• Gilmar Reis, Eduardo A S M Silva, Daniela C M Silva, Lehana Thabane, Aline C Milagres, Thiago S Ferreira, Castilho V Q Dos Santos, Vitoria H S Campos, Ana M R Nogueira, Ana P F G de Almeida, Eduardo D Callegari, Adhemar D F Neto, Leonardo C M Savassi, Maria I C Simplicio, Luciene B Ribeiro, Rosemary Oliveira, Ofir Harari, Jamie I Forrest, Hinda Ruton, Sheila Sprague, Paula McKay, Christina M Guo, Karen Rowland-Yeo, Gordon H Guyatt, David R Boulware, Craig R Rayner, Edward J Mills, and TOGETHER Investigators.
• From the Research Division, Cardresearch-Cardiologia Assistencial e de Pesquisa (G.R., E.A.S.M.S., D.C.M.S., T.S.F., C.V.Q.S., V.H.S.C., M.I.C.S., L.B.R., R.O.), and the Department of Medicine, Pontifical Catholic University of Minas Gerais (G.R., E.A.S.M.S., D.C.M.S., C.V.Q.S., V.H.S.C.), Belo Horizonte, the Department of Public Health and Mental and Family Medicine, Ouro Preto Federal University, Ouro Preto (A.C.M., L.C.M.S.), the Public Health Care Division, Ibirité (A.C.M.), the Department of Public Health and the Family Medicine Fellowship Program, UNIFIPMoc, Montes Claros (A.M.R.N., A.P.F.G.A.), the Public Health Care Division, Brumadinho (E.D.C.), and the Public Health Fellowship Program, Governador Valadares Public Health Authority, Governador Valadares (A.D.F.N.) - all in Brazil; the Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON (L.T., S.S., P.M., G.H.G., E.J.M.), and Cytel (O.H., H.R., E.J.M.) and Platform Life Sciences (J.I.F., C.M.G., E.J.M.), Vancouver, BC - all in Canada; Certara, Princeton, NJ (K.R.-Y., C.R.R.); the Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis (D.R.B.); and Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, VIC, Australia (C.R.R.).
• N. Engl. J. Med. 2022 May 5; 386 (18): 172117311721-1731.

BackgroundThe efficacy of ivermectin in preventing hospitalization or extended observation in an emergency setting among outpatients with acutely symptomatic coronavirus disease 2019 (Covid-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is unclear.MethodsWe conducted a double-blind, randomized, placebo-controlled, adaptive platform trial involving symptomatic SARS-CoV-2-positive adults recruited from 12 public health clinics in Brazil. Patients who had had symptoms of Covid-19 for up to 7 days and had at least one risk factor for disease progression were randomly assigned to receive ivermectin (400 μg per kilogram of body weight) once daily for 3 days or placebo. (The trial also involved other interventions that are not reported here.) The primary composite outcome was hospitalization due to Covid-19 within 28 days after randomization or an emergency department visit due to clinical worsening of Covid-19 (defined as the participant remaining under observation for >6 hours) within 28 days after randomization.ResultsA total of 3515 patients were randomly assigned to receive ivermectin (679 patients), placebo (679), or another intervention (2157). Overall, 100 patients (14.7%) in the ivermectin group had a primary-outcome event, as compared with 111 (16.3%) in the placebo group (relative risk, 0.90; 95% Bayesian credible interval, 0.70 to 1.16). Of the 211 primary-outcome events, 171 (81.0%) were hospital admissions. Findings were similar to the primary analysis in a modified intention-to-treat analysis that included only patients who received at least one dose of ivermectin or placebo (relative risk, 0.89; 95% Bayesian credible interval, 0.69 to 1.15) and in a per-protocol analysis that included only patients who reported 100% adherence to the assigned regimen (relative risk, 0.94; 95% Bayesian credible interval, 0.67 to 1.35). There were no significant effects of ivermectin use on secondary outcomes or adverse events.ConclusionsTreatment with ivermectin did not result in a lower incidence of medical admission to a hospital due to progression of Covid-19 or of prolonged emergency department observation among outpatients with an early diagnosis of Covid-19. (Funded by FastGrants and the Rainwater Charitable Foundation; TOGETHER ClinicalTrials.gov number, NCT04727424.).Copyright © 2022 Massachusetts Medical Society.

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