ACTIV-3b: Therapeutics for Severely Ill Inpatients With COVID-19

NCT04843761 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: 015 / ACTIV-3b
• Study Type: interventional
• Target: 473
• Locations: 1 country
• Sites: 40

Brief Summary

This study looks at the safety and effectiveness of different drugs 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 either a study drug plus current standard of care (SOC), or with placebo plus current SOC. Substudy H1: Aviptadil for Severely Ill Inpatients With COVID-19 (NCT06729606) Substudy H2: Remdesivir for Severely Ill Inpatients With COVID-19 (NCT06729593)

Conditions

Covid19

Keywords

COVID-19; COVID 19; Coronaviridae Infections; Coronavirus Infections; RNA Virus Infections; Virus Diseases; Nidovirales Infections; SARS-CoV-2; SARS Coronavirus; ACTIV-3; ACTIV3

Outcome Measures

Primary Outcomes (1)

• Substudy Analysis Cohorts

  The primary analysis for each agent was to pool across applicable groups to compare each agent vs. matched placebo. Refer to the agent-specific records for results by agent (H1 \[Aviptadil\]: NCT06729606; H2 \[Remdesivir\]: NCT06729593).

  Screening, within 24 hours

Study Arms (10)

Stratum 1 - Aviptadil + Remdesivir + SOC

EXPERIMENTAL

Eligible for both Aviptadil and Remdesivir and no prior use of Remdesivir Participants enrolled in Stratum 1 were analyzed in both substudies (H1: NCT06729606; H2: NCT06729593)

Biological: Remdesivir; Biological: Aviptadil; Drug: Corticosteroid

Stratum 1 - Aviptadil + Remdesivir Placebo + SOC

EXPERIMENTAL

Eligible for both Aviptadil and Remdesivir and no prior use of Remdesivir Participants enrolled in Stratum 1 were analyzed in both substudies (H1: NCT06729606; H2: NCT06729593)

Drug: Remdesivir Placebo; Biological: Aviptadil; Drug: Corticosteroid

Stratum 1 - Aviptadil Placebo + Remdesivir + SOC

EXPERIMENTAL

Eligible for both Aviptadil and Remdesivir and no prior use of Remdesivir Participants enrolled in Stratum 1 were analyzed in both substudies (H1: NCT06729606; H2: NCT06729593)

Biological: Remdesivir; Drug: Aviptadil Placebo; Drug: Corticosteroid

Stratum 1 - Aviptadil Placebo + Remdesivir Placebo + SOC

PLACEBO COMPARATOR

Eligible for both Aviptadil and Remdesivir and no prior use of Remdesivir Participants enrolled in Stratum 1 were analyzed in both substudies (H1: NCT06729606; H2: NCT06729593)

Drug: Remdesivir Placebo; Drug: Aviptadil Placebo; Drug: Corticosteroid

Stratum 2 - Aviptadil + SOC

EXPERIMENTAL

Eligible for Aviptadil and Remdesivir contraindicated * Contraindications: eGFR less than 30 or ALT/AST greater than 10x the upper limit of normal Participants enrolled in this arm were analyzed in substudy H1 (NCT06729606)

Biological: Aviptadil; Drug: Corticosteroid

Stratum 2 - Aviptadil Placebo + SOC

PLACEBO COMPARATOR

Eligible for Aviptadil and Remdesivir contraindicated * Contraindications: eGFR less than 30 or ALT/AST greater than 10x the upper limit of normal Participants enrolled in this arm were analyzed in substudy H1 (NCT06729606)

Drug: Aviptadil Placebo; Drug: Corticosteroid

Stratum 3 - Remdesivir + SOC

EXPERIMENTAL

Eligible for Remdesivir and Aviptadil contraindicated * Contraindications: refractory hypotension (norepinephrine equivalent greater than or equal to 0.1 mcg/kg/min), severe diarrhea, end-stage liver disease, c-diff infection Participants enrolled in this arm were analyzed in substudy H2 (NCT06729593)

Biological: Remdesivir; Drug: Corticosteroid

Stratum 3 - Remdesivir Placebo + SOC

PLACEBO COMPARATOR

Eligible for Remdesivir and Aviptadil contraindicated * Contraindications: refractory hypotension (norepinephrine equivalent greater than or equal to 0.1 mcg/kg/min), severe diarrhea, end-stage liver disease, c-diff infection Participants enrolled in this arm were analyzed in substudy H2 (NCT06729593)

Drug: Remdesivir Placebo; Drug: Corticosteroid

Stratum 4 - Aviptadil + SOC

EXPERIMENTAL

Eligible for Aviptadil and prior/current use of Remdesivir Participants enrolled in this arm were analyzed in substudy H1 (NCT06729606)

Biological: Aviptadil; Drug: Corticosteroid

Stratum 4 - Aviptadil Placebo + SOC

PLACEBO COMPARATOR

Eligible for Aviptadil and prior/current use of Remdesivir Participants enrolled in this arm were analyzed in substudy H1 (NCT06729606)

Drug: Aviptadil Placebo; Drug: Corticosteroid

Interventions

Remdesivir BIOLOGICAL

Administered by IV infusion, daily for 10 days. Initial loading dose is 200 mg with all subsequent doses 100 mg.

Stratum 1 - Aviptadil + Remdesivir + SOC; Stratum 1 - Aviptadil Placebo + Remdesivir + SOC; Stratum 3 - Remdesivir + SOC

Remdesivir Placebo DRUG

Commercially available 0.9% sodium chloride solution. Administered by IV infusion daily for 10 days.

Stratum 1 - Aviptadil + Remdesivir Placebo + SOC; Stratum 1 - Aviptadil Placebo + Remdesivir Placebo + SOC; Stratum 3 - Remdesivir Placebo + SOC

Aviptadil BIOLOGICAL

Administered by IV infusion over 12 hours per day for 3 days. The Day 1 infusion rate is 50 pmol/kg/hr, the Day 2 infusion rate is 100 pmol/kg/hr, and the Day 3 infusion rate is 150 pmol/kg/hr.

Also known as: Vasoactive Intestinal Peptide, VIP

Stratum 1 - Aviptadil + Remdesivir + SOC; Stratum 1 - Aviptadil + Remdesivir Placebo + SOC; Stratum 2 - Aviptadil + SOC; Stratum 4 - Aviptadil + SOC

Aviptadil Placebo DRUG

Commercially available 0.9% sodium chloride solution. Administered by IV infusion over 12 hours per day for 3 days.

Stratum 1 - Aviptadil Placebo + Remdesivir + SOC; Stratum 1 - Aviptadil Placebo + Remdesivir Placebo + SOC; Stratum 2 - Aviptadil Placebo + SOC; Stratum 4 - Aviptadil Placebo + SOC

Corticosteroid DRUG

In line with NIH treatment guidelines, corticosteroids such as dexamethasone, prednisone, methylprednisolone or hydrocortisone may be administered as SOC.

Stratum 1 - Aviptadil + Remdesivir + SOC; Stratum 1 - Aviptadil + Remdesivir Placebo + SOC; Stratum 1 - Aviptadil Placebo + Remdesivir + SOC; Stratum 1 - Aviptadil Placebo + Remdesivir Placebo + SOC; Stratum 2 - Aviptadil + SOC; Stratum 2 - Aviptadil Placebo + SOC; Stratum 3 - Remdesivir + SOC; Stratum 3 - Remdesivir Placebo + SOC; Stratum 4 - Aviptadil + SOC; Stratum 4 - Aviptadil Placebo + SOC

Eligibility Criteria

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

You may qualify if:

• Signed informed consent.
• Requiring admission for inpatient hospital acute medical care for clinical manifestations of COVID-19 (not for purely public health or quarantine purposes).
• Current respiratory failure (i.e. receipt of high-flow nasal cannula, non-invasive ventilation, invasive mechanical ventilation, or ECMO used to treat acute hypoxemic respiratory failure).
• SARS-CoV-2 (COVID-19) infection, documented by a nucleic acid test (NAT) or equivalent testing with most recent rest within 14 days prior to randomization.
• Respiratory failure is believed to be due to SARS-CoV-2 pneumonia.

You may not qualify if:

• Known allergy to investigational agent or vehicle.
• More than 4 days since initiation of support for respiratory failure.
• Moribund patient (i.e. not expected to survive 24 hours).
• Active use of "comfort care" or other hospice-equivalent SOC.
• Expected inability to participate in study procedures.
• In the opinion of the investigator, any condition for which, participation would not be in the best interest of the participant or that could limit protocol-specified assessments.
• Previous enrollment in TESICO
• Additional agent-specific criteria also apply, and are listed in the substudy records Substudy H1: Aviptadil for Severely Ill Inpatients With COVID-19 (NCT06729606) Substudy H2: Remdesivir for Severely Ill Inpatients With COVID-19 (NCT06729593)

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• International Network for Strategic Initiatives in Global HIV Trials (INSIGHT): collaborator
• University of Copenhagen: collaborator
• Medical Research Council: collaborator
• Kirby Institute: collaborator
• Washington D.C. Veterans Affairs Medical Center: collaborator
• Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections: collaborator
• US Department of Veterans Affairs: collaborator
• Prevention and Early Treatment of Acute Lung Injury (PETAL) Network: collaborator
• NeuroRx, Inc.: collaborator
• Gilead Sciences: collaborator

Study Sites (40)

Banner University Medical Center Tucson (Site 206-004), 1625 N. Campbell Avenue

Tucson, Arizona, 85719, United States

Location

UCSF Fresno (Site 203-005), 155 N. Fresno Street

Fresno, California, 93701, United States

Location

VA Loma Linda Healthcare System (Site 074-017), 11201 Benton Street

Loma Linda, California, 92357, United States

Location

Cedars-Sinai Medical Center (Site 208-002), 8700 Beverly Boulevard

Los Angeles, California, 90048, United States

Location

Ronald Reagan UCLA Medical Center (Site 203-002), 757 Westwood Plaza

Los Angeles, California, 90095, United States

Location

UCSF Medical Center at Mount Zion (Site 203-007), 1600 Divisadero St.

San Francisco, California, 94115, United States

Location

UCSF Medical Center (Site 203-001), Moffit-Long Hospital, 505 Parnassus Ave.

San Francisco, California, 94143, United States

Location

Stanford University Hospital & Clinics (Site 203-003), 300 Pasteur Dr.

Stanford, California, 94305, United States

Location

University of Colorado Hospital (Site 204-001), 12605 E. 16th Avenue

Aurora, Colorado, 80045, United States

Location

Denver Health Medical Center (Site 204-004), 780 Delaware Street, Pavilion B

Denver, Colorado, 80204, United States

Location

MedStar Health Research Institute (Site 009-021), 110 Irving St., NW.

Washington D.C., District of Columbia, 20010, United States

Location

Washington DC VA Medical Center (Site 009-004), 50 Irving Street, NW.

Washington D.C., District of Columbia, 20422, United States

Location

Emory University (Site 301-008), Bldg. A, Suite 2236, 1365 Clifton Rd., NE.

Atlanta, Georgia, 30322, United States

Location

Massachusetts General Hospital (Site 202-002), 55 Fruit Street

Boston, Massachusetts, 02114, United States

Location

Baystate Medical Center (Site 201-001), Critical Care Research, 759 Chestnut Street

Springfield, Massachusetts, 01199, United States

Location

Mount Sinai Medical Center (Site 301-012), Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place

New York, New York, 10029, United States

Location

Columbia University Irving Medical Center (Site 301-027), 177 Fort Washington Ave.

New York, New York, 10032, United States

Location

Montefiore Medical Center - Moses Hospital (Site 206-001), 111 E. 210th Street

The Bronx, New York, 10467, United States

Location

Montefiore Medical Center - Weiler campus (Site 206-003), 111 E. 210th Street

The Bronx, New York, 10467, United States

Location

Duke University Hospital (Site 301-006), 2301 Erwin Road

Durham, North Carolina, 27710, United States

Location

Wake Forest Baptist Health (Site 210-001), Medical Center Blvd

Winston-Salem, North Carolina, 27157, United States

Location

University of Cincinnati Medical Center (Site 207-003), 234 Goodman Street, ML 0740

Cincinnati, Ohio, 45219, United States

Location

Cleveland Clinic Fairview Hospital (Site 207-005), 18101 Lorain Ave.

Cleveland, Ohio, 44111, United States

Location

Cleveland Clinic Foundation (Site 207-001), 9500 Euclid Ave.

Cleveland, Ohio, 44195, United States

Location

The Ohio State University Wexner Medical Center (Site 207-004), 410 W. 10th Avenue

Columbus, Ohio, 43210, United States

Location

Cleveland Clinic Marymount Campus (Site 207-006), 12300 McCracken Road

Garfield Heights, Ohio, 44125, United States

Location

Cleveland Clinic Hillcrest Hospital (Site 207-007), 6780 Mayfield Road

Mayfield Heights, Ohio, 44124, United States

Location

Oregon Health & Science University (Site 208-003), 3181 SW Sam Jackson Park Rd.

Portland, Oregon, 97239-3098, United States

Location

Medical University of South Carolina (Site 210-002), 96 Jonathan Lucas St., CSB 214

Charleston, South Carolina, 29425, United States

Location

Vanderbilt University Medical Center (Site 212-001), 1211 Medical Center Drive

Nashville, Tennessee, 37232, United States

Location

Baylor, Scott and White Health (Site 301-003), Baylor University Medical Center, 3500 Gaston Ave.

Dallas, Texas, 75246, United States

Location

Houston Methodist Hospital (Site 301-028), 6565 Fannin Street

Houston, Texas, 77030, United States

Location

Texas Heart Institute (Site 301-017), 6770 Bertner, MC4-266

Houston, Texas, 77030, United States

Location

University of Texas Health Science Center (Site 203-006), 7000 Fannin St.

Houston, Texas, 77030, United States

Location

Intermountain Medical Center (Site 211-001), 5121 South Cottonwood Street

Murray, Utah, 84107, United States

Location

University of Utah Hospital (Site 211-002), 50 North Medical Drive

Salt Lake City, Utah, 84132, United States

Location

UVA School of Medicine (Site 210-003), University of Virginia Health System, University Hospital, 1215 Lee St.

Charlottesville, Virginia, 22908, United States

Location

Harborview Medical Center (Site 208-001), 325 9th Ave.

Seattle, Washington, 98104, United States

Location

Swedish Medical Center (Site 208-005), 747 Broadway

Seattle, Washington, 98122, United States

Location

West Virginia University Medicine (Site 301-023), One Medical Center Drive

Morgantown, West Virginia, 26506, United States

Location

Related Publications (3)

• Brown SM, Barkauskas CE, Grund B, Sharma S, Phillips AN, Leither L, Peltan ID, Lanspa M, Gilstrap DL, Mourad A, Lane K, Beitler JR, Serra AL, Garcia I, Almasri E, Fayed M, Hubel K, Harris ES, Middleton EA, Barrios MAG, Mathews KS, Goel NN, Acquah S, Mosier J, Hypes C, Salvagio Campbell E, Khan A, Hough CL, Wilson JG, Levitt JE, Duggal A, Dugar S, Goodwin AJ, Terry C, Chen P, Torbati S, Iyer N, Sandkovsky US, Johnson NJ, Robinson BRH, Matthay MA, Aggarwal NR, Douglas IS, Casey JD, Hache-Marliere M, Georges Youssef J, Nkemdirim W, Leshnower B, Awan O, Pannu S, O'Mahony DS, Manian P, Awori Hayanga JW, Wortmann GW, Tomazini BM, Miller RF, Jensen JU, Murray DD, Bickell NA, Zatakia J, Burris S, Higgs ES, Natarajan V, Dewar RL, Schechner A, Kang N, Arenas-Pinto A, Hudson F, Ginde AA, Self WH, Rogers AJ, Oldmixon CF, Morin H, Sanchez A, Weintrob AC, Cavalcanti AB, Davis-Karim A, Engen N, Denning E, Taylor Thompson B, Gelijns AC, Kan V, Davey VJ, Lundgren JD, Babiker AG, Neaton JD, Lane HC; ACTIV-3b/Therapeutics for Severely Ill Inpatients with COVID-19 (TESICO) Study Group. Intravenous aviptadil and remdesivir for treatment of COVID-19-associated hypoxaemic respiratory failure in the USA (TESICO): a randomised, placebo-controlled trial. Lancet Respir Med. 2023 Sep;11(9):791-803. doi: 10.1016/S2213-2600(23)00147-9. Epub 2023 Jun 19.

  PMID: 37348524 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

• Tsiatis AA, Davidian M, Holloway ST. Estimation of the odds ratio in a proportional odds model with censored time-lagged outcome in a randomized clinical trial. Biometrics. 2023 Jun;79(2):975-987. doi: 10.1111/biom.13603. Epub 2021 Dec 17.

  PMID: 34825704 DERIVED

Related Links

• FDA Safety Alerts and Recalls
• CDC (Centers for Disease Control and Prevention): Coronavirus (COVID-19) website
• 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)
• WHO COVID-19 treatment guidelines

MeSH Terms

Conditions

COVID-19; Coronaviridae Infections; Coronavirus Infections; RNA Virus Infections; Virus Diseases; Nidovirales Infections; Severe Acute Respiratory Syndrome

Interventions

remdesivir; aviptadil; Vasoactive Intestinal Peptide; Adrenal Cortex Hormones

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Gastrointestinal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptide Hormones; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Nerve Tissue Proteins; Proteins

Results Point of Contact

• Title: Shweta Sharma Mistry
• Organization: University of Minnesota

shwetas@ccbr.umn.edu

612-626-9021

Study Officials

• Samuel Brown, MD

  Intermountain Medical Center/University of Utah

  PRINCIPAL INVESTIGATOR

• Prof. James Neaton

  INSIGHT Statistical and Coordinating Centre, University of Minnesota

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: April 9, 2021
• First Posted: April 14, 2021
• Study Start: April 20, 2021
• Primary Completion: August 22, 2022
• Study Completion: November 20, 2022
• Last Updated: October 24, 2025
• Results First Posted: October 24, 2025

Record last verified: 2025-09

Locations

US (40)