A Randomized Trial of Carotid Artery Stenting With and Without Cerebral Protection

This study is a single center, prospective, randomized trial evaluating the safety and
effectiveness of CAS with and without CP. The study population will be comprised of subjects
with atherosclerotic, post endarterectomy restenotic or other obstructive lesions in native
carotid arteries. Other carotid artery pathology not amenable to surgical repair (for
example carotid artery dissection) will also be considered. Subjects at high risk for
complications from standard CEA will be the target population for this study. High risk
status will be confirmed by two physicians, one of whom is a vascular surgeon. Both
symptomatic and asymptomatic subjects will be enrolled. This will ensure that the proportion
of symptomatic subjects is the same in the two arms of the study. "Symptomatic" is defined
in the exclusion criteria. The expected duration of this clinical trial is 3 years.

In this study there are there are two arms that a subject may be randomized to:

Group1: CAS with the use of the RX ACCUNET Group 2: CAS without the use of the RX ACCUNET
This study has been designed to test whether the addition of CP enhances the safety and
effectiveness of CAS.

Inclusion Criteria:

- To participate in this study, the subject MUST have all of the following for
inclusion in the study:

• The subject (male or non-pregnant female) must be > 18 years of age.

• The subject should have a stenosis in the common or internal carotid artery of at
least 70% determined by one of the modalities listed below.

• The subject should be considered a relatively high risk for carotid endarterectomy.
This determination has to be made and documented by two physicians, at least one of
who must be a vascular surgeon acting as an investigator on this trial. High risk
considerations should include at least one of the following:

1. Cardiac dysfunction. NYHA class III or above, compensated or active congestive
heart failure (CHF), incomplete coronary revascularization, ejection fraction of
<35%, pulmonary hypertension, or recommendation of a cardiologist against open
CEA.

2. Pulmonary dysfunction, history of respiratory failure, severe chronic
obstructive pulmonary Disease (COPD) on bronchodilators or recommendation of a
pulmonary specialist against open CEA.

3. Multi-system dysfunction, defined as any combination of medical problems in
three distinct systems.

4. Anatomic issues: previous CEA or neck dissection, neck irradiation, inaccessible
lesions, neck fusion or other anatomic considerations increasing the risk of
CEA.

5. Age >80 AND symptomatic (defined below)

6. General debilitation documented by the subject's primary physician.

7. Increased anesthetic risk as documented by an anesthesiologist.

- Subjects can be either clinically symptomatic or asymptomatic (less than 80
years of age). Symptomatic subjects will have experienced an event within
the previous 120 days in the ipsilateral carotid artery distribution. The
event will be classified as either 1) one or more TIAs, characterized by
distinct focal neurologic dysfunction or monocular blindness with clearing
of signs and symptoms within 24 hours, or 2) 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).

**Patients with major non-hemorrhagic strokes will be included if their
clinical status has been stable for 5 days (based on an exam performed by a
neurologist participating as a Co-Investigator in this trial).

- If an angiogram is performed to qualify the subject, it should be as recent
as feasible and will not be acceptable if done > 120 days from study entry.
Angiograms from other institutions will be acceptable.

- Other non-invasive qualifying imaging modalities include:

1. Duplex ultrasound (DU) performed at UPMC Presbyterian or Shadyside hospitals.

2. Magnetic Resonance Angiography (MRA) performed at UPMC Presbyterian or Shadyside
hospitals.

3. Computed Tomographic Angiography (CTA) performed at UPMC Presbyterian or
Shadyside hospitals.

- The degree of stenosis from these non-invasive studies has to be confirmed
on the pre-deployment diagnostic angiography prior to proceeding with stent
deployment.

- However, if two of the non-invasive studies listed above report a stenosis
of >70%, AND the pre-deployment angiogram reveals a 50 -70% stenosis, the
patient will be randomized and entered into the trial as the angiogram can
on occasion underestimate the stenosis.

- Female subjects of childbearing potential must have a documented
negative pregnancy test during the index hospitalization.

- The subject must sign a written informed consent, prior to the
procedure, using a form that is approved by the local Institutional
Review Board or Medical Ethics Committee.

- If a patient's creatinine is 3.5 or greater, their nephrologist must
clear them to participate in the trial.

Exclusion Criteria:

- To participate in this study, the subject may NOT HAVE any of the following at
enrollment to the study:

- The subject has had an intracranial hemorrhage, hemorrhagic stroke, or any
stroke with mass effect demonstrated on CT scan or MRI within 30 days of the
index procedure.

- The subject has a persisting ischemic stroke (defined as either a score > 15 on
the NIH stroke scale, a Rankin score > 3 or a Barthel score < 60 measured within
one week prior to study entry).

- The subject has an intracranial mass lesion (i.e., abscess, tumor, or other
infection).

- The subject has known allergies to heparin, to both ticlopidine and clopidogrel
or to metals used in stents.

- There is any visual angiographic evidence of intraluminal thrombus thought to
increase the risk of plaque fragmentation and distal embolization.

- The subject has peripheral vascular, supra-aortic or internal carotid artery
tortuosity precluding use of catheter-based techniques required for successful
results.

- The subject, if female, has a positive pregnancy test.

- The subject has an arterio-venous malformation in the territory of the target
carotid artery.

- Subjects with highly calcified lesions resistant to predilation by PTA

- The subject has unstable angina (defined as Class IV or at rest), evolving MI or
recent MI (within 14 days).

- The subject has any condition that precludes adequate local hemostasis.

- Patients who are not candidates for MRI scanning (pacemaker, etc).