A multicenter, randomized, controlled study to investigate EXtending the time for Thrombolysis in Emergency Neurological Deficits with Intra-Arterial therapy (EXTEND-IA)
- Conflict of interest: None declared.
- Funding: The study is managed by the steering committee and executive sub-committees and financially supported by the National Health and Medical Research Council (NHMRC) of Australia, National Heart Foundation of Australia (NHF), National Stroke Foundation of Australia (NSF), a Royal Melbourne Hospital Home Lottery Project Grant, and the Royal Australasian College of Physicians (RACP). In kind logistic support is provided by the Commonwealth Scientific and Industrial Research Organisation (CSIRO), Neuroscience Trials Australia, the Melbourne Brain Centre at the Royal Melbourne Hospital, and the Florey Institute of Neuroscience and Mental Health. Covidien (manufacturer of the Solitaire FR device) will provide the study device free of charge and additional infrastructure funding but have no role in the design or analysis of the study. The sponsor of the study is the National Stroke Research Institute (NSRI), a division of the Florey Institute of Neuroscience and Mental Health.
- Trial registration: ClinicalTrials.gov NCT01492725 (registered 20/11/2011), ANZCTR.org.au ACTRN12611000969965.
Background and Hypothesis
Thrombolysis with tissue plasminogen activator is proven to reduce disability when given within 4·5 h of ischemic stroke onset. However, tissue plasminogen activator only succeeds in recanalizing large vessel arterial occlusion in a minority of patients. We hypothesized that anterior circulation ischemic stroke patients, selected with ‘dual target’ vessel occlusion and evidence of salvageable brain using computed tomography or magnetic resonance imaging ‘mismatch’ within 4·5 h of onset, would have improved reperfusion and early neurological improvement when treated with intra-arterial clot retrieval after intravenous tissue plasminogen activator compared with intravenous tissue plasminogen activator alone.
EXTEND-IA is an investigator-initiated, phase II, multicenter prospective, randomized, open-label, blinded-endpoint study. Ischemic stroke patients receiving standard 0·9 mg/kg intravenous tissue plasminogen activator within 4·5 h of stroke onset who have good prestroke functional status (modified Rankin Scale <2, no upper age limit) will undergo multimodal computed tomography or magnetic resonance imaging. Patients who also meet dual target imaging criteria: vessel occlusion (internal carotid or middle cerebral artery) and mismatch (perfusion lesion : ischemic core mismatch ratio >1·2, absolute mismatch >10 ml, ischemic core volume <70 ml) will be randomized to either clot retrieval with the Solitaire FR device after full dose intravenous tissue plasminogen activator, or tissue plasminogen activator alone.
The coprimary outcome measure will be reperfusion at 24 h and favorable clinical response (reduction in National Institutes of Health Stroke Scale by ≥8 points or reaching 0–1) at day 3. Secondary outcomes include modified Rankin Scale at day 90, death, and symptomatic intracranial hemorrhage.