Safety and Efficacy Study for Reverse Flow Used During Carotid Artery Stenting Procedure (ROADSTER)

INVESTIGATION of FLOW ALTERED, SHORT TRANSCERVICAL CAROTID ARTERY STENTING in PATIENTS With SIGNIFICANT CAROTID ARTERY DISEASE With Filter.

The purpose of this study is to obtain and establish the safety and efficacy of The MICHI™ Neuroprotection System with Filter (MICHI™ NPS+f) for providing cerebral embolic protection during angioplasty and stenting procedures in carotid arteries. The MICHI NPS+f also facilitates access to the carotid and neuro anatomy for the introduction of therapeutic or diagnostic endovascular devices and/or agents. It will be used in conjunction with a FDA approved carotid artery stent for the treatment of carotid artery disease.

Study Overview

• Status: Completed
• Conditions: Carotid Artery Disease
• Intervention / Treatment: Device: MICHI NPS+f

Detailed Description

Cerebral embolization during carotid artery stenting (CAS) can often precipitate severe adverse neurological effects. Most major clinical studies of CAS have used distal filters for cerebral protection and have compared the neurologic complication rates with those of carotid endarterectomy (CEA). Many currently available embolic protection devices, however, have limited efficacy in capturing microembolic debris that is liberated during stenting, pre-dilatation and post-dilatation. Distal protection systems are furthermore limited by the need to cross the lesion prior to deployment. Some studies have shown a relatively high incidence of cerebral infarction even when distal protection devices are employed.

Cerebral protection with carotid flow reversal is a method that was developed as an alternative to the use of distal protection devices. While novel in its approach, this method too has its limitations. Another technique developed employs carotid flow reversal prior to traversing the stenosis and can be accomplished by directly accessing the carotid anatomy without the use of the transfemoral approach. Major benefits to this method include a simpler route to the target lesion and the ability to perform the procedure on patients with severe carotid tortuosity and difficult aortic arch anatomy.

• Study Type: Interventional
• Enrollment (Actual): 219
• Phase: Phase 3

Contacts and Locations

Study Locations

• Spain
  • Toledo, Spain, 45004
    • Hospital Virgen de la Salud
• United States
  • California
    • Los Angeles, California, United States, 90095
      • Peter Morton UCLA Medical Center
  • Florida
    • Orlando, Florida, United States, 32804
      • Florida Hospital
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • Johns Hopkins Bayview Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48109-5967
      • University of Michigan Medical Center
    • Flint, Michigan, United States, 48507
      • McLaren Regional Medical Center
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New York
    • Albany, New York, United States, 12208
      • Albany Medical Center
    • Buffalo, New York, United States, 14203
      • University at Buffalo Neurosurgery, Inc
    • New York, New York, United States, 10032
      • Columbia University
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Cleveland Clinic Foundation
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Case Medical Center and Case Western Reserve University School of Medicine
    • Columbus, Ohio, United States, 43214
      • Riverside Methodist Hospital
    • Toledo, Ohio, United States, 43606
      • Jobst Vascular Institute
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73120
      • Oklahoma Heart
  • South Carolina
    • Greenville, South Carolina, United States, 29615
      • Greenville Hospital System
  • Texas
    • Austin, Texas, United States, 78756
      • Cardiothoracic & Vascular Surgeons
    • Dallas, Texas, United States, 75216
      • Dallas VA Medical Center
    • Dallas, Texas, United States, 75208
      • Methodist Medical Center
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • Sentara Vascular Specialists

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

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

   • Symptomatic: Stenosis must be greater than or equal to 50% as determined by angiogram and the patient has a history of stroke (minor or non-disabling), TIA and/or amaurosis fugax within 180 days of the procedure.
   • Asymptomatic: Stenosis must be greater than or equal to 70% as determined by angiogram without any neurological symptoms within the prior 180 days.
2. Target vessel must meet diameter requirements for stent (refer to selected stent IFU for diameter 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 greater or equal to 18 years of age.
5. Patient has no childbearing potential or has a negative pregnancy test within one week prior to the study procedure.
6. 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 Investigational Review Board/Ethics Committee of the respective clinical site prior to the procedure. This will be obtained prior to participation in the study.
7. Patient is willing to comply with the protocol requirements and return to the treatment center for all required clinical evaluations.
8. Patient meets at least one of the anatomic or clinical high-risk criteria.

Exclusion Criteria:

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. Patient has an evolving stroke.
4. Patient has severe dementia.
5. Patient has a history of spontaneous intracranial hemorrhage within the past 12 months.
6. Patient 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.
7. Patient had hemorrhagic transformation of an ischemic stroke within the past 60 days.
8. Patient has active bleeding diathesis or coagulopathy or will refuse blood transfusion.
9. Patient had or will have CABG, endovascular stent procedure, valve intervention or vascular surgery within 30 days before or after the intervention.
10. Patient has had a recent GI bleed that would interfere with antiplatelet therapy.
11. Life expectancy of < 12 months post procedure.
12. 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.
13. Myocardial Infarction within 72 hours prior to the intervention.
14. Presence of a previous placed intravascular stent in target vessel or the planned arteriotomy site.
15. Patient has had neurologic illnesses within the past two years characterized by fleeting or fixed neurologic deficit which cannot be distinguished from TIA or stroke (e.g. 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, moderate to severe dementia, or intracranial hemorrhage).
16. Patient with a history of major stroke (CVA or retinal embolus) with major neurological deficit likely to confound study endpoints within 1 month of index procedure.
17. Patient has Hgb <10 g/dl, platelet count <125,000/μl, uncorrected INR >1.5, bleeding time >1 minute beyond upper limit normal, or heparin-associated thrombocytopenia.
18. Patient has an intracranial tumor.
19. Patient is actively participating in another drug or device trial (IND or IDE) that has not completed the required protocol follow-up period.
20. Patient has inability to understand and cooperate with study procedures or provide informed consent.
21. Occlusion or [Thrombolysis In Myocardial Infarction Trial (TIMI 0)] "string sign" >1cm of the ipsilateral common or internal carotid artery.
22. Patient has vertebrobasilar insufficiency symptoms only, without clearly identifiable symptoms referable to the study carotid artery.
23. 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).
24. Recently (<60 days) implanted heart valve (either surgically or endovascularly), which is a known source of emboli as confirmed on echocardiogram.
25. Ostium of Common Carotid Artery (CCA) requires revascularization.
26. Presence of extensive or diffuse atherosclerotic disease involving the proximal common carotid artery that would preclude the safe introduction of the study device.
27. The patient has less than 5cm between the clavicle and bifurcation, as assessed by duplex Doppler ultrasound.
28. Bilateral carotid stenosis if intervention is planned within 37 days of the index procedure.
29. 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) that is not associated with an ulcerated target lesion.
30. Abnormal angiographic findings: ipsilateral intracranial or extracranial arterial stenosis 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.
31. Patient has had a previous intervention in the ipsilateral proximal CCA.
32. Patient has had a TIA or amaurosis fugax within 48 hours prior to the procedure.
33. Patient has contralateral lateral recurrent, laryngeal or vagus nerve injury.
34. Patient is otherwise unsuitable for intervention in the opinion of the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MICHI NPS+f; The MICHI™ NPS+f is a flow reversal circuit consisting of two proprietary sheaths connected by standard surgical tubing. The sheaths each have a standard hemostasis valve and sidearm. An in-line flow regulator allows the clinician to modify to the flow through the circuit (either high flow or low flow) in addition to permitting temporary cessation of flow.	Device: MICHI NPS+f; Cerebral protection with carotid flow reversal; Other Names: ENROUTE Transcarotid Neuroprotection System

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hierarchical Composite of Stroke, Myocardial Infarction, and Death	The primary endpoint was a hierarchical composite of any stroke, myocardial infarction and death during a 30-day post-procedural period in the ITT (pivotal and extended enrollment) population comprised of subjects deemed to be high risk for complications from CEA.	30-day post-procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All Death (Non-hierarchical)	The analyses to be conducted on the secondary endpoints are intended to provide additional supportive evidence of the efficacy and safety of the device.	0 to 30 days
All Myocardial Infarctions (Non-hierarchical)	The analyses to be conducted on the secondary endpoints are intended to provide additional supportive evidence of the efficacy and safety of the device.	0 to 30 days
All Stroke (Non-hierarchical)	The analyses to be conducted on the secondary endpoints are intended to provide additional supportive evidence of the efficacy and safety of the device.	0 to 30 days
Ipsilateral Stroke (Non-hierarchical)	Data on ipsilateral stroke 31-365 days post procedure will be collected to provide additional supportive evidence of the safety of the device.	31-365 days

Collaborators and Investigators

• Sponsor: Silk Road Medical
• Investigators: Principal Investigator: Christopher Kwolek, MD, Massachusetts General Hospital; Principal Investigator: Richard Cambria, MD, Massachusetts General Hospital

Publications and helpful links

General Publications

• Alpaslan A, Wintermark M, Pinter L, Macdonald S, Ruedy R, Kolvenbach R. Transcarotid Artery Revascularization With Flow Reversal. J Endovasc Ther. 2017 Apr;24(2):265-270. doi: 10.1177/1526602817693607. Epub 2017 Feb 17.
• Kwolek CJ, Jaff MR, Leal JI, Hopkins LN, Shah RM, Hanover TM, Macdonald S, Cambria RP. Results of the ROADSTER multicenter trial of transcarotid stenting with dynamic flow reversal. J Vasc Surg. 2015 Nov;62(5):1227-34. doi: 10.1016/j.jvs.2015.04.460.
• Malas MB, Leal Lorenzo JI, Nejim B, Hanover TM, Mehta M, Kashyap V, Kwolek CJ, Cambria R. Analysis of the ROADSTER pivotal and extended-access cohorts shows excellent 1-year durability of transcarotid stenting with dynamic flow reversal. J Vasc Surg. 2019 Jun;69(6):1786-1796. doi: 10.1016/j.jvs.2018.08.179. Epub 2019 Jan 2.

Helpful Links

• Transcarotid Artery Revascularization with Flow Reversal: the PROOF Study
• Results of the ROADSTER multicenter trial of transcarotid stenting with dynamic flow reversal.

Study record dates

Study Major Dates

• Study Start: November 1, 2012
• Primary Completion (Actual): March 1, 2016
• Study Completion (Actual): July 1, 2016

Study Registration Dates

• First Submitted: September 10, 2012
• First Submitted That Met QC Criteria: September 11, 2012
• First Posted (Estimate): September 14, 2012

Study Record Updates

• Last Update Posted (Actual): July 7, 2017
• Last Update Submitted That Met QC Criteria: June 12, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Keywords: carotid artery disease; reverse flow
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Carotid Artery Diseases
• Other Study ID Numbers: SRM-2012-02