tetano
Editor, Senior Moderator
N Engl J Med
. 2022 Mar 30.
doi: 10.1056/NEJMoa2115869. Online ahead of print.
Effect of Early Treatment with Ivermectin among Patients with Covid-19
Gilmar Reis[SUP] 1 [/SUP], Eduardo A S M Silva[SUP] 1 [/SUP], Daniela C M Silva[SUP] 1 [/SUP], Lehana Thabane[SUP] 1 [/SUP], Aline C Milagres[SUP] 1 [/SUP], Thiago S Ferreira[SUP] 1 [/SUP], Castilho V Q Dos Santos[SUP] 1 [/SUP], Vitoria H S Campos[SUP] 1 [/SUP], Ana M R Nogueira[SUP] 1 [/SUP], Ana P F G de Almeida[SUP] 1 [/SUP], Eduardo D Callegari[SUP] 1 [/SUP], Adhemar D F Neto[SUP] 1 [/SUP], Leonardo C M Savassi[SUP] 1 [/SUP], Maria I C Simplicio[SUP] 1 [/SUP], Luciene B Ribeiro[SUP] 1 [/SUP], Rosemary Oliveira[SUP] 1 [/SUP], Ofir Harari[SUP] 1 [/SUP], Jamie I Forrest[SUP] 1 [/SUP], Hinda Ruton[SUP] 1 [/SUP], Sheila Sprague[SUP] 1 [/SUP], Paula McKay[SUP] 1 [/SUP], Christina M Guo[SUP] 1 [/SUP], Karen Rowland-Yeo[SUP] 1 [/SUP], Gordon H Guyatt[SUP] 1 [/SUP], David R Boulware[SUP] 1 [/SUP], Craig R Rayner[SUP] 1 [/SUP], Edward J Mills[SUP] 1 [/SUP], TOGETHER Investigators
Affiliations
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.).
. 2022 Mar 30.
doi: 10.1056/NEJMoa2115869. Online ahead of print.
Effect of Early Treatment with Ivermectin among Patients with Covid-19
Gilmar Reis[SUP] 1 [/SUP], Eduardo A S M Silva[SUP] 1 [/SUP], Daniela C M Silva[SUP] 1 [/SUP], Lehana Thabane[SUP] 1 [/SUP], Aline C Milagres[SUP] 1 [/SUP], Thiago S Ferreira[SUP] 1 [/SUP], Castilho V Q Dos Santos[SUP] 1 [/SUP], Vitoria H S Campos[SUP] 1 [/SUP], Ana M R Nogueira[SUP] 1 [/SUP], Ana P F G de Almeida[SUP] 1 [/SUP], Eduardo D Callegari[SUP] 1 [/SUP], Adhemar D F Neto[SUP] 1 [/SUP], Leonardo C M Savassi[SUP] 1 [/SUP], Maria I C Simplicio[SUP] 1 [/SUP], Luciene B Ribeiro[SUP] 1 [/SUP], Rosemary Oliveira[SUP] 1 [/SUP], Ofir Harari[SUP] 1 [/SUP], Jamie I Forrest[SUP] 1 [/SUP], Hinda Ruton[SUP] 1 [/SUP], Sheila Sprague[SUP] 1 [/SUP], Paula McKay[SUP] 1 [/SUP], Christina M Guo[SUP] 1 [/SUP], Karen Rowland-Yeo[SUP] 1 [/SUP], Gordon H Guyatt[SUP] 1 [/SUP], David R Boulware[SUP] 1 [/SUP], Craig R Rayner[SUP] 1 [/SUP], Edward J Mills[SUP] 1 [/SUP], TOGETHER Investigators
Affiliations
- PMID: 35353979
- DOI: 10.1056/NEJMoa2115869
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.).
