Conditions: Peripheral Artery Disease Atherosclerosis Artery Diseases, Peripheral Plaque, Atherosclerotic Occlusive Arterial Disease
Keywords: Artery Atherosclerosis Arterial Peripheral Plaque Angioplasty PTA
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 440
Healthy volunteers: no

Brief summary:
To evaluate the safety and effectiveness of the Ranger™ Paclitaxel Coated Balloon for treating lesions located in the superficial femoral and proximal popliteal arteries (SFA/PPA).

Long Balloon substudy: To evaluate the safety and effectiveness of the Boston Scientific Corporation (BSC) Ranger™ Paclitaxel Coated Balloon in the 120, 150 and 200 mm lengths for treating Superficial Femoral Artery (SFA) and/or Proximal Popliteal Artery (PPA) lesions.

Detailed description:
The RANGER II SFA is a global, prospective, multi-center clinical trial. Approximately 446 subjects will be enrolled at up to 80 study centers worldwide. Regions participating include the United States, Canada, European Union, Japan and New Zealand.

The trial consists of a single-blind, superiority, 3:1 (Ranger Drug-Coated Balloon (DCB) vs. Standard PTA) randomized controlled trial (RCT) and a concurrent, non-randomized, single-arm, pharmacokinetic (PK) substudy, and a concurrent, non-blinded, non-randomized, Long balloon substudy.

Arms:
arm 1: RANGER™ Paclitaxel Coated Balloon Catheter angioplasty in the SFA/PPA at the index procedure.

Subjects will be randomized 3:1 to the drug coated or standard angioplasty balloon. arm 2: Standard Balloon Catheter angioplasty in the SFA/PPA at the index procedure. Subjects will be randomized 3:1 to the drug coated or standard angioplasty balloon.

Interventions: intervention 1: RANGER™ Paclitaxel Coated Balloon intervention 2: Paclitaxel intervention 3: Standard Balloon Angioplasty
Intervention descriptions: intervention 1: A procedure that utilizes a balloon coated with paclitaxel (drug) which can open up a blocked blood vessel using a small, flexible plastic tube, or catheter, with a "balloon" at the end of it. When the tube is in place, it inflates to open the blood vessel, or artery, so that normal blood flow is restored. The tube is then removed. The blood vessels that will be treated in the RANGER II SFA study include the superficial femoral arteries and the proximal popliteal arteries. intervention 2: The RANGER™ Balloon is coated with the drug Paclitaxel. intervention 3: A procedure that utilizes an uncoated balloon which can open up a blocked blood vessel using a small, flexible plastic tube, or catheter, with a "balloon" at the end of it. When the tube is in place, it inflates to open the blood vessel, or artery, so that normal blood flow is restored. The tube is then removed. The blood vessels that will be treated in the RANGER II SFA study include the superficial femoral arteries and the proximal popliteal arteries.

Protocol document:
Prot_SAP_000.pdf: 
RANGER II SFA  
A 3:1 Randomized Trial Comparing the Boston Scientific RANGERTM Paclitaxel Coated Balloon vs 
Standard Balloon Angioplasty for the Treatment of Superficial Femoral Arteries (SFA) and Proximal 
Popliteal Arteries (PPA) 
 
Clinical Investigation Plan Version AE 
October 15, 2018 
 
NCT03064126 


S2062 
         Form/Template 90702637 Rev/Ver AJ 
Confidential 
  RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
 Page 1 of 110 
A 3:1 Randomized Trial Comparing the Boston Scientific RANGER™ Paclitaxel 
Coated Balloon vs Standard Balloon Angioplasty for the Treatment of Superficial 
Femoral Arteries (SFA) and Proximal Popliteal Arteries (PPA) 
RANGER II SFA 
CLINICAL INVESTIGATION PLAN 
Study Reference Number S2062 
IDE Number G160172 
Sponsored By 
Boston Scientific Corporation 
300 Boston Scientific Way 
Marlborough, MA 01752, United States 
Boston Scientific International SA 
Parc Val Saint Quentin, Bâtiment H 
2 Rue René Caudron 
78960 Voisins-le-Bretonneux 
France 
Japanese Representative 
Boston Scientific Japan K.K. 
4-10-2, Nakano Nakano-ku
Tokyo 164-0001, Japan
This protocol contains confidential information for use by the Investigators and their 
designated representatives participating in this clinical investigation. The protocol should be held 
confidential and maintained in a secure location. 
Do not copy or distribute without written permission from Boston Scientific Corporation. 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 2 of 110 
 
 
 
 
Contact Information 
Role 
Contact 
Clinical Contact 
Philip Ghizoni 
Global Clinical Project Manager 
Peripheral Interventions 
Three Scimed Place 
Maple Grove, MN  55311 
Office:  +1 763-255-0036 
email:  Philip.Ghizoni@bsci.com 
 
Clayton Miller 
Global Clinical Project Manager 
Peripheral Interventions 
Three Scimed Place 
Maple Grove, MN  55311 
Office:  +1 763-494-2512 
email:  Clayton.Miller@bsci.com 
 
Hiroshi Sakamoto 
Japan, Project Management 
4-10-2, Nakano Nakano-ku 
Tokyo 164-0001, Japan 
Office:  +81 (3) 6853.7500 
email:  Hiroshi.Sakamoto@bsci.com 
Coordinating 
Principal Investigator 
Prof. Thomas Zeller, MD 
Clinic Cardiology and Angiology II 
Head Physician Department Angiology 
Universitaets-Herzzentrum Freiburg 
Interventional Cardiology & Vascular Medicine 
Bad Krozingen, Germany 
Coordinating 
Co-Principal 
Investigator 
Ravish Sachar, MD, FACC 
Interventional Cardiology & Cardiovascular Disease 
Physician-in-Chief 
UNC-REX Heart and Vascular Service Line 
University of North Carolina 
Raleigh, NC, USA 
 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 3 of 110 
 
 
 
 
Investigational Sites 
A list of investigational sites is provided in the Manual Of 
Operations. 
A list of investigational sites for Japanese sites only, is provided as a 
separate attachment to the protocol. 
Vendors/Labs 
A list of vendors/laboratories involved in the trial is maintained by 
the sponsor. A complete listing of applicable vendors will be 
provided to investigational sites.  
 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 4 of 110 
 
 
 
 
Original Release: June 30, 2016 
Current Version: October 15, 2018 
Revision History 
 
Revision  
Release Date 
Template 
number and 
version 
Section 
Change 
Reason for 
Change 
AA- 
Initial 
June 30, 2016 
90702637 
Rev./Ver. AG 
NA 
NA 
NA 
vAB 
September 19,  
2016 
90702637 
Rev./Ver. AG 
Title page 
Added IDE number 
New information 
Title page 
Updated address for BSC 
European representative   
Administrative 
Change 
Title page 
Deleted New Zealand BSC 
office 
Administrative 
Change 
Synopsis & 
Exclusion 9.3 
Added platelet count 
exclusion 
Test to ensure 
subject safety 
Synopsis, 
Statistic Sections 
8.3, 12,1,2, 12,2 
and 12,4,2 
Interim analysis to occur 
with 75% of enrolled 
subjects instead of 50% of 
subjects 
Revisions to 
address FDA 
comments on IDE 
submission. 
Synopsis and 
Secondary 
Endpoint 
Change: Deleted 
Thrombosis endpoint 
 
Endpoint not 
required for 
balloon study 
TOC 
Updated  
Updated to match 
amended changes 
Introduction 
Added prevalence 
information for subject >65 
yrs. of age 
New Supportive 
information 
4.1.2 
FIM Study enrolled 105 
instead of 105 subjects 
Correction 
10.1, Table 11-1 
and 21 
Added language to allow 
sites to include SOC testing 
completed within 30 days 
prior to index procedure that 
aligns with protocol-
required baseline testing 
Practical testing  
11.10 Follow up 
visits 
Added PK testing  
Clarification 
16 Device 
Accountability 
Removed Equipment 
Accountability 
No additional 
equipment is sent 
to the sites 
16 Device 
Accountability 
Entered name of Device 
management vendors:  
Cenduit and Fisher 
New Information 
19.5 Risk 
Minimization 
Added:  No treatment of 
pregnant or breast feeding 
females nor men intending 
to father children 
Clarification 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 5 of 110 
 
 
 
 
Revision  
Release Date 
Template 
number and 
version 
Section 
Change 
Reason for 
Change 
19.519.5 Risk 
Minimization 
Added birth 
control/pregnancy 
prevention for at least 90 
days after index procedure 
Clarification  
26 Bibliography 
Added reference #5 related 
to prevalence 
New Information 
26 Bibliography 
Updated numbering of 
references 
Formatting 
vAC 
May 11, 2017 
90702637 
Rev./Ver. AH 
Whole document 
  
Updated to current BSC 
protocol template 90702637 
Rev/Ver AH 
Update 
Contact 
Information 
Updated study contacts 
Update 
2.0 Protocol 
Synopsis 
Revised number of potential 
centers from 70 to 80. 
Clarified Exclusion #2 that 
cardiac events (e.g. STEMI, 
unstable angina) within 6 
months is an exclusion 
criteria. 
Reworded Exclusion #15 for 
clarification and added 
example (in-stent 
restenosis).Clarified 
contralateral and ipsilateral 
iliac only lesions may be 
treated at index. 
Removed full CMP at 
screening and 12 month 
follow-up. 
Revised statistical methods. 
Clarification & 
Update 
5.2 Device 
Labeling of 
Investigation
al Devices 
Updated investigational 
device label information 
Update 
7. Trial Endpoints 
Clarified unsuccessful 
randomized angioplasty 
treatment and ITT 
population. 
Clarification 
8.1 
Pharmacokinetic 
Sub-study 
Clarified the PK sub-study 
is planned for the U.S. only. 
Clarification 
8.2 Required 
medication 
therapy 
Clarified all enrolled 
subjects  (RCT: Ranger 
DCB, Standard PTA and PK 
sub-study) should follow the 
protocol-required 
antiplatelet regimen.  
Clarification 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 6 of 110 
 
 
 
 
Revision  
Release Date 
Template 
number and 
version 
Section 
Change 
Reason for 
Change 
Clarified a subject is exempt 
from the antiplatelet 
requirements if the 
randomized angioplasty 
treatment is unsuccessful.  
 
8.3 Scale & 
Duration 
Revised number of potential 
centers from 70 to 80. 
Clarified unsuccessful 
randomized angioplasty 
treatment and ITT 
population. Revised number 
of patients enrolled in the 
U.S. to approximately 50%. 
Update 
8.4 Treatment 
Assignment 
Clarified unsuccessful 
randomized angioplasty 
treatment and ITT 
population. 
Clarification 
 
 
8.7 Non-target 
lesions 
Clarified contralateral and 
ipsilateral iliac only lesions 
may be treated at index. 
Update 
9.3 Exclusion 
Criteria 
Clarified Exclusion #2 that 
cardiac events (e.g. STEMI, 
unstable angina) within 6 
months is an exclusion 
criteria. 
Reworded Exclusion #15 for 
clarification and added 
example (in-stent 
restenosis). 
Clarification 
Table 11.1 Data 
Collection 
Schedule  
Removed full CMP at 
screening and 12 month 
follow-up and replaced with 
only serum creatinine at 
screening. 
Update 
11.4 Pre-
procedure 
Assessments 
Removed full CMP at 
screening and replaced with 
only serum creatinine at 
screening. 
Update 
11.7.1 Treatment 
of Non-target 
Lesions 
Clarified contralateral and 
ipsilateral iliac only lesions 
may be treated at index. 
Update 
11.7.3 Enrollment 
Clarified unsuccessful 
randomized angioplasty 
treatment and ITT 
population. 
Clarification 
11.7.4 Treatment 
of Target 
Lesion(s) 
Clarified a major (≥Grade 
D) flow-limiting dissection 
at pre-dilatation would 
exclude the patient. 
Removed specification of 
pre-dilatation of optimal 
sized balloon of “reference 
size of artery”. 
Update 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 7 of 110 
 
 
 
 
Revision  
Release Date 
Template 
number and 
version 
Section 
Change 
Reason for 
Change 
11.10 Follow-Up 
Visits 
Clarified unsuccessful 
randomized angioplasty 
treatment and ITT 
population. 
Clarification 
12. Statistical 
Considerations 
Updated statistical methods 
throughout. 
Update 
13.3 Core 
Laboratories 
Added Covance as PK sub-
study core lab 
Update 
27.2 Definitions 
Added P1 Segment 
definition 
Clarification 
vAD 
November 7, 
2017 
90702637 
Rev./Ver. AH 
Appendix A 
Added RANGER Long 
Balloon Sub Study. For use 
in selected centers in the EU 
and New Zealand 
Update 
vAE 
October 15, 
2018 
90702637 
Rev./Ver. AJ 
2.0 Protocol 
Synopsis 
Clarified PK blood draw 
timing is based on last 
Ranger DCB removal  
Clarification 
8.3 Scale and 
Duration  
Clarified PK blood draw 
timing is based on last 
Ranger DCB removal  
Clarification 
Figure 8-2 
Ranger II SFA 
PK Substudy 
Design 
Clarified PK blood draw 
timing is based on last 
Ranger DCB removal  
Clarification 
Table 11-1 Data 
Collection Table 
Respiratory rate data 
collection not required if not 
local standard of care. 
Clarified PK blood draw 
timing is based on last 
Ranger DCB removal 
Update & 
Clarification 
11.4 Pre-
procedure 
Assessments 
Respiratory rate data 
collection not required if not 
local standard of care 
Update 
11.9 Post-
procedure/Pre-
Discharge 
Respiratory rate data 
collection not required if not 
local standard of care. 
Clarified PK blood draw 
timing is based on last 
Ranger DCB removal 
Update & 
Clarification 
Table 11-2 Blood 
Draw Schedule 
for Analysis of 
Paclitaxel 
Pharmacokinetics 
Clarified PK blood draw 
timing is based on last 
Ranger DCB removal  
Clarification 
11.10 Follow-up 
Visits 
Corrected reference from 
“occluded stent” to 
“occluded lesion”. 
Respiratory rate data 
collection not required if not 
local standard of care 
 
Correction & 
Update 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 8 of 110 
 
 
 
 
Revision  
Release Date 
Template 
number and 
version 
Section 
Change 
Reason for 
Change 
11.12 Missed or 
Late Visit 
Clarified that access to a 
patient locator service may 
be provided, but will not be 
required 
Clarification 
13.2. Data 
Retention 
Data retention period for 
using as part of use-results 
evaluation was 
clarified/corrected in 
accordance with current 
regulation. 
Correction & 
Update 
Appendix A 
Corrected Follow-up 
Schedule required 
timepoints for Rutherford 
Classification in the Long 
Balloon Substudy Synopsis. 
Clarification that 12 month 
DUS patency data will be 
provided for Long Balloon 
Substudy subjects  
Correction & 
Clarification  
 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 9 of 110 
 
 
 
 
2. Protocol Synopsis 
RANGER II SFA: A 3:1 Randomized Trial Comparing the Boston Scientific RANGER™ 
Paclitaxel Coated Balloon vs Standard Balloon Angioplasty for the Treatment of Superficial 
Femoral Arteries (SFA) and Proximal Popliteal Arteries (PPA) 
Trial 
Objective(s) 
To evaluate the safety and effectiveness of the Ranger™ Paclitaxel Coated 
Balloon for treating lesions located in the superficial femoral and 
proximal popliteal arteries (SFA/PPA). 
Planned 
Indication(s) for 
Use 
The Ranger drug coated balloon (DCB) is indicated for percutaneous 
transluminal angioplasty (PTA), after successful pre-dilatation, of de novo 
or restenotic lesions up to 180 mm in length located in native superficial 
femoral and proximal popliteal arteries (SFA/PPA) with reference vessel 
diameters of 4-8 mm. 
Test Device 
Ranger™ Paclitaxel Coated PTA Balloon Catheter (Ranger DCB) 
Control Device 
Standard Percutaneous Angioplasty (PTA) Balloon: Balloon Angioplasty 
Device Sizes 
I. Ranger™ Paclitaxel Coated PTA Balloon Catheter (Test Device)  
The working catheter length is 135 cm for all diameters with two 
exceptions:  The 4 mm diameter balloons (80 mm and 100 mm length 
balloons) are only available with a working shaft length of 80 cm. 
 
The Ranger DCB balloons (test device) are provided by the Sponsor. 
 
 
Balloon Length (mm) 
30 
40 
60 
80 
100 
Balloon 
Diameter 
(mm) 
4.0 
X 
X 
X 
 X 
 X 
5.0 
X 
X 
X 
X 
X 
6.0 
X 
X 
X 
X 
X 
7.0 
X 
X 
X 
X 
X 
8.0 
X 
X 
X 
X 
 
II. Standard PTA (Control Device) 
Standard PTA (non-scoring) device size (diameter, balloon and 
catheter lengths) utilization is determined by the research investigator. 
Standard PTA balloons (non-scoring) are commercially available 
balloons that the investigative sites utilize from their inventory. 
Note: Drug coated balloons must be overlapped to cover targeted lesion(s) 
as specified in the inclusion criteria. 
Trial Design 
The clinical trial is a global, prospective, multicenter, single-blind, 
superiority, 3:1 (Ranger DCB vs. Standard PTA) controlled randomized 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 10 of 110 
 
 
 
 
clinical trial (RCT) evaluating the safety and effectiveness of the Ranger 
DCB in subjects with claudication and/or rest pain and with a positive 
diagnostic finding of de novo, non-stented and  non-atherectomy-treated 
or restenotic lesion(s) in the SFA and/or PPA. 
Pharmacokinetic Substudy 
Concurrently, a human pharmacokinetics (PK) investigation (substudy) of 
this trial is also planned. This substudy is a prospective, multicenter, non-
randomized study arm (Ranger DCB), conducted at multiple pre-specified 
investigational sites designed to evaluate the levels of paclitaxel in the 
systemic circulation of subjects at multiple time points after treatment 
with the Ranger DCB. 
Although an investigative center can participate in both the RCT and PK 
trial arms, a subject can either be enrolled in the RCT study arm or the PK 
sub-study, but not both. 
Blinding / 
Unblinding 
The RANGER II SFA trial is conducted as single blind. Subjects will be 
blinded to treatment assigned and treatment received. All subjects must 
remain blinded until completion of all 12 month follow-up visits (primary 
endpoint). 
Packaging of the investigational Ranger DCB and control PTA devices 
differ. Therefore the Investigator and staff performing the procedure will 
not be blinded to the assigned treatment arm or resulting treatment. 
Trial center personnel will be trained not to disclose the treatment 
assignment to the subject in order to minimize the potential unblinding of 
the subjects. 
The Duplex Ultrasound (DUS) Core Laboratory personnel, Angiography 
Core Laboratory personnel, and Clinical Events Committee (CEC) will 
remain blinded to each subject’s treatment assignment through primary 
endpoint. 
Those involved in data analysis for the Sponsor will remain blinded until 
the primary endpoint interim analysis. 
Planned 
Number of 
Subjects 
Up to 396 subjects may be enrolled in this trial. 
At least 376 subjects will be enrolled into the randomized arm of the trial 
to yield: 
 
282 subjects to receive treatment with the Ranger DCB; 
investigational test device  
 
94 subjects to receive treatment with Standard PTA; control device  
From 12 to 20 subjects will receive treatment with the Ranger DCB for 
the non-randomized PK substudy.  Approximately 25% of those enrolled 
into the PK substudy will have long lesions (≥100 mm) treated with the 
Ranger DCB. 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 11 of 110 
 
 
 
 
Planned 
Number of 
Investigational 
Sites / Countries 
Up to 80 trial centers worldwide may enroll subjects into the RANGER II 
SFA global pivotal DCB trial. Countries that may participate include 
centers located in Australia, Canada, European Union, Japan, New 
Zealand and the United States. 
Approximately 10 trial centers may enroll subjects into the PK substudy. 
Primary Safety 
Endpoint 
The primary safety endpoint assesses the occurrence of Major Adverse 
Events (MAE) defined as all-cause death through 1 month, target limb 
major amputation through 12 months, and/or target lesion 
revascularization (TLR) through 12 months post-index procedure. This 
safety endpoint is designed to demonstrate that the Ranger DCB 12-month 
MAE-free rate is non-inferior to the control group. 
Primary 
Effectiveness 
Endpoint 
The primary effectiveness endpoint assesses the primary lesion patency 
within 12 months post-index procedure.  Primary effectiveness is defined 
as a binary endpoint determined by duplex ultrasound (DUS) peak systolic 
velocity ratio (PSVR) ≤ 2.4 in the absence of clinically-driven TLR. This 
effectiveness endpoint is designed to demonstrate that the 12-month 
primary patency for the Ranger DCB treated test group is superior to the 
control group.  
Notes: 
 
Lesion patency is defined as freedom from more than 50% stenosis 
based on DUS PSVR comparing data within the treated segment to 
the proximal normal arterial segment.  
 
PSVR >2.4 suggests >50% stenosis. 
The treated segment will be assessed for patency as a single segment 
regardless of the number of tandem lesions within the ballooned segment. 
Secondary 
Endpoints 
 
Technical success defined as successful delivery, balloon inflation 
and deflation and retrieval of the intact trial device without burst 
below the rated burst pressure (RBP) 
 
Procedural success defined as residual stenosis of ≤ 50% (non-stented 
subjects) or ≤ 30% (stented subjects) by core laboratory evaluation (if 
core laboratory assessment is not available then the site-reported 
estimate is used) 
 
Clinical success defined as procedural success without procedural 
complications (i.e. death, major target limb amputation, thrombosis of 
the target lesion, or clinically-driven TLR) prior to discharge  
 
Major Adverse Events (MAE) through 60 months. MAEs are defined 
as all-cause death post-index procedure, TLR, and major target limb 
amputation 
 
Death of any cause within 30 days, 6, 12, 24, 36, 48 and 60 months  
 
TVR rates at 6, 12, 24, 36, 48 and 60 months 
 
TLR rates at 6, 12, 24, 36, 48 and 60 months 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 12 of 110 
 
 
 
 
 
Rate of Primary and Secondary sustained clinical improvement as 
assessed by changes in Rutherford Classification from baseline at 1, 
6, 12, 24 and 36 months post-procedure 
 
Rate of Hemodynamic Improvement as assessed by changes in 
Ankle-Brachial Index (ABI) from baseline at 1, 6, 12, 24 and 36 
months post-procedure 
 
Duplex-defined binary restenosis (PSVR > 2.4) of the target lesion at 
1, 6, 12, 24 and 36 months 
 
Walking Improvement (distance) at 6 months and 12 months as 
assessed by changes in the Six Minute Hall Walk Test (6MWT) from 
baseline 
 
Walking Improvement and Patient Utility Values assessed at 1, 6, 12, 
24 and 36 months as assessed by change in Walking Impairment 
Questionnaire (WIQ) and EQ-5D™ from baseline 
 
Changes in healthcare utilization over time 
 
PK parameters calculated for subjects in the PK substudy 
Method of 
Assigning 
Patients to 
Treatment 
Subjects presenting with claudication or ischemic rest pain, an 
angiographically significant lesion in the superficial femoral and/or 
proximal popliteal artery and a patent outflow artery to the foot are 
considered for the trial.  
If after consenting, meeting inclusion criteria and none of the exclusion 
criteria, confirmed angiographically significant lesion in the superficial 
femoral and/or proximal popliteal artery and successful protocol-defined 
pre-dilatation, subjects are randomized 3:1 to either a Ranger DCB (test) 
or a Standard PTA balloon (control). 
In the PK substudy, subjects will not be randomized; all subjects will be 
treated with the Ranger DCB.  
Subjects are considered enrolled when the Ranger DCB or Standard PTA 
is introduced into the subject’s vasculature. 
Note: If the subject is found to meet exclusion criteria during the 
angiographic eligibility assessment, the subject will be considered a 
screen failure and should not be entered into this trial (no randomization 
nor enrollment) The subject should be cared for and followed outside of 
the trial based on the physician’s treatment plan. 
Note: If the balloon angioplasty attempt with the assigned treatment 
device (the test device Ranger DCB or control device Standard PTA) is 
not successful, follow-up through the 1 month visit only will occur as part 
of the Intent to Treat (ITT) population.  Data for assessment of MAE will 
be collected for these subjects.  No other testing or follow up is required. 
Follow-up 
Schedule 
Follow-up visits will occur pre-discharge, at Day 7, 1 month, 6 months, 12 
months, 24 months, 36 months, 48 months and 60 months post-index 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 13 of 110 
 
 
 
 
procedure.  Office or clinic visits are required for testing during each 
protocol required follow-up visit, with the exception of the 48 and 60 
month visits.  These two visits can be conducted in the office/clinic or by 
phone to obtain MAE and medication data. 
Planned procedures and testing include the following: 
 
Physical Exam at  screening, pre-discharge, 1 month, 6 month, 12 
month, 24 month  and 36 month  
 
Angiogram at time of index procedure and during any subsequent 
revascularization procedure (up to12  months post index procedure) 
 
Duplex Ultrasound at 1 month, 6 month, 12 month, 24 month  and 36 
month  
 
Rutherford Classification at screening, 6 month, 12 month, 24 month 
and 36 month 
 
Resting ABI exam at screening, 1 month, 6 month, 12 month, 24 
month  and 36 month 
 
Exercise Testing (6MWT) at  screening, 6 month and 12 month  
 
Questionnaires (WIQ and EQ5D) at screening, 1 month, 6 month, 12 
month, 24 month and 36 month 
 
Lab tests: 
– Complete Blood Count (CBC) containing WBC, RBC and PLT at 
screening  
– PK substudy subjects: venous blood drawn at screening, 10 min, 
30 min, 1 hr., 3 hr., 6 hr., 24 or 48 hr. after last Ranger DCB 
balloon removal, Day 7 and Day 30 post index procedure 
– Pregnancy testing (serum or urine) within 24hrs prior to index 
procedure if of child bearing age 
 
Medication compliance at screening, procedure, pre-discharge, 1 
month, 6 month, 12 month, 24 month,  36 month, 48 month and 60 
month 
 
Adverse event monitoring at procedure, pre-discharge, 1 month, 6 
month, 12 month, 24 month, 36 month, 48 month and 60 month 
Study Duration 
The trial will be considered complete (with regard to the primary 
endpoint) after all subjects have completed the 12 month follow-up visit, 
were discontinued prior to the 12 month follow-up visit, have died, or the 
last 12 month follow-up visit window is closed. 
The trial will be considered complete (with regard to all subject follow-
up) after all subjects have completed the 60 month (5 year) follow-up 
visit, were discontinued prior to the 60 month (5 year) follow-up visit, 
have died, or the last 60 month (5 year) follow-up visit window is closed. 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 14 of 110 
 
 
 
 
Required 
Medication 
Therapy 
Anti-platelet therapy is recommended throughout the length of the trial 
participation. Investigators must prescribe concomitant anti-coagulant and 
anti-platelet medications consistent with current local clinical practice. 
Antiplatelet medication and peripheral artery disease (PAD) medication 
usage will be collected and reported for compliance throughout the trial. 
Minimum protocol requirements: 
 
Anti-coagulation therapy administered prior to and during the 
procedure should be consistent with current clinical practice. 
 
A minimum of 30 days of dual antiplatelet therapy for non-stented 
subjects and a minimum of 3 months (90 days) dual antiplatelet 
therapy for stented subjects post index procedure.  
Minimum recommendation: 
 
Antiplatelet monotherapy is recommended for administration 
throughout the 5 year follow-up (trial completion). 
Note: A subject is exempt from the above-mentioned antiplatelet 
requirements if he/she requires Coumadin or other similar anti-coagulant 
due to known comorbidities and in the opinion of the investigator, the 
combination of antiplatelet and anticoagulant could put the subject at an 
unreasonable risk of bleeding. 
Inclusion 
Criteria 
Enrollment into the RANGER II SFA trial is limited to the following 
inclusion criteria: 
1. Subject (or Legal Guardian) is willing and able to provide consent 
before any study-specific tests or procedures are performed and agree 
to attend all required follow-up visits; 
2. Subject at least 20 years of age; 
3. Chronic symptomatic lower limb ischemia defined as Rutherford 
classification 2, 3, or 4; 
4. Target lesion is in the native SFA and/or PPA down to the P1 
segment; 
5. Patent popliteal and infrapopliteal arteries, i.e., single vessel runoff or 
better with at least one of three vessels patent (<50% stenosis) to the 
ankle or foot; 
6. Reference vessel diameter ≥ 4 mm and ≤ 8 mm by visual estimate  
(Use of a radiopaque ruler is recommended); and 
7. Angiographic evidence that target lesion consists of a single de novo, 
non-stented and non-atherectomy treated or restenotic lesion (or 
tandem lesions or a combination lesion as defined below) that is: 
a. 
≥ 70% -99% stenotic with total lesion length up to180 mm by 
visual estimate.  
Use of a radiopaque ruler is recommended. 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 15 of 110 
 
 
 
 
b. Occluded with total lesion length ≤ 100 mm by visual estimate. 
Use of a radiopaque ruler is recommended. 
c. 
If lesion is restenotic, most recent PTA treatment must be > 3 
months prior to enrollment 
Notes: 
Combination lesions (a non-occlusive lesion that includes a totally 
occluded segment along its length) are eligible provided that the combined 
total lesion length is ≤180 mm. 
Tandem (or “adjacent”) lesions may be enrolled providing they meet all of 
the following criteria: 
 
Separated by a gap of ≤ 30 mm (3 cm)  
 
Total combined lesion length meets requirements (Angiographic 
inclusion criteria (7) including 30 mm gap);  
 
Able to be treated as a single lesion. 
Exclusion 
Criteria  
Patients are not permitted to enroll into the RANGER II SFA trial if they 
meet any of the following exclusion criteria: 
1. Life expectancy, documented in the Investigator’s opinion, of less 
than 12 months; 
2. Hemorrhagic stroke or cardiac event (e.g. STEMI, unstable angina) 
within 6 months prior to enrollment; 
3. Known allergies or sensitivities to heparin, aspirin, other 
anticoagulant/antiplatelet therapies, and/or paclitaxel; 
4. Known hypersensitivity or contraindication to contrast dye that, in the 
opinion of the investigator, cannot be adequately pre-medicated; 
5. Chronic renal insufficiency with serum creatinine > 2.0 mg/dL within 
30 days of index procedure or treatment with dialysis; 
6. Platelet count <80,000 mm3 or >600,000 mm3 or history of bleeding 
diathesis; 
7. Receiving immunosuppressive therapy; 
8. Septicemia at the time of enrollment; 
9. Any major (e.g., cardiac, peripheral, abdominal) intervention 
(including in the contralateral SFA/PPA) planned within 30 days post 
index procedure; 
10. Presence of other hemodynamically significant outflow lesions in the 
target limb requiring intervention within 30 days of enrollment; 
11. Failure to successfully cross the target lesion with a guidewire 
(successful crossing means tip of the crossing device is distal to the 
target lesion in the absence of flow-limiting dissections or 
perforations); 
12. Failure to successfully pre-dilate the target vessel; 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 16 of 110 
 
 
 
 
13. Patient has lesion that requires the use of adjunctive primary 
treatment modalities (i.e. laser, atherectomy, scoring/cutting balloon, 
other debulking devices, etc.) during the index procedure; 
14. History of major amputation in the target limb; 
15. Target lesion or vessel has ever been previously treated with stent 
(e.g. in-stent restenosis) or surgery. Target lesion or vessel has been 
treated with atherectomy or a DCB in the past 12 months; 
16. Pregnant or breast feeding; 
17. Presence of aneurysm in the target vessel; 
18. Acute ischemia and/or acute thrombosis of the SFA/PPA prior to 
enrollment; 
19. Patient has significant inflow disease which cannot be treated prior to 
the target lesion treatment; 
20. Patient has perforated targeted vessel as evidenced by extravasation 
of contrast media; 
21. Patient has severe calcification that renders the lesion undilatable;  
22. Current participation in another investigational drug or device clinical 
trial that has not completed the primary endpoint at the time of 
randomization/enrollment or that clinically interferes with the current 
trial endpoints.  
Note: studies requiring extended follow-up for products that were 
investigational, but have become commercially available since then 
are not considered investigational studies. 
Multiple 
Interventions 
During Index 
Procedure 
Contralateral & Ipsilateral Limb Lesions 
Using the same access site, iliac lesion(s) in the contralateral and 
ipsilateral limb may be treated during the index procedure under the 
following conditions: 
 
Treatment with a commercially (non-drug coated) available device 
occurs prior to randomization of the target SFA/PPA lesion(s); 
 
Treatment of the lesion(s) is deemed an angiographic success without 
clinical sequelae (success is measured as <30% residual stenosis by 
visual estimation) and  
If the above criteria are not met, the subject may not be randomized into 
the trial but may be rescreened for eligibility after 30 days. 
Note: Provisional stenting of the target lesion with bare-metal stents can 
be completed in cases where adequate results could not be obtained after 
using post-dilatation balloons; such as in the case of remaining residual 
stenosis[≥ 50%] or major [≥ Grade D] flow-limiting dissection after post-
dilatation. 
Statistical Methods 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 17 of 110 
 
 
 
 
Adaptive 
Sequential 
Testing 
Hypotheses 
Strategy 
The primary effectiveness and safety hypotheses will be tested 
simultaneously in an adaptive group sequential manner at the overall 
significance level of one-sided 2.5%. The Lan-DeMets alpha spending 
function by  Power Family Method with Rho=2 will be used to determine 
the interim and the final type I error adjustment. With a minimum of 75% 
of 12-month required subjects planned to be assessed in the interim 
analysis, the adjusted type I error will be distributed as 1.41% for the 
interim analysis (i.e. 75%) and 1.92% for the final analysis (i.e. 100%). 
The actual interim and final alpha adjustments will be calculated based on 
the alpha spending function when the exact interim proportion is observed 
(e.g. >75%). 
Note: when Rho=2, the alpha adjustments are between Pocock’s method 
(Rho=1) and O’Brien-Fleming’s method (Rho=3). 
Primary 
Effectiveness 
Statistical 
Hypothesis 
The primary effectiveness hypothesis to be tested is that 12-month 
primary patency in subjects treated with Ranger DCB is superior to 
subjects treated with Standard PTA at an overall one-sided significance 
level of 2.5%. 
Primary 
Effectiveness 
Statistical Test 
Method 
Parameters 
The Chi-Square Test will be used to assess the hypothesis of superiority in 
proportions: 
H0: Pt - Pc  ≤ 0 
H1: Pt - Pc  > 0 
where Pt and Pc are the 12-month primary patency for the Ranger DCB 
and Standard PTA, respectively. 
Primary Safety 
Statistical 
Hypothesis 
The primary safety hypothesis to be tested is that 12-month MAE-free rate 
in subjects treated with Ranger DCB is as safe as the subjects treated with  
Standard PTA at an overall one-sided significance level of 2.5%. 
Primary Safety 
Statistical Test 
Method 
The Chi-Square Test will be used to assess the hypothesis of non-
inferiority in proportions: 
H0: Pt - Pc  ≤ ∆ 
H1: Pt - Pc  > ∆ 
where Pt and Pc are the 12-month MAE-free rates for the Ranger DCB 
and Standard PTA, respectively, and Δ (delta) is the non-inferiority 
margin of -10%. 
Success Criteria 
for the RCT 
Success Criteria for the Interim Analysis 
(for example, 75% subjects to be assessed at the interim analysis) 
Ranger DCB will be concluded to be superior to Standard PTA for device 
effectiveness in the interim analysis if the one-sided lower 98.59% 
confidence bound on the difference between treatment groups (Ranger 
DCB – Standard PTA) in 12-month primary patency is greater than zero.  


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 18 of 110 
 
 
 
 
Ranger DCB will be concluded to be as safe as Standard PTA if the one-
sided lower 98.59% confidence bound on the difference between 
treatment groups (Ranger DCB – Standard PTA) in 12-month MAE-free 
is greater than -0.1. 
The study success will be concluded as both primary effectiveness and 
primary safety endpoints being achieved in the interim analysis.  
Success Criteria for the Final Analysis 
(all subjects to be assessed at the final analysis when the interim analysis 
is not able to be concluded)  
If for any reason the final analysis is required to demonstrate superiority, 
Ranger DCB will be concluded to be superior to Standard PTA for device 
effectiveness in the final analysis if the one-sided lower 98.08% 
confidence bound on the difference between treatment groups (Ranger 
DCB – Standard PTA) in 12-month primary patency is greater than zero. 
Ranger DCB will be concluded to be as safe as Standard PTA if the one-
sided lower 98.08% confidence bound on the difference between 
treatment groups (Ranger DCB – Standard PTA) in 12-month MAE-free 
is greater than -0.1. 
As required, the study success will be concluded as both primary 
effectiveness and primary safety endpoints being achieved in the final 
analysis. 
Sample Size 
Parameters 
The overall sample size for RCT is driven by the primary effectiveness 
endpoint. 
Primary Effectiveness Endpoint 
 
Power ≥ 85% 
 
One-sided overall significance level (alpha) = 2.5% 
 
Lan-DeMets alpha spending function with Power Family Method 
(Rho=2) is used for adjusted alphas for the interim and final 
assessments: 
– One interim assessment for a minimum of 75% subjects to be 
assessed 
– The final assessment for the overall subjects  
 
Expected Standard PTA 12-month primary patency = 52.5% 
 
Ranger DCB to demonstrate 20% treatment effect 
 
Allocation (Ranger DCB vs. Standard PTA) = 3:1 
 
Attrition rate in 12 months = 15% 
 
N = 320 (total) evaluable subjects are required at 12 months (240 in 
Ranger DCB and 80 in the Standard PTA) 
 
N = 376 (total) subjects to be randomized prior to the procedure (282 
in Ranger DCB and 94 in Standard PTA) 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 19 of 110 
 
 
 
 
Primary Safety Endpoint 
 
One-sided overall significance level (alpha) = 2.5% 
 
The primary safety endpoint will be tested simultaneously with the 
primary effectiveness endpoint at the same significance level for the 
interim analysis and/or for the final analysis as needed 
 
Expected Standard PTA 12-month MAE-free = 75% 
 
Expected Ranger DCB 12-month MAE-free rate = 90%  
 
Non-inferiority margin (∆) = -10%(clinically meaningful)  
The sample size is driven by the primary effectiveness endpoint to provide 
at least 94% power to assess the primary safety endpoint. 
 
Sample Size and 
Statistical 
Method for PK 
Substudy 
In order to support the stated objectives for the PK substudy, the sample 
size for this substudy will be 12 to 20 subjects in addition to the RCT. 
Descriptive statistics will be presented to describe the PK substudy results. 
Core 
Laboratories 
The following core laboratories will be established for the central 
assessment of key data collected during the trial: 
 
Angiography: to assess angiograms taken during the index procedure 
and during any subsequent revascularization procedure (up to12  
months post index procedure) 
 
Ultrasound:  to assess ultrasounds taken during the follow-up periods 
(1 month, 6 months, 12 months, 24 months and 36 months follow-up 
visits) 
 
Pharmacokinetics: to assess paclitaxel levels at baseline and at 
defined time points. 
 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 20 of 110 
 
 
 
 
3. Table of Contents 
1. TITLE PAGE  ........................................................................................................................ 1 
2. 
PROTOCOL SYNOPSIS .......................................................................................................... 9 
3. 
TABLE OF CONTENTS ........................................................................................................ 20 
3.1. 
Table of Figures ............................................................................................................... 23 
3.2. 
Table of Tables ................................................................................................................. 23 
4. 
INTRODUCTION .................................................................................................................. 24 
4.1. 
Clinical Program Development ...................................................................................... 26 
4.1.1. 
Ranger DCB Platform ........................................................................................ 26 
4.1.2. 
First In Man Feasibility Trial ............................................................................. 27 
5. 
DEVICE DESCRIPTION ....................................................................................................... 27 
5.1. 
Ranger™ Paclitaxel Coated PTA Balloon Catheter .................................................... 27 
5.1.1. 
Drug Components Description ........................................................................... 30 
5.2. 
Device Labeling of Investigational Device ..................................................................... 31 
5.3. 
Control Device ................................................................................................................. 32 
6. 
TRIAL OBJECTIVES ........................................................................................................... 32 
7. 
TRIAL ENDPOINTS ............................................................................................................. 32 
7.1. 
Primary Endpoints .......................................................................................................... 32 
7.1.1. 
Primary Safety Endpoint .................................................................................... 32 
7.1.2. 
Primary Effectiveness Endpoint ......................................................................... 32 
7.2. 
Secondary Endpoints ...................................................................................................... 33 
8. 
TRIAL DESIGN ................................................................................................................... 34 
8.1. 
Pharmacokinetic Substudy ............................................................................................. 34 
8.2. 
Required Medication Therapy ....................................................................................... 34 
8.3. 
Scale and Duration .......................................................................................................... 35 
8.4. 
Treatment Assignment .................................................................................................... 38 
8.5. 
Blinding and Unblinding ................................................................................................. 38 
8.6. 
Target Lesions .................................................................................................................. 39 
8.7. 
Non-target Lesions .......................................................................................................... 39 
8.8. 
Justification for the Trial Design ................................................................................... 40 
9. 
SUBJECT SELECTION ......................................................................................................... 40 
9.1. 
Trial Population and Eligibility ..................................................................................... 40 
9.2. 
Inclusion Criteria ............................................................................................................ 40 
9.3. 
Exclusion Criteria ............................................................................................................ 41 
10. SUBJECT ACCOUNTABILITY .............................................................................................. 42 
10.1. 
Point of Enrollment ......................................................................................................... 42 
10.2. 
Withdrawal ...................................................................................................................... 43 
10.3. 
Enrollment Controls ........................................................................................................ 43 
11. TRIAL METHODS ............................................................................................................... 43 
11.1. 
Data Collection ................................................................................................................ 43 
11.2. 
Trial Candidate Screening .............................................................................................. 45 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 21 of 110 
 
 
 
 
11.3. 
Informed Consent ............................................................................................................ 45 
11.4. 
Pre-Procedure Assessments – Within 30 Days Prior to Index Procedure .................. 45 
11.5. 
Pre-Procedure Assessments – Within 24 hrs. prior to index procedure .................... 45 
11.6. 
Pre-Procedure Requirement ........................................................................................... 46 
11.7. 
Index Procedure .............................................................................................................. 46 
11.7.1. 
Treatment of Non-target Lesions ....................................................................... 46 
11.7.2. 
Angiographic Imaging of Target Lesion(s)........................................................ 46 
11.7.3. 
Enrollment .......................................................................................................... 47 
11.7.4. 
Treatment of Target Lesion(s) ........................................................................... 47 
11.7.5. 
Post-procedure Angiogram ................................................................................ 48 
11.8. 
End of the Index Procedure ............................................................................................ 48 
11.9. 
Post-procedure/Pre-Discharge ....................................................................................... 49 
11.10. Follow-up Visits ............................................................................................................... 51 
11.10.1. Day 7 Follow-up Visit (±1 Day) ........................................................................ 51 
11.10.2. 1 Month Follow-up Visit (±7 Days) .................................................................. 52 
11.10.3. Duplex Ultrasound Assessment of Target Lesion(s) ......................................... 52 
11.10.4. 6 Month Follow-up Visit (±30 Days) ................................................................ 53 
11.10.5. 12 Month Follow-up (±30 Days) ....................................................................... 53 
11.10.6. 24 Month and 36 Month Follow-up (±30 Days) ................................................ 54 
11.10.7. 48 Month and 60 Month Follow-up (±30 Days):  The 48 and 60 month visits can 
occur in office/clinic or by phone. ..................................................................... 54 
11.11. Trial Completion ............................................................................................................. 54 
11.12. Missed or Late Visits ....................................................................................................... 54 
11.13. Source Documents ........................................................................................................... 55 
12. STATISTICAL CONSIDERATIONS ....................................................................................... 55 
12.1. 
Primary Endpoints .......................................................................................................... 55 
12.1.1. 
Primary Effectiveness Endpoint ......................................................................... 55 
12.1.2. 
Primary Safety Endpoints .................................................................................. 57 
12.2. 
Success Criteria ............................................................................................................... 58 
12.2.1. 
Success Criteria for the Interim Analysis........................................................... 58 
12.2.2. 
Success Criteria for the Final Analysis .............................................................. 58 
12.3. 
General Statistical Methods............................................................................................ 58 
12.3.1. 
Analysis Sets ...................................................................................................... 58 
12.3.2. 
Randomization Scheme...................................................................................... 59 
12.3.3. 
Control of Systematic Error/Bias ....................................................................... 59 
12.3.4. 
Number of Subjects per Investigative Site ......................................................... 59 
12.4. 
Baseline Data Analyses ................................................................................................... 59 
12.4.1. 
Secondary Endpoint Assessments ...................................................................... 60 
12.4.2. 
Interim Analyses ................................................................................................ 60 
12.4.3. 
Subgroup Analyses ............................................................................................ 60 
12.4.4. 
Justification of Pooling ...................................................................................... 61 
12.4.5. 
Missing Data, Drop-Outs, and Protocol Deviation Handling ............................ 61 
12.4.6. 
Sensitivity Analyses for Missing Outcome Data ............................................... 62 
12.4.7. 
Multivariable Analyses ...................................................................................... 62 
12.4.8. 
Analyses Software ............................................................................................. 62 
12.4.9. 
Changes to Planned Analyses ............................................................................ 62 
13. DATA MANAGEMENT ........................................................................................................ 62 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 22 of 110 
 
 
 
 
13.1. 
Data Collection, Processing, and Review....................................................................... 62 
13.2. 
Data Retention ................................................................................................................. 63 
13.3. 
Core Laboratories ........................................................................................................... 63 
14. AMENDMENTS .................................................................................................................... 64 
15. DEVIATIONS ....................................................................................................................... 64 
16. DEVICE ACCOUNTABILITY ................................................................................................ 64 
17. COMPLIANCE ..................................................................................................................... 65 
17.1. 
Statement of Compliance ................................................................................................ 65 
17.2. 
Investigator Responsibilities ........................................................................................... 65 
17.2.1. 
Delegation of Responsibility .............................................................................. 67 
17.3. 
Institutional Review Board/ Ethics Committee ............................................................ 67 
17.4. 
Sponsor Responsibilities ................................................................................................. 67 
17.4.1. 
Role of Boston Scientific Representatives ......................................................... 68 
17.5. 
Insurance .......................................................................................................................... 68 
18. MONITORING ..................................................................................................................... 68 
19. POTENTIAL RISKS AND BENEFITS ..................................................................................... 69 
19.1. 
Anticipated Adverse Events and Risks Associated with Use of the Ranger DCB ..... 69 
19.2. 
Risks Associated with the Trial Device(s) Unique to Paclitaxel .................................. 70 
19.3. 
Risks associated with Participation in the Clinical Trial ............................................. 70 
19.4. 
Possible Interactions with Concomitant Medical Treatments..................................... 70 
19.5. 
Risk Minimization Actions ............................................................................................. 71 
19.6. 
Anticipated Benefits ........................................................................................................ 71 
19.7. 
Risk to Benefit Rationale ................................................................................................ 71 
20. SAFETY REPORTING .......................................................................................................... 71 
20.1. 
Reportable Events by investigational site to Boston Scientific .................................... 71 
20.2. 
Definitions and Classification ......................................................................................... 72 
20.3. 
Relationship to Trial Device(s) ....................................................................................... 74 
20.4. 
Investigator Reporting Requirements ........................................................................... 75 
20.5. 
Boston Scientific Device Deficiencies ............................................................................. 77 
20.6. 
Reporting to Regulatory Authorities/IRBs/ECs/REB Investigators ........................... 77 
21. INFORMED CONSENT ......................................................................................................... 77 
22. COMMITTEES ..................................................................................................................... 79 
22.1. 
Executive Committee....................................................................................................... 79 
22.2. 
Safety Monitoring Process .............................................................................................. 79 
22.3. 
Clinical Events Committee (CEC) ................................................................................. 79 
22.4. 
Independent Data Review (IDR) .................................................................................... 80 
23. SUSPENSION OR TERMINATION ......................................................................................... 80 
23.1. 
Premature Termination of the Trial .............................................................................. 80 
23.1.1. 
Criteria for Premature Termination of the Trial ................................................. 80 
23.2. 
Termination of Trial Participation by the Investigator or Withdrawal of IRB/EC/REB 
Approval ........................................................................................................................... 80 
23.3. 
Requirements for Documentation and Subject Follow-up .......................................... 81 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 23 of 110 
 
 
 
 
23.4. 
Criteria for Suspending/Terminating a Study Center ................................................. 81 
24. PUBLICATION POLICY ....................................................................................................... 81 
25. REIMBURSEMENT AND COMPENSATION FOR SUBJECTS .................................................. 82 
25.1. 
Subject Reimbursement .................................................................................................. 82 
25.2. 
Compensation for Subject’s Health Injury ................................................................... 82 
26. BIBLIOGRAPHY .................................................................................................................. 83 
27. ABBREVIATIONS AND DEFINITIONS .................................................................................. 85 
27.1. 
Abbreviations ................................................................................................................... 85 
27.2. 
Definitions ........................................................................................................................ 87 
APPENDIX A: RANGER LONG BALLOON SUBSTUDY ............................................................ 95 
1. 
RANGER LONG BALLOON SUBSTUDY SYNOPSIS ........................................................... 95 
 
3.1. Table of Figures 
Figure 5-1: Ranger Paclitaxel-Coated PTA Balloon Catheter with Balloon Protector and Loading Tool .. 28 
Figure 5-2: Chemical Structure of Paclitaxel .............................................................................................. 30 
Figure 5-3: Chemical Structure of Acetyltributyl Citrate (ATBC) ............................................................. 31 
Figure 8-1: RANGER II SFA Randomized Control Study Design ............................................................. 36 
Figure 8-2: RANGER II SFA PK Substudy Design ................................................................................... 37 
 
3.2. Table of Tables 
Table 5-1: 
Ranger DCB Characteristics..................................................................................................... 28 
Table 5-2: 
Ranger DCB Device Sizes ....................................................................................................... 29 
Table 5-3: 
Paclitaxel Dose per Balloon Diameter and Length .................................................................. 29 
Table 5-4: 
Ranger DCB Compliance Chart ............................................................................................... 29 
Table 9-1: 
Inclusion Criteria ...................................................................................................................... 40 
Table 9-2: 
Exclusion Criteria ..................................................................................................................... 41 
Table 11-1: Data Collection Schedule ......................................................................................................... 44 
Table 11-2: Blood Draw Schedule for Analysis of Paclitaxel Pharmacokinetics ........................................ 50 
Table 20-1: Safety Definitions ..................................................................................................................... 73 
Table 20-2: Criteria for Assessing Relationship of Trial Device or Index Procedure to AE ....................... 74 
Table 20-3: Criteria for Assessing Relationship of Antiplatelet Medication to AE .................................... 75 
Table 20-4: Investigator Reporting Requirements ....................................................................................... 76 
Table 27-1: Abbreviations ........................................................................................................................... 85 
Table 27-2: Definitions ................................................................................................................................ 87 
 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 24 of 110 
 
 
 
 
4. Introduction 
Peripheral Arterial Disease (PAD) is the third leading cause of cardiovascular morbidity after 
myocardial infarction (MI) and stroke. Current estimates state that there are over 8 million US 
and 200 million global patients with PAD1, 2 with an age–adjusted prevalence ranging from 12 to 
20 percent3, 4. The prevalence of PAD among individuals age 65-69 years is 10.08% for women 
and 10.33% for men with advances to 18.38% for women and 18.83% for men by age 85-89 
years5. Less than twenty percent of patients with PAD have typical symptoms of intermittent 
claudication such as leg muscle discomfort on exertion that is relieved by rest, or critical limb 
ischemia (CLI) (i.e., rest pain, ulceration or gangrene); whereas, another third have atypical 
exertional leg symptoms. In very serious cases, this blocked blood flow can lead to leg 
amputation.  
PAD is a progressive disease of the circulatory system; excluding the heart and brain.  
Atherosclerosis is a build-up of plaque in the circulatory system. Over time, plaque hardens 
narrowing the arteries and limiting oxygen-rich blood flow to parts of the body. Treatment 
includes lifestyle interventions, medical treatment to prevent cardiovascular events as well as 
surgery and endovascular interventions. The majority of the patients remain stable or improve in 
response to lifestyle modification. But there are also patients who do not improve with this 
conservative management. They need revascularisation procedures to restore or improve their 
peripheral circulation. Notably, the risk of cardiovascular morbidity and mortality is equally high 
in patients with PAD, regardless of the presence of symptoms6.  Non-revascularized lower 
extremity PAD is the most common cause of lower extremity amputation7. 
Endovascular Treatment of PAD in the SFA/PPA 
In general, the debate for state-of-the-art therapy in SFA disease involves endovascular 
intervention versus bypass surgery. Historically, surgery is generally reserved for resting pain 
and critical limb ischemia.  However, surgical therapy carries significant morbidity, including 
wound infection, MI and even death. In addition, up to 17 percent of the post-bypass surgery 
patients do not experience satisfactory clinical improvement8.  Over the past decade, 
percutaneous catheter-based techniques have improved such that acute procedural success is high 
even in complex anatomy. Patency rates have also increased with the use of atherectomy devices 
and drug-eluting stents (DES). Often, patients with PAD have comorbidities that increase the 
risk of cardiovascular complications with surgical procedures. These factors have led to the 
adoption of an endovascular first strategy with surgical management reserved for selected 
patients2, 9. 
Patients with very short pain-free walking distance are typically candidates for revascularization. 
According to American College of Cardiologists/ American Heart Association (ACC/AHA) 
guidelines, endovascular treatment of SFA disease is indicated for individuals with significant 
disability due to intermittent claudication (IC) or CLI. 
The femoropopliteal segment is a challenging vascular territory and has been among the least 
effective of all endovascular procedures in terms of long-term patency10,11,12.  The SFA is the 
longest artery in the human body and is located between two major flexion points, the knee and 
the hip. The relatively small vessel lumen, in conjunction with a high plaque burden, slow flow, 
and a high frequency of primary occlusions, contributes to considerable technical difficulties. In 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 25 of 110 
 
 
 
 
recent years, however, improvements in device technology and the skill-sets of the 
interventionalists have facilitated the treatment of complex lesions, including long-segment 
chronic occlusions with or without moderate calcification. In fact, the current evolution towards 
treating more complex femoropopliteal lesions as seen in the renewed TransAtlantic Inter-
Society Consensus (TASC) II recommendations clearly reflects the continuous evolutions in 
femoropopliteal stent design15. In most cases, the progression of atherosclerotic flow-limiting 
lesions in the blood vessels of the legs frequently involves the infra-popliteal arteries, resulting in 
a worsening diagnosis of CLI.  
In the past, balloon angioplasty alone was the treatment of choice for the femoropopliteal artery 
segment14. Percuteous transluminal angioplasty (PTA) is a procedure that can open up a blocked 
blood vessel using a small, flexible plastic tube, or catheter, with a "balloon" at the end of it. 
When the tube is in place, it inflates to open the blood vessel, or artery, so that blood flow is 
restored. The TASC working group suggested that primary success rates were above 90% with a 
very low rate of complications (< 4%)14,15. However, within one year, patency failure rates above 
70% were observed after balloon angioplasty in lesions longer than 10 cm15,16. 
The application of self-expanding nitinol stent technology seemed to improve the safety and 
durability of stenting in the SFA10, 17, 18, 19.  The theoretical basis for improved performance with 
the use of nitinol stents is due to the unique properties of nitinol such as flexibility, persistent 
radial force when oversized to a vessel, and ability for crush recovery in these high flexion and 
torsion force areas in the femoropopliteal arteries. In addition, self-expanding nitinol stents are 
not as prone to external compression as are balloon-expandable stents.  Moreover, due to its 
smaller arterial diameter and complex nature, the femoropopliteal segment does not respond well 
to rigid stents. As such, the most flexible nitinol stent is needed to mitigate stent fracture that 
often occurs in the femoropopliteal arteries. 
Although above the knee use of nitinol bare metal stents (BMS) is safe and feasible, it is 
evidently associated with significant neointimal hyperplasia and early restenosis 20, 21 which may 
be due to the chronic external forces on the vessel/stent interface resulting in a chronic stimulus 
for restenosis22. Therefore, the interest of investigators turned towards the pharmaceutical 
ingredients such as paclitaxel and everolimus to suppress neointimal growth and restenosis after 
stent deployment. DES technology was developed to prevent early thrombosis and late luminal 
loss to potentially improve long-term patency rates for SFA23.  
The use of drug coated balloon (DCB) treatment has emerged as a therapeutic alternative in the 
treatment of PVD/PAD in the superficial femoral and proximal popliteal arteries (SFA/PPA). In 
many European countries, DCBs have been utilized to treat PAD since 2003. Based on the 
results of the following three clinical trials, two DCBs are approved for use in the United States. 
LEVANT I (Lutonix Paclitaxel-Coated Balloon for the Prevention of Femoropopliteal 
Restenosis) was a prospective, single blind (to patient), randomized (1:1) trial comparing LLL in 
femoropopliteal lesions treated with the Lutonix DCB versus an uncoated balloon. Demographic, 
peripheral vascular disease, and lesion characteristics were matched, with mean lesion length of 
8.1 ± 3.8 cm and 42% total occlusions. At 6 months, late lumen loss was 58% lower for the 
Lutonix DCB group (0.46 ± 1.13 mm) than for the control group (1.09 ± 1.07 mm; p = 0.016). 
Composite 24-month major adverse events were 39% for the DCB group, including 15 target 
lesion revascularizations, 1 amputation, and 4 deaths versus 46% for uncoated balloon group, 
with 20 target lesion revascularizations, 1 thrombosis, and 5 deaths. Pharmacokinetics showed 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 26 of 110 
 
 
 
 
biexponential decay with peak concentration (Cmax) of 59 ng/ml and total observed exposure 
(AUCall) of 73 ng h/ml. For successful DCB deployment excluding 8 malfunctions, 6-month late 
lumen loss was 0.39 mm and the 24-month target lesion revascularization rate was 24%24. 
The Lutonix Paclitaxel-Coated Balloon for the Prevention of Femoropopliteal Restenosis 
(LEVANT) 2 trial was a prospective, multicenter, randomized, controlled trial. Between July 20, 
2011, and July 10, 2012, 543 patients were enrolled at 54 sites in the United States and Europe. 
A total of 56 patients were enrolled in the roll-in phase, 11 patients with predilatation results 
indicating flow-limiting dissection or clinically significant residual stenosis were excluded from 
randomization but were treated according to the standard of care and followed for 30 days 
(standard-practice subgroup), and 476 patients were randomly assigned, in a 2:1 ratio, to undergo 
angioplasty with a drug-coated balloon (316 patients) or standard angioplasty (160). With respect 
to the primary composite safety end point, the proportion of patients free from perioperative 
death from any cause or free at 12 months from index-limb amputation, index-limb 
reintervention, and index-limb–related death was 83.9% in the drug-coated–balloon group versus 
79.0% in the standard-angioplasty group, which met the prespecified criterion for noninferiority 
(P=0.005 for noninferiority). The proportion of patients who had primary patency at 12 months 
(the primary efficacy end point) was significantly greater with the drug-coated balloon than with 
the standard angioplasty balloon (65.2% vs. 52.6%, P=0.02)25. 
The IN.PACT SFA Trial is a prospective, multicenter, single-blinded, randomized trial in which 
331 patients with intermittent claudication or ischemic rest pain due to superficial femoral and/or 
popliteal peripheral artery disease (PAD) were randomly assigned in a 2:1 ratio to treatment with 
DCB or PTA.  One year (12 mth) data results are as follows: The DCB resulted in higher 
primary patency vs. PTA (82.2% vs. 52.4%; P<.001). The rate of clinically-driven target lesion 
revascularization was 2.4% in the DCB arm compared with 20.6% in the PTA arm (P<.001). 
There was a low rate of vessel thrombosis in both arms (1.4% after DCB and 3.7% after PTA 
(P=.10)). There were no device- or procedure-related deaths and no major amputations26. 
4.1. Clinical Program Development 
4.1.1. 
Ranger DCB Platform 
The Ranger DCB is a paclitaxel-coated Percutaneous Transluminal Angioplasty (PTA) balloon 
catheter developed as a collaborative effort between BSC and Hemoteq AG [HTQ, Wuerselen, 
Germany]. This co-development relationship leverages BSC’s extensive Sterling™ catheter 
experience and HTQ’s coating expertise for DCBs. The Ranger DCB is based on BSC’s well 
characterized Sterling PTA balloon catheters. These catheters are coated with the paclitaxel 
(active ingredient) drug that is formulated with the excipient acetyltributyl citrate (ATBC) to 
effectively deliver paclitaxel to the vessel wall. Paclitaxel has been widely used for both stent 
and DCB applications as a safe and effective drug to inhibit neointimal proliferation and thereby 
reduce the rate of restenosis. 
In some countries, the Ranger Paclitaxel-Coated PTA balloon catheter is CE Marked and 
indicated for Percutaneous Transluminal Angioplasty (PTA) in the peripheral vasculature, 
including iliac and infrainguinal arteries. 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 27 of 110 
 
 
 
 
The justification of the leveraged data regulatory strategy for Ranger DCB’s current indicated 
use is based on the following: 
 
The safety and performance of PTA balloon catheters in the revascularization of peripheral 
artery disease have been demonstrated with over 20 years of clinical experience with these 
devices. 
 
The safety and performance of the predicate device: Sterling PTA balloon catheter in the 
treatment of the peripheral vasculature is established via the extensive market experience 
with these devices. Field experience with the catheters demonstrates a favorable and 
reliable safety profile. 
 
The Ranger experience since CE-mark certification in July, 2014, demonstrates a favorable 
and reliable safety profile. 
 
The usefulness of paclitaxel in the treatment of peripheral arterial disease has been 
clinically established. Review of the literature demonstrates that paclitaxel is safe in 
peripheral applications and effective when delivered from a stent or a DCB platform. Both 
paclitaxel-coated drug-eluting stents27 and paclitaxel-coated PTA balloons28, 29, 30, 31  
showed superiority to plain balloon angioplasty in the treatment of peripheral vascular 
disease in prospective, randomized clinical trials. 
4.1.2. 
First In Man Feasibility Trial 
The first-in-man clinical feasibility trial with the Ranger DCB completed the enrollment of 105 
subjects from centers located in Germany, Austria, and France in October 2015.  The trial design 
was a prospective, randomized; multicenter controlled (2:1 Ranger DCB vs uncoated balloon) 
clinical trial of the Ranger™ Paclitaxel-Coated PTA Balloon Catheter in comparison to uncoated 
PTA balloons in femoropopliteal lesions.  The objective of the trial was to prove the superior 
performance of the Ranger DCB for angioplasty in femoropopliteal artery lesions when 
compared to non-coated balloons at six months post-procedure when comparing Late Lumen 
Loss (LLL). The primary endpoint was in-segment late lumen loss of the treated segment, as 
observed by core lab analyzed angiography at six months post-procedure. Subject eligibility 
criteria included clinically significant symptomatic limb ischemia defined as Rutherford 
classification 2, 3, or 4, and de novo, non-stented and non-atherectomy treated or restenotic 
lesions (≥70% stenosis) located in the native superficial femoral artery or proximal popliteal 
artery with a total lesion length ≥ 20 mm and ≤ 150 mm. The trial’s Clinical Study Report (CSR) 
with results will be provided with the investigational device exemption submission.    
5. Device Description 
5.1. Ranger™ Paclitaxel Coated PTA Balloon Catheter 
The Ranger Paclitaxel-Coated PTA balloon catheter (Figure 1) is an Over-the-Wire (OTW) 
Percutaneous Transluminal Angioplasty (PTA) balloon catheter with a semi-compliant balloon 
coated with a formulation of paclitaxel (drug) and ATBC (excipient). 
The Ranger catheter is designed to inhibit restenosis by delivering drug to diseased arterial 
tissue. 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 28 of 110 
 
 
 
 
The Ranger DCB catheter has a coaxial shaft design. The outer lumen is used for inflation of the 
balloon, and the wire lumen permits the use of guide wires 0.014 in (0.36 mm) or 0.018 in (0.46 
mm) to facilitate advancement of the catheter. The balloon is designed to provide an inflatable 
segment of known diameter and length at recommended pressures. The Ranger DCB catheter 
includes a tapered tip to facilitate advancement of the catheter to and through the stenosis. 
The Ranger DCB catheter has two radiopaque marker bands (one proximal and one distal) 
which, in conjunction with fluoroscopy, aid in the placement of the balloon. The working lengths 
of the Ranger DCB catheters are 80 cm and 135 cm. The proximal portion of the Ranger DCB 
catheter include one female Luer-lock port connected to the inflation lumen, and one female 
Luer-lock port for the guidewire lumen. 
In addition, the Ranger DCB catheter is equipped with a balloon protector and a loading tool. 
The balloon protector is provided to help protect the coated balloon during transportation and is 
removed prior to use. The loading tool is provided to help protect the drug coating prior to sheath 
insertion and minimize the potential handing of the coated balloon by the operator.  An image of 
the Ranger Paclitaxel-Coated PTA Balloon Catheter is below (Figure 5-1). 
 
 
Figure 5-1: 
Ranger Paclitaxel-Coated PTA Balloon Catheter with 
Balloon Protector and Loading Tool 
 
 
Technical characteristics of the device component of the Ranger DCB are identical to BSC’s 
globally approved PTA balloon catheters: Sterling. Key device characteristics of the Ranger 
DCB are summarized in Table 5-1. 
Table 5-1: Ranger DCB Characteristics 
Characteristic 
Description 
Guidewire compatibility 
0.014 in. (0.36 mm) or 0.018 in. (0.46 mm) 
Working lengths (cm) 
80 cm and 135 cm 
Balloon diameters (mm) 
4.0, 5.0, 6.0, 7.0, 8.0 
Balloon lengths (mm) 
30, 40, 60, 80, 100 
Balloon type 
Semi-compliant 
Nominal pressure 
6 atm 
 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 29 of 110 
 
 
 
 
The Ranger DCB is available in a variety of diameters and balloon lengths.  Device sizes 
intended for use in this global trial are exhibited in Table 5-2. The shaft lengths utilized for this 
trial is 135 cm for all diameters with two exceptions: The 4 mm diameter balloons (80 mm and 
100 mm length balloons) are only available with a working shaft length of 80 cm.  Table 5-3 
exhibits the dose of paclitaxel for each balloon by length and diameter. Table 5-4 exhibits the 
Ranger DCB balloon compliance chart. 
 
Table 5-2: Ranger DCB Device Sizes 
 
Balloon Length (mm) 
30 
40 
60 
80 
100 
Balloon Diameter 
(mm) 
4.0 
X 
X 
X 
X 
X 
5.0 
X 
X 
X 
X 
X 
6.0 
X 
X 
X 
X 
X 
7.0 
X 
X 
X 
X 
X 
8.0 
X 
X 
X 
X 
 
 
 
Table 5-3: Paclitaxel Dose per Balloon Diameter and Length 
 
Balloon Length (mm) 
30 
40 
60 
80 
100 
Balloon Diameter 
(mm) 
4.0 
782 µg 
1043 µg 
1564 µg 
2086 µg 
2607 µg 
5.0 
975 µg 
1301 µg 
1951 µg 
2601 µg 
3251 µg 
6.0 
1100 µg 
1467 µg 
2200 µg 
3108 µg 
3889 µg 
7.0 
1283 µg 
1711 µg 
2714 µg 
3626 µg 
4538 µg 
8.0 
1468 µg 
1957 µg 
2935 µg 
3913 µg 
 
 
 
 
 
Table 5-4: Ranger DCB Compliance Chart 
Pressure 
Mean Balloon Diameter (mm) 
(Balloon Lengths: mm) 
4.0 
5.0 
6.0 
7.0 
8.0 
atm 
kPa 
(all lengths) 
(all lengths) 
(30 - 60) 
(80 - 100) 
(30 - 40) 
(60 - 100) 
(all lengths) 
6* 
608 
4.01 
5.02 
6.01 
6.22 
6.92 
7.13 
7.92 
7 
709 
4.09 
5.11 
6.09 
6.32 
7.02 
7.25 
8.03 
8 
811 
4.15 
5.19 
6.17 
6.40 
7.11 
7.35 
8.12 
9 
912 
4.20 
5.25 
6.24 
6.47 
7.18 
7.43 
8.19 
10 
1013 
4.25 
5.31 
6.29 
6.53 
7.25 
7.49 
8.25 
11 
1115 
4.29 
5.36 
6.35 
6.57 
7.31 
7.56 
8.31 
12** 
1216 
4.34 
5.41 
6.39 
6.62 
7.36 
7.61 
8.37 
13 
1317 
4.37 
5.45 
6.43 
6.67 
7.41 
7.66 
 
14** 
1419 
4.40 
5.49 
6.48 
6.72 
7.46 
7.73 
  *6 = Nominal all sizes  
**12 = RBP for 8.0 mm  
**14 = RBP for 4.0 mm to 7.0 mm 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 30 of 110 
 
 
 
 
5.1.1. 
Drug Components Description 
The balloon coating consists of paclitaxel (PTx) and the excipient, acetyltributyl citrate (ATBC). 
PTx is a widely utilized drug in both stent and drug-coated balloon applications for reducing the 
rate of neointimal proliferation and thereby the rate of restenosis.  The drug to excipient 
formulation ratio is 80:20 PTx/ATBC.  The resulting drug dose density (total weight of drug per 
unit of balloon surface area) on the coated balloon is 2 µg/mm2. 
Paclitaxel (PTx) is the active pharmaceutical ingredient on the Ranger DCB. Paclitaxel is a white 
powder, isolated from a spectrum of TAXUS species and hybrids. It is a terpenoid with a 
characteristic taxane skeleton of 20 carbon atoms, a molecular weight of 853.91 g/mol, and a 
molecular formula of C47H51NO14 as shown in Figure 5-2 below. It is highly lipophilic and 
insoluble in water, but is freely soluble in methanol, ethanol, chloroform, ethyl acetate, and 
dimethyl sulfoxide. 
The principal mechanism by which PTx inhibits neointimal growth is through the stabilization of 
microtubules by preventing deploymerization during the final G2/M phase of cell division. 
 
Figure 5-2: Chemical Structure of Paclitaxel 
The coating utilizes the inactive ingredient acetyltributyl Citrate (ATBC) as an excipient to 
facilitate the release and transfer of paclitaxel into the arterial wall. ATBC is a carboxylic acid 
ester with a molecular weight of 402.48 g/mol. ATBC is a colorless, slightly viscous liquid with 
very faint sweet herbaceous odor. The chemical structure of ATBC is provided in Figure 5-3. 
 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 31 of 110 
 
 
 
 
 
Figure 5-3: Chemical Structure of Acetyltributyl Citrate (ATBC) 
Studies have shown that paclitaxel inhibits neointimal hyperplasia by disrupting normal 
microtubule function, thereby inhibiting smooth muscle cell migration, proliferation, and 
extracellular matrix secretion thus supporting short-term local delivery of paclitaxel for 
inhibiting restenosis in the SFA25, 28.  Subjects with PAD will require treatment options that best 
fit their individual clinical presentation. No one therapy technique can treat all subjects.  
Although effective treatment with drug coated balloons has been proven, more research is 
needed. 
5.2. Device Labeling of Investigational Device 
A copy of the Directions for Use (DFU) for the Ranger DCB will be included in the Manual of 
Operations. The trial device is labeled on the front, back and bottom spine of the outer carton, 
and on the inside sterile pouch. Packaging will include peelable, self-adhesive labels for each 
unit shipped. The labeling will include the following information. 
 
Product Name 
 
Universal Part Number (UPN)/Catalog Number 
 
Serial number 
 
GTIN 
 
Lot number 
 
Balloon dimensions (balloon diameter and length in mm), and working catheter length (in 
cm) 
 
Expiration (use by) date 
The following statements appear on the Ranger DCB product labeling:  
Caution: Investigational Device. Limited by United States law to Investigational Use. 
Specifically, the following statement appears on the product labeling in relevant local languages: 
Exclusively for Clinical Investigations. 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 32 of 110 
 
 
 
 
Device labeling will be provided in local language(s) per national regulations. In Japan, 
identification code, local contact information, and storage condition also appear on the product 
labeling. 
The Ranger DCB should be stored at room temperature, in a dry and dark place. 
5.3. Control Device 
Standard PTA (non-scoring) balloons are the control device for the global trial. The standard 
PTA device size (diameter, balloon and catheter lengths) utilization is determined by the research 
investigator. 
6. Trial Objectives 
The objective of the RANGER II SFA global pivotal trial is to evaluate the safety and 
effectiveness of the RANGER™ Paclitaxel Coated Balloon for treating superficial femoral and 
proximal popliteal arteries (SFA/PPA) lesions up to 180 mm. 
7. Trial Endpoints 
The primary and secondary endpoints will be evaluated on an intent-to-treat analysis and a per-
treatment analysis. If the balloon angioplasty with the assigned treatment device (the test device 
Ranger DCB or control device Standard PTA) is not successfully deployed, the subject will be 
followed through the 1 month follow-up visit only as part of the ITT population.  Data to assess 
1 month MAE rate will be collected for these subjects. No other testing is required. 
7.1. Primary Endpoints 
7.1.1. 
Primary Safety Endpoint 
The primary safety endpoint assesses the occurrence of Major Adverse Events (MAE) defined as 
all-cause death through 1 month, target limb major amputation through 12 months, and/or target 
lesion revascularization (TLR) through 12 months post-index procedure. This safety endpoint is 
designed to demonstrate that the Ranger DCB 12-month MAE-free rate is non-inferior to the 
control group. 
7.1.2. 
Primary Effectiveness Endpoint 
The primary effectiveness endpoint assesses the primary lesion patency within 12 months post-
index procedure.  Primary effectiveness is defined as a binary endpoint determined by (DUS) 
peak systolic velocity ratio (PSVR) ≤ 2.4 in the absence of clinically-driven TLR. This 
effectiveness endpoint is designed to demonstrate that the 12-month primary patency for the 
Ranger treated test group is superior to the control group.  
Notes: 
 
Lesion patency is defined as freedom from more than 50% stenosis based on DUS PSVR 
comparing data within the treated segment to the proximal normal arterial segment.  


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 33 of 110 
 
 
 
 
 
PSVR >2.4 suggests >50% stenosis.32 
 
The treated segment will be assessed for patency as a single segment regardless of the 
number of tandem lesions within the ballooned segment. 
 
7.2. Secondary Endpoints 
Secondary endpoints that will be evaluated, but are not necessarily powered to make statistically-
based conclusions are as follows: 
 
Technical success defined as successful delivery, balloon inflation and deflation and 
retrieval of the intact trial device without burst below the rated burst pressure (RBP)  
 
Procedural success defined as residual stenosis of ≤ 50% (non-stented subjects) or ≤ 30% 
(stented subjects) by core laboratory evaluation (if core laboratory assessment is not 
available then the site-reported estimate is used)  
 
Clinical success defined as procedural success without procedural complications (i.e. 
death, major target limb amputation, thrombosis of the target lesion, or clinically-driven 
TLR) prior to discharge  
 
Major Adverse Events (MAE) through 60 months. MAEs are defined as all-cause death 
post-index procedure, TLR, and  major target limb amputation   
 
Death of any cause within 30 days, 6, 12, 24, 36, 48 and 60 months  
 
TVR rates at 6, 12, 24, 36, 48 and 60 months  
 
TLR rates at 6, 12, 24, 36, 48 and 60 months  
 
Rate of Primary and Secondary sustained clinical improvement as assessed by changes in 
Rutherford Classification from baseline at 1, 6, 12, 24 and 36 months post-procedure 
 
Rate of Hemodynamic Improvement as assessed by changes in Ankle-Brachial Index 
(ABI) from baseline at 1, 6, 12, 24 and 36 months post-procedure  
 
Duplex-defined binary restenosis (PSVR > 2.4) of the target lesion at 1, 6, 12, 24 and 36 
months  
 
Walking Improvement (distance) at 6 months and 12 months as assessed by changes in the 
Six Minute Hall Walk Test (6MWT) from baseline  
 
Walking Improvement and Patient Utility Values assessed at 1, 6, 12, 24 and 36 months as 
assessed by change in Walking Impairment Questionnaire (WIQ) and EQ-5D™ from 
baseline 
 
Changes in healthcare utilization over time  
 
PK parameters calculated for subjects in the PK substudy 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 34 of 110 
 
 
 
 
8. Trial Design 
The RANGER II SFA clinical trial is a global, prospective, multicenter, single-blind, superiority, 
3:1 (Ranger DCB vs. Standard PTA) controlled randomized clinical trial (RCT) evaluating the 
safety and effectiveness of the Ranger DCB in subjects with claudication and/or rest pain and 
with a positive diagnostic finding of de novo, non-stented and non-atherectomy-treated or 
restenotic lesion(s) in the SFA and/or PPA.  
8.1. Pharmacokinetic Substudy 
Concurrently, a human pharmacokinetics (PK) investigation (substudy) of this trial is also 
planned in the U.S. This substudy is a prospective, multicenter, non-randomized substudy arm 
(Ranger DCB), conducted at multiple pre-specified investigational sites. This substudy is 
designed to evaluate the levels of paclitaxel in the systemic circulation of subjects at multiple 
time points after treatment with the Ranger DCB. 
Although an investigative center can participate in both the RCT and PK trial arms, a subject can 
either be enrolled in the RCT study arm or the PK sub-study, but not both.” 
8.2. Required Medication Therapy 
There is risk of acute, sub-acute, or late thrombosis, vascular complications, and/or bleeding 
events. It is strongly advised that the treating physician follow the Inter-Society Consensus 
(TASC II) Guidelines recommendations (or other applicable country guidelines) for antiplatelet 
therapy pre – and post –procedure to reduce the risk of thrombosis.  Anti-platelet therapy is 
recommended throughout the length of the trial participation. Investigators must prescribe 
concomitant anti-coagulant and anti-platelet medications consistent with current local clinical 
practice. 
Antiplatelet medication and peripheral artery disease (PAD) medication usage will be collected 
and reported for compliance throughout the trial.  
Minimum protocol requirements: 
 
Anti-coagulation therapy administered prior to and during the procedure should be 
consistent with current clinical practice33. 
 
A minimum of 30 days of dual antiplatelet therapy for non-stented subjects and a minimum 
of 3 months (90 days) dual antiplatelet therapy for stented subjects post index procedure.  
Minimum recommendation: 
 
Antiplatelet monotherapy is recommended for administration throughout the 5 year follow-
up (trial completion). 
 
All enrolled subjects (RCT: Ranger DCB, Standard PTA and PK sub-study) should follow the 
above-mentioned antiplatelet requirements. 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 35 of 110 
 
 
 
 
A subject is exempt from the above-mentioned antiplatelet requirements if he/she requires 
Coumadin or other similar anti-coagulant due to known comorbidities and in the opinion of the 
investigator, the combination of antiplatelet and anticoagulant could put the subject at an 
unreasonable risk of bleeding. 
A subject is also exempt from the above-mentioned antiplatelet requirements if the randomized 
angioplasty treatment is unsuccessful.  
8.3. Scale and Duration 
The RANGER II SFA trial plans to enroll up to 396 subjects. At least 376 of the subjects will be 
enrolled into the randomized arm of the trial to yield: 
 
282 subjects to receive treatment with the Ranger DCB; investigational test device and 
 
94 subjects to receive treatment with Standard PTA; control device  
From 12 to 20 subjects will receive treatment with the Ranger DCB for the non-randomized PK 
substudy.  Approximately 25% of those enrolled into the PK substudy will have long lesions 
(≥100 mm) treated with the Ranger DCB.  
Up to 80 study centers worldwide may enroll subjects into the RANGER II SFA pivotal trial. 
Countries that may participate include centers located in Australia, Canada, European Union, 
Japan, New Zealand and the United States. 
Approximately 10 study centers may enroll subjects into the PK substudy. 
All subjects will be screened according to the protocol inclusion and exclusion criteria. Subjects 
meeting all inclusion criteria and no exclusion criteria will be randomized in a 3:1 allocation to 
either Ranger DCB or Standard PTA, respectively. 
For subjects undergoing successful balloon deployment, clinical follow up assessments are 
required at the following time points:  pre-discharge, Day 7, 1 month, 6 months, 12 months, 24 
months, 36 months, 48 months and 60 months post index procedure. Office or clinic visits are 
required for testing during each protocol required follow-up visit, with the exception of the 48 
and 60 month visits.  These two visits can be conducted in the office/clinic or by phone to obtain 
MAE and medication data. 
Subjects for whom the deployment of the randomly assigned balloon is unsuccessful (the test 
device Ranger DCB or control device Standard PTA) will be included in the Intent to Treat (ITT) 
population and followed for MAEs through 1 month.  
In addition, for those enrolled into the PK substudy, PK sampling from venous blood are 
required at the following time points:  pre-Ranger DCB deployment, 10 minutes, 30 minutes, 1 
hour, 3 hours, 6 hours, 24 or 48 hours after last Ranger DCB removal, Day 7 and Day 30 post 
index procedure. 
The enrollment is estimated to take up to 20 months to complete after the first patient is enrolled.  
Approximately fifty percent (50%) of the subjects enrolled will come from the United States. 
The trial will be considered complete (with regard to the primary endpoint) after all enrolled 
subjects have completed the 12 month follow-up visit, were discontinued prior to the 12 month 
follow-up visit, have died, or the last 12 month follow-up visit window is closed. 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 36 of 110 
 
 
 
 
The trial will be considered complete (with regard to all follow-up) after all enrolled subjects 
have completed the 60 month (5 year) follow-up assessment, were discontinued prior to the 60 
month (5 year) follow-up visit, have died, or the last 60 month (5 year) follow-up visit window is 
closed. 
It is estimated that it will take approximately 7 years to complete the entire trial. 
Figure 8-1 and Figure 8-2 exhibit the RCT and PK substudy designs, respectively. 
 
Figure 8-1: RANGER II SFA Randomized Control Study Design 
Will subject sign informed consent? 
Obtain randomization code (3:1) 
282 treated with 
RANGER DCB 
(Investigational/Test) 
94 treated with 
Standard PTA 
(Commercial/Control) 
Assigned Balloon 
successfully deployed? 
INTENT TO TREAT 
Pre-discharge Assessments 
Follow-up Evaluation 
at 1 month in office 
Do Not Enroll 
Post-procedure / Pre-discharge 
Assessments 
Follow-up Evaluations 
1 Month, 6 Month, 12 Month,  
24 Month and 36 Month 
in office/clinic, 
48 Month and 60 Month via phone 
or in office/clinic visit  
End of Trial 
No 
No 
No 
Yes 
Yes 
Yes 
Does subject meet eligibility criteria? 
Guidewire successfully crosses target 
lesion? Successful Pre-dilatation? 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 37 of 110 
 
 
 
 
 
 
 
Figure 8-2: RANGER II SFA PK Substudy Design 
Will subject sign informed consent? 
Does subject meet eligibility criteria? 
Baseline Blood Draw, 
T=0 (within 30 days prior or just prior to DCB 
deployment) 
12-20 treated with RANGER DCB: 
Investigational/Test balloon 
RANGER DCB 
Successfully deployed? 
INTENT TO TREAT 
Pre-discharge Assessments 
Follow-up Evaluation 
at 1 month in office 
Do Not Enroll 
Post-procedure / Pre-discharge Assessments;  
Additional venous blood draws at: 
a. 10 and 30 minutes after last Ranger DCB removal 
b. 1, 3, 6, hours after last Ranger DCB removal 
c. 24 or 48 hours after last Ranger DCB removal  
d. Day 7 and Day 30 post index procedure 
 
Follow-up Evaluations 
1 Month, 6 Months, 12 Months, 
24 Months and 36 Months 
Follow-up in office/clinic 
48 Months and 60 Months follow-up via 
telephone or in office/clinic 
End of Study 
No 
No 
No 
Yes 
Yes 
Yes 
Guidewire successfully crosses target lesion? 
Successful Pre-dilatation? 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 38 of 110 
 
 
 
 
8.4. Treatment Assignment 
Subjects presenting with claudication or ischemic rest pain, an angiographically significant 
lesion in the superficial femoral and/or proximal popliteal artery and a patent outflow artery to 
the foot are considered for the RANGER II SFA trial.  
If after consenting, meeting inclusion criteria and none of the exclusion criteria, confirmed 
angiographically significant lesion in the superficial femoral and/or proximal popliteal artery and 
successful protocol-defined pre-dilatation, subjects are randomized 3:1 to either a Ranger DCB 
(test) or a Standard PTA balloon (control).  Randomization will be stratified by site. After the 
guidewire successfully crosses the target lesion and successfully pre-dilates the target lesion, a 
randomization custom function within the Rave EDC database will be used to assign subjects to 
the test or control treatment group. 
In the PK substudy, subjects will not be randomized; all subjects will be treated with the Ranger 
DCB.  
Subjects are considered enrolled when the Ranger DCB or Standard PTA is introduced into the 
subject’s vasculature. 
Note: If the subject is found to meet exclusion criteria during the angiographic eligibility 
assessment, the subject will be considered a screen failure and should not be entered into this 
trial (no randomization nor enrollment) The subject should be cared for and followed outside of 
the trial based on the physician’s treatment plan. 
Note: If the balloon angioplasty with either the test device (Ranger DCB) or control device 
(Standard PTA) is not successfully deployed, follow-up through the 1 month visit only will occur 
as part of the ITT population.  Data for assessment of MAE will be collected for these subjects.  
No other testing or follow up is required. 
8.5. Blinding and Unblinding 
The RANGER II SFA trial is conducted as single blind. Subjects will be blinded to treatment 
assigned and treatment received. All subjects must remain blinded until completion of all 12 
month follow-up visits (primary endpoint).  
Packaging of the investigational Ranger DCB and control PTA devices differ. Therefore the 
Investigator and staff performing the procedure will not be blinded to the assigned treatment arm 
or resulting treatment.  
Study center personnel will be trained not to disclose the treatment assignment to the subject in 
order to minimize the potential unblinding of the subjects. 
The DUS Core Laboratory personnel, Angiography Core Laboratory personnel, and Clinical 
Events Committee (CEC) will remain blinded to each subject’s treatment assignment through 
primary endpoint. 
Those involved in data analysis for the Sponsor will remain blinded until the primary endpoint 
interim analysis.  


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 39 of 110 
 
 
 
 
8.6. Target Lesions  
The RANGER II SFA trial is designed to treat lesions located in the superficial femoral and/or 
proximal popliteal arteries (SFA/PPA). These arteries are located in the lower extremities above 
the knee. The arteries, with a reference vessel diameter (RVD) of ≥ 4 mm and ≤ 8 mm by visual 
estimate (use of a radiopaque ruler is recommended), must show angiographic evidence of a 
single de novo, non-stented and non-atherectomy-treated or restenotic lesion (or tandem lesions 
or a combination lesion as defined below) that is: 
 
≥ 70% -99% stenotic with total lesion length up to180 mm by visual estimate. Use of a 
radiopaque ruler is recommended. 
 
Occluded with total lesion length ≤ 100 mm by visual estimate. Use of a radiopaque ruler 
is recommended. 
 
If lesion is restenotic, most recent PTA treatment must be > 3 months  prior to enrollment 
Combination lesions (a non-occlusive lesion that includes a totally occluded segment along its 
length) are eligible provided that the total combined lesion length is ≤180 mm.  
Tandem (or “adjacent”) lesions may be enrolled providing they meet all of the following criteria: 
 
Separated by a gap of ≤ 30 mm (3 cm) 
 
Total combined lesion length meets requirements (Angiographic inclusion criteria (7) 
including 30 mm gap); and 
 
Able to be treated as a single lesion 
The Ranger DCB must be overlapped to cover targeted lesion(s) as specified in the inclusion 
criteria. 
Provisional stenting of the target lesion with bare-metal stents can be completed in cases where 
adequate results could not be obtained after using post-dilatation balloons; such as in the case of 
remaining residual stenosis[≥ 50%] or major [≥ Grade D] flow-limiting dissection after post-
dilatation. 
8.7. Non-target Lesions 
Multiple interventions using the same access site may occur at the time of the index procedure.  
Using the same access site, iliac lesion(s) in the contralateral and ipsilateral limb may be treated 
during the index procedure under the following conditions: 
 
Treatment with a commercially (non-drug coated) available device occurs prior to 
randomization of the target SFA/PPA lesion(s); 
 
Treatment of the lesion(s) is deemed an angiographic success without clinical sequelae 
(success is measured as <30% residual stenosis by visual estimation) 
If the above criteria are not met, the subject may not be randomized into the trial but may be 
rescreened for eligibility after 30 days. 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 40 of 110 
 
 
 
 
8.8. Justification for the Trial Design 
The RANGER II SFA trial will evaluate the safety and effectiveness of the Ranger DCB balloon 
for the treatment of atherosclerotic lesion(s) in native SFA and/or PPA vessels compared with 
Standard PTA balloons. Standard PTA balloons have been utilized to treat atherosclerotic lesions 
in these arteries for more than 20 years.  There are many documented studies that show 
effectiveness and safety with use of commercially available Standard PTA balloons.  Further, the 
two DCBs, approved for use in the United States (US) have patency rates that differ 
significantly.  This significant patency variance makes it extraordinarily difficult to ascertain 
which of the two approved US DCBs to compare with the Ranger DCB.  Therefore a randomized 
controlled trial was required by the US Food and Drug Administration. 
9. Subject Selection 
9.1. Trial Population and Eligibility  
Clinical and angiographic inclusion and exclusion criteria are included in Table 9-1 and Table 
9-2. Prior to enrollment, a subject must meet all of the clinical and angiographic inclusion 
criteria and none of the clinical and angiographic exclusion criteria. 
9.2. Inclusion Criteria 
Subjects who meet all of the following criteria (Table 9-1) may be given consideration for 
inclusion in this clinical investigation, provided no exclusion criterion (see Section 9.3) is met. 
Table 9-1: Inclusion Criteria 
Inclusion 
Criteria 
1. Subject (or Legal Guardian) is willing and able to provide consent 
before any study-specific tests or procedures are performed and agree to 
attend all required follow-up visits; 
2. Subject at least 20 years of age; 
3. Chronic symptomatic lower limb ischemia defined as Rutherford 
classification 2, 3, or 4; 
4. Target lesion is in the native SFA and/or PPA down to the P1 segment; 
5. Patent popliteal and infrapopliteal arteries, i.e., single vessel runoff or 
better with at least one of three vessels patent (<50% stenosis) to the 
ankle or foot; 
6. Reference vessel diameter ≥ 4 mm and ≤ 8 mm by visual estimate  
(Use of a radiopaque ruler is recommended);  
7. Angiographic evidence that target lesion consists of a single de novo, 
non-stented and non-atherectomy treated or restenotic lesion (or tandem 
lesions or a combination lesion as defined below) that is: 
a. 
≥ 70% -99% stenotic with total lesion length up to180 mm by 
visual estimate. Use of a radiopaque ruler is recommended. 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 41 of 110 
 
 
 
 
b. Occluded with total lesion length ≤ 100 mm by visual estimate.  
Use of a radiopaque ruler is recommended. 
c. 
If lesion is restenotic, most recent PTA treatment must be > 3 
months prior to  enrollment  
Notes: 
Combination lesions (a non-occlusive lesion that includes a totally occluded 
segment along its length) are eligible provided that the total combined lesion 
length is ≤180 mm. 
Tandem (or “adjacent”) lesions may be enrolled providing they meet all of 
the following criteria: 
 
Separated by a gap of ≤ 30 mm (3 cm) 
 
Total combined lesion length meets requirements (Angiographic 
inclusion criteria (7) including 30 mm gap); and 
 
Able to be treated as a single lesion. 
 
9.3. Exclusion Criteria 
Subjects who meet any one of the following criteria (Table 9-2) will be excluded from this 
clinical trial. 
Table 9-2: Exclusion Criteria 
Exclusion 
Criteria 
1. Life expectancy, documented in the Investigator’s opinion, of less than 12 
months; 
2. Hemorrhagic stroke or cardiac event (e.g. STEMI, unstable angina) 
within 6 months prior to enrollment; 
3. Known allergies or sensitivities to heparin, aspirin, other 
anticoagulant/antiplatelet therapies, and/or paclitaxel; 
4. Known hypersensitivity or contraindication to contrast dye that, in the 
opinion of the investigator, cannot be adequately pre-medicated; 
5. Chronic renal insufficiency with serum creatinine > 2.0 mg/dL within 30 
days of index procedure or treatment with dialysis; 
6. Platelet count <80,000 mm3 or >600,000 mm3 or history of bleeding 
diathesis; 
7. Receiving immunosuppressive therapy; 
8. Septicemia at the time of enrollment; 
9. Any major (e.g., cardiac, peripheral, abdominal) intervention (including 
in the contralateral SFA/PPA) planned within 30 days post index 
procedure; 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 42 of 110 
 
 
 
 
10. Presence of other hemodynamically significant outflow lesions in the 
target limb requiring intervention within 30 days of enrollment; 
11. Failure to successfully cross the target lesion with a guidewire (successful 
crossing means tip of the crossing device is distal to the target lesion in 
the absence of flow-limiting dissections or perforations); 
12. Failure to successfully pre-dilate the target vessel; 
13. Patient has lesion that requires the use of adjunctive primary treatment 
modalities (i.e. laser, atherectomy, scoring/cutting balloon, other 
debulking devices, etc.) during the index procedure; 
14. History of major amputation in the target limb; 
15. Target lesion or vessel has ever been previously treated with stent (e.g. 
in-stent restenosis) or, surgery. Target lesion or vessel has been treated 
with atherectomy or a DCB  in the past 12 months; 
16. Pregnant or breast feeding; 
17. Presence of aneurysm in the target vessel; 
18. Acute ischemia and/or acute thrombosis of the SFA/PPA prior to 
enrollment; 
19. Patient has significant inflow disease which cannot be treated prior to the 
target lesion treatment; 
20. Patient has perforated targeted vessel as evidenced by extravasation of 
contrast media; 
21. Patient has severe calcification that renders the lesion undilatable;  
22. Current participation in another investigational drug or device clinical 
trial that has not completed the primary endpoint at the time of 
randomization/enrollment or that clinically interferes with the current trial 
endpoints.  
Note: studies requiring extended follow-up for products that were 
investigational, but have become commercially available since then are 
not considered investigational studies. 
Abbreviations: STEMI- ST elevation myocardial infraction 
10. Subject Accountability 
10.1. Point of Enrollment 
Once the subject has signed the IRB/IEC/REB-approved trial informed consent (ICF), and has 
met all clinical inclusion and no clinical exclusion criteria, the subject will be considered eligible 
to be enrolled in the trial. If the subject does  not meet inclusion criteria during the angiographic 
eligibility assessment, the subject will be considered a screen failure and should not be 
enrolled/randomized or receive an investigational device, nor should the subject be followed 
post-procedure per protocol.  


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 43 of 110 
 
 
 
 
If the subject is found to meet the eligibility criteria during the angiographic phase of the 
procedure, the subject will be considered eligible to be enrolled. After the Investigator 
successfully crosses the target lesion with the guidewire and successfully pre-dilates the target 
lesion, a randomization custom function within the Rave EDC database will be used to assign 
RCT subjects to the test or control treatment group. Subjects are considered enrolled when the 
Ranger DCB or Standard PTA is introduced into the subject’s vasculature. 
Testing (including CBC, platelets, ABI, and Rutherford Classification) completed as a part of the 
subject’s standard of care, within 30 days of the index procedure and that meets the study 
(inclusion/exclusion) criteria, are not required to be repeated after consenting is complete. 
 
10.2. Withdrawal 
All subjects enrolled in the clinical trial (including those withdrawn from the clinical trial or lost 
to follow-up) shall be accounted for and documented. 
While trial withdrawal is discouraged, subjects may choose to withdraw from the trial at any 
time, with or without reason and without prejudice to further treatment. Withdrawn subjects will 
not undergo any additional trial follow-up, nor will they be replaced (the justified sample size 
considers an estimated allowance for attrition). The reason for withdrawal will be recorded (if 
given) in all cases of withdrawal. The Investigator may discontinue a subject from participation 
in the trial if the Investigator feels that the subject can no longer fully comply with the 
requirements of the trial or if any of the trial procedures are deemed potentially harmful to the 
subject. Data that have already been collected on withdrawn subjects will be retained and used 
for analysis but no new data will be collected after withdrawal. 
10.3. Enrollment Controls 
The RANGER II SFA trial will develop a formal Enrollment Communication Plan.  The plan 
will outline the specific activities and responsibilities of BSC employees and representatives, the 
nature and timing of communications to Investigators during the enrollment period and as 
enrollment draws to a close. 
The objective of the plan is to minimize the risk of enrollment beyond the protocol-specified 
overall enrollment cap, including regional and site-specific caps. 
11. Trial Methods 
11.1. Data Collection 
The data collection schedule for the RANGER II SFA trial is summarized in Table 11-1. 
 


S2062 
 
                             
 Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                               
 
 
 
 
 
                    RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 44 of 110 
 
 
 
Table 11-1: 
Data Collection Schedule 
Procedure/Assessment 
Pre-
procedure[2] 
During 
Index 
Procedure 
Pre-Discharge 
Day 1 or 2[6] 
Day 7 
(±1 days) 
1-month 
(30±7 days) 
6-month 
(182±30 days) 
12-month 
(365±30 days) 
24-month 
(730±30 days) 
36-month 
(1095±30 days) 
48-month[5] 
(1460 ± 30 days) 
(office/clinic visit 
or telephone) 
60-month[5] 
(1825 ± 30 days) 
(office/clinic visit 
or telephone) 
Informed Consent[1] 
X 
 
 
 
 
 
 
 
 
 
 
 
Confirm Inclusion/Exclusion 
X 
X 
 
 
 
 
 
 
 
 
 
 
Demographics and Medical 
History, Height and Weight 
X 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy Test[2] 
X 
 
 
 
 
 
 
 
 
 
 
 
Physical Exam[3] 
X 
 
X 
 
 
X 
X 
X 
X 
X 
 
 
Complete Blood Count 
(CBC) and platelet count 
X 
 
 
 
 
 
 
 
 
 
 
 
Serum Creatinine 
X 
 
 
 
 
 
 
 
 
 
 
 
ABI Measurements 
X 
 
 
 
 
X 
X 
X 
X 
X 
 
 
Rutherford Classification 
X 
 
 
 
 
X 
X 
X 
X 
X 
 
 
Walking Impairment 
Questionnaire (WIQ) 
X 
 
 
 
 
X 
X 
X 
X 
X 
 
 
EQ-5D Questionnaire 
X 
 
 
 
 
X 
X 
X 
X 
X 
 
 
6 Minute Walk Test (6MWT) 
X 
 
 
 
 
 
X 
X 
 
 
 
 
Angiogram[4] 
 
X 
 
 
 
 
 
 
 
 
 
 
Randomization/Enrollment 
 
X 
 
 
 
 
 
 
 
 
 
 
PK venous draw 
X 
X[6] 
X 
X 
X 
X 
 
 
 
 
 
 
Duplex Ultrasound[4] 
 
 
 
 
 
X 
X 
X 
X 
X 
 
 
Medication Assessment 
X 
X 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
Adverse Events Assessment 
 
X 
X 
 
 
X 
X 
X 
X[7] 
X[7] 
X[7] 
X[7] 
[1] Subject’s consent obtained and informed consent form signed prior to obtaining any study-specific tests or procedures. Testing (CBC, platelets, ABI, and Rutherford Classification) 
completed as a part of the subject’s standard of care, within 30 days of the index procedure and that meets the study (inclusion/exclusion) criteria, are not required to be repeated.  
[2] Performed within 30 days of procedure, except urine or blood pregnancy test required for females of childbearing potential performed within 24 hrs. of procedure 
[3] Physical exam includes obtaining Vital signs (B/P, HR, RR*), Rutherford Classification and ABI at 1 mth, 6 mth, 12 mth, 24 mth and 36 mth follow up visits.  Pre-discharge: Vital signs 
only. * Respiratory rate is not mandatory if not local standard of care. 
[4] Angiograms and Ultrasounds will be sent to the respective core lab for analysis.   
[5] The 48 month and 60 month visit may be conducted in the office/clinic or by telephone. 
[6] PK venous draw at screening, 10 min, 30 min, 1 hr., 3 hr., 6 hr., 24 or 48 hr. after last Ranger DCB removal, Day 7 and Day 30 post index procedure. 
[7] Reporting required through the end of trial for SAEs, UADEs and ADEs/Device Deficiencies.  AEs not related to the investigational device or procedure reported only through 12 month 
follow-up visit. 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 45 of 110 
 
 
 
 
 
11.2. Trial Candidate Screening 
A Screening Log will be maintained by each investigational site to document selected 
information about subjects who fail to meet the RANGER II SFA trial eligibility criteria, 
including the reason for screen failure. 
11.3. Informed Consent 
Before any study-specific tests or procedures are performed, subjects who meet the clinical 
eligibility criteria will be asked to read and sign the IRB/IEC/REB-approved trial ICF. Subjects 
must be given ample time to review the ICF and have questions answered before signing.  
Trial personnel should explain to the subject that even if the subject agrees to participate in the 
trial and signs the ICF, the angiography assessment may demonstrate that the subject is not a 
suitable candidate for the trial.  
Refer to section 10.1 for definition of point of enrollment 
11.4. Pre-Procedure Assessments – Within 30 Days Prior to Index Procedure 
The following pre-procedure data must be collected after the subject has submitted consent and 
within 30 days prior to the index procedure (unless otherwise specified) for all subjects: 
 
Demographics and medical history obtained 
 
Physical assessment including: 
– Vital Signs:  Blood pressure (B/P), Heart rate (HR), Respiratory rate (RR)*  
– Weight and height 
– Rutherford Classification 
– Ankle-Brachial Indices (ABI) measurements 
 
*Respiratory rate data collection is not mandatory if not local standard of care 
 
Laboratory tests 
– Complete blood count (CBC) with platelets 
– Serum Creatinine  
– PK baseline 
 
6 Minute Walk Test 
 
Administer Questionnaire Assessments 
– Walking Impairment Questionnaire (WIQ) 
– EQ-5D 
11.5. Pre-Procedure Assessments – Within 24 hrs. prior to index procedure 
A pregnancy test for females of childbearing potential with analysis per local practice (serum or 
urine) is required within 24 hours prior to the index procedure. 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 46 of 110 
 
 
 
 
 
11.6. Pre-Procedure Requirement 
Anti-platelet therapy is recommended throughout the length of trial participation. Investigators 
must prescribe concomitant anti-coagulant and anti-platelet medications consistent with current 
local clinical practice. 
Antiplatelet medication and peripheral artery disease (PAD) medication usage will be collected 
and reported for compliance throughout the trial. 
Anti-coagulation therapy administered prior to and during the procedure should be consistent 
with current clinical practice.  
Note: A subject is exempt from the above-mentioned antiplatelet requirement if he/she requires 
Coumadin or other similar anti-coagulant due to known comorbidities and in the opinion of the 
investigator, the combination of antiplatelet and anticoagulant could put the subject at an 
unreasonable risk of bleeding. 
11.7. Index Procedure 
Investigators will manage the cardiovascular risk factors and comorbidities for all patients 
according to standards of care.  Investigators should ensure close monitoring of the amount of 
contrast for subjects with elevated serum creatinine levels and consider preventive measures 
(medication and hydration) to reduce the risk of contrast-induced nephropathy (CIN).  
The start of the index procedure is defined as the time the guide (catheter or sheath) is inserted. 
11.7.1. 
Treatment of Non-target Lesions 
Multiple interventions may occur using the same access site at the time of the index procedure.  
Using the same access site iliac lesion(s) in the contralateral and ipsilateral limb may be treated 
during the index procedure under the following conditions: 
 
Treatment with a commercially (non-drug coated) available device occurs prior to 
randomization of the target SFA/PPA lesion(s); 
 
Treatment of the lesion(s) is deemed an angiographic success without clinical sequelae 
(success is measured as <30% residual stenosis by visual estimation)  
If the above criteria are not met, the subject may not be randomized into the trial but may be 
rescreened for eligibility after 30 days. 
11.7.2. 
Angiographic Imaging of Target Lesion(s) 
Diagnostic angiography of the lower extremities must be performed using standard techniques to 
confirm angiographic eligibility of the target lesion. Visual angiographic assessment may be 
used to determine if criteria are met. 
Refer to the BIDMC Angiographic Core Lab Protocol for Angiographic Film Acquisition.  This 
manual is located in the RANGER II SFA manual of operations and has detailed trial 
requirements. 
A few key steps are below: 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 47 of 110 
 
 
 
 
 
 
Obtain both pre-procedure (2 views) and post-procedure (2 views) utilizing the standard 
DICOM 3.  The first frame of the series should be unmasked. 
 
A ruler or radiopaque marking tape with centimeter markings should be used as the 
calibration source to determine the image calibration. The core lab will need to observe the 
ruler for analysis. 
 
Perform run-off vessel images demonstrating patency to the foot. This imaging should be 
taken once at the beginning (pre-procedural views), and once at the end of the procedure, 
after all target lesions have been treated (post-procedural views). 
 
For the most accurate analysis of lesions, it is necessary to have matching projection angles 
in the pre-procedural and post-intervention angiographic projections. 
Angiographic images must be sent to the BIDMC Angiographic Core Laboratory for evaluation.  
If the core lab is unable to analyze the angiogram, then site reported assessment is used. 
11.7.3. 
Enrollment 
Prior to enrollment, a subject must meet all of the clinical and angiographic inclusion criteria and 
none of the clinical and angiographic exclusion criteria. 
If the subject is found to meet the eligibility criteria during the angiographic phase of the 
procedure, the subject will be considered eligible to be enrolled. After the Investigator 
successfully crosses the target lesion with the guidewire and successfully pre-dilates the target 
lesion, a randomization custom function within the Rave EDC database will be used to assign 
randomized subjects to the Ranger DCB (test) or Standard PTA (control treatment group). The 
Ranger DCB balloons are provided by the Sponsor.  Standard PTA balloons are commercially 
available balloons that the investigative sites utilize from their inventory.  Subjects are 
considered enrolled when the Ranger DCB or Standard PTA is introduced into the subject’s 
vasculature. 
If the balloon angioplasty attempt with the assigned treatment device (the test device Ranger 
DCB or control device Standard PTA) is not successful, follow-up through the 1 month visit only 
will occur as part of the ITT population.  Data for assessment of MAE will be collected for these 
subjects.  No other testing or follow up is required. 
11.7.4. 
Treatment of Target Lesion(s) 
The Directions For Use (DFU) for the Ranger DCB is located in the Manual of Operations. Prior 
to use of the device, the treating physician must carefully read and be familiar with the entire 
DFU. The Ranger DFU must be followed for deploying the investigational DCB.  
Procedural information must be reported (specific data fields are noted in the electronic 
database). Refer to the DFU for detailed instructions about delivery system preparation and 
placement of the Ranger DCB. 
Ranger DCB Procedure: 
Optimal target lesion/vessel preparation is required. Successful pre-dilatation of the target 
lesion(s) with optimally sized balloon(s) is required before DCB deployment.  Successful pre-


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 48 of 110 
 
 
 
 
 
dilatation occurs when the selected balloon opens vessel entry at nominal pressure without major 
(≥ Grade D) flow-limiting dissection or need for intervention (i.e. stenting). 
Note: If major dissection occurs at this step, subject should not be enrolled into the trial.  
No follow up is required. 
Record the following information on pre-dilatation balloon(s) used: 
 
Maximum balloon diameter (mm) inflated 
 
Maximum pressure (atmospheres) inflated 
 
Maximum length of time (seconds) inflated 
The recommended Ranger DCB inflation time is three (3) minutes to ensure apposition to the 
arterial wall and to reduce the chance of vessel recoil. Post-dilatation may be performed at the 
discretion of the Investigator.   
Record the following information on post-dilatation balloon(s), if utilized: 
 
Maximum balloon diameter (mm) inflated 
 
Maximum pressure (atmospheres) inflated 
 
Maximum length of time (seconds) inflated 
Peri-procedure dissections should be treated conservatively, with low pressure prolonged balloon 
inflation, or with provisional stenting of the target lesion with bare-metal stents. Bare metal 
stents can be utilized in cases where adequate results could not be obtained after using post-
dilatation balloons; such as in the case of remaining residual stenosis [≥ 50%] or major [≥ Grade 
D] flow-limiting dissection after post-dilatation. 
Haziness, lucency, or filling defects within or adjacent to the ballooned area, and angiographic 
complications such as distal thromboemboli or no reflow, should also be treated per standard 
practice. All angiographic complications that occur should be documented by angiography and 
submitted to the BIDMC Angiographic Core Laboratory for analysis. 
For subjects randomized to the Standard PTA (non-scoring), treatment with commercially 
available Standard PTA (control) balloons should be completed according to each individual 
device labelling. 
11.7.5. 
Post-procedure Angiogram 
Perform the post-procedure angiography according to BIDMC Angiographic Core Laboratory 
protocol. The final angiogram must be performed and recorded, including distal run-off to the 
foot. Angiographic images must be sent to the angiographic core laboratory for evaluation. 
11.8. End of the Index Procedure 
The end of the index procedure is defined as the time the guide (catheter or sheath) is removed 
(post final angiography). The introducer(s) sheaths should be removed as per standard local 
practice. The following procedures must be completed:  


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 49 of 110 
 
 
 
 
 
 
Document procedural, target lesion, pre-dilatation, post-dilatation (if applicable), and trial 
balloon information on the appropriate eCRFs 
 
Record antithrombotic/antiplatelet medications 
 
Complete AE assessment  
 
Finalize angiographic procedure film and related required documentation to submit to the 
BIDMC Angiographic Core Laboratory per instructions set in the Manual of Operations. 
11.9. Post-procedure/Pre-Discharge 
The subject may be discharged from the hospital when clinically stable at the Investigator’s 
discretion. The following assessments must be completed prior to hospital discharge.  
 
Physical Exam:  Vital signs only (B/P, HR and RR*)  
*Respiratory rate data collection is not mandatory if not local standard of care 
 
Medication assessment 
 
Adverse Event (AE) assessment 
 
Pharmacokinetic (PK) venous blood should be obtained at 10 min, 30 min, 1 hr., 3 hr., 6 
hr., 24 or 48 hr. after last Ranger DCB balloon removal for subjects enrolled into the PK 
sub-study 
Assessment of Whole Blood Paclitaxel Levels 
The PK profile of the Ranger DCB will be analyzed for subjects enrolled in the PK substudy. 
Nine (9) venous blood samples will be drawn according to the schedule shown in Table 11-2. 
Treatment of the SFA/PPA with a drug coated or uncoated balloon is most often performed as an 
out-patient procedure and sampling time points greater than 5 hours post-procedure will require 
most subjects to return to the research site for blood draws. 
To encourage all enrolled PK subjects to comply with the PK sampling schedule after release 
from the hospital/facility, the research team will allow the subject to choose to return for either 
the 24 hours or 48 hour time point.  The day 7 and day 30 time points will be scheduled for all 
PK subjects. 
A stipend may have to be provided to cover lodging or travel expenses incurred by subjects as a 
result of participation in the PK substudy in accordance with pertinent country laws and 
regulations and per the trial site’s regulations. 
All samples must be forwarded to the PK core laboratory for analysis of whole blood paclitaxel 
levels. 
Instructions for blood sample collection, storage, and shipment are provided in the PK core 
laboratory Instruction Manual. This manual is located in the Manual of Operations. 
 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 50 of 110 
 
 
 
 
 
Table 11-2: 
Blood Draw Schedule for Analysis of Paclitaxel Pharmacokinetics 
Day 
Blood Draw Schedule 
Before balloon treatment 
Within 30 Days  prior to index procedure 
After balloon treatment 
Day 0 
10 minutes (±5 minutes) after last Ranger DCB balloon removal  
30 minutes (±10 minutes) after last Ranger DCB balloon removal 
1 hour (±10 minutes) after last Ranger DCB balloon removal 
3 hours (±10 minutes) after last Ranger DCB balloon removal 
6 hours (±10 minutes) after last Ranger DCB balloon removal 
Day 1-2 * 
24 hours (±4 hours) OR 48 hours (±4 hours) after last Ranger DCB 
balloon removal 
Day 7 
Day 7 (±1 Day) 
Day 30 
Day 30 (±7 Days) 
*Either draw blood on Day 1 (24 hr) or Day 2 (48 hr) for each subject 
Bioanalytical Method 
The blood samples collected from patients at the specified time points will be analyzed for levels 
of paclitaxel using HPLC/GC with UV/Fluorescence/MS/MS detection by Covance Core Lab. 
Pharmacokinetics Parameters 
Values for the following paclitaxel PK parameters will be calculated by a standard non-
compartment analysis for subjects in the PK substudy. 
 
Maximum observed blood concentration (Cmax) 
 
First time of occurrence of Cmax (tmax) will be the actual observed values 
 
Terminal phase rate constant (λz) will be estimated from log-linear regression analysis of 
the terminal phase of the blood concentration-time profile 
 
Associated apparent terminal phase half-life (t½) will be calculated as t½ = ln(2/λz) 
 
Area under the blood concentration versus time curve from time zero to 1 hour (AUC0-1), 
time zero to 24 hours (AUC0-24), time zero to the time of the last quantifiable concentration 
(AUC0-t) and extrapolated to infinite time (AUC0-∞) will be calculated by a combination of 
linear and logarithmic trapezoidal methods 
 
Percentage of AUC0-∞ obtained by extrapolation (%AUCex) will be calculated as [(AUC0 ∞ 
– AUC0-t)/AUC0-∞] × 100 
 
Total blood clearance (CL) 
For AUC calculation, the linear method will be employed for all incremental trapezoids arising 
from increasing concentrations and the logarithmic trapezoidal method will be used for those 
arising from decreasing concentrations. 
Descriptive statistics (mean, standard deviation, sample size, 95% confidence interval) will be 
used to summarize these parameters for subjects in the PK substudy. No formal statistical testing 
will be done for these parameters. 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 51 of 110 
 
 
 
 
 
11.10. Follow-up Visits  
RANGER II SFA trial is a single blind trial. Subjects will be blinded to treatment assigned and 
treatment received. All subjects (excluding subjects in the PK substudy) must remain blinded 
until completion of all 12 month follow-up visits (primary endpoint).  
It is important that trial site personnel review the trial requirements with the subject to maximize 
compliance with the follow-up schedule and required medication regimen. It is also important 
that trial site personnel instruct subjects to return for follow-up assessments according to the trial 
event schedule in Table 11-1. Trial staff should establish a date for the follow-up visit with the 
subject and if possible, schedule the visit prior to hospital discharge. 
All randomized and enrolled subjects who receive a test or control balloon, Ranger DCB or 
Standard PTA, will continue to be evaluated at 1 month, 6 months, 12 months, 24 months, 36 
months, 48 months, and 60 months after the index procedure.  
Subjects enrolled in the PK substudy who receive the RANGER DCB will have blood drawn at 
24 or 48 hours, Day 7 and Day 30 as well as complete protocol required assessments at 1 month, 
6 months, 12 months, 24 months, 36 months, 48 months, and 60 months after the index 
procedure. 
Subjects who underwent advancement of the Ranger DCB or Standard PTA into the body but 
deployment was unsuccessful, will be considered enrolled under Intent to Treat population and 
will be followed for safety through the 1-month follow-up visit only. Data for assessment of 
MAE will be collected for these subjects; other testing is not required. 
For each follow-up visit, the results of the subjects’ clinical status and functional testing 
(Rutherford Classification and ABI) should be completed prior to initiating the DUS imaging, if 
required.  Subjects requiring reintervention should be treated according to the Investigator’s 
discretion and standard of care. These subjects should receive an approved, commercially 
available treatment (if appropriate) and must not receive an investigational device for 
retreatment.  
Note: Follow-up angiograms and ultrasounds will not be required for any subject who undergoes 
bypass surgery of the target lesion or has a documented occluded lesion during the 60 month 
follow-up timeframe. 
Requirements of each follow-up evaluation are described below. 
11.10.1. Day 7 Follow-up Visit (±1 Day)  
Ranger DCB Successful Angioplasty 
Unsuccessful Angioplasty 
(Intent to Treat) 
PK substudy: venous Blood Draw 
 
None 
 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 52 of 110 
 
 
 
 
 
11.10.2. 1 Month Follow-up Visit (±7 Days) 
Ranger DCB or Standard PTA Successful 
Angioplasty 
Unsuccessful Angioplasty  
(Intent to Treat) 
Physical Exam: 
 
Vital signs (B/P, HR, RR*)  
 
ABI measurement 
 
Rutherford Classification 
WIQ Questionnaire 
EQ-5D Questionnaire 
DUS 
PK substudy:  venous blood draw 
AE assessment** 
Medication assessment 
AE assessment 
* Respiratory rate data collection is not mandatory if not local standard of care. 
** Reporting required through the end of trial for SAEs, UADEs and ADEs/Device Deficiencies.  AEs not related to the 
investigational device or procedure reported only through 12 month follow-up visit. 
 
11.10.3. Duplex Ultrasound Assessment of Target Lesion(s) 
DUS are utilized to assess the primary effectiveness endpoint of the RANGER II SFA trial.  The 
primary effectiveness endpoint assesses the primary lesion patency within 12 months post-index 
procedure.   
Primary effectiveness is defined as a binary endpoint determined by (DUS) peak systolic 
velocity ratio (PSVR) ≤ 2.4 in the absence of clinically-driven TLR.  
Clinically-driven TLR is defined as any re-intervention at the target lesion due to recurrent 
symptoms (≥ 1 change in Rutherford Classification or associated with decreased ABI/TBI of ≥ 
20% or > 0.15 when compared to post-procedure baseline ABI/TBI in the treated segment. TBI 
allowed in cases of incompressible vessels). 
This effectiveness endpoint is designed to demonstrate that the 12-month primary patency for the 
Ranger DCB treated test group is superior to the control group.  
Lesion patency is defined as freedom from more than 50% stenosis based on DUS PSVR 
comparing data within the treated segment to the proximal normal arterial segment. PSVR >2.4 
suggests >50% stenosis. 
It is imperative that the DUS examinations be completed according to the VASCORE Vascular 
Core Lab protocol. The DUS protocol will be located in the Manual of Operations.  


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 53 of 110 
 
 
 
 
 
11.10.4. 6 Month Follow-up Visit (±30 Days) 
Ranger DCB or Standard PTA Successful 
Angioplasty 
Unsuccessful Angioplasty 
(Intent to Treat) 
Physical Exam 
 
Vital signs (B/P, HR, RR*) 
 
ABI measurement 
 
Rutherford Classification 
WIQ Questionnaire 
EQ-5D Questionnaire 
6 Minute Walk Test 
DUS 
AE assessment** 
Medication assessment 
Not Applicable 
* Respiratory rate data collection is not mandatory if not local standard of care. 
** Reporting required through the end of trial for SAEs, UADEs and ADEs/Device Deficiencies.  AEs not related to the 
investigational device or procedure reported only through 12 month follow-up visit. 
 
 
11.10.5. 12 Month Follow-up (±30 Days) 
Ranger DCB or Standard PTA Successful 
Angioplasty 
Unsuccessful Angioplasty 
(Intent to Treat) 
Physical Exam 
 
Vital signs (B/P, HR, RR*) 
 
ABI measurement 
 
Rutherford Classification 
WIQ Questionnaire 
EQ-5D Questionnaire 
6 Minute Walk Test 
DUS 
AE assessment** 
Medication assessment 
Not Applicable 
* Respiratory rate data collection is not mandatory if not local standard of care. 
** Reporting required through the end of trial for SAEs, UADEs and ADEs/Device Deficiencies.  AEs not related to the 
investigational device or procedure reported only through 12 month follow-up visit. 
 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 54 of 110 
 
 
 
 
 
11.10.6. 24 Month and 36 Month Follow-up (±30 Days) 
Ranger DCB or Standard PTA Successful 
Angioplasty 
Unsuccessful Angioplasty 
(Intent to Treat) 
Physical Exam 
 
Vital signs (B/P, HR, RR*) 
 
ABI measurement 
 
Rutherford Classification 
WIQ Questionnaire 
EQ-5D Questionnaire 
DUS 
AE assessment** 
Medication assessment 
Not Applicable 
* Respiratory rate data collection is not mandatory if not local standard of care. 
** Reporting required through the end of trial for SAEs, UADEs and ADEs/Device Deficiencies.  AEs not related to the 
investigational device or procedure reported only through 12 month follow-up visit. 
 
11.10.7. 48 Month and 60 Month Follow-up (±30 Days):  The 48 and 60 month visits can 
occur in office/clinic or by phone. 
Ranger DCB or Standard PTA Successful 
Angioplasty 
Unsuccessful Angioplasty 
(Intent to Treat) 
AE assessment* 
Medication assessment 
Not Applicable 
* Reporting required through the end of trial for SAEs, UADEs and ADEs/Device Deficiencies.  AEs not related to the 
investigational device or procedure reported only through 12 month follow-up visit. 
 
11.11. Trial Completion 
The trial will be considered complete (with regard to the primary endpoints) after all subjects 
have completed the 12-month follow-up visit, were discontinued prior to the 12-month follow-up 
visit, have died or the follow-up visit window is closed. 
The trial will be considered complete (with regard to all follow-up) after all subjects have 
completed the 60 month (5 year) follow-up visit, were discontinued prior to the 60 month (5 
year) follow-up visit, have died or the follow-up visit window is closed. 
11.12. Missed or Late Visits 
Every effort must be made by the site to retain trial subjects for the duration of the trial.   
A minimum of 3 attempts (i.e., 2 phone calls followed by a certified letter, or other traceable 
letter, if necessary) should be made to contact the subject or subject’s next of kin for each missed 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 55 of 110 
 
 
 
 
 
follow-up visit and this information should be documented in the source.  Missed or late visits 
will be recorded as Protocol Deviations. For subjects who miss their 12 Month follow-up visit 
(primary endpoint), BSC may provide sites access to a patient locator service (if allowed by the 
site’s IRB/IEC/REB).  A subject will be considered lost to follow-up after the subject misses 2 
consecutive annual follow-up visits without due cause. No subject will be considered lost to 
follow-up prior to the 24 Month follow-up visit in order to make every effort to collect evaluable 
data for the primary endpoint. 
11.13. Source Documents 
It is preferable that original source documents (see Section 27.2 for definition) are maintained, 
when available. Where copies of the original source document as well as printouts of original 
electronic source documents are retained, it is required that the copies be signed and dated by a 
member of the investigation center team with a statement that it is a true reproduction of the 
original source document.  
12. Statistical Considerations 
The sample size justification and the power analyses for the primary endpoints described in this 
section are mainly for the RCT. For the PK substudy, the sample size determination is arbitrary 
and the analysis is based on observation. The details of all statistical analyses will be described 
in the Statistical Analysis Plan. 
12.1. Primary Endpoints 
The overall sample size in the RCT is justified by hypothesis parameters and driven by the 
primary effectiveness 12-month endpoint to preserve adequate statistical testing power for both 
primary effectiveness and safety endpoints.  
The primary effectiveness and safety hypotheses are planned for being tested simultaneously in 
an adaptive group sequential manner at the overall significance level of one-sided 2.5%. The 
Lan-DeMets alpha spending function with Power Family Method will be used to determine the 
interim and the final type I error adjustment. 
For the PK sub-study, the sample size determination is arbitrary and the analysis is based on 
observation. There is no primary endpoint for the PK substudy. 
12.1.1. 
Primary Effectiveness Endpoint 
The 12-month primary patency is chosen to be assessed for the primary effectiveness endpoint in 
the RCT. The goal is set to demonstrate that the primary patency for the Ranger DCB treatment 
group (i.e. Test) is superior to the Standard PTA treatment group (i.e. Control) through 12 
months post-procedure. For the definition of primary patency, refer to the section 7.1 Primary 
Endpoints. 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 56 of 110 
 
 
 
 
 
12.1.1.1. Effectiveness Hypotheses 
The primary effectiveness hypothesis to be tested is that 12-month primary patency in subjects 
treated with Ranger DCB is superior to subjects treated with  Standard PTA at an overall one-
sided significance level of 2.5%. 
The null hypothesis (H0) states that there is no pre-specified treatment effect of Ranger DCB vs. 
Standard PTA as opposed to the alternative hypothesis (H1) which states that there is a pre-
specified treatment effect. The hypotheses inequalities are shown below: 
H0: Pt - Pc  ≤ 0 
H1: Pt - Pc  > 0 (superior) 
where Pt and Pc are the 12-month primary patency for Ranger DCB and Standard PTA, 
respectively. 
12.1.1.2. Effectiveness Sample Size 
The overall sample size is driven by the primary effectiveness endpoint. Approximately 376 
subjects are planned to be enrolled in the RCT. The sample size justification for the RCT is 
based on the following assumptions. 
 
Power ≥ 85% 
 
One-sided overall significance level (alpha) = 2.5% 
 
Lan-DeMets alpha spending function with Power Family Method: 
– One assessment for a minimum of 75% subjects to be assessed subjects to be assessed 
– The final assessment for the overall subjects  
 
Expected Standard PTA 12-month primary patency = 52.5% 
 
Ranger DCB to demonstrate 20% treatment effect 
 
Allocation (Ranger DCB vs. Standard PTA) = 3:1 
 
Attrition rate in 12 months = 15% 
 
N = 320 (total) evaluable subjects are required at 12 months (240 in Ranger DCB and 80 in 
the Standard PTA) 
 
N = 376 (total) subjects to be randomized prior to the procedure (282 in Ranger DCB and 
94 in Standard PTA) 
12.1.1.3. Effectiveness Statistical Methods 
A Chi-Square Test for the difference in 12-month primary patency will be used to assess the 
effectiveness hypotheses. 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 57 of 110 
 
 
 
 
 
12.1.2. 
Primary Safety Endpoints 
The 12-month MAE-free rate is selected to be assessed for the primary safety composite 
endpoint. The safety goal is designed to demonstrate that Ranger DCB is non-inferior to 
Standard PTA in terms of MAE-free rate through 12 months post-procedure. 
 
12.1.2.1. Safety Hypotheses 
The primary safety hypothesis to be tested is that 12-month MAE-free rate in subjects treated 
with Ranger DCB is as safe as the subjects treated with  Standard PTA at an overall one-sided 
significance level of 2.5%. 
The null hypothesis (H0) states that there is no marginal treatment effect of RANGER DCB vs. 
Standard PTA as opposed to the alternative hypothesis (H1) states that there is a marginal 
treatment effect. The hypotheses inequalities are shown below: 
H0: Pt - Pc  ≤ ∆  
H1: Pt - Pc  > ∆ (non-inferior) 
where Pt and Pc are the 12-month MAE-free rate for Ranger DCB and Standard PTA, 
respectively, and Δ (delta) is the non-inferiority margin of -10%. 
12.1.2.2. Safety Sample Size/Power Analysis 
The power analysis for the primary safety endpoint is based on the following assumptions. 
 
One-sided overall significance level (alpha) = 2.5% 
 
The primary safety endpoint will be tested simultaneously with the primary effectiveness 
endpoint at the same significance level for the interim analysis and/or for the final analysis 
as needed 
 
Expected Standard PTA 12-month MAE-free = 75% 
 
Expected Ranger DCB 12-month MAE-free rate = 90% 
 
Non-inferiority margin (∆) = -10%* 
The sample size is driven by the primary effectiveness endpoint to provide at least 94% power to 
assess the primary safety endpoint. 
* The margin of -10% is clinically meaningful for the safety endpoint per physicians’ consensus. Due to the interim alpha 
adjustment, the observed Ranger DCB will require to outperform the Standard PTA such that the lower confidence bound of 
the observed difference within the margin to claim a success. For an example of 75% subjects to be assessed for the interim 
analysis, the margin of -10% will require the observed MAE-free rate of 79.4% in Ranger DCB when the Standard PTA is 
observed as 75% to demonstrate non-inferiority at interim alpha level of one-sided 1.41%. 
12.1.2.3. Safety Statistical Methods 
A Chi-Square Test will be used to assess the hypothesis of for the difference in 12-month MAE-
free rate will be used to assess the safety hypotheses. 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 58 of 110 
 
 
 
 
 
12.2. Success Criteria 
The following success criteria are defined for the RCT. For the group sequential design, a 
minimum of 75% evaluable subjects are required for the interim analysis. Since the Lan-DeMets 
alpha spending function is continuous, the confidence levels and adjusted alpha levels will 
depend on the actual observed proportion of subjects (e.g. >75%). Without loss of generality, an 
example of 75% subjects is described below. 
12.2.1. 
Success Criteria for the Interim Analysis 
For example, exact 75% subjects are to be assessed at the interim analysis. 
Ranger DCB will be concluded to be superior to Standard PTA for device effectiveness in the 
interim analysis if the one-sided lower 98.59% confidence bound on the difference between 
treatment groups (Ranger DCB – Standard PTA) in 12-month primary patency is greater than 
zero. 
Ranger DCB will be concluded to be as safe as Standard PTA if the one-sided lower 98.59% 
confidence bound on the difference between treatment groups (Ranger DCB – Standard PTA) in 
12-month MAE-free is greater than -0.1. 
The study success will be concluded as both primary effectiveness and primary safety endpoints 
being achieved in the interim analysis. 
12.2.2. 
Success Criteria for the Final Analysis 
All subjects are to be assessed at the final analysis when the interim analysis is not able to be 
concluded. 
If for any reason, the final analysis is required to prove superiority, Ranger DCB will be 
concluded to be superior to Standard PTA for device effectiveness in the final analysis if the one-
sided lower 98.08% confidence bound on the difference between treatment groups (Ranger DCB 
– Standard PTA) in 12-month primary patency is greater than zero. 
Ranger DCB will be concluded to be as safe as Standard PTA if the one-sided lower 98.08% 
confidence bound on the difference between treatment groups (Ranger DCB – Standard PTA) in 
12-month MAE-free is greater than -0.1. 
As required, the study success will be concluded as both primary effectiveness and primary 
safety endpoints being achieved in the final analysis. 
12.3. General Statistical Methods 
12.3.1. 
Analysis Sets 
The intention-to-treat (ITT) analysis set will be the primary analysis set for assessing superiority 
of Ranger DCB to the Standard PTA in the RCT. The per-protocol and/or the as-treated analysis 
sets will be assessed in RCT for reference. However per-protocol analysis will be performed 
only when the ITT and the per-protocol analysis sets are not identical. As-treated analysis will be 
performed as deemed necessary. 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 59 of 110 
 
 
 
 
 
All subjects who sign the informed consent form (ICF) and are randomized in the RCT will be 
included in the ITT analysis set, regardless of whether the subjects receive the assigned 
treatment.  
For per-protocol analysis, only randomized subjects who meet the eligibility criteria and receive 
the assigned treatment will be included in the per-protocol analysis set. For subjects who do not 
receive randomized devices will be excluded from the per-protocol analysis set. 
For as-treated analysis, all subjects who actually receive either Ranger DCB or Standard PTA at 
procedure will be included in the as-treated analysis set. For subjects who do not receive Ranger 
DCB or PTA will be excluded from the as-treated analysis set. 
12.3.2. 
Randomization Scheme 
Randomization to treatments will be stratified by study site. A computer generated random 
treatment allocations (i.e., a randomization schedule) will be used to assign subjects to treatments 
in a 3:1 ratio of Ranger DCB to Standard PTA. This list will be specific to the subject’s site. 
Random permuted blocks of varying sizes will be employed to ensure approximate balance of 
treatment allocation within each site. 
12.3.3. 
Control of Systematic Error/Bias 
Selection of subjects will be made from the Investigators’ general or professional referral 
population. All subjects meeting the inclusion/exclusion criteria and have signed the protocol-
specific ICF will be eligible for enrollment in the trial. Consecutively eligible subjects should be 
enrolled into the trial to minimize selection bias. Trial subjects will be randomly assigned to a 
treatment group within the investigational site. In determining subject eligibility for the trail, the 
investigator’s assessment of imaging will be used. However, BIDMC Angiographic Core 
Laboratory will independently analyze the angiograms and the data obtained from the core 
laboratory will be utilized for analyses.  
An independent CEC composed of medical experts will adjudicate safety assessments, as defined 
in the CEC Charter. In addition, an independent data reviewer (IDR) is responsible for the 
oversight review of the aggregate safety data, as defined in the IDR charter. The IDR will not 
participate in the trial and who have no affiliation with BSC. 
12.3.4. 
Number of Subjects per Investigative Site 
Study sites will not be allowed to randomize more than 10% (N=37) of the total number of 
randomized subjects without prior approval from the sponsor. No study center will be allowed to 
enroll more than 20% (N=76) of the total number of randomized subjects. 
12.4. Baseline Data Analyses 
Baseline covariates will be summarized for RCT and PK sub-study. Subject baseline 
demographics and clinical characteristics, site-reported and core lab reported lesion 
characteristics, procedure assessment, device information, and medication compliance will be 
summarized using descriptive statistics. The analysis unit may be (but will not be limited to) by 
subject, lesion, procedure, or device. 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 60 of 110 
 
 
 
 
 
For continuous and/or ordinal variables, the descriptive statistics will include mean, standard 
deviation, number evaluated, minimum and maximum. Some specific variables may also include 
additional statistics such as median and confidence intervals. For binary or categorical variables, 
the descriptive statistics will include percentage, numerator, denominator, and number evaluated. 
Some variables may include confidence intervals as needed.   
12.4.1. 
Secondary Endpoint Assessments  
Secondary assessments may refer to (but not limited to) technical/procedural success, 
safety/effectiveness endpoints, any type of AE rates, distribution of Rutherford classification, 
hemodynamic improvement, walking improvement at time points that data is collected (refer to 
Section 7.2). All additional assessments are observational. 
12.4.2. 
Interim Analyses 
One interim analysis is planned for the purpose of early declaring device effectiveness and 
safety. The interim analysis data will be used as submission for approval.  The RCT will proceed 
to the study end for all planned number of subjects regardless of the interim result. The Lan-
DeMets alpha spending function with Power Family Method is pre-specified for the type I error 
adjustment to determine the interim and the final significance levels to retain the overall 
significance level under one-sided 2.5%. Both levels are adaptive based on accumulating study 
data in the interim. However a minimum of 75% of 12-month required subjects for the interim 
analysis is recommended. 
Without loss of generality, for 75% of subjects to be assessed in the interim analysis, the adjusted 
type I error will be distributed (i.e. spending) as 1.41% and 1.92% for the interim and the final 
analyses respectively.  Due to the nature of continuous function, the adjusted alphas will be 
based on the observed interim proportion (e.g. >75%).  
 
The primary effectiveness and primary safety endpoints will be tested simultaneously at the same 
significance level for the interim analysis and/or for the final analysis as needed. 
12.4.3. 
Subgroup Analyses 
Primary endpoints and/or additional assessments will be summarized and treatment groups may 
be compared in each subgroup identified by the following categories (but not limit to): 
 
Region (e.g. by US/OUS, by country, by site) 
 
Race 
 
Gender (male vs. female) 
 
Age (≥ 65 and < 65) 
 
Diabetic status (medically-treated vs. non-diabetic) 
 
Lesion characteristics (vessel diameter/lesion length) 
 
Balloon matrix (balloon diameter/length) 
 
Adjunctive devices used (e.g. provisional stents) 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 61 of 110 
 
 
 
 
 
 
Other significant predictors identified by regression models 
No formal tests of hypotheses are proposed for subgroups and therefore alpha-adjustment for 
multiple comparisons will not be used. 
In addition, an interaction test for the primary efficacy assessment at two-sided significance level 
of 0.15 will be performed for the following subgroups: 
 
Region (e.g. US/OUS) 
 
Gender (male vs. female) 
12.4.4. 
Justification of Pooling 
The poolability analysis regarding the primary effectiveness and/or safety endpoint across sites 
as well as between US and OUS will be assessed only when the success criteria are met, by using 
the logistic regression model with a two-sided significance level of 0.15. If the p-value of an 
interaction test is greater than or equal to 0.15, the non-significance suggests that the 
homogeneity of treatment effect is shown and the primary endpoints data are poolable. However, 
when the p-value of an interaction test is smaller than 0.15, the significance suggests that the 
heterogeneity of treatment effect is detected and poolability analysis regarding prognostic factors 
and/or poolability adjusted for prognostic factors will be performed. 
12.4.4.1. Site Poolability 
 Due to the 3:1 randomization scheme using random permuted blocks (i.e. blocks of 4 and 8) 
employed within each site, ideally there will be 3 Ranger DCB subjects for every 1 Standard 
PTA subject. Therefore the poolability method is described as below. 
The sites with enrollment of 8 subjects or more are reported individually. 
The sites with enrollment of 7 or less subjects are pooled into super-sites according to their 
geographical closeness so that the combined super-sites would have 8 or more enrolled subjects. 
If a super-site has 8 or more subjects and at least 2 subjects in each treatment group, the pooling 
of this super-site should stop and the pooling of the next super-site should start. 
12.4.4.2. US vs. OUS Poolability 
The focus is mostly on the applicability of OUS data to the US population. If the treatment effect 
is significantly different between US and OUS, possible/plausible explanation is required and/or 
potential bias needs to be addressed. 
12.4.5. 
Missing Data, Drop-Outs, and Protocol Deviation Handling 
Boston Scientific will employ robust oversight in order to minimize the loss of subjects 
throughout any trial follow-up.  Additionally, we have created easy-to-follow case report forms 
that maximize the data collection required at each follow-up visit without placing undue burden 
on the subject. Strategies that are planned to be utilized in the RCT include: 
• Ensure that site personnel are properly trained on the data that is required to be collected 
and the importance of planning for the follow-up visits. 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 62 of 110 
 
 
 
 
 
• Tools in the site’s Manual of Operations to assist with follow-up visit planning (e.g. 
follow-up wheels or similar tools). 
• The use of trial reports and newsletters to remind sites of upcoming visits and other 
project-related milestones to ensure data is being entered promptly and is complete. 
12.4.6. 
Sensitivity Analyses for Missing Outcome Data 
Sensitivity analyses for the primary effectiveness and/or safety endpoints assessment will be 
conducted to assess the impact of missing data on the result’s robustness. In addition to the use 
of the worst-case analysis, the tipping point analysis will be performed for the ITT analysis set to 
consider all combinations of present/absent for all subjects with missing primary outcome in 
Ranger DCB and Standard PTA groups. 
12.4.7. 
Multivariable Analyses 
Univariate and multivariable analyses will be performed as post-hoc analysis after unblinding to 
assess the effect of potential predictors for the primary outcomes in a logistic regression model. 
Clinically and/or statistically meaningful baseline covariates will be selected in the regression 
model. No formal conclusion will be made by this secondary post-hoc analysis. 
12.4.8. 
Analyses Software 
All statistical analyses will be performed using the Statistical Analysis Software (SAS), version 
9.2 or later (Copyright © 2002-2010 by SAS Institute Inc., Cary, North Carolina 27513, USA. 
All rights reserved). 
12.4.9. 
Changes to Planned Analyses 
Any changes to the planned statistical analyses made prior to performing the interim and full 
primary analyses (i.e. unblinding) will be documented in an amended Statistical Analysis Plan 
approved prior to performing the analyses. Changes from the planned statistical methods after 
performing the analyses will be documented in the clinical trial report along with a reason for the 
deviation. 
13. Data Management 
13.1. Data Collection, Processing, and Review 
Subject data will be recorded in a limited access secure electronic data capture (EDC) system.  
The clinical database will reside on a production server hosted by Medidata RAVE EDC System. 
All changes made to the clinical data will be captured in an electronic audit trail and available for 
review by the sponsor or its representative. The associated RAVE software and database have 
been designed to meet regulatory compliance for deployment as part of a validated system 
compliant with laws and regulations applicable to the conduct of clinical studies pertaining to the 
use of electronic records and signatures. Database backups are performed regularly. 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 63 of 110 
 
 
 
 
 
The Investigator provides his/her electronic signature on the appropriate electronic case report 
forms (eCRFs) in compliance with local regulations. A written signature on printouts of the 
eCRFs must also be provided if required by local regulation. Changes to data previously 
submitted to the sponsor require a new electronic signature by the Investigator acknowledging 
and approving the changes. 
Visual and/or electronic data review will be performed to identify possible data discrepancies. 
Manual and/or automatic queries will be created in the EDC system and will be issued to the site 
for appropriate response. Site staff will be responsible for resolving all queries in the database. 
13.2. Data Retention 
The Principal Investigator or his/her designee or Investigational site will maintain, at the 
investigative site, all essential trial documents and source documentation that support the data 
collected on the trial subjects in compliance with ICH/GCP guidelines.  Documents must be 
retained for at least 2 years after the last approval of a marketing application or until at least 2 
years (at least 3 years in Japan) have elapsed since the formal discontinuation of the clinical 
investigation of the product. These documents will be retained for a longer period of time by 
agreement with BSC or in compliance with other local regulations. It is BSC’s responsibility to 
inform the Investigator when these documents no longer need to be maintained. 
The Principal Investigator or his/her designee will take measures to ensure that these essential 
documents are not accidentally damaged or destroyed. If for any reason the Principal Investigator 
or his/her designee withdraws responsibility for maintaining these essential documents, custody 
must be transferred to an individual who will assume responsibility and BSC must receive 
written notification of this custodial change. Sites are required to inform Boston Scientific in 
writing where paper or electronic files are maintained in case files are stored off site and are not 
readily available. 
In Japan, BSC must maintain necessary essential documents for 5 years from the date of the 
marketing application approval (or during the period of use-results evaluation, if applicable and 
if longer than 5 years) or until 3 years have elapsed since the formal discontinuation of the 
clinical investigation of the device, whichever is longer. 
If trial follow-up is continued beyond 3 years in Japan as part of a post market clinical trial after 
receiving marketing approval and using the data as part of a use-results evaluation, the 
investigator and investigational center must retain essential documents during the period of use-
results evaluation. 
13.3. Core Laboratories 
Core laboratories will be established for the central assessment of key data collected during the 
RANGER II SFA trial.  Detailed guidelines for the collection, analysis, and interpretation of the 
following data will be provided in the Manual of Operations.  The following core laboratories 
have been assigned for this trial: 
 
BIDMC Angiographic: to assess angiograms taken during the index procedure and during 
any subsequent revascularization procedure (up to12 months post index procedure). 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 64 of 110 
 
 
 
 
 
 
VASCORE Vascular Ultrasound: to assess DUS  taken during the follow-up period (1 
month, 6 month, 12 month, 24 month, and 36 month visits). 
 
COVANCE Pharmacokinetics: to assess baseline paclitaxel levels and at defined time 
points. 
14. Amendments 
If a protocol revision is necessary which affects the rights, safety or welfare of the subject or 
scientific integrity of the data, an amendment is required. Appropriate approvals (e.g., 
IRB/EC/REB/FDA/CA) of the revised protocol must be obtained prior to implementation. 
15. Deviations 
An Investigator must not make any changes or deviate from this protocol, except to protect the 
life and physical well-being of a subject in an emergency. An investigator shall notify the 
sponsor and the reviewing IRB/EC/REB of any deviation from the investigational plan to protect 
the life or physical well-being of a subject in an emergency, and those deviations which affect 
the scientific integrity of the clinical investigation. Such notice shall be given as soon as 
possible, but no later than 5 working days after the emergency occurred, or per prevailing local 
requirements, if sooner than 5 working days.  
All deviations from the investigational plan, with the reason for the deviation and the date of 
occurrence, must be documented and reported to the sponsor using the EDC system. Sites may 
also be required to report deviations to the IRB/EC/REB, per local guidelines and government 
regulations.  
Deviations will be reviewed and evaluated on an ongoing basis and, as necessary, appropriate 
corrective and preventive actions (including IRB/EC/REB notification, site re-training, or site 
discontinuation/termination) will be put into place by the sponsor. 
16. Device Accountability 
The investigational devices shall be securely maintained, controlled, and used only in this 
clinical trial. The Medidata RAVE EDC will be used to track subjects and the device 
management vendor, Cenduit LLC, will track device allocations throughout the trial enrollment.  
The sponsor’s device management vendor shall keep records to document the physical location 
of all investigational devices from shipment of investigational devices from BSC or designated 
facility/equipment to the investigation sites until return or disposal. 
Records shall be kept by the device management vendor, Fisher Clinical Services, to document 
the physical location and conditions of storage of all investigational devices.  
The principal investigator or an authorized designee shall keep records documenting the receipt, 
use, return and disposal of the Ranger DCB (test) devices, which shall include the following 
 
Date of receipt 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 65 of 110 
 
 
 
 
 
 
Identification of each investigational device (lot number or unique code) 
 
Expiry date, as applicable 
 
Date or dates of use 
 
Subject identification 
 
Date on which the investigational device was returned, if applicable 
 
Date of return (and number) of unused, expired, or malfunctioning investigational devices, 
if applicable. 
17. Compliance 
17.1. Statement of Compliance 
This trial will be conducted in accordance with ISO 14155 Clinical Investigation of Medical 
Devices for Human Subjects-GCP, or the relevant parts of the ICH Guidelines for GCP, ethical 
principles that have their origins in the Declaration of Helsinki, and pertinent individual country 
laws and regulations. The trial shall not begin until the required approval/favorable opinion from 
the IRB/IEC/REB and/or regulatory authority has been obtained, if appropriate. Any additional 
requirements imposed by the IRB/IEC/REB or regulatory authority shall be followed, if 
appropriate. 
17.2. Investigator Responsibilities 
The Principal Investigator of an investigational site is responsible for ensuring that the trial is 
conducted in accordance with the Clinical Study Agreement, the clinical investigation plan/, ISO 
14155, ethical principles that have their origins in the Declaration of Helsinki, any conditions of 
approval imposed by the reviewing IRB/EC/REB, and prevailing local and/or country laws 
and/or regulations, whichever affords the greater protection to the subject. 
The Principal Investigator’s responsibilities include, but are not limited to, the following.  
 
Prior to beginning the trial, sign the Clinical Study documenting his/her agreement to 
comply with the Investigator responsibilities as described in such Agreement, if applicable.  
 
Prior to beginning the trial, sign the Investigator Brochure Signature Page, if applicable 
and Protocol Signature page documenting his/her agreement to conduct the trial in 
accordance with the protocol. 
 
Provide his/her qualifications and experience to assume responsibility for the proper 
conduct of the trial and that of key members of the site team through up-to-date curriculum 
vitae or other relevant documentation and disclose potential conflicts of interest, including 
financial, that may interfere with the conduct of the clinical trial or interpretation of results. 
 
Make no changes in or deviate from this protocol, except to protect the life and physical 
well-being of a subject in an emergency; document and explain any deviation from the 
approved protocol that occurred during the course of the clinical investigation. 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 66 of 110 
 
 
 
 
 
 
Create and maintain source documents throughout the clinical trial and ensure their 
availability with direct access during monitoring visits or audits; ensure that all clinical-
investigation-related records are retained per requirements. 
 
Ensure the accuracy, completeness, legibility, and timeliness of the data reported to the 
sponsor in the CRFs and in all required reports. 
 
Record, report, and assess (seriousness and relationship to the device/procedure) every 
adverse event as applicable per the protocol and observed device deficiency. 
 
Report to sponsor, per the protocol requirements, all SAEs and device deficiencies that 
could have led to a SADE and potential/USADE or UADE. 
 
Report to the IRB/EC/REB and regulatory authorities any SAEs and device deficiencies 
that could have led to a SADE and potential/USADE or UADE, if required by the national 
regulations or this protocol or by the IRB/EC/REB, and supply BSC with any additional 
requested information related to the safety reporting of a particular event. 
 
Maintain the device accountability records and control of the device, ensuring that the 
investigational device is used only by authorized/designated users and in accordance with 
this protocol and instructions/directions for use. 
 
Allow the sponsor to perform monitoring and auditing activities, and be accessible to the 
clinical research monitor or auditor and respond to questions during monitoring visits or 
audit(s). 
 
Allow and support regulatory authorities and the IRB/EC/REB when performing auditing 
activities. 
 
Ensure that informed consent is obtained in accordance with applicable laws, this protocol 
and local IRB/EC/REB requirements. 
 
Provide adequate medical care to a subject during and after a subject’s participation in a 
clinical trial in the case of adverse events, as described in the Informed Consent Form 
(ICF). 
 
Inform the subject of the nature and possible cause of any adverse events experienced. 
 
As applicable, provide the subject with necessary instructions on proper use, handling, 
storage, and return of the investigational device when it is used/operated by the subject. 
 
Inform the subject of any new significant findings occurring during the clinical 
investigation, including the need for additional medical care that may be required. 
 
Provide the subject with well-defined procedures for possible emergency situations related 
to the clinical trial, and make the necessary arrangements for emergency treatment, 
including decoding procedures for blinded/masked clinical investigations, as needed. 
 
Ensure that clinical medical records are clearly marked to indicate that the subject is 
enrolled in this clinical trial. 
 
Ensure that, if appropriate, subjects enrolled in the clinical investigation are provided with 
some means of showing their participation in the clinical investigation, together with 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 67 of 110 
 
 
 
 
 
identification and compliance information for concomitant treatment measures (contact 
address and telephone numbers shall be provided). 
 
Inform, with the subject’s approval or when required by national regulations, the subject’s 
personal physician about the subject’s participation in the clinical investigation. 
 
Make all reasonable efforts to ascertain the reason(s) for a subject’s premature withdrawal 
from clinical investigation while fully respecting the subject’s rights. 
 
Ensure that an adequate investigation site team and facilities exist and are maintained and 
documented during the clinical investigation. 
 
Ensure that maintenance and calibration of the equipment relevant for the assessment of 
the clinical investigation is appropriately performed and documented, where applicable. 
17.2.1. 
Delegation of Responsibility 
When specific tasks are delegated by an investigator, including but not limited to conducting the 
informed consent process, the Principal Investigator is responsible for providing appropriate 
training and adequate supervision of those to whom tasks are delegated. The investigator is 
accountable for regulatory violations resulting from failure to adequately supervise the conduct 
of the clinical trial.  
17.3. Institutional Review Board/ Ethics Committee 
Prior to gaining Approval-to-Enroll status, the investigational site will provide to the sponsor 
documentation verifying that their IRB/EC/REB is registered or that registration has been 
submitted to the appropriate agency, as applicable according to national/regulatory requirements.   
A copy of the written IRB/EC/REB and/or competent authority approval of the protocol (or 
permission to conduct the trial) and Informed Consent Form, must be received by the sponsor 
before recruitment of subjects into the trial and shipment of investigational product/equipment. 
Prior approval must also be obtained for other materials related to subject recruitment or which 
will be provided to the subject. 
Annual IRB/EC/REB approval and renewals will be obtained throughout the duration of the trial 
as required by local/country or IRB/EC/REB requirements. Copies of the Investigator’s reports 
and the IRB/EC/REB continuance of approval must be provided to the sponsor.  
The clinical trial organization in Japan, including investigational sites in Japan, is provided as a 
separate attachment to the protocol only in Japan.  Also, BSC or Boston Scientific Japan (BSJ) 
may utilize CROs or other contractors to act as their representative for carrying out designated 
tasks. Responsibilities for these entities are defined in the applicable contracts or agreements. 
Contact information for the CROs is provided as a separate attachment to the protocol only in 
Japan or in the Manual of Operation (MOP) for Japanese sites. 
17.4. Sponsor Responsibilities 
All information and data sent to BSC concerning subjects or their participation in this trial will 
be considered confidential by BSC. Only authorized BSC personnel or a BSC representative 
including, but not limited to Contract Research Organization (CRO) will have access to these 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 68 of 110 
 
 
 
 
 
confidential records. Authorized regulatory personnel have the right to inspect and copy all 
records pertinent to this trial. Trial data collected during this trial may be used by BSC for the 
purposes of this trial, publication, and to support future research and/or other business purposes. 
All data used in the analysis and reporting of this trial will be without identifiable reference to 
specific subject name. 
Boston Scientific will keep subjects’ identifiable health information confidential in accordance 
with all applicable laws and regulations.  Boston Scientific may use subjects’ health information 
to conduct this research, as well as for additional purposes, such as overseeing and improving the 
performance of its device, new medical research and proposals for developing new medical 
products or procedures, and other business purposes. Information received during the trial will 
not be used to market to subjects; subject names will not be placed on any mailing lists or sold to 
anyone for marketing purposes.  
17.4.1. 
Role of Boston Scientific Representatives 
Boston Scientific personnel can provide technical support to the investigator and other health 
care personnel (collectively HCP) as needed during implant, testing required by the protocol 
during the index procedure. Support may include HCP training, addressing HCP questions, or 
providing clarifications to HCPs concerning the operation of BSC investigational device. 
Boston Scientific personnel will not do the following. 
 
Practice medicine 
 
Provide medical diagnosis or treatment to subjects 
 
Discuss a subject’s condition or treatment with a subject without the approval and presence 
of the investigator 
 
Independently collect critical trial data (defined as primary or secondary endpoint data) 
 
Enter data in electronic data capture systems or on paper case report forms 
17.5. Insurance  
Where required by local/country regulation, proof and type of insurance coverage, by BSC for 
subjects in the trial will be obtained. 
18. Monitoring 
Monitoring will be performed during the trial, according to the trial Monitoring Plan, to assess 
continued compliance with the current, approved protocol/amendments and applicable 
regulations. In addition, the monitor verifies that trial records are adequately maintained, that 
data are reported in a satisfactory manner with respect to timeliness, adequacy, and accuracy, and 
that the Investigator continues to have sufficient staff and facilities to conduct the trial safely and 
effectively. Pre-defined thresholds for protocol deviation and compliance once met or exceeded, 
can also trigger increased monitoring frequency and/or the implementation of corrective action 
plans at clinical sites. For the RANGER II SFA trial, source documents include, at a minimum 
but are not limited to, the ICF; patient medical records, including nursing records and 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 69 of 110 
 
 
 
 
 
catheterization laboratory records; imaging records; laboratory results; reports of SAEs; and 
device accountability logs. Data documented in the eCRF relevant to device deficiencies, 
relationship of AE to trial device(s), index procedure, antiplatelet medication; and the anticipated 
assessment of ADEs, may be considered source data for the trial. 
The Investigator/institution guarantees direct access to original source documents by BSC 
personnel, their designees, and appropriate regulatory authorities. In the event that the original 
medical records cannot be obtained for a subject that is seen by a non-trial physician at a non-
trial institution, all reasonable attempts must be made to obtain photocopies of the original 
source documents for review. Photocopies of original source documents related to MAEs that are 
adjudicated by the CEC (from either the trial site or a non-trial institution, if applicable) must 
also be made available for submission to the BSC Safety Group. 
The trial may also be subject to a quality assurance audit by BSC or its designees, as well as 
inspection by appropriate regulatory authorities. It is important that the Investigator and relevant 
trial personnel are available during on-site monitoring visits or audits and that sufficient time is 
devoted to the process. 
19. Potential Risks and Benefits 
19.1. Anticipated Adverse Events and Risks Associated with Use of the Ranger DCB  
The following anticipated adverse events (AE) have been identified for this trial.  
These adverse events include but are not limited to, the following: 
 
Allergic reaction (device, contrast medium, medications) 
 
Arrhythmias 
 
Arteriovenous fistula 
 
Death 
 
Hematoma 
 
Hemodynamic instability 
 
Hemorrhage 
 
Pseudoaneurysm 
 
Sepsis/infection 
 
Thromboembolic episodes 
 
Vascular thrombosis 
 
Vessel injury (e.g., dissection, perforation, rupture) 
 
Vessel occlusion 
 
Vessel spasm 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 70 of 110 
 
 
 
 
 
19.2. Risks Associated with the Trial Device(s) Unique to Paclitaxel 
Certain side effects and discomforts have been reported in subjects that have received paclitaxel 
in intravenous forms as part of chemotherapy treatment.  These subjects may have other 
comorbid conditions and/or have received concomitant medications that may also contribute to 
the reported side effects.  Under these circumstances the dose is delivered throughout the body 
by the blood and in doses hundreds of times higher than the total amount on the coated balloon 
for use in the proposed clinical trial. Potential adverse events that may be unique to the paclitaxel 
drug coating include but are not limited to the following: 
 
Allergic/immunologic reactions to drug (paclitaxel or structurally-related compounds) or 
coating or its individual components 
 
Alopecia 
 
Anemia 
 
Gastrointestinal symptoms 
 
Hematologic dyscrasia (including leukopenia, neutropenia, and thrombocytopenia) 
 
Hepatic enzyme changes 
 
Histologic changes in the vessel wall, including inflammation, cellular damage or necrosis 
 
Myalgia/arthralgia 
 
Peripheral neuropathy 
It is unlikely with the total dosages and the way paclitaxel is coated onto the balloon and 
delivered in the vessel that the side effects associated with intravenous, high dose chemotherapy 
would occur. There may be other potential adverse events that are unforeseen at this time. 
19.3. Risks associated with Participation in the Clinical Trial 
There may be additional risks linked to the procedure, and follow-up testing which are 
unforeseen at this time. All testing planned for the first year of follow-up is standard of care in 
the United States. Follow up assessments after the first year are included to monitor the long 
term effectiveness and safety profile of the SFA/PPA treatment.  These additional requirements 
should not create additional risk to the subject. 
In addition, risks associated with venipuncture and the additional blood draws required in the PK 
substudy include, but are not limited to: 
 
Ecchymosis 
 
Hematoma 
 
Infection/inflammation  
 
Pain 
19.4. Possible Interactions with Concomitant Medical Treatments 
In addition to the aforementioned risks associated with the treatment of drug coated balloons and 
the use of paclitaxel, the use of prolonged dual antiplatelet therapy after the index procedure may 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 71 of 110 
 
 
 
 
 
increase the risk of bleeding. Refer to the local package insert for further information on drug 
interactions and side effects associated with paclitaxel or antithrombotic/antiplatelet medications. 
19.5. Risk Minimization Actions 
Additional risks may exist. Do not utilize in pregnant or breastfeeding women, or in men 
intending to father children, as this product has not been tested in this population. Birth 
control/pregnancy prevention should be utilized for up to ninety (90) days after the index 
procedure. 
Risks can be minimized through compliance with this protocol, performing procedures in the 
appropriate hospital environment, adherence to subject selection criteria, close monitoring of the 
subject's physiologic status during research procedures and/or follow-ups and by promptly 
supplying BSC with all pertinent information required by this protocol. 
19.6. Anticipated Benefits 
Potential anticipated benefits include the effective treatment of atherosclerotic SFA/PPA lesions 
with improvement in the symptoms of disease. However, the Ranger DCB is an investigational 
device and these potential benefits may or may not actually be present. 
19.7. Risk to Benefit Rationale 
The Ranger DCB is expected to be suitable for its intended purpose. There are no unacceptable 
residual risks/intolerable risks and all applicable risks have been addressed through the provision 
of appropriate Directions for Use (DFU). Evaluation of the risks and benefits that are expected to 
be associated with the use of the Ranger DCB demonstrate that when used under the conditions 
intended, the benefits associated with the use of the Ranger DCB should outweigh the risks. 
20. Safety Reporting 
20.1. Reportable Events by investigational site to Boston Scientific 
It is the responsibility of the investigator to assess and report to BSC any event which occurs in 
any of following categories: 
 
All Adverse Events (reporting ends after 12 month follow up visit for non-serious, non-
device related and non-procedure related Adverse Events ) 
 
All Serious Adverse Events 
 
All Device Related Adverse Events/Device Related Serious Adverse Events 
 
All Investigational Device Deficiencies  
 
Unanticipated Adverse Device Effects/Unanticipated Serious Adverse Device Effects 
 
New findings/updates in relation to already reported events 
When possible, the medical diagnosis should be reported as the Event Term instead of individual 
symptoms. 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 72 of 110 
 
 
 
 
 
If it is unclear whether or not an event fits one of the above categories, or if the event cannot be 
isolated from the device or procedure, it should be submitted as an adverse event and/or device 
deficiency. 
Any AE event required by the protocol, experienced by the trial subject after informed consent 
and once considered enrolled in the trial (as defined in trial subject classification section), 
whether during or subsequent to the procedure, must be recorded in the eCRF. 
Underlying diseases are not reported as AEs unless there is an increase in severity of frequency 
during the course of the investigation. For centers in Austria, cancer must always be reported as a 
Serious Adverse Event. Death should not be recorded as an AE, but should only be reflected as 
an outcome of ONE (1) specific SAE (see Table 20.2-1 for AE definitions). 
Refer to Section 19 for the known risks associated with the trial device(s). 
Device deficiencies and other device issues should not be reported as AEs. Instead, they should 
be reported on the appropriate eCRF per the trial CRF Completion Guidelines. If an AE results 
from a device deficiency or other device issue, the AE should be reported on the appropriate 
eCRF. 
In-patient hospitalization is defined as the subject being admitted to the hospital (≥ 24 hours), 
with the following exceptions. 
 
A hospitalization for routine follow-up per standard of care. 
 
A hospitalization that is uncomplicated and elective/planned (i.e., planned prior to 
enrollment) does not have to be reported as an SAE or AE. 
 
If complications or AEs occur during an elective/planned (i.e., planned prior to enrollment) 
hospitalization after enrollment, the complications and AEs must be reported as AEs or 
SAEs if they meet the protocol-specified definitions. However, the original 
elective/planned hospitalization(s) itself should not be reported as an SAE. 
20.2. Definitions and Classification 
Adverse event definitions for the RANGER II SFA trial are provided in Table 20.2-1. 
Administrative edits were made to combine definitions from ISO 14155-2011 and MEDDEV 
2.7/3 (2015). In addition, country-specific definitions may apply per local reporting 
requirements. 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 73 of 110 
 
 
 
 
 
Table 20-1: 
Safety Definitions 
Term 
Definition 
Adverse Event (AE) 
 
Ref: ISO 14155-2011 
 
Ref: MEDDEV 2.7/3(2015) 
Any untoward medical occurrence, unintended disease or injury, or any untoward 
clinical signs (including an abnormal laboratory finding) in subjects, users or 
other persons, whether or not related to the investigational medical device.  
NOTE 1: This includes events related to the investigational medical device or 
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 the investigational medical device.  
Adverse Device Effect (ADE) 
 
Ref: ISO 14155-2011 
 
Ref: MEDDEV 2.7/3(2015) 
Adverse event related to the use of an investigational medical device 
NOTE 1: This includes any adverse event resulting from insufficiencies or 
inadequacies in the instructions for use, the deployment, the 
implantation, the installation, the operation, or any malfunction of the 
investigational medical device. 
NOTE 2: This definition includes any event resulting from use error or 
intentional abnormal use of the investigational medical device. 
Serious Adverse Event (SAE) 
 
Ref: ISO 14155-2011 
 
Ref: MEDDEV 2.7/3(2015) 
Adverse event that: 
 
Led to death, 
 
Led to  serious deterioration in the health of the subject, as defined by 
either:  
– 
a life-threatening illness or injury, or 
– 
a permanent impairment of a body structure or a body function, or 
– 
in-patient hospitalization or prolongation of existing hospitalization, or 
– 
medical or surgical intervention to prevent life-threatening illness, or 
injury or permanent impairment to a body structure or a body function 
 
Led to fetal distress, fetal death, or a congenital abnormality or birth defect. 
NOTE 1: Planned hospitalization for a pre-existing condition, or a procedure 
required by the clinical investigational plan, without serious 
deterioration in health, is not considered a serious adverse event.  
Serious Adverse Device Effect 
(SADE) 
 
Ref: ISO 14155-2011 
 
Ref: MEDDEV 2.7/3(2015) 
Adverse device effect that has resulted in any of the consequences characteristic 
of a serious adverse event. 
Unanticipated Adverse Device 
Effect (UADE) 
 
Ref: 21 CFR Part 812 
Any serious adverse effect on health or safety or any life-threatening problem or 
death caused by, or associated with, a device, if that effect, problem, or death was 
not previously identified in nature, severity, or degree of incidence in the 
investigational plan or application (including a supplementary plan or 
application), or any other unanticipated serious problem associated with a device 
that relates to the rights, safety, or welfare of subjects. 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 74 of 110 
 
 
 
 
 
Term 
Definition 
Unanticipated Serious 
Adverse Device Effect 
(USADE) 
 
Ref: ISO 14155-2011 
 
Ref: MEDDEV 2.7/3(2015) 
Serious adverse device effect which by its nature, incidence, severity, or outcome 
has not been identified in the current version of the risk analysis report. 
NOTE 1: Anticipated serious adverse device effect (ASADE) is an effect which 
by its nature, incidence, severity or outcome has been identified in the 
risk analysis report. 
Device Deficiency 
 
Ref: ISO 14155-2011 
 
Ref: MEDDEV 2.7/3(2015) 
An Inadequacy of an investigational medical device related to its identity, 
quality, durability, reliability, safety or performance. This may include 
malfunctions, use error, or inadequacy in the information supplied by the 
manufacturer. 
Abbreviations: EC=Ethics Committee; IRB=Institutional Review Board 
20.3. Relationship to Trial Device(s) 
The Investigator must assess the relationship of the AE to the trial device or procedure. See 
criteria in Table 20-2. 
Table 20-2: 
Criteria for Assessing Relationship of Trial Device or 
Index Procedure to AE 
Classification 
Description 
Not Related 
Relationship to the device or procedure can be excluded when: 
 
the event is not a known side effect of the product category the device belongs to or of 
similar devices and procedures; 
 
the event has no temporal relationship with the use of the device or the procedure; 
 
the event does not follow a known response pattern to the medical device (if the 
response pattern is previously known) and is biologically implausible; 
 
the discontinuation of medical device application or the reduction of the level of 
activation/exposure - when clinically feasible – and reintroduction of its use (or increase 
of the level of activation/exposure), do not impact on the event; 
 
the event involves a body-site or an organ not expected to be affected by the device or 
procedure; the event can be attributed to another cause (e.g. an underlying or concurrent 
illness/ clinical condition, an effect of another device, drug, treatment or other risk 
factors); 
 
the event does not depend on a false result given by the device used for diagnosis, when 
applicable; harms to the subject are not clearly due to use error; 
 
In order to establish the non-relatedness, not all the criteria listed above might be met at 
the same time, depending on the type of device/procedures and the event. 
Unlikely 
Related 
The relationship with the use of the device or procedure seems not relevant and/or the event 
can be reasonably explained by another cause, but additional information may be obtained. 
Possibly 
Related 
The relationship with the use of the device or procedure is weak but cannot be ruled out 
completely. Alternative causes are also possible (e.g. an underlying or concurrent 
illness/clinical condition or/and an effect of another device, drug or treatment). Cases were 
relatedness cannot be assessed or no information has been obtained should also be classified 
as possible related. 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 75 of 110 
 
 
 
 
 
Classification 
Description 
Probably 
Related 
The relationship with the use of the device or procedure seems relevant and/or the event 
cannot reasonably be explained by another cause, but additional information may be obtained. 
Causal 
Relationship 
The event is associated with the device or with procedure beyond reasonable doubt when: 
 
the event is a known side effect of the product category the device belongs to or of 
similar devices and procedures; 
 
the event has a temporal relationship with device use/application or procedure; 
 
the event involves a body-site or organ that 
– 
the device or procedure are applied to; 
– 
the device or procedure have an effect on; 
 
the event follows a known response pattern to the medical device (if the response pattern 
is previously known); 
 
the discontinuation of medical device application (or reduction of the level of 
activation/exposure) and reintroduction of its use (or increase of the level of 
activation/exposure), impact on the event (when clinically feasible); 
 
other possible causes (e.g. an underlying or concurrent illness/clinical condition or/and 
an effect of another device, drug or treatment) have been adequately ruled out; 
 
harm to the subject is due to error in use; 
 
the event depends on a false result given by the device used for diagnosis, when 
applicable; 
 
In order to establish the relatedness, not all the criteria listed above might be met at the 
same time, depending on the type of device/procedure and the event. 
 
The Investigator must assess the relationship of the AE to the antiplatelet medication as related 
or unrelated.  Criteria are defined in Table 20-3. 
Table 20-3: 
Criteria for Assessing Relationship of Antiplatelet Medication to AE 
Classification 
Description 
Unrelated 
The adverse event is determined to be due to a concurrent illness or effect of a device/drug 
and is not determined to be potentially related to the antiplatelet medication. 
Related 
The adverse event is determined to be potentially related to the antiplatelet medication, and 
an alternative etiology is equally or less likely compared to the potential relationship to 
antiplatelet medication. 
20.4. Investigator Reporting Requirements 
The communication requirements for reporting to BSC are as shown in Table 20-4. An Event 
Document Checklist included in the MOP specifies the required source documents for events 
requiring CEC adjudication. 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 76 of 110 
 
 
 
 
 
Table 20-4: 
Investigator Reporting Requirements 
Event Classification 
Communication Method 
Communication Timeline 
pre-market studies* 
(MEDDEV 2.7/3: 
CLINICAL INVESTIGATIONS: 
SERIOUS ADVERSE EVENT 
REPORTING UNDER DIRECTIVES 
90/385/EEC AND 93/42/EEC) 
Unanticipated Adverse Device 
Effect / Unanticipated Serious 
Adverse Device Effect 
Complete AE eCRF page with all 
available new and updated 
information. 
 
Within 1 business day of first 
becoming aware of the event. 
 
Terminating at the end of the trial 
Serious Adverse Event  
Complete AE eCRF page with all 
available new and updated 
information.  
 
Within 3 calendar days of first 
becoming aware of the event or as per 
local/regional regulations.  
 
Reporting required through the end of 
the trial 
Provide all relevant source 
documentation (unidentified) for 
reported event upon request of the 
sponsor 
 
At request of sponsor 
Serious Adverse Device Effects 
Complete AE eCRF page with all 
available new and updated 
information. 
 
Within 3 calendar days of first 
becoming aware of the event or as per 
local/regional regulations.  
 
Reporting required through the end of 
the trial 
Provide all relevant source 
documentation (unidentified) for 
reported event 
 
When documentation is available 
Device Deficiencies (including 
but not limited to failures, 
malfunctions, and product 
nonconformities) 
Note: Any Investigational Device 
Deficiency that might have led to 
a serious adverse event if a) 
suitable action had not been taken 
or b) intervention had not been 
made or c) if circumstances had 
been less fortunate is considered a 
reportable event. 
Complete Device Deficiencies 
CRF with all available new and 
updated information.  
 
Within 3 calendar days of first 
becoming aware of the event.  
 
Reporting required through the end of 
the trial  
Adverse Event including Adverse 
Device Effects 
Complete AE eCRF page, which 
contains such information as date 
of AE, treatment of AE 
resolution, assessment of 
seriousness and relationship to the 
device. 
 
In a timely manner  (e.g. Recommend 
within 10 business days) after 
becoming aware of the information 
 
ADE Reporting required through the 
end of the study 
 
AE reporting required through the 12 
month follow-up 
Abbreviations: AE=adverse event; CRF=case report form; UADE=unanticipated adverse device effect 
* Please note that pre-market studies are clinical studies with investigational devices or with medical devices that 
bear the regulatory approval and are not being used for the same approved indications. 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 77 of 110 
 
 
 
 
 
20.5. Boston Scientific Device Deficiencies 
All device deficiencies (including but not limited to failures, malfunctions, use errors, product 
nonconformities, and inadequacy in the information supplied by the manufacturer) will be 
documented and reported to BSC. If possible, the device(s) should be returned to BSC for 
analysis. Instructions for returning the investigational device(s) will be provided. If it is not 
possible to return the device, the investigator should document why the device was not returned 
and the final disposition of the device. Device failures and malfunctions should also be 
documented in the subject’s medical record. 
Device deficiencies (including but not limited to failures, malfunctions, and product 
nonconformities) are not adverse events. However, an adverse event that results from a device 
failure or malfunction would be recorded as an adverse event on the appropriate eCRF. 
Any Device Deficiency that might have led to a serious adverse event if a) suitable action had 
not been taken or b) intervention had not been made or c) if circumstances had been less 
fortunate is considered a reportable event. 
Device deficiencies may include, but are not limited to the following: 
 
Packaging or labeling deficiency 
 
Difficulty advancing or tracking device  
20.6. Reporting to Regulatory Authorities/IRBs/ECs/REB Investigators 
BSC will notify all participating study centers if SAEs/SADEs occur which imply a possible 
increase in the anticipated risk of the procedure or use of the device or if the occurrence of 
certain SAEs/SADEs demands changes to the protocol or the conduct of the trial in order to 
further minimize the unanticipated risks. 
BSC is responsible for reporting AE and device deficiencies information to all participating 
investigators, IRBs/IECs/REBs, and regulatory authorities as applicable according to local 
reporting requirements. 
BSC, Investigator, or Site must notify the IRB/IEC/REB of any UADEs, USADEs, SADEs, 
SAEs, device deficiencies, and other CEC events as applicable according to local reporting 
requirements (refer to section 22.3) for information pertaining to the CEC and CEC Events). A 
copy of the Investigator’s reports and other relevant reports (if applicable) to the IRB/IEC/REB 
must be provided to BSC in accordance with local requirements. 
Safety reporting on the control device, which is approved in all regions at the time of the trial 
initiation, will be handled separately according to local regulations. 
21. Informed Consent 
Subject participation in this clinical trial is voluntary.  Informed Consent is required from each 
subject or his/her legally authorized representative. The Investigator is responsible for ensuring 
that Informed Consent is obtained prior to the use of any investigational devices, study-required 
procedures and/or testing, or data collection. Testing (including CBC, platelets, ABI, and 
Rutherford Classification) completed as a part of the subject’s standard of care, within 30 days of 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 78 of 110 
 
 
 
 
 
the index procedure and that meets the study (inclusion/exclusion) criteria, are not required to be 
repeated after consenting is complete.   
The obtaining and documentation of Informed Consent must be in accordance with the principles 
of the Declaration of Helsinki, ISO 14155, any applicable national regulations, and local Ethics 
Committee and/or Regulatory authority body, as applicable. The ICF must be accepted by BSC 
or its delegate (e.g. CRO), and approved by the site’s IRB/EC/REB or central IRB, if applicable. 
Boston Scientific will provide a trial-specific template of the ICF to investigators participating in 
this trial. The ICF template may be modified to meet the requirements of the investigative site’s 
IRB/EC/REB.  Any modification requires acceptance from BSC prior to use of the form.  The 
ICF must be in a language understandable to the subject and if needed, BSC will assist the site in 
obtaining a written consent translation. Translated consent forms must also have IRB/EC/REB 
approval prior to their use.  Privacy language shall be included in the body of the form or as a 
separate form as applicable.   
The process of obtaining Informed Consent shall at a minimum include the following steps, as 
well as any other steps required by applicable laws, rules, regulations and guidelines: 
 
be conducted by the Principal Investigator or designee authorized to conduct the process,  
 
include a description of all aspects of the clinical trial that are relevant to the subject’s 
decision to participate throughout the clinical trial, 
 
avoid any coercion of or undue influence of subjects to participate, 
 
not waive or appear to waive subject’s legal rights, 
 
use native language that is non-technical and understandable to the subject or his/her legal 
representative, 
 
provide ample time for the subject to consider participation and ask questions if necessary, 
 
ensure important new information is provided to new and existing subjects throughout the 
clinical trial. 
The ICF shall always be signed and personally dated by the subject or legal representative 
competent to sign the ICF under the applicable laws, rules, regulations and guidelines and by the 
investigator and/or an authorized designee responsible for conducting the informed consent 
process. If a legal representative signs, the subject shall be asked to provide informed consent for 
continued participation as soon as his/her medical condition allows. The original signed ICF will 
be retained by the site and a copy of the signed and dated document and any other written 
information must be given to the person signing the form. In Japan, Informed Consent signature 
can be replaced by printed name and seals of appropriate individuals. 
Failure to obtain subject consent will be reported by BSC to the applicable regulatory body 
according to their requirements (e.g., FDA requirement is within 5 working days of learning of 
such an event). Any violations of the informed consent process must be reported as deviations to 
the sponsor and local regulatory authorities (e.g. IRB/EC/REB), as appropriate. 
If new information becomes available that can significantly affect a subject's future health and 
medical care, that information shall be provided to the affected subject(s) in written form via a 
revised ICF or, in some situations, enrolled subjects may be requested to sign and date an 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 79 of 110 
 
 
 
 
 
addendum to the ICF. In addition to new significant information during the course of a trial, 
other situations may necessitate revision of the ICF, such as if there are amendments to the 
applicable laws, protocol, a change in Principal Investigator, administrative changes, or 
following annual review by the IRB/EC/REB. The new version of the ICF must be approved by 
the IRB/EC/REB. Acceptance by Boston Scientific is required if changes to the revised ICF are 
requested by the site’s IRB/EC/REB. The IRB/EC/REB will determine the subject population to 
be re-consented. 
Trial personnel should explain to the subject that even if the subject agrees to participate in the 
trial and signs the ICF, catheterization may demonstrate that the subject is not a suitable 
candidate for the trial. A Screening Log will be maintained by the investigational site to 
document select information about candidates who fail to meet the trial eligibility criteria, 
including, but not limited to, the reason for screen failure. 
22. Committees 
22.1. Executive Committee 
An Executive Committee composed of BSC Clinical Management and selected Global and 
National Principal Investigators has been developed. This committee will be responsible for the 
overall conduct of the trial which will include protocol development, trial progress, subject 
safety, overall data quality and integrity, and timely dissemination of trial results through 
appropriate scientific sessions and publications. As appropriate the Executive Committee may 
request participation of RANGER II SFA Investigators on the committee. 
22.2. Safety Monitoring Process 
To promote early detection of safety issues, the independent Clinical Events Committee (CEC) 
and Independent Data Review (IDR) will provide evaluations of safety events. Success of this 
program requires dynamic collection of unmonitored data as soon as the event is reported. This is 
expedited through BSC’s Safety Group, which is responsible for coordinating the collection of 
information for the subject dossier from Medidata Rave EDC database that is entered by the 
centers and core laboratories. During regularly scheduled monitoring visits, clinical research 
monitors will support the dynamic reporting process through their review of source document 
information 
22.3. Clinical Events Committee (CEC) 
The CEC is an independent group of individuals with no affiliation with BSC. Committee 
membership will include expert practitioners of peripheral endovascular procedures, as well as 
other experts with the necessary therapeutic and subject matter expertise to review and 
adjudicate the following endpoints and major adverse events reported by the trial Investigators: 
 
All Deaths 
 
TLR 
 
TVR 
 
Target limb amputations 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 80 of 110 
 
 
 
 
 
CEC members will be blinded to a subject’s treatment assignment through primary endpoint of 
all participating subjects. Responsibilities, qualifications, membership, and committee 
procedures are outlined in the CEC charter. 
Contact information for the CEC is included in the Manual of Operations for Japanese sites. 
22.4. Independent Data Review (IDR) 
The independent data reviewer (IDR) provides external oversight and review for potential safety 
concerns. The IDR is a physician expert in peripheral interventional therapy who is not 
participating in the clinical trial and is independent to BSC. 
Aggregate accumulating safety data will be reviewed to monitor for the incidence of MAEs and 
other trends that would warrant modification or termination of the trial. During the course of the 
trial, data will be supplied to and reviewed by the IDR in blinded fashion (i.e., group A and 
group B). If, after review of blinded data, the IDR wants to review unblinded data, a request will 
be made to the Executive Committee for consideration and final decision. 
Any IDR recommendations for clinical trial modification or termination because of concerns 
over subject safety or issues relating to data monitoring or quality control will be submitted in 
writing to BSC for consideration. 
Contact information for the IDR is included in the Manual of Operations for Japanese sites. 
23. Suspension or Termination 
23.1. Premature Termination of the Trial 
Boston Scientific Corporation reserves the right to terminate the trial at any stage but intends to 
exercise this right only for valid scientific or administrative reasons and reasons related to 
protection of subjects.  Investigators, associated IRBs/ECs, and regulatory authorities, as 
applicable, will be notified in writing in the event of trial termination. 
23.1.1. 
Criteria for Premature Termination of the Trial 
Possible reasons for premature trial termination include, but are not limited to, the following. 
 
The occurrence of unanticipated adverse device effects that present a significant or 
unreasonable risk to subjects enrolled in the trial. 
 
An enrollment rate far below expectation that prejudices the conclusion of the trial.  
 
A decision on the part of Boston Scientific to suspend or discontinue development of the 
device. 
23.2. Termination of Trial Participation by the Investigator or Withdrawal of IRB/EC/REB 
Approval 
Any investigator, or IRB/ EC in the RANGER II SFA Trial may discontinue participation in the 
trial or withdrawal approval of the trial, respectively, with suitable written notice to Boston 
Scientific. Investigators, associated IRBs/ECs, and regulatory authorities, as applicable, will be 
notified in writing in the event of these occurrences. 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 81 of 110 
 
 
 
 
 
23.3. Requirements for Documentation and Subject Follow-up 
In the event of premature trial termination a written statement as to why the premature 
termination has occurred will be provided to all participating sites by Boston Scientific. The 
IRB/EC/REB and regulatory authorities, as applicable, will be notified. Detailed information on 
how enrolled subjects will be managed thereafter will be provided.  
In the event an IRB or EC terminates participation in the trial, participating investigators, 
associated IRBs/ECs, and regulatory authorities, as applicable, will be notified in writing. 
Detailed information on how enrolled subjects will be managed thereafter will be provided by 
Boston Scientific. 
In the event a Principal Investigator terminates participation in the trial, trial responsibility will 
be transferred to another investigator, if possible. In the event there are no opportunities to 
transfer Principal Investigator responsibility; detailed information on how enrolled subjects will 
be managed thereafter will be provided by BSC. 
The Principal Investigator or his/her designee must return all study-related documents and 
investigational product to Boston Scientific, unless this action would jeopardize the rights, 
safety, or welfare of the subjects. 
23.4. Criteria for Suspending/Terminating a Study Center 
BSC reserves the right to stop the inclusion of subjects at a trial site at any time after the trial 
initiation visit if no subjects have been enrolled for a period beyond 2 months after site initiation, 
or if the site has multiple or severe protocol violations/noncompliance without justification 
and/or fails to follow remedial actions. 
In the event of termination of site participation, all trial devices and testing equipment, as 
applicable, will be returned to BSC unless this action would jeopardize the rights, safety or well-
being of the subjects. The IRB/EC/REB and regulatory authorities, as applicable, will be 
notified. All subjects enrolled in the trial at the site will continue to be followed as required by 
the protocol trial schedule. The Principal Investigator at the site must make provision for these 
follow-up visits unless BSC notifies the investigational site otherwise. 
24. Publication Policy 
BSC requires disclosure of its involvement as a sponsor or financial supporter in any publication 
or presentation relating to a BSC trial or its results. BSC will submit trial results for publication 
(regardless of trial outcome) following the conclusion or termination of the trial. Boston 
Scientific Corporation adheres to the Contributorship Criteria set forth in the Uniform 
Requirements of the International Committee of Medical Journal Editors (ICMJE; 
http://www.icmje.org). In order to ensure the public disclosure of trial results in a timely manner, 
while maintaining an unbiased presentation of trial outcomes, BSC personnel may assist authors 
and investigators in publication preparation provided the following guidelines are followed. 
 
All authorship and contributorship requirements as described above must be followed. 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 82 of 110 
 
 
 
 
 
 
BSC involvement in the publication preparation and the BSC Publication Policy should be 
discussed with the Coordinating Principal Investigator(s) and/or Executive/Steering 
Committee at the onset of the project. 
 
The First and Senior authors are the primary drivers of decisions regarding publication 
content, review, approval, and submission. 
25. Reimbursement and Compensation for Subjects 
25.1. Subject Reimbursement 
Travel expenses (and other expenses for Japan only) incurred by subjects as a result of 
participation in the trial can be reimbursed in accordance with pertinent country laws and 
regulations and per the trial site’s regulations. 
25.2. Compensation for Subject’s Health Injury 
Boston Scientific Corporation will purchase an insurance policy to cover the cost of potential 
health injury for trial subjects, and if required by applicable law. 
 
 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 83 of 110 
 
 
 
 
 
26. Bibliography 
1. 
Litsky J, Chanda A, Stilp E, Lanksy A, Mena C. "Critical evaluation of stents in the peripheral arterial disease 
of the superficial femoral artery - Focus on the paclitaxel eluting stent." Med Devices (Auckl) 7, no. 1 (2014): 
149-156. 
2. 
Kakkar AM, Abbott JD. "Percutaneous versus surgical management of lower extremity peripheral artery 
disease." Curr Atheroscler Rep 17, no. 2 (2015): 479. 
3. 
Aghel A, Armstrong EJ. "Recent advances in self-expanding stents for use in the superficial femoral and popliteal 
arteries." Expert Rev Cardiovasc Ther 12, no. 7 (July 2014): 833-842. 
4. 
Katsanos K, Tepe G, Tsetis D, Fanelli F. "Standards of practice for superficial femoral and popliteal artery 
angioplasty and stenting." Cardiovasc Intervent Radiol 37, no. 3 (June 2014): 592-603. 
5. 
Fowkes FGR, Rudan D, Rudan I, et al. “Comparison of global estimates of prevalence and risk factors for  
peripheral artery disease in 2000 and 2010: a systematic review and analysis”. Lancet. 2013;382:1329–40. 
6. 
Kapsis C, Gurm HS. "Current approach to the diagnosis and treatment of femoral popliteal artery angioplasty 
and stenting." Current Cardiology Reviews 5, no. 4 (November 2009): 296-311. 
7. 
Gandhi S, Sakhuja R, Slouvut DP. "Recent advances in percutaneous management of iliofemoral and superficial 
femoral artery disease." Cardiology Clinics 29, no. 3 (August 2011): 381-394. 
8. 
Das, T. "Optimal therapeutic approaches to femoropopliteal artery intervention." Catheter Cardio Interven 63, 
no. 1 (September 2004): 21-30. 
9. 
Razavi MK, Mustapha JA, Miller LE. "Contemporary systematic review and meta-analysis of early outcomes 
with percutaneous treatment for infrapopliteal atherosclerotic disease." J Vasc Interv Radiol 25, no. 10 (2014): 
1489-1496. 
10. Schillinger M, Minar E. "Claudication: Treatment options for femoropopliteal disease." Progress in 
Cardiovascular Diseases 54, no. 1 (2011): 41-46. 
11. Tepe G. Schmehl J, Heller S, Wiesinger B, Claussen CD, Duda SH. "Superficial femoral artery: Current 
Treatment Options." European Radiology 16, no. 6 (June 2006): 1316-1322. 
12. Erwin PA, Shishehbor MH. "Contemporary managmenet of femoral popliteal revascularization." Intervent 
Cardiol Clinics 3, no. 4 (2014): 517-530. 
13. Bosiers M, Deloose K, Verbist J, Peeters P. "Present and future of endovascular SFA treatment: Stents, stent-
grafts, drug coated balloons and drug coated stents." J Cardiol Surg 49, no. 2 (April 2008): 159-65. 
14. Dormandy JA, Rutherford RB. “Management of peripheral arterial disease (PAD): TASC Working Group: 
TransAtlantic Inter-Society Consensus (TASC).” J Vasc Surg no. 31: 2000: S1–S296. 
15. Norgren L, Hiatt WR, Dormandy JA, Nehler MR, Harris KA, Fowkes FG. “Inter-society consensus for the 
management of peripheral arterial disease (TASC II).” J Vasc Surg no. 45 2007: S5–S67. 
16. Nakgawa Y, Yajima J, Oikawa Y, et al. "Clinical outcomes after percutaneous peripheral intervention for chronic 
total occlusion of the superficial femoral arteries: Comparison between self-expandable nitinol stent and stainless 
steel stent." Journal of Cardiology 53, no. 3 (June 2009): 417-421. 
17. Laird JR, Katzen BT, Scheinert D, et al. "Nitinol stent implantation versus balloon angioplasty for lesions in the 
superficial femoral artery and proximal popliteal artery: Twelve month results from the RESILIENT randomized 
trial." Circulation: Cardiovascular Interventions 3, no. 3 (June 2010): 267-276. 
18. Dake MD, Scheinert D, Tepe G, et al. "Nitinol stents with polymer-free paclitaxel coating for lesions in the 
superficial femoral and popliteal arteries above the knee: Twelve-month safety and effectivess results from the 
Zilver PTX single-arm clinical study." J Endovasc Therapy 18, no. 5 (2011): 613-23. 
19. Laird JR, Katzen BT, Scheinert D, et al. "Nitinol stent implantation vs. balloon angioplasty for lesions in the 
superficial femoral and proximal popliteal arteries of patients with claudication: Three-year follow-up from the 
RESILIENT randomized trial." J Endovasc Ther 19, no. 1 (2012): 1-9. 
20. G.Ansel. "Drug-eluting stents are widely applicable: The choice of drug is the only differential factor when 
treating the patient." Vascular 18, no. Suppl 2 (June 2010): S52-53. 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 84 of 110 
 
 
 
 
 
21. Mongiardo A, Curcio A, Spaccarotella C, Parise S, Indolfi C. "Molecular mechanisms of restenosis after 
percutaneous peripheral angioplasty and approach to endovascular therapy." Current Drug Targets - Cardiovasc 
Haematol Disorders 4, no. 3 (September 2004): 275-87. 
22. Ansel G. "What is the next big thing in cardiac revascularization?" Vascular 18, no. Suppl 2 (June 2010): S54. 
23. Bosiers M, Deloose K, Keirse K, Verbist J, Peeters R. "Are drug-eluting stents the future of SFA treatment?" J 
Cardiovasc Surg 51, no. 1 (February 2010): 115-19. 
24. Scheinert D, Duda S, et al. “The LEVANT I (Lutonix Paclitaxel-Coated Balloon for the Prevention of 
Femoropopliteal Restenosis) Trial for Femoropopliteal Revascularization” JACC: Cardiovascular Interventions 
7, no.1 2014: 10-19. 
25. Rosenfield K, Jaff M, et al. “Trial of a Paclitaxel-Coated Balloon for Femoropopliteal Artery Disease” N Engl J 
Med 373 2015: 145-153. 
26. Tepe G, Laird J, et al. “Drug-Coated Balloon versus Standard Percutaneous Transluminal Angioplasty for the 
Treatment of Superficial Femoral and/or Popliteal Peripheral Artery Disease: 12-Month Results from the 
IN.PACT SFA Randomized Trial” Circulation AHA no. 114:1-22. 
27. Dake MD, Ansel GM, Jaff MR, et al. Paclitaxel-eluting stents show superiority to balloon angioplasty and bare 
metal stents in femoropopliteal disease: twelve-month Zilver PTX randomized study results. Circ Cardiovasc 
Interv. Oct 1 2011;4(5):495-504. 
28. Tepe G, Zeller T, Albrecht T, et al. “Local delivery of paclitaxel to inhibit restenosis during angioplasty of the 
leg.” New England Journal of Medicine. 14 2008;358(7):689-699. 
29. Werk M, Langner S, Reinkensmeier B, et al. “Inhibition of restenosis in femoropopliteal arteries. Paclitaxel-
coated versus uncoated balloon: Femoral paclitaxel randomized pilot trial.” Circulation. 23 2008;118(13):1358-
1365. 
30. Cannavale A, Fanelli F, Allegritti M, Bruni A, Lucatelli P, Passariello R. “Paclitaxel-coated balloon angioplasty 
for lower extremity revascularization: Better way to fight restenosis?” [abstract]. Cardiovascular and 
Interventional Radiology. September 2011;34 SUPPL. 3:528-529. 
31. Fanelli F, Cannavale A. “Endovascular treatment of infrapopliteal arteries: Angioplasty vs stent in the drug-
eluting era.” Eur. Radiol. April 2014;24(4):793-798. 
32. Schlager O, Francesconi M, Haumer M, Dick P, Sabeti S, Amighi J, et al. Duplex Sonography Versus 
Angiography for Assessment of Femoropopliteal Arterial Disease in a "Real-World" Setting. J Endovasc Ther 
14 (2007): 452-9. 
33. Rooke TW, et al. 2011 ACCF / AHA Focused Update of the Guideline for the Management of Patients with 
Peripheral Artery Disease (Updating the 2005 Guideline): A Report of the American College of Cardiology 
Foundation/American Heart Association Task Force. 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 85 of 110 
 
 
 
 
 
27. Abbreviations and Definitions 
27.1. Abbreviations 
Abbreviations are shown in Table 27-1. 
Table 27-1: 
Abbreviations 
Abbreviation 
Terminology 
ABI 
Ankle Brachial Index 
ACC/AHA 
American College of Cardiology/American Heart Association 
ADE 
Adverse Device Effect 
AE 
Adverse Event 
BSC 
Boston Scientific Corporation 
CE 
Conformité Européenne (meaning European Conformity) 
CEC 
Clinical Events Committee 
CIN 
Contrast-Induced Nephropathy 
CRA 
Clinical Research Associate 
CRF 
Case Report Form 
CVA 
Cerebrovascular Accident 
DCB 
Drug Coated Balloon 
DFU 
Directions for Use 
DUS 
Duplex Ultrasound 
eCRF 
Electronic Case Report Form 
EDC 
Electronic Data Capture 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonisation 
IDE 
Investigational Device Exemption  
IEC 
Institutional Ethics Committee 
ITT 
Intent to Treat 
IRB 
Institutional Review Board 
MAE 
Major Adverse Event 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 86 of 110 
 
 
 
 
 
Abbreviation 
Terminology 
OUS 
Outside United States 
PMDA 
Pharmaceutical Medical Device Agency 
PPA 
Proximal Popliteal Artery 
PSVR 
Peak Systolic Velocity Ratio 
PTA 
Percutaneous Transluminal Angioplasty 
RBP 
Rated Burst Pressure 
REB 
Research Ethic Board 
SADE 
Serious Adverse Device Effect 
SAE 
Serious Adverse Event 
SFA 
Superficial Femoral Artery 
TBI 
Tibial Brachial Index 
TLR 
Target Lesion Revascularization 
TM 
Transmetatarsal 
TVR 
Target Vessel Revascularization 
UADE 
Unanticipated Adverse Device Effect 
UPN 
Universal Product Number 
US 
United States 
 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 87 of 110 
 
 
 
 
 
27.2. Definitions 
Terms are defined in Table 27-2. 
Table 27-2: 
Definitions 
Term 
Definition 
AMPUTATION 
 
Major Amputation: amputation of the lower limb at the ankle 
level or above. 
 
Minor Amputation: amputation of the lower limb below the 
ankle level, i.e. forefoot or toes. 
ANKLE-BRACHIAL 
INDEX (ABI) 
The ratio between the systolic pressure measured at the ankle and 
the systolic pressure measured in the arm as follows:  
 
Ankle: The systolic pressure will be measured in the target 
limb at the arteria dorsalis pedis and/or the arteria tibialis 
posterior. If both pressures are measured, the highest pressures 
will be used for the ABI calculation.  
 
Brachial: The systolic pressure will be measured in both arms, 
and the highest of both pressures will be used for the ABI 
calculation. 
ARRHYTHMIA 
Any variation from the normal rhythm of the heartbeat, including 
but not limited to, sinus arrhythmia, premature beats, heart block, 
ventricular or atrial fibrillation, ventricular tachycardia, or atrial 
flutter. 
ASSISTED 
PRIMARY 
PATENCY 
Percentage (%) of lesions without clinically-driven TLR and those 
with clinically-driven TLR (not due to complete occlusion or by-
pass) that reach endpoint without restenosis. 
BLEEDING 
COMPLICATION 
Includes, but is not limited to, intracranial hemorrhage, GI 
bleeding, hematoma, bleeding at percutaneous catheterization site, 
and/or retroperitoneal bleeding. Bleeding that requires surgery 
qualifies as an SAE. 
CALCIFICATION 
Readily apparent densities seen within the artery wall and site of 
lesion as an x-ray-absorbing mass. 
CEREBRO-
VASCULAR 
ACCIDENT (CVA) 
CEREBRO-VASCULAR ACCIDENT / STROKE 
An acute symptomatic episode of neurological dysfunction 
attributed to a vascular cause lasting more than 24 hours or lasting 
24 hours or less with a brain imaging trial or autopsy showing 
infarction.  
CLINICAL 
DETERIORATION 
Downgrade in Rutherford classification of 1 or more categories as 
compared to pre-procedure. 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 88 of 110 
 
 
 
 
 
Term 
Definition 
COMPLETE BLOOD 
COUNT (CBC) 
A blood test used to measure several components and features of 
blood, including:  Red Blood Cells, White Blood Cells, 
Hemoglobin, Hematocrit and Platelets. 
COMPLICATION 
An undesirable clinical event that results in death, injury, or 
invasive intervention. Complications may include, but are not 
limited to perforation, occlusion, intimal flap, dissection, loss of 
side branch, distal embolization, hypotension, hematoma, 
arrhythmias, etc. Complications may or may not be related to the 
investigational product(s). 
DEATH 
All deaths are considered cardiac unless an unequivocal non-
cardiac cause can be established. Specifically, an unexpected death 
in subjects with coexisting potentially fatal non-cardiac diseases 
(e.g. Cancer, infection) should be classified as cardiac. 
All death events will be submitted to CEC and will be categorized 
as: 
Cardiac death: any death due to immediate cardiac cause (e.g. MI, 
low-output failure, fatal arrhythmia). Unwitnessed death and death 
of unknown cause will be classified as cardiac death. This includes 
all procedure related deaths including those related to concomitant 
treatment. 
Vascular death: death due to cerebrovascular disease, pulmonary 
embolism, ruptured aortic aneurysm, dissecting aneurysm, or other 
vascular cause. 
Non-cardiovascular death:  any death not covered by the above 
definitions, including death due to infection, sepsis, pulmonary 
causes, accident, suicide, or trauma. 
DIAMETER 
STENOSIS 
The maximal narrowing of the target lesion relative to the reference 
vessel diameter. 
DISSECTION- 
NHLBI GRADE 
TYPES 
Type A: 
Small radiolucent area within the lumen of the vessel 
disappearing with the passage of the 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 or without delayed run-
off of the contrast material in the antegrade flow. 
Type E: 
Persistent luminal filling defect with delayed run-off of 
the contrast material in the distal lumen. 
Type F: 
Filling defect accompanied by total vessel occlusion. 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 89 of 110 
 
 
 
 
 
Term 
Definition 
DISTAL 
EMBOLIZATION 
Migration of a filling defect, or thrombus, to distally occlude the 
target vessel or one of its branches. 
EQ-5D™ 
Descriptive system of health-related quality of life states consisting 
of five dimensions (mobility, self-care, usual activities, 
pain/discomfort, anxiety/depression) each of which can take one of 
five responses. The responses record five levels of severity (no 
problems/slight problems/moderate problems/severe 
problems/extreme problems) within a particular EQ-5D dimension. 
END OF INDEX 
PROCEDURE 
(TIME) 
The end of the index procedure is defined as the time the guide 
(catheter or sheath) is removed (post final angiography). 
HEMATOMA 
A localized swelling filled with blood resulting from a break in a 
blood vessel. 
HEMODYNAMIC 
IMPROVEMENT 
Improvement of ABI by ≥ 0.1 or to an ABI ≥ 0.90 as compared to 
the pre-procedure value without the need for repeat 
revascularization. 
HYPOTENSION 
Systolic blood pressure < 80 mmHg lasting more than 30 minutes 
or requiring intervention (e.g. pacing, IABP, intra venous 
vasopressors to sustain systolic blood pressure). This excludes 
transient hypotension or vagal reactions, which are self-limited or 
readily reversible. 
INTIMAL FLAP 
An extension of the vessel wall into the arterial lumen.  
LESION LENGTH 
Measured as the distance from the proximal shoulder to the distal 
shoulder of the lesion, in the view that demonstrates the stenosis in 
its most elongated projection. 
MINIMAL LUMEN 
DIAMETER 
The vessel diameter as measured at the most narrow point of the 
lesion. 
OCCLUSION 
Lesion with no flow; implies 100% diameter stenosis. 
PERFORATION 
Perforations are classified as follows: 
Angiographic perforation: perforation detected by the clinical site 
or Angiographic Core Laboratory at any point during the 
procedure. 
Clinical perforation: perforation requiring additional treatment 
(including efforts to seal the perforation), or resulting in significant 
hemodynamic compromise, abrupt closure, or death. 
PRIMARY 
PATENCY 
Percentage (%) of lesions that reach endpoint without a 
hemodynamically significant stenosis on DUS and without 
clinically-driven TLR or, bypass of the target lesion. 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 90 of 110 
 
 
 
 
 
Term 
Definition 
PRIMARY 
SUSTAINED 
CLINICAL 
IMPROVEMENT 
Endpoint determined to be a success when there is an improvement 
in Rutherford classification of one or more categories as compared 
to pre-procedure without the need for repeat TLR. 
PROCEDURAL 
SUCCESS 
Procedural success defined as residual stenosis of ≤ 50% (non-
stented subjects) or ≤ 30% (stented subjects) by core laboratory 
evaluation (if core laboratory assessment is not available then the 
site-reported estimate is used) 
PSEUDO-
ANEURYSM 
An encapsulated hematoma in communication with an artery. 
PRODUCT NON-
CONFORMITY 
A departure of a quality characteristic from its intended level or 
state that occurs with a severity sufficient to cause an associated 
product or service not to meet a specification requirement.  
P1 SEGMENT 
The P1 segment (above the knee popliteal artery) is from the 
Hunter’s canal to the proximal edge of the patella. Target lesion 
must be in the native SFA and/or PPA down to the P1 segment to 
the edge of the patella. 
REPEAT 
INTERVENTION 
(PERCUTANOUS 
AND/OR SURGERY) 
Either repeat percutaneous transluminal angioplasty (PTA) or artery 
bypass surgery, performed subsequently to the subject leaving the 
cath lab after the index procedure.  
REFERENCE 
VESSEL DIAMETER 
(RVD) OF NORMAL 
ARTERY SEGMENT 
Angiographic measurement of the artery proximal and/or distal to 
the lesion intended for treatment. 
RESTENOSIS 
DUS systolic velocity ratio (SVR) > 2.4 suggest stenosis >50%. 
RUTHERFORD / 
BECKER 
CLASSIFICATION 
Category 
Clinical Description 
Objective Criteria 
0 
Asymptomatic 
Normal Treadmill /stress test 
1 
Mild claudication 
Completes treadmill exercise; ankle 
pressure (AP) after exercise but at least 
20 mm Hg lower than resting  
value  
2 
Moderate claudication 
Between categories 1 and 3 
3 
Severe claudication 
Cannot complete treadmill exercise and 
AP after exercise < 50 mm Hg 
4 
Ischemic rest pain 
Resting AP < 40 mm Hg, flat or barely 
pulsatile ankle or metatarsal pulse 
volume recording (PVR); toe pressure 
(TP) < 30 mm Hg 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 91 of 110 
 
 
 
 
 
Term 
Definition 
5 
Minor tissue loss – 
nonhealing ulcer, focal 
gangrene with diffuse 
pedal edema 
Resting AP < 60 mm Hg, ankle or 
metatarsal (MT) PVR flat or barely 
pulsatile; TP < 40 mm Hg  
6 
Major tissue loss – 
extending above TM level 
Same as Category 5 
SECONDARY 
SUSTAINED 
CLINICAL 
IMPROVEMENT 
Endpoint determined to be a success when there is an improvement 
in Rutherford classification of one or more categories as compared 
to pre-procedure including those subjects with repeat TLR. 
SOURCE DATA 
All information in original records and certified copies of original 
records of clinical findings, observations, or other activities in a 
clinical investigation, necessary for the reconstruction and 
evaluation of the trial. Source data are contained in the source 
documents (original records or certified copies). 
SOURCE 
DOCUMENT 
Original documents, data or records. 
Examples:  Hospital records, laboratory notes, device 
accountability records, photographic negatives, radiographs, 
records kept at the investigation site, at the laboratories and at the 
medico-technical departments involved in the clinical investigation. 
START OF INDEX 
PROCEDURE 
(TIME) 
The start of the index procedure is defined as the time the guide 
(catheter or sheath) is inserted. 
SUCCESSFUL PRE-
DILATATION 
Successful pre-dilatation occurs when the selected balloon opens 
vessel entry at nominal pressure without major (≥ Grade D) flow-
limiting dissection or need for intervention (i.e. stenting). 
TARGET LESION 
A target lesion is identified as a clinical trial lesion intended to be 
treated with a clinical trial device during the index procedure. 
TARGET LESION 
REVASCULARIZATION 
(TLR) 
Any surgical or percutaneous intervention to the target lesion(s) 
after the index procedure. 
  
Clinically-driven TLR  
 
A target lesion revascularization will be considered clinically-
driven by CEC if the subject has recurrent symptoms (≥ 1 change in 
Rutherford Classification or associated with decreased ABI/TBI of 
≥20% or ≥ 0.15 when compared to post-procedure baseline 
ABI/TBI in the treated segment. TBI allowed in cases of 
incompressible vessels.) 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 92 of 110 
 
 
 
 
 
Term 
Definition 
TARGET VESSEL 
 
Target vessel is defined as the vessel containing the target lesion(s).  
If the target lesion is entirely within the right superficial femoral 
artery, then the target vessel is the right superficial femoral artery.  
If the target lesion extends from the right superficial femoral artery 
into the right proximal popliteal artery, then both the right 
superficial femoral artery and right proximal popliteal artery would 
be considered part of the target vessel. 
TARGET VESSEL 
REVASCULARIZATI
ON (TVR) 
 
Any surgical or percutaneous intervention to the target vessel(s) 
after the index procedure.  
  
Clinically-driven TVR:  
 
A target vessel revascularization will be considered as clinically-
driven by CEC if the subject has recurrent symptoms (≥ 1 change in 
Rutherford Classification or associated with decreased ABI/TBI of 
≥20% or ≥ 0.15 when compared to post-procedure baseline 
ABI/TBI in the treated segment. TBI allowed in cases of 
incompressible vessels.) 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 93 of 110 
 
 
 
 
 
Term 
Definition 
TRANSATLANTIC 
INTER-SOCIETAL 
CONSENSUS (TASC) 
LESION 
GUIDELINES 
Type A lesion: 
 
Single stenosis ≤ 10 cm in length. 
 
Single occlusion ≤ 5 cm in length. 
Type B lesion: 
 
Multiple lesions (stenoses or occlusions), each ≤ 5 cm 
 
Single stenosis or occlusion ≤ 15cm not involving the infra 
geniculate popliteal artery 
 
Single or multiple lesions in the absence of continuous tibial 
vessels to improve inflow for a distal bypass 
 
Heavily calcified occlusion ≤ 5cm in length 
 
Single popliteal stenosis 
Type C lesion: 
 
Multiple stenoses or occlusions totaling > 15 cm with or 
without heavy calcification 
 
Recurrent stenoses or occlusions that need treatment after two 
endovascular interventions 
Type D lesion: 
 
Chronic total occlusions of the CFA or SFA (> 20 cm, 
involving the popliteal artery) 
 
Chronic total occlusion of the popliteal artery and proximal 
trifurcation vessels 
TECHNICAL 
SUCCESS 
Successful delivery, balloon inflation and deflation and retrieval of 
the intact trial device without burst below the rated burst pressure 
(RBP) 
THROMBUS 
(ANGIOGRAPHIC) 
Discrete, mobile intraluminal filling with defined borders 
with/without associated contrast straining; these are classified as 
either absent or present. 
UNSUCCESSFUL 
ANGIOPLASTY 
Unsuccessful deployment of assigned balloon 
VASCULAR 
COMPLICATION 
An occurrence of hematoma > 5 cm, pseudoaneurysm, 
arteriovenous (AV) fistula, or need for vascular surgical repair. 
VESSEL PATENCY 
Freedom from more than 50% stenosis based on DUS peak systolic 
velocity ratio (PSVR) comparing data within the treated segment to 
the proximal normal arterial segment. A PSVR > 2.4 suggests 
>50% stenosis.  All DUS readings are assessed by an independent 
core lab. 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 94 of 110 
 
 
 
 
 
Term 
Definition 
WALKING 
IMPAIRMENT 
QUESTIONNAIRE 
(WIQ) 
The WIQ is a functional-assessment questionnaire that evaluates 
walking ability with regard to speed, distance and stair climbing 
ability as well as the reasons that walking ability might be limited. 
Range of scores is between 0% and 100% with 100% being the best 
and 0% being the worst score. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 95 of 110 
 
 
 
 
 
Appendix A: RANGER Long Balloon Substudy 
1. RANGER Long Balloon Substudy Synopsis 
RANGER Long Balloon Substudy to RANGER II SFA 
Substudy 
Objective(s) 
To evaluate the safety and effectiveness of the Boston Scientific 
Corporation (BSC) Ranger™ Paclitaxel Coated Balloon  in the 120, 150 
and 200 mm lengths for treating Superficial Femoral Artery (SFA) and/or 
Proximal Popliteal Artery (PPA) lesions. 
Indication(s) for 
Use 
The Ranger Paclitaxel Coated Balloon is intended to be used for 
Percutaneous Transluminal Angioplasty (PTA) in the peripheral 
vasculature, including iliac and infrainguinal arteries. 
Test Device 
Ranger Paclitaxel Coated PTA Balloon Catheter (Ranger DCB) 
Device Sizes 
The working catheter length is 90 cm and 150 cm for all diameters. 
The Ranger DCB Long Balloons (test device) are commercially available 
in Europe and New Zealand (CE Mark #0344, received on 12 July 2017). 
 
 
Balloon Length (mm) 
120 
150 
200 
Balloon 
Diameter 
(mm) 
4.0 
X 
X 
X 
5.0 
X 
X 
X 
6.0 
X 
X 
X 
7.0 
X 
X 
X 
8.0 
 
 
 
 
Substudy 
Design 
A non-blinded, non-randomized, Long Balloon substudy run concurrent to 
the RANGER II SFA Global Pivotal Trial in Europe and New Zealand in 
order to meet DEKRA’s Post-Market Clinical Follow-up (PMCF) 
Requirement. 
Although an investigative center can participate in both the RCT and Long 
Balloon trial arms, a subject can either be enrolled in the RCT study arm 
or the RANGER Long Balloon substudy, but not both.   
Blinding / 
Unblinding 
All subjects in the RANGER Long Balloon substudy will be treated with 
the Ranger DCB.  Therefore, all subjects, Investigators, trial center 
personnel, Duplex Ultrasound (DUS) Core Laboratory personnel, 
Angiography Core Laboratory personnel, and Clinical Events Committee 
(CEC) will not be blinded to the assigned treatment arm.   


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 96 of 110 
 
 
 
 
 
Planned 
Number of 
Subjects 
A minimum of 50 subjects will be treated with the Ranger DCB in the 
RANGER Long Balloon substudy, with at least 20 subjects treated with 
the 200 mm balloon. 
Planned 
Number of 
Investigational 
Sites / Countries 
Up to 12 trial centers in Europe and New Zealand may enroll subjects into 
the RANGER Long Balloon substudy. 
Primary Safety 
Endpoint 
The primary safety endpoint assesses the occurrence of Major Adverse 
Events (MAE) defined as all-cause death through 1 month, target limb 
major amputation and/or target lesion revascularization (TLR) at 6 and 12 
months post-index procedure.  It is expected that the MAE-free rate will 
be similar to the rates observed by the RANGER II SFA group observed 
in the RCT.  The MAE-free rate as well as its individual components will 
be reported separately for this subgroup.  
Primary 
Effectiveness 
Endpoint 
The primary effectiveness endpoint assesses primary lesion patency at 6 
months as determined by duplex ultrasound (DUS). 
Primary effectiveness is defined as a binary endpoint determined by 
duplex ultrasound (DUS) peak systolic velocity ratio (PSVR) ≤ 2.4 in the 
absence of clinically-driven TLR.  
Notes: 
 
Lesion patency is defined as freedom from more than 50% stenosis 
based on DUS PSVR comparing data within the treated segment to 
the proximal normal arterial segment.  
 
PSVR >2.4 suggests >50% stenosis. 
The treated segment will be assessed for patency as a single segment 
regardless of the number of tandem lesions within the ballooned segment. 
Secondary 
Endpoints 
 
Technical success defined as successful delivery, balloon inflation 
and deflation and retrieval of the intact trial device without burst 
below the rated burst pressure (RBP) 
 
Procedural success defined as residual stenosis of ≤ 50% (non-stented 
subjects) or ≤ 30% (stented subjects) by core laboratory evaluation (if 
core laboratory assessment is not available then the site-reported 
estimate is used) 
 
Clinical success defined as procedural success without procedural 
complications (i.e. death, major target limb amputation, thrombosis of 
the target lesion, or clinically-driven TLR) prior to discharge  
 
Major Adverse Events (MAE) through 12 months. MAEs are defined 
as all-cause death post-index procedure, TLR, and major target limb 
amputation 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 97 of 110 
 
 
 
 
 
 
Death of any cause within 30 days, 6, 12 months  
 
TVR rates at 6, 12 months 
 
TLR rates at 6, 12 months 
 
Rate of Primary and Secondary sustained clinical improvement as 
assessed by changes in Rutherford Classification from baseline at 1, 
6, 12 months post-procedure 
 
Rate of Hemodynamic Improvement as assessed by changes in 
Ankle-Brachial Index (ABI) from baseline at 1, 6, 12 months post-
procedure 
 
Duplex-defined binary restenosis (PSVR > 2.4) of the target lesion at 
1, 6, 12 months 
Method of 
Assigning 
Patients to 
Treatment 
In the RANGER Long Balloon substudy, subjects will not be randomized; 
all subjects will be treated with the Ranger DCB. Subjects are considered 
enrolled when the Ranger DCB is introduced into the subject’s 
vasculature. 
Note: If the subject is found to meet exclusion criteria during the 
angiographic eligibility assessment, the subject will be considered a 
screen failure and should not be entered into this substudy. The subject 
should be cared for and followed outside of the trial based on the 
physician’s treatment plan. 
Note: If the balloon angioplasty attempt with the assigned treatment 
device (the test device Ranger DCB) is not successful, follow-up through 
the 1 month visit only will occur as part of the Intent to Treat (ITT) 
population.  Data for assessment of MAE will be collected for these 
subjects.  No other testing or follow up is required. 
Follow-up 
Schedule 
Follow-up visits for the RANGER Long Balloon substudy will occur at 
pre-discharge, 1 month, 6 months, and 12 months post-index procedure.  
Office or clinic visits are required for testing during each protocol 
required follow-up visit. Planned procedures and testing include the 
following: 
 
Physical Exam at  screening, pre-discharge, 1 month, 6 month, and 12 
month 
 
Angiogram at time of index procedure and during any subsequent 
revascularization procedure (up to12 months post index procedure) 
 
Duplex Ultrasound at 1 month, 6 month, and 12 month  
 
Rutherford Classification at screening, 1 month, 6 month, and 12 
month  
 
Resting ABI exam at screening, 1 month, 6 month, and 12 month 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 98 of 110 
 
 
 
 
 
 
Lab tests: 
– Complete Blood Count (CBC) containing WBC, RBC and PLT at 
screening 
– Serum creatinine at screening  
– Pregnancy testing (serum or urine) within 24 hrs prior to index 
procedure if of child bearing age 
 
Medication compliance at screening, procedure, pre-discharge, 1 
month, 6 month, and 12 month,  
 
Adverse event monitoring at procedure, pre-discharge, 1 month, 6 
month, and 12 month 
Study Duration 
The Long Balloon substudy primary endpoint will be considered complete 
after all subjects have completed the 6 month follow-up visit, were 
discontinued prior to the 6 month follow-up visit, have died, or the last 6 
month follow-up visit window is closed. 
The RANGER Long Balloon substudy will be considered complete after 
all subjects have completed the 12 month follow-up visit, were 
discontinued prior to the 12 month follow-up visit, have died, or the last 
12 month follow-up visit window is closed. 
Required 
Medication 
Therapy 
Anti-platelet therapy is recommended throughout the length of the trial 
participation. Investigators must prescribe concomitant anti-coagulant and 
anti-platelet medications consistent with current local clinical practice. 
Antiplatelet medication and peripheral artery disease (PAD) medication 
usage will be collected and reported for compliance throughout the trial. 
Minimum protocol requirements: 
 
Anti-coagulation therapy administered prior to and during the 
procedure should be consistent with current clinical practice. 
 
A minimum of 30 days of dual antiplatelet therapy for non-stented 
subjects and a minimum of 3 months (90 days) dual antiplatelet 
therapy for stented subjects post index procedure.  
Minimum recommendation: 
 
Antiplatelet monotherapy is recommended for administration 
throughout the 12 month follow-up (trial completion). 
Note: A subject is exempt from the above-mentioned antiplatelet 
requirements if he/she requires Coumadin or other similar anti-coagulant 
due to known comorbidities and in the opinion of the investigator, the 
combination of antiplatelet and anticoagulant could put the subject at an 
unreasonable risk of bleeding. 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 99 of 110 
 
 
 
 
 
Inclusion 
Criteria 
Enrollment into the RANGER Long Balloon substudy is limited to the 
following inclusion criteria: 
1. Subject (or Legal Guardian) is willing and able to provide consent 
before any study-specific tests or procedures are performed and agree 
to attend all required follow-up visits; 
2. Subject at least 20 years of age; 
3. Chronic symptomatic lower limb ischemia defined as Rutherford 
classification  2, 3, or 4; 
4. Target lesion is in the native SFA and/or PPA down to the P1 
segment; 
5. Patent popliteal and infrapopliteal arteries, i.e., single vessel runoff or 
better with at least one of three vessels patent (<50% stenosis) to the 
ankle or foot; 
6. Reference vessel diameter ≥ 4 mm and ≤ 8 mm by visual estimate  
(Use of a radiopaque ruler is recommended); and 
7. Angiographic evidence that target lesion consists of a single de novo, 
non-stented and non-atherectomy treated or restenotic lesion (or 
tandem lesions or a combination lesion as defined below) that is: 
a. 
≥ 70% -99% stenotic with total lesion length up to180 mm by 
visual estimate.  
Use of a radiopaque ruler is recommended. 
b. Occluded with total lesion length ≤ 150 mm by visual estimate. 
Use of a radiopaque ruler is recommended. 
c. 
If lesion is restenotic, most recent PTA treatment must be > 3 
months prior to enrollment 
Notes: 
Combination lesions (a non-occlusive lesion that includes a totally 
occluded segment along its length) are eligible provided that the combined 
total lesion length is ≤180 mm. 
Tandem (or “adjacent”) lesions may be enrolled providing they meet all of 
the following criteria: 
 
Separated by a gap of ≤ 30 mm (3 cm)  
 
Total combined lesion length meets requirements (Angiographic 
inclusion criteria (7) including 30 mm gap); and 
 
Able to be treated as a single lesion. 
Exclusion 
Criteria  
Patients are not permitted to enroll into the RANGER Long Balloon 
substudy if they meet any of the following exclusion criteria: 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 100 of 110 
 
 
 
 
 
1. Life expectancy, documented in the Investigator’s opinion, of less 
than 12 months; 
2. Hemorrhagic stroke or cardiac event (e.g. STEMI, unstable angina) 
within 6 months prior to enrollment; 
3. Known allergies or sensitivities to heparin, aspirin, other 
anticoagulant/antiplatelet therapies, and/or paclitaxel; 
4. Known hypersensitivity or contraindication to contrast dye that, in the 
opinion of the investigator, cannot be adequately pre-medicated; 
5. Chronic renal insufficiency with serum creatinine > 2.0 mg/dL within 
30 days of index procedure or treatment with dialysis; 
6. Platelet count <80,000 mm3 or >600,000 mm3 or history of bleeding 
diathesis; 
7. Receiving immunosuppressive therapy; 
8. Septicemia at the time of enrollment; 
9. Any major (e.g., cardiac, peripheral, abdominal) intervention 
(including in the contralateral SFA/PPA) planned within 30 days post 
index procedure; 
10. Presence of other hemodynamically significant outflow lesions in the 
target limb requiring intervention within 30 days of enrollment; 
11. Failure to successfully cross the target lesion with a guidewire 
(successful crossing means tip of the crossing device is distal to the 
target lesion in the absence of flow-limiting dissections or 
perforations); 
12. Failure to successfully pre-dilate the target vessel; 
13. Patient has lesion that requires the use of adjunctive primary 
treatment modalities (i.e. laser, atherectomy, scoring/cutting balloon, 
other debulking devices, etc.) during the  index procedure; 
14. History of major amputation in the target limb; 
15. Target lesion or vessel has ever been previously treated with stent 
(e.g. in-stent restenosis) or surgery. Target lesion or vessel has been 
treated with atherectomy or a DCB  in the past 12 months; 
16. Pregnant or breast feeding; 
17. Presence of aneurysm in the target vessel; 
18. Acute ischemia and/or acute thrombosis of the SFA/PPA prior to 
enrollment; 
19. Patient has significant inflow disease which cannot be treated prior to 
the target lesion treatment; 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 101 of 110 
 
 
 
 
 
20. Patient has perforated targeted vessel as evidenced by extravasation 
of contrast media; 
21. Patient has severe calcification that renders the lesion undilatable;  
22. Current participation in another investigational drug or device clinical 
trial that has not completed the primary endpoint at the time of 
randomization/enrollment or that clinically interferes with the current 
trial endpoints.  
Note: studies requiring extended follow-up for products that were 
investigational, but have become commercially available since then 
are not considered investigational studies. 
Multiple 
Interventions 
During Index 
Procedure 
Contralateral & Ipsilateral Limb Lesions 
Using the same access site, iliac lesion(s) in the contralateral and 
ipsilateral limb may be treated during the index procedure under the 
following conditions: 
 
Treatment with a commercially (non-drug coated) available device 
occurs prior to enrollment of the target SFA/PPA lesion(s); 
 
Treatment of the lesion(s) is deemed an angiographic success without 
clinical sequelae (success is measured as <30% residual stenosis by 
visual estimation) and  
If the above criteria are not met, the subject may not be enrolled into the 
substudy but may be rescreened for eligibility after 30 days. 
Note: Provisional stenting of the target lesion with bare-metal stents can 
be completed in cases where adequate results could not be obtained after 
using post-dilatation balloons; such as in the case of remaining residual 
stenosis [≥ 50%] or major [≥ Grade D] flow-limiting dissection after post-
dilatation. 
Statistical Methods: Descriptive statistics will be used in the RANGER Long Balloon 
substudy. 
Sample Size and 
Statistical 
Method for 
Long Balloon 
substudy 
In order to support the stated objectives for the RANGER Long Balloon 
substudy, the sample size for this substudy will be a minimum of 50 
subjects; 20 subjects will be treated with a 200 mm Long Balloon. 
Descriptive statistics will be presented to describe the Long Balloon 
substudy results. 
Core 
Laboratories 
The following core laboratories will be established for the central 
assessment of key data collected during the trial: 
 
Angiography: to assess angiograms taken during the index procedure 
and during any subsequent revascularization procedure (up to 12  
months post index procedure) 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 102 of 110 
 
 
 
 
 
 
Ultrasound:  to assess ultrasounds taken during the follow-up periods 
(1 month, 6 months, and 12 months) 
 
 
2.  RANGER Long Balloon Substudy 
2.1. Objectives 
To evaluate the safety and effectiveness of the Boston Scientific Corporation (BSC) Ranger™ 
Paclitaxel Coated Balloon  in the 120, 150 and 200 mm lengths for treating Superficial Femoral 
Artery (SFA) and/or Proximal Popliteal Artery (PPA) lesions. 
2.2. Design 
The RANGER Long Balloon substudy is a non-blinded, non-randomized, single arm, substudy 
run concurrent with the RANGER II SFA Global Pivotal Clinical Trial. The substudy will be 
conducted in Europe and New Zealand in order to meet DEKRA’s Post-Market Clinical Follow-
up (PMCF) Requirement. 
2.2.1. Scale and Duration 
A minimum of 50 subjects will be enrolled in the RANGER Long Balloon substudy. 
All subjects will receive treatment with test device (Ranger DCB) in the RANGER Long Balloon 
substudy; 20 subjects will receive treatment with the 200mm test device.  The RANGER Long 
Balloon substudy will be conducted at the RANGER II SFA Global Pivotal Trial sites in Europe 
and New Zealand. The Ranger Long Balloons are commercially available in Europe and New 
Zealand.  The Directions for Use (DFU) will be followed. 
Clinical follow-up will be required at the following time points: pre-discharge, 1 month, 6 
months, and 12 months post index procedure.  Testing required at these at these visits are 
described in section 11.10 of the RANGER II SFA Global Pivotal Protocol. 
The enrollment period will run concurrent with the RANGER II SFA Global Pivotal Trial. 
Figure 2-1 shows the schematic of the RANGER Long Balloon substudy design. 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 103 of 110 
 
 
 
 
 
 
 
 
Figure 2-1: 
RANGER Long Balloon Substudy 
 
 
Will subject sign informed consent? 
A minimum of 50 subjects will be 
treated with Ranger Long 
Balloons 
 
A minimum of 20 subjects will be 
treated with Ranger 200 mm 
DCB 
RANGER DCB 
successfully deployed? 
INTENT TO TREAT 
Pre-discharge Assessments 
Follow-up Evaluation 
at 1 month in office 
Do Not Enroll 
Post-procedure / Pre-discharge 
Assessments 
Follow-up Evaluations 
1 Month, 6 Month, 12 Month 
in office/clinic 
  
End of Trial 
No 
No 
No 
Yes 
Yes 
Yes 
Does subject meet eligibility criteria? 
Guidewire successfully crosses target 
lesion? Successful Pre-dilatation? 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 104 of 110 
 
 
 
 
 
 
2.2.2. Treatment Assignment 
Once the subject has signed the Ethics Committee (IEC/REB) approved study informed consent 
form (ICF), and has met all clinical inclusion and no clinical exclusion criteria, the subject will 
be considered eligible to be enrolled in the RANGER Long Balloon substudy.  Subjects cannot 
be simultaneously enrolled in the RCT and the RANGER Long Balloon substudy.   
If the subject is found to meet exclusion criteria during the angiographic eligibility assessment, 
the subject will be considered a screen failure and should not be enrolled nor should the subject 
be followed post-procedure per protocol.  
All subjects enrolled in the RANGER Long Balloon substudy will be treated with a commercial 
available Ranger DCB. 
   
2.2.3. Device Description 
The Ranger DCB is available in a variety of diameters and balloon lengths.  Device sizes 
intended for use in this RANGER Long Balloon substudy are summarized below in Table 2-2. 
The shaft lengths utilized for the Long Balloon sizes in this substudy are 90 cm and 150 cm for 
diameters 4-7 mm. The Ranger DCB Long Balloons are commercially available in Europe and 
New Zealand (CE Mark #0344, received on 12 July 2017). 
 
Table 2-2: Ranger DCB Long Balloon Device Sizes 
 
 
Balloon Length (mm) 
120 
150 
200 
Balloon 
Diameter 
(mm) 
4.0 
X 
X 
X 
5.0 
X 
X 
X 
6.0 
X 
X 
X 
7.0 
X 
X 
X 
8.0 
 
 
 
 
2.3. Multiple Interventions Using Same Access Site During Index Procedure 
Target Limb 
The target lesion may include two or more tandem lesions, provided that the entire segment of 
tandem lesions is ≤ 180 mm and can be covered with Ranger DCB(s) according to the Directions 
for Use (DFU). 
 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 105 of 110 
 
 
 
 
 
3. Subject Selection 
3.1. Study Population and Eligibility 
Clinical and angiographic inclusion criteria and exclusion for the RANGER Long Balloon 
substudy are included in Table 3-1 and 3-2. Inclusion and exclusion criteria identical to that of 
RANGER II SFA Global Pivotal Protocol (Sections 9.2 and 9.3) except for the CTO length in 
the RANGER Long Balloon substudy are ≤ 150 mm.  Prior to enrollment, a subject must meet 
all of the clinical and angiographic inclusion criteria and none of the clinical and angiographic 
exclusion criteria. 
 
Table 3-1: RANGER Long Balloon Substudy Inclusion Criteria 
Inclusion 
Criteria 
1. Subject (or Legal Guardian) is willing and able to provide consent before 
any study-specific tests or procedures are performed and agree to attend 
all required follow-up visits; 
2. Subject at least 20 years of age; 
3. Chronic symptomatic lower limb ischemia defined as Rutherford 
classification 2, 3, or 4; 
4. Target lesion is in the native SFA and/or PPA down to the P1 segment; 
5. Patent popliteal and infrapopliteal arteries, i.e., single vessel runoff or 
better with at least one of three vessels patent (<50% stenosis) to the 
ankle or foot; 
6. Reference vessel diameter ≥ 4 mm and ≤ 8 mm by visual estimate  
(Use of a radiopaque ruler is recommended);  
7. Angiographic evidence that target lesion consists of a single de novo, 
non-stented and non-atherectomy treated or restenotic lesion (or tandem 
lesions or a combination lesion as defined below) that is: 
a. 
≥ 70% -99% stenotic with total lesion length up to180 mm by visual 
estimate. Use of a radiopaque ruler is recommended. 
b. Occluded with total lesion length ≤ 150 mm by visual estimate.  
Use of a radiopaque ruler is recommended. 
c. 
If lesion is restenotic, most recent PTA treatment must be > 3 months 
prior to  enrollment  
Notes: 
Combination lesions (a non-occlusive lesion that includes a totally occluded 
segment along its length) are eligible provided that the total combined lesion 
length is ≤180 mm. 
Tandem (or “adjacent”) lesions may be enrolled providing they meet all of the 
following criteria: 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 106 of 110 
 
 
 
 
 
 
Separated by a gap of ≤ 30 mm (3 cm) 
 
Total combined lesion length meets requirements (Angiographic 
inclusion criteria (7) including 30 mm gap); and 
 
Able to be treated as a single lesion. 
 
 
Table 3-2: RANGER Long Balloon Substudy Criteria 
Exclusion 
Criteria 
1. Life expectancy, documented in the Investigator’s opinion, of less than 12 
months; 
2. Hemorrhagic stroke or cardiac event (e.g. STEMI, unstable angina) 
within 6 months prior to enrollment; 
3. Known allergies or sensitivities to heparin, aspirin, other 
anticoagulant/antiplatelet therapies, and/or paclitaxel; 
4. Known hypersensitivity or contraindication to contrast dye that, in the 
opinion of the investigator, cannot be adequately pre-medicated; 
5. Chronic renal insufficiency with serum creatinine > 2.0 mg/dL within 30 
days of index procedure or treatment with dialysis; 
6. Platelet count <80,000 mm3 or >600,000 mm3 or history of bleeding 
diathesis; 
7. Receiving immunosuppressive therapy; 
8. Septicemia at the time of enrollment; 
9. Any major (e.g., cardiac, peripheral, abdominal) intervention (including 
in the contralateral SFA/PPA) planned within 30 days post index 
procedure; 
10. Presence of other hemodynamically significant outflow lesions in the 
target limb requiring intervention within 30 days of enrollment; 
11. Failure to successfully cross the target lesion with a guidewire (successful 
crossing means tip of the crossing device is distal to the target lesion in 
the absence of flow-limiting dissections or perforations); 
12. Failure to successfully pre-dilate the target vessel; 
13. Patient has lesion that requires the use of adjunctive primary treatment 
modalities (i.e. laser, atherectomy, scoring/cutting balloon, other 
debulking devices, etc.) during the  index procedure; 
14. History of major amputation in the target limb; 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 107 of 110 
 
 
 
 
 
15. Target lesion or vessel has ever been previously treated with stent (e.g. 
in-stent restenosis) or, surgery. Target lesion or vessel has been treated 
with atherectomy or a DCB  in the past 12 months; 
16. Pregnant or breast feeding; 
17. Presence of aneurysm in the target vessel; 
18. Acute ischemia and/or acute thrombosis of the SFA/PPA prior to 
enrollment; 
19. Patient has significant inflow disease which cannot be treated prior to the 
target lesion treatment; 
20. Patient has perforated targeted vessel as evidenced by extravasation of 
contrast media; 
21. Patient has severe calcification that renders the lesion undilatable;  
22. Current participation in another investigational drug or device clinical 
trial that has not completed the primary endpoint at the time of 
randomization/enrollment or that clinically interferes with the current trial 
endpoints.  
Note: studies requiring extended follow-up for products that were 
investigational, but have become commercially available since then are 
not considered investigational studies. 
Abbreviations: STEMI- ST elevation myocardial infraction 
3.2. Subject Accountability 
Subject accountability is as described in Section 10 of the RANGER II SFA Global Pivotal 
Protocol. 
3.3. Substudy Methods 
The RANGER Long Balloon substudy will follow the RANGER II SFA Global Pivotal Protocol 
for all aspects of study execution including but not limited to Data Management (section 13), 
Deviations (section 15), Compliance (section 17) monitoring (section 18)  and Safety Reporting 
(section 20), with the exception of Device Accountability (section 16)  as commercial devices 
will be used in this substudy.  
3.4. Data Collection 
Subjects enrolled in the RANGER Long Balloon substudy will follow the Data Collection 
schedule as summarized in Table 3-3.  Clinical follow-up will be required at the following time 
points: pre-discharge, 1 month, 6 months, and 12 months post index procedure.  The Data 
Collection schedule in the RANGER Long Balloon substudy is the same as the RANGER II SFA 
Global Pivotal Protocol (section 11.1) with the exception of the following tests that are not 
required:   
• 
Walking Impairment Questionnaire (WIQ) 
• 
EQ-5D Questionnaire 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 108 of 110 
 
 
 
 
 
• 
6 Minute Walk Test (6MWT) 
Table 3-3-: RANGER Long Balloon Substudy Data Collection 
Procedure/Assessment 
Pre-
procedur
e  
During 
Initial 
Procedure 
Pre-
Discharge 
1-month 
 
6-month 
 
12-month 
 
Informed Consent 
X 
 
 
 
 
 
Confirm Inclusion/Exclusion 
X 
X 
 
 
 
 
Demographics and Medical 
History, Height and Weight 
X 
 
 
 
 
 
Pregnancy Test 
X 
 
 
 
 
 
Physical Exam 
X 
 
X 
X 
X 
X 
Complete Blood Count 
(CBC) and platelet count 
X 
 
 
 
 
 
Serum Creatinine 
X 
 
 
 
 
 
Ankle Brachial Index 
Measurements 
X 
 
 
X 
X 
X 
Rutherford Classification 
X 
 
 
X 
X 
X 
Angiogram 
 
X 
 
 
 
 
Enrollment 
 
X 
 
 
 
 
Duplex Ultrasound 
 
 
 
X 
X 
X 
Medication Assessment 
X 
X 
X 
X 
X 
X 
Adverse Events Assessment 
 
X 
X 
X 
X 
X 
 
4. Statistical Considerations 
The RANGER Long Balloon Substudy is an observational substudy.  The non-statistically driven 
performance goal will be compared against the observed 6-month and 12-month primary patency 
in the evaluable long balloon subjects.  
4.1. Primary Endpoint 
The sample size determination for the RANGER Long Balloon substudy is arbitrary and not 
statistically driven. 
4.1.1. Primary Effectiveness Endpoint 
The primary effectiveness endpoint assesses 6-month primary patency as determined by duplex 
ultrasound (DUS).  Lesion patency is defined as freedom from greater than 50% stenosis in the 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 109 of 110 
 
 
 
 
 
absence of clinically-driven TLR. Primary effectiveness is defined as a binary endpoint 
determined by duplex ultrasound (DUS) peak systolic velocity ratio (PSVR) ≤ 2.4 in the absence 
of clinically-driven TLR.   
Statistical Methods 
The non-statistically driven performance goal will be compared against the observed 6-month 
primary patency in the evaluable long balloon subjects. If the observed 6-month primary patency 
is greater than or equal to 50%, the RANGER DCB will be considered to have acceptable 
effectiveness performance in the long balloon population. 
4.1.2. Primary Safety Endpoint 
The primary safety endpoint assesses the occurrence of Major Adverse Events (MAE) defined as 
all-cause death through 1 month, target limb major amputation and/or target lesion 
revascularization (TLR) at 6 and 12 months post-index procedure.  
It is expected that the MAE-free rate will be similar to the rates observed by the RANGER II 
group observed in the RCT.  The MAE-free rate as well as its individual components will be 
reported separately for this subgroup.  
4.2. Additional Endpoints 
Secondary endpoints that will be evaluated, but are not necessarily powered to make statistically-
based conclusions, will be reported separately for this subgroup including: 
 
Technical success defined as successful delivery, balloon inflation and deflation and 
retrieval of the intact trial device without burst below the rated burst pressure (RBP)  
 
Procedural success defined as residual stenosis of ≤ 50% (non-stented subjects) or ≤ 30% 
(stented subjects) by core laboratory evaluation (if core laboratory assessment is not 
available then the site-reported estimate is used)  
 
Clinical success defined as procedural success without procedural complications (i.e. death, 
major target limb amputation, thrombosis of the target lesion, or clinically-driven TLR) prior 
to discharge  
 
Major Adverse Events (MAE) through 12 months. MAEs are defined as all-cause death 
post-index procedure, TLR, and  major target limb amputation   
 
Death of any cause within 30 days, 6, and 12 months  
 
TVR rates at 6, and 12 months  
 
TLR rates at 6, and 12 months  
 
Rate of Primary and Secondary sustained clinical improvement as assessed by changes in 
Rutherford Classification from baseline at 1, 6 and 12 months post-procedure 
 
Rate of Hemodynamic Improvement as assessed by changes in Ankle-Brachial Index (ABI) 
from baseline at 1, 6 and 12 months post-procedure  
 
Duplex-defined binary restenosis (PSVR > 2.4) of the target lesion at 1, 6 and 12 months  
 


S2062 
                            Form/Template 90702637 Rev/Ver AJ 
Confidential 
                                              RANGER II Global Pivotal Protocol 91161457 Rev/Ver AE 
                                                                                                                       Page 110 of 110 
 
 
 
 
 
 
The following endpoints will not be collected in the RANGER Long Balloon substudy: 
 
Walking Improvement (distance) at 6 months and 12 months as assessed by changes in the 
Six Minute Hall Walk Test (6MWT) from baseline  
 
Walking Improvement and Patient Utility Values assessed at 1, 6 and 12 months as assessed 
by change in Walking Impairment Questionnaire (WIQ) and EQ-5D™ from baseline