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Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial.
Wang, Yeming; Zhang, Dingyu; Du, Guanhua; Du, Ronghui; Zhao, Jianping; Jin, Yang; Fu, Shouzhi; Gao, Ling; Cheng, Zhenshun; Lu, Qiaofa; Hu, Yi; Luo, Guangwei; Wang, Ke; Lu, Yang; Li, Huadong; Wang, Shuzhen; Ruan, Shunan; Yang, Chengqing; Mei, Chunlin; Wang, Yi; Ding, Dan; Wu, Feng; Tang, Xin; Ye, Xianzhi; Ye, Yingchun; Liu, Bing; Yang, Jie; Yin, Wen; Wang, Aili; Fan, Guohui; Zhou, Fei; Liu, Zhibo; Gu, Xiaoying; Xu, Jiuyang; Shang, Lianhan; Zhang, Yi; Cao, Lianjun; Guo, Tingting; Wan, Yan; Qin, Hong; Jiang, Yushen; Jaki, Thomas; Hayden, Frederick G; Horby, Peter W; Cao, Bin; Wang, Chen.
  • Wang Y; Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, China-Japan Friendship Hospital, Beijing, China; Department of Respiratory Medicine, Capital Medical University, Beijing, China.
  • Zhang D; Jin Yin-tan Hospital, Wuhan, Hubei, China.
  • Du G; Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
  • Du R; Wuhan Lung Hospital, Wuhan, China.
  • Zhao J; Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China.
  • Jin Y; Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China.
  • Fu S; Wuhan Third Hospital, Wuhan, China.
  • Gao L; Renmin Hospital of Wuhan University, Wuhan, China.
  • Cheng Z; Zhongnan Hospital of Wuhan University, Wuhan, China.
  • Lu Q; Wuhan Fourth Hospital, Wuhan, China.
  • Hu Y; The Central Hospital of Wuhan, Wuhan, China.
  • Luo G; Wuhan First Hospital, Wuhan, China.
  • Wang K; Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
  • Lu Y; Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
  • Li H; Jin Yin-tan Hospital, Wuhan, Hubei, China.
  • Wang S; Jin Yin-tan Hospital, Wuhan, Hubei, China.
  • Ruan S; Jin Yin-tan Hospital, Wuhan, Hubei, China.
  • Yang C; Wuhan Lung Hospital, Wuhan, China.
  • Mei C; Wuhan Lung Hospital, Wuhan, China.
  • Wang Y; Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China.
  • Ding D; Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China.
  • Wu F; Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China.
  • Tang X; Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China.
  • Ye X; Wuhan Third Hospital, Wuhan, China.
  • Ye Y; Renmin Hospital of Wuhan University, Wuhan, China.
  • Liu B; Zhongnan Hospital of Wuhan University, Wuhan, China.
  • Yang J; Wuhan Fourth Hospital, Wuhan, China.
  • Yin W; The Central Hospital of Wuhan, Wuhan, China.
  • Wang A; Wuhan First Hospital, Wuhan, China.
  • Fan G; Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, China.
  • Zhou F; Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, China-Japan Friendship Hospital, Beijing, China.
  • Liu Z; Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, China-Japan Friendship Hospital, Beijing, China.
  • Gu X; Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, China.
  • Xu J; Tsinghua University School of Medicine, Beijing, China.
  • Shang L; Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, China-Japan Friendship Hospital, Beijing, China; Beijing University of Chinese Medicine, Beijing, China.
  • Zhang Y; Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, China-Japan Friendship Hospital, Beijing, China.
  • Cao L; Tigermed Consulting, Hangzhou, China.
  • Guo T; Tigermed Consulting, Hangzhou, China.
  • Wan Y; Tigermed Consulting, Hangzhou, China.
  • Qin H; Teddy Clinical Research Laboratory, Shanghai, China.
  • Jiang Y; Hangzhou DI'AN Medical Laboratory, Hangzhou, China.
  • Jaki T; Lancaster University, Lancaster, UK; University of Cambridge, Cambridge, UK.
  • Hayden FG; University of Virginia School of Medicine, Charlottesville, VA, USA.
  • Horby PW; International Severe Acute Respiratory and Emerging Infection Consortium, University of Oxford, Oxford, UK.
  • Cao B; Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, China-Japan Friendship Hospital, Beijing, China; Department of Respiratory Medicine, Capital Medical University, Beijing, China; Institute of Respiratory Me
  • Wang C; Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, China-Japan Friendship Hospital, Beijing, China; Institute of Respiratory Medicine, Chinese Academy of Medical Science, Beijing, China; Tsinghua University-
Lancet ; 395(10236): 1569-1578, 2020 05 16.
Article in English | MEDLINE | ID: covidwho-824547
ABSTRACT

BACKGROUND:

No specific antiviral drug has been proven effective for treatment of patients with severe coronavirus disease 2019 (COVID-19). Remdesivir (GS-5734), a nucleoside analogue prodrug, has inhibitory effects on pathogenic animal and human coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro, and inhibits Middle East respiratory syndrome coronavirus, SARS-CoV-1, and SARS-CoV-2 replication in animal models.

METHODS:

We did a randomised, double-blind, placebo-controlled, multicentre trial at ten hospitals in Hubei, China. Eligible patients were adults (aged ≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection, with an interval from symptom onset to enrolment of 12 days or less, oxygen saturation of 94% or less on room air or a ratio of arterial oxygen partial pressure to fractional inspired oxygen of 300 mm Hg or less, and radiologically confirmed pneumonia. Patients were randomly assigned in a 21 ratio to intravenous remdesivir (200 mg on day 1 followed by 100 mg on days 2-10 in single daily infusions) or the same volume of placebo infusions for 10 days. Patients were permitted concomitant use of lopinavir-ritonavir, interferons, and corticosteroids. The primary endpoint was time to clinical improvement up to day 28, defined as the time (in days) from randomisation to the point of a decline of two levels on a six-point ordinal scale of clinical status (from 1=discharged to 6=death) or discharged alive from hospital, whichever came first. Primary analysis was done in the intention-to-treat (ITT) population and safety analysis was done in all patients who started their assigned treatment. This trial is registered with ClinicalTrials.gov, NCT04257656.

FINDINGS:

Between Feb 6, 2020, and March 12, 2020, 237 patients were enrolled and randomly assigned to a treatment group (158 to remdesivir and 79 to placebo); one patient in the placebo group who withdrew after randomisation was not included in the ITT population. Remdesivir use was not associated with a difference in time to clinical improvement (hazard ratio 1·23 [95% CI 0·87-1·75]). Although not statistically significant, patients receiving remdesivir had a numerically faster time to clinical improvement than those receiving placebo among patients with symptom duration of 10 days or less (hazard ratio 1·52 [0·95-2·43]). Adverse events were reported in 102 (66%) of 155 remdesivir recipients versus 50 (64%) of 78 placebo recipients. Remdesivir was stopped early because of adverse events in 18 (12%) patients versus four (5%) patients who stopped placebo early.

INTERPRETATION:

In this study of adult patients admitted to hospital for severe COVID-19, remdesivir was not associated with statistically significant clinical benefits. However, the numerical reduction in time to clinical improvement in those treated earlier requires confirmation in larger studies.

FUNDING:

Chinese Academy of Medical Sciences Emergency Project of COVID-19, National Key Research and Development Program of China, the Beijing Science and Technology Project.
Subject(s)

Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Pneumonia, Viral / Adenosine Monophosphate / Coronavirus Infections / Alanine Type of study: Experimental Studies / Prognostic study / Randomized controlled trials Limits: Aged / Female / Humans / Male / Middle aged Country/Region as subject: Asia Language: English Journal: Lancet Year: 2020 Document Type: Article Affiliation country: S0140-6736(20)31022-9

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antiviral Agents / Pneumonia, Viral / Adenosine Monophosphate / Coronavirus Infections / Alanine Type of study: Experimental Studies / Prognostic study / Randomized controlled trials Limits: Aged / Female / Humans / Male / Middle aged Country/Region as subject: Asia Language: English Journal: Lancet Year: 2020 Document Type: Article Affiliation country: S0140-6736(20)31022-9