Grand Rounds July 8, 2022: Results From the COVID-OUT Trial, A Phase-3 Trial of Outpatient Treatment for Covid-19 Using Metformin, Ivermectin, and Fluvoxamine (Carolyn Bramante, MD, MPH; Thomas Murray, PhD; Jared Huling, PhD)

Posted on by Elizabeth Mccamic

Speakers

Carolyn Bramante, MD, MPH
Assistant Professor, General Internal Medicine and Pediatrics
Core Faculty, Center for Pediatric Obesity Medicine
Core Faculty, Program for Health Disparities Research
University of Minnesota Medical School

Thomas Murray, PhD
Assistant Professor of Biostatistics
Division of Biostatistics
University of Minnesota School of Public Health

Jared Huling, PhD
Assistant Professor of Biostatistics
Division of Biostatistics
University of Minnesota School of Public Health

 

 

Keywords

COVID-19, COVID-OUT

 

Key Points

  • The COVID-OUT Trial is a remotely delivered, Phase 3, de-centralized clinical trial at 6 participating institutions to see if Ivermectin, Metformin or Fluvoxamine would prevent severe COVID-19. The primary outcome was a 4-part composite: hypoxemia on a home oxygen monitor, ED visit, hospitalization or death due to COVID-19.
  • The dosing for the drugs during the trial was Ivermectin 390 (470mcg/kg/day x 3 days), Metformin titration to 1,500mg/day over 7 days, and Fluvoxamine 50mg.
  • Trial participants were adults ages 30-85, who tested positive for SARS-CoV-2 within 3 days, with fewer than 7 days of symptoms, no known prior infection with SARS-CoV-2, no severe kidney, liver, or heart failure. Patients with diabetes or prediabetes were not excluded (except for those on insulin or sulfonylurea); pregnant patients were not excluded for the Metformin arm; the trial restricted participants to people who were overweight or obese to enrich the population for having a high risk of outcomes and for anti-inflammatory hypotheses around Metformin.
  • Initially, the randomization of the trial was 1:1 Metformin or Placebo. When Ivermectin and Fluvoxamine were added enrollment was even across 6 arms (except for pregnant participants). When the DSMB recommended stopping Fluvoxamine, the trial reduced to 4 arms.
  • The primary outcome of the trial was negative. Some aspects were a success, particularly delivery of study medication nation-wide within 1 day of consent. None of the medications appeared to have any effects on symptoms. A pre-specified secondary analysis of the primary outcome indicates a substantial reduction in ED visits, hospitalizations, and death from COVID-19 with Metformin.

Discussion Themes

-How did the trial handle recruitment? It was a huge challenge. We started only looking within the participating health system and sites. We used Google Ads and partnerships with some testing clinics. We worked together between the sites when there were issues with bandwidth at one of the sites, the main site would call those participants. We also kept equal focus on follow-up.

Learn more about COVID-OUT.

Tags

#pctGR, @Collaboratory1