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 - 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 -