Meta-analysis of randomized trials of ivermectin to treat SARS-CoV-2 infection
Authors: Anna Garratt
Jacob Levi
Victoria Pilkington
Ambar Qavi
Junzheng Wang
Leah Ellis
Jonathan Falconer
Hannah Wentzel
Kaitlyn McCann
Andrew Hill
Journal: Open Forum Infectious Diseases (2021)
Discipline: IMMUNOLOGY
Keywords: COVID-19; SARS-CoV-2; ivermectin; repurposed.
Affiliations: Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool, L7 3NY, UK, Department of Infectious Diseases, University Hospital of Wales, Cardiff and Vale University Health Board, UK, Department of Intensive Care, University College London Hospital, ULCH NHS Trust, London, UK, Department of Infectious Diseases, Chelsea and Westminster Hospital, Imperial NHS Trust, London, UK, Faculty of Medicine, Imperial College London, UK, Oxford University Clinical Academic Graduate School, University of Oxford, UK

Abstract:  Ivermectin is an antiparasitic drug being investigated for repurposing against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Ivermectin showed in vitro activity against SARS-COV-2, but only at high concentrations. This meta-analysis investigated ivermectin in 23 randomized clinical trials (3349 patients) identified through systematic searches of PUBMED, EMBASE, MedRxiv, and trial registries. The primary meta-analysis was carried out by excluding studies at a high risk of bias. Ivermectin did not show a statistically significant effect on survival (risk ratio [RR], 0.90; 95% CI, 0.57 to 1.42; P = .66) or hospitalizations (RR, 0.63; 95% CI, 0.36 to 1.11; P = .11). Ivermectin displayed a borderline significant effect on duration of hospitalization in comparison with standard of care (mean difference, -1.14 days; 95% CI, -2.27 to -0.00; P = .05). There was no significant effect of ivermectin on time to clinical recovery (mean difference, -0.57 days; 95% CI, -1.31 to 0.17; P = .13) or binary clinical recovery (RR, 1.19; 95% CI, 0.94 to 1.50; P = .15). Currently, the World Health Organization recommends the use of ivermectin only inside clinical trials. A network of large clinical trials is in progress to validate the results seen to date. 

Retracted: No

PubPeer comments:
 https: twitter.com GidMK status 1412635807702142982 , 
 Copy pasted from https: doi.org 10.1093 ofid ofab394 :  Expression of Concern: u201cMeta-analysis of Randomized Trials of Ivermectin to Treat SARS-CoV-2 Infectionu201d. On July 6, 2021, Open Forum Infectious Diseases published the article u201cMeta-analysis of Randomized Trials of Ivermectin to Treat SARS-CoV-2 Infectionu201d by Hill, et al. Subsequently, we and the authors have learned that one of the studies on which this analysis was based has been withdrawn due to fraudulent data. The authors will be submitting a revised version excluding this study, and the currently posted paper will be retracted. Published: 06 July 2021. See also https: retractionwatch.com 2021 08 10 ivermectin-meta-analysis-to-be-retracted-revised-say-authors , 
 The preprint was withdrawn, and states:  Research Square withdrew this preprint on 14 July, 2021 due to an expression of concern communicated directly to our staff. These concerns are now under formal investigation. https: www.researchsquare.com article rs-100956 v2 The expression of concern states:  we and the authors have learned that one of the studies on which this analysis was based has been withdrawn due to fraudulent data.  https: academic.oup.com ofid article 8 8 ofab394 6346765 Can the authors indicate which study that is? Why is it not clearly indicated in the expression of concern? , 
 #3 https: retractionwatch.com 2021 08 10 ivermectin-meta-analysis-to-be-retracted-revised-say-authors , 
 The revised version was published on [17 January 2022] , with a shorter list of authors.  We present a subgroup meta-analysis to assess the effects of stratifying by trial quality on the overall results. The stratification is based on the Cochrane Risk of Bias measures and raw data analysis where possible. The results suggest that **the significant effect of ivermectin on survival was dependent on largely poor-quality studies.** ,