Remdesivir for 5 or 10 Days in Patients with Severe Covid-19

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.).

Figure 1. Enrollment and Randomization.

Figure 2. Oxygen Support on Day 14 According to Oxygen Support on Day 5.

Shown is the distribution of oxygen-support status on day 14 for the 5-day and 10-day treatment groups according to oxygen-support status at day 5 of therapy. Percentages are based on patients with both day 5 and day 14 oxygen-support data available and exclude those with missing oxygen-support data for day 14. Oxygen-support status is derived from the clinical status according to the seven-point ordinal scale, as follows: 1, death; 2, receiving invasive mechanical ventilation; 3, receiving high-flow oxygen; 4, receiving low-flow oxygen; 5 or 6, breathing ambient air; and 7, discharge. Data on high-flow oxygen were missing for 1 patient in the 10-day group; data on low-flow oxygen were missing for 3 patients in the 5-day group and 6 patients in the 10-day group, and data on ambient air were missing for 3 patients in the 5-day group.