Observational Study of Remdesivir Group Participants in the Adaptive COVID-19 Treatment Trial. Ann Intern Med. 2022 Dec;175(12):1716-1727. doi: 10.7326/M22-2116. Epub 2022 Nov 29.

  PMID: 36442063 DERIVED

• 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.

  PMID: 34473343 DERIVED

• Ansems K, Grundeis F, Dahms K, Mikolajewska A, Thieme V, Piechotta V, Metzendorf MI, Stegemann M, Benstoem C, Fichtner F. Remdesivir for the treatment of COVID-19. Cochrane Database Syst Rev. 2021 Aug 5;8(8):CD014962. doi: 10.1002/14651858.CD014962.

  PMID: 34350582 DERIVED

• Sultana J, Crisafulli S, Gabbay F, Lynn E, Shakir S, Trifiro G. Challenges for Drug Repurposing in the COVID-19 Pandemic Era. Front Pharmacol. 2020 Nov 6;11:588654. doi: 10.3389/fphar.2020.588654. eCollection 2020.

  PMID: 33240091 DERIVED

• Maleszewski JJ, Young PM, Ackerman MJ, Halushka MK. Urgent Need for Studies of the Late Effects of SARS-CoV-2 on the Cardiovascular System. Circulation. 2021 Mar 30;143(13):1271-1273. doi: 10.1161/CIRCULATIONAHA.120.051362. Epub 2020 Sep 24. No abstract available.

  PMID: 32969710 DERIVED

• Beigel JH, Tomashek KM, Dodd LE, Mehta AK, Zingman BS, Kalil AC, Hohmann E, Chu HY, Luetkemeyer A, Kline S, Lopez de Castilla D, Finberg RW, Dierberg K, Tapson V, Hsieh L, Patterson TF, Paredes R, Sweeney DA, Short WR, Touloumi G, Lye DC, Ohmagari N, Oh MD, Ruiz-Palacios GM, Benfield T, Fatkenheuer G, Kortepeter MG, Atmar RL, Creech CB, Lundgren J, Babiker AG, Pett S, Neaton JD, Burgess TH, Bonnett T, Green M, Makowski M, Osinusi A, Nayak S, Lane HC; ACTT-1 Study Group Members. Remdesivir for the Treatment of Covid-19 - Final Report. N Engl J Med. 2020 Nov 5;383(19):1813-1826. doi: 10.1056/NEJMoa2007764. Epub 2020 Oct 8.

  PMID: 32445440 DERIVED

MeSH Terms

Conditions

COVID-19

Interventions

remdesivir

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: John Beigel, MD
• Organization: Organization:NIAID

jbeigel@niaid.nih.gov

3014519881

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 20, 2020
• First Posted: February 21, 2020
• Study Start: February 21, 2020
• Primary Completion: May 21, 2020
• Study Completion: May 21, 2020
• Last Updated: March 14, 2022
• Results First Posted: September 25, 2020

Record last verified: 2020-04

Locations

DK (1); ME (2); ES (2); GB (5); DE (3); JP (1); GR (2); SG (1); KR (2); US (41)