Prospective, Multi-center, Single-arm Study of the Shockwave Medical Peripheral Intravascular Lithotripsy (IVL) System for Treatment of Calcified Peripheral Arterial Disease (PAD) in Below-the-Knee (BTK) Arteries
Phase: NA
Conditions: Peripheral Artery Disease
Sponsor: Shockwave Medical, Inc.

Confidential – This document is property of Shockwave Medical, Inc. 
 
 
NO.: CP 65007 
REV. C 
TITLE: Disrupt PAD BTK II Study 
CLASS: CLINICAL PROTOCOL 
PAGE 1 OF 71 
CONFIDENTIAL 
THIS STUDY PROTOCOL CONTAINS CONFIDENTIAL INFORMATION FOR USE BY THE INVESTIGATORS AND THEIR 
DESIGNATED REPRESENTATIVES. IT SHOULD BE HELD CONFIDENTIAL AND MAINTAINED IN A SECURE 
LOCATION. IT SHOULD NOT BE COPIED OR MADE AVAILABLE FOR REVIEW BY ANY UNAUTHORIZED PERSON OR 
FIRM WITHOUT WRITTEN PERMISSION FROM SHOCKWAVE MEDICAL, INC. 
 
 
 
 
 
Prospective, Multi-center, Single-arm Study of the Shockwave Medical Peripheral 
Intravascular Lithotripsy (IVL) System for Treatment of Calcified Peripheral Arterial Disease 
(PAD) in Below-the-Knee (BTK) Arteries 
(Disrupt PAD BTK II) 
 
Protocol Number: CP 65007 
Protocol Date: 08/22/2023 
Revision: C 
Study Device: Shockwave Medical Peripheral Intravascular Lithotripsy System 
 
Study Sponsor Name and Address:  Shockwave Medical, Inc. 
5403 Betsy Ross Drive 
Santa Clara, CA 95054 
USA 
 
 

Confidential – This document is property of Shockwave Medical, Inc. 
 
 
NO.: CP 65007 
REV. C 
TITLE: Disrupt PAD BTK II Study 
CLASS: CLINICAL PROTOCOL 
PAGE 2 OF 71 
1.0 INVESTIGATOR SIGNATURE PAGE .......................................................................... 6 
2.0 STUDY SUMMARY ...................................................................................................... 7 
3.0 INTRODUCTION ........................................................................................................ 14 
3.1 
Background ........................................................................................................................ 14 
3.1.1 Peripheral Arterial Disease ..................................................................................... 14 
3.1.2 Intravascular Lithotripsy ......................................................................................... 14 
3.2 
Study Rationale .................................................................................................................. 15 
4.0 STUDY DEVICE / TEST ARTICLE DESCRIPTION .................................................... 16 
4.1 
Peripheral IVL System ........................................................................................................ 16 
4.2 
Peripheral IVL Catheters .................................................................................................... 17 
4.2.1 Shockwave M5 IVL Catheter ................................................................................... 17 
4.2.2 Shockwave M5+ IVL Catheter .................................................................................. 17 
4.2.3 Shockwave S4 IVL Catheter ..................................................................................... 17 
4.2.4 Generator and Connector Cable ............................................................................. 18 
4.3 
Indication for Use............................................................................................................... 18 
4.3.1 United States .......................................................................................................... 18 
4.3.2 Outside of the US (excluding Australia) .................................................................. 18 
5.0 STUDY OBJECTIVES ................................................................................................ 19 
5.1 
Primary Endpoint(s) ........................................................................................................... 19 
5.1.1 Primary Safety Endpoint ......................................................................................... 19 
5.1.2 Primary Effectiveness Endpoint .............................................................................. 19 
5.2 
Secondary Endpoints ......................................................................................................... 19 
5.3 
Exploratory Endpoints ....................................................................................................... 20 
6.0 STUDY DESIGN ......................................................................................................... 21 
6.1 
Regulatory Status ............................................................................................................... 21 
6.2 
Clinical Development Stage ............................................................................................... 21 
6.3 
Type of Clinical Investigation Design ................................................................................. 21 
6.4 
Description of Clinical Investigation ................................................................................... 21 
6.5 
Burden to Subjects ............................................................................................................. 21 
6.6 
Site Selection ..................................................................................................................... 22 
6.7 
Number of Subjects ........................................................................................................... 22 
6.8 
Clinical Study Duration ....................................................................................................... 22 
6.9 
IVUS Sub-study................................................................................................................... 22 
7.0 STUDY PROCEDURES ............................................................................................. 23 
7.1 
Screening ........................................................................................................................... 23 
7.2 
Subject Selection ................................................................................................................ 23 
7.2.1 Inclusion Criteria..................................................................................................... 23 
7.2.2 Exclusion Criteria .................................................................................................... 24 
7.3 
Informed Consent .............................................................................................................. 26 
7.3.1 Process for Obtaining Informed Consent ............................................................... 26 
7.3.2 Subjects Needing Legally Designated Representative ............................................ 26 
7.3.3 Subjects Unable to Read or Write .......................................................................... 27 

Confidential – This document is property of Shockwave Medical, Inc. 
 
 
NO.: CP 65007 
REV. C 
TITLE: Disrupt PAD BTK II Study 
CLASS: CLINICAL PROTOCOL 
PAGE 3 OF 71 
7.3.4 Addition of New Information ................................................................................. 27 
7.4 
Schedule of Events and Evaluations .................................................................................. 27 
7.5 
Medications ....................................................................................................................... 29 
7.6 
Screening/Baseline Procedures ......................................................................................... 29 
7.7 
Index Procedure ................................................................................................................. 30 
7.7.1 Procedural Imaging Requirements ......................................................................... 30 
7.7.2 Assessment of Calcification .................................................................................... 31 
7.7.3 Treatment of Non-Target Lesions ........................................................................... 31 
7.7.4 Tandem Lesion(s) ................................................................................................... 31 
7.7.5 Definition of Enrollment ......................................................................................... 31 
7.7.6 Pre-IVL Dilatation (if required) ............................................................................... 32 
7.7.7 IVL Device Crossing Failures ................................................................................... 32 
7.7.8 IVL Treatment ......................................................................................................... 32 
7.7.9 Post-Dilatation ........................................................................................................ 33 
7.7.10 Assessment for Acute PTA Failure .......................................................................... 33 
7.7.11 IVUS Assessment (optional Sub-study) ................................................................... 33 
7.8 
Follow-Up ........................................................................................................................... 34 
7.8.1 Discharge or Within 12-24 Hours Post-Procedure ................................................. 34 
7.8.2 30-Day Follow-Up ................................................................................................... 34 
7.8.3 6-Month Follow-Up ................................................................................................ 35 
7.8.4 12-Month Follow-Up .............................................................................................. 35 
7.8.5 24-Month Follow-Up .............................................................................................. 36 
7.8.6 Prior to Target Limb Revascularization ................................................................... 36 
7.9 
Subject Withdrawal ........................................................................................................... 36 
7.9.1 When and How to Withdraw Subjects ................................................................... 36 
8.0 BENEFITS AND RISKS ............................................................................................. 38 
8.1 
Anticipated Clinical Benefits .............................................................................................. 38 
8.2 
Anticipated Adverse Device Effects ................................................................................... 38 
8.3 
Risks Associated with Participation in the Clinical Investigation........................................ 38 
8.4 
Possible Interactions with Concomitant Medical Treatments ........................................... 38 
8.5 
Steps that will be taken to Control or Mitigate the Risks .................................................. 39 
8.6 
Rationale for Benefit-Risk Ratio ......................................................................................... 39 
9.0 DATA ANALYSIS PLAN ............................................................................................ 40 
9.1 
General Statistical Methods ............................................................................................... 40 
9.2 
Primary Endpoints.............................................................................................................. 40 
9.2.1 Primary Safety Endpoint ......................................................................................... 40 
9.2.2 Primary Effectiveness Endpoint .............................................................................. 40 
9.3 
Sample Size Determination ................................................................................................ 41 
9.4 
Populations for Analysis..................................................................................................... 41 
9.5 
Handling of Dropouts or Missing Data ............................................................................... 41 
9.6 
Sub-Group Analyses ........................................................................................................... 41 
10.0 SAFETY EVENTS ...................................................................................................... 43 
10.1 Adverse Event Definitions .................................................................................................. 43 

Confidential – This document is property of Shockwave Medical, Inc. 
 
 
NO.: CP 65007 
REV. C 
TITLE: Disrupt PAD BTK II Study 
CLASS: CLINICAL PROTOCOL 
PAGE 4 OF 71 
10.1.1 Adverse Event (AE) ................................................................................................. 43 
10.1.2 Serious Adverse Event (SAE) ................................................................................... 43 
10.1.3 Adverse Device Effect (ADE) ................................................................................... 44 
10.1.4 Serious Adverse Device Effect (SADE) .................................................................... 44 
10.1.5 Unanticipated Serious Adverse Device Effect (USADE) .......................................... 44 
10.2 Adverse Event Device and Procedure Relatedness ............................................................ 44 
10.3 Device Deficiencies ............................................................................................................ 45 
10.3.1 Definitions .............................................................................................................. 45 
10.3.2 Reporting ................................................................................................................ 45 
10.4 Serious and Non-serious Adverse Event Reporting Requirements .................................... 46 
10.4.1 AE Reporting Requirements ................................................................................... 46 
10.4.2 SAE Reporting Requirements ................................................................................. 46 
10.4.3 Non-serious ADE Reporting Requirements............................................................. 46 
10.4.4 SADE Reporting Requirements ............................................................................... 47 
10.4.5 USADE Reporting Requirements............................................................................. 47 
10.4.6 AE and Device Deficiency Reporting Time Frames ................................................. 47 
11.0 INVESTIGATOR RESPONSIBILITIES ....................................................................... 48 
11.1 IRB/EC Approval ................................................................................................................. 48 
11.2 Informed Consent .............................................................................................................. 48 
11.3 Protocol Compliance and Delegation of Authority ............................................................ 48 
11.4 Medical Care of Subjects.................................................................................................... 48 
11.5 Safety Reporting ................................................................................................................ 49 
11.6 Protocol Amendment(s) ..................................................................................................... 49 
11.7 Records Retention ............................................................................................................. 49 
12.0 STUDY SPONSOR RESPONSIBILITIES ................................................................... 50 
12.1 Selection and Training of Study Sites ................................................................................. 50 
12.2 Monitoring ......................................................................................................................... 50 
12.2.1 Monitoring Methods .............................................................................................. 50 
12.2.2 Monitoring Visits .................................................................................................... 50 
12.3 Study Deviations ................................................................................................................ 51 
12.4 Device Accountability ......................................................................................................... 51 
12.5 Study/Site Suspension or Early Termination ...................................................................... 51 
12.6 Study Completion .............................................................................................................. 52 
12.7 Audits / Inspections ........................................................................................................... 53 
12.8 Publication Policies ............................................................................................................ 53 
12.9 Data Management ............................................................................................................. 53 
12.9.1 Case Report Forms ................................................................................................. 54 
12.9.2 Transmission of Data .............................................................................................. 54 
12.9.3 Data Queries ........................................................................................................... 54 
12.9.4 Data Retention ....................................................................................................... 55 
13.0 STUDY COMMITTEES ............................................................................................... 56 
13.1 Clinical Events Committee (CEC) ........................................................................................ 56 
14.0 ETHICAL AND REGULATORY CONSIDERATIONS ................................................. 57 
14.1 Role of Shockwave Medical ............................................................................................... 57 

Confidential – This document is property of Shockwave Medical, Inc. 
 
 
NO.: CP 65007 
REV. C 
TITLE: Disrupt PAD BTK II Study 
CLASS: CLINICAL PROTOCOL 
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14.2 Subject Confidentiality ....................................................................................................... 57 
15.0 DEFINITIONS AND ABBREVIATIONS ...................................................................... 58 
15.1 Study Definitions ................................................................................................................ 58 
15.2 List of Abbreviations .......................................................................................................... 63 
16.0 REFERENCES ........................................................................................................... 66 
17.0 SUBJECT INFORMED CONSENT ............................................................................. 68 
18.0 CASE REPORT FORMS ............................................................................................ 69 
19.0 REVISION HISTORY .................................................................................................. 70 
Table of Figures 
Figure 1. Shockwave Peripheral IVL System .......................................................................................... 16 
Figure 2. BTK IVL Treatment Algorithm ................................................................................................. 34 
Table of Tables 
Table 1. Schedule of Events and Evaluations......................................................................................... 27 
Table 2. IVL System Sequence Chart ..................................................................................................... 33 
Table 3. Investigator Responsibilities for Reporting Adverse Events .................................................... 47 

Confidential – This document is property of Shockwave Medical, Inc. 
 
 
NO.: CP 65007 
REV. C 
TITLE: Disrupt PAD BTK II Study 
CLASS: CLINICAL PROTOCOL 
PAGE 6 OF 71 
 
1.0 INVESTIGATOR SIGNATURE PAGE 
Study Title: Prospective, Multi-center, Single-arm Study of the Shockwave Medical Peripheral 
Intravascular Lithotripsy (IVL) System for Treatment of Calcified Peripheral Arterial Disease 
(PAD) in Below-the-Knee (BTK) Arteries (Disrupt PAD BTK II) 
Study Device:  Shockwave Medical Peripheral IVL System 
Protocol Revision: C 
Protocol Revision Date: 22 August 2023 
Study Sponsor: Shockwave Medical, Inc. 
5403 Betsy Ross Drive 
Santa Clara, CA 95054 
USA 
 
Principal Investigator Acknowledgement Signature 
I have received and reviewed this version of the above noted study protocol and will conduct the study in 
accordance with the outlined protocol requirements, all attachments, and applicable local and United 
States Food and Drug Administration regulations. This investigation will be conducted in accordance with 
the ethical principles as noted in the Declaration of Helsinki, the requirements of EU Medical Device 
Regulation (EU MDR) 2017/745, the ISO 14155:2020 Good Clinical Practices, and applicable IRB/EC 
requirements. 
 
 
Principal Investigator’s Name (print) 
 
 
Principal Investigator’s Signature 
Date 

Confidential – This document is property of Shockwave Medical, Inc. 
 
 
NO.: CP 65007 
REV. C 
TITLE: Disrupt PAD BTK II Study 
CLASS: CLINICAL PROTOCOL 
PAGE 7 OF 71 
 
2.0 STUDY SUMMARY 
 
Study Title 
Prospective, Multi-center, Single-arm Study of the Shockwave Medical 
Peripheral Intravascular Lithotripsy (IVL) System for Treatment of 
Calcified Peripheral Arterial Disease (PAD) in Below-the-Knee (BTK) 
Arteries (Disrupt PAD BTK II) 
Study Objective 
To assess the continued safety and effectiveness of the Shockwave 
Medical Peripheral IVL System for the treatment of calcified, stenotic 
BTK arteries. 
Study Device(s) 
Shockwave Medical Peripheral IVL System 
Manufacturer 
Shockwave Medical, Inc. 
Indications for Use 
The Shockwave Medical IVL System is intended for lithotripsy-enhanced 
balloon dilatation of lesions, including calcified lesions, in the peripheral 
vasculature, including the iliac, femoral, ilio-femoral, popliteal, infra- 
popliteal, and renal arteries. Not for use in the coronary or cerebral 
vasculature. 
Study Design 
Post-market, prospective, multi-center, single-arm study 
Enrollment 
Up to 250 subjects at up to 40 global sites 
Subject Population 
Subjects with moderate to severe calcified peripheral artery disease 
below the knee presenting with Rutherford Category (RC) 3 to 5 with the 
RC 3 cohort capped at 20% of total enrollment. Up to two (2) target 
lesions allowed for each subject. 
Study Duration / Follow- 
Up Period 
Study subjects will be followed through discharge, 30 days, 6, 12, & 24 
months. Duplex Ultrasound (DUS) assessments required at 6 and 12 
months. Total anticipated study duration approximately 48 months. 
Primary Safety Endpoint 
Major Adverse Limb Events (MALE) or Post-Operative Death (POD) at 30 
days defined as a composite of: 
• 
all-cause death 
• 
above-ankle amputation of the index limb 
• 
major reintervention (new bypass graft, jump/interposition graft 
revision, or thrombectomy/thrombolysis) of the index limb involving 
a BTK artery 

Confidential – This document is property of Shockwave Medical, Inc. 
 
 
NO.: CP 65007 
REV. C 
TITLE: Disrupt PAD BTK II Study 
CLASS: CLINICAL PROTOCOL 
PAGE 8 OF 71 
 
 
Primary Effectiveness 
Endpoint 
• 
Procedure Success defined as ≤50% residual stenosis for all 
treated target lesions without serious angiographic complications 
(flow-limiting dissection, perforation, distal embolization, or acute 
vessel closure) as assessed by the angiographic core lab at the final 
timepoint. 
Secondary Endpoints: 
• 
Serious angiographic complications (flow-limiting dissection, 
perforation, distal embolization, or acute vessel closure) as assessed 
by the angiographic core lab 
• 
Lesion Success defined as final residual stenosis ≤50% in the target 
lesion without serious angiographic complications as assessed by the 
angiographic core lab 
• 
Primary Patency at 6 and 12 months (assessed for subject and 
lesion) defined as the absence of both total occlusion (100% 
diameter stenosis as assessed by DUS core lab) in all of the target 
lesions in a flow pathway, as well as any CEC adjudicated Clinically- 
Driven Target Lesion Revascularization (CD-TLR) 
• 
Clinically-Driven Target Lesion Revascularization (CD-TLR), CEC 
adjudicated, at 30 days, 6, 12, & 24 months 
• 
Major Adverse Events (MAE), CEC adjudicated at 30 days defined as 
a composite of: 
o Need for emergency surgical revascularization of target limb 
o Unplanned target limb major amputation (above the ankle) 
o Symptomatic thrombus or distal emboli that require surgical, 
mechanical, or pharmacologic means to improve flow, and 
extend hospitalization 
o Perforations that require an intervention, including bail-out 
stenting 
• 
Quality of Life (QoL) assessed by VascuQoL questionnaire at 30 days, 
6, 12, & 24 months, reported as change from baseline 
• 
Ankle-brachial index (ABI) or toe-brachial index (TBI) at 30 days, 6, 
12, & 24 months, reported as change from baseline 
• 
Major Target Limb Amputation, CEC adjudicated, at 30 days, 6, 12, & 
24 months 
• 
Rutherford Category at 30 days, 6, 12, & 24 months, reported as 
change from baseline 

Confidential – This document is property of Shockwave Medical, Inc. 
 
 
NO.: CP 65007 
REV. C 
TITLE: Disrupt PAD BTK II Study 
CLASS: CLINICAL PROTOCOL 
PAGE 9 OF 71 
 
 
• 
Number of existing, new, and recurrent wounds at 30 days, 6, 12, & 
24 months 
• 
Number of healed wounds at 30 days, 6, 12, & 24 months 
• 
Number of non-healed wounds by category (improving, stagnant, 
worsening) at 30 days, 6, 12, & 24 months 
IVUS Sub-study 
• 
Up to 50 subjects; IVUS required at baseline, immediately post-IVL, 
and end of procedure 
Study Inclusion Criteria 
General Inclusion Criteria 
1. Age of subject is ≥ 18. 
2. Subject is able and willing to comply with all assessments in the 
study. 
3. Subject or subject’s legal representative has been informed of the 
nature of the study, agrees to participate, and has signed the 
approved consent form. 
4. Rutherford Category 3, 4, or 5 in the target limb. 
5. Estimated life expectancy >1 year. 
Angiographic Inclusion Criteria 
6. Up to 2 below-the-knee target lesion(s) in native vessels in one or 
both limbs. 
7. Target lesion from the distal segment (P3) of the popliteal artery to 
the ankle joint. 
8. Target lesion reference vessel diameter (RVD) between 2.0mm and 
4.0mm by investigator visual estimate. 
9. Target lesion with ≥70% stenosis by investigator visual estimate. 
10. Target lesion length is ≤200mm by investigator visual estimate. 
Target lesion can be all or part of the 200mm treated zone. 
11. Distal reconstitution of at least one pedal vessel (<50% stenosis) 
(desert foot excluded) in the target limb. 
12. Evidence of at least moderate calcification at the target lesion site by 
angiography/IVUS OR non-dilatable lesion indicating presence of 
calcium. Must meet one of the following: 

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NO.: CP 65007 
REV. C 
TITLE: Disrupt PAD BTK II Study 
CLASS: CLINICAL PROTOCOL 
PAGE 10 OF 71 
 
 
a. Angiography requires fluoroscopic evidence of calcification 
on parallel sides of the vessel and extending > 50% the 
length of the lesion. 
b. IVUS requires presence of ≥270 degrees of calcium over the 
course of at least 10mm. 
c. Non-dilatable lesion requires attempted treatment with PTA 
during the index procedure with residual stenosis > 50% and 
no serious angiographic complications. 
Study Exclusion Criteria 
General Exclusion Criteria 
1. Rutherford Category 0, 1, 2 or 6 (target limb). 
2. Subjects with osteomyelitis or deep soft tissue infection are 
excluded unless infection can be treated with an individual toe ray 
amputation or transmetatarsal amputation (TMA) in the target limb 
in the opinion of the investigator.. 
3. History of endovascular or surgical procedure on the target limb 
within the last 30 days, or planned within 30 days of the index 
procedure with the exception of toe amputation. 
4. Subject in whom antiplatelet or anticoagulant therapy is 
contraindicated. 
5. Subject has known allergy to contrast agents or medications used to 
perform endovascular intervention that cannot be adequately pre- 
treated. 
6. Subject has known allergy to urethane, nylon, or silicone. 
7. Myocardial infarction within 30 days prior to enrollment. 
8. History of stroke within 60 days prior to enrollment. 
9. Subject has acute or chronic renal disease with eGFR <30 
ml/min/1.73m2 (using CKD-EPI formula), unless on renal 
replacement therapy. 
10. Subject is pregnant or nursing. 
11. Subject is participating in another research study involving an 
investigational agent (pharmaceutical, biologic, or medical device) 
that has not reached the primary endpoint. 
12. Subject has other medical, social or psychological problems that, in 
the opinion of the investigator, preclude them from receiving this 

Confidential – This document is property of Shockwave Medical, Inc. 
 
 
NO.: CP 65007 
REV. C 
TITLE: Disrupt PAD BTK II Study 
CLASS: CLINICAL PROTOCOL 
PAGE 11 OF 71 
 
 
treatment, and the procedures and evaluations pre- and post- 
treatment. 
13. Covid-19 diagnosis within 30 days. 
14. The planned use of cutting/scoring balloons, re-entry or 
atherectomy devices in target lesions during the index procedure. 
15. Planned major amputation (of either leg). 
16. Acute limb ischemia (of either leg). 
17. Occlusion of all the inframalleolar outflow arteries/vessels (i.e., 
desert foot) in the target limb. 
18. Subject has an anticipated life span of less than one (1) year. 
19. Subject already enrolled into this study. 
Angiographic Exclusion Criteria 
20. Failure to treat clinically significant inflow lesions in the ipsilateral 
iliac, femoral, or popliteal arteries with ≤30% residual stenosis, and 
no serious angiographic complications (e.g., embolism). 
21. Failure to successfully treat significant non-target infra-popliteal 
lesions prior to treatment of target lesion(s). Successful treatment is 
defined as obtaining ≤50% residual stenosis with no serious 
angiographic complications (e.g., embolism). 
22. Treatment of vessels below the ankle joint. 
23. Failed pre-dilatation in target lesion during index procedure with 
angiographic evidence of serious angiographic complications. 
24. Target lesion includes in-stent restenosis. 
25. Evidence of aneurysm or thrombus in target vessel. 
26. No calcium or mild calcium in the target lesion. 
27. Target lesion within native or synthetic vessel grafts. 
28. Failure to successfully cross the guidewire across the target lesion; 
successful crossing defined as tip of the guidewire distal to the 
target lesion in the absence of flow limiting dissections or 
perforations. 
Study Statistical Methods 
• 
Intent-to-Treat (ITT) analysis with pre-defined subgroups (e.g., renal 
failure) 

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NO.: CP 65007 
REV. C 
TITLE: Disrupt PAD BTK II Study 
CLASS: CLINICAL PROTOCOL 
PAGE 12 OF 71 
 
 
• 
Designed to assess exact 95% confidence interval (CI) for primary 
endpoints; no formal hypothesis testing 
Study Sponsor/Study 
Management 
Shockwave Medical, Inc. 
5403 Betsy Ross Drive 
Santa Clara, CA 95054 
USA 
Contact: Birgit Greschner 
Title: Senior Clinical Research Manager 
Telephone (direct): (408) 385-7557 
Email: bgreschner@shockwavemedical.com 
EU Legal Representative 
Medpace Finland OY 
Kaikukatu 4 C 
00530 Helsinki 
Finland 
EU Authorized 
Representative 
ICON (LR) Limited 
South County Business Park 
Leopardstown 
Dublin 18 
D18 X5R3 
Ireland 
Study Principal 
Investigators 
Ehrin Armstrong, MD, FACC 
Medical Director 
Interventional Cardiologist, Advanced Heart and Vein Center 
4105 E Florida AVE, Suite 200 
Denver, CO 80222 
Venita Chandra, MD 
Clinical Associate Professor, Division of Vascular Surgery 
Stanford University Medical Center 
300 Pasteur Drive 
Palo Alto, CA 94304 
USA 
Coordinating Investigator 
in Germany 
Professor Thomas Zeller, MD 
Universitäts-Herzzentrum Freiburg & Bad Krozingen 
Klinik für Kardiologie and Angiologie II 
Südring 15 
79189 Bad Krozingen 
Germany 
Clinical Research 
Organization 
Medpace, Inc. 
5375 Medpace Way 
Cincinnati, OH 45227 
USA 

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NO.: CP 65007 
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TITLE: Disrupt PAD BTK II Study 
CLASS: CLINICAL PROTOCOL 
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Contact: Patricia Bobzin 
Title: Clinical Trial Manager – Global 
Telephone: +1 (513) 579-9911 ext. 7623788 
Email: p.bobzin@medpace.com 
Angiographic Core Lab & 
Intravascular Ultrasound 
Core Lab 
Yale Cardiovascular Research Group 
1 Church Street, Suite 330 
New Haven, CT 06510 
USA 
Contact: Alexandra J. Lansky, MD 
Title: Director 
Telephone: +1 (203) 737-2142 
Fax: +1 (203) 737-7457 
Email: Alexandra.lansky@yale.edu 
Clinical Events Committee 
Yale Cardiovascular Research Group 
1 Church Street, Suite 330 
New Haven, CT 06510 
USA 
Contact: Louise Gambone, RN, BA 
Title: Director of Operations 
Telephone: +1 (203) 737-2023 
Fax: +1 (203) 737-3427 
Email: louise.gambone@yale.edu 
Duplex Ultrasound Core 
Lab 
Vascular Ultrasound Core Laboratory (VasCore) 
Massachusetts General Hospital 
One Bowdoin Square, 10th Floor 
Boston, MA 02114 
USA 
Contact: Ido Weinberg, MD 
Title: Medical Director 
Telephone: +1 (617) 726-5552 
Fax: +1 (617) 726-1977 
Email: iweinberg@mgh.harvard.edu 
Emergency Safety Contact 
Email: swmbtk2@shockwavemedical.com 

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NO.: CP 65007 
REV. C 
TITLE: Disrupt PAD BTK II Study 
CLASS: CLINICAL PROTOCOL 
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3.0 INTRODUCTION 
3.1 Background 
3.1.1 Peripheral Arterial Disease 
Peripheral arterial disease (PAD) is one of the most common indications of atherosclerotic 
disease and impacts more than 200 million people globally [1]. PAD is caused by the 
accumulation of plaque in the arteries that do not supply the brain or the heart. Although it 
can involve the renal arteries and/or the arteries of the neck or arms, PAD normally develops 
in the lower extremities. The reduced blood flow may lead to pain, tissue loss and eventual 
foot/leg amputation or death. Risk factors for PAD include advanced age, smoking, 
hypertension, diabetes, and concomitant cardiovascular disease [1]. Calcified PAD is 
associated with coronary artery disease, diabetes and chronic kidney disease [2]. 
Early diagnosis and treatment of PAD reduces an individual’s risk of cardio- or cerebrovascular 
disease morbidity and mortality [3]. Percutaneous endovascular therapies are being 
increasingly employed as the primary revascularization treatment for PAD, including calcified 
occlusions [4-6]. Endovascular therapies include percutaneous angioplasty (PTA), nitinol 
stents, directional and rotational atherectomy, laser atherectomy, drug-eluting stents (DES) 
and drug-coated balloons (DCB) [6]. 
Infrapopliteal atherosclerosis is a multilevel disease affecting below-the-knee (BTK) arteries 
and is often associated with critical limb ischemia (CLI). CLI represents the most severe form 
of PAD and is characterized by ischemic rest pain and/or nonhealing ulcers [7]. BTK lesions are 
often technically challenging to treat due to long length, small vessel diameter, poor outflow, 
and severe calcification [8]. Vessel wall calcification is more severe in BTK lesions compared to 
more proximal lesions, with medial calcification being most prevalent in the infrapopliteal 
segment. Due to the severity and unequal distribution of calcium in infrapopliteal lesions, 
vessel wall expansion can occur in a non-uniform manner increasing the risk for severe 
dissection with high pressure balloon dilatation [8]. Procedural success for infrapopliteal 
lesions has improved; however, recoil, dissections, and restenosis remain limitations of 
infrapopliteal endovascular procedures [9]. 
3.1.2 Intravascular Lithotripsy 
Intravascular lithotripsy is a balloon-based calcium modification treatment modality that uses 
acoustic pressure waves to modify vessel wall calcium. Peripheral IVL is designed to improve 
vessel wall compliance to optimize acute gain while minimizing acute vessel injury. The safety 
and effectiveness of IVL has been reported in several clinical studies in moderate to severe 
calcified PAD across multiple vessel beds [10-18], including the Disrupt PAD BTK study and the 
Disrupt PAD III Observational Study (OS), which evaluated peripheral IVL in BTK lesions. 
The DISRUPT BTK study enrolled 20 patients with moderate to severe calcified infrapopliteal 
lesions with 30-day follow-up [13]. After treatment with IVL using the first generation M5 
catheter, all patients achieved a residual stenosis < 50%. There was only one type B dissection, 

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NO.: CP 65007 
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TITLE: Disrupt PAD BTK II Study 
CLASS: CLINICAL PROTOCOL 
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and a total of two (2) stents were placed. These initial promising results supported the use of 
IVL to maximize luminal gain while minimizing dissections when treating severely calcified 
infrapopliteal lesions. 
Introduction of the Shockwave S4 IVL catheter allowed for expanded treatment of BTK lesions 
due to a smaller crossing profile and balloon diameters relative to the M5 catheter. Adams et 
al recently analyzed a cohort of patients from the PAD III Observational Study (OS) with 
calcified BTK disease treated with the S4 IVL catheter [10]. A total of 101 patients with 114 
calcified infrapopliteal arteries were enrolled at 15 sites and were followed through discharge. 
This study included a challenging patient and lesion cohort with 69% of patients presenting 
with CLI and 35% with chronic total occlusion (CTO) lesions. The continued safety and 
effectiveness of peripheral IVL was demonstrated as 99% of lesions achieved a residual 
stenosis < 50% with no occurrences of serious angiographic complications at the end of the 
procedure, regardless of BTK lesion location. Notably, acute results in this “real world” setting 
with complex lesions were consistent with prior outcomes reported in other peripheral IVL 
studies [10]. 
3.2 Study Rationale 
In an effort to continually improve IVL therapy, the Disrupt PAD BTK II study is being conducted to 
assess the continued safety, effectiveness and optimal clinical use of the Shockwave Medical 
Peripheral IVL System for the treatment of calcified, stenotic BTK arteries. Relative to the previous 
Disrupt BTK study, the BTK II study includes longer lesions and has long-term follow-up. Relative to 
the PAD III OS cohort, this study limits use of adjunctive therapy like atherectomy which can 
confound results. 
The Disrupt PAD BTK II study also includes a treatment algorithm designed to standardize IVL 
treatment of BTK lesions with the goal of optimizing outcomes. Based on a recently proposed 
algorithm for balloon angioplasty [8], the IVL treatment strategy includes assessment of 
calcification, optimal balloon sizing, comprehensive IVL treatment along the full length of the target 
lesion, and assessment of post-IVL residual stenosis. Lastly, this study includes an IVUS Sub-study. 

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4.0 STUDY DEVICE / TEST ARTICLE DESCRIPTION 
4.1 Peripheral IVL System 
The Shockwave Peripheral IVL System is a proprietary balloon catheter system designed to enhance 
percutaneous transluminal angioplasty by enabling delivery of the calcium-disrupting capability of 
lithotripsy prior to balloon dilatation at low pressures. The application of lithotripsy mechanical 
pulse waves alters the structure of an occlusive vascular deposit (stenosis) prior to low-pressure 
balloon dilatation of the stenosis and facilitates the passage of blood. 
The IVL System consists of a balloon catheter with integrated lithotripsy emitters, an IVL Generator, 
Connector Cable, and related accessories and replacement components (Figure 1). The Shockwave 
IVL System is built on traditional balloon angioplasty catheter technology, rendering it inherently 
familiar and easy to use for interventional cardiologists, interventional radiologists, and vascular 
surgeons. Accordingly, the device should be used only by physicians who are familiar with 
interventional vascular procedures and who have read and understood the device instructions for 
use. Refer to the Instructions for Use (IFU) for product descriptions. 
The IVL System components do not contain any medicinal substances, blood derivatives or 
materials derived from animal or human tissue. The balloon materials (PEBAX for M5 and M5+ IVL 
catheters and Nylon for the S4 IVL catheter) will come in contact with tissues or body fluids. 
There are specific Instructions For Use (IFU) and labelling for the United States (US) and for Outside 
of the US (OUS). 
 
 
 
 
 
 
Figure 1. Shockwave Peripheral IVL System 

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4.2 Peripheral IVL Catheters 
The Shockwave Peripheral IVL Catheters (models M5, M5+ and S4) are available in multiple balloon 
sizes ranging from 2.5mm to 8.0mm in diameter, and 40 or 60mm lengths, depending on the model. 
The catheters have a working length of 110cm to 135cm and are compatible with 300cm length, 
0.014” guidewires. The Shockwave IVL Catheter is compatible with 5 to 7F introducer sheaths, 
depending on the balloon size and catheter model. The catheter kits include a sterile sleeve for the 
connector cable. 
For all catheter types, energy is delivered from the IVL Generator through the Connector Cable to 
the pulse emitters located inside the balloon in the IVL Catheter. The IVL Generator software can 
detect the different catheter sizes through a unique PCB installed inside the catheter connector. 
The IVL Generator and Connector Cable are used exclusively with the IVL Catheters. The IVL 
Connector Cable is a remote actuator that connects the IVL Generator to the IVL Catheter and is 
used to activate energy delivery from the IVL Generator. During use, it is covered by a sterile drape. 
The IVL Generator and Connector Cable are supplied non-sterile and are reusable. The IVL Catheter 
is supplied sterile via E-beam sterilization. It is intended for single use only and is not intended for 
reuse or re-sterilization. 
4.2.1 Shockwave M5 IVL Catheter 
The Shockwave M5 IVL Catheters are available in multiple balloon sizes ranging from 3.5mm to 
7.0mm diameter and 60mm length. The Over-the-Wire (OTW) catheters have a working length 
of 110cm and are compatible with 300cm length, 0.014” guidewires. The Shockwave M5 IVL 
Catheter is compatible with 6 or 7F introducer sheaths depending on balloon size. There is no 
coating on the Shockwave M5 IVL Catheters. The M5 catheter has 5 emitters and can deliver a 
maximum of 300 lithotripsy pulses per catheter at a rate of 1 pulse per second (1 Hz). 
4.2.2 Shockwave M5+ IVL Catheter 
The Shockwave M5+ IVL Catheter is a line extension of the Shockwave M5. It has the same 
balloon sizes as the Shockwave M5 with the addition of an 8.0mm balloon. The treatment 
frequency of the Shockwave M5+ was increased from 1 pulse/sec to 2 pulses/sec (1 Hz to 2 Hz). 
The catheter working length was extended to 135cm and is still compatible with 300cm length, 
0.014” guidewires. All other characteristics are the same as the Shockwave M5 catheter. 
4.2.3 Shockwave S4 IVL Catheter 
The Shockwave S4 IVL Catheters are available in balloon sizes of 40mm in length and diameter 
sizes: 2.5mm, 3.0mm, 3.5mm and 4.0mm diameter. The OTW catheters have a working length 
of 135cm and are compatible with 300cm length, 0.014” guidewires. The Shockwave S4 IVL 
Catheter is compatible with 5F introducer sheaths. There is a hydrophilic coating on the S4 IVL 
Catheters. The S4 catheter has 4 emitters and can deliver a maximum of 160 lithotripsy pulses 
per catheter at a rate of 1 pulse per second (1 Hz). 

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4.2.4 Generator and Connector Cable 
The Shockwave IVL Generator (Model 825D) and Connector Cable are provided as a kit. The 
catalog number for the kit is IVLGCCD. 
4.3 Indication for Use 
The Shockwave Peripheral IVL System with all IVL catheter models (M5, M5+ and S4) is cleared by the 
FDA and is CE marked. 
4.3.1 United States 
The Shockwave Medical M5, M5+, and S4 Peripheral Intravascular Lithotripsy Systems are 
intended for lithotripsy-enhanced balloon dilatation of lesions, including calcified lesions, in 
the peripheral vasculature, including the iliac, femoral, ilio-femoral, popliteal, infra-popliteal, 
and renal arteries. Not for use in the coronary or cerebral vasculature. 
4.3.2 Outside of the US (excluding Australia) 
The Shockwave Medical M5 and Shockwave Medical S4 Peripheral Intravascular Lithotripsy 
Systems are indicated for lithotripsy-enhanced, low-pressure balloon dilatation of calcified, 
stenotic peripheral arteries in patients who are candidates for percutaneous therapy. 
The Shockwave Medical M5+ Peripheral Intravascular Lithotripsy System is indicated for 
lithotripsy-enhanced, low-pressure balloon dilatation of lesions, including calcified lesions, in 
the peripheral vasculature, including the iliac, femoral, ilio-femoral, popliteal, infra-popliteal, 
and renal arteries. This device is not intended for use in coronary, carotid, or cerebrovascular 
arteries. 

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5.0 STUDY OBJECTIVES 
The objective of this study is to assess the continued safety and effectiveness of the Shockwave Medical 
Peripheral IVL System for the treatment of calcified, stenotic BTK arteries. 
5.1 Primary Endpoint(s) 
5.1.1 Primary Safety Endpoint 
The primary safety endpoint is Major Adverse Limb Events (MALE) or Post-Operative Death 
(POD) at 30 days defined as a composite of: 
• 
all-cause death 
• 
above-ankle amputation of the index limb 
• 
major reintervention (new bypass graft, jump/interposition graft revision, or 
thrombectomy/thrombolysis) of the index limb involving a BTK artery 
5.1.2 Primary Effectiveness Endpoint 
The primary effectiveness endpoint is Procedure Success defined as ≤50% residual stenosis for 
all treated target lesions without serious angiographic complications (flow-limiting dissection, 
perforation, distal embolization, or acute vessel closure) as assessed by the angiographic core 
lab at the final timepoint. 
 
5.2 Secondary Endpoints 
• 
Serious angiographic complications (flow-limiting dissection, perforation, distal embolization, 
or acute vessel closure) as assessed by the angiographic core lab 
• 
Lesion Success defined as final residual stenosis ≤50% in the target lesion without serious 
angiographic complications as assessed by the angiographic core lab 
• 
Primary Patency at 6 and 12 months as assessed by both subject and lesion level defined as the 
absence of both total occlusion (100% diameter stenosis as assessed by DUS core lab) in all of 
the target lesions in a flow pathway, as well as any CEC adjudicated Clinically-Driven Target 
Lesion Revascularization (CD-TLR) 
• 
Clinically-Driven Target Lesion Revascularization (CD-TLR), CEC adjudicated, at 30 days, 6, 12, & 
24 months 
• 
Major Adverse Events (MAE), CEC adjudicated, at 30 days defined as a composite of: 
o Need for emergency surgical revascularization of target limb 
o Unplanned target limb major amputation (above the ankle) 
o Symptomatic thrombus or distal emboli that require surgical, mechanical, or 
pharmacologic means to improve flow, and extend hospitalization 

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o Perforations that require an intervention, including bail-out stenting 
• 
Quality of Life (QoL) assessed by VascuQoL questionnaire at 30 days, 6, 12, & 24 months, 
reported as change from baseline 
• 
Major Target Limb Amputation, CEC adjudicated, at 30 days, 6, 12, & 24 months 
• 
Ankle-brachial index (ABI) or toe-brachial index (TBI) at 30 days, 6, 12, & 24 months, reported 
as change from baseline 
• 
Rutherford Category at 30 days, 6, 12, & 24 months, reported as change from baseline 
• 
Number of existing, new, and recurrent wounds at 30 days, 6, 12, & 24 months 
• 
Number of healed wounds at 30 days, 6, 12, & 24 months 
• 
Number of non-healed wounds by category (improving, stagnant, worsening) at 30 days, 6, 
12, & 24 months 
5.3 Exploratory Endpoints 
• 
Exploratory endpoints will be defined in the Statistical Analysis Plan (SAP). 

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6.0 
STUDY DESIGN 
The Disrupt PAD BTK II study is a post-market, prospective, multi-center, single-arm study of the 
Shockwave Peripheral IVL System to treat calcified peripheral arteries. There is no control arm as 
all Peripheral IVL catheters evaluated in this clinical study have received market approval. 
Adjunctive therapy usage is limited to minimize bias in regard to study results. Use of adjunctive 
therapy like cutting/scoring balloons, re-entry or atherectomy devices in target lesions is therefore 
not allowed. 
6.1 Regulatory Status 
Per ISO 14155:2020, the PAD BTK II study is a post-market clinical investigation defined as a study 
carried out following market approval of a medical device, intended to answer specific questions 
relating to effectiveness or safety of a medical device when used in accordance with its approved 
labeling. 
6.2 Clinical Development Stage 
Per ISO 14155:2020, the medical devices being used in the PAD BTK II study are in the post-market 
stage which includes additional confirmatory clinical investigations to establish effectiveness of the 
medical device in a broader population of users and subjects in comparison to previous studies. 
Also included are observational clinical investigations for better understanding of device safety, 
such as rare adverse events and long-term outcomes. 
6.3 Type of Clinical Investigation Design 
Per ISO 14155:2020, the PAD BTK II study is considered to be an observational clinical investigation 
defined as a study that draws inferences about the possible effect of an intervention on subjects, 
but does not require the investigator to assign subjects into intervention groups or to collect data 
variables beyond those available throughout the course of normal clinical practice and burden to 
the subject. See Sections 7.6 through 7.8 for information on data collection requirements and 
assessment of burden to the subject. 
6.4 Description of Clinical Investigation 
Per ISO 14155:2020, the PAD BTK II study is considered to be a post-market clinical investigation as 
it is intended to answer specific questions relating to effectiveness or safety of a medical device 
when used in accordance with its approved labelling. 
6.5 Burden to Subjects 
Per ISO 14155:2020, the PAD BTK II study is considered to be a non-interventional clinical 
investigation. No additional invasive or burdensome diagnostic or monitoring procedures are 
applied to the subjects and epidemiological methods are used for the analysis of collected data. 

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Subjects are not assigned to an intervention group and the majority of data collection requirements 
fall within the course of normal clinical practice including physical exam, ABI/TBI, Rutherford 
Category assessment, and duplex ultrasound. The VascuQol questionnaire may not be standard of 
care at all centers; however, the assessment is non-invasive, introduces no additional risk, and is 
not considered to be an additional burden to the subject. 
6.6 Site Selection 
Up to 40 global sites will participate in the study. 
6.7 Number of Subjects 
Up to 250 subjects with moderate to severe calcified peripheral artery disease below the knee 
presenting with Rutherford Category (RC) 3 to 5 will be enrolled. The RC 3 will be capped at 20% of 
total enrollment. If a subject has a target lesion in each limb and one of the limbs is RC 3, this subject 
will count toward the Rutherford Category 3 cap. Up to two (2) target lesions allowed for each 
subject. Each site will be allowed to enroll up to 15% (37 subjects) of total study enrollment. 
6.8 Clinical Study Duration 
Enrollment is anticipated to last approximately 24 months. Study subjects will be followed through 
hospital discharge, 30 days, and 6-, 12-, and 24-months post-procedure. Duplex ultrasound (DUS) 
assessments will be completed at 6 and 12 months. Total anticipated study duration is 48 months. 
6.9 IVUS Sub-study 
Up to 50 subjects will be enrolled in an optional IVUS Sub-study. All study centers with intravascular 
ultrasound (IVUS) imaging capability will have the opportunity to participate in the Sub-study. A 
separate IVUS protocol will be provided to participating study centers. 

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7.0 
STUDY PROCEDURES 
7.1 Screening 
Patients presenting to the institution with known infrapopliteal disease requiring an interventional 
procedure will be evaluated for eligibility and participation in the clinical study. A member of the 
participating site’s study team will perform an initial evaluation of the potential participant’s 
medical history and previously performed examinations to assess for initial eligibility. Pre- 
procedure imaging (DUS, angiogram, CTA, MRA) should be performed according to the institution’s 
standard of care. 
Potential subjects will be screened for eligibility. Written informed consent will be obtained prior 
to any study-specific requirements. A potential subject will be informed of the elements of the 
clinical study including risks, potential benefits, and required follow-up procedures prior to 
obtaining the potential subject’s informed consent. 
7.2 Subject Selection 
Subjects who meet the clinical inclusion/exclusion criteria will undergo an angiogram performed 
according to the institution’s standard of care. If all angiographic eligibility criteria are met, the 
subject is considered to be enrolled once the peripheral IVL catheter has been inserted over a 
0.014” guidewire that crossed the target lesion. A subject is considered an angiographic screen 
failure if they do not meet angiographic eligibility criteria. Subjects who screen fail will be 
documented as such in the electronic data capture (EDC) system. 
7.2.1 Inclusion Criteria 
Subjects are required to meet all of the following inclusion criteria in order to be enrolled in the 
clinical study. For lesion characteristics, each target lesion must meet eligibility. The subject would, 
at the investigator's discretion, receive the treatment required per Study Protocol which also may 
be per standard of care (SOC). 
General Inclusion Criteria 
1. Age of subject is ≥ 18. 
2. Subject is able and willing to comply with all assessments in the study. 
3. Subject or subject’s legal representative has been informed of the nature of the 
study, agrees to participate, and has signed the approved consent form. 
4. Rutherford Category 3, 4, or 5 in the target limb. 
5. Estimated life expectancy >1 year. 
Angiographic Inclusion Criteria 
6. Up to 2 below-the-knee target lesion(s) in native vessels in one or both limbs. 
7. Target lesion from the distal segment (P3) of the popliteal artery to the ankle joint. 

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8. Target lesion reference vessel diameter (RVD) between 2.0mm and 4.0mm by 
investigator visual estimate. 
9. Target lesion with ≥70% stenosis by investigator visual estimate. 
10. Target lesion length is ≤200mm by investigator visual estimate. Target lesion can be 
all or part of the 200mm treated zone. 
11. Distal reconstitution of at least one pedal vessel (<50% stenosis) (desert foot 
excluded) in the target limb. 
12. Evidence of at least moderate calcification at the target lesion site by 
angiography/IVUS OR non-dilatable lesion indicating presence of calcium. Must meet 
one of the following: 
a. Angiography requires fluoroscopic evidence of calcification on parallel sides 
of the vessel and extending >50% the length of the lesion.: 
b. IVUS requires presence of ≥270 degrees of calcium over the course of at least 
10mm. 
c. Non-dilatable lesion requires attempted treatment with PTA during the index 
procedure with residual stenosis >50% and no serious angiographic 
complications. 
7.2.2 Exclusion Criteria 
Subjects who meet any of the following exclusion criteria may not be enrolled in the 
study: 
General Exclusion Criteria 
1. Rutherford Clinical Category 0, 1, 2, and 6 (target limb). 
2. Subjects with osteomyelitis or deep soft tissue infection are excluded unless 
infection can be treated with an individual toe ray amputation or transmetatarsal 
amputation (TMA) in the target limb in the opinion of the investigator. 
3. History of endovascular or surgical procedure on the target limb within the last 30 
days, or planned within 30 days of the index procedure with the exception of toe 
amputation(s). 
4. Subject in whom antiplatelet or anticoagulant therapy is contraindicated. 
5. Subject has known allergy to contrast agents or medications used to perform 
endovascular intervention that cannot be adequately pre-treated. 
6. Subject has known allergy to urethane, nylon, or silicone. 
7. Myocardial infarction within 30 days prior to enrollment. 
8. History of stroke within 60 days prior to enrollment. 

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9. Subject has acute or chronic renal disease with eGFR <30 ml/min/1.73m2 (using 
CKD-EPI formula), unless on renal replacement therapy. 
10. Subject is pregnant or nursing. 
11. Subject is participating in another research study involving an investigational agent 
(pharmaceutical, biologic, or medical device) that has not reached the primary 
endpoint. 
12. Subject has other medical, social or psychological problems that, in the opinion of 
the investigator, preclude them from receiving this treatment, and the procedures 
and evaluations pre- and post-treatment. 
13. Covid-19 diagnosis within 30 days. 
14. The planned use of cutting/scoring balloons, re-entry or atherectomy devices in 
target lesions during the index procedure. 
15. Planned major amputation (of either leg). 
16. Acute limb ischemia (of either leg). 
17. Occlusion of all the inframalleolar outflow arteries/vessels (i.e., desert foot) in the 
target limb. 
18. Subject has an anticipated life span of less than one (1) year. 
19. Subject already enrolled into this study. 
Angiographic Exclusion Criteria 
20. Failure to treat clinically significant inflow lesions in the ipsilateral iliac, femoral, or 
popliteal arteries with ≤30% residual stenosis, and no serious angiographic 
complications (e.g., embolism). 
21. Failure to successfully treat significant non-target infra-popliteal lesions prior to 
treatment of target lesion(s). Successful treatment is defined as obtaining ≤50% 
residual stenosis with no serious angiographic complications (e.g., embolism). 
22. Treatment of vessels below the ankle joint. 
23. Failed pre-dilatation in target lesion during index procedure with angiographic 
evidence of serious angiographic complications. 
24. Target lesion includes in-stent restenosis. 
25. Evidence of aneurysm or thrombus in target vessel. 
26. No calcium or mild calcium in the target lesion. 
27. Target lesion within native or synthetic vessel grafts. 

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28. Failure to successfully cross the guidewire across the target lesion; successful 
crossing defined as tip of the guidewire distal to the target lesion in the absence of 
flow limiting dissections or perforations. 
7.3 Informed Consent 
Prior to undergoing any study-specific tests or procedures, the subject or their legally designated 
representative must sign and date the site’s current and approved Institutional Review Board (IRB)/ 
Ethics Committee (EC) informed consent form (ICF) in order to be eligible for study participation. 
The informed consent must contain all elements required by 21 CFR Part 50, EU MDR 2017/745 
Article 63, and ISO 14155:2020 and comply with the ethical principles of the Declaration of Helsinki. 
7.3.1 Process for Obtaining Informed Consent 
The process for obtaining informed consent is outlined below: 
• 
The Investigator or his/her authorized designee conducts the informed consent process 
• 
All aspects of the clinical study that are relevant to the subject’s decision to participate 
will be included in the consent form 
• 
Investigators will avoid any coercion or undue improper influence on, or inducement 
of, the subject to participate 
• 
The consent process shall not waive or appear to waive the subject’s legal rights 
• 
The consent must use native non-technical language that is understandable to the 
subject 
• 
The Investigator or designee will provide ample time for the subject to read and 
understand the informed consent form and to consider participation in the clinical 
investigation 
• 
The consent must include personally dated signatures of the subject and the 
Investigator, or an authorized designee responsible for conducting the informed 
consent process, and/or all signatures required by the reviewing IRB/EC 
• 
The Investigator or designee will provide the subject with a copy of the signed and dated 
informed consent form and any other written information 
7.3.2 Subjects Needing Legally Designated Representative 
Informed consent may be given by a legally designated representative only if a subject is 
unable to make the decision to participate in a clinical study. In such cases, the subject shall 
also be informed about the clinical study within his/her ability to understand. 
Please follow the local IRB/EC guidelines on this process. 

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7.3.3 Subjects Unable to Read or Write 
Informed consent shall be obtained through a supervised oral process if a subject or legally 
designated representative is unable to read or write, if allowed by the IRB/EC. An 
independent witness shall be present throughout the process. The written informed 
consent form and any other information shall be explained to the prospective subject or 
his/her legally designated representative and, whenever possible, either shall sign and 
personally date the informed consent form. The witness also signs and personally dates the 
informed consent form attesting that the information was accurately explained, and that 
informed consent was freely given. 
7.3.4 Addition of New Information 
Shockwave Medical will revise the written informed consent form whenever new 
information becomes available that may be relevant to the subject’s confirmed 
participation in the clinical study. The revised information will be sent to the Investigator 
for approval by the IRB/EC. After approval by the IRB/EC, a copy of this information must 
be provided to the participating subjects, and the informed consent process as described 
above needs to be repeated. 
Please follow the local IRB/EC guidelines on the process of re-consenting subjects. 
7.4 Schedule of Events and Evaluations 
Table 1 lists the schedule of events and evaluations required for the study. 
Table 1. Schedule of Events and Evaluations 
 
Assessment 
Screening 
/ 
Baseline 
Enrollment 
and 
Procedure 
Discharge4 
30 
Days 
(±7 
days) 
6 
Months 
(180±30 
days) 
12 Months 
(365±30 days) 
24 Months 
(730±30 days) 
TLR 
Eligibility 
√ 
Informed 
Consent 1 
√ 
Medical 
History 
√ 
Physical Exam 
√ 
√ 
√ 
√ 
√ 
Baseline Labs 
(eGFR) 
√ 

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Assessment 
Screening 
/ 
Baseline 
Enrollment 
and 
Procedure 
Discharge4 
30 
Days 
(±7 
days) 
6 
Months 
(180±30 
days) 
12 Months 
(365±30 days) 
24 Months 
(730±30 days) 
TLR 
Pregnancy Test 
√ 
Ankle-Brachial 
Index/Toe- 
Brachial Index 
(ABI/TBI) 
√2 
√ 
√ 
√ 
√ 
Rutherford 
Category (RC) 
√ 
√ 
√ 
√ 
√ 
VascuQoL-6 
Questionnaire 
√ 
√ 
√ 
√ 
√ 
Wound 
Healing 
Assessment 
(including 
photographs) 
√6 
√ 
√ 
√ 
√ 
Medications 
(anticoagulants 
& 
antiplatelets) 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Angiogram 
√ 
√5 
IVUS (sub- 
study 
√3 
Duplex 
Ultrasound 
(DUS) 
√7 
√7 

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Assessment 
Screening 
/ 
Baseline 
Enrollment 
and 
Procedure 
Discharge4 
30 
Days 
(±7 
days) 
6 
Months 
(180±30 
days) 
12 Months 
(365±30 days) 
24 Months 
(730±30 days) 
TLR 
Adverse Events 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
TLR = target lesion revascularization; DUS = duplex ultrasound; ABI = ankle-brachial index; TBI = toe-brachial index; QoL = quality of life 
1. Consent to be obtained within 30 days prior to procedure. 
2. Within 60 days prior to procedure. 
3. For the IVUS Sub-study, IVUS imaging is required at baseline, immediately post-IVL, and end of procedure. 
4. Within 12-24 hours post procedure or prior to hospital discharge, whichever occurs first. 
5. Angiographic images acquired as standard of care prior to the TLR should be submitted to the core lab. 
6. Within 45 days of procedure. 
7. In the event of a non-diagnostic DUS, a 90-day extension is allowed on the upper limit of the window for the 6- and 12-month visits. 
7.5 Medications 
Anticoagulation/antiplatelet medications should be administered according to the 2017 European 
Society of Cardiology (ESC) and European Society of Vascular Surgery (ESVS) PAD guidelines [19] and 
the 2016 American College of Cardiology (ACC) and American Heart Association (AHA) PAD 
guidelines [5]. 
Additional recommendations for anticoagulation and antiplatelet medications include: 
• 
Unfractionated heparin dosing should be undertaken according to hospital standard of 
care. 
• 
Prasugrel or ticagrelor may be used as an alternative to clopidogrel for existing 
management of acute coronary syndrome (ACS). 
• 
Follow antiplatelet and anticoagulation guidelines for the management of patients with 
atrial fibrillation. 
7.6 Screening/Baseline Procedures 
Baseline assessments must be completed within 30 days of the procedure. The following are 
exceptions: wound assessment which can be completed within 45 days of procedure, ankle-brachial 
index (ABI) / toe-brachial index (TBI), which can be completed within 60 days of the procedure, and 
a pregnancy test which must be done within 7 days of the procedure. Informed consent must be 
obtained prior to any study-specific evaluations needed to assess eligibility which are not 
considered standard of care. Subjects on warfarin or direct thrombin inhibitors should be followed 
per institutional standard of care by the physician. 
Baseline assessments include: 
• 
Medical history 
• 
Physical examination 

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o Vital signs 
o Height and weight 
o Baseline Labs (eGFR) 
• 
ABI or TBI (at rest; use same test for subject throughout study) 
• 
Rutherford Category 
• 
VascuQoL-6 Questionnaire 
• 
Wound Healing Assessment (including photographs) 
• 
Review of medications (anticoagulants and antiplatelets) 
• 
Urine pregnancy test if female of child-bearing age 
 
Note: If treatment of two target lesions is planned across both limbs, the RC category and 
ABI/TBI for each limb must be assessed. If ABI/TBI cannot be assessed due to non-compressible 
vessels, this should be documented. If TBI is used, subject should have TBI at each follow-up 
visit. 
eGFR should be calculated using the CKD-EPI formula in absence of a standardized lab test 
provided by the site. 
 
Wound healing assessments of the target limb(s) must be performed at baseline and all follow-up visits. 
Photographs must be taken of the wound(s) to document the progression of wound healing throughout 
the study and kept in the subject’s study binder. Photographs will be retained at the site in the study 
subject’s medical record but will not be provided to the Study Sponsor via upload. If photographs are not 
obtained, a protocol deviation will be issued. At the follow-up visits, the wounds will be recorded in the 
EDC as healed (completely epithelialized), not healed, recurrent, new, or amputated. If the wound is not 
healed, it will be further classified as improving, stagnant, or worsening. A wound can only be considered 
recurrent if it was healed at a prior study visit and subsequently re-appears at the same location. 
 
7.7 Index Procedure 
The IVL treatment algorithm is described in the steps below and illustrated in Figure 2. Each 
investigative site will be using one generator and one connector cable for enrollment in 
accordance with the IFU. Multiple IVL catheters can be used per subject enrollment. 
7.7.1 Procedural Imaging Requirements 
An angiographic cine will be obtained for each lesion treated including pre-procedure, post- 
IVL and end of procedure. (If any non-target lesions are treated, an additional cine will be 
obtained prior to IVL treatment of any target lesion(s) to ensure no serious angiographic 
complications have occurred and that the subject still meets criteria to be enrolled.) All 
angiographic images must be submitted to the core lab for analysis. If intravascular imaging 
(i.e., IVUS) is performed, images from the three timepoints (baseline, immediately post-IVL, 
and end of procedure) should be submitted to the IVUS core lab for analysis. 

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For subjects enrolled in the IVUS Sub-study, angiographic and IVUS images are required at 
three (3) timepoints: baseline, immediately post-IVL, and end of procedure. The core lab will 
provide separate angio and IVUS protocols to participating study centers. 
7.7.2 Assessment of Calcification 
Up to two (2) target lesions may be treated per subject. Calcification of the target lesion(s) 
may be assessed by angiography or IVUS. To meet eligibility requirements, angiography 
requires fluoroscopic evidence of calcification on parallel sides of the vessel and extending > 
50% the length of the lesion. If assessed by IVUS, there must be ≥270 degrees of calcium over 
the course of at least 10mm. Note: if calcification does not meet imaging criteria, a lesion may 
be eligible if found to be non-dilatable, suggestive of calcification. 
7.7.3 Treatment of Non-Target Lesions 
Non-target lesions must be treated successfully prior to treatment of the target lesion(s). After 
the maximum number (2) of target lesions has been reached, any additional lesions should be 
assigned as non-target lesions. Non-target lesions may be treated with any commercially 
available device; treating a non-target lesion with a device that is not approved or considered 
investigational will result in a protocol deviation. 
Note: In the case where non-target lesions and target lesion are present in both limbs, non- 
target lesions should be treated successfully first per limb. 
Clinically significant inflow lesions in the ipsilateral iliac, femoral, or popliteal arteries must be 
treated with ≤30% residual stenosis and no serious angiographic complications (e.g., 
embolism). Significant non-target infra-popliteal lesions must be treated with ≤50% residual 
stenosis with no serious angiographic complications (e.g., embolism). If there are serious 
angiographic complications following treatment of non-target lesions, the subject should not 
be enrolled. 
7.7.4 Tandem Lesion(s) 
Tandem lesions (lesions < 3 cm apart) are allowed if the total treated area covers the entire 
diseased segment. Total treated area is defined as the area treated by any PTA device (pre- 
dilatation, IVL, post-dilatation, or DCB). Each tandem lesion/diseased segment is considered 
one target lesion. As tandem lesions are considered one single target lesion, angiographic 
eligibility must be met as a single lesion. 
7.7.5 Definition of Enrollment 
The definition of enrollment is when the subject signs informed consent, meets all general & 
angiographic eligibility criteria, and the IVL catheter has been inserted over a 0.014” guidewire 
(which had been previously passed across the target lesion). 

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7.7.6 Pre-IVL Dilatation (if required) 
If the operator is unable to pass the IVL balloon across the lesion, a standard PTA balloon up 
to 2.5mm should be used for pre-dilatation prior to treatment with the IVL Balloon (not 
applicable for enrollment of non-dilatable lesions). 
7.7.7 IVL Device Crossing Failures 
If the investigator is not able to advance the IVL Catheter across the target lesion after 
exhausting pre-dilatation efforts AND no pulses were delivered, this will be defined as a Device 
Crossing Failure. Any further treatment will be done per standard of care without the use of 
IVL. In the case of a Device Crossing Failure, the subject is considered enrolled; but as 
treatment with IVL did not occur, will be exited from the study following hospital discharge. 
However, if the investigator cannot fully cross the target lesion with the IVL catheter and 
pulses were delivered, this is not considered a device crossing failure. Under those 
circumstances, a subject is considered enrolled and follow up is required through 24 months 
(see Protocol Section 7.4, Schedule of Events and Evaluations.) 
Note: 
• 
Device crossing failures and devices that did not fully cross still should be documented 
as a device deficiency/malfunction. 
• 
Use of IVL (i.e., for the purpose of enrollment of lesion/subject) is not permitted if non- 
conventional PTA treatments -- including atherectomy, laser or cutting/scoring 
balloons -- were previously used to treat the target lesion. 
7.7.8 IVL Treatment 
A full description of the IVL procedure is detailed in the Instructions for Use (IFU) including 
appropriate balloon sizing. Note that there are specific IFUs and labelling provided for the 
United States (US) and for Outside of the US (OUS). 
Select an IVL balloon catheter size that is 1.1:1 based on balloon compliance chart and 
reference vessel diameter; the largest diameter balloon should be used if 1.1:1 sizing is not 
available. 
Once the IVL balloon is placed in the target lesion area, the balloon must be inflated to 4 atm 
to deliver one cycle of IVL pulses. Table 2 lists the pulsing sequence for each IVL catheter. For 
the M5 and M5+ catheters, one cycle = 30 pulses; for the S4 catheter, one cycle = 20 pulses. 
Insertion of any size IVL Catheter into the IVL Generator will automatically program the IVL 
Generator with the appropriate treatment sequence. Note that the generator is programmed 
to force a minimum pause time of 10 seconds following every cycle. 
Following delivery of the first IVL cycle, the balloon must be inflated to 6 atm (nominal 
pressure; refer to IFU) and record lesion response on fluoroscopy. Deflate the balloon and 
wait 10 seconds to re-establish blood flow. Repeat the steps above to complete a second cycle 
of pulses to complete a single treatment. Additional treatment cycles can be performed if 
deemed necessary. 

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Additional pulses can be performed in a single location to obtain residual stenosis 
<50%. Multiple treatment locations should be done for long lesions with IVL balloon overlap 
of 1 cm. For optimal results, treat the entire lesion length with IVL; do not use “spot” IVL. 
Caution: Care must be taken not to exceed 160 pulses in the same segment. 
 
Table 2. IVL System Sequence Chart 
 
M5 
M5+ 
S4 
Treatment Frequency 
1 Pulse per 
Second 
2 Pulses per 
Second 
1 Pulse per 
Second 
Maximum Number of 
Continuous Pulses 
(1 cycle) 
30 Pulses 
30 Pulses 
20 Pulses 
Minimum Pause Time 
(between cycles) 
10 Seconds 
10 Seconds 
10 Seconds 
Maximum Total Pulses 
Per Catheter 
300 (10 Cycles) 
300 (10 Cycles) 
160 (8 Cycles) 
 
7.7.9 Post-Dilatation 
Post-dilatation with a semi or non-compliant PTA balloon catheter must be completed 
when post-IVL results in one of the following: 
• 
Residual stenosis ≥50% by visual estimate, or 
• 
Presence of a flow-limiting (≥Grade D) dissection, or if 
• 
Trans-lesional gradient >10mm Hg is observed. 
Post-dilatation may also be performed per physician discretion. The physician should use a 
1:1 balloon catheter to artery ratio and may post-dilate for several minutes. Follow the 
angiographic core lab guidelines to complete angiography showing all target lesions with 
reproducible landmarks for follow-up evaluation and assessment. 
7.7.10 Assessment for Acute PTA Failure 
Treatment with a stent or Tack implant is allowed for the following: 
• 
Residual stenosis ≥ 50% by visual estimate, or 
• 
Un-resolved flow-limiting (≥ Grade D) dissection, or if 
• 
Trans-lesional gradient >10mm Hg is observed. 
7.7.11 IVUS Assessment (optional Sub-study) 
For subjects enrolled in the IVUS Sub-study, angiographic and IVUS images must be assessed 
at baseline, immediately post-IVL, and end of procedure. The core lab will provide a separate 
IVUS protocol to participating study centers. 

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Figure 2. BTK IVL Treatment Algorithm 
 
 
7.8 Follow-Up 
7.8.1 Discharge or Within 12-24 Hours Post-Procedure 
The following assessments and procedures will be performed within 12-24 hours post 
procedure or prior to hospital discharge, whichever occurs first: 
• 
Adverse event assessment 
• 
Review of medications (anticoagulants and antiplatelets) 
7.8.2 30-Day Follow-Up 
The following evaluations will be performed at 30 days (+/-7 days) post procedure: 
• 
Physical examination 
o Vital signs 
o Target review of symptoms 
• 
ABI or TBI (at rest; keep consistent with screening) 
• 
Rutherford Category 
• 
VascuQoL-6 Questionnaire 
• 
Wound Healing Assessment (including photographs) 
• 
Review of medications (anticoagulants and antiplatelets) 
• 
Adverse event assessment 

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Note: If treatment of two target lesions is planned across both limbs, the Rutherford Category 
and ABI/TBI for each limb must be assessed. If ABI/TBI cannot be assessed due to non- 
compressible vessels, this should be documented. 
7.8.3 6-Month Follow-Up 
The following evaluations will be performed at 6 months (180 +/-30 days) post procedure: 
• 
Physical examination 
o Vital signs 
o Target review of symptoms 
• 
ABI or TBI (at rest; keep consistent with screening) 
• 
Rutherford Category 
• 
VascuQoL-6 Questionnaire 
• 
Wound Healing Assessment (including photographs) 
• 
Review of medications (anticoagulants and antiplatelets) 
• 
Adverse event assessment 
• 
Duplex ultrasound (DUS) 
Note: 
• 
If treatment of two target lesions is planned across both limbs, the Rutherford 
Category and ABI/TBI for each limb must be assessed. If ABI/TBI cannot be assessed 
due to non-compressible vessels, this should be documented. 
• 
In the event of a non-diagnostic DUS, a 90-day extension is allowed on the upper limit 
of the window for the 6- and 12-month visits 
7.8.4 12-Month Follow-Up 
The following evaluations will be performed at 12 months (365 +/-30 days) post procedure: 
• 
Physical examination 
o Vital signs 
o Target review of symptoms 
• 
ABI or TBI (at rest; keep consistent with screening) 
• 
Rutherford Category 
• 
VascuQol-6 Questionnaire 
• 
Wound Healing Assessment (including photographs) 
• 
Review of medications (anticoagulants and antiplatelets) 
• 
Adverse event assessment 
• 
Duplex ultrasound (DUS) 
 
Note: 

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• 
If treatment of two target lesions is planned across both limbs, the Rutherford 
Category and ABI/TBI for each limb must be assessed. If ABI/TBI cannot be assessed 
due to non-compressible vessels, this should be documented. 
• 
In the event of a non-diagnostic DUS, a 90-day extension is allowed on the upper 
limit of the window for the 6- and 12-month visits 
7.8.5 24-Month Follow-Up 
The following evaluations will be performed at 24 months (730 +/-30 days) post procedure: 
• 
Physical examination 
o Vital signs 
o Target review of symptoms 
• 
ABI or TBI (at rest; keep consistent with screening) 
• 
Rutherford Category 
• 
VascuQoL-6 Questionnaire 
• 
Wound Healing Assessment (including photographs) 
• 
Review of medications (anticoagulants and antiplatelets) 
• 
Adverse event assessment 
 
Note: If treatment of two target lesions is planned across both limbs, the Rutherford Category 
and ABI/TBI for each limb must be assessed. If ABI/TBI cannot be assessed due to non- 
compressible vessels, this should be documented. 
7.8.6 Prior to Target Limb Revascularization 
If a target limb procedure is performed during the follow-up period, angiographic images 
acquired as standard of care should be submitted to the core lab for purposes of adjudication. 
7.9 Subject Withdrawal 
A study subject has the right to discontinue participation at any time without penalty or loss of 
benefits to which the subject is otherwise entitled. A subject that has withdrawn from the study 
will be treated according to standard of medical care and will not be replaced. 
Potential reasons for withdrawal from the study are, but not limited to: 
• 
Subject lost to follow-up 
• 
Pregnancy 
• 
Subject meets exclusion criteria not previously recognized or newly developed 
Safety concerns regarding the device 
7.9.1 When and How to Withdraw Subjects 
Subjects may be withdrawn at the medical discretion of the physician, or they may voluntarily 
withdraw their consent at any time without impact to their medical treatment. 

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Prior to enrollment, the investigative site should provide contact information and detailed 
instructions to subjects on how to withdraw from the study. When a subject is withdrawn, all 
data obtained prior to the time of withdrawal may be submitted to the Study Sponsor and be 
included in the study database, unless otherwise requested by the subject in writing. 
In the event a subject is lost to follow-up or cannot be contacted for post-treatment 
assessments, at least three attempts (two phone calls and a certified letter) will be made to 
locate the study subject, and these efforts will be documented. If the subject cannot be 
located, the subject’s lost to follow-up status will be documented in the EDC and they will be 
exited from the clinical study. 
Should the subject expire, an adverse event form and a study exit/withdrawal form must be 
completed. Physician assessment is required to determine if the cause of death was possibly, 
probably, or definitely related to the IVL System. If available, copies of the death certificate 
and/or an autopsy report should be included in the research records. The Investigator may 
need to provide written notification to the IRB/EC upon the death of the study subject, 
dependent on the IRB/EC policies. 

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8.0 BENEFITS AND RISKS 
8.1 Anticipated Clinical Benefits 
There may be no additional benefit from participation since subjects can receive IVL treatment per 
standard of care. The clinical study will provide safety and effectiveness data associated with 
Peripheral IVL System treatment of calcified BTK arteries. These clinical results may inform 
physicians in determining the optimal treatment strategy for this patient population. 
8.2 Anticipated Adverse Device Effects 
For detailed information on the risks of the devices used in the study procedure, including a 
complete list of warnings, precautions, and potential adverse events, please refer to the 
Instructions for Use (IFU) for the Peripheral IVL System. There are specific IFUs and labelling 
provided for the US and for OUS. 
It is important to ensure that the IFU referred to represents the generation of the device used in 
the study procedure. Unanticipated risks can occur. 
Possible adverse effects are consistent with standard angioplasty. Risks identified as unique to the 
device and its use are outlined in the IFUs for the M5, M5+, and S4 IVL catheters. They include: 
• 
Allergic/immunologic reaction to the catheter material(s) or coating [Incidence is 
Uncommon or Infrequent (≥0.1% to <1%)] 
• 
Device malfunction or failure [Incidence is Rare (≥0.01% to <0.1%)] 
• 
Excess heat at target site due to malfunction of IVL Generator* 
*Note: Because of testing and clinical evidence, this risk is being removed from later 
revisions of the IFU. 
8.3 Risks Associated with Participation in the Clinical Investigation 
All assessments (with the exception of questionnaires) are considered to be standard of care, but 
may be conducted more frequently to comply with the follow-up visit schedule. Non-invasive 
testing includes physical exams, ABI/TBI, Rutherford Category assessments, wound healing 
assessments, and duplex ultrasounds. All of this testing poses minimal risk to the subject. The 
VascuQol questionnaire may not be standard of care at all centers; however, the assessment is non- 
invasive, introduces no additional risk, and is not considered to be an additional burden to the 
subject. For procedure-related risks, please refer to the current IFUs. 
A risk management plan was established to outline the study-specific approach that will be 
implemented to focus on specific risks and area(s) of greatest need, which are considered to have 
the most potential to impact subject safety and data quality. 
8.4 Possible Interactions with Concomitant Medical Treatments 
There are no known possible interactions within this study. 

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8.5 Steps that will be taken to Control or Mitigate the Risks 
Only those subjects meeting each inclusion and no exclusion criteria will be enrolled into this clinical 
study. Investigators will be qualified by education, training, and experience to assume responsibility 
for the proper conduct of the clinical investigation. Risks of observed or theoretical adverse events 
will be mitigated through the Instructions for Use, physician training, subject selection in the study 
protocol, and close monitoring of protocol adherence. 
All efforts will be made to minimize risks specifically by: 
• Site selection 
• Ensuring compliance to the protocol and IFU 
• Data Review 
• Study monitoring 
• Statistical Evaluation 
• Vendor Management 
• Safety processes – protocol adverse event reporting requirements, CEC oversight, and safety 
reporting to regulatory authorities including Vigilance reporting 
• Review of all device malfunctions and complaints by Shockwave Medical Quality. Risk 
acceptability thresholds and trend identification methods have been established, and 
actions will be taken if those are met. 
8.6 Rationale for Benefit-Risk Ratio 
The Shockwave Peripheral IVL System is market approved for the United States (US) and the 
European Union (EU) markets and will be used as per standard of care (SOC) at the investigational 
sites. The safety profile of the Shockwave Peripheral IVL System is well understood and the system 
is already used as part of standard of care at many sites. Previous clinical investigations have 
shown that the Shockwave Peripheral IVL System is safe and effective. 
Risks and benefits of the Shockwave Peripheral IVL System are evaluated throughout the lifetime 
of the device as part of the risk management process in accordance with ISO 14971 which includes 
risk analysis, risk-to-benefit assessment, and risk control. Risk management activities, 
documentation, and records are held and/or referenced in the Risk Management File. The benefit- 
risk analysis provides objective evidence that all risks have been reduced as low as possible and no 
individual risks are unacceptable. Results indicated that the benefits of using the Shockwave 
Peripheral IVL System outweigh any residual risks. 

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9.0 DATA ANALYSIS PLAN 
9.1 General Statistical Methods 
Descriptive statistics will be provided in this clinical study. Analyses will be conducted at pre- 
specified time points including 30 days, 6, 12 and 24 months. 
Categorical variables will be summarized by the number of observations available, frequency, and 
percentage. Unless otherwise noted, missing data will be excluded from the denominator. 
Comparisons will utilize a Chi-square test, or Fisher’s exact test when 20% or more of expected cell 
frequencies are less than 5. Clinical outcomes analyzed at 30 days will be evaluated as categorical 
(binary) data. McNemar’s chi-square may be used to assess within-subject changes in a bivariate 
response variable. Exact confidence intervals will be generated for estimates of proportions. 
Continuous variables will be summarized by the mean, standard deviation, median, minimum, and 
maximum. Within-subject changes will be analyzed parametrically using the Paired t-test if the 
differences are normally distributed, or non-parametrically using the Sign-Rank Test if the 
differences are not normally distributed. Asymptotic confidence intervals will be generated for 
estimates of means. 
Exploratory analyses and clarifications to the protocol specified analysis plan will be documented 
in the SAP. Statistical analyses will be performed using SAS System® Version 9.4 or higher. 
9.2 Primary Endpoints 
Exact 95% confidence intervals will be generated for primary endpoints and estimates of 
proportions. 
9.2.1 Primary Safety Endpoint 
The primary safety endpoint is Major Adverse Limb Events (MALE) or Post-Operative Death 
(POD) at 30 days defined as a composite of: 
• 
all-cause death 
• 
above-ankle amputation of the index limb 
• 
major reintervention (new bypass graft, jump/interposition graft revision, or 
thrombectomy/thrombolysis) of the index limb involving a BTK artery 
9.2.2 Primary Effectiveness Endpoint 
The primary effectiveness endpoint is Procedure Success defined as ≤50% residual stenosis for 
all treated target lesions without serious angiographic complications (flow-limiting dissection, 
perforation, distal embolization, or acute vessel closure) as assessed by the angiographic core 
lab at the final timepoint. 

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9.3 Sample Size Determination 
The sample size was calculated based on the precision of the exact 2-sided 95% confidence interval 
(CI) of the primary effectiveness endpoint, using the LIBERTY 360 study results as a reference. The 
LIBERTY 360 study of endovascular interventions for PAD is one of the largest, real-world, core 
laboratory–adjudicated studies to include patients with varying degrees of PAD severity. Procedural 
Success for the RC 4-5 cohort of this large contemporary data set was 75.8% [71.9, 79.3] [20]. 
The calculation of the Disrupt PAD BTK II sample size was based on a procedural success estimate 
of 75.8%. Combined with a desired precision of +/- 5.8% and an alpha of 0.05 (95% CI), a sample 
size of 225 was selected to provide a probability width (“power”) of 0.827. Assuming a lost-to- 
follow-up rate of 10%, up to 250 subjects will be enrolled. 
9.4 Populations for Analysis 
The primary analysis population will be the Intent-to-Treat (ITT) cohort which includes all enrolled 
subjects. 
9.5 Handling of Dropouts or Missing Data 
No imputation of or adjustments for missing data will be performed for the primary analyses. All 
available data will be presented. For time to event analyses, subjects who do not experience the 
event in question will be censored at their last known follow-up. 
9.6 Sub-Group Analyses 
Analyses to examine the consistency of results across different subgroups will be performed for 
the primary safety and effectiveness endpoints for the following subgroups, and results will be 
reported using descriptive statistics: 
• 
Age (>75 vs ≤75 years) 
• 
Gender 
• 
Diabetes (medically treated vs no diabetes or not medically treated) 
• 
Renal insufficiency (eGFR: <30, 30-59, ≥60) 
• 
Lesion length (<100 mm, 100-150mm, >150mm) 
• 
Chronic Total Occlusion (CTO) 
• 
Calcification (moderate vs severe) 
• 
IVUS Sub-study at baseline, immediately post-IVL, and end of procedure 
• 
Wounds at baseline 
• 
Claudicant (RC 3) vs. CLI (RC 4 & 5) 

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No formal hypothesis testing for subgroup analyses will be performed. However, to examine 
the consistency of results across different subgroups, the primary safety and effectiveness 
endpoints will be compared between subgroups using a logistic regression model including an 
intercept term and fixed effect for the subgroup, with corresponding 95% confidence interval 
and p-value presented. 

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10.0 
SAFETY EVENTS 
Standard definitions and reporting requirements for reportable adverse events for the study are provided 
below. All adverse events will be coded using MedDRA. 
Note: For any of the Adverse Event Definitions listed below, diagnosis should be reported versus individual 
symptoms leading to diagnosis. 
10.1 Adverse Event Definitions 
10.1.1 Adverse Event (AE) 
Untoward medical occurrence, unintended disease or injury, or untoward clinical signs (including 
abnormal laboratory findings) in subjects, users or other persons, whether or not related to the 
investigational medical device and whether anticipated or unanticipated. 
Note: Abnormal laboratory findings will be reviewed by the site Principal investigator (PI) and/or 
site Sub-investigator (Sub-I) who use their medical judgement to determine if these abnormal 
clinical signs are clinically significant (CS) or non-clinically significant (NCS). If the PI or Sub-I deem 
the abnormal laboratory finding to be clinically significant, it should be treated as an adverse event 
and documented as such. If found to be non-clinically significant, the PI/Sub-I should document this 
by writing “NCS” on source document and initial and date. 
Note: This definition includes events related to the investigational medical device or the comparator. 
Note: This definition includes events related to the procedures involved. 
Note: For users or other persons, this definition is restricted to events related to the use of 
investigational medical devices or comparators. 
10.1.2 Serious Adverse Event (SAE) 
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 one or 
more of the following: 
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 or prolonged 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) fetal distress, fetal death, a congenital abnormality, or birth defect including physical or mental 
impairment. 

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Note: Planned hospitalization for a pre-existing condition, or a procedure required by the CIP, 
without serious deterioration in health, is not considered a serious adverse event. 
 
 
10.1.3 Adverse Device Effect (ADE) 
Adverse event related to the use of an investigational device. 
Note: This definition includes adverse events resulting from insufficient or inadequate instructions 
for use, deployment, implantation, installation, or operation, or any malfunction of the 
investigational medical device. 
Note: This definition includes any event resulting from use error or from intentional misuse of the 
investigational medical device. 
Note: This includes “comparator” if the comparator is a medical device. 
10.1.4 Serious Adverse Device Effect (SADE) 
Adverse device effect that has resulted in any of the consequences characteristic of a serious 
adverse event. 
10.1.5 Unanticipated Serious Adverse Device Effect (USADE) 
Serious adverse device effect which by its nature, incidence, severity or outcome has not been 
identified in the current risk assessment. 
Note: Anticipated serious adverse device effect (ASADE) is an effect which by its nature, incidence, 
severity or outcome has been identified in the risk assessment. 
10.2 Adverse Event Device and Procedure Relatedness 
Based on clinical judgment, the Investigator must provide a determination of device and procedure 
relationship for adverse events according to the following categories: 
• Causal Relationship (Definite) – The adverse event is clearly related to the study device: the 
event has a temporal relationship to the study device, follows a known pattern of response, or 
is otherwise logically related to the study device, and no alternative cause is present. 
• Probable – The adverse event is likely related to the study device: the event has a temporal 
relationship to the study device, follows a known or suspected pattern of response, or is 
otherwise logically related to the study device, but an alternative cause may be present. 
• Possible – The adverse event is unlikely related to the study device: the event does not follow a 
clear temporal relationship to the study device or does not follow a known pattern of response, 
or is otherwise possibly to be due to the subject’s clinical state or other modes of therapy. 
In some cases, the adverse event may not be adequately assessed because information is 
insufficient or contradictory and/or the data cannot be verified or supplemented. Maximum 
effort will be made to define and categorize the event and avoid these situations. If relatedness 
remains uncertain, then classify the event as “possible”. 

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• Not Related – The adverse event is clearly not related to the study device: the event has no 
temporal or other relationship to the administration of the investigational device, follows no 
known or suspected pattern of response, and an alternative cause is present. 
10.3 Device Deficiencies 
10.3.1 Definitions 
Device Deficiency is an inadequacy of a medical device with respect to its identity, quality, durability, 
reliability, usability, safety, or performance. 
Note: Device deficiencies include malfunctions, use errors, failure to fully cross lesion and inadequacy 
in the information supplied by the manufacturer including labelling. 
Note: This definition includes device deficiencies related to the investigational medical device or the 
comparator. 
Device Malfunction is a failure of an investigational medical device to perform in accordance with 
its intended purpose when used in accordance with the instructions for use or Clinical 
Investigation Plan (CIP), or Investigator Brochure (IB). 
Note: An IB is deemed not required as the IFUs and product labelling together with available 
commercial product information is deemed sufficient information for the use of the device within 
its approved indication. 
 
 
10.3.2 Reporting 
All device deficiencies and malfunctions will be documented on the eCRF and reported to the Study 
Sponsor within 48 hours after the designated study site personnel first learns of the event, and 
reported to the IRB/EC (if required) within the IRB/EC required timeframe. Device deficiencies and 
malfunctions will trigger an EDC notification to be sent directly to the Study Sponsor. All 
deficient/malfunctioned devices should be securely stored and prepared for return to Shockwave 
Medical. 
In the event that EDC is unavailable, a paper Device Malfunction CRF must be submitted by the site 
to swmbtk2@shockwavemedical.com. 
If a deficiency or malfunction meets the definition of a product complaint (any written, electronic, 
or oral communication that alleges deficiencies related to the identity, quality, durability, reliability, 
safety, or performance of a device after it is released for distribution), a Complaint Form will be 
completed by a Shockwave representative and entered into the company’s complaint system, as 
per Shockwave Medical’s internal procedure. The Shockwave Medical Quality representative is 
responsible for assessing the need for and submitting any Vigilance reports, and/or Medical Device 
Reporting (MDR) reports to the relevant regulatory agencies in line with country specific regulations 
and guidance documents, if required. 

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10.4 Serious and Non-serious Adverse Event Reporting Requirements 
10.4.1 AE Reporting Requirements 
All AE information will be collected from enrollment through 24 months follow-up. Reporting will 
be carried out in accordance with national regulations. Site personnel will enter all AEs into an AE 
eCRF in EDC. AEs should be reported in the subject’s medical records as applicable and on the 
Adverse Event Case Report Form (AE CRF). Data reported should include date of onset, treatment, 
resolution, and an assessment of both seriousness and relationship to the study device and 
procedure. AEs will be followed until the event has resolved (in the case of permanent impairment, 
the event will be followed until it stabilizes, and the overall clinical outcome has been ascertained). 
Any AEs that meet IRB/EC reporting requirements must be reported per the institution’s policy. 
10.4.2 SAE Reporting Requirements 
Any AE meeting any of the criteria for an SAE occurring at any time during the study (enrollment 
through 24 months) must be reported to the Study Sponsor within 48 hours after the designated 
study site personnel first learns of the event. The SAE must also be reported to the IRB/EC per the 
institution’s policy for reporting SAEs. SAEs should be reported in the subject’s medical records as 
applicable and on the Adverse Event Case Report Form (AE CRF). Data reported should include date 
of onset, treatment, resolution, and an assessment of both seriousness and relationship to the study 
device and procedure. SAEs will be followed until the event has resolved (in the case of permanent 
impairment, the event will be followed until it stabilizes, and the overall clinical outcome has been 
ascertained). 
It is the responsibility of the Investigator to inform their IRB/EC of SAEs as required by their IRB/EC 
policies. The Investigator should forward a copy of this report to the Study Sponsor and file in the 
site regulatory binder. 
SAEs will trigger an EDC notification to be sent directly to the Study Sponsor. 
In the event that EDC is unavailable, a paper AE CRF must be submitted by the site to 
swmbtk2@shockwavemedical.com. 
After data entry completion, a notification of SAE and/or device/procedure-related AE will be 
triggered and sent to the Study Sponsor, and any device and/or procedure related AE notifications 
will be sent directly to Shockwave Medical Quality for review. 
10.4.3 Non-serious ADE Reporting Requirements 
All ADE information will be collected from enrollment through 24 months. ADEs will be recorded in 
the subject’s medical records as applicable and on the Adverse Event Case Report Form (AE CRF). 
Each ADE must be evaluated to determine if the event meets the definition of SADEs. Data reported 
should include date of onset, treatment, resolution, and an assessment of both seriousness and 
relationship to the study device and procedure. ADEs will be followed until the event has resolved 
(in the case of permanent impairment, the event will be followed until it stabilizes, and the overall 

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clinical outcome has been ascertained). All ADEs must be reported to the Study Sponsor as soon as 
possible after the designated study site personnel first learns of the event. 
10.4.4 SADE Reporting Requirements 
All ADEs will be evaluated by the Study Sponsor or designee to determine if the ADE meets the 
definition of a SADE. All SADEs must be reported within 48 hours after the designated study site 
personnel first learns of the event. All SADEs should be reported to the IRB/EC in accordance with 
their requirements. 
10.4.5 USADE Reporting Requirements 
Investigators are required to submit a report of a USADE to the Study Sponsor as soon as possible, 
but not later than 48 hours after the designated study site personnel first learns of the event and to 
the ECs within the required timeframe. Investigators are required to report a UADE to the reviewing 
IRB/EC and the Study Sponsor as soon as possible, but in no event later than 10 working days after 
the Investigator first learns of the effect. 
10.4.6 AE and Device Deficiency Reporting Time Frames 
Table 3 summarizes the time sensitive reporting requirements for serious and non-serious adverse 
events and device deficiencies. The Study Sponsor or designee is the contact person for these 
reporting requirements. 
 
Table 3. Investigator Responsibilities for Reporting Adverse Events 
 
Type of Event 
Process 
Device deficiencies 
(including malfunctions) 
Report to the Study Sponsor within 48 hours after the 
designated study site personnel first learns of the event and to 
the IRB/EC (if required) within the IRB/EC required timeframe. 
Serious adverse events 
(SAE, SADE) 
Report to the Study Sponsor within 48 hours after the 
designated study site personnel first learns of the event and to 
the IRB/EC within the IRB/EC required timeframe. 
Unanticipated serious 
adverse device effect 
(USADE) 
Report to the Study Sponsor as soon as possible, but no later 
than 48 hours, after the designated study site personnel first 
learns of the event and to the IRB/EC within the IRB/EC 
required timeframe. 
Non-serious adverse 
events 
(AE, ADE) 
Report to the Study Sponsor as soon as possible after the 
designated study site personnel first learns of the event, and to 
the IRB/EC (if required) within the IRB/EC required timeframe. 

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11.0 
INVESTIGATOR RESPONSIBILITIES 
The role of the Principal Investigator is to implement and manage the conduct of the clinical study at 
their site, as well as ensure data integrity and the rights, safety, and well-being of the participating 
subjects. 
11.1 IRB/EC Approval 
The Investigator must obtain approval to conduct the clinical study prior to screening any potential 
subjects and comply with annual continuing approval requirements where applicable. The role of 
the IRB/EC is to ensure that the rights of the study subjects are protected and to ensure that the 
research meets high ethical and scientific standards. All correspondence with the IRB/EC should be 
maintained in the site’s study files. 
11.2 Informed Consent 
The Investigator is responsible for ensuring that all applicable local, national, Declaration of 
Helsinki, EU MDR 2017/745, and ISO 14155:2020 requirements in the clinical study are met when 
completing the informed consent process. It is the responsibility of the Investigator to ensure 
written informed consent from each subject, or the legally designated representative of a 
vulnerable subject, is obtained prior to the initiation of any study-related procedures. As per ISO 
14155:2020, vulnerable subjects are defined as individuals who are unable to fully understand all 
aspects of the investigation that are relevant to the decision to participate, or who could be 
manipulated or unduly influenced as a result of a compromised position, expectation of benefits, 
or fear of retaliatory response. 
 
Inclusion of vulnerable subjects in this clinical study is considered ethical given that this is a post- 
market clinical investigation without additional invasive or burdensome procedures. 
 
The Investigator must comply with the requirements specified in protocol Section 7.3. 
11.3 Protocol Compliance and Delegation of Authority 
The Investigator shall conduct the clinical study in compliance with this study protocol and ensure 
that the clinical study is appropriately staffed with qualified study personnel throughout the 
duration of the clinical study. In addition, the facilities where the clinical study is being conducted 
must be maintained to allow for proper study conduct. Changes to either study staff or facilities 
must be documented. The Investigator must maintain a Delegation of Authority Form of 
appropriately qualified persons to whom the Investigator has delegated significant study related 
duties. 
11.4 Medical Care of Subjects 
The Investigator shall: 
• Provide adequate medical care to a subject during and after a subject’s participation in the 
clinical study in the case of adverse events, as described in the informed consent, 

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• 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 study, 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, 
• Ensure vulnerable subjects are identified and protected, 
• Ensure that clinical records are clearly marked to indicate that the subject is enrolled in a 
particular clinical study, 
• Inform, with the subject’s approval or when required by national regulations, the subject’s 
personal physician about the subject’s participation in the clinical study, 
• Make all reasonable efforts to ascertain the reason(s) for a subject’s premature withdrawal from 
the clinical study while fully respecting the subject’s rights, and 
• Continue to treat subjects at his/her discretion according to local standard of care following 
study exit, temporary halt, or early termination of the clinical study. 
11.5 Safety Reporting 
The Investigator must comply with the safety reporting requirements specified in protocol Section 
10.0. 
11.6 Protocol Amendment(s) 
The Investigator or clinical site staff will not make any modifications to this protocol or the Informed 
Consent form without prior written approval from the Study Sponsor. Study Sponsor and 
Investigator will agree to all amendments made to the protocol or the Informed Consent form 
before submitting to the local IRB/EC for approval. If protocol changes affect the scientific 
soundness of the clinical investigation, or affect the health, welfare, safety and rights of subjects, 
Investigator and/or Study Sponsor will submit all amendments to the local IRB/EC to obtain written 
approval before implementing changes. 
11.7 Records Retention 
All study records and documentation must be maintained by the Investigator and are subject to 
inspection and copying and must be retained for a period of two (2) years after the clinical study is 
completed or terminated. The Study Sponsor must be contacted if the Investigator plans to leave 
the study site. An Investigator may withdraw responsibility to maintain records for the time 
required by the study protocol by transferring custody to another qualified person willing to accept 
responsibility for him/her. 

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12.0 
STUDY SPONSOR RESPONSIBILITIES 
As the Study Sponsor, Shockwave Medical is responsible for the overall conduct and quality of the clinical 
study. Shockwave Medical will ensure that qualified monitors and designated personnel are monitoring 
the clinical study according to the pre-determined monitoring plan and that the Informed Consent process 
is followed per the study site’s requirements. The Study Sponsor is responsible for the classification and 
reporting of adverse events, review of medical coding, and ongoing safety evaluation of the clinical study. 
12.1 Selection and Training of Study Sites 
Investigators will be qualified by education, training, and experience to assume responsibility for 
the proper conduct of the clinical investigation. Investigators must disclose potential conflicts of 
interest, including financial, that may interfere with the conduct of the clinical investigation or 
interpretation of results. 
Shockwave Medical and/or its designees are responsible for the training of appropriate clinical site 
personnel, including the Principal Investigator, Sub-Investigator(s), and Research Coordinator(s). 
Initial protocol and device training will be conducted by Shockwave Medical or its designees and 
will be ongoing as required. The Principal Investigator will delegate roles and responsibilities to the 
Sub-Investigator(s) and Research Coordinators(s) as documented on the Delegation of Authority 
Log. 
A training record must be signed and dated by both Shockwave Medical and/or its designee 
conducting the training, and each member of the research team that attended the training session 
before any study activity is performed. A copy of the signed training record must be submitted to 
Shockwave Medical or its designee, and the original signed training record(s) should be filed in the 
site’s study Regulatory Binder. 
12.2 Monitoring 
12.2.1 Monitoring Methods 
Monitoring functions will be conducted by Shockwave Medical and/or its designated Contract 
Research Organization (CRO). Specific monitoring requirements are detailed in the study-specific 
Monitoring Plan maintained in the Shockwave Medical and/or the CRO clinical study project files. 
All monitoring activities shall be documented in a written report. Corrective action will be taken 
to resolve any issues of noncompliance. If Shockwave Medical finds that an Investigator is not 
complying with the executed Investigator Agreement, the study protocol, the applicable laws and 
regulations, or the requirements of the reviewing IRB/EC, prompt action will be taken to secure 
compliance. Shockwave Medical will reserve the right to suspend or terminate the participation 
of the Investigator or the study site. 
12.2.2 Monitoring Visits 
Scheduled monitoring visits to the clinical study site may occur at the following times: prior to the 
start of the study, interim visits throughout the duration of the clinical study as required per the 

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monitoring plan, and upon completion of the clinical study. Sites that enroll rapidly may be visited 
more frequently at Shockwave Medical’s discretion. A final Close-Out Visit will be conducted upon 
completion of the entire clinical study or at the time a site is terminated. Restrictions to on-site 
monitoring visits may require that alternative monitoring strategies be implemented including 
the use of remote monitoring or risk-based approaches. 
12.3 Study Deviations 
A study deviation is defined as an instance(s) of failure to follow, intentionally or unintentionally, 
the requirements of the study protocol, applicable laws or regulations, or the Investigator 
Agreement. The investigators shall not deviate from the study protocol. The Investigator must 
document and notify Shockwave Medical of any deviation from the study protocol as soon as 
possible. The use of waivers from the protocol is not permitted. 
Major deviations include those that involve the primary endpoint, the informed consent process, 
the inclusion/exclusion criteria of the clinical study, or any deviation that involves or leads to a 
serious adverse event in a study subject. 
Under certain circumstances, deviations from the study protocol to protect the rights, safety and 
well-being of human subjects may proceed without prior approval of the Study Sponsor and the 
IRB/EC. Such deviations shall be documented in writing and reported to the Study Sponsor and the 
IRB/EC as soon as possible, and no later than 5 working days. 
Subject-specific deviations will be reported within the applicable study management system. 
Investigators will also adhere to procedures for reporting study deviations to their IRB/EC in 
accordance with their requirements. Deviations from clinical protocol will be reviewed and 
evaluated by Shockwave Medical on an ongoing basis and, as necessary, and appropriate corrective 
actions will be put into place. 
12.4 Device Accountability 
The Study Sponsor will only provide investigational devices to the site once evidence of required 
IRB/EC approval has been provided to the Study Sponsor or designee. 
Lot numbers are applied to all finished investigational devices and associated components. It is the 
responsibility of each investigational site to maintain records of the lot numbers of the IVL Systems 
and components received, used, returned, or disposed of by the site via accountability logs. 
All unused and/or expired study devices will be collected and returned to Shockwave Medical as 
per instruction by the Study Sponsor. In case of a device deficiency or malfunction, study staff must 
contact the Study Sponsor for a Return Material Authorization (RMA) Number and a return kit, and 
will be required to return the device(s) in question to Shockwave Medical as soon as possible. The 
site should observe their site-specific instructions pertaining to handling of biohazardous materials. 
12.5 Study/Site Suspension or Early Termination 
The Study Sponsor may suspend or prematurely terminate the study at either an individual site or 
the entire clinical study for significant and documented reasons. A Principal Investigator, IRB/EC, or 

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regulatory authority may suspend or prematurely terminate participation in a clinical study at the 
sites for which they are responsible. 
If suspicion of an unacceptable risk to subjects arises during the clinical study, or when so instructed 
by the IRB/EC or regulatory authorities, the Study Sponsor shall suspend the clinical study while the 
risk is assessed. The Study Sponsor shall terminate the clinical study if an unacceptable risk is 
confirmed. 
Shockwave Medical shall consider terminating or suspending the participation of a particular study 
site or Investigator in the clinical study if monitoring or auditing identifies serious or repeated 
deviations on the part of an Investigator such as insufficient Investigator involvement in the 
clinical study, inappropriate delegation of authority, or non-compliance to GCP 
If suspension or premature termination occurs, the terminating party shall justify its decision in 
writing and promptly inform the other parties with whom they are in direct communication. The 
Principal Investigator and Study Sponsor shall keep each other informed of any communication 
received from the IRB/EC or any regulatory authority. 
If, for any reason, Shockwave Medical suspends or prematurely terminates the clinical study at an 
individual site, the Study Sponsor shall inform the IRB/EC. If the suspension or premature 
termination was in the interest of safety, the Study Sponsor shall inform all other Principal 
Investigators. 
If suspension or premature termination occurs, Shockwave Medical will remain responsible for 
providing resources to fulfill the obligations from the study protocol and existing agreements for 
follow up of the subjects enrolled in the clinical study, and the Principal Investigator or authorized 
designee shall promptly inform the enrolled subjects at his/her site, if appropriate. It is the 
Investigator’s responsibility to follow subjects according to local standard of care in such instances. 
Routine closeout activities shall be conducted to ensure that the Principal Investigator’s records are 
complete, all documents needed for the Study Sponsor’s files are retrieved, remaining clinical study 
materials are disposed of, previously identified issues have been resolved, and all parties are 
notified. 
Resumption of a Clinical Study after Temporary Suspension: 
When the Study Sponsor completes an analysis of the reason(s) for the suspension, implements the 
necessary corrective actions, and decides to lift the temporary suspension, the Study Sponsor shall 
inform the Principal Investigators and the IRB/EC, and provide them with the relevant data 
supporting this decision. Concurrence shall be obtained from the IRB/EC before the clinical study 
resumes. If subjects have been informed of the suspension, the Principal Investigator or authorized 
designee shall inform them of the reasons for resumption. 
12.6 Study Completion 
The clinical study is considered completed after all subjects have undergone all of their protocol 
required follow-up visits, data entry for all eCRFs has been completed, all queries have been 
resolved, all action items have been closed, and all site payments have been made. All unused study 

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materials and study devices will be collected and returned to Shockwave Medical as per instruction 
by the Study Sponsor. A final clinical study report will be completed no later than 12 months after 
clinical study completion, even if the clinical study was terminated prematurely. 
12.7 Audits / Inspections 
Shockwave Medical, regulatory agencies, and ECs may conduct audits or inspections at the study 
sites during the course of or after completion of the clinical study. Access to all study records, 
including source documents, for inspection and duplication may be requested. 
12.8 Publication Policies 
The Study Sponsor and the study investigators are committed to timely and complete dissemination 
of the clinical study results. Publications based on the results of the clinical study will follow the 
process outlined in the Investigator Agreement. At the conclusion of the clinical study, a multi- 
center manuscript will be prepared for publication in a reputable peer-reviewed scientific journal. 
The principal results will also be presented at a scientific congress. 
The publication of the results from any single site experience within the clinical study is not allowed 
until the preparation and publication of the multi-center results has occurred. Exceptions to this 
rule require the prior approval of Shockwave Medical. 
After publication of the multi-center manuscript, a single site may publish the results of its subjects 
after first complying with the requirements in the Investigator Agreement. Any proposed 
publications must be submitted to Shockwave Medical for review and comment at least forty-five 
(45) days in advance of submitting such proposed publications to a publisher or other third party. 
If no response is received from Shockwave Medical within thirty (30) days of the date submitted, 
the Investigator may proceed with publication as long as all work and research on the clinical study 
has been completed. 
This clinical study is registered with www.clinicaltrials.gov and anzctr.org.au. 
12.9 Data Management 
Shockwave Medical and Data Management designees will oversee and/or perform all data 
management functions. Data management functions include database development, system 
maintenance, user training, data queries, and report generation. The Principal Investigator and/or 
study staff are responsible for the accuracy and completeness of all study data recorded. The 
Principal Investigator is responsible for confirming the integrity of the data and for full, transparent 
public reporting of the results. Aspects with respect to the management and storage of data will 
also be outlined in the Patient Informed Consent Form for site specific factors. 
Shockwave Medical intends to utilize the data obtained from the clinical study for commercial uses 
including publication and/or presentation of results at congresses, regulatory agency submissions, 
continued product development activities, and marketing of their vascular products. All data when 
used in these activities will be in a de-identified format. Data obtained during this clinical study will 
not be utilized in a database without first gaining the consent of participants. 

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All required data for this study will be collected via a web-based electronic data capture (EDC) 
system (ClinTrak®) as supplied by the Clinical Research Organization (CRO) Medpace. 
ClinTrak® EDC provides a centralized location for the study team to review real-time case report 
form (CRF) data. The system allows for the secure and accurate collection and cleaning of the data 
from each study. This comprehensive tool provides functionality in the areas of study design, data 
entry, data clean-up, coding of terms, data changes, reporting, real-time web access, audit trail, and 
export of the clinical data for analysis purposes. 
ClinTrak® EDC has been validated in accordance with Medpace Standard Operating Procedures 
(SOPs) that describe the processes, activities, and deliverables necessary to comply with applicable 
predicate rules (GxP) and FDA 21 CFR Part 11. The system has been confirmed to be fit for purpose 
and the features and functionality have been determined to perform reliably and consistently as 
intended. Appropriate controls of the system are in place and documented evidence is available to 
support the application of those controls. 
Medpace will provide training in the use of ClinTrak® EDC to all necessary site personnel. Each 
investigator and staff participant will be assigned a unique password and only that individual should 
access subject records under that password. 
12.9.1 Case Report Forms 
All required data for this clinical study will be entered in electronic Case Report Forms (eCRFs). 
All data collected during the clinical study will be de-identified. For this purpose, a unique study 
identifier will be assigned to each study subject. All information about the subject, including the 
study identifier, will be recorded on the eCRF. The database will contain only the study identifier 
to identify the subject. The code with subject name and study number will be maintained by the 
Principal Investigator in a secured location. Subject names will not be released to Shockwave 
Medical at any stage of the clinical study. 
12.9.2 Transmission of Data 
Required data will be recorded on the appropriate eCRFs at the time of or as soon as possible 
after the subject visit. The eCRF and any requested supporting source documents (including 
medical imaging files) must be sent to Shockwave Medical and/or retrieved from the Investigator 
during monitoring visits. Where possible, data sent to Shockwave Medical will be done so utilizing 
a password secured web-based system. 
12.9.3 Data Queries 
Any data discrepancies identified during data review or a monitoring visit will be queried by 
Shockwave Medical or its designee and must be resolved by the investigational site staff and 
Investigator in a timely manner. 
Data audits may be performed for quality assurance of data handling. Any discrepancies will be 
queried by Shockwave Medical or its designee and must be resolved by the investigational site 

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staff and Investigator in a timely manner, particularly during those times data is being prepared 
for CEC safety reviews and reports required by the regulatory authorities. 
12.9.4 Data Retention 
Shockwave Medical will retain all study data received for a period of two (2) years after the 
investigation is completed or terminated, or longer if required by applicable local regulations. The 
data will be retained in a secure, password protected database and stored in the United States of 
America. 

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13.0 
STUDY COMMITTEES 
13.1 Clinical Events Committee (CEC) 
To meet the ethical responsibilities and standards for research subjects, an independent Clinical 
Events Committee shall serve as forum for adjudication of certain pre-specified clinical event types 
described in the CEC charter. In order to enhance objectivity and reduce the potential for bias, the 
CEC shall be independent of the Study Sponsor as well as the study sites / Investigators. 
The CEC is made up of clinicians with pertinent expertise who are not participants in the clinical 
study and who do not have any other real or potential conflicts of interest. The CEC is charged with 
the development of specific criteria used for the categorization of adverse events and clinical 
endpoints in the clinical study. Criteria will be established for selected complications and clinical 
events. 
At the onset of the clinical study, the CEC will establish explicit rules outlining the minimum amount 
of data required and the algorithm followed in order to classify an event. The methodology for 
performing these responsibilities shall be developed and outlined in the CEC Charter. Operational 
provisions shall be established to minimize potential bias (i.e., CEC members shall be blinded to the 
clinical site to the extent possible during adverse event review and adjudication). The methodology 
for performing these responsibilities shall be developed and outlined in the CEC Charter. 

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14.0 
ETHICAL and REGULATORY CONSIDERATIONS 
14.1 Role of Shockwave Medical 
As the Study Sponsor of this clinical study, Shockwave Medical has the overall responsibility for 
conduct of the clinical study, including assurance that the clinical study will be conducted according 
to ICH Good Clinical Practices (GCP), applicable elements of 21 CFR 812, 820, 50, 54, and 56, 
Declaration of Helsinki, applicable IRB/EC requirements, as well as EU MDR 2017/745 and ISO 
14155:2020 and/or national requirements. In this study, Shockwave Medical will have certain direct 
responsibilities and may delegate other responsibilities to qualified consultants and/or contract 
research organizations. The specific federal regulations, international standards, and/or guidelines 
required to be followed are outlined within the protocol. The Study Sponsor will provide insurance 
coverage to subjects for any clinical investigation related damages according to applicable legal 
requirements and will maintain a valid subject liability insurance for the duration of the clinical 
study. 
This protocol and any amendments will be submitted to each site’s IRB/EC and, where applicable, 
to the competent Regulatory Authority, for formal approval of the clinical study. All subjects 
considered for this clinical study will be provided a consent form describing this study and providing 
sufficient information for them to make an informed decision about their participation. 
Shockwave Medical as the Study Sponsor will ensure financing of the clinical investigation in line 
with the contracts between the Study Sponsor or its designee and study sites. 
14.2 Subject Confidentiality 
Subject confidentiality will be maintained throughout the clinical study. A unique subject 
identification code will be assigned and used to allow identification of all data reported for each 
subject. 
Study data may be made available to third parties, e.g., in the case of an audit, provided the data 
are treated confidentially and that the subject’s privacy is guaranteed. The identity of a subject will 
never be disclosed in the event that study data are published. 

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15.0 
DEFINITIONS and ABBREVIATIONS 
15.1 Study Definitions 
Abrupt or Acute Closure: Angiographic documentation of significantly reduced flow due to mechanical 
dissection, thrombus, or severe vessel spasm in the treatment area. 
Acute Limb Ischemia: A sudden decrease in limb perfusion that causes a potential threat to limb 
viability (manifested by ischemic rest pain, ischemic ulcers, and/or gangrene) in patients who present 
within two weeks of the acute event. 
Adverse Device Effect (ADE): Adverse event related to the use of an investigational medical device. 
Note: This definition includes adverse events resulting from insufficient or inadequate 
instructions for use, deployment, implantation, installation, or operation, or any malfunction of 
the investigational medical device. 
Note: This definition includes any event resulting from use error or from intentional misuse of the 
investigational medical device. 
Note: This includes “comparator” if the comparator is a medical device. 
Adverse Event (AE): Untoward medical occurrence, unintended disease or injury, or untoward clinical 
signs (including abnormal laboratory findings) in subjects, users or other persons, whether or not 
related to the investigational medical device and whether anticipated or unanticipated. 
Note: This definition includes events related to the investigational medical device or the 
comparator. 
Note: This definition includes events related to the procedures involved. 
Note: For users or other persons, this definition is restricted to events related to the use of 
investigational medical devices or comparators. 
Amputation (major): Any requirement for amputation above the ankle. 
Amputation (minor): Any requirement for amputation below the ankle. 
Amputation, Unplanned: An amputation associated with the target limb that occurs between the index 
procedure and 30 days post-procedure that was not previously planned as part of the overall treatment 
strategy. 
Ankle-Brachial Index (ABI): The ratio of systolic blood pressure measured at the ankle to systolic blood 
pressure measured at the brachial artery. 
Below the Knee (Lesion Location): From center of knee joint space to ankle joint. 
Calcification Classification (PARC): Calcification will be assessed by the angiographic core lab according 
to the Peripheral Academic Research Consortium (PARC) definition [21]. 

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PARC Degree of Lesion Calcification 
 
Focal 
Degree of lesion calcification 
Mild 
<180° and greater than one-half of the total lesion length 
Moderate 
≥180° (both sides of vessel at same location) and less than one-half of 
the total lesion length 
Severe 
>180° (both sides of the vessel at the same location) and greater than 
one-half of the total lesion length 
 
Closure, Abrupt: Occurrence of new (during the index procedure), persistent slow, reduced, or loss of 
flow within the target vessel that requires intervention other than the index or adjunct treatment. 
Abrupt closure may also be referred to as acute occlusion if there is a total loss of flow. 
Closure, Subacute: Target lesion site occlusion that occurs after the index procedure is completed (e.g., 
the subject has left the treatment area) and within 30 days of procedure. 
Critical Limb Ischemia: Clinical manifestation of peripheral arterial disease characterized by Rutherford 
Category of 4-6. (For the purposes of this clinical study, only subjects with Rutherford Category of 3, 4, 
and 5 are eligible for enrollment). 
Death: (divided into 2 categories) 
Cardiac death is death due to any of the following: 
1. Acute myocardial infarction 
2. Cardiac perforation/pericardial tamponade 
3. Arrhythmia or conduction abnormality 
4. Stroke within 30 days of the procedure or stroke suspected of being related to the procedure 
5. Death due to complication of the procedure, including bleeding, vascular repair, transfusion 
reaction, or bypass surgery 
6. Any death for which a cardiac cause cannot be excluded 
Non-cardiac death is a death not due to cardiac causes (as defined immediately above). 
Device Deficiency: Inadequacy of a medical device with respect to its identity, quality, durability, 
reliability, usability, safety or performance. 
Note: Device deficiencies include malfunctions, use errors, and inadequacy in the information 
supplied by the manufacturer including labelling. 

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Note: This definition includes device deficiencies related to the investigational medical device or 
the comparator. 
Device Malfunction: A failure of an investigational medical device to perform in accordance with its 
intended purpose when used in accordance with the instructions for use or Clinical Investigation Plan 
(CIP), or Investigator Brochure (IB). 
Note: An IB is deemed not required as the IFUs and product labelling together with available 
commercial product information is deemed sufficient information for the use of the device within 
its approved indication. 
Dissection: Disruption of an arterial wall resulting in separation of the intimal layer. May or may not be 
flow limiting. 
Dissection Classifications (National Heart, Lung and Blood Institute – NHLBI) 
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 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 coronary occlusion. 
Embolization, Distal: Any distal emboli confirmed by imaging considered to be related to the target 
lesion(s). 
Embolization, Symptomatic: Clinical signs or symptoms of distal emboli detected in the treated limb 
distal to the treated lesion after the index procedure or noted angiographically and requiring 
mechanical or pharmacologic means to improve flow. This includes new abrupt occlusions or filling 
defects. 
Intravascular Lithotripsy (IVL): Shockwave Medical’s proprietary balloon angioplasty catheter including 
lithotripsy technology that creates pulsatile mechanical energy for disrupting calcified vascular plaque. 
Limb Ischemia: Deficient supply of oxygenated blood to the tissues in the limbs that is due to 
obstruction of the inflow of arterial blood characterized by pain and/or discoloration of the limb. 
Lithotripsy: A medical procedure for disrupting calculus in the body. 
Luminal Patency: Post-procedure residual stenosis <50% as determined by investigator visual 
assessment or quantitative analysis of the end of procedure angiogram. 

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Major Adverse Event (MAE): For the purposes of this study, the definition of Major Adverse Event(s) 
includes: 
• 
Need for emergency surgical revascularization of target limb 
• 
Unplanned target limb major amputation (above the ankle) 
• 
Symptomatic thrombus or distal emboli that require surgical, mechanical or pharmacologic 
means to improve flow and extend hospitalization 
• 
Perforations that require an intervention, including bail-out stenting 
 
Non-Target Lesion: A lesion not intended to be treated per BTK II protocol eligibility but treated per 
institutional standard of care in the same enrollment procedure. 
 
Note: If there are excess lesions after the maximum number of target lesions has been reached, these 
excess lesions should be assigned as non-target lesions AND treated successfully first. 
 
P3 segment of popliteal artery: From center of knee joint space to origin of anterior tibial artery. 
Perforation: Puncture of an arterial wall. 
Restenosis: Reoccurrence of narrowing or blockage of target lesion. 
Rutherford Category: Clinical scale identifying three grades of claudication and three grades of critical 
limb ischemia ranging from rest pain alone to minor and major tissue loss. (ACC/AHA PAD Practice 
Guidelines – Hirsch et al. 2005) 

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Grade 
Category 
Clinical Description 
0 
Asymptomatic 
I 
1 
Mild claudication 
2 
Moderate claudication 
3 
Severe claudication 
II 
4 
Ischemic rest pain 
5 
Minor tissue loss- nonhealing ulcer, 
focal gangrene with diffuse pedal 
ischemia. 
III 
6 
Ulceration or gangrene- extending 
above TM (transmetatarsal) level, 
functional foot no longer salvageable. 
 
Serious Adverse Device Effect (SADE): Adverse device effect that has resulted in any of the 
consequences characteristic of a serious adverse event. 
Serious Adverse Event (SAE): Adverse event that led to any of the following: 
• 
death, 
• 
serious deterioration in the health of the subject, user, or other persons as defined by one or 
more of the following: 
o a life-threatening illness or injury, or 
o a permanent impairment of a body structure or a body function including chronic 
diseases, or 
o in-patient or prolonged hospitalization, or 
o medical or surgical intervention to prevent life-threatening illness or injury, or 
permanent impairment to a body structure or a body function, or 
• 
fetal distress, fetal death, a congenital abnormality, or birth defect including physical or mental 
impairment. 
Note: Planned hospitalization for a pre-existing condition, or a procedure required by the CIP, 
without serious deterioration in health, is not considered a serious adverse event. 
Target Lesion: A lesion eligible per BTK II protocol and intended to be treated with BTK II provided 
research IVL catheter. 
Note: Device crossing failures or device malfunction causing no actual IVL treatment are still 
considered target lesions. 

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Target Lesion Revascularization, Clinically-driven (TLR): A target lesion revascularization performed 
due to target lesion diameter stenosis ≥50% and either evidence of clinical or functional ischemia 
(e.g., recurrent/progressive life-limiting intermittent claudication, claudication unresponsive to 
medical therapy, CLI) or recurrence of the clinical syndrome for which the initial procedure was 
performed. Clinically driven target lesion revascularization occurs in the absence of protocol directed 
surveillance ultrasound or angiography. 
Target Vessel Revascularization, Clinically-driven (TVR), non-TLR: A target vessel revascularization 
performed due to non-target lesion diameter stenosis ≥50% and either evidence of clinical or functional 
ischemia (e.g., recurrent/progressive life-limiting intermittent claudication, claudication unresponsive 
to medical therapy, CLI) or recurrence of the clinical syndrome for which the initial procedure was 
performed. Clinically driven target vessel revascularization occurs in the absence of protocol directed 
surveillance ultrasound or angiography. 
Total Occlusion: A 100% stenotic lesion as documented by angiographic absence of flow. 
Toe Brachial Index (TBI): The ratio of systolic blood pressure measured at the toe to systolic blood 
pressure measured at the brachial artery. 
Unanticipated Serious Adverse Device Effect (USADE): Serious adverse device effect which by its 
nature, incidence, severity or outcome has not been identified in the current risk assessment. 
Note: Anticipated serious adverse device effect (ASADE) is an effect which by its nature, 
incidence, severity or outcome has been identified in the risk assessment. 
Wound: Foot ulcer or gangrene. After debridement and/or minor amputation, a wound is characterized 
as a healed wound when it is completely epithelialized. 
 
 
15.2 List of Abbreviations 
 
ABI 
Ankle-Brachial Index 
ACC 
American College of Cardiology 
ACS 
Acute Coronary Syndrome 
ADE 
Adverse Device Effect 
AE 
Adverse Event 
AHA 
American Heart Association 
BTK 
Below-the-Knee 
CD-TLR 
Clinically-Driven Target Lesion Revascularization 
CE 
European Conformity 
CEC 
Clinical Events Committee 
CFR 
Code of Federal Regulations 
CI 
Confidence Interval 

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CIP 
Clinical Investigation Plan 
CKD 
Chronic Kidney Disease 
CLI 
Critical Limb Ischemia 
CRF 
Case Report Form 
CRO 
Contract Research Organization 
CR-TLF 
Clinically Relevant Target Lesion Failure 
CTA 
Computed Tomography Angiogram 
CTO 
Chronic Total Occlusion 
DCB 
Drug-Coated Balloon 
DES 
Drug-Eluting Stent 
DUS 
Duplex Ultrasound 
eCRF 
Electronic Case Report Form 
EDC 
Electronic Data Capture 
EC 
Ethics Committee 
ESC 
European Society of Cardiology 
ESVS 
European Society of Vascular Surgery 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
GFR 
Glomerular Filtration Rate 
IB 
Investigator Brochure 
ICF 
Informed Consent Form 
ICH 
International Council for Harmonisation 
IFU 
Instruction for Use 
IRB 
Institutional Review Board 
ISO 
International Organization for Standardization 
ITT 
Intent-to-Treat 
IVL 
Intravascular Lithotripsy 
IVUS 
Intravascular Ultrasound 
MAE 
Major Adverse Event 
MALE 
Major Adverse Limb Event 
MDR 
Medical Device Reporting (US) 
MedDRA 
Medical Dictionary for Regulatory Activities 
MRA 
Magnetic Resonance Angiography 
OTW 
Over-the-Wire 
PAD 
Peripheral Artery Disease 
PARC 
Peripheral Academic Research Consortium 

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PCB 
Printed Circuit Board 
POD 
Post-Operative Death 
PTA 
Percutaneous Transluminal Angioplasty 
QoL 
Quality of Life 
RC 
Rutherford Category 
RMA 
Return Material Authorization 
RVD 
Reference Vessel Diameter 
SADE 
Serious Adverse Device Effect 
SAE 
Serious Adverse Event 
TBI 
Toe-Brachial Index 
TLR 
Target Lesion Revascularization 
TMA 
Transmetatarsal Amputation 
TVR 
Target Vessel Revascularization 
USADE 
Unanticipated Serious Adverse Device Effect 

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16.0 
REFERENCES 
1. 
Song, P., et al., Global, regional, and national prevalence and risk factors for peripheral 
artery disease in 2015: an updated systematic review and analysis. Lancet Glob Health, 
2019. 7(8): p. e1020-e1030. 
2. 
Rocha-Singh, K.J., T. Zeller, and M.R. Jaff, Peripheral arterial calcification: prevalence, 
mechanism, detection, and clinical implications. Catheter Cardiovasc Interv, 2014. 
83(6): p. E212-20. 
3. 
Walker, C.M., et al., Multidisciplinary approach to the diagnosis and management of 
patients with peripheral arterial disease. Clin Interv Aging, 2015. 10: p. 1147-53. 
4. 
Committee, T.S., et al., An Update on Methods for Revascularization and Expansion of 
the TASC Lesion Classification to Include Below-the-Knee Arteries: A Supplement to the 
Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II). J 
Endovasc Ther, 2015. 22(5): p. 663-77. 
5. 
Gerhard-Herman, M.D., et al., 2016 AHA/ACC Guideline on the Management of Patients 
With Lower Extremity Peripheral Artery Disease: Executive Summary: A Report of the 
American College of Cardiology/American Heart Association Task Force on Clinical 
Practice Guidelines. Circulation, 2017. 135(12): p. e686-e725. 
6. 
Shishehbor, M.H. and M.R. Jaff, Percutaneous Therapies for Peripheral Artery Disease. 
Circulation, 2016. 134(24): p. 2008-2027. 
7. 
Shishehbor, M.H., et al., Critical Limb Ischemia: An Expert Statement. J Am Coll Cardiol, 
2016. 68(18): p. 2002-2015. 
8. 
Giannopoulos, S., et al., Balloon Angioplasty of Infrapopliteal Arteries: A Systematic 
Review and Proposed Algorithm for Optimal Endovascular Therapy. J Endovasc Ther, 
2020. 27(4): p. 547-564. 
9. 
Armstrong, E.J., K. Bishu, and S.W. Waldo, Endovascular Treatment of Infrapopliteal 
Peripheral Artery Disease. Curr Cardiol Rep, 2016. 18(4): p. 34. 
10. 
Adams, G., Intravascular lithotripsy for treatment of infrapopliteal lesions: Results from 
the Disrupt PAD III Observational Study, in LINC 2021. 2021: Virtual. 
11. 
Adams, G., et al., Intravascular Lithotripsy for Treatment of Calcified Lower Extremity 
Arterial Stenosis: Initial Analysis of the Disrupt PAD III Study. J Endovasc Ther, 2020. 
27(3): p. 473-480. 
12. 
Armstrong, E.J., et al., Intravascular Lithotripsy for Treatment of Calcified, Stenotic Iliac 
Arteries: A Cohort Analysis From the Disrupt PAD III Study. Cardiovasc Revasc Med, 
2020. 21(10): p. 1262-1268. 
13. 
Brodmann, M., A. Holden, and T. Zeller, Safety and Feasibility of Intravascular 
Lithotripsy for Treatment of Below-the-Knee Arterial Stenoses. J Endovasc Ther, 2018. 
25(4): p. 499-503. 

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14. 
Brodmann, M., et al., Safety and Feasibility of Intravascular Lithotripsy for Treatment of 
Common Femoral Artery Stenoses. J Endovasc Ther, 2019. 26(3): p. 283-287. 
15. 
Brodmann, M., et al., Safety and Performance of Lithoplasty for Treatment of Calcified 
Peripheral Artery Lesions. J Am Coll Cardiol, 2017. 70(7): p. 908-910. 
16. 
Brodmann, M., et al., Primary outcomes and mechanism of action of intravascular 
lithotripsy in calcified, femoropopliteal lesions: Results of Disrupt PAD II. Catheter 
Cardiovasc Interv, 2019. 93(2): p. 335-342. 
17. 
Shammas, N. Intravascular lithotripsy treatment of severely calcified common femoral 
arteries - Results from the Disrupt PAD III Observational Study. in Cardiovascular 
Research Technologies. 2021. Virtual: https://www.crtonline.org/video- 
detail/intravascular-lithotripsy-treatment-of-severely-ca-4. 
18. 
Tepe, G., Intravascular Lithotripsy for Peripheral Artery Calcification. 30-Day Outcomes 
From the Randomized Disrupt PAD III Trial. J Am Coll Cardiol, 2021. 
19. 
Aboyans, V., et al., 2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral 
Arterial Diseases, in collaboration with the European Society for Vascular Surgery 
(ESVS). Rev Esp Cardiol (Engl Ed), 2018. 71(2): p. 111. 
20. 
Mustapha, J., et al., One-Year Results of the LIBERTY 360 Study: Evaluation of Acute 
and Midterm Clinical Outcomes of Peripheral Endovascular Device Interventions. J 
Endovasc Ther, 2019. 26(2): p. 143-154. 
21. 
Patel, M.R., et al., Evaluation and treatment of patients with lower extremity peripheral 
artery disease: consensus definitions from Peripheral Academic Research Consortium 
(PARC). J Am Coll Cardiol, 2015. 65(9): p. 931-41. 

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17.0 
SUBJECT INFORMED CONSENT 
The subject informed consent template will be provided as a separate attachment. 

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18.0 
CASE REPORT FORMS 
Draft case report forms will be provided as a separate attachment. 

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19.0 
REVISION HISTORY 
 
Revision 
Release Date 
DCO # 
Reason(s) for Revision 
Doc Owner 
A 
07/29/2021 
22175 
Initial release. 
Clinical 
B 
04/25/2022 
23339 
• 
Revisions throughout the document to be in 
compliance with EU MDR 2017/745 and ISO 
14155:2020. 
• 
General administrative changes and 
corrections throughout document. 
• 
Changed Primary Performance Endpoint to 
Primary Effectiveness Endpoint and included 
time point for evaluation by angiographic core 
lab throughout document. 
• 
Changed from significant to serious 
angiographic complications for lesion success 
secondary endpoint. 
• 
Clarified primary patency endpoint will be 
assessed by DUS core lab, and CD-TLR will be 
adjudicated by CEC. 
• 
Clarified CEC will adjudicate Clinically Relevant 
Target Lesion Failure secondary endpoint. 
• 
Added IVUS sub-study information throughout 
document. 
• 
Created, clarified, or changed inclusion and 
exclusion criteria. 
• 
Indicated there are specific IFUs and labelling 
for each geography. 
• 
Added Baseline Labs (eGFR) to list of baseline 
assessments and indicated how eGFR should 
be calculated in absence of lab value. 
• 
Specified photographs needed for Wound 
Healing Assessments. 
• 
Added incidence of risks for IVL catheters and 
verbiage regarding risk management plan; 
updated risk sections. 
• 
Removed unlikely from relatedness categories 
for AE assessments. 
• 
Updated device malfunction definition and 
abbreviation list. 
Clinical 

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Revision 
Release Date 
DCO # 
Reason(s) for Revision 
Doc Owner 
C 
08/22/2023 
26506 
• 
Updated language to include primary 
patency at lesion level. 
• 
CR-TLF endpoint was removed and 
updated to clearer definition of CD-TLR 
• 
MAE language added 
• 
Amputation language added to clarify 
major target limb amputations 
• 
Added exploratory endpoints. These do 
not have any impact on patient safety or 
existing data. 
• 
Added language regarding toe 
amputation 
• 
Clarified window for sites to submit 
wound assessment images extended 
from 30 days to 45 days. 
• 
Added definition of recurrent wound. 
• 
Providing tandem lesion definition to 
ensure clearer guidelines for labeling 
lesions <3 cm apart. 
• 
Added clearer adverse event 
documentation 
Clinical