The ENROUTE Transcarotid Neuroprotection System (ENROUTE Transcarotid NPS) DW-MRI Evaluation
Conditions: Carotid Artery Diseases, Carotid Atherosclerosis, Carotid Stenosis, Carotid Artery Plaque, Carotid Disease
Sponsor: Silk Road Medical

 
 
 
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The ENROUTE Transcarotid Neuroprotection System (ENROUTE 
Transcarotid NPS)  
DW-MRI Evaluation 
 
 
 
Clinical Protocol 
SRM–2018-01 
Version 
0.9 
Version Date 
August 8, 2018 
 
 
 
 
 
 
Sponsored by: 
 
Silk Road Medical, Inc. 
1213 Innsbruck Drive 
Sunnyvale, CA  94089 
United States of America 
Phone: +1 (408) 720-9002 
Fax: +1 (408) 720 9013 
 
 

 
 
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_____________________________________________________________________________________________________________________________________________________ 
 
 
PROTOCOL SIGNATURE PAGE 
 
This is a prospective, single-arm, multi-center evaluation of patients requiring carotid 
revascularization who are treated with the  FDA-cleared  ENROUTE® Transcarotid Neuroprotection 
System (ENROUTE® Transcarotid NPS) in conjunction with the FDA-approved ENROUTE 
Transcarotid Stent System. 
 
 
Clinical Protocol:   
SRM-2018-01 
Version: 
 
0.9 
Version Date:   
August 8, 2018 
 
 
 
 
 
 
I have read this protocol and agree to adhere to the requirements.  The protocol, other documents 
and all necessary information will be made available to the participating sites and their personnel.  
As required, will discuss this material with them and ensure they are fully informed regarding 
protocol.  The evaluation will be conducted in compliance with the protocol, Good Clinical Practice 
(GCP), and all applicable regulatory requirements as required. 
 
 
 
 
 
 
 
 
Site Name 
 
Site Location (City, State) 
 
 
 
Physician Printed Name 
 
 
 
 
 
 
Physician Signature 
 
Date 
 
 
 

 
 
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Table of Contents 
1 
Protocol Summary ..................................................................................................................... 5 
2 
Principal Contacts ...................................................................................................................... 6 
3 
Introduction............................................................................................................................... 6 
4 
Device Overview and Usage ...................................................................................................... 7 
4.1 
Device Description ....................................................................................................... 7 
4.2 
Intended Use ................................................................................................................ 9 
4.2.1 
ENROUTE Transcarotid Stent ................................................................................. 9 
4.2.2 
ENROUTE Transcarotid Neuroprotection System.................................................. 9 
5 
Objective ................................................................................................................................... 9 
6 
Design ........................................................................................................................................ 9 
7 
Endpoints................................................................................................................................. 10 
7.1 
Primary Endpoint ....................................................................................................... 10 
7.2 
Secondary Endpoints .................................................................................................. 10 
8 
Population ............................................................................................................................... 10 
8.1 
Patient Eligibility ......................................................................................................... 10 
8.2 
Inclusion Criteria ........................................................................................................ 10 
8.3 
Exclusion Criteria ........................................................................................................ 11 
8.4 
Enrollment Determination ......................................................................................... 13 
9 
Patient Enrollment .................................................................................................................. 13 
9.1 
Enrollment Phase ....................................................................................................... 13 
9.2 
Patient Numbering ..................................................................................................... 13 
9.3 
Patient Discontinuation .............................................................................................. 13 
10 Procedures .............................................................................................................................. 14 
10.1 Informed Consent ...................................................................................................... 14 
10.2 Diffusion-Weighted Magnetic Resonance Imaging (DW-MRI) Evaluation ................. 14 
10.3 Pre-Procedure ............................................................................................................ 14 
10.3.1 Pre-Procedure Medication Regimen ................................................................... 15 
10.3.2 Pre-Procedure Contrast Preparation ................................................................... 16 
10.4 TransCarotid Revascularization .................................................................................. 16 
10.4.1 Index Procedure ................................................................................................... 16 
10.4.2 Procedural Medications ....................................................................................... 16 
10.4.3 Stenting TCAR Procedure ..................................................................................... 16 
10.5 Criteria for Bailout ...................................................................................................... 17 
10.6 Mechanical Failures, Malfunctions or Device Defects ............................................... 17 
10.7 Post-Index Procedure Medications ............................................................................ 17 
11 Post Procedure Evaluation ...................................................................................................... 17 
11.1 Follow-up .................................................................................................................... 18 
12 Assessment of Safety and Performance .................................................................................. 18 
12.1 Clinical Follow-up Visits .............................................................................................. 18 
12.2 Additional Follow-up Visits ......................................................................................... 18 
13 Adverse Events ........................................................................................................................ 19 

 
 
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14 Statistical Methods .................................................................................................................. 19 
14.1 General Considerations .............................................................................................. 19 
14.2 Endpoint Analyses and Hypothesis Testing ................................................................ 19 
15 Data Collection ........................................................................................................................ 19 
15.1 Required Data ............................................................................................................ 19 
15.2 Source Documentation .............................................................................................. 19 
15.3 Case Report Forms ..................................................................................................... 20 
15.4 Record Retention ....................................................................................................... 20 
15.5 Confidentiality ............................................................................................................ 20 
16 Sponsor Responsibilities .......................................................................................................... 20 
16.1 Training of Physicians and Site Personnel .................................................................. 20 
17 Monitoring ............................................................................................................................... 21 
18 Site Responsibilities ................................................................................................................. 21 
18.1 Site Personnel Responsibilities ................................................................................... 21 
18.1.1 Principal Physician ............................................................................................... 21 
18.2 Physician Responsibilities ........................................................................................... 21 
18.2.1 Physician Records ................................................................................................ 21 
18.2.2 Patient Records .................................................................................................... 21 
18.2.3 IRB/EC Information .............................................................................................. 22 
18.2.4 Other .................................................................................................................... 22 
19 Core and Central Laboratories ................................................................................................ 22 
19.1 DW-MRI Core Laboratory ........................................................................................... 22 
20 Protocol Deviations ................................................................................................................. 22 
21 Device Accountability .............................................................................................................. 22 
22 Ethics ....................................................................................................................................... 22 
22.1 Protocol Amendments ............................................................................................... 22 
22.2 Data Release Consent ................................................................................................. 23 
22.2.1 Data Release Consenting Procedures .................................................................. 23 
23 Use of Information and Publication ........................................................................................ 23 
24 Termination ............................................................................................................................. 23 
Appendix 1.  Schedule of Events ..................................................................................................... 24 
Appendix 2.  Case Report Forms ..................................................................................................... 25 
Appendix 3. Physician List ............................................................................................................... 26 
Appendix 4.  Definitions .................................................................................................................. 27 
Appendix 5. Procedural Guidelines ................................................................................................. 31 
 
 
 

 
 
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1 Protocol Summary 
Title 
The ENROUTE Transcarotid Neuroprotection System (ENROUTE 
Transcarotid NPS)  DW-MRI Evaluation. 
Objective 
 
To correlate pre and post procedure DW-MRI  for patients treated 
with the transcarotid artery revascularization (TCAR) procedure. 
Design 
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. 
Enrollment 
A minimum of 50 patients and a maximum of 75. 
Locations 
Up to 10 sites in the United States of America and up to 2 sites in 
the European Union. 
Primary Endpoint 
Incidence of ipsilateral new white lesions by DW-MRI post 
procedure. 
Secondary Endpoints 
The following secondary endpoints will be assessed 0 to 30 days: 
 
All Stroke 
 
Neurological Death 
 
Stroke/Death in 
patients eligible for 
ROADSTER 2 
 
• Volume of DW-MRI lesions 
• Location of DW-MRI Lesions 
• Stroke/Death in patients 
ineligible for ROADSTER 2 
• Rate of contralateral new 
white lesions by DW-MRI 
Patient Population 
Symptomatic or Asymptomatic patients with atherosclerotic 
extracranial internal carotid stenosis (ICA) with or without 
involvement of the contiguous common artery (CCA). 
 
Planned Schedule 
First patient enrolled: November 2018 
Last patient enrolled: November 2019 
Last 30-day follow-up visit: December 2019 
 
 
 

 
 
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2 Principal Contacts 
 
Sponsor 
Silk Road Medical, Inc. 
1213 Innsbruck Drive 
Sunnyvale, CA 94085 
DW-MRI Core Laboratory 
Max Wintermark, MD 
Stanford University 
1705 El Camino Real 
Palo Alto, CA  94306-1106 
Study Monitors 
Silk Road Medical, Inc. 
1213 Innsbruck Drive 
Sunnyvale, CA 94085 
US National Principal Investigator 
Raghu Motaganahalli, MD 
Division Chief, Vascular Surgery 
Indiana University Health Methodist Hospital 
1701 N Senate Blvd 
Indianapolis, IN 46202 
EU Principal Investigator 
Jose Ignacio Leal Lorenzo, MD, PhD, RPVI, 
FACS 
Co-Director Department of Vascular Surgery 
Clinica Universidad de Navarra, Madrid 
 
3 Introduction 
Cerebral embolization during carotid artery stenting (CAS) can often precipitate severe adverse 
neurological effects. Most major clinical studies of CAS have used distal filters (from a transfemoral 
route) for cerebral protection and have compared the neurologic complication rates with those of 
carotid endarterectomy (CEA). The contemporary absolute stroke/death rates for CEA and filter-
protected CAS within a tightly proscribed randomized trial are low (2.3% versus 4.4%) (CREST). To 
power a trial to compare the impact of procedural and/or technical modifications (such as improved 
embolic protection strategies) would require several thousand patients at the minimum. New white 
lesions on DW-MRI of the brain occur at a much higher rate than stroke and death. Many of these 
lesions remain clinically covert but the impact on cognition in the long term is unknown. The ICSS 
sub-study revealed a 50% new white lesion rate following transfemoral CAS (which rose to 73% for 
filter-protected transfemoral CAS) compared with 17% for CEA. Although the incidence of new DW-
MRI lesions is far higher than the incidence of clinically apparent neurological deficits. In the ICSS 
MRI subset, the DW-MRI lesions with the largest volume were significantly associated with the 
occurrence of neurologic events. Although the fate and clinical relevance of these lesions remain 

 
 
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unknown, their incidence makes them an attractive surrogate to maintain adequate power whilst 
reducing the size of the study population. 
4 Device Overview and Usage 
The ENROUTE Transcarotid Neuroprotection System (NPS)  was 510(k) cleared by the FDA on 
February 9, 2015, and the ENROUTE Transcarotid Stent System was PMA Approved by FDA on 
May 18, 2015. Both devices are commercially available in the United States.  The ENROUTE 
Transcarotid Neuroprotection System was granted the CE marking of conformity on January 27, 
2016. The ENROUTE Transcarotid Stent System was granted the CE marking of conformity on July 
2, 2013. 
4.1 Device Description 
The ENROUTE Transcarotid Stent System 
The Silk Road ENROUTE Transcarotid Stent System consists of a nitinol self-expanding stent 
preloaded on a 5F (.065" / 1.65 mm) or 6F (.078" / 1.98 mm) sheathed delivery system. The rapid 
exchange delivery system consists mainly of an inner shaft and an outer sheath with radiopaque 
markers, and a Tuohy Borst valve. The inner shaft consists of a support member and wire lumen. The 
proximal portion of the support member is comprised of a hub connected to a stainless steel wire and 
hypotube and distally of a stainless steel coil. The wire lumen originates distally in a catheter tip and 
terminates proximally at a guidewire exit port designed to accept a .014" (0.36 mm) guidewire. The 
outer sheath has a proximal shaft and distal outer sheath with a nominal working length of 57 cm. The 
self-expanding ENROUTE Transcarotid Stent System is constrained within the space between the 
inner shaft and the distal outer sheath, located between distal and proximal stent markers on the inner 
shaft. The stent expands to its unconstrained diameter when released from the deployment catheter 
into the carotid artery. Upon deployment, the stent forms a lattice to cover the diseased arterial segment 
and to push outward on the luminal surface, helping to maintain the patency of the artery. Due to the 
self-expanding behavior of nitinol, the stents are indicated for placement into vessels that are 1-2 mm 
smaller in diameter than the unconstrained diameter of the stent. Device depictions and components 
are provided in Figure 1. The ENROUTE Transcarotid Stent (nitinol implant) is available in 18 sizes 
mounted on delivery systems in two (2) crossing profiles depending on stent diameter (unconstrained). 
Refer to Table 1. 
Non-clinical testing has demonstrated that the ENROUTE Transcarotid Stent is MR Conditional. A 
patient with this device can be scanned safely in an MR system meeting the following conditions:  
• 
Static magnetic field of 1.5-Tesla or 3-Tesla, only 
• 
Maximum spatial gradient magnetic field of 4,000 Gauss/cm (40 Tesla/m) or less 
• 
Maximum MR system reported, whole body averaged specific absorption rate (SAR) of 2-
W/kg (Normal Operating Mode).  
Under the scan conditions defined above, the ENROUTE Transcarotid Stent is expected to produce 
a maximum temperature rise of 2.4°C after 15 minutes of continuous scanning. In non-clinical 
testing, the image artifact caused by the device extends approximately 5 mm from the ENROUTE 
Transcarotid Stent when imaged with a gradient echo pulse sequence and a 3-Tesla MRI system. 
The artifact does obscure the device lumen. 
 
 

 
 
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Figure 1.  ENROUTE Transcarotid Stent System 
 
1. Tuohy Borst valve 
9. Tuohy Borst Y-Connection 
2. Hypotube 
10. Proximal Inner Shaft Marker (Stop) 
3. Coil 
11. Outer Sheath Radiopaque Marker 
4. Catheter Inner Shaft Tip 
12. Proximal Valve End 
5. Inner Shaft Hub 
13. Distal Inner Shaft Stent Marker 
6A. Proximal Shaft 
14. Coil Sleeve 
6B. Distal Outer Sheath 
15. Wire Lumen 
7. Outer Sheath Luer Hub 
16. Guidewire Exit Port 
8. Pod Housing Crimped Stent 
 
Table 1. ENROUTE Transcarotid Stent and Delivery System Dimensions 
 
 
 
 
 
 
 
 
 
 
 
 
ENROUTE CODES 
UNCONSTRAINED STENT 
DIMENSIONS 
Diameter x Length (mm) 
CROSSING PROFILE 
SR-0520-CS 
5 x 20 
5F (.078”, 1.98mm) 
SR-0530-CS 
5 x 30 
5F (.078”, 1.98mm) 
SR-0540-CS 
5 x 40 
5F (.078”, 1.98mm) 
SR-0620-CS 
6 x 20 
5F (.078”, 1.98mm) 
SR-0630-CS 
6 x 30 
5F (.078”, 1.98mm) 
SR-0640-CS 
6 x 40 
5F (.078”, 1.98mm) 
SR-0720-CS 
7 x 20 
5F (.078”, 1.98mm) 
SR-0730-CS 
7 x 30 
5F (.078”, 1.98mm) 
SR-0740-CS 
7 x 40 
5F (.078”, 1.98mm) 
SR-0820-CS 
8 x 20 
5F (.078”, 1.98mm) 
SR-0830-CS 
8 x 30 
5F (.078”, 1.98mm) 
SR-0840-CS 
8 x 40 
5F (.078”, 1.98mm) 
SR-0920-CS 
9 x 20 
6F (.087”, 2.21mm) 
SR-0930-CS 
9 x 30 
6F (.087”, 2.21mm) 
SR-0940-CS 
9 x 40 
6F (.087”, 2.21mm) 
SR-1020-CS 
10 x 20 
6F (.087”, 2.21mm) 
SR-1030-CS 
10 x 30 
6F (.087”, 2.21mm) 
SR-1040-CS 
10 x 40 
6F (.087”, 2.21mm) 

 
 
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The ENROUTE Transcarotid Neuroprotection System (NPS) 
The ENROUTE Transcarotid Neuroprotection System (NPS) consists of three primary 
components: the Transcarotid Arterial Sheath, the Flow Controller, and the Venous Return Sheath. 
When assembled, the ENROUTE Transcarotid NPS creates an arteriovenous shunt that reverses 
the flow of blood at the treatment site of the carotid arteries from antegrade to retrograde due to the 
pressure gradient between arterial and venous pressure thereby shunting embolic particles away 
from the cerebral circulation. The rate of reverse flow (low or high) through the arteriovenous shunt 
is regulated by the Flow Controller. Subsequent iterations of the ENROUTE Transcarotid 
Neuroprotection System (NPS) may be used during this study. 
4.2 Intended Use 
4.2.1 ENROUTE Transcarotid Stent 
The ENROUTE Transcarotid Stent System used in conjunction with the ENROUTE Transcarotid 
Neuroprotection System is indicated for the treatment of patients at high risk for adverse events 
from carotid endarterectomy, who require carotid revascularization and meet the criteria outlined 
below. 
• 
Patients with neurological symptoms and > 50% stenosis of the common or internal 
carotid artery by ultrasound or angiogram OR patients without neurological symptoms and 
> 80% stenosis of the common or internal carotid artery by ultrasound or angiogram, AND 
• 
Patients must have a vessel diameter of 4-9 mm at the target lesion, AND 
• 
Carotid bifurcation is located at minimum 5 cm above the clavicle to allow for placement of 
the ENROUTE Transcarotid Neuroprotection System. 
4.2.2 ENROUTE Transcarotid Neuroprotection System 
The ENROUTE® Transcarotid Neuroprotection System is intended to provide transcarotid vascular 
access, introduction of diagnostic agents and therapeutic devices, and embolic protection during 
carotid artery angioplasty and stenting procedures for patients diagnosed with carotid artery stenosis 
and who have the appropriate anatomy described below: 
• 
Adequate femoral venous access 
• 
Patients must have a vessel diameter of 6 mm of the common carotid artery and is free of 
significant disease at the access point, AND 
• 
Carotid bifurcation is located at minimum 5 cm above the clavicle to allow for placement of 
the ENROUTE Transcarotid Neuroprotection System. 
5 Objective 
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. 
6 Design 
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 

 
 
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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.  
7 Endpoints 
7.1 Primary Endpoint  
Incidence of ipsilateral new white lesions by DW-MRI 30 days post procedure.  
7.2 Secondary Endpoints  
The following secondary endpoints will be assessed 0 to 30 days: 
 
All Stroke 
 
Neurological Death 
 
Volume of DW-MRI lesions 
 
Location of DW-MRI Lesions 
 
Stroke/Neurological Death in patients eligible for ROADSTER 2 
 
Stroke/Neurological Death in patients ineligible for ROADSTER 2 
 
Rate of contralateral new white lesions by DW-MRI 
8 Population 
Patients participating in this evaluation will be comprised of male and female symptomatic or 
asymptomatic patients requiring carotid revascularization.  
8.1 Patient Eligibility 
Patients must meet ALL of the inclusion criteria to be considered for the study. If ANY of the 
exclusion criteria are met, the patient cannot be enrolled in this study or treated using the study 
devices.   
Note: Patients treated with TCAR within the ROADSTER 2 Post Approval Study are eligible to 
participate in this evaluation since this evaluation only adds non-invasive imaging before and after a 
routine TCAR procedure. ROADSTER 2 only excludes patients who are participating in 
investigational device or drug studies and does not preclude the enrollment of patients subjected to 
other routine medical care. 
8.2 Inclusion Criteria 
1. Patient must meet one of the following criteria regarding neurological symptom status and 
degree of stenosis: 
Symptomatic:  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. 
OR 
Asymptomatic:  Stenosis must be >80% as determined by ultrasound or angiogram 
without any neurological symptoms within the prior 180 days. 
                                                            
1 For this protocol, this is limited to CT angiogram. 

 
 
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2. Target vessel must meet diameter requirements for stent (refer to 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 willing to comply with the protocol requirements and return to the treatment center for 
all required clinical evaluations. 
5. 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.   
6. Patient meets at least one of the surgical high-risk criteria listed in CMS National Coverage 
Determination (NCD) for Percutaneous Transluminal Angioplasty (20.7) 
8.3 Exclusion Criteria 
Each potential patient must be screened to ensure that they do not meet any of the following 
exclusion criteria.  This screening is to be based on known medical history and data available at the 
time of eligibility determination and enrollment. 
 
1. Patient has an alternative source of cerebral embolus, including but not limited to:  
a. Patient has chronic atrial fibrillation.  
b. Patient has had any episode of paroxysmal atrial fibrillation within the past 6 months, or 
history of paroxysmal atrial fibrillation requiring chronic anticoagulation. 
c. 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). 
d. Recently (<60 days) implanted heart valve (either surgically or endovascularly), which is 
a known source of emboli as confirmed on echocardiogram. 
e. 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. 
2. 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). 
3. Patient had hemorrhagic transformation of an ischemic stroke within the past 60 days. 
4. 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. 
5. Patient has an evolving stroke. 
6. Patient has an intracranial tumor.  

 
 
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7. 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). 
8. Patient has had a TIA or amaurosis fugax within 48 hrs prior to the procedure. 
9. Patient has an isolated hemisphere defined as the ipsilateral middle cerebral artery being 
supplied only by the ipsilateral internal carotid artery. 
10. Patient has active bleeding diathesis or coagulopathy or will refuse blood transfusion. 
11. Patient had or will have CABG, endovascular stent procedure, valve intervention or vascular 
surgery within 30 days before or after the intervention. 
12. Myocardial Infarction within 72 hours prior to the intervention. 
13. Occlusion 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. 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.). 
16. Ostium of Common Carotid Artery (CCA) requires revascularization (>50% stenosis).  
17. Patient has an open stoma in the neck. 
18. Patients with hostile necks due to prior neck irradiation 
19. Female patients who are pregnant 
20. 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. 
21. 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. 
22. Patient has had a recent GI bleed that would interfere with antiplatelet therapy. 
23. Patient is actively participating in an investigational drug or device trial (IND or IDE) that has not 
completed the required protocol follow-up period.  
24. Patient has inability to understand and cooperate with study procedures. 
25. Presence of extensive or diffuse atherosclerotic disease involving the proximal common carotid 
artery that would preclude the safe introduction of the study device. 
26. Patient is otherwise unsuitable for intervention in the opinion of the physician. 
27. Patients who cannot have MRI due to metallic implants (e.g. orthopedic implants, pacemakers, 
etc.) 

 
 
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8.4 Enrollment Determination 
Patients meeting all of the inclusion criteria and none of the exclusion criteria, can be considered for 
inclusion in the study. 
9 Patient Enrollment  
A minimum of 50 patients and a maximum of 75 patients.  
The first 2 cases performed at each participating site will be evaluated to ensure compliance with the 
procedural guidelines and to determine the suitability of the imaging for review by the core lab. If it is 
determined that additional training on the procedural guidelines or revisions to the imaging 
parameters are required, then these patients will be excluded from the primary endpoint analysis. 
9.1 Enrollment Phase 
Patients are considered to be enrolled after signing the informed consent and having undergone a 
successful TCAR procedure (e.g. the procedure was not aborted due to technical issues or due to 
local complications the preclude stent implantation). Patients who are screened but do not meet all 
study criteria are considered screen failures and may not be enrolled. 
9.2 Patient Numbering  
Patients will be identified by a Patient Identification (ID) number, which is a combination of the 
specified site number and a sequential number assigned by the site.  The Patient ID will consist of a 
3-digit number and will be consecutively assigned.  
 
Examples: 
First Patient Enrolled at site #801: 801-001 
9.3 Patient Discontinuation 
If possible, every patient should remain in the study until completion of the required follow-up period; 
however, the patient’s participation in the study may be discontinued at any time during the study.  If 
this occurs, the reason for discontinuation should be documented in the source documentation, and 
Study Exit form must be completed.  Factors leading to patient discontinuation may include, but are 
not limited to the following: 
• 
Patient Withdrawal:  Patient participation is voluntarily and the patient may discontinue 
participation (refuse all subsequent testing and follow-up) or withdraw their consent from the 
study at any time without affecting their future medical treatment or benefits. 
• 
Physician Termination:  The physician may terminate the patient’s participation without 
regard to the patient’s consent if the Physician believes it is medically necessary. 
• 
Lost to Follow-up:  A patient will be considered lost to follow-up only after three 
unsuccessful, documented attempts to contact the patient have been made.   

 
 
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10 
Procedures 
10.1 Informed Consent 
Prior to patient participation in this evaluation, the Physician must obtain written Institutional Review 
Board approval for the protocol and the informed consent form.  The approved consent form should 
clearly reflect the IRB/EC approval date and protocol version.  
 
Once the patient’s eligibility has been determined, the Physician or person designated by the 
Physician who has been trained to the protocol, will explain the nature and scope of the study, 
potential risks and benefits of participation, answer questions for the patient and ask the patient to 
participate in the study.  The study will be explained to the study patient in lay terms and native 
language.  If the patient agrees to participate, the informed consent must be signed and personally 
dated by the patient and the person completing the consent process.  A copy of the signed and 
dated informed consent will be provided to the study patient.  Study patients will be assured that they 
may withdraw from the study at any time and for any reason.   
 
Failure to obtain a signed informed consent form prior to the procedure constitutes a major protocol 
deviation and non-compliance with internationally recognized good clinical practices per ISO 14155, 
the Declaration of Helsinki and the Code of Federal Regulations (21 CFR 50.20 General 
requirements for informed consent). 
10.2 Diffusion-Weighted Magnetic Resonance Imaging (DW-MRI) 
Evaluation 
A DW-MRI evaluation is to be done pre, post and 30 days post the index procedure.  The following 
sequences should be used for each evaluation.  
Magnetic resonance using a 3 Tesla MR imaging scanner.  Sequences : T1, T2, T2*, GRE, FLAIR, 
DWI and ADC map.  Slice thickness: 4mm 
 
Table 1.  DW-MRI visit windows 
Visit Window 
Imaging Timing 
Pre-procedure  
≤ 72 hours prior to procedure 
Post-procedure 
Within 12 – 60 hours post procedure 
30 days Post-procedure 
30 days(-7/+15 days) post procedure 
 
 
10.3 Pre-Procedure 
Dual antiplatelet therapy and statin medications taken during the course of the study should be 
documented on the CRFs and a dosage indicated if possible.   
 
 

 
 
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Table 2.  Pre-procedure Testing and Evaluations 
Test / Evaluation 
Timeframe Prior to Procedure  
(within # days) 
180 
days 
60 
days 
30 
days 
7 days 
≤ 72 hours 
General Examination 
 
 
 
 
 
Medical History 
 
 
 
√ 
 
 
Neurological Examination1 
 
 
 
 
 
NIH Stroke Scale 
Modified Rankin Scale 
 
 
 
√ 
 
Imaging 
 
 
 
 
 
Bilateral Duplex Ultrasound (% of stenosis) 
 
√ 
 
 
 
DW-MRI  
 
 
 
 
√ 
CTA of the head and neck 
√ 
 
 
 
 
 
1Every attempt should be made to have the same person conduct the exam at each visit. 
10.3.1 Pre-Procedure Medication Regimen  
All medications should be administered per the following medication guidelines.  All medications 
administered should be recorded on the patient’s medical record and on the CRF throughout the 
duration of the trial. Prior to the procedure, all patients should receive the following medications: 
Table 3. Pre-Procedure Medication Regimen 
Medication 
Dose 
Time prior to 
procedure 
Notes 
Aspirin 
75-325 mg*  
At least 72 hrs 
A 650 mg loading dose of aspirin, 
provided that it is not enteric coated or 
extended release, at least 4 hours prior 
to procedure is acceptable if 325 mg 
dosing was not administered prior to 
procedure or per the Institution’s 
standard of care. 
Clopidogrel 
75 mg* 
At least 72 hrs 
A 450 mg clopidogrel loading dose at 
least 4 hours prior to procedure is 
acceptable if 75 mg dosing was not 
administered prior to procedure. 
 
The physician may substitute 
Prasugrel, ticlopidine, ticagrelor  or a 
generic version of Clopidogrel per the 
manufacturer’s published guidelines. 
 
If ticlopidine or ticagrelor is prescribed, 
it must be administered with the 
appropriate safety monitoring at two 
weeks and at one month. 

 
 
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Medication 
Dose 
Time prior to 
procedure 
Notes 
Statin 
Therapeutic dose 
Daily for at 
least 7 days  
If possible, patients who are not 
currently on a statin should be started 
on a therapeutic dose for 7 days pre-
procedure if not, use loading dose. 
A loading dose at least  12 hours 
before procedure is acceptable if the 
patient is not already on a statin. 
*As stated in the "2011 ASA/ACCF/AHA/AANN/AANS/ACR/ASNR/CNS/SAIP/SCAI/SIR/SNIS/SVM/SVS guideline on 
the management of patients with extracranial carotid and vertebral artery disease: executive summary." and "ESVS 
Guidelines. Invasive Treatment for Carotid Stenosis: Indications, Techniques." 
10.3.2 Pre-Procedure Contrast Preparation 
Contrast should be drawn in to a manifold contrast injection system and allowed to rest undisturbed 
for a minimum of 20 minutes prior to planned usage. 
 
At the discretion of the physician a syringe may be used for contrast injection.  At least 20 minutes 
prior to use contrast should be drawn up into a least five 10ml luer lock syringes.  Allow syringes to 
rest undisturbed for a minimum of 20 minutes prior to planned usage. Use of an automated contrast 
injector is recommended but not required. 
10.4 TransCarotid Revascularization 
10.4.1 Index Procedure 
Responsibility for performing the index procedure may not be delegated to a Physician who has not 
been approved by the sponsor.   
10.4.2 Procedural Medications 
Heparin should be administered to achieve the desired activated clotting time (ACT).  A sufficient 
dose should be given to achieve a target activated clotting time (ACT) of ≥ 250 seconds and 
maintained throughout the procedure.  
 
At the discretion of the physician, procedural anticoagulation may be achieved with Angiomax 
(bivalirudin) which must be administered accordingly during the procedure. 
 
The use of local or general anesthetic during the procedure is at the discretion of the physician. 
 
IMPORTANT:  Pre-treatment with a thrombolytic agent or GP IIb/IIIa blocker is NOT allowed. 
10.4.3 Stenting TCAR Procedure 
The ENROUTE Transcarotid Neuroprotection System (ENROUTE Transcarotid NPS) will be used 
for all index procedures in conjunction with the ENROUTE Transcarotid Stent System.  Please refer 
to the IFU supplied with the ENROUTE Transcarotid NPS and Stent System for device preparation 
and placement.   
 
Standard surgical means should be used to occlude the CCA during the index procedure. 
 
After the ENROUTE Transcarotid NPS has been positioned, pre-dilatation of the lesion may be done 
prior to stent placement.  Use an appropriately sized balloon to achieve a lumen diameter large 

 
 
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enough for passage of the stent delivery system.  The appropriate size stent shall be selected after 
review of the patient’s pre-procedure angiogram for determination of the reference vessel.   
 
The choice of stent length should ensure complete coverage of the lesion.  Only one stent should be 
used unless there is incomplete coverage of the target lesion or in the case of complications.  For 
complications, an additional commercially available stent may be used. 
 
IMPORTANT:  Debulking devices, such as directional or rotational atherectomy and/or transluminal 
extraction coronary (TEC) devices may NOT be used.  
10.5 Criteria for Bailout 
Bailout measures are at the discretion of the physician. Emergent endovascular therapy 
(neurovascular rescue) may be employed as necessary to provide the best medical care for the 
patient. 
10.6 Mechanical Failures, Malfunctions or Device Defects 
All mechanical failures, malfunctions or defects involving any device component must be reported to 
the Sponsor in accordance with the FDA device reporting guidelines and EU Vigilance Reporting 
requirements. 
10.7 Post-Index Procedure Medications 
All medications should be administered per the following medication guidelines.  All medications 
administered should be recorded on the patient’s medical record and on the CRF throughout the 
duration of the trial. After the procedure, all patients (lead-in and pivotal) should receive the following 
medications: 
Table 4.Post Procedure Medication Regimen 
Medication 
Dose 
Duration post-procedure 
Aspirin 
75 – 325 mg 
Daily, continued indefinitely 
Clopidogrel 
75 mg 
Daily, for minimum of 4 weeks 
Statin 
Therapeutic dose 
Daily, for minimum of 4 weeks 
11 
Post Procedure Evaluation  
The following tests or procedures must be obtained as per schedule.  These tests must be 
performed whether or not they are considered part of the Physician’s standard of care. 
 
 
 

 
 
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Table 5.  Post-Procedure Testing and Evaluations 
Test / Evaluation 
Timeframe Post-Procedure  
Within 12 – 60 
hrs post 
procedure 
Within 
24 hrs 
Prior to 
Discharge 
Neurological Examination1 
 
 
 
NIH Stroke Scale 
Modified Rankin Scale 
 
√ 
 
Imaging 
 
 
 
DW-MRI  
√ 
 
 
1Every attempt should be made to have the same person conduct the exam at each visit. 
 
Prior to hospital discharge the study coordinator and/or Principal Physician at the site should ensure 
that the patient understands and complies with the required follow-up schedule.  If possible, patients 
or family members may be given a calendar of required follow-up visits and telephoned by a member 
of the research team for a visit reminder, just prior to the follow-up date. 
11.1 Follow-up  
Study patient clinic evaluations must occur at multiple time-points post-procedure.  The following 
tests or evaluations must be obtained: 
 
Table 6. 30-day Testing and Evaluations 
 
Test / Evaluation 
30-days 
(-7/+15 days) 
Neurological Examination1 
 
NIH Stroke Scale 
Modified Rankin Scale 
√ 
Imaging 
 
Duplex Ultrasound (Bilateral) 
√ 
DW-MRI 
√ 
1 Every attempt should be made to have the same person conduct the exam at each visit. 
12 
Assessment of Safety and Performance 
Performance and safety will be monitored continuously throughout the conduct of the study.  
12.1 Clinical Follow-up Visits 
Patients will be contacted for clinical follow-up office visit between 30 and 45 days post procedure.  
 
Appendix 1. Schedule of Events outlines the evaluations that are be done at each time point. 
12.2 Additional Follow-up Visits 
Additional patient visits may occur as clinically warranted.   

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13 
Adverse Events 
Adverse event (AE) data will be collected throughout the study and will be recorded on the Adverse 
Event CRF.  For the purposes of this evaluation, adverse events include any stroke or neurological 
death. 
14 
Statistical Methods 
No formal hypothesis testing is planned; parameter estimates will be defined using descriptive and 
inferential statistics.  
14.1 General Considerations 
Inferential statistical tests will be identified as being either one- or two-sided, and the construct of the 
confidence limits will be defined (e.g. 90% or 95%).  Exact confidence intervals will be used for all 
presentations. 
14.2 Endpoint Analyses and Hypothesis Testing 
The objective of this registry is to provide contemporaneous estimates ascribed to the event rates 
(rate of new white lesions on DW-MRI) under commercial use conditions. No formal statistical 
hypotheses regarding safety or efficacy will be made.  Additional summaries and tabulations may be 
presented by demographic and disease-related parameters. 
15 
Data Collection 
15.1 Required Data 
All required data for this evaluation will be collected on standardized Case Report Forms (CRFs).  
For the duration of the evaluation, the Physician will maintain complete and accurate documentation, 
including but not limited to, medical records, evaluation progress notes, laboratory reports, CRFs, 
device accountability logs, correspondence with the reviewing IRB/EC, sponsor and Monitor, 
adverse event reports, and information regarding patient discontinuation or completion of the 
evaluation. 
The physician/institution will permit direct access to source data and documents in order for 
evaluation-related monitoring, audits, IRB/EC reviews, event adjudication and regulatory inspections 
to be performed.  The physician should obtain, as part of the Data Release Consent process, 
permission for authorized sponsor employees, monitors or regulatory authorities to review, in 
confidence, and records that identify patients in this trial.   
15.2 Source Documentation 
Regulations require that the Physician maintain information in the patient’s medical records, which 
corroborate data collected for the evaluation.  In order to comply with these regulatory requirements, 
at minimum, the following is a list of information that should be maintained: 

Medical history / general physical condition of the patient before involvement in the
evaluation of a sufficient nature to verify the protocol eligibility criteria.

Dated and signed notes on the date of entry into the evaluation documenting the following:

 
 
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 
The general health of the patient,  
 
Dated and signed notes from each patient visit to support all data recorded on the CRFs. 
 
Adverse events reported and their continuation or resolution at EACH visit, including 
supporting documents such as discharge summaries, catheterization lab reports, ECGs, lab 
results, CT/MRI reports. 
 
Notes regarding protocol-required and prescription medications taken during the evaluation 
(including start and stop dates if known). 
 
Patient’s general health and medical condition upon completion of or withdrawal from the 
evaluation. 
15.3 Case Report Forms 
Data will be accurately recorded on the Case Report Forms (CRFs) in an electronic data capture 
system by site personnel that have been trained on the protocol and CRF completion.  
15.4 Record Retention 
All clinical sites will maintain all records pertaining to this evaluation for a minimum of two years (or 
as long as required by specific institutional guidelines) after the evaluation is discontinued.  The 
sponsor will notify the clinical sites of the discontinuation or planned end of evaluation as well as 
where applicable, the Physician and/or Silk Road Medical will inform the IRB or EC/Competent 
Authorities 
15.5 Confidentiality 
All data and information collected during this evaluation will be considered confidential by the 
Sponsor.  All data used in the analysis and summary of this evaluation will be anonymous, and 
without reference to specific patient names.  Access to patient files will be limited to authorized 
personnel of the Sponsor, the Physician, Clinical site research staff and authorized Regulatory 
Authorities.  Authorized regulatory personnel have the right to inspect and copy all records pertinent 
to this evaluation. 
16 
Sponsor Responsibilities 
As the Sponsor, Silk Road Medical, has the overall responsibility for the conduct of the evaluation 
including assurance that the evaluation satisfies the regulatory requirements of the appropriate 
regulatory agencies.   
16.1 Training of Physicians and Site Personnel 
Physicians and site personnel will be trained on the following aspects of the evaluation: 
 
Protocol 
 
Case Report Forms 
 
Reporting Responsibilities 
 
Device Instructions for Use 
 
Confidentiality 

 
 
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17 
Monitoring 
The Sponsor or designee may regularly monitor the evaluation throughout its duration.  Monitors will 
visit each site to review clinical data for accuracy and completeness and to ensure compliance with 
the protocol.  The Monitor may inspect all documents and required records that are maintained by 
the Physician, including medical records (office, clinic or hospital) for the patients in this evaluation.  
The Physician will facilitate access to these records by authorized representatives of the Sponsor, 
and appropriate regulatory agencies.   
 
A termination (close-out) monitoring visit will be conducted at the completion of the evaluation to 
ensure that all clinical trial materials and patient data are properly documented and stored until SRM 
(Sponsor) informs the Physician that data collection has been completed.  The Sponsor will notify 
each site during the closeout visit of the current data storage requirements.   
18 
Site Responsibilities 
18.1 Site Personnel Responsibilities  
18.1.1 
Principal Physician 
 
Ensures that the appropriate IRB or EC approvals are obtained as required, 
 
is responsible for the overall conduct of the evaluation at the site, 
 
is trained in the use of the devices, 
 
is trained on the evaluation protocol, forms, and procedures. 
18.2 Physician Responsibilities 
The Physician is responsible for ensuring that this evaluation is conducted according to this Clinical 
Protocol, and all conditions of IRB/EC approval and applicable regulations.  The Physician is 
responsible for ensuring that Data Release Consent is obtained, if required.  The data release form 
may be translated into the applicable language.   
 
Patients must be informed that their medical records may be subject to review by SRM (Sponsor), its 
authorized designee, or local regulatory representatives.  Patients will be informed that they are free 
to refuse to participate in this evaluation without loss of benefits to which they are otherwise entitled, 
and that if they choose to participate, they may withdraw at any time without prejudice to future care.   
18.2.1 Physician Records 
The Physician will maintain complete, accurate and current evaluation records.  Records shall be 
maintained during the evaluation and for two years (or as long as required by specific institutional 
guidelines) after the date on which the evaluation is terminated or completed, or the date the records 
are no longer required.   
18.2.2 Patient Records 
Patient records include copies of all completed Case Report Forms and supporting documents 
(laboratory reports, reports of diagnostic tests, medical records, etc.). 
 

 
 
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At any time, patients are entitled to ask the Physician for access to all the information collected in 
this study relating to him or her. If any of the information is inaccurate, the subject is entitled to 
request to the physician that the appropriate changes or corrections are made.  
18.2.3  IRB/EC Information 
The physician is responsible for maintaining any information pertaining to the IRB/EC review and 
approval as required by local law. 
18.2.4 Other 
The physician is responsible for any other records that may be required by applicable laws. 
19 
Core and Central Laboratories 
19.1 DW-MRI Core Laboratory 
All DW-MRI evaluations will be sent to the DW-MRI core laboratory for review. The evaluation will be 
reviewed using a standard method per the core laboratory guidelines and these data will be used for 
final analysis. 
20 
Protocol Deviations 
A protocol deviation is defined as an event where the physician or site personnel deviate from the 
protocol or procedures.   
 
In the event that a physician does not comply with the Physician agreement, and/or the protocol, the 
physician will be notified of their non-compliance, and the circumstances will be reviewed by the 
sponsor.   
21 
Device Accountability 
Product used in this evaluation are FDA approved/cleared and have CE marking. The devices are 
commercially available and device accountability is not required.  
22 
Ethics 
This evaluation is a non-interventional post market evaluation, which means that IRB/EC approval 
depends on local law / hospital requirements.  If not required, written documentation from the 
physician should be maintained with the records 
22.1 Protocol Amendments 
Approved protocol amendments will be provided to the Physicians by the sponsor prior to 
implementing the amendment.  The Physician will be responsible for notifying or obtaining approval 
from the reviewing IRB/EC of the protocol amendment, if required by local law/hospital.   The 
IRB/EC acknowledgement/ approval of the protocol amendment must be documented in writing prior 
to implementation of the protocol amendment.  Copies of this documentation must also be provided 
to the Sponsor. 

 
 
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22.2 Data Release Consent 
If required, by local law / hospital the physician should obtain written Data Release Consent prior to 
releasing personal information of the patient. An IRB/EC approved Data Release Consent may be 
required according to local law/hospital requirements. 
22.2.1 Data Release Consenting Procedures 
During the Data Release Consent discussion, the physician or his/her designee must fully inform the 
subject of the evaluation in a non-technical wording understandable for the patient. The patient must 
have ample time and opportunity to inquire about details of the evaluation, and to decide whether or 
not to participate. All questions about the evaluation should be answered to the satisfaction of the 
patient.    
 
After all persons have signed and dated the Data Release Consent form the physician must provide 
the patient with a copy of the signed and dated Data Release Consent form. 
23 
Use of Information and Publication 
All information and data generated in association with this evaluation will be held in strict confidence 
according to local regulation and remains the sole property of Silk Road Medical.  The Physician 
agrees to use this information for the sole purpose of completing this evaluation and for no other 
purpose without written consent from the Sponsor. 
 
At the conclusion of this evaluation, a multi-center abstract reporting the primary results may be 
prepared and presented in an appropriate scientific forum.  A multi-center peer-reviewed manuscript 
may also be prepared for publication in a reputable scientific journal.  The publication of the principal 
results from any single center experience within the evaluation will be coordinated with the Sponsor.  
The site shall have the right to publish their individual results but only after publication of the multi-
center publication is complete, provided, however, that at least thirty (30) days prior to any 
submission of a publication or presentation, the site provides Silk Road Medical with a copy of the 
publication or presentation for Silk Road Medical’s review and approval.  Silk Road Medical reserves 
the right to delay approval either to prevent bias in ongoing clinical trials or to prevent adverse 
impact on the completion of the planned evaluation. 
24 
Termination 
The Sponsor will monitor the progress of the evaluation.  If warranted, the evaluation may be 
suspended or discontinued early if there is inadequate patient enrollment. 
 

 
 
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Appendix 1.  Schedule of Events 
 
PROCEDURE/TEST 
Pre-Procedure 
(within # of days) 
Procedure 
Post-Procedure 
Follow-up Visits 
180 
days 
60 
days 
30 
days 
7 
days 
≤72 hrs 
Within 
24 hrs 
Prior to 
Discharge 
Within 12 – 60 hours 
post procedure 
30-days 
(-7/+15 days) 
Informed Consent  
 
X 
 
 
 
 
 
 
 
 
Neurological Examinations1 
 
 
 
 
 
 
 
 
 
 
NIH Stroke Scale 
Modified Rankin Scale 
 
 
 
X 
 
 
X 
 
 
X 
Imaging 
 
 
 
 
 
 
 
 
 
 
Bilateral Duplex Ultrasound 
(% of stenosis) 
 
X 
 
 
 
 
 
 
 
X 
CTA2 
X 
 
 
 
 
 
 
 
 
 
DW-MRI  
 
 
 
 
X 
 
 
 
X 
X 
Other Assessments 
 
 
 
 
 
 
 
 
 
 
Medical History 
 
 
X 
 
 
 
 
 
 
 
Medications 
 
X 
 
 
 
X 
X 
X 
 
X 
Adverse events 
 
 
 
 
 
X 
X 
X 
 
X 
1  Must be performed by a Neurologist, NIHSS-certified personnel or other designee.  Every attempt should be made to have the same person conduct the exam at each visit.  The 
primary operator may not conduct the neurological exam on the treated patient. 
2 The suitability of access site and distance from the clavicle to the bifurcation (as part of standard of care) may be measured by computerized axial tomography (CT) angiography 
in accordance with the FDA approved labeling. 

 
 
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Appendix 2.  Case Report Forms 
Case Report Forms are on file separately at Silk Road Medical 
Document  # 
Title 
SRM-2018-08-CRF01 
Pt Registration 
SRM-2018-08-CRF02 
Medical History 
SRM-2018-08-CRF03 
Procedure 
SRM-2018-08-CRF04 
Devices 
SRM-2018-08-CRF05 
Follow-up 
SRM-2018-08-CRF06 
Neuro Exam 
SRM-2018-08-CRF08 
Protocol Deviation 
SRM-2018-08-CRF09 
Adverse Events 
SRM-2018-08-CRF07 
Study Exit 
SRM-2018-08-CRF010 
DW-MRI 
 
 
 

 
 
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Appendix 3. Physician List 
 
Physician list will be kept on file separately. 
 
 

 
 
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Appendix 4.  Definitions 
 
Access Site Complication 
A localized collection of extravasated blood in subcutaneous tissue at the access site as described 
and stratified as Procedural in section 12.1 Post Procedure Surgical Wound Management of this 
protocol. 
 
Acute Device Success 
Defined as ENROUTE Transcarotid NPS was delivered (vascular access achieved), reverse flow was 
attempted and established, and the device retrieved / removed from vasculature.  If sheath placement 
is attempted but unsuccessful it will be considered an acute device failure.  If procedure is aborted 
(e.g. patient isn’t cooperative, change in health status, other extenuating circumstance, etc.) before 
both sheaths are placed or reverse flow is attempted it is not considered a device failure.  Aborted 
procedures will not be included in Success rate calculations. 
 
Amaurosis Fugax 
A temporary (<24 hours) loss of vision in one eye due to insufficient blood flow to the retina. 
 
Asymptomatic Patient 
Patient does not have a history of symptoms, stroke or TIA (hemispheric or ocular), in the prior 180 
days. 
 
CABG  
Coronary artery bypass graft. 
 
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. 
 
CEA—Carotid Endarterectomy 
A surgical procedure in which atherosclerotic plaque is removed from the diseased carotid artery.  
 
Closure 
Closure is divided into two categories: 
Abrupt Closure     The occurrence of new severely reduced flow within the target vessel that 
persists, and requires rescue by a non-assigned treatment strategy, (including 
emergency surgery) or results in stroke or death.  Abrupt closure requires a 
proved association with a mechanical dissection of the treatment site or 
instrumented vessel, thrombus or severe spasm.  Abrupt closure does not 
connote “no reflow” (due to microvascular flow limitation), in which the carotid 
artery is patent but has reduced flow.  Abrupt closure also does not connote 
transient closure with reduced flow in which the index treatment application 
does reverse the closure. 

 
 
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Late Closure     Defined as abrupt closure that occurs after the index procedure is completed, and 
the patient has left the angiography suite, and before the 30-day follow-up 
endpoint. 
 
Cranial Nerve Palsy or Injury 
Injury to cranial nerves in the vicinity of the treated carotid artery that has not resolved by one month 
and six months after the initial procedure. Symptoms will depend on the specific nerve that is injured, 
such as difficulty swallowing or paralysis of facial muscles. 
 
CVA—Cerebral Vascular Accident (See definition for Stroke)  
 
Death 
Cessation of brain, cardiac, and pulmonary functions 
Neurologic Death    Death due to stroke or other neurologic cause. 
Cardiac Death    Death due to MI or other cardiac cause. 
Other    Death that cannot be attributed to neurologic or cardiac causes. 
 
Device Malfunction 
The failure of a device to meet any of its performance specifications or perform as intended.  
Performance specifications include all claims made in the labeling of the device.  
 
Device Related Adverse Event 
An undesirable event that was directly caused by the device.  
 
Dissection 
A tear or damage to the intimal wall or lining of an artery (may or may not be flow limiting). 
 
Emergent CEA 
Carotid endarterectomy performed on an urgent or emergent basis for severe vessel dissection, 
treatment failure resulting in vessel occlusion or inability to access the target vessel. 
 
Intolerance to Reverse Flow 
The inability of a patient to tolerate the reversal of blood flow in the carotid artery during the index 
procedure.  Defined as unresolved neurological deficit after antegrade flow restoration.  Transient 
intra-procedural neurological changes, attributed to reverse flow, are not considered intolerance or an 
adverse event. 
 
Isolated Hemisphere 
Intracranial circulation that is fed only by the ipsilateral ICA and may be detected on prior CTA/MRA 
Life Expectancy  
Defined as ≥ 3 years at the time of the index procedure without contingencies related to other medical, 
surgical or endovascular intervention.  Also defined as <3 years without 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. 

 
 
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Major Adverse Event (MAE) Rate 
A composite rate of death, stroke and myocardial infarction  
 
Procedure Related Adverse Event 
An undesirable event that occurred as a direct cause of the procedure that was not a direct cause of 
the device. 
 
Procedure Success 
Technical Success without the occurrence of MAE 30-days post procedure. 
 
Restenosis 
Any narrowing of the treated segment occurring greater than 30 days after the procedure. 
 
Serious Adverse Event (SAE) 
Any adverse event that: 
 
led to death 
 
led to a serious deterioration in the health of the patient that 
o 
resulted in a life-threatening illness or injury 
o 
resulted in a permanent impairment of a body structure or a body function 
o 
required in-patient hospitalization or prolongation of existing hospitalization 
o 
resulted in medical or surgical intervention to prevent permanent impairment to body 
structure or a body function.   

 
 
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Stroke 
A neurological deficit attributed to an acute focal injury of the central nervous system (CNS) by a 
vascular cause, including cerebral infarction, intracerebral hemorrhage (ICH), and subarachnoid 
hemorrhage (SAH). 
 
Major Stroke 
NIH ≥5 
Rankin ≥3 
 
Note: If NIH ≥4 at enrollment, any change ≥5 is considered a major stroke.  If Rankin ≥3 at 
enrollment, and change ≥1 is considered a major stroke  
 
 
Minor Stroke 
NIH ≤4 
Rankin ≤2 
 
Note: If NIH ≥4 at enrollment, any change ≤4 is considered a minor stroke 
 
IMPORTANT: The determination of stroke and stroke severity is based upon clinical presentation only. 
Imaging will not be used to confirm a diagnosis of stroke. 
 
Symptomatic Patient 
Patient with history of ipsilateral TIA, amaurosis fugax or stroke (minor or non-disabling; NIHSS ≤4, 
OR mRS ≤2) within 180 days prior to the index procedure. 
 
Technical Success: 
Acute Device Success with successful introduction of interventional tools. 
 
 
Transient Ischemic Attack (TIA) 
Temporary focal brain or retinal deficits caused by vascular disease that clear completely in less than 
24 hours. 
 
 
Vascular Complication 
Includes dissection, psuedoaneurysm, hematoma, arteriovenous fistula, thrombus formation, 
embolization and any vascular complication that may be attributed to the procedure or devices used 
during the carotid stenting procedure AND that requires surgical repair, surgical wound revision, 
transfusion, etc. 
 

 
 
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Appendix 5. Procedural Guidelines  
 
The following are procedural guidelines for contrast injection and for pre-dilatation and post-dilatation 
regardless of stent type: 
• 
Contrast injection should be through an automated contrast injector with manifold system. The 
injector (100mls or 150mls) should be filled with contrast 20 minutes in advance of the first 
contrast injection in order to allow the contrast to “degass”. 
• 
Manifold settings: 
o 
Flow rate: 10 ml/s 
o 
Volume: 5ml 
o 
Injection duration: 0.5 
o 
Pressure limit: 600 psi 
o 
Delay: 0 
• 
Post dilatation balloon size: 
o 
Females ≤ 4.5 mm x 20 mm 
o 
Males ≤ 5.5 mm x 20 mm 
• 
Inflation pressure should be according to the balloon instructions for use and the balloon 
should be slowly deflated. 
• 
Flow reversal should be continued ≥ 1 minute after post dilatation. 
• 
Aspirate through the side-arm of the NPS arterial sheath when removing it.