Meta-analysis of randomized trials of ivermectin to treat SARS-CoV-2 infection

doi:10.21203/rs.3.rs-148845/v1

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Systematic Review

Meta-analysis of randomized trials of ivermectin to treat SARS-CoV-2 infection

https://doi.org/10.21203/rs.3.rs-148845/v1

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Journal Publication

published 05 Jul, 2021

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Version 1

posted 19 Jan, 2021

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Editorial Note: On July 6, 2021, Open Forum Infectious Diseases published a version of this preprint. The authors subsequently learned that one of the studies on which this analysis was based had been withdrawn due to fraudulent data. An expression of concern was issued on August 9, 2021. The authors have submitted a revised version excluding the problematic study, and the originally published paper has been retracted. The revised version is now available at the journal.

Editorial notes are used to provide important context regarding the topic of a preprint or to alert readers to potential issues concerning that preprint or a downstream publication associated with it. For more information on editorial notes, see our Editorial Policies.

Ivermectin is an antiparasitic drug being investigated for repurposing to SARS-CoV-2. In-vitro, ivermectin showed limited antiviral activity and a COVID-19 animal model demonstrated pathological benefits but no effect on viral RNA. This meta-analysis investigated ivermectin in 18 randomized clinical trials (2282 patients) identified through systematic searches of PUBMED, EMBASE, MedRxiv and trial registries. Ivermectin was associated with reduced inflammatory markers (C-Reactive Protein, d-dimer and ferritin) and faster viral clearance by PCR. Viral clearance was treatment dose- and duration-dependent. In six randomized trials of moderate or severe infection, there was a 75% reduction in mortality (Relative Risk=0.25 [95%CI 0.12-0.52]; p=0.0002); 14/650 (2.1%) deaths on ivermectin; 57/597 (9.5%) deaths in controls) with favorable clinical recovery and reduced hospitalization. Many studies included were not peer reviewed and meta-analyses are prone to confounding issues. Ivermectin should be validated in larger, appropriately controlled randomized trials before the results are sufficient for review by regulatory authorities.

Infectious Diseases

ivermectin

COVID-19

SARS-CoV-2