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Systematic Review and Meta-Analysis of Ivermectin for Treatment of COVID-19: Evidence Beyond the Hype

39 Pages Posted: 14 Jan 2022

See all articles by Milena Soriano Marcolino

Milena Soriano Marcolino

Federal University of Minas Gerais (UFMG) - Department of Internal Medicine

Karina Cardoso Meira

Universidade Federal do Rio Grande do Norte (UFRN) - School of Health

Victor Schulthais Chagas

Universidade Federal de Viçosa (UFV)

Nathalia Sernizon Guimarães

Federal University of Bahia (UFBA) - Institute of Collective Health

Paula Perdigão Motta

Federal University of Minas Gerais (UFMG)

Silvana Márcia Bruschi Kelles

Pontifícia Universidade Católica de Minas Gerais

Laura Caetano de Sá

Fundação Hospitalar do Estado de Minas Gerais (FHEMIG)

Reginaldo Aparecido Valacio

affiliation not provided to SSRN

Patricia K. Ziegelmann

Universidade Federal do Rio Grande do Sul

More...

Abstract

Background: The role of ivermectin in the treatment of COVID-19 is still under debate, yet the drug has been widely used in some parts of the world, as shown by impressive market data and ivermectin-related adverse event reports. The available body of evidence may have changed over the last months, as studies have been retracted and "standards of care" (SOC) used in control groups have changed with rapidly evolving knowledge on COVID-19 rapidly. This review aims to summarize and critically appraise the evidence of randomized controlled trials (RCTs) of ivermectin, assessing clinical outcomes in COVID-19 patients.

Methods: RCTs evaluating the effects of ivermectin in adult patients with COVID-19 were searched through December 14, 2021, in four databases, L.OVE platform, clinical trial registries and pre-prints platforms. Primary endpoints included all-cause mortality and invasive ventilation requirement. Secondary endpoint was the occurrence of adverse events. Risk of bias was evaluated using the Cochrane Risk of Bias 2.0 tool. Random-effects were used to pool the risk ratios (RRs) of individual trials. The quality of evidence was evaluated using GRADE. Subgroup and sensitivity analysis were performed.

Findings: Twenty-one RCTs fulfilled inclusion criteria (n=2592). Of those, 12 compared ivermectin with placebo and in seven ivermectin associated with SOC was compared to SOC. Most RCTs had some concerns or high risk of bias. Ivermectin did not show an effect in reducing mortality (RR=0 . 76; 95%CI 0.44-1.32) or mechanical ventilation (RR=0.83; 95%CI 0.31-2 . 22) in COVID-19 patients. This effect was consistent when comparing ivermectin vs. placebo, and ivermectin associated with SOC vs. SOC, as well as in sensitivity analysis. Additionally, there was very low quality of evidence regarding adverse effects (RR=0 . 95; 95%CI 0.86-1.04).

Interpretation: The evidence suggests that ivermectin does not reduce mortality risk and the risk of mechanical ventilation requirement. Although we did not observe an increase in the risk of adverse effects, the evidence is very uncertain regarding this endpoint.

Registration Details: The protocol was register in PROSPERO (CRD42021257471).

Funding Information: FAPEMIG (APQ-01154-21), IATS/CNPq (465518/2014-1).

Declaration of Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Keywords: COVID-19, SARS-CoV-2, novel coronavirus, therapeutics, systematic review, meta-analysis, ivermectin, evidence-based Medicine, mortal

Suggested Citation

Marcolino, Milena Soriano and Meira, Karina Cardoso and Schulthais Chagas, Victor and Guimarães, Nathalia Sernizon and Perdigão Motta, Paula and Bruschi Kelles, Silvana Márcia and de Sá, Laura Caetano and Aparecido Valacio, Reginaldo and Ziegelmann, Patricia K., Systematic Review and Meta-Analysis of Ivermectin for Treatment of COVID-19: Evidence Beyond the Hype (May 1, 2022). Available at SSRN: https://ssrn.com/abstract=4009120 or http://dx.doi.org/10.2139/ssrn.4009120

Milena Soriano Marcolino (Contact Author)

Federal University of Minas Gerais (UFMG) - Department of Internal Medicine ( email )

Porto Alegre
Brazil

Karina Cardoso Meira

Universidade Federal do Rio Grande do Norte (UFRN) - School of Health ( email )

Lagoa Nova
Brazil

Victor Schulthais Chagas

Universidade Federal de Viçosa (UFV) ( email )

Rua Padre Anchieta, 90
504
Viçosa, Minas Gerais 36570-242
Brazil

Nathalia Sernizon Guimarães

Federal University of Bahia (UFBA) - Institute of Collective Health ( email )

Paula Perdigão Motta

Federal University of Minas Gerais (UFMG) ( email )

Av. Antonio Carlos, 6627
Belo Horizonte, Minas Gerais 31270-901
Brazil

Silvana Márcia Bruschi Kelles

Pontifícia Universidade Católica de Minas Gerais ( email )

Praça da Liberdade
Brazil

Laura Caetano De Sá

Fundação Hospitalar do Estado de Minas Gerais (FHEMIG) ( email )

Belo Horizonte
Brazil

Reginaldo Aparecido Valacio

affiliation not provided to SSRN ( email )

No Address Available

Patricia K. Ziegelmann

Universidade Federal do Rio Grande do Sul ( email )

Rua Washington Luiz #855
Porto Alegre, 90010460
Brazil