TY - JOUR
T1 - Remdesivir for 5 or 10 days in patients with severe covid-19
AU - GS-US-540-5773 Investigators
AU - Goldman, Jason D.
AU - Lye, David C.B.
AU - Hui, David S.
AU - Marks, Kristen M.
AU - Bruno, Raffaele
AU - Montejano, Rocio
AU - Spinner, Christoph D.
AU - Galli, Massimo
AU - Ahn, Mi Young
AU - Nahass, Ronald G.
AU - Chen, Yao Shen
AU - SenGupta, Devi
AU - Hyland, Robert H.
AU - Osinusi, Anu O.
AU - Cao, Huyen
AU - Blair, Christiana
AU - Wei, Xuelian
AU - Gaggar, Anuj
AU - Brainard, Diana M.
AU - Towner, William J.
AU - Muñoz, Jose
AU - Mullane, Kathleen M.
AU - Marty, Francisco M.
AU - Tashima, Karen T.
AU - Diaz, George
AU - Subramanian, Aruna
N1 - Publisher Copyright:
Copyright © 2020 Massachusetts Medical Society.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/11/5
Y1 - 2020/11/5
N2 - 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.
AB - 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.
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U2 - 10.1056/NEJMoa2015301
DO - 10.1056/NEJMoa2015301
M3 - Article
C2 - 32459919
AN - SCOPUS:85094950659
VL - 383
SP - 1827
EP - 1837
JO - New England Journal of Medicine
JF - New England Journal of Medicine
SN - 0028-4793
IS - 19
ER -