Remdesivir for 5 or 10 Days in Patients with Severe Covid-19.
The New England journal of medicine
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.).
Goldman, Jason D; Lye, David C B; Hui, David S; Marks, Kristen M; Bruno, Raffaele; Montejano, Rocio; Spinner, Christoph D; Galli, Massimo; Ahn, Mi-Young; Nahass, Ronald G; Chen, Yao-Shen; SenGupta, Devi; Hyland, Robert H; Osinusi, Anu O; Cao, Huyen; Blair, Christiana; Wei, Xuelian; Gaggar, Anuj; Brainard, Diana M; Towner, William J; Muñoz, Jose; Mullane, Kathleen M; Marty, Francisco M; Tashima, Karen T; Diaz, George; and Subramanian, Aruna, "Remdesivir for 5 or 10 Days in Patients with Severe Covid-19." (2020). Articles, Abstracts, and Reports. 3121.