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Covid19Phase 3TESICONCT04843761

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

A Phase 3 study testing Remdesivir, Aviptadil and Corticosteroid in people with Covid19, run by National Institute of Allergy and Infectious Diseases (NIAID) at 40 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Covid19
What is being tested?
Remdesivir, Aviptadil and Corticosteroid
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
473 participants
Where
40 sitesUnited States
Study dates
20 Apr 2021to 20 Nov 2022
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • Known allergy to investigational agent or vehicle.
  • More than 4 days since initiation of support for respiratory failure.
  • Chronic/home mechanical ventilation (invasive or non-invasive) for chronic lung or neuromuscular disease (non-invasive ventilation used solely for sleep-disordered breathing is not an exclusion).
  • 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.
Show all 9Show fewer
  • 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)

Trial locations and contacts

40 sites in 1 country.

40 sites in 1 country

United States40 sites

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

    Atlanta, Georgia, 30322

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

    Aurora, Colorado, 80045

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

    Boston, Massachusetts, 02114

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

    Charleston, South Carolina, 29425

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

    Charlottesville, Virginia, 22908

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

    Cincinnati, Ohio, 45219

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

    Cleveland, Ohio, 44111

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

    Cleveland, Ohio, 44195

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

    Columbus, Ohio, 43210

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

    Dallas, Texas, 75246

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

    Denver, Colorado, 80204

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

    Durham, North Carolina, 27710

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

    Fresno, California, 93701

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

    Garfield Heights, Ohio, 44125

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

    Houston, Texas, 77030

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

    Houston, Texas, 77030

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

    Houston, Texas, 77030

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

    Loma Linda, California, 92357

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

    Los Angeles, California, 90048

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

    Los Angeles, California, 90095

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

    Mayfield Heights, Ohio, 44124

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

    Morgantown, West Virginia, 26506

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

    Murray, Utah, 84107

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

    Nashville, Tennessee, 37232

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

    New York, New York, 10029

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

    New York, New York, 10032

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

    Portland, Oregon, 97239-3098

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

    Salt Lake City, Utah, 84132

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

    San Francisco, California, 94115

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

    San Francisco, California, 94143

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

    Seattle, Washington, 98104

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

    Seattle, Washington, 98122

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

    Springfield, Massachusetts, 01199

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

    Stanford, California, 94305

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

    The Bronx, New York, 10467

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

    The Bronx, New York, 10467

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

    Tucson, Arizona, 85719

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

    Washington D.C., District of Columbia, 20010

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

    Washington D.C., District of Columbia, 20422

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

    Winston-Salem, North Carolina, 27157

Other trials in United States

About this study

Official title: 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

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)

Read the detailed description

This is a master protocol to evaluate the safety and efficacy of investigational agents aimed at improving outcomes for patients with acute respiratory failure related to COVID-19.

Trials within this protocol will be adaptive, randomized, blinded and initially placebo-controlled. Participants will receive standard of care (SOC) treatment as part of the protocol. If an investigational agent shows superiority over placebo, SOC for the study of future investigational agents may be modified accordingly.

The international trials within 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 platform study that allows investigational agents to be added and dropped during the course of the study. This allows for efficient testing of new agents against control within the same trial infrastructure. When more than one agent is being tested concurrently, participants may be randomly allocated across agents (as well as between the agent and its placebo) so the same control group can be shared, when feasible. In some situations, a factorial design may be used to study multiple agents.

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 an investigational agent versus placebo with use of the ordinal outcome. The planned sample size is 640 participants (320 per group) for each investigational agent/placebo. 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.

Investigational agents suitable for testing in the inpatient setting will be prioritized based on in vitro data, preclinical data, Phase 1 pharmacokinetic and safety data, and clinical data from completed and ongoing trials. In some cases, a vanguard cohort/initial pilot phase may be incorporated into the trial.

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.

Conditions
Covid19
Being tested
Remdesivir, Remdesivir Placebo, Aviptadil, Aviptadil Placebo, Corticosteroid
Keywords
COVID-19, COVID 19, Coronaviridae Infections, Coronavirus Infections, RNA Virus Infections, Virus Diseases, Nidovirales Infections, SARS-CoV-2, SARS Coronavirus, ACTIV-3, ACTIV3
Medical subject headings
COVID-19, Coronaviridae Infections, Coronavirus Infections, RNA Virus Infections, Virus Diseases, Nidovirales Infections, Severe Acute Respiratory Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RemdesivirBiological

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

  • Remdesivir PlaceboDrug

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

  • AviptadilBiological

    Also called Vasoactive Intestinal Peptide, VIP

    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.

  • Aviptadil PlaceboDrug

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

  • CorticosteroidDrug

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

Study groups in NCT04843761
Study groupRoleWhat they receive
Stratum 1 - Aviptadil + Remdesivir + SOCExperimentalEligible 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)
Receives: Biological: Remdesivir; Biological: Aviptadil; Drug: Corticosteroid
Stratum 1 - Aviptadil + Remdesivir Placebo + SOCExperimentalEligible 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)
Receives: Drug: Remdesivir Placebo; Biological: Aviptadil; Drug: Corticosteroid
Stratum 1 - Aviptadil Placebo + Remdesivir + SOCExperimentalEligible 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)
Receives: Biological: Remdesivir; Drug: Aviptadil Placebo; Drug: Corticosteroid
Stratum 1 - Aviptadil Placebo + Remdesivir Placebo + SOCPlacebo comparatorEligible 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)
Receives: Drug: Remdesivir Placebo; Drug: Aviptadil Placebo; Drug: Corticosteroid
Stratum 2 - Aviptadil + SOCExperimentalEligible 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)
Receives: Biological: Aviptadil; Drug: Corticosteroid
Stratum 2 - Aviptadil Placebo + SOCPlacebo comparatorEligible 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)
Receives: Drug: Aviptadil Placebo; Drug: Corticosteroid
Stratum 3 - Remdesivir + SOCExperimentalEligible 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)
Receives: Biological: Remdesivir; Drug: Corticosteroid
Stratum 3 - Remdesivir Placebo + SOCPlacebo comparatorEligible 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)
Receives: Drug: Remdesivir Placebo; Drug: Corticosteroid
Stratum 4 - Aviptadil + SOCExperimentalEligible for Aviptadil and prior/current use of Remdesivir Participants enrolled in this arm were analyzed in substudy H1 (NCT06729606)
Receives: Biological: Aviptadil; Drug: Corticosteroid
Stratum 4 - Aviptadil Placebo + SOCPlacebo comparatorEligible for Aviptadil and prior/current use of Remdesivir Participants enrolled in this arm were analyzed in substudy H1 (NCT06729606)
Receives: Drug: Aviptadil Placebo; Drug: Corticosteroid

What is being measured

The primary outcome is the main question the study is designed to answer.

  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).

    Measured: Screening, within 24 hours

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Apr 2021
  2. Study start20 Apr 2021
  3. Primary completion22 Aug 2022
  4. Study completion20 Nov 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
473 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04843761
Sponsor's protocol ID
015 / ACTIV-3b
Acronym
TESICO
Status last verified
Sep 2025
First submitted
9 Apr 2021
Last updated
24 Oct 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • 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.

    PubMed 37348524

  • 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.

    PubMed 36695483

  • 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.

    PubMed 34825704

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Remdesivir, Aviptadil and Corticosteroid in people with Covid19, run by National Institute of Allergy and Infectious Diseases (NIAID) at 40 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 40 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Oct 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Substudy Analysis Cohorts (time frame: Screening, within 24 hours). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04843761, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Oct 2025.

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