Remdesivir for Severely Ill Inpatients With COVID-19 (An ACTIV-3b/TESICO Treatment Trial)

A Multicenter, Adaptive, Randomized, Blinded Controlled Trial of the Safety and Efficacy of Investigational Therapeutics for Hospitalized Patients With Acute Respiratory Distress Syndrome Associated With COVID-19 (Trial H2: Remdesivir)

This study looks at the safety and effectiveness of Remdesivir in treating COVID-19 in people who have been hospitalized with the infection and who have acute respiratory failure. Participants in the study will be treated with Remdesivir plus current standard of care (SOC), or with placebo plus current SOC.

Study Overview

• Status: Completed
• Conditions: Covid19
• Intervention / Treatment: Biological: Remdesivir; Drug: Corticosteroid; Biological: Remdesivir Placebo

Detailed Description

This is a treatment trial of the ACTIV-3b/TESICO master protocol (NCT04843761) to evaluate the safety and efficacy of Remdesivir at improving outcomes for patients with acute respiratory failure related to COVID-19.

This protocol will be adaptive, randomized, blinded and initially placebo-controlled. Participants will receive standard of care (SOC) treatment as part of the protocol.

This protocol will be conducted in up to several hundred clinical sites. Participating sites are affiliated with networks funded by the United States National Institutes of Health (NIH) and the US Department of Veterans Affairs.

The protocol is for a Phase 3 study.

Participants will be followed for 90 days following randomization for the primary endpoint and most secondary endpoints. Selected secondary endpoints will be measured at 180 days.

This study is planned to provide 80% power to detect an odds ratio of 1.5 for improvement in recovery status at Day 90 for Remdesivir versus placebo with use of the ordinal outcome. The planned sample size is 320 participants. Sample size may be re-estimated before enrollment is complete based on an assessment of whether the pooled proportions of the outcome are still consistent with adequate power for the hypothesized difference measured by the odds ratio.

Randomization will be stratified by study site pharmacy and by receipt of invasive mechanical ventilation, or ECMO (extracorporeal membrane oxygenation) at enrollment. Other agent-specific stratification factors may be considered.

An independent Data and Safety Monitoring Board (DSMB) will review interim safety and efficacy data at least monthly. Pre-specified guidelines will be established to recommend early stopping of the trial for evidence of harm or substantial efficacy. The DSMB may recommend discontinuation of an investigational agent if the risks are judged to outweigh the benefits.

• Study Type: Interventional
• Enrollment (Actual): 87
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85719
      • Banner University Medical Center Tucson (Site 206-004), 1625 N. Campbell Avenue
  • California
    • Fresno, California, United States, 93701
      • UCSF Fresno (Site 203-005), 155 N. Fresno Street
    • Loma Linda, California, United States, 92357
      • VA Loma Linda Healthcare System (Site 074-017), 11201 Benton Street
    • Los Angeles, California, United States, 90095
      • Ronald Reagan UCLA Medical Center (Site 203-002), 757 Westwood Plaza
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center (Site 208-002), 8700 Beverly Boulevard
    • San Francisco, California, United States, 94115
      • UCSF Medical Center at Mount Zion (Site 203-007), 1600 Divisadero St.
    • San Francisco, California, United States, 94143
      • UCSF Medical Center (Site 203-001), Moffit-Long Hospital, 505 Parnassus Ave.
    • Stanford, California, United States, 94305
      • Stanford University Hospital & Clinics (Site 203-003), 300 Pasteur Dr.
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital (Site 204-001), 12605 E. 16th Avenue
    • Denver, Colorado, United States, 80204
      • Denver Health Medical Center (Site 204-004), 780 Delaware Street, Pavilion B
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20010
      • MedStar Health Research Institute (Site 009-021), 110 Irving St., NW.
    • Washington D.C., District of Columbia, United States, 20422
      • Washington DC VA Medical Center (Site 009-004), 50 Irving Street, NW.
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University (Site 301-008), Bldg. A, Suite 2236, 1365 Clifton Rd., NE.
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital (Site 202-002), 55 Fruit Street
    • Springfield, Massachusetts, United States, 01199
      • Baystate Medical Center (Site 201-001), Critical Care Research, 759 Chestnut Street
  • New York
    • New York, New York, United States, 10029
      • Mount Sinai Medical Center (Site 301-012), Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place
    • New York, New York, United States, 10032
      • Columbia University Irving Medical Center (Site 301-027), 177 Fort Washington Ave.
    • The Bronx, New York, United States, 10467
      • Montefiore Medical Center - Moses Hospital (Site 206-001), 111 E. 210th Street
    • The Bronx, New York, United States, 10467
      • Montefiore Medical Center - Weiler campus (Site 206-003), 111 E. 210th Street
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Hospital (Site 301-006), 2301 Erwin Road
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Baptist Health (Site 210-001), Medical Center Blvd
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati Medical Center (Site 207-003), 234 Goodman Street, ML 0740
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation (Site 207-001), 9500 Euclid Ave.
    • Cleveland, Ohio, United States, 44111
      • Cleveland Clinic Fairview Hospital (Site 207-005), 18101 Lorain Ave.
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Wexner Medical Center (Site 207-004), 410 W. 10th Avenue
    • Garfield Heights, Ohio, United States, 44125
      • Cleveland Clinic Marymount Campus (Site 207-006), 12300 McCracken Road
    • Mayfield Heights, Ohio, United States, 44124
      • Cleveland Clinic Hillcrest Hospital (Site 207-007), 6780 Mayfield Road
  • Oregon
    • Portland, Oregon, United States, 97239-3098
      • Oregon Health & Science University (Site 208-003), 3181 SW Sam Jackson Park Rd.
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina (Site 210-002), 96 Jonathan Lucas St., CSB 214
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center (Site 212-001), 1211 Medical Center Drive
  • Texas
    • Dallas, Texas, United States, 75246
      • Baylor, Scott and White Health (Site 301-003), Baylor University Medical Center, 3500 Gaston Ave.
    • Houston, Texas, United States, 77030
      • Texas Heart Institute (Site 301-017), 6770 Bertner, MC4-266
    • Houston, Texas, United States, 77030
      • Houston Methodist Hospital (Site 301-028), 6565 Fannin Street
    • Houston, Texas, United States, 77030
      • University of Texas Health Science Center (Site 203-006), 7000 Fannin St.
  • Utah
    • Murray, Utah, United States, 84107
      • Intermountain Medical Center (Site 211-001), 5121 South Cottonwood Street
    • Salt Lake City, Utah, United States, 84132
      • University of Utah Hospital (Site 211-002), 50 North Medical Drive
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • UVA School of Medicine (Site 210-003), University of Virginia Health System, University Hospital, 1215 Lee St.
  • Washington
    • Seattle, Washington, United States, 98104
      • Harborview Medical Center (Site 208-001), 325 9th Ave.
    • Seattle, Washington, United States, 98122
      • Swedish Medical Center (Site 208-005), 747 Broadway
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • West Virginia University Medicine (Site 301-023), One Medical Center Drive

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Refer to the master protocol (NCT04843761)

Exclusion Criteria:

Refer to the master protocol (NCT04843761)

Additional Exclusion Criteria:

• Prior receipt of any dose of remdesivir during the present illness
• GFR (glomerular filtration rate) < 30 ml/min and not receiving dialysis
• ALT (alanine aminotransferase) or AST (aspartate aminotransferase) > 10 times upper limit of normal
• Unwillingness to commit to avoid sex that may result in pregnancy for at least 7 days after completion of remdesivir vs. placebo

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo + SOC	Drug: Corticosteroid; In line with NIH treatment guidelines, corticosteroids such as dexamethasone, prednisone, methylprednisolone or hydrocortisone may be administered as SOC.; Biological: Remdesivir Placebo; Commercially available 0.9% sodium chloride solution. Administered by IV infusion daily for 10 days.
Experimental: Remdesivir + SOC	Biological: Remdesivir; Administered by IV infusion, daily for 10 days. Initial loading dose is 200 mg with all subsequent doses 100 mg.; Drug: Corticosteroid; In line with NIH treatment guidelines, corticosteroids such as dexamethasone, prednisone, methylprednisolone or hydrocortisone may be administered as SOC.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With a 6-category Primary Ordinal Outcome (Recovery) at Day 90	The primary outcome was a 6-category ordinal outcome defining the participant's status at Day 90: (1) at home (defined as the type of residence before hospitalization) and off oxygen (recovered) for at least 77 days, (2) at home and off oxygen for 49-76 days, (3) at home and off oxygen for 1-48 days, (4) not hospitalized but either on supplemental oxygen or not at home, (5) hospitalized or in hospice care, or (6) dead.	Status on Day 90

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With a Safety Outcome Through Day 5	Composite safety outcome of a serious adverse event, Grade 3/4 adverse event, organ failure/serious infection, or death through Day 5	Through Day 5
Number of Participants With a Safety Outcome Through Day 28	Composite safety outcome of a serious adverse event, Grade 3/4 adverse event, organ failure/serious infection, or death through Day 28	Through Day 28
Number of Participants Who Died Through Day 90		Through Day 90
Number of Participants Who Died Through Day 180		Through Day 180

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: Gilead Sciences; University of Copenhagen; US Department of Veterans Affairs; Medical Research Council; Kirby Institute; Washington D.C. Veterans Affairs Medical Center; International Network for Strategic Initiatives in Global HIV Trials (INSIGHT); Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections; Prevention and Early Treatment of Acute Lung Injury (PETAL) Network
• Investigators: Study Chair: Prof. James Neaton, INSIGHT Statistical and Coordinating Centre, University of Minnesota; Principal Investigator: Samuel Brown, MD, Intermountain Medical Center/University of Utah

Publications and helpful links

Helpful Links

• FDA Safety Alerts and Recalls
• CDC (Centers for Disease Control and Prevention): Coronavirus (COVID-19) website
• WHO COVID-19 treatment guidelines
• A Participant's Guide to Clinical Trials (NIAID)
• Find a Clinical Trial (NIAID)
• Clinical Trials at NIAID
• National Institute for Allergy and Infectious Diseases (NIAID)

Study record dates

Study Major Dates

• Study Start (Actual): April 20, 2021
• Primary Completion (Actual): August 22, 2022
• Study Completion (Actual): November 20, 2022

Study Registration Dates

• First Submitted: December 10, 2024
• First Submitted That Met QC Criteria: December 10, 2024
• First Posted (Actual): December 11, 2024

Study Record Updates

• Last Update Posted (Estimated): October 9, 2025
• Last Update Submitted That Met QC Criteria: September 23, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Coronavirus Infections; SARS-CoV-2; COVID 19; COVID-19; Virus Diseases; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; SARS Coronavirus; ACTIV-3; ACTIV3
• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; Respiratory Tract Diseases; Lung Diseases; Pneumonia, Viral; Pneumonia; COVID-19; Virus Diseases; Coronavirus Infections; Severe Acute Respiratory Syndrome; RNA Virus Infections; Coronaviridae Infections; Nidovirales Infections; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; remdesivir; Adrenal Cortex Hormones
• Other Study ID Numbers: 015/ACTIV-3b/H2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No