Protection Against Emboli During Carotid Artery Stenting Using the Neuroguard IEP System
Protection Against Emboli During Carotid Artery Stenting Using the Neuroguard IEP System
A prospective, multicenter single-arm, open label study to evaluate the safety and
 effectiveness of the Neuroguard IEP System for the treatment of carotid artery stenosis in
 subjects at elevated risk for adverse events following carotid endarterectomy (CEA). The
 Neuroguard IEP System is a 3-in-1 carotid stent delivery system consisting of an angioplasty
 balloon, an integrated embolic protection device and a nitinol self-expanding stent loaded
 over the balloon and constrained by an outer sheath. Eligible patients between 20 and 80
 years of age have been diagnosed with either de-novo atherosclerotic or post CEA restenotic
 lesion(s) in the internal carotid arteries (ICA) or at the carotid bifurcation with ≥50%
 stenosis if symptomatic or ≥80% stenosis if asymptomatic (both defined by angiography using
 NASCET methodology). Symptomatic patients are defined as having stroke or TIA ipsilateral to
 the carotid lesion within 180 days of the procedure within the hemisphere supplied by the
 target vessel. Enrolled subjects will be followed at 30 days, 6 months, 12 months, 24 months
 and 36 months.
Inclusion Criteria:

 General Inclusion Criteria

 1. Male and non-pregnant female subjects whose age is ≥ 20 years and ≤ 80.

 2. Patient is willing and capable of complying with all study protocol requirements,
 including the specified follow-up visits and can be contacted by telephone.

 3. Patient or his/her authorized legal representative must sign a written informed
 consent form that has been approved by the local governing Institutional Review Board
 (IRB)/ Ethics Committee (EC) of the respective clinical site.

 4. Patient is diagnosed with carotid artery stenosis treatable with carotid artery
 stenting and is considered a high operative risk for CEA.

 5. Patient is diagnosed with either:

 1. Symptomatic carotid stenosis ≥ 50% as determined by angiography using NASCET
 methodology. Symptomatic is defined as ipsilateral transient monocular blindness:
 amaurosis fugax; ipsilateral carotid transient ischemic attack (TIA), with
 neurologic symptoms persisting less than 24 hours; or ipsilateral non-disabling
 stroke within 180 days of the procedure; or

 2. Asymptomatic carotid stenosis ≥ 80% as determined by angiography using NASCET
 methodology.

 6. Patient has a modified Rankin Scale score of ≤ 2 at the time of informed consent.

 7. Patient is willing and able to take dual antiplatelet therapy for a minimum of 30
 days.

 Angiographic Inclusion Criteria

 1. Target lesion located at the carotid bifurcation and/or proximal internal carotid
 artery (ICA).

 2. Single de novo or restenotic (post carotid endarterectomy (CEA)) target lesion or
 severe tandem lesions that can be covered by a single Neuroguard stent.

 3. Target lesion length is ≤ 20 mm (for 30 mm stents) or is ≤ 30 mm (for 40 mm stents)

 4. Index vessel diameter (segment covered by the mid-portion of the stent) between 4.0 mm
 and 6.0 mm at the site of the target lesion.

 5. Distal vessel diameter at the site of filter deployment is between 4.0 mm to 7.0 mm.

 6. Distal common carotid artery diameter (segment covered by proximal portion of the
 stent) between 4.0 mm and 8.0 mm

 7. Sufficient landing zone exists in the cervical internal carotid artery distal to the
 target lesion to allow for the safe and successful deployment of both the primary
 embolic protection filter and the Neuroguard integrated filter.

 High Risk for CEA Conditions For inclusion in the study, a patient must meet at least one
 significant anatomic or comorbid high risk conditions listed below. Patients at high risk
 for CEA are defined as having significant comorbidities and/or anatomic risk factors and
 would be poor candidates for carotid endarterectomy (CEA) in the opinion of a physician.

 High Anatomic Risk for CEA Conditions

 1. Target lesion at or above C2 (level of jaw) or below the clavicle.

 2. Inability to extend the head due to cervical arthritis or other cervical disorders.

 3. History of radiation treatment to the neck or radical neck dissection

 4. Prior head and neck surgery in the region of the carotid artery.

 5. Spinal immobility of the neck.

 6. Tracheostomy or tracheostoma.

 7. Hostile neck or surgically inaccessible lesion

 8. Laryngeal palsy or laryngectomy.

 9. Severe tandem lesions (total length must be ≤ 30 mm and must be covered with one
 stent).

 10. Occlusion of the contralateral CCA or ICA.

 11. Severe bilateral ICA stenosis requiring treatment.

 High Co-morbid Risk Conditions for CEA

 1. Patient is ≥ 70 years of age (maximum 80 years) at the time of enrollment.

 2. NYHA Class III or IV congestive heart failure (CHF)

 3. Chronic obstructive pulmonary disease (COPD) with FEV1 < 50

 4. Left ventricular ejection fraction (LVEF) ≤ 35%

 5. Unstable angina

 6. History of recent MI (Between 14 days and 6 weeks prior to index the procedure)

 7. Coronary artery disease with two or more vessels with ≥ 70% stenosis

 8. Planned coronary artery bypass grafting (CABG) or valve replacement surgery between 31
 - 60 days after CAS procedure

 9. Peripheral vascular surgery or abdominal aortic aneurysm repair is required between 31
 - 60 days following CAS procedure

 10. Contralateral laryngeal nerve paralysis

 11. Restenosis following a prior carotid endarterectomy (CEA).

 Exclusion Criteria:

 1. Life expectancy of less than one year, cancer with metastatic spread and/or undergoing
 active chemotherapy treatment, or currently requiring an organ transplantation.

 2. An evolving, acute, or recent disabling stroke in the last 30 days.

 3. Anticipated or potential 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,
 known previously symptomatic PFO, left atrial thrombus, any intracardiac mass or DVT
 or PE treated within the past 12 months.

 4. History of paroxysmal atrial fibrillation that requires chronic anticoagulation

 5. History of chronic atrial fibrillation.

 6. Anticoagulation with Phenprocoumon (Marcumar®), warfarin, or a direct thrombin
 inhibitor, or anti-Xa agents.

 7. Acute myocardial infarction < 14 days prior to index procedure.

 8. Any major surgical procedure (i.e. intraabdominal or intrathoracic surgery or any
 surgery / interventional procedure involving cardiac or vascular system) 30 days prior
 to or following the index procedure.

 9. History of major disabling stroke with substantial residual disability (modified
 Rankin score ≥ 3)

 10. Known severe carotid stenosis or complete occlusion contralateral to the target lesion
 requiring treatment within 30 days of the index procedure.

 11. Other neurological deficit not due to stroke that may confound the neurological
 assessments.

 12. Dementia considered other than mild.

 13. Known hypersensitivity to nitinol or its components (e.g. nickel, titanium).

 14. History of intracranial hemorrhage within 90 days prior to the index procedure.

 15. History of GI bleed within 30 days prior to the index procedure

 16. Chronic renal insufficiency (serum creatinine ≥ 2.5 ml/dL or estimated GFR < 30
 cc/min)

 17. History of severe hepatic impairment, malignant hypertension, and/or is morbidly
 obese.

 18. Known hypersensitivity to contrast media that cannot be adequately premedicated.

 19. Hemoglobin (Hgb) < 8 gm/dL, platelet count < 100,000, INR > 1.5 (irreversible), or
 heparin-induced thrombocytopenia.

 20. History or current indication of bleeding diathesis or coagulopathy including
 thrombocytopenia or an inability to receive heparin in amounts sufficient to maintain
 an activated clot time at > 250 seconds

 21. Contraindication to standard of care study medications, including antiplatelet therapy
 or aspirin.

 22. Currently enrolled in another interventional device or drug study that has not yet
 reached the primary endpoint.

 Angiographic Exclusion Criteria

 1. Total occlusion of the target carotid artery.

 2. Previously placed stent in the ipsilateral carotid artery.

 3. Severe calcification or vascular tortuosity of the target vessel that may preclude the
 safe introduction of the sheath, guiding catheter, integrated EPD or stent. Severe
 vascular tortuosity is defined as 2 or more bends of 90 degrees or more within 4 cm of
 the target lesion.

 4. Qualitative characteristics of stenosis and stenosis-length of carotid bifurcation
 (common carotid) and/or ipsilateral external carotid artery, that preclude the safe
 introduction of the sheath.

 5. Angulation or tortuosity (≥ 90 degree) of the innominate and common carotid artery
 (CCA) that precludes safe, expeditious sheath placement or that will transmit a severe
 loop to the internal carotid after sheath placement.

 6. Angiographic evidence of a mobile filling defect or fresh thrombus in the target
 carotid artery.

 7. Presence of "string sign" of the target lesion (a tiny, long segment of contrast in
 the true lumen of the artery).

 8. Non-atherosclerotic carotid stenosis (e.g. dissection, fibromuscular dysplasia)

 9. Proximal/ostial CCA, innominate stenosis, or intracranial stenosis located distal to
 the target stenosis that is more severe that target stenosis. Excessive
 circumferential calcification of the target lesion is defined as > 3 mm of thickness
 of calcification seen in orthogonal views on fluoroscopy.

 10. Patient in whom femoral access is not possible. Furthermore, occlusive or critical
 iliofemoral disease, including severe tortuosity or stenosis that requires additional
 endovascular procedures to facilitate aortic arch access or that prevents safe and
 expeditious femoral access to the aortic arch.

 11. Arteriovenous malformations of the territory of the target carotid artery and cerebral
 vasculature.

 12. Known mobile plaque or thrombus in the aortic arch.

 13. Type III aortic arch.

 14. Angiographic, CT, MR or ultrasound evidence of severe atherosclerosis, tortuosity or
 angulation 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.