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

Abstract

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 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 2.0 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. Results: Ten 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 1.11, 95%CI 0.16-7.65, 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). Subgroup analyses by severity of COVID-19 disease or RoB were consistent with main analyses. Sensitivity analyses excluding RCTs with follow up <21 days showed no difference in all-cause mortality but diminished heterogeneity (I2=0%). 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 effect on AEs or SAEs. IVM is not a viable option to treat COVID-19 patients.

Safety and Efficacy of a MEURI Program for the Use of High Dose Ivermectin in COVID-19 Patients

“…The situation is worsened by confusing messages through social and traditional media plus articles from peer-reviewed journals that are published and afterwards retracted as well as the uncontrolled use of medical and veterinary products by the population ( 27 ). Meta-analyses that included studies with a variety of regimens have reached different interpretations and conclusions, preventing the achievement of consistent findings ( 14 , 18 , 28 , 29 ). In this context, a MEURI Program appears as the mean to attempt monitored and controlled use of a treatment not approved for the indication but with preliminary results of adequate safety and potential efficacy.…”

Drug-Induced Liver Injury in COVID-19 Patients: A Systematic Review

“…IVN, a well-known antiparasite medication, is considered a safe drug, and reports on its hepatotoxic effects are rare. There are growing and controversial evidences about IVN efficacy in treatment of COVID-19 patients but it seems to be a safe medication in overall (63)(64)(65)(66). Of course there is a case report of IVN caused DILI (elevated aminotransferase, acute hepatocellular necrosis, lobular infiltration of lymphocytes, and without fibrosis) 1 month after drug administration and the patient clinically improved after 3 months (67).…”

Ivermectin and the Integrity of Healthcare Evidence During COVID-19

“…Another systematic review (search conducted 25 April 2021) conducted a meta-analysis of 15 RCTs measuring mortality and concluded that ivermectin compared to no ivermectin reduced the risk of death by an average of 62% ( 37 ) with the GRADE approach used to evaluate this as “moderate-certainty” evidence. Another systematic review (search conducted 22 March 2021) of 10 RCTs concluded “that ivermectin did not reduce all-cause mortality” ( 45 ). The Cochrane review (search conducted 26 May 2021) included 14 RCTs and concluded that it was uncertain whether ivermectin increased or decreased mortality and the evidence was “very low-certainty” ( 36 ).…”