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

N Engl J Med. 2022 Jan 27;386(4):305-315. doi: 10.1056/NEJMoa2116846. Epub 2021 Dec 22.

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.).

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Monophosphate / adverse effects
  • Adenosine Monophosphate / analogs & derivatives*
  • Adenosine Monophosphate / therapeutic use
  • Adult
  • Aged
  • Aged, 80 and over
  • Alanine / adverse effects
  • Alanine / analogs & derivatives*
  • Alanine / therapeutic use
  • Antiviral Agents / adverse effects
  • Antiviral Agents / therapeutic use*
  • COVID-19 / complications
  • COVID-19 / drug therapy*
  • COVID-19 / mortality
  • Comorbidity
  • Disease Progression
  • Double-Blind Method
  • Female
  • Hospitalization / statistics & numerical data
  • Humans
  • Male
  • Middle Aged
  • Outpatients
  • SARS-CoV-2 / drug effects
  • Time-to-Treatment
  • Viral Load

Substances

  • Antiviral Agents
  • remdesivir
  • Adenosine Monophosphate
  • Alanine

Supplementary concepts

  • COVID-19 drug treatment

Associated data

  • ClinicalTrials.gov/NCT04501952
  • EudraCT/2020-003510-12

Grant support