| Randomised double-blinded placebo-controlled trial  

Early Remdesivir to Prevent Progression to Severe COVID-19 in Outpatients

Remdesivir improves clinical outcomes in patients hospitalized with moderate-to-severe coronavirus disease 2019 (COVID-19). Whether the use of remdesivir in symptomatic, nonhospitalized patients with COVID-19 who are at high risk for disease progression prevents hospitalization is uncertain.

This randomized, double-blind, placebo-controlled trial involved nonhospitalized patients with COVID-19 who had symptom onset within the previous 7 days and who had at least one risk factor for disease progression (age ≥60 years, obesity, or certain coexisting medical conditions). Patients were randomly assigned to receive intravenous remdesivir (200 mg on day 1 and 100 mg on days 2 and 3) or placebo. The primary efficacy end point was a composite of COVID-19–related hospitalization or death from any cause by day 28. The primary safety end point was any adverse event. A secondary end point was a composite of a COVID-19–related medically attended visit or death from any cause by day 28.
A total of 562 patients who underwent randomization and received at least one dose of remdesivir or placebo were included in the analyses: 279 patients in the remdesivir group and 283 in the placebo group. The mean age was 50 years, 47.9% of the patients were women, and 41.8% were Hispanic or Latinx. The most common coexisting conditions were diabetes mellitus (61.6%), obesity (55.2%), and hypertension (47.7%). COVID-19–related hospitalization or death from any cause occurred in 2 patients (0.7%) in the remdesivir group and in 15 (5.3%) in the placebo group (hazard ratio, 0.13; 95% confidence interval [CI], 0.03 to 0.59; P=0.008). A total of 4 of 246 patients (1.6%) in the remdesivir group and 21 of 252 (8.3%) in the placebo group had a COVID-19–related medically attended visit by day 28 (hazard ratio, 0.19; 95% CI, 0.07 to 0.56). No patients had died by day 28. Adverse events occurred in 42.3% of the patients in the remdesivir group and in 46.3% of those in the placebo group. The authors concluded that among nonhospitalized patients who were at high risk for COVID-19 progression, a 3-day course of remdesivir had an acceptable safety profile and resulted in an 87% lower risk of hospitalization or death than placebo.
Gottlieb RL, Vaca CE, Paredes R, Mera J, Webb BJ, Perez G, Oguchi G, Ryan P, Nielsen BU, Brown M, Hidalgo A, Sachdeva Y, Mittal S, Osiyemi O, Skarbinski J, Juneja K, Hyland RH, Osinusi A, Chen S, Camus G, Abdelghany M, Davies S, Behenna-Renton N, Duff F, Marty FM, Katz MJ, Ginde AA, Brown SM, Schiffer JT, Hill JA; GS-US-540-9012 (PINETREE) Investigators. Early Remdesivir to Prevent Progression to Severe COVID-19 in Outpatients. N Engl J Med. 2021 Dec 22.

doi: 10.1056/NEJMoa2116846.