Clinical trial NCT05365490: Post-approval Study of Transcarotid Artery Revascularization in Standard Risk Patients With Significant Carotid Artery Disease
Official title: Post-approval Study of Transcarotid Artery Revascularization in Standard Risk Patients With Significant Carotid Artery Disease. The ROADSTER 3 Study
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Carotid Artery Diseases
Lead sponsor: Silk Road Medical
Sponsor class: INDUSTRY
First posted: 2022-05-09
Enrollment: 344
Sex: ALL
Minimum age (years): 18
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patient with 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.

-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

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. 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.
2. 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
3. Target vessel must meet all requirements for ENROUTE Transcarotid Neuroprotection System and ENROUTE Stent System (refer to IFU for requirements).
4. Patient is ≥18 and \<80 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 of the respective clinical site prior to the study 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.

Exclusion Criteria:

1. Patient meets any of the surgical high-risk criteria listed below.

   1. 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
   2. 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
2. Patient has an alternative source of cerebral embolus, including but not limited to:

   1. Chronic atrial fibrillation.
   2. 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 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).
   4. Recently implanted heart valve (either surgically or endovascularly) within 60 days prior to index procedure with confirmed emboli on echocardiogram.
   5. 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.
3. 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.
4. Patient had hemorrhagic transformation of an ischemic stroke within the past 60 days.
5. 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).
6. Patient has an intracranial tumor.
7. Patient has an evolving stroke.
8. 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.
9. Patient has had a TIA or amaurosis fugax within 48 hrs. prior to the procedure
10. Patient has an isolated hemisphere
11. 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.
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 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 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..
19. 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.
20. 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.
21. Patient has an unresolved/uncorrected bleeding disorder.
22. Patient has a known allergy to nitinol
23. 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).

Primary outcomes:
measure: Hierarchical composite of Major Adverse Events (MAEs)
timeFrame: within 30 days of the index procedure
measure: Ipsilateral Stroke
timeFrame: within 31 to 365 days following the index procedure
Secondary outcomes:
measure: Incidence of cranial nerve injury
timeFrame: within 30 days of the index procedure
measure: Stroke
timeFrame: within 30 days of the index procedure
measure: Death
timeFrame: within 30 days of the index procedure
measure: MI
timeFrame: within 30 days of the index procedure
measure: Stroke/Death/MI
timeFrame: within 30 days of the index procedure
measure: Ipsilateral Stroke
timeFrame: 31-365 days
measure: Persistent cranial nerve injury
timeFrame: at 6 months and 1 year
measure: Rate of hierarchical ipsilateral stroke, death, and myocardial infarction
timeFrame: within 30 days of the index procedure
measure: Cardiac death
timeFrame: 1 year
measure: Access site complications
timeFrame: within 30 days of the index procedure
measure: Serious Hematoma/Bleeding complications
timeFrame: within 30 days of the index procedure
measure: Rate of stent thrombosis or occlusion
timeFrame: within 30 days of the index procedure
measure: Rate of dissection
timeFrame: within 30 days of the index procedure
Other outcomes:
Locations:
city: Huntsville
country: United States
facility: Valley Vascular Consultants
state: Alabama
city: Scottsdale
country: United States
facility: HonorHealth
state: Arizona
city: Tucson
country: United States
facility: Pima Heart & Vascular
state: Arizona
city: La Jolla
country: United States
facility: University of California, San Diego (UCSD)
state: California
city: La Mesa
country: United States
facility: Sharp Grossmont
state: California
city: Los Angeles
country: United States
facility: University of California, Los Angeles (UCLA)
state: California
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Washington
country: United States
facility: Medstar Washington Hospital Center
state: District of Columbia
city: Clearwater
country: United States
facility: Morton Plant Hospital
state: Florida
city: Delray Beach
country: United States
facility: Delray Medical Center
state: Florida
city: Miami Beach
country: United States
facility: Mount Sinai Medical Center
state: Florida
city: Ocala
country: United States
facility: AdventHealth Ocala
state: Florida
city: Cumming
country: United States
facility: Northside Vascular
state: Georgia
city: Elk Grove Village
country: United States
facility: Alexian Brothers Medical Center
state: Illinois
city: Urbana
country: United States
facility: Carle Health
state: Illinois
city: Evansville
country: United States
facility: Deaconess Research / Evansville Surgical Associates
state: Indiana
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Lafayette
country: United States
facility: Acadiana Vascular Clinic / Our Lady Lourdes Heart Hospital
state: Louisiana
city: Portland
country: United States
facility: Maine Medical Center
state: Maine
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Bay City
country: United States
facility: McLaren Heart & Vascular
state: Michigan
city: Grand Rapids
country: United States
facility: Corewell Health
state: Michigan
city: Minneapolis
country: United States
facility: Abbott Northwestern
state: Minnesota
city: Chesterfield
country: United States
facility: St. Luke's Hospital
state: Missouri
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: New York City
country: United States
facility: The Mount Sinai Hospital
state: New York
city: New York
country: United States
facility: New York University
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Charlotte
country: United States
facility: Atrium Health
state: North Carolina
city: Raleigh
country: United States
facility: Duke University
state: North Carolina
city: Cincinnati
country: United States
facility: Bethesda North Hospital
state: Ohio
city: Bend
country: United States
facility: St. Charles Health System
state: Oregon
city: Portland
country: United States
facility: Providence St. Vincent
state: Oregon
city: Bethlehem
country: United States
facility: St. Luke's University Hospital
state: Pennsylvania
city: Harrisburg
country: United States
facility: UPMC Pinnacle
state: Pennsylvania
city: Lancaster
country: United States
facility: Lancaster General Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny General Hospital
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina (MUSC)
state: South Carolina
city: Germantown
country: United States
facility: Stern Cardiovascular
state: Tennessee
city: Memphis
country: United States
facility: Cardiovascular Surgery Clinic
state: Tennessee
city: Austin
country: United States
facility: Cardiothoracic and Vascular Surgeons
state: Texas
city: Dallas
country: United States
facility: Baylor Scott & White Dallas
state: Texas
city: Houston
country: United States
facility: Memorial Hermann Southeast
state: Texas
city: Plano
country: United States
facility: Baylor Scott & White Plano
state: Texas
city: Sugarland
country: United States
facility: Houston Methodist Sugarland
state: Texas
city: Norfolk
country: United States
facility: Sentara
state: Virginia
city: Roanoke
country: United States
facility: Carilion Roanoke Memorial
state: Virginia
city: Charleston
country: United States
facility: Charleston Area Medical Center (CAMC)
state: West Virginia
Study officials:
affiliation: Lancaster General Hospital
name: Meghan Dermody, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Abbott Northwestern Minneapolis Heart Institute Foundation
name: Jeffrey Jim, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Beth Israel Deaconess Medical Center
name: Marc Schermerhorn, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Malas MB, Dakour-Aridi H, Kashyap VS, Eldrup-Jorgensen J, Wang GJ, Motaganahalli RL, Cronenwett JL, Schermerhorn ML. TransCarotid Revascularization With Dynamic Flow Reversal Versus Carotid Endarterectomy in the Vascular Quality Initiative Surveillance Project. Ann Surg. 2022 Aug 1;276(2):398-403. doi: 10.1097/SLA.0000000000004496. Epub 2020 Sep 15.
citation: Schermerhorn ML, Liang P, Eldrup-Jorgensen J, Cronenwett JL, Nolan BW, Kashyap VS, Wang GJ, Motaganahalli RL, Malas MB. Association of Transcarotid Artery Revascularization vs Transfemoral Carotid Artery Stenting With Stroke or Death Among Patients With Carotid Artery Stenosis. JAMA. 2019 Dec 17;322(23):2313-2322. doi: 10.1001/jama.2019.18441.
citation: Vilain KR, Magnuson EA, Li H, Clark WM, Begg RJ, Sam AD 2nd, Sternbergh WC 3rd, Weaver FA, Gray WA, Voeks JH, Brott TG, Cohen DJ; CREST Investigators. Costs and cost-effectiveness of carotid stenting versus endarterectomy for patients at standard surgical risk: results from the Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST). Stroke. 2012 Sep;43(9):2408-16. doi: 10.1161/STROKEAHA.112.661355. Epub 2012 Jul 19.