Bruce Cv Campbell1,2, Peter J Mitchell3, Leonid Churilov4, Nawaf Yassi1,2, Timothy J Kleinig5, Bernard Yan1,3, Vincent Thijs2,4, 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, Victoria, Australia. 2. Florey Institute of Neuroscience and Mental Health, University of Melbourne, Victoria, Australia. 3. Department of Radiology, the Royal Melbourne Hospital, University of Melbourne, Victoria, Australia. 4. Department of Medicine, Austin Health, University of Melbourne, Heidelberg, Australia. 5. Royal Adelaide Hospital, Adelaide, South Australia, Australia.
Abstract
BACKGROUND AND HYPOTHESIS: Intravenous thrombolysis with tenecteplase is more effective than alteplase in achieving substantial reperfusion at initial angiographic assessment and improves functional outcome. However, the optimal dose of tenecteplase remains uncertain. We hypothesized that 0.40 mg/kg tenecteplase is superior to 0.25 mg/kg tenecteplase in achieving reperfusion at initial angiogram, when administered within 4.5 h of ischemic stroke onset, in patients planned to undergo endovascular therapy. STUDY DESIGN: EXTEND-IA TNK part 2 is an investigator-initiated, phase II, multicenter, prospective, randomized, open-label, blinded-endpoint (PROBE) study. Eligibility requires a diagnosis of ischemic stroke within 4.5 h of stroke onset, pre-stroke modified Rankin Scale (mRS)≤3 (no upper age limit), absence of contraindications to intravenous thrombolysis, and large vessel occlusion (internal carotid, basilar, or middle cerebral artery) on multimodal CT. Patients are randomized to IV tenecteplase at either 0.40 mg/kg (max 40 mg) or 0.25 mg/kg (max 25 mg) prior to thrombectomy. STUDY OUTCOMES: The primary outcome measure is reperfusion on the initial catheter angiogram, assessed as modified Treatment In Cerebral Infarction (mTICI) 2b/3, or the absence of retrievable intracranial thrombus. Secondary outcomes include mRS at day 90 and early neurological improvement (reduction in National Institutes of Health Stroke Scale (NIHSS) by ≥8 points or reaching 0-1) at day 3. Safety outcomes are death and symptomatic intracerebral hemorrhage. Trial registration: ClinicalTrials.gov NCT03340493.
RCT Entities:
BACKGROUND AND HYPOTHESIS: Intravenous thrombolysis with tenecteplase is more effective than alteplase in achieving substantial reperfusion at initial angiographic assessment and improves functional outcome. However, the optimal dose of tenecteplase remains uncertain. We hypothesized that 0.40 mg/kg tenecteplase is superior to 0.25 mg/kg tenecteplase in achieving reperfusion at initial angiogram, when administered within 4.5 h of ischemic stroke onset, in patients planned to undergo endovascular therapy. STUDY DESIGN: EXTEND-IA TNK part 2 is an investigator-initiated, phase II, multicenter, prospective, randomized, open-label, blinded-endpoint (PROBE) study. Eligibility requires a diagnosis of ischemic stroke within 4.5 h of stroke onset, pre-stroke modified Rankin Scale (mRS)≤3 (no upper age limit), absence of contraindications to intravenous thrombolysis, and large vessel occlusion (internal carotid, basilar, or middle cerebral artery) on multimodal CT. Patients are randomized to IV tenecteplase at either 0.40 mg/kg (max 40 mg) or 0.25 mg/kg (max 25 mg) prior to thrombectomy. STUDY OUTCOMES: The primary outcome measure is reperfusion on the initial catheter angiogram, assessed as modified Treatment In Cerebral Infarction (mTICI) 2b/3, or the absence of retrievable intracranial thrombus. Secondary outcomes include mRS at day 90 and early neurological improvement (reduction in National Institutes of Health Stroke Scale (NIHSS) by ≥8 points or reaching 0-1) at day 3. Safety outcomes are death and symptomatic intracerebral hemorrhage. Trial registration: ClinicalTrials.gov NCT03340493.
Authors: Bruce C V Campbell; Peter J Mitchell; Leonid Churilov; Nawaf Yassi; Timothy J Kleinig; Richard J Dowling; Bernard Yan; Steven J Bush; Vincent Thijs; Rebecca Scroop; Marion Simpson; Mark Brooks; Hamed Asadi; Teddy Y Wu; Darshan G Shah; Tissa Wijeratne; Henry Zhao; Fana Alemseged; Felix Ng; Peter Bailey; Henry Rice; Laetitia de Villiers; Helen M Dewey; Philip M C Choi; Helen Brown; Kendal Redmond; David Leggett; John N Fink; Wayne Collecutt; Thomas Kraemer; Martin Krause; Dennis Cordato; Deborah Field; Henry Ma; Bill O'Brien; Benjamin Clissold; Ferdinand Miteff; Anna Clissold; Geoffrey C Cloud; Leslie E Bolitho; Luke Bonavia; Arup Bhattacharya; Alistair Wright; Abul Mamun; Fintan O'Rourke; John Worthington; Andrew A Wong; Christopher R Levi; Christopher F Bladin; Gagan Sharma; Patricia M Desmond; Mark W Parsons; Geoffrey A Donnan; Stephen M Davis Journal: JAMA Date: 2020-04-07 Impact factor: 56.272
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: Nadinda A M van der Ende; Bob Roozenbeek; Lucas E M Smagge; Sven P R Luijten; Leo A M Aerden; Petra Kraayeveld; Ido R van den Wijngaard; Geert J Lycklama À Nijeholt; Heleen M den Hertog; H Zwenneke Flach; Alexis C Wallace; Victor Gurewich; Gregory J Del Zoppo; William J Meurer; Hester F Lingsma; Aad van der Lugt; Diederik W J Dippel Journal: Trials Date: 2022-08-09 Impact factor: 2.728