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

BackgroundWe systematically assessed benefits and harms of the use of ivermectin (IVM) in COVID-19 patients. MethodsPublished and preprint randomized controlled trials (RCTs) assessing IVM effects on COVID-19 adult patients were searched until March 15, 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. We evaluated risk of bias (RoB) using the Cochrane RoB 2{middle dot}0 tool. Inverse variance random effect meta-analyses were performed with quality of evidence (QoE) evaluated using GRADE methodology. Subgroup analyses by severity of disease and RoB, and sensitivity analyses by time of follow-up were conducted. ResultsTen RCTs (n=1173) were included. Controls were standard of care [SOC] in five RCTs and placebo in five RCTs. RCTs sample size ranged from 24 to 398 patients, mean age from 26 to 56 years-old, and severity of COVID-19 disease 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). IVM did not reduce 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 (low QoE for these three outcomes). 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. Sensitivity analyses excluding RCTs with follow up <21 days showed no difference in all-cause mortality. ConclusionsIn 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 effect on AEs or SAEs. IVM is not a viable option to treat COVID-19 patients.