Proximal Internal Carotid Artery Acute Stroke Secondary to Tandem or Local Occlusion Thrombectomy Trial

Study Overview
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Brief Summary
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The primary objective is to establish the efficacy of intra-arterial (IA) mechanical thrombectomy (MT) with extracranial proximal carotid artery acute stenting versus non-stenting approaches in patients with acute ischemic stroke (AIS) from intracranial vessel occlusion (IVO) in the anterior circulation and have a proximal carotid occlusive disease (occlusion or severe stenosis) within 24 hours of symptom onset.

Detailed Description
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Independent Investigator-initiated, designed and conducted non-industry study. A prospective, phase III, randomized, open-label, blinded-endpoint controlled trial (PROBE Design). Patients presenting with symptoms of AIS in the anterior circulation with proximal carotid occlusion or severe stenosis will be assigned to either: ARM1 (Control): Non-stenting group constitutes best medical management (BMM)+intra-arterial treatment (IAT) with mechanical thrombectomy (for IVO) added to extra-cranial proximal carotid occlusion angioplasty or aspiration (MT+CAT) VERSUS ARM2 (Intervention): Acute carotid stenting (ACS) approach constitutes BMM+IAT with acute carotid stenting (ACS) of the extracranial proximal carotid artery, spanning the cervical internal carotid artery (ICA), ICA origin, and the distal common carotid artery (CCA, across the bifurcation) as in the example of left (L) carotid stenting figure below (MT+CAS) Randomization will be 1:1, with stratification by: 1) age, 2) ASPECT score, 3. National Institute of Health Stroke Scale (NIHSS), 4) time from onset to randomization CTA imaging confirming ICA occlusion/tandem lesion, 5) degree of proximal extra-cranial carotid stenosis (complete occlusion versus stenosis), 6) IV thrombolysis administration, Within the stenting arm, there will be 2 different subgroups based on the antiplatelet treatment protocol per the site standard of care (oral antiplatelet or IV antiplatelet medication (e.g., Cangrelor or others). Each arm will be assessed at the first interim analysis to consider dropping an arm if predetermined safety boundaries are exceeded. Mechanical thrombectomy and proximal angioplasty or stenting will be performed with an FDA-cleared devices in accordance with the instructions for use (IFU). The order of each procedure (revascularization of the proximal extra-cranial carotid lesion first or after the intracranial lesion) will be left at discretion of the treating proceduralist. Each treated patient will be followed and assessed for the primary outcome at 3 months and one year after randomization by an independent adjudicator not involved in the procedure. Optional utilization of remote assessment of NIHSS, mRS scale may be provided to selected site

Official Title
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Proximal Internal Carotid Artery Acute Stroke Secondary to Tandem or Local Occlusion Thrombectomy Trial

Conditions
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Acute Ischemic Stroke

Intervention / Treatment
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* Drug: IV-Antiplatelet Drugs
* Procedure: MT+CAS with IV-AP
* Procedure: MT+CAS with PO-AP
* Procedure: MT+CAT with PO-AP
* Drug: PO-Antiplatelet Drugs
* Device: RX ACCULINK Carotid Stent System
* Procedure: Balloon Angioplasty
* Device: EMBOGUARD Balloon Guide Catheter


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 to 85 years of age Presenting with symptoms consistent with AIS Imaging evidence of an anterior circulation occlusion of the Internal Carotid Artery (ICA) terminus and/or Middle Cerebral Artery Main Stem (MCA M1), or proximal M2 segment AND extra-cranial proximal carotid occlusion / severe stenosis related to atherosclerosis requiring treatment on non-invasive imaging ≥70% NIHSS ≥ 4 Ability to randomize within 24 hours of stroke onset Pre-stroke mRS score 0-2 Ability to obtain signed informed consent ASPECTS Score ≥7 via non-contrast CT or MRI (DWI) for subjects ≤6 hours from stroke onset OR ASPECTS Score ≥7 + infarct core volume <50 cc quantified by MRI DWI (AxBxC/2) or CTP (rCBF<30%) for subjects >6h to -24 hours from stroke onset, given the need for antiplatelet therapy. Imaging obtained within 24 hours (after the first symptoms or last seen well. Arterial Access Obtained < 25 hours from stroke symptoms onset. Both study groups must adhere to identical blood pressure (BP) recommendations, which will be dependent on the cerebral perfusion status. Individuals with TICI2b or higher scores will be subject to BP recommendations ranging from 100-140 mmHg in cases of reperfusion and 120-180 mmHg in instances of no reperfusion and no evidence of intracranial hemorrhage (ICH) (TICI score < 2b). Acute Neurological Deficit with Imaging evidence of Tandem Lesion: Extracranial carotid occlusion (70% to 100% Using NACET criteria) With or without intracranial vascular occlusion Exclusion Criteria: Females who are pregnant, or those of child-bearing potential with positive urine or serum beta Human Chorionic Gonadotropin (HCG) test Known severe allergy (more than a rash) to contrast media uncontrolled by medications Refractory hypertension (defined as persistent systolic blood pressure >185 mmHg or diastolic blood pressure >110 mmHg) despite medication CT evidence of the following conditions: Midline shift or herniation Evidence of intracranial hemorrhage Mass effect with effacement of the ventricles Acute bilateral strokes Contraindication to antiplatelet (Aspirin, Plavix, Ticagrelor, Cangrelor), or thrombolytic therapy, or contrast agents. Intracranial tumors other than small meningioma that does not require surgery for one year post randomization Known hemorrhagic diathesis, coagulation factor deficiency, or on anticoagulant therapy with an International Normalized Ratio (INR) of >1.7 or Partial Thromboplastin Time (PTT) > 3 times of normal Baseline platelet count <100,000 per microliter (μl) Life expectancy less than one year prior to stroke onset Participation in another randomized clinical trial that could confound the evaluation of the study outcomes Any other condition (in the opinion of the site investigator) that precludes an endovascular procedure or poses a significant hazard to the patient if an endovascular procedure was performed Proximal carotid stenosis secondary to dissection or vasculitis (.e.g. Takayasu's Arteritis)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Independent Investigator-initiated, designed and conducted non-industry study. A prospective, phase III, randomized, open-label, blinded-endpoint controlled trial (PROBE Design).
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MT+CAT<br>Non-stenting group constitutes best medical management (BMM)+intra-arterial treatment (IAT) with mechanical thrombectomy (for IVO) added to extra-cranial proximal carotid occlusion angioplasty or aspiration (MT+CAT) | Procedure: MT+CAT with PO-AP<br>* Mechanical Thrombectomy is a treatment for stroke that removes clots that block large blood vessels. Carotid stenting is a procedure that is deployed within the lumen of the carotid artery which treats the narrowing of the carotid artery. With added oral antiplatelet therapy<br>* Other names: Thrombectomy;Drug: PO-Antiplatelet Drugs<br>* Within the stenting arm, there will be 2 different subgroups based on the antiplatelet treatment protocol per the site standard of care (oral antiplatelet or IV antiplatelet medication (e.g.,Cangrelor or others). Each arm will be assessed at the first interim analysis to consider dropping an arm if predetermined safety boundaries are exceeded.<br>* Other names: Tricagrelor (Brilinta);Procedure: Balloon Angioplasty<br>* A medical procedure that is used to treat the narrowing and blocking of the the blood vessels.<br>Device: EMBOGUARD Balloon Guide Catheter<br>* The primary purpose of a balloon guide catheter is to temporarily block blood flow in the target vessel or artery during procedures like clot retrieval or the placement of embolic coils in the brain.<br>|
| Experimental: MT+CAS<br>Acute carotid stenting (ACS) approach constitutes BMM+IAT with acute carotid stenting (ACS) of the extracranial proximal carotid artery, spanning the cervical internal carotid artery (ICA), ICA origin, and the distal common carotid artery (CCA, across the bifurcation) as in the example of left (L) carotid stenting figure below (MT+CAS). Within the stenting arm, there will be 2 different subgroups based on the antiplatelet treatment protocol per the site standard of care (oral antiplatelet or IV antiplatelet medication (e.g., Cangrelor or others). | Drug: IV-Antiplatelet Drugs<br>* Within the stenting arm, there will be 2 different subgroups based on the antiplatelet treatment protocol per the site standard of care (oral antiplatelet or IV antiplatelet medication (e.g.,Cangrelor or others). Each arm will be assessed at the first interim analysis to consider dropping an arm if predetermined safety boundaries are exceeded.<br>* Other names: Abciximab (ReoPro);Procedure: MT+CAS with IV-AP<br>* Mechanical Thrombectomy is a treatment for stroke that removes clots that block large blood vessels. Carotid stenting is a procedure that is deployed within the lumen of the carotid artery which treats the narrowing of the carotid artery. With added intravenous antiplatelet therapy.<br>* Other names: Thrombectomy;Procedure: MT+CAS with PO-AP<br>* Mechanical Thrombectomy is a treatment for stroke that removes clots that block large blood vessels. Carotid stenting is a procedure that is deployed within the lumen of the carotid artery which treats the narrowing of the carotid artery. With added oral antiplatelet therapy.<br>* Other names: Thrombectomy;Drug: PO-Antiplatelet Drugs<br>* Within the stenting arm, there will be 2 different subgroups based on the antiplatelet treatment protocol per the site standard of care (oral antiplatelet or IV antiplatelet medication (e.g.,Cangrelor or others). Each arm will be assessed at the first interim analysis to consider dropping an arm if predetermined safety boundaries are exceeded.<br>* Other names: Tricagrelor (Brilinta);Device: RX ACCULINK Carotid Stent System<br>* Abbott Carotid Stenting System used within the MT+CAS ARM<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Utility-weighted 90-day Modified Rankin Score | Scale used for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. Scale ranges from 0-6 where 0 represents no symptoms and 6 represents death. 0 = No symptoms at all. No significant disability despite symptoms; able to carry out all usual duties and activities. Slight disability; unable to carry out all previous activities but able to look after own affairs without assistance. Moderate disability requiring some help, but able to walk without assistance. Moderately severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance. Severe disability; bedridden, incontinent, and requiring constant nursing care and attention. Death | Time Frame: 90 days post randomization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stroke, Ischemic Stroke, Thrombectomy