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Roman YM, Burela PA, Pasupuleti V, et al. Ivermectin for the treatment of COVID-19: A systematic review and meta-analysis of randomized controlled trials. Clin Infect Dis. 2021 Jun 28. pii: 6310839. doi: 10.1093/cid/ciab591. (Systematic review)
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 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.

Ratings
Discipline Area Score
Infectious Disease 6 / 7
Emergency Medicine 6 / 7
Hospital Doctor/Hospitalists 6 / 7
Internal Medicine 6 / 7
Comments from MORE raters

Emergency Medicine rater

Clinicians` faith in the construct of evidence-based medicine (EBM) were tested over the past 18 months during COVID-19 (http://pmid.us/32651176). Clinicians and academicians appeared on daily news shows promoting largely untested and certainly unproven therapies for SARS CoV2, providing intellectual shelter for world leaders who viewed COVID-19 through the lens of political opportunity rather than societal health. Ivermectin remains the poster child for the abandonment of EBM in the rush to stem panic, as evidenced by a recent non-peer reviewed "systematic review" (https://journals.lww.com/americantherapeutics/Fulltext/2021/08000/Ivermectin_for_Prevention_and_Treatment_of.7.aspx) that included 9 pre-prints with significant risk of bias. This systematic review provides a meaningful analysis of the current state of knowledge of ivermectin as a COVID-19 therapeutic and should be incorporated into ACEP`s resource page (https://www.acep.org/covid19-management-tool).

Emergency Medicine rater

Many keep holding out hope for ivermectin in the treatment of COVID. This paper again shows it has no benefit.
Comments from EvidenceAlerts subscribers

Dr. Zsolt Nagykaldi (9/3/2021 9:17 AM)

They did not evaluate decreased hospitalization rate. They only evaluated treatment of already hospitalized patients. This is not really a fair shake. Several of our new monoclonal antibody drugs also show no benefit on mortality or decreased length-of-stay in already hospitalized patients. This is why they are advised for treatment of high-risk patients who are not yet hospitalized.

Dr. bruce macleod (9/2/2021 12:18 PM)

Given the evidence I've seen so far, this review is highly suspect for bias against ivermectin.