Please select the eligibility criteria that correspond to the clinical trial below.
Title: Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST)
Brief Summary: The purpose of the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) is to compare the relatively new procedure of stent-assisted carotid angioplasty (CAS) to the traditional and accepted surgical approach of carotid endarterectomy (CEA) for the treatment of carotid artery stenosis to prevent recurrent strokes in those patients who have had a TIA (transient ischemic attack) or a mild stroke within the past 6 months (symptomatic) and in those patients who have not had any symptoms within the past 6 months (asymptomatic).


Options:
A: Inclusion Criteria:

* Symptomatic patients with recent neurological events (TIA or non-disabling stroke) with an associated carotid stenosis greater than or equal to 50% by angiography or greater than or equal to 70% by ultrasound or greater than or equal to 70% by Computed Tomography Angiography (CTA) or Magnetic Resonance Angiography (MRA) are eligible for randomization.
* Asymptomatic patients with no recent (in the last 6 months) neurological events referable to the study with artery and carotid stenosis (patients with symptoms beyond 180 days are considered asymptomatic) greater than or equal to 60% by angiography or greater than or equal to 70% by ultrasound or greater than or equal to 80% by CTA or MRA are eligible for randomization.

Exclusion Criteria:

* Conditions that: (1) interfere with the evaluation of endpoints, (2) are known to interfere with the completion of CEA or CAS, or (3) affect the likelihood of survival for the study period (4 years). Chronic atrial fibrillation and/or anti-coagulation or episodic atrial fibrillation within the last 6 months.
B: General Inclusion Criteria

1. Patients ≥35 years old.
2. Carotid stenosis defined as:

   * Stenosis ≥70% by catheter angiography (NASCET Criteria); OR
   * by Doppler ultrasonography (DUS) with ≥70% stenosis defined by a peak systolic velocity of at least 230 cm/s plus at least one of the following:

     1. an end diastolic velocity ≥100 cm/s, or
     2. internal carotid/common carotid artery peak systolic velocity ratio ≥4.0, or
     3. computed tomography angiography (CTA) with ≥ 70% stenosis, or
     4. magnetic resonance angiography (MRA) with ≥ 70% stenosis.
3. No medical history of stroke or transient ischemic attack (TIA) ipsilateral to the stenosis within 180 days of randomization. Life-long asymptomatic patients will be defined as having no medical history of stroke or transient ischemic attack and negative responses to all of the symptom items on the Questionnaire for Verifying Stroke-free Status (QVSS).
4. Patients must have a modified Rankin Scale (mRS) score of 0 or 1 at the time of informed consent.
5. Women must not be of childbearing potential or, if of childbearing potential, have a negative pregnancy test prior to randomization.
6. Patients must agree to comply with all protocol-specified follow-up appointments.
7. Patients must sign a consent form that has been approved by the local governing Institutional Review Board (IRB)/Medical Ethics Committee (MEC) of the respective clinical site.
8. Randomization to treatment group will apply to only one carotid artery for patients with bilateral carotid stenosis. Management of the non-randomized stenosis may be done in accordance with local PI recommendation. Treatment of the non-study internal carotid artery must take place at least 30 days prior to randomization, or greater than 44 days after randomization and 30 days after the study procedure is completed (whichever is longer).
9. Carotid stenosis must be treatable with carotid endarterectomy (CEA), carotid artery stenting (CAS), or either procedure.

General Exclusion Criteria

1. Intolerance or allergic reaction to a study medication without a suitable management alternative.
2. GI hemorrhage within 1 month prior to enrollment that would preclude antiplatelet therapy.
3. Prior major ipsilateral stroke in the past with substantial residual disability (mRS ≥ 2) that is likely to confound study outcomes.
4. Severe dementia.
5. History of major symptomatic intracranial hemorrhage within 12 months that was not related to anticoagulation.
6. Prior Intracranial hemorrhage that the investigator believes represents a contraindication to the perioperative or periprocedural antithrombotic and antiplatelet treatments necessary to complete endarterectomy or stenting per protocol.
7. Current neurologic illness characterized by fleeting or fixed neurologic deficits that cannot be distinguished from TIA or stroke.
8. Patient objects to future blood transfusions.
9. Platelet count \<100,000/microliter or history of heparin-induced thrombocytopenia.
10. Anticoagulation with Phenprocoumon (Marcumar®), warfarin, or a direct thrombin inhibitor, or anti-Xa agents.
11. Chronic atrial fibrillation, unless the patient has had successful atrial appendage closure (e.g., Watchman Device) and no longer requires chronic therapeutic anticoagulation.
12. Any episode of atrial fibrillation within the past 6 months or history of paroxysmal atrial fibrillation that is deemed to require chronic anticoagulation.
13. Other high-risk cardiac sources of emboli, including left ventricular aneurysm, severe cardiomyopathy, aortic or mitral mechanical heart valve, severe calcific aortic stenosis (valve area \< 1.0 cm2), endocarditis, moderate to severe mitral stenosis, left atrial thrombus, or any intracardiac mass, or known unrepaired patent foramen ovale (PFO) with prior paradoxical embolism.
14. Unstable angina defined as rest angina with electrocardiogram (ECG) changes that is not amenable to revascularization (patients should undergo planned coronary revascularization at least 30 days before randomization).
15. Left Ventricular Ejection fraction \<30% or admission for heart failure in prior 6 months.
16. Respiratory insufficiency with life expectancy \< 4 years or forced expiratory volume (FEV1) \<30% of predicted value.
17. Known malignancy other than basal cell non-melanoma skin cancer. There are two exceptions to this rule: patients with prior cancer treatment and no recurrence for \>5 years are eligible for enrollment and cancer patients with life expectancy of greater than 5 years are eligible for enrollment.
18. Any major surgery, major trauma, revascularization procedure, or acute coronary syndrome within the past 1 month.
19. Either the serum creatinine is ≥ 2.5 mg/dl or the estimated glomerular filtration rate (GFR) is \< 30 cc/min.
20. Major (non-carotid) surgery/procedures planned within 3 months after enrollment.
21. Currently listed or being evaluated for major organ transplantation (i.e. heart, lung, liver, kidney).
22. Actively participating in another drug or aortic arch or cerebrovascular device trial for which participation in CREST-2 would be compromised with regard to follow-up assessment of outcomes or continuation in CREST-2.
23. Inability to understand and cooperate with study procedures or provide informed consent.
24. Non-atherosclerotic carotid stenosis (dissection, fibromuscular dysplasia, or stenosis following radiation therapy).
25. Previous ipsilateral CEA or CAS.
26. Ipsilateral internal or common carotid artery occlusion.
27. Intra-carotid floating thrombus.
28. Ipsilateral intracranial aneurysm \> 5 mm.
29. Extreme morbid obesity that would compromise patient safety during the procedure or would compromise patient safety during the periprocedural period.
30. Coronary artery disease with two or more proximal or major diseased coronary arteries with 70% stenosis that have not, or cannot, be revascularized.

Specific Carotid Endarterectomy Exclusion Criteria

Patients who are being considered for revascularization by CEA must not have any of the following criteria:

1. Serious adverse reaction to anesthesia not able to be overcome by pre-medication.
2. Distal/intracranial stenosis greater than index lesion.
3. Any of the following anatomical: radical neck dissection; surgically inaccessible lesions (e.g. above cervical spine level 2 (C2)); adverse neck anatomy that limits surgical exposure (e.g. spinal immobility - inability to flex neck beyond neutral or kyphotic deformity, or short obese neck); presence of tracheostomy stoma; laryngeal nerve palsy contralateral to target vessel; or previous extracranial-intracranial or subclavian bypass procedure ipsilateral to the target vessel.

Specific Carotid Artery Stenting Exclusion Criteria

Patients who are being considered for revascularization by CAS must not have any of the following criteria:

1. Allergy to intravascular contrast dye not amenable to pre-medication.
2. Type III, aortic arch anatomy.
3. Angulation or tortuosity (≥ 90 degree) of the innominate and common carotid artery that precludes safe, expeditious sheath placement or that will transmit a severe loop to the internal carotid after sheath placement.
4. Severe angulation or tortuosity of the internal carotid artery (including calyceal origin from the carotid bifurcation) that precludes safe deployment of embolic protection device or stent. Severe tortuosity is defined as 2 or more ≥ 90 degree angles within 4 cm of the target stenosis.
5. Proximal/ostial common carotid artery (CCA), innominate stenosis or distal/intracranial stenosis greater than index lesion.

   Excessive circumferential calcification of the stenotic lesion defined as \>3mm thickness of calcification seen in orthogonal views on fluoroscopy.(Note: Anatomic considerations such as tortuosity, arch anatomy, and calcification must be evaluated even more carefully in elderly subjects (≥ 70 years).)
6. Target ICA vessel reference diameter \<4.0 mm or \>9.0 mm. Target internal carotid artery (ICA) measurements may be made from angiography of the contralateral artery. The reference diameter must be appropriate for the devices to be used.
7. Inability to deploy or utilize an FDA-approved Embolic Protection Device (EPD).
8. Non-contiguous lesions and long lesions (\>3 cm).
9. Qualitative characteristics of stenosis and stenosis-length of the carotid bifurcation (common carotid) and/or ipsilateral external carotid artery, that preclude safe sheath placement.
10. Occlusive or critical ilio-femoral disease including severe tortuosity or stenosis that necessitates additional endovascular procedures to facilitate access to the aortic arch or that prevents safe and expeditious femoral access to the aortic arch. "String sign" of the ipsilateral common or internal carotid artery.
11. Angiographic, computed tomography (CT), magnetic resonance (MR) or ultrasound evidence of severe atherosclerosis of the aortic arch or origin of the innominate or common carotid arteries that would preclude safe passage of the sheath and other endovascular devices to the target artery as needed for carotid stenting.
C: Inclusion Criteria:

* Subject is at high risk for carotid endarterectomy due to either anatomic or co-morbid conditions; AND
* Symptomatic patients (TIA or non-disabling stroke within 6 months of the procedure), with carotid stenosis ≥ 50% as diagnosed by angiography, using NASCET methodology (50); OR
* Asymptomatic patients with carotid stenosis ≥ 80% as diagnosed by angiography, using NASCET methodology

Exclusion Criteria:

* Conditions that interfere with the evaluation of endpoints
* Subject has anticipated or potential sources of cardiac emboli
* Subject plans to have a major surgical procedure within 30 days after the index procedure.
* Subject has intracranial pathology that makes the subject inappropriate for study participation.
* Subject has a total occlusion of the ipsilateral carotid artery (i.e., CCA).
* Severe circumferential lesion calcification that may restrict the full deployment of the carotid stent.
* Carotid stenosis located distal to the target stenosis that is more severe than the target stenosis.
D: 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).

Answer: A