Post-approval Study of Transcarotid Artery Revascularization in Standard Risk Patients With Significant Carotid Artery Disease

Study Overview
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Brief Summary
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The study objective is to evaluate real world usage of the ENROUTE Transcarotid Stent when used with the ENROUTE Transcarotid Neuroprotection System in patients at standard risk for adverse events from carotid endarterectomy

Detailed Description
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This is an open label, single arm, multi-center post-approval study for the treatment of patients at standard risk for adverse events from carotid endarterectomy who require carotid revascularization and who are eligible for treatment using the ENROUTE Transcarotid Stent System and the ENROUTE Transcarotid Neuroprotection System. The study will enroll a maximum of 400 patients treated per protocol at 30-60 sites in the United States.

Official Title
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Post-approval Study of Transcarotid Artery Revascularization in Standard Risk Patients With Significant Carotid Artery Disease. The ROADSTER 3 Study

Conditions
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Carotid Artery Diseases

Intervention / Treatment
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* Procedure: Transcarotid Artery Revascularization (TCAR)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient has a discrete lesion located in the internal carotid artery (ICA) with or without involvement of the contiguous common carotid artery (CCA) determined by duplex ultrasound, CT/CTA, MR/MRA or angiography. Patient must meet one of the following criteria regarding neurological symptom status and degree of stenosis: Symptomatic: ≥70% stenosis of the common or internal carotid artery by ultrasound or ≥50% stenosis of the common or internal carotid artery by angiogram OR Asymptomatic: ≥70% stenosis of the common or internal carotid artery by ultrasound or ≥60% stenosis of the common or internal carotid artery by angiogram Target vessel must meet all requirements for ENROUTE Transcarotid Neuroprotection System and ENROUTE Stent System (refer to IFU for requirements). Patient is ≥18 and <80 years of age. 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 of the respective clinical site prior to the study procedure. This will be obtained prior to participation in the study. Patient is willing to comply with the protocol requirements and return to the treatment center for all required clinical evaluations. Exclusion Criteria: Patient meets any of the surgical high-risk criteria listed below. Anatomic high risk exclusion criteria: Contralateral carotid artery occlusion Tandem stenoses in the ICA >70% diameter reducing High cervical carotid artery stenosis above the C2 vertebra Restenosis after prior ipsilateral carotid endarterectomy Bilateral carotid artery stenosis requiring treatment within 30 days after index procedure Hostile Necks including prior neck irradiation, radical neck dissection, and cervical spine immobility Clinical high risk exclusion criteria: Patient is ≥80 years of age Patient has ≥2-vessel coronary artery disease (or has had revascularization procedure within the last 30 days) and/or angina Patient has history of unresolved angina - Canadian Cardiovascular Society (CCS) angina class 3 or 4 OR unstable angina Patient has congestive heart failure (CHF) - New York Heart Association (NYHA) Functional Class III or IV Patient has a known severe left ventricular dysfunction - LVEF <30% Patient has had a myocardial infarction within 6 weeks prior to the procedure Patient has severe obstructive pulmonary disease (COPD) with either: FEVI <50% predicted OR chronic oxygen therapy OR resting PO2 of ≤60 mmHG (room air) Patient has permanent contralateral cranial and/or laryngeal nerve injury Patient has chronic renal insufficiency (serum creatinine ≥2.5 mg/dL) or is on dialysis Patient has an alternative source of cerebral embolus, including but not limited to: Chronic atrial fibrillation. Any episode of paroxysmal atrial fibrillation within the past 6 months, or history of paroxysmal atrial fibrillation requiring chronic anticoagulation. Knowledge of cardiac sources of thrombus. (If patient has 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 AND there is no confirmed thrombus on an echocardiogram performed within 3 months prior to index procedure, the patient may be eligible for enrollment). Recently implanted heart valve (either surgically or endovascularly) within 60 days prior to index procedure with confirmed emboli on echocardiogram. Abnormal angiographic findings: ipsilateral intracranial or extracranial arterial stenosis (as determined by pre-procedure 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. 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. Patient had hemorrhagic transformation of an ischemic stroke within the past 60 days. Patient with a history of major stroke prior to the TCAR procedure attributable to either carotid artery (CVA or retinal embolus) with major neurological deficit (NIHSS ≥5 OR mRS ≥3) likely to confound study endpoints 1 month after the TCAR procedure (because the deficit persists post-operatively). Patient has an intracranial tumor. Patient has an evolving stroke. Patient has neurologic illnesses within the past 2 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. Patient has had a TIA or amaurosis fugax within 48 hrs. prior to the procedure Patient has an isolated hemisphere Patient had or will have open heart (e.g., CABG), endovascular stent procedure, valve intervention, vascular surgery, other major operation within 30 days of the index procedure. Presence of a previous placed intravascular stent in target vessel or ipsilateral CCA or significant CCA inflow lesion. Occlusion or [Thrombolysis in Myocardial Infarction Trial (TIMI 0)] string sign >1cm of the ipsilateral common or internal carotid artery. 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. Ostium of CCA requires revascularization. Patient has an open stoma in the neck. Female patients who are pregnant or may become pregnant. Patient has history of intolerance or allergic reaction to any of the study medications or stent materials (refer to ENROUTE stent IFU), including aspirin (ASA), ticlopidine, clopidogrel, statin or contrast media (that cannot be pre-medicated). Patients must be able to tolerate statins (or a permitted non-statin substitute) and a combination of ASA and ticlopidine or ASA and clopidogrel or alternative P2Y12 inhibitor.. Patient has a life expectancy <5 years without contingencies related to other medical, surgical, or interventional procedures or is at High Risk as per the Wallaert Score. Estimation of life expectancy and scoring per the Wallaert Score is to be performed prior to enrollment. Patient has primary, recurrent or metastatic malignancy and does not have independent assessment of life expectancy of ≥5 years performed by the treating oncologist or an appropriate specialist other than the physician performing TCAR. Patient has an unresolved/uncorrected bleeding disorder. Patient has a known allergy to nitinol Patient is known to have an active SARS-CoV-2 infection (Coronavirus-19 [COVID-19]) or has been previously diagnosed with COVID-19 with neurological sequelae that could confound endpoint assessments (e.g., baseline mRS>3).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 79 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Standard-risk patients requiring carotid intervention<br>Symptomatic or asymptomatic patients with a discrete lesion located in the internal carotid artery (ICA) with or without involvement of the contiguous common carotid artery (CCA), who require carotid artery revascularization. | Procedure: Transcarotid Artery Revascularization (TCAR)<br>* Carotid artery revascularization treated with the FDA-cleared ENROUTE Transcarotid NPS in conjunction with the FDA-approved ENROUTE Transcarotid Stent<br>* Other names: Carotid Artery Stenting;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hierarchical composite of Major Adverse Events (MAEs) | Hierarchical composite of Major Adverse Events (MAEs) defined as any death, stroke, or myocardial infarction within 30 days of the index procedure | within 30 days of the index procedure | 
| Ipsilateral Stroke | Ipsilateral stroke within 31 days to 365 days following the index procedure | within 31 to 365 days following the index procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of cranial nerve injury | Incidence of cranial nerve injury within 30 days of the index procedure | within 30 days of the index procedure | 
| Stroke | Stroke within 30 days of the index procedure | within 30 days of the index procedure | 
| Death | Death within 30 days of the index procedure | within 30 days of the index procedure | 
| MI | MI within 30 days of the index procedure | within 30 days of the index procedure | 
| Stroke/Death/MI | Stroke/Death/MI within 30 days of the index procedure | within 30 days of the index procedure | 
| Ipsilateral Stroke | Ipsilateral stroke within 31 to 365 days of the index procedure | 31-365 days | 
| Persistent cranial nerve injury | Persistent cranial nerve injury at 6 months and 1 year | at 6 months and 1 year | 
| Rate of hierarchical ipsilateral stroke, death, and myocardial infarction | Rate of hierarchical ipsilateral stroke, death, and myocardial infarction within 30 days of the index procedure | within 30 days of the index procedure | 
| Cardiac death | Cardiac death at 1 year for patients who experienced an MI within 30 days of the index procedure | 1 year | 
| Access site complications | Access site complications (arterial/venous) | within 30 days of the index procedure | 
| Serious Hematoma/Bleeding complications | Serious Hematoma/Bleeding complications (arterial/venous) | within 30 days of the index procedure | 
| Rate of stent thrombosis or occlusion | Rate of stent thrombosis or occlusion within 30 days of the index procedure | within 30 days of the index procedure | 
| Rate of dissection | Rate of dissection within 30 days of the index procedure (during index procedure or a reintervention procedure) | within 30 days of the index procedure |