Iwata Satoshi, Kobayashi Osamu, Kurashima Kazuyoshi, Doi Yohei, Kunishima Hiroyuki, Shinkai Masaharu, Tsushima Kenji, Yamato Masaya, Kano Akira, Hibino Makoto, Yamatake Takahiro, Sakurai Tsutomu, Ogura Takashi
Department of Infectious Diseases, National Cancer Center Hospital, Tokyo, Japan; Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
Department of Infectious Diseases, National Cancer Center Hospital, Tokyo, Japan.
J Infect Chemother. 2024 Mar;30(3):219-227. doi: 10.1016/j.jiac.2023.10.010. Epub 2023 Oct 12.
Favipiravir terminates severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication. Accordingly, early administration of favipiravir to SARS-CoV-2-infected coronavirus disease 2019 (COVID-19) patients may be expected to suppress disease progression.
A randomized double-blind placebo-controlled trial was conducted to demonstrate efficacy of favipiravir in reducing disease progression in patients with mild COVID-19. The participants were unvaccinated patients with comorbidities and at risk of progression to severe disease. Patients were enrolled within 72 h of disease onset and randomized to receive either favipiravir (1800 mg/dose on Day 1 followed by 800 mg/dose) or matching placebo twice daily for 10 days. The primary endpoint was the proportion of patients requiring oxygen therapy within 28 days of randomization.
The trial was discontinued after enrolling 84 patients due to slower than anticipated enrollment caused by rapid uptake of SARS-CoV-2-vaccines and the emergence of the Omicron variant. Results from the 84 patients demonstrated no significant difference in all clinical outcomes. In post-hoc analyses, favipiravir treatment showed higher efficacy in patients within 48 h of onset. No deaths or severe adverse events were documented in the favipiravir group. Plasma concentrations of favipiravir from Day 2 onward were maintained above 40 μg/mL.
Conducting clinical trials for pathogens like SARS-CoV-2 that rapidly accumulate mutations leading to altered disease characteristics carries significant risks unless it can be done in a short period. Therefore, it would be important to prepare the comprehensive clinical trial platform that can appropriately and promptly evaluate drugs even under a pandemic.
法匹拉韦可终止严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的复制。因此，预计对感染SARS-CoV-2的2019冠状病毒病（COVID-19）患者早期给予法匹拉韦可抑制疾病进展。
进行了一项随机双盲安慰剂对照试验，以证明法匹拉韦在降低轻度COVID-19患者疾病进展方面的疗效。参与者为未接种疫苗且有合并症并有进展为重症疾病风险的患者。患者在发病72小时内入组，并随机接受法匹拉韦（第1天1800mg/剂量，随后800mg/剂量）或匹配的安慰剂，每日两次，共10天。主要终点是随机分组后28天内需要吸氧治疗的患者比例。
由于SARS-CoV-2疫苗的快速接种和奥密克戎变种的出现导致入组速度慢于预期，在招募了84名患者后试验停止。84名患者的结果显示所有临床结局均无显著差异。在事后分析中，法匹拉韦治疗在发病48小时内的患者中显示出更高的疗效。法匹拉韦组未记录到死亡或严重不良事件。从第2天起，法匹拉韦的血浆浓度维持在40μg/mL以上。
对像SARS-CoV-2这样迅速积累突变导致疾病特征改变的病原体进行临床试验存在重大风险，除非能在短时间内完成。因此，准备一个即使在大流行情况下也能适当且迅速评估药物的综合临床试验平台非常重要。
