Remdesivir for 5 or 10 Days in Patients with Severe Covid-19
Remdesivir for 5 or 10 Days in Patients with Severe Covid-19
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DOI：
10.1056/nejmoa2015301
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发表时间：
2020-11-05
影响因子：
158.5
通讯作者：
Subramanian, Aruna
中科院分区：
文献类型：
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作者：
Goldman, Jason D.;Lye, David C. B.;Subramanian, Aruna
背景Remdesivir是一种RNA聚合酶抑制剂，在体外具有有效的抗病毒活性，在2019冠状病毒病（Covid-19）动物模型中有效。MethodsWe进行了一项随机、开放标签、3期试验，涉及确诊SARS-CoV-2感染的住院患者，呼吸环境空气时血氧饱和度为94%或更低，并有肺炎的放射学证据。患者以1：1的比例随机分配接受静脉注射Remdesivir 5天或10天。所有患者在第1天接受200 mg remdesivir，在随后的几天每天接受100 mg remdesivir。主要终点是第14天的临床状态，在一个7点顺序scale.ResultsIn总，397例患者进行随机分组，并开始治疗（200例患者为5天，197为10天）进行评估。5天组的中位治疗持续时间为5天（四分位距，5 - 5），10天组为9天（四分位距，5 - 10）。在基线时，随机分配到10天组的患者的临床状态显著差于分配到5天组的患者（P=0.02）。到第14天，5天组中64%的患者和10天组中54%的患者在顺序量表上出现2分或以上的临床改善。校正基线临床状态后，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%）。然而，由于没有安慰剂对照，无法确定获益的程度。（由吉利德科学公司资助; GS-US-540-5773 ClinicalTrials.gov编号，NCT 04292899。）一项在尚未接受机械通气的新型冠状病毒肺炎和低氧血症患者中比较静脉注射Remdesivir 5天疗程与10天疗程的随机试验显示，与治疗持续时间相关的结局无显著差异。
BackgroundRemdesivir is an RNA polymerase inhibitor with potent antiviral activity in vitro and efficacy in animal models of coronavirus disease 2019 (Covid-19).MethodsWe 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.ResultsIn 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%).ConclusionsIn 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.)A randomized trial comparing a 5-day course of intravenous remdesivir with a 10-day course in patients with Covid-19 pneumonia and hypoxemia who were not yet receiving mechanical ventilation showed no significant differences in outcome related to the duration of treatment.