COVID-19 患者早期使用伊维菌素治疗的效果。

Effect of Early Treatment with Ivermectin among Patients with Covid-19.

机构信息

From the Research Division, Cardresearch-Cardiologia Assistencial e de Pesquisa (G.R., E.A.S.M.S., D.C.M.S., T.S.F., C.V.Q.S., V.H.S.C., M.I.C.S., L.B.R., R.O.), and the Department of Medicine, Pontifical Catholic University of Minas Gerais (G.R., E.A.S.M.S., D.C.M.S., C.V.Q.S., V.H.S.C.), Belo Horizonte, the Department of Public Health and Mental and Family Medicine, Ouro Preto Federal University, Ouro Preto (A.C.M., L.C.M.S.), the Public Health Care Division, Ibirité (A.C.M.), the Department of Public Health and the Family Medicine Fellowship Program, UNIFIPMoc, Montes Claros (A.M.R.N., A.P.F.G.A.), the Public Health Care Division, Brumadinho (E.D.C.), and the Public Health Fellowship Program, Governador Valadares Public Health Authority, Governador Valadares (A.D.F.N.) - all in Brazil; the Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON (L.T., S.S., P.M., G.H.G., E.J.M.), and Cytel (O.H., H.R., E.J.M.) and Platform Life Sciences (J.I.F., C.M.G., E.J.M.), Vancouver, BC - all in Canada; Certara, Princeton, NJ (K.R.-Y., C.R.R.); the Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis (D.R.B.); and Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, VIC, Australia (C.R.R.).

出版信息

N Engl J Med. 2022 May 5;386(18):1721-1731. doi: 10.1056/NEJMoa2115869. Epub 2022 Mar 30.

DOI:10.1056/NEJMoa2115869

PMID:35353979

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9006771/

Abstract

BACKGROUND

The efficacy of ivermectin in preventing hospitalization or extended observation in an emergency setting among outpatients with acutely symptomatic coronavirus disease 2019 (Covid-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is unclear.

METHODS

We conducted a double-blind, randomized, placebo-controlled, adaptive platform trial involving symptomatic SARS-CoV-2-positive adults recruited from 12 public health clinics in Brazil. Patients who had had symptoms of Covid-19 for up to 7 days and had at least one risk factor for disease progression were randomly assigned to receive ivermectin (400 μg per kilogram of body weight) once daily for 3 days or placebo. (The trial also involved other interventions that are not reported here.) The primary composite outcome was hospitalization due to Covid-19 within 28 days after randomization or an emergency department visit due to clinical worsening of Covid-19 (defined as the participant remaining under observation for >6 hours) within 28 days after randomization.

RESULTS

A total of 3515 patients were randomly assigned to receive ivermectin (679 patients), placebo (679), or another intervention (2157). Overall, 100 patients (14.7%) in the ivermectin group had a primary-outcome event, as compared with 111 (16.3%) in the placebo group (relative risk, 0.90; 95% Bayesian credible interval, 0.70 to 1.16). Of the 211 primary-outcome events, 171 (81.0%) were hospital admissions. Findings were similar to the primary analysis in a modified intention-to-treat analysis that included only patients who received at least one dose of ivermectin or placebo (relative risk, 0.89; 95% Bayesian credible interval, 0.69 to 1.15) and in a per-protocol analysis that included only patients who reported 100% adherence to the assigned regimen (relative risk, 0.94; 95% Bayesian credible interval, 0.67 to 1.35). There were no significant effects of ivermectin use on secondary outcomes or adverse events.

CONCLUSIONS

Treatment with ivermectin did not result in a lower incidence of medical admission to a hospital due to progression of Covid-19 or of prolonged emergency department observation among outpatients with an early diagnosis of Covid-19. (Funded by FastGrants and the Rainwater Charitable Foundation; TOGETHER ClinicalTrials.gov number, NCT04727424.).

摘要

背景

伊维菌素在预防因急性症状性 2019 年冠状病毒病（COVID-19）而住院或在急诊环境中延长观察时间方面的疗效在门诊 SARS-CoV-2 阳性成年人中尚不清楚，这种疾病是由严重急性呼吸系统综合症冠状病毒 2（SARS-CoV-2）引起的。

方法

我们进行了一项双盲、随机、安慰剂对照、适应性平台试验，涉及从巴西 12 个公共卫生诊所招募的有症状的 SARS-CoV-2 阳性成年人。症状出现 COVID-19 不超过 7 天且有疾病进展至少一个风险因素的患者被随机分配接受伊维菌素（400μg/公斤体重），每日一次，连续 3 天，或安慰剂。（试验还涉及此处未报告的其他干预措施。）主要复合结局是随机分组后 28 天内因 COVID-19 住院或随机分组后 28 天内因 COVID-19 临床恶化（定义为参与者仍需观察 >6 小时）而到急诊就诊。

结果

共有 3515 名患者被随机分配接受伊维菌素（679 名患者）、安慰剂（679 名患者）或其他干预措施（2157 名患者）。总体而言，伊维菌素组有 100 名患者（14.7%）发生主要结局事件，而安慰剂组有 111 名患者（16.3%）（相对风险，0.90；95%贝叶斯可信区间，0.70 至 1.16）。211 例主要结局事件中，171 例（81.0%）为住院治疗。在一项仅包括至少接受一次伊维菌素或安慰剂治疗的患者的改良意向治疗分析中，发现结果与主要分析相似（相对风险，0.89；95%贝叶斯可信区间，0.69 至 1.15），在一项仅包括报告 100%依从性的方案分析中，发现结果也与主要分析相似（相对风险，0.94；95%贝叶斯可信区间，0.67 至 1.35）。伊维菌素使用对次要结局或不良事件没有显著影响。