tetano
Editor, Senior Moderator
N Engl J Med
. 2020 May 27.
doi: 10.1056/NEJMoa2015301. Online ahead of print.
Remdesivir for 5 or 10 Days in Patients With Severe Covid-19
Jason D Goldman[SUP] 1 [/SUP], David C B Lye[SUP] 1 [/SUP], David S Hui[SUP] 1 [/SUP], Kristen M Marks[SUP] 1 [/SUP], Raffaele Bruno[SUP] 1 [/SUP], Rocio Montejano[SUP] 1 [/SUP], Christoph D Spinner[SUP] 1 [/SUP], Massimo Galli[SUP] 1 [/SUP], Mi-Young Ahn[SUP] 1 [/SUP], Ronald G Nahass[SUP] 1 [/SUP], Yao-Shen Chen[SUP] 1 [/SUP], Devi SenGupta[SUP] 1 [/SUP], Robert H Hyland[SUP] 1 [/SUP], Anu O Osinusi[SUP] 1 [/SUP], Huyen Cao[SUP] 1 [/SUP], Christiana Blair[SUP] 1 [/SUP], Xuelian Wei[SUP] 1 [/SUP], Anuj Gaggar[SUP] 1 [/SUP], Diana M Brainard[SUP] 1 [/SUP], William J Towner[SUP] 1 [/SUP], Jose Mu?oz[SUP] 1 [/SUP], Kathleen M Mullane[SUP] 1 [/SUP], Francisco M Marty[SUP] 1 [/SUP], Karen T Tashima[SUP] 1 [/SUP], George Diaz[SUP] 1 [/SUP], Aruna Subramanian[SUP] 1 [/SUP], GS-US-540-5773 Investigators
Affiliations
Abstract
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.).
. 2020 May 27.
doi: 10.1056/NEJMoa2015301. Online ahead of print.
Remdesivir for 5 or 10 Days in Patients With Severe Covid-19
Jason D Goldman[SUP] 1 [/SUP], David C B Lye[SUP] 1 [/SUP], David S Hui[SUP] 1 [/SUP], Kristen M Marks[SUP] 1 [/SUP], Raffaele Bruno[SUP] 1 [/SUP], Rocio Montejano[SUP] 1 [/SUP], Christoph D Spinner[SUP] 1 [/SUP], Massimo Galli[SUP] 1 [/SUP], Mi-Young Ahn[SUP] 1 [/SUP], Ronald G Nahass[SUP] 1 [/SUP], Yao-Shen Chen[SUP] 1 [/SUP], Devi SenGupta[SUP] 1 [/SUP], Robert H Hyland[SUP] 1 [/SUP], Anu O Osinusi[SUP] 1 [/SUP], Huyen Cao[SUP] 1 [/SUP], Christiana Blair[SUP] 1 [/SUP], Xuelian Wei[SUP] 1 [/SUP], Anuj Gaggar[SUP] 1 [/SUP], Diana M Brainard[SUP] 1 [/SUP], William J Towner[SUP] 1 [/SUP], Jose Mu?oz[SUP] 1 [/SUP], Kathleen M Mullane[SUP] 1 [/SUP], Francisco M Marty[SUP] 1 [/SUP], Karen T Tashima[SUP] 1 [/SUP], George Diaz[SUP] 1 [/SUP], Aruna Subramanian[SUP] 1 [/SUP], GS-US-540-5773 Investigators
Affiliations
- PMID: 32459919
- DOI: 10.1056/NEJMoa2015301
Abstract
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.).