Arturo Renú1,2, Jordi Blasco3, Mónica Millán4, Joan Martí-Fàbregas5, Pere Cardona6, Laura Oleaga3, Juan Macho3, Carlos Molina7, Jaume Roquer8, Sergio Amaro1,2, Antonio Dávalos4, Federico Zarco3, Carlos Laredo1,2, Alejandro Tomasello9, Leopoldo Guimaraens10, Roger Barranco11, Carlos Castaño12, Elío Vivas10, Anna Ramos4, Antonio López-Rueda3, Xabier Urra1,2, Marián Muchada7, Elisa Cuadrado-Godía8, Pol Camps-Renom5, Luis S Román3, José Ríos13,14, Enrique C Leira15, Tudor Jovin16, Ferran Torres11, Ángel Chamorro1,2. 1. Comprehensive Stroke Center, Hospital Clínic of Barcelona; Institut d'Investigacions Biomèdiques August Pi i Sunyer (146245IDIBAPS), Barcelona, Spain. 2. 16724University of Barcelona, Spain. 3. Radiology Department, Hospital Clinic, Barcelona, Spain. 4. Department of Neuroscience, Hospital Germans Trias i Pujol, Barcelona, Spain. 5. Department of Neurology, 16689Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute, Barcelona, Spain. 6. Department of Neurology, Stroke Unit, Hospital Universitari Bellvitge, Barcelona, Spain. 7. Department of Neurology, Stroke Unit, Hospital Universitari Vall d'Hebrón, Barcelona, Spain. 8. Department of Neurology, IMIM-Hospital del Mar (Institut Hospital del Mar d'Investigacions Mèdiques), Universitat Autònoma de Barcelona i DCEXS-Universitat Pompeu Fabra, Barcelona, Spain. 9. Department of Neuroradiology, Hospital Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain. 10. Department of Neuroradiology, Hospital del Mar, Barcelona, Spain. 11. Department of Neuroradiology, Hospital Universitari Bellvitge, Barcelona, Spain. 12. Department of Neuroradiology, Hospital Germans Trias i Pujol, Barcelona, Spain. 13. Medical Statistics Core Facility, Institut d'Investigacions Biomèdiques August Pi i Sunyer (146245IDIBAPS), Barcelona, Spain. 14. Biostatistics Unit, Universitat Autónoma de Barcelona, Barcelona, Spain. 15. Departments of Neurology, Neurosurgery and Epidemiology, University of Iowa, Iowa City, USA. 16. Cooper Neurological Institute, Cooper Medical School of Rowan University, Camden, USA.
Abstract
RATIONALE: The potential value of rescue intraarterial thrombolysis in patients with large vessel occlusion stroke treated with mechanical thrombectomy has not been assessed in randomized trials. AIM: The CHemical OptImization of Cerebral Embolectomy trial aims to establish whether rescue intraarterial thrombolysis is more effective than placebo in improving suboptimal reperfusion scores in patients with large vessel occlusion stroke treated with mechanical thrombectomy. SAMPLE SIZE ESTIMATES: A sample size of 200 patients allocated 1:1 tointraarterial thrombolysis or intraarterial placebo will have >95% statistical power for achieving the primary outcome (5% in the control versus 60% in the treatment group) for a two-sided (5% alpha, and 5% lost to follow-up). METHODS AND DESIGN: We conducted a multicenter, randomized, placebo-controlled, double blind, phase 2b trial. Eligible patients are 18 or older with symptomatic large vessel occlusion treated with mechanical thrombectomy resulting in a modified treatment in cerebral ischemia score 2b at end of the procedure. Patients will receive 20-30 min intraarterial infusion of recombinant tissue plasminogen activator or placebo (0.5 mg/ml, maximum dose limit 22.5 mg). STUDY OUTCOME(S): The primary outcome is the proportion of patients with an improved modified treatment in cerebral ischemia score 10 min after the end of the study treatment. Secondary outcomes include the shift analysis of the modified Rankin Scale, the infarct expansion ratio, the proportion of excellent outcome (modified Rankin Scale 0-1), the proportion of infarct expansion, and the infarction volume. Mortality and symptomatic intracerebral bleeding will be assessed. DISCUSSION: The study will provide evidence whether rescue intraarterial thrombolysis improves brain reperfusion in patients with large vessel occlusion stroke and incomplete reperfusion (modified treatment in cerebral ischemia 2b) at the end of mechanical thrombectomy.
RCT Entities:
RATIONALE: The potential value of rescue intraarterial thrombolysis in patients with large vessel occlusion stroke treated with mechanical thrombectomy has not been assessed in randomized trials. AIM: The CHemical OptImization of Cerebral Embolectomy trial aims to establish whether rescue intraarterial thrombolysis is more effective than placebo in improving suboptimal reperfusion scores in patients with large vessel occlusion stroke treated with mechanical thrombectomy. SAMPLE SIZE ESTIMATES: A sample size of 200 patients allocated 1:1 to intraarterial thrombolysis or intraarterial placebo will have >95% statistical power for achieving the primary outcome (5% in the control versus 60% in the treatment group) for a two-sided (5% alpha, and 5% lost to follow-up). METHODS AND DESIGN: We conducted a multicenter, randomized, placebo-controlled, double blind, phase 2b trial. Eligible patients are 18 or older with symptomatic large vessel occlusion treated with mechanical thrombectomy resulting in a modified treatment in cerebral ischemia score 2b at end of the procedure. Patients will receive 20-30 min intraarterial infusion of recombinant tissue plasminogen activator or placebo (0.5 mg/ml, maximum dose limit 22.5 mg). STUDY OUTCOME(S): The primary outcome is the proportion of patients with an improved modified treatment in cerebral ischemia score 10 min after the end of the study treatment. Secondary outcomes include the shift analysis of the modified Rankin Scale, the infarct expansion ratio, the proportion of excellent outcome (modified Rankin Scale 0-1), the proportion of infarct expansion, and the infarction volume. Mortality and symptomatic intracerebral bleeding will be assessed. DISCUSSION: The study will provide evidence whether rescue intraarterial thrombolysis improves brain reperfusion in patients with large vessel occlusion stroke and incomplete reperfusion (modified treatment in cerebral ischemia 2b) at the end of mechanical thrombectomy.