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Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
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TY - JOUR
T1 - Evaluation of the efficacy and safety of intravenous remdesivir in adult patients with severe COVID-19
T2 - Study protocol for a phase 3 randomized, double-blind, placebo-controlled, multicentre trial
AU - Wang, Y.
AU - Zhou, F.
AU - Zhang, D.
AU - Zhao, J.
AU - Du, R.
AU - Hu, Y.
AU - Cheng, Z.
AU - Gao, L.
AU - Jin, Y.
AU - Luo, G.
AU - Fu, S.
AU - Lu, Q.
AU - Du, G.
AU - Wang, K.
AU - Lu, Y.
AU - Fan, G.
AU - Zhang, Y.
AU - Liu, Y.
AU - Ruan, S.
AU - Liu, W.
AU - Jaki, T.
AU - Hayden, F.G.
AU - Horby, P.W.
AU - Cao, B.
AU - Wang, C.
PY - 2020/5/24
Y1 - 2020/5/24
N2 - 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. © 2020 The Author(s).
AB - 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. © 2020 The Author(s).
KW - Administrative information
KW - Antiviral
KW - China
KW - Clinical trial
KW - COVID-19
KW - Remdesivir
KW - adenosine phosphate
KW - alanine
KW - antivirus agent
KW - remdesivir
KW - Betacoronavirus
KW - Coronavirus infection
KW - double blind procedure
KW - drug effect
KW - equivalence trial (topic)
KW - female
KW - human
KW - intravenous drug administration
KW - male
KW - multicenter study (topic)
KW - pandemic
KW - pathogenicity
KW - patient safety
KW - phase 3 clinical trial (topic)
KW - risk assessment
KW - risk factor
KW - severity of illness index
KW - time factor
KW - treatment outcome
KW - virology
KW - virus pneumonia
KW - Adenosine Monophosphate
KW - Alanine
KW - Antiviral Agents
KW - Clinical Trials, Phase III as Topic
KW - Coronavirus Infections
KW - Double-Blind Method
KW - Equivalence Trials as Topic
KW - Female
KW - Humans
KW - Infusions, Intravenous
KW - Male
KW - Multicenter Studies as Topic
KW - Pandemics
KW - Patient Safety
KW - Pneumonia, Viral
KW - Risk Assessment
KW - Risk Factors
KW - Severity of Illness Index
KW - Time Factors
KW - Treatment Outcome
U2 - 10.1186/s13063-020-04352-9
DO - 10.1186/s13063-020-04352-9
M3 - Journal article
VL - 21
JO - Trials
JF - Trials
SN - 1745-6215
IS - 1
M1 - 422
ER -