Protected Carotid Artery Stenting in Subjects at High Risk for Carotid Endarterectomy (CEA) (PROTECT)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the long-term safety and efficacy of the Xact™ Rapid Exchange Carotid Stent System used in conjunction with the Emboshield® Pro Rapid Exchange Embolic Protection System (Generation 5) and the Emboshield® BareWire™ Rapid Exchange Embolic Protection System (Generation 3), in the treatment of atherosclerotic carotid artery disease in high-surgical risk subjects.

Official Title
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Protected Carotid Artery Stenting in Subjects at High Risk for Carotid Endarterectomy (CEA)

Conditions
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Carotid Artery Disease

Intervention / Treatment
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* Device: Xact Stent with either Emboshield Pro (Gen 5) or Emboshield (Gen 3)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Subject must be ≥ 18 years of age. Subject has the ability to cooperate with study procedures and agrees to return for all required follow-up visits, tests and exams. Female subjects of childbearing potential must have a documented negative pregnancy test within 30 days prior to the index procedure. Subjects taking warfarin may be included if their dosage is reduced before the index procedure to result in an INR of 1.5 or less. Warfarin may be restarted to therapeutic dose after the index procedure. The subject must sign a written informed consent prior to the initiation of any study procedures, using a form that is approved by the Institutional Review Board (IRB) or Medical Ethics Committee (EC). The life expectancy of the subject is at least two years. The subject has a lesion located in the internal carotid artery (ICA); the carotid bifurcation may be involved. The target lesion is intended to be treated with a single stent. Target ICA vessel diameter must be visually estimated to be: ≥2.5 mm and ≤7.0 for the Emboshield Pro (Gen 5) ≥ 2.8 mm and ≤6.2 for the Emboshield (Gen 3) And ≥4.0 mm and ≤9.0 mm for the Xact Stent treatment area. The subject has a carotid artery stenosis determined by ultrasound or angiography (visual estimate) to be: ≥50% for symptomatic subjects Or ≥80% for asymptomatic subjects High-risk inclusion criteria for either anatomical or co-morbid risk factors are present. The subject must fulfill at least one of the criteria, Category I or II risk factors, listed below to meet the inclusion criteria. Category I Anatomic Risk Factors Previous radiation treatment to the neck or radical neck dissection Target lesion is at or above the second vertebral body C2 (level of jaw) Inability to extend the head due to cervical arthritis or other cervical disorders Tracheostomy or tracheal stoma Laryngectomy Contralateral laryngeal nerve palsy Severe tandem lesions Category II Co-morbid Risk Factors Previous CEA with significant restenosis (as defined for symptomatic or asymptomatic subjects) Total occlusion of the contralateral carotid artery Left ventricular ejection fraction < 35% Congestive Heart failure New York Heart Association (NYHA) Functional Class III or higher Dialysis dependent renal failure Canadian Cardiovascular Society Angina Classification III or higher or unstable angina Requires coronary artery bypass surgery, cardiac valve surgery, peripheral vascular surgery, or abdominal aortic aneurysm repair within 60 days •≥80 years of age Myocardial infarction within previous 6 weeks Abnormal stress test. Treadmill, thallium or dobutamine echo are acceptable. The stress tests should be sufficiently abnormal to place the subject at increased risk for CEA. This includes subjects with two or more proximal diseased coronary arteries of >70% stenosis that have not or cannot be revascularized or <30 days since revascularization. Severe pulmonary disease, including at least one of the following: requires chronic O2 therapy; resting PO2 ≤60 mm Hg, Hematocrit ≥50%, FEV₁ or DLCO ≤50% of normal. Exclusion Criteria The subject is participating in another investigational trial that would interfere with the conduct or result of this study. The subject has dementia or a neurological illness that may confound the neurological evaluation. Total occlusion of the target vessel. There is an existing, previously placed stent in the target artery. The subject has a known life-threatening allergy to the contrast media that cannot be treated. 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 or aspirin and Ticlopidine. The subject has a GI bleed that would interfere with antiplatelet therapy. The subject has known cardiac sources of emboli, including but not limited to current or past history of paroxysmal or sustained atrial fibrillation (treated or untreated), valve replacement, etc. Subject has Hemoglobin (Hgb) less than 8 gm/dL (unless on dialysis), platelet count <50,000/mm3, or known heparin associated thrombocytopenia. The subject has a history of bleeding diathesis or coagulopathy including thrombocytopenia or an inability to receive heparin or Bivalirudin (Angiomax™) in amounts sufficient to maintain an ACT of >250, or will refuse blood transfusion. The subject has atherosclerotic disease involving adjoining vessels that precludes safe placement of the guiding catheter or sheath. The subject has other abnormal angiographic findings that indicate the subject is at risk for a stroke due to a problem other than that of the target lesion, such as: ipsilateral arterial stenosis greater in severity than the target lesion, cerebral aneurysm, or arteriovenous malformation of the cerebral vasculature. There is evidence of a carotid artery dissection prior to the initiation of the index procedure. There is an angiographically visible thrombus. There is any condition that precludes proper angiographic assessment, placement of the cerebral protective system or makes percutaneous arterial access unsafe, e.g. morbid obesity, sustained systolic blood pressure >180 mm Hg, tortuosity, occlusive disease, vessel anatomy, or aortic arch anatomy. Occlusion (TIMI 0 flow), or string sign of the ipsilateral common or internal carotid artery. There is evidence of bilateral carotid stenosis that would require intervention within 30 days of the index procedure. There is evidence of a stroke within the previous 30 days of the index procedure. There is a planned treatment of a non-target lesion within 30 days post-index procedure. There is a history of intracranial hemorrhage within the previous 3 months, including hemorrhagic transformation of an ischemic stroke. There is a history of an ipsilateral stroke with fluctuating neurologic symptoms within one year of the index procedure.

Ages Eligible for Study
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Minimum Age: 18 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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Device: Xact Stent with either Emboshield Pro (Gen 5) or Emboshield (Gen 3)|All subjects will receive the Xact™ Rapid Exchange Carotid Stent System. The first 220 consecutively enrolled subjects will be treated with the investigational filter system, the Emboshield® Pro Rapid Exchange Embolic Protection System (Generation 5). The remaining subjects will be treated with the FDA approved Emboshield® BareWire™ Rapid Exchange Embolic Protection System (Generation 3).|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Kaplan-Meier Estimate of Freedom From the Composite of Any Death, Stroke and MI During the 30 Day Post Procedural Period (DSMI), Plus Fatal and Non-fatal Ipsilateral Stroke From 31-365 Days and Annually Thereafter for a Total of 3 Years. | Freedom from DSMI to 30 days or ipsilateral stroke from 31 days to 3 years. KM event free (%) curve. | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute Device Success | Defined by the attainment of <50% residual stenosis covering an area no longer than the original lesion treated with the stent. | Post-procedure | 
| Procedural Success | Defined as the attainment of less than 50% residual stenosis (per angiographic core lab) of the target lesion and the absence of DSMI at 30 days post-index procedure. | 30 Days | 
| Composite of Any Transient Ischemic Attack (TIA) and Amaurosis Fugax | Includes only each subject's first occurrence of each event. | ≤30 days | 
| Kapan-Meier Estimate of Freedom From Clinically Driven Target Lesion Revascularization Through Three Years. |  | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Carotid, Artery, Disease, Stent, PROTECT, XACT, EMBOSHIELD