The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), this week announced that the fourth iteration of the Adaptive COVID-19 Treatment Trial (ACTT-4) has closed to enrollment because the study met pre-defined futility criteria indicating that neither treatment regimen studied is likely significantly better than the other.
The NIAID-sponsored trial aimed to determine which of two drug combinations—baricitinib plus remdesivir or dexamethasone plus remdesivir—was more effective at preventing adults hospitalized with COVID-19 on supplemental oxygen from progressing to requiring mechanical ventilation or death, among other outcomes.
An independent data and safety monitoring board (DSMB) overseeing the trial met on March 30, 2021 to perform a planned interim efficacy analysis. The DSMB found that neither treatment regimen was significantly better than the other. The trial continued enrollment and the DSMB met again on April 13, 2021 for a pre-planned review for futility. The DSMB determined that it is unlikely that the study will show a significant difference between these two arms even if the trial continued to full enrollment of 1,500 participants.
As such, NIAID closed enrollment on April 13, 2021 with just more than 1,000 participants. The DSMB determined there are no safety issues with either treatment regimen. The trial will remain blinded and investigators will continue monitoring and follow up of those currently on study treatment per protocol.
Participants in ACTT-4 were assigned at random to one of two treatment arms of equal size. One group received intravenous (IV) remdesivir, IV dexamethasone, and oral placebo tablets (to mimic baricitinib). The second group received IV remdesivir, baricitinib tablets, and an IV placebo (to mimic dexamethasone).
The trial primarily aims to evaluate the difference in the proportion of participants surviving without requiring invasive mechanical ventilation between the two treatment arms. The trial also aims to compare the overall clinical status at day 15 in each group.
A more detailed report on trial results is forthcoming. For more information about the trial, please visit ClinicalTrials.gov and search identifier NCT04640168.
Edited by Gary Cramer