Hemasse Amiri1, Erich Bluhmki2, Martin Bendszus3, Christoph C Eschenfelder4, Geoffrey A Donnan5, Didier Leys6, Carlos Molina7, Peter A Ringleb8, Peter D Schellinger9, Stefan Schwab10, Danilo Toni11, Nils Wahlgren12, Werner Hacke8. 1. Department of Neurology, University Hospital Heidelberg, Heidelberg, Germany Hemasse.Amiri@med.uni-heidelberg.de. 2. Department of Statistics, Boehringer Ingelheim, Bieberach, Germany. 3. Department of Neuroradiology, University Hospital Heidelberg, Heidelberg, Germany. 4. Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim, Germany. 5. Florey Neuroscience Institutes, University of Melbourne, Parkville, Australia. 6. Department of Neurology, Roger Salengro Hospital, Lille, France. 7. Department of Neurology, Hospital Vall d'Hebron-Barcelona, Barcelona, Spain. 8. Department of Neurology, University Hospital Heidelberg, Heidelberg, Germany. 9. Department of Neurology, Johannes-Wesling-Medical-Centre Minden, Minden, Germany. 10. Department of Neurology, University of Erlangen-Nuernberg, Erlangen, Germany. 11. Emergency Department Stroke Unit, La Sapienza University Hospital, Rome, Italy. 12. Department of Neurology, Karolinska University Hospital-Solna, Solna, Sweden.
Abstract
RATIONALE AND HYPOTHESIS: Thrombolytic therapy with recombinant tissue plasminogen activator (rt-PA) is an effective and approved therapy for acute ischemic stroke within 4.5 h of onset except for USA, Canada, Croatia, and Moldovia with a current 3 h label. We hypothesized that ischemic stroke patients selected with significant penumbral mismatch on magnetic resonance imaging (MRI) at 4.5-9 h after onset of stroke will have improved clinical outcomes when given intravenous rt-PA (alteplase) compared to placebo. STUDY DESIGN:ECASS-4: ExTEND is an investigator driven, phase 3, randomized, multi-center, double-blind, placebo-controlled study. Ischemic stroke patients presenting within 4.5 and 9 h of stroke onset, who fulfil clinical requirements (National Institutes of Health Stroke Score (NIHSS) 4-26 and pre-stroke modified Rankin Scale (mRS) 0-1) will undergo MRI. Patients who meet imaging criteria (infarct core volume <100 ml, perfusion lesion: infarct core mismatch ratio >1.2 and perfusion lesion minimum volume of 20 ml) additionally will be randomized to either rt-PA or placebo. STUDY OUTCOME: The primary outcome measure will be the categorical shift in the mRS at day 90. Clinical secondary outcomes will be disability at day 90 dichotomized as favorable outcome mRS 0-1 at day 90. Tertiary endpoints include reduction in the NIHSS by 11 or more points or reaching 0-1 at day 90, reperfusion and recanalization at 24 h post stroke as well as depression, life quality, and cognitive impairment at day 90. Safety endpoints will include symptomatic intracranial hemorrhage (ICH) and death.
RCT Entities:
RATIONALE AND HYPOTHESIS: Thrombolytic therapy with recombinant tissue plasminogen activator (rt-PA) is an effective and approved therapy for acute ischemic stroke within 4.5 h of onset except for USA, Canada, Croatia, and Moldovia with a current 3 h label. We hypothesized that ischemic strokepatients selected with significant penumbral mismatch on magnetic resonance imaging (MRI) at 4.5-9 h after onset of stroke will have improved clinical outcomes when given intravenous rt-PA (alteplase) compared to placebo. STUDY DESIGN: ECASS-4: ExTEND is an investigator driven, phase 3, randomized, multi-center, double-blind, placebo-controlled study. Ischemic strokepatients presenting within 4.5 and 9 h of stroke onset, who fulfil clinical requirements (National Institutes of Health Stroke Score (NIHSS) 4-26 and pre-stroke modified Rankin Scale (mRS) 0-1) will undergo MRI. Patients who meet imaging criteria (infarct core volume <100 ml, perfusion lesion: infarct core mismatch ratio >1.2 and perfusion lesion minimum volume of 20 ml) additionally will be randomized to either rt-PA or placebo. STUDY OUTCOME: The primary outcome measure will be the categorical shift in the mRS at day 90. Clinical secondary outcomes will be disability at day 90 dichotomized as favorable outcome mRS 0-1 at day 90. Tertiary endpoints include reduction in the NIHSS by 11 or more points or reaching 0-1 at day 90, reperfusion and recanalization at 24 h post stroke as well as depression, life quality, and cognitive impairment at day 90. Safety endpoints will include symptomatic intracranial hemorrhage (ICH) and death.
Authors: Johannes Ar Pfaff; Martin Bendszus; Geoffrey Donnan; Carlos Molina; Didier Leys; Peter D Schellinger; Stefan Schwab; Danilo Toni; Nils Wahlgren; Werner Hacke; Peter Arthur Ringleb Journal: Eur Stroke J Date: 2020-04-23
Authors: Raphael Meier; Paula Lux; B Med; Simon Jung; Urs Fischer; Jan Gralla; Mauricio Reyes; Roland Wiest; Richard McKinley; Johannes Kaesmacher Journal: Radiol Artif Intell Date: 2019-09-11