Evaluation of the efficacy and safety of intravenous remdesivir in adult patients with severe COVID-19: study protocol for a phase 3 randomized, double-blind, placebo-controlled, multicentre trial
单位：[1]Department of Pulmonary and Critical Care Medicine, Center of RespiratoryMedicine, National Clinical Research Center for Respiratory Diseases,China-Japan Friendship Hospital, Beijing, China[2]Jin Yin-tan Hospital, Wuhan,Hubei Province, China[3]Tongji Hospital, Tongji Medical College of HuazhongUniversity of Science & Technology, Wuhan, China华中科技大学同济医学院附属同济医院[4]Wuhan Lung Hospital,Wuhan, China[5]The Central Hospital of Wuhan, Wuhan, China[6]ZhongnanHospital of Wuhan University, Wuhan, China[7]Renmin Hospital of WuhanUniversity, Wuhan, China[8]Union Hospital, Tongji Medical College ofHuazhong University of Science & Technology, Wuhan, China华中科技大学同济医学院附属协和医院[9]Wuhan FirstHospital, Wuhan, China[10]Wuhan Third Hospital, Wuhan, China[11]WuhanFourth Hospital, Wuhan, China[12]Institute of Medicine, Chinese Academy ofMedical Sciences, Beijing, China[13]Institute of Clinical Medical Sciences,China-Japan Friendship Hospital, Beijing, China[14]Lancaster University,Lancaster, UK[15]University of Virginia School of Medicine, Charlottesville, VA,USA[16]ISARIC, University of Oxford, Oxford, UK[17]Institute of RespiratoryMedicine, Chinese Academy of Medical Sciences, Beijing, China[18]PekingUnion Medical College, Beijing, China
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 30(th) 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 6(th) February 2020.
基金：
Emergency project for novel coronavirus pneumonia of the Ministry of Science and Technology [2020YFC0841300]; Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences [CIFMS 2018-I2M-1-003]; National Science Grant for Distinguished Young Scholars [81425001/H0104]; National Key Research and Development Program of China [2018YFC1200102]; Beijing Science and Technology Project [Z19110700660000]; National Mega-projects for Infectious Diseases in China [2017ZX10103004, 2018ZX10305409]; National Institute for Health Research (NIHR) Senior Research FellowshipNational Institute for Health Research (NIHR) [2015-08-001]; Bill & Melinda Gates FoundationBill & Melinda Gates FoundationCGIAR; Wellcome TrustWellcome TrustEuropean Commission; UK Department of Health and Social Care; China Evergrande Group; Jack Ma Foundation; Sino Biopharmaceutical Limited; Ping An Insurance (Group); New Sunshine Charity Foundation
第一作者单位：[1]Department of Pulmonary and Critical Care Medicine, Center of RespiratoryMedicine, National Clinical Research Center for Respiratory Diseases,China-Japan Friendship Hospital, Beijing, China
通讯作者：
通讯机构：[1]Department of Pulmonary and Critical Care Medicine, Center of RespiratoryMedicine, National Clinical Research Center for Respiratory Diseases,China-Japan Friendship Hospital, Beijing, China[17]Institute of RespiratoryMedicine, Chinese Academy of Medical Sciences, Beijing, China[18]PekingUnion Medical College, Beijing, China
推荐引用方式(GB/T 7714)：
Yeming Wang,Fei Zhou,Dingyu Zhang,et al.Evaluation of the efficacy and safety of intravenous remdesivir in adult patients with severe COVID-19: study protocol for a phase 3 randomized, double-blind, placebo-controlled, multicentre trial[J].TRIALS.2020,21(1):doi:10.1186/s13063-020-04352-9.
APA：
Yeming Wang,Fei Zhou,Dingyu Zhang,Jianping Zhao,Ronghui Du...&Chen Wang.(2020).Evaluation of the efficacy and safety of intravenous remdesivir in adult patients with severe COVID-19: study protocol for a phase 3 randomized, double-blind, placebo-controlled, multicentre trial.TRIALS,21,(1)
MLA：
Yeming Wang,et al."Evaluation of the efficacy and safety of intravenous remdesivir in adult patients with severe COVID-19: study protocol for a phase 3 randomized, double-blind, placebo-controlled, multicentre trial".TRIALS 21..1(2020)
