Carotid Artery Diseases, Carotid Artery Plaque, Carotid Atherosclerosis, Carotid Disease, Carotid Stenosis
Conditions
Brief summary
The goal of this evaluation is to document the incidence of post procedure DW-MRI lesions (relative to baseline) in patients treated with the transcarotid artery revascularization (TCAR) procedure.
Detailed description
This is a prospective, single-arm, multi-center evaluation of patients requiring carotid revascularization who are treated with the FDA-cleared ENROUTE Transcarotid NPS in conjunction with the FDA-approved ENROUTE Transcarotid Stent System. Both the ENROUTE Transcarotid NPS and ENROUTE Transcarotid Stent System have received CE mark and are commercially available in the European Union. Patients enrolled in this study will have been offered the TCAR intervention as part of standard of care for the treatment of carotid artery stenosis, regardless of whether or not they agree to be in the study. Therefore, the act of participation in this procedure will not be the determining factor in whether or not the patient receives the TCAR treatment. Subject participation means they agree to undergo two additional DW-MRI imaging procedures immediately after the procedure and at 30 days to determine whether there is an increase in new white lesions. Any other procedure other than the active collection of consent and data by the sponsor is standard of care for the treatment of carotid artery stenosis. These patients will be monitored to document the incidence of post procedure DW-MRI lesions (relative to baseline).
Interventions
PROCEDURETranscarotid Revascularization (TCAR)
Carotid revascularization treated with the FDA-cleared ENROUTE Transcarotid NPS in conjunction with the FDA-approved ENROUTE Transcarotid Stent
Sponsors
Silk Road Medical
Study design
Observational model
CASE_ONLY
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Stenosis must be \>50% as determined by ultrasound or angiogram1 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 ipsilateral to the carotid artery to be stented. * Stenosis must be \>80% as determined by ultrasound or angiogram without any neurological symptoms within the prior 180 days. * Target vessel must meet diameter requirements for stent (refer to stent IFU for diameter requirements). * Patient has a discrete lesion located in the internal carotid artery (ICA) with or without involvement of the contiguous common carotid artery (CCA). * Patient is willing to comply with the protocol requirements and return to the treatment center for all required clinical evaluations. * 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. * Patient meets at least one of the surgical high-risk criteria listed in CMS National Coverage Determination (NCD) for Percutaneous Transluminal Angioplasty (20.7)
Exclusion criteria
* Alternative source of cerebral embolus * Patient has chronic atrial fibrillation. * Patient has had 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 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). * Recently (\<60 days) implanted heart valve (either surgically or endovascularly), which is a known source of emboli as confirmed on echocardiogram. * 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. * 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 (less than one-third middle cerebral artery volume). * Patient had hemorrhagic transformation of an ischemic stroke within the past 60 days. * 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. * Patient has an evolving stroke. * Patient has an intracranial tumor. * 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). * Patient has had a TIA or amaurosis fugax within 48 hrs prior to the procedure. * Patient has an isolated hemisphere defined as the ipsilateral middle cerebral artery being supplied only by the ipsilateral internal carotid artery. * Patient has active bleeding diathesis or coagulopathy or will refuse blood transfusion. * Patient had or will have CABG, endovascular stent procedure, valve intervention or vascular surgery within 30 days before or after the intervention. * Myocardial Infarction within 72 hours prior to the intervention. * Occlusion 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. * Patients with carotid string sign (a very high-grade carotid stenosis to the skull base with a long, thin, barely visible string of contrast within the true lumen of the artery.). * Ostium of Common Carotid Artery (CCA) requires revascularization (\>50% stenosis). * Patient has an open stoma in the neck. * Patients with hostile necks due to prior neck irradiation * Female patients who are pregnant * 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, prasugrel, statin or contrast media (that can't be pre medicated). Patients must be able to tolerate statins and a combination of ASA and ticlopidine, ASA and clopidogrel or ASA and prasugrel. * Patient has a life expectancy \<3 years with 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. * Patient has had a recent GI bleed that would interfere with antiplatelet therapy. * Patient is actively participating in an investigational drug or device trial (IND or IDE) that has not completed the required protocol follow-up period. * Patient has inability to understand and cooperate with study procedures. * Presence of extensive or diffuse atherosclerotic disease involving the proximal common carotid artery that would preclude the safe introduction of the study device. * Patient is otherwise unsuitable for intervention in the opinion of the physician. * Patients who cannot have MRI due to metallic implants (e.g. orthopedic implants, pacemakers, etc.)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Ipsilateral New White Lesions, by Patient | Between 12-60 hours after procedure end time to 30 days post-procedure. | Number of Participants with new white lesions from baseline (pre-procedure) by Diffusion-Weighted Magnetic Resonance Imaging (DW-MRI) between 12-60 hours after procedure end time up to 30 days post-procedure. |
| Incidence of Ipsilateral Persistent Lesions, by Patient | 30-days | Number of participants at 30 day post-procedure with persistent ipsilateral new white lesions post-procedure by Diffusion-Weighted Magnetic Resonance Imaging (DW-MRI). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Location of DW-MRI Lesions | 30-day | Number persistent new white lesions post-procedure by location by Diffusion-Weighted Magnetic Resonance Imaging (DW-MRI) at 30-Days, categorized by location. |
| All Stroke and Neurological Death | 0 to 30 days | Number of Participants who experienced Stroke or Neurological death between 12-60 hours after procedure end time up to 30 days post-procedure. |
| Rate of Contralateral New White Lesions by Diffusion-Weighted Magnetic Resonance Imaging (DW-MRI), by Patient | 30-day | Subjects with persistent contralateral new white lesions post-procedure by Diffusion-Weighted Magnetic Resonance Imaging (DW-MRI), at 30-Days. |
| Stroke/Neurological Death in Patients Eligible and Ineligible for ROADSTER 2 | 0 to 30-day | No patients enrolled in this study were enrolled in ROADSTER 2 trial; therefore, ROADSTER 2 specific endpoints were not evaluated. |
| Volume of DW-MRI White Lesions | 30-days | Volume of Persistent new white lesions post-procedure by Diffusion-Weighted Magnetic Resonance Imaging (DW-MRI) at 30-Days. |
Countries
Spain, United States
Participant flow
Pre-assignment details
Patients were considered enrolled after signing the informed consent and having undergone a successful Transcarotid artery revascularization (TCAR) procedure (e.g., the procedure was not aborted due to technical issues or due to local complications that precluded stent implantation). Patients who were screened but did not meet all study criteria were considered screen failures and were not enrolled.
Participants by arm
| Arm | Count |
|---|---|
| Single-arm Patients requiring carotid revascularization who were treated with the FDA-cleared ENROUTE Transcarotid NPS in conjunction with the FDA-approved ENROUTE Transcarotid Stent System. | 55 |
| Total | 55 |
Baseline characteristics
| Characteristic | Single-arm |
|---|---|
| Age, Customized ≤64 Years Old | 6 Participants |
| Age, Customized 65-69 Years old | 9 Participants |
| Age, Customized 70-74 Years old | 19 Participants |
| Age, Customized 75-79 Years old | 11 Participants |
| Age, Customized ≥80 Years old | 10 Participants |
| Height (cm) | 169.5 CM STANDARD_DEVIATION 9.63 |
| High Risk Factors ≥2-vessel coronary artery disease and history of angina No | 47 Participants |
| High Risk Factors ≥2-vessel coronary artery disease and history of angina Yes | 8 Participants |
| High Risk Factors ≥75 years of age No | 34 Participants |
| High Risk Factors ≥75 years of age Yes | 21 Participants |
| High Risk Factors Bilateral carotid artery stenosis requiring treatment No | 55 Participants |
| High Risk Factors Bilateral carotid artery stenosis requiring treatment Yes | 0 Participants |
| High Risk Factors Congestive heart failure (CHF), NYHA Functional Class III or IV No | 53 Participants |
| High Risk Factors Congestive heart failure (CHF), NYHA Functional Class III or IV Yes | 2 Participants |
| High Risk Factors Contralateral carotid artery occlusion No | 48 Participants |
| High Risk Factors Contralateral carotid artery occlusion Yes | 7 Participants |
| High Risk Factors High cervical carotid artery stenosis No | 32 Participants |
| High Risk Factors High cervical carotid artery stenosis Yes | 23 Participants |
| High Risk Factors History of angina, unstable or CCS of 3 or 4 No | 53 Participants |
| High Risk Factors History of angina, unstable or CCS of 3 or 4 Yes | 2 Participants |
| High Risk Factors Hostile Necks safe for transcarotid access No | 54 Participants |
| High Risk Factors Hostile Necks safe for transcarotid access Yes | 1 Participants |
| High Risk Factors Hostile Necks safe for transcarotid access Cervical spine immobility No | 50 Participants |
| High Risk Factors Hostile Necks safe for transcarotid access Cervical spine immobility Yes | 5 Participants |
| High Risk Factors Hostile Necks safe for transcarotid access Radical neck dissection No | 53 Participants |
| High Risk Factors Hostile Necks safe for transcarotid access Radical neck dissection Yes | 2 Participants |
| High Risk Factors Myocardial infarction >72 hours and <6 weeks prior to the procedure No | 55 Participants |
| High Risk Factors Myocardial infarction >72 hours and <6 weeks prior to the procedure Yes | 0 Participants |
| High Risk Factors Patient has chronic renal insufficiency No | 53 Participants |
| High Risk Factors Patient has chronic renal insufficiency Yes | 2 Participants |
| High Risk Factors Permanent contralateral cranial nerve injury No | 54 Participants |
| High Risk Factors Permanent contralateral cranial nerve injury Yes | 1 Participants |
| High Risk Factors Restenosis after carotid endarterectomy No | 44 Participants |
| High Risk Factors Restenosis after carotid endarterectomy Yes | 11 Participants |
| High Risk Factors Severe left ventricular dysfunction: LVEF <30% No | 55 Participants |
| High Risk Factors Severe left ventricular dysfunction: LVEF <30% Yes | 0 Participants |
| High Risk Factors Severe pulmonary disease (COPD) No | 52 Participants |
| High Risk Factors Severe pulmonary disease (COPD) Yes | 3 Participants |
| High Risk Factors Tandem stenoses >70% No | 53 Participants |
| High Risk Factors Tandem stenoses >70% Yes | 2 Participants |
| Race/Ethnicity, Customized Black or African American | 4 Participants |
| Race/Ethnicity, Customized Caucasian | 35 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 15 Participants |
| Race/Ethnicity, Customized Unknown | 1 Participants |
| Sex: Female, Male Female | 20 Participants |
| Sex: Female, Male Male | 35 Participants |
| Subjects with Multiple High-Risk Criteria. Number of High-Risk Factors 0 High-Risk Factors | 0 Participants |
| Subjects with Multiple High-Risk Criteria. Number of High-Risk Factors 1 High-Risk Factors | 30 Participants |
| Subjects with Multiple High-Risk Criteria. Number of High-Risk Factors 2 High-Risk Factors | 18 Participants |
| Subjects with Multiple High-Risk Criteria. Number of High-Risk Factors 3 or More High-Risk Factors | 7 Participants |
| Weight (kg) | 81.9 kg STANDARD_DEVIATION 13.48 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 55 |
| other Total, other adverse events | 0 / 55 |
| serious Total, serious adverse events | 0 / 55 |
Outcome results
Primary
Incidence of Ipsilateral New White Lesions, by Patient
Number of Participants with new white lesions from baseline (pre-procedure) by Diffusion-Weighted Magnetic Resonance Imaging (DW-MRI) between 12-60 hours after procedure end time up to 30 days post-procedure.
Time frame: Between 12-60 hours after procedure end time to 30 days post-procedure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Single-arm | Incidence of Ipsilateral New White Lesions, by Patient | 12 Participants |
Primary
Incidence of Ipsilateral Persistent Lesions, by Patient
Number of participants at 30 day post-procedure with persistent ipsilateral new white lesions post-procedure by Diffusion-Weighted Magnetic Resonance Imaging (DW-MRI).
Time frame: 30-days
Population: 3 patients did not complete the 30-day DW-MRI.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Single-arm | Incidence of Ipsilateral Persistent Lesions, by Patient | 3 Participants |
Secondary
All Stroke and Neurological Death
Number of Participants who experienced Stroke or Neurological death between 12-60 hours after procedure end time up to 30 days post-procedure.
Time frame: 0 to 30 days
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Single-arm | All Stroke and Neurological Death | Stroke | Yes | 0 Participants |
| Single-arm | All Stroke and Neurological Death | Stroke | No | 55 Participants |
| Single-arm | All Stroke and Neurological Death | Neurological Death | Yes | 0 Participants |
| Single-arm | All Stroke and Neurological Death | Neurological Death | No | 55 Participants |
Secondary
Location of DW-MRI Lesions
Number persistent new white lesions post-procedure by location by Diffusion-Weighted Magnetic Resonance Imaging (DW-MRI) at 30-Days, categorized by location.
Time frame: 30-day
Population: Out of the 55 subjects who participated in this study, 3 participants had a total of 5 persistence white lesions located in the Middle Cerebral Artery at 30 days.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Single-arm | Location of DW-MRI Lesions | Middle Cerebral Artery (MCA) Territory - Persistent 30-day lesion | 5 Lesion |
| Single-arm | Location of DW-MRI Lesions | Posterior Cerebral Artery (PCA) Territory - Persistent 30-day lesion | 0 Lesion |
| Single-arm | Location of DW-MRI Lesions | Anterior Cerebral Artery (ACA) Territory - Persistent 30-day lesion | 0 Lesion |
Secondary
Rate of Contralateral New White Lesions by Diffusion-Weighted Magnetic Resonance Imaging (DW-MRI), by Patient
Subjects with persistent contralateral new white lesions post-procedure by Diffusion-Weighted Magnetic Resonance Imaging (DW-MRI), at 30-Days.
Time frame: 30-day
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Single-arm | Rate of Contralateral New White Lesions by Diffusion-Weighted Magnetic Resonance Imaging (DW-MRI), by Patient | 0 Participants |
Secondary
Stroke/Neurological Death in Patients Eligible and Ineligible for ROADSTER 2
No patients enrolled in this study were enrolled in ROADSTER 2 trial; therefore, ROADSTER 2 specific endpoints were not evaluated.
Time frame: 0 to 30-day
Population: None of the patients enrolled in this study were enrolled in ROADSTER 2 study. Therefore, ROADSTER 2 specific endpoints were not evaluated.
Secondary
Volume of DW-MRI White Lesions
Volume of Persistent new white lesions post-procedure by Diffusion-Weighted Magnetic Resonance Imaging (DW-MRI) at 30-Days.
Time frame: 30-days
Population: Out of the 55 subjects who participated in this study, 3 participants had a total of 5 persistence white lesions at 30 days. The volume relates to the number of persistent white lesions (5).
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Single-arm | Volume of DW-MRI White Lesions | 0.21 Cubic Centimeter (cc) |