Ivermectin not effective against COVID-19

Treatment with ivermectin does not reduce all-cause mortality, length of stay (LOS), or respiratory viral clearance in randomized controlled trials (RCTs) of patients with mild to moderate COVID-19 when compared with placebo or standard of care (SOC), results of a systematic review and meta-analysis have shown. In addition, it has failed to moderate adverse events (AEs) or severe AEs.

“Additional ongoing RCTs should be completed in order to update our analyses,” the investigators said. “In the meanwhile, ivermectin is not a viable option to treat COVID-19 patients and only should be used within clinical trials context.”

A search was conducted using five engines for published and preprint RCTs that examined the effects of ivermectin on adult COVID-19 patients until March 22, 2021. The investigators assessed risk of bias (ROB) using Cochrane ROB 2.0 tool. They also performed inverse variance random effect meta-analyses and evaluated quality of evidence (QOE) using the GRADE methodology.

Ten RCTs, including a total of 1,173 patients, met the eligibility criteria. SOC served as control in five RCTs and placebo in the remaining half. Severity of COVID-19 was mild in eight RCTs, moderate in one, and mild and moderate in one. [Clin Infect Dis 2021;doi:10.1093/cid/ciab591]

The meta-analysis revealed no significant benefit with ivermectin, compared with controls, in reducing all-cause mortality (relative risk, 0.37, 95 percent confidence interval [CI], 0.12–1.13; very low QOE) or LOS (mean difference, 0.72 days, 95 percent CI, –0.86 to 2.29; very low QOE). Moreover, AEs, severe AE, and viral clearance did not differ between ivermectin and controls (all outcomes: low QOE).

Subgroup analysis by COVID-19 severity or ROB confirmed the main findings. For three RCTs with high ROB, a decrease in all-cause mortality was observed with ivermectin.

The World Health Organization only recommended the use of ivermectin in RCTs. [WHO/2019-nCoV/therapeutics/2021]

In a recent living systematic review, ivermectin reduced mortality (risk difference per 1,000 vs SOC, –1.03, 95 percent CI, –117 to –78), but the QOE was very low. The study concluded that the effects of ivermectin were highly uncertain, with no definitive evidence of important health benefits and harms. [BMJ 2020;370:m2980]

“The nonrational use of ivermectin to treat COVID-19 patients has shown several limitations in management strategies: absence of transparency by some political leaders or media in order to avoid drug use without evidence of efficacy and safety; lack of leadership to implementing therapeutic science-based guidelines; and misuse of effective scientific communication,” the investigators said. [Lancet 2020;396:295-298; PNAS 2021;118:e2104068118]

“Therefore, there is an urgent need to establish collaborative efforts among scientists, practitioners, communicators, and policy-makers,” they added.

In approved indications, ivermectin is safe at conventional doses, but safety becomes a concern with longer use and higher doses in COVID-19 patients. In addition, use of ivermectin warrant further research when combined with other agents for COVID-19. [TrendsParasitol 2021;37:48-64; Am J Trop Med Hyg 2020;102:1156-1157; J Clin Pharmacol 2002;42:1122-1133; Am J Trop Med Hyg 2007;76:1153-1157; Drug Res (Stuttg) 2020;70:337-340]

“Well-designed RCTs with longer ivermectin use and higher doses are necessary in COVID-19 to further evaluate its safety,” the investigators said.