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, Christopher J. Lindsell, Thomas G. Stewart, G. Michael Felker, Dushyantha Jayaweera, Mark Sulkowski, Nina Gentile, Carolyn Bramante, Upinder Singh, Rowena J. Dolor, Juan Ruiz-Unger, Sybil Wilson, Allison Delong, April Remaly, Rhonda Wilder, Sean Collins, Sarah E. Dunsmore, Stacey J. AdamFlorence Thicklin, George Hanna, Adit A. Ginde, Mario Castro, Kathleen McTigue, Elizabeth Shenkman, Adrian F. Hernandez

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)296-305
Number of pages10
JournalJAMA
Volume329
Issue number4
DOIs
StatePublished - Jan 24 2023

Bibliographical note

Funding Information:
Funding/Support: This trial was supported by grant 3U24TR001608-06S1 from the National Center for Advancing Translational Sciences . Additional support was provided by contract 75A50122C00037 from the Office of the Assistant Secretary for Preparedness and Response, Biomedical Advanced Research and Development Authority ; translational science award UL1TR002243 from the National Center for Advancing Translational Sciences (awarded to Vanderbilt University Medical Center); the REDCap infrastructure; and grant U24TR001579 from the National Center for Advancing Translational Sciences (awarded to the Vanderbilt University Medical Center Recruitment Innovation Core).

Publisher Copyright:
© 2023 American Medical Association. All rights reserved.

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

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