Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial - PubMed (original) (raw)

Randomized Controlled Trial

. 2020 May 16;395(10236):1569-1578.

doi: 10.1016/S0140-6736(20)31022-9. Epub 2020 Apr 29.

Dingyu Zhang 2, Guanhua Du 3, Ronghui Du 4, Jianping Zhao 5, Yang Jin 6, Shouzhi Fu 7, Ling Gao 8, Zhenshun Cheng 9, Qiaofa Lu 10, Yi Hu 11, Guangwei Luo 12, Ke Wang 3, Yang Lu 3, Huadong Li 2, Shuzhen Wang 2, Shunan Ruan 2, Chengqing Yang 4, Chunlin Mei 4, Yi Wang 5, Dan Ding 5, Feng Wu 6, Xin Tang 6, Xianzhi Ye 7, Yingchun Ye 8, Bing Liu 9, Jie Yang 10, Wen Yin 11, Aili Wang 12, Guohui Fan 13, Fei Zhou 14, Zhibo Liu 14, Xiaoying Gu 13, Jiuyang Xu 15, Lianhan Shang 16, Yi Zhang 14, Lianjun Cao 17, Tingting Guo 17, Yan Wan 17, Hong Qin 18, Yushen Jiang 19, Thomas Jaki 20, Frederick G Hayden 21, Peter W Horby 22, Bin Cao 23, Chen Wang 24

Affiliations

Randomized Controlled Trial

Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial

Yeming Wang et al. Lancet. 2020.

Erratum in

Abstract

Background: No specific antiviral drug has been proven effective for treatment of patients with severe coronavirus disease 2019 (COVID-19). Remdesivir (GS-5734), a nucleoside analogue prodrug, has inhibitory effects on pathogenic animal and human coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro, and inhibits Middle East respiratory syndrome coronavirus, SARS-CoV-1, and SARS-CoV-2 replication in animal models.

Methods: We did a randomised, double-blind, placebo-controlled, multicentre trial at ten hospitals in Hubei, China. Eligible patients were adults (aged ≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection, with an interval from symptom onset to enrolment of 12 days or less, oxygen saturation of 94% or less on room air or a ratio of arterial oxygen partial pressure to fractional inspired oxygen of 300 mm Hg or less, and radiologically confirmed pneumonia. Patients were randomly assigned in a 2:1 ratio to intravenous remdesivir (200 mg on day 1 followed by 100 mg on days 2-10 in single daily infusions) or the same volume of placebo infusions for 10 days. Patients were permitted concomitant use of lopinavir-ritonavir, interferons, and corticosteroids. The primary endpoint was time to clinical improvement up to day 28, defined as the time (in days) from randomisation to the point of a decline of two levels on a six-point ordinal scale of clinical status (from 1=discharged to 6=death) or discharged alive from hospital, whichever came first. Primary analysis was done in the intention-to-treat (ITT) population and safety analysis was done in all patients who started their assigned treatment. This trial is registered with ClinicalTrials.gov, NCT04257656.

Findings: Between Feb 6, 2020, and March 12, 2020, 237 patients were enrolled and randomly assigned to a treatment group (158 to remdesivir and 79 to placebo); one patient in the placebo group who withdrew after randomisation was not included in the ITT population. Remdesivir use was not associated with a difference in time to clinical improvement (hazard ratio 1·23 [95% CI 0·87-1·75]). Although not statistically significant, patients receiving remdesivir had a numerically faster time to clinical improvement than those receiving placebo among patients with symptom duration of 10 days or less (hazard ratio 1·52 [0·95-2·43]). Adverse events were reported in 102 (66%) of 155 remdesivir recipients versus 50 (64%) of 78 placebo recipients. Remdesivir was stopped early because of adverse events in 18 (12%) patients versus four (5%) patients who stopped placebo early.

Interpretation: In this study of adult patients admitted to hospital for severe COVID-19, remdesivir was not associated with statistically significant clinical benefits. However, the numerical reduction in time to clinical improvement in those treated earlier requires confirmation in larger studies.

Funding: Chinese Academy of Medical Sciences Emergency Project of COVID-19, National Key Research and Development Program of China, the Beijing Science and Technology Project.

Copyright © 2020 Elsevier Ltd. All rights reserved.

PubMed Disclaimer

Figures

Figure 1

Figure 1

Trial profile

Figure 2

Figure 2

Time to clinical improvement in the intention-to-treat population Adjusted hazard ratio for randomisation stratification was 1·25 (95% CI 0·88–1·78). *Including deaths before day 28 as right censored at day 28, the number of patients without clinical improvement was still included in the number at risk.

Figure 3

Figure 3

Viral load by quantitative PCR on the upper respiratory tract specimens (A) and lower respiratory tract specimens (B) Data are mean (SE). Results less than the lower limit of quantification of the PCR assay and greater than the limit of qualitative detection are imputed with half of actual value; results of patients with viral-negative RNA are imputed with 0 log10 copies per mL.

Comment in

Similar articles

Cited by

References

    1. Johns Hopkins University and Medicine COVID-19 map. Johns Hopkins Coronavirus Resource Centre. https://coronavirus.jhu.edu/map.html
    1. Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention. JAMA. 2020 doi: 10.1001/jama.2020.2648. published online Feb 24. - DOI - PubMed
    1. Chen N, Zhou M, Dong X. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395:507–513. - PMC - PubMed
    1. Zhou F, Yu T, Du R. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395:1054–1062. - PMC - PubMed
    1. Bhatraju PK, Ghassemieh BJ, Nichols M. Covid-19 in critically ill patients in the Seattle region–case series. N Engl J Med. 2020 doi: 10.1056/NEJMoa2004500. published online March 30. - DOI - PMC - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources