A collaborative sequential meta-analysis of individual patient data from randomized trials of endovascular therapy and tPA vs. tPA alone for acute ischemic stroke: <u>T</u>h<u>R</u>omb<u>E</u>ctomy <u>A</u>nd <u>t</u>PA (TREAT) analysis: statistical analysis plan for a sequential meta-analysis performed within the VISTA-Endovascular collaboration

Abstract

Rationale Endovascular treatment has been shown to restore blood flow effectively. Second-generation medical devices such as stent retrievers are now showing overwhelming efficacy in clinical trials, particularly in conjunction with intravenous recombinant tissue plasminogen activator. Aims and Design This statistical analysis plan utilizing a novel, sequential approach describes a prospective, individual patient data analysis of endovascular therapy in conjunction with intravenous recombinant tissue plasminogen activator agreed upon by the Thrombectomy and Tissue Plasminogen Activator Collaborative Group. Study outcomes This protocol will specify the primary outcome for efficacy, as ‘favorable’ outcome defined by the ordinal distribution of the modified Rankin Scale measured at three-months poststroke, but with modified Rankin Scales 5 and 6 collapsed into a single category. The primary analysis will aim to answer the questions: ‘what is the treatment effect of endovascular therapy with intravenous recombinant tissue plasminogen activator compared to intravenous tissue plasmi-nogen activator alone on full scale modified Rankin Scale at 3 months?’ and ‘to what extent do key patient characteristics influence the treatment effect of endovascular therapy?’. Key secondary outcomes include effect of endovascular therapy on death within 90 days; analyses of modified Rankin Scale using dichotomized methods; and effects of endovascular therapy on symptomatic intracranial hemorrhage. Several secondary analyses will be considered as well as expanding patient cohorts to intravenous recombinant tissue plasminogen activator-ineligible patients, should data allow. Discussion This collaborative meta-analysis of individual participant data from randomized trials of endovascular therapy vs. control in conjunction with intravenous thrombolysis will demonstrate the efficacy and generalizability of endovascular therapy with intravenous thrombolysis as a concomitant medication.

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Affiliated Institutions

• University at Buffalo, State University of New York US
• The University of Melbourne AU
• University Hospital Heidelberg DE
• University Medical Center Hamburg-Eppendorf DE
• Newcastle University GB
• St. Antonius Ziekenhuis NL
• Universität Hamburg DE
• Amsterdam UMC Location University of Amsterdam NL
• Imagerie Adaptative Diagnostique et Interventionnelle FR
• The Royal Melbourne Hospital AU
• Melbourne Health AU
• Icahn School of Medicine at Mount Sinai US
• Erasmus MC NL
• Erasmus University Rotterdam NL
• Ontario Brain Institute CA
• Hospital de Clínicas de Porto Alegre BR
• Massachusetts General Hospital US
• University of Glasgow GB
• Hospital Universitari Germans Trias i Pujol ES
• Southern General Hospital GB
• University of Cincinnati US
• University of Pittsburgh US
• University of Arizona US
• Medical College of Wisconsin US
• Azienda Ospedaliera Carlo Poma IT
• Florey Institute of Neuroscience and Mental Health AU
• University of Calgary CA
• Stony Brook University US
• Medical University of South Carolina US
• Heidelberg University DE
• Essen University Hospital DE
• Banner - University Medical Center Tucson US
• UCLA Health US

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