美国吉利德科学公司Diana M. Brainard团队研究了瑞德西韦与标准治疗对中症COVID-19患者第11天临床状态的影响。2020年8月21日，该成果发表在《美国医学会杂志》上。

瑞德西韦在COVID-19患者的安慰剂对照试验中证明有临床益处，但在中症患者中的作用尚不清楚。

为了确定与标准治疗相比，在治疗后的第11天，瑞德西韦治疗5天或10天的临床改善程度，2020年3月15日至4月18日，研究组在美国、欧洲和亚洲的105家医院进行了一项随机、开放标签试验，招募了596名确诊为SARS-CoV-2感染和中度COVID-19肺炎（肺部浸润，室内空气血氧饱和度> 94%）的患者。将其按1：1随机分组，其中197名接受10天疗程的瑞德西韦，199名接受5天疗程的瑞德西韦，200名接受标准治疗。主要终点是第11天的临床状态，从死亡（1级）到出院（7级）分为7个等级。

共有584名参与者接受瑞德昔韦或标准治疗，中位年龄为57岁，女性占39%，心血管疾病患者占42％，高血压患者占42%，糖尿病患者占40％，共有533名（91%）完成了试验。瑞德西韦5天组的患者中位治疗时间为5天，而10天组的患者中位治疗时间为6天。在第11天，与接受标准治疗的患者相比，瑞德西韦5天组的患者具有更好的临床状态，差异显著。但瑞德西韦10天组与标准治疗相比无显著差异。

到第28天，参与者中共有9名患者死亡：瑞德西韦5天组有2例（1％），瑞德西韦10天组有3例（2％），标准治疗组有4例（2％）。与标准治疗相比，接受瑞德西韦治疗的患者中恶心（10％与3％）、低钾血症（6％与2％）和头痛（5％与3％）的发生率更高。

研究结果表明，对于中症COVID-19患者，瑞德西韦5天疗程与标准治疗相比，第11天时的临床状态得以显著改善，但瑞德西韦10天疗程的改善并不显著。

附：英文原文

Title: Effect of Remdesivir vs Standard Care on Clinical Status at 11 Days in Patients With Moderate COVID-19: A Randomized Clinical Trial

Author: Christoph D. Spinner, Robert L. Gottlieb, Gerard J. Criner, José Ramón Arribas López, Anna Maria Cattelan, Alex Soriano Viladomiu, Onyema Ogbuagu, Prashant Malhotra, Kathleen M. Mullane, Antonella Castagna, Louis Yi Ann Chai, Meta Roestenberg, Owen Tak Yin Tsang, Enos Bernasconi, Paul Le Turnier, Shan-Chwen Chang, Devi SenGupta, Robert H. Hyland, Anu O. Osinusi, Huyen Cao, Christiana Blair, Hongyuan Wang, Anuj Gaggar, Diana M. Brainard, Mark J. McPhail, Sanjay Bhagani, Mi Young Ahn, Arun J. Sanyal, Gregory Huhn, Francisco M. Marty

Issue&Volume: 2020-08-21

Abstract:

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.

DOI: 10.1001/jama.2020.16349

Source: https://jamanetwork.com/journals/jama/fullarticle/2769871