Remdesivir for 5 or 10 Days in Patients with Severe Covid-19.
Adenosine Monophosphate
/ administration & dosage
Adult
Aged
Alanine
/ administration & dosage
Antiviral Agents
/ administration & dosage
Betacoronavirus
COVID-19
Coronavirus Infections
/ drug therapy
Drug Administration Schedule
Female
Hospitalization
Humans
Male
Middle Aged
Oxygen Inhalation Therapy
Pandemics
Pneumonia, Viral
/ drug therapy
SARS-CoV-2
Treatment Outcome
COVID-19 Drug Treatment
Journal
The New England journal of medicine
ISSN: 1533-4406
Titre abrégé: N Engl J Med
Pays: United States
ID NLM: 0255562
Informations de publication
Date de publication:
05 11 2020
05 11 2020
Historique:
pubmed:
28
5
2020
medline:
2
12
2020
entrez:
28
5
2020
Statut:
ppublish
Résumé
Remdesivir is an RNA polymerase inhibitor with potent antiviral activity in vitro and efficacy in animal models of coronavirus disease 2019 (Covid-19). We conducted a randomized, open-label, phase 3 trial involving hospitalized patients with confirmed SARS-CoV-2 infection, oxygen saturation of 94% or less while they were breathing ambient air, and radiologic evidence of pneumonia. Patients were randomly assigned in a 1:1 ratio to receive intravenous remdesivir for either 5 days or 10 days. All patients received 200 mg of remdesivir on day 1 and 100 mg once daily on subsequent days. The primary end point was clinical status on day 14, assessed on a 7-point ordinal scale. In total, 397 patients underwent randomization and began treatment (200 patients for 5 days and 197 for 10 days). The median duration of treatment was 5 days (interquartile range, 5 to 5) in the 5-day group and 9 days (interquartile range, 5 to 10) in the 10-day group. At baseline, patients randomly assigned to the 10-day group had significantly worse clinical status than those assigned to the 5-day group (P = 0.02). By day 14, a clinical improvement of 2 points or more on the ordinal scale occurred in 64% of patients in the 5-day group and in 54% in the 10-day group. After adjustment for baseline clinical status, patients in the 10-day group had a distribution in clinical status at day 14 that was similar to that among patients in the 5-day group (P = 0.14). The most common adverse events were nausea (9% of patients), worsening respiratory failure (8%), elevated alanine aminotransferase level (7%), and constipation (7%). In patients with severe Covid-19 not requiring mechanical ventilation, our trial did not show a significant difference between a 5-day course and a 10-day course of remdesivir. With no placebo control, however, the magnitude of benefit cannot be determined. (Funded by Gilead Sciences; GS-US-540-5773 ClinicalTrials.gov number, NCT04292899.).
Sections du résumé
BACKGROUND
Remdesivir is an RNA polymerase inhibitor with potent antiviral activity in vitro and efficacy in animal models of coronavirus disease 2019 (Covid-19).
METHODS
We conducted a randomized, open-label, phase 3 trial involving hospitalized patients with confirmed SARS-CoV-2 infection, oxygen saturation of 94% or less while they were breathing ambient air, and radiologic evidence of pneumonia. Patients were randomly assigned in a 1:1 ratio to receive intravenous remdesivir for either 5 days or 10 days. All patients received 200 mg of remdesivir on day 1 and 100 mg once daily on subsequent days. The primary end point was clinical status on day 14, assessed on a 7-point ordinal scale.
RESULTS
In total, 397 patients underwent randomization and began treatment (200 patients for 5 days and 197 for 10 days). The median duration of treatment was 5 days (interquartile range, 5 to 5) in the 5-day group and 9 days (interquartile range, 5 to 10) in the 10-day group. At baseline, patients randomly assigned to the 10-day group had significantly worse clinical status than those assigned to the 5-day group (P = 0.02). By day 14, a clinical improvement of 2 points or more on the ordinal scale occurred in 64% of patients in the 5-day group and in 54% in the 10-day group. After adjustment for baseline clinical status, patients in the 10-day group had a distribution in clinical status at day 14 that was similar to that among patients in the 5-day group (P = 0.14). The most common adverse events were nausea (9% of patients), worsening respiratory failure (8%), elevated alanine aminotransferase level (7%), and constipation (7%).
CONCLUSIONS
In patients with severe Covid-19 not requiring mechanical ventilation, our trial did not show a significant difference between a 5-day course and a 10-day course of remdesivir. With no placebo control, however, the magnitude of benefit cannot be determined. (Funded by Gilead Sciences; GS-US-540-5773 ClinicalTrials.gov number, NCT04292899.).
Identifiants
pubmed: 32459919
doi: 10.1056/NEJMoa2015301
pmc: PMC7377062
doi:
Substances chimiques
Antiviral Agents
0
remdesivir
3QKI37EEHE
Adenosine Monophosphate
415SHH325A
Alanine
OF5P57N2ZX
Banques de données
ClinicalTrials.gov
['NCT04292899']
Types de publication
Clinical Trial, Phase III
Comparative Study
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1827-1837Investigateurs
Christoph Spinner
(C)
David Hui
(D)
Tak Yin Owen Tsang
(TYO)
Raffaele Bruno
(R)
Massimo Galli
(M)
Francesco Castelli
(F)
Anna Maria Cattelan
(AM)
Gabriele Missale
(G)
Angelo Pan
(A)
Mi Young Ahn
(MY)
BumSik Chin
(B)
David Chien Boon Lye
(DCB)
Shirin Kalimuddin
(S)
Louis Yi Ann Chai
(LYA)
Sean Wei Xiang Ong
(SWX)
Alex Soriano Viladomiu
(AS)
José Ramón Arribas
(JR)
Ane Josune Goikoetxea
(AJ)
Jose Muñoz
(J)
Yao-Shen Chen
(YS)
Farshad Bagheri
(F)
Bindu Balani
(B)
Norbert Brau
(N)
Gerard Criner
(G)
George Diaz
(G)
Jason Goldman
(J)
Robert Gottlieb
(R)
Philip Grant
(P)
Kevin Grimes
(K)
Terese Hammond
(T)
Leila Hojat
(L)
Uma Malhotra
(U)
Vinay Malhotra
(V)
Kristen Marks
(K)
Francisco Marty
(F)
Kathleen Mullane
(K)
Ronald G Nahass
(RG)
Paul Nee
(P)
Tobias Pusch
(T)
Stacey Rizza
(S)
Philip Robinson
(P)
Arun Sanyal
(A)
Kathryn Stephenson
(K)
Aruna Subramanian
(A)
Karen T Tashima
(KT)
William J Towner
(WJ)
Richard Zuckerman
(R)
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2020 Massachusetts Medical Society.
Références
Lancet Gastroenterol Hepatol. 2020 May;5(5):428-430
pubmed: 32145190
N Engl J Med. 2020 May 7;382(19):1787-1799
pubmed: 32187464
Cell Res. 2020 Mar;30(3):269-271
pubmed: 32020029
JAMA. 2020 May 26;323(20):2052-2059
pubmed: 32320003
N Engl J Med. 2020 Sep 3;383(10):994
pubmed: 32649078
Lancet. 2020 May 16;395(10236):1569-1578
pubmed: 32423584
Cell Rep Med. 2020 Jul 21;1(4):100059
pubmed: 32835306
Br J Surg. 2020 Jun;107(7):785-787
pubmed: 32191340
N Engl J Med. 2019 Dec 12;381(24):2293-2303
pubmed: 31774950
N Engl J Med. 2020 May 7;382(19):1851-1852
pubmed: 32187463
Lancet. 2020 May 16;395(10236):1525-1527
pubmed: 32423580
Nature. 2020 Sep;585(7824):273-276
pubmed: 32516797
N Engl J Med. 2020 Apr 30;382(18):1708-1720
pubmed: 32109013
Sci Transl Med. 2017 Jun 28;9(396):
pubmed: 28659436
Proc Natl Acad Sci U S A. 2020 Mar 24;117(12):6771-6776
pubmed: 32054787
N Engl J Med. 2020 Mar 26;382(13):1268-1269
pubmed: 32109011
Nature. 2016 Mar 17;531(7594):381-5
pubmed: 26934220
Nat Commun. 2020 Jan 10;11(1):222
pubmed: 31924756