Open AccessDetails of a prospective protocol for a collaborative meta‐analysis of individual participant data from all randomized trials of intravenous rt‐ PA vs. control: statistical analysis plan for the S troke T hrombolysis T rialists’ C ollaborative meta‐analysis
Author(s) -
Jonathan Emberson,
Kennedy R. Lees,
George Howard,
Erich Bluhmki,
Barbara C. Tilley,
Gregory W. Albers,
Colin Baigent,
Lisa Blackwell,
Stephen M. Davis,
Geoffrey A. Donnan,
James C. Grotta,
Werner Hacke,
Markku Kaste,
Ruediger von Kummer,
Maarten G. Lansberg,
Richard I. Lindley,
Patrick D. Lyden,
Peter Sandercock,
Danilo Toni,
Nils Wahlgren,
Joanna M. Wardlaw,
William Whiteley,
Gregory J. del Zoppo
Publication year - 2013
Publication title -
international journal of stroke
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.375
H-Index - 74
eISSN - 1747-4949
pISSN - 1747-4930
DOI - 10.1111/ijs.12040
Subject(s) - medicine , thrombolysis , stroke (engine) , randomized controlled trial , modified rankin scale , clinical trial , protocol (science) , intracerebral hemorrhage , fibrinolytic agent , emergency medicine , physical therapy , ischemic stroke , tissue plasminogen activator , ischemia , subarachnoid hemorrhage , alternative medicine , myocardial infarction , mechanical engineering , pathology , engineering
Rationale Thrombolysis with intravenous alteplase is both effective and safe when administered to particular types of patient within 4·5 hours of having an ischemic stroke. However, the extent to which effects might vary in different types of patient is uncertain. Aims and Design We describe the protocol for an updated individual patient data meta‐analysis of trials of intravenous alteplase, including results from the recently reported third I nternational S troke Trial, in which a wide range of patients enrolled up to six‐hours after stroke onset were randomized to alteplase vs. control. Study Outcomes This protocol will specify the primary outcome for efficacy, specified prior to knowledge of the results from the third I nternational S troke Trial, as the proportion of patients having a ‘favorable’ stroke outcome, defined by modified R ankin S core 0–1 at final follow‐up at three‐ to six‐months. The primary analysis will be to estimate the extent to which the known benefit of alteplase on modified R ankin S core 0–1 diminishes with treatment delay, and the extent to which it is independently modified by age and stroke severity. Key secondary outcomes include effect of alteplase on death within 90 days; analyses of modified R ankin S core using ordinal, rather than dichotomous, methods; and effects of alteplase on symptomatic intracranial hemorrhage, fatal intracranial hemorrhage, symptomatic ischemic brain edema and early edema, effacement and/or midline shift. Discussion This collaborative meta‐analysis of individual participant data from all randomized trials of intravenous alteplase vs. control will demonstrate how the known benefits of alteplase on ischemic stroke outcome vary across different types of patient.