Results of the Adaptive COVID-19 Treatment Trial (ACTT)-2 investigating combination treatment with baricitinib, a Janus kinase inhibitor, and remdesivir for the treatment of COVID-19 in hospitalized adults were published in the New England Journal of Medicine (NEJM) on March 4, 2021. The trial found that a combination of baricitinib and remdesivir was superior to the combination of remdesivir and placebo at shortening recovery time and improving clinical status in adults hospitalized with COVID-19, particularly for those who were receiving high-flow oxygen or noninvasive ventilation.
Of the FHI Clinical study team members, Danielle Fisher, Clinical Research Project Manager, is listed in the manuscript’s appendix for her contribution to the study. FHI Clinical is an ACTT-2 clinical site via a subcontract with the Frederick National Laboratory, currently operated by Leidos Biomedical Research, Inc.
The analysis showed that combination remdesivir + baricitinib performed better than remdesivir + placebo in treating hospitalized patients with COVID-19. Patients receiving combination treatment had a significantly shorter median recovery time of 7 days (95% confidence interval [CI] 6-8), compared with 8 days (95% CI 7-9) with remdesivir + placebo; this corresponds to a statistically significant rate ratio for recovery of 1.16 (95% CI 1.01-1.32). At day 15 with remdesivir + baricitinib, there was also a 30% higher odds of improvement in clinical status (odds ratio 1.3; 95% CI 1.0-1.6). Differences in time to recovery were particularly notable in patients receiving high-flow oxygen or noninvasive ventilation at enrollment: 10 days with combination treatment, 18 days with remdesivir + placebo (rate ratio for recovery 1.51; 95%
This trial is the second stage in a series of phase 3, randomized, double-blind, placebo-controlled trials to evaluate the clinical efficacy and safety of investigational therapeutic agents in hospitalized adults with laboratory-confirmed COVID-19. The results from the first trial in the series, ACTT-1 investigating remdesivir alone, were published in NEJM in October 2020.
The trial was funded by the National Institute of Allergy and Infectious Diseases and enrolled participants between May 8 and July 1, 2020. A total of 1033 participants were enrolled at 67 study sites in 8 countries: United States (55 sites), Singapore (4), South Korea (2), Mexico (2), Japan (1), Spain (1), United Kingdom (1) and Denmark (1). Intravenous remdesivir + oral/nasogastric baricitinib (515 participants) or remdesivir + placebo (518 participants) were administered to determine the effect on time to recovery.
The FHI Clinical team is excited to be part of this important work to find efficacious and safe treatments for COVID-19. Additional information about the study can be found on clinicaltrials.gov, including the next trial in the series: ACTT-3, which is evaluating the effect of combination interferon beta-1a + remdesivir compared with remdesivir + placebo on recovery.