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  • THELANCET-S-20-09798 (2)

    Rights statement: This is the author’s version of a work that was accepted for publication in The Lancet. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in The Lancet, ?, ?, 2020 DOI: 10.1016/S0140-6736(20)31022-9

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

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Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial. / Wang, Y.; Zhang, D.; Du, G. et al.
In: The Lancet, 16.05.2020, p. 1569-1578.

Research output: Contribution to Journal/MagazineJournal articlepeer-review

Harvard

Wang, Y, Zhang, D, Du, G, Du, R, Zhao, J, Jin, Y, Fu, S, Gao, L, Cheng, Z, Lu, Q, Hu, Y, Luo, G, Wang, K, Lu, Y, Li, H, Wang, S, Ruan, S, Yang, C, Mei, C, Ding, D, Wu, F, Tang, X, Ye, X, Ye, Y, Liu, B, Yang, J, Yin, W, Wang, A, Fan, G, Zhou, F, Liu, Z, Gu, X, Xu, J, Shang, L, Zhang, Y, Cao, L, Guo, T, Wan, Y, Qin, H, Jiang, Y, Jaki, T, Hayden, FG, Horby, PW, Cao, B & Wang, C 2020, 'Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial', The Lancet, pp. 1569-1578. https://doi.org/10.1016/S0140-6736(20)31022-9

APA

Wang, Y., Zhang, D., Du, G., Du, R., Zhao, J., Jin, Y., Fu, S., Gao, L., Cheng, Z., Lu, Q., Hu, Y., Luo, G., Wang, K., Lu, Y., Li, H., Wang, S., Ruan, S., Yang, C., Mei, C., ... Wang, C. (2020). Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial. The Lancet, 1569-1578. https://doi.org/10.1016/S0140-6736(20)31022-9

Vancouver

Wang Y, Zhang D, Du G, Du R, Zhao J, Jin Y et al. Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial. The Lancet. 2020 May 16;1569-1578. Epub 2020 Apr 29. doi: 10.1016/S0140-6736(20)31022-9

Author

Wang, Y. ; Zhang, D. ; Du, G. et al. / Remdesivir in adults with severe COVID-19 : a randomised, double-blind, placebo-controlled, multicentre trial. In: The Lancet. 2020 ; pp. 1569-1578.

Bibtex

@article{9e03d44d939043aea9db754328307e4a,
title = "Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial",
abstract = "SummaryBackgroundNo 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.MethodsWe 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.FindingsBetween 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.InterpretationIn 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.",
author = "Y. Wang and D. Zhang and G. Du and R. Du and J. Zhao and Y. Jin and S. Fu and L. Gao and Z. Cheng and Q. Lu and Y. Hu and G. Luo and K. Wang and Y. Lu and H. Li and S. Wang and S. Ruan and C. Yang and C. Mei and D. Ding and F. Wu and X. Tang and X. Ye and Y. Ye and B. Liu and J. Yang and W. Yin and A. Wang and G. Fan and F. Zhou and Z. Liu and X. Gu and J. Xu and L. Shang and Y. Zhang and L. Cao and T. Guo and Y. Wan and H. Qin and Y. Jiang and T. Jaki and F.G. Hayden and P.W. Horby and B. Cao and C. Wang",
note = "This is the author{\textquoteright}s version of a work that was accepted for publication in The Lancet. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in The Lancet, ?, ?, 2020 DOI: 10.1016/S0140-6736(20)31022-9",
year = "2020",
month = may,
day = "16",
doi = "10.1016/S0140-6736(20)31022-9",
language = "English",
pages = "1569--1578",
journal = "The Lancet",
issn = "0140-6736",
publisher = "Lancet Publishing Group",

}

RIS

TY - JOUR

T1 - Remdesivir in adults with severe COVID-19

T2 - a randomised, double-blind, placebo-controlled, multicentre trial

AU - Wang, Y.

AU - Zhang, D.

AU - Du, G.

AU - Du, R.

AU - Zhao, J.

AU - Jin, Y.

AU - Fu, S.

AU - Gao, L.

AU - Cheng, Z.

AU - Lu, Q.

AU - Hu, Y.

AU - Luo, G.

AU - Wang, K.

AU - Lu, Y.

AU - Li, H.

AU - Wang, S.

AU - Ruan, S.

AU - Yang, C.

AU - Mei, C.

AU - Ding, D.

AU - Wu, F.

AU - Tang, X.

AU - Ye, X.

AU - Ye, Y.

AU - Liu, B.

AU - Yang, J.

AU - Yin, W.

AU - Wang, A.

AU - Fan, G.

AU - Zhou, F.

AU - Liu, Z.

AU - Gu, X.

AU - Xu, J.

AU - Shang, L.

AU - Zhang, Y.

AU - Cao, L.

AU - Guo, T.

AU - Wan, Y.

AU - Qin, H.

AU - Jiang, Y.

AU - Jaki, T.

AU - Hayden, F.G.

AU - Horby, P.W.

AU - Cao, B.

AU - Wang, C.

N1 - This is the author’s version of a work that was accepted for publication in The Lancet. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in The Lancet, ?, ?, 2020 DOI: 10.1016/S0140-6736(20)31022-9

PY - 2020/5/16

Y1 - 2020/5/16

N2 - SummaryBackgroundNo 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.MethodsWe 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.FindingsBetween 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.InterpretationIn 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.

AB - SummaryBackgroundNo 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.MethodsWe 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.FindingsBetween 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.InterpretationIn 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.

U2 - 10.1016/S0140-6736(20)31022-9

DO - 10.1016/S0140-6736(20)31022-9

M3 - Journal article

SP - 1569

EP - 1578

JO - The Lancet

JF - The Lancet

SN - 0140-6736

ER -