Bruce C V Campbell1,2, Peter J Mitchell3, Leonid Churilov1,2,4, Nawaf Yassi1,2,5, Timothy J Kleinig6, Richard J Dowling3, Bernard Yan1,3, Steven J Bush3, Vincent Thijs2,7, Rebecca Scroop8, Marion Simpson7, Mark Brooks9, Hamed Asadi2,9,10, Teddy Y Wu11, Darshan G Shah12, Tissa Wijeratne13, Henry Zhao1, Fana Alemseged1, Felix Ng1, Peter Bailey14, Henry Rice15, Laetitia de Villiers15, Helen M Dewey16, Philip M C Choi16, Helen Brown12, Kendal Redmond17, David Leggett17, John N Fink11, Wayne Collecutt18, Thomas Kraemer19, Martin Krause20, Dennis Cordato21, Deborah Field22, Henry Ma23, Bill O'Brien24, Benjamin Clissold25, Ferdinand Miteff26, Anna Clissold27, Geoffrey C Cloud28, Leslie E Bolitho29, Luke Bonavia30, Arup Bhattacharya31, Alistair Wright32, Abul Mamun33, Fintan O'Rourke34, John Worthington35, Andrew A Wong36, Christopher R Levi37, Christopher F Bladin2,16,38, Gagan Sharma1, Patricia M Desmond3, Mark W Parsons1, Geoffrey A Donnan1, Stephen M Davis1. 1. Department of Medicine and Neurology, Melbourne Brain Centre at the Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria, Australia. 2. The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Australia. 3. Department of Radiology, the Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria, Australia. 4. Department of Medicine (Austin Health), The University of Melbourne, Heidelberg, Victoria, Australia. 5. Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia. 6. Department of Neurology, Royal Adelaide Hospital, Adelaide, South Australia, Australia. 7. Department of Neurology, Austin Hospital, Austin Health, Heidelberg, Victoria, Australia. 8. Department of Radiology, Royal Adelaide Hospital, Adelaide, South Australia, Australia. 9. Department of Radiology, Austin Hospital, Austin Health, Heidelberg, Victoria, Australia. 10. School of Medicine, Faculty of Health, Deakin University, Victoria, Australia. 11. Department of Neurology, Christchurch Hospital, Christchurch, New Zealand. 12. Department of Neurology, Princess Alexandra Hospital, Brisbane, Queensland, Australia. 13. Melbourne Medical School, Department of Medicine and Neurology, The University of Melbourne and Western Health, Sunshine Hospital, St Albans Victoria, Australia. 14. Department of Neurology, Gold Coast University Hospital, Southport, Queensland, Australia. 15. Department of Radiology, Gold Coast University Hospital, Southport, Queensland, Australia. 16. Eastern Health and Eastern Health Clinical School, Department of Neurosciences, Monash University, Clayton, Victoria, Australia. 17. Department of Radiology, Princess Alexandra Hospital, Brisbane, Queensland, Australia. 18. Department of Radiology, Christchurch Hospital, Christchurch, New Zealand. 19. Department of Medicine, Ballarat Base Hospital, Ballarat, Victoria, Australia. 20. Department of Neurology, Royal North Shore Hospital and Kolling Institute, University of Sydney, St Leonards, New South Wales, Australia. 21. Department of Neurology, Liverpool Hospital, Liverpool, New South Wales, Australia. 22. Department of Neurology, Lyell McEwin Hospital, Adelaide, South Australia, Australia. 23. School of Clinical Sciences, Department of Medicine, Monash University, Clayton, Victoria, Australia. 24. Department of Neurology, Gosford Hospital, Gosford, New South Wales, Australia. 25. Department of Neurology, University Hospital Geelong, Deakin University, Geelong, Victoria, Australia. 26. Department of Neurology, Priority Research Centre for Brain and Mental Health Research, John Hunter Hospital, University of Newcastle, Newcastle, New South Wales, Australia. 27. Department of Medicine, Southwest Healthcare, Warrnambool, Victoria, Australia. 28. Department of Neurology, Alfred Hospital, Prahran, Victoria, Australia. 29. Department of Medicine, Northeast Health, Wangaratta, Victoria, Australia. 30. Department of Medicine, Albury Base Hospital, Albury, New South Wales, Australia. 31. Department of Medicine, Goulburn Valley Health, Shepparton, Victoria, Australia. 32. Department of Medicine, Latrobe Regional Health, Traralgon, Victoria, Australia. 33. Department of Medicine, Campbelltown Hospital, Campbelltown, New South Wales, Australia. 34. Department of Aged Care and Rehabilitation, Bankstown-Lidcombe Hospital, Bankstown, New South Wales, Australia. 35. Department of Neurology, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia. 36. Department of Neurology, Royal Brisbane and Women's Hospital and the University of Queensland, Brisbane, Queensland, Australia. 37. Maridulu budyari gumal, The Sydney Partnership for Health Education Research & Enterprise (SPHERE), University of New South Wales, Sydney, Australia. 38. Victorian Stroke Telemedicine service, Ambulance Victoria, Melbourne, Victoria, Australia.
Abstract
Importance: Intravenous thrombolysis with tenecteplase improves reperfusion prior to endovascular thrombectomy for ischemic stroke compared with alteplase. Objective: To determine whether 0.40 mg/kg of tenecteplase safely improves reperfusion before endovascular thrombectomy vs 0.25 mg/kg of tenecteplase in patients with large vessel occlusion ischemic stroke. Design, Setting, and Participants: Randomized clinical trial at 27 hospitals in Australia and 1 in New Zealand using open-label treatment and blinded assessment of radiological and clinical outcomes. Patients were enrolled from December 2017 to July 2019 with follow-up until October 2019. Adult patients (N = 300) with ischemic stroke due to occlusion of the intracranial internal carotid, \basilar, or middle cerebral artery were included less than 4.5 hours after symptom onset using standard intravenous thrombolysis eligibility criteria. Interventions: Open-label tenecteplase at 0.40 mg/kg (maximum, 40 mg; n = 150) or 0.25 mg/kg (maximum, 25 mg; n = 150) given as a bolus before endovascular thrombectomy. Main Outcomes and Measures: The primary outcome was reperfusion of greater than 50% of the involved ischemic territory prior to thrombectomy, assessed by consensus of 2 blinded neuroradiologists. Prespecified secondary outcomes were level of disability at day 90 (modified Rankin Scale [mRS] score; range, 0-6); mRS score of 0 to 1 (freedom from disability) or no change from baseline at 90 days; mRS score of 0 to 2 (functional independence) or no change from baseline at 90 days; substantial neurological improvement at 3 days; symptomatic intracranial hemorrhage within 36 hours; and all-cause death. Results: All 300 patients who were randomized (mean age, 72.7 years; 141 [47%] women) completed the trial. The number of participants with greater than 50% reperfusion of the previously occluded vascular territory was 29 of 150 (19.3%) in the 0.40 mg/kg group vs 29 of 150 (19.3%) in the 0.25 mg/kg group (unadjusted risk difference, 0.0% [95% CI, -8.9% to -8.9%]; adjusted risk ratio, 1.03 [95% CI, 0.66-1.61]; P = .89). Among the 6 secondary outcomes, there were no significant differences in any of the 4 functional outcomes between the 0.40 mg/kg and 0.25 mg/kg groups nor in all-cause deaths (26 [17%] vs 22 [15%]; unadjusted risk difference, 2.7% [95% CI, -5.6% to 11.0%]) or symptomatic intracranial hemorrhage (7 [4.7%] vs 2 [1.3%]; unadjusted risk difference, 3.3% [95% CI, -0.5% to 7.2%]). Conclusions and Relevance: Among patients with large vessel occlusion ischemic stroke, a dose of 0.40 mg/kg, compared with 0.25 mg/kg, of tenecteplase did not significantly improve cerebral reperfusion prior to endovascular thrombectomy. The findings suggest that the 0.40-mg/kg dose of tenecteplase does not confer an advantage over the 0.25-mg/kg dose in patients with large vessel occlusion ischemic stroke in whom endovascular thrombectomy is planned. Trial Registration: ClinicalTrials.gov Identifier: NCT03340493.
Importance: Intravenous thrombolysis with tenecteplase improves reperfusion prior to endovascular thrombectomy for ischemic stroke compared with alteplase. Objective: To determine whether 0.40 mg/kg of tenecteplase safely improves reperfusion before endovascular thrombectomy vs 0.25 mg/kg of tenecteplase in patients with large vessel occlusion ischemic stroke. Design, Setting, and Participants: Randomized clinical trial at 27 hospitals in Australia and 1 in New Zealand using open-label treatment and blinded assessment of radiological and clinical outcomes. Patients were enrolled from December 2017 to July 2019 with follow-up until October 2019. Adult patients (N = 300) with ischemic stroke due to occlusion of the intracranial internal carotid, \basilar, or middle cerebral artery were included less than 4.5 hours after symptom onset using standard intravenous thrombolysis eligibility criteria. Interventions: Open-label tenecteplase at 0.40 mg/kg (maximum, 40 mg; n = 150) or 0.25 mg/kg (maximum, 25 mg; n = 150) given as a bolus before endovascular thrombectomy. Main Outcomes and Measures: The primary outcome was reperfusion of greater than 50% of the involved ischemic territory prior to thrombectomy, assessed by consensus of 2 blinded neuroradiologists. Prespecified secondary outcomes were level of disability at day 90 (modified Rankin Scale [mRS] score; range, 0-6); mRS score of 0 to 1 (freedom from disability) or no change from baseline at 90 days; mRS score of 0 to 2 (functional independence) or no change from baseline at 90 days; substantial neurological improvement at 3 days; symptomatic intracranial hemorrhage within 36 hours; and all-cause death. Results: All 300 patients who were randomized (mean age, 72.7 years; 141 [47%] women) completed the trial. The number of participants with greater than 50% reperfusion of the previously occluded vascular territory was 29 of 150 (19.3%) in the 0.40 mg/kg group vs 29 of 150 (19.3%) in the 0.25 mg/kg group (unadjusted risk difference, 0.0% [95% CI, -8.9% to -8.9%]; adjusted risk ratio, 1.03 [95% CI, 0.66-1.61]; P = .89). Among the 6 secondary outcomes, there were no significant differences in any of the 4 functional outcomes between the 0.40 mg/kg and 0.25 mg/kg groups nor in all-cause deaths (26 [17%] vs 22 [15%]; unadjusted risk difference, 2.7% [95% CI, -5.6% to 11.0%]) or symptomatic intracranial hemorrhage (7 [4.7%] vs 2 [1.3%]; unadjusted risk difference, 3.3% [95% CI, -0.5% to 7.2%]). Conclusions and Relevance: Among patients with large vessel occlusion ischemic stroke, a dose of 0.40 mg/kg, compared with 0.25 mg/kg, of tenecteplase did not significantly improve cerebral reperfusion prior to endovascular thrombectomy. The findings suggest that the 0.40-mg/kg dose of tenecteplase does not confer an advantage over the 0.25-mg/kg dose in patients with large vessel occlusion ischemic stroke in whom endovascular thrombectomy is planned. Trial Registration: ClinicalTrials.gov Identifier: NCT03340493.
Authors: Nils Wahlgren; Niaz Ahmed; Antoni Dávalos; Gary A Ford; Martin Grond; Werner Hacke; Michael G Hennerici; Markku Kaste; Sonja Kuelkens; Vincent Larrue; Kennedy R Lees; Risto O Roine; Lauri Soinne; Danilo Toni; Geert Vanhooren Journal: Lancet Date: 2007-01-27 Impact factor: 79.321
Authors: Bruce Cv Campbell; Peter J Mitchell; Leonid Churilov; Nawaf Yassi; Timothy J Kleinig; Bernard Yan; Vincent Thijs; Patricia M Desmond; Mark W Parsons; Geoffrey A Donnan; Stephen M Davis Journal: Int J Stroke Date: 2019-09-30 Impact factor: 5.266
Authors: Xuya Huang; Rachael MacIsaac; John Lp Thompson; Bruce Levin; Richard Buchsbaum; E Clarke Haley; Christopher Levi; Bruce Campbell; Christopher Bladin; Mark Parsons; Keith W Muir Journal: Int J Stroke Date: 2016-04-05 Impact factor: 5.266
Authors: Bruce C V Campbell; Charles B L M Majoie; Gregory W Albers; Bijoy K Menon; Nawaf Yassi; Gagan Sharma; Wim H van Zwam; Robert J van Oostenbrugge; Andrew M Demchuk; Francis Guillemin; Philip White; Antoni Dávalos; Aad van der Lugt; Kenneth S Butcher; Aboubaker Cherifi; Henk A Marquering; Geoffrey Cloud; Juan M Macho Fernández; Jeremy Madigan; Catherine Oppenheim; Geoffrey A Donnan; Yvo B W E M Roos; Jai Shankar; Hester Lingsma; Alain Bonafé; Hélène Raoult; María Hernández-Pérez; Aditya Bharatha; Reza Jahan; Olav Jansen; Sébastien Richard; Elad I Levy; Olvert A Berkhemer; Marc Soudant; Lucia Aja; Stephen M Davis; Timo Krings; Marie Tisserand; Luis San Román; Alejandro Tomasello; Debbie Beumer; Scott Brown; David S Liebeskind; Serge Bracard; Keith W Muir; Diederik W J Dippel; Mayank Goyal; Jeffrey L Saver; Tudor G Jovin; Michael D Hill; Peter J Mitchell Journal: Lancet Neurol Date: 2018-11-06 Impact factor: 44.182
Authors: David S Liebeskind; Serge Bracard; Francis Guillemin; Reza Jahan; Tudor G Jovin; Charles Blm Majoie; Peter J Mitchell; Aad van der Lugt; Bijoy K Menon; Luis San Román; Bruce Cv Campbell; Keith W Muir; Michael D Hill; Diederik Wj Dippel; Jeffrey L Saver; Andrew M Demchuk; Antoni Dávalos; Philip White; Scott Brown; Mayank Goyal Journal: J Neurointerv Surg Date: 2018-09-07 Impact factor: 5.836
Authors: Eivind Berge; William Whiteley; Heinrich Audebert; Gian Marco De Marchis; Ana Catarina Fonseca; Chiara Padiglioni; Natalia Pérez de la Ossa; Daniel Strbian; Georgios Tsivgoulis; Guillaume Turc Journal: Eur Stroke J Date: 2021-02-19
Authors: Felix C Ng; Leonid Churilov; Nawaf Yassi; Timothy J Kleinig; Vincent Thijs; Teddy Y Wu; Darshan Shah; Helen M Dewey; Gagan Sharma; Patricia M Desmond; Bernard Yan; Mark W Parsons; Geoffrey A Donnan; Stephen M Davis; Peter J Mitchell; Bruce Cv Campbell Journal: J Cereb Blood Flow Metab Date: 2021-05-17 Impact factor: 6.200
Authors: Bruce C V Campbell; Maarten G Lansberg; Gregory W Albers; Joseph P Broderick; Colin P Derdeyn; Pooja Khatri; Amrou Sarraj; Jeffrey L Saver; Achala Vagal Journal: Stroke Date: 2021-07-08 Impact factor: 10.170