Journal Article

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

Zhang, Dingyu, Du, Ronghui, Lu, Qiaofa, Jaki, Thomas, Horby, Peter W., Zhao, Jianping, Zhang, Yi, Ruan, Shunan, Fu, Shouzhi, Du, Guanhua, Jin, Yang, Cheng, Zhenshun, Wang, Yeming, Gao, Ling, Wang, Ke, Lu, Yang, Hayden, Frederick G., Fan, Guohui, Liu, Ying, Cao, Bin, Hu, Yi, Luo, Guangwei, Wang, Chen, Zhou, Fei, Liu, Wen

2020

Overview

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. Trial registration ClinicalTrials.gov : NCT04257656. Registered on 6 February 2020.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Adenosine Monophosphate - administration & dosage / Adenosine Monophosphate - adverse effects / Adenosine Monophosphate - analogs & derivatives / Administrative information / Adults / Alanine - administration & dosage / Alanine - adverse effects / Alanine - analogs & derivatives / Analysis / Antiviral / Antiviral agents / Antiviral Agents - administration & dosage / Antiviral Agents - adverse effects / Antiviral drugs / Betacoronavirus - drug effects / Betacoronavirus - pathogenicity / Biological products industry / Biomedicine / China / Chloride / Clinical trial / Clinical trials / Clinical Trials, Phase III as Topic / Coronavirus Infections - diagnosis / Coronavirus Infections - drug therapy / Coronavirus Infections - virology / Coronaviruses / COVID-19 / COVID-19 Drug Treatment / Decision making / Disease transmission / Double-Blind Method / Double-blind studies / Drug dosages / Drug withdrawal / Ebola virus / Equivalence Trials as Topic / Female / Health aspects / Health Sciences / Hospitalization / Humans / Infections / Informed consent / Infusions, Intravenous / Laboratories / Male / Medical research / Medicine / Medicine & Public Health / Middle East respiratory syndrome / Multicenter Studies as Topic / Palliative care / Pandemics / Patient Safety / Patients / Pneumonia / Pneumonia, Viral - diagnosis / Pneumonia, Viral - drug therapy / Pneumonia, Viral - virology / R&D / Remdesivir / Research & development / Respiratory failure / Risk Assessment / Risk Factors / RNA polymerase / SARS-CoV-2 / Severe acute respiratory syndrome coronavirus 2 / Severity of Illness Index / Sodium / Statistics for Life Sciences / Study Protocol / Time Factors / Treatment Outcome / Viral infections / Virus diseases / Viruses