Prospective, Single-Arm, Global Multi-Center Study to Evaluate Treatment of Obstructive Superficial Femoral Artery (SFA) and/or Popliteal Lesions With a Novel Paclitaxel-Coated Percutaneous Angioplasty (PTA) Balloon and in In-Stent Restenosis
Phase: NA
Conditions: Peripheral Arterial Disease
Sponsor: Spectranetics Corporation

 
 
 
 
 
 
Study Protocol 
 
 
ProspectIve, SingLe-Arm, Global MuLti-
Center Study to EvalUate TreatMent of 
Obstructive SupErficial Femoral Artery and/or 
Popliteal LesioNs With A Novel PacliTaxel-
CoatEd Percutaneous Angioplasty Balloon and 
in In-Stent Restenosis 
 
 
ILLUMENATE Global and ISR 
 
 
Version 11.0 
 
 15 Nov 2016 
 
CP-1005 
 
 
 
 
Sponsor:  Spectranetics Corporation 
9965 Federal Drive I 
Colorado Springs 
CO 80921 
USA  
 
 

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Study Protocol Acceptance 
Study Title:  ProspectIve, SingLe-Arm, Global MuLti-Center Study to EvalUate TreatMent of 
Obstructive SupErficial Femoral Artery and/or Popliteal LesioNs With A Novel PacliTaxel-CoatEd 
Percutaneous Angioplasty Balloon and in In-Stent Restenosis 
 
I have read this Study Protocol and agree to adhere to the requirements.  I will provide copies of this 
Study Protocol and all pertinent information to the study personnel.  I will discuss this material with 
them and ensure they are fully informed regarding the study devices and the conduct of the study 
according to the International Standard ISO 14155:2011, the Declaration of Helsinki, and the 
pertinent individual country laws/regulations. 
 
 
 
 
 
_______________________________ 
 
 
_____/______/_______ 
Principal Investigator Signature 
 
 
 
  DD MMM   YYYY 
 
 
________________________________ 
Principal Investigator Printed Name 
 
________________________________ 
Study Site 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Study Protocol Synopsis 
 
ILLUMENATE Global and In-Stent Restenosis (ISR) 
Protocol Number CP-1005 
Device 
Cohort 1:  
CVI Paclitaxel-Coated, Percutaneous Transluminal Angioplasty (PTX PTA) 
Balloon Catheter 
 
In-Stent Restenosis ISR (Cohort 2):  
The same device now commercially available with CE Mark renamed to: 
Stellarex 0.035” OTW drug-coated angioplasty balloon (Stellarex 035 DCB) 
Primary Purpose 
Cohort 1:  
The purpose of this single arm study is to continue to assess safety and 
performance of the CVI Paclitaxel-Coated PTA Balloon Catheter in the 
treatment of de novo or restenotic lesions in the superficial femoral (SFA) 
and/or popliteal arteries. 
 
Cohort 2:  
A second cohort is being added to evaluate this patient population for 
treatment of in-stent restenotic lesions. 
Study Design 
Cohort 1:  
Prospective, multi-center, single-arm study.    
Cohort 2:  
Prospective, multi-center, single-arm study compared to a historical control 
patients.  
Follow-Up 
Schedule 
Cohort 1:  
Follow-up assessments will occur at discharge, 1 month, 6 months,                    
12 months, 24 months,36 months, 48 months, and 60 months following the 
study procedure.   
Cohort 2:  
Follow-up assessments will occur at discharge, 1 month, 6 months, 12 
months, 24 months and 36 months following the study procedure.   
Number of 
Subjects 
Cohort 1: Up to 500 subjects 
Cohort 2: Up to 130 subjects 
Number of Sites 
Cohort 1: Up to 65 study sites globally 
Cohort 2: Up to 25 study sites globally 

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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 (TLR) through 12 months post-
procedure.   
Primary Efficacy 
Endpoint  
Primary patency at 12 months post-procedure.  Primary patency is defined as 
the absence of target lesion restenosis per duplex ultrasound (peak systolic 
velocity ratio [PSVR] ≤ 2.5) and freedom from clinically-driven target lesion 
revascularization. 
Secondary 
Endpoints 
The following secondary outcomes will be summarized in this study:   
1. 
Major Adverse Event (MAE) rate defined as a composite rate of 
cardiovascular death, major target limb amputation, and clinically-
driven target lesion revascularization (TLR):  
i. 
Cohort 1: through discharge and at 1, 6, 12, 24, 36, 48, and 60 
months post-procedure. 
ii. 
Cohort 2: through discharge and at 1, 6, 12, 24, and 36 months 
post-procedure. 
2. 
Rate of adverse events: 
i. 
Cohort 1: through discharge and at 1, 6, 12, 24, 36, 48, and 60 
months post-procedure. 
ii. 
Cohort 2: through discharge and at 1, 6, 12, 24, and 36 months 
post-procedure. 
3. 
Rate of clinically-driven TLR at:  
i. 
 Cohort 1: 6, 12, 24,36, 48 and 60 months post-procedure. 
ii. 
Cohort 2: 6, 12, 24, and 36 months post procedure. 
4. 
Rate of clinically-driven target vessel revascularization (TVR) at: 
i. 
Cohort 1: 6, 12, 24,36, 48, and 60 months post-procedure. 
ii. 
Cohort 2: 6, 12, 24, and 36 months post procedure. 
5. 
Rate of major amputation of the target limb at:  
i. 
Cohort 1:  6, 12, 24, 36, 48 and 60 months post-procedure. 
ii. 
Cohort 2: 6, 12, 24, and 36 months post procedure. 
6. 
All-cause mortality rate at: 
i. 
Cohort 1:  6, 12, 24, 36, 48 and 60 months post-procedure. 
ii. 
Cohort 2: 6, 12, 24, and 36 months post procedure. 
7. 
Rate of occurrence of arterial thrombosis of the treated segment at 
i. 
Cohort 1: 1, 6, 12, 24,36, 48 and 60 months post-procedure. 
ii. 
Cohort 2: 1, 6, 12, 24, and 36 months post procedure. 

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8. 
Rate of ipsilateral embolic events of the study limb within 30 days post-
procedure. 
9. 
Primary patency rate at 6, 24, and 36 months post-procedure.  Primary 
patency is defined as the absence of target lesion restenosis per duplex 
ultrasound (peak systolic velocity ratio [PSVR] ≤ 2.5) and freedom 
from clinically-driven TLR.  
10. Alternative patency rate at 6, 24 and 36 months post-procedure. 
Alternative patency is defined as the absence of target lesion restenosis 
per duplex ultrasound PSVR < 2.4 and < 2.0 and freedom from 
clinically-driven TLR. 
11. Lesion success, defined as achievement of a final in-lesion residual 
diameter stenosis of ≤ 50%, after using the study device. 
12. Technical success, defined as achievement of a final in-lesion residual 
diameter stenosis of ≤ 50% (per angiographic core lab), using the 
paclitaxel-coated PTA balloon catheter without a device malfunction. 
13. Clinical success (per subject) defined as technical success without the 
occurrence of major adverse events during procedure. 
14. Procedural success (per subject) defined as lesion success without the 
occurrence of major adverse events during procedure. 
15. Change in Ankle-Brachial Index (ABI) from baseline to 6, 12, 24, and 
36 months post-procedure in subjects with: 
i. 
Cohort 1:  compressible arteries and baseline ABI < 0.9. 
ii. 
Cohort 2: compressible arteries.   
16. Change in Walking Impairment Questionnaire (WIQ) score from 
baseline to 6, 12, 24, and 36 months post-procedure. 
17. Change in Rutherford Clinical Category (RCC) from baseline to 6, 12, 
24, and 36 months post-procedure. 
18. Change in EQ-5D from baseline to 6, 12, 24, and 36 months post-
procedure. 
 
 
 
 
 
 
 
 

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Inclusion/ Exclusion Criteria COHORT 1 
Cohort 1 - General 
Inclusion Criteria 
1. Has symptomatic leg ischemia, requiring treatment of the SFA and/or 
popliteal artery. 
2. Has a Rutherford Clinical Category of 2 - 4.  Note: Rutherford Clinical 
Category 2 subjects should be entered into the study if conservative 
treatment has been unsuccessful. 
3. Is ≥ 18 years old.   
4. Has life expectancy > 1 year.  
5. Is able and willing to provide written informed consent prior to study 
specific procedures. 
6. Is willing and capable of complying with the required follow-up visits, 
testing schedule and medication regimen. 
 
Cohort 1 -
Angiographic 
Inclusion Criteria 
1. Has evidence at the target lesion(s) of clinically and hemodynamically 
significant de novo stenosis or restenosis, or occlusion, in the SFA (1 cm 
distal to the ostium of the profunda) and/or popliteal artery (proximal to 
the popliteal trifurcation), confirmed by angiography.   
2. Has target limb with at least one patent (<50% stenosis) tibio-peroneal 
run-off vessel to the foot confirmed by baseline angiography or magnetic 
resonance angiography (MRA) or computed tomography angiography 
(CTA).  Note:  Treatment of outflow disease is NOT permitted. 
3. Has 1 or 2 target lesion(s) with a cumulative lesion(s) length of no more 
than 20 cm.  NOTE: A maximum of two (2) lesions can be treated if the 
cumulative total lesion length (i.e. the combined length of both lesions) is 
less than or equal to 20cm.  
4. Has target lesion(s) located >2 cm from any stent if the target vessel was 
previously stented. 
5. Has a reference vessel diameter of 4 - 6 mm by visual estimate.  
6. Has a successful exchangeable guidewire crossing of the lesion(s). 
Cohort 1 - General 
Exclusion Criteria 
1. A female who is pregnant, of childbearing potential not taking adequate 
contraceptive measures, or nursing; or a male intending to father children 
during the study. 
2. Has significant gastrointestinal bleeding or any coagulopathy that would 
contraindicate the use of anti-platelet therapy 
3. Has known intolerance to study medications, paclitaxel or contrast agents 
that in the opinion of the investigator cannot be adequately pre-treated. 
4. Is currently participating in another investigational device or drug study 
that would interfere with study endpoints. 
5. Has history of hemorrhagic stroke within 3 months. 
6. Has surgical or endovascular procedure of the target limb within 14 days 

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prior to the index procedure.  
7. Has any planned surgical intervention (requiring hospitalization) or 
endovascular procedure within 30 days after the index procedure. 
8. Has had a previous peripheral bypass affecting the target limb. 
9. Has unstable angina pectoris, myocardial infarction, liver failure, renal 
failure or chronic kidney disease (dialysis dependent, or serum creatinine 
 2.5 mg/dL) within 30 days of the index procedure.  
Cohort 1 - 
Angiographic 
Exclusion Criteria 
1. Has significant stenosis (≥ 50%) or occlusion of inflow tract that is not 
successfully revascularized (< 30% residual stenosis without death or 
major vascular complication) prior to treatment of the target lesion(s).  
Only treatment of target lesion(s) is acceptable after successful treatment 
of inflow iliac artery lesion(s).  
2. Has an acute or sub-acute intraluminal thrombus within the target vessel. 
3. Has in-stent restenosis or restenosis of the target lesion following 
previous treatment with a drug-coated balloon.  
4. Has an aneurysm (at least twice the reference vessel diameter) located in 
the target vessel, abdominal aorta, iliac, or popliteal arteries.   
5. Has perforation, dissection or other injury of the access or target vessel 
requiring stenting or surgical intervention prior to enrollment. 
6. Has no normal arterial segment proximal to the target lesion in which 
duplex ultrasound velocity ratios can be measured. 
7. Requires use of adjunctive therapies (i.e., laser, atherectomy, cryoplasty, 
scoring/cutting balloons, brachytherapy). 
8. Has severe calcification that precludes adequate PTA treatment. 
 
Inclusion/ Exclusion Criteria COHORT 2 
Cohort 2 - General 
Inclusion Criteria 
1. Has symptomatic leg ischemia, requiring treatment of the SFA and/or 
popliteal artery. 
2. Has a Rutherford Clinical Category of 2 - 4.  Note: Rutherford Clinical 
Category 2 subjects should be entered into the study if conservative 
treatment has been unsuccessful. 
3. Is between 18-85 years old.   
4. Has life expectancy > 1 year.  
5. Is able and willing to provide written informed consent prior to study 
specific procedures. 
6. Is willing and capable of complying with the required follow-up visits, 
testing schedule and medication regimen. 
7. History of previous femoropopliteal nitinol stenting which is suspect for 
in-stent restenosis. 
8. The patient has a resting ankle-brachial index (ABI) <0.9 or an abnormal 
exercise ABI (<0.9) if resting ABI is normal. Patient with incompressible 

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arteries (ABI>1.2) must have a toe-brachial index (TBI) <0.7 in target 
limb.  
Cohort 2 -
Angiographic 
Inclusion Criteria 
1. Has  angiographic evidence of significant restenosis (≥50% by visual 
estimate) within a previously deployed femoropopliteal bare nitinol 
stent(s) including ISR Class I, II or III.   
2. Has target limb with at least one patent (<50% stenosis) tibio-peroneal 
run-off vessel to the foot confirmed by baseline angiography or magnetic 
resonance angiography (MRA) or computed tomography angiography 
(CTA).  Note:  Treatment of outflow disease is NOT permitted. 
3. Total target treatment length of in-stent restenosis must be ≥ 4.0 cm in 
length and may include a single lesion or a multifocal lesion within the 
femoropopliteal segment (This includes the proximal, mid, and/or distal 
SFA and P1, P2 and/or P3 segment of the popliteal artery). Edge 
restenosis may be treated provided the lesion extends no more than 3 cm 
outside the margin of the stent (proximal and/or distal margin).   
4. Has a reference vessel diameter of 4 - 6 mm by visual estimate.  
5. Has a successful exchangeable guidewire crossing of the lesion(s). 
Cohort 2 - General 
Exclusion Criteria 
1. A female who is pregnant, of childbearing potential not taking adequate 
contraceptive measures, or nursing; or a male intending to father children 
during the study. 
2. Has significant gastrointestinal bleeding or any coagulopathy that would 
contraindicate the use of anti-platelet therapy 
3. Has known intolerance to study medications, paclitaxel or contrast agents 
that in the opinion of the investigator cannot be adequately pre-treated. 
4. Is currently participating in another investigational device or drug study 
that would interfere with study endpoints. 
5. Has history of hemorrhagic stroke within 3 months including those within 
<60 days with an unresolved walking impairment. 
6. Has surgical or endovascular procedure of the target limb within 3 months 
prior to the index procedure.  
7. Has any planned surgical intervention (requiring hospitalization) or 
endovascular procedure within 30 days after the index procedure. 
8. Has had a previous peripheral bypass affecting the target limb. 
9. Has unstable angina pectoris, myocardial infarction within 60 days, liver 
failure, renal failure or chronic kidney disease (dialysis dependent, or 
serum creatinine  2.5 mg/dL) within 30 days of the index procedure.  
10. History of previous femoropopliteal stenting in the target lesion with drug 
eluting stents or covered stents (endografts).  
 

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Cohort 2 - 
Angiographic 
Exclusion Criteria 
1. Ipsilateral and/or contralateral iliac (or common femoral) artery stenosis 
≥50%  Diameter Stenosis (DS) that is not successfully treated prior to 
index procedure (e.g. where a perforation occurred requiring a covered 
stent) or with final residual stenosis ≥ 30% documented by angiography.  
2. Identification of any lesion of the native vessel (excludes ISR) above the 
target stent in the femoropopliteal segment >50% that is not successfully 
treated prior to index procedure (e.g. complication requiring additional 
treatment) or with final residual stenosis > 30% documented by 
angiography. DES and DCB will not be allowed. The lesion length must 
be treatable with a single stent (if required). The lesion must not be 
contiguous with the target lesion; at least 2 cm of normal appearing vessel 
between the lesion and target lesion/ target stent or between deployed 
stent (if required) and the target lesion/ target stent. 
3. Has an acute or sub-acute intraluminal thrombus within the target vessel. 
4. Has an aneurysm (at least twice the reference vessel diameter) located in 
the target vessel, abdominal aorta, iliac, or popliteal arteries.   
5. Has perforation, dissection or other injury of the access or target vessel 
requiring stenting or surgical intervention prior to enrollment. 
6. Has no normal arterial segment proximal to the target lesion in which 
duplex ultrasound velocity ratios can be measured. 
7. Requires use of adjunctive therapies (i.e., laser, atherectomy, cryoplasty, 
scoring/cutting balloons, brachytherapy). 
8. Grade 4 or 5 stent fracture affecting target stent or proximal to the target 
stent, or where evidence of stent protrusion into the lumen is noted on 
angiography in 2 orthogonal views. 

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TABLE OF CONTENTS 
1.0 
INTRODUCTION................................................................................................................. 11 
2.0 
DEVICE DESCRIPTION .................................................................................................... 13 
3.0 
BACKGROUND AND SIGNIFICANCE ........................................................................... 14 
4.0 
METHODOLOGY ............................................................................................................... 20 
5.0 
STATISTICAL METHODS ................................................................................................ 41 
6.0 
RISK/BENEFIT ANALYSIS ............................................................................................... 46 
7.0 
SITE REQUIREMENTS ..................................................................................................... 49 
8.0 
MONITORING PROCEDURES ........................................................................................ 50 
9.0 
RESPONSIBILITIES, RECORDS and REPORTS .......................................................... 51 
10.0 
TRIAL TERMINATION ..................................................................................................... 55 
11.0 
ABBREVIATIONS AND DEFINITIONS .......................................................................... 56 
REFERENCES .................................................................................................................................. 70 
 
List of Tables 
 
Table 1:  Nominal Paclitaxel Dose (µg) per Catheter Length/Diameter ............................................ 13 
Table 2:  Study Assessment Requirements ......................................................................................... 27 
Table 3:  Baseline Requirements ........................................................................................................ 29 
Table 4:  Discharge Assessment Requirements .................................................................................. 34 
Table 5:  1-Month Follow-Up Visit Requirements ............................................................................. 35 
Table 6:  6-Month Follow-Up Visit Requirements ............................................................................. 35 
Table 7:  12-Month Follow-up Visit Requirements ............................................................................ 35 
Table 8:  24-Month Follow-up Visit Requirements ............................................................................ 36 
Table 9:  36-Month Follow-up Visit Requirements ............................................................................ 36 
Table 10:  48-Month Follow-up Visit Requirements (Cohort 1 only) ................................................ 36 
Table 11:  60-Month Follow-up Visit Requirements (Cohort 1 only) ................................................ 37 
Table 12:  Reporting Responsibilities ................................................................................................. 53 
 
 

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1.0 INTRODUCTION 
1.1 
Purpose 
The purpose of this study is to continue to assess the safety and performance of the CVI Paclitaxel-
Coated Percutaneous Transluminal Angioplasty (PTX PTA) Balloon Catheter in the treatment of de 
novo or restenotic lesions in the superficial femoral (SFA) and/or popliteal arteries. In Cohort 2 – 
ISR, the study is expanded to include treatment of in-stent restenotic lesions. 
1.2 
Device Name 
The CVI Paclitaxel-Coated PTA Balloon Catheter will be used in this study. In Cohort 1, the device 
is investigational. 
 
For Cohort 2, the CE Marked device commercially available in Europe, Stellarex 0.035” OTW 
drug-coated angioplasty balloon, will be used with an investigational Instructions for Use (IFU). 
For regions outside of Europe, the device will be marked for investigational use only. 
 
An investigational IFU will be used for Cohort 2 as there will be changes within the body of the 
commercial IFU including the following main changes (see IFU attachment for all details): deletion 
of maximum of 2 balloons per lesion, detailed paclitaxel dosing chart, and specification of total 
maximum paclitaxel dose per lesion treated.  
 
1.3 
Intended Use 
Cohort 1:  
The CVI Paclitaxel-coated PTA Balloon Catheter is intended to be used for the treatment of de-
novo or restenotic lesions (excluding in-stent lesions) in the superficial and/or popliteal arteries to 
establish blood flow and to maintain vessel patency. 
Cohort 2 – ISR:  
The Stellarex 0.035” OTW drug-coated angioplasty balloon (DCB) is indicated for the treatment of 
de-novo or restenotic lesions in the lower extremities to establish blood flow and to maintain vessel 
patency.  
1.4 
Study Overview 
1.5 
Duration of the Study 
The estimated duration of the study is approximately six to seven years from the time of first 
subject enrollment to the last study protocol-required follow-up visit for each cohort of the study.  
Each subject of Cohort 1 will be followed for five years. Each subject of Cohort 2 will be followed 
for three years.  
1.6 
Number of Sites and Subjects 
In Cohort 1, up to 500 subjects are planned for enrollment into the study at up to 65 study sites 
globally. Cohort 2 has been added and will include up to 130 subjects with in-stent restenosis at up 
to 25 sites.        

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1.7 
Sponsor Contact Information 
 
Sponsor: Spectranetics  
 
 
 
 
 
 
6655 Wedgwood Road N, Suite 105 
 
 
 
Maple Grove, MN 55311 USA 
 
 Contact:   Colleen Holthe 
  
 
Clinical Program Manager Clinical Affairs 
  
 
Phone:   +1763-955-1137 
  
 
Email:  colleen.holthe@spectranetics.com 
 
 

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2.0 DEVICE DESCRIPTION 
The CVI PTX PTA balloon catheter (Spectranetics Corporation, formerly Covidien, formerly CV 
Ingenuity Corporation, Fremont, CA 94555 USA) is an over-the-wire dual lumen catheter with a 
distally mounted semi-compliant inflatable balloon and an atraumatic tapered tip.  The balloon is 
coated with a proprietary coating containing the drug paclitaxel.   
The catheter accommodates a 0.035” (0.89 mm) guidewire.  The shaft is 135 cm in length.  The 
catheter is available in balloon lengths of 40, 80, and 120 mm with balloon diameters of 4, 5 and 6 
mm.  It is compatible with a 6 French or greater sheath.  Each device has a protective sheath over 
the drug-coated balloon portion of the catheter.  A compliance chart is included on the product label 
for each device.   
The balloon has two radiopaque makers for positioning the balloon relative to the treatment area.  
The radiopaque maker bands indicate the working length of the balloon and facilitate fluoroscopic 
visualization during delivery and placement.  
The CVI PTX PTA balloon catheter utilizes a CE-marked, commercially available PTA balloon 
catheter (EverCross® 0.035” PTA Balloon Catheter, Medtronic, formerly Covidien, formerly ev3, 
Plymouth, MN 55441, USA) coated with paclitaxel using a proprietary carrier.  The paclitaxel 
coating is a formulation consisting of paclitaxel as the active pharmaceutical agent.  The paclitaxel 
coating covers the working length of the balloon catheter.   
The nominal dose density of paclitaxel on the CVI PTX PTA Balloon Catheter is 2.0 µg/mm2.  The 
nominal dose of paclitaxel on a specific catheter size 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 
 
In Cohort 1, the CVI Paclitaxel-coated PTA Balloon Catheter is an investigational device and may 
only be used if the patient has provided study informed consent.  Use is restricted to investigators 
who are experienced in the clinical and technical aspects of angioplasty.  The investigational device 
is provided sterile with the device packaged in a foil pouch and contained within a single unit box.  
Each balloon catheter is intended for single patient use. 
For Cohort 2, the CE Marked, commercially available in Europe Stellarex 035 DCB (formerly CVI 
PTX PTA Balloon Catheter) will be used with an investigational IFU. For regions outside of 
Europe, the device will be marked for investigational use only. There are no design changes 
between the investigational device used in Cohort 1 and the CE Marked device in Cohort 2.  
For specific information on device components and steps on how to operate the catheter, refer to 
the most current Instructions for Use (IFU). 
 
 

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3.0 BACKGROUND AND SIGNIFICANCE 
3.1 
Disease Overview 
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 a 
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.13-15  Exercise therapy can produce clinical improvements in walking ability and reductions in 
claudication pain.16-18  Pharmacological options include antiplatelet and anticoagulant therapies.19-21  
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.21,22  Patency rates for surgical 
revascularization of the lower extremities have been reported to be 23-74%.5,21,22 
Multiple published studies report on the short and long-term results of performing percutaneous 
angioplasty interventions and/or stenting for PAD.  Patency rates have been reported to range 
between 29-93%.23-42  A meta-analysis of percutaneous angioplasty with provisional stenting 
compared to stenting alone for treatment of SFA lesions showed similar rates of target vessel 
revascularization (TVR), making both reasonable choices as endovascular treatments.43 
However, 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.44-54   

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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.55-66  The use of drug-eluting stents in the 
superficial femoral and proximal popliteal arteries had promising early results that have not been 
sustained over time.  The SIROCCO I and SIROCCO II trials evaluated the local application of 
sirolimus for prevention of restenosis in the superficial femoral artery in 95 patients comparing use 
of an uncoated to a drug-coated nitinol self-expanding stent.  At 24 months there were no significant 
differences in Ankle Brachial Index (ABI) or in-stent restenosis as measured by peak systolic 
velocity ratio using duplex ultrasound.  Both groups showed an improvement in Rutherford 
classification post-procedure which was sustained over 24 months.67  The STRIDES trial evaluated 
104 patients with superficial femoral or proximal popliteal artery lesions treated with an everolimus 
self-expandable nitinol stent with disappointing results at 12 months.68  The Zilver PTX peripheral 
stent with the use of paclitaxel has shown positive results at 12 months but long-term results are 
currently unknown.69 
3.2 
Paclitaxel-Coated Angioplasty Balloons 
Paclitaxel is an antineoplastic drug that has demonstrated sustained inhibition of smooth muscle cell 
proliferation in several pre-clinical studies.70-73  Recent 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. 74,75   
The THUNDER (Local Taxane with Short Exposure for Reduction of Restenosis in Distal Arteries) 
trial74 was a prospective, multicenter study that randomized 154 patients with femoropopliteal 
disease to treatment with standard PTA (control, n=54), paclitaxel dissolved in the contrast medium 
(PTX-contrast, n=54), or PTA with a PTX-coated balloon catheter (PTX PTA, n=48).  The primary 
endpoint was late lumen loss (LLL) at 6 months.  The mean lesion length was 7.4±6.5 cm; 27% of 
lesions were total occlusions and 36% were restenotic.  There were no adverse events related to the 
drug-coated balloons.  During the study procedure, 17 patients required stent implantation for 
suboptimal outcomes (12 in the control arm, 2 in the PTX PTA arm, and 3 in the PTX-contrast arm).  
At 6 months the mean LLL was significantly less in the PTX PTA group compared to the control 
group (p<0.001, 0.4±1.2 mm vs. 1.7±1.8 mm).  The group treated with PTX-contrast had a mean 
LLL of 2.2±1.6 mm (p=0.11 vs. control).  The rate of TLR at 6 months was 37% (20/54) in the 
control group and 4% (2/48) in the PTX PTA group (p<0.001 vs. control) and 29% (15/52) in the 
PTX-contrast group (p=0.41 vs. control).  At 24 months the TLR rate was lower for the PTX PTA 
group in comparison to the control or the PTX-contrast arms (15% versus 52% and 40% 
respectively).74  At 5 years, the angiographic follow-up showed mean LLL lower, but not statistically 
significant, for the group treated with PTX PTA compared to the control group (0.7±1.9 mm vs. 
1.5±1.3 mm, p=0.54).  The authors concluded the use of PTX PTA was associated with significant 
reductions in LLL and TLR, while PTX-contrast did not show a significant benefit.  
An analogous study published by Werk et al,75 called Femoral Paclitaxel (FemPac), reported results 
similar to those seen in the THUNDER study.  The trial enrolled 87 patients who were randomized 
to treatment with paclitaxel-coated balloons (n=45) or to uncoated balloons (n=42).  To achieve 
optimal outcomes, 6 patients in the control arm and 4 patients in the PTX PTA arm required 
adjunctive stent implantation during the study procedure.  The 6-month LLL was significantly less in 
the group treated with PTX PTA (0.5±1.1) as compared to the control group (1.0±1.1, p = 0.031).  
Restenosis occurred in 19% of patients in the paclitaxel-coated arm and 47% of the control arm.75 

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The rate of TLR at 6 months was 31% (14/45) in the control group and 8.8% (4/45) in the PTX PTA 
group (P=0.007).  There were no adverse events related to the drug-coated balloons. The authors 
concluded that PTX PTA reduces restenosis without causing any apparent adverse events (AEs).   
The PACIFIER trial evaluating the use of paclitaxel-coated PTA catheters to reduce restenosis of 
femoral and popliteal artery stenosis and occlusions compared to standard PTA showed mean LLL 
by angiography at 6 months was significantly lower for the group treated with PTX PTA than the 
control group (-0.01 mm vs. 0.65 mm, p=0.001).  The binary stenosis rate was 8.6% for the PTX 
PTA group and 32.4% for the control group (p=0.01).76 Additionally, the major adverse event rates, 
including deaths, amputations, and target lesion revascularizations, were significantly lower for the 
PTX PTA group at both 6 and 12 months (7.1% vs. 26.2% at 6 months, p=0.04, and 7.1% vs. 34.9% 
at 12 months, p<0.01, for the PTX PTA group vs. the control group).  The authors conclude that 
drug-coated balloons are “associated with significant reductions in late lumen loss and restenosis at 6 
months, and reinterventions after femoro-popliteal percutaneous transluminal angioplasty up to 1 
year of follow-up.”  
 
Fanelli et al. reported on the independent, prospective, randomized trial, DEBELLUM (Drug-Eluting 
Balloon Evaluation for Lower Limb MUltilevel TreatMent), comparing angioplasty with drug-
eluting balloons to conventional angioplasty.77  The study included 50 patients with 122 lesions (25 
patients with 57 lesions randomized to treatment with PTX PTA and 25 patients with 65 lesions 
randomized to control).  Lesions in the femoropopliteal arteries (75.4%) and below-the-knee (BTK) 
arteries (24.6%) were included.  The late lumen loss at 6 months was significantly less in the PTX 
PTA group (0.5±1.4 mm) in comparison to control (1.6±1.7 mm; p<0.01).  Similarly, the binary 
restenosis rate at 6 months was significantly lower in the PTX PTA group (9.1% vs. 28.9% control, 
p=0.03).  Target lesion revascularization rates were 6.1% for the PTX PTA group and 23.6% for the 
control group at 6 months (p=0.02).  Thrombosis rates and amputation rates were lower in the PTX 
PTA group in comparison to control (3.0% vs. 5.2% for thrombosis and 3.0% vs. 7.9% for 
amputation) but the differences were not statistically significant.   No adverse events were noted.  
The authors concluded that “the DEBELLUM trial confirmed the ability of paclitaxel-eluting 
balloons to reduce restenosis vs. conventional balloons at 6 months after treatment of multilevel 
(femoropopliteal and BTK) arterial disease in patients affected by claudication and CLI [critical limb 
ischemia].”77 
Three publications by Micari et al. summarized results from a multicenter, Italian registry including 
treatment with paclitaxel-coated balloons for femoropopliteal stenoses and occlusions.78-80  The 
initial publication reported on 66 patients (74 lesions) treated with the IN.PACT Admiral paclitaxel-
coated balloon.79  The mean lesion length was 7.4±3.8 cm with the majority of lesions being de novo 
(95.9%).  Stent placement was required in 10.8% of cases due to vessel wall recoil or flow limiting 
dissection, resulting in a technical success of 89.2% and a procedural success rate of 100%.  The 
mean ankle-brachial index (ABI) improved from 0.58±0.13 pre-procedure to 0.82±0.25 at 3 months 
post-procedure.  No serious adverse events or target lesion revascularizations occurred within the 
initial 3 month follow-up period.79    The other two publications reported on 12-month and 2-year 
results from 105 patients with 114 treated lesions enrolled in the registry.78,80  The overall technical 
success rate was 89.6% with 12.3% of lesions stented.  At 12-months, the primary patency rate was 
83.7% and the target lesion revascularization rate was 7.6%.78  The ABI remained high at 0.86±0.15 
at the 12 month follow-up.  Two deaths occurred which were unrelated to the device or procedure.  
Improvements in quality of life, as measured with the EQ-5D questionnaire, included improved 
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through 12 months (p<0.01).78  At 2 years, the primary patency was 72.4% and secondary patency 
was 84.7%.  Improvements in ABI and quality of life seen at 12 months continued through the 2-
year follow-up.80  Overall, the major adverse event rate through 2 years was 17.5%, with 2 deaths, 1 
amputation, and 14 target lesion revascularizations.  The authors concluded that treatment with 
paclitaxel-coated balloons is “associated with favorable functional and clinical outcomes at 2 years 
in patients with femoropopliteal artery disease requiring percutaneous revascularization.”80 
 
LEVANT I81 was a first-in-human study of a low-dose PTX-coated angioplasty balloon (Lutonix™ 
DCB, coated with 2 µg/mm2 versus the typical 3 µg/mm2 of PTX).  The study included 101 patients 
randomized to treatment with the PTX PTA or uncoated PTA.  Randomization occurred after 
patients were stratified by whether balloon-only (n = 75) treatment or stenting (n = 26) was 
anticipated. The primary endpoint was LLL at 6 months.  There were 8 deployment malfunctions 
caused by twisting of the balloon, which confounded the outcomes. There were no procedural 
complications.   The mean lesion length was 8.1 cm and 42% of lesions were total occlusions. LLL 
at 6 months was 0.46 mm in the DCB arm and 1.09 mm in the PTA arm.  The rates of major adverse 
events were similar between groups. It was 39% in the DCB group, including 15 TLRs, 1 
amputation and 4 deaths.  The MAE rate was 46% in the PTA group which included 20 TLRs, 1 
thrombosis and 5 deaths. The primary patency rates at 12 months were 67% in the DCB arm and 
55% in the PTA arm.  At 24 months, the patency rates were 57% in the DCB arm and 40% in the 
PTA arm.  When the 8 patients with balloon twist malfunctions were excluded, the 12- and 24-
month patency rates were 76% and 66%, respectively. Further, the data showed that use before or 
after provisional stenting did resulted in similar outcomes out to 24 months. The authors concluded 
treatment with the Lutonix DCB reduced LLL and had a comparable safety profile as PTA. 
 
The DEBATE-SFA Randomized Trial was designed to compare PTX PTA with PTA followed by 
stent placement (DCB + BMS vs. PTA+BMS) in patients at risk of restenosis.82 A total of 104 
patients with 110 lesions were enrolled and randomized. Procedural success, defined as technical 
success without procedural complications, was met in all patients. The primary endpoint was 12-
month binary restenosis which occurred significantly less (p=0.008) in the DCB + BMS arm [9 
(17%) vs. 26 (47.3%) of lesions in the DCB + BMS and PTA+BMS groups, respectively].  The 
freedom from TLR rate was 83% in the DCB+BMS group and 66.7% in the PTA + BMS group 
(p=0.07); a near-significant difference. The authors concluded that pre-dilation with a DCB prior to 
BMS placement reduces restenosis and TLR at 12 months.  
 
The use of atherectomy prior to delivery of the drug-coated balloon has been explored. 83,84 Use of 
laser debulking in a CLI population was reported by Gandini et al.83 Forty-eight (48) patients with 
SFA in-stent occlusions were randomized to treatment with DCB alone or laser prior to DCB use.  
The patency rates the in the Laser + DCB group were significantly higher (p=0.01) at 6 and 12 
months (91.7% and 66.7%) as compared to the in the DCB only group (58.3% and 37.5%). No 
adverse events were related to laser or the drug coating in either group. Sixt et al. reported on their 
experience treating restenotic lesions with directional atherectomy (DA) followed by a drug-coated 
balloon. This retrospective study included 89 lesions; 60 treated with DA + PTA and 29 treated with 
DA+DCB. There were 2 (3.3%) device-related complications (perforations at the treatment site in 
the DA + PTA cohort). The freedom from restenosis rates at one year were 84.7% and 43.8% in the 
DA + DCB and DA + PTA groups, respectively.         
 

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The use of DCBs to treat SFA in-stent-restenosis (ISR) has also been assessed.  The first report came 
from a single-center study of 39 patients.  There were no procedure-related adverse events reported 
and the primary patency at one year was 92.1% and 70% at 2 years.85  86.  The DEBATE ISR trial 
assessed DCB treatment of SFA ISR in patients with diabetes 87,88.  The study included 44 patients 
and compared outcomes to historical data on diabetic ISR patients treated with POBA. The mean 
lesion length was 13.2 cm in the DCB group and 13.7 in the POBA group. More than half of the 
lesions were classified as Tosaka class 3 in both groups.  Two patients (1 in each group) experienced 
distal embolisation after one dilation of occlusive ISR, which was treated with aspiration. Procedural 
success was obtained in all patients.  At one year, the TLR rate was significantly lower in the DCB 
group (13.6% vs. 31%, p=0.045). At the 3 year follow-up however, the TLR rates in the DCB group 
was 40%, similar to the 43% rate observed in the historical data set.   
The first randomized trial assessing POBA vs. DCB for ISR was recently published.89 The trial 
randomized 119 patients (62 in the DCB group and 57 in the POBA group) with SFA ISR.  The 
mean lesion length was 8.2 cm and 28.6% were totally occluded.  Procedure-related complications 
included one late stent thrombosis in the DCB group and one subacute stent thrombosis after TLR 
with DCB in a POBA patient. Two distal embolizations in the DCB group resolved without 
intervention.  The primary  endpoint was binary recurrent restenosis assessed by duplex ultrasound 
and adjudicated by a core lab at 6 months.  This was observed in 15.4% (8/52) in the DCB group and 
44.7% (21/47) in the POBA group (p=0.002).  At 12 months, the rates were 29.5% (13/44) and 
62.5% (25/40), respectively (p=0.004).  The authors concluded that treatment of ISR with DCB is 
associated with lower rates of recurrent restenosis, without an apparent difference in safety. 
Two articles have been recently published on the cost effectiveness of drug-coated balloons 
(DCB).90,91 Diehm and Schneider90 created a decision-analytic model based on reported TLR rates 
and applied that data to associated costs over one year (Swiss Francs and Swiss DRG reimbursement 
figures). After one year, use of DCB was associated with substantially lower costs when compared 
to PTA, despite the higher cost during the initial treatment.  However, because DCBs do not have a 
dedicated reimbursement,   DCBs were less financially favorable for the provider.  The authors 
concluded a specific DRG reimbursement structure for the use of DCBs would benefit everyone. A 
group from the United Kingdom performed an economic evaluation of endovascular interventions 
(PTA, PTA + stent, drug-eluting stents, DCB).  The model assessed the relative cost-effectiveness 
from a health service prospective over a patient lifetime.91 Patients with CLI and claudication were 
evaluated separately. In both populations, DCBs had a lower lifetime cost and greater effectiveness 
than all other treatment options. 
CVI developed a paclitaxel-coated PTA balloon catheter that addresses some of the limitations of 
first generation paclitaxel-coated PTA balloon catheters relative to coating integrity while 
maintaining an excellent safety profile and possible therapeutic advantages as demonstrated in series 
of pre-clinical evaluations in swine and rabbit animal models.  The extensive bench and pre-clinical 
studies conducted demonstrated that the CVI Paclitaxel-coated PTA Catheter is safe for its intended 
use with no adverse reactions associated with drug delivery for the treated vessel segment at 30 days 
post-treatment in the animal model.  The presence of paclitaxel in the vessel up to 30 days post-
procedure, as demonstrated by pharmacokinetic studies, was associated with the possible prevention 
of restenotic reaction, characterized by signs of drug effects in the histopathology studies at the time 
point in the animal model.  
 

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A First-in-Human (FIH) investigation using the CVI Paclitaxel-coated PTA Catheter has been 
conducted to establish the safety profile of the device.92  A total of eighty (80) subjects were treated 
with the CVI Paclitaxel-coated PTA Catheter in two cohorts. The first fifty (50) patients were treated 
with pre-dilatation prior to treatment with the CVI Paclitaxel-coated PTA Catheter: the second thirty 
(30) patients were treated without the pre-dilatation step (direct cohort). The primary safety endpoint 
was 6-month MAE rate, defined as a combined rate of cardiovascular death, amputation and target 
lesion revascularization.   The observed rate was 4% (95% CI: 0.5%-13.7%).  The lower bound 
(13.7%) was below the objective performance criterion of 30%, therefore, the endpoint was met.  
The primary effectiveness endpoint was 6-month late lumen loss (LLL), which was 0.54mm 
(95%CI:0.28-0.81).  The historical control was 1.1mm, which is greater than the upper bound of 
0.82mm, therefore the effectiveness endpoint was also met.  The primary patency rate, defined as 
PSVR ≤ 2.5, per Kaplan-Meier estimate, was 89.5% at 12 months and 80.3% at 24 months.  The 
freedom from clinically-driven target lesion revascularization rate, per Kaplan-Meier estimate, was 
90.0% at 12 months and at 85.8% at 24 months.  Additionally, there were no amputations or 
cardiovascular deaths reported through 24 months.   
The two-year results from the direct cohort were recently presented.93  Twenty-eight patients, with 
37 lesions, were included in the direct cohort analysis; two patients were excluded because they were 
pre-dilatated.  The mean lesion length was 6.4cm and calcification was present in 48.6% of lesions.  
At 6 months, the mean LLL was 0.03 mm, indicating a good drug effect.  The MAE rate was 14.5% 
at 12 motnsh and 18.5% at 24 months, primarily driven by CD-TLR.  There was one index limb 
amputation observed in a patient who had a stent placed during the procedure within 6 months in 
conjunction with lower limb vessel thrombosis.  The primary patency rate was 86.2% at 12 months 
and 78.2% at 24 months, similar to the rates observed in the pre-dilatation cohort.  The freedom from 
clinically-driven target lesion revascularization rate, per Kaplan-Meier estimate, was 85.4% at 12 
months and 81.7% at 24-months.  This early data suggests that the CVI Paclitaxel-coated PTA 
Catheter is a safe and effective treatment option. 
 
 
No long-term studies have been performed to evaluate the carcinogenic potential of the CVI PTX-
coated PTA Catheter. Paclitaxel is a known genotoxin. The CVI PTX-coated PTA Catheter should 
not be used in women who are pregnant or intending to become pregnant, or in men intending to 
father children. 
 

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4.0 METHODOLOGY 
4.1 
Study Design 
This is a prospective, international, multi-center, single-arm study. All subjects will be treated with 
paclitaxel-coated balloon angioplasty.  Subjects meeting the definition of Rutherford Clinical 
Category (RCC) 2, 3 or 4 with atherosclerotic lesion(s) ≤20 cm located in the superficial femoral 
artery (SFA) and/or popliteal artery are eligible for enrollment.   
 
A second cohort (Cohort 2-ISR) is being added to the study to evaluate patients with in-stent 
restenosis as compared to a historical control. Subjects meeting the definition of Rutherford 
Clinical Category (RCC) 2, 3 or 4 with in-stent restenosis in the superficial femoral artery (SFA) 
and/or popliteal artery are eligible for enrollment. 
4.2 
Study Purpose  
The purpose of this single-arm study is to continue to assess the safety and performance of the CVI 
Paclitaxel-Coated Percutaneous Transluminal Angioplasty (PTA) Balloon Catheter in the treatment 
of de novo or restenotic lesions in the superficial femoral (SFA) and/or popliteal arteries in a broad 
patient population. 
 
A second cohort (Cohort 2-ISR) is being added to compare the safety and performance of the 
Stellarex 0.035” DCB to a historical control (the PTA control arm of the Spectranetics EXCITE 
Study; Dippel JACC CV Interv. Vol 8, No 1, Jan 2015) in restenotic lesions in the SFA and/or 
popliteal arteries in a broad patient population.   
 
4.3 
 Primary Safety Endpoint 
The primary safety endpoint 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 12 months post-procedure.   
4.4 
Primary Efficacy Endpoint 
The efficacy endpoint is primary patency at 12 months post-procedure.  Primary patency is defined 
as the absence of target lesion restenosis per duplex ultrasound (peak systolic velocity ratio [PSVR] 
≤ 2.5) and freedom from clinically-driven target lesion revascularization. 
4.5 
Secondary Endpoints 
The following secondary outcomes will be summarized in this study:   
1. Major Adverse Event (MAE) rate, defined as a composite rate of cardiovascular death, major 
target limb amputation, and clinically-driven target lesion revascularization (TLR): 
i. Cohort 1: through discharge and at 1, 6, 12, 24, 36, 48 and 60 months post procedure. 
ii. Cohort 2: through discharge and at 1, 6, 12, 24, and 36 months post procedure. 
2. Rate of adverse events:  
i. Cohort 1: through discharge, and at 1, 6, 12, 24, 36, 48, and 60 months post-procedure. 

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ii. Cohort 2: through discharge and at 1, 6, 12, 24, and 36 months post procedure. 
3. Rate of clinically-driven TLR at: 
i. Cohort 1:  6, 12, 24, 36, 48 and 60 months post-procedure. 
ii. Cohort 2: 6, 12, 24, and 36 months post-procedure. 
4. Rate of clinically-driven target vessel revascularization (TVR) at:  
i. Cohort 1:  6, 12, 24, 36, 48 and 60 months post-procedure. 
ii. Cohort 2: 6, 12, 24, and 36 months post-procedure. 
5. Rate of major amputation of the target limb at:  
i. Cohort 1: 6, 12, 24, 36, 48 and 60 months post-procedure. 
ii. Cohort 2: 6, 12, 24, and 36 months post-procedure. 
6. All-cause mortality rate at:  
i. Cohort 1: 6, 12, 24, 36, 48 and 60 months post-procedure. 
ii. Cohort 2: 6, 12, 24, and 36 months post-procedure. 
7. Rate of occurrence of arterial thrombosis of the treated segment at:  
i. Cohort 1: 1, 6, 12, 24, 36, 48 and 60 months post-procedure. 
ii. Cohort 2: 1, 6, 12, 24, and 36 months post-procedure. 
8. Rate of ipsilateral embolic events of the study limb within 30 days post-procedure. 
9. Primary patency rate at 6, 24, and 36 months post-procedure.  Primary patency is defined as the 
absence of target lesion restenosis per duplex ultrasound (peak systolic velocity ratio [PSVR] 
≤ 2.5) and freedom from clinically-driven target lesion revascularization. 
10. Alternative patency rate at 6, 24 and 36 months post-procedure. Alternative patency is defined 
as the absence of target lesion restenosis per duplex ultrasound PSVR < 2.4 and < 2.0 and 
freedom from clinically-driven TLR. 
11. Lesion success, defined as achievement of a final in-lesion residual diameter stenosis of ≤ 50% 
after using the study device. 
12. Technical success, defined as achievement of a final in-lesion residual diameter stenosis of ≤ 
50% (per angiographic core lab), using the paclitaxel-coated PTA balloon catheter without a 
device malfunction. 
13. Clinical success (per subject) defined as technical success without the occurrence of major 
adverse events during procedure. 
14. Procedural success (per subject) defined as lesion success without the occurrence of major 
adverse events during procedure. 
15. Change in Ankle-Brachial Index (ABI) from baseline to 6, 12, 24, and 36 months post-
procedure in subjects with: 
i. Cohort 1:  compressible arteries and baseline ABI < 0.9.  
ii. Cohort 2: compressible arteries. 

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16. Change in Walking Impairment Questionnaire (WIQ) score from baseline to 6, 12, 24, and 36 
months post-procedure. 
17. Change in Rutherford Clinical Category (RCC) from baseline to 6, 12, 24, and 36 months post-
procedure. 
18. Change in EQ-5D from baseline to 6, 12, 24, and 36 months post-procedure. 
4.6 
Subject Selection Criteria 
The study population includes those subjects with documented symptomatic stenosis of the 
superficial femoral artery (SFA) and/or popliteal artery.  Assessment of eligibility is based on data 
available to the Investigator at the time of subject enrollment. 
 
Cohort 2-ISR will allow the treatment of in-stent restenosis. 
 
4.6.1 Inclusion/ Exclusion Criteria Cohort 1 
Cohort 1 - General Inclusion Criteria 
Subject must meet all of the following general inclusion criteria.   
1. Has symptomatic leg ischemia, requiring treatment of the SFA and/or popliteal artery. 
2. Has a Rutherford Clinical Category of 2 - 4.  Note: Rutherford Clinical Category 2 
subjects should be entered into the study if conservative treatment has been unsuccessful. 
3. Is ≥ 18 years old.   
4. Has life expectancy > 1 year.  
5. Is able and willing to provide written informed consent prior to study-specific procedures. 
6. Is willing and capable of complying with the required follow-up visits, testing schedule 
and medication regimen. 
Cohort 1 - Angiographic Inclusion Criteria 
Subject must meet all of the following angiographic inclusion criteria.  Unless otherwise specified, 
the Investigator performing the procedure bases all angiographic inclusion criteria on visual 
determination at the time of the procedure. 
1. Has evidence at the target lesion(s) of clinically and hemodynamically significant de novo 
stenosis or restenosis, or occlusion, in the SFA (1 cm distal to the ostium of the profunda) 
and/or popliteal artery (proximal to the popliteal trifurcation), confirmed by angiography.   
2. Has target limb with at least one patent (<50% stenosis) tibio-peroneal run-off vessel to 
the foot confirmed by baseline angiography or magnetic resonance angiography (MRA) or 
computed tomography angiography (CTA).  Note:  Treatment of outflow disease is NOT 
permitted. 
3. Has 1 or 2 target lesion(s) with a cumulative lesion(s) length of no more than 20 cm.  
NOTE: A maximum of two (2) lesions can be treated if the cumulative total lesion length 
(i.e. the combined length of both lesions) is less than or equal to 20cm. 
4. Has target lesion(s) located >2 cm from any stent if the target vessel was previously 
stented. 
5. Has a reference vessel diameter of 4 - 6 mm by visual estimate.  

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6. Has a successful exchangeable guidewire crossing of the lesion(s).   
Cohort 1 - General Exclusion Criteria 
The subject must not meet any of the following general exclusion criteria. 
1. A female who is pregnant, of childbearing potential not taking adequate contraceptive 
measures, or nursing; or a male intending to father children during the study. 
2. Has significant gastrointestinal bleeding or any coagulopathy that would contraindicate the 
use of anti-platelet therapy 
3. Has known intolerance to study medications, paclitaxel or contrast agents that in the 
opinion of the investigator cannot be adequately pre-treated. 
4. Is currently participating in another investigational device or drug study that would 
interfere with study endpoints. 
5. Has history of hemorrhagic stroke within 3 months. 
6. Has surgical or endovascular procedure of the target limb within 14 days prior to the index 
procedure.  
7. Has any planned surgical intervention (requiring hospitalization) or endovascular procedure 
within 30 days after the index procedure. 
8. Has had a previous peripheral bypass affecting the target limb. 
9. Has unstable angina pectoris, myocardial infarction, liver failure, renal failure or chronic 
kidney disease (dialysis dependent, or serum creatinine  2.5 mg/dL) within 30 days of the 
index procedure.  
 
Cohort 1 - Angiographic Exclusion Criteria 
The subject must not meet any of the following angiographic exclusion criteria.  The Investigator 
performing the procedure bases all angiographic exclusion criteria on visual determination at the 
time of the procedure. 
1. Has significant stenosis (≥ 50%) or occlusion of inflow tract that is not successfully 
revascularized (< 30% residual stenosis without death or major vascular complication) 
prior to treatment of the target lesion(s).  Only treatment of target lesion(s) is acceptable 
after successful treatment of inflow iliac artery lesion(s).  
2. Has an acute or sub-acute intraluminal thrombus within the target vessel. 
3. Has in-stent restenosis or restenosis of the target lesion following previous treatment with a 
drug-coated balloon.  
4. Has an aneurysm (at least twice the reference vessel diameter) located in the target vessel, 
abdominal aorta, iliac, or popliteal arteries.   
5. Has perforation, dissection or other injury of the access or target vessel requiring stenting 
or surgical intervention prior to enrollment. 
6. Has no normal arterial segment proximal to the target lesion in which duplex ultrasound 
velocity ratios can be measured. 
7. Requires use of adjunctive therapies (i.e., laser, atherectomy, cryoplasty, scoring/cutting 
balloons, brachytherapy). 
8. Has severe calcification that precludes adequate PTA treatment. 

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4.6.2 Inclusion/ Exclusion Criteria Cohort 2 
Cohort 2 - General Inclusion Criteria 
Subject must meet all of the following general inclusion criteria.   
1. Has symptomatic leg ischemia, requiring treatment of the SFA and/or popliteal artery. 
2. Has a Rutherford Clinical Category of 2 - 4.  Note: Rutherford Clinical Category 2 
subjects should be entered into the study if conservative treatment has been unsuccessful. 
3. Is between 18-85 years old.   
4. Has life expectancy > 1 year.  
5. Is able and willing to provide written informed consent prior to study-specific procedures. 
6. Is willing and capable of complying with the required follow-up visits, testing schedule 
and medication regimen. 
7. History of previous femoropopliteal nitinol stenting which is suspect for in-stent 
restenosis. 
8. The patient has a resting ankle-brachial index (ABI) <0.9 or an abnormal exercise ABI 
(<0.9) if resting ABI is normal.  Patient with incompressible arteries (ABI >1.2) must 
have a toe-brachial index (TBI) <0.7 in target limb. 
 
Cohort 2 - Angiographic Inclusion Criteria 
Subject must meet all of the following angiographic inclusion criteria.  Unless otherwise specified, 
the Investigator performing the procedure bases all angiographic inclusion criteria on visual 
determination at the time of the procedure. 
1. Has angiographic evidence of significant restenosis (≥50% by visual estimate) within a 
previously deployed femoropopliteal bare nitinol stent(s) including ISR Class I, II or III.   
2. Has target limb with at least one patent (<50% stenosis) tibio-peroneal run-off vessel to 
the foot confirmed by baseline angiography or magnetic resonance angiography (MRA) or 
computed tomography angiography (CTA).  Note:  Treatment of outflow disease is NOT 
permitted. 
3. Total target treatment length of in-stent restenosis must be ≥ 4.0 cm in length and may 
include a single lesion or a multifocal lesion within the femoropopliteal segment (This 
includes the proximal, mid, and/or distal SFA and P1, P2 and/or P3 segment of the 
popliteal artery). Edge restenosis may be treated provided the lesion extends no more than 
3 cm outside the margin of the stent (proximal and/or distal margin). 
4. Has a reference vessel diameter of 4 - 6 mm by visual estimate.  
5. Has a successful exchangeable guidewire crossing of the lesion(s).   
 
Cohort 2 - General Exclusion Criteria 
The subject must not meet any of the following general exclusion criteria. 
1. A female who is pregnant, of childbearing potential not taking adequate contraceptive 
measures, or nursing; or a male intending to father children during the study. 

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2. Has significant gastrointestinal bleeding or any coagulopathy that would contraindicate the 
use of anti-platelet therapy 
3. Has known intolerance to study medications, paclitaxel or contrast agents that in the 
opinion of the investigator cannot be adequately pre-treated. 
4. Is currently participating in another investigational device or drug study that would 
interfere with study endpoints. 
5. Has history of hemorrhagic stroke within 3 months including those within <60 days with an 
unresolved walking impairment. 
6. Has surgical or endovascular procedure of the target limb within 3 months prior to the 
index procedure.  
7. Has any planned surgical intervention (requiring hospitalization) or endovascular procedure 
within 30 days after the index procedure. 
8. Has had a previous peripheral bypass affecting the target limb. 
9. Has unstable angina pectoris, myocardial infarction within 60 days, liver failure, renal 
failure or chronic kidney disease (dialysis dependent, or serum creatinine  2.5 mg/dL) 
within 30 days of the index procedure.  
10. History of previous femoropopliteal stenting in the target lesion with drug eluting stents or 
covered stents (endografts).  
 
Cohort 2 - Angiographic Exclusion Criteria 
The subject must not meet any of the following angiographic exclusion criteria.  The Investigator 
performing the procedure bases all angiographic exclusion criteria on visual determination at the 
time of the procedure. 
1. Ipsilateral and/or contralateral iliac (or common femoral) artery stenosis ≥ 50% Diameter 
Stenosis (DS) that is not successfully treated prior to index procedure (e.g. where a 
perforation occurred requiring a covered stent) or with final residual stenosis ≥ 30% 
documented by angiography.  
2. Identification of any lesion of the native vessel (excludes ISR) above the target stent in the 
femoropopliteal segment > 50% that is not successfully  treated prior to index procedure 
(e.g. complication requiring additional treatment) or with final residual stenosis > 30% 
documented by angiography. DES and DCB will not be allowed. The lesion length must be 
treatable with a single stent (if required). The lesion must not be contiguous with the target 
lesion; at least 2 cm of normal appearing vessel between the lesion and target lesion/target 
stent or between deployed stent (if required) and the target lesion/target stent. 
3. Has an acute or sub-acute intraluminal thrombus within the target vessel. 
4. Has an aneurysm (at least twice the reference vessel diameter) located in the target vessel, 
abdominal aorta, iliac, or popliteal arteries.   
5. Has perforation, dissection or other injury of the access or target vessel requiring stenting 
or surgical intervention prior to enrollment. 
6. Has no normal arterial segment proximal to the target lesion in which duplex ultrasound 
velocity ratios can be measured. 

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7. Requires use of adjunctive therapies (i.e., laser, atherectomy, cryoplasty, scoring/cutting 
balloons, brachytherapy). 
8. Grade 4 or 5 stent fracture affecting target stent or proximal to the target stent, or where 
evidence of stent protrusion into the lumen is noted on angiography in 2 orthogonal views. 
4.7 
Patient Screening 
It is recommended that all eligible patients be approached for enrollment in the study and be 
screened at the study site.  Study personnel will explain to the patient that even if the patient agrees 
to participate in the study and signs the written informed consent, angiography may demonstrate that 
the patient is not a suitable candidate for the study. 
4.8 
Informed Consent Process 
Prior to conducting any study-related assessments and prior to administration of any pre-procedure 
medications or sedation, the principal investigator, or qualified designee, will explain to each subject 
all aspects of the clinical study that are relevant to the subject’s decision to participate throughout the 
clinical study including, but not limited to, the following: purpose and nature of the study, study 
procedures, expected study duration, available alternative therapies, and the benefits and risks 
involved with study participation and the potential treatment.  The principal investigator, or qualified 
designee, shall avoid any coercion or undue improper influence on, or inducement of, the subject to 
participate and will not waive or appear to waive the subject’s legal rights. Subjects will be given a 
copy of the informed consent form and will be provided ample time to read and understand the 
document and the opportunity to ask questions. Subjects will be informed of their right to withdraw 
from the study at any time without prejudice; consent forms will use local non-technical language 
and be provided in a language understandable to the subject.  After this explanation, and before any 
study-specific procedures have been performed, the subject and the principal investigator, or 
qualified designee, responsible for conducting the informed consent process will voluntarily sign and 
personally date the informed consent form.  Prior to participation in the study, the subject will 
receive a copy of the signed and dated written informed consent and any other written information 
provided to the subject. 
The principal investigator or qualified designee will document in the medical records and/or on the 
informed consent document the informed consent process, including the date of consent and name of 
the person conducting the consent process.  Documentation of the time of consent is recommended if 
the informed consent process occurs on the same day as the index procedure.  The principal 
investigator or qualified designee shall ensure important new information is provided to new and 
existing subjects throughout the clinical investigation. 
4.9 
Subject Enrollment 
The subject is enrolled in the study after he/she has signed the subject informed consent, it has been 
determined that he/she meets all of the inclusion criteria and none of the exclusion criteria, and the 
pre-dilatation has been completed.  The point of enrollment is defined as the moment the study 
device enters the vasculature. 
4.10 Overview of Study Conduct 
Table 2 provides an overview of the assessment requirements for the study.  All testing and 
assessments should be conducted at the study site 

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Follow-up visits at 48 and 60 Months (Cohort 1)  can  be conducted via a telephone call to assess 
adverse events and record concomitant medication (name, dose, duration). 
Table 2:  Study Assessment Requirements  
 
Follow-Up Visits 
 
 
 
Baseline (within 30 days 
prior to enrollment) 
Procedure 
Discharge 
1-Month  
(15-45 days) 
6-Month 
(150 – 210 days) 
12-Months 
(335 – 395 days) 
24-Months 
(670 – 790 days) 
36-Months 
(1035-1155 days) 
48-Month             
(1400-1520 days)*** 
60-Month 
  (1765-1885 days)*** 
Informed Consent  
X 
 
 
 
 
 
 
 
 
 
Medical History and 
Physical Exam 
X 
 
 
 
 
 
 
 
 
 
Laboratory Tests**  
X 
 
 
 
 
 
 
 
 
 
Concomitant 
Medication Use 
(anticoagulants and  
antiplatelet only) 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
Rutherford Clinical 
Category Assessment 
X 
 
X* 
X 
X 
X 
X 
 
 
Walking Impairment 
Questionnaire (WIQ) 
X 
 
 
 
X 
X 
X 
X 
 
 
EQ-5D Questionnaire 
X 
 
 
 
X 
X 
X 
X 
 
 
Ankle Brachial Index 
(ABI)/Toe Brachial 
Index (TBI)+  
X 
 
 
X* 
X 
X 
X 
X 
 
 
Angiogram 
 
X 
 
 
 
 
 
 
 
 
Duplex Ultrasound 
 
 
X* 
X 
X 
X 
X 
 
 
Adverse Event 
Evaluation 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Stent Fracture 
Assessment (Cohort 2 
only) 
 
X 
 
 
 
 
 
 
 
 
*One Duplex Ultrasound, RCC and ABI occurring prior to 45 days post-procedure can occur at 
either the discharge visit or 1 month visit. 
** Within 7 days prior to enrollment 
*** 48 and 60 month follow-up visit only applicable for Cohort 1 
+ TBI if applicable only for Cohort 2 

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4.11 Required Assessments and Tests  
The following section details the study-required assessments and tests.   
4.11.1 Medical History and Physical Examination 
The subject’s clinical history and pre-existing conditions will be assessed and documented at 
baseline. 
4.11.2 Medication Use   
The subject’s medication use will be documented at baseline and all follow-up visits.  Medication 
collection will include only anticoagulants and antiplatelet medications.     
4.11.3 Laboratory Testing 
Serum creatinine will be obtained and documented within 7 days prior to enrollment. Note: Chronic 
renal disease to be assessed in the exclusion criteria is defined as dialysis dependent, or sCr  2.5 mg 
/ dL.Pregnancy test will be completed as appropriate.  
4.11.4 Rutherford Clinical Category Assessment  
The subject’s clinical status as indicated by RCC per clinical description will be assessed and 
documented at baseline and all follow-up visits beginning at pre-discharge or 1 month.  Refer to the 
Manual of Operations for complete instructions on determining RCC.   
4.11.5 Ankle-Brachial Index (ABI)/ Toe-Brachial Index (TBI) (Cohort 2 only)  
The subject’s ABI will be measured and documented at baseline and all follow-up visits beginning at 
pre-discharge or1 month.  An ABI is the ratio of the highest ankle systolic pressure to the highest 
brachial systolic pressure.  Refer to the Manual of Operations for complete instructions on 
measuring ABI and TBI (Cohort 2 only).   
4.11.6 Walking Impairment Questionnaire (WIQ)  
Each subject will undergo a WIQ assessment and the results will be documented at baseline and all 
follow-up visits beginning at 6 months.  The WIQ is an interviewer-administered subject-reported 
functional assessment focused on difficulty in walking.  Refer to the Manual of Operations for 
complete instructions on the WIQ.   
4.11.7 EQ-5D Questionnaire 
Each subject will complete an EQ-5D questionnaire and the results will be documented.  The EQ-5D 
is a self-reported quality of life assessment used to measure health outcomes.  EQ-5Ds questionnaire 
must be completed at baseline and all follow-up visits beginning at 6 months.  Refer to the Manual 
of Operations for complete instructions on completing the EQ-5D questionnaire. 
4.11.8 Angiogram 
For procedural angiogram requirements see Section 4.13.1.  Angiograms will be obtained per the 
Angiographic Protocol located in the Manual of Operations.  
4.11.9 Duplex Ultrasound (DUS) 
The subject will undergo a DUS, the results will be documented and copies of the scan will be sent 
to the core laboratory.  DUS is required prior to 45 days post-procedure (completed at either 
discharge or 1 month visit), 6 months, 12 months, 24 months, and 36 months post-procedure. Refer 
to the Manual of Operations for the Duplex Ultrasound Protocol.    

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4.11.10 Stent Fracture Assessment (Cohort 2 only) 
Pre-intervention radiographs of the target leg must be taken in two orthogonal views to assess stent 
fractures, and will be done according to the Angiographic Core Lab protocol. The operator must 
assess the stent(s) in the target lesion for stent fracture and grade prior to procedure to determine if 
the subject  meets Angiographic Inclusion Criteria, of stent fracture Grade 0‐3. Stent fractures Grade 
4‐5 are an Angiographic Exclusion 
 
4.11.11Adverse Event (AE) Evaluation  
For enrolled subjects, all adverse events will be collected, starting at the point of enrollment and 
throughout the duration of the study.  Refer to Section 4.24 for AE definitions.  
4.12 Baseline Requirements 
Informed consent must be obtained from each subject prior to obtaining any study-related 
assessments (not standard of care for the institution)  into the study in accordance with ISO 
14155:2011, Declaration of Helsinki, and pertinent individual country laws/regulations.   
Table 3 summarizes the list of all assessments and tests that are required at baseline.     
 
Table 3:  Baseline Requirements 
Baseline Requirements 
Timeframe Window 
Informed consent  
Within 30 days prior to enrollment 
Medical history and physical exam 
 Laboratory testing* 
Concomitant medication use 
Rutherford Clinical Category assessment 
Walking Impairment Questionnaire (WIQ) 
EQ-5D questionnaire 
Ankle Brachial Index (ABI)**/ Toe Brachial Index 
(TBI)+ 
*Labs collected within 7 days prior to enrollment. 
**Not required if subject has non-compressible arteries. 
+ TBI if applicable only for Cohort 2 
 
4.13 Procedure Requirements 
The subject will undergo percutaneous revascularization of the superficial femoral and/or popliteal 
arteries. The target lesion(s) must be at least 1 cm distal to the ostium of the profunda. 
See Section 4.14 for the required pre-procedure anticoagulation/antiplatelet therapy. 
The following describes the required assessments and activities during the procedure.   

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4.13.1 Angiogram  
A sheath will be inserted and after insertion the subject should receive anticoagulation medications 
as indicated by the Investigator to maintain appropriate clotting time.  Selective angiography of the 
limb to be treated including the distal aorta, bilateral iliac, ipsilateral femoral, popliteal and tibial-
peroneal vessels (to the pedal level) will be performed to identify the anatomical characteristics of 
the vasculature and to best isolate and define the lesion.  If a pre-procedure assessment has been 
completed with CTA/MRA or DUS including imaging of the distal aorta, the angiography can be 
limited to the target vessel, with a baseline assessment of run-off.  Angiography must be conducted 
according the Angiographic Core Laboratory Protocol (refer to Manual of Operations).  Gadolinium 
and CO2 are not allowed for use as contrast medium. 
During angiography the Investigator performing the procedure will assess the subject for the 
angiographic inclusion and exclusion criteria. The presense of severe calcification (defined as 
radioopacities noted on both sides of the arterial wall and extending  more than 1cm in length prior 
to contrast injection or digital subtraction angiography), which may preclude an adequate PTA 
treatment, must be assessed to determine subject eligibility for Cohort 1 only.  A radiopaque ruler 
will be used to define lesion length and define anatomical measurement references.  If the subject 
meets all the inclusion criteria and does not meet any of the exclusion criteria, the subject is enrolled 
when the study device enters the vasculature.   
Angiographic films, including run-off, will be obtained immediately prior to and after treatment 
according to the Angiographic Core Laboratory Protocol.  Capture images that demonstrate the 
stenosis in two views that minimize the degree of vessel overlap and demonstrate the stenosis in its 
most severe view.  A final angiogram of the target lesion and run-off will be done following 
adjunctive procedures (if required).  Angiographic results of patients enrolled must be sent to the 
Angiographic Core Laboratory. 
The Angiographic Core Laboratory assessments will supersede the measurements by the Investigator 
performing the procedure for data analysis purposes; however, the measurements by the Investigator 
performing the procedure will be used to determine subject eligibility at the time of enrollment.   
4.13.2 Treatment of Target Lesions 
Cohort 1:  
The lesion(s) intended for treatment at the time of the index procedure that meet the inclusion 
criteria and none of the exclusion criteria will be considered the “target lesions”.  Each subject can 
have up to 2 target lesions as long as the maximum cumulative lesion length is no more than 20 cm.  
If there are 3 cm or less between diseased segments needing treatment in the SFA and/or popliteal 
artery of the target limb (i.e., target vessel), then it can be considered one lesion if the total length is 
no more than 20 cm (see examples below).  If there are more than 3 cm between diseased segments, 
they will be considered separate lesions and count as two lesions. 
 
Examples of 1 or 2 Lesions:  
 

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Cohort 2:  
One lesion of length ≥ 4cm meeting the inclusion and none of the exclusion criteria may be 
considered for enrollment.  
4.13.3 Treatment of Non-Target Lesions 
Prior to Study Procedure: 
Any lesions in the non-target limb may be treated up to 1 day prior to target lesion treatment.  
Lesions in the target limb may be treated up to 14 days (Cohort 1) or 3 months (Cohort 2) prior to 
the target lesion treatment.   
 
During Study Procedure: 
Cohort 1:  
Lesions in the iliac arteries, in either limb, that require treatment may be revascularized during the 
index procedure (prior to target lesion treatment).  No other non-target lesions in the ipsilateral or 
contralateral limb may be treated during the index procedure.  Iliac artery treatment must be 
successful, per Inclusion/Exclusion criteria, in order to enroll the subject except for stent placement. 
If stent placement is required, the stent placement in the iliac arteries may occur after the treatment 
of the target lesion(s). 
Cohort 2:  
Non-target lesions may be treated according to the following guidelines. Ipsilateral and/or 
contralateral iliac, common femoral artery and/ or proximal target vessel stenoses 50% DS may be 
treated prior to the target lesion by local standard of care; however, unsuccessful treatment (e.g. 
where a perforation occurred requiring a covered stent) or final residual stenosis 30% documented 
by angiography) would constitute an angiographic exclusion to participation in the Study. Treatment 
of in-flow lesions with DES and DCB is not allowed Angiographic exclusions to enrollment include: 
the need for any other cardiac or vascular surgical or interventional procedure, planned or predicted, 
prior to completion of the 30–day follow–up (including, but not limited to aortic, renal, cardiac, 
carotid, contralateral femoro‐popliteal, and contralateral below the knee); and/or identification of any 
lesion below the target stent in the treated leg >50% that will require preplanned or predicted 
treatment during the index procedure or within 30 days of follow up. 
 
The non‐target lesions should be treated and complete run‐off to the distal foot performed prior to 
completion of Angiographic Criteria assessment and target lesion treatment. 
 

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Following Study Procedure: 
Treatment of other non-target lesions (ipsilateral or contralateral limb) following the index procedure 
must not occur within 30 days of the index procedure.     
4.13.4 Vessel Preparation 
Target lesion must be crossed by an exchangeable guidewire in an antegrade manner and without 
using a re-entry device. Retrograde access and/or re-entry devices are not permitted.  
Pre-dilatation of the target lesion(s) is required with a non-drug coated balloon prior to study 
treatment.  A lower profile balloon (i.e., at least 1 mm smaller diameter than necessary for the study 
balloon) should be used for pre-dilatation.  In the event a subject has two target lesions, it is required 
that both lesions be pre-dilated prior to treatment with the study device (Cohort 1 only). 
4.13.5 PTX PTA (DCB) Procedure  
The diameter of the study balloon will be selected based on the vessel reference diameter distal to 
the target lesion.  The balloons should be sized to ensure the full length of the lesion is treated and 
the balloon has full apposition to the arterial wall without oversizing.  The length of the balloon will 
be selected in lengths approximately 10 mm longer than the target treatment area to allow the 
balloon to extend approximately 5 mm beyond the proximal and distal edges of the target lesion (per 
Investigator’s visual estimate).  In the event the target lesion length cannot be treated with a single 
catheter, a second treatment catheter is allowed.  The second study balloon will be placed such that 
there is approximately 1 cm of overlap (marker to marker) between the coverage areas (per 
Investigator’s visual estimate) to maintain continuous coverage of the target lesion. A maximum of 
two study balloons may be used for each target lesion treated. 
The PTX PTA balloon catheters will be delivered and deployed per the Instructions for Use (IFU).  
All balloon inflations will be maintained for at least one minute.   
If a study balloon enters the vasculature but isn’t used to treat the subject, the subject is considered 
enrolled in the study and must complete the 30 day follow-up period and AE reporting through 30 
days. 
4.13.6 Adjunctive Procedures  
Cohort 1:  
For post-treatment residual stenosis >50% or flow-limiting dissection (grade D or greater), after 
study treatment, post-dilation must be performed using a commercially available bare balloon with 
prolonged inflations(s) (minimum 2 minutes) Thereafter, stent implantation, using a commercially 
available, non-drug eluting, bare metal stent, is allowed if residual stenosis remains >50%, a flow-
limiting dissection (grade D or greater) is present, or there is a translesional pressure gradient >10 
mmHg.  The translesional pressure gradient can be measured using a pressure wire and 
simultaneously measuring pressures proximal and distal to the target lesion. 
Cohort 2:  
If upon completion of prescribed treatment, the Investigator determines that there is a suboptimal 
angiographic result (>50% residual stenosis in target treatment segment post assigned treatment), 
Provisional PTA with conventional balloons and/or stenting may be performed. Bailout stenting is 
only allowed to manage occurrence of flow‐limiting dissection (grade D or greater), or threatened or 

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acute closure of target lesion. Elective use of stents is a protocol deviation. Additional procedures 
may be performed as medically necessary. 
4.13.7 Procedure Completion 
An angiogram of the treated segment(s) must be recorded for subsequent Angiographic Core 
Laboratory analysis of the post-treatment residual stenosis.  
The end of the procedure is defined as the time after a complete angiogram, including runoff, has 
been performed AND the last guidewire and catheter have been removed.  If the subject returns to 
the procedure room and a guiding catheter is reinserted and dilation is performed, this is considered 
a re-intervention and should be documented accordingly.  The sheath(s) may be removed at the 
physician’s discretion. 
4.13.8 Adverse Event Evaluation  
For enrolled subjects, all adverse events will be collected, starting at the point of enrollment.   See 
Section 4.24 for the AE definitions.  Adverse event evaluations will also occur prior to discharge and 
at all follow-up visits.   
4.14 Medical Anticoagulant/Antiplatelet Therapy  
4.14.1 Pre-Procedure 
All subjects are required to receive dual antiplatelet therapy with aspirin and clopidogrel (preferred 
medication), prasugrel, or ticlopidine per hospital standard of care prior to the procedure.  The 
following doses for aspirin and clopidogrel are recommended:   
 Aspirin (may be enteric-coated):  ≥81 mg every day.  If not currently taking aspirin, a 
bolus of 500 mg can be given the day before or the day of the procedure. 
 Clopidogrel:  75 mg every day for 7 days prior to procedure, or 300 mg every day for 
3 days prior to procedure, or 600 mg within 24 hours prior to or immediately after the 
procedure (while the subject is still on the table).   
 
If prasugrel is administered, the recommended dose is 10 mg daily. 
 
Ticlopidine should only be administered if the subject has a known allergy to clopidogrel or 
prasugrel.  Recommended dose for ticlopidine is 250 mg twice a day.  If a subject is prescribed 
ticlopidine, a complete blood cell count and differential is required prior to administration.   
4.14.2 Peri-Procedure 
The subject should receive anticoagulation as indicated by the Investigator to maintain appropriate 
clotting time.  Medications provided during the study procedure do not need to be reported on the 
Case Report Forms. 
4.14.3 Post-Procedure 
The optimal duration of antiplatelet therapy for each subject is to be determined by the investigator.  
All subjects are recommended to receive antiplatelet therapy with aspirin and/or clopidogrel after the 
procedure.  The following doses are recommended:   
 Aspirin (may be enteric-coated):  ≥81 mg every day indefinitely.  
 Clopidogrel:  75 mg every day for a minimum of 4 weeks after the procedure.  If the subject 
is intolerant of clopidogrel and prasugrel, ticlopidine may be used. 

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Recommendation Note: Subjects receiving ticlopidine should have a complete blood cell count and 
differential blood count completed. 
4.15 Follow-Up requirements 
All enrolled subjects are required to complete all follow-up visits. 
4.16 Discharge Follow-up Requirements 
All subjects are required to have a discharge assessment.  Discharge assessment requirements are 
listed in Table 4. 
 
Table 4:  Discharge Assessment Requirements 
Discharge Requirements 
Timeframe 
Concomitant medication use 
Prior to discharge 
Adverse event evaluation 
Duplex Ultrasound* 
Rutherford Clinical assessment* 
Ankle-brachial index*/ Toe brachial index+ 
         *One Duplex Ultrasound, RCC and ABI occurring prior to 45 days post-procedure can occur at either the  
          discharge visit or 1 month visit. 
         + TBI if applicable only for Cohort 2 
 
4.17 Follow-up Visit Requirements 
Following hospital discharge, all subjects are required to have follow-up visits at pre-determined 
time points during the study.  Table 5 lists the requirements and visit windows for the 1-Month visit 
(One Duplex Ultrasound, RCC and ABI occurring prior to 45 days post-procedure can occur at 
either the discharge visit or 1 month visit),                    *One Duplex Ultrasound, RCC and ABI occurring prior 
to 45 days post-procedure can occur at either the  
       discharge visit or 1 month visit. Must be conducted per Duplex Ultrasound Protocol.  Copies must be sent to the 
Duplex Ultrasound Core Laboratory for review. 
                    + TBI if applicable only for Cohort 2 
 
 
Table 6 for the 6-Month visit, 
Table 7 for the 12-Month visit,  
Table 8 for the 24-Month visit, and Table 9 for the 36-Month visit.  The visit windows are specified 
according to number days following the index procedure.  
 

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The 1-Month follow-up visit can be conducted via a telephone call or a physician office visit. If a 
Duplex Ultrasound, RCC or ABI is required at the 1 month visit, the visit will be conducted in 
office.  The 6, 12, 24, and 36 Month follow-up visits require a physician office visit and in-person 
evaluation. 
For Cohort 1, the 48 and 60 Month follow-up visits (Tables 10 and 11) may be conducted via a 
telephone call or a physician office visit  to assess adverse events and record concomitant medication 
(name, dose, duration). 
 
 
Table 5:  1-Month Follow-Up Visit Requirements  
Follow-up Requirements 
Target 
Window 
Concomitant medication use 
30 Days 
15-45 Days 
Adverse event evaluation 
Duplex Ultrasound* 
Rutherford Clinical assessment* 
 
 
Ankle-brachial index*/ Toe-brachial index+ 
 
 
                    *One Duplex Ultrasound, RCC and ABI occurring prior to 45 days post-procedure can occur at either the  
       discharge visit or 1 month visit. Must be conducted per Duplex Ultrasound Protocol.  Copies must be sent to the 
Duplex Ultrasound Core Laboratory for review. 
                    + TBI if applicable only for Cohort 2 
 
 
Table 6:  6-Month Follow-Up Visit Requirements 
Follow-up Requirements 
Target 
Window 
Concomitant medication use 
180 Days 
150-210 Days 
Rutherford Clinical Category assessment 
Ankle-brachial index/ Toe Brachial index+ 
WIQ  
Duplex Ultrasound* 
EQ-5D questionnaire  
Adverse event evaluation 
*Must be conducted per Duplex Ultrasound Protocol.  Copies must be sent to the Duplex Ultrasound 
Core Laboratory for review.  
+ TBI if applicable only for Cohort 2 
 
Table 7:  12-Month Follow-up Visit Requirements 
Follow-up Requirements 
Target 
Window 
Concomitant medication use 
365 Days 
335-395 Days 
Rutherford Clinical Category assessment 

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Ankle-brachial index/ Toe Brachial index+ 
WIQ  
Duplex Ultrasound* 
EQ-5D questionnaire  
Adverse event evaluation 
*Must be conducted per Duplex Ultrasound Protocol.  Copies must be sent to the Duplex Ultrasound 
Core Laboratory for review. 
+ TBI if applicable only for Cohort 2 
 
Table 8:  24-Month Follow-up Visit Requirements 
Follow-up Requirements 
Target 
Window 
Concomitant medication use 
730 Days 
670-790 Days 
Rutherford Clinical Category assessment 
Ankle-brachial index/ Toe Brachial index+ 
WIQ  
Duplex Ultrasound* 
EQ-5D questionnaire  
Adverse event evaluation 
*Must be conducted per Duplex Ultrasound Protocol.  Copies must be sent to the Duplex Ultrasound 
Core Laboratory for review. 
+ TBI if applicable only for Cohort 2 
 
Table 9:  36-Month Follow-up Visit Requirements 
Follow-up Requirements 
Target 
Window 
Concomitant medication use 
1095 Days 
1035-1155 Days 
Rutherford Clinical Category assessment 
Ankle-brachial index/ Toe Brachial index+ 
WIQ  
Duplex Ultrasound* 
EQ-5D questionnaire  
Adverse event evaluation 
*Must be conducted per Duplex Ultrasound Protocol.  Copies must be sent to the Duplex Ultrasound 
Core Laboratory for review. 
+ TBI if applicable only for Cohort 2 
 
Table 10:  48-Month Follow-up Visit Requirements (Cohort 1 only) 
Follow-up Requirements 
Target 
Window 
Concomitant medication use 
1 460 Days 
1 400-1 520 
Days 
Adverse event evaluation 
 

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Table 11:  60-Month Follow-up Visit Requirements (Cohort 1 only) 
Follow-up Requirements 
Target 
Window 
Concomitant medication use 
1 825 Days 
1 765-1 885 
Days 
Adverse event evaluation 
 
4.18 Unscheduled and Re-intervention Visits During Follow-up 
Completion of study assessments at unscheduled follow-up visits prior to the 60-month (Cohort 1) or 
36 month (Cohort 2) visit should be done as clinically indicated and corresponding data should be 
documented and submitted to the sponsor. 
If a subject is clinically indicated for a re-intervention of a target lesion prior to the 60-month 
follow-up (Cohort 1) or 36-month follow-up (Cohort 2) visit and the subject does not want to 
proceed with an invasive angiogram or re-intervention, it will not be considered a deviation from the 
Study Protocol.   If possible, all non-invasive assessments should be captured for the study, 
including ABI, RCC, WIQ, EQ-5D and duplex ultrasound, even if the re-intervention and angiogram 
are declined.  Copies of any angiographic or duplex ultrasound results must be sent to the 
appropriate core laboratory. These data will be collected and used for adjudication by the Clinical 
Event Committee for “clinically-driven” reintervention. 
4.19 Termination of Participation 
All subjects have the right to withdraw from participation at any point during the study.  In addition, 
Principal Investigators also have the ability to terminate subject participation in the study.  A 
description of the reason for a subject’s termination will be documented in the subject’s medical 
records.  Reasons for termination include but are not limited to:  study completion, subject 
withdrawal, physician-directed subject withdrawal, lost-to-follow-up or death.   
4.20 Lost to Follow-Up 
Every attempt must be made to have all subjects complete the required follow-up visits according to 
the visit schedule.  A subject will not be considered lost-to-follow-up unless efforts to obtain 
compliance are unsuccessful.  At a minimum, the effort to obtain follow-up information must 
include three attempts to make contact via telephone and sites must send at least one certified letter.  
Telephone contact efforts to obtain follow-up must be documented in both the subject’s medical 
records and on the study electronic case report forms (eCRFs).   
4.21 Subject Withdrawal 
All study subjects have the right to withdraw their consent at any time during the study.  Whenever 
possible, the site staff should obtain written documentation from the subject that wishes to withdraw 
his/her consent for future follow-up visits and contact.  If the site staff is unable to obtain written 
documentation, all information regarding the subject’s withdrawal must be recorded in the subject’s 
medical record.  In addition, the appropriate eCRFs must be completed for the subject and clear 
documentation of the subject’s withdrawal must be provided to the Sponsor.   
Withdrawal of a subject from the study can occur at the discretion of the Principal Investigator or the 
Sponsor.  Reasons for physician and/or Sponsor-directed subject withdrawal include, but are not 

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limited to: the subject is not adhering to the Study Protocol requirements, the subject has enrolled in 
another study that conflicts with this Study Protocol outcomes, or if it is in the best interest for the 
safety or welfare of the subject to withdraw. 
4.22 Deviations to the Study 
Principal Investigators and site support staff must avoid protocol deviations. Any deviations from 
clinical protocol requirements will be considered protocol deviations and need to be reported to the 
sponsor.  The sponsor will not make any exceptions to the protocol and will not provide waivers to 
subjects with any protocol deviations.  Any emergency deviations (deviations from the study 
protocol to protect the life or physical well-being of a subject, such as, surgical repair of the target 
vessel) that occur must be reported to the sponsor and the site Ethics Committee (EC) per their local 
guidelines.   
4.23 Device Deficiency 
A device deficiency is defined as inadequacy of a medical device with respect to its identity, quality, 
durability, reliability, safety, or performance.  Device deficiencies include malfunctions, use errors, 
and inadequate labeling.  All device malfunctions must be reported to the sponsor. 
If a device deficiency results in an adverse event for the subject, this adverse event (AE) will be 
considered reportable and must be reported as an adverse event.  Device deficiencies that do not 
result in an adverse event for the subject do not need to be recorded as an AE, as they are not 
considered an AE. 
If a device malfunction occurs with the Stellarex 035 DCB catheter, return the device as per the 
device return procedure . 
4.24 Adverse Events 
Adverse event reporting requirements and time frames are provided in Table 12 of Section 9.2. 
4.24.1 Adverse Event Definitions1 
Adverse Event (AE) is 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.   
Adverse Device Effect (ADE) is an adverse event related to the use of an investigational medical 
device.  
Serious Adverse Event (SAE) is defined as an adverse event that: 
 Led to a death,  
 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 
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,   

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 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.   
 
For purposes of reporting within this protocol, pre-existing conditions and/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 Device Effect (SADE) is an adverse device effect that has resulted in any of the 
consequences characteristic of a serious adverse event.   
Unanticipated Serious Adverse Device Effect (USADE) is a 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.   
4.24.2 Adverse Event Classifications 
In addition to the definitions above, adverse events will be classified as a major adverse event 
defined as any clinically-driven TLR, major amputation of treated limb, or cardiovascular death.  
4.24.3 Adverse Event Severity 
The investigator will use the following definitions to rate the severity of each adverse event: 
Mild:  Awareness of a sign or symptom that does not interfere with the subject’s usual activity or is 
transient, resolved without treatment and with no sequalae. 
Moderate:  Interferes with the subject’s usual activity and/or requires symptomatic treatment. 
Severe:  Symptom(s) causing severe discomfort and significant impact of the subject’s usual activity 
and requires treatment. 
4.24.4 Adverse Event Relationships 
The Investigators will evaluate whether or not the adverse events were related to the procedure, 
study requirements, and/or study device according to the following categories: 
Not Related:  The event is definitely not associated with the study device or 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 device or procedure 
and/or a more likely alternative etiology exists. 
Possible:  The temporal sequence between device application and or 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 between device application or study procedure and the event is 
relevant or the event abates upon device application completion/removal or procedure completion or 
the event cannot be reasonably explained by the subject’s condition.   

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Highly Probable:  The temporal sequence between device application or study procedure and the 
event is relevant and the event abates upon device application completion/removal or procedure 
completion, or reappearance of the event on repeat application or on repeat interventional procedures 
(re-challenge).   
4.25 Deaths 
Each subject death must be reported to the Sponsor.  A death must be reported to the Sponsor or 
representative as soon as possible after the site’s knowledge of the event.  A written report will be 
provided to the Sponsor within 3 calendar days after the Investigator learns of a death and will be 
provided to the ethics committee according to the committee’s reporting guidelines.   It is requested 
that a copy of the death certificate, autopsy report, and any other source documents related to the 
death be sent to the Sponsor or representative when available.  In the event that no source documents 
are available, the PI will be required to submit a letter to the Sponsor describing the circumstances of 
the subject’s death. 
4.26 Core Laboratory Requirements 
4.26.1 Angiographic Core Laboratory 
An independent Angiographic Core Laboratory will review all scheduled and unscheduled 
angiographic procedure data.  See Angiographic Core Laboratory Protocol in the Manual of 
Operations.  
4.26.2 Ultrasound Core Laboratory 
An independent Ultrasound Core Laboratory will review all scheduled and unscheduled duplex 
scans.  See Duplex Ultrasound Protocol in the Manual of Operations.   
4.27 Committees 
4.27.1 Clinical Events Committee 
The Clinical Events Committee (CEC) is made up of angiologists, interventional radiologists, 
interventional cardiologists or vascular surgeons who are not participants in the study.  The CEC is 
charged with the development of specific criteria used for the categorization of clinical events and 
clinical endpoints in the study 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 is responsible for reviewing all reported adverse events (Cohort 1 only).  The CEC will 
adjudicate and classify all primary and secondary endpoint events as defined in the clinical protocol.  
In addition, the CEC will be responsible for adjudicating and classifying any site reported device 
related or procedure related adverse events.  The CEC will determine if any device related adverse 
event is an unanticipated serious adverse device effect. The committee will rule on all deaths that 
occur throughout the trial.  
 
 

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4.27.2 Study Steering Committee 
The Steering Committee (SC) is the main policy and decision making committee of the study and 
has final responsibility for the scientific conduct. The specific tasks of the SC are to: 
 
Ensure proper design and conduct of the trial 
 
Verify ethical and professional standards of the trial 
 
Ensure that the results of the clinical trial and the scientific accomplishments are 
arrived at in the most efficient manner possible 
 
Enforce the publication policy 
The steering committee will be composed of the global principal investigator and the international 
principal investigator from each geographic region (European Union, Asia Pacific and the 
Americas). 
4.27.3 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. 
 
4.28 Case Report Forms 
Electronic case report forms (eCRFs) will be used to collect study data.  The eCRFs will be reviewed 
and electronically signed by the Principal Investigator.  All appropriate sections of the eCRFs must 
be completed.   
Case report forms related to the index procedure should be completed within two weeks following 
subject discharge.  The follow-up forms must be completed in a timely manner after the follow-up 
visit.  
Study monitors designated by the sponsor will review the information documented in the eCRFs and 
verify the information recorded is consistent with medical records and other source documents.  
Errors or incomplete entries will be rectified.   
The sponsor will use the study data for statistical and tracking purposes and will treat the 
information as confidential.  A regulatory representative may review or copy study records during an 
audit. 
5.0 STATISTICAL METHODS  
5.1 
Statistical Methods – Cohort 1 
5.1.1 Sample Size  
This study is designed to continue to assess the safety and performance of the PTX PTA balloon 
catheter in a broad patient population.  The predefined statistical analysis of the outcomes is detailed 

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below; however, no formal statistical success criteria are proposed.  Therefore, the sample size of the 
study is not based on statistical formulas for hypothesis testing of the primary outcome. 
5.1.2 General Principles 
All statistical analyses will be performed using Statistical Analysis System (SAS) for Windows 
(version 9.1 or higher, SAS Institute Inc. Cary, NC) or other widely accepted statistical or graphical 
software.  Unless otherwise specified, data for all enrolled study subjects will be presented.   
Descriptive statistics will be used to present the data and to summarize the results.  Discrete 
variables will be presented using frequency distributions and cross tabulations.  Continuous variables 
will be summarized by presenting the number of observations (N), mean, standard deviation, 
median, minimum, and maximum values.    
For AE reporting, the primary analysis will be based on subject counts.  A subject with more than 
one event will be counted only once toward the event rate based on the total number of subjects with 
AEs.  An event rate based on event counts will also be presented.  For example, if a subject 
experiences one major unplanned amputation of the treated limb and two clinically-driven TLRs 
within 30 days, the subject will be counted once in the rate of total subjects with a 30-day MAE; the 
same subject will be counted once in the individual event category of “Major Unplanned Amputation 
of the Treated Limb” and twice in the “Clinically-Driven TLR” category.     
5.1.3 Analysis of Baseline Demographics and Procedural Characteristics 
All clinically relevant baseline demographics and procedure characteristics will be tabulated.  
5.1.4 Analysis of Outcomes   
Descriptive statistics will be provided for all study endpoints including the primary safety endpoint, 
the efficacy endpoint and all secondary endpoints.    Categorical variables will be analyzed using 
frequency tabulation and event rate.  For continuous variables, analysis will include mean, median, 
standard deviation, and ranges.  Time-to-event variables including the primary safety endpoint will 
be analyzed using survival analysis and reported at 1 year (365 days), 2 years (730 days) 3 years 
(1095 days), 4 years (1,460 days) and 5 years (1,825 days) with Kaplan-Meier plots provided. 
Prior to receipt of all 12 month data, results may be reviewed for submission to regulatory bodies.  In 
these circumstances, data cut-off dates will be determined and documented prospectively. 
5.1.5 Handling Discontinued Subjects 
The primary endpoints will be analyzed using Kaplan-Meier survival analysis.  This method includes 
each patient’s data through evaluable time periods in order to predict event rates and rates of 
freedom from events. Since all patients contribute to the analysis regardless of whether they had the 
event of interest, discontinued subjects will not be analyzed with methods common to randomized 
controlled clinical trials, including simulations and last-event-carried-forward.  The reasons for 
mortality and other study exits will be provided in a tabular format, and the number of patients 
analyzed at each study interval will be clearly listed. 
5.1.6 Analysis of Ability to Pool Data across Investigational Sites 
This is a multicenter clinical study with standardization of subject enrollment, data entry and adverse 
event reporting.  All investigational sites will follow the requirements of a common protocol, and 
common data collection procedures and forms.   

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To present the data from this clinical study in a summary form, a comparison across all sites will be 
completed to determine if the generated data could be pooled. The following variables will be 
completed to assess the appropriateness of pooling data from across all sites:   
 Baseline demographics such as age and gender 
 Lesion characteristics such as lesion length and percent stenosis 
The distributions of the above variables across the sites will be tabulated.  To detect site differences, 
t-tests or Wilcoxon’s rank-sum test will be used for continuous variables and Fisher’s exact test for 
categorical variables.   
5.2 
Statistical Methods – Cohort 2 
 
5.2.1 Statistical Overview 
 
The ISR cohort study design is that of a single-arm trial in which there are two co-primary 
endpoints. The Stellarex 035 DCB treated group (Cohort 2) will be compared to historical control 
patients.  The historical control patients  include 68 patients who were randomized to the 
Spectranetics EXCITE ISR PTA control arm. The two 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 
target lesion revascularization through 12 months post-procedure. (label π the 
probability of an event for the corresponding treatment group). 
o H0: πStellarex ≤ πEXCITE PTA + δ 
o H1: πStellarex > πEXCITE PTA + δ where δ is the non-inferiority margin of 0.05. 
 Superior Effectiveness: Patency at 12 months post-procedure, defined as the absence of 
target lesion restenosis determined by duplex ultrasound PSVR ≤ 2.5 and freedom from 
target lesion revascularization. (label θ the probability of an event for the corresponding 
treatment group).  
o H0: Stellarex ≤ EXCITE PTA 
o H1: Stellarex > EXCITE PTA 
 
The analysis populations are Intention-to-Treat (ITT) , modified ITT (mITT), and Per-Protocol (PP); 
they are fully defined below in the next subsection. 
 
5.2.2 Analysis Populations 
The Intention-to-Treat (ITT) population will be comprised of all subjects who successfully complete 
the preliminary qualification procedures and are subsequently enrolled to receive the Stellarex 035 
DCB.  

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The Modified Intention-to-Treat (mITT) will be comprised of all subjects in the ITT population who 
do not receive a bailout stent and did not receive provisional treatment for >50% residual stenosis 
post all assigned treatment or bailout stenting. The primary analysis for both safety and efficacy will 
be based on the mITT population. 
 
The Per-Protocol (PP) population will consist of ITT subjects who had no bail-out stenting and no 
major protocol deviations defined by the study management team.  The data for each subject will be 
reviewed by an independent angiographic core laboratory.  
 
All trial endpoints will be analyzed using both the Intention-to-Treat, Modified Intention-to-Treat, 
and Per-Protocol populations, with the mITT analysis a priori designated as the primary analysis 
population. 
 
5.2.3 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. 
The statistical analysis plan (SAP) 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 Endpoints 
The primary analysis of the primary safety endpoint will be performed on the mITT analysis 
set.  The primary efficacy and safety endpoints will be analyzed as dichotomous endpoints 
(success/failure) based on each subject’s observed status at their 12 month followup visit. Patients 
who had an event prior to their 12 month follow-up will be considered as an event at the 12 month 
follow-up visit.    
For the primary safety endpoint, the probability of non-inferiority is the probability the 
ILLUMENATE Global DCB Cohort 2 12-month rate is within the 0.05 non-inferiority margin from 
the EXCITE PTA 12-month rate. For the primary efficacy endpoint, the probability of superiority is 
defined as the probability the 12-month rate in the ILLUMENATE Global DCB Cohort 2 is greater 
than the EXCITE PTA 12-month rate. The 12 month rates will be estimated with multiple 
imuptation for missing values. 
At the final analysis, study success will be declared if there is at least a 97.6% probability of 
superiority for the primary efficacy endpoint and at least a 97.5% probability of non-inferiority for 

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the primary safety endpoint. If non-inferiority is declared for the safety endpoint at the final analysis, 
a test of superiority will be conducted.  Superiority in terms of safety will be declared if there is at 
least a 97.5% probability of superiority. 
 
Because the treatments being compared are based on patients from two different clinical studies, a 
propensity score for membership in each patient group will be constructed as a function of baseline 
covariates. The primary analyses of efficacy and safety will be stratified according to the quantiles of 
the propensity scores. For the primary efficacy endpoint the probability of superiority and for the 
primary safety endpoint the probability of non-inferiority based on 5% non-inferiority margin will be 
determined across the strata.  The final analysis will be conducted when all enrolled patients have 
had the opportunity to complete 12 months of follow-up.  Missing data will be imputed by multiple 
imputation.  If non-inferiority is declared for the safety endpoint at the final analysis with complete 
12-month data, a test of superiority will be conducted.  Superiority in terms of safety will be 
declared if there is at least a 97.5% probability of superiority. All tests are similar to a one-sided test 
at the 2.5% alpha level 
  
Interim Analysis 
There will be one interim analysis during the enrollment of the ISR cohort, to be conducted 
approximately 6 months from the date the last patient is enrolled.  At this time, all enrolled ISR 
patients will have completed 6 months of follow-up.  Based on the interim data, we will determine 
the predictive probability of success  at the final analysis with complete 12 month data for the 
primary efficacy and primary safety endpoints. If, at the interim analysis, there is at least a 95% 
predictive probability of success on the primary efficacy endpoint and at least a 95% predictive 
probability of success on the primary safety endpoint, early trial success  will be  declared. If early 
trial success is not declared, the trial will continue to the final analysis with  complete 12 month data. 
Even if early success is declared, follow-up of patients will continue to be followed in order to 
further refine the estimated efficacy and safety at 12 months.  The critical values for early success 
and for declaring success at the final analysis have been calibrated to ensure the overall one-sided 
Type I error rate is controlled to ≤2.5% for each primary endpoint independently.   
 
Study Operating Characteristics 
The interim and final analyses for the ISR Cohort 2 will be characterized by simulation across 
varying assumptions of the efficacy and safety for the ISR cohort. For the purpose of simulation, 
efficacy and safety endpoints were considered as independent of each other.  While the primary 
analysis will stratify by propensity score, propensity scores have not been included in the 
simulations to determine the trial’s operating characteristics. Operating characteristics are based on 
1,000 simulations per scenario.  
In the EXCITE historical control patients, the 12-month rate for the primary efficacy endpoint is 
66.6% (95% CI = 53.8%, 78.7%).  Similarly, for the primary safety endpoint, the 12 month rate is 
51.0% (95% CI = 38.2%, 63.8%). The one-sided simulated Type I error rate for the primary efficacy 
endpoint was 2.50% and the one-sided simulated Type I error rate for the primary safety endpoint 
was 2.23%.  Type I error is based on 10,000 simulations.  Assuming a fixed underlying true rate, if 
the I Global ISR Cohort 2 has equivalent 12-month efficacy and safety to that of the EXCITE 
historical control patients, there is essentially a 0% probability of declaring superiority on efficacy, 
and a 0% probability of declaring non-inferiority on safety.    

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If 12-month rate for the primary efficacy endpoint in the I Global ISR Cohort 2 is 46%, a 20% 
absolute improvement over the EXCITE historical control patients, there is an 83% probability of 
declaring success on the efficacy endpoint and a 41% probability of declaring an early success on 
efficacy. If 12-month rate for the primary safety endpoint in the Global ISR cohort is 36%, a 15% 
absolute improvement over the EXCITE historical control patients, there is an 83% probability of 
declaring success on the safety endpoint and a 38% probability of declaring an early success on 
safety.   
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.   
 
Analysis of Subgroups 
Subgroup analyses will be performed separately for subgroups defined by the following baseline 
characteristics; sex, race, age (< 65 versus ≥ 65), lesion length ≤ 180 mm versus ≥ 180 mm , lesion 
length < 200 mm versus ≥ 200 mm and reference vessel diameter (< 4 mm, 4 up to 5 mm, 5 mm up 
to 6 mm, and ≥ 6 mm). Separately for each subgroup, a  time-to-event analysis will be performed. A 
Cox proportional hazards model through 12 months (365 days) will be fit with terms for study 
(EXCITE ISR PTA versus ILLUMINATE Global ISR  DCB), subgroup membership, and the 
interaction between study and subgroup. This model will be stratified by the propensity score 
quartile to account for the non-randomized nature. If the p-value associated with the interaction term 
is less than 0.15, additional analyses will be performed to further understand these results. Results 
comparing study groups will also be presented for each level of each subgroup. Subgroup analyses 
will be descriptive in nature and are intended to examine possible heterogeneity of the treatment 
effect. 
 
Analysis of Other Data 
The clinical laboratory analyses may be analyzed by tabulating the number and percentage of 
subjects with clinically significant changes from baseline for each parameter at each time point. 
 
6.0 RISK/BENEFIT ANALYSIS 
The study is designed to minimize risk through observance of strict site and investigator selection 
criteria, careful subject selection and management, and rigorous adherence to a standardized 
schedule of post-procedure evaluations. 
6.1 
Potential Benefits 
There are no guaranteed benefits from participation in this study; however, it has been shown that 
treatment with a PTX PTA balloon catheter improves blood flow through the treated artery in some 
patients.  Information gained from the conduct of this study may be of benefit to other persons with 
the same medical condition.   

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6.2 
Potential Risks - Cohort 1 (PTX PTA Balloon Catheter) 
Potential complications which may be associated with a peripheral balloon dilatation procedure 
include, but may not be limited to, the following:
 Abnormal heart rhythms 
 Abrupt closure 
 Allergic reaction to contrast 
medications 
 Amputation 
 Aneurysm 
 Arrhythmias (bradycardia, 
tachycardia)  
 Arterial dissection 
 Arterial perforation or rupture 
 Artery spasm 
 Arterio-venous (AV) fistula 
 Bleeding 
 Bypass graft surgery 
 Chest pain 
 Coagulopathy 
 Congestive heart failure 
 Death 
 Discomfort during procedure 
 Embolism/Device embolism 
 Endocarditis 
 Femoral nerve compression with 
associated neuropathy 
 Fever 
 Groin bruising/discomfort 
 Hematoma 
 Hemorrhage 
 Hypertension 
 Hypotension 
 Infection or pain at insertion site 
 Injury to groin blood vessel 
 Inflammation 
 Ischemia 
 Leucopenia 
 Lymphocele 
 Myocardial infarction 
 Nausea 
 Pseudoaneurysm 
 Renal failure 
 Respiratory failure 
 Restenosis 
 Sepsis 
 Seizure 
 Shock 
 Stroke/CVA 
 Thrombocytopenia 
 Thrombus 
 Total occlusion 
 Unstable/stable angina 
 Vessel trauma that may require 
intervention or surgical repair 
 Vomiting 
 Wound complication 
 
Potential complications which may be associated with the addition of paclitaxel to a PTA balloon 
catheter include, but may not be limited to, the following:   
 Abdominal pain 
 Abnormal liver function 
 Acne 
 Allergic reaction to paclitaxel 
 Alopecia 
 Anemia 
 Coagulopathy 
 Edema (non-pulmonary) 
 Gastrointestinal symptoms (e.g., 
diarrhea, nausea, pain, vomiting) 
 Hemolysis 
 Hematologic dyscrasia (including 
neutropenia) 
 Hypercholesterolemia 
 Hyperlipidemia 
 Hypertension 
 Hypertriglyceridemia 
 Leucopenia 
 Male hypogonadism 
 Myalgia 
 Pain 
 Peripheral neuropathy 

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 Pneumonia 
 Pyelonephritis 
 Rash 
 Renal tubular necrosis 
 Sepsis 
 Thrombocytopenia 
 Transfusion 
 Urinary tract infection 
 Viral, bacterial, fungal infections 
 
 
 
6.3 
Potential Risks - Cohort 2 (CE-marked Stellarex 035 DCB) 
Potential complications which may be associated with the addition of paclitaxel to a PTA balloon 
catheter include, but may not be limited to, the following:   
 Abnormal heart rhythms 
 Allergic reaction to contrast medium, 
antiplatelet therapy, or catheter system 
components (drug, excipients, and 
materials) 
 Amputation / loss of limb 
 Aneurysm 
 Arrhythmias  
 Arterio-venous fistula (AVF) 
 Bleeding 
 Death 
 Embolism/device embolism 
 Fever 
 Hematoma 
 Hemorrhage 
 Hypertension / hypotension 
 Infection or pain at insertion site 
 Inflammation 
 Ischemia 
 Occlusion 
 Pain or tenderness 
 Pseudoaneurysm 
 Renal failure 
 Restenosis 
 Sepsis / Infection 
 Shock 
 Stroke/CVA 
 Thrombosis 
 Vessel dissection, perforation, rupture 
 Spasm 
 
Potential complications which may be associated with the addition of paclitaxel to a PTA balloon 
catheter include, but may not be limited to, the following:   
 Allergic / immunologic reaction to paclitaxel 
 Alopecia 
 Anemia 
 Gastrointestinal symptoms (Diarrhea, nausea, pain, vomiting) 
 Hemolysis 
 Hematologic dyscrasia (including neutropenia, leucopenia, thrombocytopenia) 
 Histologic changes in vessel including inflammation, cellular damage, or necrosis 
 Myalgia / arthralgia 
 Peripheral neuropathy 
 Rash 
 Transfusion 
 
As with any device requiring mechanical deployment and retraction, such as the Stellarex DCB 
catheter, there exists a risk of mechanical failure of the device resulting in potential surgical 
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It is expected that the fluoroscopy time of the index procedure will be similar to that required for 
similar procedures conducted outside of a clinical study and will not pose additional risks to the 
subject or laboratory personnel.   
All risks listed above could cause prolonged illness, permanent impairment of daily function, or, in 
rare cases, death.  Possible treatments could include, but are not limited to cardiac surgery and 
vascular surgery. 
Extensive reliability engineering testing has been performed on the Stellarex DCB catheter to 
mitigate risks to the subject due to product failure.  Additionally, studies using the study device have 
been conducted to ensure that the system performs as intended without introducing more risks during 
the index procedure or during follow-up.  Risks may be further limited by providing medications 
such as aspirin or clopidogrel and continuing to monitor subjects following the index procedure.   
While some of the potential risks identified have occurred in prior PTX PTA studies, and while 
Spectranetics believes that the risk for significant injury or death due to the study device is quite low, 
these risks have yet to be adequately and fully quantified.  Eligibility criteria that exclude subjects 
who are at higher risk for experiencing an anticipated adverse event have been selected in order to 
reduce the potential risks to subjects that participate in this study. 
7.0 SITE REQUIREMENTS 
7.1 
Site Selection  
The sponsor or a representative of the sponsor will evaluate each potential site to ensure the principal 
investigator and his/her staff has the facilities and expertise required for the study. 
Principal investigators, sub-investigators and sites will be selected based upon the following factors, 
including, but not limited to: 
 Previous experience with clinical research and percutaneous procedures, including 
substantial experience treating the superficial femoral artery in the past 12 months  
 Currently treating subjects who meet the inclusion/exclusion criteria 
 Ability to enroll an adequate number of subjects in the study 
 Ability to perform required clinical testing, including: fluoroscopy, angiography and 
duplex ultrasound 
 Ability and willingness to provide the sponsor’s representatives access to the hospital 
records, study files, and subject files as they pertain to the study 
 Willingness to participate, including compliance with all aspects of the study 
 Adequate staffing to conduct the study. This includes: 
 
Principal Investigator 
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 protocol, applicable laws, and applicable 
regulations; ensures informed consents are signed, and reviews and signs 
CRFs indicating documents are accurate and complete. 
 

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Sub-Investigator(s) 
Responsible for study activities in coordination with Principal Investigator 
and in accordance to the investigational plan.  A site is not required to have 
a sub-investigator. 
 
Study/Research Coordinator  
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 CRFs to the sponsor in a timely manner. 
 
7.2 
Training/Initiation Visit 
The sponsor or a representative of the sponsor will conduct a training session with each Investigator 
and his/her staff to review the protocol, and supporting documentation, including but not limited to, 
the Instructions for Use of the study device, CRFs, the informed consent process, Ethics Committee 
involvement, responsibilities and obligations, reporting requirements and general guidelines for good 
clinical practices. 
Prior to enrolling subjects at an investigational site, the following documentation must be provided 
to the sponsor: 
 EC and CA (if applicable) approval for the study protocol  
 EC and CA (if applicable) approval for the principal investigator to conduct the study 
 EC and Sponsor approved informed consent form for the study 
 Investigator(s’) curriculum vitae (CV) 
 Financial disclosure documentation from the principal investigator, sub-investigators, and 
study staff, as applicable 
 Signed Clinical Study/Trial Agreement and if applicable, Sub-Investigator Agreement(s)  
 Completed training documentation form (provided by Sponsor or representative) to verify 
each physician conducting the procedure has been trained on the study device and the 
appropriate study staff has been trained on the protocol, device, CRFs, and study conduct, 
accordingly  
8.0 MONITORING PROCEDURES 
8.1 
Monitoring Procedures 
Spectranetics as the sponsor will be responsible for ensuring that adequate monitoring at each site is 
completed to ensure protection of the rights of subjects, the safety of subjects, and the quality and 
integrity of the data collected and submitted.  Appropriately trained personnel appointed by 
Spectranetics will conduct monitoring at each site.  Monitors will conduct site visits to ensure 
accuracy of data, timeliness of data submissions, adequate subject enrollment, investigational device 
accountability (if applicable), compliance with applicable laws and regulations, compliance with the 
protocol, compliance with the signed investigator agreement, and compliance with EC conditions 
and guidelines.  Any non-compliance with these items that is not adequately addressed by the 
principal investigator/site staff is cause for the sponsor to put the investigator/site staff on probation 
or withdraw the investigator/site staff from the study.  Frequency of monitoring will be based upon 
enrollment, study duration, compliance, and any suspected inconsistency in data that requires 
investigation.  

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8.2 
Monitoring Reports 
After each monitoring visit, the monitor will send to the principal investigator a letter summarizing 
the monitoring visit.  A monitoring report will be sent to the sponsor. The report will include the date 
of the monitoring visit, the site name, the name of the monitor, the name of the investigator, the 
names of other individuals present for the monitoring visit, items reviewed during the visit, findings, 
and any required follow-up.  The principal investigator will be responsible for ensuring that follow-
up actions needed to resolve issues at the site are completed in an accurate and timely manner. 
8.3 
Final Monitoring Visit 
Final monitoring visits at the sites will be conducted at the close of the study.  The purpose of the 
final visit is to collect all outstanding study data documents, ensure that the principal investigator’s 
files are accurate and complete, review record retention requirements with the principal investigator, 
make a final accounting of all study supplies shipped to the principal investigator/site, provide for 
appropriate disposition of any remaining supplies, and ensure that all applicable requirements are 
met for the study. 
9.0 RESPONSIBILITIES, RECORDS and REPORTS 
9.1 
Responsibilities and Record Retention 
The Principal Investigator/site must maintain adequate records on all aspects of the study, including 
the following: 
 Ethics Committee/ Competent 
Authority approvals 
 Subject termination information 
 Informed Consent Forms 
 Protocol deviations 
 Electronic Case Report Forms 
(eCRFs) 
 Correspondence file regarding study 
 Adverse event forms (and 
source documents) 
 Device disposition 
 
The principal investigator/site must maintain the study records for at least two years after cessation 
of the study and must contact the Sponsor prior to disposal of study records. 
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 Ethics Committee per Ethics 
Committee 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 Ethics Committee, except in the 
event of an immediate hazard to the subject.  The investigator will report the deviation in accordance 
with the applicable regulations.   

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9.3 
Reports 
Reports that are the sponsor or the principal investigator’s responsibility to generate are listed in 
Table 12.  The table also displays information regarding to whom this information is to be sent, and 
the frequency and time constraints around report submission.  If applicable laws, regulations, or EC 
requirements mandate stricter reporting requirements than those listed, the stricter requirements must 
be followed.   
 
 

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Table 12:  Reporting Responsibilities 
Type of Report 
Reporting Responsibilities 
Report Prepared 
For 
Reporting Time Frame 
Adverse Events, 
observed device 
deficiencies and 
malfunctions with 
assessment 
PI to Sponsor 
Recorded as of point of subject enrollment; report 
within 10 business days of the investigator learning 
of the event. 
Serious Adverse 
Events (SAE) or 
device deficiencies 
(including 
malfunctions) that 
could have led to a 
SAE  
PI to Sponsor and 
Ethics Committee.  
Recorded as of point of enrollment, (immediately), 
but not later than 3 calendar days, to Sponsor or 
representative after the principal investigator is first 
aware of the event.  To Ethics Committee according 
to local guidelines. 
 
 
Serious Adverse 
Events (SAE) or 
device deficiencies 
(including 
malfunction) that 
could have led to a 
SAE 
Sponsor to all 
competent authorities 
of the participating 
Member States. 
Immediately, but not later than 2 calendar days after 
awareness by the Sponsor, for SAEs with imminent 
risk of death, serious injury, or serious illness and 
that requires prompt remedial action for other 
subjects, users or other persons; or a new finding. 
 
Immediately, but not later than 7 calendar days after 
awareness by the Sponsor, for all other SAEs and 
device deficiencies that could have led to a SAE. 
All SAEs in a multi-
center study 
Sponsor to all 
participating sites.  PI 
to Ethics Committee 
if required by 
national regulations 
or Ethics Committee. 
All SAE must be reported to all investigational sites. 
Withdrawal of Ethics 
Committee approval 
(or other action on the 
part of the Ethics 
Committee that affects 
the study) 
PI to Sponsor 
Written - Within 5 working days of Ethics 
Committee decision. 
Progress reports 
PI to Sponsor and 
Ethics Committee 
At intervals dictated by the Ethics Committee, but 
no less than yearly. 
Emergency protocol 
deviations 
PI to Sponsor and 
Ethics Committee 
ASAP, but to Sponsor no later than 5 working days 
after the deviation occurs.  To Ethics Committee 
according to local guidelines. 
Inappropriate 
Informed Consent  
PI to Sponsor and 
Ethics Committee 
To Sponsor within 5 working days after the 
deviation occurs.  To Ethics Committee according to 
local guidelines. 
Final report 
PI to Sponsor and 
Ethics Committee 
To Sponsor within 3 months after termination or 
completion of study or Investigator’s participation.  
To Ethics Committee according to local guidelines. 

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Type of Report 
Reporting Responsibilities 
Report Prepared 
For 
Reporting Time Frame 
Other 
As Required 
Upon request by the Ethics Committee to provide 
accurate, complete, and current information about 
any aspect of the study.  
9.4 
Device Accountability 
Cohort 1:  
This trial is an investigational trial and devices may not be used for the treatment of subjects not 
qualified for the study per the required entrance criteria. The Principal Investigator will maintain 
adequate records of the receipt and disposition of the investigational devices, including lot numbers, 
date used, subject identification (ID) number and treating physician. A device accountability log 
supplied by the Sponsor will be used. The device accountability log will be reviewed by the 
monitor during regular monitoring visits. 
 
Use of any investigational device outside of the protocol is strictly forbidden and may constitute 
grounds for removal of the investigator/site from the clinical investigation.  
 
Cohort 2:  
This cohort will use Stellarex 0.035” OTW drug-coated angioplasty balloon commercially available 
devices with an investigational IFU (in Europe). In regions outside Europe, the device will be 
investigational use only. The Principal Investigator will maintain adequate records of the receipt 
and disposition of these devices, including lot numbers, date used, subject identification (ID) 
number and treating physician. A device accountability log supplied by the Sponsor will be used. 
The device accountability log will be reviewed by the monitor during regular monitoring visits. 
 
9.5 
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’s Agreement 
9.6 
 Records Custody 
An Investigator may withdraw from the study.  If the Principal Investigator withdraws from the 
study, responsibility for follow-up and maintaining the records must be transferred to a responsible 

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party (such as another study Investigator).  Notice of transfer must be provided in writing by the 
Principal Investigator to the Sponsor and the EC no later than 10 working days after transfer occurs. 
10.0 TRIAL TERMINATION 
The Sponsor, DSMB 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 Ethics Committees, health authorities and all 
investigators. A suspended or terminated study may not be reinitiated without approval of the 
reviewing Ethics Committees (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. 
 
 

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11.0 ABBREVIATIONS AND DEFINITIONS 
Abbreviations 
ABI 
Ankle-Brachial Index 
ADE 
Adverse Device Effect 
AE 
Adverse Event 
ASAP 
As Soon As Possible 
AV 
Arterio-venous 
BBC 
Bare balloon catheter 
BMI 
Body Mass Index 
CBC 
Complete Blood Count 
CE 
Conformité Européene 
CEC 
Clinical Events Committee 
CLI 
Critical Limb Ischemia 
CRF 
Case Report Form 
CTA 
Computed Tomography Angioplasty 
CV 
Curriculum Vitae 
CVA 
Cerebrovascular Accident 
CVD 
Cardiovascular Disease 
CVI 
CV Ingenuity 
DCB 
Drug Coated Balloon 
DSMB 
Data Safety Monitoring Board 
DUS 
Duplex Ultrasound 
EC 
Ethics Committee 
ID 
Identification 
IFU 
Instructions for Use 
ISO 
International Organization for Standardization 
ISR 
In-stent Restenosis 
ITT 
Intent-to-Treat 
IV 
Intravenous 
LLL 
Late Lumen Loss 
MAE 
Major Adverse Event 
MI 
Myocardial Infarction 
MLD 
Minimum Lumen Diameter 
MRA 
Magnetic Resonance Angioplasty 
O.U.S. 
Outside the United States 
PAD 
Peripheral Artery Disease 
PI 
Principal Investigator 
PP 
Per Protocol 
PSVR 
Peak Systolic Velocity Ratio 
PTA 
Percutaneous Transluminal Angioplasty 
PTX PTA 
Paclitaxel-Coated Percutaneous Transluminal Angioplasty 
QA 
Quantitative Angiography 
QALY 
Quality-adjusted Life Year 
RCC 
Rutherford Clinical Category 
RVD 
Reference Vessel Diameter 
SAE 
Serious Adverse Event 

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SADE 
Serious Adverse Device Effect 
SAP 
Statistical Analysis Plan 
SC 
Steering Committee 
SFA 
Superficial Femoral Artery 
TLR 
Target Lesion Revascularization 
TVR 
Target Vessel Revascularization 
USADE 
Unanticipated Serious Adverse Device Effect 
WIQ 
Walking Impairment Questionnaire 
 
Definitions 
Abrupt Closure: Vessel occlusion at the site of treatment within 24 hours after successful index 
procedure. 
Adjunctive Treatment: A procedure performed after treatment with the protocol-defined treatment  
Adverse Event Definitions2 
Adverse Event 
Any untoward medical occurrence, unintended disease or injury, or 
untoward clinical signs (including abnormal laboratory findings) in 
subjects, users or other persons, whether or not related to the 
investigational medical device. 
NOTE 1: This definition includes events related to the investigational 
medical device or the comparator. 
NOTE 2: This definition includes events related to the procedures 
involved. 
NOTE 3: For users or other persons, this definition is restricted to events 
related to investigational medical devices. 
Serious Adverse 
Event (SAE) 
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  
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.   
 
For purposes of reporting within this protocol, pre-existing conditions 

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and/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.   
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. 
 
Adverse Event Relationship Categories (procedure, study device, or study requirement): 
Not Related:  The event is definitely not associated with the study device or 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 device or 
procedure and/or a more likely alternative etiology exists. 
Possible:  The temporal sequence between device application and or 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 between device application or study procedure and the event 
is relevant or the event abates upon device application completion/removal or procedure 
completion or the event cannot be reasonably explained by the subject’s condition.   
Highly Probable:  The temporal sequence between device application or study procedure and 
the event is relevant and the event abates upon device application completion/removal or 
procedure completion, or reappearance of the event on repeat application or on repeat 
interventional procedures (re-challenge).   
Amputation: 
Major Amputation:  Surgical removal of a limb or a part of a limb above the ankle .  
Minor Amputation: Surgical removal of toes at or below the ankle.  

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Aneurysm: A localized, pathological, blood-filled dilatation of a blood vessel at least twice the 
reference vessel diameter 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: An 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 Dissection:  
Intimal disruption of the vessel wall with or without medial or adventitial contrast staining.  
 
National Heart, Lung, and Blood Institute (NHLBI) Dissection Classification System: (0, A, B, 
C, D, E, F) 
 0: 
No dissection 

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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 Flow:  
During and following deployment, each vessel will be evaluated and graded, according to the 
following arterial flow parameters. These findings will be recorded and included in the study 
records. 
Flow 0:  No antegrade flow beyond the point of occlusion or target site. 
Flow 1:  Contrast passes the point of obstruction but “hangs up” and fails to opacify the 
entire distal vasculature during the duration of the cine-angiographic filming sequence. 
Flow 2:  Antegrade filling of contrast with complete filling of the artery and its major and 
minor branches, but with visually determined decreased rate of flow compared to flow rate 
observed during pretreatment angiogram. Alternatively, delayed contrast washout in the 
target site territory may occur. 
Flow 3:  Antegrade flow of contrast with complete filling of the artery and its major and 
minor branches with visually determined flow rate from equal to the flow rate observed 
during pretreatment angiogram.  
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 lesions (≥ 50%). 
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, 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 lesions (≥ 
50%) and that there is in-line flow into the foot. 
Arterial Perforation:  Identifiable by extravasation of contrast media outside the arterial adventitial 
space. 

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Arterial Rupture:  Large transmural disruption of a vessel with gross extravasation and 
hemorrhage. 
Arterio-venous (AV) Fistula:  A communication between an artery and a vein in which the arterial 
blood flows directly into a neighboring vein. 
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. 
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.  
Clinical Success (per subject): Defined as technical success without the occurrence of major 
adverse events during procedure. 
Chronic Kidney Disease: Dialysis dependent, or serum creatinine  2.5 mg/dL. 
Death: 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 (eg, myocardial infarction (MI), low-output failure, fatal 
arrhythmia), unwitnessed death, or death of unknown cause. 
Device Deficiency:  An inadequacy of a medical device with respect to its identity, quality, 
durability, reliability, safety or performance.  NOTE: Device deficiencies include malfunctions, use 
errors, and inadequate labeling. 
Device Malfunction: A malfunction is a failure of a device to meet its performance specifications or 
otherwise perform as intended.  Performance specifications include all claims made in the labeling 
of the device. The intended performance of a device refers to the intended use for which the device 
is labeled. 
Discharge:  The time point when the subject is released from the admitting hospital, transferred to 
another facility, or has expired. 
Embolism:  Obstruction of a blood vessel by a foreign substance (air, plaque, debris) or a blood clot. 
Enrollment: The subject is enrolled in the study after he/she has signed the subject informed 
consent, it has been determined that he/she meets all of the inclusion criteria and none of the 
exclusion criteria, and the pre-dilatation has been completed.  The point of enrollment is defined as 
the moment the investigational device enters the vasculature. 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. 
Hematoma:  Localized mass of extravasated blood ≥ 5 cm that prolongs hospitalization. 
Hemorrhage:  Bleeding requiring hospitalization, repeat procedure, operation or transfusion.  
                                                 
1 Creager Mark, Victor Dzau, and Joseph Loscalzo, eds.  Vascular Medicine: A Companion to Braunwald’s Heart 
Disease.  Philadelphia, PA: Saunders Elsevier, 2006. 

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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. 
Inflow Tract:  Vascular access point to the area of the target lesion. 
In-Stent Restenosis Classifcation:  
 
Class I: Focal ISR (≤ 50 mm in length) 
 
Class II: Diffuse ISR (> 50 mm in length) 
 
Class III: Totally occluded ISR 
Tosaka et al. Journal of the American College of Cardiology; Vol. 59, No. 1, 2012.  
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. 
Ischemia: a restriction in arterial blood flow by stenosis, restenosis or occlusion that, if prolonged, 
can lead to tissue damage.  
Lesion Success: Defined as achievement of a final in-lesion residual diameter stenosis of ≤ 50% 
(per angiographic core lab), after using the investigational device. 
Major Adverse Event (MAE): Defined as clinically-driven target lesion revascularization, major 
amputation of the treated limb, or cardiovascular death. 
Multilevel Disease: Presence of obstructive lesions at more than one level in the same extremity as 
the treatment lesion. 
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: 
 Symptoms of ischemia. 
 New or presumed new significant ST-segment–T wave (ST–T) changes or new left bundle 
branch block (LBBB). 
 Development of pathological Q waves in the ECG. 
 Imaging evidence of new loss of viable myocardium or new regional wall motion 
abnormality. 

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 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 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.3 
 
 
National Heart, Lung and Blood Institute (NHLBI) Classification of Dissection2: 
Dissection 
Description 
Type A 
Small radiolucent area within the lumen of the vessel disappearing with 
the passage of contrast material 
Type B 
Appearance of contrast medium parallel to the lumen of the vessel 
disappearing within a few cardiac cycles 
Type C 
Dissection protruding outside the lumen of the vessel persisting after 
passage of the contrast material 
 
Type D 
Spiral shaped filling defect with delayed runoff of the contrast material 
in the distal vessel 
Type E 
Persistent luminal filling defect with delayed runoff of the contrast 
material in the distal vessel 
                                                 
2 Huber MS, Mooney JF, Madison J, Mooney MR.  Use of a morphologic classification to predict clinical outcome after dissection 
from coronary angioplasty.  Am J Cardiol 1991; 68: 467-71. 
3 Third universal definition of myocardial infarction. Thygesen K, et al. Eur Heart J. 2012 Oct;33(20):2551-67 

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Dissection 
Description 
Type F 
Filling defect accompanied by total coronary occlusion 
 
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.  
 
If both ultrasound and angiographic images are available at a given time point, and there is 
a conflict with respect to patency, the images will be provided to the Clinical Events 
Committee for adjudication.  
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 Stenosis: Native vessel diameter as measured at the most narrow point of the lesion divided 
by the estimated native vessel diameter (the mean of the vessel diameters proximal and distal to the 
lesion) at that location.  
% Stenosis =        
  
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 Global 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 
Pre-Procedure:  The time until the procedure begins (before arterial access is obtained). 
Primary Patency via Duplex (Peak Systolic Velocity ≤ 2.5):  Defined by duplex ultrasound 
measurement of peak systolic velocity (PSV) ratio ≤ 2.5 at the target lesion without clinically-driven 
revascularization within the target lesion. 

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Principal Investigator:  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. 
Procedural Success (per subject): Defined as lesion success without the occurrence of major 
adverse events during procedure. 
Protocol Deviation:  Any divergence from the Study Protocol. 
Pseudoaneurysm: Perforation of the vessel with arterial blood flow outside of the vessel.  
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 lab. 
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 of a hemodynamically significant restenosis 
(≥ 50%), 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.  
Rutherford Clinical Category3:  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, focal gangrene with diffuse pedal ischemia 
6* 
Major tissue loss--extending above TM level, functional foot no longer salvageable 
*Categories 4, 5, and 6 are embraced by the term chronic critical ischemia. 
†Five minutes at 2 mph on a 12% incline. 
 
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. 
                                                 
3 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. 

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Stent Integrity: Assessed by fluoroscopy or radiography, using two orthogonal views – AP and 
lateral) for subject eligibility using a 5 point scoring system.  
Category 
Clinical Description 
0 
No Strut Fractures 
I 
Single Tine Fracture 
II 
Multiple Tine Fracture 
III 
Stent fracture(s) with preserved alignment of the components 
IV 
Stent fracture(s) with mal-alignment of the components 
V 
Stent fracture(s) in a trans-axial spiral configuration 
 
 
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. 
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.   
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. 
Target Limb: The entire limb in which the target lesion is located. 
Target Lesion:  The lesion meeting all of the angiographic inclusion criteria and none of the 
exclusion criteria is the target lesion. Only one target lesion is allowed per subject (Cohort 2).  
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 non-clinically driven through an 
adjudication process.  Diameter stenosis will be determined per Angiographic Core Laboratory 
assessment. 
Clinically-Driven Target Lesion Revascularization:  
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 Clinical Category or ABI that is clearly referable to the target 
lesion. [Worsening is defined as deterioration (an increase) in the Rutherford Clinical Category 
by more than 1 category (>1 category) from the earliest post-procedural measurement, or 

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deterioration in the Ankle Brachial Index (ABI) by more than 0.15 from the maximum early 
post-procedural level]) 
TASC: See Trans-Atlantic Inter-Society Consensus 
Target Vessel: The entire vessel in which the target lesion is located.  
Target Vessel Revascularization (TVR): Any reintervention in the target vessel.  
Clinically Driven Target Vessel Revascularization 
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 considered 
clinically-driven 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.) 
Technical Success:  Defined as achievement of a final in-lesion residual diameter stenosis of ≤ 50% 
(per angiographic core laboratory), using the CVI paclitaxel-coated PTA balloon catheter without a 
device malfunction. 
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. 
Trans-Atlantic Inter-Society Consensus (TASC)4: A classification scheme for the assessment and 
management of peripheral arterial disease published in 2000.   
Trans-Atlantic Inter-Society Consensus II (TASC II)5: A classification scheme for the 
assessment and management of peripheral arterial disease published in 2007.   
Transient Ischemic Attack (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. 
Vascular 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. 
                                                 
4 Dormandy JA, Rutherford RB. Management of peripheral arterial disease (PAD). TASC Working Group. TransAtlantic 
Inter-Society Consensus (TASC). J Vasc Surg. Jan 2000;31(1 Pt 2):S1-S296 
5 Norgren L, Hiatt WR, Dormandy JA, et al. Inter-Society Consensus for the Management of Peripheral Arterial Disease 
(TASC II). Eur J Vasc Endovasc Surg. 2007;33 Suppl 1:S1-75 

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Peripheral Embolization  
Peripheral embolization is defined as a loss of distal pulse, pain and/or discoloration 
(especially the toes).  This can include cholesterol emboli.  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. 
Retroperitoneal Bleed  
An accumulation of blood in the retroperitoneal space.  
Peripheral Ischemia  
Inadequate blood supply in the study limb due to a blockage of blood vessels.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 as an alternative to treadmill testing.  It is a measure of 
patient-perceived walking performance for patients with PAD and/or intermittent claudication.   
 
 

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