RT Journal Article SR Electronic T1 Effectiveness and safety of ivermectin in the treatment of COVID-19: protocol for a systematic review and meta-analysis JF BMJ Open JO BMJ Open FD British Medical Journal Publishing Group SP e050532 DO 10.1136/bmjopen-2021-050532 VO 11 IS 9 A1 Maria Letícia de Lima Machado A1 Amaxsell Thiago Barros Souza A1 Paula Vívian Andrade Linhares A1 Caio Fernando Martins Ferreira A1 David Franciole Oliveira Silva A1 Rand Randall Martins A1 Ricardo Ney Cobucci YR 2021 UL http://bmjopen.bmj.com/content/11/9/e050532.abstract AB Introduction Ivermectin is a drug with antiviral properties and has been proposed as an alternative treatment for patients with COVID-19, in some countries; however, there is limited evidence to support its clinical use. Accordingly, the aim of this review and meta-analysis is to obtain superior evidence on the effectiveness and safety of ivermectin in treatment of COVID-19.Methods and analysis We will search in the medical databases and International Clinical Trials Registry Platform databases for randomised clinical trials and quasi-randomised trials published from December 2019. The criteria for inclusion are that infection needs to be confirmed by a real-time PCR or serology test, and the effect of ivermectin has been compared with placebo, symptomatic treatment or no treatment. We will exclude observational studies and clinical trials that involved patients with symptoms suggestive of COVID-19, but without a laboratorial diagnosis. Outcomes of interest include mortality, time to symptom resolution, time of hospitalisation, frequency of invasive mechanical ventilation and extracorporeal membrane oxygenation, incidence of severe acute respiratory syndrome, admission to intensive care unit, viral load, PCR-negative status, percentage of infection after prophylactic use, and total incidence of adverse and side effects. Study selection will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Two reviewers will independently select the studies and assess their eligibility. Two other reviewers will independently extract data from each study. Meta-analysis will then be carried out using fixed-effects or random-effects model, using the mean difference for continuous outcomes and the relative risk for dichotomous outcomes. Bias risk will be assessed using the Cochrane risk-of-bias tool. The quality of evidence for each outcome will be assessed using GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology. Review Manager V.5.3.5 will be used for synthesis and subgroup analysis.Ethics and dissemination Owing to the nature of the review, ethical approval is not required. The results will be disseminated through peer-reviewed publications.PROSPERO registration number CRD42020197395.