Randomized Study of IN.PACT™ AV Access Paclitaxel-Coated Percutaneous Transluminal Angioplasty (PTA) Balloon vs. Standard PTA for the Treatment of Obstructive Lesions in the Native Arteriovenous Dialysis Fistulae (AVF)
Phase: NA
Conditions: Arteriovenous Fistula Stenosis, Arteriovenous Fistula Occlusion, Arteriovenous Fistula, Fistula
Sponsor: Medtronic Endovascular

IN.PACT AV Access 
 
Randomized Study of IN.PACT™ AV Access Paclitaxel-Coated 
Percutaneous Transluminal Angioplasty (PTA) Balloon vs. Standard PTA 
for the Treatment of Obstructive Lesions in the Native Arteriovenous 
Dialysis Fistulae (AVF) 
 
Clinical Investigation Plan Version 4.0 
20/JAN/2022 
 
NCT03041467 

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Clinical Investigation Plan 
Clinical Investigation Plan/Study Title IN.PACT™ AV Access Study 
Randomized Study of IN.PACT™ AV Access Paclitaxel-Coated 
Percutaneous Transluminal Angioplasty (PTA) Balloon vs. 
Standard PTA for the Treatment of Obstructive Lesions in 
the Native Arteriovenous Dialysis Fistulae (AVF) 
Clinical Investigation Plan Identifier APV-IN.PACT AV Access 
Study Product Name IN.PACT™ AV Access Paclitaxel-Coated PTA Balloon Catheter 
(“IN.PACT™ AV Access DCB1”) 
Global Sponsor Medtronic Vascular, Inc. 
3576 Unocal Place 
Santa Rosa, CA 95403 
USA 
Local Sponsors Medtronic Japan Co., Ltd 
1-2-70 Konan, Minato-ku, Tokyo 108-0075 Japan 
Protocol No.: MDT2-16-16 
Investigational Device No.: MDT-2116 
Medtronic Australasia Pty Ltd 
2 Alma Road 
Macquarie Park NSW 2113 
Australia 
Document Version 4.0; 20JAN2022 
Lead Principal Investigators Lead Principal Investigator(s) information will be provided 
under a separate cover. 
Confidentiality Statement 
The information contained in this document is confidential and the proprietary property of 
Medtronic. Any distribution, copying, or disclosure without the prior written authorization of 
Medtronic is strictly prohibited. Persons to whom the information is disclosed must know that it is 
confidential and that it may not be further disclosed by them. 
1IN.PACT AV Access DCB was the device name used during the clinical study. Medtronic has changed the name of the device to IN.PACT™ AV 
Paclitaxel-Coated Balloon Catheter (also referred as IN.PACT AV DCB). 
 
 
 
 
 
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1. Investigator Statement 
The Investigator Statement will be a separate document from the clinical investigation plan.

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Table of Contents  
 
1. 
INVESTIGATOR STATEMENT ......................................................................................................................... 2 
TABLE OF CONTENTS ............................................................................................................................................... 3 
2. 
GLOSSARY .......................................................................................................................................................... 6 
3. 
SYNOPSIS ..........................................................................................................................................................11 
4. 
INTRODUCTION ...............................................................................................................................................19 
4.1 BACKGROUND ....................................................................................................................................................19 
4.2 PURPOSE ............................................................................................................................................................20 
5. 
OBJECTIVES AND ENDPOINTS ....................................................................................................................21 
5.1 
OBJECTIVES ....................................................................................................................................................21 
5.1.1 Primary Objectives ...............................................................................................................................21 
5.2 
ENDPOINTS .....................................................................................................................................................21 
5.2.1 Primary Endpoints ................................................................................................................................21 
5.2.2 Secondary Endpoints ...........................................................................................................................21 
6. 
STUDY DESIGN ................................................................................................................................................23 
6.1 DURATION ............................................................................................................................................................24 
6.2 RATIONALE ...........................................................................................................................................................24 
6.3 BLINDING .............................................................................................................................................................24 
7. 
PRODUCT DESCRIPTION...............................................................................................................................25 
7.1 
GENERAL ........................................................................................................................................................25 
7.2 MANUFACTURER ....................................................................................................................................................29 
7.3 PACKAGING ...........................................................................................................................................................29 
7.4 INTENDED POPULATION ..........................................................................................................................................29 
7.5 EQUIPMENT ...........................................................................................................................................................29 
7.6 PRODUCT TRAINING REQUIREMENTS........................................................................................................................29 
7.7 PRODUCT RECEIPT AND TRACKING ..........................................................................................................................30 
7.8 PRODUCT STORAGE ...............................................................................................................................................31 
7.9 PRODUCT RETURN .................................................................................................................................................31 
8. 
SELECTION OF SUBJECTS .............................................................................................................................31 
8.1 STUDY POPULATION ...............................................................................................................................................31 
8.2 SUBJECT ENROLLMENT ...........................................................................................................................................31 

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8.3 INCLUSION CRITERIA .............................................................................................................................................32 
8.4 EXCLUSION CRITERIA .............................................................................................................................................33 
9. 
STUDY PROCEDURES .....................................................................................................................................34 
9.1 SCHEDULE OF EVENTS ............................................................................................................................................34 
9.2 SUBJECT SCREENING ..............................................................................................................................................45 
9.3 PRIOR AND CONCOMITANT MEDICATIONS ................................................................................................................45 
9.4 SUBJECT CONSENT .................................................................................................................................................45 
9.5 RANDOMIZATION AND TREATMENT ASSIGNMENT .......................................................................................................47 
9.6 ASSESSMENT OF SAFETY .........................................................................................................................................47 
9.7 RECORDING DATA..................................................................................................................................................47 
9.8 DEVIATION HANDLING ...........................................................................................................................................48 
9.9 SUBJECT WITHDRAWAL OR DISCONTINUATION .........................................................................................................49 
10. 
RISKS AND BENEFITS ................................................................................................................................50 
10.1 POTENTIAL RISKS ................................................................................................................................................50 
10.2 POTENTIAL BENEFITS ...........................................................................................................................................53 
10.3 RISK-BENEFIT RATIONALE ....................................................................................................................................53 
11. 
ADVERSE EVENT ASSESSMENTS .............................................................................................................54 
11.1 DEFINITIONS/CLASSIFICATIONS ............................................................................................................................54 
11.2 REPORTING OF ADVERSE EVENTS ..........................................................................................................................56 
11.3 EMERGENCY CONTACT DETAILS .............................................................................................................................58 
12. 
DATA REVIEW COMMITTEES AND CORE LABORATORIES ...............................................................58 
12.1 DATA MONITORING COMMITTEE ...........................................................................................................................58 
12.2 CLINICAL EVENT COMMITTEE ................................................................................................................................58 
12.3 DUPLEX ULTRASOUND CORE LABORATORY .............................................................................................................59 
12.4 ANGIOGRAPHIC CORE LABORATORY .............................................................................................................................59 
13. 
STATISTICAL DESIGN AND METHODS ..................................................................................................59 
13.1 HYPOTHESES AND SAMPLE SIZE CALCULATION ........................................................................................................59 
13.2 ANALYSIS STRATEGY ............................................................................................................................................62 
13.3 ANALYSIS SETS ...................................................................................................................................................63 
13.3.1 Primary Analysis Set .........................................................................................................................63 
13.3.2 Secondary Analysis Set .....................................................................................................................63 
13.4 ANALYSIS OF THE PRIMARY ENDPOINTS .................................................................................................................63 
13.4.1 Primary Analysis of the Primary Endpoints .................................................................................................63 
13.4.2 Additional Analysis of the Primary Endpoints ............................................................................64 
13.4.3 Sensitivity Analysis of the Primary Endpoints ............................................................................64 
13.4.4 Poolability Analysis of the Primary Endpoints ...........................................................................65 
13.5 ANALYSIS OF THE SECONDARY ENDPOINTS .............................................................................................................65 
13.6 SUBSET ANALYSES ...............................................................................................................................................66 
13.7 PATIENT WITHDRAWAL AND MISSING DATA ............................................................................................................67 

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14. 
ETHICS ...........................................................................................................................................................67 
14.1 STATEMENT(S) OF COMPLIANCE ............................................................................................................................67 
15. 
STUDY ADMINISTRATION ........................................................................................................................69 
15.1 INVESTIGATOR AND INVESTIGATIONAL SITE SELECTION...........................................................................................69 
15.2 TRAINING OF INVESTIGATIONAL SITES ...................................................................................................................69 
15.3 INVESTIGATOR RESPONSIBILITY / PERFORMANCE ....................................................................................................69 
15.4 ROLE OF SPONSOR REPRESENTATIVES ...................................................................................................................70 
15.5 MONITORING ......................................................................................................................................................70 
15.6 AUDITS / INSPECTIONS ........................................................................................................................................71 
15.7 DATA MANAGEMENT.............................................................................................................................................71 
15.8 DIRECT ACCESS TO SOURCE DATA/DOCUMENTS .....................................................................................................72 
15.9 CONFIDENTIALITY ................................................................................................................................................72 
15.10 CIP AMENDMENTS .............................................................................................................................................73 
15.11 RECORD RETENTION ..........................................................................................................................................73 
15.11 INVESTIGATOR REPORTS .....................................................................................................................................74 
15.13 SPONSOR REPORTS ............................................................................................................................................76 
15.14 PUBLICATION AND USE OF INFORMATION .............................................................................................................77 
15.15 SUSPENSION OR EARLY TERMINATION .................................................................................................................78 
15.16 LIABILITY .........................................................................................................................................................79 
16. 
REFERENCES ................................................................................................................................................80 
17. 
APPENDICES.................................................................................................................................................82 
17.1 INSTRUCTIONS FOR USE .......................................................................................................................................82 
17.2 INVESTIGATOR BROCHURE ....................................................................................................................................83 
17.3 LABELING............................................................................................................................................................84 
17.4 MASTER INFORMED CONSENT FORM ......................................................................................................................85 
17.5 SITE AND INVESTIGATOR LIST ..............................................................................................................................86 
17.6 IRB/EC COMMITTEE LIST ....................................................................................................................................87 
17.7 CRO/CORE LABORATORIES ..................................................................................................................................88 
17.8 
SAMPLE CASE REPORT FORMS ..........................................................................................................................89 
17.9 EQ-5D ...............................................................................................................................................................90 
17.10 MEDICARE COVERAGE ........................................................................................................................................91 
FIGURE A: TREND IN DISTRIBUTION OF PAYER TYPE, BY MODALITY, AMONG PREVALENT ESRD PATIENTS, 1978-2012 (HEMODIALYSIS) ....91 
17.11 RECOMMENDED GUIDELINES FOR RE-INTERVENTIONS ...........................................................................................92 
18. VERSION HISTORY ..........................................................................................................................................93 

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2.  Glossary 
Abbreviations  
 
AE 
Adverse Event 
AVF 
Arteriovenous “Dialysis” Fistula 
CBC 
Complete Blood Count 
CD-TLR 
Clinically Driven Target Lesion Revascularization 
CEC 
Clinical Events Committee 
CIP 
Clinical Investigation Plan 
CRF 
Case Report Form 
CRO 
Clinical Research Organization 
CTA 
Clinical Trial Agreement 
DCB 
Drug Coated Balloon 
DD 
Device Deficiency 
DMC 
Data Monitoring Committee 
DOA/DTL 
Delegation of Authority/Delegated Tasks List 
DUS 
Duplex Ultrasound 
EC 
Ethical Committee 
eCRF 
Electronic Case Report Form 
EDC 
Electronic Data Capture 
ESRD 
End-Stage Renal Disease 
FDA 
Food and Drug Administration 
HD 
Hemodialysis 
IB 
Investigator Brochure 
ICF 
Informed Consent Form 
ICH-GCP 
International Conference on Harmonization – Good Clinical Practice 
IDE 
Investigational Device Exemption 
IFU 
Instructions for Use 
IMRS 
Interactive Mobile Response System 
IRB 
Institutional Review Board 
ITT 
Intent to Treat 
ISO 
International Organization for Standardization 
IVRS 
Interactive Voice Response System 
IWRS 
Interactive Web Response System 
OTW 
Over-the-Wire 
PHI 
Protected Health Information 
PI 
Principal Investigator 
PMA 
Premarket Approval 

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PTA 
Percutaneous Transluminal Angioplasty 
RA 
Regulatory Affairs 
RBP 
Rated Burst Pressure 
RVD 
Reference Vessel Diameter 
SADE 
Serious Adverse Device Effect 
SAE 
Serious Adverse Event 
SID 
Subject Identification Number 
TLR 
Target Lesion Revascularization 
UADE 
Unanticipated Adverse Device Effect 
U.S. 
United States 
USADE 
Unanticipated Serious Adverse Device Effect 
Definitions 
 
Term 
Definition 
Access Circuit 
The area from the AV access fistula arterial anastomosis to the 
axillosubclavian junction. 
Access Thrombosis 
A total occlusion within the AV access circuit due to thrombus 
formation which is rapidly evolving as confirmed by sudden 
onset of symptoms and documented by duplex ultrasound 
and/or angiography 
Adverse Device Effect (ADE) 
See section 11.1 
Adverse Event (AE) 
See section 11.1 
Arteriovenous “Dialysis” Fistulae 
(AVF) 
The joining of an artery and vein for the purpose of 
hemodialysis access 
Clinical Success 
Resumption of successful dialysis for at least one session after 
index procedure 
De Novo Lesion 
A lesion that has not been previously treated 
Device Deficiency 
See section 11.1 
Device Malfunction 
Unexpected change to the device that is contradictory to the 
IFU and may or may not affect device performance 

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Term 
Definition 
Device Success 
Successful delivery, inflation, deflation and retrieval of the 
intact study balloon device without burst at or below rated 
burst pressure (RBP) at index procedure 
Dissection 
Types A-F 
Intimal disruption of the vessel wall with or without medial or 
adventitial contrast staining, classified as per the NHLBI 
(National Heart, Lung, and Blood Institute) criteria as follows: 
A) Luminal Haziness: Minor radiolucent areas in the lumen 
without impairment of flow or persistent dye staining after 
contrast runoff. 
B) Linear Dissection: Luminal flap that is radiolucent and that 
runs parallel to the vessel wall with contrast injection but 
without impairment of flow or persistent dye staining after 
contrast runoff. 
C) Extraluminal Contrast (i.e., "cap dissection"): Contrast 
appears outside of the vessel lumen as an "extraluminal cap." 
The staining appears even after contrast clears the lumen. 
D) Spiral Dissection: Spiral radiolucent luminal filling defects; 
often persistent staining after contrast clears from the vessel. 
E) Dissection with Reduced Flow: New and persistent filling 
defects in the vessel lumen 
F) Dissection with Total Occlusion: Lesions that progress to 
impaired flow or total occlusion 
Embolism 
The obstruction of a blood vessel by a foreign substance or a 
blood clot that travels through the bloodstream, lodging in a 
blood vessel or plugging the vessel. 
Enrollment 
The time of randomization 

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Term 
Definition 
EQ-5D 
EQ-5D is a standardized measure of health status developed by 
the EuroQol Group in order to provide a simple, generic 
measure of health for clinical and economic appraisal* 
Geographic Miss 
Balloon dilatation (or stent placement) at an unintended area 
of the vessel wall. 
Optimal PTA 
Repeated and prolonged balloon inflations aimed to achieve 
<50% residual stenosis (visual estimate) without stenting. 
Procedural Success 
Maintenance of patency (≤30% residual stenosis) in the 
absence of peri-procedural serious adverse device effect 
(SADE) 
Provisional Stenting 
Placement of a stent due to sub-optimal PTA resulting in either 
of the following conditions: 
• 
Residual stenosis of ≥50% (by visual estimate); 
• 
Major (≥ Grade D) flow-limiting dissection 
Serious Adverse Event (SAE) 
See section 11.1 
Spot Stenting 
Utilization of a single, shortest stent which minimal length is 
sufficient to cover the residual stenosis 
Steal Syndrome** 
Dialysis-associated steal 
syndrome (DASS) 
Ischemic signs and symptoms (pain, diminished radial pulse, 
coldness, cyanosis, necrosis) produced by an access device as a 
result of the diversion of arterial blood flow into the AV fistula 
Successful Dialysis 
A complete dialysis session includes: 
• 
Normal cannulation and 
• 
Is not stopped prematurely 
Target Lesion Revascularization 
(TLR) 
Any repeat invasive procedure, including angioplasty, stenting, 
or thrombolysis, performed to open or increase the lumen 
diameter within the previously treated lesion. 
Clinically-Driven Target Lesion Revascularization (CD-TLR): Any 
re-intervention involving the target lesion in which: 

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Term 
Definition 
• 
The subject has a ≥50% diameter stenosis (per 
angiographic core lab assessment) in the presence of 
clinical or physiologic abnormalities that indicate 
dialysis access dysfunction OR 
• 
≥70% stenosis with or without the presence of clinical 
or physiologic abnormalities indicating dialysis access 
dysfunction 
Non-Clinically-Driven Target Lesion Revascularization: any re- 
intervention involving the target lesion which does not meet 
the criteria for CD-TLR. 
Vital Status 
The state or condition of being living or deceased; also 
includes the case where the vital status is unknown. 
* EuroQol Group. EuroQol-a new facility for the measurement of health-related quality of life. Health Policy 1990;16:199-208 
 
** Defined by National Kidney Foundation KDOQI Guidelines 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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3. Synopsis 
 
Title 
IN.PACT™ AV Access 
Randomized Study of IN.PACT™ AV Access Paclitaxel-Coated 
Percutaneous Transluminal Angioplasty (PTA) Balloon vs. Standard PTA 
for the Treatment of Obstructive Lesions in the Native Arteriovenous 
Dialysis Fistulae (AVF) 
Clinical Study Type 
Pivotal 
Investigational Device 
IN.PACT™ AV Access Paclitaxel-Coated PTA Balloon Catheter1 
(“IN.PACT™ AV Access DCB”) 
Global Sponsor 
Medtronic Vascular, Inc. 
3576 Unocal Place 
Santa Rosa 
California 95403, United States 
Local Sponsor(s) 
Medtronic Japan Co., Ltd 
1-2-70 Konan, Minato-ku, Tokyo 108-0075 Japan 
Protocol No.: MDT2-16-16 
Investigational Device No.: MDT-2116 
Medtronic Australasia Pty Ltd 
2 Alma Road 
Macquarie Park NSW 2113 
Australia 
Indication Under 
Investigation2 
The IN.PACT™ AV Access Paclitaxel-Coated PTA balloon catheter is 
indicated for percutaneous transluminal angioplasty, after pre- 
dilatation, for the treatment of obstructive lesions up to 100 mm in 
length in the native arteriovenous dialysis fistulae with reference vessel 
diameters of 4 to 12 mm. 
 
1 IN.PACT AV Access DCB was the device name used during the IDE clinical study. Medtronic has changed the name of 
the device to IN.PACT™ AV Paclitaxel-Coated Balloon Catheter (also referred as IN.PACT AV DCB). 
2 The indication for use for the commercial IN.PACT AV DCB device is as follows: The IN.PACT™ AV Paclitaxel-Coated 
PTA balloon catheter is indicated for percutaneous transluminal angioplasty, after appropriate vessel preparation, for 
the treatment of obstructive lesions up to 100 mm in length in the native arteriovenous dialysis fistulae with 
reference vessel diameters of 4 to 12 mm. 

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Investigation Purpose 
To evaluate the safety and efficacy of the IN.PACT™ AV Access Drug 
Coated Balloon (DCB) compared to percutaneous transluminal 
angioplasty (PTA) for treatment of subjects presenting with de novo or 
non-stented restenotic obstructive lesion of native arteriovenous 
dialysis fistulae (AVF) in the upper extremity. 
Product Status 
The IN.PACT AV Access DCB was investigational in the United 
States, New Zealand, and Japan at the time of subject enrollment.  
IN.PACT AV DCB is currently approved for commercial use and 
distribution in United States, Japan, and Canada. 
Primary Efficacy Endpoint 
Target Lesion Primary Patency Rate through 6 Months 
Defined as freedom from clinically-driven target lesion 
revascularization (CD-TLR) or access circuit thrombosis measured 
through 6 months post- procedure. 
Primary Safety Endpoint 
Serious Adverse Event Rate within 30 Days 
Defined as the Serious Adverse Event (SAE) rate involving the AV 
access circuit through 30 days post-procedure. 
Secondary Endpoints 
Secondary endpoints assessed through 24-month for the study are as 
follows: 
Access Circuit Primary Patency through 3 Months, 6 Months, 9 
Months, 12 Months, 18 Months, and 24 Months Post-procedure 
Defined as freedom from re-intervention in the access circuit or access 
circuit thrombosis through 3 months, 6 months, 9 months, 12 months, 
18 months, and 24 months post-procedure. 
Target Lesion Primary Patency through 3 Months, 9 Months, 12 
Months, 18 Months, and 24 Months Post-procedure 
Defined as freedom from CD-TLR or access thrombosis occurring in the 
target lesion through 3 months, 9 months, 12 months, 18 months, and 
24 months post-procedure. 
 

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Cumulative Target Lesion Revascularizations Measured through 3 
Months, 6 Months, 9 Months, 12 Months, 18 Months, and 24 Months 
Post-procedure 
Defined as proportion of subjects with TLR through 3 months, 6 
months, 9 months, 12 months, 18 months, and 24 months post-
procedure. 
 
Number of Interventions Required to Maintain Target Lesion Patency 
through 3 Months, 6 Months, 9 Months, 12 Months, 18 Months, and 
24 Months Post-procedure 
Defined as number of TLR through 3 months, 6 months, 9 months, 12 
months, 18 months, and 24 months post-procedure. 
Number of Interventions Required to Maintain Access Circuit Patency 
through 3 Months, 6 Months, 9 Months, 12 Months, 18 Months, and 
24 Months Post-procedure 
Defined as number of reinterventions in the target lesion and/or access 
circuit through 3 months, 6 months, 9 months, 12 months, 18 months, 
and 24 months post-procedure. 
Cumulative Access Circuit Thromboses Measured through 3 Months, 6 
Months, 9 Months, 12 Months, 18 Months, and 24 Months Post- 
procedure 
Defined as proportion of subjects with access circuit thrombosis 
through 3 months, 6 months, 9 months, 12 months, 18 months, and 24 
months post-procedure. 
Device, Procedure, and Clinical Success 
Device Success: Defined as successful delivery, inflation, deflation and 
retrieval of the intact study balloon device without burst at or below 
rated burst pressure (RBP) at index procedure 
Procedural Success: defined as maintenance of patency (≤30% residual 
stenosis) in the absence of peri-procedural serious adverse device effect 
(SADE) 
 
 

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Clinical Success: defined as resumption of successful dialysis for at least 
one session after index procedure 
Rate of Device and Procedure Related Adverse Events Reported 
through 30 Days, 3 Months, 6 Months, 9 Months, 12 Months, 18 
Months, and 24 Months Post-procedure 
Device Related Adverse Event Rate: defined as proportion of subjects 
with device related Adverse Events reported through 30 days, 3 months, 
6 months, 9 months, 12 months, 18 months, and 24 months post- 
procedure. 
 
Procedure Related Adverse Event Rate: defined as proportion of subjects 
with procedure related Adverse Events reported post-index procedure 
until the first successful dialysis session. 
The following endpoints will be assessed annually up to 36 months in 
addition to the assessment through 24 months where applicable: 
Target Lesion Revascularizations 
Defined as proportion of subjects with TLR up to 36 months post-index 
procedure 
Clinically-Driven Target Lesion Revascularizations 
Defined as proportion of subjects with CD-TLR up to 36 months post- 
index procedure 
Re-interventions in the access circuit 
Defined as proportion of subjects with reinterventions occurring within 
the access circuit up to 36 months post-index procedure 
Abandonment of Target AVF 
Defined as proportion of subjects with abandonment of the target AV 
abandonment up to 36 months post-index procedure 
Serious Adverse Events 
Defined as the Serious Adverse Event (SAE) rate up to 36 months post- 
index procedure. 
 
 

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Vital Status 
Vital status will be collected annually through 60 months for all  
current subjects. Vital status will be requested for any subjects who 
have exited the study in the US. As for the subjects in Japan and New 
Zealand, once a subject exits the study, no medical information can be 
retrieved. Time to survival /death will be evaluated according to the 
Kaplan-Meier method up to 60 months. 
 
Study Design 
A prospective, global, multicenter, single-blinded, randomized (1:1) 
clinical study evaluating the IN.PACT™ AV Access DCB (study arm) vs 
standard PTA (control arm) for the treatment of obstructive lesions up 
to 100 mm in length in the native arteriovenous dialysis fistulae. 
Randomization 
Subjects will be randomized in a ratio of 1:1 to either the 
IN.PACT™ AV Access DCB (study arm) or a standard PTA balloon 
(control arm). 
Randomization will be stratified based on lesion status: de novo or 
restenotic within study sites. 
Sample Size 
330 Subjects 
Number of Sites 
Up to 30 global investigational sites in the United States, New Zealand 
and Japan. 
Study Population 
Subjects with a de novo or non-stented restenotic obstructive lesion up 
to 100 mm in length, located in the native arteriovenous dialysis 
fistulae. 

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Inclusion/Exclusion 
Criteria 
Inclusion 
1. Patient is ≥21 years of age 
2. Patient has a life expectancy of ≥12 months 
3. Patient has a native AV fistula created ≥ 60 days prior to the 
index procedure 
4. The target AV fistula has undergone successful dialysis for at 
least 8 of 12 sessions during a four week period 
5. Patient has a de novo and/or non-stented restenotic lesion 
located between the arteriovenous anastomosis and 
axillosubclavian junction with ≥50% stenosis 
Note: If the lesion is located in the anastomosis, the treatment 
may be delivered up to 2 cm upstream on the arterial side 
Note: If the lesion is located in the cephalic arch, the treatment 
may be delivered up to 2 cm into the subclavian vein 
6. Patient has a target lesion or a tandem lesion that is ≤ 100 mm 
in length (by visual estimate) 
Note: Tandem lesions may be enrolled provided they meet all of 
the following criteria: 
• 
Separated by a gap of ≤ 30mm (3 cm) 
• 
Total combined lesion length, including 30 mm gap, ≤ 100 
mm 
• 
Able to be treated as a single lesion 
7. Patient has a target vessel diameter of 4.0 – 12.0 mm (by visual 
estimate) 
8. Patient underwent successful crossing of the target lesion with 
the guide wire and pre-dilatation with a high pressure PTA 
balloon defined as: 
• 
Residual stenosis of ≤ 30% AND 
• 
Absence of a flow limiting dissection (Grade ≥C) or 
perforation 
9. Patient provides written informed consent prior to enrollment 
in the study 
10. Patient is willing to comply with all follow-up evaluations at 
specified times 
 

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Exclusion Criteria: 
1. Women who are breastfeeding, pregnant, or are intending to 
become pregnant, or men intending to father children 
2. Patient is receiving immunosuppressive therapy 
3. Patient is anticipating a kidney transplant within 6 months of 
enrollment into the study 
4. Patient has undergone prior intervention of access site within 
30 days of index procedure 
5. Patient with anticipated conversion to peritoneal dialysis 
6. Patient has an infected AV access or systemic infection 
7. Patient has planned surgical revision of access site 
8. Patient with secondary non-target lesion requiring treatment 
within 30-days post index procedure 
9. Patient with hemodynamically significant central venous 
stenoses that cannot be successfully treated prior to treatment 
of the target lesion 
10. Patient with target AVF or access circuit which previously had or 
currently has a thrombosis 
11. Patients judged to have a lesion that prevents complete 
inflation of an angioplasty balloon or proper placement of the 
delivery system 
12. Patient with target lesion located central to the axillosubclavian 
junction 
13. Patient has significant arterial inflow lesion requiring treatment 
more than 2 cm upstream from the anastomosis in the AV 
access 
14. Patient has presence of pseudoaneurysm or aneurysm requiring 
treatment at the lesion site 
15. Patient has presence of a stent located in the target AV access 
circuit 
16. Patients with known allergies or sensitivities to paclitaxel 
17. Patient with known contraindication, including allergic reaction, 
or sensitivity to contrast material that cannot be adequately 
pre-treated 
18. Patient who cannot receive recommended antiplatelet and/or 
anticoagulant therapy 
 
 

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19. Patient with clinically significant Steal Syndrome requiring 
treatment 
20. Patient is enrolled in another investigational drug, device, or 
biologic study and has not completed the primary endpoint, or 
was previously enrolled in this study 
21. Patient has a co-morbid condition that, in the judgment of the 
Investigator, may cause him/her to be non-compliant with the 
protocol or confound the data interpretation. 
Subject Follow-up 
Subjects randomized and enrolled in the study will be followed up to 5 
years. Follow-up assessments are scheduled for 30-day, 3, 6, 9, 12, 18, 
24, 36 months post index procedure, in addition, only vital status will be 
collected for the 48, and 60-month visits. 
Time Course 
Start of enrollment: 25-APR-2017 
Enrollment completed: 10-MAY-2018 
Planned study close-out: approximately October 2023 

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4. Introduction  
4.1 Background  
The incidence of end-stage renal disease (ESRD) has been escalating and the creation of the hemodialysis 
(HD) access has become a common vascular procedure in the form of either an autologous arteriovenous 
dialysis fistula (AVF) or prosthetic graft (AVG), see Figure 11. In the United States and Japan, according to 
the United States Renal Data System (USRDS), the incidence rates of ESRD in 2010 were 369 per million 
and 288 per million, respectively, with a prevalence rate in the U.S. of 1,870 per million and 2,260 per 
million in Japan2. In Europe, there are an estimated 65,000 new ESRD patients/year, ~80% of which 
received HD treatment3. 
Figure 1: Hemodialysis Access by Arteriovenous Fistula or Arteriovenous Graft 
Dysfunction of the dialysis circuit is a significant cause of morbidity and mortality in patients undergoing 
HD which can eventually lead to loss of vascular access4,5. At 12 months, primary patency rates of 49% 
and 14% for forearm AVFs and AVGs, respectively, have been reported by Turmel-Rodrigues et al.6 These 
conduits have a high rate of failure mainly because of the development of a neointimal hyperplasia 
response after endothelial and smooth muscle injury that results in the formation of stenotic lesions at 
the anastomotic site and/or along the venous outflow tract.7 Mortality rates vary depending on the ESRD 
treatment. After one year of treatment, those on dialysis have a 20-25% mortality rate, with a 5-year 
survival rate of 35%8. 
 
PTA is the current standard for the treatment of flow limiting stenotic lesions within the dialysis circuit, 
however, angioplasty itself results in vessel trauma that can further drive the intimal hyperplasia and the 

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subsequent development of restenosis that necessitates repeat procedures. Balloon angioplasty of 
vascular access is characterized by poor midterm patency and high rate of reintervention.9 
Acceptable secondary patency rates require multiple repeated reinterventions which adds to the patient 
hospitalization time and contributes to the economic burden of maintaining functioning dialysis access. 
Localized delivery of antiproliferative drugs, such as paclitaxel, have been proven safe and effective in 
inhibition of neointimal hyperplasia and effective reduction of vascular restenosis after PTA in coronary 
and peripheral arteries.10,11,12 
Initial clinical data following treatment of failing AV access with IN.PACT™ DCB reports improved primary 
patency of the target lesion and a reduction in the need for future revascularizations. In addition, no new 
safety concerns were identified in this patient population with limited options who represents a 
significantly unmet clinical need. 
Therefore, Medtronic is seeking to obtain an indication for use for the IN.PACT™ AV Access DCB. 
For further literature review, pre-clinical testing and previous clinical experience refer to the Investigator 
Brochure. 
 
4.2 Purpose 
The purpose of this study was to collect and evaluate safety and efficacy data of the IN.PACT™ AV Access 
DCB in order to support regulatory applications in seeking market approval with the following indication3 
in the U.S./Japan and possibly other geographies: 
The IN.PACT™ AV Access Paclitaxel-Coated PTA balloon catheter is indicated for percutaneous 
transluminal angioplasty, after pre-dilatation, for the treatment of obstructive lesions up to 100 mm in 
length in the native arteriovenous dialysis fistulae with reference vessel diameters of 4 to 12 mm. 
 
3 This indication is applicable for the IDE clinical study. The indication for use for the commercial IN.PACT AV DCB 
device is as follows: The IN.PACT™ AV Paclitaxel-Coated PTA balloon catheter is indicated for percutaneous 
transluminal angioplasty, after appropriate vessel preparation, for the treatment of obstructive lesions up to 100 
mm in length in the native arteriovenous dialysis fistulae with reference vessel diameters of 4 to 12 mm. 

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5. Objectives and Endpoints 
5.1 Objectives 
 
5.1.1 Primary Objectives 
To evaluate the safety and efficacy of the IN.PACT™ AV Access Drug Coated Balloon (DCB) compared to PTA 
for treatment of subjects presenting with de novo or non-stented restenotic obstructive lesions of native 
arteriovenous dialysis fistulae (AVF) in the upper extremity. 
 
5.2 Endpoints 
 
5.2.1 Primary Endpoints 
Primary endpoints for the study are as follows: 
Primary Efficacy Endpoint: Target Lesion Primary Patency Rate through 6 Months 
Defined as freedom from clinically-driven target lesion revascularization (CD-TLR) or access circuit 
thrombosis measured through 6 months post-procedure. 
Primary Safety Endpoint: Serious Adverse Event Rate within 30 Days 
Defined as the Serious Adverse Event (SAE) rate involving the AV access circuit through 30 days post- 
procedure. 
 
5.2.2 Secondary Endpoints 
Secondary endpoints assessed through 24-month for the study are as follows: 
Access Circuit Primary Patency through 3 Months, 6 Months, 9 Months, 12 Months, 18 Months, and 24 
Months Post-procedure 
Defined as freedom from re-intervention in the access circuit or access circuit thrombosis through 3 months, 
6 months, 9 months, 12 months, 18 months, and 24 months post-procedure. 
Target Lesion Primary Patency through 3 Months, 9 Months, 12 Months, 18 Months, and 24 Months Post-
procedure 
Defined as freedom from CD-TLR or access thrombosis occurring in the target lesion through 3 months, 9 
months, 12 months, 18 months, and 24 months post-procedure. 

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Cumulative Target Lesion Revascularizations Measured through 3 Months, 6 Months, 9 Months, 12 Months, 
18 Months, and 24 Months Post-procedure 
Defined as proportion of subjects with TLR through 3 months, 6 months, 9 months, 12 months, 18 months, 
and 24 months post-procedure. 
Number of Interventions Required to Maintain Target Lesion Patency through 3 Months, 6 Months, 9 
Months, 12 Months, 18 Months, and 24 Months Post-procedure 
Defined as number of TLR through 3 months, 6 months, 9 months, 12 months, 18 months, and 24 months 
post-procedure. 
Number of Interventions Required to Maintain Access Circuit Patency through 3 Months, 6 Months, 9 
Months, 12 Months, 18 Months, and 24 Months Post-procedure 
Defined as number of reinterventions in the target lesion and/or access circuit through 3 months, 6 months, 9 
months, 12 months, 18 months, and 24 months post-procedure. 
Cumulative Access Circuit Thromboses Measured through 3 Months, 6 Months, 9 Months, 12 Months, 18 
Months, and 24 Months Post-procedure 
Defined as proportion of subjects with access circuit thrombosis through 3 months, 6 months, 9 months, 12 
months, 18 months, and 24 months post-procedure. 
Device, Procedure, and Clinical Success 
Device Success: Defined as successful delivery, inflation, deflation and retrieval of the intact study balloon 
device without burst at or below rated burst pressure (RBP) at index procedure 
Procedural Success: defined at maintenance of patency (≤30% residual stenosis) in the absence of peri- 
procedural serious adverse device effect (SADE) 
Clinical Success: defined as resumption of successful dialysis for at least one session after index procedure 
Rate of Device and Procedure Related Adverse Events Reported through 30 Days, 3 Months, 6 Months, 9 
Months, 12 Months, 18 Months, and 24 Months Post-procedure. 
Device Related Adverse Event Rate: defined as proportion of subjects with device related Adverse Events 
reported through 30 days, 3 months, 6 months, 9 months, 12 months, 18 months, and 24 months post-
procedure. 
Procedure Related Adverse Event Rate: defined as proportion of subjects with procedure related Adverse 
Events reported post-index procedure until the first successful dialysis session. 

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The following endpoints will be assessed annually up to 36 months in addition to the assessment through 24 
months where applicable: 
Target Lesion Revascularizations 
Defined as proportion of subjects with TLR up to 36 months post-index procedure 
Clinically-Driven Target Lesion Revascularizations 
Defined as proportion of subjects with CD-TLR up to 36 months post-index procedure 
Re-interventions in the access circuit 
Defined as proportion of subjects with reinterventions occurring within the access circuit up to 36 months 
post-index procedure 
Abandonment of Target AVF 
Defined as proportion of subjects with abandonment of the target AV abandonment up to 36 months post-
index procedure 
Serious Adverse Events 
Defined as the Serious Adverse Event (SAE) rate up to 36 months post-index procedure. 
Vital status will be collected annually through 60 months for all current subjects. Vital status will be requested 
for any subjects who have exited the study in the US.  As for the subjects in Japan and New Zealand, once a 
subject exits the study, no medical information can be retrieved. Time to survival/death will be evaluated 
according to the Kaplan-Meier method up to 60 months. 
6. Study Design  
This is a prospective, global, multicenter, single-blinded, randomized (1:1) clinical study evaluating the 
IN.PACT™ AV Access DCB (study arm) vs. standard PTA (control arm) for the treatment of de novo or non-
stented restenotic obstructive lesions up to 100 mm in length in the arteriovenous dialysis fistulae. All eligible 
subjects who provide informed consent and meet all inclusion/exclusion criteria will be randomized 1:1 based 
upon lesion type (de novo, restenotic) to the control or study arm. Total enrollment will be 330 subjects at up 
to 30 global sites, with a minimum of 50% (165) of subjects coming from the U.S. sites, and a minimum of 
30% (99) of subjects coming from the Japan sites. There is no minimum enrollment requirement at each site; 
however, individual sites may enroll no more than 20% of the total study subjects. Approximately 165 study 
devices will be used in this study. 
 
 
 

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6.1 Duration 
Once enrolled, subjects will remain in the study through completion of the required follow-up duration unless 
the subject withdraws consent, the investigator withdraws the subject, or Medtronic terminate the study for 
any reason. The enrollment phase is expected to take 15 months. The follow-up duration for each subject is 
up to 60 months. For the 48 and 60 month visits, the only data collection required will be vital status. The 
total expected duration of the study is approximately 6 years. 
 
6.2 Rationale 
The clinical performance of the IN.PACT™ AV Access DCB will be evaluated through a prospective, global, 
multicenter, single-blinded, randomized (1:1) clinical study in a total of 330 subjects with a hypothesis- based 
30-day primary safety endpoint and a 6-month primary efficacy endpoint. The study has been designed with 
the assumption of a target lesion primary patency rate of 60% for the study arm and 40% for the control arm. 
The safety endpoint composite rate is assumed 5% for both study arms. The assumptions for endpoint rates 
were based upon publicly available information from currently marketed devices and the literature. See 
Section 14.1 for further details on the statistical method. 
PTA is the current standard for treatment of flow limiting stenotic lesions within the dialysis circuit. PTA may 
cause vessel trauma leading to neointimal hyperplasia resulting in poor midterm patency, and therefore, an 
increased rate of reinterventions. The addition of the antiproliferative drug, paclitaxel, has been proven in 
other vessel beds to be safe and effective in the inhibition of neointimal hyperplasia and reduction of 
vascular restenosis. 8 
 
6.3 Blinding 
The study subjects will remain blinded through completion of the 6-month primary efficacy endpoint, 
including completion of all associated evaluations. Independent Core Laboratories and the Clinical Events 
Committee (CEC) will be blinded to the treatment assigned through the entire study duration. 
Study site staff (implanting physicians, catheterization lab staff, and other research staff) will not be blinded 
to treatment assignment due to the macroscopic visual differences between the investigational device and 
the control device. As study investigators are not blinded to the subject’s treatment assignment, no 
procedures to break the blind in the case of an emergency are required. 
Medtronic representatives whose responsibilities require knowledge of treatment assignment to perform 
their respective roles will not be blinded. Designated individuals within the IN.PACT™ AV Access study team, 
Data Solutions, Safety, Customer Service (responsible for device shipment and accountability), and 
Regulatory will not be blinded. Clinical Customer Service, a small group of individuals who will be responsible 
for device shipment and reconciliation, will be unblinded, as will the team of monitors assigned to the study. 
Unblinded individuals within Medtronic and at the study sites will receive guidance on preserving the blind as 

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required. 
7. Product Description 
7.1 
General 
Device Description 
The investigational device being evaluated in this study is the IN.PACT™ AV Access Paclitaxel-Coated PTA 
Balloon Catheter (“IN.PACT™ AV Access DCB”), see Figure 2. The IN.PACT™ AV Access DCB is an over-the-wire 
(OTW) balloon catheter with a drug coated balloon at the distal tip. The drug component consists of 
paclitaxel and the excipient, urea. IN.PACT™ AV Access DCB catheter is dual-lumen shaft which is branched at 
the proximal end so that one tube forms the entrance to the central lumen for the guide wire, while the 
other tube is used to inflate and deflate the dilation balloon with a mixture of contrast medium and saline 
solution. 
The catheter construction and the balloon material are designed so that a specific balloon diameter can be 
reached, depending on the balloon size and defined pressure. 
 
 
 
Figure 2: Schematic of the IN.PACT™ AV Access Paclitaxel-coated PTA Balloon Catheter 
1. Guidewire Port 
2. Hub 
3. Inflation Port 
4. Strain Relief 
5. Shaft 
6. Usable Catheter Length 
7. Radiopaque Marker 
8. Balloon 
The device has two modes of action: the balloon’s PTA mechanical dilatation of the vessel lumen and drug 
delivery to the vessel wall intended to inhibit the restenosis normally caused by the proliferative 

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response to the PTA. IN.PACT™ AV Access DCB is based on the design of the currently FDA- approved IN.PACT™ 
Admiral DCB indicated for treatment of de novo, restenotic, or in-stent restenotic lesions in the superficial 
femoral (SFA) or popliteal arteries (PA). 
The investigational Instructions for Use (IFU), see Section 17.1- Instructions for Use, will be the primary 
source of information for the device and will be packaged with the investigational device or provided to the 
study sites as needed throughout the study. Table 1 summarizes the IN.PACT™ AV Access DCB balloon and 
catheter working lengths characteristics including available sizes, nominal pressures, rated burst pressures, 
and sheath compatibility. Table 2 lists the IN.PACT™ AV Access model numbers for all geographies. 

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Table 1: IN.PACT™ AV Access DCB Characteristics 
 
Available Balloon 
Diameters (mm) and 
Lengths (mm) 
Balloon 
Diameter 
(mm) 
Balloon Length (mm) 
40 
60 
80 
120 
1504 
4.0 
X 
X 
X 
X 
X 
5.0 
X 
X 
X 
X 
X 
6.0 
X 
X 
X 
X 
X 
7.0 
X 
X 
X 
--- 
--- 
8.0 
X 
X 
X 
--- 
--- 
9.0 
X 
X 
X 
--- 
--- 
10.0 
X 
--- 
--- 
--- 
--- 
12.0 
X 
--- 
--- 
--- 
--- 
Note: “---” indicates size not offered; “x” indicates sizes offered 
Usable Catheter 
Lengths 
40 cm, 80 cm and 130 cm* 
Balloon Inflation 
Pressure 
Balloon Diameter 
(mm) 
Nominal Pressure 
(atm) 
Rated Burst Pressure 
(atm) 
4.0 
8 
14 
5.0 
6.0 
7.0 
8.0 
10 
9.0 
10.0 
6 
9 
12.0 
Minimum Introducer 
Sheath Compatibility 
Balloon Diameter 
(mm) 
Max Crossing Profile 
(mm) 
Introducer Sheath 
4.0 
1.88 
5 Fr 
5.0 
2.00 
6 Fr 
6.0 
2.10 
7.0 
2.33 
7 Fr 
8.0 
9.0 
10.0 
12.0 
3.00 
9 Fr 
Guidewire 
Compatibility 
The catheter is compatible with a guidewire diameter of 0.035 in (0.89 mm). 
* For the clinical trial only the 40 cm and 80 cm catheter lengths will be made available 
 
4 IN.PACT AV DCB 150 mm balloon length is not approved for commercial use and distribution. 

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Table 2: Study Device Model Numbers (All Geographies) 
 
Balloon 
Diameter 
(mm) 
Balloon 
Length 
(mm) 
Model Number 
(40 cm Catheter) 
Model Number 
(80 cm Catheter) 
Model Number 
(130 cm Catheter*) 
4.0 
40 
AVC 040 040 04P 
AVC 040 040 08P 
AVC 040 040 13P 
4.0 
60 
AVC 040 060 04P 
AVC 040 060 08P 
AVC 040 060 13P 
4.0 
80 
AVC 040 080 04P 
AVC 040 080 08P 
AVC 040 080 13P 
4.0 
120 
AVC 040 120 04P 
AVC 040 120 08P 
AVC 040 120 13P 
4.0 
150** 
AVC 040 150 04P 
AVC 040 150 08P 
AVC 040 150 13P 
5.0 
40 
AVC 050 040 04P 
AVC 050 040 08P 
AVC 050 040 13P 
5.0 
60 
AVC 050 060 04P 
AVC 050 060 08P 
AVC 050 060 13P 
5.0 
80 
AVC 050 080 04P 
AVC 050 080 08P 
AVC 050 080 13P 
5.0 
120 
AVC 050 120 04P 
AVC 050 120 08P 
AVC 050 120 13P 
5.0 
150** 
AVC 050 150 04P 
AVC 050 150 08P 
AVC 050 150 13P 
6.0 
40 
AVC 060 040 04P 
AVC 060 040 08P 
AVC 060 040 13P 
6.0 
60 
AVC 060 060 04P 
AVC 060 060 08P 
AVC 060 060 13P 
6.0 
80 
AVC 060 080 04P 
AVC 060 080 08P 
AVC 060 080 13P 
6.0 
120 
AVC 060 120 04P 
AVC 060 120 08P 
AVC 060 120 13P 
6.0 
150** 
AVC 060 150 04P 
AVC 060 150 08P 
AVC 060 150 13P 
7.0 
40 
AVC 070 040 04P 
AVC 070 040 08P 
AVC 070 040 13P 
7.0 
60 
AVC 070 060 04P 
AVC 070 060 08P 
AVC 070 060 13P 
7.0 
80 
AVC 070 080 04P 
AVC 070 080 08P 
AVC 070 080 13P 
8.0 
40 
AVC 080 040 04P 
AVC 080 040 08P 
AVC 080 040 13P 
8.0 
60 
AVC 080 060 04P 
AVC 080 060 08P 
AVC 080 060 13P 
8.0 
80 
AVC 080 080 04P 
AVC 080 080 08P 
AVC 080 080 13P 
9.0 
40 
AVC 090 040 04P 
AVC 090 040 08P 
AVC 090 040 13P 
9.0 
60 
AVC 090 060 04P 
AVC 090 060 08P 
AVC 090 060 13P 
9.0 
80 
AVC 090 080 04P 
AVC 090 080 08P 
AVC 090 080 13P 
10.0 
40 
AVC 100 040 04P 
AVC 100 040 08P 
AVC 100 040 13P 
12.0 
40 
AVC 120 040 04P 
AVC 120 040 08P 
AVC 120 040 13P 
* For the clinical trial only the 40 cm and 80 cm catheter lengths will be made available 
 
** IN.PACT AV DCB 150 mm balloon length is not approved for commercial use and distribution.

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7.2 Manufacturer 
The IN.PACT™ AV Access DCB will be manufactured in accordance with standard procedures and 
specifications under 21 CFR 820 and EN ISO13485. The manufacturer is listed below: 
Medtronic, Inc. 
710 Medtronic Parkway 
Minneapolis,  MN 55432 
USA 
 
7.3 Packaging 
The IN.PACT™ AV Access DCB is delivered in a sterile package for single use only. See Section 17.3 – Labeling, 
for specific language on the device label. 
 
7.4 Intended Population 
Subjects will be 21 years of age or older with a de novo or non-stented restenotic lesion in the AVF in the 
upper extremity with a reference vessel diameter (RVD) between 4.0 - 12.0 mm which is amenable to PTA. 
The IN.PACT™ AV Access Paclitaxel-Coated PTA balloon catheter is indicated for percutaneous transluminal 
angioplasty, after pre-dilatation, for the treatment of obstructive lesions up to 100 mm in length in the native 
arteriovenous dialysis fistulae with reference vessel diameters of 4 to 12 mm. 
 
7.5 Equipment 
Any test equipment critical to be used for assessing endpoints (e.g., Duplex Ultrasound, angiography, etc.) 
will be maintained/calibrated according to the site’s standard protocol. Maintenance and calibration reports 
will be monitored periodically. 
 
7.6 Product Training Requirements 
The treating investigator will be evaluated to ensure that he/she is qualified by training, education, and 
experience in PTA. The treating investigators will be trained on the IN.PACT™ AV Access CIP prior to 
performing study related procedures. 
 
 
 
 
 
 
 
 

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7.7 Product Receipt and Tracking 
Medtronic will provide study sites with Investigational devices per the site specific Clinical Trial Agreement 
(CTA) terms. Investigational devices will not be shipped to the study sites until they have received approval 
from their corresponding regulatory agency and IRB/EC, and an executed CTA is in place. The investigational 
device must be used only in the IN.PACT™ AV Access Study. 
All sites will be trained on device accountability, including the return of opened or unopened devices (for 
defect, damage, malfunction, expired inventory). Device accountability should be captured on the Product 
Accountability Log if the site does not perform direct data entry into the Device Tracking eCRF. 
The Principal Investigator (PI) is responsible for maintaining adequate records of the receipt and disposition 
of all IN.PACT™ AV Access DCB systems. All sites are required to maintain investigational device records that 
contain the following information on all components shipped to the site for the study: 
• 
Subject ID 
• 
Party Responsible (upon receipt) 
• 
Product Received by (name) 
• 
Receipt Date 
• 
Model/Reference Identifier 
• 
Serial Number 
• 
Expiration Date 
• 
Date Used 
• 
State of the device (unused, returned, disposed, in use) 
• 
Date of Return or Disposal 
• 
Method of Return or Disposal 
• 
Product Disposal By (name) 
• 
Reason for Tracking/ Disposition Event 
• 
Quantity of Tracked Device 
 
For devices that are returned to Medtronic or disposed of, sites are required to document the following 
additional information: 
 
• 
The reason for the device being returned to Medtronic or disposed of 
• 
Name of the person who returned or disposed of each device 
• 
Date shipped to Medtronic, if returned 
• 
If device is disposed of, the method of disposal 
The monitor will check the device storage/management conditions. 
In Japan, the procedures for managing the study device will be provided by the sponsor. 

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7.8 Product Storage 
The investigational device, IN.PACT™ AV Access DCB, must be stored per the investigational IFU at the site in 
a secure area that is accessible and controlled only by the assigned, trained study personnel. 
 
7.9 Product Return 
In the event of a device deficiency of the IN.PACT™ AV Access DCB system prior to, during, or after device 
use, the device should be returned to Medtronic, if possible. Sites should contact their Medtronic clinical 
study representative to obtain further instruction on device return procedures. All returned devices will be 
analyzed by Medtronic. At the end of the study enrollment period, all remaining investigational devices must 
be returned to Medtronic. 
8. Selection of Subjects 
8.1 Study Population 
This study will enroll subjects with a de novo or non-stented restenotic obstructive lesions up to 100 mm in 
length, located in the native arteriovenous dialysis fistulae. The complete lists of eligibility criteria can be found 
in Section 8.3 - Inclusion Criteria and Section 1 - Exclusion Criteria. 
 
8.2 Subject Enrollment 
A subject will be enrolled in the study after he/she has signed the informed consent, it has been determined 
that he/she meets all of the inclusion criteria and none of the exclusion criteria, and successful pre-dilatation 
has been performed. 
The point of enrollment is defined as the moment randomization occurs. 
See Section9.5 - Randomization and Treatment Assignment, for further information. 

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8.3 Inclusion Criteria 
1. Patient is ≥21 years of age 
2. Patient has a life expectancy of ≥12 months 
3. Patient has a native AV fistula created ≥ 60 days prior to the index procedure 
4. The target AV fistula has undergone successful dialysis for at least 8 of 12 sessions during a four 
week period 
5. Patient has a de novo and/or non-stented restenotic lesion located between the arteriovenous 
anastomosis and axillosubclavian junction with ≥50% stenosis 
Note: If the lesion is located in the anastomosis, the treatment may be delivered up to 2 cm 
upstream on the arterial side 
Note: If the lesion is located in the cephalic arch, the treatment may be delivered up to 2 cm 
into the subclavian vein 
6. Patient has a target lesion or a tandem lesion that is ≤ 100 mm in length (by visual estimate) 
Note: Tandem lesions may be enrolled provided they meet all of the following criteria: 
• Separated by a gap of ≤ 30mm (3 cm) 
• Total combined lesion length, including 30 mm gap, ≤ 100 mm 
• Able to be treated as a single lesion 
7. Patient has a target vessel diameter of 4.0 – 12.0 mm (by visual estimate) 
8. Patient underwent successful crossing of the target lesion with the guide wire and pre-dilatation 
with a high pressure PTA balloon defined as: 
• Residual stenosis of ≤ 30% AND 
• Absence of a flow limiting dissection (Grade ≥C) or perforation 
9. Patient provides written informed consent prior to enrollment in the study 
10. Patient is willing to comply with all follow-up evaluations at specified times 

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8.4 Exclusion Criteria 
1. Women who are breastfeeding, pregnant, or are intending to become pregnant, or men 
intending to father children 
2. Patient is receiving immunosuppressive therapy 
3. Patient is anticipating a kidney transplant within 6 months of enrollment into the study 
4. Patient has undergone prior intervention of access site within 30 days of index procedure 
5. Patient with anticipated conversion to peritoneal dialysis 
6. Patient has an infected AV access or systemic infection 
7. Patient has planned surgical revision of access site 
8. Patient with secondary non-target lesion requiring treatment within 30 days post index 
procedure 
9. Patient with hemodynamically significant central venous stenoses that cannot be successfully 
treated prior to treatment of the target lesion 
10. Patient with target AVF or access circuit which previously had or currently has a thrombosis 
11. Patients judged to have a lesion that prevents complete inflation of an angioplasty balloon or 
proper placement of the delivery system 
12. Patient with target lesion located central to the axillosubclavian junction 
13. Patient has significant arterial inflow lesion requiring treatment more than 2 cm upstream from 
the anastomosis in the AV access 
14. Patient has presence of pseudoaneurysm or aneurysm requiring treatment at the lesion site 
15. Patient has presence of a stent located in the target AV access circuit 
16. Patients with known allergies or sensitivities to paclitaxel 
17. Patient with known contraindication, including allergic reaction, or sensitivity to contrast 
material that cannot be adequately pre-treated 
18. Patient who cannot receive recommended antiplatelet and/or anticoagulant therapy 
19. Patient with clinically significant Steal Syndrome requiring  treatment 
20. Patient is enrolled in another investigational drug, device, or biologic study and has not 
completed the primary endpoint, or was previously enrolled in this study 
21. Patient has a co-morbid condition that, in the judgment of the Investigator, may cause him/her 
to be non-compliant with the protocol or confound the data interpretation 

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9. Study Procedures  
 
9.1 Schedule of Events 
Figure 3 provides a flow diagram from the point of subject screening through the follow-up visits. Table 3 
provides an overview of the assessment requirements for the study, and Tables 4-10 provide specific 
requirements at each stage of the study. 

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Figure 3: Study Flow Diagram 

 
 
Table 3: Study Assessment Requirements† 
 
Assessments/ 
Procedure 
Baseline/ 
Screening 
  Index 
Procedure 
Discharge 
(within 7 
days post- 
procedure) 
30 Days 
(± 7 days) 
3 Months* 
(90 ± 15 
days) 
6 Months 
(180 ± 30 
days) 
9 Months* 
(270 ± 30 
days) 
12 
Months 
(360 ± 30 
days) 
18 Months* 
(540  ± 30 
days) 
24 Months 
(720 days ± 
30 days) 
36 Months 
(1,080 days 
± 30 days) 
 
48 Months 
(1440 days ± 
30 days) 
60 Months†† 
(1880 days ± 
30 days) 
Unscheduled 
Visit** 
Target AVF 
Abandonment 
Informed Consent 
X1 
Medical History 
X2 
Physical Exam 
X2 
 
X4 
Medication 
Assessment 
X2 
X 
X 
X 
X 
X 
X 
X 
X 
X 
EQ-5D 
X2 
X 
X 
X 
X 
Duplex Ultrasound 
X 
X 
X 
 
X6 
Angiography¥ 
X3 
 
X4 
Randomization 
X 
Adverse Event 
X 
X 
X 
X 
X 
X 
X5 
X5 
X5 
X5 
X           
(death only) 
X5 
       X5 
Abandonment 
eCRF 
X 
Vital Status7  
 
 
 
 
X 
 
†Follow-up dates are calculated based on 30-day months 
*Subjects will be contacted by telephone 3 months, 9 months, and 18 months post index procedure to assess adverse events and medications 
††After assessments for the 60 month visit are completed, the subject will be exited from the study 
**See Appendix 17.11 Recommended Guidelines for Re-interventions 
¥ Angiograms performed outside of the index procedure and unscheduled visits (e.g. standard of care angiograms at 6 months post index-procedure) should be submitted to the angiographic core laboratory. 
1 Consent process may occur within 14 days prior to enrollment. Signing on the same day as procedure is allowed if allowed by the IRB/EC and source records document that the consent process was conducted and 
consent was signed pre-procedure 
2 Within 14 days prior to enrollment 
3Angiogram must include all pre- and post-procedure images. Refer to the Angiographic Core Laboratory guidelines for full requirements. 
4Repeat at unscheduled visit only if clinically warranted or institutional standard 
5After the primary endpoints are met (6 months), only SAEs, TLRs, and/or device related events will be collected 
6Duplex Ultrasounds conducted within 2 years of index procedure should be submitted to the Core Laboratory; after the 24 month assessment DUS exams should no longer be submitted for evaluation 
7 Collection of mortality status for all current subjects. Vital status will  be collected on subjects who have previously exited the study for reasons other than death in the United States only. 
 
 
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Baseline Requirements 
Baseline data collection requirements are identified in Table 4. Baseline assessment results will be submitted 
to the sponsor. The subjects will undergo a standard physical exam including a physical examination of the 
target limb, and medical history (review of symptoms, pre-existing conditions, and medications). The 
baseline review will also capture information on the target AVF (location, age, and previous 
revascularizations). Although not required by the protocol, the treating physician should obtain and evaluate 
laboratory tests, e.g. CBC/creatinine/coagulation profile, per their institution’s standard of care prior to the 
index procedure. 
Table 4: Baseline Requirements 
 
Baseline Requirements 
Timeframe Window 
Informed Consent 
Within 14 days of the index procedure* 
Medical History 
Physical Exam 
Medication Use Documentation 
EQ-5D 
* Ensure ICF is signed prior to conducting study specific assessments or procedures 
 
 
Index Procedure Requirements 
The Investigator performing the study index procedure must be both approved by Medtronic and delegated 
by the study site’s Principal Investigator (as documented on the Delegation of Authority/Delegated Tasks List 
Form). 
The treating Investigator must use the study device in accordance with the investigational IFU. The 
corresponding manufacturer’s IFU should be followed for all ancillary devices (e.g., guide wires, 
sheath/guiding catheters, pre-dilatation balloons, etc.) used during the index procedure. 
The following describes required assessments and procedures associated with the index procedure. All 
activities should be documented. 
Target Lesion: only one target lesion per subject is eligible for study treatment. Tandem lesions may be 
treated provided they meet all requirements for a single lesion (as defined in the Inclusion Criteria) and can 
be treated as a single lesion. 
Preparation / Medications 
Single antiplatelet therapy, at a minimum, (e.g. aspirin, clopidogrel, ticlopidine or Prasugrel) should be 
administered before the procedure and for a minimum of 4 weeks after the intervention as stated in the 
investigational IFU. If antiplatelet therapy is not standard of care at the study site, ensure the informed 
consent form has been reviewed and signed by the patient prior to administering antiplatelet medications 
Access will be gained at the appropriate vascular site utilizing a sheath with a hemostatic valve. 
 
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Angiogram 
Angiography should be performed according to the Angiographic Imaging Protocol provided by the 
Angiographic Core Lab. 
During pre-enrollment angiography the Investigator will assess the subject for the anatomic eligibility 
criteria including verifying the target lesion or tandem lesions are up to 100 mm in length. 
Angiograms of the AV access circuit will be obtained immediately prior to and after the index procedure to 
document pre- and post-treatment results. Copies of all angiograms must be sent to the angiographic core 
lab. 
The angiographic core lab values will supersede the physician’s measurement assessments for data analysis 
purposes; however, the physician’s assessment will be used to determine subject eligibility at the time of 
enrollment. 
Pre-Dilatation 
In both treatment groups, pre-dilatation is required for all target lesions and must be performed successfully 
before a subject can be randomized (inclusion criteria 8). Pre-dilatation must be performed with a high 
pressure PTA balloon (no other devices, such as cutting/scoring balloons, or DCBs are allowed). The pre-
dilatation balloon must have a diameter matching the RVD distal to the target lesion. Patients must be 
excluded from enrolling in the study if pre-dilatation is unsuccessful. Up to two balloons may be used to 
achieve successful pre-dilatation prior to considering the patient a screen failure. Pre-dilatation is 
considered unsuccessful if any of the following occur: 
• 
The tip of the guide wire or PTA balloon is unable to cross and extend beyond the target lesion 
• 
A flow-limiting dissection (Grade ≥C) or perforation occurs 
• 
Inability to pre-dilate 
• 
Residual stenosis > 30% 
If pre-dilatation is successful, the patient will be randomized to receive either standard PTA (control arm) or 
IN.PACT™ AV Access DCB (study arm), see Section 9.5 – Randomization and Treatment Assignment. Subjects 
randomized to the standard PTA arm will receive additional PTA treatment with a low pressure balloon. 
Drug Coated Balloon Angioplasty and Post-Dilatation 
Balloon Sizing: Balloon size must match the RVD and fully cover and extend beyond the lesion length: 
• 
Nominal balloon diameter must match the inner diameter of the reference vessel distal to the target 
lesion. 
• 
Nominal balloon length must exceed the total target lesion length by approximately 1 cm at the 
proximal and distal edge in order to ensure full lesion coverage and prevent geographic miss. 
Inflation Pressure: Balloon inflation pressure should be at the nominal pressure and should never exceed 
rated burst pressure. 

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Inflation Time: Balloon inflation must be at least 180 seconds (3 minutes). The IN.PACT™ AV Access DCB 
releases the drug into the vessel wall on first expansion and adequate drug transfer occurs in the first 60 
seconds of inflation. The additional 120 seconds is intended solely for mechanical dilatation purposes to fulfill 
optimal PTA requirements. 
Prolonged and Repeat Inflations: Longer inflation times are possible at the discretion of the Investigator 
for the purpose of optimizing lesion dilatation. 
A second dilatation must be performed with a non-DCB when the initial dilation results in any of the 
following: 
• 
Residual stenosis > 30% (by visual estimate); 
• 
Presence of flow-limiting dissection 
Use of Multiple Study Balloons: In subjects with a total target lesion length that is longer than the longest 
available balloon, two or more IN.PACT™ AV Access DCBs may be used and they should overlap by 
approximately 1 cm. 
The use of a second IN.PACT™ AV Access DCB to complete treatment is allowed only under either of the 
following circumstances: 
• 
The first IN.PACT™ AV Access DCB bursts prior to 60 seconds of inflation time 
• 
The total length of the eligible target lesion requires more than one IN.PACT™ AV Access DCB to 
fully cover the lesion and extend about 1 cm beyond the lesion at the proximal and distal edges 
If a second IN.PACT™ AV Access DCB is required under the circumstances described above, the second 
IN.PACT™ AV Access DCB must be a newly opened device, and may be of a different diameter. 
Post-dilatation: Post-dilatation should be completed according to the investigator’s discretion. It is 
important to provide drug delivery to the entire length of the treated vessel prior to post-dilatation or 
provisional stenting. If adequate PTA results are not obtained after the IN.PACT™ AV Access DCB(s) 
inflation, post-dilatation using a non–drug-coated PTA balloon of shorter length than the previously used 
IN.PACT™ AV Access DCB is recommended. For both treatment arms, all balloon dilatations in enrolled 
subjects, including the pre-randomization dilatation, must be documented with angiographic images and 
submitted to the angiographic core lab. 
Only study subjects randomized to treatment with the IN.PACT™ AV Access DCB may be treated with the 
investigational product. 
No alternative therapies are allowed (DES, grafts, laser, atherectomy, cryoplasty, brachytherapy, etc.). 
Intention to use such alternative therapies to treat the target lesion either pre- or peri-procedure 
constitutes a violation of exclusion criterion. 
 
 

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Provisional Stenting 
Provisional stenting should be avoided unless required for subject safety. Only non-drug-coated stents that 
are approved in country of the study site and for this indication may be used in this study. 
Since the purpose of this study is to evaluate the safety and efficacy of the IN.PACT™ AV Access DCB 
investigational device, provisional stenting should be avoided, if possible. Provisional stenting should be 
performed only after repeated and prolonged balloon inflations result in either of the following conditions: 
• 
Residual stenosis of ≥50% (by visual estimate); 
• 
Major (≥ Grade D) flow-limiting dissection 
All subjects who undergo a provisional stenting are required to be followed per the protocol-required 
follow-up schedule. These subjects will be analyzed in the Intent-to-Treat (ITT) population. 

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Follow-Up Requirements Discharge 
All subjects will be assessed pre-discharge. At this time, an evaluation for adverse events (AEs) per protocol 
requirements will be completed and documented and medications will be recorded. Discharge assessment 
requirements are listed in Table 5. 
Table 5: Discharge Requirements 
 
Discharge Requirements 
Timeframe Window 
Adverse Event Documentation 
Prior to discharge 
(within 7 days post-procedure) 
Documentation of Medication Use 
 
30-Day Follow-up Requirements 
All subjects are required to have a follow-up visit 30-days post-procedure. At this time, an evaluation for 
AEs per protocol requirements will be completed and documented. A duplex ultrasound will be performed, 
medication use will be documented and the EQ-5D questionnaire will be administered. Table 6 lists the 30-
day follow-up requirements. 
 
Table 6: 30-Day Follow-up Requirements 
30-Day Follow-up Requirements 
Target 
Follow-up Window 
Adverse Event Documentation 
30 days post-procedure 
23-37 days post-procedure 
Documentation of Medication Use 
EQ-5D 
Duplex Ultrasound 
 
3-Month, 9-Month, 18-Month Follow-up Requirements 
All subjects will be contacted by telephone at 3-months, 9-months, and 18-months post-procedure. At this 
time, an evaluation for AEs per protocol requirements will be completed and documented and medication 
use will be documented. The physician may choose to perform an in-office visit to meet the study follow-up 
requirement. Table 7 lists the 3-, 9-, and 18-month follow-up requirements. 

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Table 7: 3-Month, 9-Month, 18-Month Follow-up Requirements 
 
3-Month, 9-Month, 18-
Month Follow-up 
Requirements
Target 
Follow-up Window 
Adverse Event Documentation 
3-month follow-up: 90 days 
post-procedure 
9-month follow-up: 270 
days post-procedure 
18-month follow-up: 540 
days post-procedure 
3-month: 75-105 days post- 
procedure 
9-month: 240-300 days post- 
procedure 
18-month: 510-570 days post- 
procedure 
Documentation of Medication Use 
 
6-Month and 12-Month Follow-up Requirements 
All subjects are required to have a follow-up visit 6-months and 12-months post-procedure. At this time, 
an evaluation for AEs per protocol requirements will be completed and documented. A duplex 
ultrasound will be performed, medication use will be documented and the EQ-5D questionnaire will be 
administered. Subjects should be unblinded at the 6-month visit after completing follow-up 
requirements. Table 8 lists the 6-month and 12-month follow-up requirements. 
 
Table 8: 6-Month and 12-Month Follow-up Requirements 
 
6-Month and 12-Month Follow-up 
Requirements 
Target 
Follow-up Window 
Adverse Event Documentation 
6-month follow-up: 180 days 
post-procedure 
12-month follow-up: 360 
days post-procedure 
6-month: 150-210 days post- 
procedure 
12-month: 330-390 days post- 
procedure 
Documentation of Medication Use 
EQ-5D 
Duplex Ultrasound 
 
24-Month and 36-Month Follow-up Requirements 
All subjects are required to have annual visits up to 3 years post-procedure. At these times, an 
evaluation for AEs per protocol requirements will be completed and documented. Medication use will 
be documented and the EQ-5D questionnaire will be administered. Table 9 lists the 24- month and 
36-month follow-up requirements. 
 
 
 
 

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Table 9: 24-Month and 36-Month Follow-up Requirements. 
 
24-Month and 36-Month 
Follow-up Requirements 
Target 
Follow-up Window 
Informed Consent* 
 
24-month follow-up: 720 
days post-procedure 
 
36-month follow-up: 1,080 
days post-procedure 
 
 
24-month: 690-750 days post- 
procedure 
 
36-month: 1,050 - 1,110 days 
post-procedure 
 
Adverse Event Documentation 
Documentation of Medication Use 
EQ-5D 
* Ensure subject is reconsented prior to conducting any study specific assessments after 24-months 
 
48-Month and 60-Month Follow-up Requirements 
The 48-month and 60-month follow-up visit will be the collection of vital status for all current subjects on 
the Vital Status eCRF and SAE event for death only. After completion of the 60-month vital status, the 
subject will be exit from the study. Table 10 lists the 48-month and 60-month follow-up requirements.  
 
Table 10: 48-Month and 60-Month Follow-up Requirements. 
 
 
48-Month and 60 Month Follow-up 
Requirements 
Target 
Follow-up Window 
Vital Status 
48-month follow-up: 1440 
days post-procedure 
60-month follow-up: 1800 
days post-procedure 
48-month follow-up: 1410 – 1470 
days post-procedure 
60-month follow-up: 1770 – 1830 
days post-procedure 
Adverse Event Documentation – 
Death event only 
 
Collection of vital status 
Vital status will be collected annually through 60 months for all current subjects. Vital status will be 
requested for any subjects who have exited the study in the US.  As for the subjects in Japan and New 
Zealand, once a subject exits the study, no medical information can be retrieved. Table 11 provides 
examples of acceptable data collection methods for the vital status.  
 
 
 

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Table 11: Data Collection Methods for Vital Status. 
 
 
Data Collection Methods 
Current Subjects (Japan, New Zealand, United 
States) 
• 
May call subject 
• 
May review EMR 
Subjects in the United States who exited the 
study but consented for up to 3 years of 
additional follow-up  
• 
May call subject or next of kin 
• 
May review EMR 
Subjects in the United States who exited the 
study but did not consent for up to 3 years of 
additional follow-up 
• 
Publicly available sources: 
social media, obituaires, 
legacy.com etc.   
 
 
Unscheduled Visit 
A subject who returns to the investigational site between protocol-required visits for a clinical event in the 
target limb is considered to have an Unscheduled Visit, and all appropriate assessments must be completed 
and captured in the appropriate electronic case report forms (eCRFs). Appendix 17.11 details the 
recommended guidelines for re-interventions. 
Angiography and/or duplex ultrasound should be repeated if clinically indicated and/or within the 
institution’s standard of care. As much as possible, imaging studies performed during an Unscheduled Visit 
should be performed in accordance with the Core Lab imaging protocols. Angiographic and/or duplex 
ultrasound and/or arterial flow studies results must be submitted to the appropriate core lab with the Core 
Lab Technician Worksheet. 
If the subject refuses an angiogram, duplex ultrasound or re-intervention at an unscheduled visit, it will not 
be considered a deviation from the protocol. Table 12 lists the assessments to be performed if clinically 
indicated at unscheduled and re-intervention visits. Unscheduled visits will no longer be collected or 
required.  
Table 12: Unscheduled Visit 
 
Assessments to be Performed if Clinically Indicated 
Physical Exam 
Adverse Event Documentation 
Angiogram 
Duplex Ultrasound 
 
 
 
 

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9.2 Subject Screening 
It is expected that all potentially eligible patients be approached for enrollment in the study and be 
screened at the site. Eligible patients will be given an explanation of the study, educated on the possible 
risks and benefits of participating, and be asked to provide written informed consent prior to any study- 
specific screening or testing. Patients will be informed that, despite signing the informed consent 
document, screening procedures outlined in Table 3 may demonstrate the patient is not a suitable 
candidate for the study. 
During the course of the study, Medtronic may limit enrollment to a specific IN.PACT™ AV Access balloon 
size if needed in order to achieve an acceptable distribution of sizes. Investigators would be notified of 
what balloon sizes are needed for enrollment, and patients who are not candidates for treatment with 
those sizes would no longer be considered for enrollment. This determination may be made during the 
procedure after the initial angiogram, at which point the patient would become a screen failure. 
 
9.3 Prior and Concomitant Medications 
Single antiplatelet therapy, at a minimum, (e.g. aspirin, clopidogrel, ticlopidine or Prasugrel) should be 
administered before the procedure and for a minimum of 4 weeks after the intervention as stated in the 
investigational IFU. If antiplatelet therapy is not standard of care at the study site, ensure the informed 
consent form has been reviewed and signed by the patient prior to administering antiplatelet medications. 
Use of anticoagulant and antiplatelet medications will be documented on the Concomitant Medication 
eCRF. Use of medications other than antiplatelet and anticoagulants will not be collected. 
Note: medications and dose as market approved in geography 
 
9.4 Subject Consent 
All subjects must undergo the consent process, possess the mental capacity to provide Informed Consent, 
and sign the ICF prior to enrollment and prior to undergoing any assessments or procedures that are study-
specific (defined as those that would not be conducted if the subject was not participating in the study). 
Some general inclusion/exclusion criteria that are standard of care may be evaluated prior to the subject 
signing the Informed Consent Form. An exam previously conducted, but repeated solely for the study (for 
example, to determine eligibility) is considered a study-specific assessment. 
The subject must personally sign and date the site’s current Institutional Review Board (IRB)/Ethics 
Committee (EC) – approved version of the Informed Consent to be eligible for the study. A legally 
appointed representative may sign the consent form in cases where a subject has mental capacity but 
cannot sign due to physical inability. If a patient is illiterate, an impartial witness must be present during 
the entire informed consent discussion. All items addressed in the patient informed consent must be 
explained. 

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The study site Principal Investigator and/or his/her delegated designee must conduct the informed consent 
process. The content of the ICF must be explained to the subject in a language that is as non- technical as 
possible and is understandable to the subject (and witness, if required/applicable). The patient must be 
given ample opportunity to ask questions and will be informed about their rights to withdraw from the 
study at any time, for any reason, and without any disadvantage. 
When the patient has thoroughly understood this information, he/she will be asked if he/she is willing to 
sign or seal (with printed name) and date consent form. A subject may participate in the study when he/she 
consents to do so of their own free will and signs the informed consent form. 
After all required parties have signed and dated the ICF, the subject must be provided with a copy of the 
signed and dated ICF. The original signed ICF should be retained in the Investigator Site File or medical 
record. 
The informed consent process for all subjects must be documented in the source records. 
The ICF and other written explanatory information will be revised if significant new information that may 
be relevant to the subject’s consent becomes available, or there is an amendment to the protocol which 
necessitates a change to the ICF. The subjects should be re-consented in a timely manner and will be asked 
to confirm willingness to continue his/her participation in the study and obtain his/her signature or seal 
(with printed name) on the revised consent form. All revisions to the consent form and information sheet 
must be approved in advance by the IRB/EC. 
Medtronic revised the written informed consent template to include the extension of follow-up from the 
originally planned 24 months up to 5 years post index procedure. Subjects who are currently participating 
in the clinical study shall be asked to sign the updated informed consent to confirm their continuing 
informed consent in writing for up to 5 years of follow-up. The revised informed consent documents will be 
provided to the investigational sites for approval by the local EC/IRB. 
Enrolled subjects who decline to continue to participate in follow-up beyond 24-months shall exit the study 
upon the completion of their 24-month visit. 

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9.5 Randomization and Treatment Assignment 
After a patient has signed informed consent, the eligibility criteria has been verified and undergone 
successful pre-dilatation, the patient will be enrolled via randomization to one of two treatment arms in a 
1:1 ratio: 
1. IN.PACT™ AV Access DCB (study arm) 
2. Standard PTA Balloon (control arm) 
Randomization will be accomplished using an Interactive Voice Response System (IVRS), or Interactive Web 
Response System (IWRS) or Interactive Mobile Response System (IMRS). Randomization should occur as 
closely as possible to the time of index procedure. Randomization will be stratified based on lesion status: 
de novo vs. restenotic and with pre-specified block sizes within study sites. A separate protocol for 
instructions on how to randomize subjects will be provided to the study sites. 
Confirmation of randomization reports will be provided to the site immediately after randomization occurs. 
These reports must be maintained in the site files. 
Once randomized (enrolled), a subject must be followed per protocol, regardless of whether or not a 
subject ultimately receives study treatment. 
If a subject inadvertently undergoes the wrong treatment (e.g. randomized to the control arm but 
undergoes PTA with the study device), the subject will be analyzed in accordance with the treatment 
assignment, not the treatment actually administered. 
If a subject is inadvertently randomized more than once, the subject must be treated in accordance with 
the first treatment assignment and the subject will be followed per protocol and will be analyzed in the 
intent-to-treat (ITT) data set. 
 
9.6 Assessment of Safety 
The primary safety endpoint is based on the Adverse Event data collected. Further information on collection 
of Adverse Events is discussed in Section 11 – Adverse Event Assessments. 
 
9.7 Recording Data 
 
Source Documents 
Data entered into the electronic database must be traceable to source documents. Source documentation 
is defined as the first time data appear and may include original documents, data and records (e.g. hospital 
records, clinical and office charts, laboratory notes, memoranda, or evaluation checklists, pharmacy 
records, recorded data from automated instruments, copies or transcriptions 

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certified after verification of accuracy and other documents/records required by geographies regulation 
where required). 
In general, eCRFs (or paper copies/worksheets) may not serve as source documents. An exception is the 
quality of life questionnaire or for data elements not routinely captured in medical records. This should be 
documented as being the source documents, printed out, signed and dated by a delegated member from 
the study site. 
Copies of source documents will be requested to support event adjudication by the Clinical Events 
Committee. Any private health information (PHI) in source document copies provided to the CEC should be 
masked. In Japan, availability of source documentation may be limited due to hospital policies. If a specific 
source document is not available, necessary information may be transcribed onto the relevant CRF page. 
The Investigator must ensure the availability of source documents as outlined in Section 15.8 - Direct 
Access to Source Data/Documents. 
 
9.8 Deviation Handling 
A deviation is any event in which the study is not conducted according to the CIP, applicable laws or 
regulations or the Investigator Agreement. Deviations may include, but are not limited to the following: 
• 
Failure to obtain informed consent prior to participation 
• 
Incorrect version of the informed consent form used 
• 
Failure to obtain IRB/EC approval before the start of enrolling subjects in the study 
• 
Included subject did not meet inclusion/exclusion criteria 
• 
Required testing and/or measurements not done or incorrectly done 
• 
Subject did not attend follow-up visit 
• 
Follow-up visit was completed outside window 
• 
Unauthorized use of IN.PACT™ AV Access DCB(s) 
• 
Adverse events/UADE or device deficiencies not reported in the required timeframe by 
country regulation or as specified in the CIP 
• 
Control of study devices not maintained 
• 
Source data permanently lost 
• 
Enrollment of subjects during lapse of IRB/EC approval 
• 
Enrollment limits exceeded 
Investigators are required, whenever possible, to obtain prior approval from Medtronic before initiating 
changes in or deviations from the investigational plan, except where necessary to protect the life or 
physical well-being of a subject in an emergency. Such approval will be documented in writing and 

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maintained in the study files. Prior approval is generally not expected in situations where unforeseen 
circumstances are beyond the Investigator’s control, (e.g., subject did not attend scheduled follow-up visit), 
the event, however, is still considered a deviation. 
In the event the deviation involves a failure to obtain a subject’s consent, or is made to protect the life or 
physical well-being of a subject in an emergency, the deviation must be reported to the IRB/EC as well as 
Medtronic as soon as possible but no later than five (5) working days from the date of the deviation 
occurrence. 
Reporting of all deviations should comply with IRB/EC policies and/or local laws and/or regulatory agencies 
and must be reported to Medtronic as soon as possible upon the site becoming aware of the deviation. 
Subject specific deviations will be reported on the Protocol Deviation eCRF; all non-subject specific 
deviations (e.g. unauthorized use of an investigational device outside the study, unauthorized use of an 
investigational device by a physician who has not signed an Investigator Agreement, etc.) will be reported 
to Medtronic in writing. 
Medtronic is responsible for analyzing deviations, assessing their significance, and identifying any 
additional corrective and/or preventive actions which may include amending the CIP, conducting additional 
training, terminating the investigation, etc. Repetitive or serious investigator compliance issues may 
represent a need to initiate a corrective action plan with the investigator and site, and in some cases, 
necessitate suspending enrollment at that site until the problem is resolved or ultimately terminating the 
investigator's participation in the study. Medtronic may provide site-specific reports to investigators 
summarizing information on deviations that occurred at the investigational site on a periodic basis. 
 
9.9 Subject Withdrawal or Discontinuation 
Every subject should be encouraged to remain in the study until they have completed the required follow-
up per the CIP. Subjects will be included in the analyses up to the time that consent was withdrawn, unless 
a subject specifically instructs Medtronic that none of their data may be used. Subjects who discontinue 
participation prior to study completion will be included in the analysis of results, but will not be replaced in 
the inclusion of total study subjects. For subjects in the US, vital status will be requested for any subjects 
who have exited the study for any reasons other than Death.  
Loss to Follow-Up 
Every attempt must be made to have all subjects complete the follow up visit schedule. A subject will be 
considered lost-to-follow-up if efforts to obtain compliance are unsuccessful. At a minimum, the effort to 
obtain follow-up information must include three documented attempts to make contact (e.g. phone, email, 
text), followed by a certified letter from the Principal Investigator. Once deemed lost-to-follow- up, the 
subject will be exited from the study.

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Subject Withdrawal 
All study subjects have the right to withdraw their consent to participate at any time during the study. 
Whenever possible, the site staff should obtain written documentation from the subject of his/her request 
to withdraw his/her consent. If the site is unable to obtain written documentation, all information 
regarding the subject’s withdrawal must be recorded in the subject’s medical record. In addition, the 
appropriate eCRFs must be completed. 
Withdrawal of a subject from the study can also occur at the direction of the Principal Investigator without 
the subject’s consent. Reasons for physician-directed subject withdrawal include, but are not exclusive to: 
protocol requirements, the subject has enrolled in another study that conflicts with the primary outcome, 
or the physician deems it in the best interest for the safety or welfare of the subject to withdraw. 
Medical Care after Study Exit 
After study exit, the subjects may be followed as per routine standard of care by the investigational site or 
a treating physician. Relevant medical records may be made available by the investigational sites for the 
treating physician per local laws and regulations if needed for further subject treatment. As per local law 
and regulation the investigator may be contacted by the treating physician in case of questions related to 
the study device and treatment. 
10. Risks and Benefits 
 
10.1 Potential Risks 
Potential risks or complications anticipated with the use of the IN.PACT™ AV Access DCB in PTA are similar 
to those associated with standard PTA and drug-eluting stent procedures. Such risks, as listed in the 
IN.PACT™ AV Access DCB investigational IFU, include but may not be limited to those listed below (in 
alphabetical order). Table 13 below also includes potential risks and complications that may occur. 
 
Table 13: Potential Risks Associated with the Study Procedure 
 
Potential adverse effects which may be associated with balloon catheterization may include, 
but are not limited to: 
• 
abrupt vessel closure 
• 
access site pain 

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• 
allergic reaction to contrast medium, antiplatelet therapy, or catheter system 
components (materials, drugs, and excipients) 
• 
arrhythmias 
• 
arm edema 
• 
arterial or venous aneurysm 
• 
arterial or venous thrombosis 
• 
arteriovenous (AV) fistula 
• 
death 
• 
dissection 
• 
embolization 
• 
fever 
• 
hematoma 
• 
hemorrhage 
• 
hypotension/hypertension 
• 
inflammation 
• 
ischemia or infarction of tissue/organ 
• 
local infection at access site 
• 
local or distal embolic events 
• 
perforation or rupture of the artery or vein 
• 
pseudoaneurysm 
• 
pulmonary embolism 
• 
renal insufficiency or failure 
• 
restenosis of the dilated artery or vein 
• 
sepsis or systemic infection 
• 
shock 
• 
stroke 
• 
systemic embolization 
• 
vessel spasms or recoil 
• 
vessel trauma which requires surgical repair 
Potential complications of peripheral balloon catheterization include, but are not limited to: 
• 
balloon rupture 
• 
detachment of a component of the balloon and/or catheter system 
• 
failure of the balloon to perform as intended 
• 
failure to cross the lesion 

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As with any device requiring mechanical deployment and retraction, there exists a risk of mechanical failure 
of the device resulting in potential surgical intervention to remove the balloon or delivery system. 
 
It is expected that the fluoroscopy time during the procedure may be minimally longer (in order to confirm 
inclusion and exclusion criteria) than the time required for standard PTA procedures using other devices. 
Following the fluoroscopic procedure, the skin area exposed to the x-rays could react to produce an effect 
similar to a sun burn. 
 
All of the above could cause prolonged illness, permanent impairment of daily function or, in rare cases, 
death. Possible treatments could include, but are not limited to medication, surgery, medical monitoring or 
other applicable treatments, and will be provided at the discretion of the Investigator. 
 
Potential Side Effects of Paclitaxel 
Paclitaxel is a drug commonly used in the treatment of oncology patients; particularly in patients with 
breast cancer. In that setting, paclitaxel is usually administered as an intravenous infusion and side effects 
associated with this systemic administration are known. 
High systemic safety margins were reported in the IN.PACT™ SFA II Pharmacokinetic Report. Paclitaxel 
systemic exposures in 24 study subjects was brief, declining in one hour by over 87% from the peak of 
7.9 ng/mL to 1.0 ng/mL, followed by a continued decline to very low concentration levels of 0.1ng/mL at 
day 7. 
Some of the common side effects known to occur in cancer patients treated with paclitaxel include, but are 
not limited to, the side effects listed in Table 14. 
Table 14: Potential Risks Associated with Paclitaxel 
 
• 
allergic/immunologic reaction 
• 
alopecia 
• 
anemia 
• 
gastrointestinal symptoms 
• 
hematologic dyscrasia (including leucopenia, neutropenia, thrombocytopenia) 
• 
hepatic enzyme changes 
• 
histologic changes in vessel wall, including inflammation, cellular damage, or 
necrosis 
• 
myalgia/arthralgia 
• 
myelosuppression 
• 
peripheral neuropathy 

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Refer to the Physician's Desk Reference for more information on the potential adverse events observed 
with paclitaxel. 
As with the use of any investigational product, there may be other potential adverse events that are 
unforeseen at this time. 
 
10.2 Potential Benefits 
There are no guaranteed benefits from participation in the study. It is possible that treatment with 
IN.PACT™ AV Access DCB may improve and maintain blood flow through the treated AVF, resulting in the 
need for fewer treatments. This may allow for continued/resumption of AV access for the purpose of 
hemodialysis. Information gained from the conduct of this study may be of benefit to other persons with 
the same medical condition. 
 
10.3 Risk-Benefit Rationale 
It has been demonstrated that standard PTA for obstructive lesions in the native AVF can be performed 
safely and that these devices are effective in restoring and maintaining AVF patency. The risks associated 
with the IN.PACT™ AV Access DCB or the participation in this study are not anticipated to be worse than the 
risks normally associated with the use of other commercially available devices. 
Potential risks with this study are minimized by selecting Investigators who are trained in the use of the study 
device and trained to the study protocol, by clearly defining inclusion/exclusion criteria to ensure only 
appropriate subjects are enrolled. In addition, the investigator performs a continuous monitoring, 
assessment, and documentation of any risks. 
Medtronic will establish a CEC and DMC to independently review and evaluate subject health status, device 
performance, and identify any safety concerns regarding subjects’ wellbeing. Medtronic has further 
minimized the possibility of risks by completing product testing prior to the use of the IN.PACT™ AV Access 
DCB in this clinical study, implementing quality control measures into production processes, providing 
guidelines for subject selection and evaluation, and providing adequate instructions and labeling. 
Risk management for IN.PACT™ AV Access is performed in accordance with EN ISO 14971:2012. The 
Indication, warnings, and contraindications are provided in the investigational IFU. 

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11. Adverse Event Assessments 
 
11.1 Definitions/Classifications 
 
Definitions 
For the purpose of this clinical study, Medtronic will define and classify the following events per EN 
ISO14155:2011 and Title 21 CFR 812.3. Definitions are provided in Table 15. 
 
Table 15: Definitions of Adverse Events 
 
Event Type 
Definition 
Adverse Event (AE) 
(ENISO14155:2011
3.2) 
Any untoward medical occurrence, unintended disease or injury, or 
untoward clinical signs (including abnormal laboratory findings) in 
subjects, users or other persons, whether or not related to the 
investigational medical device. 
NOTE 1: This definition includes events related to the investigational 
medical device or the comparator. 
NOTE 2: This definition includes events related to the procedures involved. 
NOTE 3: For users or other persons, this definition is restricted to events 
related to investigational medical devices. 
Serious 
Adverse Event 
(SAE) 
(EN 
ISO14155:2011 
3.37) 
Adverse event that 
a) led to death, 
b) led to a serious deterioration in the health of the subject, resulting in 
1) a life-threatening illness or injury, or 
2) a permanent impairment of a body structure or a body function, 
or 
3) in-patient or prolonged hospitalization, or 
4) medical or surgical intervention to prevent life-threatening illness 
or 
injury or permanent impairment to a body structure or a body 
function, 

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c) led to foetal distress, foetal death or a congenital abnormality or birth 
defect. 
NOTE: Planned hospitalization for a pre-existing condition, or a procedure 
required by the CIP, without serious deterioration in health, is not 
considered a serious adverse event. 
Adverse 
Device Effect 
(ADE) 
(EN ISO14155:2011 3.1) 
Adverse event related to the use of an investigational medical device. 
NOTE 1: This definition includes adverse events resulting from insufficient 
or inadequate instructions for use, deployment, implantation, 
installation, or operation, or any malfunction of the investigational 
medical device. 
NOTE 2: This definition includes any event resulting from an error use or 
from intentional misuse of the investigational medical device. 
Serious 
Adverse Device 
Effect (SADE) 
(EN ISO14155:2011 3.36) 
Adverse device effect that has resulted in any of the consequences 
characteristic of a Serious Adverse Event. 
Unanticipated 
Adverse 
Device Effect 
(UADE) 
(21 CFR 812.3) 
Any serious adverse effect on health or safety or any life-threatening 
problem or death caused by, or associated with, a device, if that effect, 
problem, or death was not previously identified in nature, severity, or 
degree of incidence in the investigational plan or application, or any other 
unanticipated serious problem associated with a device that relates to the 
rights, safety, or welfare of subjects. 
Unanticipated 
Serious 
Adverse Device 
Effect (USADE) 
(EN 
ISO14155:2011 
Serious adverse device effect which by its nature, incidence, severity or 
outcome has not been identified in the current version of the risk analysis 
report. 
NOTE: Anticipated serious adverse device effect (ASADE) is an effect which 
by its nature, incidence, severity or outcome has been identified in the risk 
analysis report. 
Device Deficiency 
(EN ISO14155:2011 3.15) 
Inadequacy of a medical device with respect to its identity, quality, 
durability, reliability, safety or performance. 

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NOTE: Device deficiencies include malfunctions, use errors, and 
inadequate labeling. 
 
Classification of Causal Relationships 
For each reported AE, the causal relationship between the AE and the study device, interventional 
procedure, and therapy will be classified as not related, unlikely, possible, probable, or causal 
relationship by the Investigator and Sponsor. 
In the case where the AE may not be adequately assessed because of insufficient data, data cannot be 
verified, or if data is contradictory, Medtronic will classify the relatedness as ‘possible’. 
The causal relationships are defined in Table 16, and should be collected for subjects randomized to 
either the control arm or study arm. 
Table 16: Causal Relationship Definitions 
 
Related To 
Definition 
Study Procedure 
Complication associated with the initial use of the device or any necessary 
secondary interventions after the point of enrollment through the resumption of 
successful dialysis for one session. This includes morbidity associated with either 
anesthesia or surgical procedure. This also includes inappropriate subject 
selection and errors attributed to inappropriate operator techniques, 
measurements or judgment. 
Device 
Complication associated with the device design as it relates to placement, 
efficacy or durability, (these may involve the delivery system). 
Therapy 
Complication associated with a subject’s physiological response to the paclitaxel 
drug. 
 
11.2 Reporting of Adverse Events 
The investigator is required to assess and document in the medical record all Adverse Events (AEs) and 
Device Deficiencies (DDs) (per the definitions in Table 15) observed in subjects from the time of consent. 
All AEs (except those listed in Table 18) regardless of relatedness, seriousness, expectedness or 
outcome, must be reported through the primary endpoint after which only SAEs, ADEs, SADEs, and 
UADEs will be collected through 36 months. After 36 months, only SAE related to Death events together 
with vital status will be reported. AEs will be followed until the event has resolved or until study exit. In 
case of permanent impairment, the event will be followed until the event stabilizes and the overall 
clinical outcome has been ascertained. Reporting of AEs and DDs will end once the subject exits the 
study. In case AEs are unresolved at the time of study exit, this will be documented on the eCRF. 

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The investigator is responsible for reporting AEs to Medtronic as outlined in Table 17 by completing the 
Adverse Event eCRF and/or Device Deficiency eCRF. For the purposes of this CIP, planned/elective 
procedures for pre-existing conditions will not be considered or reported as adverse events (AE).  A list 
of AEs that may be associated with the device and/or the interventional procedure is provided in Section 
10.1 – Potential Risks. 
 
 
Table 17: Adverse Event Reporting Guidelines (Site Reporting to Medtronic)* 
 
Type of Event 
Reporting Time Frame 
Reported Through Study Visit 
Adverse Event 
At time of procedure and follow-up 
visits 
6 Month Follow-up Visit¥ 
Serious 
Adverse 
Event (SAE) 
As soon as possible, but within 10 
working days after Principal 
Investigator** is first aware of the 
event. 
36-Month Follow-up Visit 
Adverse Device Effect (ADE) 
Serious Adverse Device 
Effect (SADE) 
Unanticipated 
Adverse Device 
Device Deficiency 
SAE related to Death Event 
At time of vital status review. 
Recommended within 10 working 
days after Principal Investigator** is 
first aware of the event. 
48-60 Month Follow-up Visit 
* Study sites are responsible for reporting AEs/Device Deficiencies to the IRB/EC per the IRB/EC reporting policy; where 
applicable. 
** Principal Investigator also includes all designated study personnel at the site 
¥AEs associated with a TLR and not considered an SAE should be reported up to the 36-month follow-up visit 
 
Non-Reportable Medical Occurrences 
Documented pre-existing conditions are not considered AEs and should not be reported unless there is a 
change in the nature or severity of the condition.  Pre-existing  events should be reported as Adverse 
Events in the situation where a new treatment has to be started or an existing treatment has to be changed 
to treat the adverse event and the event is accompanied with signs and symptoms. 
 
Clinical events that are inherent to a surgical procedure and expected to occur in the majority of subjects 
for a projected duration may be considered unavoidable. Such events include, but are not 

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limited to, those listed in Table 18. These events should not be reported as adverse events during this 
study. 
Table 18: Expected and Unavoidable Adverse Events Related to the Procedure 
 
Description of the Event 
Time Frame from the Index Procedure 
Anesthesia-related nausea and/or vomiting 
Within 24 hours 
Access site bleeding controlled by usual 
means 
Within 24 hours 
Low-grade fever (< 100° F or < 37.8° C) 
Within 48 hours 
Back pain related to laying on OR table 
Within 72 hours 
Incisional pain (pain at access site) 
Within 72 hours 
Sleep problems or insomnia 
Within 72 hours 
Mild to moderate bruising or ecchymosis 
Within 168 hours 
Suture irritation 
After suture removal 
 
11.3 Emergency Contact Details 
For any study related emergency, the investigators can contact the Medtronic Clinical Research Specialist 
assigned to the site. Contact information for the Clinical Research Specialist and the Medical Expert are 
listed on the Study Contact List. 
12. Data Review Committees and Core Laboratories 
12.1 Data Monitoring Committee 
An independent Data Monitoring Committee (DMC), will be established with the responsibility to assess 
the progress of the clinical investigation, the safety data, and the critical performance endpoints and to 
recommend to Medtronic whether to continue, modify, or stop the investigation. All final decisions 
regarding study modifications or termination will be made by Medtronic. Detailed information, such as the 
DMC member selection, composition, duties, procedures, and deliberation rules are detailed and 
documented in the DMC Charter. 
 
12.2 Clinical Event Committee 
An independent Clinical Events Committee (CEC) will be responsible for the adjudication of selected 
adverse events and clinical endpoints in the study, using criteria established at the outset of the study and 
specified by the CIP, the CEC Charter and relevant societal reporting standards. The CEC Charter will 

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specify explicit rules outlining the minimum amount of data required and the algorithm followed in order 
to classify an event. Detailed information such as the CEC member selection, composition, duties, 
procedures, and deliberation rules are detailed and documented in the CEC Charter. 
For any events after 36 months, only serious adverse event related to death will be adjudicated.  
 
12.3 Duplex Ultrasound Core Laboratory 
The Duplex Ultrasonography Core Laboratory (DUS Core lab) is responsible for developing protocol 
requirements, reviewing DUS exams, interpreting subject DUS data, and providing feedback on the 
quality of the DUS exams to participating sites. The DUS Core lab will review, analyze, and record data 
on the Duplex Core laboratory Assessment eCRF. The DUS Core laboratory’s interpretation of all DUS 
exams will be used for the data analyses through 24-months post index procedure. 
 
12.4 Angiographic Core Laboratory 
The Angiographic Core Laboratory is responsible for review of the index procedural angiograms to assess 
lesion characteristics as well as procedural outcomes. The Angiographic Core Laboratory will also review any 
angiograms performed during the follow-up period and any re-interventions. The Angiographic Core 
laboratory’s interpretation of all angiograms will be used for the data analyses. 
 
13. Statistical Design and Methods 
 
This is a prospective, global, multi-center, single-blinded, randomized (1:1) study of balloon dilatation 
with IN.PACT™ AV Access DCB (study arm) vs. standard non-coated PTA balloons (control arm) for the 
treatment of de novo and non-stented restenotic lesions in the native AVF. The study will enroll in three 
geographies: U.S., Japan, and New Zealand. Further details on the statistical methods, including 
justification, timing of interim analysis can be found in the Statistical Analysis Plan. 
 
13.1 Hypotheses and Sample Size Calculation 
There are two primary hypotheses for the study. One is for the primary efficacy endpoint – target lesion 
primary patency through 6 months, and one is for the primary safety endpoint – SAE rate involving the AV 
access circuit through 30 days post-procedure. 
 
 
 

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For the primary efficacy endpoint – target lesion primary patency through 6 months, the treatment (pT) 
and control (pC) groups will be compared in a superiority format under the following hypothesis. 
H0: pT ≤ pC 
HA:   pT   >  pC 
 
 
For the primary safety endpoint - SAE rate involving the AV access circuit through 30 days, the treatment 
(πT) and control (πC) groups will be compared in a non-inferiority format under the following hypothesis. 
H0: πT ≥ πC  +  0.075 
HA:   πT   <  πC   +  0.075 
For primary efficacy endpoint, with one-sided alpha of 0.025 and assuming 60% primary patency rate in 
treatment and 40% in control, a Z-test of proportions will provide at least 92% statistical power to test 
for superiority, when the effective sample size is 140 in each arm. After accounting for 15% of attrition 
rate through 6 months, the total sample size will be 330. 
 
For primary safety endpoint, an effective sample size of 161 in each arm provides at least 80% power 
using a Farrington-Manning test based on a one-sided alpha of 0.025, with the assumed event rate of 
5% in each arm and a non-inferiority margin of 7.5%15. After accounting for 2% of attrition at 30-day 
follow-up, the total sample size will be 330. 
According to above the consideration of both primary endpoints, the total sample size is therefore 330. 
The power and sample size calculations were performed by using PASS v14.0.7 (NCSS LLC, Kaysville, 
Utah). The establishment of the assumptions for endpoint rates was based upon publicly available 
information from currently marketed devices and the literature. 
 
Device Name 
Source (SSED, 
Literature) 
Target Lesion Patency Definition 
Results 
IN.PACT DCB, 
PTA 
NCT01174472 
Kitrou, P. M., et al. 
(2015). Eur J Radiol 
84(3): 418-423. 
Katsanos, K., et al. 
(2012).  J Endovasc 
Ther  19(2): 263-272. 
Angiographic visualization of a lesion 
with <50% restenosis and no need for 
any additional repeat interventional 
procedure within the previously 
treated lesion, due to failing access. 
70% [50%, 90%] in DCB vs 
25% [6%, 44%] in PTA 
IN.PACT DCB 
Patanè D et al. 
(2014). J Vasc Access 
15(5):338-43 
The absence of dysfunction of the 
vascular access, patent lesion or 
residual stenosis <30% and no need 
for further reintervention of the TL; 
92.3% [82%, 100%] in 
DCB 

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GORE 
VIABAHN 
Endoprosthesi 
s, PTA 
Vesely, REVISE 
Clinical Trial 
presented at 
Scientific Meeting, 
2014. SSED 
time interval of uninterrupted 
patency from initial study treatment 
to the next access thrombosis or 
intervention performed on the target 
lesion. 
52.9% [43.8%, 61.6%] in 
stent graft vs 
35.5% [27.4%, 43.6%] in 
PTA 
FLAIR 
Patency (open to blood flow) after 
Endovascular 
Stent Graft, 
PTA 
Haskal et. al. NEJM 
362, 6, 494-503, 
2010. SSED 
the study index procedure until 
reintervention in the treatment area 
(within 5 mm proximal or 5 mm distal 
to the study device or index balloon 
angioplasty treated area), or 
thrombotic occlusion that involved 
KM rate: 
50.6%[40.0%, 60.8%] in 
stent graft 
vs 23.3% [14.3%, 32.2%] 
in PTA 
the treatment area. 
Bard Fluency 
Stent Graft, 
PTA 
Dolmatch et. al. J 
Vasc Interv 
Radiology, 23, 4, 479- 
487, 2012. SSED 
Interval after the index intervention 
until the next re-intervention at the 
original treatment site or until the 
extremity (access) is abandoned for 
permanent access 
KM rate: 
65.2%[55.6%, 74.9%] in 
stent graft 
vs 10.4% [4.3%, 16.6%] in 
PTA 
 
 
 
Device Name 
Source 
Primary Safety Endpoint 
Results 
Bard Fluency Stent 
Dolmatch et. al. J 
Freedom through 30 days from 
96.6% (114/118) in 
Graft, PTA 
Vasc Interv 
any localized or systemic 
stent graft vs 96.8% 
Radiology, 23, 4, 
adverse events, which 
(122/126) in PTA group 
479-487, 2012. 
reasonably suggests the 
SSED 
involvement of the AV access 
circuit (not including stenosis 
or thrombosis) that require or 
result in any of the following 
alone or in combination: 
additional interventions 
(including surgery); inpatient 
hospitalization or prolongation 
of an existing hospitalization; or 
death. 

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FLAIR Endovascular 
Stent Graft, PTA* 
Haskal et. al. 
NEJM 362, 6, 
494-503, 2010. 
SSED 
Incidence of adverse events at 
6 months 
No significant 
difference in two arms, 
except for restenosis 
which was higher in 
control PTA group 
GORE VIABAHN 
Endoprosthesis, 
PTA 
Vesely, REVISE 
Clinical Trial 
presented at 
Scientific 
Meeting, 2014. 
SSED 
Freedom from major device-, 
procedure-, and treatment 
site-related adverse events 
through 30 days post- 
procedure 
0% in stent graft group 
vs 1.4% in the PTA 
group 
*The key adverse events reported include death (5%), CVA (2%), CHF (4%), edema of arm/hand (3%), vessel rupture (3%), 
and pseudoaneurysm (5%) in the stent graft arm at 6 months 
 
13.2 Analysis Strategy 
The primary efficacy endpoint will be tested for superiority of treatment to control using a one-sided Z- 
test and the primary safety endpoint will be tested for non-inferiority of treatment to control using the 
Farrington Manning Method and a predefined non-inferiority margin of 7.5%. The study will be claimed 
successful if both primary efficacy and primary safety tests showed significance at 0.025. The family-wise 
type I error will therefore be controlled at 0.025. 
Once the hypothesis tests succeed for both primary endpoints, key secondary endpoints will be 
compared between treatments sequentially in a superiority manner as detailed in Section 14.5. If all of 
the selected key secondary endpoints pass the test, an exact test of superiority of the IN.PACT™ AV 
Access DCB compared to PTA in 30-day primary safety endpoint will follow; this sequential approach 
does not inflate the Type I error for superiority. 
Any deviation(s) and change(s) from the original statistical plan and justifications will be documented in 
the CIP amendment and in the Statistical Analysis Plan (SAP). 

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13.3 Analysis Sets 
 
13.3.1 Primary Analysis Set 
Intent-to-treat (ITT) Analysis Set 
All primary analyses will be performed using Intent-to-treat (ITT) Analysis Set which includes all 
randomized subjects. The ITT subjects will be analyzed according to their randomized group assignment 
irrespective of the treatment actually delivered and subject follow-up time, and all events post- 
randomization will be counted toward study endpoints. In general, all analyses will be performed on 
evaluable subjects in ITT analysis set. For Primary efficacy endpoint, the evaluable subjects include all 
ITT subjects that had a patency-related event (i.e., CD-TLR or access circuit thrombosis) within 210 days 
post procedure or had no patency-related event but followed up for at least 150 days. For primary 
safety endpoint, the evaluable subjects include all ITT subjects that had AV-access-circuit-related-SAE 
within 30 days post-procedure or had no AV-access-circuit-related-SAE but were followed up for at least 
23 days. 
 
13.3.2 Secondary Analysis Set 
As treated analysis set 
As treated analysis set include randomized subjects who received a DCB or PTA. The as treated subjects 
will be analyzed according to the device they actually received. If the as treated analysis set is different 
from ITT analysis set, the primary and secondary endpoints will be analyzed on as treated analysis set to 
assess the sensitivity. 
Per-Protocol Analysis set 
Per-Protocol Analysis set include subjects who have: (a) received the randomized treatment as assigned 
without provisional stenting or other potential bailout procedure; (b) no pre-specified 
inclusion/exclusion violation(s); and (c) available endpoint data post-index procedure. Per-Protocol 
Analysis set will be applied to primary and key secondary endpoint analyses. 
 
13.4 Analysis of the Primary Endpoints 
 
13.4.1 Primary Analysis of the Primary Endpoints 
Both the primary efficacy outcome and primary safety outcome will be analyzed as observed. The count 
and percentage of subjects with each outcome will be presented by treatment. The percentage of the 
efficacy endpoint will be based on the subjects who had non-patency event (i.e., CD-TLR or access circuit 

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thrombosis) within 210 days post procedure or had no non-patency event but followed up for at least 
150 days. The efficacy endpoint will be compared between treatments using the Z-test as the primary 
analysis method. 
The percentage of the primary safety endpoint will be based on subjects who had AV-access-circuit- 
related-SAE within 30 days post-procedure or had no AV-access-circuit-related-SAEs but were 
followed up for at least 23 days. Non-inferiority on the safety endpoint will be tested using the 
Farrington- Manning method. The differences between treatments and the corresponding 95% 
confidence interval (CI) will be calculated. 
To control the overall Type I error (one-sided P=0.025 superiority and one-sided P=0.025 non-
inferiority) the following sequential analysis approach will be taken: 
Primary efficacy superiority; if significant at one-sided alpha=0.025, and 
Primary safety non-inferiority; if significant at one-sided alpha=0.025, 
then proceed to key secondary endpoints detailed in section 14.5. 
The study will be deemed a success if both the superiority of efficacy and non-inferiority of safety 
are demonstrated. 
 
13.4.2 Additional Analysis of the Primary Endpoints 
The time to the events will be evaluated according to Kaplan-Meier method, and the log-rank tests will 
be applied to compare the survival curves over time between the treatments for each primary 
endpoint respectively. 
Primary endpoints will also be analyzed using per-protocol analysis set and as treated analysis 
set respectively when applicable. 
 
13.4.3 Sensitivity Analysis of the Primary Endpoints 
• 
Multiple Imputation: ITT subjects with missing clinical follow-up data will be imputed using 
multiple imputation procedure. 
• 
Tipping point analyses in which the number of successes or failures amongst missing data 
necessary to reverses the study conclusion are determined; 
• 
Worst case analysis in which all missing endpoint in the treatment arm will be imputed as 
failures and all missing endpoint in the control arm will be imputed as successes. 
Multiple Imputation will be conducted for primary efficacy endpoint. Tipping point analysis and 
worse case analysis will be conducted for both primary efficacy and primary safety endpoints. 

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13.4.4 Poolability Analysis of the Primary Endpoints 
Poolability of subjects across clinical sites for the primary efficacy and safety endpoint analysis will be 
tested using Cox proportional hazards regression. Included as independent variables in the Cox models 
will be treatment, site and the treatment-by-site interaction effect; if the interaction effect is not 
statistically significant (defined as p>0.15 on the interaction test) or the interaction effect is significant 
but not qualitative in nature, all data irrespective of site will be collected in a single analysis cohort. It 
may be necessary to combine two or more low enrolling study sites into pseudo-sites to allow these 
analyses. Sites with fewer than 10 subjects will be ranked by enrollment from low to high, then starting 
from the lowest enrollment site, sites will be combined into a pseudo site until the combined size 
reaches the median enrollment among all sites. This process will be repeated until all resulting sites 
have enrollment equal to or greater than 10 subjects. This will be done in a manner to preserve the 
structure of the study and prevent bias. Similar poolability analyses will be conducted to assess 
treatment-by- geography (U.S. vs. Japan vs. New Zealand) interaction and treatment-by-lesion status 
(de novo vs. restenotic) interaction. 
 
13.5 Analysis of the Secondary Endpoints 
Descriptive statistics for the secondary endpoints will be provided. Unless otherwise specified, for 
categorical variables, the count and percentage of subjects with each outcome will be presented. 
They will be evaluated by using chi-square tests or Fisher’s exact tests depending on the event counts. 
Continuous variables will be compared with t-tests. The differences between treatments together 
with the corresponding 95% confidence interval will be calculated. Additional time to event survival 
analysis will be employed when applicable. Secondary endpoints will be analyzed using ITT analysis 
set, per- protocol analysis set and as treated analysis set respectively when applicable. 
 
In addition, vital status will be collected annually through 60 months for all current subjects. Vital 
status will be requested for any subjects who have exited the study for reasons other than death in 
the US. As for the subjects in Japan and New Zealand, once a subject exits the study, no medical 
information can be retrieved. Time to survival /death will be evaluated according to the Kaplan-Meier 
method up to 60 months using ITT analysis set. 
 
The following key secondary endpoints will be compared between treatments sequentially by using 
ITT analysis set in a superiority manner if the two primary endpoint tests pass, each at a one sided 
significance level of 0.025, for potential inclusion in the label, in the following order: 
 
(1) Cumulative target lesion revascularizations(TLR) measured through 6 months post-procedure; 
H0:   tT   ≥   tC 
HA:   tT   <  tC 
tx refer to the expected cumulative TLR rate through 6 month (x=T for DCB x=C for PTA). One-sided Z- 
test will be performed at a significance level of 0.025. 

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(2) Number of interventions required to maintain target lesion patency through 6 months post- 
procedure; 
H0: lT ≥ lC 
HA:   lT   <  lC 
lx refer to the expected number of interventions to maintain target lesion patency through 6 
months(x=T for DCB x=C for PTA). The comparison will be performed at one-sided significance level of 
0.025 using Wilcoxon Rank Sum Test. 
 
(3) Number of interventions required to maintain access circuit patency through 6 months post- 
procedure 
H0: cT ≥ cC 
HA:   cT   <  cC 
cx refer to the expected number of interventions to maintain access circuit patency through 6 
months(x=T for DCB x=C for PTA). The comparison will be performed at one-sided significance level of 
0.025 using Wilcoxon Rank Sum Test. 
 
(4) Access circuit primary patency through 6 months post-procedure; 
H0:   aT   ≤   aC 
HA:   aT   >  aC 
ax refer to the expected access circuit primary patency rate through 6 month (x=T for DCB x=C for PTA). 
One-sided Z-test will be performed at a significance level of 0.025. 
If (1) – (4) all pass the test, the superiority test of primary safety endpoint will be performed 
H0:   πT   ≥  πC 
HA:   πT   <  πC 
πx refer to the expected event rate of primary safety endpoint at 30-day (x=T for DCB x=C for PTA). 
Exact test will be performed to compare DCB and PTA. 
The testing procedure will stop at the first rejection failure. This fixed sequence preserves overall type I 
error. 
 
13.6 Subset Analyses 
The following subset analyses of primary and key secondary endpoints will be performed: 
 
• 
Lesion Type (de novo, restenotic) 
• 
AVF type 
• 
Lesion location 
• 
Single and multiple balloon use 
• 
Gender 
• 
Age (≤ Median, > Median) 
• 
Diabetics 

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• 
Subjects without provisional stenting or other bailout procedure 
Subset analysis based on Race and Ethnicity will be performed if applicable. There will be no formal 
hypothesis testing on these subsets due to insufficient power. The primary purpose of this subset 
analysis is to assess consistency of results across subgroups. 
 
13.7 Patient withdrawal and Missing Data 
In general, all analyses will be performed using the ITT analysis set, which constitutes all available (or 
observed) cases.  Imputation of missing data will not be performed unless otherwise specified. 
For primary endpoints, sensitivity analyses such as Multiple imputation tipping point analysis and worst 
case analysis will be performed as specified in 14.4.2. 
14. Ethics 
 
14.1 Statement(s) of Compliance 
The IN.PACT™ AV Access Study will be conducted under an FDA Investigational Device Exemption (IDE) 
in compliance with EN ISO 14155:2011 3.1, 3.15, 3.2, 3.36, 3.37, 3.42, laws and regulations of the 
countries in which the clinical study is conducted, including data protection laws, the Clinical 
Investigation Agreement and the Clinical Investigation Plan. These include the protection of the rights, 
safety and well-being of human subjects, controls to ensure the scientific conduct and credibility of the 
clinical investigation and the definition of responsibilities of Medtronic and investigators. 
 
The study will be conducted according to the study protocol, federal, national and local laws, 
regulations, standards, and requirements of the countries/geographies where the study is being 
conducted. 
 
• 
In the US, the study will be conducted under an FDA Investigational Device Exemption (IDE) in 
compliance with 21 CFR Parts 11, 50, 54, 56, and 812 and 45 CRF part 46. 
• 
In Japan, the study will be conducted in accordance with the ethical principles of the Japan GCP 
Ordinance and the Pharmaceutical and Medical Device Act. 
• 
In addition, the study will be conducted in compliance with 21 CFR Part 11 and 54 in all 
participating geographies. 
 
The study will also be conducted in accordance with the Declaration of Helsinki. The principles of the 
Declaration of Helsinki are implemented in this study by means of the patient informed consent (IC) 
process, IRB/EC approval, study training, clinical study registration, pre-clinical testing, risk benefit 
assessment, and publication policy. 
Where applicable, regulatory authority notification/approval will be done/obtained. Investigational sites 
will not be activated, nor begin enrolling subjects until the required approval/favorable opinion from the 

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respective regulatory agency and IRB/EC has been obtained (as appropriate). 
Additionally, any requirements imposed by a local regulatory agency or IRB/EC shall be followed, as 
appropriate. 
Each site must provide Medtronic with a copy of the investigational site’s IRB/EC approval letter and 
the IRB/EC-approved Informed Consent Form. IRB/EC approval letters must contain the following 
elements: 
• 
Study Title and the Medtronic Protocol Number; 
• 
Medtronic’s Protocol Version (revision letter and/or date of issue); 
• 
A list of the documents reviewed at the meeting covered by the approval letter; 
• 
If applicable, the required interval for the site’s continuing review by the IRB/EC; and 
• 
Expiration date, if applicable and/or allowed by the site’s system, of the current approval. 
If applicable, approvals for the continuation of the study at each investigational site must be kept 
current in accordance with the IRB/EC’s review schedule, but at a minimum, the study must be re- 
reviewed by the IRB/EC regularly based on local requirements. All site communications to and from the 
IRB/EC must be forwarded to Medtronic as they are sent/received. 
Medtronic will be informed by the IRB/EC and/or the investigator in case any action is taken by an 
IRB/EC with respect to this investigation. 
This study was publicly registered on www.clinicaltrials.gov prior to first enrollment in accordance with 
the 2007 Food and Drug Administration Amendments Act (FDAAA) and Declaration of Helsinki.

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15. Study Administration 
15.1 Investigator and Investigational Site Selection 
The primary requirements of Investigator selection for this study are relevant experience, adequate 
institutional facilities and equipment, appropriate site research staff to support the conduct of the 
study, commitment to safety and adherence to the investigational plan, and patient volume. 
Throughout the conduct of the study, Medtronic and/or its designees will closely monitor compliance 
with the investigational plan, the applicable laws and regulations, the requirements of the IRB, and the 
terms of the Clinical Trial Agreement. Medtronic may suspend or terminate the study prematurely at 
any site with repeated occurrences of significant non-compliance. 
 
15.2 Training of Investigational Sites 
Medtronic and/or its designees are responsible for the training of appropriate clinical site personnel. 
Medtronic or its designees will present a formal training session to review proper reporting of adverse 
events, device usage, uniform data collection and compliance with the Clinical Investigation Plan (i.e., 
protocol and consent processes), the device IFU, techniques for the identification of eligible subjects, 
instructions on data collection, schedules for follow-up, and applicable regulatory requirements. The site 
Principal Investigator is responsible for key center personnel to be appropriately trained to the tasks 
they have been delegated. Ongoing assistance regarding completion and submission of eCRFs as well as 
retraining (if necessary) will be provided by Medtronic and/or its designee. 
 
15.3 Investigator Responsibility / Performance 
The Investigator is responsible to ensure that all work and services related to this study described 
herein, or incidental to those described herein, are conducted in accordance with the highest standards 
of medical and clinical research practice, the requirements of the IRB/EC, the clinical investigation plan, 
and the terms of the Investigator Agreement, and all applicable local laws and regulations, U.S. 
Investigational Device Exemption regulations, including: 
• 
21 CFR 812: Investigational Device Exemptions 
• 
21 CFR 50 (Subpart B): Informed Consent of Human Subjects (21 CFR 50.20 General 
requirements for informed consent) 
• 
21 CFR 54 (Part 54): Financial Disclosure by Clinical Investigators 
Upon completion or termination of the study, the Investigator will submit a final written report to 
Medtronic and the IRB/EC as required by the IDE regulations in 21 CFR 812.150.  The report will be 

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submitted to Medtronic within three (3) months of completion or termination of the study and to the 
local IRB/EC in accordance with the IRB/EC policies and procedures. 
The Investigator must maintain a DOA/DTL of appropriately qualified persons to whom the Investigator 
has delegated significant study related duties. 
 
15.4 Role of Sponsor Representatives 
Sponsor’s representatives may provide support as required for the clinical study, including technical 
support during the index procedure. The sponsor representative is an experienced expert of device 
sizing, placement and the technical features of the device and will advise the investigator during the 
index procedure if needed. 
 
15.5 Monitoring 
Monitoring and monitoring oversight will be provided by Medtronic and detailed in a Monitoring Plan 
separate from this CIP. Representatives of Medtronic (i.e. contractors and authorized designees) may 
also act as the study monitors to the site. A list of the study monitors will be kept separate from the 
Monitoring Plan and provided under a separate cover. 
Medtronic will be responsible for ensuring adequate monitoring, including site initiation and study 
closure, at each study site is completed to ensure the protection of the rights of subjects, the safety of 
the subjects, and the quality and integrity of the data collected and submitted. Appropriately trained 
personnel appointed by Medtronic will conduct site visits to ensure accuracy of data, timeliness of data 
submissions, adequate subject enrollment, investigational device accountability, as well as compliance 
with the protocol, IRB/EC conditions and guidelines. Any non-compliance with these items that is not 
adequately addressed by the principal investigator/site staff may be cause for the sponsor to put the 
investigator/site staff on probation or withdraw the investigator/site staff from the study. Frequency of 
monitoring will be based upon enrollment, study duration, compliance, and any suspected inconsistency 
in data that requires investigation. After each monitoring visit, the monitor will send the principal 
investigator a letter summarizing the monitoring visit. The principal investigator will be responsible for 
ensuring that follow-up actions needed to resolve issues are completed in an accurate and timely 
manner. 
See Section 15.8- Direct Access to Source Data/Documents, for further details on source data 
verification. 

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15.6 Audits / Inspections 
Medtronic initiated audits or regulatory authority initiated inspections at the investigational sites may 
occur during the course or after completion of the study. In the event that an audit is initiated by 
Medtronic or a designee (only in geographies where approved), the Investigator shall allow access to the 
original medical records and provide all requested information.  In the event that an inspection is 
initiated by a regulatory authority, the Investigator shall immediately notify Medtronic of the impending 
inspection and allow the regulatory body access to the medical records and other information as 
required by applicable laws and regulations. 
 
15.7 Data Management 
Study sites will designate a unique subject ID number (SID) at the point of subject enrollment, which is 
assigned by Medtronic in the EDC system. Records of the subject/SID relationship will be maintained by 
the study site. 
Electronic Data Capture 
Medtronic will use the Oracle Clinical Remote Data Capture database system for data collection. The 
database is located on a secure server at a Medtronic facility located in the US. All users will be trained 
on the use of the database prior to obtaining access. Once access is granted, users will have a unique 
User ID and will create their own password. Data stored electronically shall be maintained in compliance 
with 21CFR Part 11. The database for this study will be maintained according to corporate policy and 
record retention schedule. 
Data Validation 
Medtronic and/or assigned designee will be responsible for the processing and quality control of the 
data (data management) per the Data Management Plan, which describes the procedures for data 
review, database cleaning and issue/resolution of data queries. Data will be collected and stored in a 
validated, password protected database. Data analysis will be conducted utilizing validated software and 
analysis programs by qualified biostatisticians. 
Study data collected will be monitored and verified against source documents in accordance with 
EN ISO 14155:2011 sections 3.1, 3.15, 3.2, 3.36, 3.37, 3.42 and international standards. Any data 
discrepancies will be addressed through queries posted within the EDC system. 
Data Collection 
It is the responsibility of the participating investigator to ensure the quality of the data being collected. 

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Required data will be recorded on electronic case report forms (eCRFs) by authorized site personnel as 
indicated on the Delegation of Authority/Delegated Task List. The eCRFs must be completed and/or 
updated to reflect the latest observations on the subjects participating in the study. It is recommended 
that all data is entered into the database/eCRF within 10 business days of the completion of the 
protocol-specified assessments or sooner as requested by the sponsor. 
The investigator (or authorized sub-investigator) will electronically approve each eCRF. The EDC system 
maintains an audit trail on entries, changes or corrections in eCRFs, once the eCRF is saved. If changes 
are made to an already signed eCRF, the investigator shall re-sign this eCRF. 
Data Queries 
During the review of source documents and eCRFs at the monitoring visits, any discrepancies noted will 
be queried by Medtronic or its designee (only in geographies where approved), and must be resolved by 
the investigational site staff and investigator in a timely manner. In addition, Medtronic or its designee 
may also generate data queries during routine or remote review of the data. These queries will be sent 
to the site and must also be resolved in a timely manner. 
 
15.8 Direct Access to Source Data/Documents 
When source data verification is performed, the monitor must be granted direct access to original 
source documentation or certified copies of the original source must be provided. Direct access must 
also be permitted for individuals conducting audits, IRB/EC review and regulatory inspections. 
If electronic source documentation is used at the site, the site must provide to the monitor: 
• 
Direct access to the electronic medical record (e.g. the monitor is given a guest password 
to directly access the system) or 
• 
Direct access to the electronic medical record by reviewing alongside appropriate study 
staff (e.g. a research coordinator) or 
• 
Certified copies of the electronic medical record. The monitor shall verify that he/she has 
complete access to all original source required for the study (e.g. the monitor does not 
have a lower level of access to the original source documentation than the research 
coordinator or principal investigator necessary for the study). 
 
15.9 Confidentiality 
Subject confidentiality will be maintained throughout the clinical study in a way that ensures the 
information can always be tracked back to the source data. For this purpose, a unique subject 
identification code consisting of the unique Site Number and Subject Number will be assigned and used 
to allow identification of all data reported for each subject. 
 

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To maintain confidentiality, the subject’s name or any other PHI should not be recorded on any study 
document other than the informed consent form. This scenario will be covered in the Patient  
 
Information-Informed Consent Form. In the event a subject’s name/PHI is included for any reason, it will 
be blinded as applicable. In the event of inability to blind the identification (e.g., digital media), it will be 
handled in a confidential manner by the authorized personnel. 
 
Study data may be made available to third parties, e.g., in the case of an audit performed by regulatory 
authorities, provided the data are treated confidentially and that the subject’s privacy is guaranteed. 
The identity of a subject will never be disclosed in the event that study data are published. 
The study sites in the US must comply with applicable subject confidentiality provisions of the Health 
Insurance Portability and Accountability Act (HIPAA) issued by the U.S. Department of Health and 
Human Services (HHS). All sites should maintain subject privacy in accordance to federal regulations (45 
CFR Parts 160 and 164), local regulations, and institutional requirements. 
 
15.10 CIP Amendments 
Any revisions or amendments to the CIP or Informed Consent document, along with a statement of 
justification for the changes, will be submitted to all affected Regulatory Authorities (FDA, PMDA (per 
GCP, if needed, these documents will be submitted to PMDA, and Medsafe, if needed), Competent 
Authority) and governing IRBs/ECs, according to applicable regulations. All amendments to the CIP shall 
be agreed between Medtronic and the principal investigator(s). Approval by regulatory agencies and 
IRB/EC (where applicable) must be obtained prior to implementing a CIP revision at the site. 
 
15.11 Record Retention 
The investigator must retain the Investigator Site File, subject medical files, including images 
(angiograms and duplex ultrasound), and CRFs in accordance with local law and regulations for a 
minimum period of 2 year (or longer if local laws require) after market-release in his/her region. The 
investigator should take measures to prevent accidental or early destruction of the clinical study related 
materials. 
Medtronic will retain the study records according to Medtronic corporate policy and record retention 
schedule. 

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15.11 Investigator reports 
The investigator is responsible for the preparation (review and signature) and submission to the sponsor 
of all case report forms, adverse events and adverse device effects (reported per the country-specific 
collection requirements), device deficiencies, deaths, and any deviations from the clinical investigation 
plan. If any action is taken by an IRB/EC with respect to this clinical study, copies of all pertinent 
documentation must be forwarded to Medtronic in a timely manner. Reports are subject to inspection 
and to the retention requirements as described above for investigator records. 
Safety data investigator reporting requirements are listed in Section 11.2 – Reporting of Adverse Events. 
The investigator shall prepare and submit in a complete, accurate and timely manner the reports listed 
in this section. 
If any action is taken by an IRB/EC with respect to this clinical study, copies of all pertinent 
documentation must be forwarded to Medtronic in a timely manner. 

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Table 19: Investigator Reports per Medtronic Requirements 
Report 
Submit to 
Description/Constraints 
Withdrawal of IRB/EC 
approval 
Sponsor and 
Relevant 
Authorities, if 
applicable 
The investigator must report a withdrawal of approval by the 
reviewing IRB/EC of the investigator’s part of the 
investigation within 5 working days. 
Study Deviations 
Sponsor and 
IRB/EC 
Notice of deviations from the CIP to protect the life or 
physical wellbeing of a subject in an emergency shall be given 
as soon as possible, but no later than 5 working days after the 
emergency occurred. Except in such emergency, prior 
approval is required for changes in the plan or deviations. If 
the deviation may affect the scientific soundness of the plan 
or the rights, safety and welfare of the subjects, the deviation 
must be approved by Medtronic, the IRB/EC, and the 
FDA/applicable regulatory authorities. If the deviation does 
not affect these issues then only Medtronic must approve it. 
(21 CFR 812.150(a)(4)) 
Withdrawal of IRB/EC 
approval (either 
suspension or 
termination) 
Sponsor 
The investigator must report a withdrawal of approval by the 
reviewing IRB/EC of the investigator’s part of the 
investigation within 5 working days. (21 CFR 812.150(a)(2)) 
Progress report 
Sponsor and 
IRB/EC 
The investigator must submit this report to the sponsor and 
IRB/EC at regular intervals, but in no event less than yearly. 
(21 CFR 812.150 (a)(3)). 
Failure to obtain 
informed consent prior 
to investigational 
device use 
Sponsor and 
IRBs/ECs 
If an investigator uses a device without obtaining informed 
consent, the investigator shall report such use within 5 
working days after device use. (21 CFR 812.150(a)(5)) 
Final report 
Sponsor and 
IRBs/ECs 
This report must be submitted within 3 months of study 
completion or termination of the investigation or the 
investigator’s part of the investigation. (21 CFR 812.150(a)(6)) 

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15.13 Sponsor Reports 
Medtronic shall prepare and submit the following complete, accurate, and timely reports listed in the 
table below. In addition to the reports listed below, Medtronic shall, upon request of reviewing IRB/EC 
and/or regulatory agency, provide accurate, complete and current information about any aspect of the 
investigation. Safety data Medtronic reporting requirements are listed in Section 11.2 – Reporting of 
Adverse Events. 
 
Table 20: Sponsor Reports 
 
Report 
Submit to 
Description/Constraints 
Premature 
Investigators, 
Provide prompt notification of termination or 
termination or 
IRB/EC, and 
suspension and reason(s). 
suspension of the 
relevant 
clinical investigation authorities 
Investigators, 
Withdrawal of IRB/EC IRB/EC, FDA and 
Notification within 5 working days. (21 CFR 
approval 
relevant 
812.150(b)(2)) 
Authorities 
Investigators, 
Withdrawal of FDA 
IRB/EC, and 
Notification within 5 working days. (21 CFR 
approval 
relevant 
812.150(b)(3)) 
Authorities 
Progress Reports 
IRB/EC and FDA, 
Progress reports will be submitted at least annually. 
(21 CFR 812.150(b)(5), 812.36(f) 
Investigator List 
FDA 
Submit at 6-month intervals, a current list of the 
names and addresses of all investigators participating 
in the investigation.  (21 CFR 812.150(b)(4)) 
Investigators, 
Notification within 30 working days and will include 
Recall and device 
IRB/EC, 
the reasons for any request that an investigator return, 
disposition 
FDA, and relevant 
repair, or otherwise dispose of any devices.  (21 CFR 
Authorities 
812.150(b)(6)) 
Failure to obtain 
informed consent 
FDA and relevant 
Authorities 
Investigator’s report will be submitted to FDA within 5 
working days of notification. (21 CFR 812.150(b)(8)) 

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Report 
Submit to 
Description/Constraints 
Final report 
Investigators, 
IRB/EC, FDA, and 
relevant 
Authorities 
Medtronic will notify FDA within 30 working days of 
the completion or termination of the investigation. A 
final report will be submitted to the FDA, investigators, 
and IRBs/ECs within six months after completion or 
termination of this study. (21 CFR 812.150(b)(7)) 
Medtronic shall prepare, according to the procedure, a 
clinical study report that summarizes the results, etc., 
of a clinical study when it is completed or 
discontinued.  (MHLW Ordinance 36, Article) 
Study deviation 
Investigators 
Ensure that all deviations from the Clinical 
Investigation Plan are reviewed with the appropriate 
clinical investigator(s), are reported on the case report 
forms and the final report of the clinical investigation. 
Medtronic may provide center-specific reports to 
investigators summarizing information on deviations 
that occurred at the investigational site on a periodic 
basis. 
Other 
IRB/EC and FDA 
Accurate, complete, and current information about any 
aspect of the investigation. (21 CFR 812.150(b)(10)) 
 
Medtronic records and reports will be stored in a password-protected document management system. 
The sponsor and principal investigator shall maintain the clinical investigation documents as required by 
the applicable regulatory requirement(s). They shall take measures to prevent accidental or premature 
destruction of these documents. The principal investigator or sponsor may transfer custody of records 
to another person/party and document the transfer at the investigation site or at the sponsor's facility. 
 
15.14 Publication and Use of Information 
Publications and presentations referring to this clinical study will be coordinated by Medtronic to allow 
the use of all available data. The following publication policy will have to be adhered to by all 
participating investigation sites: 

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Medtronic may use the study data for Regulatory Authority submission results, may publish the results 
in peer reviewed scientific journal(s) and present the data at major congresses. 
Authorship on any publication(s) resulting from this clinical study will be assigned according to 
substantial contributions to conception and design, acquisition of data, or analysis and interpretation of 
data, drafting the article or revising it critically for important intellectual content and final approval of 
the version to be published. This is in accordance with the Vancouver principles (The Uniform 
Requirements for Manuscripts Submitted to Biomedical Journals: Writing and Editing for Biomedical 
Publication, ICMJE, October 2008), as agreed upon by the editors of all major medical journals. 
The number of authors will be dependent on the regulations of the concerning journal. Names of all 
participating investigators will appear in the Acknowledgment of the paper. 
Based on the principle that Medtronic owns the data of this clinical study, a single investigation site may 
access and use the data provided by itself for scientific publications following prior approval by 
Medtronic. 
Pooling data from several investigation sites for publication purposes, national projects and 
international projects all require prior approval from Medtronic. 
Medtronic as the owner of the data can use the data and/or any results derived from the data or 
publications based on that data for marketing purposes, further research and development of devices or 
educational use. 
The study sponsor will collect data in such way that no subject can be identified, and monitor study 
records. 
Participating subjects will not be identified by name in any published reports about the clinical study. 
 
15.15 Suspension or Early Termination 
Early Study Suspension or Termination 
Medtronic or Regulatory Authority may decide to suspend or prematurely terminate the clinical study 
(e.g. if information becomes available that the risk to study subject is higher than initially indicated, if 
interim analysis indicates that the results significantly differ from the clinical study objectives or 
statistical endpoints). If the clinical study is terminated prematurely or suspended, Medtronic shall 
promptly inform the investigators of the termination or suspension and the reason(s) for this. The 
investigator shall then promptly inform the reviewing IRB/EC and the study subjects. 
Early Site Suspension or Termination 
Medtronic, IRB/EC or Regulatory Authority may decide to suspend or prematurely terminate an 
investigation site (e.g. in case of expiring approval of the reviewing IRB/EC, non-compliance to the 
Clinical Investigation Plan or lack of enrollment). 

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If an investigation site is suspended or prematurely terminated: 
• 
Medtronic shall promptly inform the clinical investigator(s) of the termination or suspension and 
the reason(s) for this 
• 
The investigator shall then promptly inform the reviewing IRB/EC 
• 
The investigator shall then promptly inform study subjects 
• 
The investigator agreement will be terminated 
• 
The investigator will inform the institution (where required by applicable regulatory 
requirements) 
• 
Medtronic will inform the Regulatory Authority(ies) (where required by applicable regulatory 
requirements) 
When the risks are found to outweigh the potential benefits or when there is conclusive proof of 
definite outcomes, investigators must assess whether to continue, modify or immediately stop the 
clinical study in the respective investigation site and immediately inform the sponsor and IRB/EC, if 
applicable. 
 
15.16 Liability 
Medtronic, Inc. (including all wholly owned subsidiaries) maintains appropriate clinical study liability 
insurance coverage as required under applicable laws and regulations and will comply with applicable 
local law and custom concerning specific insurance coverage. If required, a clinical study insurance 
statement/certificate will be provided to the IRB/EC. 

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16. References 
 
 
1. Bittl JA. Catheter interventions for hemodialysis fistulas and grafts. JACC Cardiovasc Interv 
2010;3:1-11. 
2. United States Renal Data System. 2010 Annual Data Report: Volume Two. American Journal 
of Kidney Diseases. 2011; 57(Suppl 1):192. 
3. Patane D (2011) Superior patency with DEB in stenotic arteriovenous fistulae. Inverventional 
News Educational Supplement (September):1-3. 
4. Schwartz CI, McBrayer CV, Sloan JH, et al. Thrombosed dialysis grafts: comparison of 
treatment with transluminal angioplasty and surgical revision. Radiology. 1995;194:337– 
341. 
5. Rodriguez JA, Armadans L, Ferrer E, et al. The function of permanent vascular access. Nephrol 
Dial Transplant. 2000;15:402–408. 
6. Turmel-Rodrigues L, Pengloan J, Rodrigue H, Brillet G, Lataste A, Pierre D, Jourdan JL, 
Blanchard D. Kidney Int. 2000;57(3):1124-40. 
7. Diskin CJ. Novel insights into the pathobiology of the vascular access - do they translate into 
improved care? Blood Purif. 2010;29:216–229. 
8. United States Renal Data System, USRDS 2013 Annual Data Report: Atlas of End-Stage Renal 
Disease in the United States, National Institutes of Health, National Institute of Diabetes and 
Digestive and Kidney Diseases, Bethesda, MD, 2014. 
9. Schwab SJ. Hemodialysis vascular access: the Achilles’ heel remains. Kidney Int. 2007;72:665– 
666. 
10. Manzi M, Cester G, Palena LM. Paclitaxel located balloon angioplasty for lower extremity 
revascularization: a new way to fight in-stent restenosis. J Cardiovasc Surg (Torino). 
2010;51:567–571. 
11. Unverdorben M, Vallbracht C, Cremers B, et al. Paclitaxel-coated balloon catheter vs. 
paclitaxelcoated stent for the treatment of coronary in-stent restenosis. Circulation. 
2009;119:2986–2994. 
12. Scheller B, Hehrlein C, Bocksch W, et al. Treatment of coronary in-stent restenosis with a 
paclitaxel-coated balloon catheter. N Engl JMed. 2006;355:2113–2124. 
13. National Kidney Foundation KDOQI Guidelines: Clinical Practice Guidelines and Clinical 
Practice Recommendations 2006 Updates. 
14. Ohira S, Naito H, Amano I, et al. 2005 Japanese Society for Dialysis Therapy Guidelines for 
Vascular Access Construction and Repair for Chronic Hemodialysis. Ther Apher Dial. 2006 
Oct;10(5):449-62. 

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15. Farrington, C. P., and Manning, G. Test Statistics and Sample Size Formulae for Comparative 
Binomial Trials with Null Hypothesis of Non-zero Risk Difference or Non-unity Relative Risk. 
Statistics in Medicine 9:1447–1454. 1990. 

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17. Appendices  
 
 
17.1 Instructions for Use 
IN.PACT™ AV Access DCB Instructions for Use will be provided under separate cover. 

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17.2 Investigator Brochure 
The IN.PACT™ AV Access DCB Investigator Brochure will be provided under separate cover. 

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17.3 Labeling 
Labeling for IN.PACT™ AV Access DCB will be provided under separate cover. Labeling for all other 
market approved system components can be found with each package insert. 

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17.4 Master Informed Consent Form 
Patient Informed Consent Form will be provided under separate cover. 

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17.5 Site and Investigator List 
This information will be updated throughout the course of the study. The updated list will be maintained 
at Medtronic and will be available upon request. 

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17.6 IRB/EC Committee List 
This information will be updated throughout the course of the study. The updated list will be maintained 
at Medtronic and will be available upon request. 

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17.7 CRO/Core Laboratories 
A complete list of selected CROs and core laboratories will be distributed under a separated cover. 

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17.8 Sample Case Report Forms 
Draft Case Report Forms for the IN.PACT™ AV Access Study will be provided under a separate cover. 
Final CRFs will be provided to sites via the electronic data management system after the site has fulfilled 
all requirements for database access. 

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17.9 EQ-5D 
The EQ-5D-5L will be provided under a separate cover. 

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17.10 Medicare Coverage 
It is anticipated that Medicare beneficiaries would be affected by this device because a predominant 
proportion of ESRD patients undergoing hemodialysis requiring the need for a dialysis access fistula, are 
covered by Medicare as shown in Figure A, below, from the 2014 USRDS Annual Data Report-Vol 2, 
found at: https://www.usrds.org/2014/view/v2_01.aspx. 
Figure A: Trend in Distribution of Payer Type, by Modality, Among Prevalent ESRD Patients, 1978-2012 
(Hemodialysis) 
 
 
In addition, claims data analysis including Medicare and commercial populations showed that 80% or 
more cases of dialysis vessel PTAs were performed in Medicare beneficiaries. The results of the 
IN.PACT™ AV Access IDE Study are therefore expected to be applicable to and generalizable to the 
Medicare beneficiary population since Medicare is the predominant payer of services for ESRD patients, 
including treatment of dialysis vessels with PTA. 

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17.11 Recommended Guidelines for Re-interventions 
Significant stenosis requiring treatment based on US KDOQI Guidelines13 and Japanese Society for 
Dialysis Therapy Guidelines14: Significant stenosis defined as a decrease 50% or greater of normal vessel 
diameter accompanied by hemodynamic or clinical abnormality, including but not limited to: 
- 
Decreased blood flow 
- 
Elevated venous pressures 
- 
Unexplained reduction in Kt/V 
- 
Abnormal recirculation values* 
- 
Swollen extremity or Aneurysm formation 
- 
Elevated negative arterial prepump pressures 
- 
Unexplained reduction of dialysis efficiency 
- 
Abnormal physical findings (thrill, murmur, arm swelling, etc.) 
- 
Abnormally high BUN 
*Japanese guidelines state that it is possible to use recirculation rates for AVF surveillance 

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18. Version History 
 
 
Version 
Summary of Changes 
Author(s)/Title 
1.0 
• 
Not applicable, new document 
Stephanie Cihlar, Sr. 
Clinical Research 
Specialist 
2.0 
• 
Minor administrative, language, grammatical and 
punctuation changes for clarity throughout CIP 
• 
Definitions table: added “successful dialysis” for 
standardization of reporting successful dialysis 
• 
Section 5.2: Updated the indication statement per FDA 
• 
Section 8.1: added a footnote stating that for the 
clinical trial only the 40 cm and 80 cm catheter lengths 
will be made available 
• 
Section 10 and throughout: replaced the KD-QOL 
questionnaire with the EQ-5D questionnaire for 
healthcare economic analysis purposes 
• 
Section 14: 
• 
Changed the statement of “two-sided Chi- 
square test at α=0.05” to “one-sided Z-test at 
α=0.025” for primary efficacy endpoint per FDA 
recommendation to be consistent with the 
alternative hypothesis 
• 
Added worst case analysis per FDA 
recommendation to assess the sensitivity of the 
primary endpoints 
• 
Explicitly expressed the hypotheses of key 
secondary endpoints in mathematical form per 
FDA recommendation 
Stephanie Cihlar, Sr. 
Clinical Research 
Specialist 
 
 

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• 
Clearly distinguished the “secondary analysis” 
and “sensitivity analysis” per FDA 
recommendation. Specified the additional 
analysis on primary endpoints, including time- 
to-event analysis, analysis on as-treated 
subjects and per-protocol subjects. The 
sensitivity analysis, including multiple 
imputation, Tipping Point and Worst Case 
analysis were added. 
• 
Added “As-Treated Analysis Set” and “Per- 
Protocol Analysis Set” and reworded the “as- 
treated analysis” and “per-protocol analysis” by 
applying pre-defined analysis set for 
clarification. 
• 
Changed the test method of evaluating the 
primary safety endpoint from Z-test to 
Farrington-Manning test per FDA 
recommendation. The exact test provides a 
stronger control on type I error for the small 
event rates. 
• 
Changed the cutoff day for the 6 month target 
lesion primary patency from 180 days to 210 
days. The Target lesion primary patency is a 
composite endpoint that has two component 
events- a clinical endpoint of CD-TLR and an 
imaging based endpoint of thrombosis, using 
upper limit of clinical visit window (180+30 
days) helps to maximize the assessment of 
imaging data. 
• 
Added Appendix 17.11 Recommended Guidelines for 
Re-interventions, per FDA and PMDA 
recommendations, to provide investigators with 
guidelines for when to intervene on subjects if there is 
suspicion of recurrent stenosis 

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3.0 
• 
Update template version to v A: 
• Moved version history to end of 
document – sections numbers updated 
accordingly 
• Moved “Study Insurance/Subject 
Indemnification” language to “Liability” 
section 15.16. No changes to the 
technical content. 
• 
Extension of follow-up period for up to 5 years (60 
months) to collect data on long-term safety and 
effectiveness: 
• 
Section 3.0: Synopsis “follow-up” and “time course” 
updated to extend the study up to 5 years in order to 
collect long term safety and effectiveness data; long 
term assessments added to the secondary endpoints 
• 
Section 5.0: Long term assessment measures added 
• 
Section 6.1: Follow-up and total expected duration 
updated to account for up to 5 year follow-up 
• 
Section 10.1: Updated to account for up to 5 year follow-
up and to capture abandoned target fistula data 
• 
Section 9.1: Updated study flow diagram to reflect 
reconsenting and extended follow-up; updated table 3 
to reflect extension and collection of abandonment 
data; updated follow-up tables to extend for up to 5 
years 
• 
Section 9.4: updated with language regarding 
Stephanie Cihlar, 
Prin. Clinical 
Research 
Specialist 

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4.0 
• 
Definition: Addition of vital status 
• 
Synopsis:  
• Footnote added to clarify device status. 
• Update secondary endpoint assessment to 
36-Months instead of 60-Months. The 
addition of Vital Status collection through 60 
months. 
• Subject follow-up, addition of vital status at 
48-60 Months. 
• 
Section 5.1.1: de novo or non-stented restenotic added 
• 
Section 5.2.2: Secondary assessments up to 36-Months 
instead of 60-Months. Vital Status collection annually 
through 60 months. 
• 
Section 6.1: Vital Status collection at 48-60 months. 
• 
Section 7.1: Commercial availability and Table 2 updated. 
• 
Section 8.2: Randomization and Treatment assignment 
section number updated. 
• 
Section 9:  
• Figure 3 Addition of Vital Status collection 
• Table 3 Addition of Vital Status collection 
• Clarification of Vital Status collection for the 
48-60 months follow-up visits. 
• Unscheduled visits will not be collected after 
36 month. 
• Table 9 updated and the addition of Table 
10-11. Tables 12-20 were renumbered. 
• 
Section 11.2: SAE only related to death are to be reported. 
• 
Section 12.2: Only events related to death will be 
adjudicated. 
• 
Section 13.5: Vital status added to secondary endpoints. 
• 
Section 14.1: Removal of outdated requirement for New 
Zealand Note for Guidance on Good Clinical Practice 
(CMP/ICH/135/95).  
Phally Roffe, 
Clinical Research 
Program 
Manager