法匹拉韦与羟氯喹联合治疗中重度新型冠状病毒肺炎患者（FACCT试验）：一项开放标签、多中心、随机对照试验
Favipiravir and Hydroxychloroquine Combination Therapy in Patients with Moderate to Severe COVID-19 (FACCT Trial): An Open-Label, Multicenter, Randomized, Controlled Trial.
作者信息
Bosaeed Mohammad, Mahmoud Ebrahim, Alharbi Ahmad, Altayib Hadeel, Albayat Hawra, Alharbi Faisal, Ghalilah Khalid, Al Arfaj Abdulmajid, AlJishi Jumana, Alarfaj Abdullatif, Alqahtani Hajar, Almutairi Badriah M, Almaghaslah Manar, Alyahya Nawaf M, Bawazir Abdullah, AlEisa Saud, Alsaedy Abdulrahman, Bouchama Abderrezak, Alharbi Malak, AlShamrani Majid, Al Johani Sameera, Aljeraisy Majed, Alzahrani Mohammed, Althaqafi Abdulhakeem O, Almarhabi Hassan, Alotaibi Athari, Alqahtani Nasser, Arabi Yaseen M, Aldibasi Omar S, Alaskar Ahmad
机构信息
Department of Medicine, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia.
College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia.
出版信息
Infect Dis Ther. 2021 Dec;10(4):2291-2307. doi: 10.1007/s40121-021-00496-6. Epub 2021 Jul 28.
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 (SaO) 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).
引言
抗病毒药物在治疗2019冠状病毒病（COVID-19）患者方面效果有限。我们旨在评估法匹拉韦和羟氯喹联合用药对治疗中重度COVID-19患者的效果。
方法
在9家医院开展了一项由研究者发起的多中心、开放标签、随机试验。符合条件的患者为中重度COVID-19成人患者，定义为在呼吸环境空气时氧饱和度（SaO）≤94%，或有明显临床症状且胸部X光有变化需要住院治疗。随机按1:1比例分为接受标准治疗（对照组）或标准治疗加用 法匹拉韦和羟氯喹。主要结局是在七分类序贯量表上临床改善两分（从随机分组时的状态开始）的时间或在14天内出院。分析在意向性分析人群中进行。
结果
2020年5月至2021年1月，共纳入254例患者；129例被分配至标准治疗组，125例被分配至治疗组。平均年龄为52（±13）岁，女性103例（41%）。随机分组时，6例患者接受有创机械通气，229例（90.15%）仅需补充氧气（有或无无创通气），19例（7.48%）两者均未接受。两组间临床改善时间无显著差异：治疗组中位数为9天，对照组为7天（风险比：0.845；95%置信区间0.617 - 1.157；p值 = 0.29）。两组间28天死亡率无显著差异（治疗组为7.63%）对比（对照组为10.32%）；p值 = 0.45。治疗组最常见的不良事件为头痛、谷丙转氨酶升高和QTc间期延长。
结论
法匹拉韦和羟氯喹联合用药对中重度COVID-19患者未产生具有统计学意义的临床获益。
临床试验注册
ClinicalTrials.gov（NCT04392973）
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