Efficacy and safety of different doses of tenecteplase for the treatment of acute ischemic stroke: A protocol for a systematic review and network meta-analysis

BACKGROUND: Acute ischemic stroke (AIS) has become the major reason of causing death around the world. As a newer generation fibrinolytic agent, the potential of tenecteplase in treating AIS has been determined in clinical studies and meta-analysis. However, various doses have been prescribed for tenecteplase in clinical practice, and the optimal dose is not yet clear. METHODS: We will perform a systematic search to capture all potential randomized controlled trials (RCTs) of persons with confirmed AIS who were instructed to administer tenecteplase that report at least one outcome in PubMed, Embase, and the Cochrane Library. Two reviewers will independently check the titles, abstracts, and full-texts, extracting data, assessing the risk of bias and evaluating the certainty of evidence. We will use a random-effect model based on the Bayesian framework to completely direct and network meta-analyses. We will also test the robustness of all pooled results through conducting subgroup analyses according to the following criteria: 1. low and high risk of bias; 2. impact factors (≥5, 3–5, and ≤3); 3. usage of endovascular thrombectomy or not. DISCUSSION: Our systematic review and network meta-analysis will generate several valuable findings and have several strengths including: 1. a systematic search string; 2. predesigned criteria for subgroup analysis; 3. determination of level of evidence with the GRADE system; and 4. graphic illustration of numerical results. We therefore believe that findings from this network meta-analysis will benefit future study design and improve evidence-based treatment of AIS. ETHICS AND DISSEMINATION: We will disseminate the results from the present study through submitting it to conferences or peer-reviewed journal. PROTOCOL REGISTRY: The protocol of our systematic review and network meta-analysis was registered in International Plateform of Registered Systematic Review and Meta-Analysis Protocols (INPLASY) platform with an approval number of INPLASY2020100086 (https://inplasy.com/inplasy-2020-10-0086/). Moreover, this protocol was funded through a protocol registry.