Endovascular Acute Stroke Intervention - Tandem OCclusion Trial
Endovascular Acute Stroke Intervention - Tandem OCclusion Trial
Patients with tandem occlusion or tandem lesion (TL), that is, stroke with an acute
 intracranial anterior circulation occlusion and an ipsilateral cervical ICA (c-ICA)
 high-grade stenosis or occlusion, constitute about 25% of patients undergoing endovascular
 thrombectomy (EVT).

 However, the optimal treatment of acute stroke patients with TL remains uncertain, as
 relatively few patients with TL were included in the major randomized controlled trials of
 EVT and management of the c-ICA was generally not specified by protocol nor analyzed
 post-hoc.

 Recent large multi-centre retrospective cases series suggest that acutely stented patients
 may have more favorable outcomes than patients treated with angioplasty alone or those with
 no acute ICA intervention, but high quality randomized trial data are lacking.

 EASI-TOC, a phase 3, academic multi-centre, controlled trial (PROBE design) with embedded
 pilot phase, will seek to determine if in patients undergoing acute intracranial thrombectomy
 for anterior circulation stroke with concurrent ipsilateral symptomatic high-grade (≥70%)
 atherosclerotic stenosis or occlusion of the extracranial ICA, endovascular ICA
 revascularization with stenting is superior to intracranial thrombectomy alone with regards
 to functional outcome at 90 days. Patients will be randomized to Acute stenting or No acute
 stenting (1:1 allocation).
EASI-TOC is a phase III multi-centre, prospective, randomized, open-label, blinded endpoint
 (PROBE) controlled trial (1:1 allocation).

 The trial will seek to determine if in patients undergoing acute intracranial thrombectomy
 for anterior circulation stroke with concurrent ipsilateral symptomatic high-grade (≥70%)
 atherosclerotic stenosis or occlusion of the extracranial ICA, endovascular ICA
 revascularization with stenting is superior to intracranial thrombectomy alone with regards
 to functional outcome at 90 days (measured using the Modified Rankin Scale).

 EASI-TOC will be conducted at 8 high-volume comprehensive stroke centres in Canada with
 planned expansion to 10-12 Canadian sites within 2 years.

 450 male and female adult (aged ≥ 18 years) patients will be enrolled.

 Patients will be randomized (1:1) to undergo acute ICA stenting during the thrombectomy
 procedure (either before or after intracranial thrombectomy, at the discretion of the
 treating physician) or to intracranial thrombectomy alone without ICA stenting. Deferred ICA
 intervention is allowed, if indicated. Randomization will be centralized and web-based.
 Stratification will be performed for use or not of IV alteplase.

 Patients will be treated acutely and followed up to one year.

 Our primary hypothesis assumes a greater proportion of patients with 90-day mRS 0-2 in the
 stenting group versus the no stenting group (55% versus 40%). Assuming a minimal clinically
 important difference of 15 % between groups experiencing no crossover, a total of 173
 patients per group would be sufficient to detect this difference, with a power of 80 % and a
 significance level of 5 %. Taking into account a cross-over rate of 10% (5% in either
 direction) and a loss to follow-up of 5 %, the total sample size will increase to 450
 patients.

 Primary analysis will be by Intention-to-treat. Pre-specified as-treated and sex-specific
 analyses will also be performed.

 Informed consent will be obtained from patients or their surrogate. Deferral of consent will
 be allowed if permitted by local ethics committees.
Inclusion Criteria:

 -  Acute ischemic anterior circulation stroke eligible for endovascular therapy according
 to local guidelines, with or without prior intravenous thrombolysis:

 -  Occlusion of the carotid terminus, M1 or M2 segments of the middle cerebral
 artery (MCA)

 -  A neurological deficit judged to be disabling by the patient and/or treating
 physician

 -  Any acute imaging judged by the treating physician to demonstrate salvageable
 brain tissue possibly amenable to EVT

 -  Groin puncture within 24-hours of onset or last known normal

 -  Tandem ipsilateral high-grade (≥70%) cervical internal carotid artery (ICA) stenosis
 or occlusion of presumed atherosclerotic etiology on initial non-invasive vascular
 imaging

 -  Informed consent from patient or surrogate or deferral of consent, according to local
 ethics policies

 Exclusion Criteria:

 -  Pre-existing neurological impairment (modified Rankin score ≥3)

 -  Any underlying disease or condition making protocol adherence and/or 3-month follow-up
 unlikely

 -  Any known contra-indication to EVT, angioplasty/stenting, or antiplatelet therapy

 -  Tandem ipsilateral high-grade (≥70%) cervical internal carotid artery (ICA) stenosis
 or occlusion NOT confirmed on conventional angiography

 -  Ipsilateral ICA stenosis or occlusion attributable to clinically or radiologically
 confirmed arterial dissection

 -  Isolated cervical carotid occlusion without intracranial occlusion

 -  Pregnancy