Please select the eligibility criteria that correspond to the clinical trial below.
Title: Stenting and Angioplasty With Protection in Patients at High Risk for Endarterectomy
Brief Summary: The primary objective of this study is to compare the safety and effectiveness of the Cordis Nitinol Carotid Stent and Delivery Systems (5.5 F and 7 F) with the ANGIOGUARD XP distal protective device to CEA in the treatment of carotid artery disease in patients at increased risk for surgery.


Options:
A: Inclusion Criteria:

* In brief, patients are eligible if they have experienced a carotid TIA or non disabling stroke within 4 months before randomisation and if they have an atherosclerotic stenosis of the region of the ipsilateral carotid bifurcation of 60% or more, as determined by the North American Symptomatic Carotid Endarterectomy Trial (NASCET) method, that investigators believe is suitable for both carotid endarterectomy and endovascular treatment. The degree of stenosis warranting treatment initially set at 70% or more was subsequently set at 60% or greater to reflect current generally accepted practice in the treatment of symptomatic carotid stenosis. The presence of a 60% or more ipsilateral carotid stenosis has to be confirmed by conventional digital subtraction angiography or the combination of carotid Duplex scanning and magnetic resonance angiography, provided the results of these non-invasive techniques are concordant.

Exclusion Criteria:

* Patients cannot be included if they have a disabling stroke (mRS \>=3), a non atherosclerotic carotid disease, a severe intracranial carotid artery stenosis, contra-indications to heparin, ticlopidine or clopidogrel.
* There is no age limit.
* The presence of contralateral occlusion and/or the angiographic appearance of the stenotic lesion are not factors in treatment selection. The randomisation algorithm takes centre and degree of stenosis (more or less than 90% stenosis) into account. Patients must be treated as soon as possible after random assignment, in any case within 2 weeks of randomisation.
B: Inclusion Criteria:

* stenosis of internal carotid artery
* indication to endarterectomy or stenting
* age 40-80 years
* sufficient temporal bone window for TCD with detectable blood flow in MCA
* independent patient (modified Rankin score 0-2)
* informed consent signed by the patient.

Exclusion Criteria:

* contraindication to MRI examination (pace-maker, implanted metal material, claustrophobia)
C: Inclusion Criteria:

1. The patient must be \> 18 years of age.
2. The patient has a 50% stenosis (as determined by ultrasound or angiogram) of the common or internal carotid artery and is clinically symptomatic; i.e., within the previous 180 days has experienced symptoms in the ipsilateral carotid artery distribution, defined as:

   * one or more TIAs, characterized by distinct focal neurologic dysfunction or monocular blindness with clearing of signs and symptoms within 24 hours, or
   * one or more completed strokes (as defined by this protocol) with persistence of symptoms or signs for more than 24 hours (the most recent event is used as the qualifying event), except as excluded below, with stenosis \>50%, (as determined by ultrasound or angiogram) of the common or internal carotid artery, OR The patient must have a \>80% diameter stenosis (as determined by ultrasound or angiogram) of the internal or common carotid artery without neurological symptoms.
3. To be entered into the study, the patient must have one or more of the following conditions:

   * congestive heart failure (class III/IV) and/or known severe left ventricular dysfunction LVEF \< 30%
   * open heart surgery within six weeks
   * recent MI (\>24 hours and \<4 weeks)
   * unstable angina (CCS class III/IV)
   * synchronous severe cardiac and carotid disease requiring open heart surgery and carotid revascularization
   * Age greater than 80 years as a single risk factor.

Exclusion Criteria:

1. The patient is experiencing an acute ischemic neurologic stroke or has experienced a stroke within the past 48 hours.
2. The patient has an intracranial mass lesion (i.e., abscess, tumor, or infection).
3. The reference segment diameter (distal common carotid and internal carotid artery segment cephalic to the lesion) is less than 4mm or greater than 9mm by quantitative analysis. See Instructions For Use, for proper stent sizing. The exception to this would be with a lesion having \>95% stenosis where the true diameter of the distal vessel can not be determined such as the case with a string sign or distal vessel collapse. In this case the judgment of the interventionalist will prevail with the intention not to oversize the stent to the distal vessel by more than 2mm.
4. The patient has known peripheral vascular, supra-aortic or internal carotid artery tortuosity which preclude the use of catheter-based techniques if so randomized.
5. The patient has any intracranial aneurysm (\> 9 mm).
D: 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.

Answer: C