Oral Simnotrelvir for Adult Patients with Mild-to-Moderate Covid-19

作者：Bin Cao, Yeming Wang, Hongzhou Lu, Chaolin Huang, Yumei Yang, Lianhan Shang, Chen Zhu, Rongmeng Jiang, Yihe Liu, Ling Lin, Ping Peng, Fuxiang Wang, Fengyun Gong, Honglin Hu, Cong Cheng, Xiangyang Yao, Xianwei Ye, Hourong Zhou, Yinzhong Shen, Chenfan Liu, Chunying Wang, Zhennan Yi, Bijie Hu, Jiuyang Xu, Xiaoying Gu, Jingshan Shen, Yechun Xu, Leike Zhang, Jia Fan, Renhong Tang, Chen Wang · 发表于：New England Journal of Medicine · 年份：2024 · DOI：10.1056/nejmoa2301425 · 被引用次数：108 · 研究领域：SARS-CoV-2 and COVID-19 Research、COVID-19 Clinical Research Studies、Long-Term Effects of COVID-19

Background Simnotrelvir is an oral 3-chymotrypsin–like protease inhibitor that has been found to have in vitro activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and potential efficacy in a phase 1B trial. Methods In this phase 2–3, double-blind, randomized, placebo-controlled trial, we assigned patients who had mild-to-moderate coronavirus disease 2019 (Covid-19) and onset of symptoms within the past 3 days in a 1:1 ratio to receive 750 mg of simnotrelvir plus 100 mg of ritonavir or placebo twice daily for 5 days. The primary efficacy end point was the time to sustained resolution of symptoms, defined as the absence of 11 Covid-19–related symptoms for 2 consecutive days. Safety and changes in viral load were also assessed. Results A total of 1208 patients were enrolled at 35 sites in China; 603 were assigned to receive simnotrelvir and 605 to receive placebo. Among patients in the modified intention-to-treat population who received the first dose of trial drug or placebo within 72 hours after symptom onset, the time to sustained resolution of Covid-19 symptoms was significantly shorter in the simnotrelvir group than in the placebo group (180.1 hours [95% confidence interval {CI}, 162.1 to 201.6] vs. 216.0 hours [95% CI, 203.4 to 228.1]; median difference, −35.8 hours [95% CI, −60.1 to −12.4]; P=0.006 by Peto–Prentice test). On day 5, the decrease in viral load from baseline was greater in the simnotrelvir group than in the placebo group (mean diffe...