Introduction

Antiviral drugs have shown limited effectiveness in treating patients with coronavirus disease 2019 (COVID-19). We aimed to assess the effects of a favipiravir and hydroxychloroquine combination on treating moderate-to-severe COVID-19 patients.

Methods

An investigator-initiated, multicenter, open-label, randomized trial at nine hospitals. Eligible patients were adults with moderate-to-severe COVID-19 defined as oxygen saturation (SaO₂) of ≤ 94% while breathing ambient air or significant clinical symptoms with chest x-ray changes requiring hospital admission. Randomization was in a 1:1 ratio to receive standard care (control group) or standard care plus favipiravir and hydroxychloroquine. The primary outcome was time to clinical improvement of two points (from the status at randomization) on a seven-category ordinal scale or live discharge from the hospital within 14 days. Analyses were done in an intention-to-treat population.

Results

From May 2020 to Jan 2021, 254 patients were enrolled; 129 were assigned to standard of care and 125 to the treatment. The mean age was 52 (± 13) years, and 103 (41%) were women. At randomization, six patients were on invasive mechanical ventilation, 229 (90.15%) were requiring supplemental oxygen only (with or without non-invasive ventilation), and 19 (7.48%) were receiving neither. The time to clinical improvement was not significantly different between the groups: median of 9 days in the treatment group and 7 days in the control group (HR: 0.845; 95% CI 0.617–1.157; p-value = 0.29). The 28-day mortality was not significantly different between the groups (7.63% treatment) vs. (10.32% control); p-value = 0.45. The most prevalent adverse events were headache, elevation in ALT, and the prolonged QTc interval in the treatment group.

Conclusion

The combination of favipiravir and hydroxychloroquine did not result in a statistically significant clinical benefit in patients with moderate-to-severe COVID-19.

Clinical Trial Registration

ClinicalTrials.gov (NCT04392973).

中文翻译：

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法匹拉韦和羟氯喹联合治疗中度至重度 COVID-19 患者（FACCT 试验）：一项开放标签、多中心、随机、对照试验

介绍

抗病毒药物在治疗 2019 年冠状病毒病 (COVID-19) 患者方面的效果有限。我们旨在评估法匹拉韦和羟氯喹组合对治疗中度至重度 COVID-19 患者的影响。

方法

在九家医院进行的一项由研究者发起的、多中心、开放标签的随机试验。符合条件的患者是患有中度至重度 COVID-19 的成人，其定义为氧饱和度 (SaO ₂ ) ≤ 94%，同时呼吸环境空气或具有需要住院的胸部 X 射线变化的显着临床症状。随机化以 1:1 的比例接受标准治疗（对照组）或标准治疗加法匹拉韦和羟氯喹。主要结果是在 14 天内按七类顺序量表临床改善两点（从随机化状态）或从医院出院的时间。在意向治疗人群中进行了分析。

结果

2020年5月至2021年1月，入组患者254人；129 人被分配到标准护理，125 人被分配到治疗。平均年龄为 52 (± 13) 岁，103 (41%) 名女性。随机化时，6 名患者接受有创机械通气，229 名 (90.15%) 仅需要补充氧气（有或没有无创通气），19 名 (7.48%) 两者均未接受。两组之间的临床改善时间没有显着差异：治疗组的中位数为 9 天，对照组为 7 天（HR：0.845；95% CI 0.617–1.157；p值 = 0.29）。各组（7.63% 治疗）与（10.32% 对照组）之间的 28 天死亡率没有显着差异；磷-值 = 0.45。治疗组最常见的不良事件是头痛、ALT 升高和 QTc 间期延长。

结论

法匹拉韦和羟氯喹的组合对中度至重度 COVID-19 患者没有产生统计学上显着的临床益处。

临床试验注册

ClinicalTrials.gov (NCT04392973)。