Abstract
BACKGROUND AND PURPOSE: The safety and efficacy of endovascular therapy for large-artery stroke in the extended time window is not yet well-established. We performed a subgroup analysis on subjects enrolled within an extended time window in the Endovascular Treatment for Small Core and Proximal Occlusion Ischemic Stroke (ESCAPE) trial.
MATERIALS AND METHODS: Fifty-nine of 315 subjects (33 in the intervention group and 26 in the control group) were randomized in the ESCAPE trial between 5.5 and 12 hours after last seen healthy (likely to have groin puncture administered 6 hours after that). Treatment effect sizes for all relevant outcomes (90-day mRS shift, mRS 0–2, mRS 0–1, and 24-hour NIHSS scores and intracerebral hemorrhage) were reported using unadjusted and adjusted analyses.
RESULTS: There was no evidence of treatment heterogeneity between subjects in the early and late windows. Treatment effect favoring intervention was seen across all clinical outcomes in the extended time window (absolute risk difference of 19.3% for mRS 0–2 at 90 days). There were more asymptomatic intracerebral hemorrhage events within the intervention arm (48.5% versus 11.5%, P = .004) but no difference in symptomatic intracerebral hemorrhage.
CONCLUSIONS: Patients with an extended time window could potentially benefit from endovascular treatment. Ongoing randomized controlled trials using imaging to identify late presenters with favorable brain physiology will help cement the paradigm of using time windows to select the population for acute imaging and imaging to select individual patients for therapy.
ABBREVIATION:
- ICH
- intracerebral hemorrhage
Footnotes
Disclosures: Jeremy L. Rempel—UNRELATED: Consulting Fee or Honorarium: Memorial University, Comments: speaking honorarium. Ashfaq Shuaib—UNRELATED: Board Membership: Canadian Stroke Consortium*; Employment: University of Alberta. David Williams—RELATED: Grant: University of Calgary, Comments: I was a site investigator (Ireland) for the ESCAPE study*; Support for Travel to Meetings for the Study or Other Purposes: University of Calgary, Comments: I was a site investigator (Ireland) for the ESCAPE study and was supported to attend investigator meetings*; UNRELATED: Board Membership: Boehringer Ingelheim, Bayer, Bristol Myers Squibb, Daiichi Sankyo, Comments: member of the Advisory Board on the safe use of novel anticoagulants. Daniel F. Roy—RELATED: Grant: University of Calgary, Comments: Angiography Core Lab for the ESCAPE trial. Alexander Y. Poppe—RELATED: Grant: University of Calgary, Comments: fees paid per patient enrolled for participation of our center in the ESCAPE trial*; UNRELATED: Board Membership: Bayer, Bristol-Myers Squibb–Pfizer, Comments: Advisory Boards 2016; Grants/Grants Pending: CaSTOR, The Canadian Stroke Trials for Optimized Results, Comments: catalyst grant for developing a study network on tandem carotid lesions in acute stroke; Payment for Lectures Including Service on Speakers Bureaus: Medtronic, Comments: speaker fees 2016; Payment for Development of Educational Presentations: EMD Serono, Comments: examiner in mock exam for neurology residents. Tudor G. Jovin—UNRELATED: Consultancy: Neuravi, Codman Neurovascular, Comments: Neuravi, Steering Committee member; Codman Neurovascular, Data and Safety Monitoring Board member; Stock/Stock Options: Anaconda, Silk Road, Route 92, Blockade Medical; Travel/Accommodations/Meeting Expenses Unrelated to Activities Listed: Stryker* (Principal Investigator DAWN). Thomas Devlin—RELATED: Grant: Medtronic, Comments: research support; UNRELATED: Consultancy: BrainsGate, San Bio, Ornim Medical, Daiichi Sankyo, Comments: research support*; Payment for Lectures Including Service on Speakers Bureaus: Medtronic, Comments: speakers bureau.* Michael D. Hill—RELATED: Grant: Medtronic, University of Calgary, Alberta Innovates, Heart and Stroke Foundation, Canadian Institutes of Health Research, Alberta Health Services, Comments: grants or support-in-kind to the University of Calgary for the ESCAPE trial*; UNRELATED: Board Membership: Canadian Neuroscience Federation, Comments: volunteer governance board for a not-for-profit organization; Consultancy: Merck, Comments: remuneration for clinical trial adjudication of outcomes panel; Grants/Grants Pending: Medtronic, Comments: grant support for the HERMES collaboration; Stock/Stock Options: Calgary Scientific, Comments: stock ownership in a Calgary imaging and data company. Philip A. Barber—UNRELATED: Consultancy: Ablynx Pharmaceutical*; Employment: University of Calgary; Grants/Grants Pending: Heart and Stroke Foundation of Canada*. Daniela Iancu—RELATED: Grant, Comments: ESCAPE Trial*. Bijoy K. Menon—RELATED: Grant: Covidien*; UNRELATED: Patents (Planned, Pending or Issued), Comments: US patent pending, patent on systems of triage for stroke; Stock/Stock Options: Quikflo Health. Blaise W. Baxter—UNRELATED: Consultancy/Speakers Bureau: Penumbra, Medtronic, Stryker, Pulsar, Route 92; Patents (Planned, Pending or Issued): Advanced Catheter Therapies, Comments: Patent US8622992, no royalties. Mayank Goyal—RELATED: Grant: Medtronic, Comments: part funding of the ESCAPE trial, funding for HERMES collaboration*; Consulting Fee or Honorarium: Medtronic, Comments: consulting fee for design and conduct of SWIFT PRIME trial; UNRELATED: Consultancy: Stryker, MicroVention, Ablynx, Comments: for educational activities and product advice; Patents (Planned, Pending or Issued): GE Healthcare, MicroVention, Comments: licensing agreement for systems of stroke diagnosis and systems of intracranial access. Donald F. Frei—UNRELATED: Consultancy: Stryker, MicroVention, Penumbra; Payment for Lectures Including Service on Speakers Bureaus: Stryker, MicroVention, Penumbra; Stock/Stock Options: Penumbra. Donatella Tampieri—UNRELATED: Consultancy: Canadian Medical Protective Association; Grants/Grants Pending: Fonds de recherche du Québec.* Andrew M. Demchuk—RELATED: Grant: Medtronic, Comments: unrestricted grant to support enrollment and coordination of the ESCAPE trial*; Consulting Fee or Honorarium: Medtronic, Comments: honoraria for Continuing Medical Education events. Frank L. Silver—UNRELATED: Consultancy: Boehringer Ingelheim Canada, Comments: National Coordinator, REPECT ESUS clinical trial. *Money paid to the institution.
The study sponsor was the University of Calgary. Covidien provided major funding through an unrestricted grant to the University of Calgary. Additional active and in-kind support for the trial was from a consortium of funding public and charitable sources (Heart and Stroke Foundation Canada, Alberta Innovates Health Solutions, Alberta Health Services, Canadian Stroke Prevention Intervention Network through Canadian Institutes of Health Research) and the University of Calgary (Hotchkiss Brain Institute, Department of Clinical Neurosciences, Department of Radiology, and Calgary Stroke Program).
The sponsor of the trial was the Governors of the University of Calgary. The sponsor had no role in the design, data gathering, analysis, or reporting of the trial. The University of Calgary received unrestricted grants from Medtronic (Covidien), Alberta Innovates Health Solutions, Heart and Stroke Foundation Canada, Canadian Institute for Health Research through the Canadian Stroke Prevention Intervention Network, and Alberta Health Services. The University of Calgary provided internal funding from the Hotchkiss Brain Institute, the Department of Clinical Neurosciences, and Department of Radiology.
Clinical Trial Registration: www.clinicaltrials.gov NCT01778335.
- © 2018 by American Journal of Neuroradiology
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