Alleviation of COVID-19 Symptoms and Reduction in Healthcare Utilization Among High-Risk Patients Treated With Nirmatrelvir/Ritonavir (NMV/R): A phase 3 randomized trial

IF 8.2 1区医学 Q1 IMMUNOLOGY

Clinical Infectious Diseases Pub Date : 2024-11-11 DOI:10.1093/cid/ciae551

Jennifer Hammond, Heidi Leister-Tebbe, Annie Gardner, Paula Abreu, Weihang Bao, Wayne Wisemandle, Wajeeha Ansari, Magdalena Alicja Harrington, Abraham Simón-Campos, Kara W Chew, Rienk Pypstra, James M Rusnak

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引用次数: 0

Abstract

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

查看原文本刊更多论文

用尼马瑞韦/利托那韦（NMV/R）治疗高危患者可减轻 COVID-19 症状并减少医疗服务使用量：3期随机试验

背景 Nirmatrelvir/ritonavir（NMV/r）是一种口服抗病毒药物，可治疗轻度至中度 COVID-19。方法该 2/3 期双盲随机（1:1）研究评估了口服 NMV/r 300 毫克/100 毫克与安慰剂每 12 小时一次，连续 5 天的对比情况，研究对象是来自 21 个国家 343 个研究点的高风险、未接种疫苗、未住院、有症状的 COVID-19 成人患者。在检测与 COVID-19 相关的住院和全因死亡这一主要终点以及症状持续时间和与 COVID-19 相关的就诊次数等关键次要终点时，通过预设顺序检测和霍赫伯格程序控制了 I 类误差。结果在2021年7月至2021年12月期间入组的2113名随机患者中，1966人（NMV/r，977人；安慰剂，989人）被纳入预先指定的分析人群（症状发作时间≤5天，未接受单克隆抗体治疗）。NMV/r显著缩短了症状持续缓解（中位数，13天 vs 15天；危险比[HR]=1.27，p<0.0001）和缓解（16天 vs 19天；HR=1.20，p=0.0022）至第28天的时间，并显著减少了COVID-19相关就诊次数和就诊患者比例。接受NMV/r治疗的住院患者的住院时间更短，没有人需要住进重症监护室或进行机械通气，所有患者都能出院回家/自我护理。接受 NMV/r 治疗的患者中需要额外治疗 COVID-19 的人数较少。接受 NMV/r 治疗的患者在第 24 周内没有死亡，而接受安慰剂治疗的患者则有 15 例死亡。结论 NMV/r与安慰剂相比，除了能减少第28天COVID-19相关的住院或任何原因导致的死亡，还能缩短COVID-19症状持续时间，减少高危重症患者对医疗资源的使用。临床试验信息 ClinicalTrials.gov, NCT04960202, https://clinicaltrials.gov/study/NCT04960202

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来源期刊

Clinical Infectious Diseases 医学-传染病学

CiteScore

25.00

自引率

2.50%

发文量

900

审稿时长

3 months

期刊介绍： Clinical Infectious Diseases (CID) is dedicated to publishing original research, reviews, guidelines, and perspectives with the potential to reshape clinical practice, providing clinicians with valuable insights for patient care. CID comprehensively addresses the clinical presentation, diagnosis, treatment, and prevention of a wide spectrum of infectious diseases. The journal places a high priority on the assessment of current and innovative treatments, microbiology, immunology, and policies, ensuring relevance to patient care in its commitment to advancing the field of infectious diseases.