Effects of Cerebral Protection With Filters vs. Flow Reversal on Cerebral Embolization After Carotid Artery Stenting
Effects of Cerebral Protection With Filters vs. Flow Reversal on Cerebral Embolization After Carotid Artery Stenting
Carotid artery stenting (CAS) with cerebral embolic protection is the preferred treatment for
 narrowing of the carotid arteries in patients at high risk for open surgery. Special devices
 are used to protect the brain from particles(emboli) that may break off when the narrowing or
 blockage is cleared during the angioplasty and stenting procedure. Although filters are most
 frequently used, protection systems consisting of balloons and flow reversal are also
 available for cerebral embolic protection. However, there is little information about the
 effectiveness of filters compared with balloons and flow reversal for prevention of
 embolization during CAS. The aim of our study is to address this major problem. Our study was
 designed to answer two specific questions: First, the study will investigate whether
 balloon-based protection systems are more effective than filters in reducing the amount of
 particles that break off and travel to the brain during CAS. For this purpose two imaging
 techniques will be used: magnetic resonance imaging of the brain (MRI), and transcranial
 doppler (detection of microparticles in the small brain vessels using ultrasound). Second, it
 will be investigated whether the use of balloon-based protection devices are more effective
 than filters for prevention of stroke, heart attacks, and death after carotid stenting. The
 results of the study will provide important information to find out the best way to protect
 the brain from plaque fragments that may break off during CAS.
Description of Procedures to be performed

 Pre-Procedure Medication Regimen The standard of care premedication with antiplatelet therapy
 for CAS will be used for the study. To minimize the risk of neurological events related to
 stent thrombosis during the procedure, subjects should be provided antiplatelet therapy for a
 minimum of 48 to 72 hours prior to the procedure, to include: 1) Aspirin 325 mg daily and 2)
 Clopidogrel (Plavix®) 75 mg twice daily OR Ticlopidine (Ticlid®) 250 mg twice daily

 A protracted dose of premedication may be substituted by administering a loading dose of
 antiplatelet therapy at least 4 hours prior to the carotid intervention on the day of the
 procedure, to include: 1) Aspirin A 650 mg loading dose of aspirin, provided that it is not
 enteric coated or extended release, and 2) Clopidogrel (Plavix ®) 450 mg.

 Procedure: Patients will undergo CAS with FDA-approved carotid stents under embolic
 protection with the Accunet device or the Gore NPS. All CAS procedures will be performed
 through retrograde access from the common femoral artery. CAS procedures will be performed
 using a fixed angiographic unit (Allura Xper FD20, Philips, Bothell, WA). Procedural details
 and CAS protocols will follow techniques described in detail before.14 The procedure will be
 performed under local anesthesia with minimal sedation to facilitate continuous neurological
 evaluation. Baseline angiographic studies will be performed concurrently with the CAS
 procedure. The diagnostic angiography will be reviewed to ensure that the patient does not
 meet any applicable angiographic exclusion criteria. Once this has been determined,
 randomization will be performed. The Accunet filter or the Gore NPS will be used according to
 the instructions for use. Ultrasound-guided access to the ipsilateral or contralateral
 femoral vein will be obtained if the patient is randomized to CAS with the Gore NPS.
 Neurological monitoring of the subject's level of awareness will be evaluated every 5 to 10
 minutes during the CAS procedure. Patients deemed ineligible by angiographic criteria will be
 considered screen failures and will be excluded from the study. These patients may receive
 further treatment outside of the study protocol according to usual practice and standard of
 care.

 Transcranial Doppler Protocol: Transcranial Doppler signals, using a portable digital 2-MHz
 PMD/spectral TCD unit (PMD150, Spencer Technologies, Seattle, WA), will be recorded from
 bilateral middle cerebral arteries via transtemporal windows. Monitoring will be started in
 the operative room immediately before CAS and continued until the end of the case or for at
 least 15 minutes after removal of the neuroprotection system. A head frame will be used for
 ultrasound probe fixation and continuous flow assessment in M1 segment of the middle cerebral
 artery (MCA). Several TCD parameters will be recorded: MES counts and microemboli shower
 detection during the different steps of the procedure, initial MCA mean velocity, mean MCA
 velocity during CAS, and final mean MCA velocity. MES will be identified according to the
 recommended guidelines.31 Data will be stored on a hard disk using a coding system and will
 be analyzed off-line on a later day by readers who will be blinded to patient information.

 Diffusion-weighted MRI exams: All patients will have DW-MRI scans of the brain obtained
 within 24 hours prior to CAS and 18 to 24 hours after CAS. Postprocedural DW-MRI studies will
 be compared to preprocedural studies to identify new procedure-related ischemic cerebral
 lesions.32, 33 DW-MRI will be obtained using standard head coils on 1.5 Tesla Siemens
 scanners (Siemens Avanto or Magnetom Sonata, Siemens, Erlangen, Germany). DW-MRI with
 echo-planar imaging sequence (B0 = 1000) and fluid-attenuated inversion recovery (FLAIR)
 images will be obtained in axial and coronal sections. The DW-MRI studies will then be
 evaluated by neuroradiologists blinded to the clinical status, the type of embolic protection
 and TCD data of the patients. On the postprocedural MRI, acute embolic lesions will be
 defined as focal hyperintense areas with restricted diffusion signal, which will be confirmed
 by apparent diffusion coefficient mapping to rule out artifacts. New postprocedural cerebral
 lesions consistent with microemboli will be recorded in terms of location and number for all
 DW-MRI exams performed.
Inclusion Criteria:

 1. Patient is at least 18 years old;

 2. Patient is willing and capable of complying with the study protocol requirements,
 including the specified follow-up period;

 3. Patient is willing to provide written informed consent prior to enrollment in the
 study;

 4. Male, infertile female, or non-lactating female of child bearing potential practicing
 an acceptable method of birth control with a negative pregnancy test within 7-days
 prior to study procedure;

 5. Patient is either symptomatic, i.e. with a history of TIAs or non-disabling stroke
 within 6 months of the procedure, with carotid stenosis ≥ 50%, or asymptomatic with
 carotid stenosis ≥ 80%, as diagnosed by angiography using NASCET methodology;4

 6. The target lesion is located in the internal carotid artery (ICA) and the reference
 vessel diameter, i.e. the common carotid artery (CCA) is < 10 mm based on angiographic
 assessment.

 Exclusion Criteria:

 1. Acute evolving or recent stroke within 7 days of study evaluation;

 2. Cardiac embolism;

 3. Acute myocardial infarction less than 72 hours prior to the procedure;

 4. Major surgical procedure within 30 days preceding CAS;

 5. Major surgical procedure within 30 days after the index procedure;

 6. Prior major ipsilateral stroke with residual deficit or other neurologic conditions
 that may affect neurological assessments;

 7. Pregnancy or breastfeeding;

 8. Severe chronic renal insufficiency (serum creatinine is ≥ 2.5 mg/dL);

 9. Contraindication to study medications, including antiplatelet therapy;

 10. Prior sensitivity to contrast media that cannot adequately be controlled with
 pre-medication;

 11. Untreatable bleeding diathesis or hypercoagulable state or refusal to blood
 transfusions;

 12. History of uncontrolled pulmonary hypertension;

 13. Intracranial pathology;

 14. Patient unable or unwilling to undergo DW-MRI of the brain

 15. Patient without adequate transtemporal window for transcranial Doppler examination

 16. Other anatomic or co-morbid conditions that, in the investigator's opinion, could
 limit the patient's ability to participate in the study or to comply with follow-up
 requirements, or impact the scientific soundness of the study results.

 17. Isolated ipsilateral hemisphere leading to subject intolerance to flow reversal;

 18. Anatomic conditions that preclude performance of carotid artery stenting.