Division of Infectious Diseases, Department of Medicine, McGill University Health Centre, Montréal, Québec, Canada.
Clinical Practice Assessment Unit, Department of Medicine, McGill University Health Centre, Montréal, Québec, Canada.
JAMA Netw Open. 2022 Apr 1;5(4):e226269. doi: 10.1001/jamanetworkopen.2022.6269.
Widely available and affordable options for the outpatient management of COVID-19 are needed, particularly for therapies that prevent hospitalization.
To perform a meta-analysis of the available randomized clinical trial evidence for fluvoxamine in the outpatient management of COVID-19.
World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov.
Studies with completed outpatient trials with available results that compared fluvoxamine with placebo were included.
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.
All-cause hospitalization.
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%.
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.
需要有广泛可用且负担得起的选择来进行 COVID-19 的门诊管理，特别是对于预防住院的治疗方法。
对氟伏沙明用于 COVID-19 门诊管理的现有随机临床试验证据进行荟萃分析。
世界卫生组织国际临床试验注册平台和 ClinicalTrials.gov。
纳入了已完成并提供可用结果的门诊试验，比较了氟伏沙明与安慰剂。
遵循 PRISMA 2020 指南，并提取了纳入标准、试验人口统计学和所有原因住院的预定结局等研究细节。通过 Cochrane 风险偏倚 2 工具评估风险偏倚，并进行了具有不同先验概率估计的贝叶斯随机效应荟萃分析：弱中性先验（疗效的可能性为 50%，风险比 [RR]的 95%置信区间在 0.5 到 2.0 之间）和适度乐观先验（85%的疗效可能性）。还进行了频率论随机效应荟萃分析作为敏感性分析，并通过估计与减少住院相关的任何关联（RR≤1）和中度关联（RR≤0.9）的可能性对结果进行了上下文化。
所有原因住院。
本系统评价和荟萃分析纳入了 3 项随机临床试验，共 2196 名参与者。贝叶斯弱中性先验的住院 RR 为 0.78（95%CI，0.58-1.08），贝叶斯适度乐观先验的 RR 为 0.73（95%CI，0.53-1.01），频率论分析的 RR 为 0.75（95%CI，0.58-0.97）。根据不同的情况，与减少住院相关的任何关联的可能性范围为 94.1%至 98.6%，中度关联的可能性范围为 81.6%至 91.8%。
在这项对 3 项试验数据的系统评价和荟萃分析中，根据各种假设，氟伏沙明在 COVID-19 门诊患者中显示出与降低住院率高度相关的可能性。正在进行的随机试验对于评估替代剂量、探索在接种疫苗患者中的有效性以及进一步完善这些估计值非常重要。同时，氟伏沙明可以作为一种管理选择推荐，特别是在资源有限的环境中，或者对于无法获得 SARS-CoV-2 单克隆抗体治疗或直接抗病毒药物的个体。
