March 9, 2022
Remdesivir Compared to Standard of Care for the Treatment of COVID-19Reviewed by Zeina Kanafani, MD, MS, FIDSA
Remdesivir is a nucleotide analog prodrug targeting the RNA polymerase of coronaviruses. In vitro and in vivo data have shown antiviral activity of remdesivir against SARS-CoV-2, but early clinical trials have yielded inconsistent results as to the efficacy of remdesivir in patients with COVID-19. DisCoVeRy is a phase III, randomized, controlled, open-label trial that compared remdesivir plus standard of care to standard of care alone in hospitalized COVID-19 patients requiring oxygen supplementation or mechanical ventilation.
The trial, described in Lancet Infectious Diseases, was conducted in 48 sites in Europe. At first, subjects had to have laboratory-confirmed SARS-CoV-2 infection for a maximum of 72 hours before randomization, but this period was later extended to 9 days. The primary outcome was the clinical status at day 15, using seven possible outcomes designated by the WHO Master Protocol: (1) not hospitalized, no limitation on activities; (2) not hospitalized, limitation on activities; (3) hospitalized, not requiring supplemental oxygen; (4) hospitalized, requiring supplemental oxygen; (5) hospitalized, on noninvasive ventilation or high-flow oxygen devices; (6) hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation; and (7) dead.
A total of 414 patients were allocated to remdesivir plus standard of care and 418 to standard of care alone in the intention-to-treat analysis. There was no difference in the baseline characteristics between the two groups. In the overall population, the median age was 64 years, 39% of subjects had severe COVID-19 at randomization, and the median time from symptom onset to randomization was 9 days (interquartile range, 7-12 days). The seven-point health status at day 15 (primary outcome) was not different between the patients randomized to remdesivir or to standard of care (P = .85). Secondary outcomes were also similar between the two study groups, including clinical status at day 29, days to improvement of two categories on the seven-point ordinal scale, hospital discharge within 29 days, and death within 28 days. Among the 677 patients in whom viral loads were measured, the median decrease in viral loads between baseline and day 3 after randomization was similar in the remdesivir and control groups. Remdesivir had no significant effect on viral kinetics throughout the treatment period. Safety analysis showed similar adverse events (59% vs. 57%) and serious adverse events (33% vs. 31%) in the remdesivir and control groups.
The investigators concluded that the addition of remdesivir to standard of care did not improve outcomes in patients hospitalized with COVID-19 who have had symptoms for 7 days or more.
