A Prospective, Multicenter, Single-Blind, Randomized, Controlled Trial Comparing the Lutonix® Drug Coated Balloon vs. Standard Balloon Angioplasty for Treatment of Femoropopliteal In-Stent Restenosis
Phase: NA
Conditions: Femoral Artery Stenosis, Femoral Artery Occlusion, Restenosis
Sponsor: C. R. Bard

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  A Prospective, Multicenter, Single-Arm Trial of the 
Lutonix® Drug Coated Balloon for Treatment of 
Femoropopliteal In-Stent Restenosis 
 
 
Investigational Plan  
CL0018-01 
Version 4.0 
 
Sponsor: 
 
 
 
9409 Science Center Drive 
New Hope, MN 55428 USA 
 
 
Study Device: LUTONIX® Drug Coated Balloon 
 
 
 
 
This study will be conducted in compliance with the protocol and all other applicable regulatory 
requirements including the archiving of essential documents. 
 
 
Confidential Information 
No use or disclosure of this document outside Lutonix, Inc. is permitted without prior written 
authorization from Lutonix.  Shred to dispose of document. 
 
 
 

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PROTOCOL SIGNATURE PAGE 
 Lutonix DCB: SFA-ISR Investigational Plan 
A Prospective, Multicenter, Single-Arm Trial of the Lutonix® Drug Coated Balloon for 
Treatment of Femoropopliteal In-Stent Restenosis 
 
I have read this protocol and agree to adhere to the requirements.  I will provide copies of this 
protocol and all pertinent information to the study personnel under my supervision and my 
hospital Institutional Review Board/Ethics Committee.  I will discuss this material with them and 
ensure they are fully informed regarding the investigational device and the conduct of the study 
according to ICH Good Clinical Practice (GCP), Declaration of Helsinki, 21CFR 50, 56 and 812, 
and any local regulations. 
 
 
 
Clinical Site Name____________________________________ 
 
 
_______________________ 
 
_____________________________________ 
Site Principal Investigator 
 
Site Principal Investigator 
     Date 
(Print Name) 
 
 
 
(Signature) 
 
 
 
 
 
 
 
 
 
 
 

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The Lutonix SFA ISR Study Summary 
Title 
A Prospective, Multicenter, Single-Arm Trial of the Lutonix® Drug Coated 
Balloon for Treatment of Femoropopliteal In-Stent Restenosis  
Treatment 
Device 
LUTONIX® Drug Coated Balloon  
Study Design 
Prospective, Multicenter, Single-Arm Trial 
Overview 
The study will enroll patients presenting with claudication or ischemic rest pain 
(Rutherford Category 2-4) and occlusion or ≥50% stenosis of a previously 
deployed bare, or drug-eluting nitinol stent(s) placed ≥ 6 months prior to the 
study index procedure, in the femoropopliteal artery that is appropriate for 
angioplasty.  After successful protocol-defined pre-dilatation, subjects will 
receive treatment with the LUTONIX® Drug Coated Balloon (DCB).  
The primary safety and efficacy endpoint assessments are performed at 12 
months.  Clinical follow-up continues through 2 years and telephone follow-up 
through 3 years.   
Purpose 
To assess the safety and efficacy of the LUTONIX® Drug Coated Balloon for 
treatment of femoropopliteal artery (SFA) in-stent restenosis (ISR). 
Objective 
To demonstrate efficacy and safety of the LUTONIX® Drug Coated Balloon for 
treatment of SFA ISR by comparison to an objective performance goal (OPG). 
Enrollment 
127 Subjects at up to 30 US clinical sites (inclusive of all subjects currently 
enrolled) 
Subject 
Follow-Up 
Schedule 
Clinical: 6, 12, and 24 Months 
Duplex Ultrasound (DUS):  0-6 weeks, 6, 12, and 24 months 
Telephone: 30 days and 3 years (36 months) 
Primary 
Endpoints 
Efficacy: Primary Patency at 12 months  
Safety: Freedom from all-cause perioperative (≤30 day) death and freedom at 1 
year from index limb amputation (above and below the ankle) index limb re-
intervention, and index-limb-related death.   
Secondary 
Endpoints 
 
 
 
Secondary 
Efficacy 
 Device, Technical and Procedural success  
The following endpoints will be reported at 6, 12 and 24 Months: 
 Primary and Secondary Patency  
 Target Lesion Revascularization (TLR) 
o Clinically-driven 
o All TLR 

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Endpoints 
(Continued) 
 Sustained Clinical Benefit (improvement in Rutherford Class 
compared to baseline AND freedom from target vessel 
revascularization)  
 Change of Rutherford classification from baseline 
 Change of resting Ankle Brachial Index (ABI) from baseline 
 Change in Walking Impairment Questionnaire from baseline 
 Change in quality of life from baseline, as measured by EQ-5D  
Safety 
 Major vascular complications (≤30 day) 
The following endpoints will be reported at 1, 6, 12, 24, and 36 Months: 
 Composite Safety (criteria of the primary safety endpoint) 
 Death  
 Amputation (major and minor separately) 
 Target Vessel Revascularization (TVR)  
 Target Limb Reintervention  
Inclusion 
Criteria 
Clinical Criteria 
1. Male or non-pregnant female ≥18 years of age;  
2. Rutherford Clinical Category 2-4;  
3. Patient is willing to provide informed consent, is geographically stable 
and willing to comply with the required follow up visits, testing schedule 
and medication regimen; 
Angiographic Criteria 
4. Significant (≥ 50%) restenosis of a previous bare or drug-eluting nitinol 
stent(s) in the femoropopliteal artery. Drug-eluting stents must have been 
placed ≥ 6 months prior to study index procedure.  
        NOTE: Discrete or composite lesions allowed within a continuous single 
or overlapped stented segment. 
NOTE: Edge restenosis allowed ≤ 3 cm beyond stent margin (confirmed 
after pre-dilatation).  
5. The intended target lesion measures between 4 and 22 cm and can be 
treated with single or multiple balloons of cumulative balloon length ≤ 
26cm  
         NOTE: This balloon length requirement (≤ 26 cm) applies to the total 
length of all devices intended for use, not the length of the treated 
segment (which is less, since 5mm balloon overlap is required for 
treatment)  
6. Target vessel diameter between ≥4 and ≤ 6 mm and able to be treated 
with available device size matrix; 
7. A patent inflow artery free from significant lesion (≥50% stenosis) as 

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confirmed by angiography (treatment of target lesion acceptable after 
successful treatment of iliac inflow artery lesions);  
NOTE: Successful inflow treatment is defined as attainment of residual 
diameter stenosis ≤30% without death or major vascular complication. 
8. Successful crossing with a guidewire and pre-dilatation of the target 
lesion;  
NOTE: Successful pre-dilatation is defined as attainment of residual 
diameter stenosis < 50%. 
9. At least one patent native outflow artery to the ankle, free from 
significant (≥50%) stenosis as confirmed by angiography that has not 
previously been (nor planned to be) revascularized;  
10. No other prior vascular or surgical interventions within 2 weeks before 
and/or planned 30 days after the protocol treatment, except for 
contralateral iliac treatment.  
Exclusion 
Criteria 
1. 
Pregnant or planning on becoming pregnant or men intending to father 
children; 
2. 
Life expectancy of <1 year; 
3. 
Patient is currently participating in an investigational drug or other device 
study which could, in the opinion of the investigator, affect the results of 
this study, or previously enrolled in this study;  
NOTE: Enrollment in another drug or device clinical trial during the 
follow up period is not allowed. 
4. 
History of stroke within 3 months; 
5. 
History of MI, thrombolysis or angina within 2 weeks of enrollment;  
6. 
Prior vascular surgery of the index limb, with the exception of remote 
common femoral patch angioplasty separated by at least 2 cm from the 
target lesion; 
7. 
SFA disease in the opposite leg that requires treatment at the time of index 
procedure (note inclusion #10- no planned procedure for 30 days post 
index procedure); 
8. 
Target lesion involves either a previously placed covered stent or drug-
eluting stent. Treatment of drug-eluting stents is only allowed if stent was 
placed ≥ 6 months prior to study index procedure; 
9. 
Grade 4 or 5 stent fracture (mal-aligned components or trans-axial spiral 
configuration) in the restenotic stent(s); 
10. Inability to take study medications or allergy to contrast that cannot be 
adequately managed with pre- and post-procedure medication; 
11. Significant distal aortic vessel or common femoral artery disease. 
Successful treatment of iliac disease allowed prior to target lesion 

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treatment; 
12. Known inadequate distal outflow (>50 % stenosis of distal popliteal 
and/or all three tibial vessels), or planned future treatment of vascular 
disease distal to the target lesion; 
13. Sudden symptom onset, acute vessel occlusion, or acute or sub-acute 
thrombus in target vessel; 
14. Intended use of adjunctive treatment modalities (i.e. laser, atherectomy, 
cryoplasty, scoring/cutting balloon, stents, etc.).  
Principal 
Investigator 
To be determined  
Sponsor/ 
Contact: 
Lutonix, Inc. 
9409 Science Center Drive 
New Hope, MN 55428 USA 
763-445-2352 
CRO 
Harvard Clinical Research Institute 
930 Commonwealth Ave 
Boston MA 02215 
Contact: Lisa Beck 
(617) 307-5523 
Angiographic 
Core Lab 
SynvaCor 
319 N. 5th St. 
Springfield IL 62701 USA 
217-492-9132 
DUS Core 
Lab 
VasCore 
One Bowdoin Square,  
10th Floor 
Boston MA 02114 USA 
617-726-5552 
 

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Table of Contents 
1 
INTRODUCTION ........................................................................................................................ 9 
1.1 
CLINICAL BACKGROUND ..................................................................................................... 9 
1.2 
DEVICE AND STUDY RATIONALE ..................................................................................... 11 
2 
STUDY OBJECTIVES AND ENDPOINTS ............................................................................ 12 
2.1 
PRIMARY OBJECTIVE ........................................................................................................... 12 
2.2 
PRIMARY ENDPOINTS .......................................................................................................... 12 
2.3 
SECONDARY ENDPOINTS.................................................................................................... 12 
3 
DEVICE DESCRIPTION .......................................................................................................... 13 
3.1 
INTENDED USE FOR TRIAL ................................................................................................. 13 
3.2 
ACTIVE PHARMACEUTICAL INGREDIENT (API): PACLITAXEL ................................. 13 
3.3 
EXCIPIENT (Drug Carrier) ...................................................................................................... 14 
3.4 
STUDY DEVICES AND INSTRUCTIONS ............................................................................ 14 
4 
RISK-BENEFIT ANALYSIS .................................................................................................... 14 
4.1 
POTENTIAL RISKS ................................................................................................................. 14 
4.2 
RISK MANAGEMENT PROCEDURES ................................................................................. 15 
4.3 
POTENTIAL BENEFITS.......................................................................................................... 16 
4.4 
EARLY TERMINATION ......................................................................................................... 16 
5 
CLINICAL STUDY DESIGN ................................................................................................... 17 
5.1 
SCREENING PROCEDURES .................................................................................................. 17 
5.2 
PATIENT SELECTION FOR ENROLLMENT ....................................................................... 17 
5.3 
SUBJECT INCLUSION AND EXCLUSION CRITERIA ....................................................... 18 
6 
STUDY/TREATMENT PROCEDURES ................................................................................. 19 
6.1 
ENROLLMENT ........................................................................................................................ 19 
6.2 
LUTONIX® DRUG COATED BALLOON INSTRUCTIONS FOR USE (IFU) ..................... 20 
6.3 
BASELINE ANGIOGRAM ...................................................................................................... 20 
6.4 
IN-FLOW LESION TREATMENT .......................................................................................... 20 
6.5 
PRE-DILATATION .................................................................................................................. 21 
6.6 
TREATMENT WITH LUTONIX® DRUG COATED BALLOON ......................................... 21 
6.7 
POST TREATMENT AND PROVISIONAL (BAILOUT) STENTING ................................. 21 
6.8 
UNSCHEDULED ANGIOGRAPHY/REVASCULARIZATION ........................................... 23 
7 
TREATMENT OF SUBJECT ................................................................................................... 23 
7.1 
BLINDING PLAN .................................................................................................................... 23 
7.2 
MEDICATIONS ........................................................................................................................ 23 
7.3 
STANDARD TESTS, PROCEDURES, AND FOLLOW-UP .................................................. 23 
8 
ADVERSE EVENTS .................................................................................................................. 25 
8.1 
ADVERSE EVENT REPORTING ........................................................................................... 26 

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9 
SUBJECT WITHDRAWAL CRITERIA ................................................................................ 26 
10 
DATA COLLECTION AND MONITORING ........................................................................ 26 
10.1 
DATA COLLECTION .............................................................................................................. 26 
10.2 
MONITORING ......................................................................................................................... 26 
10.3 
SOURCE DOCUMENTATION ............................................................................................... 27 
10.4 
RECORD RETENTION............................................................................................................ 27 
11 
DEVICE ACCOUNTABILITY ................................................................................................ 27 
11.1 
DEVICE SUPPLY ..................................................................................................................... 28 
12 
STUDY MANAGEMENT ......................................................................................................... 28 
12.1 
DATA SAFETY MONITORING BOARD .............................................................................. 28 
12.2 
CLINICAL EVENTS COMMITTEE ....................................................................................... 28 
13 
REGULATORY RESPONSIBILITIES ................................................................................... 28 
13.1 
ETHICS APPROVAL ............................................................................................................... 28 
13.2 
INFORMED CONSENT ........................................................................................................... 29 
13.3 
SELECTION OF CLINICAL SITES AND INVESTIGATORS .............................................. 29 
13.4 
INVESTIGATOR’S RESPONSIBILITIES .............................................................................. 29 
13.5 
LUTONIX RESPONSIBILITIES ............................................................................................. 29 
14 
PUBLICATIONS ....................................................................................................................... 30 
15 
STATISTICAL ANALYSIS PLAN .......................................................................................... 30 
15.1 
OVERVIEW OF STUDY DESIGN .......................................................................................... 30 
15.2 
ANALYSIS POPULATIONS ................................................................................................... 30 
15.3 
HANDLING MISSING DATA ................................................................................................. 31 
15.4 
ASSESSMENT OF POOLABILTY OF SITES AND SECONDARY ANALYSIS ................ 31 
15.5 
PRIMARY ENDPOINTS .......................................................................................................... 32 
15.6 
SECONDARY ENDPOINTS.................................................................................................... 36 
APPENDIX A:  DEFINITIONS ........................................................................................................ 38 
APPENDIX B:  SAMPLE WALKING IMPAIRMENT QUESTIONNAIRE .............................. 47 
APPENDIX C:  SAMPLE EQ5D QUESTIONNAIRE.................................................................... 49 
APPENDIX D:  SAMPLE INFORMED CONSENT FORM ......................................................... 51 
 
Table 1: Bailout Criteria .......................................................................................................................... 22 
Table 2: Follow Up Schedule and Testing Requirements for Subjects ................................................ 23 
Table 3: Primary Patency for Standard of Care Treatment for SFR ISR .......................................... 32 
Table 4: Primary Patency for Drug Coated Balloon Treatment for SFR ISR .................................... 33 
 
Figure 1:  LUTONIX® Drug Coated Balloon ......................................................................................... 13 
 

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1 INTRODUCTION 
The purpose of this investigation is to assess the safety and efficacy of the LUTONIX® Drug 
Coated Balloon for treatment of femoropopliteal artery (SFA) in-stent restenosis (ISR). 
1.1 CLINICAL BACKGROUND 
In-stent restenosis remains a common problem, occurring in 20-40% of patients within the first 
year following femoropopliteal artery stent placement.  Various treatment modalities have been 
utilized for treatment of SFA ISR; including cutting balloons, additional stenting and rotational 
or directional artherectomy, and laser. Although some treatments have demonstrated initial 
technical success, many add complexity to the interventional procedure, and all have 
documented suboptimal patency rates at 12 months following treatment.1,2,3,4    
The principle mechanism in the development of primary atherosclerotic plaque in the SFA is 
thought to be quite different from that of restenotic disease.  While white blood cells contribute 
considerably to primary plaque, restenotic lesions are cellular, comprised mostly of smooth 
muscle cells (SMC).5  This may be why current standard of care treatment modalities for in stent 
restenosis are not proving to be effective over time.  The active pharmaceutical ingredient (API) 
of paclitaxel on the LUTONIX® Drug Coated Balloon is known to inhibit smooth muscle cell 
proliferation and migration;6 thereby it is considered to be a viable option for treating ISR in the 
SFA. 
Initial trials with drug coated balloons in de novo SFA lesions have been proven safe and have 
demonstrated lower rates of re-intervention compared to standard percutaneous transluminal 
angioplasty (PTA).7,8 However, only preliminary data is available with DCBs in ISR.  
Medtronic’s In.Pact DCB has shown promising results in a single center registry trial9 using a 
similar DCB coated with the same paclitaxel API as the LUTONIX® Drug Coated Balloon.  In 
summary, despite its frequent occurrence in clinical practice, few studies have been conducted 
regarding the effectiveness of endovascular interventions for ISR, and a durable treatment for 
                                                     
1 Zeller, T et al.  Long-term results after directional atherectomy of femoro-popliteal lesions. J Am Coll Cardiol. 2006;48(8), 
1573-1578. doi: 10.1016/j.jacc.2006.07.031 
2 Dick, P et. al.  Conventional balloon angioplasty versus peripheral cutting balloon angioplasty for treatment of femoropopliteal 
artery in-stent restenosis: initial experience. Radiology. 2008; 248(1), 297-302. doi: 10.1148/radiol.2481071159 
3 Laird, JR et.al. Excimer laser with adjunctive balloon angioplasty and heparin-coated self-expanding stent grafts for the 
treatment of femoropopliteal artery in-stent restenosis: twelve-month results from the SALVAGE study. Catheter Cardiovasc 
Interv. 2012; 80(5), 852-859. doi: 10.1002/ccd.23475 
4 Yeo, K. K., Malik, U., & Laird, J. R. Outcomes following treatment of femoropopliteal in-stent restenosis: a single center 
experience. Catheter Cardiovasc Interv., 2011; 78(4), 604-608. doi: 10.1002/ccd.23022 
5 Edlin R, et al. Characterization of primary and restenotic atherosclerotic plaque from the superficial femoral artery: Potential 
role of Smad3 in regulation of SMC proliferation. J Vasc Surg, 2009; 49(5), 1289-1295, doi: 10.1016/j.jvs.2008.11.096 
6 Axel DI, et al. Paclitaxel inhibits arterial smooth muscle cell proliferation and migration in vitro and in vivo using local drug 
delivery.  Circulation. 1997 Jul 15;96(2):636-45. 
7  Tepe G, et al. Local delivery of paclitaxel to inhibit restenosis during angioplasty of the leg. N Engl J Med. Feb 
2008;14;358(7):689-99. 
8 Scheinert, D. (2010), “LEVANT I: A Prospective Randomized Trial of a Paclitaxel-Eluting Balloon Compared to a Non-Drug-
Eluting Balloon With and Without Stenting in Patients with Diseased Femoropopliteal Arteries,” TCT, Washington DC 
9 Stabile, E et al. Drug-eluting balloon for treatment of superficial femoral artery in-stent restenosis. J Am Coll Cardiol, 2012; 
60(18), 1739-1742. doi: 10.1016/j.jacc.2012.07.033 

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ISR remains elusive.10   The LUTONIX® Drug Coated Balloon is being evaluated in this clinical 
trial to provide a viable alternative to current standard of care.  
1.1.1 CLINICAL EXPERIENCE WITH THE LUTONIX® DRUG COATED BALLOON  
1.1.1.1 THE LEVANT I FIRST IN MAN STUDY 
The LEVANT I trial (NCT00930813) compared femoropopliteal treatment with the LUTONIX® 
Drug Coated Balloon to a standard PTA catheter (with and without stenting) in one hundred one 
subjects.  In the ITT population, the primary endpoint of mean late lumen loss at 6 months was 
significantly lower in the LUTONIX® Drug Coated Balloon arm (0.46±1.13) compared to the 
PTA arm (1.09±1.07), with a p value of 0.016, consistent with efficacy of LUTONIX® Drug 
Coated Balloon for this indication.  There were no unanticipated adverse device effects in the 
drug-coated balloon arm, and overall adverse event rates were similar to conventional uncoated 
balloon angioplasty. Secondary clinical endpoints trended in favor of the LUTONIX® Drug 
Coated Balloon arm, particularly TLR (12.8% vs. 22.2% in PTA arm) and target vessel 
revascularization (TVR) (12.8% vs. 32.6%).  
1.1.1.2 THE LEVANT 2 TRIAL AND CONTINUED ACCESS REGISTRY 
As a continuation of the LEVANT I study, the LEVANT 2 clinical study was designed to 
demonstrate improved results over current standard of care in a larger patient population at 
expanded clinical sites. Similar to LEVANT I, this study randomized treatment of patients with a 
symptomatic lesion in the SFA or popliteal artery to either the LUTONIX® Drug Coated Balloon 
or standard balloon angioplasty.  Enrollment of 535 subjects (476 randomized- 2:1 DCB:POBA)) 
was completed in July of 2012 and follow up is currently ongoing.    
Levant 2 met both pre-specified primary endpoints.  Primary patency for Lutonix DCB (65.2%) 
was superior to control PTA (52.6%, p= 0.015) at 12 months, demonstrating superior 
efficacy.  The primary safety endpoint success rate for Lutonix DCB (83.9%) was non-inferior to 
control PTA (79.0%, p = 0.005).   
Several secondary endpoints were also analyzed but not hypothesis tested. Procedural success (< 
30% residual stenosis without SAE) was similar for Lutonix DCB and control PTA (88.9% vs. 
86.8%), demonstrating effectiveness at acute restoration of patency. Freedom from TLR was 87.7% 
for DCB compared to 83.2% for control PTA. The Rutherford scores, walking impairment (WIQ) 
scores, ABI, six minute walk test, and quality of life questionnaires each showed improvements 
from before treatment through 12 months in both treatment groups. 
Secondary safety endpoints were generally similar for Lutonix DCB and control PTA. These 
included, respectively, all-cause death (2.4% vs. 2.8%), amputation (0.3% vs. 0.0%), 
amputation-free survival (97.6% vs. 97.2%), thrombosis (0.4% vs. 0.7%), target vessel 
revascularization (TVR, 13.3% vs. 18.2%), cardiovascular hospitalization (9.1% vs. 7.1%), and 
                                                     
10  Laird, J. R., & Yeo, K. K. (2012). The treatment of femoropopliteal in-stent restenosis: back to the future. 
  J Am Coll Cardiol, 59(1), 24-25. doi: 10.1016/j.jacc.2011.09.037 

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major vascular complications (6.3% vs. 4.9%; defined as hematoma >5 cm, false aneurysm, AV 
fistula, retroperitoneal bleed, peripheral ischemia/nerve injury, transfusion). Adverse events were 
similar for both treatment groups and consistent with historic data for the enrolled population 
with symptomatic PAD.  
Levant 2 successfully demonstrated superior efficacy and non-inferior safety of Lutonix DCB 
compared to control PTA. 
Levant 2 Continued Access (NCT01628159) and Safety (NCT01790243) registries were initiated 
for collection of additional safety data after completion of Levant 2 enrollment. Enrollment was 
completed on September 27, 2013.  A total of 657 subjects were enrolled at 63 sites across the 
United States (US) and Europe (EU). Clinical follow-up, monitoring, and CEC adjudications are 
ongoing.  
Together with the randomized study, n = 1029 patients have been treated with Lutonix DCB and 
followed for a mean duration of 438 days. There are no unanticipated device- or drug-related 
adverse events, the primary endpoint, as of this reporting date. 
Overall freedom from TLR for the all DCB-treated patients was 97.0% (914/942) at 6 months 
and 92.5% (719/777) at 12 months.  Rutherford Class was improved at all time points compared 
to baseline; through 12 months, 87% of patients had an improvement in Rutherford Class, 72% 
by 2 or more grades. Sustained improvement in Rutherford Class without TVR was observed in 
79% of patients. These clinical endpoints compare favourably to historic results and provide 
further support for the clinical benefit of Lutonix DCB.  
Taken as a whole, the Levant 2 randomized and registry studies demonstrate that treatment of 
native femoropopliteal lesions with Lutonix DCB provides more durable patency than standard 
PTA through 12 months with comparable safety and provides a reasonable assurance of safety 
and effectiveness.  
Further information on the LUTONIX® Drug Coated Balloon can be found in the Investigator 
Brochure. 
1.2 DEVICE AND STUDY RATIONALE 
The drug coating on the LUTONIX® Drug Coated Balloon contains paclitaxel and drug carrier 
(excipients polysorbate and sorbitol) with a history of human safety for intravenous use.  Each 
component has been safely used in other products.  PTA catheters have been in commercial use 
for over 25 years, and the LUTONIX® Drug Coated Balloon meets international standards (e.g. 
ISO 10555) developed over time to validate the mechanical safety of dilation catheters. The anti-
proliferative drug paclitaxel is a well understood active pharmaceutical ingredient (API) with an 
extensive history of human use in oncology11 and drug-eluting stents (DES).12   
                                                     
11 Pacific Yew: Draft Environmental Impact Statement. Appendices. U.S. Departments of Agriculture, Interior, and Health and 
Human Services. January 1993. 

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2 STUDY OBJECTIVES AND ENDPOINTS 
2.1 PRIMARY OBJECTIVE 
The primary objective of the Lutonix SFA ISR Study is to demonstrate superior efficacy and 
non-inferior safety of the LUTONIX® Drug Coated Balloon for treatment of SFA ISR by direct 
comparison to an objective performance goal (OPG). 
2.2 PRIMARY ENDPOINTS 
2.2.1 SAFETY 
Freedom from all-cause perioperative (≤30 day) death and freedom at 1 year from index limb 
amputation (above and below the ankle) index limb re-intervention, and index-limb-related 
death. 
2.2.2 EFFICACY 
The primary efficacy endpoint is primary patency at 12 months. 
Primary Patency is defined as Freedom from Clinically-Driven TLR and from Binary Restenosis.  
Binary restenosis is adjudicated by the independent, core laboratory based on threshold Doppler 
PSVR ≥ 2.5 (together with waveform analysis & color mosaic appearance) or based on 
angiographic ≥ 50% diameter stenosis (if angiography is performed although not required per 
protocol). Clinically-Driven TLR is adjudicated by the CEC.  The core labs and CEC will remain 
blinded to the treatment arm of subjects randomized and enrolled under previous versions of the 
protocol. 
2.3 SECONDARY ENDPOINTS 
2.3.1 SECONDARY EFFICACY ENDPOINTS 
Efficacy measurements of Device, Technical and Procedural Success will be assessed following 
the procedure. 
Efficacy measurements of the following endpoints will be reported at 6, 12 and 24 Months: 
 
Primary and Secondary Patency (DUS PSVR <2.5) 
 
Target Lesion Revascularization (TLR) 
o 
Clinically-driven 
o 
All TLR 
 
Sustained Clinical Benefit (improvement in Rutherford Class compared to baseline 
AND freedom from target vessel revascularization)  
 
Change of Rutherford classification from baseline 
 
Change of resting Ankle Brachial Index (ABI) from baseline 
 
Change in Walking Impairment Questionnaire from baseline 
 
Change in quality of life from baseline, as measured by EQ-5D  
                                                                                                                                                                           
12 Lasala J, et.al.  An Overview of the TAXUS® Express®, Paclitaxel-Eluting Stent Clinical Trial Program.  Journal of 
Interventional Cardiology. 2006, Vol 19: 5 pp431-442 

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2.3.2 SECONDARY SAFETY ENDPOINTS 
The following secondary safety endpoints will be reported: 
 Major vascular complications (≤30 day) 
The following endpoints will be reported at 1, 6, 12, 24, and 36 Months: 
 Composite Safety (criteria of the primary safety endpoint) 
 Death  
 Amputation (major and minor separately) 
 Target Vessel Revascularization (TVR)  
 Target limb Reintervention  
 
3 DEVICE DESCRIPTION  
The LUTONIX® Drug Coated Balloon (Figure 1) is a standard PTA catheter with a drug coating 
on the balloon portion of the catheter.  The LUTONIX® Drug Coated Balloon is an over-the-wire 
type design with working lengths of 100 and 130 cm and is compatible with 0.035” guidewires.  
Marker bands are located at the proximal and distal ends of the balloons to assist in delivery and 
placement.  The balloon surface between the marker bands is coated with a specialized 
immediate release non-polymer based coating formulation that includes the anti-proliferative 
drug – paclitaxel - at a surface concentration of 2μg/mm2. 
 
 
FIGURE 1:  LUTONIX® DRUG COATED BALLOON 
 
All devices are provided sterile and for single-use only. 
3.1 INTENDED USE FOR TRIAL 
The LUTONIX® Drug Coated Balloon is intended for use in percutaneous transluminal 
angioplasty of restenotic lesions in stented femoropopliteal arteries that are ≥ 4.0 to ≤ 6.0mm in 
diameter. 
3.2 ACTIVE PHARMACEUTICAL INGREDIENT (API): PACLITAXEL 
Paclitaxel, discovered in 1967 and commercially developed by Bristol-Myers Squibb, is a well 
known mitotic inhibitor indicated for use in the treatment of patients with lung, ovarian, breast, 
head and neck cancers and advanced forms of Kaposi’s sarcoma.  Paclitaxel is also approved for 
the prevention of restenosis.  Various dosages are used depending on target treatment and range 

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from multiple 300 mg IV infusions for oncology therapy to a single maximal nominal dose of 
282 µg for devices that treat restenosis, such as coronary stents.  Please refer to the Investigator’s 
Brochure for a more detailed review of paclitaxel. 
3.3 EXCIPIENT (DRUG CARRIER) 
The balloon coating includes small amounts of the well known excipients (drug carrier) 
polysorbate and sorbitol, each approved by the Food and Drug Administration (FDA) as inactive 
ingredients in drug products for intravenous (IV) drug delivery.  
3.4 STUDY DEVICES AND INSTRUCTIONS 
LUTONIX® Drug Coated Balloons will be made available to all activated study sites. Always 
confirm current site inventory supply prior to enrolling subjects into the study.  Please refer to 
the most current IFU for complete details on procedural use and preparation of the device 
selected for patient treatment.  
4 RISK-BENEFIT ANALYSIS 
4.1 POTENTIAL RISKS 
The potential risks and benefits of participation in this study are clearly identified in the subject 
Informed Consent Form (ICF) and are to be explained to the subject and/or their legal 
representative prior to participating in the study. The LUTONIX® Drug Coated Balloon and 
standard uncoated percutaneous angioplasty catheters used for pre-dilatation are intended to be 
the only devices used for treatment of the target lesion.   
Due to the high similarity of the LUTONIX® Drug Coated Balloon to other marketed balloon 
catheters, procedural use is not expected to significantly change or increase risks during the 
initial procedure.  However, it shares the risks of conventional balloon angioplasty treatment of 
patients with femoropopliteal disease.  
4.1.1 RISKS FOR PERIPHERAL CATHETERIZATION PROCEDURE 
Potential adverse events, which may be associated with a peripheral balloon dilatation 
catheterization procedure, include, but are not limited to, the following: 
 Additional intervention 
 Allergic reaction to drugs or contrast medium 
 Aneurysm or pseudoaneurysm 
 Arrhythmias 
 Embolization 
 Hematoma 
 Hemorrhage, including bleeding at the puncture site 
 Hypotension/hypertension 
 Inflammation 
 Occlusion 
 Pain or tenderness 

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 Pneumothorax or hemothorax 
 Sepsis/infection 
 Shock 
 Thrombosis 
 Vessel dissection, perforation, rupture, or spasm 
Patients undergoing an interventional procedure are often treated with courses of thienopyridines 
such as clopidogrel or prasugrel, which may cause thrombocytopenic purpura and/or bleeding 
complications.  In rare cases, these drugs may cause a significant reduction in white blood cell 
count, which may in turn result in serious infections.  Aspirin is also a common drug used before 
and after such procedures.  Aspirin is known to contribute occasionally to causing 
gastrointestinal ulcers (bleeding or non-bleeding).  Aspirin may also affect platelet function to 
the extent of causing bleeding complications (which may be minor, major, or life threatening).  If 
such conditions occur, the patient may require surgery, blood transfusion, or platelet transfusion.   
Any 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 emergency PTA and 
vascular surgery.  It is expected that the fluoroscopy time of the interventional procedure will be 
similar to the time required for conventional percutaneous lower extremity interventional 
procedures and not pose additional risks to the subject or lab personnel.  
4.1.2 ASSOCIATED RISKS FROM THE DRUG COATING 
The balloon coating includes the API paclitaxel and small amounts of well-known excipients 
(drug carrier) that are approved by the Food and Drug Administration (FDA) as inactive 
ingredients in drug products for intravenous (IV) drug delivery. The anti-proliferative drug 
paclitaxel is a well understood API with extensive history of human use in oncology and drug-
eluting stents (DES).  The maximum total dose on the largest peripheral Lutonix PTA Catheter is 
less than 2% of the typical dose infused during a single course of cancer therapy (300mg).  
Adverse events that may be associated with the paclitaxel drug coating on the LUTONIX® Drug 
Coated Balloon:   
 Allergic/immunologic reaction 
There may be other risks associated with the drug coating that are unknown at this time.   
There are no adequate and well-controlled studies published in pregnant women or men 
intending to father children who have received paclitaxel in the studied device.  Therefore 
women who are pregnant or intend to become pregnant and men intending to father children will 
be excluded from the trial.  
4.2 RISK MANAGEMENT PROCEDURES 
The investigational plan is specifically designed to manage and minimize risks through careful 
subject selection, thorough training of investigators, adherence to the pre-determined time points 

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to assess subject clinical status and regular clinical monitoring visits by Sponsor appointed 
monitoring personnel. 
Follow-up exams including duplex ultrasound will be performed to assess the target vessel 
patency and assess overall patient status.  A Clinical Events Committee (CEC) and an 
independent Data Safety Monitoring Board (DSMB) will monitor safety of the subjects 
throughout the trial. 
4.3 POTENTIAL BENEFITS 
There are no guaranteed benefits from participation in this study; however, it is possible that 
treatment with the LUTONIX® Drug Coated Balloon may reduce the potential for restenosis of 
the stented lesion, thereby reducing the need for repeat hospitalization and/or procedure(s).  
Additionally, information gained from the conduct of this study may be of benefit to others with 
the same medical condition. As with all investigational medical devices, the long-term results of 
using the LUTONIX® Drug Coated Balloon are not known at the present time. Alternatives to 
the use of the LUTONIX® Drug Coated Balloon for ISR include standard or cutting balloon 
angioplasty, laser, atherectomy, cryoplasty, restenting or surgery (vessel bypass with native or 
synthetic vessel).  Lutonix believes that the risk for significant injury or death due to the 
LUTONIX® Drug Coated Balloon is extremely low, and the potential benefits of decreased need 
for reintervention is likely, but these potential risks and benefits have yet to be quantified. 
4.4 EARLY TERMINATION 
Lutonix, Inc. (Sponsor) and the CEC will monitor the progression of the study.  If warranted, the 
study may be suspended or discontinued early if there is an observation of serious adverse 
reactions presenting an unreasonable risk to the study population.   
The Sponsor may terminate Investigator and site participation in the study for issues including 
but not limited to the following issues: 
 Evidence of an Investigator’s failure to maintain adequate clinical standards  
 Evidence of an Investigator or staff’s failure to comply with the protocol 
 Inaccuracy or late submission of data forms and core lab images 
 Conditions of approval imposed by the reviewing IRB and/or regulatory agencies 
 Evidence of safety concerns or protocol non-compliance 
 Change of staff at site that adversely impacts trial conduct   
Any evident pattern of non-compliance with respect to these standards will be cause for the site 
to be put on probation.  If corrective actions are not subsequently undertaken, the clinical site 
will be asked to withdraw from the study and their site may be replaced. 
In the event of study suspension or termination, the Sponsor will send a report outlining the 
circumstances to the Institutional Review Board (IRB) and all Investigators and Regulatory 

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Authorities as required by regulation.  A suspended or terminated study may not be reinitiated 
without approval of the reviewing IRB and Regulatory Authorities, as required by regulation. 
The Investigator must notify the IRB in writing as soon as possible but no later than within 10 
days if the premature termination is related to safety or compliance issues.  
5 CLINICAL STUDY DESIGN   
The study will enroll 127 subjects presenting with an angiographically significant (≥ 50%) 
restenosis of previous bare or drug eluting nitinol stent(s) in the superficial femoral or popliteal 
artery.  Drug-eluting stents must have been placed ≥ 6 months prior to study index procedure.  
Subjects will have ultrasound and clinical follow-up through 2 years and telephone follow-up 
through 3 years. A table highlighting schedule of assessments can be found in Section 7.3. 
5.1 SCREENING PROCEDURES 
All patients admitted for a percutaneous revascularization of a previously stented 
femoropopliteal artery should be screened for study eligibility.  If inclusion criteria are met and 
no exclusion criteria are present at the time of screening, the Investigator will discuss the study 
and ask the patient to participate. Prior to enrollment, the patient must sign the informed consent 
form approved for use by the IRB or other appropriate committee.  A copy of the signed and 
dated Informed Consent will be provided to the subject.  Subjects will be assured that they may 
withdraw from the study at any time and for any reason.  The background and purpose of the 
study, participation requirements, as well as the potential benefits and risks of the procedure(s) 
must be explained to the subject.   
If not already performed as standard practice, the following assessments and tests must be 
performed after obtaining informed consent and prior to the index procedure (within 30 days 
unless otherwise noted) to verify and complete eligibility: 
 Physical examination  
 Relevant medical history 
 Rutherford Classification 
 Pregnancy Test (blood or urine; if female of child bearing potential) 
 Resting Ankle-Brachial Index (ABI) (within 90 days) 
 Walking Impairment Questionnaire 
 EQ5D Questionnaire 
5.2 PATIENT SELECTION FOR ENROLLMENT 
Subjects must meet all the clinical eligibility criteria, agree to participate and comply with study 
protocol requirements and follow-up schedule, and provide informed consent. 
All subjects are expected to remain available (geographically stable) for the duration of the study 
follow-up period. If any subject moves away, every effort must be made to maintain the follow-

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up schedule including having an appropriate physician follow the subject.  The Investigator is 
responsible for ensuring that each follow-up visit occurs at the specified time and that all 
applicable data is reviewed and entered into the electronic case report form system (eCRF) in a 
timely fashion. 
5.3 SUBJECT INCLUSION AND EXCLUSION CRITERIA 
5.3.1 
 INCLUSION CRITERIA 
Subjects must meet all inclusion criteria to be enrolled in the study. 
Clinical Criteria 
1. Male or non-pregnant female ≥18 years of age;  
2. Rutherford Clinical Category 2-4;  
3. Patient is willing to provide informed consent, is geographically stable and willing to 
comply with the required follow up visits, testing schedule and medication regimen; 
Angiographic Criteria 
4. Significant (≥ 50%) restenosis of a previous bare or drug-eluting nitinol stent(s) in the 
femoropopliteal artery. Drug-eluting stents must have been placed ≥ 6 months prior to 
study index procedure.   
NOTE: Discrete or composite lesions allowed within a continuous single or 
overlapped stented segment. 
NOTE: Edge restenosis allowed ≤ 3 cm beyond stent margin  (confirmed after pre-
dilatation).  
5. The intended target lesion measures between 4 and 22 cm and can be treated with 
single or multiple balloons of cumulative balloon length ≤ 26 cm  
NOTE: This balloon length requirement (≤ 26 cm) applies to the total length of all 
devices intended for use, not the length of the treated segment (which is less, since 
5mm balloon overlap is required for treatment);  
6. Target vessel diameter between ≥4 and ≤6 mm and able to be treated with available 
device size matrix; 
7. A patent inflow artery free from significant lesion (≥50% stenosis) as confirmed by 
angiography (treatment of target lesion acceptable after successful treatment of iliac 
inflow artery lesions);  
NOTE: Successful inflow treatment is defined as attainment of residual diameter 
stenosis ≤30% without death or major vascular complication. 
8. Successful crossing with a guidewire and pre-dilatation of the target lesion;  
NOTE: Successful pre-dilatation is defined as attainment of residual diameter stenosis 
< 50%. 
9. At least one patent native outflow artery to the ankle, free from significant (≥50%) 
stenosis as confirmed by angiography that has not previously been (nor planned to be) 
revascularized;  

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10. No other prior vascular or surgical interventions within 2 weeks before and/or 
planned 30 days after the protocol treatment, except for contralateral iliac treatment. 
5.3.2 EXCLUSION CRITERIA 
Patients will be excluded if ANY of the following conditions apply:  
1. Pregnant or planning on becoming pregnant or men intending to father children; 
2. Life expectancy of <1 year; 
3. Patient is currently participating in an investigational drug or other device study which 
could, in the opinion of the investigator, affect the results of this study, or previously 
enrolled in this study; 
NOTE: Enrollment in another drug or device clinical trial during the follow up period is 
not allowed. 
4. History of stroke within 3 months; 
5. History of MI, thrombolysis or angina within 2 weeks of enrollment;  
6. Prior vascular surgery of the index limb, with the exception of remote common femoral 
patch angioplasty separated by at least 2 cm from the target lesion; 
7. SFA disease in the opposite leg that requires treatment at the time of index procedure 
(Note inclusion #10- no other planned procedure allowed for 30 days post index 
procedure); 
8. Target lesion involves either a previously placed covered stent or drug-eluting stent. 
Treatment of drug-eluting stents is only allowed if stent was placed ≥ 6 months prior to 
study index procedure; 
9. Grade 4 or 5 stent fracture (mal-aligned components or trans-axial spiral configuration) in 
the restenotic stent(s); 
10. Inability to take study medications or allergy to contrast that cannot be adequately 
managed with pre- and post-procedure medication; 
11. Significant distal aortic vessel or common femoral artery disease. Successful treatment of 
iliac disease allowed prior to target lesion treatment; 
12. Known inadequate distal outflow (>50 % stenosis of distal popliteal and/or all three tibial 
vessels), or planned future treatment of vascular disease distal to the target lesion; 
13. Sudden symptom onset, acute vessel occlusion, or acute or sub-acute thrombus in target 
vessel; 
14.  Intended use of adjunctive treatment modalities (i.e. laser, atherectomy, cryoplasty, 
scoring/cutting balloon, stents, etc.). 
6 STUDY/TREATMENT PROCEDURES 
6.1 ENROLLMENT 
After signing the informed consent document, a subject is considered enrolled in the study after 
baseline angiographic results and pre-dilatation confirm that the target lesion meets all 
appropriate inclusion/exclusion criteria.  

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Subjects that meet baseline angiographic criteria but do not meet post-pre-dilatation criteria will 
not be enrolled in the study. 
6.2 LUTONIX® DRUG COATED BALLOON INSTRUCTIONS FOR USE (IFU) 
Always follow the current IFU for procedural information, preparation and use of the 
LUTONIX® Drug Coated Balloon.  Any devices found to be defective or that do not perform as 
expected should be returned immediately to the Sponsor for evaluation and a Device 
Malfunction Form must be completed.  
A balloon compliance chart is included on each device product label.   
In order to achieve the best procedural outcomes, the following steps should be completed: 
 The Lutonix DCB catheter should be advanced to the target site as fast as possible (i.e. ~ 
30 seconds). 
 The DCB should be immediately inflated to appropriate pressure to ensure full wall 
apposition (balloon to artery ratio of ≥1:1).  
 If the deployment of the DCB exceeds 3 minutes, the catheter requires replacement with 
a new unit. 
 Maintain the DCB inflation for a minimum of 2 minutes (120 seconds). The balloon may 
remain inflated as long as is required by the standard of care to achieve a good 
angioplasty outcome. 
 For optimal results, the final percent stenosis should be 0-20%. 
If more than one LUTONIX® Drug Coated Balloon will be needed to treat the entire pre-dilated 
segment(s)/lesion(s), the combination of lengths available should be carefully considered 
beforehand to ensure complete coverage of the target lesions and, at the same time, reduce 
unnecessary vessel dilatation.  Per protocol, cumulative balloon length must be ≤ 26 cm. The 
IFU also contains detailed information on lesion coverage and minimal inflation times. 
6.3 BASELINE ANGIOGRAM 
Digital Subtraction Angiography (DSA)- or Cine- angiograms should be obtained per core lab 
guideline.  Standard off-line Quantitative Vascular Angiography (QVA) acquisition procedures 
will be followed for analysis at the independent Imaging Core Laboratory. All angiography 
procedures (both index and non-scheduled) must be recorded in such a way that they are suited 
for off-line QVA.  For purposes of ensuring protocol compliance, all angiograms must be 
submitted to the core laboratory as soon after the case as possible. Please refer to the trial 
specific Angiographic Acquisition Guidelines provided by the core laboratory for specific 
procedural imaging and submission instructions. 
6.4 IN-FLOW LESION TREATMENT 
Absence of inflow disease (≥50% stenosis) as confirmed by angiography is required for 
enrollment in the study. Enrollment is allowed following complete successful treatment per 

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standard practice of inflow iliac artery lesions, with successful treatment defined as attainment of 
a residual diameter stenosis ≤30% without death or major vascular complication. Treatment of 
aortic and common femoral inflow lesions is not allowed. 
6.5 PRE-DILATATION 
Always refer to the current IFU packaged with the device for complete pre-dilatation 
requirements. 
Lesion(s) pre-dilatation(s) is required for all patients.  The pre-dilatation balloon should be a 
standard PTA balloon inflated to a diameter approximately 1 mm less than the reference vessel 
diameter (RVD).  Successful pre-dilatation is defined as attainment of residual diameter stenosis 
< 50%.  Always limit the longitudinal length of the pre-dilatation balloon to avoid creating a 
region of vessel injury that is outside the boundaries of the area to be treated by the LUTONIX® 
Drug Coated Balloon.  
6.6 TREATMENT WITH LUTONIX® DRUG COATED BALLOON 
If after pre-dilatation(s) patients are determined to meet the criteria for enrollment, they will be 
treated with the LUTONIX® Drug Coated Balloon. A stented segment with multiple stents may 
be treated per this protocol; however, the stented area must be continuous.  
The Investigator should determine the appropriate size of the balloon(s) to be used by online 
QVA (if possible) or by visual estimate. Inflate approximately to RVD for as long as necessary 
to achieve an optimal procedural result. Post-dilatations are allowed. 
In order to achieve the best procedural outcomes, the following steps should be completed: 
 The Lutonix DCB catheter should be advanced to the target site as fast as possible (i.e. ~ 
30 seconds). 
 The DCB should be immediately inflated to appropriate pressure to ensure full wall 
apposition (balloon to artery ratio of ≥1:1).  
 If the deployment of the DCB exceeds 3 minutes, the catheter requires replacement with 
a new unit. 
 Maintain the DCB inflation for a minimum of 2 minutes (120 seconds). The balloon may 
remain inflated as long as is required by the standard of care to achieve a good 
angioplasty outcome. 
 For optimal results, the final percent stenosis should be 0-20%. 
Please refer to the current LUTONIX® Drug Coated Balloon IFU for detailed information on 
device use. 
6.7 POST TREATMENT AND PROVISIONAL (BAILOUT) STENTING 
There is no consensus or established objective criteria that are validated regarding the 
appropriate threshold for provisional SFA stenting for ISR treatment.  In the absence of an 

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established threshold, the determination to bailout has previously been based on criteria that are 
either subjective or largely left to the discretion of the individual operator and his/her judgment. 
The current trial design is intended to minimize the need for bailout stenting.  Due to the need 
within the medical community to establish validated criteria for provisional stenting, this trial 
will utilize more rigorous criteria for bailout stenting.  Specifically, the trial will employ the 
additional requirement of a pressure gradient measurement to document an unsatisfactory 
balloon-only outcome (obtained by measuring pressures proximal and distal to the lesion 
simultaneously).   
If immediate procedural results are not satisfactory, e.g., residual stenosis >30% or flow-limiting 
dissection, then prolonged balloon dilations are recommended. Post dilatation may be performed 
using either the used Drug Coated Balloon (note that drug delivery occurs during the first 
inflation ONLY) or another plain angioplasty catheter, taking great care to avoid injury of a 
segment to which drug is not delivered. Stenting is allowed only in cases with flow-limiting 
dissection or stenosis >50% and documented pressure gradient refractory to postdilatation and 
nitroglycerine administration.  
Table 1: Bailout Criteria 
Bailout Prevention 
Treatment requirement prior to bailout stenting: 
 
Prolonged (>2 minutes) balloon inflation(s) 
 
Vasodilators and/or thrombolytic agents per investigator discretion 
Bailout Criteria 
 
Residual stenosis of  >50%  (based on careful in-lab review of angiograms including QVA if 
available)  or  major flow-limiting dissection  (Record angiography in 2 orthogonal views) 
and 
 
Documented translesional pressure gradient of >20mmHg (using ≤4F end-hole catheter) or 
>10mmHg (pressure wire) measured immediately distal to the target lesion 
These criteria are set as the minimum baseline pressure gradient requirement for allowing bailout 
stenting; however, bailout stenting is not required for pressures equal to or exceeding these 
thresholds (i.e. presence of a gradient at/above these thresholds does not require that the operator 
place a stent).  Rather, these thresholds are seen as minimum requirements for bailout stenting; 
below these thresholds, bailout stenting is not allowed. 
If the criteria for bailout stenting are fulfilled, placement of a bare nitinol stent (not DES) is 
permissible at the physician’s discretion. 
The angiographic core lab will be monitoring cases of bailout stenting throughout the course of 
enrollment for compliance to provisional (bailout) criteria listed in this section. 

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6.8 UNSCHEDULED ANGIOGRAPHY/REVASCULARIZATION 
A DUS is required prior to any subsequent angiography of the index limb, and the images must 
be submitted to the DUS Core Lab.  A DUS at any time point post index procedure but prior to 
the re-intervention will suffice.  Clinical status should be evaluated prior to angiography, 
including physical exam, Rutherford classification and ABI. In the event that a subject undergoes 
repeat angiography after the index procedure is complete, all subsequent angiograms for the 
index limb or, in the event of an index limb revascularization, all procedural angiograms must be 
forwarded to the Angiographic Core Lab for review and analysis.  Attempts should be made to 
record the same views and angles as from the index procedure.   
7 TREATMENT OF SUBJECT 
Lutonix (or its designee) reserves the right to attend index or DUS procedures in order to ensure 
protocol compliance, proper device handling and adequate image capture.  
7.1 BLINDING PLAN 
In order to minimize the introduction of bias into the study, a pre-specified blinding plan has 
been developed for subjects randomized under protocol versions 2.0 and 3.0.  All Duplex 
Ultrasound operators, core lab evaluators, and members of the Clinical Events Committee (CEC) 
will be blinded to the subject’s treatment assignment.  The study subject will be blinded to 
treatment until the completion of the 12 month visit.  
All subjects enrolled under protocol version 4.0 or later will be treated with the LUTONIX® 
Drug-Coated Balloon; therefore a blinding plan is not applicable. 
7.2 MEDICATIONS 
Subjects should be given standard dual antiplatelet loading and treatment doses per institution 
standard of care for at least one month post procedure.  These medications will be captured on 
the eCRFs for each subject enrolled.  
7.3 STANDARD TESTS, PROCEDURES, AND FOLLOW-UP 
Table 2 displays the required schedule treatment and evaluation.  This schedule is consistent 
with standard clinical care pre- and post-interventional procedures.  The times for each test are 
broad enough to fit into most hospital routine testing procedures.  
 
At 6, 12, and 24 month follow-up visits, the clinical status of the subject (for assessment of 
clinical and safety endpoints) should be established prior to performing the required DUS (for 
assessment of patency).  
 
Table 2: Follow Up Schedule and Testing Requirements for Subjects 

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EVENT 
Pre-Procedure 
Procedure 
Post-Procedure 
1 Month1 
6 Month 
12 Month 
24 Month 
36 months1 
Repeat 
Angio/Revasc 
Visit Window 
30 Days 
-- 
 
±14 
days 
±30 
days 
±30 
days 
±60 
days 
±60 
days 
- 
Inc/Exc Criteria 
√ 
√ 
 
 
 
 
 
 
 
Inf. Consent 
√ 
 
 
 
 
 
 
 
 
Med Hx 
√ 
 
 
 
 
 
 
 
 
Pregnancy Test2 
√ 
 
 
 
 
 
 
 
 
Physical Exam 
√ 
 
√ 
√3 
√ 
√ 
√ 
 
√5 
Medication Compliance 
√ 
 
 
√ 
√ 
√ 
√ 
√ 
√ 
Resting ABI 
√4 
 
√5 
√3 
√ 
√ 
√ 
 
√5 
Rutherford Classification 
√ 
 
 
 
√ 
√ 
√ 
 
√5 
WIQ & EQ5D 
Questionnaires 
√ 
 
 
 
√ 
√ 
√ 
 
 
Angiogram 
 
√ 
 
 
 
 
 
 
√ 
Adverse Event Monitoring 
 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Duplex Ultrasound6 
 
 
√7 
√ 
√ 
√ 
 
√ 
1Follow-up can be by telephone or clinical visit 
2 For females of childbearing potential 
3Required only if clinical visit occurs 
4Resting ABI is required within 90 days prior to index procedure.   
5 Not required, but encouraged to capture if possible 
6DUS to be performed after Clinical Assessment 
7DUS may be capture anytime 0-6 weeks post procedure 
 
7.3.1 TESTING 
7.3.1.1  PREGNANCY TESTING   
For women of childbearing potential, a pre-procedure pregnancy test must be done (blood or 
urine). Pre-procedure samples may be taken up to 30 days prior to the index procedure. 
7.3.1.2 ANKLE-BRACHIAL INDEX (ABI) 
A resting ABI must be performed per local hospital standard, and consistently among subjects 
over the lifespan of the study (within 90 days prior to index procedure).   
7.3.1.3 RUTHERFORD SCALE 
Rutherford classification can be measured with or without treadmill, but must be performed 
consistently among subjects over the lifespan of the study. 
7.3.1.4 WALKING IMPAIRMENT QUESTIONNAIRE 
The WIQ form will be completed at pre-procedure and at 6, 12 and 24 months. 

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See Appendix B for a sample questionnaire form. 
7.3.1.5 QUALITY OF LIFE QUESTIONNAIRE 
The EQ5D survey will be completed at pre-procedure and at 6, 12 and 24 months. 
See Appendix C for a sample questionnaire form. 
7.3.1.6 DUPLEX ULTRASOUND AND ANGIOGRAPHY GUIDELINES 
The initial baseline DUS must be performed after the index procedure (or at anytime up to 6 
weeks post-procedure), and again at 6, 12 and 24 months.  Since DUS and angiography are 
critical to assessing study endpoints, the quality of these tests are extremely important.  The Core 
Labs will be closely monitoring the quality of all incoming images for compliance.   
Sites should ensure that only DUS operators who are trained on the DUS guidelines are 
performing these tests.  Refer to the Duplex Ultrasound and Angiography Guidelines Manual of 
Operations for the most current version of the documentation requirements.   
7.3.2 FOLLOW-UP PROCEDURES 
The Investigator or Research Coordinator will contact subjects via phone (or via clinical visit if 
preferred or as part of a regular follow-up) at 30 days, and 36 months (and possibly longer if 
required) in order to assess for any adverse events and medication compliance.    
All subjects will return for follow-up at 6, 12 and 24 months post procedure for required testing 
at each follow-up visit time point. If DUS was not performed post index procedure, a clinic visit 
will be required within 6 weeks of initial treatment to obtain images.  
All subjects are required to complete all assigned follow-up visits and procedures.  During the 
duration of the study, all events need to be reported in the web-based eCRF. Subjects will be 
instructed to report adverse events to their study physician between evaluation visits. 
8 ADVERSE EVENTS 
An adverse event (AE) is defined as any untoward medical occurrence in a subject.  This 
definition does not imply that there is a relationship between the adverse event and the device 
under investigation.  See Appendix A for detailed AE definitions. 
The following adverse events are required to be reported in this study: 
 All SAEs 
 All protocol defined Major Vascular Complications (MVC) occurring ≤ 30 days of 
the index procedure (See Appendix A for definition of MVC) 
 Non-serious adverse events involving the target limb  

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8.1 ADVERSE EVENT REPORTING 
All adverse events occurring since the start of the study procedure must be recorded in the eCRF 
for enrolled subjects that meet all criteria after pre-dilatation. All adverse events occurring in this 
study will be classified in accordance with the adverse event signs or symptoms.  The CEC will 
review and adjudicate all deaths, all index limb reinterventions, all index limb amputations, 
Unanticipated Adverse Device Effects (UADEs) and device related SAEs.  Any Serious Adverse 
Event must be reported in the EDC within 5 working days of knowledge. Adverse events will be 
reported to the IRB per local requirements. 
9 SUBJECT WITHDRAWAL CRITERIA 
Subjects can withdraw from the study at any time for any reason; the reason for withdrawal will 
be documented.  All data available at the time of withdrawal (if any) will be used for analysis. 
There will be no further follow-up (per this study protocol) on the subject who has withdrawn.  
Subjects who withdraw from the study will not be replaced, however loss-to-follow-up has been 
considered for sample size statistics. 
10 DATA COLLECTION AND MONITORING 
10.1  DATA COLLECTION 
The Investigator (or designated hospital staff) will assure primary data collection based on 
source-documented hospital chart reviews. These documents will be completed in an expedited 
fashion.  
10.1.1 ELECTRONIC CASE REPORT FORMS (ECRF) 
All required clinical data for this trial will be collected in web-based standardized eCRFs. Site 
and subject numbers will be used to track subject information throughout the study. 
The eCRF is designed to accommodate the specific features of the study design.  Modification of 
the eCRF will only be made if deemed necessary by Lutonix and/or the appropriate regulatory 
body.   
10.1.2 ANGIOGRAMS AND DUPLEX ULTRASOUNDS 
All core lab raw data will be sent to the independent Core Lab for analysis. All Core Lab 
evaluators will be blinded to the randomized treatment of subjects enrolled under protocol 
versions 2.0 and 3.0.  
10.2  MONITORING 
Each site will have an initiation visit performed by a Study Monitor and/or a member of the 
Lutonix clinical staff.  This visit will ensure that the investigator understands his/her 
responsibility for conducting this study at his/her center.   
Sites will be monitored according to the approved monitoring plan.  Monitoring personnel will 
monitor for accuracy and timely submission of data forms and core lab images, and compliance 

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with the study protocol, meeting enrollment commitments, applicable regulations, the signed 
Investigator Agreement and any conditions of approval imposed by the reviewing IRB and/or 
regulatory agencies.  
The Study Monitors will maintain personal contact with the Investigator and staff throughout the 
study by phone, mail, and on-site visits.  The Study Monitors will compile and submit to Lutonix 
a monitoring report after each visit that will include any findings, conclusions, and actions taken 
to correct deficiencies.  
At the close of the study at an investigational site, appropriately trained personnel appointed by 
Lutonix will make a final on-site visit or a remote (i.e. telephone) visit if no subjects were 
enrolled at a site.  The purpose of this visit is to collect all outstanding study data documents, 
ensure that the Investigator's files are accurate and complete, review record retention 
requirements with the Investigator, make a final accounting of all study supplies shipped to the 
Investigator, provide for appropriate disposition of any remaining supplies, and ensure that all 
applicable requirements are met for the study.   
10.3  SOURCE DOCUMENTATION 
Auditors, monitors, the study Sponsor and regulatory authorities may have access to the medical 
records related to this study. Original or certified copies of all relevant clinical findings, 
observations, and other activities throughout the clinical investigation must be recorded and 
maintained in the medical file of each enrolled subject. (No source documentation will be 
recorded directly on an eCRF). The Investigator will permit study–related monitoring, audits, 
IRB review and authority inspections by allowing direct access to the source data.  
In case of electronic source data, access will be allowed or dated print-outs will be available 
prior to the monitoring visits. Print-outs should not be limited to the vascular data only, but 
should include all available data related to the identified subject(s).  
10.4   RECORD RETENTION 
The Sponsor and Investigator will maintain the following accurate, complete, and current records 
relating to the conduct of the investigation according to national requirements.  The data for 
some of these records may be available in computerized form from the CRO, but the final 
responsibility for maintaining study records remains with the Investigator. 
11 DEVICE ACCOUNTABILITY 
The Investigator must ensure that the study devices are used only in accordance with the protocol 
and current IFU.  The Investigator must maintain records that adequately document the device(s) 
the subject received.  In the case where a Lutonix device has failed, the Investigator must make 
every possible effort to return the device to Lutonix; instructions for this procedure will be 
provided in the Investigator Site Binder. 

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11.1 DEVICE SUPPLY 
Investigational LUTONIX® Drug Coated Balloon will be utilized for this study.   
12 STUDY MANAGEMENT 
12.1 DATA SAFETY MONITORING BOARD 
The Data Safety Monitoring Board (DSMB) is responsible for the oversight and safety 
monitoring of the study. The DSMB advises the Sponsor regarding the continuing safety of the 
trial subjects and those yet to be recruited to the trial, as well as the continuing validity and 
scientific merit of the trial.  The DSMB members are experts in peripheral vascular disease, 
cardiovascular medicine and biostatistics who are not participating in the trial and have no 
affiliation with Lutonix. 
During the enrollment phase of the trial, the DSMB will review accumulating safety data to 
monitor for incidence of serious vascular events that would warrant modification or termination 
of the trial. 
Any DSMB recommendations for study modification or termination because of concerns over 
subject safety or issues relating to data monitoring or quality control will be submitted in writing 
to the Study PI and sponsor for consideration and final decision.  
The DSMB will meet at regular intervals to review the safety data. DSMB responsibilities, 
membership, meeting frequencies, and procedures will be outlined in the DSMB charter. 
12.2  CLINICAL EVENTS COMMITTEE 
The Clinical Events Committee (CEC) is made up of a minimum of three clinicians with 
expertise in vascular intervention and who are not participants in the study. The CEC is charged 
with the development of specific criteria used for the categorization of clinical events and 
clinical endpoints in the study that are based on the protocol.  
All members of the CEC will be blinded to the primary results of the trial.  The CEC will meet 
regularly to review and adjudicate all subject deaths, index limb reinterventions and device 
related SAEs.  
13 REGULATORY RESPONSIBILITIES 
13.1 ETHICS APPROVAL 
Investigators must submit the study protocol to their IRB and obtain written approval before 
being allowed to conduct and participate in the study. The Investigator is also responsible for 
fulfilling any conditions of approval imposed by the IRB, such as regular safety reporting, study 
timing, etc.  The Investigator will provide Lutonix or designee with copies of such approvals and 
reports. 
Any amendments to the protocol, as well as possible associated information and consent form 
changes, will be submitted to the IRB and written approval obtained prior to implementation.  

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13.2 INFORMED CONSENT 
Part of the IRB approval must include approval of an Informed Consent Form (ICF) that is 
specific to the study.  The Investigator must administer this approved ICF to each prospective 
study subject, and obtain the subject's signature on the ICF prior to enrollment in the study.  The 
ICF may be modified to suit the requirements of the individual site.  Lutonix or designee must 
pre-approve each ICF prior to initial submission to the IRB. The Investigator will provide 
Lutonix or designee with a copy of the approved ICF for his/her site.   
The study must be explained in a language that is understandable to the subject and he/she must 
be allowed sufficient time to decide whether to participate. All subjects will be assured that they 
have the right to withdraw from the study at any time during the course of the protocol and this 
decision will not influence his/her relationship with the Investigator (treating physician) and/or 
study staff.  
13.3  SELECTION OF CLINICAL SITES AND INVESTIGATORS 
The Sponsor will select Investigators who are qualified and experienced to participate in this 
study. Sites will be selected based upon a review of site assessments or questionnaires and the 
overall qualifications of the site.  
Any site that becomes deactivated prior to initial enrollment, either by the sponsor or by the 
individual site itself, may be replaced. 
13.4 INVESTIGATOR’S RESPONSIBILITIES 
Each Investigator is responsible for ensuring the study is conducted according to all signed 
agreements, the Investigational Plan and applicable laws and regulations. The site Principal 
Investigator will select qualified co-investigators at each site and will maintain responsibility for 
oversight of all procedures and data collection.  All co-investigators must be trained on all 
aspects of the protocol prior to enrolling and performing procedures.  
13.4.1 STUDY COORDINATOR 
To ensure proper execution of the Investigational Plan, each Investigator must identify a Study 
Coordinator for the site.  Working with and under the authority of the Investigator, the Study 
Coordinator helps ensure that all study requirements are fulfilled, and is the main contact person 
at the site for all aspects of study administration.   
13.5   LUTONIX RESPONSIBILITIES 
A site initiation visit will occur with each study site in order to orient the Investigator and staff to 
information such as:  the investigational device, the Investigational Plan, applicable regulations 
and requirements, and expectations of the study, including the numbers and time frame for 
subject enrollment, subject selection, informed consent, required clinical data, and record 
keeping. 

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14 PUBLICATIONS 
The trial will be registered in the ClinicalTrials.gov website upon approval by a human subject 
review board of the appropriate national health authorities in order to meet the criteria of the 
International Committee of Medical Journal Editors.  All publications will follow the Uniform 
Requirements for Manuscripts Submitted to Biomedical Journals (www.icmje.org, October 
2008). 
After the conclusion and final analysis of the trial results, a formal abstract presentation may be 
made at a major cardiovascular conference and the study results will be submitted to a reputable 
scientific journal.   
Following the publication of the main manuscript, secondary analyses proposals will be 
considered for publication from individual Investigators.  No submissions may be made without 
the written approval from Lutonix.    
15 STATISTICAL ANALYSIS PLAN  
15.1 OVERVIEW OF STUDY DESIGN 
The SFA ISR study is a multi-center, single-arm trial comparing the LUTONIX® Drug Coated 
Balloon to safety and effectiveness performance goals based on standard balloon angioplasty for 
the treatment of femoropopliteal in-stent restenosis.  The study will enroll patients presenting 
with claudication or ischemic rest pain (Rutherford Category 2-4) and occlusion or ≥50% 
stenosis of a previously deployed bare nitinol stent(s) or drug-eluting stent if placed ≥ 6 months 
prior to the index procedure in the femoropopliteal artery that is appropriate for angioplasty.  
After successful protocol-defined pre-dilatation, subjects are treated with the LUTONIX® Drug 
Coated Balloon. 
The objective of the study is to demonstrate the effectiveness and safety of the LUTONIX® Drug 
Coated Balloon for treatment of SFA ISR by comparison to objective performance goals (OPGs).  
Both primary endpoint criteria must be met in order for the study to be considered successful. 
15.2 ANALYSIS POPULATIONS 
Intent-To-Treat (ITT) population: All subjects who have signed the Informed Consent Form and 
are determined by the site to be suitable to receive treatment with the LUTONIX® Drug Coated 
Balloon or standard PTA. 
As-treated (AT) population: All ITT subjects that were treated with the LUTONIX® Drug Coated 
Balloon.  This may also be referred to as the Modified Intent-to-Treat (mITT) population. 
Per-Protocol population (PP): All AT (mITT) subjects characterized by appropriate exposure to 
treatment (procedurally correct as pre-specified) and the absence of major protocol violations 
(including violations of entry criteria) that if not met for a given patient may obscure the 
evaluation of efficacy in that patient. 

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All baseline analyses will be completed using the mITT population.  All effectiveness and safety 
analyses will be completed with the AT (mITT) population. . 
PTA Population:  The set of subjects originally randomized to and treated with PTA under the 
previous versions of the protocol.    
The results of the PTA population will be listed or summarized separately from the Lutonix DCB 
subjects using descriptive statistics. 
15.3 HANDLING MISSING DATA 
Endpoints may be missing because subjects have died, have uninterpretable imaging data or have 
withdrawn from the study prior to the time the endpoint is measured.  The reason for the 
censoring of all subjects with missing results for the primary endpoints will be reported. The 
primary safety and effectiveness endpoints will also be supportively analyzed using Kaplan-
Meier survival analysis techniques as sensitivity analyses. In survival analyses, unobserved 
endpoints are a standard part of the analysis and, as long as the missing data is unrelated to the 
treatment or the actual (unobserved) outcome, the Kaplan-Meier method will produce unbiased 
estimates of the freedom-from-event rates. A tipping-point analysis will also be performed for 
the binary primary patency endpoint, in which assumptions about missing data are varied from 
worst-case to best-case to examine at what point the missing data would alter the conclusion of 
the analysis.  These analyses will constitute sensitivity analyses of the effect of missing data on 
the study results. 
15.4 ASSESSMENT OF POOLABILTY OF SITES AND SECONDARY ANALYSIS 
All primary endpoints will also be presented by site and sites with 3 or fewer AT subjects will be 
combined for this purpose.  In addition, the endpoints will also be summarized by site without 
pooling though no test of homogeneity will be performed.     
An analysis will be performed to examine the potential for homogeneity of response rates across 
pooled sites.   A logistic regression model will be fit for site.  If the p-value for the site effect is 
<0.15, it will be considered evidence of a potential lack of homogeneity across the study sites, 
and additional analyses will be performed to explore the differences between sites to assess their 
potential causes and whether or not they are clinically meaningful.  A non-significant site effect 
or a significant effect that is only quantitative and not qualitative on nature will be taken to 
support the pooling sites for the primary analysis.  Analyses may include testing for differences 
between sites for the covariates listed later in this section and the use of modeling involving the 
covariates along with study site to determine if they potentially explain any lack of homogeneity 
across the study sites. 
In addition, a descriptive analysis that examines the impact of important covariates on study 
results will be performed. Baseline covariates are age, gender, smoking, obesity, 
hypercholesterolemia, diabetes mellitus, total target lesion length (sum of core lab-reported 
lesion lengths of more than one), and maximum percent stenosis of subject target lesion(s) (via 

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core lab analysis), previous target lesion intervention, ABI of the target limb, and Rutherford 
grade.    Additional variables may be identified in the statistical analysis plan and will be 
identified prior to the completion of the study.  The covariates will be included in a logistic 
regression model in order to understand their potential impact on study results. 
An additional supportive analysis of patients without bailout stenting will also be performed 
based on descriptive statistics, and data will further be presented for subjects without bailout 
stenting. 
15.5 PRIMARY ENDPOINTS 
15.5.1 PRIMARY EFFICACY ENDPOINT: BACKGROUND  
The primary efficacy endpoint is primary patency at 12 months. Primary Patency is defined as 
Freedom from CEC-adjudicated Clinically-Driven TLR and from Core laboratory-adjudicated 
Binary Restenosis.  Binary restenosis is based on threshold Doppler PSVR ≥ 2.5 (together with 
waveform analysis & color mosaic appearance) or based on angiographic ≥ 50% diameter 
stenosis (if angiography is performed although not required per protocol). 
In order to establish an objective performance goal (OPG) for primary patency for this 
uncontrolled study, results from three sources were considered:  a meta-analysis of published 
results, the LEVANT 2 randomized primary patency result, and the Lutonix SFA Global 
Registry primary patency findings.  Based on the evaluation of the data sources, an OPG of 45% 
for primary patency was proposed for this study and the rationale is provided below. 
Meta-analysis results   
Estimated 12-month primary patency response rates for PTA were 34.2% (95% CI = 29.5%, 
39.0%) and for DCB were 84.5% (95% CI = 78.2%, 90.7%).  These results would indicate a 
large treatment effect in ISR subjects and low expectations for PTA alone.   The large range of 
responses in controlled studies may be explained by the use of additional therapies.   
Nonetheless, the results indicate the clear potential for an unmet need in treating ISR lesions with 
significant benefit in the use of DCB therapies.  
The performance of PTA from six publications is shown below.  Table 3 provides a meta-
analysis of reported outcomes after standard of care treatment of SFA ISR.  A very high 
restenosis rate is observed, with only 34% patency at 12 months. 
Table 3: Primary Patency for Standard of Care Treatment for SFR ISR 
Source 
Design 
Cohort 
CTO% 
Length 
(mm) 
N 
n 
patent 
p 
w =       
n/p(1-p) 
w*p 
13Tosaka 
Retrosp Observ 
CTO (III) 
100.0% 
198 
44 
10 
22.73% 
250.541 
56.941 
13Tosaka 
Retrosp Observ 
stenosis (I&II) 
0.0% 
91 
89 
61 
68.54% 
412.745 
282.893 
                                                     
13 Tosaka, A., Soga, Y., Iida, O., Ishihara, T., Hirano, K., Suzuki, K., . . . Nobuyoshi, M. (2012). Classification and clinical 
impact of restenosis after femoropopliteal stenting. J Am Coll Cardiol, 59(1), 16-23. doi: 10.1016/j.jacc.2011.09.036 

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4Yeo-Laird 
Retrosp Observ 
combined 
40.9% 
132 
21 
10 
47.62% 
84.191 
40.091 
14Liistro 
RCT-DEBATE ISR 
POBA 
NA 
138 
39 
11 
28.21% 
192.594 
54.321 
2Dick 
RCT-PTA v. cutting 
POBA (6m) 
9.1% 
80 
22 
6 
27.27% 
110.917 
30.250 
 15Dippel 
RCT – EXCITE ISR 
POBA 
36.8% 
193 
51 
6 
11.8% 
491.300 
57.800 
16Krankenberg 
RCT - FAIR Trial 
POBA 
33.3% 
81 
40 
15 
37.5% 
170.667 
64.000 
 
17D'Agostino meta -> 
1712.966 
586.30 
Standard-of-Care Rate -> 
0.342 
95% CI  [LL   UL]-> 
0.295 
0.390 
 
The above analysis is confounded by sporadic adjunctive use of laser, atherectomy, and stents in 
the observational standard-of-care studies, which may result in an overestimated primary patency 
rate for on label therapy – POBA – for which only 12% to 38% patency was observed in the 
RCT control arms. 
Preliminary data is available for drug-coated balloons.  The promising results from another 
manufacturer’s DCB (Medtronic In.Pact) suggest that DCB may provide a much more durable 
solution.  Available data for DCB and meta-analytic patency rate are provided in Table 4. 
 
 
 
Table 4: Primary Patency for Drug Coated Balloon Treatment for SFR ISR 
Source 
Design 
Cohort 
CTO% 
Length 
(mm) 
N 
n patent 
p 
w =       
n/p(1-p) 
w*p 
9Stabile 
Prosp Registry 
In.Pact DCB 
20.50 
83 
38 
35 
92.11% 
522.591 
481.333 
14Liistro 
RCT-DEBATE ISR 
In.Pact DCB 
NA 
131 
41 
33 
80.49% 
261.064 
210.125 
16Krankenberg 
RCT - FAIR Trial 
In.Pact DCB 
24.2 
82 
44 
31 
70.50% 
211.375 
148.923 
 
17D'Agostino meta -> 
995.030 
840.381 
DCB Rate -> 
84.5% 
95% CI  [LL   UL]-> 
78.2% 
90.7% 
 
The primary patency rate of 84.5% reported above for DCB (Table 4) cannot be assumed, given 
the limited number of subjects treated in only three studies.  Furthermore, the test device of the 
present study differs from the Lutonix DCB. 
Randomized Comparison of PTA and Lutonix DCB 
                                                     
14 Liistro F, et al, JACC Vol 60/17/Suppl B | October 22–26, 2012 | TCT Abstracts/POSTER/Diabetic Patients 
15 Dippel E, et al, Randomized Controlled Study of Excimer Laser Atherectomy for Treatment of Femoropopliteal In-Stent 
Restenosis, JACC Vol 8(1), Jan 2015:92-101 
16 Krankenberg H, et al, Drug-Coated Balloon Versus Standard Balloon for Superficial Femoral Artery In-Stent Restenosis: The 
Randomized Femoral Artery In-Stent Restenosis (FAIR) Trial; DOI:10.1161/CIRCULATION AHA. 115.017364 
17 D'Agostino, R. B. et al, Meta-analysis: A method for synthesizing research. Clinical Pharmacology & Therapeutics, 58: 605–
616. doi: 10.1016/0009-9236(95)90016-0 

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The LEVANT 2 pivotal study included a randomized comparison of the primary patency at 12 
months in the PTA and DCB subjects.  The subjects were not ISR subjects, but LEVANT 2 
provides reference rates based on the primary patency methodology proposed for this study.  
Response rates for primary patency were 52.6% (71/135) for PTA subjects and 65.2% (172/264) 
in DCB subjects.  These indicate a potential higher primary patency rate in PTA subjects and a 
potentially more model effect for primary patency in DCB subjects. 
Lutonix SFA Global Registry Results 
The SFA Global Registry was an open-label registry containing 691 subjects.  This study 
included a subset of subjects with one or more ISR lesions.  Overall site based primary patency 
response at 12 month was 80.5% (62/77) in ISR subjects and 82.7% (416/503) in non-ISR 
subjects.  A similar trend was observed in the TLR-Free response rate at 12 months which was 
91.5% (75/82) in ISR subjects and 94.6% (524/554) in non-ISR subjects.   
Selection of an Objective Performance Goal 
The poor PTA alone results in the meta-analysis suggest that the ISR subjects may do very 
poorly with regard to primary patency.  However, given the wide range response rates, the 
pooled response rate of 34.2% may be overly pessimistic even though the total number of treated 
subjects is 306.  A proposed OPG based for this study is 45% (this is slightly above the average 
of the LEVANT 2 PTA response rate and the meta-analysis estimate).  This OPG balances the 
poor response in ISR subjects observed in the meta-analysis with the higher PTA response from 
LEVANT 2.   
For sample size purposes, the DCB response rate is assumed to be 63.0% which reflects a small 
adjustment to the DCB reduction in the 65.2% response rate observed in the LEVANT 2 study in 
line with the 2.2% difference in response rates for primary patency in ISR subjects in the SFA 
Global Registry.   
 
15.5.2 EFFICACY ENDPOINT: HYPOTHESIS TEST AND SAMPLE SIZE CALCULATION 
The primary efficacy endpoint is primary patency at 12 months. Primary Patency is defined as 
Freedom from Clinically-Driven TLR and from Binary Restenosis.  Binary restenosis is 
adjudicated by the independent, blinded core laboratory based on threshold Doppler PSVR ≥ 2.5 
(together with waveform analysis & color mosaic appearance) or based on angiographic ≥ 50% 
diameter stenosis (if angiography is performed although not required per protocol). Clinically-
Driven TLR is adjudicated by the CEC. 
Objective:  To assess whether the proportion of subjects with Primary Patency (π) in DCB 
subjects is less than or equal to or greater than the primary patency OPG (45.0%) through 12-
months post-index procedure. 

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H0: The proportion of Lutonix DCB subjects with Primary Patency is less than or equal to 
the OPG to 0.45 (45.0%) at 12 months  (H0:  ≤ 0.45).  
H1: The proportion of Lutonix DCB subjects with Primary Patency is greater than the OPG 
of 0.45 (45.0%) at 12 months (H1:  > 0.45). 
The statistical analysis will be performed using an exact binomial test with one-sided α=0.025 
based on the AT (mITT) population.  The response variable in each subject will be the presence 
or absence of at least one efficacy event (core-lab adjudicated binary restenosis or CEC-
adjudicated clinically-driven TLR) from the time following the index procedure through 12 
months.  A significant rejection of the null hypothesis will be based on a one-sided p-value less 
than or equal to 0.025.  The proportions at 12-months post-index procedure and the exact 95% 
confidence intervals will also be reported. 
Sample Size Estimate:  The sample size estimation assumed the following: 
 The true 12-month proportion in the Lutonix DCB subjects is 63% 
 The Type 1 error,  = 0.025 (one-sided). 
 The Type 2 error,  = 0.10 (Power = 1 -  = 90%). 
 Based on exact binomial test 
 
The study evaluable sample size required for 90% power is 83 subjects. Allowing for up to 15% 
of subjects with missing 12 month efficacy endpoint data, the required enrolled sample size is 98 
DCB subjects in order to obtain 83 subjects with 12 month follow-up.  The total study sample 
size of 127 includes 98 DCB subjects and 29 subjects previously treated with PTA. 
15.5.3   PRIMARY SAFETY ENDPOINT: BACKGROUND 
The primary safety endpoint is a composite of freedom from all-cause perioperative (≤30 day) 
death and freedom at 1 year from the following: index limb amputation (above and below the 
ankle) index limb re-intervention, and index-limb-related death.  These events are called “safety 
events” in the following text. 
Data for this endpoint was not reported in the SFA ISR studies cited above (Table 3 and Table 
4).  However, safety outcomes reported to date for DCB-treated in-stent and native 
femoropopliteal lesions appear similar in general.  It is therefore assumed that safety outcomes 
after DCB treatment of SFA ISR are similar to those observed in the LEVANT2 clinical study, 
84.9% for DCB compared to 79.0% for control PTA.  
Restenosis is common after use of currently available devices. A safety OPG target of 69.0% is 
proposed for the safety endpoint by applying a 10% margin to the PTA event rates from the 
LEVANT 2 study. This is intended to reflect that these subjects may be at somewhat greater risk 
of previous need for stent placement. 

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15.5.4 SAFETY ENDPOINT: HYPOTHESIS TEST AND SAMPLE SIZE CALCULATION 
The primary safety endpoint is a composite of freedom from all-cause perioperative (≤30 day) 
death and freedom at 1 year from the following: index limb amputation (above and below the 
ankle) index limb re-intervention, and index-limb-related death.   
Objective:  To assess whether the proportion of Lutonix DCB subjects free from any safety 
event* is greater than the OPG target of 69% through 12 months post-index procedure. 
H0: The proportion of Lutonix DCB subjects free from safety events post-index 
procedure is less than or equal to the OPG of 0.69 (69%) at 12 months (H0: φDCB ≤ 
0.69).  
H1: The proportion of Lutonix DCB subjects free from safety events post-index 
procedure is greater than then OPG of 0.69 (69%) at 12 months (H1: φDCB > 0.69). 
* All-cause perioperative (≤30 day) death, index limb amputation (above or below the ankle), 
target limb reintervention, and target limb related death are safety events.  
The statistical analysis will be a one-sided exact binomial test assessed using a one-sided α=0.05 
based on the AT population.  The response variable in each subject will be the presence or 
absence of at least one safety event from the time following the index procedure through 12 
months.  A significant rejection of the null hypothesis with one-sided p-value less than 0.05 
indicates success for this endpoint.   
Sample Size Estimate:  The sample size estimation assumed the following: 
 The true 12 month proportion in the Test group is 84.9%  
 The Type 1 error,  = 0.05 (one-sided). 
 The Type 2 error,  = 0.10 (Power = 1 -  = 90%). 
 
The evaluable sample size required for 90% power is 79 DCB subjects.   While almost no 
missing data is expected for this endpoint, allowing for censoring of 10% of subjects, at least 88 
DCB subjects would be required.  Hence, the primary safety endpoint is not the sample size 
driver of the study.  
15.6 SECONDARY ENDPOINTS 
15.6.1 SECONDARY ENDPOINTS WITH DESCRIPTIVE STATISTICS 
The following secondary endpoints will have descriptive statistics estimated.  For each endpoint, 
the estimated mean and standard deviation or proportion and sample size will be calculated and 
reported.  For binary outcomes, the exact 95% confidence intervals for the rates will be provided 
for the 12 month endpoint.  In addition, descriptive statistics will also be estimated for the 
subsets of subjects with and without bailout stenting. 
Efficacy measurements of Device, Technical and Procedural Success will be assessed following 
the procedure. 

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Efficacy measurements of the following endpoints will be reported at 6, 12 and 24 Months: 
 
Primary and Secondary Patency  
 
Target Lesion Revascularization (TLR) 
o 
Clinically-driven 
o 
All TLR 
 
Sustained Clinical Benefit (improvement in Rutherford Class compared to baseline 
AND freedom from target vessel revascularization 
 
Change of Rutherford classification from baseline 
 
Change of resting Ankle Brachial Index (ABI) from baseline 
 
Change in Walking Impairment Questionnaire from baseline 
 
Change in quality of life from baseline, as measured by EQ-5D  
 
The following secondary safety endpoints will be reported: 
 Major vascular complications (≤30 day) 
The following endpoints will be reported at 1, 6, 12, 24, and 36 Months: 
 Composite Safety (criteria of the primary safety endpoint) 
 Death  
 Amputation (major and minor separately) 
 Target Vessel Revascularization (TVR)  
 Target Limb Reintervention  
Secondary Kaplan-Meier analyses may also be conducted.  These analyses will only be 
performed with the mITT population. 
 
 
 

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APPENDIX A:  DEFINITIONS 
Adverse Event 
An adverse event (AE) is defined as any untoward medical occurrence in a subject.  This 
definition does not imply that there is a relationship between the adverse event and the device 
under investigation.   
 
Adverse Device Effect  
An adverse device effect is any untoward and unintended response to a medical device.  
This definition includes any event resulting from insufficiencies or inadequacies in the 
instructions for use for preparation or deployment of the device.  It also includes any 
event that is a result of a user error. 
 
Anticipated Adverse Event  
Any undesirable health related experience occurring to a subject whether or not 
considered related to the investigational product(s) or drug regimen prescribed as part of 
the protocol, predefined in the protocol and/or Instructions For Use (IFU) that is 
identified or worsens during a clinical study. 
 
Serious Adverse Event (SAE)  
A SAE is an adverse event that:  
 led to death or led to a serious deterioration in the health of the subject  
 resulted in a life-threatening illness or injury, 
 resulted in a permanent impairment of a body structure or a body function, 
 required in-subject hospitalization or prolongation of existing hospitalization or 
 resulted in medical or surgical intervention to prevent permanent impairment to body 
structure or a body function  
 
Serious Adverse Device Effect (SADE) 
A SADE is an adverse device effect that has resulted in any of the consequences 
characteristic of a serious adverse event or that might have led to any of these 
consequences if suitable action had not been taken or intervention had not been made or 
if circumstances had been less opportune. 
 
Unanticipated Adverse Device Effect (UADE) 
A UADE is “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 (including a supplementary plan or application), or any 
other unanticipated serious problem associated with a device that relates to the rights, 
safety, or welfare of subjects” (21 CFR 812.3(s)). 

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Adverse Event Severity Stratification 
The Investigator will use the following definitions to rate the severity of each adverse 
event: 
 
Mild 
 
Awareness of a sign or symptom that does not interfere with the 
subject’s usual activity or is transient, resolved without treatment 
and with no sequelae. 
Moderate 
 
Interferes with the subject’s usual activity and/or requires 
symptomatic treatment. 
Severe 
 
Symptom(s) causing severe discomfort and significant impact of 
the subject’s usual activity and requires treatment. 
 
 
 
Relationship to study device 
The Investigator will use the following definitions to assess the relationship of the 
adverse event to the use of study device: 
 
Not Related 
 
The event is definitely not associated with device application.  
The adverse event is due to an underlying or concurrent illness or 
effect of another device or drug. 
Unlikely 
 
An adverse event has little or no temporal relationship to the 
study device and/or a more likely alternative etiology exists. 
Possible 
 
 
The temporal sequence between device application and the event 
is such that the relationship is not unlikely or subject’s condition 
or concomitant therapy could have caused the AE. 
Probable 
 
The temporal sequence is relevant or the event abates upon device 
application completion/removal or the Event cannot be 
reasonably explained by the subject’s condition. 
Highly 
Probable 
The temporal sequence is relevant and the event abates upon 
device application completion/removal, or reappearance of the 
event on repeat device application (re-challenge).   
 
 
 

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Relationship to study procedure 
The Investigator will use the following definitions to assess the relationship of the 
adverse event to the use of study procedure: 
 
Not Related 
 
The event is definitely not associated with procedure.  The 
adverse event is due to an underlying or concurrent illness or 
effect of another procedure. 
Unlikely 
 
An adverse event has little or no temporal relationship to the 
procedure and/or a more likely alternative etiology exists. 
Possible 
 
 
The temporal sequence between the procedure and the event is 
such that the relationship is not unlikely or subject’s condition or 
concomitant therapy could have caused the AE. 
Probable 
 
The temporal sequence is relevant or the event abates upon 
procedure completion or the Event cannot be reasonably 
explained by the subject’s condition. 
Highly 
Probable 
The temporal sequence is relevant and the event abates upon 
procedure completion, or reappearance of the event on repeat 
procedure (re-challenge).  
  
Abrupt or Acute Closure 
Angiographic documentation of significantly reduced flow due to mechanical dissection, 
thrombus or severe vessel spasm in the treatment area. 
All Cause Perioperative Death 
All-cause Perioperative Death is defined as death within 30 days of the index procedure. 
Amputation of the Index Limb 
Amputation includes all amputations including both Major Amputations (above the ankle) and 
Minor Amputations (including amputations below the ankle).  
Ankle Brachial Index Assessment   
Ankle systolic pressure/brachial systolic pressure, measured by constructing a ratio from the 
peak systolic pressure measured during the deflation of the ankle cuffs during Doppler detection 
to the systolic brachial pressure. 
As-Treated  
All ITT subjects that were treated with the LUTONIX® Drug Coated Balloon.  This may also be 
referred to as the Modified Intent-to-Treat (mITT) population.     
 
Binary Restenosis Rate 
The presence of a hemodynamically significant restenosis (>50%) as determined by angiography 
or by duplex ultrasound (defined by systolic velocity ratio≥2.5). 

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Bleeding Complications 
Bleeding will be classified per the TIMI definitions18 
Major 
Intracranial Hemorrhage 
≥ 5 g/dl decrease in the hemoglobin concentration 
≥ 15% absolute decrease in hematocrit 
Minor 
Observed blood loss: 
 
≥ 3 g/dl decrease in the hemoglobin concentration 
 
≥ 10% decrease in the hematocrit 
 
No observed blood loss: 
 
≥ 4 g/dl decrease in the hemoglobin concentration 
 
≥ 12% decrease in the hematocrit 
Minimal 
Any clinically overt sign of hemorrhage associated with a <3 g/dl 
decrease in the hemoglobin concentration or < 9% decrease in the 
hematocrit 
 
Clinically Driven Target Lesion Revascularization 
Revascularization at the target lesion with evidence of target lesion diameter stenosis >50% 
determined by duplex ultrasound or angiography and new distal ischemic signs (worsening ABI 
or worsening Rutherford Category associated with the target limb or due to clinical symptoms), 
OR revascularization of a target lesion with an in-lesion diameter stenosis of >70% by 
angiography, in the absence of the previously mentioned ischemic signs or symptoms. 
Clinically Driven Target Vessel Revascularization 
Revascularization of the target vessel with evidence of target vessel diameter stenosis >50% 
determined by duplex ultrasound or angiography and new distal ischemic signs (worsening ABI 
or worsening Rutherford Category associated with the target limb or due to clinical symptoms), 
OR revascularization of a target vessel with an in-lesion diameter stenosis of >70% by 
angiography, in the absence of the previously mentioned ischemic signs or symptoms. 
DUS Clinical Patency 
                                                     
18 Chesebro JH, Knatterud G, Roberts R et al.: Thrombolysis in Myocardial Infarction (TIMI) Trial, Phase I: a comparison 
between intravenous tissue plasminogen activator and intravenous streptokinase. Clinical findings through hospital discharge. 
Circulation 76,142–154 (1987). 

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Defined as patency of the target limb (based on a PSVR threshold < 2.5) without prior Clinically 
Driven TLR. 
Device Malfunction 
A malfunction is a failure of a device to meet its performance specifications or otherwise 
perform as intended. Performance specifications include all claims made in the labeling of the 
device. The intended performance of a device refers to the intended use for which the device is 
labeled or marketed. 
Device Success 
Device success is defined as, on a per device basis, the achievement of successful delivery and 
deployment of the study device(s) as intended at the intended target lesion, without balloon 
rupture or inflation/deflation abnormalities and a successful withdrawal of the study system. If a 
device is inserted into the subject but not used due to user error (e.g. inappropriate balloon length 
or transit time too long), this device will not be included in the device success assessment. 
Discharge 
The time point at which the subject was released from the admitting hospital or transferred to 
another facility. 
Dissections 
National Heart, Lung, and Blood Institute (NHLBI) Dissection Classification System:  
0:   None 
A.  Minor radiolucencies within the lumen during contrast injection with no persistence after dye 
clearance.  
B.   Parallel tracts or double lumen separated by a radiolucent area during contrast injection with 
no persistence after dye clearance. 
C.   Extraluminal cap with persistence of contrast after dye clearance from the lumen.  
D.   Spiral luminal filling defects.  
E.   New persistent filling defects.  
F.   Non-A-E types that lead to impaired flow or total occlusion.  
Note: Type E and F dissections may represent thrombus. 
 
Enrollment 
A patient is considered enrolled in the study after they have provided consent and have been 
treated or attempted to be treated with the study device. 
Intent-To-Treat (ITT) 
The principle of including outcomes of all subjects in the analysis who have signed the Informed 
Consent Form and are determined by the site to be suitable to receive treatment with the 
LUTONIX® Drug Coated Balloon or standard PTA. 
 

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Index Limb Related Death 
Any death adjudicated by the CEC as “likely related” to a complication of the index limb. 
Major Adverse Event (MAE)  
Events of death, amputation of the target limb, or target lesion revascularization (surgical or 
percutaneous 
Major Vascular Complications  
Hemorrhagic vascular complications included the following: 
 Haematoma at access site >5 cm 
 False aneurysm 
 AV fistula 
 Retroperitoneal bleed 
 Peripheral ischemia/nerve injury 
 Any transfusion required will be reported as a vascular complication unless clinical 
indication clearly other than catheterization complication 
 Vascular surgical repair 
Major Amputation 
Amputation of the lower limb above the ankle  
 
Minor Amputation 
Amputation of a part of the foot below the ankle. 
 
Patent Run-off 
At least one patent native outflow artery from the popliteal to the ankle, free from significant 
(≥50%) stenosis as confirmed by angiography or ultrasound that has not previously been 
revascularized. 
Per-Protocol (PP) 
All AT (mITT) subjects characterized by appropriate exposure to treatment (procedurally correct 
as pre-specified) and the absence of major protocol violations (including violations of entry 
criteria) that if not met for a given patient may obscure the evaluation of efficacy in that patient. 
Primary Patency 
Primary Patency is defined as Freedom from Clinically-Driven TLR and from Binary Restenosis.  
Binary restenosis is adjudicated by the independent, blinded core laboratory based on threshold 
Doppler PSVR ≥ 2.5 (together with waveform analysis & color mosaic appearance) or based on 
angiographic ≥ 50% diameter stenosis (if angiography is performed although not required per 
protocol). Clinically-Driven TLR is adjudicated by the CEC.  
Procedural success 

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Attainment of ≤30% residual stenosis in the treatment area by independent core lab analysis 
without major adverse events (defined as occurrence of death, amputation of the target limb or 
repeat revascularization of the target lesion) during the index procedure and through the hospital 
stay 
 
Popliteal Artery 
The vessel located between Hunter’s canal and the trifurcation. 
PSVR 
Peak Systolic Velocity Ratio 
 
Reference Vessel Diameter (RVD) 
The interpolated reference vessel diameter is based on a computed estimation of the original 
diameter of the artery at the level of the obstruction (minimal luminal diameter) 
Restenosis 
Either ≥50% restenosis of the diameter of the reference-vessel segment by QVA or peak systolic 
velocity ratio of ≥2.5, determined by blinded ultrasound and independent core lab analysis. 
Restenotic Lesion 
A lesion in a vessel segment that had undergone a prior percutaneous treatment 
Rutherford Categories  
Category 
Clinical Description 
0 
Asymptomatic, no hemodynamically significant occlusive disease 
1 
Mild Claudication 
2 
Moderate Claudication 
3 
Severe Claudication 
4 
Ischemic rest pain 
5 
Minor tissue loss, non-healing ulcer, or focal gangrene with diffuse pedal ischemia 
6 
Major tissue loss, extending above transmetatarsal level, functional foot no longer 
salvageable 
 
Screen Failures  
Subjects screened, but not meeting all study entry criteria and hence are not enrolled, are 
considered screening failures and will be documented as such on the Screening Logs. 
Secondary Patency 
Secondary Patency of the target lesion is defined as the absence of Binary Restenosis as 
adjudicated by the blinded, independent core laboratory, independent of whether or not patency 
is re-established via an endovascular procedure. Binary restenosis is based on threshold Doppler 

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PSVR ≥ 2.5 (together with waveform analysis & color mosaic appearance) or based on 
angiographic ≥ 50% diameter stenosis (if angiography is performed although not required per 
protocol). 
Stroke 
Clinical signs/symptoms of focal neurological deficit lasting longer than 24 hours. 
Target Lesion 
Lesion that is to be treated during the index procedure. 
Target Lesion Revascularization 
A repeat revascularization procedure (percutaneous or surgical) of the original target lesion site. 
Target Vessel Revascularization 
A repeat revascularization procedure (percutaneous or surgical) of a lesion in the target vessel. 
Target Vessel   
The entire vessel in which the target lesion is located. 
Technical Success 
Technical success of the balloon procedure is defined as the achievement of successful delivery 
and deployment of the study device(s) as intended at the intended target lesion and a successful 
withdrawal of the study system with the achievement of < 30% residual percent stenosis without 
deployment of a bail-out stent. 
 
Treatment Area 
The entire treated vessel segment in which angioplasty balloons were inflated (the injury 
segment) including the target lesion. 
Thrombosis 
A total occlusion documented by duplex ultrasound and/or angiography at the treatment site with 
or without symptoms Thrombosis may be categorized as acute (<1 day), subacute (1-30 days) 
and late (>30 days). The presence of thrombus at the target lesion must be noted as an adverse event in 
the eCRF. 
 
Transient Ischemic Attack (TIA) 
Clinical signs/symptoms of focal neurological deficit lasting up to 24 hours 
 
Walking Impairment Questionnaire (WIQ) 
A measure of subject-perceived walking performance for subjects with PAD and/or intermittent 
claudication. This questionnaire estimates walking distance, walking speed and stair climbing 
capacity. 

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Worsening of Ankle Brachial Index 
 A deterioration in the Ankle Brachial Index (ABI) by more than 0.15 from the maximum early 
post-procedural level. 
Worsening Rutherford Clinical Category 
A deterioration (an increase) in the Rutherford Category by more than 1 category from the 
earliest post-procedural measurement. 
 

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APPENDIX B:  SAMPLE WALKING IMPAIRMENT QUESTIONNAIRE 
 
 
 
 

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APPENDIX C:  SAMPLE EQ5D QUESTIONNAIRE 
 
By Placing a tick in one box in each group below, please indicate which statements best describe your 
own health state today 
 
Mobility 
 
I have no problems walking about 
 
 
 
 
 
 
I have some problems walking about 
 
 
 
 
 
 
I am confined to bed 
 
 
 
 
 
 
 
 
 
Self-Care 
 
I have no problems with self-care 
 
 
 
 
 
 
I have some problems with self-care 
 
 
 
 
 
 
I am unable to wash or dress myself 
 
 
 
 
 
 
 
Usual activities (e.g. work, study, housework, family or leisure activities) 
 
I have no problems with performing my usual activities  
 
 
 
I have some problems with performing my usual activities 
 
 
 
I am unable to perform my usual activities 
 
 
 
 
 
 
Pain/Discomfort 
 
I have no pain or discomfort 
 
 
 
 
 
 
 
I have moderate pain or discomfort 
 
 
 
 
 
 
I have extreme pain or discomfort 
 
 
 
 
 
 
 
Anxiety/Depression 
 
I am not anxious or depressed 
 
 
 
 
 
 
 
I am moderately anxious or depressed 
 
 
 
 
 
 
I am extremely anxious or depressed 
 
 
 
 
 
 
Patients own health state today  
 
 
 
 
 

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To help people say how good or bad a health state is, we  
Have drawn a scale (rather like a thermometer) on which 
The best state you can imagine is marked 100 and the worst 
State you can imagine is marked 0 
 
 
We would like you to indicate on this scale how good 
Or bad your own health is today, in your opinion.  Please 
Do this by drawing a line from the box below to whichever 
Point on the scale indicates how good or bad your health is  
today. 
 
 
 
 
 
Best 
imaginable 
health state 
100 
▬ 
9●0 
▬ 
8●0 
▬ 
7●0 
▬ 
6●0 
▬ 
5●0 
▬ 
4●0 
▬ 
3●0 
▬ 
2●0 
▬ 
1●0 
▬ 
 
0 
Worst 
imaginable 
health state 
 
Your own 
health state 
today 

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APPENDIX D:  SAMPLE INFORMED CONSENT FORM