Meta-analysis of Randomized Trials of Ivermectin to Treat SARS-CoV-2 Infection.

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.

Open Forum Infectious Diseases, Volume 8, Issue 11, November 2021, ofab358, https://doi.org/10.1093/ofid/ofab358

On July 6, 2021, Open Forum Infectious Diseases published the article “Meta-analysis of Randomized Trials of Ivermectin to Treat SARS-CoV-2 Infection” by Hill, et al. Subsequently, we and the authors learned that one of the largest studies on which this analysis was based was withdrawn due to fraudulent data; additional problems have emerged regarding other studies included in the original paper. An editorial Expression of Concern was first published under this record as the authors revised their analysis for resubmission.

The authors submitted and published a corrected version of the analysis with commentary on assessing trial quality while creating meta-analyses, available to read in OFID: “Ivermectin for COVID-19: Addressing Potential Bias and Medical Fraud” by Hill et al., https://doi.org/10.1093/ofid/ofab645. The original analysis has been retracted.