Ivermectin for the treatment of COVID-19: A systematic review and meta-analysis of randomized controlled trials.

Background We systematically assessed benefits and harms of the use of ivermectin (IVM) in COVID-19 patients. Methods Published and preprint randomized controlled trials (RCTs) assessing IVM effects on COVID-19 adult patients were searched until March 22, 2021 in five engines. Primary outcomes were all-cause mortality, length of stay (LOS), and adverse events (AE). Secondary outcomes included viral clearance and severe AEs. Risk of bias (RoB) was evaluated using Cochrane RoB 2·0 tool. Inverse variance random effect meta-analyses were performed. with quality of evidence (QoE) evaluated using GRADE methodology. Results Ten RCTs (n=1173) were included. Controls were standard of care [SOC] in five RCTs and placebo in five RCTs. COVID-19 disease severity was mild in 8 RCTs, moderate in one RCT, and mild and moderate in one RCT. IVM did not reduce all-cause mortality vs. controls (RR 0.37, 95%CI 0.12 to 1.13, very low QoE) or LOS vs. controls (MD 0.72 days, 95%CI -0.86 to 2.29, very low QoE). AEs, severe AE and viral clearance were similar between IVM and controls (all outcomes: low QoE). Subgroups by severity of COVID-19 or RoB were mostly consistent with main analyses; all-cause mortality in three RCTs at high RoB was reduced with IVM. Conclusions In comparison to SOC or placebo, IVM did not reduce all-cause mortality, length of stay or viral clearance in RCTs in COVID-19 patients with mostly mild disease. IVM did not have an effect on AEs or severe AEs. IVM is not a viable option to treat COVID-19 patients.