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Evaluation of the efficacy and safety of intravenous remdesivir

Abstract Background Coronavirus disease 2019 (COVID-19), caused by a novel corinavirus (later named SARS-CoV-2 virus), was fistly reported in Wuhan, Hubei Province, China towards the end of 2019. Large-scale spread within China and internationally led the World Health Organization to declare a Public Health Emergency of International Concern on 30th January 2020. The clinical manifestations of COVID-19 virus infection include asymptomatic infection, mild upper respiratory symptoms, severe viral pneumonia with respiratory failure, and even death. There are no antivirals of proven clinical efficacy in coronavirus infections. Remdesivir (GS-5734), a nucleoside analogue, has inhibitory effects on animal and human highly pathogenic coronaviruses, including MERS-CoV and SARS-CoV, in in vitro and in vivo experiments. It is also inhibitory against the COVID-19 virus in vitro. The aim of this study is to assess the efficacy and safety of remdesivir in adult patients with severe COVID-19. Methods The protocol is prepared in accordance with the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guidelines. This is a phase 3, randomized, double-blind, placebo-controlled, multicentre trial. Adults (≥ 18 years) with laboratory-confirmed COVID-19 virus infection, severe pneumonia signs or symptoms, and radiologically confirmed severe pneumonia are randomly assigned in a 2:1 ratio to intravenously administered remdesivir or placebo for 10 days. The primary endpoint is time to clinical improvement (censored at day 28), defined as the time (in days) from randomization of study treatment (remdesivir or placebo) until a decline of two categories on a six-category ordinal scale of clinical status (1 = discharged; 6 = death) or live discharge from hospital. One interim analysis for efficacy and futility will be conducted once half of the total number of events required has been observed. Discussion This is the first randomized, placebo-controlled trial in COVID-19. Enrolment began in sites in Wuhan, Hubei Province, China on 6th February 2020. Trial registration ClinicalTrials.gov : NCT04257656. Registered on 6 February 2020.

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AUTHORS

Yeming Wang (Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, China-Japan Friendship Hospital)

Fei Zhou (Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, China-Japan Friendship Hospital)

Dingyu Zhang (Jin Yin-tan Hospital)

Jianping Zhao (Tongji Hospital, Tongji Medical College of Huazhong University of Science & Technology)

Ronghui Du (Wuhan Lung Hospital)

Yi Hu (The Central Hospital of Wuhan)

Zhenshun Cheng (Zhongnan Hospital of Wuhan University)

Ling Gao (Renmin Hospital of Wuhan University)

Yang Jin (Union Hospital, Tongji Medical College of Huazhong University of Science & Technology)

Guangwei Luo (Wuhan First Hospital)

Shouzhi Fu (Wuhan Third Hospital)

Qiaofa Lu (Wuhan Fourth Hospital)

Guanhua Du (Institute of Medicine, Chinese Academy of Medical Sciences)

Ke Wang (Institute of Medicine, Chinese Academy of Medical Sciences)

Yang Lu (Institute of Medicine, Chinese Academy of Medical Sciences)

Guohui Fan (Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, China-Japan Friendship Hospital)

Yi Zhang (Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, China-Japan Friendship Hospital)

Ying Liu (Jin Yin-tan Hospital)

Shunan Ruan (Jin Yin-tan Hospital)

Wen Liu (Jin Yin-tan Hospital)

Thomas Jaki (Lancaster University)

Frederick G. Hayden (University of Virginia School of Medicine)

Peter W. Horby (ISARIC, University of Oxford)

Bin Cao (Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, China-Japan Friendship Hospital)

Chen Wang (Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, China-Japan Friendship Hospital)