tetano
Editor, Senior Moderator
N Engl J Med
. 2021 Dec 22.
doi: 10.1056/NEJMoa2116846. Online ahead of print.
Early Remdesivir to Prevent Progression to Severe Covid-19 in Outpatients
Robert L Gottlieb[SUP] 1 [/SUP], Carlos E Vaca[SUP] 1 [/SUP], Roger Paredes[SUP] 1 [/SUP], Jorge Mera[SUP] 1 [/SUP], Brandon J Webb[SUP] 1 [/SUP], Gilberto Perez[SUP] 1 [/SUP], Godson Oguchi[SUP] 1 [/SUP], Pablo Ryan[SUP] 1 [/SUP], Bibi U Nielsen[SUP] 1 [/SUP], Michael Brown[SUP] 1 [/SUP], Ausberto Hidalgo[SUP] 1 [/SUP], Yessica Sachdeva[SUP] 1 [/SUP], Shilpi Mittal[SUP] 1 [/SUP], Olayemi Osiyemi[SUP] 1 [/SUP], Jacek Skarbinski[SUP] 1 [/SUP], Kavita Juneja[SUP] 1 [/SUP], Robert H Hyland[SUP] 1 [/SUP], Anu Osinusi[SUP] 1 [/SUP], Shuguang Chen[SUP] 1 [/SUP], Gregory Camus[SUP] 1 [/SUP], Mazin Abdelghany[SUP] 1 [/SUP], Santosh Davies[SUP] 1 [/SUP], Nicole Behenna-Renton[SUP] 1 [/SUP], Frank Duff[SUP] 1 [/SUP], Francisco M Marty[SUP] 1 [/SUP], Morgan J Katz[SUP] 1 [/SUP], Adit A Ginde[SUP] 1 [/SUP], Samuel M Brown[SUP] 1 [/SUP], Joshua T Schiffer[SUP] 1 [/SUP], Joshua A Hill[SUP] 1 [/SUP], GS-US-540-9012 (PINETREE) Investigators
Affiliations
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.).
. 2021 Dec 22.
doi: 10.1056/NEJMoa2116846. Online ahead of print.
Early Remdesivir to Prevent Progression to Severe Covid-19 in Outpatients
Robert L Gottlieb[SUP] 1 [/SUP], Carlos E Vaca[SUP] 1 [/SUP], Roger Paredes[SUP] 1 [/SUP], Jorge Mera[SUP] 1 [/SUP], Brandon J Webb[SUP] 1 [/SUP], Gilberto Perez[SUP] 1 [/SUP], Godson Oguchi[SUP] 1 [/SUP], Pablo Ryan[SUP] 1 [/SUP], Bibi U Nielsen[SUP] 1 [/SUP], Michael Brown[SUP] 1 [/SUP], Ausberto Hidalgo[SUP] 1 [/SUP], Yessica Sachdeva[SUP] 1 [/SUP], Shilpi Mittal[SUP] 1 [/SUP], Olayemi Osiyemi[SUP] 1 [/SUP], Jacek Skarbinski[SUP] 1 [/SUP], Kavita Juneja[SUP] 1 [/SUP], Robert H Hyland[SUP] 1 [/SUP], Anu Osinusi[SUP] 1 [/SUP], Shuguang Chen[SUP] 1 [/SUP], Gregory Camus[SUP] 1 [/SUP], Mazin Abdelghany[SUP] 1 [/SUP], Santosh Davies[SUP] 1 [/SUP], Nicole Behenna-Renton[SUP] 1 [/SUP], Frank Duff[SUP] 1 [/SUP], Francisco M Marty[SUP] 1 [/SUP], Morgan J Katz[SUP] 1 [/SUP], Adit A Ginde[SUP] 1 [/SUP], Samuel M Brown[SUP] 1 [/SUP], Joshua T Schiffer[SUP] 1 [/SUP], Joshua A Hill[SUP] 1 [/SUP], GS-US-540-9012 (PINETREE) Investigators
Affiliations
- PMID: 34937145
- DOI: 10.1056/NEJMoa2116846
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.).
