In the ACTIV-6 trial, fluvoxamine was not effective in reducing the duration of mild-to-moderate COVID-19 among ambulatory patients. “Although one-third fewer health care use events occurred in the fluvoxamine intervention group, the difference did not meet prespecified decision thresholds for concluding a treatment effect,” the authors conclude.
Designed to evaluate repurposed medications for COVID-19, the ACTIV-6 platform randomized clinical trial enrolled 1,175 participants at 103 U.S. sites who were 30 years or older with confirmed SARS-CoV-2 infection and at least 2 acute COVID-19 symptoms for 7 days or less. Fluvoxamine 50 mg twice daily on day 1 followed by 100 mg twice daily for 12 additional days or placebo had these effects on a primary outcome of time to sustained recovery (≥3 consecutive days without symptoms): “Among 1,208 participants who were randomized and received the study drug, the median (IQR) age was 50 (40-60) years, 65.8% were women, 45.5% identified as Hispanic/Latino, and 76.8% reported receiving at least 2 doses of a SARS-CoV-2 vaccine. Among 589 participants who received fluvoxamine and 586 who received placebo included in the primary analysis, differences in time to sustained recovery were not observed (adjusted hazard ratio [HR], 0.99 [95% credible interval, 0.89-1.09]; P for efficacy = .40]). Additionally, unadjusted median time to sustained recovery was 10 (95% CI, 10-11) days in both the intervention and placebo groups. No deaths were reported. Thirty-five participants reported health care use events (a priori defined as death, hospitalization, or emergency department/urgent care visit): 14 in the fluvoxamine group compared with 21 in the placebo group (HR, 0.69 [95% credible interval, 0.27-1.21]; P for efficacy = .86) There were 7 serious adverse events in 6 participants (2 with fluvoxamine and 4 with placebo) but no deaths.”
Editorial: “There are important opportunities to learn from the success of the ACTIV platform, including its decentralized approach that intentionally integrated clinical research into clinical care,” editorialists write. “There is also its spirit of collaboration that brought hundreds of geographically diverse recruitment sites together in partnership. Additionally, its leadership has focused on minimizing bureaucratic barriers while protecting patients, such as the use of centralized institutional review boards. Given the limited resources available for pragmatic trials, efforts are needed to coordinate and launch additional clinical trial research networks that can leverage platform designs to advance the understanding of the diagnosis and treatment of other diseases and conditions, not only COVID-19.”