TY - JOUR
T1 - Fluvoxamine for Outpatient Management of COVID-19 to Prevent Hospitalization
T2 - A Systematic Review and Meta-analysis
AU - Lee, Todd C.
AU - Vigod, Simone
AU - Bortolussi-Courval, Émilie
AU - Hanula, Ryan
AU - Boulware, David R.
AU - Lenze, Eric J.
AU - Reiersen, Angela M.
AU - McDonald, Emily G.
N1 - Funding Information:
Conflict of Interest Disclosures: Dr Lee reported receiving personal fees from Fonds de Recherche du Quebec— Sante and grants from the Canadian Institutes Health Research outside the submitted work. Dr Boulware reported receiving grants from the National Institutes of Health (NIH) and serving as the NIH ACTIV-6 trial steering committee co-chair during the conduct of the study. Dr Lenze reported receiving personal fees from IngenioRx, Prodeo, and Boeringer-Ingelheim outside the submitted work. Drs Lenze and Reiersen reported having a patent application filed by Washington University for methods of treating COVID-19 during the conduct of the study. Dr Reiersen reported receiving grants from COVID-19 Early Treatment during the conduct of the study and receiving grants from FastGrants outside the submitted work. Dr McDonald reported receiving financial support for trial recruitment from the University of Washington during the conduct of the study and receiving personal fees from Fonds de Recherche du Quebec—Sante outside the submitted work. No other disclosures were reported.
Publisher Copyright:
© 2022 American Medical Association. All rights reserved.
PY - 2022/4/6
Y1 - 2022/4/6
N2 - Importance: Widely available and affordable options for the outpatient management of COVID-19 are needed, particularly for therapies that prevent hospitalization. Objective: To perform a meta-analysis of the available randomized clinical trial evidence for fluvoxamine in the outpatient management of COVID-19. Data Sources: World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov. Study Selection: Studies with completed outpatient trials with available results that compared fluvoxamine with placebo were included. Data Extraction and Synthesis: The PRISMA 2020 guidelines were followed and study details in terms of inclusion criteria, trial demographics, and the prespecified outcome of all-cause hospitalization were extracted. Risk of bias was assessed by the Cochrane Risk of Bias 2 tool and a bayesian random effects meta-analysis with different estimates of prior probability was conducted: a weakly neutral prior (50% chance of efficacy with 95% CI for risk ratio [RR] between 0.5 and 2.0) and a moderately optimistic prior (85% chance of efficacy). A frequentist random-effects meta-analysis was conducted as a senstivity analysis, and the results were contextualized by estimating the probability of any association (RR ≤ 1) and moderate association (RR ≤ 0.9) with reduced hospitalization. Main Outcomes and Measures: All-cause hospitalization. Results: This systematic review and meta-analysis of 3 randomized clinical trials and included 2196 participants. The RRs for hospitalization were 0.78 (95% CI, 0.58-1.08) for the bayesian weakly neutral prior, 0.73 (95% CI, 0.53-1.01) for the bayesian moderately optimistic prior, and 0.75 (95% CI, 0.58-0.97) for the frequentist analysis. Depending on the scenario, the probability of any association with reduced hospitalization ranged from 94.1% to 98.6%, and the probability of moderate association ranged from 81.6% to 91.8%. Conclusions and Relevance: In this systematic review and meta-analysis of data from 3 trials, under a variety of assumptions, fluvoxamine showed a high probability of being associated with reduced hospitalization in outpatients with COVID-19. Ongoing randomized trials are important to evaluate alternative doses, explore the effectiveness in vaccinated patients, and provide further refinement to these estimates. Meanwhile, fluvoxamine could be recommended as a management option, particularly in resource-limited settings or for individuals without access to SARS-CoV-2 monoclonal antibody therapy or direct antivirals..
AB - Importance: Widely available and affordable options for the outpatient management of COVID-19 are needed, particularly for therapies that prevent hospitalization. Objective: To perform a meta-analysis of the available randomized clinical trial evidence for fluvoxamine in the outpatient management of COVID-19. Data Sources: World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov. Study Selection: Studies with completed outpatient trials with available results that compared fluvoxamine with placebo were included. Data Extraction and Synthesis: The PRISMA 2020 guidelines were followed and study details in terms of inclusion criteria, trial demographics, and the prespecified outcome of all-cause hospitalization were extracted. Risk of bias was assessed by the Cochrane Risk of Bias 2 tool and a bayesian random effects meta-analysis with different estimates of prior probability was conducted: a weakly neutral prior (50% chance of efficacy with 95% CI for risk ratio [RR] between 0.5 and 2.0) and a moderately optimistic prior (85% chance of efficacy). A frequentist random-effects meta-analysis was conducted as a senstivity analysis, and the results were contextualized by estimating the probability of any association (RR ≤ 1) and moderate association (RR ≤ 0.9) with reduced hospitalization. Main Outcomes and Measures: All-cause hospitalization. Results: This systematic review and meta-analysis of 3 randomized clinical trials and included 2196 participants. The RRs for hospitalization were 0.78 (95% CI, 0.58-1.08) for the bayesian weakly neutral prior, 0.73 (95% CI, 0.53-1.01) for the bayesian moderately optimistic prior, and 0.75 (95% CI, 0.58-0.97) for the frequentist analysis. Depending on the scenario, the probability of any association with reduced hospitalization ranged from 94.1% to 98.6%, and the probability of moderate association ranged from 81.6% to 91.8%. Conclusions and Relevance: In this systematic review and meta-analysis of data from 3 trials, under a variety of assumptions, fluvoxamine showed a high probability of being associated with reduced hospitalization in outpatients with COVID-19. Ongoing randomized trials are important to evaluate alternative doses, explore the effectiveness in vaccinated patients, and provide further refinement to these estimates. Meanwhile, fluvoxamine could be recommended as a management option, particularly in resource-limited settings or for individuals without access to SARS-CoV-2 monoclonal antibody therapy or direct antivirals..
UR - http://www.scopus.com/inward/record.url?scp=85127628247&partnerID=8YFLogxK
U2 - 10.1001/jamanetworkopen.2022.6269
DO - 10.1001/jamanetworkopen.2022.6269
M3 - Review article
C2 - 35385087
AN - SCOPUS:85127628247
SN - 2574-3805
VL - 5
SP - E226269
JO - JAMA network open
JF - JAMA network open
IS - 4
ER -