ABSTRACT
Background: Re-purposed medicines may have role in combating the SARS-CoV-2 virus. The antiparasitic medicine ivermectin, which has anti-viral and anti-inflammatory properties, has been tested in numerous clinical trials with promising results. Methods: We assessed the efficacy of ivermectin treatment and/or prophylaxis among people with, or at high risk of covid-19 infection. We searched bibliographic databases up to February 2021 and 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 GRADE approach. Findings: Twenty-one RCTs involving 2741 participants met review inclusion. Meta-analysis of 13 trials found ivermectin reduced risk of death compared with no ivermectin (average Risk Ratio 0.32, 95% confidence interval (CI) 0.14 to 0.72; n=1892; I 2 =57%; low to moderate-certainty evidence. Low-certainty evidence found ivermectin prophylaxis reduced covid-19 infection by an average 86% (95% CI 79% to 91%). Secondary outcomes provided very-low or low certainty evidence. Low certainty evidence suggests that that there may be no benefit with ivermectin for ‘need for mechanical ventilation’, whereas effect estimates for ‘improvement’ and ‘deterioration’ favoured ivermectin use. Severe adverse events were rare and evidence of no difference was assessed as low to very low-certainty. Evidence on other secondary outcomes was very low certainty. Interpretation Low to moderate-certainty evidence suggests reductions in covid-19 deaths and infections may be possible by using ivermectin. Employing ivermectin early on may reduce the number of people progressing to severe disease. The apparent safety and low cost suggest that ivermectin could have an impact on the SARS-CoV-2 pandemic globally.