Effect of Remdesivir vs Standard Care on Clinical Status at 11 Days in Patients With Moderate COVID-19 A Randomized Clinical Trial
Effect of Remdesivir vs Standard Care on Clinical Status at 11 Days in Patients With Moderate COVID-19 A Randomized Clinical Trial
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DOI：
10.1001/jama.2020.16349
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发表时间：
2020-09-15
影响因子：
120.7
通讯作者：
Marty, Francisco M.
中科院分区：
文献类型：
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作者：
Spinner, Christoph D.;Gottlieb, Robert L.;Marty, Francisco M.
Remdesivir在严重冠状病毒病患者的安慰剂对照试验中显示出临床获益2019（COVID-19），但其在中度疾病患者中的效果尚不清楚。目的确定5天或10天的瑞德西韦治疗与标准治疗相比对治疗开始后第11天临床状态的疗效。设计，设置和参与者随机，一项针对确诊严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）感染和中度COVID-19肺炎（肺浸润和室内空气氧饱和度>94%）住院患者的开放标签试验，于2020年3月15日至4月18日在美国、欧洲和亚洲的105家医院入组。最终随访日期为2020年5月20日。干预患者以1：1：1的比例随机接受10天疗程的remdesivir（n = 197），5天疗程的remdesivir（n = 199）或标准治疗（n = 200）。Remdesivir在第1天以200 mg静脉内给药，随后以100 mg/d给药。主要结果和测量主要终点是第11天的临床状态，在7点顺序量表上，从死亡（类别1）到出院（类别7）。使用比例优势模型计算Remdesivir治疗组和标准治疗组之间的差异，并表示为优势比。比值比大于1表示Remdesivir组与标准治疗组的临床状态分布差异朝向第7类。结果在596名随机分组的患者中，584名开始研究并接受Remdesivir或继续标准治疗（中位年龄，57 [四分位距，46-66]岁; 227 [39%]女性; 56%患有心血管疾病，42%患有高血压，40%患有糖尿病），533（91%）人完成了试验。5天Remdesivir组患者的中位治疗时间为5天，10天Remdesivir组患者的中位治疗时间为6天。在第11天，5天Remdesivir组的患者比接受标准治疗的患者具有统计学显著更高的临床状态分布优势（优势比，1.65; 95%CI，1.09-2.48; P = 0.02）。10天Remdesivir组和标准治疗组之间第11天的临床状态分布没有显著差异（Wilcoxon秩和检验P = 0.18）。到第28天，9名患者死亡：5天remdesivir组2名（1%），10天remdesivir组3名（2%），标准治疗组4名（2%）。恶心（10% vs 3%），低钾血症（6%对2%），头痛（5%对3%）更常见于Remdesivir治疗的患者与标准治疗相比。那些被随机分配到10-治疗开始后11天，与标准治疗相比，治疗随机分配至5天疗程的患者与标准治疗相比，其临床状态存在统计学显著差异，但该差异的临床重要性尚不确定。
IMPORTANCE Remdesivir demonstrated clinical benefit in a placebo-controlled trial in patients with severe coronavirus disease 2019 (COVID-19), but its effect in patients with moderate disease is unknown.OBJECTIVE To determine the efficacy of 5 or 10 days of remdesivir treatment compared with standard care on clinical status on day 11 after initiation of treatment.DESIGN, SETTING, AND PARTICIPANTS Randomized, open-label trial of hospitalized patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and moderate COVID-19 pneumonia (pulmonary infiltrates and room-air oxygen saturation >94%) enrolled from March 15 through April 18, 2020, at 105 hospitals in the United States, Europe, and Asia. The date of final follow-up was May 20, 2020.INTERVENTIONS Patients were randomized in a 1:1:1 ratio to receive a 10-day course of remdesivir (n = 197), a 5-day course of remdesivir (n = 199), or standard care (n = 200). Remdesivir was dosed intravenously at 200 mg on day 1 followed by 100 mg/d.MAIN OUTCOMES AND MEASURES The primary end point was clinical status on day 11 on a 7-point ordinal scale ranging from death (category 1) to discharged (category 7). Differences between remdesivir treatment groups and standard care were calculated using proportional odds models and expressed as odds ratios. An odds ratio greater than 1 indicates difference in clinical status distribution toward category 7 for the remdesivir group vs the standard care group.RESULTS Among 596 patients who were randomized, 584 began the study and received remdesivir or continued standard care (median age, 57 [interquartile range, 46-66] years; 227 [39%] women; 56% had cardiovascular disease, 42% hypertension, and 40% diabetes), and 533 (91%) completed the trial. Median length of treatment was 5 days for patients in the 5-day remdesivir group and 6 days for patients in the 10-day remdesivir group. On day 11, patients in the 5-day remdesivir group had statistically significantly higher odds of a better clinical status distribution than those receiving standard care (odds ratio, 1.65; 95% CI, 1.09-2.48; P =.02). The clinical status distribution on day 11 between the 10-day remdesivir and standard care groups was not significantly different (P =.18 by Wilcoxon rank sum test). By day 28, 9 patients had died: 2 (1%) in the 5-day remdesivir group, 3 (2%) in the 10-day remdesivir group, and 4 (2%) in the standard care group. Nausea (10% vs 3%), hypokalemia (6% vs 2%), and headache (5% vs 3%) were more frequent among remdesivir-treated patients compared with standard care.CONCLUSIONS AND RELEVANCE Among patients with moderate COVID-19, those randomized to a 10-day course of remdesivir did not have a statistically significant difference in clinical status compared with standard care at 11 days after initiation of treatment. Patients randomized to a 5-day course of remdesivir had a statistically significant difference in clinical status compared with standard care, but the difference was of uncertain clinical importance.