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

Abstract

Background: 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.

Methods: We conducted a randomized, double-blind, placebo-controlled trial involving 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.

Results: 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.

Conclusions: 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. (Funded by Gilead Sciences; PINETREE ClinicalTrials.gov number, NCT04501952; EudraCT number, 2020-003510-12.).

Figure 1. Primary Efficacy and Secondary End Points.

Panel A shows the Kaplan–Meier estimate of the time to hospitalization related to coronavirus disease 2019 (Covid-19) or death from any cause by day 28 (the primary efficacy end point). Panel B shows the Kaplan–Meier estimate of the time to a Covid-19–related medically attended visit or death from any cause by day 28 (a secondary end point); this end point was assessed in the modified full analysis set, which is defined in the statistical analysis plan (available with the protocol at NEJM.org). The hazard ratios, two-sided 95% confidence intervals, and P value were estimated with the use of Cox regression with the baseline stratification factors as covariates: residence in a skilled nursing facility (yes or no), age (<60 years or ≥60 years), and country (United States or outside the United States). Insets show the same data on an enlarged y axis.

Figure 2. Covid-19–Related Hospitalization or Death from Any Cause at Day 28 in More Than 5% of the Trial Population, According to Demographic and Clinical Characteristics at Baseline.

Hazard ratios and two-sided 95% confidence intervals (𝙸 bars) were estimated with the use of Cox regression with the baseline stratification factors as covariates: residence in a skilled nursing facility (yes or no), age (<60 years or ≥60 years), and country (United States or outside the United States). Analyses with stratification according to Hispanic or Latinx ethnic group were conducted post hoc. Hazard ratios and 95% confidence intervals for subgroups with no events in the remdesivir group could not be accurately calculated and are therefore omitted. The dashed line indicates a hazard ratio of 1.0.