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

• Sponsor: Silk Road Medical (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01685567
• Collaborator: (none)
• Enrollment: 219
• Locations: 21
• Arm: 1
• Duration (Months): 44
• Patients Per Site: 10.4
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Carotid Artery Disease	Device: MICHI NPS+f	Phase 3

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 Design

• Study Type: Interventional
• Actual Enrollment: 219 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: INVESTIGATION of FLOW ALTERED, SHORT TRANSCERVICAL CAROTID ARTERY STENTING in PATIENTS With SIGNIFICANT CAROTID ARTERY DISEASE With Filter.
• Study Start Date: Nov 1, 2012
• Actual Primary Completion Date: Mar 1, 2016
• Actual Study Completion Date: Jul 1, 2016

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Hierarchical Composite of Stroke, Myocardial Infarction, and Death [30-day post-procedure]

   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.

Secondary Outcome Measures

1. All Death (Non-hierarchical) [0 to 30 days]

   The analyses to be conducted on the secondary endpoints are intended to provide additional supportive evidence of the efficacy and safety of the device.

2. All Myocardial Infarctions (Non-hierarchical) [0 to 30 days]

   The analyses to be conducted on the secondary endpoints are intended to provide additional supportive evidence of the efficacy and safety of the device.

3. All Stroke (Non-hierarchical) [0 to 30 days]

   The analyses to be conducted on the secondary endpoints are intended to provide additional supportive evidence of the efficacy and safety of the device.

4. Ipsilateral Stroke (Non-hierarchical) [31-365 days]

   Data on ipsilateral stroke 31-365 days post procedure will be collected to provide additional supportive evidence of the safety of the device.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

1. Target vessel must meet diameter requirements for stent (refer to selected stent IFU for diameter requirements).

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

3. Patient is greater or equal to 18 years of age.

4. Patient has no childbearing potential or has a negative pregnancy test within one week prior to the study procedure.

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 Investigational 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 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Peter Morton UCLA Medical Center	Los Angeles	California	United States	90095
2	Florida Hospital	Orlando	Florida	United States	32804
3	Johns Hopkins Bayview Medical Center	Baltimore	Maryland	United States	21224
4	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
5	University of Michigan Medical Center	Ann Arbor	Michigan	United States	48109-5967
6	McLaren Regional Medical Center	Flint	Michigan	United States	48507
7	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
8	Albany Medical Center	Albany	New York	United States	12208
9	University at Buffalo Neurosurgery, Inc	Buffalo	New York	United States	14203
10	Columbia University	New York	New York	United States	10032
11	Cleveland Clinic Foundation	Cleveland	Ohio	United States	44106
12	University Hospitals Case Medical Center and Case Western Reserve University School of Medicine	Cleveland	Ohio	United States	44106
13	Riverside Methodist Hospital	Columbus	Ohio	United States	43214
14	Jobst Vascular Institute	Toledo	Ohio	United States	43606
15	Oklahoma Heart	Oklahoma City	Oklahoma	United States	73120
16	Greenville Hospital System	Greenville	South Carolina	United States	29615
17	Cardiothoracic & Vascular Surgeons	Austin	Texas	United States	78756
18	Methodist Medical Center	Dallas	Texas	United States	75208
19	Dallas VA Medical Center	Dallas	Texas	United States	75216
20	Sentara Vascular Specialists	Norfolk	Virginia	United States	23507
21	Hospital Virgen de la Salud	Toledo		Spain	45004

Sponsors and Collaborators

• Silk Road Medical

Investigators

• Principal Investigator: Christopher Kwolek, MD, Massachusetts General Hospital
• Principal Investigator: Richard Cambria, MD, Massachusetts General Hospital

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

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

Publications

None provided.

• Responsible Party: Silk Road Medical
• ClinicalTrials.gov Identifier: NCT01685567
• Other Study ID Numbers: SRM-2012-02
• First Posted: Sep 14, 2012
• Last Update Posted: Jul 7, 2017
• Last Verified: Jun 1, 2017

• Keywords provided by Silk Road Medical: carotid artery disease; reverse flow
• Additional relevant MeSH terms: Carotid Artery Diseases

Study Results

Participant Flow

Recruitment Details	Recruitment opened November, 2012 and ended March, 2016.

Arm/Group Title	Intention-to-Treat (ITT)
Arm/Group Description	All patients who were enrolled in the pivotal phase of the study are included. Lead-in patients are not included in this group.
Period Title: Overall Study
STARTED	219
COMPLETED	219
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Intention-to-Treat (ITT)
Arm/Group Description	All patients who were enrolled in the pivotal phase of the study are included. Lead-in patients are not included in this group.
Overall Participants	219
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	72.30 (8.574)
Sex: Female, Male (Count of Participants)
Female	83 37.9%
Male	136 62.1%
Symptomatic Status (Count of Participants)
Asymptomatic	175 79.9%
Symptomatic	44 20.1%

Outcome Measures

1. Primary Outcome

Title	Hierarchical Composite of Stroke, Myocardial Infarction, and Death
Description	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.
Time Frame	30-day post-procedure

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intention-to-Treat (ITT)
Arm/Group Description	All patients who were enrolled in the pivotal phase of the study are included. Lead-in patients are not included in this group.
Measure Participants	219
Count of Participants [Participants]	8 3.7%

2. Secondary Outcome

Title	All Death (Non-hierarchical)
Description	The analyses to be conducted on the secondary endpoints are intended to provide additional supportive evidence of the efficacy and safety of the device.
Time Frame	0 to 30 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intention-to-Treat (ITT)
Arm/Group Description	All patients who were enrolled in the pivotal phase of the study are included. Lead-in patients are not included in this group.
Measure Participants	219
Count of Participants [Participants]	2 0.9%

3. Secondary Outcome

Title	All Myocardial Infarctions (Non-hierarchical)
Description	The analyses to be conducted on the secondary endpoints are intended to provide additional supportive evidence of the efficacy and safety of the device.
Time Frame	0 to 30 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intention-to-Treat (ITT)
Arm/Group Description	All patients who were enrolled in the pivotal phase of the study are included. Lead-in patients are not included in this group.
Measure Participants	219
Count of Participants [Participants]	4 1.8%

4. Secondary Outcome

Title	All Stroke (Non-hierarchical)
Description	The analyses to be conducted on the secondary endpoints are intended to provide additional supportive evidence of the efficacy and safety of the device.
Time Frame	0 to 30 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intention-to-Treat (ITT)
Arm/Group Description	All patients who were enrolled in the pivotal phase of the study are included. Lead-in patients are not included in this group.
Measure Participants	219
Count of Participants [Participants]	2 0.9%

5. Secondary Outcome

Title	Ipsilateral Stroke (Non-hierarchical)
Description	Data on ipsilateral stroke 31-365 days post procedure will be collected to provide additional supportive evidence of the safety of the device.
Time Frame	31-365 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intention-to-Treat (ITT)
Arm/Group Description	All patients who were enrolled in the pivotal phase of the study are included. Lead-in patients are not included in this group.
Measure Participants	219
Count of Participants [Participants]	3 1.4%

Adverse Events

Arm/Group Title	Intention-to-Treat (ITT)
Arm/Group Description	All patients who were enrolled in the pivotal phase of the study are included. Lead-in patients are not included in this group.
All Cause Mortality
	Intention-to-Treat (ITT)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Intention-to-Treat (ITT)
	Affected / at Risk (%)	# Events
Total	29/219 (13.2%)
Blood and lymphatic system disorders
Anaemia	5/219 (2.3%)
Cardiac disorders
Myocardial Infarction	3/219 (1.4%)
Angina Pectoris	1/219 (0.5%)
Bradycardia	1/219 (0.5%)
Cardiac Arrest	1/219 (0.5%)
Cardiac Failure Acute	1/219 (0.5%)
Gastrointestinal disorders
Gastrointestinal Haemorrhage	1/219 (0.5%)
General disorders
Pyrexia	1/219 (0.5%)
Infections and infestations
Pneumonia	2/219 (0.9%)
Post Procedural Cellulitis	1/219 (0.5%)
Injury, poisoning and procedural complications
Wound Haematoma	3/219 (1.4%)
Incision Site Haematoma	2/219 (0.9%)
Investigations
Troponin Increased	1/219 (0.5%)
Metabolism and nutrition disorders
Diabetic Ketoacidosis	1/219 (0.5%)
Nervous system disorders
Cerebrovascular Accident	1/219 (0.5%)
Ischaemic Stroke	1/219 (0.5%)
Metabolic Encephalopathy	1/219 (0.5%)
Psychomotor Seizures	1/219 (0.5%)
Renal and urinary disorders
Renal Failure	2/219 (0.9%)
Urinary Retention	2/219 (0.9%)
Respiratory, thoracic and mediastinal disorders
Acute Respiratory Failure	2/219 (0.9%)
Dyspnoea	1/219 (0.5%)
Epistaxis	1/219 (0.5%)
Pneumothorax	1/219 (0.5%)
Pulmonary Embolism	1/219 (0.5%)
Respiratory Failure	1/219 (0.5%)
Vascular disorders
Aortic Aneurysm	1/219 (0.5%)
Artery Dissection	4/219 (1.8%)
Hypotension	4/219 (1.8%)
Hypertension	1/219 (0.5%)
Other (Not Including Serious) Adverse Events
	Intention-to-Treat (ITT)
	Affected / at Risk (%)	# Events
Total	118/219 (53.9%)
Blood and lymphatic system disorders
Anaemia	8/219 (3.7%)
Thrombocytopenia	1/219 (0.5%)
Cardiac disorders
Angina Pectoris	2/219 (0.9%)
Atrial Fibrillation	1/219 (0.5%)
Bradycardia	5/219 (2.3%)
Cardiac Arrest	1/219 (0.5%)
Cardiac Failure Acute	1/219 (0.5%)
Myocardial Infarction	4/219 (1.8%)
Sinus Bradycardia	3/219 (1.4%)
Tachycardia	1/219 (0.5%)
Ventricular Extrasystoles	1/219 (0.5%)
Ear and labyrinth disorders
Ear Pain	1/219 (0.5%)
Gastrointestinal disorders
Constipation	2/219 (0.9%)
Dysphagia	1/219 (0.5%)
Gastrointestinal Hemorrhage	2/219 (0.9%)
Nausea	6/219 (2.7%)
Vomiting	3/219 (1.4%)
General disorders
Chest Discomfort	1/219 (0.5%)
Device Occlusion	1/219 (0.5%)
Oedema	1/219 (0.5%)
Pain	25/219 (11.4%)
Pyrexia	9/219 (4.1%)
Vessel Puncture Site Haematoma	4/219 (1.8%)
Immune system disorders
Allergy To Arthropod Bite	1/219 (0.5%)
Infections and infestations
Acute Sinusitis	1/219 (0.5%)
Adenoviral Upper Respiratory Infection	1/219 (0.5%)
Bronchitis	2/219 (0.9%)
Herpes Zoster	1/219 (0.5%)
Infection	1/219 (0.5%)
Pneumonia	3/219 (1.4%)
Post Procedural Cellulitis	1/219 (0.5%)
Rash Pustular	1/219 (0.5%)
Upper Respiratory Tract Infection	1/219 (0.5%)
Urinary Tract Infection	4/219 (1.8%)
Injury, poisoning and procedural complications
Cranial Nerve Injury	1/219 (0.5%)
Incision Site Haematoma	4/219 (1.8%)
Vascular Injury	1/219 (0.5%)
Wound Haematoma	7/219 (3.2%)
Wound Secretion	8/219 (3.7%)
Investigations
Blood Creatine Phosphokinase Increased	3/219 (1.4%)
Oxygen Saturation Decreased	1/219 (0.5%)
Troponin Increased	7/219 (3.2%)
Metabolism and nutrition disorders
Dehydration	1/219 (0.5%)
Diabetic Ketoacidosis	1/219 (0.5%)
Hyperglycaemia	1/219 (0.5%)
Hypernatraemia	1/219 (0.5%)
Hypokalaemia	1/219 (0.5%)
Hypokalaemic Syndrome	1/219 (0.5%)
Hypomagnesaemia	1/219 (0.5%)
Hypophosphataemia	1/219 (0.5%)
Nervous system disorders
Carotid Artery Stenosis	1/219 (0.5%)
Cerebrovascular Accident	1/219 (0.5%)
Headache	4/219 (1.8%)
Ischaemic Stroke	1/219 (0.5%)
Metabolic Encephalopathy	1/219 (0.5%)
Psychomotor Seizures	1/219 (0.5%)
Psychiatric disorders
Hallucination, Visual	1/219 (0.5%)
Renal and urinary disorders
Dysuria	1/219 (0.5%)
Hematuria	4/219 (1.8%)
Renal Failure	2/219 (0.9%)
Urinary Retention	11/219 (5%)
Respiratory, thoracic and mediastinal disorders
Acute Respiratory Failure	2/219 (0.9%)
Cough	2/219 (0.9%)
Dysphonia	1/219 (0.5%)
Dyspnoea	3/219 (1.4%)
Epistaxis	3/219 (1.4%)
Pneumothorax	1/219 (0.5%)
Pulmonary Embolism	1/219 (0.5%)
Rales	1/219 (0.5%)
Respiratory Failure	1/219 (0.5%)
Rhinorrhoea	1/219 (0.5%)
Throat Irritation	3/219 (1.4%)
Wheezing	1/219 (0.5%)
Skin and subcutaneous tissue disorders
Dermatitis Allergic	3/219 (1.4%)
Ecchymosis	1/219 (0.5%)
Skin Irritation	1/219 (0.5%)
Surgical and medical procedures
Therapy Regimen Changed	1/219 (0.5%)
Vascular disorders
Aortic Aneurysm	1/219 (0.5%)
Artery Dissection	9/219 (4.1%)
Hemorrhage	1/219 (0.5%)
Hematoma	1/219 (0.5%)
Hypertension	9/219 (4.1%)
Hypotension	23/219 (10.5%)
Orthostatic Hypotension	2/219 (0.9%)
Vascular Occlusion	1/219 (0.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.