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法匹拉韦治疗新冠病毒肺炎的开放性对照临床研究
Qingxian Cai, Minghui Yang, Dongjing Liu, Jun Chen, Dan Shu, Junxia Xia, Xuejiao Liao, Yuanbo Gu, Qiue Cai, Yang Yang, Chenguang Shen, Xiaohe Li, Ling Peng, Deliang Huang, Jing Zhang, Shurong Zhang, Fuxiang Wang, Jiaye Liu, Li Chen, Shuyan Chen, Zhaoqin Wang, Zheng Zhang, Ruiyuan Cao, Wu Zhong, Yingxia Liu, Lei Liu
工程（英文） ›› 2020, Vol. 6 ›› Issue (10) : 1192-1198.
PDF(859 KB)
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法匹拉韦治疗新冠病毒肺炎的开放性对照临床研究
Experimental Treatment with Favipiravir for COVID-19: An Open-Label Control Study
2019年12月以来，中国暴发了一场由严重急性呼吸系统综合征冠状病毒2（SARS-CoV-2）感染所引发的新冠病毒肺炎（COVID-19）疫情。超过16%的患者出现急性呼吸窘迫综合征，病死率为1%~2%。目前尚无有关特效治疗方法的报道。在此，我们比较了法匹拉韦（Favipiravir, FPV）和洛匹那韦（Lopinavir, LPV）/利托那韦（Ritonavir, RTV）治疗COVID-19的效果。FPV治疗组给药方案为实验室确诊COVID-19感染患者口服FPV（第1天：给药2次，单次1600 mg；第2~14天：每日2次，单次600 mg），同时干扰素α（IFN-α）雾化吸入（每日2次，单次500万国际单位）。而对照组给药方案为对患者进行洛匹那韦/利托那韦治疗（第1~14天：每日2次，单次400 mg/100 mg），同时IFN-α雾化吸入（每日2次，单次500万国际单位）。FPV治疗组的35例患者和对照组的45例患者在入组时，两组之间患者的所有基线特征均具有可比性。经过比较两组患者在胸部CT、病毒清除和药物安全性方面的变化发现，在病毒清除时间[中位时间（四分位间距，IQR）]方面，FPV治疗组的病毒清除时间[4天（IQR, 2.5~9）]比对照组[11天（IQR, 8~13）]的更短（P < 0.001）。在胸部CT方面，FPV治疗组的胸部CT改善率（91.43%）相比对照组（62.22%）有显著改善（P = 0.004）。在调整了潜在的混杂因素后，FPV治疗组在胸部CT方面仍显示出明显更高的改善率。多变量Cox回归分析显示，FPV的使用与病毒清除速度的提高具有独立的相关性。此外，FPV治疗组出现的不良事件比对照组少。在本项开放的给药前后对照研究中，FPV在疾病进展控制和病毒清除方面对COVID-19表现出更好的治疗效果。这些初步的临床结果为感染SARS-CoV-2患者的治疗提供了有价值的信息。
An outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and its caused coronavirus disease 2019 (COVID-19) have been reported in China since December 2019. More than 16% of patients developed acute respiratory distress syndrome, and the fatality ratio was about 1%–2%. No specific treatment has been reported. Herein, we examined the effects of Favipiravir (FPV) versus Lopinavir (LPV)/ritonavir (RTV) for the treatment of COVID-19. Patients with laboratory-confirmed COVID-19 who received oral FPV (Day 1: 1600 mg twice daily; Days 2–14: 600 mg twice daily) plus interferon (IFN)-α by aerosol inhalation (5 million U twice daily) were included in the FPV arm of this study, whereas patients who were treated with LPV/RTV (Days 1–14: 400 mg/100 mg twice daily) plus IFN-α by aerosol inhalation (5 million U twice daily) were included in the control arm. Changes in chest computed tomography (CT), viral clearance, and drug safety were compared between the two groups. For the 35 patients enrolled in the FPV arm and the 45 patients in the control arm, all baseline characteristics were comparable between the two arms. A shorter viral clearance time was found for the FPV arm versus the control arm (median (interquartile range, IQR), 4 (2.5–9) d versus 11 (8–13) d, P < 0.001). The FPV arm also showed significant improvement in chest imaging compared with the control arm, with an improvement rate of 91.43% versus 62.22% (P = 0.004). After adjustment for potential confounders, the FPV arm also showed a significantly higher improvement rate in chest imaging. Multivariable Cox regression showed that FPV was independently associated with faster viral clearance. In addition, fewer adverse events were found in the FPV arm than in the control arm. In this open-label before-after controlled study, FPV showed better therapeutic responses on COVID-19 in terms of disease progression and viral clearance. These preliminary clinical results provide useful information of treatments for SARS-CoV-2 infection.
法匹拉韦 / 新冠病毒肺炎 / SARS-CoV-2 / 抗病毒治疗 / 开放性非随机对照研究
Favipiravir / COVID-19 / SARS-CoV-2 / Antiviral therapy / Open-label nonrandomized control study
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