Remdesivir for the Treatment of Covid-19 ‚Ä?Preliminary Report
Authors: Margaret Green
Barry S Zingman
Christopher J Colombo
Robert Jurao
Daniel A Sweeney
D Ashley Price
Anuradha Ganesan
ACTT-1 Study Group Members
Jongtak Jung
Nina St√¶rke
Richard M Novak
Michael R Wierzbicki
Diego Lopez de Castilla
Mohamed Elsafy
Susan E Chambers
Mark Holodniy
Jessica J Traenkner
Jose Mu√±oz
Anastasia Antoniadou
Isaac Thomsen
Paul Goepfert
Fayyaz Sutterwala
Stuart H Cohen
Taison D Bell
Jocelyn D Voell
Nikhil Huprikar
Maria Frank
Sarah L George
Kerry Dierberg
Aarthi Chary
Nathaniel Erdmann
Blair Merrick
Susan Kline
Justin R Ortiz
Kari Nadeau
Jos√© Arturo Martinez-Orozco
Michael Proschan
G Lynn Marks
Montserrat Roldan
Lothar Weise
Ghina Alaaeddine
Jens Lundgren
Jakob J Malin
David A Lindholm
Andre C Kalil
Rhonda E Colombo
Joanne Billings
Thomas Benfield
Jason W Van Winkle
Helen Y Chu
Philipp Koehler
Tida Lee
Christopher J A Duncan
Elizabeth Hohmann
Jack David Germain Seymour
Robert Grossberg
Edwin Swiatlo
Ioannis Kalomenidis
Dean Follmann
Jennifer P Wang
Roger Paredes
Mark G Kortepeter
Alpesh N Amin
Marie Helleberg
Birgitte Lindegaard
Jing Wang
Timothy M Uyeki
Lars √òstergaard
Lori E Dodd
Jennifer Whitaker
James D Neaton
Pierre-Cedric B Crouch
Annie Luetkemeyer
Peter Wolff
Anna Goodman
Brooke Noren
Angela R Branche
Henrik Nielsen
Barbara Philips
Lanny Hsieh
Isik Johansen
Fiona McGill
Susan L F McLellan
Trung Vu
Constance A Benson
Hana M El Sahly
Gerd F√§tkenheuer
Babafemi Taiwo
Lene Knudsen
Mariam Torres-Soto
Henry J Neumann
Jane Minton
Timothy H Burgess
Heta Javeri
Cameron Wolfe
C Buddy Creech
Kyle Widmer
Aneesh K Mehta
Valeria D Cantos
Pablo Tebas
Lone W Madsen
David S Stephens
Seema Nayak
Walla Dempsey
Kay M Tomashek
Robert Walker
Anu Osinusi
Tahaniyat Lalani
Hyung Koo
Jessie Torgersen
Jan Gerstoft
Abdel G Babiker
Emmanuel B Walter
Richard T Davey
Tyler Bonnett
Guillermo M Ruiz-Palacios
Robert L Atmar
Norio Ohmagari
Simeon Metallidis
Sandra Rajme
Lourdes Mateu
Ann R Falsey
Katrin Mende
Myoung-Don Oh
Eu Suk Kim
Jennifer L Ferreira
Sean W X Ong
Ayako Mikami
Tomas Jensen
Huyen Cao
John H Beigel
Justino Regalado Pineda
Kevin K Chung
Patrick E H Jackson
Konstantinos Protopapas
Nikolaus Jilg
Thomas F Patterson
Gregory C Utz
Michelle Green
Theofilos Chrysanthidis
Marina Lee
Nikki Gettinger
Martin Llewelyn
Benjamin Eckhardt
Alfredo Ponce de Le√≥n
William R Short
Sarah Pett
Neera Ahuja
Christoph Boesecke
Mireya Wessolossky
Andrea Wendrow
Todd W Rice
Wan Beom Park
Heather Young
Paul F Riska
Anna Wald
Christoph Stephan
H Clifford Lane
David Chien Lye
Angela Hewlett
Mat Makowski
Giota Touloumi
Brian Angus
Janice Tennant
Rhonda Pikaart-Tautges
Farhana Ali
Francis X Riedo
Zafeiria Barmparessou
Catharine I Paules
Jonathan Grein
Spyros G Zakynthinos
Jan-Christian Wasmuth
Christa Arguinchona
Lauren M Sauer
Otto O Yang
George R Thompson 3rd
Karen Krueger
Robert W Finberg
Ryan C Maves
Noreen A Hynes
Hannah Jang
Nikolaos Koulouris
Nadine G Rouphael
Victor Tapson
Henry Arguinchona
Theresa Engel
Karen L Kotloff
LuAnn Larson
Timo Wolf
Jenny Ahn
Vicky Gioukari
Effie Nomicos
Journal: New England Journal of Medicine (2020)
Discipline: CLINICAL MEDICINE
Keywords: therapeutic agents; coronavirus disease 2019; Covid-19; antiviral agents; remdesivir
Affiliations: From the National Institute of Allergy and Infectious Diseases, National Institutes of Health (J.H.B., K.M.T., L.E.D., S.N., H.C.L.), and the Infectious Disease Clinical Research Program, Uniformed Services University of the Health Sciences (T.H.B.), Bethesda, the Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research, Frederick (T. Bonnett), and Emmes, Rockville (M.G., M.M.) - all in Maryland; Emory University, Atlanta (A.K.M.); Montefiore Medical Center-Albert Einstein College of Medicine (B.S.Z.) and NYU Langone Health and NYC Health + Hospitals- Bellevue (K.D.), New York; University of Nebraska Medical Center, Omaha (A.C.K., M.G.K.); Massachusetts General Hospital, Boston (E.H.), and University of Massachusetts Medical School, Worcester (R.W.F.); University of Washington, Seattle (H.Y.C.), and Evergreen Health Medical Center, Kirkland (D.L.C.) - both in Washington; University of California, San Francisco, San Francisco (A.L.), Cedars Sinai Medical Center, Los Angeles (V.T.), University of California, Irvine, Irvine (L.H.), University of California, San Diego, La Jolla (D.A.S.), and Gilead Sciences, Foster City (A.O.) - all in California; University of Minnesota (S.K.) and University of Minnesota, School of Public Health and INSIGHT (J.D.N.), Minneapolis; University of Texas Health San Antonio, University Health System, and the South Texas Veterans Health Care System, San Antonio (T.F.P.), and Baylor College of Medicine, Houston (R.L.A.); Hospital Germans Trias i Pujol & irsiCaixa AIDS Research Institute, Badalona, Spain (R.P.); University of Pennsylvania, Philadelphia (W.R.S.); Medical School, National and Kapodistrian University of Athens, Athens (G.T.); National Center for Infectious Diseases-Tan Tock Seng Hospital-Lee Kong Chian School of Medicine-Yong Loo Lin School of Medicine, Singapore, Singapore (D.C.L.); the National Center for Global Health and Medicine Hospital, Tokyo (N.O.); Seoul National University Hospital, Seoul, South Korea (M.O.); Instituto Nacional de Ciencias M√©dicas y Nutrici√≥n Salvador Zubir√°n, Mexico City (G.M.R.-P.); the Department of Infectious Diseases, Amager Hvidovre Hospital-University of Copenhagen, Hvidovre (T. Benfield), and Rigshospitalet, Department of Infectious Diseases (CHIP) and INSIGHT, Copenhagen (J.L.) - both in Denmark; University Hospital of Cologne, Cologne, Germany (G.F.); Vanderbilt University Medical Center, Nashville (C.B.C.); and University College London, MRC Clinical Trials Unit at UCL and INSIGHT, London (A.G.B., S.P.).

Abstract:  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&lt;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.). 

Retracted: No

PubPeer comments:
 Interestingly, a 1-day shifted overlay in Fig 2A shows an almost perfect match of curves between the two groups.  , 
  Interestingly, a 1-day shifted overlay in Figure 2A shows an almost perfect match of curves between the two groups. , 
 #2 Is this particularly unexpected? , 
 Reference 1 of the following paper by Gillenwater et al. lists this paper, with the same DOI, with one different word in its title:  preliminary rather than  final .  1. Beigel JH, Tomashek KM, Dodd LE, et al. Remdesivir for the treatment of Covid-19 u2014 preliminary report. N Engl J Med. DOI: 10.1056 NEJMoa2007764. DOI: 10.1056 NEJMc2022236 Did the title change at some point during processing? From the abstract:  Serious adverse events were reported in 131 of the 532 patients who received remdesivir (24.6%) Keeping this statement in mind, how would the authors argue the safety of this antiviral drug to a regular member of the public? ,