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. 2020 May 24;21(1):422. doi: 10.1186/s13063-020-04352-9.

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.

Keywords: Administrative information; Antiviral; COVID-19; China; Clinical trial; Remdesivir.

Publication types

  • Clinical Trial Protocol

MeSH terms

  • Adenosine Monophosphate / administration & dosage
  • Adenosine Monophosphate / adverse effects
  • Adenosine Monophosphate / analogs & derivatives*
  • Alanine / administration & dosage
  • Alanine / adverse effects
  • Alanine / analogs & derivatives*
  • Antiviral Agents / administration & dosage*
  • Antiviral Agents / adverse effects
  • Betacoronavirus / drug effects*
  • Betacoronavirus / pathogenicity
  • COVID-19
  • China
  • Clinical Trials, Phase III as Topic
  • Coronavirus Infections / diagnosis
  • Coronavirus Infections / drug therapy*
  • Coronavirus Infections / virology
  • Double-Blind Method
  • Equivalence Trials as Topic
  • Female
  • Humans
  • Infusions, Intravenous
  • Male
  • Multicenter Studies as Topic
  • Pandemics
  • Patient Safety
  • Pneumonia, Viral / diagnosis
  • Pneumonia, Viral / drug therapy*
  • Pneumonia, Viral / virology
  • Risk Assessment
  • Risk Factors
  • SARS-CoV-2
  • Severity of Illness Index
  • Time Factors
  • Treatment Outcome

Substances

  • Antiviral Agents
  • remdesivir
  • Adenosine Monophosphate
  • Alanine

Supplementary concepts

  • COVID-19 drug treatment

Associated data

  • ClinicalTrials.gov/NCT04257656