A multicenter, randomized, controlled study to investigate EXtending the time for Thrombolysis in Emergency Neurological Deficits with Intra-Arterial therapy (EXTEND-IA).

Abstract

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.

STUDY DESIGN:

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.

STUDY OUTCOMES:

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.

• Authors: Bruce C V Campbell, Peter J Mitchell, Bernard Yan, Mark W Parsons, Søren Christensen, Leonid Churilov, Richard J Dowling, Helen Dewey, Mark Brooks, Ferdinand Miteff, Christopher Levi, Martin Krause, Timothy J Harrington, Kenneth C Faulder, Brendan S Steinfort, Timothy Kleinig, Rebecca Scroop, Steve Chryssidis, Alan Barber, Ayton Hope, Maurice Moriarty, Ben McGuinness, Andrew A Wong, Alan Coulthard, Tissa Wijeratne, Andrew Lee, Jim Jannes, James Leyden, Thanh G Phan, Winston Chong, Michael E Holt, Ronil V Chandra, Christopher F Bladin, Monica Badve, Henry Rice, Laetitia de Villiers, Henry Ma, Patricia M Desmond, Geoffrey A Donnan, Stephen M Davis, EXTEND-IA investigators
• Journal: International journal of stroke : official journal of the International Stroke Society (Int J Stroke) Vol. 9 Issue 1 Pg. 126-32 (Jan 2014) ISSN: 1747-4949 [Electronic] United States
• PMID: 24207098 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2013 The Authors. International Journal of Stroke © 2013 World Stroke Organization.

Chemical References

• Fibrinolytic Agents
• Tissue Plasminogen Activator

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Female
• Fibrinolytic Agents (therapeutic use)
• Humans
• Magnetic Resonance Imaging
• Male
• Middle Aged
• Multimodal Imaging
• Research Design
• Stroke (therapy)
• Thrombectomy (methods)
• Thrombolytic Therapy (methods)
• Tissue Plasminogen Activator (therapeutic use)
• Tomography, X-Ray Computed
• Young Adult