Background: Repurposed medicines may have a role against the SARS-CoV-2 virus. The antiparasitic
ivermectin, with antiviral and anti-inflammatory properties, has now been tested in numerous clinical trials.

Areas of uncertainty: We assessed the efficacy of ivermectin treatment in reducing mortality, in secondary outcomes, and in chemoprophylaxis, among people with, or at high risk of, COVID-19 infection.

Data sources: We searched bibliographic databases up to April 25, 2021. Two review authors sifted for
studies, extracted data, and assessed risk of bias. Meta-analyses were conducted and certainty of the
evidence was assessed using the GRADE approach and additionally in trial sequential analyses for
mortality. Twenty-four randomized controlled trials involving 3406 participants met review inclusion.

Therapeutic Advances: Meta-analysis of 15 trials found that ivermectin reduced risk of death compared with no ivermectin (average risk ratio 0.38, 95% confidence interval 0.19–0.73; n 5 2438; I2 5
49%; moderate-certainty evidence). This result was confirmed in a trial sequential analysis using the
same DerSimonian–Laird method that underpinned the unadjusted analysis. This was also robust
against a trial sequential analysis using the Biggerstaff–Tweedie method. Low-certainty evidence
found that ivermectin prophylaxis reduced COVID-19 infection by an average 86% (95% confidence
interval 79%–91%). Secondary outcomes provided less certain evidence. Low-certainty evidence
suggested that there may be no benefit with ivermectin for “need for mechanical ventilation,”