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 Sprague; Paula McKay; Christina M. Guo; Karen Rowland-Yeo; Gordon H. Guyatt; David R. Boulware; Craig R. Rayner; Edward J. Mills

doi:10.1056/NEJMoa2115869

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

Medicine - Infectious Disease and International Medicine

Research output: Contribution to journal › Article › peer-review

141 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 language	English (US)
Pages (from-to)	1721-1731
Number of pages	11
Journal	New England Journal of Medicine
Volume	386
Issue number	18
DOIs	https://doi.org/10.1056/NEJMoa2115869
State	Published - 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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Publisher link

10.1056/NEJMoa2115869

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Reis, G., Silva, E. A. S. M., Silva, D. C. M., Thabane, L., Milagres, A. C., Ferreira, T. S., dos Santos, C. V. Q., Campos, V. H. S., Nogueira, A. M. R., de Almeida, A. P. F. G., Callegari, E. D., Neto, A. D. F., Savassi, L. C. M., Simplicio, M. I. C., Ribeiro, L. B., Oliveira, R., Harari, O., Forrest, J. I., Ruton, H., ... Mills, E. J. (2022). Effect of Early Treatment with Ivermectin among Patients with Covid-19. New England Journal of Medicine, 386(18), 1721-1731. https://doi.org/10.1056/NEJMoa2115869

Reis, G, Silva, EASM, Silva, DCM, Thabane, L, Milagres, AC, Ferreira, TS, dos Santos, CVQ, Campos, VHS, Nogueira, AMR, de Almeida, APFG, Callegari, ED, Neto, ADF, Savassi, LCM, Simplicio, MIC, Ribeiro, LB, Oliveira, R, Harari, O, Forrest, JI, Ruton, H, Sprague, S, McKay, P, Guo, CM, Rowland-Yeo, K, Guyatt, GH, Boulware, DR, Rayner, CR & Mills, EJ 2022, 'Effect of Early Treatment with Ivermectin among Patients with Covid-19', New England Journal of Medicine, vol. 386, no. 18, pp. 1721-1731. https://doi.org/10.1056/NEJMoa2115869

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title = "Effect of Early Treatment with Ivermectin among Patients with Covid-19",

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.).",

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author = "Gilmar Reis and Silva, {Eduardo A.S.M.} and Silva, {Danie C.M.} and Lehana Thabane and Milagres, {Aline C.} and Ferreira, {Thiago S.} and {dos Santos}, {Castilho V.Q.} and Campos, {Vitoria H.S.} and Nogueira, {Ana M.R.} and {de Almeida}, {Ana P.F.G.} and Callegari, {Eduardo D.} and Neto, {Adhemar D.F.} and Savassi, {Leonardo C.M.} and Simplicio, {Maria I.C.} and Ribeiro, {Luciene B.} and Rosemary Oliveira and Ofir Harari and Forrest, {Jamie I.} and Hinda Ruton and Sheila Sprague and Paula McKay and Guo, {Christina M.} and Karen Rowland-Yeo and Guyatt, {Gordon H.} and Boulware, {David R.} and Rayner, {Craig R.} and Mills, {Edward J.}",

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 {\textcopyright} 2022 Massachusetts Medical Society",

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month = may,

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doi = "10.1056/NEJMoa2115869",

language = "English (US)",

volume = "386",

pages = "1721--1731",

journal = "New England Journal of Medicine",

issn = "0028-4793",

publisher = "Massachussetts Medical Society",

number = "18",

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TY - JOUR

T1 - Effect of Early Treatment with Ivermectin among Patients with Covid-19

AU - Reis, Gilmar

AU - Silva, Eduardo A.S.M.

AU - Silva, Danie C.M.

AU - Thabane, Lehana

AU - Milagres, Aline C.

AU - Ferreira, Thiago S.

AU - dos Santos, Castilho V.Q.

AU - Campos, Vitoria H.S.

AU - Nogueira, Ana M.R.

AU - de Almeida, Ana P.F.G.

AU - Callegari, Eduardo D.

AU - Neto, Adhemar D.F.

AU - Savassi, Leonardo C.M.

AU - Simplicio, Maria I.C.

AU - Ribeiro, Luciene B.

AU - Oliveira, Rosemary

AU - Harari, Ofir

AU - Forrest, Jamie I.

AU - Ruton, Hinda

AU - Sprague, Sheila

AU - McKay, Paula

AU - Guo, Christina M.

AU - Rowland-Yeo, Karen

AU - Guyatt, Gordon H.

AU - Boulware, David R.

AU - Rayner, Craig R.

AU - Mills, Edward J.

N1 - 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

PY - 2022/5/5

Y1 - 2022/5/5

N2 - 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.).

AB - 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.).

KW - Adult

KW - Ambulatory Care

KW - Anti-Infective Agents/adverse effects

KW - Bayes Theorem

KW - COVID-19/drug therapy

KW - Double-Blind Method

KW - Hospitalization

KW - Humans

KW - Ivermectin/adverse effects

KW - SARS-CoV-2

KW - Treatment Outcome

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DO - 10.1056/NEJMoa2115869

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JO - New England Journal of Medicine

JF - New England Journal of Medicine

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ER -

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

Abstract

Bibliographical note

Keywords

PubMed: MeSH publication types

UN SDGs

Publisher link

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