瑞德西韦治疗 COVID-19 的疗效 - 最终报告。

Remdesivir for the Treatment of Covid-19 - Final Report.

机构信息

From the National Institute of Allergy and Infectious Diseases, National Institutes of Health (J.H.B., K.M.T., L.E.D., S.N., H.C.L.), and the Infectious Disease Clinical Research Program, Uniformed Services University of the Health Sciences (T.H.B.), Bethesda, the Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research, Frederick (T. Bonnett), and Emmes, Rockville (M.G., M.M.) - all in Maryland; Emory University, Atlanta (A.K.M.); Montefiore Medical Center-Albert Einstein College of Medicine (B.S.Z.) and NYU Langone Health and NYC Health and Hospitals-Bellevue (K.D.), New York; University of Nebraska Medical Center, Omaha (A.C.K., M.G.K.); Massachusetts General Hospital, Boston (E.H.), and University of Massachusetts Medical School, Worcester (R.W.F.); University of Washington, Seattle (H.Y.C.), and Evergreen Health Medical Center, Kirkland (D.L.C.) - both in Washington; University of California, San Francisco, San Francisco (A.L.), Cedars-Sinai Medical Center, Los Angeles (V.T.), University of California, Irvine, Irvine (L.H.), University of California, San Diego, La Jolla (D.A.S.), and Gilead Sciences, Foster City (A.O.) - all in California; University of Minnesota (S.K.) and University of Minnesota School of Public Health and INSIGHT (J.D.N.), Minneapolis; University of Texas Health San Antonio, University Health System, and the South Texas Veterans Health Care System, San Antonio (T.F.P.), and Baylor College of Medicine, Houston (R.L.A.); Hospital Germans Trias i Pujol and irsiCaixa AIDS Research Institute, Badalona, Spain (R.P.); University of Pennsylvania, Philadelphia (W.R.S.); Medical School, National and Kapodistrian University of Athens, Athens (G.T.); National Center for Infectious Diseases-Tan Tock Seng Hospital-Lee Kong Chian School of Medicine-Yong Loo Lin School of Medicine, Singapore, Singapore (D.C.L.); the National Center for Global Health and Medicine Hospital, Tokyo (N.O.); Seoul National University Hospital, Seoul, South Korea (M.O.); Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City (G.M.R.-P.); the Department of Infectious Diseases, Amager Hvidovre Hospital-University of Copenhagen, Hvidovre (T. Benfield), and Rigshospitalet, Department of Infectious Diseases (CHIP) and INSIGHT, Copenhagen (J.L.) - both in Denmark; University Hospital of Cologne, Cologne, Germany (G.F.); Vanderbilt University Medical Center, Nashville (C.B.C.); and University College London, MRC Clinical Trials Unit at UCL and INSIGHT, London (A.G.B., S.P.).

出版信息

N Engl J Med. 2020 Nov 5;383(19):1813-1826. doi: 10.1056/NEJMoa2007764. Epub 2020 Oct 8.

DOI:10.1056/NEJMoa2007764

PMID:32445440

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7262788/

Abstract

BACKGROUND

Although several therapeutic agents have been evaluated for the treatment of coronavirus disease 2019 (Covid-19), no antiviral agents have yet been shown to be efficacious.

METHODS

We conducted a double-blind, randomized, placebo-controlled trial of intravenous remdesivir in adults who were hospitalized with Covid-19 and had evidence of lower respiratory tract infection. Patients were randomly assigned to receive either remdesivir (200 mg loading dose on day 1, followed by 100 mg daily for up to 9 additional days) or placebo for up to 10 days. The primary outcome was the time to recovery, defined by either discharge from the hospital or hospitalization for infection-control purposes only.

RESULTS

A total of 1062 patients underwent randomization (with 541 assigned to remdesivir and 521 to placebo). Those who received remdesivir had a median recovery time of 10 days (95% confidence interval [CI], 9 to 11), as compared with 15 days (95% CI, 13 to 18) among those who received placebo (rate ratio for recovery, 1.29; 95% CI, 1.12 to 1.49; P<0.001, by a log-rank test). In an analysis that used a proportional-odds model with an eight-category ordinal scale, the patients who received remdesivir were found to be more likely than those who received placebo to have clinical improvement at day 15 (odds ratio, 1.5; 95% CI, 1.2 to 1.9, after adjustment for actual disease severity). The Kaplan-Meier estimates of mortality were 6.7% with remdesivir and 11.9% with placebo by day 15 and 11.4% with remdesivir and 15.2% with placebo by day 29 (hazard ratio, 0.73; 95% CI, 0.52 to 1.03). Serious adverse events were reported in 131 of the 532 patients who received remdesivir (24.6%) and in 163 of the 516 patients who received placebo (31.6%).

CONCLUSIONS

Our data show that remdesivir was superior to placebo in shortening the time to recovery in adults who were hospitalized with Covid-19 and had evidence of lower respiratory tract infection. (Funded by the National Institute of Allergy and Infectious Diseases and others; ACTT-1 ClinicalTrials.gov number, NCT04280705.).

摘要

背景

尽管已经评估了几种治疗药物来治疗 2019 年冠状病毒病（Covid-19），但尚无有效的抗病毒药物。

方法

我们对因 Covid-19 住院且有下呼吸道感染证据的成年人进行了一项双盲、随机、安慰剂对照的静脉注射瑞德西韦试验。患者被随机分配接受瑞德西韦（第 1 天 200mg 负荷剂量，随后 100mg 每日，最多 9 天）或安慰剂治疗，最长 10 天。主要结局是通过出院或仅为感染控制目的住院来定义的恢复时间。

结果

共有 1062 名患者接受了随机分组（541 名接受瑞德西韦治疗，521 名接受安慰剂治疗）。接受瑞德西韦治疗的患者中位恢复时间为 10 天（95%置信区间[CI]，9 至 11），而接受安慰剂治疗的患者为 15 天（95%CI，13 至 18）（恢复率比为 1.29；95%CI，1.12 至 1.49；P<0.001，对数秩检验）。在使用具有 8 个类别有序刻度的比例优势模型进行的分析中，与接受安慰剂的患者相比，接受瑞德西韦治疗的患者在第 15 天更有可能出现临床改善（比值比，1.5；95%CI，1.2 至 1.9，在考虑实际疾病严重程度后调整）。第 15 天，瑞德西韦组死亡率为 6.7%，安慰剂组为 11.9%；第 29 天，瑞德西韦组死亡率为 11.4%，安慰剂组为 15.2%（风险比，0.73；95%CI，0.52 至 1.03）。接受瑞德西韦治疗的 532 名患者中有 131 名（24.6%）和接受安慰剂治疗的 516 名患者中有 163 名（31.6%）报告了严重不良事件。