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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.T

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.

Authors+Show Affiliations

Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, China-Japan Friendship Hospital, Beijing, China.Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, China-Japan Friendship Hospital, Beijing, China.Jin Yin-tan Hospital, Wuhan, Hubei Province, China.Tongji Hospital, Tongji Medical College of Huazhong University of Science & Technology, Wuhan, China.Wuhan Lung Hospital, Wuhan, China.The Central Hospital of Wuhan, Wuhan, China.Zhongnan Hospital of Wuhan University, Wuhan, China.Renmin Hospital of Wuhan University, Wuhan, China.Union Hospital, Tongji Medical College of Huazhong University of Science & Technology, Wuhan, China.Wuhan First Hospital, Wuhan, China.Wuhan Third Hospital, Wuhan, China.Wuhan Fourth Hospital, Wuhan, China.Institute of Medicine, Chinese Academy of Medical Sciences, Beijing, China.Institute of Medicine, Chinese Academy of Medical Sciences, Beijing, China.Institute of Medicine, Chinese Academy of Medical Sciences, Beijing, China.Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, China-Japan Friendship Hospital, Beijing, China. Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, China.Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, China-Japan Friendship Hospital, Beijing, China.Jin Yin-tan Hospital, Wuhan, Hubei Province, China.Jin Yin-tan Hospital, Wuhan, Hubei Province, China.Jin Yin-tan Hospital, Wuhan, Hubei Province, China.Lancaster University, Lancaster, UK.University of Virginia School of Medicine, Charlottesville, VA, USA.ISARIC, University of Oxford, Oxford, UK.Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, China-Japan Friendship Hospital, Beijing, China. caobin_ben@163.com. Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, China. caobin_ben@163.com.Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, China-Japan Friendship Hospital, Beijing, China. cyh-birm@263.net. Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, China. cyh-birm@263.net. Peking Union Medical College, Beijing, China. cyh-birm@263.net.

Pub Type(s)

Clinical Trial Protocol
Journal Article

Language

eng

PubMed ID

32448345

Citation

Wang, Yeming, 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, vol. 21, no. 1, 2020, p. 422.
Wang Y, Zhou F, Zhang D, 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. 2020;21(1):422.
Wang, Y., Zhou, F., Zhang, D., Zhao, J., Du, R., Hu, Y., Cheng, Z., Gao, L., Jin, Y., Luo, G., Fu, S., Lu, Q., Du, G., Wang, K., Lu, Y., Fan, G., Zhang, Y., Liu, Y., Ruan, S., ... Wang, C. (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), 422. https://doi.org/10.1186/s13063-020-04352-9
Wang Y, 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. 2020 May 24;21(1):422. PubMed PMID: 32448345.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Wang,Yeming, AU - Zhou,Fei, AU - Zhang,Dingyu, AU - Zhao,Jianping, AU - Du,Ronghui, AU - Hu,Yi, AU - Cheng,Zhenshun, AU - Gao,Ling, AU - Jin,Yang, AU - Luo,Guangwei, AU - Fu,Shouzhi, AU - Lu,Qiaofa, AU - Du,Guanhua, AU - Wang,Ke, AU - Lu,Yang, AU - Fan,Guohui, AU - Zhang,Yi, AU - Liu,Ying, AU - Ruan,Shunan, AU - Liu,Wen, AU - Jaki,Thomas, AU - Hayden,Frederick G, AU - Horby,Peter W, AU - Cao,Bin, AU - Wang,Chen, Y1 - 2020/05/24/ PY - 2020/02/18/received PY - 2020/04/27/accepted PY - 2020/5/26/entrez PY - 2020/5/26/pubmed PY - 2020/5/28/medline KW - Administrative information KW - Antiviral KW - COVID-19 KW - China KW - Clinical trial KW - Remdesivir SP - 422 EP - 422 JF - Trials JO - Trials VL - 21 IS - 1 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. SN - 1745-6215 UR - https://www.unboundmedicine.com/medline/citation/32448345/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_ L2 - https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-020-04352-9 DB - PRIME DP - Unbound Medicine ER -