Randomized Clinical Study to Evaluate the Advance® Enforcer™ 35 Focal-Force PTA Balloon Catheter in Treatment of Arteriovenous Dialysis Access Circuit Stenosis
Phase: NA
Conditions: End-Stage Renal Disease
Sponsor: Cook Research Incorporated

Cook Research Incorporated  
Version: 17-04-02 
Enforcer Post-Market Study 
 
Version Date: 03 Aug 2018 
 
COMPANY CONFIDENTIAL 
 
Page 1 of 34 
007-13 03.01T 
 
 
 
 
POST-MARKET STUDY PLAN 
 
 
Randomized Clinical Study to Evaluate the Advance® Enforcer™ 35 Focal-Force PTA 
Balloon Catheter in Treatment of Arteriovenous Dialysis Access Circuit Stenosis 
 
 
Global Clinical Number 17-04 
 
Version: 17-04-02 
Version Date: 03 Aug 2018 
 
 
Global Sponsor: 
Cook Research Incorporated 
 
 
 
 
 
 

Cook Research Incorporated 
Enforcer Post-Market Study 
Version: 17-04-02 
Version Date: 03 Aug 201 8 
STUDY PLAN SIGNATURE PAGE 
Global Sponsor Contact: 
I hereby acknowledge that the content presented in this study plan has been reviewed and 
agreed upon. 
Jennifer L. Kerr, President 
Printed Name 
I 
I < 
I 
ll '1 
;Ml/ d' 
Date (DD Mon YYYY) 
COMP ANY CONFIDENTIAL 
Page 2 of34 

Cook Research Incorporated  
Version: 17-04-02 
Enforcer Post-Market Study 
 
Version Date: 03 Aug 2018 
 
COMPANY CONFIDENTIAL 
 
Page 3 of 34 
007-13 03.01T 
STUDY PLAN SIGNATURE PAGE 
 
 
 
Principal Investigator: 
 
I hereby acknowledge that I have read and understand this study plan and agree to 
comply with its contents and requirements. 
 
 
X 
 
 
 
Signature 
Date (DD Mon YYYY) 
 
 
 
Printed Name 
 
 
 

Cook Research Incorporated  
Version: 17-04-02 
Enforcer Post-Market Study 
 
Version Date: 03 Aug 2018 
 
COMPANY CONFIDENTIAL 
 
Page 4 of 34 
007-13 03.01T 
CONFIDENTIALITY STATEMENT 
 
 
 
This document must be treated as a confidential document for the sole information 
and use of the clinical site personnel and the Institutional Review Board (IRB). 
 
 
 

Cook Research Incorporated  
Version: 17-04-02 
Enforcer Post-Market Study 
 
Version Date: 03 Aug 2018 
 
COMPANY CONFIDENTIAL 
 
Page 5 of 34 
007-13 03.01T 
Table of Contents  
1.0 
Study Plan Overview ...............................................................................................7 
2.0 
Ethical Considerations and Regulatory Compliance ...............................................8 
3.0 
Objectives of the Clinical Study ..............................................................................8 
4.0 
Device Description...................................................................................................8 
4.1 
Intended Use .................................................................................................8 
4.2 
General Device Description ..........................................................................8 
4.3 
Device Identification and Tracking ..............................................................9 
5.0 
Background Information ..........................................................................................9 
6.0 
Risk Analysis and Risk Assessment ......................................................................10 
6.1 
Risks and Foreseeable Adverse Events ......................................................10 
6.2 
Anticipated Clinical Benefits ......................................................................10 
6.3 
Methods to Minimize Risks ........................................................................10 
7.0 
Design of the Clinical Study ..................................................................................11 
7.1 
Design of the Clinical Study .......................................................................11 
7.2 
Study Design Rationale ..............................................................................11 
7.3 
Duration of the Study and Patient Participation .........................................11 
7.4 
Measures to be Taken to Avoid or Minimize Bias .....................................11 
7.4.1 Randomization ................................................................................12 
7.5 
Endpoints ....................................................................................................12 
7.5.1 Primary Endpoint ............................................................................12 
7.5.2  Secondary Endpoints ......................................................................12 
7.5.3 Additional Measures .......................................................................12 
7.5.4 Rationale for Endpoint and Additional Measures ...........................13 
7.6 
Variables to be Measured to Demonstrate Achievement of Endpoints ......13 
8.0 
Eligibility Criteria ..................................................................................................14 
8.1 
Patient Consent ...........................................................................................15 
9.0 
Methods..................................................................................................................15 
9.1 
Pre-procedure ..............................................................................................16 
9.2 
Point of Enrollment ....................................................................................17 
9.3 
Study Procedure ..........................................................................................17 
9.4 
Follow-up....................................................................................................18 
9.5 
Reintervention ............................................................................................19 
9.6 
Adverse Events ...........................................................................................19 

Cook Research Incorporated  
Version: 17-04-02 
Enforcer Post-Market Study 
 
Version Date: 03 Aug 2018 
 
COMPANY CONFIDENTIAL 
 
Page 6 of 34 
007-13 03.01T 
10.0 
Participation Endpoints of the Study .....................................................................19 
10.1 
Patient Withdrawal .....................................................................................20 
10.2 
Early Termination or Suspension of the Clinical Study .............................20 
11.0 
Statistical Considerations .......................................................................................21 
11.1 
Sample Size ................................................................................................21 
11.2  Randomization ............................................................................................21 
11.3  Analyses......................................................................................................21 
11.3.1 Primary endpoint analysis ...............................................................21 
11.3.2 Analysis of secondary endpoints .....................................................22 
11.3.3 Analysis of additional measures ......................................................22 
11.4 
Missing Data ...............................................................................................23 
11.5 
Site-level Poolability ..................................................................................23 
12.0 
Deviations from Study Plan ...................................................................................23 
13.0 
Data Collection and Management ..........................................................................24 
14.0 
Monitoring .............................................................................................................25 
15.0 
Clinical Study Administration ...............................................................................25 
15.1 
Approvals....................................................................................................25 
15.2 
Clinical Study Reporting ............................................................................26 
15.3 
Contact information ....................................................................................26 
15.4 
Insurance .....................................................................................................26 
16.0 
Publication Policy ..................................................................................................26 
17.0 
References ..............................................................................................................27 
 
Appendices  
Contact Information ........................................................................................... Appendix A 
Study Event Schedule ........................................................................................ Appendix B 
Standard Practices for Monitoring  .................................................................... Appendix C 
Definitions.......................................................................................................... Appendix D 

Cook Research Incorporated  
Version: 17-04-02 
Enforcer Post-Market Study 
 
Version Date: 03 Aug 2018 
 
COMPANY CONFIDENTIAL 
 
Page 7 of 34 
007-13 03.01T 
1.0 
Study Plan Overview 
Objective: 
To evaluate the necessity of adjunctive therapy following treatment 
of stenoses of a mature native arteriovenous (AV) dialysis access 
circuit fistula or graft with the Advance® Enforcer™ 35 Focal-Force 
PTA Balloon Catheter (hereafter referred to as the Enforcer 
balloon) compared to stenoses initially treated with commercially 
available conventional balloon angioplasty. 
Design of the clinical 
study: 
Multicenter, stratified, randomized, controlled clinical study 
Primary endpoint: 
The primary endpoint is the percentage of lesions requiring 
adjunctive treatment immediately following the study procedure.  
Number of patients: 
Approximately 200 patients (at minimum 250 lesions) 
Number of clinical sites: 
Up to 10 clinical sites 
Patient participation 
duration: 
Patient’s medical records will be reviewed through 90 days post-
procedure. 
Expected study duration: 
Patient enrollment is expected to be completed within 1 year of 
study initiation. Total study duration (from study initiation through 
patient enrollment and follow-up) is expected to be 15 months. 
 
Baseline assessments and screening in accordance with institutional standard of care. 
Informed consent. 
Study-specific baseline assessments and screening based on history, clinical assessment, 
and angiography prior to balloon catheter introduction. 
Stratification based on number of lesions requiring treatment (1 or 2) and type of AV 
access circuit (fistula or graft) and randomization. 
Angioplasty in accordance with randomization and completion angiography following 
treatment of study lesions; patient enrollment will occur when the balloon catheter is first 
introduced into the patient’s body. The physician may also perform adjunctive procedures 
(e.g., using a high-pressure balloon or cutting balloon) if in the best interest of the patient.  
Patient medical records will be reviewed through 90 days post-procedure for assessment of 
adverse events and patency. 
 

Cook Research Incorporated  
Version: 17-04-02 
Enforcer Post-Market Study 
 
Version Date: 03 Aug 2018 
 
COMPANY CONFIDENTIAL 
 
Page 8 of 34 
007-13 03.01T 
2.0 
Ethical Considerations and Regulatory Compliance 
This clinical study will be conducted in accordance with the study plan, the ethical 
principles that have their origin in the Declaration of Helsinki, and the following: 
• ISO 14155a 
 
3.0 
Objectives of the Clinical Study 
The primary objective of this study is to evaluate the necessity of adjunctive therapy 
following treatment of stenoses of a mature native AV dialysis access circuit fistula or 
graft with the Enforcer balloon compared to stenoses initially treated with commercially 
available conventional balloon angioplasty. 
 
4.0 
Device Description  
4.1 
Intended Use  
The Enforcer balloon is intended for percutaneous transluminal angioplasty (PTA) of 
lesions in peripheral arteries including iliac, renal, popliteal, infrapopliteal, femoral and 
iliofemoral as well as obstructive lesions of native or synthetic arteriovenous dialysis 
fistulae. This device is not for use in the cerebral or coronary vasculature. 
 
For this study, the Enforcer balloon will be used in the treatment of obstructive lesions of 
native or synthetic arteriovenous dialysis fistula.  
4.2 
General Device Description 
The Enforcer balloon is a double-lumen catheter with a balloon near its distal tip. Four 
polymer elements are incorporated into the balloon, which provide focal-force upon 
inflation. These elements will aid in opening lesions. Platinum/iridium, radiopaque 
markers are positioned on the shaft within the balloon to enable visualization of the 
catheter/balloon under fluoroscopy. The catheter is compatible with 0.035 inch 
(0.89 mm) wire guides. 
                                                 
 
a The study will not require strict adherence to all aspects of ISO 14155: 2011. Regarding section 6.8.1, 
Traceability of documents and data: A signature and date from a member of the investigation team will not 
be necessary for all source documentation. Regarding section 6.4.1, Adverse events and section 9.8, Safety 
Reporting: Adverse event reporting will be limited to those events listed in this Study Plan Section 9.6: 
Adverse Events. Event reporting may not occur until the patient’s medical record review for the 90-Day 
Chart Review. Regarding section 4.7.4, Information to be provided to the subject: It may not be necessary 
for the patient to document their agreement to inform their personal physician of participation in the study. 

Cook Research Incorporated  
Version: 17-04-02 
Enforcer Post-Market Study 
 
Version Date: 03 Aug 2018 
 
COMPANY CONFIDENTIAL 
 
Page 9 of 34 
007-13 03.01T 
Please reference the device for labeling information and the manufacturer’s Instructions 
for Use (IFU) for the following: 
• Detailed description of the device  
• Instructions including storage and handling requirements, preparation for use, pre-
use checks, precautions to be taken after use and disposal 
• Summary of the necessary training and experience required for use of these 
devices  
• Description of the procedures involved in the use of these device 
4.3 
Device Identification and Tracking  
The study device is FDA cleared for use in the United States and will be obtained through 
standard commercial processes. Information regarding device dimensions and lot 
numbers will be reported through an electronic data capture system. 
 
5.0 
Background Information 
The safety and performance of the Enforcer balloon were assessed through a series of 
nonclinical tests performed in accordance with verified methods and procedures to 
maintain the integrity of the results. The testing results provide reasonable assurance that 
the potential risks associated with the use of the device have been mitigated to an 
acceptable level. Additionally, conventional balloon angioplasty is a standard treatment 
for dialysis access dysfunction and several clinical evaluations have been performed and 
reported in literature, which assess safety and performance of angioplasty using different 
balloon technologies (e.g., conventional balloons, high pressure balloons, cutting 
balloons).1 
 
A prospective, single-arm, single-center clinical evaluation of the Enforcer balloon was 
previously conducted to evaluate the treatment of AV access stenoses.2 The study 
evaluated the treatment of 39 AV fistula lesions in 28 patients who were treated with 37 
Enforcer balloons; patients were followed for 6 months post-procedure. Device success, 
defined as < 30% residual stenosis immediately following treatment was 64.1% (25/39). 
Similarly, 92.3% (36/39) of lesions were reduced to < 50% residual stenosis. Overall, 
treatment with the Enforcer balloon led to a reduction in the average percent diameter 
stenosis of the treated lesion from 66.3% pre-procedure to 23.7% post-procedure. The 
average maximum inflation pressure required was 12.3 atm. Only one lesion required 
adjunctive treatment following angioplasty with the study balloon, indicating that 

Cook Research Incorporated  
Version: 17-04-02 
Enforcer Post-Market Study 
 
Version Date: 03 Aug 2018 
 
COMPANY CONFIDENTIAL 
 
Page 10 of 34 
007-13 03.01T 
clinically relevant luminal gains can be achieved with the study device alone, without the 
need for a high pressure balloon or other additional therapies.  
 
Following the study procedure, all patients could resume normal dialysis. The Kaplan-
Meier estimates for patency at 90 days and 6 months were 62.0% and 25.1%, 
respectively. The rate of access site complications were low (1/28; 3.6%). Overall, the 
data supported the safety of the Enforcer ballon for the treatment of stenotic lesions in 
mature native AV hemodialysis access circuits. 
 
6.0 
Risk Analysis and Risk Assessment 
6.1 
Risks and Foreseeable Adverse Events 
Please reference the IFU for the following: 
• Potential adverse events 
• Warnings 
• Precautions 
In addition, participation in this clinical study is associated with the following risk: 
• Release of personal information 
6.2 
Anticipated Clinical Benefits 
Percutaneous transluminal angioplasty of a stenosed lesion in an AV access circuit could 
result in a resumption of normal hemodialysis. 
6.3 
Methods to Minimize Risks  
Methods to minimize risk to patients include: 
• Design of the device (as verified in nonclinical testing) 
• Study design (e.g., monitoring of study conduct, limiting imaging requirements, 
eligibility criteria, informed consent)  
• Conduct of the study at clinical sites with principal investigators qualified by 
training and experience 
• Device will be used only by experienced investigators who have completed study 
training 
• Study oversight by IRB 
• Adverse event reporting as outlined in this study plan 

Cook Research Incorporated  
Version: 17-04-02 
Enforcer Post-Market Study 
 
Version Date: 03 Aug 2018 
 
COMPANY CONFIDENTIAL 
 
Page 11 of 34 
007-13 03.01T 
• Capture, handling, and storage of the study data are done in compliance with 
applicable regulations to minimize the risk of release of any personal health 
information  
The risks of the study have been minimized and the residual risks are considered 
acceptable because they do not outweigh the potential for benefit. 
 
7.0 
Design of the Clinical Study 
7.1 
Design of the Clinical Study 
This multicenter, stratified, randomized, controlled clinical study will evaluate the 
performance of the Enforcer balloon compared to commercially available conventional 
balloons (defined as less than 25 atm rated burst pressure) in the treatment of stenoses of 
the AV dialysis access circuit. 
 
This study will enroll approximately 200 patients at up to 10 clinical sites. Enrollment 
will end when it is determined a minimum of 250 lesions have been treated. 
7.2 
Study Design Rationale 
A randomized clinical trial allows for the direct comparison of the rates of adjunctive 
treatment between the Enforcer balloon and other commercially available standard 
angioplasty balloons. 
7.3 
Duration of the Study and Patient Participation 
Patient enrollment is expected to be completed within 1 year of study initiation. Total 
study duration (from study initiation through patient enrollment and follow-up) is 
expected to be 15 months. 
 
A review of the patient’s medical chart through 90 days after the study procedure will be 
conducted. 
7.4 
Measures to be Taken to Avoid or Minimize Bias 
This study is designed as a stratified, randomized, controlled clinical trial to minimize 
bias in both assigning patients to treatments and in analyzing the results. Each clinical 
site is limited to a maximum number of patients (as described in Section 11.1: Sample 
Size) to minimize bias that may be introduced if the majority of patients are enrolled at 

Cook Research Incorporated  
Version: 17-04-02 
Enforcer Post-Market Study 
 
Version Date: 03 Aug 2018 
 
COMPANY CONFIDENTIAL 
 
Page 12 of 34 
007-13 03.01T 
one or two clinical sites. In addition, the study will utilize uniform definitions for study 
endpoints. 
7.4.1 Randomization 
Once baseline angiography is complete and patient eligibility is confirmed, patients will 
be randomized into either the Enforcer balloon or conventional angioplasty group prior to 
treatment. At each study site, patients will be stratified for randomization based on the 
number of lesions requiring treatment (single lesion or two lesions) and type of AV 
access circuit (fistula or graft), then randomized to one of the treatment groups in a 1:1 
ratio. 
7.5 
Endpoints 
7.5.1 Primary Endpoint 
The primary endpoint is the percentage of lesions receiving adjunctive treatment 
immediately following the study procedure (initial treatment with the Enforcer or 
conventional angioplasty balloon).  
7.5.2  Secondary Endpoints 
• Numeric rating scale (NRS) for pain experienced during study procedure balloon 
inflations 
• Procedural cost 
• Procedure times 
• Maximum balloon pressure 
• Device success 
• Safety measures, including rupture, circumferential tears, and 
reintervention/patency 
7.5.3 Additional Measures 
• Anatomic success  
• Clinical success 
• Adverse events (refer to Section 9.6: Adverse Events for a list of reportable 
events) 
• Primary patency through 90 days 

Cook Research Incorporated  
Version: 17-04-02 
Enforcer Post-Market Study 
 
Version Date: 03 Aug 2018 
 
COMPANY CONFIDENTIAL 
 
Page 13 of 34 
007-13 03.01T 
7.5.4 Rationale for Endpoint and Additional Measures 
The primary endpoint was chosen as it allows for the direct comparison of the rates of 
adjunctive treatment between the Enforcer balloon and other commercially available 
standard angioplasty balloons. The secondary endpoints and additional measures were 
chosen as applicable indicators of device effectiveness because of their similarity to those 
of interest in the literature and their similarity to other clinical studies. 
7.6 
Variables to be Measured to Demonstrate Achievement of Endpoints 
The endpoints and additional measures will be assessed as described in Table 7.6-1. 
 
Table 7.6-1. Assessment of Endpoints and Measures 
Endpoint/Measure 
Measure/Assessment 
Use of adjunctive therapies 
Procedural use of high-pressure balloons, 
cutting balloons, or stents following the study 
procedure (initial treatment with Enforcer or 
conventional angioplasty balloon) 
Device success 
Residual stenosis less than 30% within the 
treated lesion immediately after angioplasty 
with the study device (Enforcer or conventional 
angioplasty balloon) 
Anatomic success 
Residual stenosis less than 30% within the 
treated lesion following procedure (including 
any adjunctive therapy) 
Procedural costs 
Procedural charges and cost-to-charge ratio 
assessed after submission of UB-04 or CMS-
1500 forms 
Procedural time 
Procedural time (defined as the time from 
needle entry for intervention to sheath 
withdrawal) will be assessed after angioplasty 
with the study device (Enforcer or conventional 
angioplasty balloon) 
Balloon pressure 
Maximum inflation pressure and duration 
Numeric rating scale (NRS) for pain 
experienced during study procedure 
balloon inflations 
Patient-reported pain assessment (scale of 0-10, 
where 0 indicates no pain and 10 indicates the 
worst possible pain) 
Clinical success 
Resumption of successful hemodialysis for at 
least one session from chart review through 90 
days 
Primary Patency 
Uninterrupted patency of the AV hemodialysis 
access circuit assessed by reporting of 
reintervention or abandonment of dialysis 

Cook Research Incorporated  
Version: 17-04-02 
Enforcer Post-Market Study 
 
Version Date: 03 Aug 2018 
 
COMPANY CONFIDENTIAL 
 
Page 14 of 34 
007-13 03.01T 
access circuit from chart review through 90 
days 
Adverse events 
Event information from chart review through 90 
days 
• Refer to Section 9.6: Adverse Events, 
for a list of reportable events  
 
8.0 
Eligibility Criteria 
Patient eligibility for enrollment will be based on existing information at the time of the 
procedure. Information obtained at a later date may contradict these criteria, but this will 
not be considered a deviation from the study plan. 
 
Inclusion Criteria  
A patient is suitable for inclusion in the study if the patient meets the following criteria: 
1. A greater than 50% stenosis (when compared to the reference vessel diameter) of 
a mature native AV dialysis access circuit fistula or graft in the upper extremity3 
2. Clinical or physiological abnormalities which indicate dialysis access dysfunction 
(e.g., decreased access blood flow, elevated venous pressure, decreased dialysis 
dose, abnormal physical exam) 
Exclusion Criteria 
Patients must be excluded from enrollment into the study if any of the following are true: 
General Exclusion Criteria: 
1. Less than 18 years old  
2. Unwilling or unable to provide informed consent  
3. Unwilling or unable to comply with the study schedule  
4. Pregnant, lactating, or planning to become pregnant in the 3 months following 
enrollment  
5. Simultaneously participating in an investigational drug or device study involving 
treatment of the AV dialysis access circuit in which the follow-up phase for that 
study’s primary endpoint has not been completed 30 days or more prior to being 
enrolled in this study 
Medical Exclusion Criteria: 
6. Underwent any surgical or interventional procedure of the access circuit less than 
or equal to 30 days prior to the enrollment  

Cook Research Incorporated  
Version: 17-04-02 
Enforcer Post-Market Study 
 
Version Date: 03 Aug 2018 
 
COMPANY CONFIDENTIAL 
 
Page 15 of 34 
007-13 03.01T 
7. Medical condition or comorbid conditions that would limit life expectancy to less 
than 6 months 
8. Scheduled for a kidney transplant 
9. Evidence of systemic or local infection associated with the AV dialysis access 
circuit 
10. Uncorrectable bleeding diathesis or coagulopathy or will refuse blood 
transfusions 
11. Stent or stent graft in or directly adjacent to the study lesion 
Anatomic Exclusion Criteria: 
12. Untreated hemodynamically significant central venous stenosis (>50%); (Central 
venous stenosis may be treated per standard of care during the study procedure) 
13. Inability to cross a study lesion with a guidewire  
14. Study lesion is greater than 4 cm in length (maximum of 4 cm per lesion and 8 cm 
total, if two lesions are treated) 
15. Reference vessel diameter is less than 6 mm or greater than 10 mm 
16. Presence of more than two distinct lesions (stenoses) in the AV dialysis access 
circuit  
8.1 
Patient Consent 
Patients who meet all of the inclusion criteria and none of the exclusion criteria may be 
invited to participate in this study. Patients eligible for enrollment will have the clinical 
study explained to them, as well as potential risks and benefits of their participation in the 
study. Each patient, or legally-authorized representative (if approved by the IRB), who 
agrees to participate must sign and date an informed consent document prior to the 
procedure or any study-specific testing or assessments. If new information is obtained 
after a patient receives treatment with the device, patients who have not exited the study 
must be informed about the new information, and will be re-consented if required by the 
clinical site’s IRB. 
 
NOTE: Patients who have completed participation in this study may not be re-enrolled.  
 
9.0 
Methods 
Refer to Appendix B for a schedule of events for the clinical study. 
 

Cook Research Incorporated  
Version: 17-04-02 
Enforcer Post-Market Study 
 
Version Date: 03 Aug 2018 
 
COMPANY CONFIDENTIAL 
 
Page 16 of 34 
007-13 03.01T 
Data associated with assessment(s)/procedure(s) required by this study plan will be 
recorded on the appropriate electronic case report forms (eCRFs). 
9.1 
Pre-procedure 
A pre-procedural clinical assessment will be completed and will include patient 
demographics and medical history. Baseline data will be collected and recorded on 
appropriate eCRFs. Baseline angiography should be performed prior to study enrollment 
to assess and document study lesion(s) characteristics including length, location, and 
percent (%) stenosis. Up to two distinct lesions can be treated within the dialysis access 
circuit. Pre-treatment for thrombosed dialysis access circuits may be performed (e.g., 
thrombectomy or thrombolysis) prior to enrollment in the study. Also, central venous 
lesions that require treatment (i.e., >50% stenosis) to meet eligibility criteria must be 
treated successfully prior to treatment of the study lesion. Successful treatment of the 
central veins is defined as less than 30% residual stenosis. 
 
Once baseline angiography is complete and patient eligibility is confirmed, patients will 
be randomized as described in Section 7.4.1 into either the Enforcer balloon or 
conventional angioplasty balloon (defined as balloons with rated burst pressure of less 
than 25 atm) group prior to treatment.  
 
Assessment(s) required to be completed prior to patient enrollment are summarized in 
Table 9.1-1. 
 
Table 9.1-1. Pre-procedure requirements 
Pre-procedure 
Assessment(s)/ 
Procedure(s) 
Review study with the patient and obtain written informed consent 
Record demographics, medical history, and AV fistula/graft location 
Perform pre-procedural (baseline) angiography, recording lesion 
characteristics such as:  
• Lesion length, location, and % stenosis 
• Estimated reference vessel diameter 
If necessary, perform treatment of central venous stenosis, 
confirming residual stenosis less than 30% 
If necessary, perform pre-treatment for thrombosed access circuit 
Confirm ability to cross the study lesion(s) with a guidewire 
Randomize patient 
 

Cook Research Incorporated  
Version: 17-04-02 
Enforcer Post-Market Study 
 
Version Date: 03 Aug 2018 
 
COMPANY CONFIDENTIAL 
 
Page 17 of 34 
007-13 03.01T 
If a subject does not qualify for study participation, the reason will be indicated on the 
appropriate eCRF. 
9.2 
Point of Enrollment 
Patients are considered enrolled in the study once the balloon catheter is first introduced 
into the patient’s body. 
9.3 
Study Procedure 
PTA with either the Enforcer balloon or conventional angioplasty balloon will be 
performed and recorded in accordance with the manufacturer’s IFU to achieve a residual 
stenosis < 30%. The balloon diameter may be chosen based on the recommendations in 
the IFU. If necessary, the balloon could be deflated, repositioned, and re-inflated to 
achieve a residual stenosis < 30%. Inflation details (e.g., maximum pressure and duration 
of inflations) will be recorded on an appropriate eCRF. Conventional angioplasty 
balloons are defined as those having a rated burst pressure less than 25 atmospheres. 
Completion angiography to assess percent residual stenosis of the treated study lesion(s) 
should be performed immediately following the study procedure (initial treatment with 
Enforcer or conventional angioplasty balloon) and prior to beginning any adjunctive 
procedures. 
 
The physician may also perform adjunctive procedures (e.g., using a high-pressure 
balloon, cutting balloon, stent, or stent graft) if in the best interest of the patient. High-
pressure angioplasty balloons are defined as those having a rated burst pressure greater 
than or equal to 25 atmospheres. The adjunctive procedure may be performed in 
accordance with the device manufacturer’s IFU to achieve a residual stenosis < 30%. 
Completion angiography following any adjunctive procedures should also be performed. 
Any additional procedures performed will be documented on the appropriate eCRF. 
 
All angiographic images and medical charges (i.e., UB-04 or CMS-1500) should be 
provided to the Sponsor on the appropriate eCRF. Total procedure time (defined as the 
time from needle entry for intervention to sheath withdrawal) as well as total procedural 
charges will be recorded on the appropriate eCRFs. 
 
Type(s) and level(s) of sedation provided during the procedure will be recorded on the 
appropriate eCRF. A single assessment representing the pain associated with balloon 
inflations during the procedure is recommended to be recorded at or before the time of 
the patient’s discharge assessment. Patients will be instructed to rate the pain they feel 

Cook Research Incorporated  
Version: 17-04-02 
Enforcer Post-Market Study 
 
Version Date: 03 Aug 2018 
 
COMPANY CONFIDENTIAL 
 
Page 18 of 34 
007-13 03.01T 
using a numeric pain rating scale (0-10, where 0 indicates no pain and 10 indicates the 
worst possible pain). A summary of the procedure is given in Table 9.3-1 below. 
 
Table 9.3-1. Procedure requirements 
Procedure 
Assessment(s)/ 
Procedure(s) 
Perform angioplasty according to study randomization  
Perform adjunctive procedures (as needed to achieve less than 30% 
residual stenosis, or if in the best interest of the patient) 
• If applicable, an additional completion angiography should 
be performed 
Record lesion treatment information on the appropriate eCRF, such 
as:  
• Post-treatment lesion % stenosis 
• Balloon information, including inflation(s), duration(s), and 
maximum balloon pressure(s) 
Complete patient-reported pain assessment 
Provide total procedural charges 
 
9.4 
Follow-up 
Patient medical records will be reviewed through 90 days post-procedure for assessment 
of adverse events and patency (including reintervention or abandonment of the AV 
dialysis access site). Adverse event reporting will be limited to those events listed in 
Section 9.6: Adverse Events. Events occurring after 90 days post-procedure will not be 
collected. Clinical success will be determined, and is defined as resumption of successful 
dialysis for at least one session. The follow-up requirements are summarized in Table 
9.4-1. 
 
Table 9.4-1. Follow-up requirements 
90 Day Follow-up 
Timing 
Through 90 days following the study procedure 
Type  
Chart Review 
 
Record if patient received at least one successful hemodialysis 
treatment after the study procedure 
Record adverse events (including, but not limited to, reintervention 
or abandonment of the study access circuit; refer to section 9.6: 
Adverse events for a list of reportable events) 

Cook Research Incorporated  
Version: 17-04-02 
Enforcer Post-Market Study 
 
Version Date: 03 Aug 2018 
 
COMPANY CONFIDENTIAL 
 
Page 19 of 34 
007-13 03.01T 
9.5 
Reintervention 
Patients requiring a reintervention within the study lesion may be treated in accordance 
with the institution’s standard of care. Treatment information will be recorded on the 
appropriate eCRF. 
9.6 
Adverse Events  
The following adverse events, occurring after the point of enrollment until the last day of 
patient participation, are to be reported to the sponsor using the appropriate eCRF: 
• Events with potential relationship to the study device or study procedure 
• Serious Adverse Events 
• Restenosis or occlusion resulting in a reintervention or abandonment of AV 
dialysis access circuit 
Information regarding occurrence of adverse events (including onset date, end date, date 
of awareness, event description, treatment, and whether the device or procedure 
contributed to the event) will be captured throughout the study and recorded on the 
appropriate eCRF.  
 
Sites are responsible for following their normal reporting process (e.g., to manufacturer, 
to regulatory authority) for commercially available devices. 
 
The sponsor is responsible for reporting events to the reviewing IRB(s) and principal 
investigator(s) as required according to applicable regulations/standards/policies. 
 
10.0 
Participation Endpoints of the Study 
A patient’s participation in the study will end after any of the following: 
• Patient withdrawal (patient- or investigator-initiated) 
• Medical records determined to be unobtainable for chart review 
• Early termination of the study  
• Patient death 
• Completion of 90-Day chart review 
After a patient exits the study for any reason (e.g., withdrawal, records determined to be 
unobtainable, study closure, or study completion), no additional data will be collected. 
Information up to the date of the participation endpoint will be provided to the Sponsor 
during the 90-Day chart review.  

Cook Research Incorporated  
Version: 17-04-02 
Enforcer Post-Market Study 
 
Version Date: 03 Aug 2018 
 
COMPANY CONFIDENTIAL 
 
Page 20 of 34 
007-13 03.01T 
10.1 
Patient Withdrawal  
A patient may decide to withdraw from the study at any time either before or after 
undergoing the study procedure without prejudice or loss of care. The principal 
investigator may also decide to withdraw the patient from the study at any time based on 
medical judgment. If a patient is withdrawn, a medical chart review will be conducted 
through and including the date of withdrawal. In all instances of withdrawal, data 
collected up to the time of patient withdrawal will be submitted and will include the 
reason why the patient has been withdrawn from the study. Any data collected on the 
patient up to the point of withdrawal may be used in the study.  
10.2 
Early Termination or Suspension of the Clinical Study 
Any decision to suspend enrollment or terminate the clinical study either completely or at 
multiple clinical sites will be made by the sponsor. The sponsor or the IRB may decide to 
suspend enrollment or terminate the study at an individual clinical site. Reasons for early 
termination or suspension of a study (or at one or more sites) may be due to safety 
concerns, effectiveness concerns, ethical concerns, alterations in accepted clinical 
practice, clinical site performance, or organizational issues. In the event of clinical site or 
study closure, all patients who have received the study treatment will be followed for 90 
days following the study procedure.  
 
The principal investigator-required notifications/reports are described in Table 10.2-1. 
The reports will be provided as required by the study plan, IRB policies, or local 
regulations, whichever is more stringent. 
 
Table 10.2-1. Early Termination or Suspension Reports 
Report 
To 
Timeframe to submit 
report (upon awareness) 
IRB initiated suspension or early 
termination 
Sponsor 
Patient 
Within 5 working days 
Sponsor initiated suspension or 
early termination 
IRB 
Patient 
Within 5 working days 
 
The sponsor is responsible for reporting early termination or suspension of the study to 
reviewing IRB(s) and principal investigator(s) as required according to applicable 
regulations/standards. 

Cook Research Incorporated  
Version: 17-04-02 
Enforcer Post-Market Study 
 
Version Date: 03 Aug 2018 
 
COMPANY CONFIDENTIAL 
 
Page 21 of 34 
007-13 03.01T 
11.0 
Statistical Considerations 
11.1 Sample Size 
The expected rates of adjunctive therapy for the Enforcer balloon and conventional 
angioplasty groups were assumed to be 5% and 15%, respectively. A sample size of at 
least 250 total lesions (125 lesions per group) is required to detect a 10% difference in the 
rate of adjunctive therapy with a power of 80% and a type I error of 0.05. Prior 
experience suggests that 40% of patients, on average, would also have a second lesion 
treated. Therefore the study will enroll approximately 200 patients (approximately 100 
patients per group) and enrollment will continue until at least 250 lesions are treated. 
Procedural outcomes are unlikely to depend on the connectivity between lesions within 
an AV dialysis access circuit or the patient-level factors which affect longer-term 
outcomes, and therefore lesions were assumed to be independent for the purposes of the 
sample size calculation.  
 
Up to 10 clinical sites will be included in the study, and the maximum enrollment per 
clinical site will be no more than 80 patients or 40% of the total enrollment. There is no 
minimum enrollment threshold. Patients that withdraw from the study will not be 
replaced. 
11.2  Randomization 
Once patient eligibility is confirmed, patients will be randomized into either the Enforcer 
balloon or conventional angioplasty group prior to treatment in a 1:1 ratio at each study 
site. Randomization will be first stratified by the number of lesions requiring treatment 
(single lesion or two lesions) and type of AV access circuit (fistula or graft). Using 
restricted randomization maximizes the balance of treatment allocations within stratum 
and vice versa. Randomization codes will be maintained by the Sponsor. 
11.3  Analyses 
11.3.1 Primary endpoint analysis 
The study is intended to compare the necessity of adjunctive therapies for lesions treated 
with the study device (Enforcer balloon) compared to those treated with the control 
device (conventional angioplasty balloon inflated to standard pressures). The null (H0) 
and alternative (HA) hypotheses are expressed as follows: 
 

Cook Research Incorporated  
Version: 17-04-02 
Enforcer Post-Market Study 
 
Version Date: 03 Aug 2018 
 
COMPANY CONFIDENTIAL 
 
Page 22 of 34 
007-13 03.01T 
H0: ATEB ≥ ATCA 
HA: ATEB < ATCA 
 
where ATEB is the rate of adjunctive therapies in the Enforcer balloon group and ATCA is 
the rate of adjunctive therapies in the conventional angioplasty balloon group. 
 
The rates of adjunctive therapies will be compared between the two treatment groups 
with a one-sided Z-test. A p-value < .05 will be used to claim statistical significance. If 
the number of patients within each strata are sufficiently large, the association of 
stratification factors and treatment will be assessed. Crude and adjusted, if applied, 
differences in rate of adjunctive therapies between the two treatment groups and 95% 
confidence intervals will be reported.  
11.3.2 Analysis of secondary endpoints 
Differences in pain, procedural costs, procedure times, and maximum balloon pressure 
will be assessed overall by one-sided t-tests, with Enforcer balloon having favorable 
outcomes. In addition, regression models will be used to incorporate the stratification 
factors as covariates and reported if found to be significant. If the parametric assumptions 
are not met, nonparametric methods will be used. The safety claim will be evaluated with 
a Z-statistic, with a non-inferiority of Enforcer balloon at a margin of 10%. The observed 
non-inferiority margin will also be presented. 
 
Adjustments for multiplicity will be made using the Holm procedure to control the 
family-wise error rate to 0.05 across the family of secondary endpoints. 
11.3.3 Analysis of additional measures 
The same analysis strategies will be applied to the additional measures. For continuous 
measures, the difference between the two treatment groups will be assessed by t-test 
statistics. The impact of the two stratification variables on the outcomes between the two 
groups will also be explored, and reported if the test suggests a difference. If the 
parametric assumptions are not met, nonparametric methods will be used. Survival 
analysis techniques such as Kaplan-Meier or Cox Proportional Hazards will be 
incorporated if censoring of data occurs. 
 
Key components of the additional measures may also be compared, including specific 
adverse events associated with the procedure, such as vessel rupture or tear. 

Cook Research Incorporated  
Version: 17-04-02 
Enforcer Post-Market Study 
 
Version Date: 03 Aug 2018 
 
COMPANY CONFIDENTIAL 
 
Page 23 of 34 
007-13 03.01T 
11.4 
Missing Data 
For the primary endpoint, minimal or no missing data is expected. Missing primary 
outcome will be assumed missing at random and excluded for analyses. However, if more 
than 5% of primary endpoint is missing, multiple imputation technique will be applied 
followed by sensitivity analyses. All the other measurements will be analyzed 
accordingly with all available data using a complete case approach. 
11.5 
Site-level Poolability 
This is a multi-center study with up to 10 clinical sites. It is not intended to incorporate 
study sites into primary endpoint analyses. However, the primary endpoint will be 
examined across sites and reported if necessary.  
 
12.0 
Deviations from Study Plan 
Except under emergency situations when necessary to preserve the rights, safety, or well-
being of study patients, principal investigators are not allowed to deviate from this study 
plan without documented prior approval by: 
• the sponsor; and  
• the IRB 
Clinical study noncompliances (i.e., deviations from the study plan, investigator 
agreement, IRB policy, and/or any applicable regulations/standards) will be documented, 
along with an explanation and corrective and preventive actions, and reported to the 
sponsor.  
 
The principal investigator-required notifications/reports are described in Table 12.0-1. 
The reports will be provided as required by the study plan, IRB policies, or local 
regulations, whichever is more stringent. 

Cook Research Incorporated  
Version: 17-04-02 
Enforcer Post-Market Study 
 
Version Date: 03 Aug 2018 
 
COMPANY CONFIDENTIAL 
 
Page 24 of 34 
007-13 03.01T 
Table 12.0-1. Clinical Study Noncompliance Reports 
Report 
To 
Timeframe to submit 
report (upon awareness) 
Deviation to protect the life or 
physical well-being of a patient in 
an emergency  
Sponsor 
IRB 
As soon as possible, but 
no later than 5 working 
days 
Deviation that affects the scientific 
soundness of the clinical study  
Sponsor 
IRB 
Within 5 working days 
All clinical study noncompliances 
Sponsor 
IRB, if required per 
local policy 
15 working days 
 
The sponsor is responsible for reporting clinical study noncompliances to the reviewing 
IRB(s) and investigator(s) as required according to applicable regulations/standards.  
In accordance with applicable regulations/standards, the sponsor will review all clinical 
study noncompliances and take suitable action(s) to secure compliance. If appropriate, 
based on the number and nature of noncompliances, actions may include discontinuation 
of device shipment and/or termination of a principal investigator’s participation in this 
clinical study.  
 
13.0 
Data Collection and Management  
Patient data will be documented and recorded by trained personnel at the clinical site onto 
eCRFs through an EDC system. This is a secure, validated, web-based system, allowing 
those with permission to access data from any location at any time. Source data must be 
retained for all data entered into the EDC system. The patient-reported pain assessment 
and the physician assessment of the quality and performance of the study product may be 
directly entered into the EDC system.  
 
Clinical site personnel are required to undergo training and will have unique login names 
and passwords in order to enter patient data. In accordance with 21 CFR Part 11, the EDC 
system creates a secure, computer-generated, time stamped audit trail to record the date 
and time of operator entries and actions that create, modify, or delete electronic records. 
Principal investigators will review and electronically sign the eCRFs to confirm that the 
data recorded are accurate and complete. 
 
Principal investigators will provide all applicable clinical data and documentation to the 
sponsor in a timely manner. All clinical study documents (including patient data) must be 
retained as required by the applicable regulations/standards. The principal investigator or 

Cook Research Incorporated  
Version: 17-04-02 
Enforcer Post-Market Study 
 
Version Date: 03 Aug 2018 
 
COMPANY CONFIDENTIAL 
 
Page 25 of 34 
007-13 03.01T 
clinical site personnel are requested to contact the sponsor before removing any 
documents pertaining to the clinical study. The sponsor is responsible for database 
management, data verification, data archiving, and data retention.  
 
As needed to assist the sponsor in its research (e.g., during evaluation of an adverse 
event), data will be accessible to the sponsor, the participating principal investigators, the 
manufacturer, and companies or individuals the sponsor authorizes. 
 
14.0 
Monitoring  
The conduct of the clinical study will be supervised through a process of centralized, 
remote, and on-site monitoring.  
 
The sponsor will perform centralized monitoring (i.e., data review) throughout the study 
for adverse events, unexpected results, and for data completeness, consistency, and 
clarity. A formal query process in the EDC system will be utilized to resolve data 
discrepancies. Queries may arise from automated processes or from manual review of 
eCRFs, procedural reports, imaging data, or correspondence received. Principal 
investigators will ensure timely resolution of queries.  
 
On-site monitoring will be implemented as necessary throughout the course of the study 
to ensure the principal investigators are fulfilling the obligations set forth in the study 
plan, agreement(s), IRB policies, and applicable regulations/standards. Source data 
verification will be performed during on-site visits. If allowed per site policy, some 
source data verification may be done remotely, according to the monitoring plan. The 
principal investigator and clinical site will provide direct access to source data/documents 
for study-related monitoring, audits, IRB review and regulatory inspection. Standard 
practices for monitoring the study are summarized in Appendix C. 
 
15.0 
Clinical Study Administration  
15.1 
Approvals  
The principal investigator is responsible for obtaining approval of this clinical study 
(including the study plan, informed consent form, and all patient materials) from the 
relevant IRB at their associated clinical site. The clinical study will not begin at a 
particular clinical site until a favorable opinion of the IRB has been obtained. The study 
plan and other clinical study documents may be revised by the sponsor, as appropriate, 

Cook Research Incorporated  
Version: 17-04-02 
Enforcer Post-Market Study 
 
Version Date: 03 Aug 2018 
 
COMPANY CONFIDENTIAL 
 
Page 26 of 34 
007-13 03.01T 
based on new or changes to important information. A summary of the study plan revision 
history will be documented by the sponsor. Changes or modifications to the study plan, 
informed consent form, or patient materials may not be initiated without IRB approval. 
The principal investigator is responsible for keeping their IRB informed as to the 
progress of the study and complying with requirements imposed by their IRB. 
Furthermore, the sponsor and the principal investigator will ensure that local regulations 
concerning data protection are followed. 
15.2 
Clinical Study Reporting 
Principal investigators will provide the notifications/reports described in Table 15.2-1. 
The reports will be provided as required by IRB policies. 
  
Table 15.2-1. Clinical Study Reports 
Report 
To 
Withdrawal of IRB approval 
Sponsor 
Progress report 
IRB 
Final report 
IRB 
 
The sponsor is responsible for providing progress reports and final reports, notification of 
study completion or termination, and reporting significant findings to the reviewing 
IRB(s) and principal investigator(s) as required according to applicable 
regulations/standards.  
15.3 
Contact information 
Refer to Appendix A for a list of the sponsor, monitor, and manufacturer. Contact 
information and qualifications for the clinical site(s), principal investigator(s), or other 
institutions involved, will be maintained by the sponsor. The sponsor will also maintain 
contact information for each reviewing IRB. 
15.4 
Insurance 
Insurance for the study will be obtained by the sponsor prior to patient enrollment. 
 
16.0 
Publication Policy 
This clinical study will be registered on www.ClinicalTrials.gov and the intent is to make 
study results public. Publication policy, rights, and obligations for this study will be 

Cook Research Incorporated  
Version: 17-04-02 
Enforcer Post-Market Study 
 
Version Date: 03 Aug 2018 
 
COMPANY CONFIDENTIAL 
 
Page 27 of 34 
007-13 03.01T 
negotiated, detailed, and defined in the clinical study’s contractual documents with the 
clinical site and principal investigator. 
  
17.0 
References 
1. Rajan DK. Balloon angioplasty for low-flow access. J Vasc Access. 2015;16 
Suppl 9:S66-7. 
2. Holden A. Advance 35 Scoring PTA Balloon Dilatation Catheter: 6-Month 
Results. Presented at: Charing Cross International Symposium; April 2016; 
Olympia, London, UK. 
3. National Kidney Foundation. NKF-K/DOQI Clinical practice guidelines and 
clinical practice recommendations for 2006 updates: hemodialysis adequacy, 
peritoneal dialysis adequacy and vascular access. Am J Kidney Dis 
2006;48(suppl.1):S188–91 
 
 
 

Cook Research Incorporated  
Version: 17-04-02 
Enforcer Post-Market Study 
 
Version Date: 03 Aug 2018 
 
COMPANY CONFIDENTIAL 
 
Page 28 of 34 
007-13 03.01T 
APPENDIX A: Contact Information 
 
Global Sponsor and Monitor 
Cook Research Incorporated 
1 Geddes Way 
West Lafayette, IN 47906 
USA 
 
Contact: 
Jennifer L. Kerr 
 
President 
Telephone: 
765.463.7537 
Fax: 
765.497.0641 
E-mail:  
Jennifer.Kerr@CookMedical.com 
 
Manufacturer 
Cook Incorporated 
750 Daniels Way 
Bloomington, IN 47404 U.S.A. 
 

Cook Research Incorporated  
Version: 17-04-02 
Enforcer Post-Market Study 
 
Version Date: 03 Aug 2018 
 
 
COMPANY CONFIDENTIAL 
 
Page 29 of 34 
007-13 03.01T 
APPENDIX B: Schedule of Events 
 
 
Pre-procedure 
Procedure 
Follow-up 
90 days 
Informed consent 
X 
 
 
Demographics 
X 
 
 
Medical history 
X 
 
 
Physical exam 
X 
 
 
Baseline angiography 
X 
 
 
Randomization 
 
X 
 
Angioplasty 
 
X 
 
Completion angiographya 
 
X 
 
Patient-reported Pain Assessment 
 
X 
 
Chart Review 
 
 
X 
Adverse events 
 
X 
Xb 
a Completion angiography should be performed after treatment with the Enforcer or conventional angioplasty 
balloon. If an adjunctive procedure is performed, an additional angiography should be performed after completion of 
that procedure. 
b Events with an onset date after 90 days post-procedure will not be collected. 
 

Cook Research Incorporated  
Version: 17-04-02 
Enforcer Post-Market Study 
 
Version Date: 03 Aug 2018 
 
COMPANY CONFIDENTIAL 
 
Page 30 of 34 
007-13 03.01T 
APPENDIX C: Standard Practices for Monitoring 
1.0 
Selection of the monitor 
Designated by the sponsor to oversee the clinical study, the monitor may be an employee 
of Cook, an employee of a Contract Research Organization (CRO), or an independent 
contractor or consultant. The monitor will be qualified by training and experience and 
will be familiar with the clinical study product(s), study plan, and applicable 
regulations/standards. 
 
2.0 
General duties of the monitor 
Clinical sites will be monitored throughout the clinical study to verify: 
• The protection of the rights, safety, and welfare of patients; 
• The clinical study is being conducted in accordance with the study plan, 
agreement(s), IRB policies, and applicable regulations/standards; 
• The proper use of the clinical study product; 
• Adverse events and clinical study noncompliances are reported; and 
• The quality and integrity of the clinical study data.  
2.1 
Initiating the study 
Prior to enrolling a patient, the monitor and/or sponsor representative will participate in a 
site initiation visit with each clinical site. 
At a minimum, the following will be addressed with the principal investigator and 
appropriate clinical site personnel: 
• Training on responsibilities and requirements per the study plan, agreement(s), 
and applicable regulations/standards; and 
• The IRB approval letter and approved informed consent are on file prior to 
initiation of the clinical study. 
2.2 
Periodic visits 
During the course of the study, the monitor may visit the clinical site to ensure that the 
obligations set forth in the study plan, agreement(s), IRB policies, and applicable 
regulations/standards are fulfilled. The frequency of site visits may vary and the 
following activities will be performed as needed during the course of the study: 

Cook Research Incorporated  
Version: 17-04-02 
Enforcer Post-Market Study 
 
Version Date: 03 Aug 2018 
 
COMPANY CONFIDENTIAL 
 
Page 31 of 34 
007-13 03.01T 
• Perform source data verification per the monitoring plan 
- 
Ensure the reviewed information recorded in the eCRFs is complete, 
accurate, and legible. 
- 
Review patient charts for adverse events and ensure that events are 
appropriately reported. 
- 
Ensure the reasons for patient(s) failing to complete the study are 
documented. 
• Review Investigator File (e.g., essential documents) 
- 
Verify that there is a signed/dated informed consent document for each 
patient enrolled to date and confirm that the correct version of the 
informed consent was signed and dated prior to performing any study-
related procedures. 
- 
Ensure applicable version of the study plan and agreements are being 
followed and any changes to the study plan, informed consent form have 
been approved. 
- 
Ensure accurate, complete, and timely reports have been made to the 
sponsor and IRBs if applicable. 
- 
Ensure the appropriate training records are on file if the Signature and 
Delegation of Responsibilities Log at the clinical site has been updated. 
2.3 
Close-out visits 
Close-out visits may be conducted via an on-site or telephone call to ensure, at minimum: 
• Reviewed data are accurate and complete or a justification has been provided for 
any missing data 
• All previously identified follow-up items and clinical study non-compliances have 
been reported and resolved, if applicable 
• All essential documents have been filed at the clinical site 
• The principal investigator understands their obligations regarding documentation 
and retention requirements. 
 
3.0 
Records and reports of the monitor 
Following each site initiation visit, periodic visit, and close-out visit, a follow-up letter to 
summarize the visit will be sent to the clinical site.  
 
 

Cook Research Incorporated  
Version: 17-04-02 
Enforcer Post-Market Study 
 
Version Date: 03 Aug 2018 
 
COMPANY CONFIDENTIAL 
 
Page 32 of 34 
007-13 03.01T 
APPENDIX D Definitions 
 
Adjunctive Therapy: Additional treatment necessary for achievement of clinical success 
immediately following treatment with the study device (Enforcer balloon) or control 
device (conventional balloon angioplasty). Adjunctive therapies may include high-
pressure balloon angioplasty, cutting balloon angioplasty, stents or stent graft. 
 
Adverse Event: Any untoward medical occurrence, unintended disease or injury, or 
untoward clinical signs (including abnormal laboratory findings) in patients, users, or 
other persons, whether or not related to the investigational medical device. Refer to 
Section 9.6: Adverse Events for a list of reportable events.  
 
Anatomic Success: Residual stenosis less than 30% within the treated lesion following 
the study procedure (including adjunctive therapy). 
 
Arteriovenous (AV) Hemodialysis Access Circuit (also Access Circuit, Dialysis 
Access Circuit): 
• AV Fistula - The vascular conduit beginning from the arterial inflow (2 cm 
upstream from the AV anastomosis) and ending at the confluence of the cephalic 
and axillary veins. 
• Graft – The vascular conduit beginning from the arterial inflow (2 cm upstream 
from the artery-graft anastomosis) and ending at the confluence of the cephalic 
and axillary veins. 
 
AV Hemodialysis Access Circuit, Mature: Native fistula has been successfully used for 
at least one hemodialysis treatment. Grafts included in the study will have also been 
successfully used for at least one hemodialysis treatment. 
 
Clinical or physiological abnormalities which indicate dialysis access dysfunction: 
Abnormalities may include the following: 
• Decreased access blood flow (e.g., <600ml/min, decrease in flow) 
• Elevated venous pressure 
• Decreased dialysis dose (Kt/V) 
• Abnormal physical exam 
 
Clinical Success: Resumption of normal dialysis for at least one session. 
 

Cook Research Incorporated  
Version: 17-04-02 
Enforcer Post-Market Study 
 
Version Date: 03 Aug 2018 
 
COMPANY CONFIDENTIAL 
 
Page 33 of 34 
007-13 03.01T 
Conventional Angioplasty Balloon: A balloon catheter having a rated burst pressure 
less than 25 atmospheres. 
 
Device Deficiency: Inadequacy of a medical device with respect to its identity, quality, 
durability, reliability, safety, or performance. 
 
Device Success: Residual stenosis less than 30% within the treated lesion immediately 
after angioplasty with the study device (Enforcer or conventional angioplasty balloon). 
 
Dissection: Linear filling defect due to disruption of the intima, staining within the vessel 
wall. 
 
High-Pressure Angioplasty Balloon: A balloon catheter having a rated burst pressure 
greater than or equal to 25 atmospheres. 
 
Numeric Rating Scale (NRS) for pain: Assessment of patient-reported pain using a 
scale from 0 to 10 where 0 indicates no pain and 10 indicates worst possible pain. 
Patients will be instructed to rate the pain they feel associated with the balloon inflations 
during the study procedure. 
 
Occlusion: No flow can be identified through the study lesion. 
 
Percent (%) stenosis: Estimated by comparing the closest segment of vessel having the 
most normal appearance (i.e. the reference vessel). 
 
Primary Patency: Uninterrupted patency of the AV hemodialysis access circuit. Loss of 
primary patency occurs when a restenosis or occlusion of the AV hemodialysis access 
circuit results in: 
• a reintervention or 
• abandonment of the AV dialysis access 
 
Reintervention: Any endovascular or surgical intervention performed in the study-
treated AV hemodialysis access circuit. 
 
Rupture: Disruption of the vessel wall allowing marked extravasation of contrast outside 
the vessel. 
 

Cook Research Incorporated  
Version: 17-04-02 
Enforcer Post-Market Study 
 
Version Date: 03 Aug 2018 
 
COMPANY CONFIDENTIAL 
 
Page 34 of 34 
007-13 03.01T 
Serious Adverse Event: Adverse event that: 
a. Led to death,  
b. Led to serious deterioration in the health of the patient, that either resulted in: 
i. 
A life-threatening illness or injury, or 
ii. 
A permanent impairment of a body structure or a body function, or 
iii. 
Medical or surgical intervention to prevent life-threatening illness or 
injury or permanent impairment to a body structure or a body function, 
NOTE: Planned hospitalization for a pre-existing condition, or a procedure required 
by the study plan, without serious deterioration in health, is not considered a serious 
adverse event.  
 
Thrombosis: Platelet or fibrin deposition within the treated segment successfully treated 
with thrombolysis or thrombectomy.