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)
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)
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.
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.
Inclusion Criteria:

 1. The subject must be > 18 and < 80 years of age.

 2. Female subjects of child bearing potential must have a documented negative pregnancy
 test within 30 days prior to the study procedure.

 3. 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.

 4. 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.

 5. 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).

 6. The subject must agree to return for all required follow-up visits.

 7. Subject has a discrete lesion located in the internal carotid artery (ICA); the
 contiguous common carotid artery (CCA) may be involved.

 8. 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.

 9. 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.

 10. Based on the subject's anatomy, the Investigator should expect to successfully deliver
 the stent to the target lesion (absence of extreme tortuosity, etc.).

 11. 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.

 1. 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.

 2. 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.

 3. Subject has inability to understand and cooperate with study procedures or provide
 informed consent.

 4. Subject has had an intracranial hemorrhage or hemorrhagic stroke within 1-year prior
 the index procedure.

 5. Subject has dementia or has a neurological illness that may confound the neurological
 evaluation.

 6. Subject has had a known untoward reaction to anesthesia or contrast media not able to
 be overcome by pre-treatment with medications.

 7. 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.

 8. Subject has Hemoglobin (Hgb) less than 10 gm/dL, platelet count <100,000/mm3 or
 >500,000/mm3, or known heparin associated thrombocytopenia.

 9. Subject has an active bleeding diathesis or coagulopathy, or will refuse blood
 transfusions.

 10. Subject has had a GI bleed that would interfere with antiplatelet therapy.

 11. Subject has known cardiac sources of emboli, including paroxysmal or sustained atrial
 fibrillation (treated or untreated).

 12. Subject has had an myocardial infarction (MI) within the previous 30 days.

 13. Subject has any condition that limits their anticipated survival to less than 3 years.

 14. Subject is a high risk surgical candidate defined as the presence of any one or more
 of a following medical conditions:

 1. Two or more proximal diseased coronary arteries of > 70% stenosis that have not
 or cannot be revascularized or < 30 days since revascularization.

 2. Ejection fraction < 30% or New York Heart Association (NYHA) heart failure
 functional class 3 or higher.

 3. Unstable angina, defined as angina at rest with ECG changes.

 4. On a list for major organ transplant or is being evaluated for such.

 5. Known history of respiratory insufficiency, forced expiratory volume (FEV1) < 30%
 (predicted).

 6. Chronic renal insufficiency (serum creatinine >2.5 mg/dL).

 7. Uncontrolled diabetes defined as fasting glucose > 400 mg/dL.

 8. Concurrent requirement for any invasive procedure 30 days pre- or post-procedure.

 9. Age ≥ 80 years.

 15. 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.

 1. Subject has had radiation treatment to the neck.

 2. Subject has had a radical neck dissection.

 3. Surgically inaccessible lesions (i.e., lesions extending above the level of C2).

 4. Spinal immobility - inability to flex neck beyond neutral or kyphotic deformity.

 5. Presence of carotid artery dissection, aneurysm, pseudoaneurysm, arteritis or
 fibromuscular dysplasia (FMD) in the target vessel.

 6. Hemodynamically significant (>60%) stenosis of the right or left common carotid
 artery (LCCA/RCCA) below the clavicle.

 7. Presence of tracheostomy stoma.

 8. Contralateral laryngeal nerve paralysis.

 9. Previous carotid endarterectomy, extracranial-intracranial or carotid subclavian
 bypass procedure ipsilateral to the carotid stenosis.

 10. 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.

 16. 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.

 17. Intraluminal filling defect thought to represent thrombus.

 18. Excessive calcification: defined as fluoroscopic evidence of calcium that extends
 circumferentially around the target lesion and includes the majority of the
 atherosclerotic plaque.

 19. Occlusion (TIMI 0 flow), or string sign of the ipsilateral common or internal carotid
 artery.

 20. The target lesion requires treatment with a device other than percutaneous
 transluminal angioplasty (PTA) prior to stent placement.

 21. Significant (> 60%) stenosis proximal or distal to the target lesion that might
 require revascularization or impede run off.

 22. Presence of a previously placed intravascular stent in the ipsilateral carotid
 distribution.

 23. Cerebral aneurysm (symptomatic or > 10 mm) or arteriovenous malformation (AVM) of the
 cerebral vasculature.

 24. Bilateral carotid stenosis (ICA/CCA contralateral stenosis > 60% by ultrasound or
 angiography).