Ivermectin and mortality in patients with COVID-19: A systematic review, meta-analysis, and meta-regression of randomized controlled trials

Zein, Ahmad Fariz Malvi Zamzam; Sulistiyana, Catur Setiya; Raffaelo, Wilson Matthew; Pranata, Raymond

AIMS: This systematic review and meta-analysis aims to investigate the effect of ivermectin on mortality in patients with COVID-19. METHODS: A comprehensive systematic literature search was performed using PubMed, Scopus, Embase, and Clinicaltrials.gov from the inception of databases up until April 9, 2021. The intervention group was ivermectin and the control group was standard of care or placebo. The primary outcome was mortality reported as risk ratio (RR). RESULTS: There were 9 RCTs comprising of 1788 patients included in this meta-analysis. Ivermectin was associated with decreased mortality (RR 0.39 [95% 0.20–0.74], p = 0.004; I(2): 58.2%, p = 0.051). Subgroup analysis in patients with severe COVID-19 showed borderline statistical significance towards mortality reduction (RR 0.42 [95% 0.18–1.00], p = 0.052; I(2): 68.3, p = 0.013). The benefit of ivermectin and mortality was reduced by hypertension (RR 1.08 [95% CI 1.03–1.13], p = 0.001); but was not influenced by age (p = 0.657), sex (p = 0.466), diabetes (p = 0.429). Sensitivity analysis using fixed-effect model showed that ivermectin decreased mortality in general (RR 0.43 [95% CI 0.29–0.62], p < 0.001) and severe COVID-19 subgroup (RR 0.48 [95% CI 0.32–0.72], p < 0.001). CONCLUSIONS: Ivermectin was associated with decreased mortality in COVID-19 with a low certainty of evidence. Further adequately powered double-blinded placebo-controlled RCTs are required for definite conclusion.