School of Data Science, University of Virginia, Charlottesville.
Department of Medicine and Global Health, Division of Infectious Diseases, Emory University School of Medicine and Rollins School of Public Health, Atlanta, Georgia.
JAMA. 2023 Dec 26;330(24):2354-2363. doi: 10.1001/jama.2023.23363.
The effect of higher-dose fluvoxamine in reducing symptom duration among outpatients with mild to moderate COVID-19 remains uncertain.
To assess the effectiveness of fluvoxamine, 100 mg twice daily, compared with placebo, for treating mild to moderate COVID-19.
DESIGN, SETTING, AND PARTICIPANTS: The ACTIV-6 platform randomized clinical trial aims to evaluate repurposed medications for mild to moderate COVID-19. Between August 25, 2022, and January 20, 2023, a total of 1175 participants were enrolled at 103 US sites for evaluating fluvoxamine; participants were 30 years or older with confirmed SARS-CoV-2 infection and at least 2 acute COVID-19 symptoms for 7 days or less.
Participants were randomized to receive fluvoxamine, 50 mg twice daily on day 1 followed by 100 mg twice daily for 12 additional days (n = 601), or placebo (n = 607).
The primary outcome was time to sustained recovery (defined as at least 3 consecutive days without symptoms). Secondary outcomes included time to death; time to hospitalization or death; a composite of hospitalization, urgent care visit, emergency department visit, or death; COVID-19 clinical progression scale score; and difference in mean time unwell. Follow-up occurred through day 28.
Among 1208 participants who were randomized and received the study drug, the median (IQR) age was 50 (40-60) years, 65.8% were women, 45.5% identified as Hispanic/Latino, and 76.8% reported receiving at least 2 doses of a SARS-CoV-2 vaccine. Among 589 participants who received fluvoxamine and 586 who received placebo included in the primary analysis, differences in time to sustained recovery were not observed (adjusted hazard ratio [HR], 0.99 [95% credible interval, 0.89-1.09]; P for efficacy = .40]). Additionally, unadjusted median time to sustained recovery was 10 (95% CI, 10-11) days in both the intervention and placebo groups. No deaths were reported. Thirty-five participants reported health care use events (a priori defined as death, hospitalization, or emergency department/urgent care visit): 14 in the fluvoxamine group compared with 21 in the placebo group (HR, 0.69 [95% credible interval, 0.27-1.21]; P for efficacy = .86) There were 7 serious adverse events in 6 participants (2 with fluvoxamine and 4 with placebo) but no deaths.
Among outpatients with mild to moderate COVID-19, treatment with fluvoxamine does not reduce duration of COVID-19 symptoms.
ClinicalTrials.gov Identifier: NCT04885530.
高剂量氟伏沙明在缩短轻度至中度 COVID-19 门诊患者症状持续时间方面的效果仍不确定。
评估氟伏沙明 100mg，每日两次，与安慰剂相比，用于治疗轻度至中度 COVID-19 的疗效。
设计、地点和参与者：ACTIV-6 平台随机临床试验旨在评估用于轻度至中度 COVID-19 的重新利用药物。2022 年 8 月 25 日至 2023 年 1 月 20 日，共有 1175 名参与者在 103 个美国地点入组评估氟伏沙明；参与者年龄 30 岁或以上，确诊 SARS-CoV-2 感染，至少有 2 种急性 COVID-19 症状持续 7 天或更短。
参与者被随机分为氟伏沙明组（n=601），每天两次服用 50mg，第 1 天，随后连续 12 天每天两次服用 100mg；或安慰剂组（n=607）。
主要结局是持续恢复的时间（定义为至少连续 3 天无症状）。次要结局包括死亡时间；住院或死亡时间；住院、紧急护理就诊、急诊就诊或死亡的综合指标；COVID-19 临床进展量表评分；以及不适时间的差异。随访至第 28 天。
在 1208 名随机接受研究药物的参与者中，中位（IQR）年龄为 50（40-60）岁，65.8%为女性，45.5%为西班牙裔/拉丁裔，76.8%报告至少接种了 2 剂 SARS-CoV-2 疫苗。在纳入主要分析的 589 名接受氟伏沙明治疗和 586 名接受安慰剂治疗的参与者中，持续恢复时间无差异（调整后的危害比[HR]，0.99[95%可信区间，0.89-1.09]；疗效 P=0.40）。此外，干预组和安慰剂组的无调整中位持续恢复时间均为 10 天（95%CI，10-11）。没有死亡报告。35 名参与者报告了医疗保健使用事件（预先定义为死亡、住院或急诊/紧急护理就诊）：氟伏沙明组 14 例，安慰剂组 21 例（HR，0.69[95%可信区间，0.27-1.21]；疗效 P=0.86）。6 名参与者（氟伏沙明组 2 名，安慰剂组 4 名）发生 7 例严重不良事件，但无死亡。
在轻度至中度 COVID-19 门诊患者中，氟伏沙明治疗不能缩短 COVID-19 症状持续时间。
ClinicalTrials.gov 标识符：NCT04885530。
