April 29, 2021 (Gephardt Daily) — Researchers at Intermountain Healthcare are at the forefront of a new, multi-center National Institutes of Health study that is being launched across the nation to test the safety and efficacy of therapeutics for COVID-19 patients with life-threatening cases of the virus, including those with acute respiratory failure.
Samuel Brown, MD, MS, critical care physician and researcher at Intermountain Healthcare in Salt Lake City, is the principal investigator of the Phase 3 trial called ACTIV-3 Critical Care, said a news release.
Brown is coordinating with scientists at study sites throughout the world, including the Data Coordinating Center at University of Minnesota, the PETAL Network based at Massachusetts General Hospital, the CTSN Network based at Mt. Sinai, the INSIGHT Washington DC Network, and others.
“The trial will test two therapeutic agents — Zyesami and Veklury/remdesivir — both alone and in combination with a placebo to determine their safety and efficacy in hospitalized COVID-19 patients who are experiencing Acute Respiratory Distress Syndrome (ARDS), a life-threatening condition in which the lungs are severely inflamed and may be unable to maintain sufficient oxygen in the blood,” the news release said.
The randomized, blinded, placebo-controlled clinical trial is part of the NIH Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) public-private partnership to prioritize and accelerate development of the most promising COVID-19 treatments.
This is the first ACTIV trial that focuses entirely on patients with COVID ARDS, the most severe phase of COVID illness, according to Brown, medical director of critical care and pulmonary research at Intermountain.
“As clinicians, we’re in great need of treatments for this group of patients,” Brown said. “The hope is that one of the two drugs will be effective in helping these patients, but that’s what needs to be determined through these trials.”
Intermountain is a pioneer in the treatment of ARDS and has been involved in numerous studies and research on best practices for more than 40 years.
“There is a strong body of previous research that supports the use of these agents in ARDS, which is associated with substantial morbidity and mortality,” said Gary H. Gibbons, MD, director of the National Heart, Lung, and Blood Institute. “Not only is this an important trial, in terms of potential new treatments for COVID-19, but it could open new understanding into the repair of damaged lungs following ARDS.”
Zyesami is a formulation of aviptadil acetate, a synthetic version of the hormone the body makes that helps protect lung cells and decrease reproduction of the COVID virus, while remdesivir is an antivirus drug that appears to work in treating patients with milder COVID disease but is unproven as a treatment option in patients with more severe COVID disease.
The ACTIV-3 Critical Care trial allows for sub-studies of different therapeutics to run concurrently. Each sub-study will enroll approximately 620 participants at 50 study sites in the United States.
“Trial participants will be randomly assigned to receive either the investigational agents in the sub-study or a placebo,” the news release said. “In the current version of the study, participants will be randomly assigned to receive one of four treatment regimens in addition to standard of care: both Zyesami and remdesivir, Zyesami and a placebo, remdesivir and placebo, or only placebo.”
Zyesami will be administered for 12 hours daily for three days, with the infusion rate increasing each day. Those randomized to receive remdesivir will receive it for up to 10 days via IV.
Researchers will enroll hospitalized patients with acute respiratory failure due to COVID-19 who require high-flow supplemental oxygen, delivered by nasal cannula, mechanical ventilation, or extracorporeal membrane oxygenation, the news release said.
“Initially, a small cohort of 40 participants will be enrolled at study sites throughout the nation,” the news release said. “If no safety concerns are identified, a larger group of participants will be enrolled at additional U.S. and international sites. If necessary, the treatment regimens may be adjusted before additional participants are enrolled.”
For the primary analysis of the trial, participants will be assessed on a six-category ordinal scale 90 days after enrollment, and outcomes will be compared among treatment groups. This scale ranges from recovered and living at home without supplemental oxygen within two weeks of enrollment, to death.
Following the assessment at the primary endpoint, participants will receive one additional follow-up at 180 days.