April 12, 2020
Beginning February 21, 2020, ACTT (the Adaptive COVID-19 Treatment Trial) began enrollment in the first of a series of adaptive, randomized, double-blind trials. The trials are designed to evaluate the safety and efficacy of novel therapeutic agents in hospitalized adults diagnosed with COVID-19. Sponsored by the National Institute of Allergy and Infectious Diseases, the multicenter study will be conducted at approximately 100 sites globally. The DoD effort is coordinated by the Uniformed Services University’s Infectious Diseases Clinical Research Program (IDCRP) with CAPT Ryan Maves serving as IDCRP Principal Investigator.
Each subsequent arm of ACTT will investigate different therapeutic agents compared to a control arm. If one therapy proves to be efficacious, then this treatment may become the control arm for comparison(s) with new experimental treatment(s). The primary outcome is time to recovery, measured at Day 29. A key secondary outcome evaluates treatment-related improvements in an eight-point ordinal scale at Day 15. Each arm may prioritize different secondary endpoints for the purpose of multiple comparison analyses.
ACTT-1, the first arm of the trial, compared Remdesivir versus a placebo for the treatment of COVID-19. ACTT-1 took place at 60 sites globally, five of which were Military Treatment Facilities. A total of 1062 patients were enrolled across all sites. Preliminary results were published in the New England Journal of Medicine on May 22, with a final manuscript undergoing peer-review at the time of writing. These results also supported the FDA emergency use authorization of Remdesivir and led to changes in clinical standards for the treatment of COVID-19.
ACTT-2, the second arm of the trial, began enrollment on May 8. ACTT-2 compared Remdesivir and a placebo versus Remdesivir and Baricitinib for the treatment of COVID-19. ACTT-2 took place at 71 sites globally, five of which were Military Treatment Facilities (the same ones that participated in ACTT-1). Enrollment completed June 30 and 1084 patients were enrolled across all sites. The team submitted the ACTT-2 manuscript to the New England Journal of Medicine in October 2020. Preliminary results have shown clinical benefit of Remdesivir and Baricitinib versus Remdesivir alone.
ACTT-3 began enrollment August 4 and was ongoing at the end of FY20. ACTT-3 is comparing Remdesivir and a placebo versus Remdesivir and Interferon beta-1a for the treatment of COVID-19. ACTT-3 is taking place at 60 sites globally, seven of which are Military Treatment Facilities.
Discussion is currently under way for ACTT-4.