Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients.
Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients.
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DOI：
10.1056/nejmoa2116044
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发表时间：
2022-02-10
期刊：
影响因子：
--
通讯作者：
MOVe-OUT Study Group
中科院分区：
文献类型：
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作者：
Jayk Bernal A;Gomes da Silva MM;Musungaie DB;Kovalchuk E;Gonzalez A;Delos Reyes V;Martín-Quirós A;Caraco Y;Williams-Diaz A;Brown ML;Du J;Pedley A;Assaid C;Strizki J;Grobler JA;Shamsuddin HH;Tipping R;Wan H;Paschke A;Butterton JR;Johnson MG;De Anda C;MOVe-OUT Study Group
需要新的治疗方法来降低2019冠状病毒病（Covid-19）进展的风险。莫努匹韦是一种口服小分子抗病毒前药，对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）有活性。我们进行了一项III期、双盲、随机、安慰剂对照试验，以评估在症状或体征发作后5天内开始莫努匹韦治疗的疗效和安全性，该试验针对的是未住院、未接种疫苗的轻度至中度、实验室确诊的Covid-19成人，且至少有一个严重Covid-19疾病的风险因素。试验参与者被随机分配接受800 mg的莫努匹韦或安慰剂，每天两次，持续5天。主要疗效终点是第29天住院或死亡的发生率;不良事件的发生率是主要安全性终点。当1550例受试者（目标入组）中有50%的受试者随访至第29天时，进行计划的中期分析。共有1433名参与者接受随机分组; 716人被分配接受莫努匹拉韦治疗，717人接受安慰剂治疗。除了性别不平衡外，两组的基线特征相似。中期分析证实了莫努匹拉韦的优越性;莫努匹拉韦组（385名参与者中的28名[7.3%]）因任何原因住院或死亡的风险低于安慰剂组（377名参与者中的53名[14.1%]）（差异，-6.8个百分点; 95%置信区间，-11.3至-2.4; P=0.001）。在对所有接受随机分组的受试者的分析中，莫努匹韦组住院或死亡的受试者百分比低于安慰剂组（6.8% [48/709] vs. 9.7% [68/699];差异，-3.0个百分点; 95%置信区间，-5.9至-0.1）。亚组分析的结果在很大程度上与这些总体结果一致;在一些亚组中，如有既往SARS-CoV-2感染证据的患者，基线病毒载量低的患者和糖尿病患者，差异的点估计值有利于安慰剂。截至第29天，莫努匹韦组报告了1例死亡，安慰剂组报告了9例死亡。莫努匹韦组710名参与者中有216名（30.4%）报告了不良事件，安慰剂组701名参与者中有231名（33.0%）报告了不良事件。莫努匹拉韦的早期治疗降低了未接种疫苗的高风险成年人的住院或死亡风险。（由Merck Sharp和Dohme资助; MOVe-OUT ClinicalTrials.gov编号，NCT 04575597。）
New treatments are needed to reduce the risk of progression of coronavirus disease 2019 (Covid-19). Molnupiravir is an oral, small-molecule antiviral prodrug that is active against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We conducted a phase 3, double-blind, randomized, placebo-controlled trial to evaluate the efficacy and safety of treatment with molnupiravir started within 5 days after the onset of signs or symptoms in nonhospitalized, unvaccinated adults with mild-to-moderate, laboratory-confirmed Covid-19 and at least one risk factor for severe Covid-19 illness. Participants in the trial were randomly assigned to receive 800 mg of molnupiravir or placebo twice daily for 5 days. The primary efficacy end point was the incidence hospitalization or death at day 29; the incidence of adverse events was the primary safety end point. A planned interim analysis was performed when 50% of 1550 participants (target enrollment) had been followed through day 29. A total of 1433 participants underwent randomization; 716 were assigned to receive molnupiravir and 717 to receive placebo. With the exception of an imbalance in sex, baseline characteristics were similar in the two groups. The superiority of molnupiravir was demonstrated at the interim analysis; the risk of hospitalization for any cause or death through day 29 was lower with molnupiravir (28 of 385 participants [7.3%]) than with placebo (53 of 377 [14.1%]) (difference, −6.8 percentage points; 95% confidence interval, −11.3 to −2.4; P=0.001). In the analysis of all participants who had undergone randomization, the percentage of participants who were hospitalized or died through day 29 was lower in the molnupiravir group than in the placebo group (6.8% [48 of 709] vs. 9.7% [68 of 699]; difference, −3.0 percentage points; 95% confidence interval, −5.9 to −0.1). Results of subgroup analyses were largely consistent with these overall results; in some subgroups, such as patients with evidence of previous SARS-CoV-2 infection, those with low baseline viral load, and those with diabetes, the point estimate for the difference favored placebo. One death was reported in the molnupiravir group and 9 were reported in the placebo group through day 29. Adverse events were reported in 216 of 710 participants (30.4%) in the molnupiravir group and 231 of 701 (33.0%) in the placebo group. Early treatment with molnupiravir reduced the risk of hospitalization or death in at-risk, unvaccinated adults with Covid-19. (Funded by Merck Sharp and Dohme; MOVe-OUT ClinicalTrials.gov number, NCT04575597.)
影响因子：
4.2
作者：
Pogue JM;Lauring AS;Gandhi TN;Marshall VD;Eschenauer GA;Nagel JL;Baang JH;Zhou S;Valesano AL;Petty LA
通讯作者：
Petty LA