ProspectIve, Randomized, SingLe-Blind, U.S. MuLti-Center Study to EvalUate TreatMent of Obstructive SupErficial Femoral Artery or Popliteal LesioNs With A Novel PacliTaxel-CoatEd Percutaneous Angioplasty Balloon Pivotal Post-Approval Study
Phase: NA
Conditions: Peripheral Artery Disease
Sponsor: Spectranetics Corporation

Protocol Number: D035940 
  ILLUMENATE Pivotal PAS 
Spectranetics 
PROTOCOL
_________________________________________________________________________________ 
Confidential 
Page 1 of 27 
ProspectIve, Randomized, SingLe-Blind, U.S. MuLti-Center Study to EvalUate 
TreatMent of Obstructive SupErficial Femoral Artery or Popliteal LesioNs With 
A Novel PacliTaxel-CoatEd Percutaneous Angioplasty Balloon 
ILLUMENATE Pivotal Post-Approval Study 
PROTOCOL 
Protocol Number:    
D035940 
Revision Date: 
14 April 2017 
Co-National Principal Investigators: 
Prakash Krishnan, MD 
Klingenstein Clinical Center 
 
 
 
 
Sean Lyden, MD 
Cleveland Clinic Foundation 
 
 
Angiographic Core Laboratory: 
BIDMC Angiographic Core Laboratory 
 
 
 
 
Duplex Ultrasound Core Laboratory: 
VasCore 
 
 
Sponsor: 
Spectranetics Corporation 
9965 Federal Drive 
Colorado Springs, CO 80921 USA 

Protocol Number: D035940 
 
  ILLUMENATE Pivotal PAS 
Spectranetics 
PROTOCOL 
_________________________________________________________________________________ 
Confidential 
 
Page 2 of 27 
 
 
TABLE OF CONTENTS 
PROTOCOL SIGNATURE PAGE ................................................................................................... 4 
SUMMARY OF CHANGES .............................................................................................................. 4 
PROTOCOL SUMMARY .................................................................................................................. 5 
1. 
Study Overview and Rationale .................................................................................................. 7 
1.1 
Background and Literature Review ...................................................................................... 7 
2. 
DESCRIPTION OF THE STELLAREX 0.035 DEVICE AND CONTROL DEVICE ........ 9 
2.1. 
Study Overview ................................................................................................................. 9 
2.2. 
Stellarex™ Device .................................................................................................................. 10 
Basic Catheter Specifications ...................................................................................................... 10 
Indications ................................................................................................................................... 10 
2.3. 
Control Device ....................................................................................................................... 10 
Basic Catheter Specifications ...................................................................................................... 10 
Indications ................................................................................................................................... 10 
3. 
STUDY DESIGN ....................................................................................................................... 11 
3.1. 
Primary Endpoints ................................................................................................................ 11 
Primary Effectiveness Endpoint .................................................................................................. 11 
Primary Safety Endpoint ............................................................................................................. 11 
3.2. 
Secondary Endpoints ............................................................................................................ 11 
3.3. 
Study Population ................................................................................................................... 11 
3.4. 
Ethical Considerations .......................................................................................................... 12 
3.5. 
Subject Discontinuation ........................................................................................................ 12 
3.6. 
Early Termination of the Clinical Trial .............................................................................. 13 
4. 
CONDUCT OF THE STUDY .................................................................................................. 13 
4.1. 
Subject Medication Management ........................................................................................ 13 
Subjects are required to be treated with ASA for the duration of the trial, (5 years) unless there 
is a contraindication to such.  Recommended ASA dose is 81 mg daily. ................................... 13 
4.2. 
Subject Follow-up .................................................................................................................. 13 
5. 
ADVERSE EVENTS ................................................................................................................. 14 
5.1. 
Adverse Events ...................................................................................................................... 14 
5.2. 
Anticipated Adverse Events ................................................................................................. 15 
5.3. 
Relationship to Study Device ................................................................................................ 17 
5.4. 
Relationship to Study Procedure ......................................................................................... 17 
5.5. 
Unanticipated Adverse Device Effect /Unanticipated Serious Adverse Device Effect .... 17 
6. 
STATISTICAL DESIGN AND ANALYSIS ........................................................................... 18 
6.1. 
Statistical Overview of the Trial .......................................................................................... 18 
6.2 
Analysis Populations ............................................................................................................. 19 
6.3 
Sample Size Justification ...................................................................................................... 19 
6.4 
Statistical Analyses ................................................................................................................ 20 
General Statistical Considerations ............................................................................................. 20 
Analyses of Primary Endpoint ..................................................................................................... 20 
Analysis of Secondary Endpoints ................................................................................................ 21 
Protection Against False Discovery ............................................................................................ 21 
6.5 
Blinding .................................................................................................................................. 21 
7. 
RISK ASSESSMENT ................................................................................................................ 21 

Protocol Number: D035940 
 
  ILLUMENATE Pivotal PAS 
Spectranetics 
PROTOCOL 
_________________________________________________________________________________ 
Confidential 
 
Page 3 of 27 
 
7.1. 
Potential Risks from Peripheral Catheterization, Stenting and PTA .............................. 21 
7.2. 
Potential Risks from Paclitaxel Coating .............................................................................. 22 
7.3. 
Risk Management Procedure ............................................................................................... 22 
7.4. 
Potential Benefits ................................................................................................................... 22 
8. 
DATA HANDLING, RECORD KEEPING AND REPORTING ......................................... 22 
8.1. 
Case Report Form (CRF) Completion ................................................................................ 22 
8.2. 
Source Documentation .......................................................................................................... 23 
8.3. 
Reports ................................................................................................................................... 23 
9. 
REGULATORY REQUIREMENTS ...................................................................................... 23 
9.1. 
Investigator’s Responsibility ................................................................................................ 23 
9.2. 
Compliance with Protocol and Protocol Amendments ...................................................... 23 
9.3. 
Investigator Requirements ................................................................................................... 24 
9.4. 
Institutional Requirements ................................................................................................... 24 
9.5. 
Subject Informed Consent .................................................................................................... 24 
9.6. 
Use of Information and Publication ..................................................................................... 25 
9.7. 
Reporting Requirements ....................................................................................................... 25 
10. 
SPONSOR RESPONSIBILITIES COMPLIANCE/QUALITY ASSURANCE.............. 26 
10.1. Role of Sponsor ...................................................................................................................... 26 
General Duties ............................................................................................................................ 26 
Training of Investigator and Site Personnel and Monitoring ..................................................... 26 
Documentation ............................................................................................................................ 26 
10.2. Committees ............................................................................................................................. 26 
Clinical Events Committee .......................................................................................................... 26 
Data Safety Monitoring Board .................................................................................................... 27 
11. 
TRIAL TERMINATION ...................................................................................................... 27 
12. 
APPENDICES ....................................................................................................................... 27 
 
• 
Appendix A:  Bibliographical References 
• 
Appendix B:  Helsinki Declaration  
• 
Appendix C:  Trial Abbreviations and Definitions 
• 
Appendix D:  Rutherford-Becker Classification Guidelines 
• 
Appendix E:  ABI Guidelines  
• 
Appendix F:  Walking Impairment Questionnaire Guidelines  
• 
Appendix G:  6 Minute Walking Test Instructions 
• 
Appendix H:  EQ-5D Instructions 
• 
Appendix I:  Investigator Responsibilities 
 
 

Protocol Number: D035940 
 
  ILLUMENATE Pivotal PAS 
Spectranetics 
PROTOCOL 
_________________________________________________________________________________ 
Confidential 
 
Page 4 of 27 
 
PROTOCOL SIGNATURE PAGE 
 
ILLUMENATE Pivotal Post-Approval Study:    
ProspectIve, Randomized, SingLe-Blind, U.S. MuLti-Center Study to EvalUate 
TreatMent of Obstructive SupErficial Femoral Artery or Popliteal LesioNs With 
A Novel PacliTaxel-CoatEd Percutaneous Angioplasty Balloon 
 
 
I have reviewed this protocol and agree to adhere to the requirements and responsibilities listed 
herein.  I am trained to the contents of this protocol, percutaneous angioplasty procedures, and the 
specific use of the devices listed in this protocol.  I will ensure that the study is conducted in 
compliance with the protocol, Instructions for Use, Good Clinical Practices, Declaration of Helsinki 
and all applicable regulatory requirements.  
 
 
_______________________________ 
 
 
_____________________ 
Site Investigator Signature 
 
 
 
 
Date 
 
 
 
_______________________________ 
 
Site Investigator Printed Name 
 
 
SUMMARY OF CHANGES 
Revision 
Level  
Change 
Order 
Description of Changes 
A  
 
Initial Release 
 

Protocol Number: D035940 
 
  ILLUMENATE Pivotal PAS 
Spectranetics 
PROTOCOL 
_________________________________________________________________________________ 
Confidential 
 
Page 5 of 27 
 
 PROTOCOL SUMMARY 
Device 
Stellarex™ 0.035” Over-the-Wire (OTW) Drug-Coated Balloon (DCB) (Stellarex DCB) 
Control  
Bare Percutaneous Transluminal Angioplasty (PTA) Balloon Catheter (bare balloon 
catheter)) 
Study Objective To continue evaluate the long-term safety and effectiveness of the Stellarex DCB 
Study Design 
Continued follow-up of premarket ILLUMENATE Pivotal Study subjects 
Number of 
Subjects 
300 subjects from the ILLUMENATE Pivotal study.  
200 DCB subjects 
100 PTA subjects   
Number of Sites 43 
Primary 
Effectiveness 
Endpoint 
Patency at 24 months post-procedure.  Patency is defined as the absence of target lesion 
restenosis as determined by duplex ultrasound (Peak Systolic Velocity Ratio (PSVR) ≤ 
2.5) and freedom from clinically-driven target lesion revascularization. 
Primary Safety 
Endpoint 
Freedom from device and procedure-related death through 30 days post-procedure and 
freedom from target limb major amputation and clinically-driven target lesion 
revascularization through 24 months post-procedure. 
Secondary 
Endpoints 
• Major adverse event (MAE) rate at 24, 36, 48 and 60 months post-procedure, defined 
as a composite rate of cardiovascular death, target limb major amputation and 
clinically-driven target lesion revascularization (TLR).  
• Rate of clinically-driven target lesion revascularization at 24, 36, 48 and 60 months. 
• Rate of target lesion revascularization at 24, 36, 48 and 60 months. 
• Rate of clinically-driven target vessel revascularization at 24 and 36, 48 and 60 
months. 
• Rate of target limb major amputation at 24, 36, 48 and 60 months. 
• Mortality rate at 24, 36, 48 and 60 months. 
• Rate of occurrence of arterial thrombosis of the treated segment at 24, 36, 48 and 60 
months. 
• Patency rate at 24 and 36 months, defined as the absence of target lesion restenosis as 
determined by duplex ultrasound (PSVR ≤ 2.5) and freedom from clinically-driven 
TLR 
• Change in ankle-brachial index (ABI) from pre-procedure to 24 and 36 months. 
• Change in walking impairment questionnaire (WIQ) from pre-procedure to 24 and 36 
months.   
• Change in walking distance from pre-procedure to 24 and 36 months. 
• Change in Rutherford-Becker classification from pre-procedure to 24 and 36 months. 
• Change in EQ-5D from pre-procedure to 24 and 36 months. 
Follow-Up 
Schedule 
• Office visits will occur at 24 and 36 months post-procedure to review medication 
compliance, clinical assessments, functional status, adverse events and patency by 
duplex ultrasound.  

Protocol Number: D035940 
 
  ILLUMENATE Pivotal PAS 
Spectranetics 
PROTOCOL 
_________________________________________________________________________________ 
Confidential 
 
Page 6 of 27 
 
• Telephone contact will occur at 48 and 60 months post-procedure to review 
medication compliance and adverse events. Office visits are optional for these 
assessments. 
Planned  
Schedule 
• Last subject last contact: 2020 
 
 

Protocol Number: D035940 
 
  ILLUMENATE Pivotal PAS 
Spectranetics 
PROTOCOL 
_________________________________________________________________________________ 
Confidential 
 
Page 7 of 27 
 
1. 
STUDY OVERVIEW AND RATIONALE 
1.1 Background and Literature Review 
Peripheral arterial disease (PAD), atherosclerosis in vessels outside of the heart and brain, is a 
common ailment affecting an estimated 27 million adults in Europe and North America and is 
associated with significant morbidity and mortality.1  Peripheral arterial disease is associated with 
significant reduction in health-related quality of life, and in extreme cases, the disease can result in 
debilitating symptoms (including loss of limbs).  Total disease prevalence has been estimated at 
between 3% and 10%, increasing to 15% to 20% in patients over 70 years.2  Only approximately 
25 percent of patients undergo treatment for the disease.3  Deterioration or progression of PAD 
occurs in one-third to one-fourth of all patients.4  One to five percent will eventually require 
amputation.4-6  
Peripheral arterial disease is associated with substantial morbidity and reduced health status 
measures.  The most common symptom of PAD is difficulty walking (intermittent claudication); 
less common is critical limb ischemia (CLI) which includes severe persistent rest pain requiring 
treatment with analgesics, ulceration or gangrene on the distal extremity.  Lower extremity arterial 
disease can lead to reduced mobility, limb pain, gangrene, and amputation, as well as increased 
mortality.2,7,8  Physical function, pain, and general health perception is similar or worse than in 
patients with congestive heart failure or recent myocardial infarction.  In addition, patients with 
PAD generally also present with cardiovascular disease (CVD), which may explain the increased 
risk of mortality from myocardial infarction (MI) and stroke,7,9,10 with mortality rates at five years 
ranging from 30% to 44%.11,12  
The superficial femoral artery (SFA) is the most commonly diseased artery in the peripheral (lower 
limb) vasculature, with PAD presenting as intermittent claudication.  Patients with intermittent 
claudication report increased pain and limitations in physical functioning compared with published 
norms, which are expected based on the nature of their disease.  They also report significant 
deficits in energy, emotional reactions, sleep, and normal activities of daily living due to emotional 
stress.  These limitations have been reported to occur at a relatively low level of exercise.4-6  
Available therapies for patients with PAD include: risk factor modification, including diabetes 
control, smoking cessation, and hyperlipidemia control; exercise therapy; pharmacological 
therapy; and surgical or endovascular revascularization.  Risk factor modification therapy is 
recommended to improve claudication and decrease the morbidity and mortality associated with 
the progression of PAD.2,13  Exercise therapy can produce clinical improvements in walking ability 
and reductions in claudication pain.2,13-15   Pharmacological options include antiplatelet and 
anticoagulant therapies.16-18  Surgery is typically reserved for patients with critical limb ischemia 
and is associated with risks such as wound complications, death, MI, infection and leg edema.18,19  
Patency rates at 1 year for surgical revascularization of the lower extremities have been reported to 
be 40-80%.20-22 
Multiple published studies report on the short and long-term results of performing percutaneous 
angioplasty interventions (including PTA without a drug coating) and/or stenting for PAD.  
Patency rates at 1 year have been reported to range between 29-93%.23-42  A meta-analysis of PTA 
to treat SFA lesions up to 15 cm in length reported a 12-month primary patency rate of only 33%.43  
Treatment with bare metal self-expanding stents yields higher but variable 1-year patency rates 

Protocol Number: D035940 
 
  ILLUMENATE Pivotal PAS 
Spectranetics 
PROTOCOL 
_________________________________________________________________________________ 
Confidential 
 
Page 8 of 27 
 
that range between 52%44 and 81%.45   
Restenosis remains a major limitation of the clinical usefulness of PTA and stenting.  Poor long-
term results, especially after the treatment of longer lesions in the femoropopliteal region, have 
been reported.46-52  Paclitaxel is an antineoplastic drug that has demonstrated sustained inhibition 
of smooth muscle cell proliferation in several pre-clinical studies.53-56  Publications related to 
effectiveness of local administration of paclitaxel on restenosis through use of drug-coated 
balloons in the femoropopliteal artery have highlighted promising results with reduction of 
neointimal proliferation in the peripheral arteries.57-60 
Cassese et al. conducted a systematic meta-analysis of 4 randomized trials comparing paclitaxel 
drug-coated balloon (DCB) angioplasty to uncoated balloon (PTA) angioplasty.61 The primary 
endpoint was target lesion revascularization, with angiographic binary restenosis, late lumen loss, 
and all-cause mortality as secondary endpoints. The studies in the meta-analysis included 
THUNDER,57 FemPac,58 PACIFIER,62 and the LEVANT I study.60 The meta-analysis included 
381 patients with a median follow-up time of 10.3 months. The rate of TLRs was significantly 
lower in the patients treated with DCB (12.2%) in comparison to PTA (27.7%), with an odds ratio 
of 0.23 (95% confidence interval: 0.13 – 0.40, p<0.00001). The authors concluded that DCB 
therapy has superior antirestenotic efficacy with no evidence of a differential safety profile.  
The IN.PACT SFA trial, a multi-center, randomized study comparing the IN.PACT Admiral DCB 
(n=220) to the uncoated control balloon (n=111) in patients with femoropopliteal PAD, showed 
significantly higher primary patency for the DCB group (82.2%) vs. control (52.4%; P<0.001) at 
12 months and at 24 months (78.9% vs. 50.1%; P<0.001).59,63  Clinically-driven TLR rates at 12 
months were 2.4% for the DCB group vs. 20.6% for control (P<0.001) and at 24 months were 
9.1% vs. 28.3% (P<0.001), respectively.59,63  A recent presentation at Vascular Interventional 
Advances (VIVA) in 2016 showed that the benefits of DCB over PTA were maintained out to 3 years with 
primary patency of 69.5% vs. 45.1% and CD TLR rates of 15.2% vs. 31.1% for the DCB vs. PTA group.64 
The Lutonix DCB was also evaluated in a multi-center, randomized trial in comparison to an 
uncoated control PTA balloon, with 316 DCB subjects and 160 PTA subjects.  The results at 12 
months showed significantly better primary patency for the DCB group (65.2%) in comparison to 
the PTA group (52.6%; p=0.02), with similar rates of target lesion revascularizations (12.3% DCB 
vs. 16.8% PTA).65  
The Stellarex DCB has been studied in several clinical studies.  The initial experience included a 
prospective, multi-center, single arm clinical study performed in Europe, referred to as the 
ILLUMENATE First-in-Human (FIH) study.  The objective of the study was to evaluate the safety 
and inhibition of restenosis of the Stellarex DCB for treatment of de novo or restenotic superficial 
femoral artery (SFA) or popliteal arteries. The first fifty (50) subjects were treated with pre-
dilatation prior to treatment with the Stellarex DCB (Cohort 1) and the second thirty (30) subjects 
were treated without the pre-dilatation step (Cohort 2). 
The results from Cohort 1 (with pre-dilatation) showed that the primary endpoint of LLL at 6 
months (mean LLL 0.54±0.97mm; 95% confidence interval: 0.28 to 0.81mm), as assessed by the 
angiographic core laboratory, was significantly less than the objective performance criterion 
(1.1mm).66 The major adverse event (MAE) rate at 6 months, defined as a composite rate of 
cardiovascular death, index limb amputation, and CD TLR, was 4.0% (95% confidence interval: 

Protocol Number: D035940 
 
  ILLUMENATE Pivotal PAS 
Spectranetics 
PROTOCOL 
_________________________________________________________________________________ 
Confidential 
 
Page 9 of 27 
 
0.5 to 13.7%), which was significantly lower than the pre-specified objective performance criterion 
(30%).66 The study endpoints were met. The primary patency rate, defined as PSVR ≤ 2.5 without 
a CD TLR, was 89.5% at 12 months and 80.3% at 24 months (based on the Kaplan-Meier 
analysis). The freedom from CD TLR Kaplan-Meier rate was 90.0% at 12 months and 85.8% at 24 
months.66 Additionally, there were no amputations or cardiovascular deaths reported through 24 
months. 
The 2-year results from Cohort 2 (Direct Cohort) were presented at Vascular Interventional 
Advances (VIVA) in 2015.67 Twenty-eight subjects with 37 lesions were included in the Cohort 2 
analysis; 2 subjects were excluded because they were pre-dilated. The mean lesion length was 
6.4cm and calcification was present in 48.6% of lesions. At 6 months, the mean LLL was 0.03mm. 
The MAE rate was 14.8% at 12 months and 18.5% at 24 months, primarily driven by CD TLRs. 
There was 1 index limb amputation observed within 6 months in conjunction with lower limb 
vessel thrombosis in a subject who had a stent placed during the procedure. The primary patency 
rate (per Kaplan-Meier analysis) was 86.2% at 12 months and 78.2% at 24 months, similar to the 
rates observed in the pre-dilatation cohort (Cohort 1). The freedom from CD TLR Kaplan-Meier 
rate was 85.4% at 12 months and 81.7% at 24 months.67 
The 12-month results from the 2 randomized, controlled trials studying the Stellarex DCB in 
comparison to PTA control devices have also been presented at scientific meetings.  Primary 
patency at 12 months was 83.9% vs. 60.6% in the ILLUMENATE EU RCT study (p<0.001) and 
76.3% vs. 57.6% in the ILLUMENATE Pivotal study (p=0.003).68,69  The CD TLR rates were also 
favourable for the Stellarex DCB in both studies (5.9% vs. 16.7% in the ILLUMENATE EU RCT 
study and 7.9% vs. 16.8% in the ILLUMENATE Pivotal study).68,69  The primary safety endpoint, 
defined as a composite of freedom from device and procedure-related death through 30 days and 
freedom from target limb major amputation and CD TLR through 12 months, was also superior for 
the Stellarex DCB in comparison to PTA in both studies (94.1% vs. 83.3% through 395 days in the 
ILLUMENATE EU RCT study and 92.1% vs. 83.2% through 410 days in the ILLUMENATE 
Pivotal study [p=0.001]).68,69 
Numerous other drug-coated catheter systems using similar technology to that used in the 
ILLUMENATE Pivotal Study are currently commercially available. The Bard Lutonix drug-coated 
balloons and the Medtronic IN.PACT Admiral paclitaxel-coated balloons are commercially 
available through CE Mark approval and Food and Drug Administration approval. Other CE 
Marked drug-coated balloons include, but may not be limited to, the Freeway balloon (Eurocor 
GmbH, Bonn, Germany), the Passeo-18 Lux balloon (Biotronik), the Legflow OTW paclitaxel-
coated balloon (Cardionovum GmbH), Advance 18 PTX (Cook Medical), Luminor35 (iVascular), 
and the Elutax SV (Aachen Resonance GmbH). 
2. 
DESCRIPTION OF THE STELLAREX 0.035 DEVICE AND CONTROL DEVICE 
2.1. Study Overview 
The ILLUMENATE Pivotal PAS is a continued follow-up study which will include 300 subjects 
from forty-three (43) sites across the United States and Austria previously enrolled in the 
ILLUMENATE Pivotal pre-market study to evaluate the Stellarex DCB compared to the PTA 
control device for the treatment of de-novo or post-PTA occluded/stenotic or reoccluded/restenotic 
(except for in-stent) SFA and/or popliteal arteries. 

Protocol Number: D035940 
 
  ILLUMENATE Pivotal PAS 
Spectranetics 
PROTOCOL 
_________________________________________________________________________________ 
Confidential 
 
Page 10 of 27 
 
2.2. Stellarex™ Device 
The Stellarex DCB is a commercially available PTA balloon catheter (EverCross™ 0.035” PTA 
Balloon Catheter, Medtronic, Plymouth, MN 55441, USA) coated with paclitaxel using a 
proprietary carrier.   
Basic Catheter Specifications 
•  Guidewire: 0.035”            
•  Balloon Length: 40/80/120 mm   
•  Sheath Compatibility: greater than or equal to 6 French 
•  Balloon Diameter: 4/5/6 mm  
•  Shaft length: 135 cm  
The nominal dose density of paclitaxel on the Stellarex DCB is 2.0 µg/mm2.  The nominal dose 
of paclitaxel on a specific Stellarex DCB is listed in Table 1.   
Table 1:  Nominal Paclitaxel Dose (µg) per Catheter Length/Diameter 
Balloon Diameter 
(mm) 
Balloon Length (mm) 
40 
80 
120 
4 
1124 µg 
2211 µg 
3307 µg 
5 
1335 µg 
2636 µg 
3880 µg 
6 
1619 µg 
3174 µg 
4721 µg 
 
Indications 
The Stellarex 0.035” OTW Drug-coated Angioplasty Balloon is indicated for percutaneous 
transluminal angioplasty (PTA), after appropriate vessel preparation, of de novo or restenotic 
lesions up to 180 mm in length in native superficial femoral or popliteal arteries with reference 
vessel diameters of 4-6 mm. 
 
2.3. Control Device 
The control device is a commercially available PTA balloon catheter (EverCross™ 0.035 PTA 
Balloon Catheter, Medtronic, Plymouth, MN 55441, USA).   
Basic Catheter Specifications 
•  Guidewire: 0.035”            
•  Balloon Length: 40/80/120 mm   
•  Sheath Compatibility: greater to or equal to 6 French 
•  Balloon Diameter: 4/5/6 mm  
•  Shaft length: 135 cm  
Indications 
The EverCross Balloon Catheter is intended to dilate stenosis in the iliac, femoral, ilio-femoral, 
popliteal, infra-popliteal, and renal arteries, and to treat obstructive lesions of native or 
synthetic arteriovenous dialysis fistulae.  This device is also indicated for stent post-dilation in 

Protocol Number: D035940 
 
  ILLUMENATE Pivotal PAS 
Spectranetics 
PROTOCOL 
_________________________________________________________________________________ 
Confidential 
 
Page 11 of 27 
 
the peripheral vasculature.  For additional information refer to the EverCross Instructions for 
Use. 
 
3. 
STUDY DESIGN 
The objective of this continued follow-up of ILLUMENATE Pivotal Study subjects is to 
demonstrate the long term safety and effectiveness of the Stellarex DCB. 
Each enrolled subject will be followed for 5 years (60 months) after treatment.  A follow-up office 
visit will occur at 24 and 36 months.  A follow-up telephone contact or an optional office visit will 
occur at 48 and 60 months.   
3.1. Primary Endpoints 
Primary Effectiveness Endpoint 
The primary effectiveness endpoint for this study is patency at 24 months post-procedure.  Patency is 
defined as the absence of target lesion restenosis as determined by duplex ultrasound (Peak Systolic 
Velocity Ratio (PSVR) ≤ 2.5) and freedom from clinically-driven target lesion revascularization.  
Primary Safety Endpoint 
The primary safety endpoint for this study is freedom from device and procedure-related death 
through 30 days post-procedure and freedom from target limb major amputation and clinically-
driven target lesion revascularization through 24 months post-procedure. 
3.2. Secondary Endpoints 
The following endpoints will be also evaluated as secondary endpoints: 
• Major adverse event (MAE) rate at 24, 36, 48 and 60 months post-procedure, defined as a 
composite rate of cardiovascular death, target limb major amputation and clinically-driven target 
lesion revascularization (TLR).  
• Rate of clinically-driven target lesion revascularization at 24, 36, 48 and 60 months. 
• Rate of clinically-driven target vessel revascularization at 24 and 36, 48 and 60 months. 
• Rate of target limb major amputation at 24, 36, 48 and 60 months. 
• Mortality rate at 24, 36, 48 and 60 months. 
• Rate of occurrence of arterial thrombosis of the treated segment at 24, 36, 48 and 60 months. 
• Patency rate at 24 and 36 months, defined as the absence of target lesion restenosis as 
determined by duplex ultrasound (PSVR ≤ 2.5) and freedom from clinically-driven TLR 
• Change in ankle-brachial index (ABI) from pre-procedure to 24 and 36 months. 
• Change in walking impairment questionnaire (WIQ) from pre-procedure to 24 and 36 months.   
• Change in walking distance from pre-procedure to 24 and 36 months. 
• Change in Rutherford-Becker classification from pre-procedure to 24 and 36 months. 
• Change in EQ-5D from pre-procedure to 24 and 36 months. 
3.3. Study Population  
Subjects included in this study will be comprised of subjects enrolled in the ILLUMENATE Pivotal 
pre-market study.  Three hundred subjects with documented symptomatic superficial femoral and/or 

Protocol Number: D035940 
 
  ILLUMENATE Pivotal PAS 
Spectranetics 
PROTOCOL 
_________________________________________________________________________________ 
Confidential 
 
Page 12 of 27 
 
popliteal artery disease who were eligible to be treated by interventional therapy and met all of the 
inclusion criteria and none of the exclusion criteria of the Pivotal study were enrolled.  
3.4. Ethical Considerations 
The trial will be conducted in accordance with the ethical principles that have their origin in the 
Declaration of Helsinki and are consistent with the International Conference on Harmonization Good 
Clinical Practices (ICH GCP), 21 Code of Federal Regulations (CFR) Parts 50, 54, 56, 812 and 814, 
International Organization for Standardization (ISO) 14155 [European Union (EU) only], and other 
applicable regulatory requirements. 
3.5. Subject Discontinuation 
Every subject should remain in the trial until completion of the required follow-up period; however, 
a subject’s participation in any clinical trial is voluntary and the subject has the right to withdraw at 
any time without penalty or loss of benefit.  Whenever possible, the investigator should obtain 
written documentation from the subject that wishes to withdraw their consent for future follow-up 
visits and contact.  The reason for withdrawal, when it occurs, must be documented in the subject’s 
medical records.  Prior to study discontinuation, it is recommended that a final visit occur to assess 
clinical status, adverse events and current medications.  The subject will be followed per the 
institution’s standard of care.  Reasons for discontinuation may include, but are not limited to, the 
following: 
• The investigator terminates the subject’s participation if discontinuation in the study is 
deemed medically necessary. 
• The subject does not complete the scheduled follow-up but has not ‘officially’ withdrawn 
from the trial (e.g. “lost to follow-up”).  This does not apply to missed visits.   
• The subject develops medical conditions such as the following: 
o Reaction to acute treatment requires alternative treatment or intervention (e.g. allergic 
reaction to paclitaxel, complication with non-study device) where study objectives 
cannot be objectively evaluated. 
o Unanticipated hospitalization requiring treatment or therapy conflictive with study 
objectives and preventing compliance with study requirements.  
Site personnel should make all reasonable efforts to locate and communicate with subjects at each 
contact time point.  A minimum of two telephone calls to contact the subject should be recorded in 
the source documents, including date, time, and initials of site personnel trying to make contact.  If 
these attempts are unsuccessful, a letter should be sent to the subject.  If the subject misses two 
consecutive scheduled contact time points and the above mentioned attempts at communicating with 
the subject are attempted but unsuccessful, the subject will be considered “lost to follow-up”.  
A study exit form must be completed when a) the subject successfully completes the study, b) the 
subject is considered “lost to follow-up” (per the above criteria), c) the subject withdraws from the 
study d) the investigator withdraws the subject from the study or e) the subject dies.  In each case of 
subject discontinuation, the Sponsor must be notified of the reason for subject discontinuation.  The 
site will provide this information on the case report form (CRF) and in the source documents.  
Withdrawn subjects will not be replaced in this trial. 

Protocol Number: D035940 
 
  ILLUMENATE Pivotal PAS 
Spectranetics 
PROTOCOL 
_________________________________________________________________________________ 
Confidential 
 
Page 13 of 27 
 
3.6. Early Termination of the Clinical Trial 
Spectranetics, the trial Sponsor, reserves the right to discontinue the clinical study at any stage, with 
suitable written notice to the investigator.  The investigator may also discontinue participation in the 
clinical trial with suitable written notice to the Sponsor.  
 Notification of suspension or termination will occur no later than five (5) business days after the 
sponsor makes the determination.  In the event of study suspension or termination, the sponsor will 
send a report outlining the circumstances to the IRBs/ECs and all investigators.  A suspended or 
terminated study may not be re-initiated without approval of the reviewing IRB/EC (where 
applicable).  The investigator should follow subjects as standard of care at the institution. 
 
4. 
CONDUCT OF THE STUDY 
4.1. Subject Medication Management 
Subjects are required to be treated with ASA for the duration of the trial, (5 years) unless there is a 
contraindication to such.  Recommended ASA dose is 81 mg daily. 
The medication history will be updated as needed to include modifications to the anticoagulants, 
anti-platelets and statins following the procedure. 
4.2. Subject Follow-up  
Subjects will be followed at pre-determined time points during the study as summarized in the 
Schedule of Events in Table 2. 
 

Protocol Number: D035940 
 
  ILLUMENATE Pivotal PAS 
Spectranetics 
PROTOCOL 
_________________________________________________________________________________ 
Confidential 
 
Page 14 of 27 
 
Table 2:  Schedule of Events: 24 Months through 60 Months 
EVENT 
24 Months 
36 Months 
48  Months 
60 Months 
Unscheduled* 
Re-
intervention* 
Visit Window 
730 ± 45 days 
1095 ± 45 
days 
1460 ± 45 
days 
1825 ± 45 
days 
As clinically 
indicated 
As clinically 
indicated 
Visit Type 
Office 
Office 
Phone 
Phone 
Office 
Office 
Anticoagulants, 
Antiplatelets, and 
Statins 
 
 
 
 
 
 
Peripheral Angiogram 
with Runoff 
 
 
 
 
 
 
Duplex Ultrasound 
Examination 
 
 
 
 
 
 
Ankle-Brachial Index 
 
 
 
 
 
 
Rutherford-Becker 
Classification 
 
 
 
 
 
 
6-Minute Walking Test  
 
 
 
 
 
 
WIQ 
 
 
 
 
 
 
EQ-5D 
 
 
 
 
 
 
Health Economic 
Evaluation 
 
 
 
 
 
 
Adverse Events 
 
 
 
 
 
 
* NOTE: While an attempt should be made to collect all non-invasive testing at unscheduled visits or re-
interventions, a protocol deviation will not be required if all assessments are not completed. For re-interventions, 
the angiogram and duplex ultrasound should be completed per the respective core laboratory guidelines. 
 
 
5. 
ADVERSE EVENTS 
5.1. Adverse Events 
At each evaluation, the investigator will determine whether any adverse events (AEs) have occurred.  
For the purposes of this protocol, an adverse event is any untoward medical occurrence in a study 
subject which occurs or worsens, whether or not considered related to the study device, study 
procedures, or study requirements. 
Serious adverse events (SAEs) are any untoward medical occurrence that results in death, is life-
threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in 
persistent or significant disability/incapacity, requires medical/surgical intervention to prevent life-
threatening illness or injury or to prevent permanent impairment of a body structure or function, or is 
a congenital anomaly/birth defect.  Emergency room visits lasting less than 24 hours are not 

Protocol Number: D035940 
 
  ILLUMENATE Pivotal PAS 
Spectranetics 
PROTOCOL 
_________________________________________________________________________________ 
Confidential 
 
Page 15 of 27 
 
considered SAEs.   
Major adverse events (MAEs) include cardiovascular death, target limb major amputation and 
clinically-driven target lesion revascularizations. Refer to Appendix C for definitions. 
Subjects should be encouraged to report AEs spontaneously or in response to general, non-directed 
questioning.  Additionally, subjects should be instructed to contact the investigator if any SAEs 
occur between study visits.  If it is determined that an AE has occurred, the investigator should 
obtain all the information required to complete the AE CRF. The sponsor may request AE source 
documentation from the site to facilitate adjudication of AEs.  
Adverse event reporting began when the subject was enrolled in the ILLUMENATE Pivotal study.  
All SAEs and MAEs are to be captured and reported to the sponsor via the AE CRF within 10 
business days of the investigator learning of the event in the US, and within 3 business days in the 
EU.  The site should not wait for full details to make the initial report to the sponsor.  The site is 
responsible for reporting AEs to the IRB/EC according to the board’s reporting guidelines.  
For each AE the following should be documented on the appropriate CRF: start date of the event, 
treatment, resolution, assessment of seriousness, relationship to the study device and relationship to 
the study procedure.  Adverse events should be followed to resolution or stabilization. 
Adverse events that are present at the end of a subject’s participation in the study should be marked 
as on-going on the CRF and the subject should receive post-treatment follow-up as appropriate and 
standard of care at the institution.  All adverse events from enrollment in the ILLUMENATE Pivotal 
study through completion of this post-approval study will be reported. 
5.2. Anticipated Adverse Events 
An anticipated adverse event is any untoward medical occurrence in 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 Instruction for Use that is identified or worsens during a 
clinical study.  
The following is a list of adverse events that may result from the PTA procedure.  
 
• Abnormal heart rhythms during the 
procedure 
• Hemorrhage 
• Abrupt closure  
• Hypertension  
• Allergic reaction to contrast, concomitant 
medications  
• Hypotension  
• Amputation  
• Injury to the groin blood vessel  
• Aneurysm 
• Infection or pain at insertion site  
• Arrhythmias (bradycardia & tachycardia)  
• Inflammation 
• Arterial dissection  
• Ischemia  
• Arterial perforation or rupture  
• Leucopenia  
• Artery spasm  
• Lymphocele 
• Arteriovenous (AV) fistula  
• Myocardial Infarction  
• Bleeding  
• Nausea  

Protocol Number: D035940 
 
  ILLUMENATE Pivotal PAS 
Spectranetics 
PROTOCOL 
_________________________________________________________________________________ 
Confidential 
 
Page 16 of 27 
 
• Bypass graft surgery (emergent or non-
emergent)  
• Pseudoaneurysm  
• Chest pain  
• Renal failure  
• Coagulopathy  
• Respiratory failure 
• Congestive heart failure  
• Restenosis  
• Death (cardiovascular or non-
cardiovascular related) 
• Sepsis  
• Discomfort during the procedure  
• Seizure  
• Distal emboli  
• Shock 
• Embolism/PTA catheter embolism  
• Stroke/cerebrovascular accident (CVA)  
• Endocarditis 
• Wound complication or wound infection  
• Femoral nerve compression with 
associated neuropathy 
• Thrombocytopenia  
• Fever  
• Thrombosis  
• Groin area bruising 
• Total occlusion  
• Hematoma 
• Unstable/stable angina 
 
The following is a list of theoretical adverse events that may result from the addition of paclitaxel 
to a PTA catheter: 
 
• Abdominal pain  
• Leucopenia  
• Abnormal liver function test  
• Male hypogonadism  
• Acne  
• Myalgia  
• Allergic reaction to paclitaxel  
• Pain  
• Alopecia 
• Peripheral neuropathy 
• Anemia  
• Pneumonia  
• Coagulopathy  
• Pyelonephritis  
• Edema (non-pulmonary)  
• Rash  
• Gastrointestinal issues (e.g.  diarrhea, 
vomiting, nausea, pain) 
• Renal tubular necrosis  
• Hematologic dyscrasia (including 
neutropenia) 
• Sepsis  
• Hemolysis  
• Thrombocytopenia  
• Hypercholesterolemia  
• Transfusion 
• Hyperlipidemia  
• Urinary tract infection  
• Hypertension  
• Viral, bacterial and fungal infections  
• Hypertriglyceridemia  
 
 

Protocol Number: D035940 
 
  ILLUMENATE Pivotal PAS 
Spectranetics 
PROTOCOL 
_________________________________________________________________________________ 
Confidential 
 
Page 17 of 27 
 
5.3. 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. 
5.4. Relationship to Study Procedure 
The investigator will use the following definitions to assess the relationship of the adverse event to 
the original ILLUMENATE Pivotal study procedure: 
 
Not Related 
 
The event is definitely not associated with the study procedure.  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 
procedure and/or a more likely alternative etiology exists. 
Possible 
 
 
The temporal sequence between the study 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 study 
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 study 
procedure completion, or reappearance of the event on repeat 
interventional procedures (re-challenge). 
 
5.5. Unanticipated Adverse Device Effect /Unanticipated Serious Adverse Device Effect  
An unanticipated adverse device effect (UADE) is defined as 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 

Protocol Number: D035940 
 
  ILLUMENATE Pivotal PAS 
Spectranetics 
PROTOCOL 
_________________________________________________________________________________ 
Confidential 
 
Page 18 of 27 
 
investigational plan or protocol, or any other unanticipated serious problem associated with a device 
that relates to the rights, safety or welfare of subjects.    
An unanticipated serious adverse device effect is defined as any serious adverse device effect which 
by its nature, incidence, severity or outcome has not been identified in the current version of the risk 
analysis report.  Anticipated serious adverse device effect (ASADE) is an effect which by its nature, 
incidence, severity or outcome has been identified in the risk analysis report. 
If a complication occurs that the investigator believes may be a potential UADE/USADE, the site 
should immediately contact the sponsor. All UADEs/USADEs must be documented by the 
investigator including the date of onset, a complete description of the event, possible reason(s) for 
the event, duration, actions taken and outcome and submitted to the sponsor as soon as possible.  
Reporting of UADEs in the US by the investigator must be no more than 10 business days after the 
investigator learns of the effect.  Reporting of USADEs in the EU by the investigator must be within 
3 business days.  Copies of all supporting documents should be submitted concurrently with the 
appropriate CRF.   
The investigator will submit to the reviewing IRB a report of any UADE that occurs as soon as 
possible, but no more than 10 business days after the investigator learns of the effect, or sooner if 
required by the board’s reporting guidelines.  USADEs should be reported as soon as possible after 
the event or being informed about the event to the EC. 
A report from the sponsor will be submitted to the Food and Drug Administration (FDA) and to all 
reviewing IRB/ECs and participating investigators within 10 business days after the sponsor first 
receives notice of the effect.   
All UADEs will be followed until resolution, stabilization or 30 days after the last patient enrolled 
has completed the trial, whichever occurs first. 
Risk Assessment 
In conjunction with the National Principal Investigator(s) and/or, if need be, the Clinical Event 
Committee and/or Data Safety Monitoring Board (Section 10.2) the sponsor shall decide 
whether, as a result of an UADE/USADE, the safety of study participants is at risk, or whether 
continuation of the trial is in jeopardy.   
Corrective Measures 
If any situation potentially jeopardizing the safety of subjects, users or third persons arise 
during a clinical trial or approved performance evaluation, then the sponsor and those persons 
carrying out the clinical trial or the performance evaluation shall immediately take all of the 
essential safety measures in order to protect subjects, users or third persons from direct or 
indirect danger. 
 
6. 
STATISTICAL DESIGN AND ANALYSIS 
6.1. Statistical Overview of the Trial 
The statistical design of this study is that of a single-blind randomized controlled trial in which there 
are two co-primary endpoints.  The endpoints and their corresponding statistical hypotheses are: 
• Non-inferior Safety: Freedom from device and procedure related death through 30 days 
post-procedure and freedom from target limb major amputation and clinically-driven 

Protocol Number: D035940 
 
  ILLUMENATE Pivotal PAS 
Spectranetics 
PROTOCOL 
_________________________________________________________________________________ 
Confidential 
 
Page 19 of 27 
 
target lesion revascularization through 24 months post-procedure. 
o H0: πDCB ≤ πPTA - δ 
o H1: πDCB > πPTA - δ 
where π is the population proportion for the 
corresponding treatment group and δ is the non-inferiority margin. 
• Superior Effectiveness: Patency at 24 months post-procedure, defined as the absence of 
target lesion restenosis determined by duplex ultrasound PSVR ≤ 2.5 and freedom from 
target lesion revascularization.   
o H0: πDCB ≤ πPTA 
o H1: πDCB > πPTA 
The analysis populations are Intention-to-Treat (ITT) and Per-Protocol (PP); they are fully 
defined below in the next subsection. 
6.2 Analysis Populations 
The Intention-to-Treat (ITT) population will be comprised of all subjects who successfully 
completed the preliminary qualification procedures and were subsequently randomized to receive 
either the Stellarex DCB or the PTA control device.  
The Per-Protocol (PP) population will consist of ITT subjects who had no bail-out stenting and no 
major protocol deviations.  The data for each subject will be reviewed by the blinded angiographic 
core laboratory. All trial endpoints will be analyzed using both the Intention-to-Treat and Per-
Protocol populations, with the ITT analysis a priori designated as primary. 
6.3 Sample Size Justification 
Statistical sample size estimation for the two co-primary endpoints are as follows:  
Effectiveness:  
• Superiority design 
• 2:1 treatment assignment ratio 
• 80% power 
• 1-tailed alpha = 0.025 
• Patency proportions: PTA = 47%, representing a reduction of approximately 10% in the 
PTA group from 12 months, and a difference between groups of 19% (approximately the 
observed difference between groups in patency at 12 months) 
• Therefore N = 236 subjects (= 157 + 79) 
Safety:  
• Non-inferiority design 
• 2:1 randomization ratio 
• 80% power 
• 1-tailed 0.025 
• Non-inferiority margin = 10% 

Protocol Number: D035940 
 
  ILLUMENATE Pivotal PAS 
Spectranetics 
PROTOCOL 
_________________________________________________________________________________ 
Confidential 
 
Page 20 of 27 
 
• Success proportions: PTA success rate = 73%, representing a reduction of 10% in the 
PTA group from month 12, and a difference between groups in favor of DCB of 7% (as 
compared to an observed difference of 8.9% at month 12) 
• Therefore N’ = 206 subjects (=137 + 69) 
The enrolled sample size of 300 will be sufficient to achieve 80% power for the primary efficacy and 
safety objectives. It is expected that no more than 20% of subjects will not be evaluable for the 
primary endpoints (due to early withdrawals, missing data or non-diagnostic/non-evaluable DUS 
assessment) providing an expected observed sample size of 240. However, all subjects will be 
included in the analysis as multiple imputation, and clinical imputation for patency, will be 
employed for subjects with missing endpoint data. 
The non-inferiority margin has been increased from 5% for the 12 month endpoint in the Pivotal 
study to 10% for the PAS endpoint at 24 months. The reason for the increase to the more 
conventional 10% margin is because an assumption of a 20% difference, the original assumption for 
the 12 month endpoint, between groups at 24 months is not reasonable given the 12 month results of 
92.1% vs. 83.2%. 
6.4 Statistical Analyses 
General Statistical Considerations 
Continuous data will be summarized using descriptive statistics:  n, mean, standard deviation, 
median, minimum and maximum.  Continuous variables that are recorded using approximate 
values (e.g., < or >) will be replaced by the closest exact value for the calculation of summary 
statistics.  Categorical variables will be summarized using frequency counts and percentages. 
For ordinal-scaled variables, a combination of the above may be employed as appropriate:  
frequency and percentage of observations within a category and means and standard deviations 
of the scores of the categories.  For categorical and ordinal variables, percentages will be 
calculated based on non-missing data. 
A statistical analysis plan (SAP) accompanies this protocol and should be referred to for 
further information on intended statistical methods; the SAP will be finalized and approved 
prior to study database lock.  The SAP will detail the analytical methodology and assumptions 
beyond those presented below. 
Analyses of Primary Endpoint 
Both co-primary endpoints are binary in nature and as such will be summarized as success (or 
failure) counts, percentages, and Clopper-Pearson 95% confidence intervals.  Superiority in 
effectiveness will be tested using chi-square contingency table methods, corrected for 
continuity.  In the unlikely event that Cochran’s Rule is violated, then Fisher’s Exact tests will 
be employed. The primary analysis of the primary endpoints will employ multiple imputation 
on the ITT cohort to replace missing values.  Details of the imputation model are provided in 
the SAP. 
Non-inferiority of safety event rates will employ Farrington-Manning non-inferiority exact 
tests.  Secondary analyses of the primary endpoints, including Kaplan-Meier methods and 
sensitivity analyses such as use of all TLR in endpoints defined with clinically-driven TLR will 
be performed and are detailed in the SAP. 

Protocol Number: D035940 
 
  ILLUMENATE Pivotal PAS 
Spectranetics 
PROTOCOL 
_________________________________________________________________________________ 
Confidential 
 
Page 21 of 27 
 
Analysis of Secondary Endpoints 
All secondary endpoints will be analyzed descriptively without hypothesis-testing. 
For binary variables such as MAE or technical success, counts, percentages and exact 95% 
confidence intervals using Clopper-Pearson’s method will be calculated.  For continuous 
variables, means, standard deviations and 95% confidence intervals will be calculated.   
Protection Against False Discovery 
Insofar as this study is not deemed a success unless both co-primary endpoints (safety and 
effectiveness) are met, the probability that the trial falsely succeeds purely due to chance is 
related to the product of the individual endpoint α-levels.  Since the endpoints are effectively 
independent, the probability that both endpoints are met purely by chance is less than 1 out of 
1000. 
6.5 Blinding 
Blinding is critical to the integrity of this clinical trial.  Blinding of the treating physician is not 
possible due to the differences between the investigational and control devices.  For the duration of 
the trial the subject and the core laboratories will be blinded.     
In the event of a medical emergency, UADE, or pregnancy in an individual subject, in which 
knowledge of the investigational product is critical to the subject’s health management, the treating 
physician may act in accordance with knowledge of the actual randomized treatment assignment of 
the subject.   
The need to act on knowledge of the treatment assignment must first be discussed with the sponsor.  
Should the trial be suspended or pre-maturely terminated, the sponsor will provide instructions 
regarding the release of the randomized treatment assignment. 
 
7. 
RISK ASSESSMENT 
7.1. Potential Risks from Peripheral Catheterization, Stenting and PTA 
It is expected that risks associated with this study to be not significantly different than those with the 
standard interventional procedure for SFA disease.  The list of adverse events that may result from 
peripheral intervention includes but is not limited to: abrupt closure, acute myocardial infarction, 
allergic reaction to contrast, amputation, aneurysm, arterial perforation, arterial rupture, 
arteriovenous fistula, atrial arrhythmias (including bradycardia and tachycardia), bleeding 
complications that may require transfusions, artery spasm, stent embolism, peripheral artery or 
catheter thrombosis or embolism, chest pain, coagulopathy, congestive heart failure, death, drug 
reactions to antiplatelet agents/contrast medium, discomfort, emergency or non-emergent bypass 
graft surgery, distal emboli (air, tissue or thrombotic), fever, hypotension, hypertension, infection 
and pain at insertion site, injury to the peripheral artery, ischemia, leucopenia, lymphocele, nausea 
and vomiting, pseudoaneurysm, restenosis of the treated segment of the artery, sepsis, seizure, 
stroke/cerebrovascular accident (CVA), thrombocytopenia, total occlusion of the peripheral artery, 
unstable or stable angina pectoris, vascular complications including entry site that may require 
vessel repair, ventricular arrhythmias including ventricular fibrillation, ventricular tachycardia, 
wound complication or wound infection, renal failure, urinary tract infection and arterial dissection.  

Protocol Number: D035940 
 
  ILLUMENATE Pivotal PAS 
Spectranetics 
PROTOCOL 
_________________________________________________________________________________ 
Confidential 
 
Page 22 of 27 
 
7.2. Potential Risks from Paclitaxel Coating 
Local vessel toxicity from the paclitaxel coating includes the possibility of thrombosis and aneurysm 
formation.  Certain side effects and discomforts have been reported in subjects that have received 
paclitaxel in intravenous (IV) form as part of chemotherapy treatment.  These subjects may have 
other comorbid conditions and/or have received concomitant medications that may also have 
contributed to the reported side effects.  In the IV setting, the dose is delivered throughout the body 
and in doses hundreds of times higher than the total amount present on the CVI Paclitaxel-coated 
PTA Catheter used in this clinical study.  The side effects reported by the chemotherapy subjects 
include allergic/immunologic reactions, alopecia, anemia, blood product transfusion, gastro-
intestinal symptoms, hematologic dyscrasia (including leukopenia, neutropenia, and 
thrombocytopenia), hepatic enzyme changes, histologic changes in vessel wall, cellular damage or 
necrosis, myalgia/arthralgia and peripheral neuropathy.  It is unlikely with the total dosage on the 
CVI Paclitaxel-coated PTA Catheter and the targeted vessel delivery of the paclitaxel that the side 
effects associated with IV high dose chemotherapy would occur. 
7.3. Risk Management Procedure 
The study will be conducted by skilled and trained investigators relative to interventional 
procedures.  The research team at each clinical site will undergo training prior to initiation of the 
study.  
Subjects will be monitored closely throughout the study duration.  Subjects will be evaluated at pre-
determined time points to assess their clinical condition.  The subject’s medication regimen will be 
in line with standard of care requirements for peripheral interventional procedures.  
7.4. Potential Benefits 
The local application of anti-proliferative drugs (e.g., sirolimus, zotarolimus, everolimus, and 
paclitaxel) for prevention of restenosis in coronary arteries via a stent delivery system has shown 
that these therapies successfully inhibit or reduce restenosis.70-81 This has reduced the need for 
subjects with coronary artery disease to undergo repeat percutaneous and surgical revascularizations. 
The success of drug-eluting stents in the coronary arteries triggered an increased interest in using 
drug-eluting or drug-coated therapies in other vasculatures.  Neointimal hyperplasia remains one of 
the major stumbling blocks of all endoluminal therapies, particularly in the small caliber peripheral 
vessels and long diseased segments.50,52 To date, most trials involving drug-coated or drug-eluting 
stents have not shown reduced restenosis rates in the superficial femoral or proximal popliteal 
arteries.   
Preliminary data suggest that drug-coated balloons using paclitaxel reduce restenosis and late lumen 
loss in the superficial femoral and proximal popliteal arteries when compared to PTA with standard 
balloon catheters.57,58 Therefore, drug-coated balloons may have more advantages than angioplasty 
alone, especially in terms of controlling neointimal hyperplasia and lowering restenosis rates.   
 
8. 
DATA HANDLING, RECORD KEEPING AND REPORTING 
8.1. Case Report Form (CRF) Completion 
All required data will be accurately recorded by authorized personnel on standard CRFs which will 
be provided by the Sponsor. CRFs should be completed within 10 business days of a completed 

Protocol Number: D035940 
 
  ILLUMENATE Pivotal PAS 
Spectranetics 
PROTOCOL 
_________________________________________________________________________________ 
Confidential 
 
Page 23 of 27 
 
study visit. 
8.2. Source Documentation 
Source documentation is defined as all information necessary for the reconstruction and evaluation 
of the clinical investigation.  Regulations require that investigators maintain information in the 
subject’s medical records, which corroborate data collected on the CRFs.  Investigators will maintain 
all records pertaining to this study as mandated by the hospital requirements and national laws and 
regulations (e.g. informed consent evidence; nurse notes; hospital charts; correspondence with the 
sponsor, regulatory authorities or other physicians).  
8.3. Reports 
A report will be created after the primary endpoint has been analyzed and a final report on the study 
will be completed at the end of the study.  Interim reports may be compiled per regulatory 
requirements. 
 
9. 
REGULATORY REQUIREMENTS 
This study will be conducted in compliance with the protocol approved by study sites’ respective 
Institutional Review Boards (IRB)/Ethics Committees (ECs) and according to the Declaration of 
Helsinki, International Conference on Harmonization Good Clinical Practice (ICH GCP), Title 21 of 
the Code of Federal Regulations (CFR) Parts 50, 54, 56, 812, and 814, and other applicable 
regulatory requirements.  No planned deviations from the protocol will be implemented without 
prior review and approval of the sponsor then submitted to IRB/EC pursuant to IRB/EC guidelines. 
In such cases, the deviation will be reported to the IRB/EC as soon as possible.  
9.1. Investigator’s Responsibility 
The investigator must read and understand the protocol and must sign and complete an investigator 
agreement form.  The investigator agreement form documents the investigator’s agreement to all 
conditions of the protocol and an agreement to conduct the study accordingly.   
Additional requirements must be met by the investigator and participating institution, such as 
compliance with the protocol and protocol amendments, investigator requirements, institutional 
requirements, subject informed consent, use of information and publication, and reporting 
requirements.  
9.2. Compliance with Protocol and Protocol Amendments 
A protocol deviation is defined as any divergence from the study protocol.  The investigator is 
responsible for promptly reporting protocol deviations to their IRB/EC per IRB/EC policy and to the 
sponsor.  The sponsor will determine the effect of the protocol deviation on the scientific soundness 
of the clinical study and subject safety and determine if additional reports or actions are required.  
Additional action may include site re-training, removal of the devices, and/or site termination.   
The investigator will not implement any changes to the protocol without first obtaining a written 
agreement from the sponsor and documented approval from the IRB/EC, except in the event of an 
immediate hazard to the subject.  The investigator will report the deviation in accordance with the 
applicable regulations.   

Protocol Number: D035940 
 
  ILLUMENATE Pivotal PAS 
Spectranetics 
PROTOCOL 
_________________________________________________________________________________ 
Confidential 
 
Page 24 of 27 
 
9.3. Investigator Requirements 
All investigators were approved by the sponsor as part of the ILLUMENATE Pivotal study and 
remain in good standing with the following required documentation 
• 
 Signed investigator’s agreement 
• 
Current curriculum vitae 
• 
Financial disclosure form 
• 
IRB/EC approval of the investigator 
Investigators must allow the Sponsor or representatives of the Sponsor to visit the site to periodically 
assess the data quality and study integrity.  On site, the Sponsor or representatives will review study 
records in comparison with source documents, discuss the conduct of the study and verify that the 
facilities remain acceptable.  In addition the study may be evaluated by government inspectors who 
must be allowed access to CRFs, source documents and other study files.   
The investigator must notify the Sponsor promptly of any inspections scheduled by regulatory 
authorities, and promptly forward copies of inspection reports to Sponsor. 
The investigator should retain essential documents at least two years after the last approval of a 
marketing application and until there are no pending or contemplated marketing applications, or at 
least two years have elapsed since the formal discontinuation of clinical development of the 
investigational product.  These documents should be retained for a longer period, however if 
required by the applicable regulatory requirements or by an agreement with the sponsor. The 
investigator must contact the sponsor prior to disposal of study records. 
If the investigator withdraws from the study, the responsibility for follow-up and maintaining the 
study records must be transferred to a responsible party (such as another study investigator).  Notice 
of transfer must be provided in writing by the investigator to the sponsor, FDA/CA and IRB/EC no 
later than 10 business days after the transfer occurs. 
9.4. Institutional Requirements 
The investigator and institution are required to submit the following documentation.. 
•  IRB/EC approved informed consent form 
•  IRB/EC approval of the protocol 
• Fully executed clinical study agreement 
Any additional requirements imposed by the IRB/EC or regulatory authorities concerning the trial 
shall be followed.  The investigation may not start at the institution until favorable IRB and/or 
regulatory approval has been obtained. 
9.5. Subject Informed Consent 
Study subjects were required to provide written informed consent using an IRB-/EC-approved 
informed consent form as part of the ILLUMENATE Pivotal study.  No additional follow-up 
requirements or testing is required as part of this post-approval study.   

Protocol Number: D035940 
 
  ILLUMENATE Pivotal PAS 
Spectranetics 
PROTOCOL 
_________________________________________________________________________________ 
Confidential 
 
Page 25 of 27 
 
9.6. Use of Information and Publication 
All information and data generated in association with this study will be held in strict confidence 
until the study completion.  The investigator agrees to use this information for the sole purpose of 
completing this study and for no other purpose without written consent from the sponsor. 
At the conclusion of each follow-up time point and the entire study, an abstract reporting the primary 
results may be prepared and presented in an appropriate international forum.  A manuscript may also 
be prepared for publication in a scientific journal. The data and results from the study are the sole 
property of the sponsor.  The sponsor shall have the right to access and use all data and results 
generated during the study.  The sponsor acknowledges that the Principal Investigator(s) might 
desire to publish a multi-center publication regarding the trial results.  The sponsor must receive any 
proposed publication and/or presentation materials at least 60 days prior to the proposed date of the 
presentation or the initial submission of the proposed publication in order for the materials to be 
reviewed by the sponsor in compliance with the sponsor’s publication policy set forth in the clinical 
study agreement or investigator agreement. 
9.7. Reporting Requirements 
Reporting requirements for the investigator are listed in Table 4.  Included are information regarding 
to whom this information is to be sent, and the frequency and time constraints around submissions.  
If applicable laws, regulations, or IRB/EC requirements mandate stricter reporting requirements than 
those listed, the stricter requirements must be followed. 
Table 2:  Site Responsibilities for Submitting Data and Reports 
Type of Report 
 Investigator Reporting Responsibilities 
Report 
Prepared For 
Reporting Time Frame 
Adverse Events 
Sponsor 
Adverse events are collected at the time of the 
procedure and follow-up visits and must be reported 
to the sponsor as soon as possible. 
Serious Adverse Events 
Sponsor and 
IRB/EC/CA 
For US: ASAP, but to sponsor within 10 business 
days of the investigator learning of the event.  To 
IRB according to board guidelines. 
For EU: ASAP, but to sponsor within 3 business 
days of the investigator learning of the event. To 
IRB/EC according to board guidelines. 
Submission to CA is done by the sponsor as soon as 
possible. 
Unanticipated Adverse Device 
Effects 
Sponsor and 
IRB/EC 
ASAP, but to sponsor within 10 business days of the 
investigator learning of the effect.  To IRB/EC 
according to board guidelines. 
Withdrawal of IRB/EC Approval or 
other action on part of the IRB/EC 
that affects the study 
Sponsor 
Within 5 business days of IRB/EC decision. 
Progress Reports (US Only) 
Sponsor and 
IRB/EC 
Every 6 months for the first two years and then at 
intervals dictated by the IRB/EC, but no less than 
yearly. 
Protocol Deviations 
Sponsor and 
IRB/EC 
ASAP to sponsor.  To IRB/EC according to board 
guidelines. 

Protocol Number: D035940 
 
  ILLUMENATE Pivotal PAS 
Spectranetics 
PROTOCOL 
_________________________________________________________________________________ 
Confidential 
 
Page 26 of 27 
 
Type of Report 
 Investigator Reporting Responsibilities 
Report 
Prepared For 
Reporting Time Frame 
Final Report 
Sponsor and 
IRB/EC 
For US: To sponsor within 3 months after 
termination or completion of study or investigator’s 
participation.   
For EU: To sponsor within 6 months after 
termination or completion of study or investigator’s 
participation.   
To IRB/EC according to board guidelines. 
Other 
IRB/EC/CA, 
FDA 
Upon request to provide accurate, complete, and 
current information about any aspect of the study.  
 
10. SPONSOR RESPONSIBILITIES COMPLIANCE/QUALITY ASSURANCE 
10.1. Role of Sponsor 
As the study sponsor, Spectranetics has the overall responsibility for the conduct of the study, 
including assurance that the study satisfies regulatory requirements. 
General Duties  
It is the sponsor’s responsibility to ensure that the study is conducted according to the ethical 
principles that have their origin in the Declaration of Helsinki and consistent with ICH GCP, 
21 CFR Parts 50, 54, 56 and 812, International Organization for Standardization (ISO) 14155 
[European Union (EU) only] and other applicable regulatory requirements, the study protocol, 
or any conditions of approval imposed by the IRB/CA/EC or regulatory authorities.  
Additionally, the sponsor will ensure proper clinical site monitoring is conducted.   
Training of Investigator and Site Personnel and Monitoring 
The training of the investigator, and appropriate clinical site personnel will be the 
responsibility of the sponsor and Principal Investigator, or designee, and may be conducted 
during an investigator meeting, a site initiation visit, or other appropriate training sessions.  
Periodic monitoring visits will be conducted frequently enough to ensure that all clinical 
subject data are properly documented and that the study is properly conducted.  
Documentation 
The sponsor will collect, store, guard and ensure completion by the relevant parties of the 
following documents: 
• Records of any UADEs reported to the sponsor during the clinical investigation 
• Any statistical analyses and underlying supporting data 
• The final report of the clinical investigation 
10.2. Committees 
Clinical Events Committee 
The Clinical Events Committee (CEC) is made up of interventional radiologists, interventional 
cardiologists or vascular surgeons who are not participants in the study.  The CEC is charged 

Protocol Number: D035940 
 
  ILLUMENATE Pivotal PAS 
Spectranetics 
PROTOCOL 
_________________________________________________________________________________ 
Confidential 
 
Page 27 of 27 
 
with the development of specific criteria used for the categorization of clinical events and 
clinical endpoints in the study which are based on the protocol.  
At the onset of the trial, the CEC will establish explicit rules outlining the minimum amount of 
data required, and the algorithm followed in order to classify a clinical event. All members of 
the CEC will be blinded to the primary results of the trial during the period of primary endpoint 
data collection. 
The CEC will meet regularly to review and adjudicate all clinical events. The committee will 
review and rule on all deaths that occur throughout the trial.  The committee will also review 
and rule on patency when there are two modalities of images available (ultrasound and 
angiographic) and they are in conflict with each other.   
Data Safety Monitoring Board 
The Data Safety Monitoring Board (DSMB) will consist of at least 5 members with 3 members 
representing a quorum.  Membership will include a biostatistician and independent 
representatives in relevant fields of clinical expertise, including but not limited to, physicians 
with one of the following specialties: interventional cardiology, vascular surgery, or 
interventional radiology.  DSMB members will be not part of the study or committees related 
to the study.  The DSMB will advise the sponsor regarding the continuing safety of trial 
subjects, including those to be recruited, as well as the continuing validity and scientific merit 
of the trial. 
 
11. TRIAL TERMINATION 
The sponsor and Steering Committee 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.   
Notification of suspension or termination will occur no later than five (5) business days after sponsor 
makes the determination.  In the event of study suspension or termination, the sponsor will send a 
report outlining the circumstances to the IRBs/ECs and all investigators.  A suspended or terminated 
study may not be reinitiated without approval of the reviewing IRB/EC (where applicable).  The 
investigator should follow any subjects as standard of care at the institution.   
The sponsor has the right to terminate the trial at any time for any reason. 
 
12. APPENDICES 
• Appendix A:   Bibliographical References 
• Appendix B:  Helsinki Declaration  
• Appendix C:   Trial Abbreviations and Definitions 
• Appendix D:  Rutherford-Becker Classification Guidelines 
• Appendix E: ABI Guidelines 
• Appendix F: WIQ Guidelines 
• Appendix G: 6 Minute Walking Test Instructions 
• Appendix H: EQ-5D Instructions 
• Appendix I:  Investigator Responsibilities 

Protocol Number: D035940 
 
  ILLUMENATE Pivotal PAS 
Spectranetics 
APPENDIX A:  Bibliographical References 
_________________________________________________________________________________ 
____________________________________________________________________________ 
Confidential                                                                                                             Page 1 of 6 
 
 
Appendix A:  Bibliographical References 
1. 
Belch JJ, Topol EJ, Agnelli G, et al. Critical issues in peripheral arterial disease detection and 
management: a call to action. Arch Intern Med. 2003;163(8):884-892. 
2. 
Norgren L, Hiatt WR, Dormandy JA, et al. Inter-Society Consensus for the Management of 
Peripheral Arterial Disease (TASC II). J Vasc Surg. 2007;45 Suppl S:S5-67. 
3. 
Bhatt DL, Steg PG, Ohman EM, et al. International prevalence, recognition, and treatment of 
cardiovascular risk factors in outpatients with atherothrombosis. JAMA. 2006;295(2):180-
189. 
4. 
Murphy TP. Medical outcomes studies in peripheral vascular disease. J Vasc Interv Radiol. 
1998;9(6):879-889. 
5. 
Pentecost MJ, Criqui MH, Dorros G, et al. Guidelines for peripheral percutaneous 
transluminal angioplasty of the abdominal aorta and lower extremity vessels. A statement for 
health professionals from a special writing group of the Councils on Cardiovascular 
Radiology, Arteriosclerosis, Cardio-Thoracic and Vascular Surgery, Clinical Cardiology, and 
Epidemiology and Prevention, the American Heart Association. Circulation. 1994;89(1):511-
531. 
6. 
Weitz JI, Byrne J, Clagett GP, et al. Diagnosis and treatment of chronic arterial insufficiency 
of the lower extremities: a critical review. Circulation. 1996;94(11):3026-3049. 
7. 
Dieter RS, Chu WW, Pacanowski JP, Jr., McBride PE, Tanke TE. The significance of lower 
extremity peripheral arterial disease. Clin Cardiol. 2002;25(1):3-10. 
8. 
McDermott MM, Criqui MH, Greenland P, et al. Leg strength in peripheral arterial disease: 
associations with disease severity and lower-extremity performance. J Vasc Surg. 
2004;39(3):523-530. 
9. 
Goshima KR, Mills JL, Sr., Hughes JD. A new look at outcomes after infrainguinal bypass 
surgery: traditional reporting standards systematically underestimate the expenditure of effort 
required to attain limb salvage. J Vasc Surg. 2004;39(2):330-335. 
10. 
Goessens BM, van der Graaf Y, Olijhoek JK, Visseren FL, Group SS. The course of vascular 
risk factors and the occurrence of vascular events in patients with symptomatic peripheral 
arterial disease. J Vasc Surg. 2007;45(1):47-54. 
11. 
Lassila R, Lepantalo M, Lindfors O. Peripheral arterial disease--natural outcome. Acta Med 
Scand. 1986;220(4):295-301. 
12. 
Vogt MT, Wolfson SK, Kuller LH. Lower extremity arterial disease and the aging process: a 
review. J Clin Epidemiol. 1992;45(5):529-542. 
13. 
Hirsch AT, Haskal ZJ, Hertzer NR, et al. ACC/AHA 2005 Practice Guidelines for the 
management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, 
and abdominal aortic): a collaborative report from the American Association for Vascular 
Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and 
Interventions, Society for Vascular Medicine and Biology, Society of Interventional 
Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to 
Develop Guidelines for the Management of Patients With Peripheral Arterial Disease): 
endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation; 
National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-
Society Consensus; and Vascular Disease Foundation. Circulation. 2006;113(11):e463-654. 
14. 
Hiatt WR, Wolfel EE, Meier RH, Regensteiner JG. Superiority of treadmill walking exercise 
versus strength training for patients with peripheral arterial disease. Implications for the 
mechanism of the training response. Circulation. 1994;90(4):1866-1874. 

Protocol Number: D035940 
 
  ILLUMENATE Pivotal PAS  
Spectranetics  
APPENDIX A:  Bibliographical References 
_________________________________________________________________________________ 
____________________________________________________________________________ 
Confidential                                                                                                             Page 2 of 6 
 
15. 
Brunelle CL, Mulgrew JA. Exercise for intermittent claudication. Physical therapy. 
2011;91(7):997-1002. 
16. 
Hiatt WR. Medical treatment of peripheral arterial disease and claudication. N Engl J Med. 
2001;344(21):1608-1621. 
17. 
Committee CS. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk 
of ischaemic events (CAPRIE). CAPRIE Steering Committee. Lancet. 1996;348(9038):1329-
1339. 
18. 
Dormandy JA, Rutherford RB. Management of peripheral arterial disease (PAD). TASC 
Working Group. TransAtlantic Inter-Society Consensus (TASC). J Vasc Surg. 2000;31(1 Pt 
2):S1-S296. 
19. 
Tisi PV, Cowan AR, Morris GE. Endoluminal femoropopliteal bypass for intermittent 
claudication. Eur J Vasc Endovasc Surg. 2000;19(5):481-488. 
20. 
Conte MS, Bandyk DF, Clowes AW, et al. Results of PREVENT III: a multicenter, 
randomized trial of edifoligide for the prevention of vein graft failure in lower extremity 
bypass surgery. J Vasc Surg. 2006;43(4):742-751; discussion 751. 
21. 
Faries PL, Logerfo FW, Arora S, et al. A comparative study of alternative conduits for lower 
extremity revascularization: all-autogenous conduit versus prosthetic grafts. J Vasc Surg. 
2000;32(6):1080-1090. 
22. 
Abbott WM, Green RM, Matsumoto T, et al. Prosthetic above-knee femoropopliteal bypass 
grafting: results of a multicenter randomized prospective trial. Above-Knee Femoropopliteal 
Study Group. J Vasc Surg. 1997;25(1):19-28. 
23. 
Minar E, Pokrajac B, Maca T, et al. Endovascular brachytherapy for prophylaxis of 
restenosis after femoropopliteal angioplasty : results of a prospective randomized study. 
Circulation. 2000;102(22):2694-2699. 
24. 
Cejna M, Thurnher S, Illiasch H, et al. PTA versus Palmaz stent placement in 
femoropopliteal artery obstructions: a multicenter prospective randomized study. J Vasc 
Interv Radiol. 2001;12(1):23-31. 
25. 
Grimm J, Muller-Hulsbeck S, Jahnke T, Hilbert C, Brossmann J, Heller M. Randomized 
study to compare PTA alone versus PTA with Palmaz stent placement for femoropopliteal 
lesions. J Vasc Interv Radiol. 2001;12(8):935-942. 
26. 
Zdanowski Z, Albrechtsson U, Lundin A, et al. Percutaneous transluminal angioplasty with 
or without stenting for femoropopliteal occlusions? A randomized controlled study. Int 
Angiol. 1999;18(4):251-255. 
27. 
Whyman MR, Fowkes FG, Kerracher EM, et al. Is intermittent claudication improved by 
percutaneous transluminal angioplasty? A randomized controlled trial. J Vasc Surg. 
1997;26(4):551-557. 
28. 
Vroegindeweij D, Vos LD, Tielbeek AV, Buth J, vd Bosch HC. Balloon angioplasty 
combined with primary stenting versus balloon angioplasty alone in femoropopliteal 
obstructions: A comparative randomized study. Cardiovasc Intervent Radiol. 
1997;20(6):420-425. 
29. 
Stanley B, Teague B, Raptis S, Taylor DJ, Berce M. Efficacy of balloon angioplasty of the 
superficial femoral artery and popliteal artery in the relief of leg ischemia. J Vasc Surg. 
1996;23(4):679-685. 
30. 
Murray JG, Apthorp LA, Wilkins RA. Long-segment (> or = 10 cm) femoropopliteal 
angioplasty: improved technical success and long-term patency. Radiology. 1995;195(1):158-
162. 
31. 
Gordon IL, Conroy RM, Tobis JM, Kohl C, Wilson SE. Determinants of patency after 

Protocol Number: D035940 
 
  ILLUMENATE Pivotal PAS  
Spectranetics  
APPENDIX A:  Bibliographical References 
_________________________________________________________________________________ 
____________________________________________________________________________ 
Confidential                                                                                                             Page 3 of 6 
 
percutaneous angioplasty and atherectomy of occluded superficial femoral arteries. Am J 
Surg. 1994;168(2):115-119. 
32. 
Matsi PJ, Manninen HI. Impact of different patency criteria on long-term results of 
femoropopliteal angioplasty: analysis of 106 consecutive patients with claudication. J Vasc 
Interv Radiol. 1995;6(2):159-163. 
33. 
Hunink MG, Donaldson MC, Meyerovitz MF, et al. Risks and benefits of femoropopliteal 
percutaneous balloon angioplasty. J Vasc Surg. 1993;17(1):183-192; discussion 192-184. 
34. 
Do dai D, Triller J, Walpoth BH, Stirnemann P, Mahler F. A comparison study of self-
expandable stents vs balloon angioplasty alone in femoropopliteal artery occlusions. 
Cardiovasc Intervent Radiol. 1992;15(5):306-312. 
35. 
Johnston KW. Femoral and popliteal arteries: reanalysis of results of balloon angioplasty. 
Radiology. 1992;183(3):767-771. 
36. 
Capek P, McLean GK, Berkowitz HD. Femoropopliteal angioplasty. Factors influencing 
long-term success. Circulation. 1991;83(2 Suppl):I70-80. 
37. 
Jeans WD, Armstrong S, Cole SE, Horrocks M, Baird RN. Fate of patients undergoing 
transluminal angioplasty for lower-limb ischemia. Radiology. 1990;177(2):559-564. 
38. 
Murray RR, Jr., Hewes RC, White RI, Jr., et al. Long-segment femoropopliteal stenoses: is 
angioplasty a boon or a bust? Radiology. 1987;162(2):473-476. 
39. 
Hewes RC, White RI, Jr., Murray RR, et al. Long-term results of superficial femoral artery 
angioplasty. AJR Am J Roentgenol. 1986;146(5):1025-1029. 
40. 
Krepel VM, van Andel GJ, van Erp WF, Breslau PJ. Percutaneous transluminal angioplasty 
of the femoropopliteal artery: initial and long-term results. Radiology. 1985;156(2):325-328. 
41. 
Gallino A, Mahler F, Probst P, Nachbur B. Percutaneous transluminal angioplasty of the 
arteries of the lower limbs: a 5 year follow-up. Circulation. 1984;70(4):619-623. 
42. 
Muradin GS, Bosch JL, Stijnen T, Hunink MG. Balloon dilation and stent implantation for 
treatment of femoropopliteal arterial disease: meta-analysis. Radiology. 2001;221(1):137-
145. 
43. 
Rocha-Singh KJ, Jaff MR, Crabtree TR, Bloch DA, Ansel G, Viva Physicians I. Performance 
goals and endpoint assessments for clinical trials of femoropopliteal bare nitinol stents in 
patients with symptomatic peripheral arterial disease. Catheter Cardiovasc Interv. 
2007;69(6):910-919. 
44. 
Sabeti S, Schillinger M, Amighi J, et al. Primary patency of femoropopliteal arteries treated 
with nitinol versus stainless steel self-expanding stents: propensity score-adjusted analysis. 
Radiology. 2004;232(2):516-521. 
45. 
Laird JR, Katzen BT, Scheinert D, et al. Nitinol stent implantation versus balloon angioplasty 
for lesions in the superficial femoral artery and proximal popliteal artery: twelve-month 
results from the RESILIENT randomized trial. Circ Cardiovasc Interv.3(3):267-276. 
46. 
Schillinger M, Sabeti S, Dick P, et al. Sustained benefit at 2 years of primary femoropopliteal 
stenting compared with balloon angioplasty with optional stenting. Circulation. 
2007;115(21):2745-2749. 
47. 
Schillinger M, Sabeti S, Loewe C, et al. Balloon angioplasty versus implantation of nitinol 
stents in the superficial femoral artery. N Engl J Med. 2006;354(18):1879-1888. 
48. 
Lugmayr HF, Holzer H, Kastner M, Riedelsberger H, Auterith A. Treatment of complex 
arteriosclerotic lesions with nitinol stents in the superficial femoral and popliteal arteries: a 
midterm follow-up. Radiology. 2002;222(1):37-43. 
49. 
Becquemin JP, Favre JP, Marzelle J, Nemoz C, Corsin C, Leizorovicz A. Systematic versus 
selective stent placement after superficial femoral artery balloon angioplasty: a multicenter 

Protocol Number: D035940 
 
  ILLUMENATE Pivotal PAS  
Spectranetics  
APPENDIX A:  Bibliographical References 
_________________________________________________________________________________ 
____________________________________________________________________________ 
Confidential                                                                                                             Page 4 of 6 
 
prospective randomized study. J Vasc Surg. 2003;37(3):487-494. 
50. 
Cheng SW, Ting AC, Lau H, Wong J. Immediate stenting of iliofemoral occlusive lesions: a 
surgeon's early experiences. J Endovasc Surg. 1999;6(3):256-263. 
51. 
Gordon IL, Conroy RM, Arefi M, Tobis JM, Stemmer EA, Wilson SE. Three-year outcome 
of endovascular treatment of superficial femoral artery occlusion. Arch Surg. 
2001;136(2):221-228. 
52. 
DeRubertis BG, Pierce M, Chaer RA, et al. Lesion severity and treatment complexity are 
associated with outcome after percutaneous infra-inguinal intervention. J Vasc Surg. 
2007;46(4):709-716. 
53. 
Albrecht T, Speck U, Baier C, Wolf KJ, Bohm M, Scheller B. Reduction of stenosis due to 
intimal hyperplasia after stent supported angioplasty of peripheral arteries by local 
administration of paclitaxel in swine. Invest Radiol. 2007;42(8):579-585. 
54. 
Scheller B, Speck U, Abramjuk C, Bernhardt U, Bohm M, Nickenig G. Paclitaxel balloon 
coating, a novel method for prevention and therapy of restenosis. Circulation. 
2004;110(7):810-814. 
55. 
Scheller B, Speck U, Schmitt A, Bohm M, Nickenig G. Addition of paclitaxel to contrast 
media prevents restenosis after coronary stent implantation. J Am Coll Cardiol. 
2003;42(8):1415-1420. 
56. 
Speck U, Scheller B, Abramjuk C, et al. Neointima inhibition: comparison of effectiveness of 
non-stent-based local drug delivery and a drug-eluting stent in porcine coronary arteries. 
Radiology. 2006;240(2):411-418. 
57. 
Tepe G, Zeller T, Albrecht T, et al. Local delivery of paclitaxel to inhibit restenosis during 
angioplasty of the leg. N Engl J Med. 2008;358(7):689-699. 
58. 
Werk M, Langner S, Reinkensmeier B, et al. Inhibition of restenosis in femoropopliteal 
arteries: paclitaxel-coated versus uncoated balloon: femoral paclitaxel randomized pilot trial. 
Circulation. 2008;118(13):1358-1365. 
59. 
Tepe G, Laird J, Schneider P, et al. Drug-coated balloon versus standard percutaneous 
transluminal angioplasty for the treatment of superficial femoral and popliteal peripheral 
artery disease: 12-month results from the IN.PACT SFA randomized trial. Circulation. 
2015;131(5):495-502. 
60. 
Scheinert D, Duda S, Zeller T, et al. The LEVANT I (Lutonix paclitaxel-coated balloon for 
the prevention of femoropopliteal restenosis) trial for femoropopliteal revascularization: first-
in-human randomized trial of low-dose drug-coated balloon versus uncoated balloon 
angioplasty. JACC Cardiovascular interventions. 2014;7(1):10-19. 
61. 
Cassese S, Byrne RA, Ott I, et al. Paclitaxel-coated versus uncoated balloon angioplasty 
reduces target lesion revascularization in patients with femoropopliteal arterial disease: a 
meta-analysis of randomized trials. Circ Cardiovasc Interv. 2012;5(4):582-589. 
62. 
Werk M, Albrecht T, Meyer DR, et al. Paclitaxel-coated balloons reduce restenosis after 
femoro-popliteal angioplasty: evidence from the randomized PACIFIER trial. Circ 
Cardiovasc Interv. 2012;5(6):831-840. 
63. 
Laird JR, Schneider PA, Tepe G, et al. Durability of Treatment Effect Using a Drug-Coated 
Balloon for Femoropopliteal Lesions: 24-Month Results of IN.PACT SFA. Journal of the 
American College of Cardiology. 2015;66(21):2329-2338. 
64. 
Krishnan P. Drug-Coated Balloons Show Superior Three-Year Outcomes vs. Angioplasty: 
Results from IN.PACT SFA Randomized Trials. Paper presented at: Vascular Interventaional 
Advances (VIVA)2016; Las Vegas, NV. 
65. 
Rosenfield K, Jaff MR, White CJ, et al. Trial of a Paclitaxel-Coated Balloon for 

Protocol Number: D035940 
 
  ILLUMENATE Pivotal PAS  
Spectranetics  
APPENDIX A:  Bibliographical References 
_________________________________________________________________________________ 
____________________________________________________________________________ 
Confidential                                                                                                             Page 5 of 6 
 
Femoropopliteal Artery Disease. N Engl J Med. 2015;373(2):145-153. 
66. 
Schroeder H, Meyer DR, Lux B, Ruecker F, Martorana M, Duda S. Two-year results of a 
low-dose drug-coated balloon for revascularization of the femoropopliteal artery: Outcomes 
from the ILLUMENATE first-in-human study. Catheter Cardiovasc Interv. 2015. 
67. 
Krishnan P. Stellarex ILLUMENATE First-in-Human study: 24-month results of the direct-
DCB cohort. Paper presented at: VIVA2015; Las Vegas, NV. 
68. 
Lyden S. ILLUMENATE Pivotal Stellarex DCB IDE Study 12-Month Result. Paper 
presented at: Transcatether Cardiovascular Therapeutics2016; Washington, D.C. 
69. 
Brodmann M. ILLUMENATE European Clinical Trial: 12-Month Final Results for the 
Stellarex DCB. Paper presented at: The Amputation Prevention Symposium2016; Chicago, 
IL. 
70. 
Sousa JE, Costa MA, Abizaid A, et al. Lack of neointimal proliferation after implantation of 
sirolimus-coated stents in human coronary arteries: a quantitative coronary angiography and 
three-dimensional intravascular ultrasound study. Circulation. 2001;103(2):192-195. 
71. 
Moses JW, Leon MB, Popma JJ, et al. Sirolimus-eluting stents versus standard stents in 
patients with stenosis in a native coronary artery. N Engl J Med. 2003;349(14):1315-1323. 
72. 
Stone GW, Ellis SG, Cox DA, et al. A polymer-based, paclitaxel-eluting stent in patients 
with coronary artery disease. N Engl J Med. 2004;350(3):221-231. 
73. 
Schampaert E, Cohen EA, Schluter M, et al. The Canadian study of the sirolimus-eluting 
stent in the treatment of patients with long de novo lesions in small native coronary arteries 
(C-SIRIUS). J Am Coll Cardiol. 2004;43(6):1110-1115. 
74. 
Stone GW, Ellis SG, Cannon L, et al. Comparison of a polymer-based paclitaxel-eluting stent 
with a bare metal stent in patients with complex coronary artery disease: a randomized 
controlled trial. JAMA. 2005;294(10):1215-1223. 
75. 
Serruys PW, Ruygrok P, Neuzner J, et al. A randomised comparison of an everolimus-eluting 
coronary stent with a paclitaxel-eluting coronary stent:the SPIRIT II trial. EuroIntervention. 
2006;2(3):286-294. 
76. 
Meredith IT, Ormiston J, Whitbourn R, et al. First-in-human study of the Endeavor ABT-
578-eluting phosphorylcholine-encapsulated stent system in de novo native coronary artery 
lesions: Endeavor I Trial. EuroIntervention. 2005;1(2):157-164. 
77. 
Fajadet J, Wijns W, Laarman GJ, et al. Randomized, double-blind, multicenter study of the 
Endeavor zotarolimus-eluting phosphorylcholine-encapsulated stent for treatment of native 
coronary artery lesions: clinical and angiographic results of the ENDEAVOR II trial. 
Circulation. 2006;114(8):798-806. 
78. 
Kandzari DE, Leon MB, Popma JJ, et al. Comparison of zotarolimus-eluting and sirolimus-
eluting stents in patients with native coronary artery disease: a randomized controlled trial. J 
Am Coll Cardiol. 2006;48(12):2440-2447. 
79. 
Leon MB, Mauri L, Popma JJ, et al. A randomized comparison of the ENDEAVOR 
zotarolimus-eluting stent versus the TAXUS paclitaxel-eluting stent in de novo native 
coronary lesions 12-month outcomes from the ENDEAVOR IV trial. J Am Coll Cardiol. 
2010;55(6):543-554. 
80. 
Stone GW, Midei M, Newman W, et al. Randomized comparison of everolimus-eluting and 
paclitaxel-eluting stents: two-year clinical follow-up from the Clinical Evaluation of the 
Xience V Everolimus Eluting Coronary Stent System in the Treatment of Patients with de 
novo Native Coronary Artery Lesions (SPIRIT) III trial. Circulation. 2009;119(5):680-686. 
81. 
Hermiller JB, Fergus T, Pierson W, et al. Clinical and angiographic comparison of 
everolimus-eluting and paclitaxel-eluting stents in small coronary arteries: a post hoc 

Protocol Number: D035940 
 
  ILLUMENATE Pivotal PAS  
Spectranetics  
APPENDIX A:  Bibliographical References 
_________________________________________________________________________________ 
____________________________________________________________________________ 
Confidential                                                                                                             Page 6 of 6 
 
analysis of the SPIRIT III randomized trial. Am Heart J. 2009;158(6):1005-1010. 
 

Protocol Number: D035940 
 
ILLUMENATE Pivotal PAS Protocol 
Spectranetics 
Appendix B:  Helsinki Declaration 
______________________________________________________________________________ 
Confidential 
Page 1 of 5 
WORLD MEDICAL ASSOCIATION DECLARATION OF HELSINKI 
Ethical Principles for Medical Research Involving Human Subjects 
• Adopted by the 18th WMA General Assembly, Helsinki, Finland, June 1964, and 
amended by the: 
• 29th WMA General Assembly, Tokyo, Japan, October 1975 
• 35th WMA General Assembly, Venice, Italy, October 1983 
• 41st WMA General Assembly, Hong Kong, September 1989 
• 48th WMA General Assembly, Somerset West, Republic of South Africa, October 
1996 
• 52nd WMA General Assembly, Edinburgh, Scotland, October 2000 
• 53rd WMA General Assembly, Washington 2002 (Note of Clarification on paragraph 
29 added) 
• 55th WMA General Assembly, Tokyo 2004 (Note of Clarification on Paragraph 30 
added) 
• 59th WMA General Assembly, Seoul, October 2008 
 
A. INTRODUCTION 
1. The World Medical Association (WMA) has developed the Declaration of Helsinki as a 
statement of ethical principles for medical research involving human subjects, including 
research on identifiable human material and data. The Declaration is intended to be read 
as a whole and each of its constituent paragraphs should not be applied without 
consideration of all other relevant paragraphs. 
2. Although the Declaration is addressed primarily to physicians, the WMA encourages 
other participants in medical research involving human subjects to adopt these principles. 
3. It is the duty of the physician to promote and safeguard the health of patients, including 
those who are involved in medical research. The physician's knowledge and conscience 
are dedicated to the fulfilment of this duty. 
4. The Declaration of Geneva of the WMA binds the physician with the words, “The health 
of my patient will be my first consideration,” and the International Code of Medical 
Ethics declares that, “A physician shall act in the patient's best interest when providing 
medical care.” 
5. Medical progress is based on research that ultimately must include studies involving 
human subjects. Populations that are underrepresented in medical research should be 
provided appropriate access to participation in research. 
6. In medical research involving human subjects, the well-being of the individual research 
subject must take precedence over all other interests. 
7. The primary purpose of medical research involving human subjects is to understand the 
causes, development and effects of diseases and improve preventive, diagnostic and 

Protocol Number: D035940 
 
ILLUMENATE Pivotal PAS Protocol 
Spectranetics 
Appendix B:  Helsinki Declaration 
______________________________________________________________________________ 
Confidential 
Page 2 of 5 
therapeutic interventions (methods, procedures and treatments). Even the best current 
interventions must be evaluated continually through research for their safety, 
effectiveness, efficiency, accessibility and quality. 
8. In medical practice and in medical research, most interventions involve risks and burdens. 
9.  Medical research is subject to ethical standards that promote respect for all human 
subjects and protect their health and rights. Some research populations are particularly 
vulnerable and need special protection. These include those who cannot give or refuse 
consent for themselves and those who may be vulnerable to coercion or undue influence. 
10. Physicians should consider the ethical, legal and regulatory norms and standards for 
research involving human subjects in their own countries as well as applicable 
international norms and standards. No national or international ethical, legal or regulatory 
requirement should reduce or eliminate any of the protections for research subjects set 
forth in this Declaration. 
B. PRINCIPLES FOR ALL MEDICAL RESEARCH 
11. It is the duty of physicians who participate in medical research to protect the life, health, 
dignity, integrity, right to self-determination, privacy, and confidentiality of personal 
information of research subjects. 
12. Medical research involving human subjects must conform to generally accepted scientific 
principles, be based on a thorough knowledge of the scientific literature, other relevant 
sources of information, and adequate laboratory and, as appropriate, animal 
experimentation. The welfare of animals used for research must be respected. 
13. Appropriate caution must be exercised in the conduct of medical research that may harm 
the environment. 
14. The design and performance of each research study involving human subjects must be 
clearly described in a research protocol. The protocol should contain a statement of the 
ethical considerations involved and should indicate how the principles in this Declaration 
have been addressed. The protocol should include information regarding funding, 
sponsors, institutional affiliations, other potential conflicts of interest, incentives for 
subjects and provisions for treating and/or compensating subjects who are harmed as a 
consequence of participation in the research study. The protocol should describe 
arrangements for post-study access by study subjects to interventions identified as 
beneficial in the study or access to other appropriate care or benefits. 
15. The research protocol must be submitted for consideration, comment, guidance and 
approval to a research ethics committee before the study begins. This committee must be 
independent of the researcher, the sponsor and any other undue influence. It must take 
into consideration the laws and regulations of the country or countries in which the 
research is to be performed as well as applicable international norms and standards but 
these must not be allowed to reduce or eliminate any of the protections for research 
subjects set forth in this Declaration. The committee must have the right to monitor 
ongoing studies. The researcher must provide monitoring information to the committee, 

Protocol Number: D035940 
 
ILLUMENATE Pivotal PAS Protocol 
Spectranetics 
Appendix B:  Helsinki Declaration 
______________________________________________________________________________ 
Confidential 
Page 3 of 5 
especially information about any serious adverse events. No change to the protocol may 
be made without consideration and approval by the committee. 
16. Medical research involving human subjects must be conducted only by individuals with 
the appropriate scientific training and qualifications. Research on patients or healthy 
volunteers requires the supervision of a competent and appropriately qualified physician 
or other health care professional. The responsibility for the protection of research subjects 
must always rest with the physician or other health care professional and never the 
research subjects, even though they have given consent. 
17. Medical research involving a disadvantaged or vulnerable population or community is 
only justified if the research is responsive to the health needs and priorities of this 
population or community and if there is a reasonable likelihood that this population or 
community stands to benefit from the results of the research. 
18. Every medical research study involving human subjects must be preceded by careful 
assessment of predictable risks and burdens to the individuals and communities involved 
in the research in comparison with foreseeable benefits to them and to other individuals or 
communities affected by the condition under investigation. 
19. Every clinical trial must be registered in a publicly accessible database before recruitment 
of the first subject. 
20. Physicians may not participate in a research study involving human subjects unless they 
are confident that the risks involved have been adequately assessed and can be 
satisfactorily managed. Physicians must immediately stop a study when the risks are 
found to outweigh the potential benefits or when there is conclusive proof of positive and 
beneficial results. 
21. Medical research involving human subjects may only be conducted if the importance of 
the objective outweighs the inherent risks and burdens to the research subjects. 
22. Participation by competent individuals as subjects in medical research must be voluntary. 
Although it may be appropriate to consult family members or community leaders, no 
competent individual may be enrolled in a research study unless he or she freely agrees. 
23. Every precaution must be taken to protect the privacy of research subjects and the 
confidentiality of their personal information and to minimize the impact of the study on 
their physical, mental and social integrity. 
24. In medical research involving competent human subjects, each potential subject must be 
adequately informed of the aims, methods, sources of funding, any possible conflicts of 
interest, institutional affiliations of the researcher, the anticipated benefits and potential 
risks of the study and the discomfort it may entail, and any other relevant aspects of the 
study. The potential subject must be informed of the right to refuse to participate in the 
study or to withdraw consent to participate at any time without reprisal. Special attention 
should be given to the specific information needs of individual potential subjects as well 
as to the methods used to deliver the information. After ensuring that the potential subject 
has understood the information, the physician or another appropriately qualified 

Protocol Number: D035940 
 
ILLUMENATE Pivotal PAS Protocol 
Spectranetics 
Appendix B:  Helsinki Declaration 
______________________________________________________________________________ 
Confidential 
Page 4 of 5 
individual must then seek the potential subject’s freely-given informed consent, 
preferably in writing. If the consent cannot be expressed in writing, the non-written 
consent must be formally documented and witnessed. 
25. For medical research using identifiable human material or data, physicians must normally 
seek consent for the collection, analysis, storage and/or reuse. There may be situations 
where consent would be impossible or impractical to obtain for such research or would 
pose a threat to the validity of the research. In such situations the research may be done 
only after consideration and approval of a research ethics committee. 
26. When seeking informed consent for participation in a research study the physician should 
be particularly cautious if the potential subject is in a dependent relationship with the 
physician or may consent under duress. In such situations the informed consent should be 
sought by an appropriately qualified individual who is completely independent of this 
relationship. 
27. For a potential research subject who is incompetent, the physician must seek informed 
consent from the legally authorized representative. These individuals must not be 
included in a research study that has no likelihood of benefit for them unless it is intended 
to promote the health of the population represented by the potential subject, the research 
cannot instead be performed with competent persons, and the research entails only 
minimal risk and minimal burden. 
28. When a potential research subject who is deemed incompetent is able to give assent to 
decisions about participation in research, the physician must seek that assent in addition 
to the consent of the legally authorized representative. The potential subject’s dissent 
should be respected. 
29. Research involving subjects who are physically or mentally incapable of giving consent, 
for example, unconscious patients, may be done only if the physical or mental condition 
that prevents giving informed consent is a necessary characteristic of the research 
population. In such circumstances the physician should seek informed consent from the 
legally authorized representative. If no such representative is available and if the research 
cannot be delayed, the study may proceed without informed consent provided that the 
specific reasons for involving subjects with a condition that renders them unable to give 
informed consent have been stated in the research protocol and the study has been 
approved by a research ethics committee. Consent to remain in the research should be 
obtained as soon as possible from the subject or a legally authorized representative. 
30. Authors, editors and publishers all have ethical obligations with regard to the publication 
of the results of research. Authors have a duty to make publicly available the results of 
their research on human subjects and are accountable for the completeness and accuracy 
of their reports. They should adhere to accepted guidelines for ethical reporting. Negative 
and inconclusive as well as positive results should be published or otherwise made 
publicly available. Sources of funding, institutional affiliations and conflicts of interest 
should be declared in the publication. Reports of research not in accordance with the 
principles of this Declaration should not be accepted for publication. 
 

Protocol Number: D035940 
 
ILLUMENATE Pivotal PAS Protocol 
Spectranetics 
Appendix B:  Helsinki Declaration 
______________________________________________________________________________ 
Confidential 
Page 5 of 5 
C. ADDITIONAL PRINCIPLES FOR MEDICAL RESEARCH COMBINED WITH 
MEDICAL CARE 
31. The physician may combine medical research with medical care only to the extent that the 
research is justified by its potential preventive, diagnostic or therapeutic value and if the 
physician has good reason to believe that participation in the research study will not 
adversely affect the health of the patients who serve as research subjects. 
32. The benefits, risks, burdens and effectiveness of a new intervention must be tested against 
those of the best current proven intervention, except in the following circumstances: 
• The use of placebo, or no treatment, is acceptable in studies where no current proven 
intervention exists; or 
• Where for compelling and scientifically sound methodological reasons the use of 
placebo is necessary to determine the efficacy or safety of an intervention and the 
patients who receive placebo or no treatment will not be subject to any risk of serious 
or irreversible harm. Extreme care must be taken to avoid abuse of this option. 
33. At the conclusion of the study, patients entered into the study are entitled to be informed 
about the outcome of the study and to share any benefits that result from it, for example, 
access to interventions identified as beneficial in the study or to other appropriate care or 
benefits. 
34. The physician must fully inform the patient which aspects of the care are related to the 
research. The refusal of a patient to participate in a study or the patient’s decision to 
withdraw from the study must never interfere with the patient-physician relationship. 
35. In the treatment of a patient, where proven interventions do not exist or have been 
ineffective, the physician, after seeking expert advice, with informed consent from the 
patient or a legally authorized representative, may use an unproven intervention if in the 
physician's judgment it offers hope of saving life, re-establishing health or alleviating 
suffering. Where possible, this intervention should be made the object of research, 
designed to evaluate its safety and efficacy. In all cases, new information should be 
recorded and, where appropriate, made publicly available. 

Protocol Number: D035940 
 
ILLUMENATE Pivotal PAS Protocol 
Spectranetics 
Appendix C:  Trial Abbreviations and Definitions 
______________________________________________________________________________ 
 
 
___________________________________________________________________________ 
Confidential 
Page 1 of 15 
 
Trial Abbreviations 
ABI 
Ankle-Brachial Index 
AE 
Adverse Event 
ADE 
Adverse Device Effect 
ASA 
Acetylsalicylic Acid 
ASAP 
As Soon As Possible 
AV 
Arteriovenous 
BBC 
Bare balloon catheter 
BMI 
Body Mass Index 
CBC 
Complete Blood Count 
CEC 
Clinical Events Committee 
CFR 
Code of Federal Regulations 
CI 
Clinically Indicated or Confidence Interval 
CLI 
Critical Limb Ischemia 
CMP 
Complete Metabolic Panel 
COPD 
Chronic Obstructive Pulmonary Disease 
CRF 
Case Report Form 
CT 
Computed Tomography 
CVA 
Cerebrovascular Accident 
CVD 
Cardiovascular Disease 
CVI 
CV Ingenuity 
DSMB 
Data Safety Monitoring Board 
DUS 
Duplex Ultrasound 
EC 
Ethics Committee 
EOB 
Explanation of Benefits 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
ICH 
International Conference on Harmonisation 
ID 
Identification 
IDE 
Investigational Device Exemption 
IFU 
Instructions for Use 
IRB 
Institutional Review Board 
ISO 
International Organization for Standardization 
ITT 
Intent-to-Treat 
IV 
Intravenous 
LLL 
Late Lumen Loss 
MAE 
Major Adverse Event 
MEC 
Medical Ethics Committee 
MI 
Myocardial Infarction 
MLD 
Minimum Lumen Diameter 
MR 
Magnetic Resonance 
OTC 
Over-the-counter 
O.U.S. 
Outside the United States 
PAD 
Peripheral Artery Disease 
PI 
Principal Investigator/Primary Investigator 
PP 
Per Protocol 
PSVR 
Peak Systolic Velocity Ratio 
PT  
Prothrombin Time 

Protocol Number: D035940 
 
ILLUMENATE Pivotal PAS Protocol 
Spectranetics 
Appendix C:  Trial Abbreviations and Definitions 
______________________________________________________________________________ 
 
 
___________________________________________________________________________ 
Confidential 
Page 2 of 15 
 
PTA 
Percutaneous Transluminal Angioplasty 
QA 
Quantitative Angiography 
QALY 
Quality-adjusted Life Year 
RVD 
Reference Vessel Diameter 
SAE 
Serious Adverse Event 
SADE 
Serious Adverse Device Effect 
SAP 
Statistical Analysis Plan 
SFA 
Superficial Femoral Artery 
TLR 
Target Lesion Revascularization 
TPG 
Translesional Pressure Gradient 
TVR 
Target Vessel Revascularization 
UADE 
Unanticipated Adverse Device Effect 
USADE 
Unanticipated Serious Adverse Device Effect 
U.S. 
United States 
WIQ 
Walking Impairment Questionnaire 
 
Trial Definitions 
Abrupt Closure 
Vessel occlusion at the site of treatment within 24 hours after successful index 
procedure. 
Acute Success 
Acute success is classified according to the following definitions: 
Clinical Success 
Clinical success (per subject) is defined as technical success without the occurrence 
of major adverse events during the procedure. 
Lesion Success 
Lesion success is defined as achievement of a final in-lesion residual diameter 
stenosis of ≤ 50% (as determined by the angiographic core laboratory), using any 
device after wire passage through the lesion.   
Technical Success 
Technical success is defined as achievement of a final in-lesion residual diameter 
stenosis of ≤ 50% (as determined by the angiographic core laboratory), using the 
CVI Paclitaxel-coated Percutaneous Transluminal Angioplasty Balloon Catheter or 
bare balloon catheter without a device malfunction after wire passage through the 
lesion.  Pre and post-dilatation of the lesion are considered part of assigned device 
treatment.  
Adjunctive Treatment 
A procedure performed after treatment with the protocol-defined treatment  
Adverse Events  
 
 

Protocol Number: D035940 
 
ILLUMENATE Pivotal PAS Protocol 
Spectranetics 
Appendix C:  Trial Abbreviations and Definitions 
______________________________________________________________________________ 
 
 
___________________________________________________________________________ 
Confidential 
Page 3 of 15 
 
Adverse Event (US) 
An adverse event is any untoward medical occurrence in a 
study subject which occurs or worsens, whether or not 
considered related to the study device, study procedures, or 
study requirements.    
Adverse Event (OUS) 
Any untoward medical occurrence, unintended disease or 
injury, or untoward clinical signs (including abnormal 
laboratory findings) in subjects, users or other persons, whether 
or not related to the investigational medical device.  
NOTE 1: This definition includes events related to the 
investigational medical device or the comparator.  
NOTE 2: This definition includes events related to the 
procedures involved.  
NOTE 3: For users or other persons, this definition is restricted 
to events related to investigational medical devices.  
Serious Adverse Event 
(US) 
Any untoward medical occurrence that results in death, is life-
threatening, requires inpatient hospitalization or prolongation of 
existing hospitalization, results in persistent or significant 
disability/incapacity, requires medical/surgical intervention to 
prevent life-threatening illness or injury or to prevent 
permanent impairment of a body structure or function, or is a 
congenital anomaly/birth defect.  Emergency room visits lasting 
less than 24 hours are not considered SAEs.   
Note: For purposes of reporting within this protocol, pre-
existing conditions or planned procedures for pre-existing 
conditions do not need to be reported as an adverse event or a 
SAE in the CRF unless there is an increase in severity or 
frequency during the course of the study. If a procedure is 
planned prior to enrollment and it is documented in the medical 
record as planned then an AE or a SAE does not need to be 
reported in the eCRF.   
Serious Adverse Event 
(OUS)  
An adverse event that  
a) led to a death or  
b) led to a serious deterioration in the health of the subject that 
either resulted in:  
1) a life-threatening illness or injury, or  
2) a permanent impairment of a body structure or a body 
function, or  

Protocol Number: D035940 
 
ILLUMENATE Pivotal PAS Protocol 
Spectranetics 
Appendix C:  Trial Abbreviations and Definitions 
______________________________________________________________________________ 
 
 
___________________________________________________________________________ 
Confidential 
Page 4 of 15 
 
3) in-patient or prolonged hospitalization, or  
4) medical or surgical intervention to prevent life –threatening 
illness or injury or permanent impairment to a body structure or 
body function.  
c) led to fetal distress, fetal death or a congenital abnormality or 
birth defect  
 
NOTE: Planned hospitalization for a pre-existing condition, or 
a procedure required by the protocol, without serious 
deterioration in health, is not considered a serious adverse 
event.  
Adverse Device Effect 
(ADE)  
An adverse event related to the use of an investigational 
medical device.  
NOTE 1: This definition includes adverse events resulting from 
insufficient or inadequate instructions for use, deployment, 
implantation, installation, or operation, or any malfunction of 
the investigational medical device.  
NOTE 2: This definition includes any event resulting from use 
error or from intentional misuse of the investigational medical 
device.  
Serious Adverse Device 
Effect (SADE)  
An adverse device effect that has resulted in any of the 
consequences characteristic of a serious adverse event (see 
definition above).  
Unanticipated Serious 
Adverse Device Effect 
(USADE)  
Any serious device effect which by its nature, incidence, 
severity, or outcome has not been identified in the current 
version of the risk analysis report.  
NOTE: Anticipated serious adverse device effect (ASADE) is 
an effect which by its nature, incidence, severity or outcome 
has been identified in the risk analysis report.  
 
Amputation  
The removal of a body extremity by surgery.     
A minor amputation will be defined as below the ankle; and a major amputation will be 
defined above the ankle.   
Aneurysm 

Protocol Number: D035940 
 
ILLUMENATE Pivotal PAS Protocol 
Spectranetics 
Appendix C:  Trial Abbreviations and Definitions 
______________________________________________________________________________ 
 
 
___________________________________________________________________________ 
Confidential 
Page 5 of 15 
 
A localized, pathological, blood-filled dilatation of a blood vessel caused by a 
weakening of the vessel wall. 
Angina Pectoris 
Braunwald Classification of Unstable Angina: 
New onset of severe or accelerated angina.  Patients with new onset (< 2 months in 
duration) exertional angina pectoris that is severe or frequent (> 3 episodes/day) or 
patients with chronic stable angina who develop accelerated angina (that is, angina 
distinctly more frequent, severe, longer in duration, or precipitated by distinctly less 
exertion than previously) but who have not experienced pain at rest during the 
preceding 2 months. 
Angina at rest, subacute.  Patients with one or more episodes of angina at rest during 
the preceding month but not within the preceding 48 hours. 
Angina at rest, acute.  Patients with one or more episodes of angina at rest within 
the preceding 48 hours. 
Canadian Cardiovascular Society (CCS) Classification of Stable Angina: 
Ordinary physical activity does not cause angina; for example walking or climbing 
stairs, angina occurs with strenuous or rapid or prolonged exertion at work or 
recreation. 
Slight limitation of ordinary activity; for example, angina occurs walking or stair 
climbing after meals, in cold, in wind, under emotional stress or only during the few 
hours after awakening, walking more than two blocks on the level or climbing more 
than one flight of ordinary stairs at a normal pace and in normal conditions. 
Marked limitation of ordinary activity; for example, angina occurs walking one or 
two blocks on the level or climbing one flight of stairs in normal conditions and at a 
normal pace. 
Inability to carry on any physical activity without discomfort - angina syndrome 
may be present at rest. 
Ankle Brachial Index (ABI) 
The ratio of the highest ankle systolic pressure to the highest brachial systolic pressure. 
Anticipated Adverse Event 
Any undesirable health related experience occurring to a subject whether or not 
considered related to the investigational device or drug regimen prescribed as part of the 
protocol that is predefined in the protocol and/or Instructions for Use that occurs or 
worsens during a clinical study. 
Arterial Inflow 
For a lesion in the superficial femoral artery (femoro-popliteal level) inflow refers to the 
aorto-iliac level.  Good inflow implies that vessels proximal to a target treatment site 
are free of hemodynamically significant lesion stenosis (≥ 50% stenosis). 
Arterial Outflow 
For a lesion in the superficial femoral artery (femoro-popliteal level) outflow refers to 
combined levels distal to the lesion, including the following arteries: distal popliteal, 

Protocol Number: D035940 
 
ILLUMENATE Pivotal PAS Protocol 
Spectranetics 
Appendix C:  Trial Abbreviations and Definitions 
______________________________________________________________________________ 
 
 
___________________________________________________________________________ 
Confidential 
Page 6 of 15 
 
tibioperoneal trunk, anterior tibial, posterior tibial, peroneal, dorsalis pedis, plantar and 
pedal.  Good outflow implies that the distal popliteal, tibioperoneal trunk and at least 
one of the infrapopliteal arteries (anterior tibial, posterior tibial, peroneal) is free of 
hemodynamically significant lesion stenosis (≥ 50% stenosis) and that there is in-line 
flow into the foot. 
Arterial Dissection 
Intimal disruption of the vessel wall with or without medial or adventitial contrast 
staining.   
Dissection Grades  
National Heart, Lung, and Blood Institute (NHLBI) Dissection Classification System: 
(0, A, B, C, D, E, F) 
 0: 
No dissection. 
A:   Minor radiolucent areas in the lumen without impairment of flow or persistent 
dye staining after contrast runoff.  
B:  
Luminal flap that is radiolucent and that runs parallel to the vessel wall with 
contrast injection but without impairment of flow or persistent dye staining 
after contrast runoff. 
C:  
Contrast appears outside of the vessel lumen as an "extra-luminal cap". The 
staining appears even after contrast clears the lumen.  
D:  Spiral radiolucent luminal filling defects. Often persistent staining after 
contrast clears from the vessel.  
E:  
New and persistent filling defects in the vessel lumen.  
F:  
Lesions that progress to impaired flow or total occlusion.  
 
Arterial Perforation 
Identifiable by extravasation of contrast media outside the arterial adventitial space. 
Arterial Rupture 
Large transmural disruption of a vessel with gross extravasation and hemorrhage. 
Artery Spasm 
A sudden, brief tightening of a blood vessel. 
Bleeding 
Blood loss resulting from the percutaneous interventional procedure or adjunctive drug 
therapy that may require transfusion of blood products. 
 
Cerebrovascular Accident (CVA) or Stroke 
Neurological dysfunction caused by a brain disturbance or ischemia, with clinical symptoms 
lasting >24 hours or imaging of an acute clinically relevant brain lesion in patients with 
rapidly vanishing symptoms. 

Protocol Number: D035940 
 
ILLUMENATE Pivotal PAS Protocol 
Spectranetics 
Appendix C:  Trial Abbreviations and Definitions 
______________________________________________________________________________ 
 
 
___________________________________________________________________________ 
Confidential 
Page 7 of 15 
 
Compressible Artery1 
An artery without significant calcification that can be evaluated by duplex ultrasound 
or an artery that results in an ABI value < 1.3.  
Death 
The termination of life.  When possible, death will be classified according to underlying 
cause.  Death within 30-days of the study procedure will be classified as procedure 
related unless demonstrated otherwise.   
Cardiovascular death:  
Any death due to proximate cardiac cause (e.g., myocardial infarction (MI), low-
output failure, fatal arrhythmia), unwitnessed death, or death of unknown cause. 
Device Malfunction 
A device malfunction is any case when the device does not perform in its intended 
function when used in accordance to the Instructions for Use. 
Discharge  
The time point at which the subject was released from the admitting hospital or 
transferred to another facility. 
Embolism 
Obstruction of a blood vessel by a foreign substance (air, plaque, debris) or a blood clot. 
Enrollment 
The patient will be considered enrolled into the study upon the completion of all the 
following: 
• 
A signed patient informed consent; 
• 
General and angiographic inclusion/exclusion criteria for enrollment has been 
met; 
• 
Successful treatment of the inflow (iliac) artery without complication, if 
applicable; 
• 
Target lesion is successfully crossed by the guidewire; 
• 
The pre-dilation has been completed (with a non-study catheter that is at least 
1 mm smaller in diameter than the nearest reference vessel diameter) without a 
flow-limiting (Grade D or greater) dissection, stent placement, or residual 
stenosis >70%; and 
• 
Randomized treatment has been assigned.  
                                                            
 
11 Creager Mark, Victor Dzau, and Joseph Loscalzo, eds.  Vascular Medicine: A Companion to Braunwald’s 
Heart Disease.  Philadelphia, PA: Saunders Elsevier, 2006. 

Protocol Number: D035940 
 
ILLUMENATE Pivotal PAS Protocol 
Spectranetics 
Appendix C:  Trial Abbreviations and Definitions 
______________________________________________________________________________ 
 
 
___________________________________________________________________________ 
Confidential 
Page 8 of 15 
 
Fever   
An increase in internal body temperature to levels that are above normal (37°C, 
98.6°F). 
Gastrointestinal (GI) bleeding 
Any bleeding that starts in the gastrointestinal tract, which may extend from the 
mouth to the anus. 
Hemorrhage 
Bleeding requiring hospitalization, repeat procedure, operation or transfusion.  
Hypertension 
Increase in systolic blood pressure above 140 mm Hg or a diastolic blood pressure 
above 90 mm Hg. 
Hypotension 
Fall in systolic blood pressure that requires intravenous treatment with vasopressors 
or inotropic agents. 
 
Index Procedure 
The procedure in which the subject has the study procedure performed or attempted. 
Infection 
Inflammation caused by bacterial or viral sources, such as, urinary tract infection, 
puncture site infection, sepsis, endocarditis, and bacteremia from IV site.   
Inflammation 
An immunologic response to infection or trauma that can result in localized redness, 
swelling, heat, pain and dysfunction of the organs involved. 
Intent-to-Treat (ITT) Population 
Subjects who successfully complete the preliminary qualification procedures and are 
subsequently randomized to receive either the investigational device (CVI Paclitaxel-
coated PTA Catheter) or the control device (bare balloon catheter).  
Intraluminal thrombus 
A blood clot within a vessel. 
Invasive Assessment/Procedure 
Any assessment, intervention or therapy that penetrates the skin, excluding 
administration of parenteral fluids or drugs. 
Late Lumen Loss (LLL) 
Calculated as Minimum Lumen Diameter (MLD) post-procedure – MLD at follow-up. Mean 
in-lesion Late Loss will also be measured:  (Mean In-lesion MLD, post-procedure) – (Mean 
In-lesion MLD at follow-up).  
 

Protocol Number: D035940 
 
ILLUMENATE Pivotal PAS Protocol 
Spectranetics 
Appendix C:  Trial Abbreviations and Definitions 
______________________________________________________________________________ 
 
 
___________________________________________________________________________ 
Confidential 
Page 9 of 15 
 
Major Adverse Event (MAE) 
Events including cardiovascular death, target limb major amputation and clinically-
driven target lesion revascularization (TLR). 
Minimum Lumen Diameter (MLD) 
The average of two orthogonal views (when possible) of the narrowest point within the 
area of assessment – in lesion, in stent or in segment.  MLD is visually estimated during 
angiography by the Investigator and is also measured by the Angiographic Core Lab. 
Multilevel Disease 
Presence of obstructive lesions at more than one level in the same extremity as the 
treatment lesion. 
Myocardial Infarction2  
 
Criteria for acute myocardial infarction: 
• Detection of a rise and/or fall of cardiac biomarker values [preferably cardiac troponin 
(cTn)] with at least one value above the 99th percentile upper reference limit (URL) 
and with at least one of the following: 
o Symptoms of ischaemia. 
o New or presumed new significant ST-segment–T wave (ST–T) changes or 
new left bundle branch block (LBBB). 
o Development of pathological Q waves in the ECG. 
o Imaging evidence of new loss of viable myocardium or new regional wall 
motion abnormality. 
o Identification of an intracoronary thrombus by angiography or autopsy. 
• Cardiac death with symptoms suggestive of myocardial ischaemia and presumed new 
ischaemic ECG changes or new LBBB, but death occurred before cardiac biomarkers 
were obtained, or before cardiac biomarker values would be increased. 
• Percutaneous coronary intervention (PCI) related MI is arbitrarily defined by 
elevation of cTn values (>5 x 99th percentile URL) in patients with normal baseline 
values (≤99th percentile URL) or a rise of cTn values >20% if the baseline values are 
elevated and are stable or falling. In addition, either (i) symptoms suggestive of 
myocardial ischaemia or (ii) new ischaemic ECG changes or (iii) angiographic 
findings consistent with a procedural complication or (iv) imaging demonstration of 
new loss of viable myocardium or new regional wall motion abnormality are required. 
• Stent thrombosis associated with MI when detected by coronary angiography or 
autopsy in the setting of myocardial ischaemia and with a rise and/or fall of cardiac 
biomarker values with at least one value above the 99th percentile URL. 
• Coronary artery bypass grafting (CABG) related MI is arbitrarily defined by elevation 
of cardiac biomarker values (>10 x 99th percentile URL) in patients with normal 
baseline cTn values (≤99th percentile URL). In addition, either (i) new pathological Q 
waves or new LBBB, or (ii) angiographic documented new graft or new native 
                                                            
 
2 Third universal definition of myocardial infarction. Thygesen K, et al. Eur Heart J. 2012 Oct;33(20):2551-67 

Protocol Number: D035940 
 
ILLUMENATE Pivotal PAS Protocol 
Spectranetics 
Appendix C:  Trial Abbreviations and Definitions 
______________________________________________________________________________ 
 
 
___________________________________________________________________________ 
Confidential 
Page 10 of 15 
 
coronary artery occlusion, or (iii) imaging evidence of new loss of viable myocardium 
or new regional wall motion abnormality. 
Criteria for prior myocardial infarction 
Any one of the following criteria meets the diagnosis for prior MI: 
• 
Pathological Q waves with or without symptoms in the absence of non-ischaemic 
causes. 
• 
Imaging evidence of a region of loss of viable myocardium that is thinned and fails to 
contract, in the absence of a non-ischaemic cause. 
• 
Pathological findings of a prior MI. 
 
National Principal Investigator 
A physician-specialist, related to the study, which is responsible for the overall conduct 
of the trial at all sites in a country.  
Occlusion 
An obstruction within an artery. 
Patency Rate 
Patency rate defined as the absence of target lesion restenosis determined by duplex 
ultrasound peak systolic velocity ratio (PSVR) of ≤ 2.5 and freedom from clinically-
driven target lesion revascularization.   
Ultrasound evidence will be used first to determine patency. 
• Ultrasound images showing a PSVR of ≤ 2.5 will be considered patent by the core 
laboratory.  In the event that the core laboratory cannot determine the PSVR, the 
core laboratory will make an assessment as to whether or not the lesion is patent, 
50-99% stenosed or occluded. 
• If ultrasound images are not available at a follow-up or analysis time point, and if 
an angiogram evaluation is available, the angiogram will be used to determine 
patency.  A result of ≤ 50% residual stenosis will be considered patent. 
Patent Run-Off 
A vessel starting at the popliteal artery going to the foot presenting with patent flow 
(hemodynamically insignificant stenosis of < 50%). 
Peak Systolic Velocity Ratio 
In-lesion duplex ultrasound measurement that measures the peak velocity of blood 
(cm/second) within a lesion or stented vessel segment divided by the peak velocity of 
blood (cm/second) proximal to the lesion or stented vessel segment. 
Percent Diameter Stenosis 
Relative changes that occur in the percent diameter stenosis are provided by the 
following relationship: % diameter stenosis= (1-[MLD/Reference diameter]) x 100 
Per Protocol 
ITT subjects who had no bail-out stenting and no major protocol deviations.  The data 
for each subject will be reviewed by the blinded angiographic core laboratory.   

Protocol Number: D035940 
 
ILLUMENATE Pivotal PAS Protocol 
Spectranetics 
Appendix C:  Trial Abbreviations and Definitions 
______________________________________________________________________________ 
 
 
___________________________________________________________________________ 
Confidential 
Page 11 of 15 
 
Physician-Directed Subject Withdrawal 
Withdrawal of a subject from the study at the direction of the Principal Investigator.  
Reasons for physician-directed subject withdrawal include, but are not exclusive to: 
the subject is not adhering to the study protocol requirements, the subject has enrolled 
in another study that conflicts with the ILLUMENATE Pivotal outcomes of interest, 
or the physician deems it in the best interest for the safety or welfare of the subject to 
withdraw. 
Popliteal Artery 
Defined as the vessel located between Hunter’s canal and the trifurcation of the anterior 
tibial, posterior tibial and peroneal arteries. 
Pre-Procedure 
The time until the procedure begins (before arterial access is obtained). 
Protocol Deviation 
Any divergence from the Study Protocol. 
Principal Investigator (PI) 
 Physician responsible for overall clinical management of subjects enrolled at his/her 
institution. Assumes overall responsibility and accountability for the clinical team and 
for data obtained from each subject participating in the study. Ensures compliance with 
the Study Protocol, applicable laws, and applicable regulations; ensures informed 
consents are signed, and reviews and signs eCRF indicating documents are accurate and 
complete. 
Reference Vessel Diameter (RVD) 
An approximation of the diameter of the vessel at the location of the target lesion.  RVD 
is the average of vessel diameters proximal and distal to the target lesion.  It will be 
estimated or measured by the Investigator and also measured by the angiographic core 
laboratory. 
Renal Failure 
Failure of the kidneys to perform essential functions that requires dialysis. 
Restenosis 
Re-narrowing of the artery following the reduction of a previous narrowing.  It is 
defined as the presence of a PSVR ≥ 2.5 by duplex ultrasound or a hemodynamically 
significant restenosis (≥ 50% stenosis), as determined by angiography.   
Restenotic Lesion 
A lesion in a vessel segment that had undergone a prior percutaneous treatment. 
Runoff Vessel 
An artery distal to treated vessel, including the popliteal, peroneal tibials and the 
dorsalis pedis.  
 

Protocol Number: D035940 
 
ILLUMENATE Pivotal PAS Protocol 
Spectranetics 
Appendix C:  Trial Abbreviations and Definitions 
______________________________________________________________________________ 
 
 
___________________________________________________________________________ 
Confidential 
Page 12 of 15 
 
Rutherford-Becker Classification Categories  
A classification system of clinical categories of chronic limb ischemia ranging from 0 
to 6.  The categories and clinical descriptions are:   
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 
 
Sepsis 
Systemic inflammatory response to infection. 
Severe Calcification   
Radiopacities noted on both sides of the arterial wall and extending more than one cm 
of length prior to contrast injection or digital subtraction angiography. 
 
Stenosis 
An abnormal narrowing of an artery. 
Study/Research Coordinator 
Employee at study site who assists Principal Investigator with study activities as 
delegated by the Principal Investigator, including tracking subjects involved in the 
study, scheduling testing and follow-up visits, maintaining study records, completing 
and providing eCRFs to the sponsor in a timely manner. 
Sub-Investigator(s) 
Physician(s) responsible for study activities in coordination with Principal 
Investigator and in accordance to the Study Protocol.   
Successful Pre-Dilation 
Pre-dilation (with a non-study catheter that is at least 1 mm smaller in diameter than the 
nearest reference vessel diameter) has been successfully completed without 
complications if all of the following apply: 

Protocol Number: D035940 
 
ILLUMENATE Pivotal PAS Protocol 
Spectranetics 
Appendix C:  Trial Abbreviations and Definitions 
______________________________________________________________________________ 
 
 
___________________________________________________________________________ 
Confidential 
Page 13 of 15 
 
• Residual diameter stenosis ≤ 70% 
• No stent placed. 
• No flow-limiting (Grade D or greater) dissections   
Superficial Femoral Artery (SFA) 
The SFA connects to the popliteal artery at the opening of adductor magnus or hunter's 
canal towards the end of the femur. 
Tandem Lesions 
Two distinct lesions with 3 cm or less of healthy vessel separating the diseased areas; 
this total area (diseased segments plus the 3 cm or less of healthy vessel) must be 
treatable by no more than 2 devices and ≤18 cm in cumulative length. 
Target Lesion 
A single diseased segment, between 3 cm and 18 cm in total length, in the superficial 
femoral or popliteal arteries that meets all the angiographic inclusion criteria and none 
of the exclusion criteria.     
Target Lesion Revascularization (TLR) 
Re-treatment by an invasive procedure, including atherectomy, angioplasty, stenting, 
endarterectomy, bypass, or thrombolysis, performed to open or increase the lumen 
diameter of the target lesion. TLRs will be classified as clinically-driven or not 
clinically-driven through an adjudication process.  Diameter stenosis will be 
determined per angiographic core laboratory assessment.  
Target Lesion Revascularization, Clinically-Driven: 
A revascularization of the target lesion is considered clinically-driven if the PSVR ≥ 2.5 
by duplex ultrasound or if angiography shows a percent diameter stenosis >50% and 
there is worsening of the Rutherford Becker Clinical Category or ABI that is clearly 
referable to the target lesion. (Worsening is defined as deterioration (an increase) in the 
Rutherford Becker Clinical Category by more than 1 (>1) category from the earliest 
post-procedural measurement or deterioration in the Ankle Brachial Index (ABI) > 0.15 
from the maximum early post-procedural level.) 
An independent ultrasound and/or angiographic core laboratory will verify that the 
severity of percent diameter stenosis meets requirements for clinically-driven and will 
overrule in cases where investigator reports are not in agreement. 
Target Limb 
The entire limb in which the target lesion is located. 
Target Vessel 
The entire vessel in which the target lesion is located. 
Target Vessel Revascularization (TVR) 
Any reintervention in the target vessel. 
Target Vessel Revascularization, Clinically Driven 
A repeat revascularization procedure (percutaneous or surgical) of a lesion in the target 
vessel, exclusive of the target lesion site.  A revascularization of the target vessel is 

Protocol Number: D035940 
 
ILLUMENATE Pivotal PAS Protocol 
Spectranetics 
Appendix C:  Trial Abbreviations and Definitions 
______________________________________________________________________________ 
 
 
___________________________________________________________________________ 
Confidential 
Page 14 of 15 
 
considered clinically-drivent the PSVR ≥ 2.5 by duplex ultrasound or if angiography 
shows a percent diameter stenosis >50% and there is worsening of the Rutherford 
Becker Clinical Category or ABI that is clearly referable to the target lesion. 
(Worsening is defined as deterioration (an increase) in the Rutherford Becker Clinical 
Category by more than 1 (>1) category from the earliest post-procedural measurement 
or deterioration in the Ankle Brachial Index (ABI) by > 0.15 from the maximum early 
post-procedural level.) 
Thrombosis 
The formation or development of thrombus inside a blood vessel, obstructing the flow 
of blood.  
Thrombus 
A blood clot within a vessel, which obstructs the flow of blood. 
Total Occlusion 
100% stenosis within an artery. 
Transient Ischemic Attach (TIA) 
Brief episode of neurological dysfunction caused by a focal disturbance of brain or 
retinal ischemia, with clinical symptoms typically lasting less than 24 hours, and 
without evidence of infarction. 
Unanticipated Adverse Device Effect (UADE)  
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 protocol, or any other unanticipated serious problem 
associated with a device that relates to the rights, safety or welfare of subjects. 
Vascular Access Complications 
Access Site Occlusion:  
Access site occlusion is defined as total obstruction of the artery usually by 
thrombus (but may have other causes) usually at the site of access requiring surgical 
repair.   
Arteriovenous Fistula 
A communication between an artery and a vein in which the arterial blood flows 
directly into a neighboring vein. 
Peripheral Embolization  
Peripheral embolization is defined as a loss of distal pulse, pain and/or discoloration 
(especially the toes).  This can include cholesterol emboli.  The site should indicate 
whether a peripheral embolization occurred distal to the arterial access site during 
the procedure or after lab visit but before any subsequent lab visits, requiring 
therapy.  
Pseudoaneurysm  
Perforation of the vessel with arterial blood flow outside of the vessel. 

Protocol Number: D035940 
 
ILLUMENATE Pivotal PAS Protocol 
Spectranetics 
Appendix C:  Trial Abbreviations and Definitions 
______________________________________________________________________________ 
 
 
___________________________________________________________________________ 
Confidential 
Page 15 of 15 
 
Hematoma 
Localized mass of extravasated blood ≥ 5 cm that prolongs hospitalization. 
Retroperitoneal Bleed 
An accumulation of blood in the retroperitoneal space. 
Peripheral Ischemia 
A restriction in arterial blood flow by stenosis, restenosis or occlusion that, if 
prolonged, can lead to tissue damage. 
Walking Impairment Questionnaire (WIQ) 
A disease-specific instrument utilized to characterize walking ability through a 
questionnaire.  It is a measure of patient-perceived walking performance for patients 
with PAD and/or intermittent claudication.   
 
 

 
Confidential  
 
Page 1 of 1 
 
ILLUMENATE Pivotal PAS 
  
APPENDIX D:  Rutherford-Becker Classification Guidelines 
 
Rutherford-Becker Classification1 is a classification system of Peripheral Arterial Disease.  
Determination of Rutherford-Becker Classification is required at the following time points: 
 
• 24 and 36 month follow-up visits  
• Unscheduled visits and re-interventions 
 
The Rutherford-Becker Classification is a global assessment based on the clinical description. 
 
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-nonhealing ulcer, focal gangrene with diffuse pedal 
ischemia 
6* 
Major tissue loss-extending above transmetatarsal level, functional foot 
no longer salvageable 
*Categories 4, 5, and 6 are also described as critical limb ischemia. 
 
 
 
 
 
 
 
 
 
 
 
 
 
______ 
1 Rutherford RB, Baker JD, Ernst C, Johnston KW, Porter JM, Ahn S, Jones DN. Recommended 
standards for reports dealing with lower extremity ischemia: revised version. J Vasc Surg. 1997 Sep; 
26(3):517-38. 
 

Confidential  
 
Page 1 of 3 
ILLUMENATE Pivotal PAS
 
 
 
 
APPENDIX E:  Ankle Brachial Index (ABI) Guidelines 
Determination of Ankle Brachial Index (ABI) is required for each subject (study treatment limb only) at the 
following time points: 
• 
24 and 36 month follow-up visits 
• 
Unscheduled and Re-intervention visits 
 
The ABI assessment is required to be attempted at the required time points given above.  If the ABI is not 
attempted at a required time point, it will be a protocol deviation (except at unscheduled or re-intervention 
visits). If the ABI result cannot be calculated due to a non-compressible artery, then it will not be a protocol 
deviation. 
Performing the ABI is a fast and effective non-invasive tool for screening for Peripheral Arterial Disease.  
Interpreting the ABI results are described in the table below.  
ABI Results 
Indication 
0.96 or Above 
Generally normal 
0.81 – 0.95 
Mild disease 
0.51-0.80 
Moderate disease 
0.31-0.50 
Moderate to severe disease 
0.30 or below 
Severe disease 
 
Preparing the Patient: 
1. The patient should have refrained from smoking for at least 1 hour prior to the testing.  
2. It is recommended that the same size cuff is used for both brachial and ankle pressures for an 
assessment and for each study visit. 
3. Have the patient remove shoes, socks/stockings and slacks if they cannot be easily rolled up to the 
knee. Shirts or blouses should be able to be easily rolled up to allow adequate placement of a blood 
pressure cuff on the arm. If clothing inhibits placement of the cuff or constricts the extremity, it 
should be removed. 
4. Make sure the patient is comfortable and warm. Cover patient with a sheet or blanket if desired. 
5. The patient should be allowed to rest quietly for at least 5 minutes prior to beginning the test. 
6. Bilateral ABI is useful at baseline if the target limb has not yet been confirmed.  At follow-up 
visits, only the target limb ABI is required.  The database only requires entry of the target limb ABI 
for all visits. 
 
Automatic vs. Manual Assessment 
ABI may be assessed using an automatic ABI machine or assessed manually.   
Automatic ABI Assessment 
For automatic ABI assessment, please follow the equipment instructions to obtain the ABI readings.   

Confidential  
 
Page 2 of 3 
Manual ABI Assessment 
For manual ABI assessments please refer to the guidelines below: 
Equipment: 
• 
Vascular Doppler with 5 or 8 MHz probe 
• 
Ultrasound gel 
• 
Blood pressure cuff (same size cuff for each subject for all visits is recommended) 
• 
Sphygmomanometer 
• 
Pen, paper, and calculator  
 
Performing the Exam: 
1. For first assessment for the subject, select the appropriate size cuff. An inappropriately sized blood 
pressure cuff will affect your results. It is recommended that the cuff bladder be 20% wider than the 
extremity diameter. 
a. Use the same size cuff for both arm and ankle measurements. 
b. It is recommended that you use the same size cuff consistently for all visits for the subject. 
2. Arm Pressure: 
Obtain brachial systolic pressure per your site’s SOC.  If using a Doppler probe, follow these 
guidelines: 
a. Place the appropriate sized cuff midway on the patient’s upper arm. Approximately two finger 
widths should exist between the crease in the antecubital space and the bottom of the cuff. The 
cuff should not be placed over the elbow area or cover the antecubital space. 
b. Attach the sphygmomanometer. 
c. Squeeze out approximately a dime sized amount of ultrasound gel and spread it over the 
antecubital space locating the brachial artery using the tip of the Doppler probe. Slowly move 
the probe across the brachial area until you hear the “whooshing” sound. Once you locate the 
brachial artery, adjust the volume on the probe so the signal can be easily heard. This position 
should be maintained throughout the rest of the procedure. To steady your hand (so you don’t 
lose placement) you may gently rest your hand on the patients arm.  
d. Begin inflating the blood pressure cuff. You will continue to hear blood moving through the 
artery. As you continue to inflate the cuff, the pressure of the cuff will stop the flow of blood 
through the artery.  Stop inflating the cuff approximately 10-20 mmHg past the point where 
you no longer heard the sound. 
e. Slowly deflate the cuff by 1-2 mm increments.  At the point where the sound returns, make note 
of the location of the gauge needle. Record this as the systolic pressure. Once you have 
accomplished this you may rapidly deflate the cuff the down to 0 mmHg. 
f. Repeat this procedure on the opposite arm. 
g. If you miss hearing the sound while deflating the cuff-allow 5 minutes before reattempting the 
procedure.  Repeat the steps above. 
h. Record the data collected. 
3. Ankle pressure: 
a. Two locations are available for obtaining ankle pressure; the posterior tibial (PT) artery is 
preferred although you can use the dorsalis pedis (DP) artery.  Attempt to locate the PT (located 
just behind the medial ankle bone) and use this as your measurement. The DP (top of foot) may 
be used for calculating the ABI only if PT is non-compressible.  Be advised that pressing too 
hard on the DP will obliterate the sound. Gentle pressure is to be used. 
b. Use the same cuff size as was used on the patient’s arm. Wrap the cuff snugly around the 
patient’s ankle, just above the foot. Have patient rotate the foot outward 
c. Attach the sphygmomanometer. 

Confidential  
 
Page 3 of 3 
d. Squeeze out approximately a dime sized amount of ultrasound gel out over the PT (or DP if 
needed) and place the probe. Spread the gel around and using the probe listen for the 
whooshing sound indicating blood flow. When you locate the sound, adjust the volume of the 
probe and maintain your position for the remainder of the procedure. Again, you may rest your 
hand gently on the patient’s foot to steady it. 
e. Begin inflating the blood pressure cuff. You will continue to hear blood moving through the 
artery. As you continue to inflate the cuff, the pressure of the cuff will stop the flow of blood 
through the artery.  Stop inflating the cuff approximately 10-20 mmHg past the point where 
you no longer heard the sound. 
f. Slowly deflate the cuff by 1-2 mm at a time. When the sound reappears record this as your 
systolic pressure. Once you have accomplished this you may rapidly deflate the cuff down to 0 
mmHg. 
g. Repeat this procedure on the other ankle if obtaining bilateral ABIs. 
h. If you miss hearing the sound while deflating the cuff-allow 5 minutes before reattempting the 
procedure. Repeat the steps above. 
i. 
Record the data collected. 
 
Calculating the ABI 
1. When both brachial pressures and at least one ankle pressure has been obtained, select the highest 
brachial value.  
2. In patients with diabetes and heavily calcified vessels, the arteries are frequently not compressible.  If 
you miss hearing the whooshing sound after repeated attempts (two or more times at one location) 
either before inflating the cuff or while deflating the cuff, the vessel is not compressible.  Non-
compressible arteries may result in artificially elevated pressure which in turn underestimates disease 
severity.   The goal of obtaining an ABI is to measure an artery without significant calcification and 
results in an ABI value < 1.3. 
3. Divide the ankle pressure by the highest brachial pressure. The result is the ABI. 
 

Confidential  
 
Page 1 of 1 
  
ILLUMENATE Pivotal PAS 
  
APPENDIX F:  Walking Impairment Questionnaire (WIQ) 
Guidelines 
 
Completion of the Walking Impairment Questionnaire is required for eligible subjects at the following time 
points: 
• 
24 and 36 month follow-up visits 
• 
Unscheduled visits and re-interventions 
 
The Walking Impairment Questionnaire is a functional assessment focusing on the difficulty a subject 
experiences when walking.  The questionnaire can be useful in determining the effectiveness of the study 
treatment by evaluating the subject’s severity of symptoms, and walking ability (distance and speed). 
 
The WIQ is an interviewer-administered questionnaire.  The interviewer should administer the WIQ by asking 
the subject the questions as they are presented on the worksheet, and recording all responses in the space 
provided. In order for the assessment to be evaluable, the subject needs to provide an answer for every 
question for walking distance and walking speed.  A response must be provided for each question. Only in the 
event an entire group of questions under a numerical category are left blank can this be left blank in the EDC.  
If a subject does not have experience with stair climbing, do not mark a response and leave the field blank.   
 
The WIQ results from each visit should be recorded on the CRFs for the 24 and 36 month follow-up visits.  
This form should also be completed if the subject returns for an unscheduled visit or a re-intervention.  After 
each assessment, enter the data into the EDC. 
 

Confidential  
 
Page 1 of 1 
 
ILLUMENATE Pivotal PAS 
  
APPENDIX G:  6 Minute Walking Test Instructions 
 
The 6 Minute Walking Test is required at the following time points: 
 
• 
24 and 36 month follow-up visits  
 
 
Instructions 
 
Set Up:   
• 
Measure out 30 meters in geographies using the metric system, or 100 feet for geographies using the 
English system of measure.  Preferably, in a long hallway (without corners or turns) or other flat, hard 
surface with interval markings every 3 meters, or 10 feet. Use of a treadmill, oval or circular track for 
this test is not recommended. 
• 
Mark the boundaries of the course with cones or brightly colored tape.   
• 
If possible, use a quiet, straight hallway for the test. 
• 
Have one or more chairs available along the course for the subject to rest in if needed during the test. 
 
Administration: 
• 
Ask the subject to wear comfortable footwear and clothing on the day of the test. 
• 
Do not walk with or behind the subject.  If the subject has an oxygen tank do not push the tank, instead 
have the subject walk with it as he/she would at home. 
• 
Do not conduct the test with multiple people at one time. 
• 
Instruct the subject to walk as far as they can in 6 minutes at their usual pace or at a comfortable pace 
and to use any walking aids normally used (e.g. a cane).  
• 
Count laps with a lap counter. 
• 
Time the test with a stopwatch. 
• 
Encouragement can affect the outcome of the test.  No encouragement should be given to subjects while 
conducting the test.  
 
 
 
 
 
 
 
 
 
 

ILLUMENATE Pivotal PAS 
 
 
APPENDIX H:  EQ-5D Instructions 
Confidential  
 
Page 1 of 1               
 
 
 
The EQ-5D Questionnaire is required for each subject at the following time points:  
 
 
24 and 36 month follow-up visits 
 
Unscheduled visits and re-interventions 
 
 
The EQ-5D is a standardized measure of health status developed by the EuroQuol Group in order to provide a simple, 
generic measure of health for clinical and economic appraisal.  Applicable to a wide range of health conditions and 
treatments, it provides a simple descriptive profile and a single index value for health status that can be used in the 
clinical and economic evaluation of health care as well as in population health surveys. 
 
EQ-5D is designed for self-completion by subjects and is intended to reflect the health status at the time of 
completion.  Instructions for completion are included within the questionnaire.  It should be completed prior to any 
other assessments in order to capture the subject’s self-assessment prior to discussions with the site personnel. 
 
EQ-5D is two pages in length with two sections, the EQ-5D descriptive system and the EQ visual analogue scale 
(VAS).  The EQ-5D descriptive system comprises the following five dimensions: mobility, self-care, usual activities, 
pain/discomfort and anxiety/depression.  Each dimension has three levels: no problems, some problems, severe 
problems.  The subject is asked to indicate his/her health state by ticking or placing a cross in the box against the most 
appropriate statement in each of the five dimensions.  The decision results in a one digit number expressing the level 
selected for that dimension.  The digits for five dimensions can be combined in a five digit number describing the 
respondent’s health state.   
 
The EQ VAS records the respondent’s self-rated health on a vertical, visual analogue scale where the endpoints are 
labeled ‘Best imaginable health state’ and ‘Worst imaginable health state.’ 
 
Reference:  EQ-5D User’s Guide, EuroQOL Group, 2009 (www.euroqol.org). 

Protocol Number: D035940 
 
ILLUMENATE Pivotal PAS Protocol 
Spectranetics 
Appendix I:  Investigators Responsibilities 
_________________________________________________________________ 
 
Confidential  
 
Page 1 of 1 
 
Investigators Responsibilities 
1. 
Have and maintain the resources necessary to conduct the clinical investigation 
properly. 
2. 
Ensure that conducting the clinical investigation is not nor will not cause a conflict of 
interest. 
3. 
Obtain from the sponsor information which the clinical investigator judges essential 
about the device and be familiar with this information. 
4. 
Understanding of the protocol prior to signing it. 
5. 
Compliance with the protocol and any amendments. 
6. 
Support the monitor in their activities to verify compliance with the protocol, to 
perform source data verification, and to correct case report forms where inconsistencies 
or missing data is identified. 
7. 
Discuss with the sponsor and monitor any question of modification of the clinical 
investigation plan and obtain written approval of the sponsor. 
8. 
Ensure the clinical investigation plan is followed by all persons responsible for the 
conduct of the clinical investigation at the institution.  Any deviation must be 
documented and reported to the sponsor. 
9. 
Make the necessary arrangements to ensure the proper conduct and completion of the 
clinical investigation. 
10. Make the necessary arrangements for emergency treatment, as needed, to protect the 
health and welfare of the subject. 
11. Ensure that appropriate Institutional Review Board (IRB) or Ethics Committee (EC) 
approval has been received prior to the start of the clinical investigation at the center. 
12. Provide the results from the IRB/EC to the sponsor. 
13. Inform the IRB/EC and request opinion and/or approval for any significant change in 
the clinical investigation plan that has been approved by the sponsor. 
14. Inform the IRB/EC about any serious adverse event and/or unanticipated adverse device 
effect, as applicable. 
15. Inform the sponsor about all adverse events, serious adverse events, and unanticipated 
adverse device effects in a timely manner. 
16. Attempt to ensure an adequate recruitment of subjects. 
17. Ensure that the subject has adequate information to give informed consent. 
18. Ensure that informed consent is obtained and documented. 
19. Ensure that clinical records are clearly marked to indicate the subject is enrolled in a 
particular clinical investigation.  If appropriate, subjects enrolled in the clinical 
investigation must be provided with some means of showing their participation in the 
investigation, together with identification and compliance information for concurrent 
treatment measures.  Contact addresses/telephone numbers must be provided.  If 
appropriate, the subject’s personal physician should, with the subject’s agreement, be 
informed. 
20. Provide subjects with well-defined procedures for any emergency situation and 
safeguard the subject’s interest.  Under these circumstances, deviations from the clinical 
investigation plan will not require the prior approval of the sponsor or the IRB/EC.  
Such deviations must not be considered as a breach of agreement but shall be 
documented and reported to the sponsor.