高剂量氟伏沙明与安慰剂对轻至中度新冠肺炎门诊患者持续恢复时间的影响：一项随机临床试验

Effect of Higher-Dose Fluvoxamine vs Placebo on Time to Sustained Recovery in Outpatients with Mild to Moderate COVID-19: A Randomized Clinical Trial.

作者信息

Naggie Susanna

出版信息

medRxiv. 2023 Sep 13:2023.09.12.23295424. doi: 10.1101/2023.09.12.23295424.

DOI:10.1101/2023.09.12.23295424

PMID:37745371

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10516082/

Abstract

BACKGROUND

The impact of fluvoxamine in reducing symptom duration among outpatients with mild to moderate coronavirus disease 2019 (COVID-19) remains uncertain. Our objective was to assess the effectiveness of fluvoxamine 100 mg twice daily, compared with placebo, for treating mild to moderate COVID-19.

METHODS

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, 1175 participants were enrolled at 103 US sites for evaluating fluvoxamine; participants were age ≥30 years with confirmed SARS-CoV-2 infection and ≥2 acute COVID-19 symptoms for ≤7 days. Participants were randomized to receive fluvoxamine 50 mg twice daily on day 1 followed by 100 mg twice daily for 12 additional days or to placebo. 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 clinical progression scale; and difference in mean time unwell.

RESULTS

Among participants who were randomized and received study drug, the median age was 50 years (IQR 40-60), 66% were female, 45% identified as Hispanic/Latino, and 77% reported ≥2 doses of a SARS-CoV-2 vaccine. Among 589 participants who received fluvoxamine and 586 who received placebo, differences in time to sustained recovery were not observed (adjusted hazard ratio [HR], 0.99 [95% credible interval, 0.89-1.09; P(efficacy) = 0.4]). Additionally, unadjusted, median time to sustained recovery was 10 days (95% CI 10-11) in both the intervention and placebo group. No deaths were reported. Thirty-five participants reported healthcare utilization events ( defined as death, hospitalization, emergency department/urgent care visit); 14 in the fluvoxamine group compared with 21 in the placebo group (HR 0.69; 95% CrI 0.27-1.21; P(efficacy)=0.86) There were 7 serious adverse events in 6 participants (2 with fluvoxamine and 4 with placebo).

CONCLUSIONS

Among outpatients with mild to moderate COVID-19, treatment with fluvoxamine does not reduce duration of COVID-19 symptoms.

TRIAL REGISTRATION

ClinicalTrials.gov ( NCT04885530 ).

摘要

背景

氟伏沙明在缩短轻度至中度2019冠状病毒病（COVID-19）门诊患者症状持续时间方面的影响仍不确定。我们的目的是评估每日两次服用100毫克氟伏沙明与安慰剂相比治疗轻度至中度COVID-19的有效性。

方法

ACTIV-6平台随机临床试验旨在评估用于轻度至中度COVID-19的 repurposed药物。在2022年8月25日至2023年1月20日期间，1175名参与者在美国103个地点登记以评估氟伏沙明；参与者年龄≥30岁，确诊感染严重急性呼吸综合征冠状病毒2（SARS-CoV-2）且有≥2种急性COVID-19症状持续≤7天。参与者被随机分配接受第1天每日两次服用50毫克氟伏沙明，随后12天每日两次服用100毫克氟伏沙明或安慰剂。主要结局是持续恢复时间（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、急诊科就诊或死亡的综合情况；COVID临床进展量表；以及平均不适时间的差异。

结果

在随机分组并接受研究药物的参与者中，中位年龄为50岁（四分位间距40 - 60），66%为女性，45%为西班牙裔/拉丁裔族裔，77%报告接种了≥2剂SARS-CoV-2疫苗。在589名接受氟伏沙明的参与者和586名接受安慰剂的参与者中，未观察到持续恢复时间的差异（调整后风险比[HR]，0.99[95%可信区间，0.89 - 1.09；P（疗效）=0.4]）。此外，未经调整的干预组和安慰剂组持续恢复的中位时间均为10天（95%CI 10 - 11）。未报告死亡病例。35名参与者报告了医疗保健利用事件（定义为死亡、住院、急诊科/紧急护理就诊）；氟伏沙明组14例，安慰剂组21例（HR 0.69；95%CrI 0.27 - 1.21；P（疗效）=0.86）。6名参与者发生了7起严重不良事件（2名服用氟伏沙明，4名服用安慰剂）。