This study looks at the safety and effectiveness of Aviptadil in treating COVID-19 inpeople who have been hospitalized with the infection and who have acute respiratoryfailure. Participants in the study will be treated with Aviptadil plus current standardof care (SOC), or with placebo plus current SOC.
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.
Biological: Aviptadil
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.
Other Name: Vasoactive Intestinal Peptide,VIP
Biological: Aviptadil Placebo
Commercially available 0.9% sodium chloride solution. Administered by IV infusion over 12
hours per day for 3 days.
Drug: Corticosteroid
In line with NIH treatment guidelines, corticosteroids such as dexamethasone, prednisone,
methylprednisolone or hydrocortisone may be administered as SOC.
Inclusion Criteria:
Refer to the master protocol (NCT04843761)
Exclusion Criteria:
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
Banner University Medical Center Tucson (Site 206-004), 1625 N. Campbell Avenue
Tucson, Arizona, United States
UCSF Fresno (Site 203-005), 155 N. Fresno Street
Fresno, California, United States
VA Loma Linda Healthcare System (Site 074-017), 11201 Benton Street
Loma Linda, California, United States
Cedars-Sinai Medical Center (Site 208-002), 8700 Beverly Boulevard
Los Angeles, California, United States
Ronald Reagan UCLA Medical Center (Site 203-002), 757 Westwood Plaza
Los Angeles, California, United States
UCSF Medical Center at Mount Zion (Site 203-007), 1600 Divisadero St.
San Francisco, California, United States
UCSF Medical Center (Site 203-001), Moffit-Long Hospital, 505 Parnassus Ave.
San Francisco, California, United States
Stanford University Hospital & Clinics (Site 203-003), 300 Pasteur Dr.
Stanford, California, United States
University of Colorado Hospital (Site 204-001), 12605 E. 16th Avenue
Aurora, Colorado, United States
Denver Health Medical Center (Site 204-004), 780 Delaware Street, Pavilion B
Denver, Colorado, United States
MedStar Health Research Institute (Site 009-021), 110 Irving St., NW.
Washington D.C., District of Columbia, United States
Washington DC VA Medical Center (Site 009-004), 50 Irving Street, NW.
Washington D.C., District of Columbia, United States
Emory University (Site 301-008), Bldg. A, Suite 2236, 1365 Clifton Rd., NE.
Atlanta, Georgia, United States
Massachusetts General Hospital (Site 202-002), 55 Fruit Street
Boston, Massachusetts, United States
Baystate Medical Center (Site 201-001), Critical Care Research, 759 Chestnut Street
Springfield, Massachusetts, United States
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
Columbia University Irving Medical Center (Site 301-027), 177 Fort Washington Ave.
New York, New York, United States
Montefiore Medical Center - Moses Hospital (Site 206-001), 111 E. 210th Street
The Bronx, New York, United States
Montefiore Medical Center - Weiler campus (Site 206-003), 111 E. 210th Street
The Bronx, New York, United States
Duke University Hospital (Site 301-006), 2301 Erwin Road
Durham, North Carolina, United States
Wake Forest Baptist Health (Site 210-001), Medical Center Blvd
Winston-Salem, North Carolina, United States
University of Cincinnati Medical Center (Site 207-003), 234 Goodman Street, ML 0740
Cincinnati, Ohio, United States
Cleveland Clinic Fairview Hospital (Site 207-005), 18101 Lorain Ave.
Cleveland, Ohio, United States
Cleveland Clinic Foundation (Site 207-001), 9500 Euclid Ave.
Cleveland, Ohio, United States
The Ohio State University Wexner Medical Center (Site 207-004), 410 W. 10th Avenue
Columbus, Ohio, United States
Cleveland Clinic Marymount Campus (Site 207-006), 12300 McCracken Road
Garfield Heights, Ohio, United States
Cleveland Clinic Hillcrest Hospital (Site 207-007), 6780 Mayfield Road
Mayfield Heights, Ohio, United States
Oregon Health & Science University (Site 208-003), 3181 SW Sam Jackson Park Rd.
Portland, Oregon, United States
Medical University of South Carolina (Site 210-002), 96 Jonathan Lucas St., CSB 214
Charleston, South Carolina, United States
Vanderbilt University Medical Center (Site 212-001), 1211 Medical Center Drive
Nashville, Tennessee, United States
Baylor, Scott and White Health (Site 301-003), Baylor University Medical Center, 3500 Gaston Ave.
Dallas, Texas, United States
Houston Methodist Hospital (Site 301-028), 6565 Fannin Street
Houston, Texas, United States
Texas Heart Institute (Site 301-017), 6770 Bertner, MC4-266
Houston, Texas, United States
University of Texas Health Science Center (Site 203-006), 7000 Fannin St.
Houston, Texas, United States
Intermountain Medical Center (Site 211-001), 5121 South Cottonwood Street
Murray, Utah, United States
University of Utah Hospital (Site 211-002), 50 North Medical Drive
Salt Lake City, Utah, United States
UVA School of Medicine (Site 210-003), University of Virginia Health System, University Hospital, 1215 Lee St.
Charlottesville, Virginia, United States
Harborview Medical Center (Site 208-001), 325 9th Ave.
Seattle, Washington, United States
Swedish Medical Center (Site 208-005), 747 Broadway
Seattle, Washington, United States
West Virginia University Medicine (Site 301-023), One Medical Center Drive
Morgantown, West Virginia, United States