Covid19Phase 3NCT06729606

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

A Phase 3 study testing 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

Search all trials

Trial summary

This study looks at the safety and effectiveness of Aviptadil 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 Aviptadil plus current standard of care (SOC), or with placebo plus current SOC. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Covid19
What is being tested?: Aviptadil and Corticosteroid
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 471 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

Refer to the master protocol (NCT04843761)

Who cannot join

Refer to the master protocol (NCT04843761)
Additional Exclusion Criteria:
Refractory hypotension
Severe diarrhea
Current C. difficile infection
Pregnancy or current breast-feeding
End-stage liver disease

Trial locations and contacts

40 sites in 1 country.

City, postcode or hospital

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 (Trial H1: Aviptadil)

Read the detailed description

This is a treatment trial of the ACTIV-3b/TESICO master protocol (NCT04843761) to evaluate the safety and efficacy of Aviptadil 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 Aviptadil 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.

Conditions: Covid19
Being tested: 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.

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 PlaceboBiological
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 NCT06729606
Study group	Role	What they receive
Aviptadil + SOC	Experimental	Not described Receives: Biological: Aviptadil; Drug: Corticosteroid
Placebo + SOC	Placebo comparator	Not described Receives: Biological: Aviptadil Placebo; Drug: Corticosteroid

What is being measured

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

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.
Measured: Status on Day 90

Secondary outcomes (4)

Number of Participants Who Died Through Day 90
Measured: Through Day 90
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
Measured: 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
Measured: Through Day 28
Number of Participants Who Died Through Day 180
Measured: Through Day 180

Timeline

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

20 Apr 202120 Nov 2022

First posted11 Dec 2024
Study start20 Apr 2021
Primary completion22 Aug 2022
Study completion20 Nov 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Covid19Studies of the same condition, open and under way.
More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

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: 471 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT06729606
Sponsor's protocol ID: 015/ACTIV-3b/H1
Status last verified: Sep 2025
First submitted: 10 Dec 2024
Last updated: 9 Oct 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Undecided

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 9 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

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 (Trial H1: Aviptadil)
ClinicalTrials.gov ID: NCT06729606
Acronym / sponsor ID: 015/ACTIV-3b/H1
Conditions: Covid19
Keywords: COVID-19, COVID 19, Coronaviridae Infections, Coronavirus Infections, RNA Virus Infections, Virus Diseases, Nidovirales Infections, SARS-CoV-2
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 471 participants (actual)
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
Collaborators: International Network for Strategic Initiatives in Global HIV Trials (INSIGHT), University of Copenhagen, Medical Research Council, Kirby Institute, Washington D.C. Veterans Affairs Medical Center, Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections, US Department of Veterans Affairs, Prevention and Early Treatment of Acute Lung Injury (PETAL) Network, NeuroRx, Inc.
Study start: 20 Apr 2021 (actual)
Primary completion: 22 Aug 2022 (actual)
Study completion: 20 Nov 2022 (actual)
First posted: 11 Dec 2024 (actual)
Results: Posted 9 Oct 2025

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

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

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.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 2

Arm	Type	Receives
Aviptadil + SOC	Experimental	Biological: Aviptadil, Drug: Corticosteroid
Placebo + SOC	Placebo comparator	Biological: Aviptadil Placebo, Drug: Corticosteroid

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (1 listed)

Refer to the master protocol (NCT04843761)

Key exclusion criteria (7 listed)

Refer to the master protocol (NCT04843761)
Refractory hypotension
Severe diarrhea
Current C. difficile infection
Pregnancy or current breast-feeding

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
AviptadilAlso: Vasoactive Intestinal Peptide, VIPAdministered 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.	Biological	Aviptadil + SOC
Aviptadil PlaceboCommercially available 0.9% sodium chloride solution. Administered by IV infusion over 12 hours per day for 3 days.	Biological	Placebo + SOC
CorticosteroidIn line with NIH treatment guidelines, corticosteroids such as dexamethasone, prednisone, methylprednisolone or hydrocortisone may be administered as SOC.	Drug	Aviptadil + SOC, Placebo + SOC

Primary outcome

Number of Participants With a 6-category Primary Ordinal Outcome (Recovery) at Day 90
Time frame: Status on 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.

4 secondary outcomes

Number of Participants Who Died Through Day 90
Time frame: Through Day 90
Number of Participants With a Safety Outcome Through Day 5
Time frame: Through Day 5
Number of Participants With a Safety Outcome Through Day 28
Time frame: Through Day 28
Number of Participants Who Died Through Day 180
Time frame: Through Day 180

Results and safety

Results posted to the registry on 9 Oct 2025, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Aviptadil + SOC	234	231
Placebo + SOC	237	230

Primary outcome: Number of Participants With a 6-category Primary Ordinal Outcome (Recovery) at Day 90

Time frame: Status on Day 90. Count of participants. Unit: Participants

Measure	Aviptadil + SOC n = 225	Placebo + SOC n = 225
category 1 = at home and off oxygen (recovered) for at least 77 days	36	31
category 2 = at home and off oxygen for 49-76 days	37	35
category 3 = at home and off oxygen for 1-48 days	43	32
category 4 = not hospitalized but either on supplemental oxygen or not at home	15	31
category 5 = hospitalized or in hospice care	8	13
category 6 = died	86	83

Aviptadil + SOC vs Placebo + SOC: Odds Ratio (OR): 1.11 (95% CI 0.80 to 1.55), p = 0.54, Proportional odds model

Population analysed: 6 participants in the Aviptadil+SOC arm and 5 participants in the Placebo+SOC arm did not have the day 90 status available to compute the primary endpoint. These participants were excluded from the analysis.

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: All-cause mortality collected through Day 180 Serious adverse events collected through Day 90 Other adverse events (not serious): Combined reporting of infusion reactions on Study days 0, 1, and 2 AND any other Adverse Events through Study Day 28.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Aviptadil + SOC	25 of 231 (10.8%)	200 of 231 (86.6%)	90 of 231
Placebo + SOC	23 of 230 (10%)	176 of 230 (76.5%)	86 of 230

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 9 Oct 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
FDA Safety Alerts and RecallsLink provided by the sponsor.
A Participant's Guide to Clinical Trials (NIAID)Link provided by the sponsor.
Find a Clinical Trial (NIAID)Link provided by the sponsor.
Clinical Trials at NIAIDLink provided by the sponsor.
National Institute for Allergy and Infectious Diseases (NIAID)Link provided by the sponsor.
WHO COVID-19 treatment guidelinesLink provided by the sponsor.
Individual participant dataSharing planned: Undecided

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Samuel Brown, MD principal investigator

Intermountain Medical Center/University of Utah

Prof. James Neaton study chair

INSIGHT Statistical and Coordinating Centre, University of Minnesota

40 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing 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 1 inclusion and 7 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 9 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 9 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?

Number of Participants With a 6-category Primary Ordinal Outcome (Recovery) at Day 90 (time frame: Status on Day 90). 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 NCT06729606.

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 9 Oct 2025.