Effects of Cerebral Protection With Filters vs. Flow Reversal on Cerebral Embolization After Carotid Artery Stenting

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.