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

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ClinicalTrials.gov Identifier: NCT04261478
Recruitment Status : Recruiting
First Posted : February 7, 2020
Last Update Posted : September 9, 2020
Sponsor:
Collaborators:
McGill University
Laval University
Queen's University
University of Ottawa
McMaster University
University of Calgary
University of British Columbia
Dalhousie University
Canadian Stroke Consortium (CSC)
Information provided by (Responsible Party):
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 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).


Condition or disease Intervention/treatment Phase
Stroke, Acute Carotid Stenosis Carotid Artery Diseases Device: Carotid artery stenting Drug: Antiplatelet Agents Not Applicable

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 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 450 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: A multi-centre, prospective, randomized, open-label, blinded endpoint (PROBE) controlled trial (1:1 allocation).
Masking: Single (Outcomes Assessor)
Masking Description: Open-label, blinded endpoint (PROBE)
Primary Purpose: Treatment
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
Actual Study Start Date : August 31, 2020
Estimated Primary Completion Date : April 2025
Estimated Study Completion Date : January 2026

Arm Intervention/treatment
Active Comparator: Acute 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.
Device: Carotid artery stenting
The type of stent should be one commonly used for ICA stenting. Balloon angioplasty before and/or after stent placement will be allowed as required. Stenting should be performed after intracranial thrombectomy unless specific technical circumstances suggest that access to the intracranial circulation requires anterograde stenting. Embolic protection devices should not be used routinely during ICA stent placement.
Other Name: Stenting

Drug: Antiplatelet Agents
The following antiplatelet regimen should be used: For patients having received IV thrombolysis, immediate post-procedural oral or intrarectal single antiplatelet agents, (Aspirin 325mg PO or 650mg PR). A second agent (usually Clopidogrel 300mg PO) is added after follow-up brain imaging at 12-24 hours confirms absence of significant ICH. For patients having not been treated with IV thrombolysis, dual antiplatelet therapy (Aspirin 325mg PO or 650mg PR and Clopidogrel 300-600mg PO) is given immediately post-procedure. Routine use of GPIIb/IIIa inhibitors, periprocedural IV Heparin is discouraged.

No Intervention: No Acute 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 not revascularized with a stent during the acute thrombectomy procedure.



Primary Outcome Measures :
  1. Clinical efficacy outcome: proportion of patients achieving a favorable modified Rankin scale score (mRS 0-2) [ Time Frame: 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 :
  1. Clinical efficacy outcome: Proportion of patients achieving a favorable modified Rankin scale score (mRS 0-2) at 90 days (dichotomized) according to sex [ Time Frame: 90 days ± 14 days ]
    Proportion of patients achieving a favorable modified Rankin scale score (mRS 0-2) at 90 days (dichotomized) according to sex

  2. Clinical efficacy outcome: Ordinal logistic regression for functional improvement on the Modified Rankin Scale (mRS) score (shift analysis) [ Time Frame: 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.

  3. Clinical efficacy outcome: Median National Institutes of Health Stroke Scale (NIHSS) score [ Time Frame: 24 hours ± 8 hours ]
    Median NIHSS score at 24 hours 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)

  4. Clinical efficacy outcome: Median National Institutes of Health Stroke Scale (NIHSS) score [ Time Frame: 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)

  5. Clinical efficacy outcome: Median Modified Rankin Scale (mRS) score [ Time Frame: 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.

  6. Clinical efficacy outcome: Rate of clinically confirmed recurrent ipsilateral stroke or retinal ischemia [ Time Frame: 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

  7. Radiological efficacy outcome: Proportion of patients with complete or near-complete recanalization [ Time Frame: 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 laboratory


  8. Radiological efficacy outcome: Proportion of patients with ICA thrombosis (with or without stent) [ Time Frame: 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.

  9. Clinical efficacy outcome: Median Montreal Cognitive Assessment (MoCA) score [ Time Frame: 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.

  10. Clinical efficacy outcome: Rate of any recurrent stroke or retinal ischemia [ Time Frame: 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

  11. Clinical efficacy outcome: Proportion of patients achieving a favorable modified Rankin scale (mRS) score [ Time Frame: 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.


Other Outcome Measures:
  1. Safety outcome: Proportion of patients with any intracranial hemorrhage (ICH) [ Time Frame: 24 hours ± 8 hours ]
    Proportion of patients with any intracranial hemorrhage on follow-up imaging at 24 hours Independent imaging core laboratory

  2. Safety outcome: Proportion of patients with a symptomatic intracranial hemorrhage (sICH) [ Time Frame: 24 hours ± 8 hours ]
    Proportion of patients with symptomatic intracranial hemorrhage (sICH) within 72 hours of EVT ECASS-2 definition. Imaging core laboratory.

  3. Safety outcome: Proportion of patients with death of any cause [ Time Frame: 90 days ± 14 days ]
    All-cause mortality at 90 days

  4. Safety outcome: Proportion of patients with procedural complications [ Time Frame: End of endovascular procedure ]
    Procedural complications, including: vessel perforation, iatrogenic vessel dissection, embolization into a previously unaffected artery, access site complications

  5. Safety outcome: Type of procedural complications [ Time Frame: End of endovascular procedure ]
    Procedural complications, including: vessel perforation, iatrogenic vessel dissection, embolization into a previously unaffected artery, access site complications

  6. Tertiary outcome: Proportion of patients with stenting performed after thrombectomy [ Time Frame: End of endovascular procedure ]
    Timing of ICA stenting relative to intracranial thrombectomy (before/anterograde or after/retrograde)

  7. Tertiary outcome: Description of type and route of administration of antiplatelet agents used peri-interventionally [ Time Frame: End of endovascular procedure ]
    Antiplatelet and/or anticoagulant regimens used peri-interventionally: aspirin, clopidogrel, GP2b3a inhibitors, Heparin, other and route of administration: oral, rectal, intravenous, intra-arterial

  8. Tertiary outcome: Proportion of patients for whom an embolic protection device was used [ Time Frame: End of endovascular procedure ]
    Use of distal or proximal embolic protection among patients undergoing stenting

  9. Tertiary outcome: Proportion of patients with internal carotid artery pseudo-occlusions confirmed on angiography [ Time Frame: End of endovascular procedure ]
    Proportion of patients with presumed internal carotid artery tandem occlusion on non-invasive imaging (CTA or MRA) having no tandem occlusion on conventional angiography (pseudo-occlusions) Patients with no confirmed tandem lesion on angiography will be included in the screening log but not randomized in the trial

  10. Tertiary outcome: Proportion of patients with delayed carotid revascularization [ Time Frame: 1 year ± 60 days ]
    The proportion of patients in the no stent group undergoing deferred ICA revascularization and the type of revascularization (endarterectomy or stenting) used, within 12 months after stroke

  11. Tertiary outcome: Type of delayed carotid revascularization [ Time Frame: 1 year ± 60 days ]
    T he type of revascularization (endarterectomy or stenting) used in patients in the no stent group undergoing deferred ICA revascularization, within 12 months after stroke

  12. Tertiary outcome: Minimum and maximum systolic and diastolic intraprocedural blood pressure (mmHg) [ Time Frame: End of endovascular procedure ]
    Minimum and maximum blood pressure (systolic and diastolic, mmHg) during EVT procedure Derived from procedural vital sign records

  13. Tertiary outcome: Minimum and maximum intraprocedural heart rate (beats per minute) [ Time Frame: End of endovascular procedure ]
    Minimum and maximum intraprocedural heart rate (beats per minute) during EVT procedure Derived from procedural vital sign records



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04261478


Contacts
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Contact: Alexandre Y Poppe, MD CM 5148908000 ext 26260 alexandre.poppe.chum@ssss.gouv.qc.ca
Contact: Marlène Y Lapierre, BSc 5148908000 ext 26242 marlene.lapierre.chum@ssss.gouv.qc.ca

Locations
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Canada, Quebec
Centre Hospitalier de l'Université de Montréal Recruiting
Montréal, Quebec, Canada, H2X 0C1
Contact: Alexandre Y Poppe, MD CM    5148908000 ext 26268    alexandre.poppe.chum@ssss.gouv.qc.ca   
Contact: Marlène Lapierre    5148908000 ext 262642    marlene.lapierre.chum@ssss.gouv.qc.ca   
Sponsors and Collaborators
Centre hospitalier de l'Université de Montréal (CHUM)
McGill University
Laval University
Queen's University
University of Ottawa
McMaster University
University of Calgary
University of British Columbia
Dalhousie University
Canadian Stroke Consortium (CSC)
Investigators
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Principal Investigator: Alexandre Y Poppe, MD CM Centre hospitalier de l'Université de Montréal (CHUM)
Additional Information:
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Responsible Party: Centre hospitalier de l'Université de Montréal (CHUM)
ClinicalTrials.gov Identifier: NCT04261478    
Other Study ID Numbers: MP-02-2020-8614
First Posted: February 7, 2020    Key Record Dates
Last Update Posted: September 9, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

Upon completion of the EASI-TOC Trial, a public use database will be prepared by stripping any and all personal identifiers. The public use database, consisting of several data files, should contain: (1) baseline and demographic characteristics; (2) outcomes assessments; (3) imaging data; (4) serious adverse events.

These data files will be made available to researchers with validated requests only after all major manuscripts (including secondary analysis papers) of the Trial are accepted for publication in peer-reviewed journals.

Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Time Frame: These data files will be made available to researchers with validated requests only after all major manuscripts (including secondary analysis papers) of the Trial are accepted for publication in peer-reviewed journals.
Access Criteria: These data files will be made available to researchers with validated requests only after all major manuscripts (including secondary analysis papers) of the Trial are accepted for publication in peer-reviewed journals.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Centre hospitalier de l'Université de Montréal (CHUM):
Thrombectomy
Tandem occlusion
Carotid stenting
Additional relevant MeSH terms:
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Stroke
Carotid Stenosis
Carotid Artery Diseases
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Arterial Occlusive Diseases
Platelet Aggregation Inhibitors