A 10-day course of remdesivir was superior to placebo in shortening the time to recovery in hospitalized patients with coronavirus disease 2019 (COVID-19), according to study results published in the New England Journal of Medicine.
In this phase 3, double-blind, multicenter international trial (ClinicalTrials.gov identifier: NCT04280705), researchers aimed to determine the clinical effect of intravenous remdesivir. They randomly assigned 1062 hospitalized patients with COVID-19 in a 1:1 ratio to receive either remdesivir (n=541) or placebo (n=521). Remdesivir was administered intravenously (200 mg on day 1, followed by 100 mg daily on days 2 through 10) or matching placebo for up to 10 days.
The trial used an 8-category ordinal scale to assess patients’ clinical status from day 1 through day 29. The primary outcome was the time to recovery, defined as the first day on which a patient satisfied 1 of the following 3 categories from the ordinal scale: not hospitalized and no limitations on activities; not hospitalized, limitation on activities and/or requiring home oxygen; or hospitalized, not requiring supplemental oxygen and no longer requiring ongoing medical care. The key secondary outcome was clinical status at day 15, as assessed on the ordinal scale.
Of the 1062 patients (mean age, 58.9 years) who underwent randomization, 957 patients (90.1%) had severe disease at enrollment. The median number of days between symptom onset and randomization was 9. In the cohort, 64.4% of patients were men and 53.3% of patients were White. A total of 517 patients in the remdesivir group and 508 in the placebo group completed the trial through day 29, which included death and recovery.
Study results show that the time to recovery was significantly shorter among patients who received remdesivir than among those who received placebo (median, 10 vs 15 days; rate ratio for recovery, 1.29; 95% CI, 1.12-1.49; P <.001). In patients with severe disease, the median time to recovery was 11 days in the remdesivir group vs 18 days in the placebo group (rate ratio for recovery, 1.31; 95% CI, 1.12-1.52).
After adjustment for disease severity, patients in the remdesivir group were more likely to show clinical improvement at day 15 than patients in the placebo group (odds ratio, 1.5; 95% CI, 1.2-1.9). In addition, there was a trend toward lower mortality in patients in the remdesivir group compared with the placebo group both at day 15 (6.7% vs 11.9%; hazard ratio [HR], 0.55; 95% CI, 0.36-0.83) and day 29 (11.4% vs 15.2%; HR, 0.73; 95% CI, 0.52-1.03).
Serious adverse events occurred in 24.6% (131/532) of patients in the remdesivir group and 31.6% (163/516) of patients in the placebo group.
Treatment with an antiviral drug alone is not sufficient for all patients given the high mortality despite the use of remdesivir, researchers noted. “A variety of therapeutic approaches including novel antivirals, modifiers of the immune response or other intrinsic pathways, and combination approaches are needed to continue to improve outcomes in patients with COVID-19,” the researchers concluded.
Beigel JH, Tomashek KM, Dodd LE, et al; for the ACTT-1 Study Group Members. Remdesivir for the treatment of Covid-19 – final report. N Engl J Med. Published online October 8, 2020 doi:10.1056/NEJMoa2007764