Please select the eligibility criteria that correspond to the clinical trial below.
Title: Risk Reduction of Symptomatic and Silent Brain Infarctions During Carotid Endarterectomy and Carotid Stenting Due to Ultrasound Activation of Endogenous Fibrinolytic System Using Transcranial Doppler Monitoring
Brief Summary: The aim of the project is to demonstrate a fibrinolytic effect of sonothrombolysis (continual transcranial Doppler monitoring) using 2 MegaHertz (MHz) diagnostic probe on the reduction of risk of brain infarctions due to the activation of endogenous fibrinolytic system during carotid endarterectomy (CEA) and carotid stenting (CS). 240 patients indicated for CEA (120 patients) and CS (120 patients) will be enrolled into the study in order to demonstrate a twenty-percent risk reduction of number and volume of brain infarctions detected using MRI examination 24 hours after CEA or CS in 5% level of significance. Patients will be randomized - subgroup 1 will undergo a 60minute non-diagnostic transcranial Doppler (TCD) monitoring during CEA or CS, subgroup 2 will undergo interventions without TCD monitoring. The second aim is to compare number of brain infarctions detected using MRI between CEA and CS patients.

Confirmation of the investigators hypothesis that sonothrombolysis is able to activate endogenous fibrinolytic system during CEA or CS with consecutive reduction of the number and volume of brain infarcts, can lead to the increase of the safety of CEA and CS in patients with internal carotid artery stenosis. The investigators can presume that up to 50% of patients indicated for CEA or CS can be treated using these methods in the future.

In the Substudy "Risk of brain infarction after carotid endarterectomy and stenting" the the risk of asymptomatic and symptomatic brain infarctions, changes in cognitive functions, as well as morbidity and mortality at 30 days between patients with symptomatic and asymptomatic severe internal carotid artery (ICA) stenoses undergoing elective CEA and CAS will be compared.

The sample size of the Substudy was based on an expected 80% difference of new ischemic lesions on DWI-MRI between CEA (estimated prevalence, 30%) and CAS (54%). Pre-study calculations showed that a minimum of 73 patients in each group was needed to reach a significant difference with an alpha value of 0.05 (two-tailed) and a beta value of 0.8 assuming that 15% of subjects would be lost to follow-up or refuse to participate in the study.


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: 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 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).
D: 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.

Answer: B