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期刊来源：N Engl J Med

原文链接：https://doi.org/10.1056/NEJMoa2301425

摘要内容如下：

背景

Simnotrelvir是一种口服3-胰凝乳蛋白酶样蛋白酶抑制剂，已发现其在体外具有抗重症急性呼吸综合征冠状病毒2（SARS-CoV-2）的活性，并在1B期试验中具有潜在功效。

方法

在这项2-3期、双盲、随机、安慰剂对照试验中，我们以1:1的比例将患有轻度至中度冠状病毒病2019（COVID-19）且在过去3天内出现症状的患者分配接受750 mg辛诺瑞韦加100 mg利托那韦或安慰剂，每天两次，持续5天。主要疗效终点是症状持续缓解的时间，定义为连续2天没有出现11种Covid-19相关症状。还评估了安全性和病毒载量的变化。

结果

在中国的35个地点共招募了1208名患者。603人被指定接受辛诺瑞韦治疗，605人接受安慰剂治疗。在症状出现后72小时内接受首剂试验药物或安慰剂的改良意向治疗人群中，辛诺瑞韦组的新冠肺炎症状持续缓解时间显著短于安慰剂组（180.1小时[95%置信区间{CI}，162.1至201.6]vs.216.0小时[95%CI，203.4至228.1]；中位数差异，-35.8小时[95%CI，-60.1至-12.4]；通过Peto-Prentice检验，P=0.006）。在第5天，辛诺瑞韦组的病毒载量相对于基线的下降幅度大于安慰剂组（平均差异[±SE]，-1.51±0.14 log10 copies/ml；95%置信区间，-1.79至-1.24）。辛诺瑞韦组治疗期间的不良事件发生率高于安慰剂组（29.0%vs.21.6%）。大多数不良事件为轻度或中度。

结论

辛诺瑞韦联合利托那韦的早期给药缩短了COVID-19成年患者症状消失的时间，没有明显的安全性问题。（由江苏先声药业资助；ClinicalTrials.gov编号，NCT05506176。）

英文原文如下：

Abstracts

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 difference [±SE], -1.51±0.14 log10 copies per milliliter; 95% CI, -1.79 to -1.24). The incidence of adverse events during treatment was higher in the simnotrelvir group than in the placebo group (29.0% vs. 21.6%). Most adverse events were mild or moderate.

CONCLUSIONS  Early administration of simnotrelvir plus ritonavir shortened the time to the resolution of symptoms among adult patients with Covid-19, without evident safety concerns. (Funded by Jiangsu Simcere Pharmaceutical; ClinicalTrials.gov number, NCT05506176.).

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