A Randomized Trial Comparing the Drug-Eluting Stent (DES) Below-the-Knee (BTK) Vascular Stent System (DES BTK Vascular Stent System) vs Percutaneous Transluminal Angioplasty (PTA) Treating Infrapopliteal Lesions in Subjects With Critical Limb Ischemia
Phase: PHASE3
Conditions: Critical Limb Ischemia
Sponsor: Boston Scientific Corporation

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The SAVAL Pivotal Trial 
A Randomized Trial comparing the Drug-Eluting Stent (DES) Below-the-
Knee (BTK) Vascular Stent System (DES BTK Vascular Stent System) vs 
Percutaneous Transluminal Angioplasty (PTA) Treating Infrapopliteal 
Lesions in Subjects With Critical Limb Ischemia  
 
S2348 
CLINICAL INVESTIGATION PLAN 
 
IDE Number: G180073 
EudaMed Number:  CIV-BE-18-05-023947 
 
 
Sponsored By 
Boston Scientific Corporation 
300 Boston Scientific Way 
Marlborough, MA 07152, United States 
 
Boston Scientific International SA 
Parc Val Saint Quentin, Bâtiment H 
2 Rue René Caudron 
78960 Voisins-le-Bretonneux 
France 
 
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. 

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Contact Information 
Role 
Contact  
Clinical Contact 
Boston Scientific Peripheral Interventions 
Three Scimed Place 
Maple Grove, MN 55311 USA 
+1 888-272-1001 
Coordinating Principal 
Investigator(s) 
Global Principal Investigator 
Jihad Mustapha, MD, FACC FSCA 
Clinical Associate Professor of Medicine 
Michigan State University College of Osteopathic Medicine 
East Fee Hall, 965 Fee Rd 
E. Lansing, MI 48825 
Advanced Cardiac & Vascular Amputation Prevention Center 
1525 E. Beltline, NE Suite 101 
Grand Rapids, MI 49525 
 
US Principal Investigator 
Patrick J. Geraghty, MD, FACS, RPVI 
Professor of Surgery and Radiology 
Co-Director, Limb Salvage Center 
Washington University in St. Louis – Department of Surgery 
Section of Vascular Surgery, Campus Box 8109 
660 S. Euclid Avenue 
St. Louis, MO  63110 
 
EU Principal Investigator 
Hendrik (Hans) van Overhagen, MD, PhD, EBIR 
Haga Teaching Hospital 
Els Borst-Eilersplein 275 
2545AA Den Haag 
The Netherlands 
 
Japan Principal Investigator  
Masato Nakamura, MD, PhD 
Professor, Division of Cardiovascular Medicine 
Toho University Ohashi Medical Center 
2-22-36, Ohashi Meguro-ku 
Tokyo 153-8515, Japan 
Investigational Centers A list of investigational centers is provided in the manual of 
operations. A list of investigational centers in Japan is provided 
as a separate attachment to the protocol for Japan centers only. 
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 the investigational centers. 

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Original Release: 19 Dec 2017 
Current Version: F 02 Jul 2021  
Revision 
Version 
Protocol 
Date 
Template number and 
version 
Protocol Section Modified 
Summary of Changes 
Justification for 
Modification 
AA 
19 Dec 2017 
90702637_Rev Ver AI 
N/A 
N/A 
N/A 
B 
19 Mar 2018 
90702637_Rev Ver AI 
• 2.  Protocol synopsis 
• 5.  Device Description 
• 8.  Subject Selection 
• 10. Trial Methods 
• 11. Statistical 
Considerations 
• 12. Health Economics 
 
Outcomes 
• 13. Data Management 
• 15. Device Accountability 
• 18. Potential Risks and 
 
Benefits 
• 19. Safety Reporting 
• 21. Committees 
• 26. Abbreviations and 
 
Definitions 
• Update of Reference Vessel 
Diameter (RVD) 
• Update of investigational device 
characteristics 
• Update of additional endpoints 
• Update of number of subjects 
• Update of definitions/terms 
• Update of eligibility criteria 
• Update of data collection 
requirements 
• Addition of independent wound 
review/assessments 
• Updates to core lab requirements 
• Update of statistical considerations 
/ approach 
• Update of success criteria 
• Addition of unscheduled visits 
related to CLI 
• Updates of potential risks and 
benefits 
• Updates of safety reporting 
requirements 
• Clarification 
• Updates to support 
enrollment for the 
trial 
• Revision to address 
FDA comments 
from pre-
submission review 
C 
26 Mar 2018 
90702637_Rev Ver AI 
• Revision Date 
• Version date updated from 05 
March 2018 to 26 March 2018 
• Correction of date 
D 
28 Mar 2018 
90702637_Rev Ver AI 
• 19. Safety Reporting 
• Updates of safety reporting 
requirements 
• Correction (missing 
text added) 

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Revision 
Version 
Protocol 
Date 
Template number and 
version 
Protocol Section Modified 
Summary of Changes 
Justification for 
Modification 
• 26. Abbreviations and 
 
Definitions 
• Update of definitions 
• Definition added 
(Technical Success) 
E 
23 Sep 2019 
90702637_Rev Ver AK 
• 2.  Protocol synopsis 
• 6. Trial Objectives and 
Endpoints 
• 7. Study Design 
• 8. Subject Selection 
• 9. Subject Accountability 
• 10. Trial Methods 
• 11. Statistical 
Considerations 
• 13. Data Management 
• 19. Safety Reporting 
• 26. Abbreviations and 
Definitions 
• Update to additional endpoints 
• Update of ‘enrolled’ definition for 
phase B 
• Update of target lesion 
requirements 
• Addition of potential sites 
• Addition of 48 and 60 month 
follow-up for survival status 
• Update of in- and exclusion criteria 
(RVD requirements for phase A 
and phase B, clarification on 
number of target vessels/lesions, 
update in timing of pre-existing 
conditions, Rutherford and wound 
requirements) 
• Update of timing of pre-procedure 
assessments 
• Clarification of core lab review and 
central assessment of study data 
• Update to follow-up after subject 
withdrawal 
• Update to potential risks and 
Benefits section to add meta-
analysis results 
• Clarification of start point for 
safety reporting and investigator 
reporting requirements 
• Update of definitions (clarification 
of inflow and outflow lesions, 
addition of definitions) 
• Correction (aligning 
protocol summary 
with body of 
protocol) 
• Clarification 
• Updates per FDA 
request 

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Revision 
Version 
Protocol 
Date 
Template number and 
version 
Protocol Section Modified 
Summary of Changes 
Justification for 
Modification 
F 
02 Jul 2021 
90702637_Rev Ver AP 
• 2. Protocol Synopsis 
• 5. Device Description 
• 6. Trial Objectives and 
Endpoints 
• 7. Study Design 
• 9. Subject Accountability 
• 10. Trial Methods 
• 11. Statistical 
Considerations 
• 13. Data Management 
• 14. Deviations 
• 15. Device Accountability 
for Products Labelled 
Investigational 
• 16. Compliance 
• 19. Safety Reporting 
• 22. Suspension or 
Termination 
• 23. Study Registration and 
Results 
• 27. Abbreviations and 
Definitions 
• Update to primary endpoint timing 
and statistical methods, stent sizes, 
removal of discussion of interim 
analysis, update to study 
assessment (12-month DSA/CTA 
for non-diagnostic DUS), update to 
trial duration and description, 
clarification to start of Phase B 
enrollment 
• Clarification to device name and 
clarification that Investigator 
Brochure is provided to study sites. 
• Clarification to study assessment 
requirements and safety event 
reporting 
• Addition of statistical 
considerations for bailout subjects 
• Clarification of EDC activities and 
access during study closure. 
• Clarification to handling of 
deviations related to COVID-19; 
clarification that sponsor will not 
approve protocol waivers.  
• Clarification of site device 
accountability requirements for 
investigational devices. 
• Clarification of site and 
investigator responsibilities 
• Clarification of reportable events, 
reporting requirements and 
definitions. 
• Clarification of circumstances that 
could lead to premature trial 
termination. 
• Updates per FDA 
discussion and 
feedback 
• Clarification 
• Correction 
• Updates per 
applicable 
regulations and 
guidance 

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Revision 
Version 
Protocol 
Date 
Template number and 
version 
Protocol Section Modified 
Summary of Changes 
Justification for 
Modification 
• Addition of study registration and 
availability of clinical investigation 
report. 
• Update of definitions (clarification 
of source document and source 
data, addition of definitions) 

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2. Protocol Synopsis 
A Randomized Trial comparing the Drug-Eluting Stent (DES) Below-the-Knee (BTK) 
Vascular Stent System (DES BTK Vascular Stent System) vs Percutaneous 
Transluminal Angioplasty (PTA) treating Infrapopliteal Lesions in Subjects with 
Critical Limb Ischemia  
The SAVAL Pivotal Trial 
Trial 
Objective(s) 
Primary objective: To demonstrate a superior patency rate and 
acceptable safety rates in below the knee arteries with lesions treated 
with the DES BTK Vascular Stent System vs percutaneous transluminal 
angioplasty (PTA). 
Secondary objective: To collect additional information on limb salvage 
and overall quality of life in this patient population. 
Planned 
Indication(s) for 
Use  
The DES BTK Vascular Stent System is intended to improve luminal 
diameter in critical limb ischemia (CLI) subjects with lesions of the 
infrapopliteal arteries with reference vessel diameters (RVD) ranging 
from 2.5 – 3.75mm and total lesion lengths up to 140mm. 
Test Device and 
Sizes 
The DES BTK Vascular Stent System for treatment of lesions in the 
infrapopliteal arteries. 
Phase A of the trial will include a single stent size. 
Stent 
Diameter 
(mm) 
Stent Length 
(mm) 
Reference Vessel 
Diameter 
3.5 
80 
2.5 – 3.25mm 
The following additional stent sizes will be added to the trial upon 
regulatory approval. 
Stent 
Diameter 
(mm) 
Stent Length 
(mm) 
Reference Vessel 
Diameter 
3.0 
30, 80, 120 
2.5 – 2.75mm 
3.5 
30, 80, 120 
2.5 – 3.25mm 
4.0 
30, 80, 120 
3.0– 3.75mm 
Control Device 
Percutaneous Transluminal Angioplasty (PTA) balloon catheter. 
Trial Design 
The trial will be conducted in 2 phases.  
Phase A is a global, pivotal, prospective, multicenter, 2:1 randomized 
controlled trial (RCT) evaluating the safety and effectiveness of the DES 

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BTK Vascular Stent System compared to PTA for the treatment of 
lesions located in the arteries below the knee in subjects with CLI.  
In phase B of the trial the DES BTK Vascular Stent will be implanted 
into an additional 100 subjects to collect ongoing safety and 
effectiveness data. 
Planned 
Number of 
Subjects 
1. Phase A randomized controlled trial (RCT): Approximately 201 
subjects are expected to be enrolled to support a 2:1 randomization. 
2. Phase B non-randomized: Approximately 100 additional subjects are 
expected to be enrolled in phase B, which is structured as a non-
randomized single arm study, in which all subjects will be treated 
with the DES BTK Vascular Stent System. 
Planned 
Number of 
Investigational 
Centers/ 
Countries 
The trial will be conducted in the United States, Europe, Japan and 
potentially Singapore, Taiwan and/or Hong Kong, at up to 50 
investigational centers, with up to 35 centers located in the US. 
Enrollment is expected to be distributed approximately equally across 
regions. 
Phase A RCT 
Primary 
Effectiveness 
Endpoint  
Primary Effectiveness Endpoint (Phase A RCT) 
The primary effectiveness endpoint assesses primary patency at 12 
months post-procedure. This effectiveness endpoint is designed to 
demonstrate that the 12-month primary patency for the DES BTK 
treatment group is superior to the PTA treatment group at an overall 
one-sided significance level of 2.5%.   
Primary vessel patency is defined as a binary endpoint to be determined 
via duplex ultrasound (DUS) measuring flow or no flow at the 12-month 
follow-up visit in the absence of clinically-driven target lesion 
revascularization (TLR) or bypass of the target lesion. All DUS readings 
will be assessed by an independent core laboratory. 
Primary Safety 
Endpoint(s) 
Primary Safety Endpoint (Phase A RCT) 
The primary safety endpoint assesses major adverse events (MAE) at 12 
months post-procedure. This safety endpoint is designed to demonstrate 
that the 12-month MAE-free rate for the DES BTK treatment group is 
non-inferior to the PTA treatment group at an overall one-sided 
significance level of 2.5%.  
A major adverse event is defined as: 
• Above ankle amputation of the index limb 
• Major re-intervention (new bypass graft, jump/interposition 
graft, or thrombectomy/thrombolysis) 

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• Perioperative (30 day) mortality 
Additional 
Endpoints 
• Primary and assisted-primary patency at 1, 6, 12, 24, and 36 
months post-procedure 
• Clinically-driven target lesion revascularization (TLR) rate at 
each time point  
• Hemodynamic outcomes (changes in Ankle-Brachial Index 
[ABI] and/or Toe-Brachial Index [TBI]) at 6 and 12 months post 
procedure 
• Wound assessment (changes in wound characteristics) 
• Major amputation rate 
• Change in Rutherford classification at 3, 6, 12, 24, and 36 
months post procedure 
• Quality of Life (QOL) changes at 1, 3, 6 and 12 months post 
procedure  
• Adverse events (AEs) at each time point (to be classified as 
major, serious, non-serious, unanticipated, procedure-related and 
device-related) 
• 30-day unplanned hospital readmission rate1 
• Survival rate at 4 years and 5 years post-procedure 
Method of 
Assigning 
Subjects to 
Treatment 
Phase A RCT: Eligible subjects will be randomized in a 2:1 fashion (2 
DES BTK to 1 PTA). 
Phase B Non-Randomized 
Primary Safety 
Endpoint 
Primary safety endpoint (Phase B non-randomized) 
The primary safety endpoint assesses MAEs at 12 months post-
procedure. This safety endpoint is designed to demonstrate that the 12-
month MAE-free rate in subjects treated with the DES BTK Vascular 
Stent System exceeds a performance goal of 71% at an overall one-sided 
significance level of 2.5%.2 
Note that the 12-month primary patency rate will be observed in phase B 
non-randomized. 
 
A major adverse event is defined as: 
• Above ankle amputation of the index limb 
• Major re-intervention (new bypass graft, jump/interposition 
graft, or thrombectomy/thrombolysis) 
• Perioperative (30 day) mortality 

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Additional 
Endpoints 
 
Patency-Based Assessments 
• Primary and assisted-primary patency at 1, 6, 12, 24, and 36 
months post procedure  
• Need for clinically-driven TLR 
Therapeutic success at 12 months post procedure 
• Rutherford 4: Ischemic pain relief  
• Rutherford 5: Partial or complete healing of wound 
Other Assessments 
• Change in Rutherford classification at 3, 6, 12, 24 and 36 months 
post procedure 
• QOL changes at 1, 3, 6, and 12 months post procedure 
• Hemodynamic outcomes (changes in ABI and/or TBI) at 6 and 
12 months post procedure 
• Wound assessment (changes in wound characteristics) 
• Limb salvage at each time point 
• Major amputation-free survival 
• Adverse events at each time point (to be classified as major, 
serious, non-serious, unanticipated, procedure-related and 
device-related) 
• 30-day unplanned hospital readmission rate 
• Survival rate at 4 years and 5 years post-procedure 
Method of 
Assigning 
Subjects to 
Treatment  
All subjects enrolled in phase B non-randomized will be treated with the 
DES BTK Vascular Stent System. 
Follow-up 
Schedule 
Follow-up visit Schedule: 
• Follow-up office visits are required at 1, 3, 6, 12, 24, and 36 months 
post procedure  
• Telephone follow-up visits are required at 18 and 30 months post 
procedure 
• Telephone follow-up visit and/or medical chart review and/or 
publicly available records consultation at 48 months and 60 months 
post-procedure 
 
Endpoint Assessment: 
• Assessment of the primary effectiveness endpoint will occur at the 
12-month follow-up visit 
• Assessment of the primary safety endpoint will occur at the 12-
month follow-up visit  
 
Planned protocol-required testing: 

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• ABI and TBI, when subject condition permits (ie, no toe amputation 
or presence of calcified/incompressible vessels) 
• Angiography during the index procedure to assess technical success 
and procedural success 
• Duplex ultrasound (Note: If a diagnostic duplex ultrasound cannot be 
adequately achieved for the 12-month follow-up visit, then 
computerized tomography angiography [CTA] or digital subtraction 
[DSA] angiography must be conducted) 
• High definition x-ray of the DES BTK test device(s) 
• Wound assessment and image 
 
Phase A RCT will be considered complete for the primary effectiveness 
endpoint and the primary safety endpoint after all subjects in phase A 
RCT have completed the 12-month follow-up visit, are withdrawn prior 
to the 12-month follow-up visit, have died or, the last 12-month follow-
up visit window has closed.  
Phase B non-randomized will be considered complete for the primary 
safety endpoint after all subjects in phase B have completed the 12-
month follow-up visit, are withdrawn prior to the 12-month follow-up 
visit, have died or, the last 12-month follow-up visit window has closed. 
The entire trial will be considered complete with regard to all follow-up, 
after all subjects have completed the 60-month follow-up visit, are 
withdrawn prior to the 60-month follow-up visit, have died or, the last 
60-month follow-up visit window has closed. 
Trial Duration 
Phase A RCT 
Enrollment in phase A RCT is expected to take approximately two years 
to enroll the approximately 201 subjects, and 5 years of follow-up is 
planned.  
Phase B non-randomized: 
Enrollment in phase B non-randomized is planned to start after 
enrollment in phase A RCT is complete.  The timing for beginning phase 
B enrollment will be communicated by the Boston Scientific clinical 
trial team. 
Enrollment of the approximately 100 additional subjects into phase B 
non-randomized is expected to take approximately 1 year, and 5 years of 
follow-up is planned. 
The total duration from the enrollment of the first subject in phase A 
RCT to the last follow-up in phase B non-randomized cohort is expected 
to be approximately 11 years. 
Participant 
Duration 
Subject participation will be 5 years post index procedure. Subjects, who 
are enrolled/randomized into the DES BTK arm but do not have the 

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DES BTK stent successfully implanted, will be followed for 30 days for 
safety, and be withdrawn from the trial afterwards. 
Trial 
Enrollment 
There are 2 stages of evaluation for a subject’s trial enrollment: 
1. Pre-procedure criteria 
Trial candidates must satisfy all pre-procedure inclusion criteria and 
none of the pre-procedure exclusion criteria prior to the intervention. 
2. Intra-procedural criteria 
Subjects must satisfy all intra-procedure inclusion criteria and none of 
the intra-procedure exclusion criteria to be eligible for 
randomization/enrollment into the trial.  
Enrollment occurs at the time of randomization (i.e. when a treatment 
assignment is received by the study site) for phase A RCT and at the 
time the DES BTK stent is introduced into the subject’s vasculature for 
phase B non-randomized. 
Pre-procedure 
Inclusion 
Criteria 
1. Subject is 18 years or older and has signed and dated the trial 
informed consent form (ICF). Note: For subjects in Japan who are 
less than 20 years of age, the subject’s legal representative must 
provide written informed consent in addition to the subject 
2. Subject is willing and able to comply with the trial testing, 
procedures and follow-up schedule 
3. Subject has chronic, symptomatic lower limb ischemia, determined 
by Rutherford categories 4 or 5 in the target limb, with wound(s) 
confined to toes/forefoot 
4. Subject is a male or non-pregnant female. If female of child-bearing 
potential, and if sexually active must be using, or agree to use, a 
medically–acceptable method of birth control as confirmed by the 
investigator 
Pre-Procedure 
Exclusion 
Criteria 
1. Life expectancy ≤ 1 year 
2. Stroke ≤ 90 days prior to the procedure date 
3. Prior or planned major amputation in the target limb 
4. Previous surgery in the target vessel(s) (including prior ipsilateral 
crural bypass) 
5. Previously implanted stent in the target vessel(s) 
6. Failed PTA of target lesion/vessel ≤ 60 days prior to the procedure 
date 
7. Renal failure as measured by a GFR ≤ 30ml/min per 1.73m2, 
measured ≤ 30 days prior to the procedure date 
8. Subject has a platelet count ≤ 50 or ≥ 600 X 103/µL ≤ 30 days prior 
to the procedure date 
9. NYHA class IV heart failure 

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10. Subject has symptomatic coronary artery disease (ie, unstable 
angina) 
11. History of myocardial infarction or thrombolysis ≤ 90 days prior to 
the procedure date 
12. Non-atherosclerotic disease resulting in occlusion (eg, embolism, 
Buerger’s disease, vasculitis) 
13. Subject is currently taking Canagliflozin 
14. Body Mass Index (BMI) <18 
15. Active septicemia or bacteremia 
16. Coagulation disorder, including hypercoagulability  
17. Contraindication to anticoagulation or antiplatelet therapy  
18. Known allergies to stent or stent components 
19. Known allergy to contrast media that cannot be adequately pre-
medicated prior to the interventional procedure 
20. Known hypersensitivity to heparin 
21. Subject is on a high dose of steroids or is on immunosuppressive 
therapy 
22. Subject is currently participating, or plans to participate in, another 
investigational trial that may confound the results of this trial (unless 
written approval is received from the Boston Scientific study team) 
Intra-Procedure 
Inclusion 
Criteria 
1. Stenotic, restenotic or occlusive target lesion(s) located in the 
tibioperoneal trunk, anterior tibial, posterior tibial and/or peroneal 
artery(ies).  
• Target lesion(s) must be at least 4cm above the ankle joint 
• A single target lesion per vessel, in up to 2 vessels, in a single 
limb 
• Degree of stenosis ≥ 70% by visual angiographic assessment 
• Reference vessel diameter (RVD) is between 2.5 – 3.25mm 
for phase A RCT 
• RVD is between 2.5 – 3.75mm for phase B non-randomized 
(Note: RVD is dependent on stent size being used. Refer to 
DFU for specific requirements) 
• Total target lesion length (or series of lesion segments) to be 
treated is ≤ 70mm for phase A RCT prior to data monitoring 
committee (DMC) approval for stent overlap 
(Note: Lesion segment(s) must be fully covered with one 
DES BTK stent, if randomized to stent) 
• Total target lesion length (or series of lesion segments) to be 
treated is ≤ 140 mm for phase A RCT after DMC approval 
for stent overlap 
(Note: Lesion segment(s) must be fully covered with up to 
two DES BTK stents, if randomized to stent) 
• Total target lesion length (or series of lesion segments) to be 
treated is ≤ 140mm for phase B non-randomized 

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(Note: Lesion segment(s) must be fully covered with up to 
two DES BTK stents) 
2. Target vessel(s) reconstitute(s) at or above the stenting limit zone 
(4cm above the ankle joint) 
3. Target lesion(s) is located in an area that may be stented without 
blocking access to patent main branches 
4. Treatment of all above the knee inflow lesion(s) is successful prior to 
treatment of the target lesion  
5. Guidewire has successfully crossed the target lesion(s) 
Intra-procedure 
Exclusion 
Criteria 
1. Angiographic evidence of intra-arterial acute/subacute thrombus or 
presence of atheroembolism  
2. Treatment required in > 2 target vessels (Note: a target lesion 
originating in one vessel and extending into another vessel is 
considered 1 target vessel) 
3. Treatment requires the use of alternate therapy in the target 
vessel(s)/lesion(s), (eg, atherectomy, cutting balloon, re-entry 
devices, laser, radiation therapy)  
4. Aneurysm is present in the target vessel(s) 
5. Extremely calcified lesions 
Multiple 
Interventions / 
Index 
Procedure 
Multiple interventions in the target limb are permitted during the index 
procedure for the treatment of above the knee inflow lesions (lesions 
located in the iliac artery, superficial femoral artery and/or popliteal 
artery). Inflow lesions may be treated according to the investigator’s 
standard procedures using commercially available devices. If 
atherectomy is performed, the use of an embolic protection device is 
strongly recommended.  
The inflow interventions must be deemed successful (eg, absence of 
distal embolization, optimal restoration of inflow, etc) prior to the 
randomization and/or treatment of the target lesion(s). 
Drug-coated balloons are not permitted for treatment of the target 
lesion(s) in the trial.  
Treatment of outflow lesion(s) (lesions located in the segment of the 
target vessel distal to the target lesion) is not permitted. 
Successful guidewire crossing of all target lesion(s) is required prior to 
randomization/enrollment into the trial.  
Statistical Methods in Phase A RCT 
Primary 
Effectiveness 
Statistical 
Hypothesis and 
The primary effectiveness hypothesis to be tested is that the 12-month 
primary patency in subjects treated with the DES BTK Vascular Stent 
System is superior to subjects treated with PTA at an overall one-sided 
significance level of 2.5%. 

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Test Method 
 
Phase A RCT 
A Wald z-test for the difference in 12-month primary patency will be 
used to assess the effectiveness hypothesis. 
H0: Pt - Pc ≤  0 
H1: Pt - Pc > 0 
where Pt and Pc are the 12-month primary patency for the DES BTK 
stent and PTA, respectively. 
Primary Safety 
Statistical 
Hypothesis and 
Test Method 
Phase A RCT 
The primary safety hypothesis to be tested is that the 12-month MAE-
free rate in subjects treated with the DES BTK Vascular Stent System is 
non-inferior to subjects treated with PTA at an overall one-sided 
significance level of 2.5%. 
A Wald z-test for the difference in 12-month MAE-free rate will be used 
to assess the safety hypothesis. 
H0: Pt - Pc  ≤ ∆ 
H1: Pt - Pc > ∆ 
where Pt and Pc are the 12-month MAE-free rate for DES BTK stent 
and PTA, respectively, and Δ (delta) is the non-inferiority margin of -
10%.3 4  
Success Criteria 
for Phase A 
RCT 
The DES BTK Vascular Stent System will be concluded to be superior 
to PTA for device effectiveness if the one-sided lower bound of 97.5% 
confidence interval on the difference between treatment groups (DES 
BTK – PTA) in 12-month primary patency is greater than zero. 
The DES BTK Vascular Stent System will be concluded to have no 
safety concerns if the one-sided lower bound of 97.5% confidence 
interval on the difference between treatment groups (DES BTK – PTA) 
in 12-month MAE-free is greater than -0.1. 
The trial will be concluded a success if both the primary effectiveness 
endpoint and the primary safety endpoint are met. 
Sample Size 
Parameters 
 
Phase A RCT 
The overall sample size is driven by the primary effectiveness endpoint. 
Approximately 201 subjects are planned to be enrolled in phase A RCT. 
The sample size justification for phase A RCT is based on the following 
assumptions. 
• Power ≥ 84% 
• One-sided overall significance level (alpha) = 2.5% 
• Expected PTA 12-month primary patency = 40% 
• DES BTK to demonstrate 25% treatment effect 
• Allocation (DES BTK vs PTA) = 2:1 
• A minimum of 150 evaluable subjects are required at 12 months 
(ideally 100 in DES BTK arm and 50 in PTA arm) 
• Attrition rate in 12 months ≤25% 

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• Approximately 201 subjects are planned to be randomized in 2:1 
fashion prior to the procedure 
Analysis Sets 
 
Phase A RCT 
 
The intention-to-treat (ITT) population will be the primary analysis set 
for assessing the primary hypotheses. Both per-protocol (PP) and as-
treated (AT) populations will be the secondary analyses sets for 
reference. 
• ITT: all randomized subjects will be included in the ITT analysis 
set, regardless of whether the subjects receive the assigned 
treatment. The DES BTK and PTA arms will be compared as 
randomized.  
• PP: only randomized subjects who receive the assigned index 
treatment will be included in the PP analysis set. The DES BTK 
and PTA arms will be compared as randomized and correctly 
received index treatment. 
• AT: all subjects who receive either the DES BTK stent or PTA at 
the index procedure will be included in the AT analysis set. DES 
BTK and PTA arms will be compared as treated, excluding 
subjects who do not receive the DES BTK stent or PTA. 
Statistical Methods in Phase B Non-randomized 
Testing 
Hypotheses 
Strategy 
Phase B Non-
randomized 
The primary safety hypothesis will be tested at 12 months post index 
procedure for all evaluable subjects from phase A RCT and the 
additional 100 phase B subjects. 
Primary Safety 
Statistical 
Hypothesis and 
Test Method 
 
Phase B Non-
randomized 
The primary safety hypothesis to be tested is that the 12-month MAE-
free rate in subjects treated with the DES BTK Vascular Stent System 
exceeds a performance goal (PG) of 71%1 at one-sided significance level 
of 2.5%. 
A Wald z-test will be used to assess the safety hypothesis of meeting the 
PG in the 12-month MAE-free rate.  
H0: Pt ≤ PG (not met) 
H1: Pt > PG (met) 
where Pt is the 12-month MAE-free rate for the subjects treated with the 
DES BTK Vascular Stent System and the PG is the performance goal. 
Success Criteria 
Phase B Non-
randomized 
The DES BTK Vascular Stent System will be concluded as meeting the 
PG for device safety if the one-sided lower bound of 97.5% confidence 
interval on the observed 12-month MAE-free rate is greater than 0.71. 
Sample Size 
Parameters 
The sample size is driven by the safety PG. 
• Power ≥ 80% 

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Phase B Non-
randomized 
• One-sided significance level (alpha) = 2.5% 
• Safety PG = 71%2 in the 12-month MAE-free rate  
• Expected 12-month MAE-free rate = 80% 
• A minimum of 186 (DES BTK) evaluable subjects are required 
at 12 months 
• Attrition rate at 12 months ≤ 20% 
• Up to 234 (DES BTK) subjects are planned to be enrolled, 
including 134 DES BTK subjects from phase A RCT and an 
additional 100 DES BTK subjects to be enrolled in phase B non-
randomized. 
Analysis Set 
Phase B Non-
randomized 
All subjects who receive the DES BTK Vascular Stent System will be 
assessed against the pre-specified safety PG.  
Medications 
Anti-coagulation and antiplatelet therapy is to be administered prior to 
and during the index procedure according to the investigator’s standard 
procedures. 
Dual antiplatelet therapy is required post-procedure through the 6-month 
visit and is strongly recommended to continue through the 12-month 
visit for subjects who receive the DES BTK stent.* 
Subjects who are randomized to PTA in phase A RCT will receive 
antiplatelet therapy according to the investigator’s standard of care. 
*A subject may be exempt from dual antiplatelet requirement when 
anticoagulation therapy is required for comorbidity treatment and when, 
in the judgement of the investigator, the addition of dual antiplatelet 
therapy would pose an unacceptable hemorrhage risk. 
DMC and CEC 
The data monitoring committee (DMC) will review overall trial conduct 
and safety. The DMC will review approximately 46 randomized 
subjects’ aggregate safety data for the approval to use overlapping stents 
in the trial. The DMC charter will outline this process. 
The clinical events committee (CEC) will adjudicate the following 
endpoints and major adverse events reported by the trial investigators: 
• All deaths 
• Clinically-driven TLR 
• TVR 
• Target limb major amputations 
• Target Lesion stent thrombosis 
Core 
Laboratories / 
Central 
The following core laboratories will be established for the central 
assessment of key data collected during the trial: 
• Angiography:  

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assessment of 
study data 
 
o To assess angiograms taken during the index procedure, 
and in the follow-up period for subsequent 
revascularization procedures when collected according to 
the investigational center’s standard procedures 
o To assess CTA or DSA angiographies taken at the 12-
month follow-up visit in case the 12-month DUS is non-
diagnostic 
o To confirm stent fractures identified by the X-ray core lab 
• Ultrasound: to assess ultrasounds taken during the follow-up 
period for lesion and stent patency 
• X-ray: to assess high definition x-rays for stent integrity 
• Independent Wound Reviewer: to review wound assessment data 
and images. 
 
 

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3. Table of Contents 
1. 
TITLE PAGE  .......................................................................................................................1 
2. 
PROTOCOL SYNOPSIS .........................................................................................................7 
3. 
TABLE OF CONTENTS .......................................................................................................19 
3.1. Table of Figures .....................................................................................................25 
3.2. Table of Tables ......................................................................................................25 
4. 
INTRODUCTION AND BACKGROUND ................................................................................26 
4.1. Boston Scientific Drug-Eluting Stent Regulatory Approval History ...............27 
4.2. Trial Rationale .......................................................................................................27 
5. 
DEVICE DESCRIPTION ......................................................................................................27 
5.1. The DES BTK Vascular Stent System ................................................................28 
5.2. DES BTK Delivery System ...................................................................................29 
5.3. DES BTK Stent Coating .......................................................................................29 
5.3.1. 
Primer Polymer and Drug Matrix Co-polymer Carrier ............................30 
5.3.2. 
Paclitaxel Drug .........................................................................................30 
5.4. Manufacturer .........................................................................................................31 
5.5. Labeling of Investigational Device .......................................................................31 
5.6. Product Receipt and Tracking .............................................................................32 
5.7. Investigational Product Storage...........................................................................32 
5.8. Product Returns ....................................................................................................32 
5.9. Control Device .......................................................................................................32 
6. 
TRIAL OBJECTIVES AND ENDPOINTS ...............................................................................32 
6.1. Phase A RCT .........................................................................................................33 
6.2. Phase B non-randomized ......................................................................................33 
7. 
STUDY DESIGN .................................................................................................................34 
7.1. Phase A RCT .........................................................................................................34 
7.2. Phase B non-randomized ......................................................................................35 
7.3. Scale and Duration ................................................................................................35 
7.4. Treatment Assignment ..........................................................................................38 
7.4.1. 
Phase A RCT ............................................................................................38 

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7.4.2. 
Phase B non-randomized ..........................................................................38 
7.5. Treatment and Control .........................................................................................38 
7.6. Target and Non-Target Lesions ...........................................................................38 
7.7. Justification for the Trial Design .........................................................................39 
8. 
SUBJECT SELECTION ........................................................................................................40 
8.1. Trial Population and Eligibility ...........................................................................40 
8.2. Inclusion Criteria ..................................................................................................40 
8.3. Exclusion Criteria .................................................................................................42 
9. 
SUBJECT ACCOUNTABILITY .............................................................................................43 
9.1. Point of Enrollment ...............................................................................................43 
9.2. Withdrawal ............................................................................................................43 
9.3. Lost to Follow-Up ..................................................................................................44 
9.4. End-of-Study Definition........................................................................................45 
10. TRIAL METHODS ..............................................................................................................45 
10.1. Data Collection ......................................................................................................45 
10.2. Visit Windows ........................................................................................................47 
10.3. Trial Candidate Screening ...................................................................................47 
10.3.1. Strategies for Recruitment and Retention ...................................................47 
10.4. Informed Consent..................................................................................................48 
10.5. Medications ............................................................................................................48 
10.6. Quality of Life ........................................................................................................48 
10.7. Wound Care and Data Collection ........................................................................49 
10.8. Pre-procedure ........................................................................................................49 
10.9. Index Procedure ....................................................................................................50 
10.9.1. Target lesion requirements: ......................................................................50 
10.9.2. Randomization/Enrollment .......................................................................51 
10.9.3. Guidelines for treatment of flow-limiting dissection or other loss of target 
vessel patency at the completion of the target lesion pre-treatment and 
definition of bailout stenting .....................................................................52 
10.9.4. Re-intervention in the target vessel ..........................................................53 
10.10. 
Follow-up visits .......................................................................................53 
10.11. 
Telephone Follow-up ..............................................................................54 

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10.12. 
Trial Completion .....................................................................................54 
10.13. 
Source Documents ..................................................................................55 
11. STATISTICAL CONSIDERATIONS ......................................................................................55 
11.1. Primary Endpoints for Phase A RCT .................................................................55 
11.1.1. Primary Effectiveness Endpoint ...............................................................56 
11.1.1.1. Effectiveness Hypothesis .........................................................56 
11.1.1.2. Effectiveness Sample Size .......................................................56 
11.1.1.3. Effectiveness Statistical Methods ............................................56 
11.1.2. Primary Safety Endpoint ...........................................................................57 
11.1.2.1. Safety Hypothesis ....................................................................57 
11.1.2.2. Safety Sample Size/Power Analysis ........................................57 
11.1.2.3. Safety Statistical Methods ........................................................57 
11.1.3. Success Criteria ........................................................................................58 
11.2. Primary Endpoint for Phase B Non-randomized ...............................................58 
11.2.1. Primary Safety Endpoint ...........................................................................58 
11.2.1.1. Safety Hypotheses ....................................................................58 
11.2.1.2. Safety Sample Size/Power Analysis ........................................58 
11.2.1.3. Safety Statistical Methods ........................................................59 
11.2.2. Success Criteria ........................................................................................59 
11.3. General Statistics Methods ...................................................................................59 
11.3.1. Analysis Sets .............................................................................................59 
11.3.1.1. Intention-to-treat (ITT) ............................................................59 
11.3.1.2. Per-protocol (PP) .....................................................................59 
11.3.1.3. As-treated (AT) ........................................................................60 
11.3.1.4. Bailout Subjects Considerations ..............................................60 
11.3.2. Randomization Scheme ............................................................................60 
11.3.3. Control for Systematic Error/Bias ............................................................60 
11.3.4. Enrollment for Each Investigative Center ................................................61 
11.3.5. Baseline Data Analysis .............................................................................61 
11.3.6. Additional Endpoint Assessments ............................................................61 
11.3.7. Interim Analyses .......................................................................................61 
11.3.8. Subgroup Analyses ...................................................................................61 
11.3.9. Justification of Pooling .............................................................................62 
11.3.9.1. Investigational Center Poolablity .............................................62 
11.3.9.2. US, Europe, and Japan Poolablity ............................................62 
11.3.10. Sensitivity Analysis for Missing Outcome Data ......................................62 
11.3.11. Multivariable Analyses .............................................................................63 
11.3.12. Analyses Software ....................................................................................63 
11.3.13. Changes to Planned Analyses ...................................................................63 

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12. HEALTH ECONOMICS OUTCOMES ...................................................................................63 
13. DATA MANAGEMENT .......................................................................................................63 
13.1. Data Collection, Processing, and Review ............................................................63 
13.2. Data and Record Retention ..................................................................................64 
13.3. Core Laboratories / Central assessment of study data ......................................64 
14. DEVIATIONS......................................................................................................................65 
15. DEVICE ACCOUNTABILITY FOR PRODUCTS LABELLED INVESTIGATIONAL ..................66 
16. COMPLIANCE ....................................................................................................................67 
16.1. Statement of Compliance ......................................................................................67 
16.2. Investigator Responsibilities ................................................................................67 
16.2.1. Delegation of Responsibility ....................................................................69 
16.3. Institutional Review Board/ Ethics Committee ..................................................69 
16.4. Sponsor Responsibilities .......................................................................................69 
16.4.1. Role of Boston Scientific Representatives ...............................................70 
16.5. Insurance ................................................................................................................70 
17. MONITORING ....................................................................................................................70 
18. POTENTIAL RISKS AND BENEFITS ...................................................................................71 
18.1. Anticipated Adverse Events Associated with use and the Implantation of the 
DES BTK Vascular Stent System during an endovascular procedure ............71 
18.2. Adverse Events Unique to the Paclitaxel Drug Coating ....................................71 
18.3. Risks Associated with Participation in the Clinical Trial..................................72 
18.4. Possible Interactions with Concomitant Medical Treatments ..........................72 
18.5. Risk Minimization Actions ...................................................................................72 
18.6. Anticipated Benefits ..............................................................................................73 
18.7. Risk to Benefit Rationale ......................................................................................73 
19. SAFETY REPORTING .........................................................................................................73 
19.1. Reportable Events by investigational center to Boston Scientific ....................73 
19.2. Definitions and Classification...............................................................................74 
19.3. Relationship to Study Device(s)(Investigational Device and Comparator 
Device) and/or Study Procedure ..........................................................................77 

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19.4. Investigator Reporting Requirements .................................................................79 
19.5. Boston Scientific Device Deficiencies ...................................................................80 
19.6. Reporting to Regulatory Authorities / IRBs / ECs / Investigators ...................81 
20. INFORMED CONSENT ........................................................................................................81 
21. COMMITTEES ...................................................................................................................83 
21.1. Executive Committee ............................................................................................83 
21.2. Safety Monitoring Process ....................................................................................83 
21.3. Clinical Events Committee ...................................................................................83 
21.4. Data Monitoring Committee ................................................................................83 
21.5. Independent Wound Assessment .........................................................................84 
22. SUSPENSION OR TERMINATION........................................................................................84 
22.1. Premature Termination of the Study ..................................................................84 
22.1.1 
Criteria for Premature Termination of the Study ......................................84 
22.2. Termination of Study Participation by the Investigator or Withdrawal of 
IRB/EC Approval ..................................................................................................85 
22.3. Requirements for Documentation and Subject Follow-up ................................85 
22.4. Criteria for Suspending/Terminating a Study Center .......................................85 
23. STUDY REGISTRATION AND RESULTS .............................................................................86 
23.1. Study Registration .................................................................................................86 
23.2. Clinical Investigation Report ...............................................................................86 
24. PUBLICATION POLICY ......................................................................................................86 
25. REIMBURSEMENT AND COMPENSATION FOR SUBJECTS .................................................87 
25.1. Subject Reimbursement ........................................................................................87 
25.2. Compensation for Subject’s Health Injury.........................................................87 
26. BIBLIOGRAPHY .................................................................................................................88 
27. ABBREVIATIONS AND DEFINITIONS .................................................................................89 
27.1. Abbreviations.........................................................................................................89 
27.2. Definitions ..............................................................................................................91 
28. APPENDICES .....................................................................................................................98 

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28.1. Appendix A: Affect to Medicare Beneficiaries (US only) ..................................98 
 
 
 

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3.1. Table of Figures 
Figure 5.1-1: DES BTK Geometry ......................................................................................... 29 
Figure 5.2-1: DES BTK Delivery System .............................................................................. 29 
Figure 5.3-1: Dual Layer Illustration ...................................................................................... 30 
Figure 5.3-2: Poly(n-butyl methacrylate) (PBMA) ................................................................ 30 
Figure 5.3-3: Poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) .................... 30 
Figure 5.3-4: Chemical Structure of Paclitaxel (PTx) ............................................................ 31 
Figure 7.3-1: DES BTK Phase A RCT Design ....................................................................... 36 
Figure 7.3-2: Phase B non-randomized Design ...................................................................... 37 
 
3.2. Table of Tables 
Table 4.1-1: Boston Scientific Drug-Eluting Stent Regulatory Approval Summary ............. 27 
Table 5.1-1: DES BTK stent size for Phase A randomized controlled trial (RCT) ................ 28 
Table 5.1-2: Additional stent sizes to be added for the trial upon regulatory approval .......... 29 
Table 8.2-1: Inclusion Criteria ................................................................................................ 41 
Table 8.3-1: Exclusion Criteria ............................................................................................... 42 
Table 10.1-1: Data Collection Requirements by Visit ............................................................ 46 
Table 10.2-1: Protocol Visit Windows ................................................................................... 47 
Table 10.2-2: Telephone/medical chart/public record Follow-up Windows .......................... 47 
Table 19.2-1: Safety Definitions ............................................................................................. 74 
Table 19.3-1: Criteria for Assessing Relationship of Trial Device(s) (Investigational Device 
and Comparator Device) or Procedure to Adverse Event ................................... 77 
Table 19.3-2: Criteria for Assessing Relationship of Antiplatelet Medication to an AE ....... 78 
Table 19.4-1: Investigator Reporting Requirements ............................................................... 79 
Table 26.2-1: Definitions ........................................................................................................ 91 
 
 

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4. Introduction and Background 
Critical Limb Ischemia (CLI) is a progression of peripheral artery disease (PAD), 
characterized by severe obstruction of arteries (especially in the lower limbs) which reduces 
blood flow to the extremities and places patient tissue viability at risk. 5  Patients with CLI 
experience severely debilitating clinical outcomes, including severe pain in the impacted 
limb even at rest, risk of open ulceration, gangrene and, if not treated properly, amputation of 
limb(s). These outcomes reduce patient mobility and quality of life. 5 Patients with CLI also 
experience increased risk of mortality, increasing further for those undergoing limb 
amputations. Diabetics with CLI are at particularly high risk for advanced complications; 
studies indicate that within one year of CLI diagnosis, 40% to 50% of diabetics will 
experience an amputation. 6   
The standard of care for CLI patients has historically utilized one of two methods for 
revascularization of diseased infrapopliteal vessels, either by surgical bypass or percutaneous 
transluminal angioplasty (PTA). While surgical bypass has shown to be a potential avenue 
for revascularization of BTK arteries and was considered the frontline therapy for CLI 
patients, the surgery is invasive and technically challenging, especially considering the 
fragile health state of the affected population. Due to these challenges, this procedure 
continues to experience significant variability in outcomes, patient healing, and costs. 7   
There are important limitations and risks associated with bypass surgery, including up to 
20% of patients experiencing significant postoperative morbidity and 10 to 20% of patients 
experiencing frequent wound complications. Additionally, new stenosis within the vein graft 
conduit occurs in 30% to 40% of patients within the first two years after surgery. 
In recent years, the arrival of endovascular treatment of CLI has been driven by the continued 
evolution of catheter-based technologies due to the benefits of a less invasive approach in 
treating this fragile population.8  It is well established that recovery from PTA is significantly 
faster than open surgery. Patients treated with PTA do not experience common surgical 
complications associated with bypass, such as wound morbidity. PTA has been shown to 
have similar outcomes to that of surgical bypass. 9,10 
Intravascular stents were developed in response to the inability of PTA to prevent immediate 
or near-term loss of arterial patency due to dissection or lesion recoil. The scaffolding 
support provided by stent technology is a primary reason for their utilization. Drug-eluting 
stents were developed to reduce neointimal hyperplasia to address the impact of restenosis 
rates associated with PTA therapy. Infrapopliteal atherosclerotic lesions characterized by 
longer calcified lesions in smaller diameter vasculature do not respond well to PTA. 11 
The benefits of using short coronary drug-eluting stents has been well-studied in 
infrapopliteal lesions; randomized clinical trials have shown a benefit in terms of patency and 
re-intervention rates as compared to PTA 3,4,12 with long-term results reported out to 5 years. 
13  However, none of these coronary drug-eluting stents have been approved in the United 
States for infrapopliteal use. There are major limitations of using coronary drug-eluting stents 
below the knee, including the limited available lengths relative to the artery lengths to be 
treated, relative inflexibility, and risk of fracture given the unique conditions of infrapopliteal 

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anatomy. The DES BTK Vascular Stent System was designed to address the requirements for 
treatment of the longer lesions associated with CLI below the knee. 
4.1. Boston Scientific Drug-Eluting Stent Regulatory Approval History 
Boston Scientific has an extensive global market history of drug-eluting stents, as 
summarized in Table 4.1-1.  
Table 4.1-1: Boston Scientific Drug-Eluting Stent Regulatory Approval Summary 
Device 
CE Mark 
Date 
Associated 
IDE# 
Associated 
PMA# 
Japan Approval 
ELUVIA 
Feb 2016 
G150171 
P180011 
Dec.6.2018 
23000BZX00374000 
PROMUS Element 
Oct. 2009 
NA 
NA 
Feb.8.2012* 
22400BZX00031000 
PROMUS Element Plus 
NA 
G080202 
P110010 
Sep.6.2012* 
22400BZX00332000 
PROMUS PREMIER 
Feb 2013 
G080202 
P110010 
Apr.7.2014* 
22600BZX00181000 
Large Vessel  
Nov.28.2014 
22600BZX00504000 
 Taxus Liberte 
NA 
G060237 
P060008 
Jan.28.2009* 
22100BZX00049000 
ION/Taxus Element 
NA 
G060237 
P100023 
Sep.5.2011* 
22300BZX00378000 
Taxus Express 2 
NA 
G060237 
P030025 
Mar.30.2007* 
21900BZX00340000 
* The first approved date.  
4.2. Trial Rationale 
Critical limb ischemia is a debilitating disease, associated with poor clinical outcomes, a high 
rate of amputations, and overall decreased quality of life. Based on the significant clinical 
complications associated with bypass surgery, the presence of chronic total occlusions, the 
restenotic characteristics with PTA therapies, and the limitations of using coronary stents in 
BTK indications, the need for an alternative therapy exists. 
 
The DES BTK Vascular Stent System aims to address these treatment gaps and clinical 
outcomes not adequately addressed by surgical bypass and/or PTA. The DES BTK Vascular 
Stent System was designed for the unique considerations of infrapopliteal disease, including 
long, tortuous lesions and the need for a mechanism of providing an anti-proliferative agent 
to calcified vessels. The DES BTK Vascular Stent System incorporates existing successful 
peripheral drug-eluting stent technology to treat a similar disease state below the knee. 
5. Device Description 
The DES BTK Vascular Stent System or DES BTK (SAVAL) Drug-Eluting Vascular Stent 
System is a medical device containing an ancillary medicinal substance, that provides a 

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mechanical scaffold for vascular lumen support (the stent component) and a pharmacological 
agent (paclitaxel) targeted towards reducing the injury response that leads to restenosis after 
stent implantation.  All references made herein to the DES BTK device and DES BTK 
Vascular Stent System are synonymous with the SAVAL device and SAVAL Drug-Eluting 
Vascular Stent System, respectively. 
The DES BTK Vascular Stent System is comprised of 3 main parts:  
• Stent component 
• Stent coating (primer layer and active layer with drug substance)  
• Delivery system 
5.1. The DES BTK Vascular Stent System 
The DES BTK stent (Figure 5.1-1) is a laser cut self-expanding stent composed of a nickel 
titanium alloy (nitinol). Shape memory alloys exhibit special properties including super 
elasticity and shape memory. Nitinol can exist in two phases: a martensite phase and an 
austenite phase. Changing from the martensite phase to the austenite phase, or the reverse, is 
referred to as a phase transformation. During a phase transformation, the atoms rearrange and 
allow the material to exhibit a different behavior. Phase transformations can occur as a result 
of temperature or stress changes in the material.  
During manufacture, the DES BTK stent undergoes heat treatments that impart “memory” on 
the nitinol material, allowing it to expand to a specified diameter when exposed to certain 
conditions of stress or temperature. Then the stent is loaded into the delivery system, which 
constrains the stent until it is deployed at the target lesion. As the stent is exposed to body 
temperature, it expands to appose the vessel wall. The blood vessel restricts full expansion of 
the stent diameter; therefore, recommended stent to vessel sizing is up to one to one fourth 
millimeter less than the stent nominal diameter. 
The DES BTK Drug-Eluting Vascular Stent System is intended to improve luminal diameter 
in the treatment of symptomatic de novo or restenotic lesions in the native infrapopliteal 
arteries with reference vessel diameters (RVD) ranging from 2.5 – 3.75mm. 
The DES BTK Vascular Stent System is designed to optimize stent flexibility, 
radial/compressive strength, and fatigue properties for performance below the knee. The stent 
has three tantalum markers on the proximal and distal ends of the stent, for a total of six 
markers on each stent. 
Table 5.1-1: DES BTK stent size for Phase A randomized controlled trial (RCT) 
Stent Diameter 
(mm) 
Stent Length (mm) 
Reference Vessel Diameter 
3.5 
80 
2.5 – 3.25mm 

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Table 5.1-2: Additional stent sizes to be added for the trial upon regulatory approval 
Stent Diameter 
(mm) 
Stent Length (mm) 
Reference Vessel Diameter 
3.0 
30, 80, 120 
2.5 – 2.75mm 
3.5 
30, 80, 120 
2.5 – 3.25mm 
4.0 
30, 80, 120 
3.0 – 3.75mm 
Figure 5.1-1: DES BTK Geometry 
 
5.2. DES BTK Delivery System 
The stent is constrained within a tapered delivery system which is 6F (2.1 mm maximum 
OD) at the proximal end and has a 5F (1.7 mm) crossing profile. The delivery system is a 
triaxial design with an outer shaft to stabilize the stent delivery system, a middle shaft to 
protect and constrain the stent, and an inner shaft to provide a guidewire lumen. The delivery 
system is intended for use with 0.014 in (0.36 mm) guidewires. A radiopaque marker at the 
distal end of the delivery system aids in visibility during deployment. The DES BTK delivery 
system is offered in a 130 cm working length (Figure 5.2-1). Additional delivery systems 
may be added upon regulatory approval to include them in the trial. 
 
Figure 5.2-1: DES BTK Delivery System 
 
5.3. DES BTK Stent Coating 
The DES BTK stent is a self-expanding stent with a drug/polymer coating. The coating 
comprises two layers, an inner primer layer and an outer polymer matrix that contains an 
active pharmaceutical ingredient (paclitaxel). (Figure 5.3-1) 

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Figure 5.3-1: Dual Layer Illustration 
 
5.3.1. Primer Polymer and Drug Matrix Co-polymer Carrier 
The stent contains a primer polymer layer poly(n-butyl methacrylate) (PBMA) between the 
bare metal stent and drug matrix layer. The chemical structure of PBMA is provided in 
Figure 5.3-2. 
Figure 5.3-2: Poly(n-butyl methacrylate) (PBMA) 
 
The drug matrix layer is comprised of a semi-crystalline random copolymer, poly(vinylidene 
fluoride-co-hexafluoropropylene) (PVDF-HFP), blended with paclitaxel. The chemical 
structure of PVDF-HFP is provided in Figure 5.3-3. 
 
Figure 5.3-3: Poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) 
 
5.3.2. Paclitaxel Drug 
The active pharmaceutical ingredient in the DES BTK vascular stent is paclitaxel (PTx). The 
chemical name of paclitaxel is: Benzenepropanoic acid, ß -(benzoylamino) - α- hydroxy –
,6,12 b – bis (acetyloxy) - 12 - (benzoyloxy) - 2a,3,4,4a,5,6,9,10,11,12,12a,12b-dodecahydro-

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4,11 - dihydroxy-4a,8,13,13- tetramethyl-5-oxo-7,11 methano-1H-cyclodeca[3,4]benz[1,2-
b]oxet-9-yl ester, [2aR- [2aα,4ß,4aß,6ß,9α (αR*,ßS*),11α,12α,12aα,12bα]]. Paclitaxel is a 
diterpenoid with a characteristic taxane skeleton of 20 carbon atoms, a molecular weight of 
853.91 g/mol and a molecular formula of C47H51NO14. It is highly lipophilic, insoluble in 
water, but freely soluble in methanol, ethanol, chloroform, ethyl acetate and dimethyl 
sulfoxide. 14,15  The chemical structure of paclitaxel is provided in Figure 5.3-4. 
 
Figure 5.3-4: Chemical Structure of Paclitaxel (PTx) 
 
 
Paclitaxel is an antiproliferative drug that induces irreversible polymerization of cell 
microtubules, thus inhibiting mitosis. It is widely used in antineoplastic chemotherapy of 
cancers; however, doses required in chemotherapeutic treatment are significantly higher per 
treatment cycle in cancer patients than in peripheral artery disease patients. 15  Paclitaxel has 
been shown to inhibit proliferation and migration of smooth muscle cells, effectively 
suppressing neointimal hyperplasia after vessel injury. 15, 16, 17 The drug-to-polymer 
formulation ratio in DES BTK stents is 1:9 with a resulting paclitaxel loading density (total 
weight of drug/unit of stent surface area) of 0.236 µg/mm2.  
5.4. Manufacturer 
The DES BTK Vascular Stent System is manufactured by the Boston Scientific Corporation. 
5.5. Labeling of Investigational Device 
A copy of the directions for use (DFU) for the DES BTK Vascular Stent System and the 
patient implant card will be included in the manual of operations.  
The DES BTK Vascular Stent System components or immediate package will be labeled 
with the following information: Name and place of the manufacturer, packer or distributor, 
Quantity of the contents, if appropriate and the following statement “CAUTION - 
Investigational device. Limited by United States law to investigational use.” 
Device labeling and patient implant cards will be provided in local language(s) per national 
regulations, as well as the Investigator Brochure. In Japan, identification code, local contact 
information, and storage condition also appear on the product labeling. 

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5.6. Product Receipt and Tracking 
In order to allow shipment of investigational product to an investigational center, Boston 
Scientific (or designee) must declare in writing that the investigational center is activated and 
ready to enroll subjects. The investigator agrees not to implant or use an investigational 
device or product on any person except subjects who are enrolled into the SAVAL trial. The 
investigational product must only be used for the purpose of the clinical trial and in 
compliance to this clinical investigation plan.  
 
Upon receipt of the investigational products, the center principal investigator or designated 
individual will visually inspect and notify Boston Scientific (or its designee) of any noted 
issues or discrepancies. The investigational product will be traced using an investigational 
product accountability log. Refer to section 15 Device/Equipment Accountability. 
5.7. Investigational Product Storage 
Investigational products must be stored in a secured and locked location accessible only to 
those delegated individuals who are authorized by the center principal investigator to access 
them. 
5.8. Product Returns 
The investigational product must be returned to Boston Scientific (or its designee) when it is 
no longer in use, regardless of the reason for removal from use. At the end of the trial 
enrollment, all unused investigational product provided for the trial will be returned to 
Boston Scientific. 
5.9. Control Device 
Commercially available percutaneous transluminal angioplasty balloons will be the control 
device for this trial. The PTA device used must be market-released in the investigational 
center’s geography and the size (ie, diameter, balloon length and catheter length) will be 
determined by the investigator. The use of alternate therapy (eg, atherectomy, drug-coated 
balloons, cutting balloons, re-entry devices, laser, radiation therapy) is not permitted for 
treatment of the target lesion(s) in the trial. 
6. Trial Objectives and Endpoints 
Primary objective: To demonstrate a superior patency rate and acceptable safety rates in 
below the knee arteries with lesions treated with the DES BTK Vascular Stent System vs 
percutaneous transluminal angioplasty (PTA). 
Secondary objective: To collect additional information on limb salvage and overall quality of 
life in this patient population. 

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6.1. Phase A RCT 
Primary Effectiveness Endpoint 
The primary effectiveness endpoint assesses primary patency at 12 months post-procedure. 
This effectiveness endpoint is designed to demonstrate that the 12-month primary patency for 
the DES BTK treatment group is superior to the PTA treatment group at an overall one-sided 
significance level of 2.5%. 
Primary vessel patency is defined as a binary endpoint to be determined via duplex 
ultrasound measuring flow or no flow at the 12-month follow-up visit in the absence of 
clinically-driven target lesion revascularization or bypass of the target lesion.   
Primary Safety Endpoint  
The primary safety endpoint assesses major adverse events (MAE) at 12 months post-
procedure. This safety endpoint is designed to demonstrate that the 12-month MAE-free rate 
for the DES BTK treatment group is non-inferior to the PTA treatment group at an overall 
one-sided significance level of 2.5%. 
A major adverse event is defined as: 
• Above ankle amputation of the index limb 
• Major re-intervention (new bypass graft, jump/interposition graft, or 
thrombectomy/thrombolysis) 
• Perioperative (30 day) mortality 
 
Additional Endpoints 
• Primary and assisted-primary patency at 1, 6, 12, 24, and 36 months post-procedure 
• Clinically-driven TLR rate at each time point  
• Hemodynamic outcomes (changes in ABI and/or TBI) at 6 and 12 months post 
procedure 
• Wound assessment (changes in wound characteristics) 
• Major amputation rate 
• Change in Rutherford classification at 3, 6, 12, 24, and 36 months post procedure 
• Quality of Life (QOL) changes at 1, 3, 6 and 12 months post procedure  
• Adverse events (AEs) at each time point (to be classified as major, serious, non-
serious, unanticipated, procedure-related and device-related) 
• 30-day unplanned hospital readmission rate 
• Survival rate at 4 years and 5 years post-procedure 
6.2. Phase B non-randomized 
Primary safety endpoint  
The primary safety endpoint assesses MAEs at 12 months post-procedure. This safety 
endpoint is designed to demonstrate that the 12-month MAE-free rate in subjects treated with 

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the DES BTK Vascular Stent System exceeds a performance goal of 71% at an overall one-
sided significance level of 2.5%. 
Note that the 12-month primary patency rate will be observed in phase B non-randomized. 
A Major adverse event is defined as: 
• Above ankle amputation of the index limb 
• Major re-intervention (new bypass graft, jump/interposition graft, or 
thrombectomy/thrombolysis) 
• Perioperative (30 day) mortality 
 
Additional Endpoints 
Patency-Based Assessments 
• Primary and assisted-primary patency at 1, 6, 12, 24, and 36 months post procedure  
• Need for clinically-driven TLR 
Therapeutic success at 12 months post procedure 
• Rutherford 4: Ischemic pain relief  
• Rutherford 5: Partial or complete healing of wound 
Other Assessments 
• Change in Rutherford classification at 3, 6, 12, 24 and 36 months post procedure 
• QOL changes at 1, 3, 6, and 12 months post procedure 
• Hemodynamic outcomes (changes in ABI and/or TBI) at 6 and 12 months post 
procedure 
• Wound assessment (changes in wound characteristics) 
• Limb salvage at each time point 
• Major amputation-free survival 
• Adverse events at each time point (to be classified as major, serious, non-serious, 
unanticipated, procedure-related and device-related) 
• 30-day unplanned hospital readmission rate 
• Survival rate at 4 years and 5 years post-procedure 
7. Study Design 
7.1. Phase A RCT 
A global, pivotal, prospective, multicenter, 2:1 randomized controlled trial evaluating the 
safety and effectiveness of the DES BTK Vascular Stent System compared to standard 
percutaneous transluminal angioplasty (PTA) for the treatment of infrapopliteal artery lesions 
in subjects with critical limb ischemia. Phase A RCT will include one size of the device: 3.5 
mm x 80 mm. Additional stent sizes will be added to the trial upon regulatory approval. 
Refer to section 5.1 The DES BTK Vascular Stent System. 

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7.2. Phase B non-randomized 
A global, prospective, multicenter, non-randomized trial collecting additional safety and 
effectiveness data for the DES BTK Vascular Stent System to treat infrapopliteal artery 
lesions in subjects with CLI.  
7.3. Scale and Duration 
Approximately 201 subjects will be randomized/enrolled to support a 2:1 randomization in 
the phase A RCT.  
Approximately 100 additional subjects are expected to be enrolled in phase B non-
randomized, which is structured as a non-randomized single arm study, in which all subjects 
will be treated with the DES BTK Vascular Stent System. 
The trial will be conducted in the United States, Europe, Japan and potentially Singapore, 
Taiwan and/or Hong Kong, at up to 50 investigational centers, with up to 35 centers located 
in the US. Enrollment is expected to be distributed approximately equally across regions. 
Inclusion and exclusion criteria will be the same for both phases of the trial, with the 
exception of the target lesion length (prior to DMC approval for stent overlap) and the 
reference vessel diameter (RVD).  
Phase A RCT is expected to take approximately 2 years to enroll the approximately 201 
subjects, and 5 years of follow-up is planned.  
Enrollment in phase B non-randomized will begin after enrollment into phase A RCT is 
complete. The timing for beginning phase B enrollment will be communicated by the Boston 
Scientific clinical trial team. 
Phase B non-randomized is expected to take approximately 1 year to enroll the additional 
100 subjects, and 5 years of follow-up is planned. 
Clinical follow-up will be the same for both trial phases, with required trial visits at 1, 3, 6, 
12, 24 and 36 months post procedure. Telephone follow-up visits will be completed at 18 and 
30 months post procedure. Telephone follow-up visit and/or medical chart review and/or 
publicly available records consultation will be completed at 48 months and 60 months post-
procedure. 
The total duration from the enrollment of the first subject into phase A RCT to the last 
follow-up in phase B non-randomized is expected to be approximately 11 years. 

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Figure 7.3-1: DES BTK Phase A RCT Design 
 

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Figure 7.3-2: Phase B non-randomized Design 
  

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7.4. Treatment Assignment 
7.4.1.   Phase A RCT 
• Trial candidates must satisfy all pre-procedure inclusion criteria and no pre-
procedure exclusion criteria prior to the intervention, and 
• Subjects must satisfy all intra-procedure inclusion criteria and no intra-procedure 
exclusion criteria to be eligible for randomization/enrollment into the trial.  
The 2:1 randomization for phase A RCT will be stratified by investigational center 
and lesion length with 2 subjects receiving the DES BTK stent for every 1 subject 
receiving treatment with standard PTA. 
For phase A RCT, the subject is considered ‘enrolled’ into the trial at the time of 
randomization (i.e. when a treatment assignment is received by the study site). 
7.4.2. Phase B non-randomized 
• Trial candidates must satisfy all pre-procedure inclusion criteria and no pre-
procedure exclusion criteria prior to the intervention, and 
• Subjects must satisfy all intra-procedure inclusion criteria and no intra-procedure 
exclusion criteria to be eligible for enrollment into the trial. 
For phase B non-randomized, the subject is considered ‘enrolled’ into the trial at the 
time the DES BTK stent is introduced into the subject’s vasculature. 
7.5. Treatment and Control 
The DES BTK Vascular Stent System is the trial test device. Refer to Section 5, Device 
Description for product information. Commercially available PTA balloons are the control 
device for this trial.  
Drug coated balloons are not permitted for treatment of the target lesion(s). 
7.6. Target and Non-Target Lesions 
Target Lesion(s) 
The target lesion(s) is defined as a stenotic, restenotic or occlusive segment located in the 
tibioperoneal trunk, anterior tibial, posterior tibial and/or peroneal artery(ies) with the 
following characteristics: 
• Target lesion(s) must be at least 4cm above the ankle joint 
• A single target lesion per vessel, in up to 2 vessels, in a single limb 
• Degree of stenosis ≥ 70% by visual angiographic assessment 
• RVD is between 2.5 – 3.25mm for phase A RCT 
• RVD is between 2.5 – 3.75mm for phase B non-randomized (Note: RVD is 
dependent on stent size being used. Refer to DFU for specific requirements) 

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• Total target lesion length (or series of lesion segments) to be treated is ≤ 70mm 
for phase A RCT prior to DMC approval for stent overlap 
(Note: Lesion segment(s) must be fully covered with one DES BTK stent, if 
randomized to stent) 
• Total target lesion length (or series of lesion segments) to be treated is ≤ 140mm 
for phase A RCT after DMC approval for stent overlap 
(Note: Lesion segment(s) must be fully covered with up to two DES BTK stents, 
if randomized to stent) 
• Total target lesion length (or series of lesion segments) to be treated is ≤ 140mm 
for phase B non-randomized 
(Note: Lesion segment(s) must be fully covered with up to two DES BTK stents) 
 
Successful guidewire crossing of all target lesion(s) is required prior to 
randomization/enrollment.  
Use of alternate therapy is not permitted for the treatment of the target lesion(s) in the trial. 
(eg, atherectomy, cutting balloon, re-entry devices, laser radiation therapy). 
Drug-coated balloons are not permitted for the treatment of the target lesion(s) in the trial. 
Non-Target Lesion(s) 
Multiple interventions in the target limb are permitted during the index procedure for the 
treatment of above the knee inflow lesions (lesions located in the iliac artery, superficial 
femoral artery and/or popliteal artery). Inflow lesions may be treated according to the 
investigator’s standard procedures using commercially-available devices. If atherectomy is 
performed, the use of an embolic protection device is strongly recommended.  
The inflow interventions must be deemed successful (eg, absence of distal embolization, 
optimal restoration of inflow, etc.) prior to the randomization and/or treatment of the target 
lesion.  
Treatment of outflow lesion(s) (lesions located in the segment of the target vessel distal to 
the target lesion) is not permitted. 
7.7. Justification for the Trial Design 
The SAVAL phase A RCT will compare the safety and effectiveness of the DES BTK 
Vascular Stent System vs PTA for the treatment of atherosclerotic lesion(s) in the 
infrapopliteal arteries. Current revascularization options for infrapopliteal atherosclerotic 
disease include both endovascular and surgical approaches. The foundation of endovascular 
revascularization is PTA, and while advancements have been made in endovascular 
approaches for below the knee disease, patency rates remain suboptimal. 2 
As described in section 4, drug-eluting stents have been used for coronary artery 
revascularization since their introduction in 2003, and this technology, used for the treatment 
in coronary vessels of similar diameters as those found in the infrapopliteal anatomy, 
supports the use of drug-eluting stents below the knee. 

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Phase A RCT will assess primary effectiveness and safety of the DES BTK Vascular Stent 
System when compared to PTA at 12 months post procedure, and phase B non-randomized is 
designed to demonstrate additional safety and effectiveness for the DES BTK Vascular Stent 
System out to 12 months post procedure.  
8. Subject Selection  
8.1. Trial Population and Eligibility 
Eligible subjects are those with chronic, symptomatic lower limb ischemia classified as 
Rutherford category 4 or 5, with a life expectancy of greater than 1 year, and who are 
expected to tolerate the interventional procedure and be compliant with the post-procedure 
follow-up course.  
There are 2 stages of evaluation for trial eligibility: pre-procedure and intra-procedure. Trial 
candidates must satisfy all pre-procedure inclusion criteria and none of the pre-procedure 
exclusion criteria prior to the intervention.  
In addition, subjects must satisfy all intra-procedure inclusion criteria and none of the intra-
procedure exclusion criteria to be eligible for randomization/enrollment into the trial. Refer 
to section 8.2 and 8.3 for the trial inclusion and exclusion criteria. 
8.2. Inclusion Criteria 
Subjects who meet all of the following criteria (see Table 8.2-1) may be given consideration 
for inclusion in this clinical investigation, provided no exclusion criterion is met.  

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Table 8.2-1: Inclusion Criteria 
Pre-
procedure 
Inclusion 
Criteria 
1. Subject is 18 years or older and has signed and dated the trial informed 
consent form (ICF). Note: For subjects in Japan who are less than 20 years of 
age, the subject’s legal representative must provide written informed consent 
in addition to the subject 
2. Subject is willing and able to comply with the trial testing, procedures and 
follow-up schedule 
3. Subject has chronic, symptomatic lower limb ischemia, determined by 
Rutherford categories 4 or 5 in the target limb, with wound(s) confined to 
toes/forefoot 
4. Subject is a male or non-pregnant female. If female of child-bearing potential, 
and if sexually active must be using, or agree to use, a medically–acceptable 
method of birth control as confirmed by the investigator 
Intra-
procedure 
Inclusion 
Criteria 
1. Stenotic, restenotic or occlusive target lesion(s) located in the tibioperoneal 
trunk, anterior tibial, posterior tibial and/or peroneal artery(ies).  
• 
Target lesion(s) must be at least 4cm above the ankle joint 
• 
A single target lesion per vessel, in up to 2 vessels, in a single limb  
• 
Degree of stenosis ≥ 70% by visual angiographic assessment 
• 
Reference vessel diameter (RVD) is between 2.5 – 3.25mm for 
phase A RCT 
• 
RVD is between 2.5 – 3.75mm for phase B non-randomized 
(Note: RVD is dependent on stent size being used. Refer to DFU 
for specific requirements) 
• 
Total target lesion length (or series of lesion segments) to be 
treated is ≤ 70mm for phase A RCT prior to DMC approval for 
stent overlap 
(Note: Lesion segment(s) must be fully covered with one DES 
BTK stent, if randomized to stent) 
• 
Total target lesion length (or series of lesion segments) to be 
treated is ≤ 140mm for phase A RCT after DMC approval for stent 
overlap 
(Note: Lesion segment(s) must be fully covered with up to two 
DES BTK stents, if randomized to stent) 
• 
Total target lesion length (or series of lesion segments) to be 
treated is ≤ 140mm for phase B non-randomized 
(Note: Lesion segment(s) must be fully covered with up to two 
DES BTK stents) 
2. Target vessel(s) reconstitute(s) at or above the stenting limit zone (4cm above 
the ankle joint) 
3. Target lesion(s) is located in an area that may be stented without blocking 
access to patent main branches 
4. Treatment of all above the knee inflow lesion(s) is successful prior to 
treatment of the target lesion  
5. Guidewire has successfully crossed the target lesion(s) 
 
 

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8.3. Exclusion Criteria 
Subjects who meet any one of the following criteria will be excluded from this clinical 
investigation. 
Table 8.3-1: Exclusion Criteria 
Pre-
procedure 
Exclusion 
Criteria 
1. Life expectancy ≤ 1 year 
2. Stroke ≤ 90 days prior to the procedure date  
3. Prior or planned major amputation in the target limb 
4. Previous surgery in the target vessel(s) (including prior ipsilateral crural 
bypass) 
5. Previously implanted stent in the target vessel(s)  
6. Failed PTA of target lesion/vessel ≤ 60 days prior to the procedure date 
7. Renal failure as measured by a GFR ≤ 30ml/min per 1.73m2, measured ≤ 
30 days prior to the procedure date 
8. Subject has a platelet count ≤ 50 or ≥ 600 X 103/µL ≤ 30 days prior to the 
procedure date 
9. NYHA class IV heart failure 
10. Subject has symptomatic coronary artery disease (ie, unstable angina) 
11. History of myocardial infarction or thrombolysis ≤ 90 days prior to the 
procedure date 
12. Non-atherosclerotic disease resulting in occlusion (eg, embolism, Buerger’s 
disease, vasculitis) 
13. Subject is currently taking Canagliflozin 
14. Body Mass Index (BMI) <18 
15. Active septicemia or bacteremia 
16. Coagulation disorder, including hypercoagulability  
17. Contraindication to anticoagulation or antiplatelet therapy  
18. Known allergies to stent or stent components 
19. Known allergy to contrast media that cannot be adequately pre-medicated 
prior to the interventional procedure 
20. Known hypersensitivity to heparin 
21. Subject is on a high dose of steroids or is on immunosuppressive therapy 
22. Subject is currently participating, or plans to participate in, another 
investigational trial that may confound the results of this trial (unless 
written approval is received from the Boston Scientific study team) 
Intra-
procedure 
Exclusion 
Criteria 
1. Angiographic evidence of intra-arterial acute/subacute thrombus or 
presence of atheroembolism  
2. Treatment required in > 2 target vessels (Note: a target lesion originating in 
one vessel and extending into another vessel is considered 1 target vessel) 
3. Treatment requires the use of alternate therapy in the target 
vessel(s)/lesion(s), (eg, atherectomy, cutting balloon, re-entry devices, 
laser, radiation therapy)  
4. Aneurysm is present in the target vessel(s) 
5. Extremely calcified lesions 
 

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9. Subject Accountability 
9.1. Point of Enrollment 
Subjects (or legal guardian, if applicable) must sign and date the institutional review board 
(IRB)/ ethics committee (EC)-approved trial-specific informed consent form (ICF) prior to 
the completion of any trial-related procedure(s).  
The subject must satisfy all pre-procedure inclusion criteria and none of the pre-procedure 
exclusion criteria prior to the intervention.  
Subjects must satisfy all intra-procedure inclusion criteria and none of the intra-procedure 
exclusion criteria to be enrolled into the trial.  
• The point of enrollment for phase A RCT is at the time a subject is randomized for 
the trial (i.e. when a treatment assignment is received by the study site) 
• The point of enrollment for phase B non-randomized is at the time the DES BTK 
stent is introduced into the subject’s vasculature. 
 
Subjects who do not satisfy the pre-procedure eligibility criteria will receive care according 
to the investigational center’s standard procedures and no further trial-related procedures will 
be completed. They will be considered a screen failure and followed according to the center’s 
standard procedures. 
 
Subjects who do not satisfy the intra-procedure eligibility criteria will not be 
randomized/enrolled into the trial, and will receive care according to the center’s standard 
procedures and considered a screen failure. 
 
Subjects, who are enrolled/randomized into the DES BTK arm but do not have the DES BTK 
stent successfully implanted, will be followed for 30 days for safety, and be withdrawn from 
the trial afterwards. 
9.2. Withdrawal 
All subjects who are enrolled into the trial will be accounted for and documented. If a subject 
withdraws from the clinical investigation, the reason(s) will be reported. If such withdrawal 
is due to problems related to investigational device safety or performance, the investigator 
will ask for the subject’s permission to follow his/her status/condition outside of the clinical 
trial.  
 
Subjects may withdraw from the trial at any time by notifying the trial investigator. The 
investigator may also terminate a subject’s participation in the trial (ie, if the subject 
routinely fails to complete required trial procedures or if the investigator believes it is in the 
subject’s best interest). 
 
Examples of reasons for trial withdrawal include, but are not limited to: 
• Failure to comply with the trial-required visit schedule 

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• Subject is lost to follow-up 
• Subject voluntarily withdraws from the trial 
• Adverse event such that continued trial participation would not be in the best interest 
of the subject 
• Withdrawal of the subject by the investigator 
• Subject death 
• Trial closure 
 
It is recommended that the reason for subject withdrawal is also documented in the subject’s 
medical record. If applicable, the investigator will complete an adverse event and/or device 
deficiency assessment prior to the subject’s withdrawal from the trial. All applicable 
electronic case report forms (eCRFs) are to be completed for all subjects who are enrolled in 
the trial and are then withdrawn from the trial for any reason. 
Withdrawn subjects will not undergo any further trial follow-up, nor will they be replaced 
because the justified sample size considers an estimated allowance for attrition. Data already 
collected will be retained and reported, however, no new data will be collected after the 
withdrawal.  
Subjects voluntarily withdrawing from the trial will be asked to participate in a limited 
capacity allowing their medical status to be followed by telephone contact, medical chart 
review, or by other agreed upon method. If a subject decides not to continue participation in a 
limited capacity, the investigator will not access their medical record or other confidential 
records for new purposes related to the study; however, study data collected prior to their 
withdrawal may be reviewed and publicly available records may be consulted prior to or after 
their withdrawal. Note: this applies to all withdrawn subjects (e.g. withdrawn by 
investigator). 
Withdrawn subjects will be followed according to the investigational center’s standard 
procedures. Serious adverse device-effects that are still ongoing at the end of the subject’s 
participation in the trial will be followed up for resolution status and this information will be 
provided to Boston Scientific for the purpose of regulatory agency reporting for the trial. 
9.3. Lost to Follow-Up 
Additional actions must be taken when a participant fails to attend a required study visit: 
The investigational center personnel will attempt to contact the study subject and reschedule 
the missed visit (within the visit window if possible) and counsel the subject on the 
importance of maintaining the assigned visit schedule. 
Prior to withdrawing a subject as lost to follow-up, the investigational center’s personnel 
must make at minimum 3 documented attempts (1 in writing and sent via a traceable method) 
to bring the subject in for a final trial visit. Other contacts (ie, telephone calls, emails) must 
be documented in the subject’s records at the investigational center. If all attempts to contact 
that subject have failed, the investigational center will withdraw the subject and follow the 
local procedures for notification. 

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9.4. End-of-Study Definition  
Phase A RCT will be considered complete for the primary effectiveness endpoint and the 
primary safety endpoint after all subjects in phase A RCT have completed the 12-month 
follow-up visit, are withdrawn prior to the 12-month follow-up visit, have died or, the last 
12-month follow-up visit window has closed. 
 
Phase B non-randomized will be considered complete for the primary safety endpoint after 
all subjects in phase B non-randomized have completed the 12-month follow-up visit, are 
withdrawn prior to the 12-month follow-up visit, have died or, the last 12-month follow-up 
visit window has closed. 
 
The entire trial will be considered complete with regard to all follow-up, after all subjects 
have completed the 60-month follow-up visit, are withdrawn prior to the 60-month follow-up 
visit, have died or, the last 60-month follow-up visit window has closed. 
10. Trial Methods 
10.1. Data Collection 
The data collection schedule is shown in Table 10.1-1.

 
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Table 10.1-1: Data Collection Requirements by Visit 
Procedure/Assessment 
Pre-
procedure(2)- 
Index 
procedure 
Pre-
discharge 
Follow-up Visits based on procedure date = time zero 
1-mon (30 ± 7 
Days) 
Office Visit 
3-mon (90 ± 30 
Days) 
Office Visit 
6-mon (182 ± 
30 Days) 
Office visit 
12-mon (365 ± 30 
Days) 
Office Visit 
24-mon 
(730 ± 90 Days) 
Office Visit 
36-mon (1095 - 
90/+30 Days 
Office Visit 
18 & 30, mon (± 
90 Days) 
Telephone 
48 & 60 mon (- 
90/+30 days)  
Informed consent(1)-  
X 
 
 
 
 
 
 
 
 
 
 
Inclusion/Exclusion 
(pre) 
X 
X 
 
 
 
 
 
 
 
 
 
Inclusion/Exclusion 
(intra) 
 
X 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
Physical assessment 
X 
 
 
 
 
 
 
 
 
 
 
BMI 
X 
 
 
 
 
 
 
 
 
 
 
Medical/surgical 
history 
X 
 
 
 
 
 
 
 
 
 
 
Glomerular filtration 
rate 
X 
 
 
 
 
 
 
 
 
 
 
Platelet count 
X 
 
 
 
 
 
 
 
 
 
 
Procedure information 
 
X 
 
 
 
 
 
 
 
 
 
Angiography(3)-  
 
X 
 
 
 
 
 
 
 
 
 
Pregnancy test(4)-  
X 
 
 
 
 
 
 
 
 
 
 
Randomization(5)- 
 
 X 
 
 
 
 
 
 
 
 
 
X-rays of DES BTK 
stent(3)- 
 
 
 
 
 
 
X 
 
 
 
 
EQ-5D & VascuQol 
X 
 
 
X 
X 
X 
X 
 
 
 
 
Medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Adverse event(6)- 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Device deficiency  
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Rutherford 
Classification 
X 
 
 
 
X 
X 
X 
X 
X 
 
 
Duplex Ultrasound(3)- 
 
 
 
X 
 
X- 
X(7) 
X 
X 
 
 
ABI &TBI 
X 
 
 
 
 
X 
X 
 
 
 
 
Wound assessment & 
image 
 
X(8)- 
 
X 
X 
X 
X 
X 
X 
 
 
Survival status 
 
 
 
 
 
 
 
 
 
 
X 
(1) Subject’s consent obtained, and informed consent form signed prior to any study-specific tests or procedures 
(2) Performed/Measured ≤ 30 days prior to the procedure date 
(3) Angiograms, Ultrasounds and X-rays will be sent to the respective core lab for analysis.  Follow-up angiograms, ultrasounds and x-rays will not be required for any subject who underwent bypass surgery of the target lesion during the 36-month follow-up timeframe or has a documented occluded target lesion. 
(4) Measured ≤ 7 days prior to the procedure date for subjects of child-bearing potential 
(5) Phase A RCT only 
(6) Reporting required through the end of trial for UADEs and Device Deficiencies.  Reporting required through 36-month follow-up visit for SAEs and ADEs.  AEs not related to the investigational device or procedure reported only through 12-month follow-up visit. 
(7) If a diagnostic DUS cannot be adequately achieved for the 12-month follow-up visit then CTA or DSA angiography must be conducted. 
(8) Wound assessment and image ≤ 1 day prior to the procedure date 

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10.2. Visit Windows 
Table 10.2-1: Protocol Visit Windows 
Visit 
Visit windows 
Informed consent 
Prior to any trial procedures 
Pre-procedure 
Testing ≤ 30 days prior to procedure unless otherwise 
specified 
Index Procedure 
Time point = zero 
1 month post procedure 
30 days (+/- 7 days) from procedure date 
3 months post procedure 
90 days (+/- 30 days) from procedure date 
6 months post procedure 
182 days (+/- 30 days) from procedure date 
12 months post procedure 
365 days (+/- 30 days) from procedure date 
24 months post procedure 
730 days (+/- 90 days) from procedure date 
36 months post procedure 
1095 days (- 90/+30 days) from procedure date 
Table 10.2-2: Telephone/medical chart/public record Follow-up Windows 
Telephone call 
Target Date 
18-Months 
547 days (+/- 90 days) from procedure date 
30-Months 
912 days (+/- 90 days) from procedure date 
Medical chart / 
public record  
Target Date 
48-Months 
1460 days (+/- 90 days) from procedure date 
60-Months 
1825 days (- 90/+30 days) from procedure date 
10.3. Trial Candidate Screening 
A screening log will be maintained by each investigational center to document selected 
information about potential subjects who fail to meet the SAVAL trial eligibility criteria, 
including the reason for screen failure. 
10.3.1. Strategies for Recruitment and Retention 
Subjects may be recruited through the investigator’s practice, referring physicians and/or the 
use of recruitment tools. Potential subjects may be identified through an investigational 
center’s database query (chart reviews) or as new or existing patients attend clinic visits. Any 
information disseminated to potential subjects (eg, advertisements, pamphlets, posters) must 
be approved by the investigational center’s IRB/EC prior to use.  
It is important that the investigational center personnel review the trial requirements with the 
subjects to maximize compliance with the follow-up schedule and required medication 
regimen. A stipend may be provided to subjects to cover lodging or travel expenses incurred 
as a result of participation in the SAVAL trial, in accordance with country laws and 
regulations, and per the trial investigational center’s regulations.  
 

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Rescreening for the Trial 
When a subject fails the pre- or intra-procedure inclusion or exclusion criteria, and it is the 
opinion of the investigator that the subject may be a suitable candidate for rescreening, the 
investigator will contact the Boston Scientific trial manager, or designee to request 
permission to rescreen the subject. 
10.4. Informed Consent 
The subject (or legal guardian, if applicable) must sign and date the ICF prior to any trial-
required testing or procedures. For individuals less than 20 years of age enrolled at a Japan 
center, the subject’s legal representative, as well as the subject, must provide written 
informed consent. 
Prior to signing the ICF, the investigator, or qualified designee, will explain to each potential 
subject the purpose and nature of the trial, procedures, expected trial duration, available 
alternative therapies, and the benefits and risks involved with trial participation.  
Refer to Section 9.1 Point of Enrollment and Section 20 Informed Consent. 
10.5. Medications 
Anticoagulant and antiplatelet medication use will be collected for the trial and reported on 
the electronic case report forms from the time of the pre-procedure visit through the 36- 
month follow up. Medication data collection at each visit will include: a complete listing of 
the anticoagulant and antiplatelet medications the subject is taking, interruptions and 
cessation. 
Anticoagulant and Antiplatelet Medication for the Trial 
• Anti-coagulation and antiplatelet therapy is to be administered prior to and during the 
index procedure according to the investigator’s standard procedures. 
• Dual antiplatelet therapy is required post-procedure through the 6-month visit and is 
strongly recommended to continue through the 12-month visit for the trial subjects who 
receive the DES BTK stent.* 
• Subjects who are randomized to PTA in phase A RCT will receive antiplatelet therapy 
according to the investigator’s standard of care.  
*A subject may be exempt from dual antiplatelet requirement when anticoagulation therapy 
is required for comorbidity treatment and when, in the judgement of the investigator, the 
addition of dual antiplatelet therapy would pose an unacceptable hemorrhage risk.  
10.6. Quality of Life 
The QOL instruments used for the trial will be the EQ-5D questionnaire for general health 
and the VascuQol questionnaire for disease specific data. 
The EQ-5D is a 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 

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problems/slight problems/moderate problems/severe problems/extreme problems) within a 
particular EQ-5D dimension. 
The VascuQol was developed to evaluate disease-specific QOL measure for patients with 
chronic lower limb ischemia. The 25-item questionnaire is subdivided into 5 domains: pain, 
symptoms, activities, social and emotional. 
10.7. Wound Care and Data Collection 
For Rutherford 5 subjects with minor tissue loss, ischemic ulcer, or focal gangrene, these 
tissue changes must be located only in the digit(s) and/or the forefoot, and these lesions must 
be able to be fully resected (if needed) by performing digit amputation(s) or complete trans 
metatarsal amputation. Study subject’s wounds must not require mid foot or hind foot 
amputation. If the investigator plans to undertake digit amputation(s) or transmetatarsal 
amputation, this plan should be indicated at the time of study enrollment. 
It is recommended investigators follow the Wound Healing Society 2014 update on 
guidelines for arterial ulcers. 18 
Target limb wound characteristics data will be collected and documented on the eCRFs. (ie, 
wound size, depth, presence of infection, and healing status). Wound images will be 
collected for the trial. Instructions for collection and submission of images will be provided 
in the manual of operations. 
A review of the wound assessment data will be completed by an independent reviewer who 
will be blinded to the randomized therapy. 
10.8. Pre-procedure  
The subject (and/or the legal guardian as applicable) must sign and date the ICF prior to the 
completion of any trial-related procedures. Subjects will be assessed to confirm trial 
eligibility requirements. The data collection elements for pre-procedure should be collected ≤ 
30 days prior to the procedure or as specified below. 
When it is determined that a subject does not satisfy the pre-procedure trial eligibility 
requirements, the trial-related procedures will stop, and the subject will be considered a 
screen failure and receive care according to the center’s standard procedures.  
When a subject fails the pre-procedure eligibility criteria, and it is in the opinion of the 
investigator that the subject may be a suitable candidate for rescreening, the investigator will 
contact the Boston Scientific trial manager, or designee to request permission to rescreen the 
subject. 
Data Collection Requirements Pre-procedure (≤ 30 days prior to procedure): 
• Informed consent (prior to any study-specific tests or procedures) 
• Pre-procedure inclusion/exclusion criteria 
• Demographics 
• Physical assessment 
• Body mass index 

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• Medical and surgical history 
• Glomerular filtration rate  
• Platelet count  
• Pregnancy test ≤ 7 days prior to procedure (if subject is of child-bearing potential) 
• EQ-5D Questionnaire 
• VascuQol Questionnaire 
• Medications 
• Rutherford classification 
• Ankle-brachial index and toe brachial index* 
        * When subject condition permits (ie, no toe amputation, calcified/incompressible vessels) 
10.9. Index Procedure 
Diagnostic angiography of the lower extremities will be performed using the investigational 
center’s standard procedures. The investigator will confirm the subject satisfies all inclusion 
criteria and no exclusion criteria prior to randomization/enrollment into the trial.  
Multiple interventions in the target limb are permitted during the index procedure for the 
treatment of above the knee inflow lesions (lesions located in the iliac artery, superficial 
femoral artery and/or popliteal artery). Inflow lesions may be treated according to the 
investigator’s standard procedures using commercially-available devices. If atherectomy is 
performed, the use of an embolic protection device is strongly recommended.  
The inflow interventions must be deemed successful (eg, absence of distal embolization, 
optimal restoration of inflow, etc) prior to the randomization and/or treatment of the target 
lesion(s). 
Successful guidewire crossing of all target lesion(s) is required prior to 
randomization/enrollment into the trial. 
Treatment of outflow lesions(s) (lesions located in the segment of the target vessel distal to 
the target lesion) is not permitted. 
Drug-coated balloons are not permitted for the treatment of the target lesion(s) in the trial.  
The use of an adjunctive therapy is not permitted for the target lesion(s) (ie, atherectomy, 
cutting balloon, re-entry devices, laser, radiation therapy). 
The DES BTK Vascular Stent System will be used in compliance with the directions for use. 
10.9.1. Target lesion requirements: 
Stenotic, restenotic, or occlusive target lesions(s) located in the tibioperoneal trunk, anterior 
tibial, posterior tribal and/or peroneal artery(ies). 
• Target lesion(s) must be below the knee and at least 4cm above the ankle joint 
• A single target lesion per vessel, in up to 2 vessels, in a single limb 
• Degree of stenosis ≥ 70% by visual angiographic assessment 
• RVD is between 2.5 – 3.25mm for phase A RCT 

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• RVD is between 2.5 – 3.75mm for phase B non-randomized (Note: RVD is 
dependent on stent size being used. Refer to DFU for specific requirements) 
• Total target lesion length (or series of lesion segments) to be treated is ≤ 70mm for 
phase A RCT prior to DMC approval for stent overlap 
(Note: Lesion segment(s) must be fully covered with one DES BTK stent, if 
randomized to stent) 
• Total target lesion length (or series of lesion segments) to be treated is ≤ 140mm for 
phase A RCT after DMC approval for stent overlap 
(Note: Lesion segment(s) must be fully covered with up to two DES BTK stents, if 
randomized to stent) 
• Total target lesion length (or series of lesion segments) to be treated is ≤ 140mm for 
phase B non-randomized 
(Note: Lesion segment(s) must be fully covered with up to two DES BTK stents) 
 
A ruler or radiopaque marking tape must be used as the calibration source to determine the 
lesion length and location. When possible the zero mark will be placed at the level of an 
anatomical landmark (ie, tibial plateau, inferior edge of the patella, bifurcation). 
10.9.2. Randomization/Enrollment 
In phase A RCT the randomization assignment will be obtained only after all of the 
following are confirmed: 
• All pre- and intra-procedure inclusion criteria are met 
• No exclusion criteria are met 
• Successful guidewire crossing of the target lesion(s) is required prior to 
randomization/enrollment 
 
The investigator (or delegate) will access the Rave electronic data capture system, and a 
randomization custom function will be used to assign subjects to the test or control treatment 
group. Treatment of the target lesion(s) will be in compliance with the randomization 
assignment.  
For phase B non-randomized, the DES BTK stent may be implanted after the following are 
confirmed: 
• All pre- and intra-procedure inclusion criteria are met 
• No exclusion criteria are met 
• Successful guidewire crossing of the target lesion(s) is required prior to enrollment  
 
If a subject does not satisfy all inclusion criteria and/or does meet one of the exclusion 
criteria, the investigator will not randomize/enroll the subject and will proceed with treatment 
according to the center’s standard procedures, and the subject will be considered a screen 
failure.  

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Subjects, who are enrolled/randomized into the DES BTK arm but do not have the DES BTK 
stent successfully implanted, will be followed for 30 days for safety, and be withdrawn from 
the trial afterwards. 
10.9.3. Guidelines for treatment of flow-limiting dissection or other loss of target vessel 
patency at the completion of the target lesion pre-treatment and definition of 
bailout stenting 
Subjects randomized to the PTA arm, who receive index angioplasty and subsequently 
demonstrate flow-limiting dissection or other loss of target vessel patency (ie, recoil), based 
on the operator visual assessment and clinical judgement (ie, presence of contrast in the sub-
intimal space), must receive repeat 2 to 5 minutes balloon inflations (up to 3 inflations) using 
standard PTA balloons. If target vessel compromise persists and requires further intervention 
(eg, “bailout stent”) a DES BTK Vascular Stent System will be used, and these subjects will 
be considered a study primary endpoint failure and continue to attend study follow-up visits. 
Investigators must submit angiography to support the decision for bailout stenting to the 
angio core lab for review. 
Note: The DES BTK Vascular Stent System may not be used for bailout in non-target 
lesions.  
Data Collection Requirements for Index procedure: 
• Confirm pre-procedure inclusion and exclusion criteria 
• Intra-procedure inclusion and exclusion criteria 
• Procedure information 
 Inflow lesion(s) location, characteristics and treatment modalities used 
 Target lesion(s) characteristics and treatment modalities used 
 PTA balloon size(s) and inflation information (if applicable) 
 Guidewire(s) information 
 Stent information (if applicable) 
 Hospitalization information 
• Angiographic imaging (to core laboratory) 
• Randomization (if applicable) 
• Medications 
• Adverse events 
• Device deficiency 
• Wound assessment and image (≤ 1 day prior to procedure) 
 
Data Collection Requirements for Pre-discharge: 
• Medications 
• Adverse events 
• Device deficiency 

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10.9.4. Re-intervention in the target vessel 
Subjects who require re-intervention of the target vessel during the 36-month follow-up 
period will be treated according to the investigational center’s standard of care. The DES 
BTK Vascular Stent System may not be used for re-intervention procedures. 
 
Data Collection for Re-interventions 
• Angiographic imaging (to core laboratory) 
• Medications 
• Adverse events 
• Device deficiency 
• Wound assessment and image (≤ 1 day prior to procedure) 
10.10. Follow-up visits 
Subjects will return for trial-required follow-up visits at: 1, 3, 6, 12, 24, and 36 months post 
procedure. Telephone follow-up visits are required at 18 and 30 months post procedure. 
Telephone follow-up visit and/or medical chart review and/or publicly available records 
consultation are required at 48 months and 60 months post-procedure. Refer to Table 10.2-1 
Protocol Visit Windows.  
At each follow-up visit the investigator will complete an assessment for the clinical need for 
target limb revascularization, and document on the eCRF, prior to reviewing the results of 
diagnostic assessments (eg, DUS, angiography). 
Data collection requirements for the follow-up visits are listed below: Refer to Table 10.1-1. 
Data Collection Requirements for1-Month Post-Procedure Visit 
• EQ-5D Questionnaire 
• VascuQol Questionnaire 
• Medications 
• Adverse events 
• Device deficiency 
• Duplex ultrasound 
• Wound assessment and image 
 
Data Collection Requirements for 3, 24, and 36 Months Post-Procedure Visits: 
• EQ-5D Questionnaire (3 months only) 
• VascuQol Questionnaire (3 months only) 
• Medications 
• Adverse events (non-serious AEs not related to the investigational device or 
procedure reported only through 12-month follow-up visit) 
• Device deficiency 
• Rutherford classification 
• Duplex ultrasound (24 and 36 months only) 
• Wound assessment and image 

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Data Collection Requirements for 6 and 12 Months Post Procedure Visits: 
• High definition x-ray of index limb with DES BTK stent (12-month visit only) 
• EQ-5D Questionnaire 
• VascuQol Questionnaire 
• Medications 
• Adverse events 
• Device deficiency 
• Rutherford classification 
• Duplex ultrasound* 
• Ankle-brachial index and toe brachial index** 
• Wound assessment and image 
* If a diagnostic duplex ultrasound cannot be adequately achieved for the 12-month follow-up visit, then 
CTA or DSA angiography must be conducted 
** When subject condition permits (ie, no toe amputation, calcified/incompressible vessels) 
10.11. Telephone Follow-up 
Telephone follow-up visits will be completed at 18 and 30 months post procedure. Telephone 
follow-up visit and/or medical chart review and/or publicly available records consultation 
will be completed at 48 months and 60 months post-procedure 
 
Data Collection Requirements for the 18 and 30 months telephone follow-ups: 
• Medications 
• Adverse events [SAEs and (U)ADEs] 
• Device deficiencies 
 
Data Collection Requirements for the 48 and 60 months telephone/medical chart review/ 
publicly available records follow-ups: 
• Survival status 
10.12. Trial Completion 
Phase A RCT will be considered complete for the primary effectiveness endpoint and the 
primary safety endpoint after all subjects in phase A RCT have completed the 12-month 
follow-up visit, are withdrawn prior to the 12-month follow-up visit, have died or, the last 
12-month follow-up visit window has closed.  
Phase B non-randomized will be considered complete for the primary safety endpoint after 
all subjects in phase B non-randomized have completed the 12-month follow-up visit, are 
withdrawn prior to the 12-month follow-up visit, have died or, the last 12-month follow-up 
visit window has closed. 
The entire trial will be considered complete with regard to all follow-up, after all subjects 
have completed the 60-month follow-up visit, are withdrawn prior to the 60-month follow-up 
visit, have died or, the last 60-month follow-up visit window has closed. 

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10.13. 
Source Documents 
The investigator is responsible for the preparation, review and retention of records used for 
the trial. It is preferable that original source documents are maintained, when available. In 
lieu of original source documents, certified copies are required to be maintained. A certified 
copy is a copy (irrespective of the type of media used) of the original record that has been 
verified (ie, by a dated signature or by generation through a validated process) to have the 
same information, including data that describes the context, content, and structure, as the 
original.  
The investigator will, at minimum, maintain the following accurate, complete and current 
records relating to the investigator’s participation in the trial. 
• Correspondence with another investigator, an IRB/EC, the sponsor, a monitor, or 
FDA including required reports 
• Records of receipt, use or disposition of investigational devices (ie, product 
accountability) 
• Records supporting each subject’s case history and exposure to the device. Case 
history supporting data (source documentation), such as: 
 Signed and dated ICFs 
 Signed HIPAA authorization if separate from the ICF (if applicable) 
 Medical records (ie, progress notes of the physicians, the subject hospital and 
clinic charts and the nurses’ notes 
 All reportable adverse event and adverse device effects information 
• The clinical investigational plan and any amendments 
• Investigator brochure 
• Curriculum vitae for all investigators 
• Signed clinical study agreement 
• Signed financial disclosure forms for all investigators 
• Center personnel trial training records 
11. Statistical Considerations 
The sample size justification and the power analyses for phase A RCT and phase B non-
randomized are described in separate subsections. The general statistical methods are 
applicable to both phases unless otherwise specified.  
The details for sample size justification and all statistical analyses will be described in the 
statistical analysis plan. 
11.1. Primary Endpoints for Phase A RCT 
The overall sample size in phase A RCT is justified by hypothesis parameters and driven by 
the 12-month primary effectiveness endpoint, to preserve adequate statistical testing power 
for both the primary effectiveness endpoint and safety endpoint. 

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The primary effectiveness and safety hypotheses will be tested simultaneously at the 
significance level of one-sided 2.5% each without adjustment.  
11.1.1. Primary Effectiveness Endpoint 
The primary effectiveness endpoint in phase A RCT is the 12-month primary patency. The 
goal is set to demonstrate that the primary patency for the DES BTK treatment group (ie, 
Test) is superior to the PTA treatment group (ie, Control) through 12 months post-procedure. 
11.1.1.1. Effectiveness Hypothesis 
The primary effectiveness hypothesis to be tested is that the 12-month primary patency in 
subjects treated with the DES BTK Vascular Stent System is superior to subjects treated with 
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 the DES BTK 
Vascular Stent System vs 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 the DES BTK stent and PTA, 
respectively. 
11.1.1.2. Effectiveness Sample Size 
The overall sample size is driven by the primary effectiveness endpoint. Approximately 201 
subjects are planned to be enrolled in phase A RCT. The sample size justification for phase A 
RCT is based on the following assumptions. 
• Power ≥ 84% 
• One-sided overall significance level (alpha) = 2.5% 
• Expected PTA 12-month primary patency = 40%  
• DES BTK to demonstrate 25% treatment effect 
• Allocation (DES BTK vs PTA) = 2:1 
• A minimum of 150 evaluable subjects are required at 12 months (ideally 100 in DES 
BTK arm and 50 in PTA arm) 
• Attrition rate in 12 months ≤25% 
• Approximately 201 subjects are planned to be randomized in 2:1 fashion prior to the 
procedure 
11.1.1.3. Effectiveness Statistical Methods 
A Wald z-test will be used to assess the primary effectiveness hypothesis. The p-value and 
corresponding confidence interval for the difference between DES BTK and PTA in 12-
month primary patency will be constructed. 

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A detailed definition of evaluable subjects for the primary effectiveness endpoint will be 
given in the statistical analysis plan.  
11.1.2. Primary Safety Endpoint 
The primary composite safety endpoint in phase A RCT is the 12-month MAE-free rate. The 
safety goal is designed to demonstrate that the DES BTK Vascular Stent System is non-
inferior to PTA in terms of MAE-free rate through 12 months post-procedure.  
11.1.2.1. Safety Hypothesis 
The primary safety hypothesis to be tested is that the 12-month MAE-free rate in subjects 
treated with the DES BTK Vascular Stent System is non-inferior to subjects treated with 
PTA at an overall one-sided significance level of 2.5%. 
The null hypothesis (H0) states that there is no marginal treatment effect of the DES BTK 
Vascular Stent System vs PTA, as opposed to the alternative hypothesis (H1) which states 
that there is a marginal treatment effect. The hypotheses inequalities are shown below: 
H0: Pt - Pc ≤ ∆  
H1: Pt - Pc > ∆ 
where Pt and Pc are the 12-month MAE-free rate for the DES BTK stent and PTA, 
respectively, and Δ (delta) is the non-inferiority margin of -10%. 
11.1.2.2. 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 
• Expected PTA 12-month MAE-free rate = 75% 
• Expected DES BTK 12-month MAE-free rate = 85% 
• Non-inferiority margin (∆) = -10% 
The sample size is driven by the primary effectiveness endpoint to provide approximately 
80% power to assess the primary safety endpoint. 
11.1.2.3. Safety Statistical Methods 
A Wald z-test will be used to assess the primary safety hypothesis. The p-value and 
corresponding confidence interval for the difference between DES BTK and PTA in 12-
month MAE-free rate will be constructed. 
A detailed definition of evaluable subjects for the primary safety endpoint will be given in 
the statistical analysis plan. 

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11.1.3. Success Criteria 
The following success criteria for phase A RCT are defined as both the primary effectiveness 
and primary safety endpoint to be met simultaneously, therefore there will be no multiplicity 
issues for the two primary endpoints. 
The DES BTK Vascular Stent System will be concluded to be superior to PTA for device 
effectiveness if the one-sided lower bound of 97.5% confidence interval on the difference 
between treatment groups (DES BTK – PTA) in 12-month primary patency is greater than 
zero. 
The DES BTK Vascular Stent System will be concluded to have no safety concerns if the 
one-sided lower bound of 97.5% confidence interval on the difference between treatment 
groups (DES BTK – PTA) in 12-month MAE-free is greater than -0.1. 
The trial will be concluded to be a success if both the primary effectiveness endpoint and the 
primary safety endpoint are met. 
11.2. Primary Endpoint for Phase B Non-randomized 
The overall sample size in phase B non-randomized is justified by hypothesis parameters and 
driven by the 12-month primary safety endpoint, to preserve adequate statistical testing 
power. The 12-month primary patency will be observed without testing hypotheses. 
11.2.1. Primary Safety Endpoint 
11.2.1.1. Safety Hypotheses 
The primary safety hypothesis to be tested is that the 12-month MAE-free rate in subjects 
treated with the DES BTK Vascular Stent System exceeds a PG of 71% at one-sided 
significance level of 2.5%. 
The null (H0) and the alternative (H1) hypotheses for the primary safety endpoint are as 
follows: 
H0: Pt ≤ PG (not met) 
H1: Pt > PG (met) 
where Pt is the 12-month MAE-free rate for the subjects treated with the DES BTK Vascular 
Stent System and the PG is the performance goal. 
11.2.1.2. Safety Sample Size/Power Analysis 
The power analysis for the primary safety endpoint to justify an additional 100 subjects in 
enrollment is based on the following assumptions. 
• Power ≥ 80% 
• One-sided significance level (alpha) = 2.5% 
• Safety PG = 71% in the 12-month MAE-free rate  
• Expected 12-month MAE-free rate = 80% 

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• A minimum of 186 (DES BTK) evaluable subjects are required at 12 months 
• Attrition rate at 12 months ≤ 20% 
• Up to 234 (DES BTK) subjects are planned to be enrolled, including 134 DES BTK 
subjects from phase A RCT and an additional 100 DES BTK subjects to be enrolled 
in phase B non-randomized 
11.2.1.3. Safety Statistical Methods 
A Wald z-test will be used to assess the primary safety hypothesis. The p-value for testing 
will be generated and the corresponding confidence interval for the observed 12-month 
MAE-free rate will be constructed. 
11.2.2. Success Criteria 
The DES BTK Vascular Stent System will be concluded as meeting the PG for device safety 
if the one-sided lower bound of 97.5% confidence interval on the observed 12-month MAE-
free rate is greater than 0.71. 
11.3. General Statistics Methods 
11.3.1. Analysis Sets 
For phase A RCT, the intention-to-treat (ITT) population will be the primary analysis set for 
assessing the primary hypotheses. Both per-protocol (PP) and as-treated (AT) populations 
will be the secondary analyses sets for reference. 
For phase B non-randomized, all subjects who receive the DES BTK stent will be assessed 
against the pre-specified PG.  
11.3.1.1. Intention-to-treat (ITT) 
All subjects who sign the informed consent form and are randomized in phase A RCT will be 
included in the ITT analysis set, regardless of whether the subjects receive the assigned 
treatment. The DES BTK and PTA arms will be compared as randomized. The ITT analysis 
will be the primary analysis for phase A RCT. 
11.3.1.2. Per-protocol (PP) 
For the PP analysis, only randomized subjects who meet the eligibility criteria and receive 
the assigned index treatment will be included in the PP analysis set. The DES BTK and PTA 
arms will be compared as randomized and correctly received index treatment. Subjects who 
do not receive the randomized index treatment will be excluded from the PP analysis set. The 
PP analysis, as well as a discussion regarding what protocol deviations excluded subjects 
from the PP analysis, will be described in the clinical study report. 

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11.3.1.3. As-treated (AT) 
For the AT analysis, all subjects who receive either the DES BTK stent or PTA at the index 
procedure will be included in the AT analysis set. The DES BTK and PTA arms will be 
compared as treated, excluding subjects who do not receive the DES BTK stent or PTA.  
11.3.1.4. Bailout Subjects Considerations 
For phase A RCT, the bailout subjects in the PTA arm will be analyzed in ITT, PP, and AT 
analysis sets.  
• For the ITT analysis, a bailout subject from the PTA arm will stay in the PTA arm 
and will count as a failure on the 12-month primary patency.  
• For the PP analysis, a bailout subject from the PTA arm will be excluded from the PP 
analysis since the bailout subjects actually receive a device (investigational or not) in 
addition to randomized PTA.  
• For the AT analysis, a bailout subject from the PTA arm will be analyzed in the DES 
BTK arm if the subject receives the DES BTK test device as a bailout and count as 
success/failure based on 12-month effectiveness assessment 
For phase B non-randomized, the AT analysis will be the primary analysis. That is, all 
subjects who receive the DES BTK stent will be assessed against the pre-specified PG. 
Therefore, bailout subjects from the RCT PTA arm (and/or even from test device) who 
receive the DES BTK stent will be included in the phase B hypothesis. 
11.3.2. Randomization Scheme 
Randomization to treatment in phase A RCT will be stratified by investigational center and 
lesion length. A computer-generated list of random treatment allocations (ie, a randomization 
schedule) will be used to assign subjects to treatments in a 2:1 ratio of DES BTK to PTA. 
This list will be specific to the investigational center. Random permuted blocks of size 3 and 
size 6 will be employed to ensure approximate balance of treatment allocation within each 
stratum. 
11.3.3. Control for Systematic Error/Bias 
Selection of subjects will be made from the investigators’ general or professional referral 
population. All subjects meeting the inclusion and no 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 center (phase A RCT). In 
determining subject eligibility for the trial, the investigator’s assessment of imaging will be 
used. However, an angiographic core laboratory will independently analyze the angiograms, 
and the data obtained from the core laboratory will be utilized for analyses. An independent 
clinical events committee (CEC), composed of medical experts, will adjudicate safety 
assessments, as defined in the CEC charter. 

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11.3.4. Enrollment for Each Investigative Center 
For phase A RCT, investigational centers will not be allowed to randomize more than 10% 
(N=20) 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=40) of the total number of 
randomized subjects. 
For phase B non-randomized, investigational centers will not be allowed to enroll more than 
10% (N=23) of the total number (including DES BTK from phase A RCT) of subjects 
without prior approval from the sponsor. No study center will be allowed to enroll more than 
20% (N=47) of the total number (including DES BTK from phase A RCT) of study subjects. 
11.3.5. Baseline Data Analysis 
Baseline covariates will be summarized for phase A RCT and phase B non-randomized. 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. 
11.3.6. Additional Endpoint Assessments 
No formal tests of hypotheses are proposed for additional endpoints. Statistical comparisons 
may be performed for exploratory purposes. No formal inferences are planned on the 
additional endpoints and therefore alpha-adjustments for multiple comparisons will not be 
used. 
All additional endpoints are observational. 
11.3.7. Interim Analyses  
No interim analyses are planned.  
11.3.8. Subgroup Analyses 
Primary endpoints and/or additional endpoints will be summarized and treatment groups may 
be compared in each subgroup identified by the following categories (but not limit to): 
• Race 
• Gender (male vs female) 
• Age (≥ 65 and < 65) 
• Diabetes status (medically-treated vs non-diabetic) 
• Lesion characteristics (vessel diameter/lesion length) 
• Device matrix (diameter/length) 
• Other significant predictors identified by regression models 
 

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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 effectiveness assessment at two-sided 
significance level of 0.15 will be performed for the following subgroups: 
• Gender (male vs female) 
11.3.9. Justification of Pooling 
The concept of poolability analysis described below is applicable to both phase A RCT and 
phase B non-randomized. 
 
The poolability analysis regarding the primary effectiveness and/or safety endpoint across 
investigational centers, as well as among US, Europe, and Japan 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. 
11.3.9.1. Investigational Center Poolablity 
Due to the 2:1 randomization scheme using random permuted blocks (ie, blocks of 3 and 6) 
employed within each center, ideally there will be 2 DES BTK subjects for every 1 PTA 
subject. Only sites that enrolled sufficient subjects (i.e. 5 or more subjects) will be included 
for this poolability analysis and these sites will be reported individually. 
11.3.9.2. US, Europe, and Japan Poolablity 
The focus is mostly on the applicability of the European and Japanese populations with the 
US population. If the treatment effect is significantly different among US, Europe, and 
Japanese populations then possible/plausible explanation is required and/or potential bias 
needs to be addressed. 
11.3.10. Sensitivity Analysis for Missing Outcome Data 
Sensitivity analyses for the primary effectiveness and/or safety endpoints 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 and PP analyses 
sets to consider all combinations of present/absent for all subjects with missing primary 
outcome in the DES BTK group and the PTA group. 

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11.3.11. Multivariable Analyses 
Univariate and multivariable analyses will be performed as post-hoc analysis 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. 
11.3.12. 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). 
11.3.13. Changes to Planned Analyses 
Any changes to the planned statistical analyses made prior to performing the interim and/or 
the final primary analyses 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. 
12. Health Economics Outcomes 
A formal health economics analysis may be completed as part of this trial, given meaningful 
clinical results are obtained. This will take into consideration any differences in survival, 
complication rates, quality of life, and resource utilization. The EQ-5D questionnaire, generic 
quality of life measure, and the VascuQol questionnaire, disease specific quality of life 
measure, will be used to assess health utilities. 
Non-inpatient health care visits related to CLI will be documented using an unscheduled visit 
eCRF. (ie, clinic visit, emergency room or urgent care visit, etc).  
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. All changes 
made to the clinical data will be captured in an electronic audit trail and available for review 
by Boston Scientific 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 trials pertaining to 
the use of electronic records and signatures. Database backups are performed regularly. 

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The investigator is responsible for the accuracy, completeness and timeliness of the data 
submitted and must review all data for accuracy and 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 Medidata EDC system 
and will be issued to the investigational center for appropriate response. Investigational 
center staff will be responsible for resolving all queries in the database. 
All access to the clinical database will be changed to “Read only” after all data is either 
“Hard Locked” or “Entry Locked”. Once acceptance of the final report or finalization of 
publications (as applicable) is received, final database storage and archiving activities can 
begin. Once all of the closeout activities are completed a request to IT is submitted to have 
the “Database Locked” or “Decommissioned” and all database access revoked. 
13.2. Data and Record Retention 
The principal investigator or his/her designee or investigational center will maintain all 
essential study documents and source documentation that support the data collected on the 
trial subjects in compliance with applicable regulatory requirements.   
The principal investigator or his/her designee will take measures to prevent accidental or 
premature destruction of these documents. 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 Boston Scientific 
must receive written notification of this custodial change. Investigational centers 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, Boston Scientific will maintain necessary essential documents for 5 years from the 
date of the marketing application approval (or during the period of user-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 5 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 / Central assessment of study data 
Core laboratories will be established for the central assessment of key data collected for the 
trial. Guidelines for the collection, analysis, and interpretation of the data will be provided in 
the manual of operations. The following core laboratories / central reviewers have been 
assigned for the SAVAL trial: 

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• Angiography: 
o To assess the angiograms collected for the trial during the index procedure 
and during subsequent revascularization procedures when collected according 
to the investigational center’s standard procedures 
o To assess CTA or DSA angiographies taken at the 12-month follow-up visit in 
case the 12-month DUS is non-diagnostic 
o To confirm stent fractures identified by the X-ray core lab 
o When bailout stenting is required the angiography core lab will assess 
angiograms collected to document the bailout process 
• X-ray: to review the x-rays collected for the trial to assess stent integrity* 
• Ultrasound: to assess duplex ultrasound studies collected for the trial for lesion and 
stent patency 
• Independent Wound Reviewer: to review wound assessment data and images. 
*Note: When a stent fracture is identified, the x-ray will be reviewed by the angiography core 
lab to confirm the fracture. 
14. Deviations 
A trial deviation is an event where the investigator or the invitational center personnel did not 
conduct the clinical trial according to the clinical protocol, clinical study agreement, or 
applicable laws and regulations. 
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 will notify the 
sponsor and the reviewing IRB/EC, and the regulatory authority if applicable 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 will 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.  
Deviations may include but are not limited to: 
• Failure to obtain subject informed consent prior to beginning trial activities 
• Violation of inclusion/exclusion criteria 
• Failure to report serious or unanticipated adverse device effect or serious or 
unexpected AEs 
• Failure to collect protocol-required assessments 
• Subject missed visit or visit outside of window 
 
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. 

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Investigational centers may also be required to report deviations to the IRB/EC, and the 
regulatory authority, per local guidelines and national government regulations.  
Deviations attributable to the worldwide COVID-19 virus pandemic will be documented and 
reported to the sponsor using the EDC system.  The statistical analysis plan provides further 
detail on the handling of missing data, drop-outs, and protocol deviation.  
Deviations will be reviewed and evaluated on an ongoing basis and, as necessary, appropriate 
corrective and preventive actions including IRB/EC and regulatory authority notification, 
investigational center re-training, or center discontinuation/termination) will be put into place 
by the sponsor. 
The sponsor will not approve protocol waivers.  
15. Device Accountability for Products Labelled Investigational 
The investigational devices/equipment will be securely maintained, controlled, and used only 
in this clinical trial. Investigational product must be stored in a secured and locked location 
accessible only to those delegated individuals who are authorized by the investigational 
center principal investigator to access them.  
For investigational-labelled items, the principal investigator or an authorized designee shall 
do the following: 
• Securely maintain and control access to these items to ensure they are used only in 
this clinical study and only per the protocol  
• Ensure the storage environment for these items is appropriate for maintaining 
conditions per the items’ labeling (e.g. temperature, humidity, etc., as applicable)  
• Return remaining items upon Sponsor request and in the condition in which they were 
provided; reasonable wear and tear excepted 
 
The sponsor (or delegate) will keep records to document the physical location of all 
investigational devices from shipment from Boston Scientific (or designated facility) to the 
investigational centers until return or disposal. 
Records will be maintained by the investigational center trial personnel to document the 
physical location and conditions of storage of all investigational devices.  
The principal investigator or an authorized designee will keep records documenting the 
receipt, use, return and disposal of the investigational devices that include the following. 
Maintain accurate and timely Device Accountability Records, providing copies to Sponsor 
upon request. Such records shall include the following content, at minimum: 
• Name(s) of person(s) who received, used, returned, or disposed of each item; 
• Date of receipt 
• Identification and quantity of each investigational device (ie, batch number) 
• Expiry date, as applicable 
• Date of use 

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• Subject identification 
• Date on which the investigational device was returned, if applicable 
• Date of return of unused, expired, no longer needed, and/or malfunctioning 
investigational device, if applicable 
• Date and documentation of disposal, as directed by sponsor, if applicable 
16. Compliance 
16.1. Statement of Compliance 
This clinical investigation is financed by the study sponsor. Before the investigational site 
can be “Authorized to Enroll,” the investigational site must enter into a Clinical Study 
Agreement with the sponsor that details the financing of the study as well as the rights and 
obligations of the investigational site and the investigator. 
 
This study will be conducted in accordance with US FDA 21 CFR 812; European Medical 
Device Regulation,  ISO 14155: Clinical Investigation of Medical Devices for Human 
Subjects – Good Clinical Practice; the relevant parts of the ICH Guidelines for Good Clinical 
Practice; Japan Medical Device GCP Ordinance ethical principles that have their origins in 
the Declaration of Helsinki and individual country laws and regulations.  
The trial will not begin until the required approval/favorable opinion from the IRB/EC and/or 
regulatory authority has been obtained, if appropriate. Also, the trial will not begin prior to 
issuance of the center authorization to enroll, as provided by the sponsor. Any additional 
requirements imposed by the IRB/EC or a regulatory authority will be followed, if 
appropriate.  
16.2. Investigator Responsibilities 
The principal investigator of an investigational center is responsible for ensuring that the 
study 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, 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 study, sign the clinical study agreement and comply with the 
investigator responsibilities as described in such agreement   
• Prior to beginning the study, sign the investigator brochure signature page and protocol 
signature page documenting his/her agreement to conduct the study in accordance with 
the protocol 
• Provide his/her qualifications and experience to assume responsibility for the proper 
conduct of the study and that of key members of the investigational center team through 
up-to-date curriculum vitae or other relevant documentation and disclose potential 

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conflicts of interest, including financial, that may interfere with the conduct of the 
clinical study 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 
• Create and maintain source documents throughout the clinical study 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 reportable events 
• Report to the IRB/EC and regulatory authorities any SAEs and device deficiencies that 
could have led to a SADE and potential/USADE or UADE, if required by applicable laws 
or regulations or this protocol or by the IRB/EC, and supply Boston Scientific (or 
delegate) 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 when performing auditing 
activities 
• Ensure that informed consent is obtained in accordance with applicable laws, this 
protocol and local IRB/EC requirements 
• Provide adequate medical care to a subject during and after a subject’s participation in a 
clinical study in the case of adverse events, as described in the informed consent form  
• Inform the subject of the nature and possible cause of any adverse events experienced 
• 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 study, and make the necessary arrangements for emergency 
treatment, as needed 
• Ensure that clinical medical records are clearly marked to indicate that the subject is 
enrolled in this clinical study 
• 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 
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 
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• 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 investigational center team and facilities exist and are maintained 
and documented during the clinical investigation 
 
All investigators will provide their qualifications and experience to assume responsibility for 
their delegated tasks 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 study or interpretation of results. 
16.2.1. 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, ensuring team members are competent to perform the tasks they have 
been delegated and adequate supervision of those to whom tasks are delegated. Where there 
is a sub investigator at a center, the sub investigator should not be delegated the primary 
supervisory responsibility for the investigational center. The principal investigator is 
accountable for regulatory violations resulting from failure to adequately supervise the 
conduct of the clinical study.  
16.3. Institutional Review Board/ Ethics Committee 
The investigational center will obtain the written and dated approval/favorable opinion of the 
IRB/EC for the clinical investigation before recruiting subjects and implementing all 
subsequent amendments, if required. 
A copy of the written IRB/EC and/or competent authority (CA) approval of the protocol (or 
permission to conduct the study) and ICF, must be received by the sponsor (or designee) 
before recruitment of subjects into the study 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. 
Any amendment to the protocol will require review and approval by the IRB/EC before the 
changes are implemented to the study. All changes to the ICF will be IRB/EC approved; a 
determination will be made regarding whether a new ICF needs to be obtained from 
participants who provided consent, using a previous version of the ICF.  
Annual IRB/EC approval and renewals will be obtained throughout the duration of the study 
as required by applicable local/country laws or regulations or IRB/EC requirements. Copies 
of the study reports and the IRB/EC continuance of approval must be provided to the 
sponsor.  
16.4. Sponsor Responsibilities 
All information and data sent to Boston Scientific (or delegate) concerning subjects or their 
participation in this study will be considered confidential by Boston Scientific and will be 

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kept confidential in accordance with all applicable laws and regulations. Only authorized 
Boston Scientific personnel and/or a Boston Scientific representative including, but not 
limited to Contract Research Organization (CRO) will have access to this information. 
Authorized regulatory personnel have the right to inspect and copy all records pertinent to 
this study. Study data collected during this study may be used by Boston Scientific for the 
purposes of this study, publication, and to support future research and/or other business 
purposes, such as overseeing and improving the performance of its device, new medical 
research and proposals for developing new medical products and procedures. All data used in 
the analysis and reporting of this study or shared with a third-party researcher will be without 
identifiable reference to specific subjects. 
Information received during the study 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.  
16.4.1. 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 the index procedure, testing required by 
the protocol, and follow-up visits. Support may include HCP training, addressing HCP 
questions, or providing clarifications to HCPs concerning the operation of the investigational 
device. 
In addition, Boston Scientific personnel may perform certain activities to ensure trial quality. 
These activities may include the following. 
• Observing testing or medical procedures to provide information relevant to protocol 
compliance 
• Reviewing collected data and trial documentation for completeness and accuracy 
 
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  
• 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 
16.5. Insurance  
Where required by local/country regulation, proof and type of insurance coverage, by Boston 
Scientific for subjects in the study will be obtained. 
17. Monitoring 
Monitoring will be performed to assess continued compliance with the protocol and 
applicable regulations. The monitoring plan contains the strategy for frequency of monitoring 
visits and source data verification to be completed for the trial.  

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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. The investigator/institution guarantees direct access to original source documents 
(ie, paper and electronic hospital charts, appointment books, laboratory records) by Boston 
Scientific personnel, their designees, and applicable regulatory authorities. 
The trial may also be subject to a quality assurance audit by Boston Scientific or its 
designees, as well as inspection by appropriate regulatory authorities. It is important that the 
principal investigator and relevant trial personnel are available during on-site monitoring 
visits or audits and that sufficient time is devoted to the process. 
18. Potential Risks and Benefits 
18.1. Anticipated Adverse Events Associated with use and the Implantation of the 
DES BTK Vascular Stent System during an endovascular procedure 
• Allergic reaction (to drug/polymer, contrast, device or other) 
• Amputation 
• Bleeding/Hemorrhage 
• Death 
• Embolization (air, plaque, thrombus, device, tissue or other) 
• Hematoma 
• Ischemia 
• Need for urgent intervention or surgery  
• Pseudoaneurysm formation 
• Renal insufficiency or failure 
• Restenosis of stented artery 
• Sepsis/infection 
• Thrombosis/thrombus 
• Transient hemodynamic instability (hypotensive/hypertensive episodes) 
• Vasospasm 
• Vessel injury, including perforation, trauma, rupture and dissection 
• Vessel occlusion  
18.2. Adverse Events Unique to the Paclitaxel Drug Coating 
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. In these circumstances the dose was delivered 
throughout the body by the blood and in doses hundreds of times higher than the total amount 
on the coated stent for use in the proposed clinical trial. Potential adverse events that may be 
unique to the paclitaxel drug coating are: 

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• Allergic/immunologic reactions to drug (paclitaxel or structurally-related compounds) or 
the polymer stent 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 
 
Meta-analyses of randomized controlled trials of paclitaxel-coated balloons and paclitaxel-
eluting stents used to treat peripheral arterial disease in the femoropopliteal arteries have 
identified an increased risk of late mortality at 2 years and beyond. The magnitude and 
mechanism for the increased risk in mortality is currently unclear. The analyses also 
demonstrated reduced revascularization rates with the drug-containing products. The impact 
of future device exposure is unknown as is the impact of other drug-containing devices. 
Inadequate information is available to evaluate the potential mortality risk associated with the 
use of paclitaxel-coated devices for the treatment of other diseases/conditions. Physicians 
should discuss the benefits and risks of all available treatment options with patients. 
18.3. Risks Associated with Participation in the Clinical Trial 
Risks associated with venipuncture include ecchymosis, hematoma, infections, inflammation 
and pain. There may be additional risks linked to the investigational device procedure and 
follow-up testing that are unknown. Tests planned for the trial follow-up phase is standard of 
care procedures except for the collection of high definition x-ray to assess stent integrity.  
18.4. Possible Interactions with Concomitant Medical Treatments 
In addition to the risks associated with the implantation of stents and the use of paclitaxel, the 
use of prolonged dual antiplatelet therapy after stent implantation may increase the risk of 
bleeding. Refer to the package insert for further information on drug interactions and side 
effects associated with paclitaxel or antithrombotic/antiplatelet medications. 
18.5. Risk Minimization Actions 
Additional risks may exist. Risks can be minimized through compliance with this protocol, 
performing procedures in the appropriate healthcare 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 Boston Scientific with all pertinent 
information required by this protocol. 

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18.6. Anticipated Benefits 
Potential anticipated benefits include the effective treatment of atherosclerotic infrapopliteal 
lesions with improvement in the symptoms of disease. However, the DES BTK Vascular 
Stent System is an investigational device and these potential benefits may or may not actually 
be present. 
18.7. Risk to Benefit Rationale 
The DES BTK Vascular Stent System 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). The DES BTK 
Vascular Stent System is expected to have an acceptable adverse event profile when used 
under the conditions intended; the benefits associated with the use of the DES BTK Vascular 
Stent System are expected to outweigh the risks. 
19. Safety Reporting 
19.1. Reportable Events by investigational center to Boston Scientific 
It is the responsibility of the investigator to assess and report to Boston Scientific (or 
delegate) the following events for enrolled subjects: 
• Adverse events/ serious adverse events related to Study Device (Investigational Device) 
and Comparator Device 
• All Serious Adverse Events related to the Procedure 
• Serious adverse events 
• Device Deficiencies  
• Unanticipated adverse device effects/unanticipated serious adverse device effects 
• New findings/updates in relation to already reported events 
• New wounds on the index limb 
• All other adverse events (through the 12-month follow-up visit) 
 
When possible, the medical diagnosis should be reported as the event term instead of 
individual symptoms. 
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. 
An AE experienced by the trial subjects after randomization/enrollment and during protocol-
required testing must be recorded in the eCRF. 
Underlying diseases are not reported as an AE unless there is an increase in severity or 
frequency during the course of the investigation.  
Death will not be recorded as an AE, but will be reflected as an outcome of a specific SAE. 
Refer to Table 19.2-1 for AE definitions. 

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Refer to Section 18 for the known risks associated with the trial device(s). 
Device deficiencies will be reported on the appropriate eCRF per the trial CRF completion 
guidelines. When an AE results from a device deficiency or other device issue, the AE will 
be reported separately. 
An in-patient hospitalization is defined as the subject being admitted to the hospital for ≥ 24 
hours with the following exceptions: 
• A hospitalization for routine follow-up per standard of care. 
• A hospitalization that is uncomplicated and elective/planned (ie, planned prior to 
enrollment) does not have to be reported as an SAE or AE. 
• If complications or AEs occur during an elective/planned 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. 
 
If subjects are hospitalized during the course of the trial, the data about the hospitalization 
associated with adverse events will be collected in the EDC system.  
Planned minor amputations (ie, below the ankle) or debridement that are performed as part of 
the subject’s care pathway will not be reported as an AE, however, clinical sequelae resulting 
from the minor amputation must be reported as an AE. 
The underlying pathology for an unplanned debridement and/or amputation procedure (ie, 
one that is not part of the care path continuum) will be reported as an AE. 
New wound development on the index limb will be reported as an AE. Images will be 
collected for all new wounds and submitted for the study. 
Serious adverse device-effects that are still ongoing at the end of the subject’s participation in 
the trial will be followed up for resolution status and this information will be provided to 
Boston Scientific for the purpose of regulatory agency reporting for the trial. 
19.2. Definitions and Classification 
Administrative edits were made on the safety definitions from applicable regulations and 
guidance including (but not limited to) 21 CFR Part 812, ISO 14155 and EU MDR 
2017/745/MDCG 2020-10/1 Guidance on Safety Reporting in Clinical Investigations for 
clarification purposes. 
 
Table 19.2-1: Safety Definitions 
Term 
Definition 
Adverse Event (AE) 
 
Ref: ISO 14155 
 
Ref: MDCG 2020-10/1 
 
Any untoward medical occurrence, unintended disease or injury, or any 
untoward clinical signs (including an abnormal laboratory finding) in 
subjects, users or other persons, in the context of a clinical investigation, 
whether or not related to the investigational medical device and whether 
anticipated or unanticipated.  

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Term 
Definition 
 
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 
 
Ref: MDCG 2020-10/1 
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 
from intentional misuse  of the investigational medical device. 
NOTE 3: This includes ‘comparator’ if the comparator is a medical 
device. 
Serious Adverse Event (SAE) 
 
Ref: ISO 14155 
 
Ref: MDCG 2020-10/1 
Adverse event that led to any of the following: 
a) death, 
b) serious deterioration in the health of the subject, users or other persons 
as defined by either: 
1) a life-threatening illness or injury, or 
2) a permanent impairment of a body structure or a body function, 
including chronic diseases or 
3) in-patient hospitalization or prolongation of existing 
hospitalization, or 
4) medical or surgical intervention to prevent life-threatening illness 
or injury or permanent impairment to a body structure or a body 
function 
c) foetal distress, foetal death, or a congenital abnormality or birth defect 
including physical or mental impairment. 
NOTE 1: Planned hospitalization for a pre-existing condition, or a 
procedure required by the clinical investigational plan, without a serious 
deterioration in health, is not considered a serious adverse event. 
Serious Adverse Device Effect 
(SADE) 
 
Ref: ISO 14155 
 
Ref: MDCG 2020-10/1 
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.   

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Term 
Definition 
Unanticipated Serious Adverse 
Device Effect (USADE) 
 
Ref: ISO 14155 
 
Ref: MDCG 2020-10/1 
Serious adverse device effect which by its nature, incidence, severity, or 
outcome has not been identified in the risk assessment. 
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 assessment. 
Serious Health Threat 
 
Ref: ISO 14155 
 
Signal from any adverse event or device deficiency that indicates an 
imminent risk of death or a serious deterioration in the health in subjects, 
users or other persons, and that requires prompt remedial action 
for other subjects, users or other persons. 
Note 1: This would include events that are of significant and unexpected 
nature such that they become alarming as a potential serious health hazard 
or possibility of multiple deaths occurring at short intervals. 
Device Deficiency 
 
Ref: ISO 14155 
Ref: MDCG 2020-10/1 
An inadequacy of a medical device related to its identity, quality, 
durability, reliability, usability, safety or performance.  
NOTE 1: Device deficiencies include malfunctions, use errors, and 
inadequacy in the information supplied by the manufacturer including 
labelling. 
NOTE 2: This definition includes device deficiencies related to the 
investigational medical device or the comparator. 
The following definitions will be used for defining hospitalization or prolongation of hospitalization for SAE 
classification purposes: 
Hospitalizations  
Hospitalization does not include: 
• 
emergency room visit that does not result in in-patient admission  
Note: although an emergency room visit does not itself meet the 
definition for hospitalization, it may meet other serious criteria 
(e.g. medical or surgical intervention to prevent permanent 
impairment or damage) 
• 
elective and pre-planned treatment/surgery for a pre-existing 
condition that is documented in the subject’s record at the time of 
consent/enrollment 
• 
admission for social reasons and/or respite care in the absence of 
any deterioration in the subject’s general condition (e.g. subject is 
homeless, caregiver relief) 
• 
pre-planned, protocol-specified admission related to the clinical 
study (e.g. procedure required by protocol)  
Prolongation of hospitalization  
In-patient admission to the hospital that is prolonged beyond the expected 
standard duration for the condition under treatment. 
Note: new adverse events occurring during the hospitalization are 
evaluated to determine if they prolonged hospitalization or meet another 
SAE criteria. 

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19.3. Relationship to Study Device(s)(Investigational Device and Comparator 
Device) and/or Study Procedure 
The investigator must assess the relationship of the reportable AE to the study device, or 
procedure.  
Table 19.3-1: Criteria for Assessing Relationship of Trial Device(s) (Investigational 
Device and Comparator Device) or Procedure to Adverse Event 
Classification 
Description 
Not Related 
Ref: MDCG 2020-10/1 
 
 
Relationship to the device, comparator or procedures can be excluded when: 
• 
The event has no temporal relationship with the use of the investigational 
device or the procedures related to the use of the investigational device; 
• 
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 that cannot be affected by the 
device or procedure;  
• 
The event can be attributed to another cause (eg, 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 investigational device 
used for diagnosis, when applicable; 
• 
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. 

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Classification 
Description 
Unlikely Related 
Ref: MEDDEV 2.7/3 
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 
Ref: MDCG 2020-10/1 
The relationship with the use of the investigational device or comparator, or the 
relationship with procedures is weak but cannot be ruled out completely. 
Alternative causes are also possible (eg, an underlying or concurrent illness/clinical 
condition or/and an effect of another device, drug or treatment). Cases where 
relatedness cannot be assessed or no information has been obtained should also be 
classified as possible. 
Probably Related 
Ref: MDCG 2020-10/1 
The relationship with the use of the investigational device or comparator, or the 
relationship with procedures seems relevant and/or the event cannot be reasonably 
explained by another cause. 
Causal Relationship 
Ref: MDCG 2020-10/1 
The event is associated with the investigational device or comparator or with 
procedures 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 investigational device 
use/application or procedures; 
• 
The event involves a body-site or organ that 
 the investigational device or procedures are applied to 
 the investigational device or procedures 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 (eg, 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 investigational 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/procedures and the 
adverse event 
The investigator must assess the relationship of an AE to the antiplatelet medication as 
related or unrelated. 
Table 19.3-2: Criteria for Assessing Relationship of Antiplatelet Medication to an 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. 

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19.4. Investigator Reporting Requirements 
The communication requirements for reporting to BSC are as shown in Table 19.4-1. An 
Event Document Checklist included in the MOP specifies the required source documents for 
events requiring CEC adjudication. 
Table 19.4-1: Investigator Reporting Requirements 
Event Classification 
Communication Method  
Communication Timeline 
(21 CFR Part 812, MDCG 2020-10/1 ) 
Unanticipated Adverse Device 
Effect/Unanticipated Serious 
Adverse Device Effect  
(UADE/USADE) 
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 
Provide all relevant source 
documentation (de-identified/ 
pseudonymized) for reported 
event 
• 
At request of sponsor 
Serious Adverse Event (SAE) 
Complete AE eCRF page with 
all available new and updated 
information.  
• 
Immediately, but not later than  3 
calendar days of first becoming 
aware of the event or as per 
local/regional regulations.  
• 
Reporting required through the 36 
Months Post-Procedure Visit 
Provide all relevant source 
documentation (de-identified/ 
pseudonymized) for events to 
be adjudicated by CEC 
• 
When documentation is available 
Serious Adverse Device 
Effects (SADE) 
Complete AE eCRF page with 
all available new and updated 
information. 
• 
Immediately, but not later than 3 
calendar days of first becoming 
aware of the event or as per 
local/regional regulations.  
• 
Reporting required through the 36 
Months Post-Procedure Visit 
Provide all relevant source 
documentation (de-identified/ 
pseudonymized) for reported 
event 
• 
At request of sponsor 
Device Deficiencies (including 
but not limited to 
malfunctions, use errors and 
inadequacy in information 
supplied by the manufacturer, 
including labeling) 
Complete Device Deficiency 
eCRF with all available new 
and updated information.  
• 
Immediately, but not later than 3 
calendar days of first becoming 
aware of the event or as per 
local/regional regulations.  
• 
Reporting required through the end 
of the trial 

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Event Classification 
Communication Method  
Communication Timeline 
(21 CFR Part 812, MDCG 2020-10/1 ) 
Note: Any Device Deficiency 
that might have led to a serious 
adverse event if appropriate 
action had not been taken, 
intervention had not occurred 
or  circumstances had been 
less fortunate is considered a 
reportable event. 
Provide all relevant source 
documentation (de-identified/ 
pseudonymized) for reported 
event 
• 
At request of sponsor 
Adverse Event (AE) including 
Adverse Device Effects (ADE) 
Complete AE eCRF, which 
contains such information as 
date of AE, treatment of AE, 
resolution, assessment of 
seriousness and relationship to 
the device.  
• 
In a timely manner (eg, 
Recommended within 10 business 
days) after becoming aware of the 
information 
• 
ADE reporting required through the 
36 Months Post-Procedure Visit 
• 
AE reporting required through the 
12-month follow-up visit 
Provide all relevant source 
documentation (de-identified/ 
pseudonymized) for reported 
event 
• 
At request of sponsor 
19.5. Boston Scientific Device Deficiencies 
Device deficiencies for the DES BTK Vascular Stent System (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 Boston 
Scientific. If possible, the device(s)/system should be returned to Boston Scientific for 
analysis. Instructions for returning the investigational device(s) will be provided in the 
manual of operations and trial training. Device deficiencies should also be documented in the 
subject’s medical records. 
Device deficiencies related to a non-BSC comparator device will not be collected. Any non-
BSC comparator device malfunction will be reported by the Investigator directly to the 
manufacturer of that device as a complaint. 
Device deficiencies are not adverse events. However, an adverse event that results from a 
device deficiency should be recorded as an adverse event on the appropriate eCRF. 
Any Device Deficiency that might have led to a SAE if appropriate action had not been 
taken, intervention had not occurred or 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 
• Difficult or unable to advance over wire 
• Difficult or unable to track through anatomy 

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• Difficult or unable to cross lesion 
• Difficult or unable to deploy stent 
• Stent damaged 
• Stent jump 
• Kinked or deformed stent 
• Difficult to remove stent delivery system from body 
• Stent fracture 
• Stent migration 
19.6. Reporting to Regulatory Authorities / IRBs / ECs / Investigators 
Boston Scientific is responsible for reporting adverse event information to all participating 
principal investigators, IRBs/ECs and regulatory authorities, as applicable.  
The principal investigator is responsible for informing the IRB/EC, and regulatory authorities 
of UADEs and SAEs as required by local/regional regulations. 
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. 
20. 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 any trial-required procedure or testing, the 
use of an investigational device, and data collection.  
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 institutional ethics committee and/or regulatory authority, as applicable. Boston 
Scientific will provide a template of the ICF to investigators participating in this trial. The 
ICF template may be modified to meet the requirements of the investigative center’s IRB/EC.  
Approval of the investigational center’s ICF is required by Boston Scientific (or designee) 
and the governing IRB/EC prior to the first use and any time the ICF is updated during the 
trial. 
The ICF must be in a language understandable to the subject and, when needed, Boston 
Scientific (or delegate) will assist the investigational center with obtaining ICF translation. 
Translated ICFs must also have IRB/EC approval prior to their use. Privacy language will be 
included in the body of the form or as a separate form in compliance with local requirements.  
The process of obtaining informed consent will, at minimum, include the following and will 
be in compliance with all local applicable laws, rules, regulations and guidelines: 
• Be conducted by the principal investigator or qualified designee authorized to conduct the 
process  

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• 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 a subject to participate 
• Will not waive or appear to waive subject’s legal rights 
• Will 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 
• Explain that important new information is to be provided to new and existing subjects 
throughout the clinical trial  
 
The ICF will 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. The original signed ICF will be retained by the investigational center and a copy of 
the signed and dated document and any other written information must be given to the person 
signing the ICF. The subject will receive a signed copy of the ICF and other written 
information as approved by the IRB/EC. 
For individuals less than 20 years of age enrolled at a Japanese center, the subject’s legal 
representative, as well as the subject, must provide written informed consent. In Japan, ICF 
signature may be replaced by printed name and seals of appropriate individuals. 
If the informed consent is obtained the same day the subject begins participation in trial-
related procedures, it must be clearly documented in the subject’s medical record that consent 
was obtained prior to participation in any trial-related procedures. 
Failure to obtain subject consent will be reported by Boston Scientific to the applicable 
regulatory authority according to the local requirements (eg, FDA requirement is within 5 
working days of learning of such an event).  
Any violation of the informed consent process must be reported as a deviation to the sponsor 
and in compliance with local requirements (ie, regulatory authority, IRB/EC). 
If new information becomes available that can significantly affect a subject's future health 
and medical care, that information will 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 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. The new version of the ICF must be approved by 
the IRB/EC. Acceptance by Boston Scientific is required if changes to the revised ICF are 
requested by the investigational center’s IRB/EC. The IRB/EC will determine the subject 
population to be re-consented. 

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21. Committees 
21.1. Executive Committee 
An executive committee composed of Boston Scientific clinical management and selected 
coordinating principal investigator(s) will be convened. 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. The executive committee may 
request participation of SAVAL trial investigators on the committee. 
21.2. Safety Monitoring Process 
To promote early detection of safety issues, the independent clinical events committee (CEC) 
and data monitoring committee (DMC) 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 the Boston Scientific safety group (or designee), which is 
responsible for coordinating the collection of information for the subject dossier from the 
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. 
21.3. Clinical Events Committee 
The CEC is an independent group of individuals with no affiliation with Boston Scientific. 
Committee membership will include 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 
• Clinically-driven target lesion revascularization 
• Target vessel revascularization 
• Target limb major amputations 
• Target Lesion stent thrombosis 
 
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 centers. 
21.4. Data Monitoring Committee 
A DMC will be established to review overall trial conduct and safety and will be comprised 
of, at minimum, 3 members who are independent of Boston Scientific and the trial 
investigators. The DMC will be comprised of at least 2 independent clinicians and 1 

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independent statistician with expertise in peripheral endovascular procedures and/or 
statistical subject matter.  
The DMC will be responsible for: 
• Assessing the progress of the trial, including safety data 
• Evaluating trial conduct (eg, trial deviations) for the impact on the validity and scientific 
merit of the trial 
• Recommending to Boston Scientific whether to continue, modify, or stop the trial 
• Provide recommendation for use of overlapping stents for the study (i.e. assessing the 
first 46 phase A RCT subjects) 
 
Boston Scientific personnel, or delegate, may facilitate the DMC meetings, provide trial 
progress updates, and answer questions. Boston Scientific personnel will not be voting 
members or participate in the closed session portion of the meetings. 
The frequency for meetings and thresholds will be defined within a DMC charter. Meetings 
may be more frequent depending on the rate of enrollment, number of AEs, and/or deviations 
collected and at the request of Boston Scientific. Meetings may be held in-person or via 
teleconference. 
21.5. Independent Wound Assessment 
Wound assessment data and images will be reviewed by an independent reviewer(s), with 
expertise in wound care and with no affiliation with Boston Scientific. The independent 
assessor(s) will be blinded to randomization assignment in phase A. 
22. Suspension or Termination 
22.1. Premature Termination of the Study 
Boston Scientific reserves the right to terminate the trial at any stage but intends to exercise 
this right only for valid scientific or business 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. 
22.1.1 Criteria for Premature Termination of the Study 
Possible reasons for premature trial termination include, but are not limited to, the following: 
• Suspicion of an unacceptable risk, including serious health threat. In this case, the 
sponsor shall suspend the clinical investigation while the risk is assessed. The sponsor 
shall terminate the clinical investigation if an unacceptable risk which cannot be 
controlled is confirmed. 
• Instructions by the IRB/EC or regulatory authorities to suspend or terminate the clinical 
investigation. 

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• 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 
22.2. Termination of Study Participation by the Investigator or Withdrawal of IRB/EC 
Approval 
Any investigator or associated IRB/EC or regulatory authority may discontinue participation 
in the trial or withdraw 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. 
22.3. 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 investigational centers by 
Boston Scientific. The IRB/EC 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 Boston Scientific. 
The principal investigator or his/her designee must return all trial-related documents and 
investigational product to Boston Scientific, unless this action would jeopardize the rights, 
safety, or welfare of the subjects 
22.4. Criteria for Suspending/Terminating a Study Center 
Boston Scientific reserves the right to stop the inclusion of subjects at a trial investigational 
center at any time after the study initiation visit, if no subjects have been enrolled for a period 
beyond 3 months after center initiation, or if the center has multiple or severe protocol 
violations/noncompliance without justification and/or fails to follow remedial actions. 
In the event of termination of an investigational center’s participation, all study devices and 
testing equipment, as applicable, will be returned to Boston Scientific unless this action 
would jeopardize the rights, safety or well-being of the subjects. The IRB/EC and regulatory 
authorities, as applicable, will be notified. Study participants will be contacted, as applicable, 
and be informed of changes to study visit schedule. 
 

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23. Study Registration and Results 
23.1. Study Registration 
To comply with applicable laws and regulations, the study will be registered on a publicly 
accessible database. 
23.2. Clinical Investigation Report 
Study results will be made available in accordance with the legal requirements and the 
recognized ethical principles, in accordance with the Boston Scientific Policy. A Clinical 
Investigation Report will be made available to all investigators, IRB/EC and regulatory 
authorities, as applicable in accordance with the Boston Scientific Policy and local 
requirements.  As applicable an abbreviated Clinical Investigation Report will be made 
available on a publicly accessible database. 
 
24. Publication Policy 
Boston Scientific requires disclosure of its involvement as a sponsor or financial supporter in 
any publication or presentation relating to a Boston Scientific trial or its results. Boston 
Scientific will submit trial results for publication (regardless of trial outcome) following the 
conclusion or termination of the trial. Boston Scientific 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, 
Boston Scientific personnel may assist authors and investigators in publication preparation 
provided the following guidelines are followed. 
• Authorship and contributorship requirements as described above must be followed 
• Boston Scientific involvement in the publication preparation and the Boston Scientific 
publication policy should be discussed with the coordinating principal investigator(s) 
and/or executive 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 
 
The data, analytic methods, and study materials for this clinical trial may be made available 
to other researchers in accordance with the Boston Scientific Data Sharing Policy 
(https://www.bostonscientific.com/). 

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25. Reimbursement and Compensation for Subjects 
25.1. Subject Reimbursement 
Travel and other expenses incurred by subjects as a result of participation in the study will be 
reimbursed in accordance with pertinent country laws and regulations and per the clinical 
study agreement. 
25.2. Compensation for Subject’s Health Injury 
Boston Scientific will purchase an insurance policy to cover the cost of potential health 
injury for study subjects, if required by applicable law.  
 
 

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26. Bibliography 
1. 
Kolte D, Kennedy KF, Shishehbor MH, et al. Thirty-Day Readmissions After 
Endovascular or Surgical Therapy for Critical Limb Ischemia: Analysis of the 2013 to 
2014 Nationwide Readmissions Databases. Circulation. 2017;136(2):167-176. 
2. 
Conte MS, Geraghty PJ, Bradbury AW, et al. Suggested objective performance goals 
and clinical trial design for evaluating catheter-based treatment of critical limb 
ischemia. J Vasc Surg. 2009;50(6):1462-1473 e1461-1463. 
3. 
Scheinert D, Katsanos K, Zeller T, et al. A prospective randomized multicenter 
comparison of balloon angioplasty and infrapopliteal stenting with the sirolimus-
eluting stent in patients with ischemic peripheral arterial disease: 1-year results from 
the achilles trial. J. Am. Coll. Cardiol. 2012;60(22):2290-2295. 
4. 
Spreen MI, Martens JM, Hansen BE, et al. Percutaneous Transluminal Angioplasty 
and Drug-Eluting Stents for Infrapopliteal Lesions in Critical Limb Ischemia (PADI) 
Trial. Circ Cardiovasc Interv. 2016;9(2):e002376. 
5. 
Kinlay S. Management of critical limb ischemia. Circ. Cardiovasc. Interv. 2016;9:2 
Article Number: e001946. 
6. 
Elsayed S, Clavijo LC. Critical limb ischemia. Cardiol Clin. 2015;33(1):37-47. 
7. 
Conte MS. Critical appraisal of surgical revascularization for critical limb ischemia. 
J. Vasc. Surg. 2013;57(2 Suppl):8S-13S. 
8. 
Gray BH, Diaz-Sandoval LJ, Dieter RS, Jaff MR, White CJ. SCAI expert consensus 
statement for infrapopliteal arterial intervention appropriate use. Catheter. 
Cardiovasc. Interv. 2014;84(4):539-545. 
9. 
Adam DJ, Beard JD, Cleveland T, et al. Bypass versus angioplasty in severe 
ischaemia of the leg (BASIL): multicentre, randomised controlled trial. Lancet. 
2005;366(9501):1925-1934. 
10. 
Popplewell MA, Davies HOB, Narayanswami J, et al. A Comparison of Outcomes in 
Patients with Infrapopliteal Disease Randomised to Vein Bypass or Plain Balloon 
Angioplasty in the Bypass vs. Angioplasty in Severe Ischaemia of the Leg (BASIL) 
Trial. European Journal of Vascular and Endovascular Surgery. 2017;54(2):195-201. 
11. 
Sadaghianloo N, Jean-Baptiste E, Declemy S, Mousnier A, Brizzi S, Hassen-Khodja 
R. Percutaneous angioplasty of long tibial occlusions in critical limb ischemia. Ann 
Vasc Surg. 2013;27(7):894-903. 
12. 
Bosiers M, Scheinert D, Peeters P, et al. Randomized comparison of everolimus-
eluting versus bare-metal stents in patients with critical limb ischemia and 
infrapopliteal arterial occlusive disease. J. Vasc. Surg. 2012;55(2):390-398. 
13. 
Spreen MI, Martens JM, Knippenberg B, et al. Long-Term Follow-up of the PADI 
Trial: Percutaneous Transluminal Angioplasty Versus Drug-Eluting Stents for 
Infrapopliteal Lesions in Critical Limb Ischemia. J Am Heart Assoc. 2017;6(4). 
14. 
de Weger VA, Beijnen JH, Schellens JH. Cellular and clinical pharmacology of the 
taxanes docetaxel and paclitaxel--a review. Anticancer Drugs. 2014;25(5):488-494. 
15. 
Ng VG, Mena C, Pietras C, Lansky AJ. Local delivery of paclitaxel in the treatment 
of peripheral arterial disease. Eur. J. Clin. Invest. 2015;45(3):333-345. 

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16. 
Dake MD, Van Alstine WG, Zhou Q, Ragheb AO. Polymer-free paclitaxel-coated 
zilver PTX stentsevaluation of pharmacokinetics and comparative safety in porcine 
arteries. Journal of Vascular and Interventional Radiology. 2011;22(5):603-610. 
17. 
Banerjee S, Sarode K, Mohammad A, et al. Femoropopliteal artery stent thrombosis: 
Report from the excellence in peripheral artery disease registry. Circ. Cardiovasc. 
Interv. 2016;9:2 Article Number: e002730. 
18. 
Federman DG, Ladiiznski B, Dardik A, et al. Wound Healing Society 2014 update on 
guidelines for arterial ulcers. Wound Repair Regen. 2016;24(1):127-135. 
19. 
Zhao Y, Yang Y. Poolability Analysis in Medical Device Trials:  A Reviewer's 
Perspective. American Statistical Association Biopharmaceutical Section Statistics 
Workshop. 2015. 
27. Abbreviations and Definitions  
27.1. Abbreviations 
 
 
Abbreviation 
Terminology 
ABI 
Ankle Brachial Index 
ADE 
Adverse Device Effect 
AE 
Adverse Event 
BSC 
Boston Scientific Corporation 
CTA 
Computerized Tomography Angiography 
CE 
Conformité Européenne (meaning European Conformity) 
CEC 
Clinical Events Committee 
DES BTK 
Drug-eluting stent below the knee 
DFU 
Directions for Use 
DSA 
Digital Subtraction Angiography 
DUS 
Duplex Ultrasound 

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eCRF 
Electronic Case Report Form 
EC 
Ethics Committee 
EDC 
Electronic Data Capture 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization 
ITT 
Intention to Treat 
IRB 
Institutional Review Board 
MAE 
Major Adverse Event 
PTA 
Percutaneous Transluminal Angioplasty 
SADE 
Serious Adverse Device Effect 
SAE 
Serious Adverse Event 
TBI 
Toe Brachial Index 
TLR 
Target Lesion Revascularization 
TVR 
Target Vessel Revascularization 
UADE 
Unanticipated Adverse Device Effect 
 
 

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27.2. Definitions 
Table 26.2-1: 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. 
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. 
Calcification 
Readily apparent densities seen within the artery wall and site of 
lesion as an x-ray-absorbing mass. 
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). 

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Term 
Definition 
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 the 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. 
Distal embolization 
Migration of a filling defect, or thrombus, to distally occlude the 
target vessel or one of its branches. 

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Term 
Definition 
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. 
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. 
Inflow and Outflow 
Lesions 
Inflow lesion – a lesion located in the iliac artery, SFA and/or 
popliteal artery, proximal to the target lesion 
Outflow lesion - a lesion located in the segment of the target vessel 
distal to the target  lesion 
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. 
Major Adverse 
Event 
Defined as: 
• Above the ankle amputation of the index limb 
• Major re-intervention (new bypass graft, jump/interposition 
graft, or thrombectomy/thrombolysis) 
• Perioperative (30 day) mortality 
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 
investigational center or angiographic core laboratory at any point 
during the procedure. 
Clinical perforation: perforation requiring additional treatment 
(eg, covered stent graft or surgery), or resulting in significant 
hemodynamic compromise, or death. 

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Term 
Definition 
Planned 
Hospitalization 
An elective/planned hospitalization (ie, planned prior to 
enrollment)  
Primary Patency 
A binary endpoint to be determined via duplex ultrasound (DUS) 
measuring flow or no flow in the absence of clinically-driven 
target lesion revascularization or bypass of the target lesion 
Procedural Success 
Technical success with no MAEs noted within 24 hours of the 
index procedure. 
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.  
Re-intervention 
(Percutaneous 
and/or Surgery) 
Either repeat endovascular treatment or bypass surgery of the 
index limb, performed subsequently to the subject leaving the 
procedure room after the index procedure.  
Reference Vessel 
Diameter (RVD) of 
Normal Arterial 
Segment 
Angiographic measurement of the artery proximal and/or distal to 
the lesion intended for treatment. 
Rutherford/Becker 
Classification 
Category 0 - Asymptomatic 
Category 1  - Mild claudication 
Category 2 - Moderate claudication 
Category 3 - Severe claudication 
Category 4 - Ischemic rest pain 
Category 5* - Minor tissue loss - nonhealing ulcer, focal gangrene 
Category 6 - Major tissue loss – extending above TM level 
*Lesions must be limited to the forefoot and should be treatable with planned 
debridement, toe amputations and never exceeding trans metatarsal amputation. 

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Term 
Definition 
Source data 
 
Ref: ISO 14155 
 
 
All information in original records, certified copies of original 
records of clinical findings, observations, or other activities in a 
clinical investigation, necessary for the reconstruction and 
evaluation of the clinical investigation. 
Note 1:  This includes source data initially recorded in an 
electronic format.  
Source document 
 
Ref: ISO 14155 
 
Original or certified copy of printed, optical or electronic 
document containing source data.   
Stent fracture 
A break in one or more places of the stent. The following 
definitions will be used to determine the type and extent of stent 
fracture (to be assessed by the x-ray core laboratory): 
• Grade 0: No strut fractures 
• Grade I: single tine fracture 
• Grade II: multiple tine fracture 
• Grade III: stent fracture(s) with preserved alignment of the 
components 
• Grade IV: stent fracture(s) with mal-alignment of the 
components 
• Grade V: Stent fracture(s) in a trans-axial spiral configuration 

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Term 
Definition 
Stent thrombosis 
The occurrence of either of the following: 
1. Angiographic documentation (or any other imaging modality if 
angiography not available) of an acute, complete occlusion of a 
previously successfully treated target lesion and/or 
2. Angiographic documentation (or any other imaging modality if 
angiography not available) of a flow-limiting thrombus within, or 
adjacent to, a previously successfully treated target lesion. 
Acute stent thrombosis is defined as occurring ≤ 24 hours 
following the clinical study procedure.  
Subacute stent thrombosis is defined as occurring > 24 hours to ≤ 
30 days following the clinical study procedure.  
Late stent thrombosis is defined as > 30 days to 365 days 
following the clinical study procedure. 
Very late stent thrombosis is defined as > 365 days following the 
clinical study procedure. 
Target Lesion 
The segment of the artery with peripheral arterial disease that 
meets the characteristics outlined in the protocol to be treated with 
either the DES BTK test device or the PTA control device.  
Target Lesion 
Revascularization 
(TLR) 
Any surgical or percutaneous intervention to the target lesion(s) 
after the index procedure when one of the following situations is 
present:  
 
• A target lesion revascularization will be considered clinically-
driven if it occurs within 5 mm proximal or distal to the 
original treatment segment with diameter stenosis ≥50% by 
quantitative angiography (QA) and the subject has recurrent 
symptoms (≥ 1 change in Rutherford Classification or 
associated with decreased ABI/TBI of ≥20% or ≥ 0.15 in the 
treated segment. TBI allowed in cases of incompressible 
vessels.) 
• A target lesion revascularization for an in-lesion diameter 
stenosis less than 50% might also be considered a MAE by the 
CEC if the subject has recurrent symptoms (≥ 1 change in 
Rutherford Classification or associated with decreased 
ABI/TBI of ≥20% or ≥ 0.15 in the treated segment. TBI 
allowed in cases of incompressible vessels.) 

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Term 
Definition 
Target Vessel 
The vessel(s) containing the target lesion, i.e. Tibial Peroneal 
Trunk, Anterior Tibial Artery, Posterior Tibial Artery and/or 
Peroneal Artery. 
Target Vessel 
Revascularization 
(TVR) 
Any surgical or percutaneous intervention to the target vessel(s) 
after the index procedure when one of the following situations is 
present:  
 
• A target vessel revascularization will be considered as 
clinically-driven if the culprit lesion stenosis is ≥50% by QA 
and the subject has recurrent symptoms (≥ 1 change in 
Rutherford Classification or associated with decreased 
ABI/TBI of ≥20% or ≥ 0.15 in the treated segment. TBI 
allowed in cases of incompressible vessels.) 
• A target vessel revascularization for a culprit lesion diameter 
stenosis less than 50% might also be considered a MAE by the 
CEC if the subject has recurrent symptoms (≥ 1 change in 
Rutherford Classification or associated with decreased 
ABI/TBI of ≥20% or ≥ 0.15 in the treated segment. TBI 
allowed in cases of incompressible vessels.) 
Technical Success 
Delivery and deployment of the assigned study therapy (stent or 
PTA) to the target lesion achieving a residual angiographic 
stenosis no greater than 30% by visual assessment. 
Thrombus 
(angiographic) 
Discrete, mobile intraluminal filling with defined borders 
with/without associated contrast straining; these are classified as 
either absent or present. 
VascuQol 
The VascuQol is a 25-item questionnaire used to measure the 
quality of life in patients with lower limb ischemia. The tool is 
sub-divided into 5 domains: pain (4 items), symptoms (4 items), 
activities (8 items), social (2 items), and emotional (7 items).  
 
 
 

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28. Appendices 
28.1. Appendix A: Affect to Medicare Beneficiaries (US only) 
Critical limb ischemia (CLI) represents the terminal stage of obstructive, atherosclerotic, 
peripheral arterial disease. Patients affected by critical limb ischemia are the most complex 
subset of those with peripheral arterial disease and typically bear the long-term pathological 
consequences of hypertension, hyperlipidemia, diabetes mellitus, and renal failure.1  When 
left untreated, CLI caused major amputation in 73% of the patients with rest pain and in 95% 
of the patients with tissue loss at 1 year.2  Diabetics with CLI are at particularly high risk for 
advanced complications; studies indicate that within one year of CLI diagnosis, 40% to 50% 
of diabetics will experience an amputation.3 Incidence of CLI increases sharply among 
Medicare beneficiaries ages 65 to 69 (0.13%) to 85 and older (0.31%). As many as 33% of 
new CLI Medicare beneficiaries may undergo primary amputation within 1 year after 
diagnosis.4    
According to HCUP National Inpatient Sample (NIS) all payer 2014 claims data*, Medicare 
is the payer for 69% of patients with lower extremity atherosclerosis and 67% of patients 
treated with Percutaneous transluminal angioplasty and/or peripheral stent**. The subjects 
eligible for inclusion in the SAVAL trial are likely to align with HCUP patients due to their 
expected age. Medicare eligible patients are not expected to respond differently to treatment 
compared to other patients, therefore the results of this trial are likely to be highly 
generalizable to the Medicare population. 
 
* https://hcupnet.ahrq.gov/#setup  
** ICD-9-CM Codes (ICD9), Principal Diagnosis: 440.20 Athscl Extrm Ntv Art Nos, 440.21 Ath Ext Ntv At W 
Claudct, 440.22 Ath Ext Ntv At W Rst Pn, 440.23 Ath Ext Ntv Art Ulcrtion, 440.24 Ath Ext Ntv Art Gngrene, 
440.29 Athrsc Extrm Ntv Art Oth, 440.30 Athscl Extrm Bps Gft Nos, 440.31 Ath Ext Autologs Bps Gft, 440.32 
Ath Ext Nonautlg Bps Gft, 440.8 Atherosclerosis Nec, 440.9 Atherosclerosis Nos, 445.02 Atheroembolism, 
Lower Ext, 444.22 Lower Extremity Embolism (after Oct 1, 2002), 440.4 Chr Tot Occl Art Extrem.  
Procedures--ICD-9-CM Codes (ICD9): Angio Oth Non-Coronary (after Oct 1, 2011) | Ins Nondrug Noncor 
Stent (after Oct 1, 2002) | Ins Drug-Elut Non-Cor St (after Oct 1, 2004) 
 
1) Mustapha, JA, Et. Al. Percutaneous Transluminal Angioplasty in Patients With 
Infrapopliteal Arterial Disease: Systematic Review and Meta-Analysis. Circ Cardiovasc 
Interv. 2016 May;9(5)]  
2) Karnabatidis D, Katsanos K, Siablis D. Infrapopliteal stents: overview and unresolved 
issues. J Endovasc Ther. 2009;16(suppl 1): 1153- 162 
3) Elsayed S, Clavijo LC. Critical limb ischemia. Cardiol Clin. 2015;33(1):37-47. 
4) Prevalence, incidence, and outcomes of critical limb ischemia in the US Medicare 
population, Baser, Vasc Dis Manag 2013