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.
BACKGROUND
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.


OBJECTIVE
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.


RESULTS
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.


CONCLUSIONS
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.
Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.
Rachael L
RL
MacIsaac
University of Cincinnati, Cincinnati, OH, USA.
Pooja
P
Khatri
Heidelberg University Hospital, Heidelberg, Germany.
Martin
M
Bendszus
CHRU NANCY, Nancy, France.
Serge
S
Bracard
University of Cincinnati, Cincinnati, OH, USA.
Joseph
J
Broderick
Royal Melbourne Hospital, Parkville, Vic., Australia.
Bruce
B
Campbell
Department of Cardio-Thoracic-Vascular, Azienda Ospedaliera Carlo Poma Mantova, Italy.
Alfonso
A
Ciccone
Department of Neurology, Hospital Universitari Germans Trias i Pujol, Barcelona, Spain.
Antoni
A
Dávalos
Department of Neurology, The Royal Melbourne Hospital, Parkville, Vic., Australia.
Stephen M
SM
Davis
University of Calgary, Calgary, AB, Canada.
Andrew
A
Demchuk
Department of Neurology, University Hospital Essen, Essen, Germany.
Hans-Christoph
HC
Diener
Department of Neurology, Erasmus MC, Rotterdam, The Netherlands.
Diederik
D
Dippel
Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Vic., Australia.
Geoffrey A
GA
Donnan
Department of Neuroradiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Jens
J
Fiehler
Stony Brook University, Stony Brook, NY, USA.
David
D
Fiorella
Hotchkiss Brain Institute, Calgary, AB, Canada.
Mayank
M
Goyal
Department of Neurology, Ruprecht-Karls-University of Heidelberg, Heidelberg, Germany.
Werner
W
Hacke
Department of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada.
Michael D
http://orcid.org/0000-0002-6269-1543
MD
Hill
Department of Radiology, UCLA, Los Angeles, CA, USA.
Reza
R
Jahan
Department of Neuroscience, Medical University of South Carolina, Charleston, SC, USA.
Edward
E
Jauch
Department of Neurology, UPMC Stroke Institute, University of Pittsburgh, Pittsburgh, PA, USA.
Tudor
T
Jovin
Department of Neurology, University of Arizona, Tucson, AZ, USA.|Department of Medical Imaging, University of Arizona, Tucson, AZ, USA.
Chelsea S
CS
Kidwell
UCLA Stroke Center, Los Angeles, CA, USA.
David
D
Liebeskind
Department of Neurology, Academic Medical Centre, Amsterdam, The Netherlands.
Charles B
CB
Majoie
Department of Neurology, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
Sheila Cristina Ouriques
SC
Martins
Melbourne Health, University of Melbourne and the Royal Melbourne Subject, Melbourne, Vic., Australia.
Peter
P
Mitchell
Mount Sinai Hospital, New York, NY, USA.
J
J
Mocco
Centre for Stroke and Brain Imaging Research, Institute of Neuroscience and Psychology, University of Glasgow, Glasgow, UK.|Institute of Neurological Sciences, Southern General Hospital, Glasgow, UK.
Keith W
KW
Muir
Massachussetts General Hospital, Boston, MA, USA.
Raul
R
Nogueira
Department of Neurology, UCLA, Los Angeles, CA, USA.
Jeffrey L
JL
Saver
Department of Neurology, St. Antonius Hospital, Utrecht, The Netherlands.
Wouter J
WJ
Schonewille
University of Buffalo, Buffalo, NY, USA.
Adnan H
AH
Siddiqui
Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Götz
G
Thomalla
University of Cincinnati, Cincinnati, OH, USA.
Thomas A
TA
Tomsick
Medical University of South Carolina, Charleston, SC, USA.
Aquilla S
AS
Turk
Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK.
Philip
P
White
Medical College of Wisconsin, Milwaukee, WI, USA.
Osama
O
Zaidat
Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.
Kennedy R
KR
Lees
D000704:Analysis of Variance; D003299:Cooperative Behavior; D057510:Endovascular Procedures / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D015201:Meta-Analysis as Topic; D016032:Randomized Controlled Trials as Topic; D020521:Stroke / Q000628:therapy*; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*; D016896:Treatment Outcome
D010959:Tissue Plasminogen Activator
acute; endovascular; ischemic stroke; meta-analysis; protocols; treatment