Background Nirmatrelvir/ritonavir (NMV/r) is an oral antiviral treatment for mild to moderate COVID-19. Methods This phase 2/3, double-blind, randomized (1:1) study assessed oral NMV/r 300 mg/100 mg versus placebo every 12 hours for 5 days in high-risk, unvaccinated, nonhospitalized, symptomatic adults with COVID-19 from 343 sites across 21 countries. In testing the primary endpoint of COVID-19‒related hospitalization and all-cause deaths and key secondary endpoints including symptom duration and COVID-19‒related medical visits, Type I error was controlled with prespecified sequential testing and the Hochberg procedure. Results Among 2113 randomized patients enrolled from July 2021 through December 2021, 1966 (NMV/r, n=977; placebo, n=989) were included in the prespecified analysis population (symptom onset ≤5 days, did not receive monoclonal antibodies). NMV/r significantly reduced times to sustained alleviation (median, 13 vs 15 days; hazard ratio [HR]=1.27, p<0.0001) and resolution (16 vs 19 days; HR=1.20, p=0.0022) through Day 28 and significantly reduced the number of COVID-19‒related medical visits and the proportion of patients with such visits. Hospitalized patients treated with NMV/r had shorter stays, none required ICU admission or mechanical ventilation, and all were discharged to home/self-care. Fewer NMV/r-treated patients required additional treatment for COVID-19. No NMV/r-treated patients died through Week 24 compared with 15 placebo-treated patients. Conclusions In addition to reducing COVID-19‒related hospitalization or death from any cause through Day 28, NMV/r was found to also reduce duration of COVID-19 symptoms and utilization of healthcare resources versus placebo in patients at high risk of progressing to severe disease. Clinical Trial Information ClinicalTrials.gov, NCT04960202, https://clinicaltrials.gov/study/NCT04960202

中文翻译：

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接受尼马曲韦/利托那韦 （NMV/R） 治疗的高危患者的 COVID-19 症状缓解和医疗保健利用率降低：一项 3 期随机试验


背景 尼马曲韦/利托那韦 （NMV/r） 是一种针对轻度至中度 COVID-19 的口服抗病毒治疗药物。方法 这项 2/3 期、双盲、随机 （1：1） 研究评估了来自 21 个国家/地区的 343 个地点的高危、未接种疫苗、非住院、有症状的 COVID-19 成人口服 NMV/r 300 mg/100 mg，每 12 小时一次，持续 5 天。在测试 COVID-19 相关住院和全因死亡的主要终点以及包括症状持续时间和 COVID-19 相关就诊在内的关键次要终点时，I 型错误通过预先指定的序贯检测和 Hochberg 程序得到控制。结果 在 2021 年 7 月至 2021 年 12 月入组的 2113 例随机患者中，1966 例 （NMV/r，n=977;安慰剂，n=989） 被纳入预先指定的分析人群 （症状发作 ≤5 天，未接受单克隆抗体）。NMV/r 显著缩短了持续缓解的时间 （中位数，13 天 vs 15 天;风险比 [HR]=1.27，p<0.0001）和分辨率 （16 天 vs 19 天;HR=1.20，p=0.0022）到第 28 天，并显着减少了与 COVID-19\u2012 相关的医疗就诊次数和此类就诊的患者比例。接受 NMV/r 治疗的住院患者住院时间较短，无需要入住 ICU 或机械通气，所有患者均出院回家/自我护理。需要额外治疗 COVID-19 的 NMV/r 治疗患者较少。与 15 名接受安慰剂治疗的患者相比，第 24 周没有 NMV/r 治疗患者死亡。结论除了在第 28 天之前减少与 COVID-19\u2012 相关的住院或任何原因死亡外，与安慰剂相比，NMV/r 还可以减少 COVID-19 症状的持续时间和医疗资源的利用对于进展为重症的高风险患者。 临床试验信息 ClinicalTrials.gov、NCT04960202 https://clinicaltrials。政府/学习/NCT04960202