Clinical trial NCT04261478: Endovascular Acute Stroke Intervention - Tandem OCclusion Trial
Official title: A Multi-centre, Prospective, Randomized, Open-label, Blinded Endpoint (PROBE) Controlled Trial Comparing Cervical Internal Carotid Artery Stenting to no Stenting During Thrombectomy for Tandem Occlusion Stroke
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Stroke, Acute
Carotid Stenosis
Carotid Artery Diseases
Keywords: Thrombectomy
Tandem occlusion
Carotid stenting
Lead sponsor: Centre hospitalier de l'Université de Montréal (CHUM)
Sponsor class: OTHER
Collaborators: name: McGill University
name: Laval University
name: Queen's University
name: University of Ottawa
name: McMaster University
name: University of Calgary
name: University of British Columbia
name: Dalhousie University
name: Health Sciences North Research Institute
name: University of Toronto
name: University of Alberta
name: Canadian Stroke Consortium (CSC)
First posted: 2020-02-07
Enrollment: 458
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A multi-centre, prospective, randomized, open-label, blinded endpoint (PROBE) controlled trial (1:1 allocation).
Primary purpose: TREATMENT

Brief summary: 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).

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Clinical efficacy outcome: proportion of patients achieving a favorable modified Rankin scale score (mRS 0-2)
timeFrame: 90 days ± 14 days
Secondary outcomes:
measure: Clinical efficacy outcome: Proportion of patients achieving a favorable modified Rankin scale score (mRS 0-2) at 90 days (dichotomized) according to sex
timeFrame: 90 days ± 14 days
measure: Clinical efficacy outcome: Ordinal logistic regression for functional improvement on the Modified Rankin Scale (mRS) score (shift analysis)
timeFrame: 90 days ± 14 days
measure: Clinical efficacy outcome: Median National Institutes of Health Stroke Scale (NIHSS) score
timeFrame: 24 hours ± 8 hours
measure: Clinical efficacy outcome: Median National Institutes of Health Stroke Scale (NIHSS) score
timeFrame: 90 days ± 14 days
measure: Clinical efficacy outcome: Median Modified Rankin Scale (mRS) score
timeFrame: 90 days ± 14 days
measure: Clinical efficacy outcome: Rate of clinically confirmed recurrent ipsilateral stroke or retinal ischemia
timeFrame: 90 days ± 14 days
measure: Radiological efficacy outcome: Proportion of patients with complete or near-complete recanalization
timeFrame: End of endovascular procedure
measure: Radiological efficacy outcome: Proportion of patients with ICA thrombosis (with or without stent)
timeFrame: 90 days ± 14 days
measure: Clinical efficacy outcome: Median Montreal Cognitive Assessment (MoCA) score
timeFrame: 90 days ± 14 days
measure: Clinical efficacy outcome: Rate of any recurrent stroke or retinal ischemia
timeFrame: 1 year ± 60 days
measure: Clinical efficacy outcome: Proportion of patients achieving a favorable modified Rankin scale (mRS) score
timeFrame: 1 year ± 60 days
Other outcomes:
measure: Safety outcome: Proportion of patients with any intracranial hemorrhage (ICH)
timeFrame: 24 hours ± 8 hours
measure: Safety outcome: Proportion of patients with a symptomatic intracranial hemorrhage (sICH)
timeFrame: 24 hours ± 8 hours
measure: Safety outcome: Proportion of patients with death of any cause
timeFrame: 90 days ± 14 days
measure: Safety outcome: Proportion of patients with procedural complications
timeFrame: End of endovascular procedure
measure: Safety outcome: Type of procedural complications
timeFrame: End of endovascular procedure
measure: Tertiary outcome: Proportion of patients with stenting performed after thrombectomy
timeFrame: End of endovascular procedure
measure: Tertiary outcome: Description of type and route of administration of antiplatelet agents used peri-interventionally
timeFrame: End of endovascular procedure
measure: Tertiary outcome: Proportion of patients for whom an embolic protection device was used
timeFrame: End of endovascular procedure
measure: Tertiary outcome: Proportion of patients with internal carotid artery pseudo-occlusions confirmed on angiography
timeFrame: End of endovascular procedure
measure: Tertiary outcome: Proportion of patients with delayed carotid revascularization
timeFrame: 1 year ± 60 days
measure: Tertiary outcome: Type of delayed carotid revascularization
timeFrame: 1 year ± 60 days
measure: Tertiary outcome: Minimum and maximum systolic and diastolic intraprocedural blood pressure (mmHg)
timeFrame: End of endovascular procedure
measure: Tertiary outcome: Minimum and maximum intraprocedural heart rate (beats per minute)
timeFrame: End of endovascular procedure
Locations:
city: Montréal
country: Canada
facility: Centre Hospitalier de l'Université de Montréal
state: Quebec
Study officials:
affiliation: Centre hospitalier de l'Université de Montréal (CHUM)
name: Alexandre Y Poppe, MD CM
role: PRINCIPAL_INVESTIGATOR
References: