POST-APPROVAL STUDY of TRANSCAROTID ARTERY REVASCULARIZATION in PATIENTS With SIGNIFICANT CAROTID ARTERY DISEASE

POST-APPROVAL STUDY of TRANSCAROTID ARTERY REVASCULARIZATION in PATIENTS With SIGNIFICANT CAROTID ARTERY DISEASE. The ROADSTER 2 Study.

The ROADSTER 2 Study is intended to evaluate real world usage of the ENROUTE Transcarotid Stent when used with the ENROUTE Transcarotid Neuroprotection System by physicians of varying experience with the transcarotid technique.

INCLUSION CRITERIA:

1. Patient must meet one of the following criteria regarding neurological symptom status and degree of stenosis:

   Symptomatic: Stenosis must be >50% as determined by an angiogram and the patient has a history of stroke (minor or non-disabling; NIHSS ≤4 or mRS ≤2), TIA and/or amaurosis fugax within 180 days of the procedure procedure ipsilateral to the carotid artery to be stented.

   OR Asymptomatic: Stenosis must be >80% as determined by angiogram without any neurological symptoms within the prior 180 days.

2. Target vessel must meet all requirements for ENROUTE Transcarotid Neuroprotection System and ENROUTE Stent System (refer to IFU for requirements).

3. Patient has a discrete lesion located in the internal carotid artery (ICA) with or without involvement of the contiguous common carotid artery (CCA).

4. Patient is ≥18 years of age.

5. Patient understands the nature of the procedure and has provided a signed informed consent using a form that has been reviewed and approved by the Institutional Review Board/Ethics Committee of the respective clinical site prior to the procedure. This will be obtained prior to participation in the study.

6. Patient is willing to comply with the protocol requirements and return to the treatment center for all required clinical evaluations.

7. Patient must have a life expectancy ≥ 3 years at the time of the index procedure without contingencies related to other medical, surgical or endovascular intervention.

8. Patient meets at least one of the surgical high-risk criteria listed below.

Anatomic High Risk Inclusion Criteria:

A. Contralateral carotid artery occlusion B. Tandem stenoses >70% C. High cervical carotid artery stenosis D. Restenosis after carotid endarterectomy E. Bilateral carotid artery stenosis requiring treatment within 30 days after index treatment.

F. Hostile Necks which the Investigator deems safe for transcarotid access including but not limited to:

I. Prior neck irradiation II. Radical neck dissection III. Cervical spine immobility

Clinical High Risk Inclusion Criteria:

G. Patient is > 75 years of age H. Patient has > 2-vessel coronary artery disease and history of angina of any severity I. Patient has a history of angina

• Canadian Cardiovascular Society (CCS) angina class 3 or 4 or
• unstable angina

J. Patient has congestive heart failure (CHF) - New York Heart Association (NYHA)

• Functional Class III or IV

K. Patient has known severe left ventricular dysfunction

• LVEF <30%.

L. Patient has had a myocardial infarction > 72 hours and < 6 weeks prior to procedure.

M. Patient has severe pulmonary disease (COPD) with either:

• FEV1 <50% predicted or
• chronic oxygen therapy or
• resting PO2 of <60 mmHg (room air)

N. Patient has permanent contralateral cranial nerve injury O. Patient has chronic renal insufficiency (serum creatinine > 2.5 mg/dL).

REMINDER: The following is a list of anatomical considerations that are not suitable for transfemoral CAS with distal protection that are NOT contraindications for enrollment in the ROADSTER 2 Study including but not limited to:

I. TypeII, III, or Bovine arch II. Arch atheroma or calcification III. Atheroma of the great vessel origins IV. Tortuous distal ICA V. Tortuous or occluded iliofemoral segments VI. Occluded aortoiliac segments

EXCLUSION CRITERIA:

Each potential patient 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. Patient has an alternative source of cerebral embolus, including but not limited to:

   1. Patient has chronic atrial fibrillation.
   2. Patient has had any episode of paroxysmal atrial fibrillation within the past 6 months, or history of paroxysmal atrial fibrillation requiring chronic anticoagulation.
   3. Knowledge of cardiac sources of emboli. e.g. left ventricular aneurysm, intracardiac filling defect, cardiomyopathy, aortic or mitral prosthetic heart valve, calcific aortic stenosis, endocarditis, mitral stenosis, atrial septal defect, atrial septal aneurysm, or left atrial myxoma).
   4. Recently (<60 days) implanted heart valve (either surgically or endovascularly), which is a known source of emboli as confirmed on echocardiogram.
   5. Abnormal angiographic findings: ipsilateral intracranial or extracranial arterial stenosis (as determined by angiography or CTA/MRA ≤ 6 months prior to index procedure) greater in severity than the lesion to be treated, cerebral aneurysm > 5 mm, AVM (arteriovenous malformation) of the cerebral vasculature, or other abnormal angiographic findings.

2. Patient has a history of spontaneous intracranial hemorrhage within the past 12 months, or has had a recent (<7 days) stroke of sufficient size (on CT or MRI) to place him or her at risk of hemorrhagic conversion during the procedure.

3. Patient had hemorrhagic transformation of an ischemic stroke within the past 60 days.

4. Patient with a history of major stroke attributable to either carotid artery (CVA or retinal embolus) with major neurological deficit (NIHSS ≥ 5 OR mRS ≥ 3) likely to confound study endpoints within 1 month of index procedure.

5. Patient has an intracranial tumor.

6. Patient has an evolving stroke.

7. Patient has neurologic illnesses within the past two years characterized by fleeting or fixed neurologic deficit which cannot be distinguished from TIA or stroke, including but not limited to: moderate to severe dementia, partial or secondarily generalized seizures, complicated or classic migraine, tumor or other space-occupying brain lesions, subdural hematoma, cerebral contusion or other post-traumatic lesions, intracranial infection, demyelinating disease, or intracranial hemorrhage).

8. Patient has had a TIA or amaurosis fugax within 48 hrs prior to the procedure.

9. Patient has an isolated hemisphere.

10. Patient had or will have CABG, endovascular stent procedure, valve intervention or vascular surgery within 30 days before or after the intervention.

11. Myocardial Infarction within 72 hours prior to the intervention.

12. Presence of a previous placed intravascular stent in target vessel or ipsilateral CCA or significant CCA inflow lesion.

13. Occlusion or [Thrombolysis In Myocardial Infarction Trial (TIMI 0)] "string sign" >1cm of the ipsilateral common or internal carotid artery.

14. An intraluminal filling defect (defined as an endoluminal lucency surrounded by contrast, seen in multiple angiographic projections, in the absence of angiographic evidence of calcification) whether or not it is associated with an ulcerated target lesion.

15. Ostium of Common Carotid Artery (CCA) requires revascularization.

16. Patient has an open stoma in the neck.

17. Female patients who are pregnant or may become pregnant.

18. Patient has history of intolerance or allergic reaction to any of the study medications or stent materials (refer to stent IFU), including aspirin (ASA), ticlopidine, clopidogrel, statin or contrast media (that can't be pre medicated). Patients must be able to tolerate statins and a combination of ASA and ticlopidine or ASA and clopidogrel.

19. Patient must have a life expectancy <3 years without contingencies related to other medical, surgical, or interventional procedures as per the Wallaert Score and patients with primary, recurrent or metastatic malignancy who do not have independent assessment of life expectancy performed by the treating oncologist or an appropriate specialist other than the physician performing TCAR.