Carotid Angioplasty and Stenting Versus Endarterectomy in Asymptomatic Subjects Who Are at Standard Risk for Carotid Endarterectomy With Significant Extracranial Carotid Stenotic Disease (ACT I)

Study Overview
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Brief Summary
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The study is being conducted to demonstrate the non-inferiority of carotid artery stenting (CAS) using the Emboshield® Embolic Protection System with the Xact® Carotid Stent System to carotid endarterectomy (CEA) for the treatment of asymptomatic extracranial carotid atherosclerotic disease.

Detailed Description
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Randomization for ACT 1 employs a 3:1 ratio of CAS versus CEA. A lead-in phase of up to 400 carotid stent subjects will provide investigators experience with the study devices prior to pivotal enrollment.

Official Title
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Carotid Angioplasty and Stenting Versus Endarterectomy in Asymptomatic Subjects Who Are at Standard Risk for Carotid Endarterectomy With Significant Extracranial Carotid Stenotic Disease (ACT I)

Conditions
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Carotid Artery Disease, Carotid Stenosis, Stroke, Atherosclerosis

Intervention / Treatment
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* Device: Carotid artery stenting with filter (interventional)
* Procedure: Carotid artery endarterectomy (surgical)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The subject must be > 18 and < 80 years of age. Female subjects of child bearing potential must have a documented negative pregnancy test within 30 days prior to the study procedure. Subject must be asymptomatic, defined as no stroke or Transient Ischemic Attack [(TIA);(hemispheric or ocular)] within the 180 days prior to the procedure. Subjects who have experienced these neurological symptoms prior to the 180 day pre-procedure window will be eligible for enrollment. An independent study neurologist or independent study neurosurgeon must confirm the subject's neurological status. Subjects taking warfarin may be included if their dosage is reduced before the procedure to result in an International Normalized Ratio (INR) of 1.5 or less. Warfarin may be restarted after the procedure. The subject must sign a written informed consent prior to the procedure, using a form that is approved by the local institutional review board (IRB). The subject must agree to return for all required follow-up visits. Subject has a discrete lesion located in the internal carotid artery (ICA); the contiguous common carotid artery (CCA) may be involved. Carotid stenosis ≥ 70% and ≤ 99% by carotid ultrasound or ≥ 70% and ≤ 99% stenosis (visual estimate) by angiography, without significant (> 60% by ultrasound or angiography) ICA/CCA contralateral stenosis. Target ICA vessel diameter must be visually estimated to be: > 2.5 mm and < 7.0 for the Emboshield Pro or for the Emboshield NAV6, > 2.8 mm and < 6.2 for the Emboshield Gen 3 And > 4.0 mm and < 9.0 mm for the Xact stent treatment segment. An untreated contralateral ICA may be used for visual estimation when a highly stenosed lesion makes measurement of the target vessel inaccurate. Based on the subject's anatomy, the Investigator should expect to successfully deliver the stent to the target lesion (absence of extreme tortuosity, etc.). De novo target lesion that can be treated with a single stent. Exclusion Criteria: Each potential subject must be screened to ensure that they do not meet any of the following exclusion criteria. This screening is to be based on known medical history and data available at the time of eligibility determination and enrollment. Subject is symptomatic and has had a stroke or exhibited TIA (hemispheric or ocular) within 180 days prior to randomization, which has been confirmed by an independent study neurologist or independent study neurosurgeon. Subject is participating in another drug or device trial (IND or IDE) that has not completed the primary endpoint or that may potentially confound the results of this trial. Subject may be enrolled only once in this trial and may not participate in any other clinical trial during a 1-year period post-index procedure. Subject has inability to understand and cooperate with study procedures or provide informed consent. Subject has had an intracranial hemorrhage or hemorrhagic stroke within 1-year prior the index procedure. Subject has dementia or has a neurological illness that may confound the neurological evaluation. Subject has had a known untoward reaction to anesthesia or contrast media not able to be overcome by pre-treatment with medications. Subject has history of intolerance or allergic reaction to any of the study medications including aspirin, Clopidogrel bisulfate (Plavix®) or Ticlopidine (Ticlid®), heparin or Bivalirudin (Angiomax™). Subjects must be able to tolerate a combination of aspirin and Clopidogrel/Ticlopidine. Subject has Hemoglobin (Hgb) less than 10 gm/dL, platelet count <100,000/mm3 or >500,000/mm3, or known heparin associated thrombocytopenia. Subject has an active bleeding diathesis or coagulopathy, or will refuse blood transfusions. Subject has had a GI bleed that would interfere with antiplatelet therapy. Subject has known cardiac sources of emboli, including paroxysmal or sustained atrial fibrillation (treated or untreated). Subject has had an myocardial infarction (MI) within the previous 30 days. Subject has any condition that limits their anticipated survival to less than 3 years. Subject is a high risk surgical candidate defined as the presence of any one or more of a following medical conditions: Two or more proximal diseased coronary arteries of > 70% stenosis that have not or cannot be revascularized or < 30 days since revascularization. Ejection fraction < 30% or New York Heart Association (NYHA) heart failure functional class 3 or higher. Unstable angina, defined as angina at rest with ECG changes. On a list for major organ transplant or is being evaluated for such. Known history of respiratory insufficiency, forced expiratory volume (FEV1) < 30% (predicted). Chronic renal insufficiency (serum creatinine >2.5 mg/dL). Uncontrolled diabetes defined as fasting glucose > 400 mg/dL. Concurrent requirement for any invasive procedure 30 days pre- or post-procedure. Age ≥ 80 years. Subject may be considered a non-surgical candidate for CEA as a result of one or more anatomic conditions or features which preclude normal surgical access or a high surgical risk because of the presence of any one or more anatomic conditions that present an increased potential for adverse events. These subjects are not eligible for enrollment. Subject has had radiation treatment to the neck. Subject has had a radical neck dissection. Surgically inaccessible lesions (i.e., lesions extending above the level of C2). Spinal immobility - inability to flex neck beyond neutral or kyphotic deformity. Presence of carotid artery dissection, aneurysm, pseudoaneurysm, arteritis or fibromuscular dysplasia (FMD) in the target vessel. Hemodynamically significant (>60%) stenosis of the right or left common carotid artery (LCCA/RCCA) below the clavicle. Presence of tracheostomy stoma. Contralateral laryngeal nerve paralysis. Previous carotid endarterectomy, extracranial-intracranial or carotid subclavian bypass procedure ipsilateral to the carotid stenosis. Severe hypertension (defined as blood pressure > Systolic of 180 mm Hg and/or a diastolic of 110 mm Hg) not adequately controlled by anti-hypertensive therapy at the time of study entry. Severe vascular disease including tortuosity and/or occlusive disease that would preclude the safe introduction of a guiding catheter/sheath, cerebral protection device, balloon catheter, stent delivery system or stent placement. Severe tortuosity is defined as 2 or more >90 degree bend points within 3cm of the target stenosis. One of these bends will be considered to be present if the ICA branches from the CCA at a 90 degree angle. This includes aortic arch anatomy that is unacceptable for carotid stent placement. Intraluminal filling defect thought to represent thrombus. Excessive calcification: defined as fluoroscopic evidence of calcium that extends circumferentially around the target lesion and includes the majority of the atherosclerotic plaque. Occlusion (TIMI 0 flow), or string sign of the ipsilateral common or internal carotid artery. The target lesion requires treatment with a device other than percutaneous transluminal angioplasty (PTA) prior to stent placement. Significant (> 60%) stenosis proximal or distal to the target lesion that might require revascularization or impede run off. Presence of a previously placed intravascular stent in the ipsilateral carotid distribution. Cerebral aneurysm (symptomatic or > 10 mm) or arteriovenous malformation (AVM) of the cerebral vasculature. Bilateral carotid stenosis (ICA/CCA contralateral stenosis > 60% by ultrasound or angiography).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 79 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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>CAS group: 3:1 ratio of Carotid Artery Stenting (CAS) versus Carotid Endarterectomy (CEA). Subjects will be followed at 30 days, six (6), and 12 months post-procedure, and annually for four (4) additional years. | Device: Carotid artery stenting with filter (interventional)<br>* Carotid artery stenting with filter (interventional)<br>|
| Active Comparator: 2<br>CEA group: 3:1 ratio of Carotid Artery Stenting (CAS) versus Carotid Endarterectomy (CEA). Subjects will be followed at 30 days, six (6), and 12 months post-procedure, and annually for four (4) additional years. | Procedure: Carotid artery endarterectomy (surgical)<br>* Carotid artery endarterectomy (surgical)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite of Death, Stroke (Ipsilateral or Contralateral; Major or Minor) and Myocardial Infarction (DSMI) Through 30 Days Post-procedure, Plus Ipsilateral Stroke 31 to 365 Days. |  | 0 to 365 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute Device Success: Xact Carotid Stent | Defined as attainment of final residual diameter stenosis of < 50% by Qualitative Comparative Analysis (QCA) (if QCA is not available, the visual estimate of diameter stenosis will be used) covering an area no longer than the original lesion with the study stent. (Routine post-dilatation of the stent may be included in this definition). Placement of an additional stent to treat a dissection or procedural complication as a bailout will not be considered a device success. | On day 0 after index procedure | 
| Acute Device Success: Embolic Protection Device System | Defined as successful deployment and retrieval of the filter in the absence of angiographic distal embolization. | On day 0 after index procedure | 
| Procedural Success | Procedural success is defined as the attainment of target lesion final residual diameter stenosis of < 50% by QCA (if QCA is not available, the visual estimate of diameter stenosis will be used) using any procedural method and freedom of Major Adverse Event at 30 days. | 0 to 30 days post procedure | 
| Composite Morbidity Measure | A pre-specified composite Morbidity Measure (CMM) of cranial and peripheral nerve injury, vascular injury, non-cerebral bleeding, wound complications related to the neck incision or femoral puncture site, and other complications (anesthetic) at 30 days post-procedure. | 0 to 30 Days Post-procedure | 
| Freedom From Clinically Indicated Target Lesion Revascularization(CI-TLR) | Freedom from CI-TLR was defined as freedom from reintervention for ≥ 50% restenosis in recently symptomatic patients and ≥ 80% restenosis in asymptomatic patients. | 0 to 180 days | 
| Freedom From Clinically Indicated Target Lesion Revascularization | Freedom from CITLR was defined as freedom from reintervention for ≥ 50% restenosis in recently symptomatic patients and ≥ 80% restenosis in asymptomatic patients. | 0 to 365 days | 
| Freedom From Clinically Indicated Target Lesion Revascularization | Freedom from CITLR was defined as freedom from reintervention for ≥ 50% restenosis in recently symptomatic patients and ≥ 80% restenosis in asymptomatic patients. | 0 to 730 days | 
| Freedom From Clinically Indicated Target Lesion Revascularization | Freedom from CITLR was defined as freedom from reintervention for ≥ 50% restenosis in recently symptomatic patients and ≥ 80% restenosis in asymptomatic patients. | 0 to 1095 days | 
| Freedom From Clinically Indicated Target Lesion Revascularization | Freedom from CITLR was defined as freedom from reintervention for ≥ 50% restenosis in recently symptomatic patients and ≥ 80% restenosis in asymptomatic patients. | 0 to 1460 days | 
| Freedom From Clinically Indicated Target Lesion Revascularization | Freedom from CITLR was defined as freedom from reintervention for ≥ 50% restenosis in recently symptomatic patients and ≥ 80% restenosis in asymptomatic patients. | 0 to 1825 days | 
| Freedom From Ipsilateral Stroke | Ipsilateral stroke was defined as stroke in the vascular distribution of the study carotid artery. If a subject experienced a bilateral stroke it was counted as an ipsilateral stroke for analysis purposes. | 31 to 365 days | 
| Freedom From Ipsilateral Stroke | Ipsilateral stroke was defined as stroke in the vascular distribution of the study carotid artery. If a subject experienced a bilateral stroke it was counted as an ipsilateral stroke for analysis purposes. | 31 to 730 days | 
| Freedom From Ipsilateral Stroke | Ipsilateral stroke was defined as stroke in the vascular distribution of the study carotid artery. If a subject experienced a bilateral stroke it was counted as an ipsilateral stroke for analysis purposes. | 31 to 1095 days | 
| Freedom From Ipsilateral Stroke | Ipsilateral stroke was defined as stroke in the vascular distribution of the study carotid artery. If a subject experienced a bilateral stroke it was counted as an ipsilateral stroke for analysis purposes. | 31 to 1460 days | 
| Freedom From Ipsilateral Stroke | Ipsilateral stroke was defined as stroke in the vascular distribution of the study carotid artery. If a subject experienced a bilateral stroke it was counted as an ipsilateral stroke for analysis purposes. | 31 to 1825 days | 
| Freedom From Mortality |  | 0 to 365 days | 
| Freedom From Mortality |  | 0 to 730 days | 
| Freedom From Mortality |  | 0 to 1095 days | 
| Freedom From Mortality |  | 0 to 1460 days | 
| Freedom From Mortality |  | 0 to 1825 days | 
| Freedom From All Stroke |  | 0 to 365 days | 
| Freedom From All Stroke |  | 0 to 730 days | 
| Freedom From All Stroke |  | 0 to 1095 days | 
| Freedom From All Stroke |  | 0 to 1460 days | 
| Freedom From All Stroke |  | 0 to 1825 days | 
| Death (Non-Hierarchical) |  | ≤ 30 Days Post Index Procedure | 
| All Stroke (Non-Hierarchical) |  | ≤ 30 Days Post Index Procedure | 
| Myocardial Infarction (MI) (Non-Hierarchical) |  | ≤ 30 Days Post Index Procedure | 
| Death, Stroke or Myocardial Infarction (MI) (Hierarchical) |  | ≤ 30 Days Post Index Procedure | 
| Death or Stroke (Hierarchical) |  | ≤ 30 Days Post Index Procedure | 
| Death or Major Stroke (Hierarchical) |  | ≤ 30 Days Post Index Procedure | 
| Freedom From Death, Stroke and MI Within 30 Days and Ipsilateral Stroke From 31 Days to 5 Years |  | 0 to 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Carotid stenting, Carotid endarterectomy, Carotid artery disease with severe narrowing of the artery, Stroke prevention