title: Recruitment to trials of late thrombolysis: lessons from the EXTEND study.
abstract: To increase the percentage of acute stroke patients benefiting from thrombolysis, the utility of expanding the time window of treatment beyond 4.5 hours after stroke onset needs to be investigated. We aimed to identify the target population and the challenges of recruitment of patients for the time window beyond 4.5 hours. Extending the time for Thrombolysis in Emergency Neurological Deficits (EXTEND), a multicentre randomised controlled trial testing the efficacy of thrombolytic therapy in patients with clinically significant ischaemic penumbra between 4.5 to 9 hours after stroke onset, was used as a model to evaluate inclusion and exclusion criteria for late thrombolysis trials. Data from all stroke patients admitted to Austin Health over a 1 year period were retrospectively analysed. Case notes were examined to determine potential trial eligibility. Of 556 patients assessed, 95 (17%) presented during the EXTEND time window. Sixty-seven of these (70.5%) were wake-up strokes (WUS) and 28 (29.5%) arrived between 4.5 and 9 hours after symptoms onset. At least one exclusion criterion was found for 78 (82%) of them. Hence, 17 (3%) patients arrived within an appropriate time frame for the study without any exclusion criteria. Most of these (13) arrived outside routine MRI hours. The number of patients recruited would have increased more than three-fold if imaging had been available 24 hours, 7 days a week. A significant proportion (17%) of ischaemic stroke patients presented between 4.5 and 9 hours after stroke onset. The majority of these were WUS. The major challenge identified for patient recruitment was imaging availability.
authors.affiliation: National Stroke Research Institute, The Florey Institute for Neurosciences and Mental Health, Melbourne Brain Centre, Austin Campus, 245 Burgundy Street, Heidelberg, VIC 3084, Australia; University of Melbourne, Melbourne, VIC, Australia. Electronic address: marie.dagonnier@unimelb.edu.au.
authors.forename: Marie
authors.initials: M
authors.lastname: Dagonnier
authors.affiliation: National Stroke Research Institute, The Florey Institute for Neurosciences and Mental Health, Melbourne Brain Centre, Austin Campus, 245 Burgundy Street, Heidelberg, VIC 3084, Australia.
authors.forename: David W
authors.initials: DW
authors.lastname: Howells
authors.affiliation: National Stroke Research Institute, The Florey Institute for Neurosciences and Mental Health, Melbourne Brain Centre, Austin Campus, 245 Burgundy Street, Heidelberg, VIC 3084, Australia; University of Melbourne, Melbourne, VIC, Australia; Department of Neurology, Austin Health, Heidelberg, VIC, Australia.
authors.forename: Geoffrey A
authors.initials: GA
authors.lastname: Donnan
authors.affiliation: National Stroke Research Institute, The Florey Institute for Neurosciences and Mental Health, Melbourne Brain Centre, Austin Campus, 245 Burgundy Street, Heidelberg, VIC 3084, Australia; University of Melbourne, Melbourne, VIC, Australia; Department of Neurology, Austin Health, Heidelberg, VIC, Australia.
authors.forename: Helen M
authors.initials: HM
authors.lastname: Dewey
mesh_terms: D005260:Female; D006801:Humans; D008297:Male; D009422:Nervous System Diseases / Q000188:drug therapy / Q000209:etiology; D018579:Patient Selection; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D020521:Stroke / Q000150:complications / Q000188:drug therapy*; D015912:Thrombolytic Therapy / Q000379:methods*; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*
chemical_list: D010959:Tissue Plasminogen Activator
keywords: Clinical trials; Imaging; Recruitment; Stroke; Thrombolysis