Efficacy and safety of ivermectin for treatment of non-hospitalized COVID-19 patients: A systematic review and meta-analysis of 12 randomized controlled trials with 7,035 participants

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An abstract of a systematic review and meta-analysis in Int J Antimicrob Agents, 2024 Aug;64(2):107248 (doi 10.1016/j.ijantimicag.2024.107248), by Hernandez AV, Liu A, Roman YM and others, on ivermectin for non-hospitalized COVID-19 patients. The authors searched five databases until October 17, 2023 for randomized controlled trials and included 12 RCTs with 7,035 participants. The abstract reports that ivermectin did not reduce hospitalization (relative risk 0.81, 95% CI 0.64-1.03; 8 RCTs, low quality of evidence), all-cause mortality (RR 0.98, 95% CI 0.73-1.33; 9 RCTs) or adverse events (RR 0.89, 95% CI 0.75-1.07; 9 RCTs), and concludes that ivermectin should not be recommended as treatment in non-hospitalized COVID-19 patients.

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1. Int J Antimicrob Agents. 2024 Aug;64(2):107248. doi: 10.1016/j.ijantimicag.2024.107248. Epub 2024 Jun 20. Efficacy and safety of ivermectin for treatment of non-hospitalized COVID-19 patients: A systematic review and meta-analysis of 12 randomized controlled trials with 7,035 participants. Hernandez AV(1), Liu A(2), Roman YM(2), Burela PA(3), Pasupuleti V(4), Thota P(5), Carranza-Tamayo CO(6), Retamozo-Palacios M(7), Benites-Zapata VA(8), Piscoya A(9), Vidal JE(10). Author information: (1)Health Outcomes, Policy, and Evidence Synthesis (HOPES) Group, University of Connecticut School of Pharmacy, Storrs, CT, USA; Vicerrectorado de Investigación, Universidad San Ignacio de Loyola (USIL), Lima, Peru. Electronic address: adrian.hernandez-diaz@uconn.edu. (2)Health Outcomes, Policy, and Evidence Synthesis (HOPES) Group, University of Connecticut School of Pharmacy, Storrs, CT, USA. (3)Facultad de Salud Pública y Administración, Universidad Peruana Cayetano Heredia, Lima, Peru. (4)Oxford PharmaGenesis, Inc., Newtown, PA, USA. (5)Hemex Health, Inc. Portland, OR, USA. (6)Faculdade de Medicina, Universidade Católica de Brasilia, Taguatinga, Brasília-DF, Brazil. (7)Department of Infectious Diseases, Hospital Regional de Taguatinga, Taguatinga, Brasília-DF, Brazil. (8)Master Program in Clinical Epidemiology and Biostatistics, Universidad Científica del Sur, Lima, Peru. (9)Servicio de Gastroenterología, Departamento de Medicina, Hospital Guillermo Kaelin de la Fuente, Lima, Peru. (10)Division of Infectious Diseases, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil; Department of Neurology, Instituto de Infectologia Emílio Ribas, São Paulo, Brazil; Laboratory of Medical Investigation, Unit 49, Hospital das Clinicas, Universidade de São Paulo, São Paulo, Brazil. INTRODUCTION: We systematically assessed benefits and harms of the use of ivermectin in non-hospitalized patients with early COVID-19. METHODS: Five databases were searched until October 17, 2023, for randomized controlled trials (RCTs) in adult patients with COVID-19 treated with ivermectin against standard of care (SoC), placebo, or active drug. Primary outcomes were hospitalization, all-cause mortality, and adverse events (AEs). Secondary outcomes included mechanical ventilation (MV), clinical improvement, clinical worsening, viral clearance, and severe adverse events (SAEs). Random effects meta-analyses were performed, with quality of evidence (QoE) evaluated using GRADE methods. Pre-specified subgroup analyses (ivermectin dose, control type, risk of bias, follow-up, and country income) and trial sequential analysis (TSA) were performed. RESULTS: Twelve RCTs (n = 7,035) were included. The controls were placebo in nine RCTs, SoC in two RCTs, and placebo or active drug in one RCT. Ivermectin did not reduce hospitalization (relative risk [RR], 0.81, 95% confidence interval [95% CI] 0.64-1.03; 8 RCTs, low QoE), all-cause mortality (RR 0.98, 95% CI 0.73-1.33; 9 RCTs, low QoE), or AEs (RR 0.89, 95% CI 0.75-1.07; 9 RCTs, very low QoE) vs. controls. Ivermectin did not reduce MV, clinical worsening, or SAEs and did not increase clinical improvement and viral clearance vs. controls (very low QoE for secondary outcomes). Subgroup analyses were mostly consistent with main analyses, and TSA-adjusted risk for hospitalization was similar to main analysis. CONCLUSIONS: In non-hospitalized COVID-19 patients, ivermectin did not have effect on clinical, non-clinical or safety outcomes versus controls. Ivermectin should not be recommended as treatment in non-hospitalized COVID-19 patients. Copyright © 2024 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved. DOI: 10.1016/j.ijantimicag.2024.107248 PMID: 38908535 [Indexed for MEDLINE]

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