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 Kidwell21,22, David Liebeskind23, Charles B Majoie24, Sheila Cristina Ouriques Martins25, Peter Mitchell26, J Mocco27, Keith W Muir28,29, 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. 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.
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.
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.
Authors: Steven J Warach; Marie Luby; Gregory W Albers; Roland Bammer; Andrew Bivard; Bruce C V Campbell; Colin Derdeyn; Jeremy J Heit; Pooja Khatri; Maarten G Lansberg; David S Liebeskind; Charles B L M Majoie; Michael P Marks; Bijoy K Menon; Keith W Muir; Mark W Parsons; Achala Vagal; Albert J Yoo; Andrei V Alexandrov; Jean-Claude Baron; David J Fiorella; Anthony J Furlan; Josep Puig; Peter D Schellinger; Max Wintermark Journal: Stroke Date: 2016-04-12 Impact factor: 7.914
Authors: Darren Flynn; Richard Francis; Kristoffer Halvorsrud; Eduardo Gonzalo-Almorox; Dawn Craig; Shannon Robalino; Peter McMeekin; Adela Cora; Joyce Balami; Gary A Ford; Phil White Journal: Eur Stroke J Date: 2017-07-10
Authors: Thanh G Phan; Jian Chen; Richard Beare; Henry Ma; Benjamin Clissold; John Van Ly; Velandai Srikanth Journal: Front Neurol Date: 2017-02-28 Impact factor: 4.003
Authors: Vaclav Prochazka; Tomas Jonszta; Daniel Czerny; Jan Krajca; Martin Roubec; Jirka Macak; Petr Kovar; Petra Kovarova; Martin Pulcer; Renata Zoubkova; Ivo Lochman; Veronika Svachova; Lubomir Pavliska; Adela Vrtkova; David Kasprak; Jaromir Gumulec; John W Weisel Journal: Med Sci Monit Date: 2018-06-11