(Updated August 2021) Adaptive COVID-19 Treatment Trial (ACTT-1)

ACTT is a clinical trial platform sponsored by NIAID to evaluate the safety and efficacy of novel therapeutic agents in hospitalized adults diagnosed with COVID-19. The studies are a multicenter trial and will be conducted in up to approximately 100 sites globally. The studies will compare different investigational therapeutic agents to a control arm. New arms can be introduced according to scientific and public health needs. This adaptive platform is used to rapidly evaluate different therapeutics in a population of those hospitalized with moderate to severe COVID-19. The platform will provide a common framework sharing a similar population, design, endpoints, and safety oversight. New stages with new therapeutics can be introduced. The initial iteration of ACTT (ACTT-1) evaluated Remdesivir vs placebo. Participants had to have a laboratory-confirmed SARS-CoV-2 and meet one of the following criteria suggestive of lower respiratory tract infection at the time of enrollment: radiographic infiltrates by imaging study, peripheral oxygen saturation (SpO2) ≤94% on room air, or requiring supplemental oxygen, mechanical ventilation, or extracorporeal membrane oxygenation (ECMO). Remdesivir was administered intravenously as a 200-mg loading dose on day 1, followed by a 100-mg maintenance dose administered daily on days 2 through 10 or until hospital discharge or death. A matching placebo was administered according to the same schedule and in the same volume as the active drug. Eligible patients were randomly assigned in a 1:1 ratio to receive either remdesivir or placebo. There were 60 trial sites and 13 subsites: United States (45 sites), Denmark (8), the United Kingdom (5), Greece (4), Germany (3), Korea (2), Mexico (2), Spain (2), Japan (1), and Singapore (1). Participants were assessed daily during their hospitalization, from day 1 through day 29. The participant’s clinical status on an eight-category ordinal scale, National Early Warning Score (NEWS), and other clinical data was recorded each day. All serious adverse events and grade 3 or 4 adverse events that represented an increase in severity from day 1 and any grade 2 or higher suspected drug-related hypersensitivity reactions were recorded. Upon discharge, participants had intermittent study visits through Day 29. The final follow-up for all participants was Day 29.