ACTIV-1 IM is a master protocol designed to evaluate multiple therapeutic agents for the treatment of moderately or severely ill patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The research objectives are to evaluate each agent with respect to speed of recovery, mortality, illness severity, and hospital resource utilization. Each agent will be evaluated as add-on therapy to the standard of care (SoC) in use at the local clinics, including remdesivir. The SoC may change during the course of the study based on other research findings. Comparisons of the agents among themselves is not a research objective.
The study population corresponds to moderately and severely ill patients infected with the COVID-19 virus. Recruitment will target patients already hospitalized for treatment of COVID-19 infection as well as patients being treated for COVID-19 infection in Emergency Departments while waiting to be admitted to the hospital. Patients both in and out of the ICU are included in the study population.
Enrollment is planned to begin when 2-3 agents have been selected for initial evaluation and are available for testing. Up to 5 agents may be evaluated in ACTIV-1 IM.
The study period is 29 days, with assessments on each day of the hospital stay. Patients will be followed after hospital discharge with periodic follow-up assessments through Day 29. There will also be a safety and clinical status assessment at 60 days. Treatment periods may vary by agent.
The trial is adaptive in that interim analyses are planned to assess the futility of each agent, with the goal of discontinuing those with lower probabilities of success to more effectively utilize trial resources for the remaining agents. Additionally, interim analyses are planned for early stopping for efficacy. Alpha spending functions are used to appropriately control the probability of making an erroneous conclusion at the interim and final analyses.
Safety monitoring will be performed throughout the trial, and formal stopping rules for each agent will be adopted. The Data and Safety Monitoring Board (DSMB) established for ACTIV-1 IM will have oversight responsibility for the study.