Peter Ringleb1, Martin Bendszus2, Erich Bluhmki3, Geoffrey Donnan4, Christoph Eschenfelder3, Marc Fatar5, Christof Kessler6, Carlos Molina7, Didier Leys8, Girish Muddegowda9, Sven Poli10, Peter Schellinger11, Stefan Schwab12, Joaquin Serena13, Danilo Toni14, Nils Wahlgren15, Werner Hacke16. 1. 1 Department of Neurology, University of Heidelberg, Heidelberg, Germany. 2. 2 Department of Neuroradiology, University of Heidelberg, Heidelberg, Germany. 3. 3 Medical Affairs, Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim, Germany. 4. 4 University of Melbourne, Florey Institute of Neuroscience and Mental Health, Melbourne, Australia. 5. 5 Department of Neurology, Universitätsmedizin Mannheim, University of Heidelber, Heidelberg, Germany. 6. 6 Department ogf Neurology, Ernst Moritz Arndt-University of Greifswald, Greifswald, Germany. 7. 7 Department of Neurology, University of Barcelona, Hospital vall d'hebron, Barcelona, Spain. 8. 8 Department of Neurology, Lille, France, Univ Lille; Inserm; CHU Lille; UMR-S. 9. 9 Department of Neurology, University of Nottingham, Nottingham, United Kingdom. 10. 10 Department of Neurology, University of Tübingen, Tübingen, Germany. 11. 11 Department of Neurology, Klinikum Minden, Minden, Germany. 12. 12 Department of Neurology, University of Erlangen-Nuremberg, Erlangen, Germany. 13. 13 Department of Neurology, Hospital Universitari de Girona Doctor Josep Trueta, Girona, Spain. 14. 14 Department of Neurology, Sapienza University of Rome, Rome, Italy. 15. 15 Department of Neurology, Karolinska University Hospital, Stockholm, Sweden. 16. 16 Ruprecht-Karls-University of Heidelberg, Heidelberg, Germany.
Abstract
BACKGROUND: Intravenous thrombolysis with alteplase within a time window up to 4.5 h is the only approved pharmacological treatment for acute ischemic stroke. We studied whether acute ischemic stroke patients with penumbral tissue identified onmagnetic resonance imaging 4.5-9 h after symptom onset benefit from intravenous thrombolysis compared to placebo. METHODS:Acute ischemic stroke patients with salvageable brain tissue identified on a magnetic resonance imaging were randomly assigned to receive standard dose alteplase or placebo. The primary end point was disability at 90 days assessed by the modified Rankin scale, which has a range of 0-6 (with 0 indicating no symptoms at all and 6 indicating death). Safety end points included death, symptomatic intracranial hemorrhage, and other serious adverse events. RESULTS: The trial was stopped early for slow recruitment after the enrollment of 119 (61 alteplase, 58 placebo) of 264 patients planned. Median time to intravenous thrombolysis was 7 h 42 min. The primary endpoint showed no significant difference in the modified Rankin scale distribution at day 90 (odds ratio alteplase versus placebo, 1.20; 95% CI, 0.63-2.27, P = 0.58). One symptomatic intracranial hemorrhage occurred in the alteplase group. Mortality at 90 days did not differ significantly between the two groups (11.5 and 6.8%, respectively; P = 0.53). CONCLUSIONS: Intravenous alteplase administered between 4.5 and 9 h after the onset of symptoms in patients with salvageable tissue did not result in a significant benefit over placebo. (Supported by Boehringer Ingelheim, Germany; ISRCTN 71616222).
RCT Entities:
BACKGROUND: Intravenous thrombolysis with alteplase within a time window up to 4.5 h is the only approved pharmacological treatment for acute ischemic stroke. We studied whether acute ischemic strokepatients with penumbral tissue identified on magnetic resonance imaging 4.5-9 h after symptom onset benefit from intravenous thrombolysis compared to placebo. METHODS: Acute ischemic strokepatients with salvageable brain tissue identified on a magnetic resonance imaging were randomly assigned to receive standard dose alteplase or placebo. The primary end point was disability at 90 days assessed by the modified Rankin scale, which has a range of 0-6 (with 0 indicating no symptoms at all and 6 indicating death). Safety end points included death, symptomatic intracranial hemorrhage, and other serious adverse events. RESULTS: The trial was stopped early for slow recruitment after the enrollment of 119 (61 alteplase, 58 placebo) of 264 patients planned. Median time to intravenous thrombolysis was 7 h 42 min. The primary endpoint showed no significant difference in the modified Rankin scale distribution at day 90 (odds ratio alteplase versus placebo, 1.20; 95% CI, 0.63-2.27, P = 0.58). One symptomatic intracranial hemorrhage occurred in the alteplase group. Mortality at 90 days did not differ significantly between the two groups (11.5 and 6.8%, respectively; P = 0.53). CONCLUSIONS: Intravenous alteplase administered between 4.5 and 9 h after the onset of symptoms in patients with salvageable tissue did not result in a significant benefit over placebo. (Supported by Boehringer Ingelheim, Germany; ISRCTN 71616222).
Entities:
Keywords:
Alteplase; endovascular; intravenous thrombolysis; magnetic resonance imaging; thrombolysis; time window
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