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

Henry Ma, Mark Parsons, Soren Christensen, Bruce Campbell, Leonid Churilov, Alan Connelly, Bernard Yan, Chris Bladin, Thanh Phan, Alan Barber, Stephen Read, Graeme Hankey, Romesh Markus, Tissa Wijeratne, Rohan Grimley, Neil Mahant, Timothy Kleinig, Jonathan Sturm, Andrew Lee, David BlackerRichard Gerraty, Martin Krause, Patricia Desmond, Simon McBride, Leanne Carey, David Howells, Chung Hsu, Stephen Davis, Geoffrey Donnan

    Research output: Contribution to journalArticle

    148 Citations (Scopus)

    Abstract

    Background and hypothesis: Thrombolytic therapy with tissue plasminogen activator is effective for acute ischaemic stroke within 4·5h 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 <2) will undergo magnetic resonance imaging or computer tomography. Patients who also meet imaging criteria (infarct core volume <70ml, perfusion lesion:infarct core mismatch ratio >1·2, and absolute mismatch >10ml) 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 24h and infarct growth at day 90.

    Original languageEnglish
    Pages (from-to)74-80
    Number of pages7
    JournalInternational Journal of Stroke
    Volume7
    Issue number1
    DOIs
    Publication statusPublished - Jan 2012

    Keywords

    • Clinical trials
    • EXTEND
    • Protocols
    • Stroke
    • Thrombolysis
    • Time window

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  • Cite this

    Ma, H., Parsons, M., Christensen, S., Campbell, B., Churilov, L., Connelly, A., Yan, B., Bladin, C., Phan, T., Barber, A., Read, S., Hankey, G., Markus, R., Wijeratne, T., Grimley, R., Mahant, N., Kleinig, T., Sturm, J., Lee, A., ... Donnan, G. (2012). A multicentre, randomized, double-blinded, placebo-controlled Phase III study to investigate EXtending the time for Thrombolysis in Emergency Neurological Deficits (EXTEND). International Journal of Stroke, 7(1), 74-80. https://doi.org/10.1111/j.1747-4949.2011.00730.x