Effect of Early Treatment with Ivermectin among Patients with Covid-19

Gilmar Reis, Eduardo A.S.M. Silva, Danie 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 SpraguePaula McKay, Christina M. Guo, Karen Rowland-Yeo, Gordon H. Guyatt, David R. Boulware, Craig R. Rayner, Edward J. Mills

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

BACKGROUND: The 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.

METHODS: We 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.

RESULTS: A 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.

CONCLUSIONS: Treatment 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.).

Original languageEnglish (US)
Pages (from-to)1721-1731
Number of pages11
JournalNew England Journal of Medicine
Volume386
Issue number18
DOIs
StatePublished - May 5 2022

Bibliographical note

Funding Information:
Funded by FastGrants and the Rainwater Charitable Foundation; TOGETHER ClinicalTrials.gov number, NCT04727424.

Funding Information:
Supported by FastGrants and the Rainwater Charitable Foundation. Disclosure forms provided by the authors are available with the full text of this article at NEJM.org. A data sharing statement provided by the authors is available with the full text of this article at NEJM.org.

Publisher Copyright:
Copyright © 2022 Massachusetts Medical Society

Keywords

  • Adult
  • Ambulatory Care
  • Anti-Infective Agents/adverse effects
  • Bayes Theorem
  • COVID-19/drug therapy
  • Double-Blind Method
  • Hospitalization
  • Humans
  • Ivermectin/adverse effects
  • SARS-CoV-2
  • Treatment Outcome

PubMed: MeSH publication types

  • Randomized Controlled Trial
  • Multicenter Study
  • Journal Article

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