Favipiravir is an oral broad-spectrum inhibitor of viral RNA-dependent RNA polymerase that is approved for treatment of influenza in Japan. We conducted a prospective, randomized, open-label, multicenter trial of favipiravir for the treatment of COVID-19 at 25 hospitals across Japan. Eligible patients were adolescents and adults admitted with COVID-19 who were asymptomatic or mildly ill and had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Patients were randomly assigned at a 1:1 ratio to early or late favipiravir therapy (in the latter case, the same regimen starting on day 6 instead of day 1). The primary endpoint was viral clearance by day 6. The secondary endpoint was change in viral load by day 6. Exploratory endpoints included time to defervescence and resolution of symptoms. Eighty-nine patients were enrolled, of whom 69 were virologically evaluable. Viral clearance occurred within 6 days in 66.7% and 56.1% of the early and late treatment groups (adjusted hazard ratio [aHR], 1.42; 95% confidence interval [95% CI], 0.76 to 2.62). Of 30 patients who had a fever (≥37.5°C) on day 1, times to defervescence were 2.1 days and 3.2 days in the early and late treatment groups (aHR, 1.88; 95% CI, 0.81 to 4.35). During therapy, 84.1% developed transient hyperuricemia. Favipiravir did not significantly improve viral clearance as measured by reverse transcription-PCR (RT-PCR) by day 6 but was associated with numerical reduction in time to defervescence. Neither disease progression nor death occurred in any of the patients in either treatment group during the 28-day participation. (This study has been registered with the Japan Registry of Clinical Trials under number jRCTs041190120.)

中文翻译：

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早期和晚期favipiravir在住院的COVID-19患者中进行的前瞻性，随机，开放标签试验。

Favipiravir是病毒RNA依赖性RNA聚合酶的口服广谱抑制剂，已在日本获准用于治疗流感。我们在日本的25家医院中进行了favipiravir的前瞻性，随机，开放标签，多中心试验，用于治疗COVID-19。符合条件的患者为无症状或轻度疾病且东部合作肿瘤学组（ECOG）的状态为0或1的COVID-19的青少年和成人。患者以1：1的比例随机分配至早期或晚期favipiravir治疗（在后一种情况下，相同的方案从第6天开始，而不是从第1天开始）。主要终点是在第6天时的病毒清除率。第二终点是在第6天时的病毒载量变化。探索性终点包括退热时间和症状缓解。招募了89名患者，其中有69位在病毒学上可评估。在早期和晚期治疗组中，分别有66.7％和56.1％的患者在6天之内发生了病毒清除（调整后的危险比[aHR]为1.42； 95％的置信区间[95％CI]为0.76至2.62）。在第1天发烧（≥37.5°C）的30例患者中，早期和晚期治疗组的退热时间分别为2.1天和3.2天（aHR，1.88； 95％CI，0.81至4.35）。在治疗过程中，有84.1％的人发展为短暂性高尿酸血症。到第6天，通过逆转录PCR（RT-PCR）测定，Favipiravir并未显着改善病毒清除率，但与去热时间的数值减少相关。在为期28天的治疗中，任一治疗组的任何患者均未发生疾病进展或死亡。