Chelsea & Westminster NHS Foundation Trust, London, UK; Department of Respiratory Medicine, Royal Brompton Hospital, London, UK; National Heart and Lung Institute, Imperial College London, London, UK.
Chelsea & Westminster NHS Foundation Trust, London, UK; Department of Respiratory Medicine, Royal Brompton Hospital, London, UK; National Heart and Lung Institute, Imperial College London, London, UK.
Lancet Respir Med. 2023 May;11(5):415-424. doi: 10.1016/S2213-2600(22)00412-X. Epub 2022 Dec 14.
COVID-19 has overwhelmed health services globally. Oral antiviral therapies are licensed worldwide, but indications and efficacy rates vary. We aimed to evaluate the safety and efficacy of oral favipiravir in patients hospitalised with COVID-19.
We conducted a multicentre, open-label, randomised controlled trial of oral favipiravir in adult patients who were newly admitted to hospital with proven or suspected COVID-19 across five sites in the UK (n=2), Brazil (n=2) and Mexico (n=1). Using a permuted block design, eligible and consenting participants were randomly assigned (1:1) to receive oral favipiravir (1800 mg twice daily for 1 day; 800 mg twice daily for 9 days) plus standard care, or standard care alone. All caregivers and patients were aware of allocation and those analysing data were aware of the treatment groups. The prespecified primary outcome was the time from randomisation to recovery, censored at 28 days, which was assessed using an intention-to-treat approach. Post-hoc analyses were used to assess the efficacy of favipiravir in patients aged younger than 60 years, and in patients aged 60 years and older. The trial was registered with clinicaltrials.gov, NCT04373733.
Between May 5, 2020 and May 26, 2021, we assessed 503 patients for eligibility, of whom 499 were randomly assigned to favipiravir and standard care (n=251) or standard care alone (n=248). There was no significant difference between those who received favipiravir and standard care, relative to those who received standard care alone in time to recovery in the overall study population (hazard ratio [HR] 1·06 [95% CI 0·89-1·27]; n=499; p=0·52). Post-hoc analyses showed a faster rate of recovery in patients younger than 60 years who received favipiravir and standard care versus those who had standard care alone (HR 1·35 [1·06-1·72]; n=247; p=0·01). 36 serious adverse events were observed in 27 (11%) of 251 patients administered favipiravir and standard care, and 33 events were observed in 27 (11%) of 248 patients receiving standard care alone, with infectious, respiratory, and cardiovascular events being the most numerous. There was no significant between-group difference in serious adverse events per patient (p=0·87).
Favipiravir does not improve clinical outcomes in all patients admitted to hospital with COVID-19, however, patients younger than 60 years might have a beneficial clinical response. The indiscriminate use of favipiravir globally should be cautioned, and further high-quality studies of antiviral agents, and their potential treatment combinations, are warranted in COVID-19.
LifeArc and CW+.
COVID-19 已使全球卫生服务不堪重负。口服抗病毒疗法已在全球范围内获得许可，但适应证和疗效率有所不同。我们旨在评估口服法匹拉韦治疗 COVID-19 住院患者的安全性和疗效。
我们在英国（n=2）、巴西（n=2）和墨西哥（n=1）的五个地点进行了一项多中心、开放性、随机对照试验，评估了新入院的确诊或疑似 COVID-19 成年患者使用口服法匹拉韦。采用随机区组设计，符合条件并同意的参与者按 1:1 随机分配（1 天内口服法匹拉韦 1800mg，每天两次；9 天内口服法匹拉韦 800mg，每天两次）接受口服法匹拉韦+标准治疗或单独接受标准治疗。所有护理人员和患者均了解分组情况，数据分析人员了解治疗组。主要结局是从随机分组到康复的时间，以 28 天为截止日期，采用意向治疗法进行评估。事后分析用于评估法匹拉韦在年龄小于 60 岁的患者和年龄在 60 岁及以上的患者中的疗效。该试验在 clinicaltrials.gov 上注册，NCT04373733。
2020 年 5 月 5 日至 2021 年 5 月 26 日，我们评估了 503 名患者的入选资格，其中 499 名随机分配接受法匹拉韦+标准治疗（n=251）或标准治疗（n=248）。与单独接受标准治疗的患者相比，接受法匹拉韦+标准治疗的患者在总体研究人群中康复时间无显著差异（风险比[HR]1.06[95%CI 0.89-1.27]；n=499；p=0.52）。事后分析显示，年龄小于 60 岁的患者接受法匹拉韦+标准治疗比单独接受标准治疗康复速度更快（HR 1.35[1.06-1.72]；n=247；p=0.01）。在接受法匹拉韦+标准治疗的 251 名患者中，观察到 36 例严重不良事件，在接受标准治疗的 248 名患者中观察到 33 例，其中感染、呼吸和心血管事件最为常见。按患者计算，严重不良事件的组间差异无统计学意义（p=0.87）。
法匹拉韦不能改善所有因 COVID-19 住院的患者的临床结局，然而，年龄小于 60 岁的患者可能有有益的临床反应。应谨慎使用法匹拉韦进行全球无差别治疗，并且有必要在 COVID-19 中进一步开展高质量的抗病毒药物及其潜在治疗组合的研究。
LifeArc 和 CW+。
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