A multicentre, randomized, double-blinded, placebo-controlled Phase III study to investigate EXtending the time for Thrombolysis in Emergency Neurological Deficits (EXTEND) -Protocols

Henry Hin Kui Ma, Mark Parsons, Soren Christensen, Leonid Churilov, Alan Connelly, Bernard Yan, Christopher Bladin, Thanh G Phan, Alan Barber, Stephen Read, Graeme John Hankey, Romesh Markus, Tissa Wijeratne, Rohan S Grimley, Neil Mahant, Timothy Kleinig, Jonathan W Sturm, Andrew Lee, David J Blacker, Richard Patrick GerratyMartin Krause, Patricia Desmond, Simon J McBride, Leeanne Carey, David William Howells, Chung Y Hsu, Stephen M Davis, Geoffrey Donnan

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BACKGROUND AND HYPOTHESIS: Thrombolytic therapy with tissue plasminogen activator is effective for acute ischaemic stroke within 4.5 h of onset. Patients who wake up with stroke are generally ineligible for stroke thrombolysis. We hypothesized that ischaemic stroke patients with significant penumbral mismatch on either magnetic resonance imaging or computer tomography at three- (or 4.5 depending on local guidelines) to nine-hours from stroke onset, or patients with wake-up stroke within nine-hours from midpoint of sleep duration, would have improved clinical outcomes when given tissue plasminogen activator compared to placebo. STUDY DESIGN: EXtending the time for Thrombolysis in Emergency Neurological Deficits is an investigator-driven, Phase III, randomized, multicentre, double-blind, placebo-controlled study. Ischaemic stroke patients presenting after the three- or 4.5-h treatment window for tissue plasminogen activator and within nine-hours of stroke onset or with wake-up stroke within nine-hours from the midpoint of sleep duration, who fulfil clinical (National Institutes of Health Stroke Score >/=4-26 and prestroke modified Rankin Scale 1.2, and absolute mismatch >10 ml) will be randomized to either tissue plasminogen activator or placebo. STUDY OUTCOME: The primary outcome measure will be modified Rankin Scale 0-1 at day 90. Clinical secondary outcomes include categorical shift in modified Rankin Scale at 90 days, reduction in the National Institutes of Health Stroke Score by 8 or more points or reaching 0-1 at day 90, recurrent stroke, or death. Imaging secondary outcomes will include symptomatic intracranial haemorrhage, reperfusion and or recanalization at 24 h and infarct growth at day 90.
Original languageEnglish
Pages (from-to)74 - 80
Number of pages7
JournalInternational Journal of Stroke
Issue number1
Publication statusPublished - 2012

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