ABSTRACT
ObjectiveTo determine the relative impact of the use of chloroquine and hydroxychloroquine on outcomes important to patients with COVID 19. DesignThis is the protocol of a living systematic review. Data sourcesWe will conduct searches in PubMed/Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), trial registries, grey literature and in a centralised repository in L{middle dot}OVE (Living OVerview of Evidence). L{middle dot}OVE is a platform that maps PICO questions to evidence from Epistemonikos database. In response to the COVID-19 emergency, L{middle dot}OVE was adapted to expand the range of evidence it covers and customised to group all COVID-19 evidence in one place. The search will cover the period until the day before submission to a journal. Eligibility criteria for selecting studies and methodsWe will follow a common protocol for multiple parallel systematic reviews, already published and submitted to PROSPERO (awaiting ID allocation). We will include randomised controlled trials evaluating the effect of chloroquine and hydroxychloroquine -- as monotherapy or in combination with other drugs -- versus placebo or no treatment in patients with COVID-19. Randomised trials evaluating chloroquine and hydroxychloroquine in infections caused by other coronaviruses, such as MERS-CoV and SARS-CoV, and non-randomised studies in COVID-19 will be searched in case no direct evidence from randomised trials is found, or if the direct evidence provides low- or very low-certainty for critical outcomes. Two reviewers will independently screen each study for eligibility, extract data, and assess the risk of bias. We will perform random-effects meta-analyses and use GRADE to assess the certainty of the evidence for each outcome. A living, web-based version of this review will be openly available during the COVID-19 pandemic. We will resubmit it if the conclusions change or there are substantial updates. Ethics and disseminationNo ethics approval is considered necessary. The results of this review will be widely disseminated via peer-reviewed publications, social networks and traditional media.
