Original Investigation 

January 12, 2023

Effect of Fluvoxamine vs Placebo on Time to Sustained Recovery in Outpatients With Mild to Moderate COVID-19: A Randomized Clinical Trial

Matthew W. McCarthy, Susanna Naggie, David R. Boulware, et al

JAMA. Published online January 12, 2023. doi:10.1001/jama.2022.24100

Key Points

Question  Does 50 mg of fluvoxamine twice daily for 10 days, compared with placebo, shorten symptom duration among adult (aged ≥30 years) outpatients with symptomatic mild to moderate COVID-19?

Findings  In this platform randomized clinical trial conducted during a period of predominance for the Delta and Omicron variants in the US, including 1288 adult outpatients with COVID-19 treated with fluvoxamine vs placebo, the hazard ratio was 0.96 (95% credible interval, 0.86-1.06) for time to sustained recovery with a posterior P = .21 for the probability of improvement. This did not meet the prespecified threshold of greater than 0.95 for posterior probability.

Meaning  These findings do not support the use of fluvoxamine at this dose and duration in patients with mild to moderate COVID-19.

Abstract

Importance  The effectiveness of fluvoxamine to shorten symptom duration or prevent hospitalization among outpatients with mild to moderate symptomatic COVID-19 is unclear.

Objective  To evaluate the efficacy of low-dose fluvoxamine (50 mg twice daily) for 10 days compared with placebo for the treatment of mild to moderate COVID-19 in the US.

Design, Setting, and Participants  The ongoing Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV-6) platform randomized clinical trial was designed to test repurposed medications in outpatients with mild to moderate COVID-19. A total of 1288 participants aged 30 years or older with test-confirmed SARS-CoV-2 infection and experiencing 2 or more symptoms of acute COVID-19 for 7 days or less were enrolled between August 6, 2021, and May 27, 2022, at 91 sites in the US.

Interventions  Participants were randomized to receive 50 mg of fluvoxamine twice daily for 10 days or placebo.

Main Outcomes and Measures  The primary outcome was time to sustained recovery (defined as the third day of 3 consecutive days without symptoms). There were 7 secondary outcomes, including a composite outcome of hospitalization, urgent care visit, emergency department visit, or death through day 28.

Results  Among 1331 participants who were randomized (median age, 47 years [IQR, 38-57 years]; 57% were women; and 67% reported receiving ≥2 doses of a SARS-CoV-2 vaccine), 1288 completed the trial (674 in the fluvoxamine group and 614 in the placebo group). The median time to sustained recovery was 12 days (IQR, 11-14 days) in the fluvoxamine group and 13 days (IQR, 12-13 days) in the placebo group (hazard ratio [HR], 0.96 [95% credible interval, 0.86-1.06], posterior P = .21 for the probability of benefit [determined by an HR >1]). For the composite outcome, 26 participants (3.9%) in the fluvoxamine group were hospitalized, had an urgent care visit, had an emergency department visit, or died compared with 23 participants (3.8%) in the placebo group (HR, 1.1 [95% credible interval, 0.5-1.8], posterior P = .35 for the probability of benefit [determined by an HR <1]). One participant in the fluvoxamine group and 2 participants in the placebo group were hospitalized; no deaths occurred in either group. Adverse events were uncommon in both groups.

Conclusions and Relevance  Among outpatients with mild to moderate COVID-19, treatment with 50 mg of fluvoxamine twice daily for 10 days, compared with placebo, did not improve time to sustained recovery. These findings do not support the use of fluvoxamine at this dose and duration in patients with mild to moderate COVID-19.

Trial Registration  ClinicalTrials.gov Identifier: NCT04885530