Liu Jiao, Pan Xiaojun, Zhang Sheng, Li Ming, Ma Ke, Fan Cunyi, Lv Ying, Guan Xiangdong, Yang Yi, Ye Xiaofei, Deng Xingqi, Wang Yunfeng, Qin LunXiu, Xia Zhijie, Ge Zi, Zhou Quanhong, Zhang Xian, Ling Yun, Qi Tangkai, Wen Zhenliang, Huang Sisi, Zhang Lidi, Wang Tao, Liu Yongan, Huang Yanxia, Li Wenzhe, Du Hangxiang, Chen Yizhu, Xu Yan, Zhao Qiang, Zhao Ren, Annane Djillali, Qu Jieming, Chen Dechang
Department of Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No.197 Ruijin 2nd Road, Shanghai, 200025, China.
Office of the President, Zhoupu Hospital Affiliated to Shanghai Health Medical College, 1500 Zhouyuan Road, Shanghai, 201318, China.
Lancet Reg Health West Pac. 2023 Apr;33:100694. doi: 10.1016/j.lanwpc.2023.100694. Epub 2023 Feb 6.
Nirmatrelvir plus ritonavir (Paxlovid) reduced the risk of hospitalization or death by 89% in high-risk, ambulatory adults with COVID-19. We aimed at studying the efficacy and safety of Paxlovid in hospitalized adult patients with SARS-Cov-2 (Omicron BA.2.2 variant) infection and severe comorbidities.
We conducted an open-label, multicenter, randomized controlled trial in which hospitalized adult patients with severe comorbidities were eligible and assigned in a 1:1 ratio to receive either 300 mg of nirmatrelvir plus 100 mg of ritonavir every 12 h for 5 days with standard treatment or only standard treatment. All-cause mortality on day 28, the duration of SARS-CoV-2 RNA clearance, and safety were evaluated.
264 patients (mean age, 70.35 years; 122 [46.21%] female) who met the criteria were enrolled at 5 sites in Shanghai from April 10 to May 19 in 2022. After randomization, a total of 132 patients were assigned to receive Paxlovid treatment plus standard treatment, and 132 patients were assigned to receive only standard treatment. The overall 28-day mortality was 4.92%, 8 patients died in the standard treatment group and 5 died in the Paxlovid plus standard treatment group. There was no significant difference in mortality from any cause at 28 days between the Paxlovid plus standard treatment group and the standard treatment group (absolute risk difference [ARD], 2.27; 95% CI -2.94 to 7.49, P = 0.39). There was no significant difference in the duration of SARS-CoV-2 RNA clearance among the two groups (mean days, 10 in Paxlovid plus standard treatment group and 10.50 in the standard treatment group; ARD, -0.62; 95% CI -2.29 to 1.05, P = 0.42). The incidence of adverse events that occurred during the treatment period was similar in the two groups (any adverse event, 10.61% with Paxlovid plus standard treatment vs. 7.58% with the standard, P = 0.39; serious adverse events, 4.55% vs. 3.788%, P = 0.76).
Paxlovid showed no significant reduction in the risk of all-cause mortality on day 28 and the duration of SARS-CoV-2 RNA clearance in hospitalized adult COVID-19 patients with severe comorbidities.
National Natural Science Foundation of China (grant number: 82172152, 81873944).
对于患有新冠病毒疾病的高危门诊成年患者，奈玛特韦片/利托那韦片组合包装（帕罗韦德）可将住院或死亡风险降低89%。我们旨在研究帕罗韦德在感染严重急性呼吸综合征冠状病毒2（SARS-CoV-2，奥密克戎BA.2.2变异株）且患有严重合并症的住院成年患者中的疗效和安全性。
我们开展了一项开放标签、多中心、随机对照试验，符合条件的患有严重合并症的住院成年患者按1:1比例随机分组，分别接受每12小时一次、每次300毫克奈玛特韦与100毫克利托那韦联合标准治疗，持续5天，或仅接受标准治疗。评估了第28天的全因死亡率、SARS-CoV-2核糖核酸清除持续时间和安全性。
2022年4月10日至5月19日，在上海的5个地点招募了264名符合标准的患者（平均年龄70.35岁；122名[46.21%]为女性）。随机分组后，共有132名患者被分配接受帕罗韦德治疗加标准治疗，132名患者被分配仅接受标准治疗。总体28天死亡率为4.92%，标准治疗组有8例死亡，帕罗韦德加标准治疗组有5例死亡。帕罗韦德加标准治疗组与标准治疗组在28天时的全因死亡率无显著差异（绝对风险差[ARD]为2.27；95%置信区间为-2.94至7.49，P=0.39）。两组间SARS-CoV-2核糖核酸清除持续时间无显著差异（帕罗韦德加标准治疗组平均为10天，标准治疗组为10.50天；ARD为-0.62；95%置信区间为-2.29至1.05，P=0.42）。两组治疗期间不良事件的发生率相似（任何不良事件，帕罗韦德加标准治疗组为10.61%，标准治疗组为7.58%，P=0.39；严重不良事件，分别为4.55%和3.788%，P=0.76）。
对于感染新冠病毒且患有严重合并症的住院成年患者，帕罗韦德在第28天的全因死亡率风险和SARS-CoV-2核糖核酸清除持续时间方面并无显著降低。
中国国家自然科学基金（批准号：82172152、81873944）
