Endovascular Acute Stroke Intervention - Tandem OCclusion Trial (EASI-TOC)

Centre hospitalier de l'Université de Montréal (CHUM)

Status: Enrolling

Conditions: Carotid Stenosis; Stroke, Acute; Carotid Artery Diseases

Treatments: Drug: Antiplatelet Agents; Device: Carotid artery stenting

Study type: Interventional

Funder types: Other

Identifiers

NCT04261478

MP-02-2020-8614

Details and patient eligibility

About

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 15-20% 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).

Full description

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 10-12 high-volume comprehensive stroke centres in Canada.

458 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 and for enrolling site.

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, sex-specific and subgroup 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.

Enrollment: 458 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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458 participants in 2 patient groups

Acute Stenting

Active Comparator group

Description:

All patients in this arm will receive standard of care with regards to intracranial thrombectomy and use of intravenous thrombolysis. In this arm, the cervical carotid artery stenosis will be revascularized with a stent during the acute thrombectomy procedure.

Treatment:

Device: Carotid artery stenting

Drug: Antiplatelet Agents

No Acute Stenting

No Intervention group

Description:

All patients in this arm will receive standard of care with regards to intracranial thrombectomy and use of intravenous thrombolysis. In this arm, the cervical carotid artery stenosis will be not revascularized with a stent during the acute thrombectomy procedure.