From the Swedish Center for Research and Innovation, Swedish Medical Center, and the University of Washington, Seattle (J.D.G.), and Providence Regional Medical Center, Everett (G.D.) - both in Washington; the National Center for Infectious Diseases, Lee Kong Chian School of Medicine, Tan Tock Seng Hospital, Singapore (D.C.B.L.); the Chinese University of Hong Kong-Prince of Wales Hospital, Hong Kong (D.S.H.); New York-Presbyterian Hospital and Weill Cornell Medicine, New York (K.M. Marks); Malattie Infettive Fondazione IRCCS Policlinico San Matteo, Pavia-Università di Pavia, Pavia (R.B.), and Università di Milano, Department of Biomedical and Clinical Sciences, L. Sacco Infectious Diseases Unit, ASST Fatebenefratelli Sacco, Milan (M.G.) - both in Italy; Hospital Universitario La Paz, IdiPAZ, Madrid (R.M.), and Barcelona Institute for Global Health (ISGlobal) Hospital Clínic-Universitat de Barcelona, Barcelona (J.M.); Technical University of Munich, School of Medicine, University Hospital rechts der Isar, Munich, Germany (C.D.S.); Seoul Medical Center, Seoul, South Korea (M.-Y.A.); ID Care, Hillsborough, and Robert Wood Johnson University Hospital Somerset, Somerville - both in New Jersey (R.G.N.); Kaohsiung Veterans General Hospital, Taiwan (Y.-S.C.); Gilead Sciences, Foster City (D.S., R.H.H., A.O.O., H.C., C.B., X.W., A.G., D.M.B.), Kaiser Permanente, Los Angeles (W.J.T.), and Stanford University, Palo Alto (A.S.) - all in California; University of Chicago, Chicago (K.M. Mullane); Brigham and Women's Hospital and Harvard Medical School, Boston (F.M.M.); and Miriam Hospital, Warren Alpert Medical School of Brown University, Providence, RI (K.T.T.).
N Engl J Med. 2020 Nov 5;383(19):1827-1837. doi: 10.1056/NEJMoa2015301. Epub 2020 May 27.
Remdesivir is an RNA polymerase inhibitor with potent antiviral activity in vitro and efficacy in animal models of coronavirus disease 2019 (Covid-19).
We conducted a randomized, open-label, phase 3 trial involving hospitalized patients with confirmed SARS-CoV-2 infection, oxygen saturation of 94% or less while they were breathing ambient air, and radiologic evidence of pneumonia. Patients were randomly assigned in a 1:1 ratio to receive intravenous remdesivir for either 5 days or 10 days. All patients received 200 mg of remdesivir on day 1 and 100 mg once daily on subsequent days. The primary end point was clinical status on day 14, assessed on a 7-point ordinal scale.
In total, 397 patients underwent randomization and began treatment (200 patients for 5 days and 197 for 10 days). The median duration of treatment was 5 days (interquartile range, 5 to 5) in the 5-day group and 9 days (interquartile range, 5 to 10) in the 10-day group. At baseline, patients randomly assigned to the 10-day group had significantly worse clinical status than those assigned to the 5-day group (P = 0.02). By day 14, a clinical improvement of 2 points or more on the ordinal scale occurred in 64% of patients in the 5-day group and in 54% in the 10-day group. After adjustment for baseline clinical status, patients in the 10-day group had a distribution in clinical status at day 14 that was similar to that among patients in the 5-day group (P = 0.14). The most common adverse events were nausea (9% of patients), worsening respiratory failure (8%), elevated alanine aminotransferase level (7%), and constipation (7%).
In patients with severe Covid-19 not requiring mechanical ventilation, our trial did not show a significant difference between a 5-day course and a 10-day course of remdesivir. With no placebo control, however, the magnitude of benefit cannot be determined. (Funded by Gilead Sciences; GS-US-540-5773 ClinicalTrials.gov number, NCT04292899.).
瑞德西韦是一种 RNA 聚合酶抑制剂，具有体外抗病毒活性和治疗 2019 年冠状病毒病（COVID-19）动物模型的疗效。
我们进行了一项随机、开放标签、3 期临床试验，纳入了住院的、经确认感染 SARS-CoV-2 的患者，这些患者在呼吸环境空气时的血氧饱和度为 94%或更低，且影像学证据显示有肺炎。患者以 1:1 的比例随机分配，接受静脉注射瑞德西韦 5 天或 10 天的治疗。所有患者在第 1 天接受 200mg 瑞德西韦，随后每天接受 100mg。主要终点为第 14 天的临床状态，采用 7 分序贯量表评估。
共有 397 名患者接受了随机分组并开始治疗（200 名患者接受 5 天治疗，197 名患者接受 10 天治疗）。5 天组的中位治疗时间为 5 天（四分位距，5 至 5），10 天组的中位治疗时间为 9 天（四分位距，5 至 10）。基线时，随机分配到 10 天组的患者临床状态明显比分配到 5 天组的患者差（P=0.02）。到第 14 天，5 天组中有 64%的患者和 10 天组中有 54%的患者的序贯量表上的临床改善达到 2 分或以上。在调整基线临床状态后，10 天组患者第 14 天的临床状态分布与 5 天组患者相似（P=0.14）。最常见的不良事件是恶心（9%的患者）、呼吸衰竭恶化（8%）、丙氨酸氨基转移酶水平升高（7%）和便秘（7%）。
在不需要机械通气的重症 COVID-19 患者中，我们的试验未显示瑞德西韦 5 天疗程与 10 天疗程之间有显著差异。由于没有安慰剂对照，因此无法确定获益的幅度。（由吉利德科学公司资助；GS-US-540-5773 ClinicalTrials.gov 编号，NCT04292899。）
