Early Remdesivir to Prevent Progression to Severe Covid-19 in Outpatients
New England Journal of Medicine, doi:10.1056/nejmoa2116846
BACKGROUND Remdesivir improves clinical outcomes in patients hospitalized with moderate-tosevere 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-19related 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-19related 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.
Appendix The authors' full names and academic degrees are as follows: Robert L. Gottlieb
Ader, Bouscambert-Duchamp, Hites, Remdesivir plus standard of care versus standard of care alone for the treatment of patients admitted to hos-The New England Journal of Medicine nloaded from
Beigel, Tomashek, Dodd, Remdesivir for the treatment of Covid-19 -final report, N Engl J Med
Cevik, Kuppalli, Kindrachuk, Peiris, Virology, transmission, and pathogenesis of SARS-CoV-2, BMJ
Chen, Winkler, Case, In vivo monoclonal antibody efficacy against SARS-CoV-2 variant strains, Nature
Dougan, Nirula, Azizad, Bamlanivimab plus etesevimab in mild or moderate Covid-19, N Engl J Med
Fintzi, Bonnett, Sweeney, Deconstructing the treatment effect of remdesivir in the Adaptive COVID-19
Gallo Marin, Aghagoli, Lavine, Predictors of COVID-19 severity: a literature review, Rev Med Virol
Goldman, Lye, Hui, Remdesivir for 5 or 10 days in patients with severe Covid-19, N Engl J Med
Gottlieb, Nirula, Chen, Effect of bamlanivimab as monotherapy or in combination with etesevimab on viral load in patients with mild to moderate COVID-19: a randomized clinical trial, JAMA
Gupta, Gonzalez-Rojas, Juarez, Early treatment for Covid-19 with SARS-CoV-2 neutralizing antibody sotrovimab, N Engl J Med
Huang, Wang, Li, Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China, Lancet
Mozaffari, Chandak, Zhang, Remdesivir treatment in hospitalized patients with COVID-19: a comparative analysis of in-hospital all-cause mortality in a large multi-center observational cohort, Clin Infect Dis
Mulangu, Dodd, Rt, A randomized, controlled trial of Ebola virus disease therapeutics, N Engl J Med
Muthuri, Venkatesan, Myles, Effectiveness of neuraminidase inhibitors in reducing mortality in patients admitted to hospital with influenza A H1N1pdm09 virus infection: a meta-analysis of individual participant data, Lancet Respir Med
Nicholson, Aoki, Osterhaus, Efficacy and safety of oseltamivir in treatment of acute influenza: a randomised controlled trial, Lancet
Pitts, Lu, Pont, Remdesivir retains potent antiviral activity against the SARS-CoV-2 delta variant and other variants of concern
Pizzorno, Padey, Julien, Characterization and treatment of SARS-CoV-2 in nasal and bronchial human airway epithelia, Cell Rep Med
Schäfer, Martinez, Won, Therapeutic efficacy of an oral nucleoside analog of remdesivir against SARS-CoV-2 pathogenesis in mice, doi:10.1101/2021.09.13.460111v3
Sheahan, Sims, Graham, Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses, Sci Transl Med
Siddiqi, Mehra, COVID-19 illness in native and immunosuppressed states: a clinical-therapeutic staging proposal, J Heart Lung Transplant
Spinner, Gottlieb, Criner, Effect of remdesivir vs standard care on clinical status at 11 days in patients with moderate COVID-19: a randomized clinical trial, JAMA
Stokes, Zambrano, Anderson, Coronavirus disease 2019 case surveillance -United States, January 22, MMWR Morb Mortal Wkly Rep
The, Group, Initiation of antiretroviral therapy in early asymptomatic HIV infection, N Engl J Med
Wang, Hu, Hu, Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China, JAMA
Weinreich, Sivapalasingam, Norton, REGN-COV2, a neutralizing antibody cocktail, in outpatients with Covid-19, N Engl J Med
Williamson, Feldmann, Schwarz, Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2, Nature