Remdesivir for the Treatment of Covid-19 - Final Report.
Adenosine Monophosphate
/ administration & dosage
Administration, Intravenous
Adult
Aged
Alanine
/ administration & dosage
Antiviral Agents
/ administration & dosage
Betacoronavirus
COVID-19
Coronavirus Infections
/ drug therapy
Double-Blind Method
Extracorporeal Membrane Oxygenation
Female
Humans
Kaplan-Meier Estimate
Male
Middle Aged
Oxygen Inhalation Therapy
Pandemics
Pneumonia, Viral
/ drug therapy
Respiration, Artificial
SARS-CoV-2
Time Factors
Young Adult
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:
24
5
2020
medline:
2
12
2020
entrez:
24
5
2020
Statut:
ppublish
Résumé
Although several therapeutic agents have been evaluated for the treatment of coronavirus disease 2019 (Covid-19), no antiviral agents have yet been shown to be efficacious. We conducted a double-blind, randomized, placebo-controlled trial of intravenous remdesivir in adults who were hospitalized with Covid-19 and had evidence of lower respiratory tract infection. Patients were randomly assigned to receive either remdesivir (200 mg loading dose on day 1, followed by 100 mg daily for up to 9 additional days) or placebo for up to 10 days. The primary outcome was the time to recovery, defined by either discharge from the hospital or hospitalization for infection-control purposes only. A total of 1062 patients underwent randomization (with 541 assigned to remdesivir and 521 to placebo). Those who received remdesivir had a median recovery time of 10 days (95% confidence interval [CI], 9 to 11), as compared with 15 days (95% CI, 13 to 18) among those who received placebo (rate ratio for recovery, 1.29; 95% CI, 1.12 to 1.49; P<0.001, by a log-rank test). In an analysis that used a proportional-odds model with an eight-category ordinal scale, the patients who received remdesivir were found to be more likely than those who received placebo to have clinical improvement at day 15 (odds ratio, 1.5; 95% CI, 1.2 to 1.9, after adjustment for actual disease severity). The Kaplan-Meier estimates of mortality were 6.7% with remdesivir and 11.9% with placebo by day 15 and 11.4% with remdesivir and 15.2% with placebo by day 29 (hazard ratio, 0.73; 95% CI, 0.52 to 1.03). Serious adverse events were reported in 131 of the 532 patients who received remdesivir (24.6%) and in 163 of the 516 patients who received placebo (31.6%). Our data show that remdesivir was superior to placebo in shortening the time to recovery in adults who were hospitalized with Covid-19 and had evidence of lower respiratory tract infection. (Funded by the National Institute of Allergy and Infectious Diseases and others; ACTT-1 ClinicalTrials.gov number, NCT04280705.).
Sections du résumé
BACKGROUND
Although several therapeutic agents have been evaluated for the treatment of coronavirus disease 2019 (Covid-19), no antiviral agents have yet been shown to be efficacious.
METHODS
We conducted a double-blind, randomized, placebo-controlled trial of intravenous remdesivir in adults who were hospitalized with Covid-19 and had evidence of lower respiratory tract infection. Patients were randomly assigned to receive either remdesivir (200 mg loading dose on day 1, followed by 100 mg daily for up to 9 additional days) or placebo for up to 10 days. The primary outcome was the time to recovery, defined by either discharge from the hospital or hospitalization for infection-control purposes only.
RESULTS
A total of 1062 patients underwent randomization (with 541 assigned to remdesivir and 521 to placebo). Those who received remdesivir had a median recovery time of 10 days (95% confidence interval [CI], 9 to 11), as compared with 15 days (95% CI, 13 to 18) among those who received placebo (rate ratio for recovery, 1.29; 95% CI, 1.12 to 1.49; P<0.001, by a log-rank test). In an analysis that used a proportional-odds model with an eight-category ordinal scale, the patients who received remdesivir were found to be more likely than those who received placebo to have clinical improvement at day 15 (odds ratio, 1.5; 95% CI, 1.2 to 1.9, after adjustment for actual disease severity). The Kaplan-Meier estimates of mortality were 6.7% with remdesivir and 11.9% with placebo by day 15 and 11.4% with remdesivir and 15.2% with placebo by day 29 (hazard ratio, 0.73; 95% CI, 0.52 to 1.03). Serious adverse events were reported in 131 of the 532 patients who received remdesivir (24.6%) and in 163 of the 516 patients who received placebo (31.6%).
CONCLUSIONS
Our data show that remdesivir was superior to placebo in shortening the time to recovery in adults who were hospitalized with Covid-19 and had evidence of lower respiratory tract infection. (Funded by the National Institute of Allergy and Infectious Diseases and others; ACTT-1 ClinicalTrials.gov number, NCT04280705.).
Identifiants
pubmed: 32445440
doi: 10.1056/NEJMoa2007764
pmc: PMC7262788
doi:
Substances chimiques
Antiviral Agents
0
remdesivir
3QKI37EEHE
Adenosine Monophosphate
415SHH325A
Alanine
OF5P57N2ZX
Banques de données
ClinicalTrials.gov
['NCT04280705']
Types de publication
Clinical Trial, Phase III
Journal Article
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1813-1826Subventions
Organisme : United States
ID : UM1AI148576
Pays : United States
Organisme : BLRD VA
ID : I01 BX003714
Pays : United States
Organisme : United States
ID : UM1AI148573
Pays : United States
Organisme : United States
ID : UM1AI148685
Pays : United States
Organisme : United States
ID : UM1AI148452
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI148685
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI148573
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI148684
Pays : United States
Organisme : Wellcome Trust
ID : 211153/Z/18/Z
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : HHSN261201500003I
Pays : United States
Organisme : United States
ID : HHSN261200800001E
Pays : United States
Organisme : NIAID NIH HHS
ID : R38 AI140299
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI148689
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI148450
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI148575
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI148576
Pays : United States
Organisme : United States
ID : UM1AI148575
Pays : United States
Organisme : NCI NIH HHS
ID : HHSN261201500003C
Pays : United States
Organisme : United States
ID : UM1AI148684
Pays : United States
Organisme : Medical Research Council
ID : MC_UU_12023/22
Pays : United Kingdom
Organisme : United States
ID : UM1AI148689
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI148452
Pays : United States
Organisme : United States
ID : HHSN261201500003I
Pays : United States
Organisme : United States
ID : UM1AI148450
Pays : United States
Investigateurs
Aneesh K Mehta
(AK)
Nadine G Rouphael
(NG)
Jessica J Traenkner
(JJ)
Valeria D Cantos
(VD)
Ghina Alaaeddine
(G)
Barry S Zingman
(BS)
Robert Grossberg
(R)
Paul F Riska
(PF)
Elizabeth Hohmann
(E)
Mariam Torres-Soto
(M)
Nikolaus Jilg
(N)
Helen Y Chu
(HY)
Anna Wald
(A)
Margaret Green
(M)
Annie Luetkemeyer
(A)
Pierre-Cedric B Crouch
(PB)
Hannah Jang
(H)
Susan Kline
(S)
Joanne Billings
(J)
Brooke Noren
(B)
Diego Lopez de Castilla
(D)
Jason W Van Winkle
(JW)
Francis X Riedo
(FX)
Robert W Finberg
(RW)
Jennifer P Wang
(JP)
Mireya Wessolossky
(M)
Kerry Dierberg
(K)
Benjamin Eckhardt
(B)
Henry J Neumann
(HJ)
Victor Tapson
(V)
Jonathan Grein
(J)
Fayyaz Sutterwala
(F)
Lanny Hsieh
(L)
Alpesh N Amin
(AN)
Thomas F Patterson
(TF)
Heta Javeri
(H)
Trung Vu
(T)
Roger Paredes
(R)
Lourdes Mateu
(L)
Daniel A Sweeney
(DA)
Constance A Benson
(CA)
Farhana Ali
(F)
William R Short
(WR)
Pablo Tebas
(P)
Jessie Torgersen
(J)
Giota Touloumi
(G)
Vicky Gioukari
(V)
David Chien Lye
(DC)
Sean W X Ong
(SWX)
Norio Ohmagari
(N)
Ayako Mikami
(A)
Gerd Fätkenheuer
(G)
Jakob J Malin
(JJ)
Philipp Koehler
(P)
Andre C Kalil
(AC)
LuAnn Larson
(L)
Angela Hewlett
(A)
Mark G Kortepeter
(MG)
C Buddy Creech
(CB)
Isaac Thomsen
(I)
Todd W Rice
(TW)
Babafemi Taiwo
(B)
Karen Krueger
(K)
Stuart H Cohen
(SH)
George R Thompson
(GR)
Cameron Wolfe
(C)
Emmanuel B Walter
(EB)
Maria Frank
(M)
Heather Young
(H)
Ann R Falsey
(AR)
Angela R Branche
(AR)
Paul Goepfert
(P)
Nathaniel Erdmann
(N)
Otto O Yang
(OO)
Jenny Ahn
(J)
Anna Goodman
(A)
Blair Merrick
(B)
Richard M Novak
(RM)
Andrea Wendrow
(A)
Henry Arguinchona
(H)
Christa Arguinchona
(C)
Sarah L George
(SL)
Janice Tennant
(J)
Robert L Atmar
(RL)
Hana M El Sahly
(HM)
Jennifer Whitaker
(J)
D Ashley Price
(DA)
Christopher J A Duncan
(CJA)
Simeon Metallidis
(S)
Theofilos Chrysanthidis
(T)
Susan L F McLellan
(SLF)
Myoung-Don Oh
(MD)
Wan Beom Park
(WB)
Eu Suk Kim
(ES)
Jongtak Jung
(J)
Justin R Ortiz
(JR)
Karen L Kotloff
(KL)
Brian Angus
(B)
Jack David Germain Seymour
(JD)
Noreen A Hynes
(NA)
Lauren M Sauer
(LM)
Neera Ahuja
(N)
Kari Nadeau
(K)
Patrick E H Jackson
(PEH)
Taison D Bell
(TD)
Anastasia Antoniadou
(A)
Konstantinos Protopapas
(K)
Richard T Davey
(RT)
Jocelyn D Voell
(JD)
Jose Muñoz
(J)
Montserrat Roldan
(M)
Ioannis Kalomenidis
(I)
Spyros G Zakynthinos
(SG)
Catharine I Paules
(CI)
Fiona McGill
(F)
Jane Minton
(J)
Nikolaos Koulouris
(N)
Zafeiria Barmparessou
(Z)
Edwin Swiatlo
(E)
Kyle Widmer
(K)
Nikhil Huprikar
(N)
Anuradha Ganesan
(A)
Guillermo M Ruiz-Palacios
(GM)
Alfredo Ponce de León
(A)
Sandra Rajme
(S)
Justino Regalado Pineda
(J)
José Arturo Martinez-Orozco
(JA)
Mark Holodniy
(M)
Aarthi Chary
(A)
Timo Wolf
(T)
Christoph Stephan
(C)
Jan-Christian Wasmuth
(JC)
Christoph Boesecke
(C)
Martin Llewelyn
(M)
Barbara Philips
(B)
Christopher J Colombo
(CJ)
Rhonda E Colombo
(RE)
David A Lindholm
(DA)
Katrin Mende
(K)
Tida Lee
(T)
Tahaniyat Lalani
(T)
Ryan C Maves
(RC)
Gregory C Utz
(GC)
Jens Lundgren
(J)
Marie Helleberg
(M)
Jan Gerstoft
(J)
Thomas Benfield
(T)
Tomas Jensen
(T)
Birgitte Lindegaard
(B)
Lothar Weise
(L)
Lene Knudsen
(L)
Isik Johansen
(I)
Lone W Madsen
(LW)
Lars Østergaard
(L)
Nina Stærke
(N)
Henrik Nielsen
(H)
Abdel G Babiker
(AG)
Sarah Pett
(S)
James D Neaton
(JD)
David S Stephens
(DS)
Timothy H Burgess
(TH)
Timothy M Uyeki
(TM)
Robert Walker
(R)
G Lynn Marks
(GL)
Anu Osinusi
(A)
Huyen Cao
(H)
Kevin K Chung
(KK)
Susan E Chambers
(SE)
Michelle Green
(M)
Mat Makowski
(M)
Jennifer L Ferreira
(JL)
Michael R Wierzbicki
(MR)
Tyler Bonnett
(T)
Nikki Gettinger
(N)
Theresa Engel
(T)
Jing Wang
(J)
John H Beigel
(JH)
Kay M Tomashek
(KM)
Seema Nayak
(S)
Lori E Dodd
(LE)
Walla Dempsey
(W)
Effie Nomicos
(E)
Marina Lee
(M)
Peter Wolff
(P)
Rhonda Pikaart-Tautges
(R)
Mohamed Elsafy
(M)
Robert Jurao
(R)
Hyung Koo
(H)
Michael Proschan
(M)
Dean Follmann
(D)
H Clifford Lane
(HC)
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Type : CommentIn
Type : CommentIn
Type : CommentIn
Type : CommentIn
Type : CommentIn
Informations de copyright
Copyright © 2020 Massachusetts Medical Society.
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