美国吉利德科学公司Diana M. Brainard团队比较了瑞德西韦治疗Covid-19重症患者5或10天的疗效。该成果发表在2020年5月27日出版的《新英格兰医学杂志》上。

瑞德西韦是一种RNA聚合酶抑制剂，在体外具有强大的抗病毒活性，在Covid-19动物模型中疗效较好。

研究组进行了一项随机、开放标签的3期临床试验，招募了397例已确诊SARS-CoV-2感染的住院患者，这些患者呼吸室内空气时血氧饱和度低于94％，且伴有影像学确定的肺炎。将其按1：1随机分组，其中200例接受瑞德西韦静脉注射5天，197例接受瑞德西韦静注10天。

5天组的中位治疗时间为5天，而10天组为9天。10天组患者的基线临床状况明显差于5天组的患者。到第14天，5天组中有64％，10天组中有54％的患者在7分顺序量表中临床改善超过2分。校正基线临床状态后，10天组患者在第14天的临床状态分布与5天组患者相差不大。最常见的不良事件是恶心（发生率为9％）、呼吸衰竭加重（8％）、丙氨酸转氨酶水平升高（7％）和便秘（7％）。

总之，在重症Covid-19且不需要机械通气的患者中，瑞德西韦5天疗程和10天疗程间的疗效无显著差异。

附：英文原文

Title: Remdesivir for 5 or 10 Days in Patients with Severe Covid-19

Author: Jason D. Goldman, M.D., M.P.H.,, David C.B. Lye, M.B., B.S.,, David S. Hui, M.D.,, Kristen M. Marks, M.D.,, Raffaele Bruno, M.D.,, Rocio Montejano, M.D.,, Christoph D. Spinner, M.D.,, Massimo Galli, M.D.,, Mi-Young Ahn, M.D.,, Ronald G. Nahass, M.D.,, Yao-Shen Chen, M.D.,, Devi SenGupta, M.D.,, Robert H. Hyland, D.Phil.,, Anu O. Osinusi, M.D.,, Huyen Cao, M.D.,, Christiana Blair, M.S.,, Xuelian Wei, Ph.D.,, Anuj Gaggar, M.D., Ph.D.,, Diana M. Brainard, M.D.,, William J. Towner, M.D.,, Jose Muoz, M.D.,, Kathleen M. Mullane, D.O., Pharm.D.,, Francisco M. Marty, M.D.,, Karen T. Tashima, M.D.,, George Diaz, M.D.,, and Aruna Subramanian, M.D.

Issue&Volume: 2020-05-27

Abstract: BACKGROUND

Remdesivir is an RNA polymerase inhibitor with potent antiviral activity in vitro and efficacy in animal models of coronavirus disease 2019 (Covid-19).

METHODS

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.

RESULTS

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%).

CONCLUSIONS

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.

DOI: 10.1056/NEJMoa2015301

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2015301