Endovascular Acute Stroke Intervention - Tandem OCclusion Trial
- Conditions
- Carotid StenosisCarotid Artery DiseasesStroke, Acute
- Interventions
- Device: Carotid artery stentingDrug: Antiplatelet Agents
- Registration Number
- NCT04261478
- Lead Sponsor
- Centre hospitalier de l'Université de Montréal (CHUM)
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 458
-
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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Acute Stenting Carotid artery stenting 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. Acute Stenting Antiplatelet Agents 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.
- Primary Outcome Measures
Name Time Method Clinical efficacy outcome: proportion of patients achieving a favorable modified Rankin scale score (mRS 0-2) 90 days ± 14 days The proportion of patients achieving a favorable modified Rankin scale score (mRS 0-2) at 90 days (dichotomized) The Modified Rankin Score (mRS) is a 7 point disability scale with possible scores ranging from 0 to 6, with 0 indicating no disability and 6 indicating death.
- Secondary Outcome Measures
Name Time Method Clinical efficacy outcome: Median National Institutes of Health Stroke Scale (NIHSS) score 90 days ± 14 days Median NIHSS score at 90 days after stroke The NIHSS is a 15 item neurologic examination that provides a quantitative measure of stroke-related neurologic deficit. (Scale from 0 to 42, with higher scores indicating a more severe neurologic deficit)
Clinical efficacy outcome: Proportion of patients achieving a favorable modified Rankin scale score (mRS 0-2) at 90 days (dichotomized) according to sex 90 days ± 14 days Proportion of patients achieving a favorable modified Rankin scale score (mRS 0-2) at 90 days (dichotomized) according to sex
Clinical efficacy outcome: Ordinal logistic regression for functional improvement on the Modified Rankin Scale (mRS) score (shift analysis) 90 days ± 14 days Ordinal logistic regression for functional improvement by at least one mRS category at 90 days ("shift analysis") The Modified Rankin Score (mRS) is a 7 point disability scale with possible scores ranging from 0 to 6, with 0 indicating no disability and 6 indicating death.
Clinical efficacy outcome: Median Modified Rankin Scale (mRS) score 90 days ± 14 days Median mRS at 90 days after stroke The Modified Rankin Score (mRS) is a 7 point disability scale with possible scores ranging from 0 to 6, with 0 indicating no disability and 6 indicating death.
Clinical efficacy outcome: Rate of clinically confirmed recurrent ipsilateral stroke or retinal ischemia 90 days ± 14 days Rate of clinically confirmed recurrent ipsilateral stroke or retinal ischemia within 90 days (imaging as clinically indicated) A structured telephone questionnaire for verifying stroke-free status will be used and relevant imaging reviewed
Radiological efficacy outcome: Proportion of patients with complete or near-complete recanalization End of endovascular procedure Proportion of patients with complete or near-complete recanalization (mTICI 2b/3) at the end of the endovascular procedure.
mTICI score (0,1,2,2a,2b,3) : Grade 0 : no perfusion Grade 1 : penetration with minimal perfusion Grade 2 : partial perfusion Grade 2a : partial filling of less than 1/2 of the vascular territory Grade 2b : partial filling 50-99% of the vascular territory Grade 3 : complete perfusion Independent imaging core laboratoryRadiological efficacy outcome: Proportion of patients with ICA thrombosis (with or without stent) 90 days ± 14 days Proportion of patients with ICA thrombosis (with or without stent) within 90 days after stroke stent patency be evaluated by angiography at the end of the EVT procedure. Furthermore, follow-up carotid vascular imaging will be required between 1 and 90 days following stent placement in the context of usual care. Any non-invasive imaging modality will be allowed, with carotid doppler or CTA strongly recommended.
Clinical efficacy outcome: Median Montreal Cognitive Assessment (MoCA) score 90 days ± 14 days Median Montreal Cognitive Assessment (MoCA) score at 90 days after stroke The MoCA is a 30-point screening tool for cognitive dysfunction (score from 0 to 30 with lower scores indicating greater cognitive impairment). The test assesses 8 domains of cognitive functioning: attention and concentration, executive functions, memory, language, visuoconstructional skills, conceptual thinking, calculations, and orientation.
Clinical efficacy outcome: Rate of any recurrent stroke or retinal ischemia 1 year ± 60 days Rate of any recurrent stroke or retinal ischemia at 12 months after stroke A structured telephone questionnaire for verifying stroke-free status will be used
Clinical efficacy outcome: Proportion of patients achieving a favorable modified Rankin scale (mRS) score 1 year ± 60 days Proportion of patients achieving a favorable modified Rankin scale score (mRS 0-2) at 12 months after stroke The Modified Rankin Score (mRS) is a 7 point disability scale with possible scores ranging from 0 to 6, with 0 indicating no disability and 6 indicating death.
Trial Locations
- Locations (1)
Centre Hospitalier de l'Université de Montréal
🇨🇦Montréal, Quebec, Canada