A collaborative sequential meta-analysis of individual patient data from randomized trials of endovascular therapy and tPA vs. tPA alone for acute ischemic stroke: ThRombEctomy And tPA (TREAT) analysis: statistical analysis plan for a sequential meta-analysis performed within the VISTA-Endovascular collaboration

Rachael L MacIsaac; Pooja Khatri; Martin Bendszus; Serge Bracard; Joseph Broderick; Bruce Campbell; Alfonso Ciccone; Antoni Dávalos; Stephen M Davis; Andrew Demchuk; Hans-Christoph Diener; Diederik Dippel; Geoffrey A Donnan; Jens Fiehler; David Fiorella; Mayank Goyal; Werner Hacke; Michael D Hill; Reza Jahan; Edward Jauch; Tudor Jovin; Chelsea S Kidwell; David Liebeskind; Charles B Majoie; Sheila Cristina Ouriques Martins; Peter Mitchell; J Mocco; Keith W Muir; Raul Nogueira; Jeffrey L Saver; Wouter J Schonewille; Adnan H Siddiqui; Götz Thomalla; Thomas A Tomsick; Aquilla S Turk; Philip White; Osama Zaidat; Kennedy R Lees; VISTA Endovascular collaboration

doi:10.1111/ijs.12622

A collaborative sequential meta-analysis of individual patient data from randomized trials of endovascular therapy and tPA vs. tPA alone for acute ischemic stroke: ThRombEctomy And tPA (TREAT) analysis: statistical analysis plan for a sequential meta-analysis performed within the VISTA-Endovascular collaboration

Int J Stroke. 2015 Oct:10 Suppl A100:136-44. doi: 10.1111/ijs.12622. Epub 2015 Sep 9.

Authors

Rachael L MacIsaac¹, Pooja Khatri², Martin Bendszus³, Serge Bracard⁴, Joseph Broderick², Bruce Campbell⁵, Alfonso Ciccone⁶, Antoni Dávalos⁷, Stephen M Davis⁸, Andrew Demchuk⁹, Hans-Christoph Diener¹⁰, Diederik Dippel¹¹, Geoffrey A Donnan¹², Jens Fiehler¹³, David Fiorella¹⁴, Mayank Goyal¹⁵, Werner Hacke¹⁶, Michael D Hill¹⁷, Reza Jahan¹⁸, Edward Jauch¹⁹, Tudor Jovin²⁰, Chelsea S Kidwell^{21

22}, David Liebeskind²³, Charles B Majoie²⁴, Sheila Cristina Ouriques Martins²⁵, Peter Mitchell²⁶, J Mocco²⁷, Keith W Muir^{28

29}, Raul Nogueira³⁰, Jeffrey L Saver³¹, Wouter J Schonewille³², Adnan H Siddiqui³³, Götz Thomalla³⁴, Thomas A Tomsick², Aquilla S Turk³⁵, Philip White³⁶, Osama Zaidat³⁷, Kennedy R Lees¹; VISTA Endovascular collaboration

Affiliations

¹ Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.
² University of Cincinnati, Cincinnati, OH, USA.
³ Heidelberg University Hospital, Heidelberg, Germany.
⁴ CHRU NANCY, Nancy, France.
⁵ Royal Melbourne Hospital, Parkville, Vic., Australia.
⁶ Department of Cardio-Thoracic-Vascular, Azienda Ospedaliera Carlo Poma Mantova, Italy.
⁷ Department of Neurology, Hospital Universitari Germans Trias i Pujol, Barcelona, Spain.
⁸ Department of Neurology, The Royal Melbourne Hospital, Parkville, Vic., Australia.
⁹ University of Calgary, Calgary, AB, Canada.
¹⁰ Department of Neurology, University Hospital Essen, Essen, Germany.
¹¹ Department of Neurology, Erasmus MC, Rotterdam, The Netherlands.
¹² Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Vic., Australia.
¹³ Department of Neuroradiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
¹⁴ Stony Brook University, Stony Brook, NY, USA.
¹⁵ Hotchkiss Brain Institute, Calgary, AB, Canada.
¹⁶ Department of Neurology, Ruprecht-Karls-University of Heidelberg, Heidelberg, Germany.
¹⁷ Department of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada.
¹⁸ Department of Radiology, UCLA, Los Angeles, CA, USA.
¹⁹ Department of Neuroscience, Medical University of South Carolina, Charleston, SC, USA.
²⁰ Department of Neurology, UPMC Stroke Institute, University of Pittsburgh, Pittsburgh, PA, USA.
²¹ Department of Neurology, University of Arizona, Tucson, AZ, USA.
²² Department of Medical Imaging, University of Arizona, Tucson, AZ, USA.
²³ UCLA Stroke Center, Los Angeles, CA, USA.
²⁴ Department of Neurology, Academic Medical Centre, Amsterdam, The Netherlands.
²⁵ Department of Neurology, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
²⁶ Melbourne Health, University of Melbourne and the Royal Melbourne Subject, Melbourne, Vic., Australia.
²⁷ Mount Sinai Hospital, New York, NY, USA.
²⁸ Centre for Stroke and Brain Imaging Research, Institute of Neuroscience and Psychology, University of Glasgow, Glasgow, UK.
²⁹ Institute of Neurological Sciences, Southern General Hospital, Glasgow, UK.
³⁰ Massachussetts General Hospital, Boston, MA, USA.
³¹ Department of Neurology, UCLA, Los Angeles, CA, USA.
³² Department of Neurology, St. Antonius Hospital, Utrecht, The Netherlands.
³³ University of Buffalo, Buffalo, NY, USA.
³⁴ Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
³⁵ Medical University of South Carolina, Charleston, SC, USA.
³⁶ Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK.
³⁷ Medical College of Wisconsin, Milwaukee, WI, USA.

PMID: 26352438
DOI: 10.1111/ijs.12622

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 plasminogen 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.

Keywords: acute; endovascular; ischemic stroke; meta-analysis; protocols; treatment.

MeSH terms

Analysis of Variance
Cooperative Behavior*
Endovascular Procedures / methods*
Female
Humans
Male
Meta-Analysis as Topic*
Randomized Controlled Trials as Topic
Stroke / therapy*
Tissue Plasminogen Activator / therapeutic use*
Treatment Outcome

Substances

Tissue Plasminogen Activator

Abstract

MeSH terms

Substances

Grants and funding