Prospective, Multi-center, Single-arm Feasibility Study of the Shockwave Medical Mini S Peripheral Intravascular Lithotripsy (IVL) System
Phase: NA
Conditions: Peripheral Arterial Disease
Sponsor: Shockwave Medical, Inc.

Mini-S Feasibility Study 
Prospective, Multi-center, Single-arm Feasibility Study of the Shockwave Medical Mini S 
Peripheral Intravascular Lithotripsy (IVL) System 
Clinical Study Protocol Version D 
21 July 2023 
NCT05058456 

 
NO.:  CP 65324 
REV. D 
TITLE:  Mini S Feasibility Study Protocol 
CLASS:  CLINICAL PROTOCOL 
PAGE 1 OF 70 
 
Confidential – This document is property of Shockwave Medical, Inc. 
 
  
 
Prospective, Multi-center, Single-arm Feasibility Study of the Shockwave Medical  
Mini S Peripheral Intravascular Lithotripsy (IVL) System 
 
Protocol Number: CP 65324 
 
Protocol Date: 21 July 2023 
 
Revision: D 
 
Study Device: Shockwave Medical Mini S Peripheral Intravascular Lithotripsy (IVL) Catheter 
 
Study Sponsor Name and Address:  Shockwave Medical, Inc. 
 
 
 
 
 
5403 Betsy Ross Drive 
 
 
 
 
 
Santa Clara, CA 95054 
 
 
 
 
 
USA 
 
 
 
 
     
 
 
 
 
 
 
 
 
 
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. 

 
NO.:  CP 65324 
REV. D 
TITLE:  Mini S Feasibility Study Protocol 
CLASS:  CLINICAL PROTOCOL 
PAGE 2 OF 70 
 
Confidential – This document is property of Shockwave Medical, Inc. 
 
Table of Contents 
1.0 
INVESTIGATOR SIGNATURE PAGE ........................................................................... 6 
2.0 
STUDY SUMMARY ....................................................................................................... 7 
3.0 
INTRODUCTION .......................................................................................................... 14 
3.1 
Background ....................................................................................................................... 14 
 Peripheral Arterial Disease .................................................................................... 14 
 Intravascular Lithotripsy ........................................................................................ 14 
 Mini S IVL Catheter ................................................................................................ 15 
3.2 
Study Rationale ................................................................................................................ 16 
4.0 
STUDY DEVICE / TEST ARTICLE DESCRIPTION .................................................... 17 
4.1 
Mini S Peripheral IVL Catheter ......................................................................................... 17 
 Mini S IVL Catheter Design Modification ............................................................... 17 
4.2 
Indication for Use ............................................................................................................. 18 
5.0 
STUDY OBJECTIVES ................................................................................................. 19 
5.1 
Safety Endpoints ............................................................................................................... 19 
5.2 
Performance Endpoints .................................................................................................... 19 
6.0 
STUDY DESIGN .......................................................................................................... 20 
6.1 
Regulatory Status ............................................................................................................. 20 
6.2 
Clinical Development Stage .............................................................................................. 20 
6.3 
Type of Clinical Investigation ............................................................................................ 20 
6.4 
Number of Sites ................................................................................................................ 20 
6.5 
Number of Subjects .......................................................................................................... 20 
6.6 
Clinical Study Duration ..................................................................................................... 20 
7.0 
STUDY PROCEDURES ............................................................................................... 21 
7.1 
Screening .......................................................................................................................... 21 
7.2 
Subject Selection .............................................................................................................. 21 
 Inclusion Criteria .................................................................................................... 21 
 Exclusion Criteria .................................................................................................... 22 
7.3 
Informed Consent ............................................................................................................. 23 
 Process for Obtaining Informed Consent ............................................................... 24 
 Subjects Needing Legally Authorized Representative ........................................... 24 
 Subjects Unable to Read or Write .......................................................................... 24 
 Addition of New Information ................................................................................. 25 
7.4 
Schedule of Events and Evaluations ................................................................................. 25 
7.5 
Medications ...................................................................................................................... 26 
7.6 
Screening/Baseline Procedures ........................................................................................ 26 
7.7 
Index Procedure ............................................................................................................... 26 
 Procedural Imaging Requirements ........................................................................ 29 
 Assessment of Calcification ................................................................................... 29 
 Treatment of Non-Target Lesions .......................................................................... 29 
 Definition of Enrollment ........................................................................................ 30 
 Catheter Delivery & Crossover (if required) .......................................................... 30 
 Pre-IVL Dilatation of Target Lesion & Crossover (if required) ............................... 30 

 
NO.:  CP 65324 
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TITLE:  Mini S Feasibility Study Protocol 
CLASS:  CLINICAL PROTOCOL 
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 IVL Treatment ........................................................................................................ 30 
 Post-Dilatation (Mandatory) .................................................................................. 31 
 Additional Target Lesion Treatment (if required) .................................................. 31 
 Destination Therapy ............................................................................................... 32 
7.8 
Follow-Up ......................................................................................................................... 32 
 Discharge or Within 12-24 Hours Post-Procedure ................................................. 32 
 30-Day Follow-Up ................................................................................................... 32 
 6-Month Follow-Up ................................................................................................ 33 
 12-Month Follow-Up .............................................................................................. 33 
 Prior to Target Limb Revascularization .................................................................. 33 
7.9 
Subject Withdrawal .......................................................................................................... 33 
 When and How to Withdraw Subjects ................................................................... 34 
8.0 
BENEFITS AND RISKS ............................................................................................... 35 
8.1 
Benefits ............................................................................................................................. 35 
8.2 
Risks .................................................................................................................................. 35 
8.3 
Risks Associated with Participation in the Clinical Investigation ..................................... 35 
8.4 
Possible Interactions with Concomitant Medical Treatments ......................................... 35 
8.5 
Mitigation of Risks ............................................................................................................ 36 
9.0 
DATA ANALYSIS PLAN ............................................................................................. 37 
9.1 
General Statistical Methods ............................................................................................. 37 
9.2 
Primary Endpoints ............................................................................................................ 37 
 Primary Safety Endpoint ........................................................................................ 37 
 Primary Performance Endpoint ............................................................................. 37 
9.3 
Sample Size Determination .............................................................................................. 37 
9.4 
Populations for Analysis ................................................................................................... 38 
9.5 
Handling of Dropouts or Missing Data ............................................................................. 38 
10.0 SAFETY EVENTS ........................................................................................................ 39 
10.1 Adverse Event Definitions ................................................................................................ 39 
 Adverse Event (AE) ................................................................................................. 39 
 Serious Adverse Event (SAE) .................................................................................. 39 
 Adverse Device Effect (ADE) .................................................................................. 40 
 Serious Adverse Device Effect (SADE) .................................................................... 40 
 Unanticipated Serious Adverse Device Effect (USADE) ......................................... 40 
10.2 Adverse Event Device and Procedure Relatedness .......................................................... 40 
10.3 Device Deficiencies ........................................................................................................... 41 
 Definitions .............................................................................................................. 41 
 Reporting ............................................................................................................... 41 
10.4 Serious and Non-serious Adverse Event Reporting Requirements .................................. 41 
 AE Reporting Requirements ................................................................................... 41 
 SAE Reporting Requirements ................................................................................. 42 
 Non-serious ADE Reporting Requirements ............................................................ 42 
 SADE Reporting Requirements .............................................................................. 42 
 USADE Reporting Requirements ............................................................................ 42 

 
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TITLE:  Mini S Feasibility Study Protocol 
CLASS:  CLINICAL PROTOCOL 
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 AE and Device Deficiency Reporting Time Frames ................................................ 43 
11.0 INVESTIGATOR RESPONSIBILITIES ........................................................................ 44 
11.1 IRB/EC Approval ............................................................................................................... 44 
11.2 Informed Consent ............................................................................................................. 44 
11.3 Protocol Compliance and Delegation of Authority .......................................................... 44 
11.4 Medical Care of Subjects .................................................................................................. 44 
11.5 Safety Reporting ............................................................................................................... 45 
11.6 Protocol Amendment(s) ................................................................................................... 45 
11.7 Records Retention ............................................................................................................ 45 
12.0 STUDY SPONSOR RESPONSIBILITIES .................................................................... 46 
12.1 Selection and Training of Study Sites ............................................................................... 46 
12.2 Monitoring ........................................................................................................................ 46 
 Monitoring Methods .............................................................................................. 46 
 Monitoring Visits .................................................................................................... 46 
12.3 Study Deviations ............................................................................................................... 47 
12.4 Device Accountability ....................................................................................................... 47 
12.5 Study/Site Suspension or Early Termination .................................................................... 47 
12.6 Study Completion ............................................................................................................. 48 
12.7 Audits / Inspections .......................................................................................................... 49 
12.8 Publication Policies ........................................................................................................... 49 
12.9 Data Management ............................................................................................................ 49 
 Data Guardianship ................................................................................................. 50 
 Case Report Forms ................................................................................................. 51 
 Transmission of Data ............................................................................................. 52 
 Data Queries .......................................................................................................... 52 
 Data Retention ....................................................................................................... 52 
13.0 STUDY COMMITTEES ................................................................................................ 53 
13.1 Clinical Events Committee (CEC) ...................................................................................... 53 
13.2 Independent Data and Safety Monitor (DSM) ................................................................. 53 
14.0 ETHICAL AND REGULATORY CONSIDERATIONS ................................................. 55 
14.1 Role of Shockwave Medical .............................................................................................. 55 
14.2 Subject Confidentiality ..................................................................................................... 55 
15.0 DEFINITIONS AND ABBREVIATIONS ....................................................................... 56 
15.1 Study Definitions .............................................................................................................. 56 
15.2 List of Abbreviations ......................................................................................................... 61 
16.0 REFERENCES ............................................................................................................. 63 
17.0 SUBJECT INFORMED CONSENT .............................................................................. 65 
18.0 CASE REPORT FORMS ............................................................................................. 66 
19.0 REVISION HISTORY ................................................................................................... 67 
 
 
 

 
NO.:  CP 65324 
REV. D 
TITLE:  Mini S Feasibility Study Protocol 
CLASS:  CLINICAL PROTOCOL 
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Confidential – This document is property of Shockwave Medical, Inc. 
 
Table of Figures 
Figure 1. Shockwave Mini S Peripheral IVL Catheter .................................................................................. 18 
Figure 2. Mini S IVL Treatment Algorithm ................................................................................................... 28 
 
Table of Tables 
Table 1. Schedule of Events and Evaluations .............................................................................................. 25 
Table 2. Mini S IVL System Sequence Chart ................................................................................................ 31 
Table 3. Investigator Responsibilities for Reporting Adverse Events ......................................................... 43 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
NO.:  CP 65324 
REV. D 
TITLE:  Mini S Feasibility Study Protocol 
CLASS:  CLINICAL PROTOCOL 
PAGE 6 OF 70 
 
Confidential – This document is property of Shockwave Medical, Inc. 
 
1.0 INVESTIGATOR SIGNATURE PAGE 
Study Title: Prospective, Multi-center, Single-arm Feasibility Study of the Shockwave Medical  
Mini S Peripheral Intravascular Lithotripsy (IVL) System 
Study Device: Shockwave Medical Mini S Peripheral Intravascular Lithotripsy (IVL) Catheter 
Protocol Revision: D 
Protocol Revision Date: 21 July 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 Food and Drug Administration regulations. This investigation will be conducted in 
accordance with the ethical principles as noted in the Declaration of Helsinki and with the 
ICH/Good Clinical Practices (ICH/GCP), ISO14155:2020, and applicable IRB/EC requirements. 
 
____________________________________________             
Principal Investigator’s Name (print)   
                                
 
____________________________________________             ___________________ 
Principal Investigator’s Signature                                                 Date 

 
NO.:  CP 65324 
REV. D 
TITLE:  Mini S Feasibility Study Protocol 
CLASS:  CLINICAL PROTOCOL 
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Confidential – This document is property of Shockwave Medical, Inc. 
 
2.0 STUDY SUMMARY 
Study Title  
Prospective, Multi-center, Single-arm Feasibility Study of the Shockwave 
Medical Mini S Peripheral Intravascular Lithotripsy (IVL) System (Mini S 
Feasibility Study) 
Study Objective  
To assess the safety and performance of the Shockwave Medical Mini S 
Peripheral IVL System for the treatment of heavily calcified, stenotic 
peripheral arteries. 
Study Device(s)  
Shockwave Medical Peripheral IVL System with Mini S IVL Catheter 
(Standard and Flex configurations) 
Indications for Use 
The Mini S IVL Catheter is intended for lithotripsy-enhanced catheter 
dilatation of lesions, including calcified lesions found in the peripheral 
vasculature, such as the iliac, femoral, ilio-femoral, popliteal, infra-
popliteal, and renal arteries. The Mini S IVL Catheter is not for use in the 
coronary or cerebral vasculature. 
Study Design 
Prospective, multi-center, single-arm feasibility study 
Enrollment 
Up to 50 subjects with a minimum of 10 BTK lesions treated at up to 6 
sites in Australia and New Zealand.  A maximum of two (2) target lesions 
may be treated per subject.   
Study Duration / Follow-
Up Period 
Subjects will be followed through discharge, 30 days, 6 and 12 months. 
Duplex Ultrasound (DUS) assessments required at 12 months. Total 
anticipated study duration approximately 26 months. 
Subject Population 
Subjects with moderate to severely calcified peripheral artery disease 
(PAD) with target lesion located in a native, de novo superficial femoral, 
popliteal or infrapopliteal artery. 
Primary Safety Endpoint 
Major Adverse Events (MAE) at 30 days defined as a composite of: 
o Cardiovascular death 
o Clinically-driven target lesion revascularization (CD-TLR) 
o Unplanned target limb major amputation (above the ankle) 
 
Primary Performance 
Endpoint 
Technical Success defined as final residual stenosis ≤50% without flow-
limiting dissection (≥ Grade D) of the target lesion by angiographic core 
lab. 

 
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REV. D 
TITLE:  Mini S Feasibility Study Protocol 
CLASS:  CLINICAL PROTOCOL 
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Confidential – This document is property of Shockwave Medical, Inc. 
 
Secondary Endpoints 
• 
Serious angiographic complications (defined as flow-limiting 
dissection (≥ grade D), perforation, distal embolization, or acute 
vessel closure as assessed by the angiographic core lab. 
• 
IVL Technical Success (post-dil) defined as post-dilatation residual 
stenosis ≤50% without flow-limiting dissection (≥ Grade D) of the 
target lesion by angiographic core lab (measured immediately 
following mandatory post-dilatation). 
• 
IVL Device Success defined as the ability to deliver, advance across 
the target lesion, pressurize, pulse, flush and retrieve the JAVELIN 
IVL Catheter.  
• 
Technical success (final) defined as final residual stenosis ≤30% 
without flow-limiting dissection (≥ Grade D) of the target lesion by 
angiographic core lab.  
• 
Major Adverse Events (MAE) at 6 and 12 months (as a composite 
and individual components)   
• 
Primary Patency at 12 months defined as: 
o Above the knee lesions: freedom from ≥50% restenosis as 
determined by Duplex Ultrasound (DUS) and freedom from 
Clinically-Driven Target Lesion Revascularization (CD-TLR) 
o Below the knee lesions: freedom from both total occlusion 
(100% diameter stenosis by DUS) in all of the target lesions 
in a flow pathway, as well as a CD-TLR 
Device performance endpoints will be reported for all Mini S IVL 
Catheters.  
Study Inclusion Criteria 
Subjects are required to meet all of the following inclusion criteria in order 
to be enrolled in the study.  For lesion characteristics, each target lesion 
must meet eligibility.  A maximum of two (2) target lesions may be treated 
per subject; target lesions may be in the same limb or in different limbs. 
General Inclusion Criteria 
1. 
Age of subject is ≥ 18 years.  
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.  

 
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CLASS:  CLINICAL PROTOCOL 
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4. 
Estimated life expectancy > 1 year. 
5. 
Rutherford Clinical Category 2, 3, 4 or 5 of the target limb(s). 
Angiographic Inclusion Criteria 
6. 
One or two target lesion(s) located in a native de novo superficial 
femoral, popliteal or infrapopliteal artery (above the ankle joint), in 
one or both limbs. 
7. 
Target lesion reference vessel diameter (RVD) between 2.0 mm and 
7.0 mm by investigator visual estimate.  
8. 
Target lesion stenosis ≥70% (for vessels below the knee defined as 
P3 to the ankle joint) or ≥90% (for vessels above the knee) by 
investigator visual estimate.  
9. 
Target lesion length is ≤150 mm by investigator visual estimate. 
Target lesion can be all or part of the 150 mm treated zone.  
• 
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 device (pre-dilatation, IVL, 
post-dilatation, or destination therapy). Each tandem 
lesion/diseased segment is considered one target lesion.  
• 
If these segments are treated independently (i.e., no PTA treatment 
between two lesions) then this is considered two separate target 
lesions. 
10. Calcification is at least moderate defined as presence of 
fluoroscopic evidence of calcification: 1) on parallel sides of the 
vessel and 2) extending > 50% the length of the lesion if lesion is 
≥50mm in length; or extending for minimum of 20mm if lesion is 
<50mm in length. 
Study Exclusion Criteria 
General Exclusion Criteria 
1. Rutherford Clinical Category 0, 1 and 6 (target limb).  
2. 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.  Note: inflow 
treatment of non-target lesions is allowed providing successful 
treatment. 
3. Subject in whom antiplatelet or anticoagulant therapy is 
contraindicated.  

 
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4. Subject has known allergy to contrast agents or medications used to 
perform endovascular intervention that cannot be adequately pre-
treated.  
5. Subject has known allergy to urethane, nylon, or silicone.  
6. Myocardial infarction within 60 days prior to enrollment.  
7. History of stroke within 60 days prior to enrollment.  
8. Subject has acute or chronic renal disease with eGFR <30 
ml/min/1.73 m2 (using CKD-EPI formula), unless on renal 
replacement therapy.  
9. Subject is pregnant or nursing.  
10. Subject is participating in another research study involving an 
investigational agent (pharmaceutical, biologic, or medical device) 
that has not reached the primary endpoint.  
11. 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.  
12. Covid-19 diagnosis within 30 days. 
13. Planned use of cutting/scoring balloons, re-entry or atherectomy 
devices in target lesion(s) during the index procedure. 
14. Planned major amputation of target limb. 
15. Acute limb ischemia. 
16. Occlusion of all the inframalleolar outflow arteries/vessels (i.e., 
desert foot). 
17. Subject already enrolled into this study. 
Angiographic Exclusion Criteria 
18. Failure to successfully treat clinically significant inflow lesions in the 
ipsilateral iliac, femoral, or popliteal arteries, defined as ≤30% 
residual stenosis with no serious angiographic complications (e.g. 
embolism). 
19. Failure to successfully treat significant non-target infra-popliteal 
lesions, if treated prior to treatment of target lesion(s). Successful 
treatment is defined as obtaining ≤50% residual stenosis with no 
serious angiographic complications (e.g., embolism). 
20. Target lesion includes in-stent restenosis. 

 
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TITLE:  Mini S Feasibility Study Protocol 
CLASS:  CLINICAL PROTOCOL 
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21. Evidence of aneurysm or thrombus in target vessel.  
22. No calcium or mild calcium in the target lesion.  
23. Target lesion within native or synthetic vessel grafts.  
24. 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 
Descriptive statistics will be reported. 
 
 

 
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TITLE:  Mini S Feasibility Study Protocol 
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Confidential – This document is property of Shockwave Medical, Inc. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
NO.:  CP 65324 
REV. D 
TITLE:  Mini S Feasibility Study Protocol 
CLASS:  CLINICAL PROTOCOL 
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Confidential – This document is property of Shockwave Medical, Inc. 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 

 
NO.:  CP 65324 
REV. D 
TITLE:  Mini S Feasibility Study Protocol 
CLASS:  CLINICAL PROTOCOL 
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Confidential – This document is property of Shockwave Medical, Inc. 
 
3.0 INTRODUCTION 
3.1 Background  
 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].  
In sub-total occlusions with the narrowest crossing channels, microcatheters, with soft tips, 
tapered shapes, and variety of wire selections may be used to cross a lesion and allow for 
subsequent dilatation. Nevertheless, severe tortuosity and severe calcification remain barriers 
to microcatheter success, leading to excessively high rates of complications (typically either 
dissection and/or perforation) [10]. 
 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 severely 

 
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calcified PAD across multiple vessel beds [11-19], 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 severely calcified infrapopliteal 
lesions with 30-day follow-up [14]. After treatment with IVL using the first generation M5 
catheter, all patients achieved a residual stenosis <50%. There was only one type B dissection, 
and a total of two (2) stents were placed. These initial promising results supported the use of 
IVL to maximize lumen 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 [11].  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 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.   
 Mini S IVL Catheter 
The Mini S catheter is designed to leverage the same safety and effectiveness of IVL balloon 
catheters (M5 and S4) but represents a low-profile option with a distally-shifted emitter that 
can be used in sub-total occlusions with extremely narrow crossing channels where other 
devices may be challenged today.  
The Shockwave Mini S Peripheral IVL Catheter has equivalent base materials and similar 
technological characteristics as the predicate device Shockwave S4 Peripheral IVL Catheter. 
The Mini S and S4 IVL Catheters have similar emitter designs that deliver unfocused 
intermittent acoustic pulses at the same pulse rate and treatment frequency at low 
treatment pressures. Sonic output mapping of the Mini S and S4 IVL Catheters demonstrate 
that the average sonic output emitted by both devices have similar peaks and distribution 
and are within the same magnitude and standard deviation. These parameters have shown 
to be effective in treating calcified lesions with the S4 IVL Catheter and are applicable to the 
Mini S given the demonstrated equivalence. 
Human cadaveric studies were conducted to assess the Mini S trackability, ability to cross and 
modify calcium, the visibility of the emitter band under fluoroscopy, and interaction with 
ancillary devices. The device was found to have an acceptable level of pushability/trackability, 
deliverability/crossability, emitter visibility, catheter working length and overall durability.  
These cadaver labs provided confirmation that Mini S IVL catheter functioned as intended by 
modifying calcium to allow for further treatment at the physician’s discretion. Additional 
information regarding the pre-clinical studies can be found in the Investigator Brochure (IB 
65349). 

 
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3.2 Study Rationale  
The Mini S Feasibility study is being conducted to assess the safety and performance of the Shockwave 
Medical Mini S Peripheral IVL System for the treatment of heavily calcified, stenotic peripheral arteries.   
 
 

 
NO.:  CP 65324 
REV. D 
TITLE:  Mini S Feasibility Study Protocol 
CLASS:  CLINICAL PROTOCOL 
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Confidential – This document is property of Shockwave Medical, Inc. 
 
4.0 STUDY DEVICE / TEST ARTICLE DESCRIPTION 
4.1 Mini S Peripheral IVL Catheter 
The Shockwave Mini S Peripheral IVL Catheter is a proprietary lithotripsy device delivered through 
the peripheral arterial system of the lower extremities to the site of an otherwise difficult to treat 
calcified stenosis. Energizing the lithotripsy device will generate pulsatile mechanical energy within 
the target treatment site, disrupting calcium within the lesion and allowing subsequent dilatation 
of a peripheral artery stenosis. The Mini S IVL Catheter comprises a distal lithotripsy emitter for the 
localized delivery of pulsatile mechanical energy. 
The Mini S IVL Catheter shaft contains a lumen to pressurize and flush the catheter, a guidewire 
lumen, and a lithotripsy emitter. The lumen is used to pressurize and flush the catheter with saline. 
The guidewire lumen enables the use of a 0.014” (0.36mm) guidewire to facilitate advancement of 
the catheter to and through the target stenosis. The system is designed as ‘Over-the-wire’ (OTW) 
with 150cm shaft working length. The emitter is positioned at the distal end of the catheter for 
delivery of pulsatile mechanical energy. The Mini S Catheter has a hydrophilic coating on the distal 
end designed to increase lubricity during advancement of the catheter to the treatment site. The 
emitter is radiopaque to facilitate catheter visibility under fluoroscopy and it is surrounded by an 
IVL Window that allows for the transmission of pulsatile mechanical energy. The proximal hub has 
three ports: one to pressurize and flush the system, one for guidewire lumen, and one for 
connection to the IVL Connector Cable. Refer to Figure 1 below for IVL Catheter components. 
The Mini S Peripheral IVL Catheter is available in two configurations: Standard and Flex. For easy 
identification, Standard has a blue shaft extrusion color and Flex has a yellow shaft.  The Mini S 
Standard has a 15 cm distal segment, and the Flex has a 25 cm distal segment for more flexibility. 
The IVL Catheter is compatible with a 5Fr sheath and has a working length of 150cm. Both 
configurations will be evaluated in the Mini S Feasibility study. 
The Mini S IVL Catheter is part of the Peripheral IVL System. The system consists of the IVL Catheter, 
an IVL Connector Cable and an IVL Generator. The Mini S IVL Catheter is to be used exclusively with 
the IVL Generator and its accessories. The IVL Generator and Connector Cable are not 
investigational; they are supplied non-sterile and are reusable. Refer to the Shockwave Medical, 
Inc. IVL Generator and Connector Cable Operator’s Manual for preparation, operation, warnings 
and precautions, and maintenance of the IVL Generator and IVL Connector Cable. 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.  Refer to the Instructions for Use (IFU) for a complete product description. 
 Mini S IVL Catheter Design Modification 
The Mini S IVL Catheter has incorporated a design modification as part of continuous 
improvement.  Two modifications were made to the Mini S IVL Catheter, the distance between 
the emitter and the distal tip and the shaft extrusion color.  The emitter to distal tip length has 
been shortened on both configurations, Standard and Flex.  A shorter distance between the 
emitter and the distal tip optimized energy delivery to facilitate crossing. There is no change 
to the energy profile or sonic output specification.  The shaft extrusion color for Flex has been 

 
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5.0 STUDY OBJECTIVES 
The objective of this study is to assess the safety and performance of the Shockwave Medical Mini S 
Peripheral IVL System for the treatment of heavily calcified, stenotic peripheral arteries. 
5.1 Safety Endpoints 
The safety endpoints for this study include: 
• 
PRIMARY: Major Adverse Events (MAE) at 30 days defined as a composite of: 
o Cardiovascular death 
o Clinically-driven target lesion revascularization (CD-TLR) 
o Unplanned target limb major amputation (above the ankle) 
• 
Serious angiographic complications defined as flow-limiting dissection (≥ grade D), 
perforation, distal embolization, or acute vessel closure as assessed by the angiographic 
core lab. 
• 
MAE at 6 and 12 months (as a composite and individual components) 
5.2 Performance Endpoints 
The performance endpoints are listed below.  Device endpoints will be reported for all Mini S IVL 
Catheters. 
• 
PRIMARY: Technical Success defined as final residual stenosis ≤50% without flow-limiting 
dissection (≥ Grade D) of the target lesion by angiographic core lab. 
• 
IVL Technical Success (post-dil) defined as post-dilatation residual stenosis ≤50% without 
flow-limiting dissection (≥ Grade D) of the target lesion by angiographic core lab (measured 
immediately following mandatory post-dilatation). 
• 
IVL Device Success defined as the ability to deliver, advance across the target lesion, 
pressurize, pulse, flush and retrieve the Mini S IVL Catheter. 
• 
Technical Success (final) defined as final residual stenosis ≤30% without flow-limiting 
dissection (≥ Grade D) of the target lesion by angiographic core lab.   
• 
Primary Patency at 12 months defined as: 
o Above the knee lesions: freedom from ≥50% restenosis as determined by Duplex 
Ultrasound (DUS) and freedom from Clinically-Driven Target Lesion 
Revascularization (CD-TLR) 
o Below the knee lesions: freedom from both total occlusion (100% diameter stenosis 
by DUS) in all of the target lesions in a flow pathway, as well as a CD-TLR 

 
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6.0 STUDY DESIGN 
The Mini S Feasibility study is a pre-market, prospective, multi-center, single-arm feasibility study of the 
Shockwave Mini S Peripheral IVL System to treat heavily calcified, stenotic peripheral arteries.   
6.1 Regulatory Status 
Per ISO 14155:2020 (Annex I, Section 1.2), the Mini S Feasibility study is a pre-market study defined 
as a clinical investigation carried out before market approval of the investigational device. 
6.2 Clinical Development Stage 
Per ISO 14155:2020 (Annex I, Section 1.3), the medical device being used in the Mini S Feasibility 
study is in the pilot stage. In keeping with this development stage, the Mini S Feasibility study will 
evaluate the limitations and advantages of the Mini S IVL catheter and will capture preliminary 
information to adequately plan further steps of device development, including needs for design 
modifications or parameters for a pivotal clinical investigation. 
6.3 Type of Clinical Investigation 
Per ISO 14155:2020 (Annex I, Section 1.4), the Mini S Feasibility study is considered to be an 
exploratory clinical investigation that does not have pre-specified primary hypotheses, but may be 
used to generate hypotheses to be confirmed in subsequent clinical investigations.  Per ISO 
14155:2020 (Annex I, Section 1.5), it is an early feasibility study in which the Mini S IVL catheter is 
being evaluated for the first time in human subjects. 
6.4 Number of Sites 
Up to 6 sites in Australia and New Zealand will participate in the study.  
6.5 Number of Subjects 
Up to 50 subjects with a minimum of 10 BTK lesions treated with moderate to severely calcified 
peripheral artery disease (PAD) with a target lesion located in a native, de novo superficial femoral, 
popliteal or infrapopliteal artery will be enrolled.  Up to two (2) target lesions may be treated per 
subject.   
6.6 Clinical Study Duration 
Enrollment is anticipated to last approximately six (14) months.  Study subjects will be followed 
through hospital discharge, 30 days, 6 and 12 months post-procedure.  Total anticipated study 
duration is 26 months. 

 
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7.0 STUDY PROCEDURES 
7.1 Screening  
Patients presenting to the institution with known peripheral artery disease requiring an 
interventional procedure will be evaluated for eligibility and participation in the 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 
study including risks, potential benefits, and required follow-up procedures prior to obtaining the 
potential subject’s informed consent.   
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 
patient is considered to be enrolled once a 0.014” guidewire has crossed the target lesion and the 
Mini S peripheral IVL catheter has been inserted over the guidewire and into the body. A subject is 
considered an angiographic screen failure if they do not meet angiographic eligibility criteria. 
Patients who screen fail will be documented as such in the electronic data capture (EDC) system.  
7.2 Subject Selection 
 Inclusion Criteria 
Subjects are required to meet all of the following inclusion criteria in order to be enrolled in 
the study.  For lesion characteristics, each target lesion must meet eligibility.  A maximum of 
two (2) target lesions may be treated per subject; target lesions may be in the same limb or in 
different limbs. 
General Inclusion Criteria 
1. Age of subject is ≥ 18 years.  
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. Estimated life expectancy > 1 year. 
5. Rutherford Clinical Category 2, 3, 4 or 5 of the target limb(s). 
Angiographic Inclusion Criteria 
6. One or two target lesion(s) located in a native de novo superficial femoral, popliteal 
or infrapopliteal artery (above the ankle joint), in one or both limbs. 

 
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7. Target lesion reference vessel diameter (RVD) between 2.0 mm and 7.0 mm by 
investigator visual estimate.  
8. Target lesion stenosis ≥70% (for vessels below the knee, defined as P3 to the ankle 
joint) or ≥90% (for vessels above the knee) by investigator visual estimate.  
9. Target lesion length is ≤150 mm by investigator visual estimate. Target lesion can be 
all or part of the 150 mm treated zone.  
• 
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 device (pre-dilatation, IVL, post-dilatation, or destination therapy). Each 
tandem lesion/diseased segment is considered one target lesion.  
• 
If these segments are treated independently (i.e., no PTA treatment between 
two lesions) then this is considered two separate target lesions. 
10. Calcification is at least moderate defined as presence of fluoroscopic evidence of 
calcification: 1) on parallel sides of the vessel and 2) extending > 50% the length of 
the lesion if lesion is ≥50mm in length; or extending for minimum of 20mm if lesion is 
<50mm in length. 
 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 and 6 (target limb).  
2. 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.   Note: inflow treatment of non-target lesions is allowed providing 
successful treatment. 
3. Subject in whom antiplatelet or anticoagulant therapy is contraindicated.  
4. Subject has known allergy to contrast agents or medications used to perform 
endovascular intervention that cannot be adequately pre-treated.  
5. Subject has known allergy to urethane, nylon, or silicone.  
6. Myocardial infarction within 60 days prior to enrollment.  
7. History of stroke within 60 days prior to enrollment.  
8. Subject has acute or chronic renal disease with eGFR <30 ml/min/1.73 m2 (using 
CKD-EPI formula), unless on renal replacement therapy.  
9. Subject is pregnant or nursing.  

 
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10. Subject is participating in another research study involving an investigational agent 
(pharmaceutical, biologic, or medical device) that has not reached the primary 
endpoint.  
11. 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.  
12. Covid-19 diagnosis within 30 days. 
13. Planned use of cutting/scoring balloons, re-entry or atherectomy devices in target 
lesion(s) during the index procedure. 
14. Planned major amputation of target limb. 
15. Acute limb ischemia. 
16. Occlusion of all the inframalleolar outflow arteries/vessels (i.e., desert foot). 
17. Subject already enrolled into this study. 
Angiographic Exclusion Criteria 
18. Failure to successfully treat clinically significant inflow lesions in the ipsilateral iliac, 
femoral, or popliteal arteries, defined as ≤30% residual stenosis with no serious 
angiographic complications (e.g. embolism). 
19. Failure to successfully treat significant non-target infrapopliteal lesions, if treated 
prior to treatment of target lesion(s).   Successful treatment is defined as obtaining 
≤50% residual stenosis with no serious angiographic complications (e.g., embolism).  
20. Target lesion includes in-stent restenosis.  
21. Evidence of aneurysm or thrombus in target vessel.  
22. No calcium or mild calcium in the target lesion.  
23. Target lesion within native or synthetic vessel grafts.  
24. 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 authorized 
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 and ISO 14155:2020 
and comply with the ethical principles of ICH/GCP and the Declaration of Helsinki.  

 
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 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 
• 
The informed consent process should be documented by the Investigator completing 
the consenting process in the subject’s institutional medical record 
 Subjects Needing Legally Authorized Representative 
Informed consent may be given by a legally authorized 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. 
 Subjects Unable to Read or Write 
Informed consent shall be obtained through a supervised oral process if a subject or legally 
authorized 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 authorized 
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. 

 
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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 [20] 
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 with the exception of 
ankle-brachial index (ABI) and toe-brachial index (TBI), which can be completed within 60 days of 
the procedure, and a pregnancy test which must be done within seven (7) days of the procedure 
for women of child-bearing age.  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 
o Vital signs 
o Height and weight 
• 
eGFR (if needed, for patients with acute or chronic renal disease) 
• 
Review of anticoagulation/antiplatelet medications 
• 
ABI or TBI of target limb (at rest; use same test for subject throughout study) 
• 
Rutherford Category of target limb 
• 
Urine pregnancy test if female of child-bearing age 
 
Note: If treatment of two target lesions is planned across both limbs, the RC category, ABI, and 
TBI for each limb must be assessed.  If ABI 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. 
7.7 Index Procedure 
The IVL procedural flow diagram is described in the steps below and illustrated in Figure 2. All 
devices used during the index procedure should be recorded including IVL catheters and adjunctive 

 
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devices (if required).  Up to two (2) target lesions may be treated per subject.  If the distal portion 
of the target lesion extends beyond the ankle joint, treatment using the Mini S IVL Catheter is 
allowed if the Investigator deems it clinically necessary to optimize the procedure outcome. 
For the first 10 consecutively enrolled subjects, the Flex configuration of the Mini S IVL Catheter 
should be used first; cross-over to the Standard configuration is allowed if needed per the IVL 
procedural steps outlined below.  For the next 10 consecutively enrolled subjects, the Standard 
configuration should be used first with crossover to Flex if needed.  For subjects enrolled after the 
first 20 subjects, the Mini S configuration may be chosen at the Investigator’s discretion.  Cross-
over to the other configuration is allowed if needed per the IVL procedural steps outlined below. 
Information on usability will be collected to help understand how operators perceive information 
from the Mini S IVL Catheter, interpret the information and make decisions about what to do, and 
how to manipulate the device. 

 
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Figure 2. Mini S IVL Treatment Algorithm 

 
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 Procedural Imaging Requirements 
An angiographic cine will be obtained at four (4) timepoints for each target lesion as follows: 
1. Pre-procedure (include run-off the foot) 
2. Post-Mini (immediately following treatment with Mini S and before post-dilatation) 
3. Post-Dil (following mandatory post-dilatation) 
4. Final (end of procedure, include run-off to the foot) 
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 patient still meets criteria to be enrolled. All angiographic images must be submitted to 
the core lab for analysis. If intravascular imaging (including IVUS or OCT) is performed as 
standard of care, images from the four timepoints (pre-procedure, post-Mini, post-Dil and 
final) should be submitted to the Sponsor for analysis.  
Core lab training materials will be provided with detailed instructions on the image acquisition 
process.  
 Assessment of Calcification 
To meet eligibility, there must be fluoroscopic evidence of calcification: 1) on parallel sides of 
the vessel and 2) extending > 50% the length of the lesion if lesion is ≥50mm in length; or 
extending for minimum of 20mm if lesion is <50mm in length. 
The 1st required angiographic cine (Pre-procedure) should be acquired following assessment 
of calcification. 
 Treatment of Non-Target Lesions 
Non-target lesions should be treated successfully prior to treatment of the target lesion(s) 
whenever possible.  Non-target lesions distal to the target lesion(s) or found after target lesion 
is treated may be treated after the target lesion(s).   
Non-target lesions may be treated with any commercially available device; treating a non-
target lesion with a device that is unapproved or considered investigational will result in a 
protocol deviation. 
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 should 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 prior to insertion of the 
Mini S IVL Catheter, the patient should not be enrolled.  

 
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 Definition of Enrollment 
The definition of enrollment is when the subject signs informed consent, meets all general and 
angiographic eligibility criteria, a 0.014” guidewire has crossed the target lesion, and the Mini 
S IVL catheter has been inserted over the guidewire and into the body. 
 Catheter Delivery & Crossover (if required) 
If the Investigator is able to pass a guidewire but is unable to deliver the Mini S IVL catheter to 
the proximal edge to the target lesion, an adjunctive tool may be used prior to re-insertion of 
the Mini S IVL Catheter.  Allowable adjunctive tools include guide catheter, guide extension 
catheter, buddy wire or buddy balloon, and PTA balloon. Atherectomy, cutting/scoring 
balloons, and specialty crossing devices should not be used.  All adjunctive tools used during 
the procedure should be documented. 
If the Mini S IVL Catheter still cannot be delivered to the proximal edge of the target lesion, 
the user may cross over to the other Mini S catheter configuration (Standard or Flex depending 
on which configuration was used first).  All crossovers should be documented. 
If the user is unable to advance any Mini S IVL Catheter to the proximal edge of the target 
lesion after crossing over to the alternate Mini S configuration, this is considered an IVL Device  
Failure.  Treatment should continue per standard of care for the subject. 
 Pre-IVL Dilatation of Target Lesion & Crossover (if required) 
If the operator is unable to cross the Mini S IVL Catheter through the entire length of the target 
lesion, a standard PTA balloon up to 2.5 mm may be used for pre-dilatation of the target lesion 
prior to treatment with the Mini S IVL Catheter.  All efforts should be made to pass the Mini S 
IVL Catheter prior to use of a standard PTA balloon. 
If the operator is unable to pass the Mini S IVL Catheter after pre-dilatation, the operator may 
attempt to cross with the alternate Mini S configuration (crossover).  Note: if the operator has 
already used the alternate configuration (prior crossover per Section 7.7.5), a second crossover 
is not permitted.  All crossovers should be documented. 
If the user is unable to advance any Mini S IVL Catheter across the target lesion, this is 
considered an IVL Device Failure.  Treatment should continue per standard of care for the 
subject. 
 IVL Treatment 
Once the Mini S IVL Catheter is placed in the target lesion area, the catheter must be 
pressurized to 4 atm to deliver one cycle of IVL pulses.  Table 2 lists the pulsing sequence for 
the Mini S IVL Catheter.  One cycle = 10 pulses. The catheter is able to deliver total of 12 cycles 
(120 pulses). Note that the generator is programmed to force a minimum pause time of 10 
seconds following every cycle.  

 
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 Destination Therapy 
Destination therapy is allowed at the discretion of the Investigator.  Destination therapy may 
include commercial IVL, bare-metal stent (BMS), drug-eluting stent (DES), drug coated balloon 
(DCB) or Tack implant.    
A BMS, DES, DCB or Tack implant is allowed for the following PTA failures: 
• 
Residual stenosis ≥ 50% by visual estimate, or 
• 
Un-resolved flow-limiting (≥ Grade D) dissection, or 
• 
Trans-lesional gradient >10 mm Hg is observed. 
If this treatment is performed at the time of procedure, it is considered standard of care to 
maximize acute luminal gain and does not meet the definition of serious deterioration in the 
SAE definition (Section 10.1.2). 
All dissection Type/Grade A, B, and C must be documented as an adverse event. Dissection 
Type/Grade D, E, and F must be documented as a SAE. 
The 4th and final required angiographic cine should be acquired after all endovascular 
procedures on the target lesion are complete. 
7.8 Follow-Up 
 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: 
• 
Review of anticoagulation/antiplatelet medications 
• 
Adverse event assessment 
 30-Day Follow-Up 
The following evaluations will be performed at 30 days (-7/+14 days) post procedure: 
• 
Physical examination 
o Vital signs 
• 
ABI or TBI of target limb (at rest; keep consistent with screening) 
• 
Rutherford Category of target limb 
• 
Review of anticoagulation/antiplatelet medications 
• 
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. 

 
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 6-Month Follow-Up 
The following evaluations will be performed at 6 months (180 +/-30 days) post procedure: 
• 
Physical examination 
o Vital signs 
• 
ABI or TBI of target limb (at rest; keep consistent with screening) 
• 
Rutherford Category of target limb 
• 
Review of anticoagulation/antiplatelet medications 
• 
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. 
 12-Month Follow-Up 
The following evaluations will be performed at 12 months (360 +/-30 days) post procedure: 
• 
Physical examination 
o Vital signs 
• 
ABI or TBI of target limb (at rest; keep consistent with screening) 
• 
Rutherford Category of target limb 
• 
Review of anticoagulation/antiplatelet medications 
• 
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. 
 Prior to Target Limb Revascularization 
If a target limb revascularization 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.  

 
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 When and How to Withdraw Subjects 
Subjects may be withdrawn with the medical discretion of the physician, or they may 
voluntarily withdraw their consent at any time without impact to their medical treatment. 
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 study.  
Should the subject expire, adverse event and study exit/withdrawal forms should be 
completed. Physician assessment is required to determine if the cause of death was possibly 
or definitely related to the Mini S Peripheral IVL Catheter.  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. Associated regulatory bodies may also be 
required to be notified depending on local jurisdiction and relatedness to the study device and 
procedures. 

 
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8.0 BENEFITS AND RISKS 
8.1 Benefits 
There may be no additional benefit from participation since patients can receive IVL treatment with 
a commercially available device per standard of care. The study will provide safety and performance 
data associated with treatment of calcified arteries using the Mini S IVL Catheter. These clinical 
results may inform physicians in determining the optimal treatment strategy for this patient 
population.  
8.2 Risks 
For detailed information on the risks of the device(s) used in the study procedure, including a 
complete list of contraindications, warnings, precautions, and potential adverse effects, please 
refer to the Instructions for Use (IFU) for the Mini S Peripheral IVL Catheter. 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 intravascular procedures. Risks identified as 
unique to the device and its use are outlined in the IFU for the Mini S Peripheral IVL Catheter. They 
include: 
• Allergic/immunologic reaction to the catheter material(s) or coating 
• Device malfunction or failure 
8.3 Risks Associated with Participation in the Clinical Investigation 
All assessments are considered to be standard of care but may be conducted more frequently to 
comply with the follow-up visit schedule. Non-invasive assessments at follow-up visits include 
physical exams, ABI/TBI, Rutherford Category assessments, and duplex ultrasounds.  All pose 
minimal risk to the patient.  For procedure-related risks, please refer to the current IFUs. 
Risks associated with the management of privacy and confidentiality with the sharing of data exist 
for subjects participating in research studies.  To mitigate these risks, each subject in the study will 
be assigned a specific study identification code that shares no identifiable factors with the Sponsor.  
Only hospital staff and the CRO will be privy to information that links the subject’s identifiable 
information to this subject code.  De-identified data (data that is attributed to the subject’s study 
identification code) will be uploaded into a password protected Electronic Data Capture (EDC) 
system.  This EDC can only be accessed by suitably trained and allocated members of the study 
team (site Investigators, Study Coordinators, personnel associated with the CRO and relevant 
personnel at the Sponsor organization). 
8.4 Possible Interactions with Concomitant Medical Treatments 
There are no known possible interactions within this study. 

 
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8.5 Mitigation of Risks  
Only those patients meeting each inclusion and no exclusion criteria will be enrolled into this 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, patient 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 
• Assignment of study identification code to protect privacy and ensure confidentiality 
• Study monitoring 
• Safety processes – protocol adverse event reporting requirements, CEC and DSM oversight, 
and safety reporting to regulatory authorities including Vigilance reporting 
• Review of all device malfunctions and complaints by Quality.  Risk acceptability thresholds 
and trend identification methods have been established, and actions will be taken if those 
are met. 
 
 

 
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9.0 DATA ANALYSIS PLAN 
9.1 General Statistical Methods 
Descriptive statistics will be provided in this study.  Analyses will be conducted at pre-specified time 
points including 30 days, 6 and 12 months post procedure.  
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. Clinical 
outcomes analyzed at 30 days will be evaluated as categorical (binary) data. Exact confidence 
intervals will be generated for estimates of proportions.   
Continuous variables will be summarized by the mean, standard deviation, median, minimum and 
maximum.  Asymptotic confidence intervals will be generated for estimates of means.   
9.2 Statistical analyses will be performed using SAS System® Version 9.4 or higher. Primary 
Endpoints   
 Primary Safety Endpoint 
Major Adverse Events (MAE) at 30 days defined as a composite of: 
o Cardiovascular death 
o Clinically-driven target lesion revascularization (CD-TLR)  
o Unplanned target limb major amputation (above the ankle)  
SAEs will be reviewed and adjudicated by the CEC.  Only those adjudicated as MAEs will 
comprise the composite safety endpoint.   
MAEs will be assessed on a per-subject basis. 
 Primary Performance Endpoint 
Technical Success defined as final residual stenosis ≤50% without flow-limiting dissection (≥ 
Grade D) of the lesion by angiographic core lab.Primary Performance will be assessed on a per-
lesion basis. 
9.3 Sample Size Determination 
Per ISO 14155:2020 (Annex I, Section 1.4), the Mini S Feasibility study is considered to be an 
exploratory clinical investigation that does not have pre-specified primary hypotheses.  For 
feasibility studies, sample sizes between 12 and 50 have been recommended [21-25]. The sample 
size for the Mini S Feasibility study (up to n=50) is in keeping with these published 
recommendations. 

 
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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. 

 
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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 
 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. 
 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.   
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. 
 

 
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 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. 
 Serious Adverse Device Effect (SADE)  
Adverse device effect that has resulted in any of the consequences characteristic of a 
serious adverse event. 
 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 
 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, 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).  
 Reporting   
All device deficiencies and malfunctions will be documented on the case report form and 
reported to the Study Sponsor within 2 business days 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. 
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 
Shockwave Medical Complaint Form will be completed by a Shockwave representative and 
entered into the company’s complaint system. The Shockwave Medical Quality representative 
is responsible for assessing the need for and submitting any Vigilance reports, and/or Medical 
Device Reporting (MDR) reports, if required.  
10.4 Serious and Non-serious Adverse Event Reporting Requirements 
 AE Reporting Requirements 
All AE information will be collected from enrollment through 12 months follow-up. 
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). 

 
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Any AEs that meet IRB/EC reporting requirements must be reported per the institution’s policy. 
 SAE Reporting Requirements 
Any AE meeting any of the criteria for an SAE occurring at any time during the study 
(enrollment through 12 months) must be reported to the Study Sponsor within 2 business days 
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 serious adverse events as 
required by their local IRB/EC policies.  The Investigator should forward a copy of this report 
to the Study Sponsor and file in the site regulatory binder. 
The Clinical Events Committee (CEC) will review and adjudicate SAEs.  See section 13.1 for 
information on the CEC. 
 Non-serious ADE Reporting Requirements 
All ADE information will be collected from enrollment through 12 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 
serious adverse device effects. 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 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. 
 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 2 business days after the designated 
study site personnel first learns of the event. All SADEs should be reported to the IRB/EC in 
accordance with their local requirements.  
 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 2 business days after the Investigator first learns of the event.  All 
USADEs should be reported to the IRB/EC in accordance with their local requirements.  

 
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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 IRB/EC approval to conduct the study prior to screening any potential 
subjects and comply with annual continuing approval requirements. 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, ICH/GCP, Declaration 
of Helsinki, and ISO 14155:2020 requirements in the 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 authorized representative of the subject, is obtained prior to the 
initiation of any study-related 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 study is appropriately staffed with qualified study personnel throughout the duration of 
the study. In addition, the facilities where the 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, 
• 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 that clinical records are clearly marked to indicate that the subject is enrolled in a 
particular clinical study, 

 
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• 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, and 
• 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. 
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 patients, 
Investigator and/or Study Sponsor will submit all amendments to the local IRB/EC and regulatory 
agency to obtain 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 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 study. 
Shockwave Medical will ensure that qualified monitors and designated personnel are monitoring the 
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 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.   
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 records 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 
 Monitoring Methods 
Monitoring functions will be conducted by Shockwave Medical’s designated Contract Research 
Organization (CRO).  See Section 2.0 for the independent CRO designated for this study.  
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. 
 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 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 (if allowed per institutional or 
jurisdictional policies) 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 Investigator must document and notify Shockwave Medical of any deviation from 
the study protocol as soon as possible.   
Major deviations include those that involve the primary endpoint, the informed consent process, 
the inclusion/exclusion criteria of the 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, appropriate corrective 
actions 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, and the site has been suitably 
trained by the sponsor in the use of the investigational device. 
The Investigator must keep complete, current, and accurate records of the receipt, use, or 
disposition of investigational devices.   
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 
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 

 
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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. 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 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. 
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 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 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 materials 
and study devices will be collected and returned to Shockwave Medical or appropriately discarded 
as per instruction. A final study report will be completed no later than 12 months after study 
completion, even if the clinical study was terminated prematurely. 

 
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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 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 study results. Publications based on the results of the study will follow the process outlined 
in the Investigator Agreement. At the conclusion of the 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 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 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, report generation, and primary system for imaging 
vendor. 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. 
Data collected during the study includes demographic data, baseline health information (including 
relevant past medical history), information regarding use of the investigational product, diagnostic 
imaging, and questionnaires regarding subject symptoms related to their vascular disease. 

 
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Data (de-identified) collected will be uploaded by the investigator (or their designee) into a 
password protected Electronic Data Capture (EDC) system.  This EDC will be administered by 
Shockwave Medical in Santa Clara, California.  In cases where certain types of data (such as 
diagnostic images) cannot be uploaded to the EDC, such data will be transferred using a secure File 
Transfer Protocol (FTP) link that is generated by the investigative site.  De-identified data may be 
securely shared with the CEC for adjudication of adverse events and accessed by trained members 
of the CEC or the CEC management team.   
For this study, 
, is being used to record de-
identified clinical trial data as well as used as the primary system for the imaging vendor. As such 
all data collected for this study will be stored in 
 
. A copy can be provided by the vendor or sponsor upon request . 
Shockwave Medical intends to utilize the data obtained from the study for commercial uses 
including publication and/or presentation of results at conferences and congresses, regulatory 
agency submissions (including but not limited to United States Food and Drug Administration [FDA], 
Australian Therapeutic Goods Administration [TGA] and CE), 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 study will not be utilized in a database without 
first gaining the consent of participants. Data will only be presented in aggregate; individual data 
will not be presented. 
 Data Guardianship 
The data collected will be managed according to the study specific Sponsor Data Management 
Plan through the life cycle of the study and any specified data retention periods (see section 
12.9.5).  The participant and/or individuals/or others, including Indigenous, geographic and 
demographic specific communities, groups, and interests in relation to data will be 
recognised. Furthermore, the participant and/or individuals, others, or groups may be 
involved in the governance of their data.  Data collected will also be subject to local data 
management guidelines as specified by local IRB/EC. 
During this study, data will be collected and stored in two formats to maintain the welfare, 
safety and privacy of subjects.  Data will be collected and managed in the following formats: 
Identifiable information  
Identifiable information is any data that could identify subjects (e.g. name, date of birth, or 
address).  This information is used to complete study specific documents that are held at study 
sites, and the following people may have access to a subject’s identifiable information: 
• Research team members, including study doctor(s) and Research Coordinator(s).  
• Lab techs, ultrasound techs and staff at radiology providers where diagnostic tests and 
study procedures are performed – they will collect and report any screening and follow up 
tests.  

 
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• Study monitor (an authorized representative of the Sponsor will be provided with access 
to review medical records to check the accuracy of the information. 
• The Sponsor and its representatives, in the instance a compensation claim for study-
related injury. Identifiable information is required in order to assess any such claims.  
• The Sponsor, Ethics Committees, or government agencies from this country or overseas 
(e.g. United States Food and Drug Administration (US FDA)), if the study or site is audited. 
Audits are done to make sure that subjects are protected, the study is run properly, and 
the data collected is correct. 
• A subject’s doctors or physicians, if a study test gives an unexpected result (incidental 
finding) that could be important for managing or maintaining health. This allows 
appropriate follow-up to be arranged.  
 
De-identified information 
To make sure a subject’s personal information is kept confidential, information that identifies 
subjects will not be included in any study information sent to the Sponsor. Instead, subjects 
will be identified by a unique study number, also known as a “code”. The research team will 
keep a list linking a subject’s code with their name, so that they can be identified by their 
coded data if needed. The following groups may have access to a subject’s de-identified and 
coded information as this will be sent and stored overseas: 
• The Sponsor, for the purposes of this study.  
• People and companies working with or for the sponsor, for the purposes of this study (this 
may include approx. 15 people across 5 organizations; Sponsor, Core lab providers (where 
imaging analysis occurs), CEC, DSM, and the Contract Research Organization (CRO).   
• Regulatory or other governmental agencies worldwide. 
 Case Report Forms  
All required data for this study will be collected via cloud-based electronic data capture (EDC) 
system and entered in electronic Case Report Forms (eCRFs).  
All data collected during the study will be de-identified. For this purpose, a unique study 
identifier will be assigned to each study subject. All information recorded on the electronic 
Case Report form (eCRF) about the subject will be recorded including the study identifier. 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 study. 

 
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 Transmission of Data  
Required data will be recorded on the appropriate electronic Case Report Forms 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 and source information associated with adverse 
events) must be sent to Shockwave Medical (if applicable to local site regulations) and/or 
verified/retrieved from the Investigator during monitoring visits.  Data sent to Shockwave 
Medical will be de-identified and done so utilizing a secure web-based system. 
 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 by Shockwave Medical or its designee 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 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. 
 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 two (2) years after the records are no longer 
required to support the application to market the device (whichever date is later), or longer if 
required by applicable local regulations. The data will be retained in a secure, password 
protected database under the custodianship of the Sponsor 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, 
including SAEs, as described in the CEC charter.  
The CEC will be managed by 
.  
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 investigators.  
The CEC is made up of clinicians with pertinent expertise who are not participants in the study and 
who do not have any other real or potential conflicts of interest.  Members have expertise in 
peripheral endovascular procedures, are experienced in the conduct of controlled clinical trials and 
have knowledge of bioethics and integrity related to the duties and responsibilities to be 
performed.  
The CEC is charged with the development of specific criteria used for the categorization of adverse 
events and clinical endpoints in the study.  Criteria will be established for selected complications 
and clinical events. Events to be adjudicated include death, MAEs, revascularizations, and 
amputations. The CEC will also adjudicate relationship to the study device and study procedure 
according to the following classifications: definitely related, probably related, possibly related, 
unlikely related and not related. 
At the onset of the 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.  In addition, 
the CEC Charter will include the number of members, responsibilities, CEC meeting procedures, and 
meeting frequency. 
13.2 Independent Data and Safety Monitor (DSM) 
An independent Data and Safety Monitor (DSM) will be responsible for reviewing study data, 
monitoring for excessive occurrence of adverse events and making recommendations to 
Shockwave Medical regarding safety issues and risks to research participants as well as the 
continuing validity and scientific merit of the study.  The DSM will make recommendations including 
(but not limited to) modification of the protocol, continuation/discontinuation of enrollment, 
and/or temporary suspension of enrollment in the trial.  The DSM will be a physician with required 
training, experience and expertise in the field of peripheral endovascular procedures and in the 
conduct of clinical trials.  

 
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The independent DSM will conduct reviews of safety data in accordance with the protocol, 
local regulations where applicable, ICH E6: Good Clinical Practice (GCP) guidelines, and 
ISO14155:2020.  At regular intervals during the course of the study, the DSM shall: 
• 
Evaluate all adverse events with regard to interim results of the study for evidence of 
undue risk to research subjects and/or safety concerns. 
• 
Provide recommendations regarding continuation/discontinuation of enrollment, and/or 
temporary suspension of enrollment due to safety concerns. 
• 
Evaluate study progress with projections of recruitment and timelines for study 
milestones.  This also includes evaluation of any significant trends of performance that may 
influence the safety or conduct of the study. 
• 
Advise the Sponsor and other responsible parties on potential protocol-related concerns 
regarding 
procedures, definitions 
or 
endpoints, allowing 
timely notification 
of regulatory authority for protocol revisions. 
In addition to regularly scheduled data reviews, the DSM will be notified immediately if any of the 
following events occur: any in-hospital death associated with the index procedure, any 
investigational device malfunction contributing to a serious adverse event, or failure to retrieve the 
investigational device. 
  
 

 
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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 study, including assurance that the study will be conducted according to ICH Good 
Clinical Practices (GCP), 21 CFR 812, 820, 50, 54, and 56, Declaration of Helsinki, applicable IRB/EC 
requirements, as well as any ISO 14155 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 should be outlined within the protocol. 
Sponsor will provide insurance for this study. 
This protocol and any amendments will be submitted to each site’s IRB/EC for formal approval of 
the study. All subjects considered for this study will be provided a consent form describing this 
study and providing sufficient information for them to make an informed decision about their 
participation.   
14.2 Subject Confidentiality 
As per the Data Management Section 12.9, 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 such as regulatory or auditing agencies (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. Data will not be provided to third party agencies that are not associated with the 
commercial or research operations of the Sponsor. 

 
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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 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. 
Calcification Classification (PARC): Calcification will be assessed by the angiographic core lab according 
to the Peripheral Academic Research Consortium (PARC) definition [26].  
PARC Degree of Lesion Calcification 
Focal 
Degree of lesion calcification 

 
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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 
 
Clinical Events Committee (CEC): Committee responsible for establishing and implementing decision 
rules, definitions for the adjudication of clinical events using the data collected in the study, and for 
providing unbiased adjudication of clinical events. 
Clinically Relevant Target Lesion Occlusion: Clinically relevant restenosis defined as the presence of a 
50% or greater narrowing accompanied by a judgement of clinical relevance. Clinical relevance 
adjudicated by independent CEC based on worsening of Rutherford score, non-healing of wounds, ABI 
drop of ≥0.15, TBI drop of ≥0.10, each as compared to post-procedural outcomes, or absolute toe 
pressure ≤30 mmHg. 
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 
Clinical Scale Category of 2-6. (For the purposes of this study, only subjects with Rutherford Clinical 
Scale Category of 2, 3, 4, and 5 are eligible for enrollment). 
Data and Safety Monitor (DSM): Data and Safety Monitor will be responsible for reviewing study data, 
monitoring for excessive occurrence of adverse events and making recommendations to Shockwave 
Medical regarding safety issues and risks to research participants as well as the continuing validity and 
scientific merit of the study. 
Death: (divided into 2 categories) 
Cardiovascular 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 

 
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5. Death due to complication of the procedure, including bleeding, vascular repair, transfusion 
reaction, or bypass surgery 
6. Any death for which a cardiovascular cause cannot be excluded 
Non-cardiovascular death is a death not due to cardiovascular 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. 
Note: This definition includes device deficiencies related to the investigational medical 
device or the comparator. 
Device Malfunction: A malfunction of a device is an unexpected change to the device that is 
contradictory to the Instructions for Use and may or may not affect device performance. 
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: Minor radiolucent areas within the lumen without impairment of flow or persistent dye 
staining after contrast runoff. 
Type B: Luminal flap that is radiolucent and runs parallel to the vessel wall with contrast injection 
but without impairment of flow or persistent dye staining after contrast runoff. 
Type C: Contrast appears outside of the vessel lumen as an “extraluminal cap”, the staining appears 
even after contrast clears off the lumen. 
Type D: Spiral radiolucent luminal filling defects, often persistent staining after contrast clears from 
the vessel. 
Type E: New and persistent filling defects in the vessel lumen. 
Type F: Lesions that progress to impaired flow or total 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. 

 
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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. 
Major Adverse Event (MAE): For the purposes of this study, the definition of Major Adverse Event(s) 
includes: 
• 
cardiovascular death 
• 
target lesion revascularization  
• 
Unplanned target limb major amputation (above the ankle) 
Perforation: Puncture of an arterial wall. 
Restenosis: Reoccurrence of narrowing or blockage of target lesion. 
Rutherford Classification of Critical Limb Ischemia:: Clinical staging system for describing PAD.  It 
includes 7 categories:  
 
Grade 
Category 
Clinical Description 
0 
0 
Asymptomatic 
I 
1 
Mild claudication 
I 
2 
Moderate claudication 
I 
3 
Severe claudication 
II 
4 
Ischemic rest pain 
III 
5 
Ischemia ulceration not exceeding 
ulcer of the digits of the foot 
IV 
6 
Severe ischemic ulcers or frank 
gangrene 
ACC/AHA/SCIA/SIR/SVM 2018 Appropriate Use Criteria for Peripheral Artery Intervention – Bailey et 
al. 2019) 
Serious Adverse Device Effect (SADE): Adverse device effect that has resulted in any of the 
consequences characteristic of a serious adverse even. 
Serious Adverse Event (SAE): Adverse event that led to any of the following: 
• 
death, 

 
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• 
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 body structure or a body function, 
o foetal distress, foetal 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 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. 

 
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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 
CEC 
Clinical Events Committee 
CFR 
Code of Federal Regulations 
CIP 
Clinical Investigation Plan 
CKD-EPI Chronic Kidney Disease Epidemiology Collaboration 
CLI 
Critical Limb Ischemia 
CRF 
Case Report Form 
CRO 
Contract Research Organization 
CTA 
Computed Tomography Angiogram 
CTO 
Chronic Total Occlusion 
DCB 
Drug-Coated Balloon 
DES 
Drug-Eluting Stent 
DSM 
Data and Safety Monitor 
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 
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 

 
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ITT 
Intent-to-Treat 
IVL 
Intravascular Lithotripsy 
IVUS 
Intravascular Ultrasound 
MAE 
Major Adverse Event 
MALE 
Major Adverse Limb Event 
MDR 
Medical Device Reporting 
MRA 
Magnetic Resonance Angiography 
OCT 
Optical Coherence Tomography 
OTW 
Over-the-Wire 
PAD 
Peripheral Artery Disease 
PARC 
Peripheral Academic Research Consortium 
POD 
Post-Operative Death 
PTA 
Percutaneous Transluminal Angioplasty 
RC 
Rutherford Category 
RVD 
Reference Vessel Diameter 
SADE 
Serious Adverse Device Effect 
SAE 
Serious Adverse Event 
TBI 
Toe-Brachial Index 
TLR 
Target Lesion Revascularization 
TVR 
Target Vessel Revascularization 
USADE 
Unanticipated Serious Adverse Device Effect 

 
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16.0 
REFERENCES 
1. 
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3. 
Walker, C.M., et al., Multidisciplinary approach to the diagnosis and management of patients 
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Committee, T.S., et al., An Update on Methods for Revascularization and Expansion of the TASC 
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Brodmann, M., A. Holden, and T. Zeller, Safety and Feasibility of Intravascular Lithotripsy for 
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Brodmann, M., et al., Safety and Performance of Lithoplasty for Treatment of Calcified Peripheral 
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Brodmann, M., et al., Primary outcomes and mechanism of action of intravascular lithotripsy in 
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considerations of precision and efficiency. J Clin Epidemiol, 2012. 65(3): p. 301-8. 
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Stallard, N., Optimal sample sizes for phase II clinical trials and pilot studies. Statistics in 
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Patel, M.R., et al., Evaluation and treatment of patients with lower extremity peripheral artery 
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NO.:  CP 65324 
REV. D 
TITLE:  Mini S Feasibility Study Protocol 
CLASS:  CLINICAL PROTOCOL
 
 
PAGE 65 OF 70 
 
Confidential – This document is property of Shockwave Medical, Inc. 
 
17.0 
SUBJECT INFORMED CONSENT 
The subject informed consent template will be provided as a separate attachment. 

 
NO.:  CP 65324 
REV. D 
TITLE:  Mini S Feasibility Study Protocol 
CLASS:  CLINICAL PROTOCOL
 
 
PAGE 66 OF 70 
 
Confidential – This document is property of Shockwave Medical, Inc. 
 
18.0 
CASE REPORT FORMS 
Draft case report forms will be provided as a separate attachment. 
 
 
 

 
NO.:  CP 65324 
REV. D 
TITLE:  Mini S Feasibility Study Protocol 
CLASS:  CLINICAL PROTOCOL
 
 
PAGE 69 OF 70 
 
Confidential – This document is property of Shockwave Medical, Inc. 
 
D 
07/21/2023 
26303 
• 
Section 2.0, Study Summary: Primary 
Safety Endpoint definition 
modification of the Major Adverse 
Events (MAE).  Secondary Endpoints, 
addition of Technical Success (final), 
clarification of MAEs as composite 
and individual components, and 
administrative changes. 
• 
Section 2.0, Study Summary:  
Clarification of Angiographic 
Inclusion criteria #9 for tandem 
lesions, added “with the exception of 
toe amputation” to exclusion criteria 
#2, clarification of angiography 
exclusion criteria #18 (successfully 
treat inflow lesion), and 
administrative clarification of 
Angiographic Exclusion Criteria #19. 
• 
Section 4.1, Mini S Peripheral IVL 
Catheter:  Clarified catheter shaft 
color.  
• 
Section 5.1, Safety Endpoints:  
Primary Safety Endpoint definition 
modification. Clarification of MAE 
reporting as a “composite and 
individual components” 
• 
Section 5.2, Performance Endpoints: 
Addition of Technical Success (final) 
endpoint.   
• 
Section 7.2.1, Inclusion Criteria:  
Clarification of Angiographic 
Inclusion criteria #9 for tandem 
lesions 
• 
Section 7.2.2, Exclusion Criteria:  
added “with the exception of toe 
amputation” to exclusion criteria #2, 
Clarification of Angiographic 
Exclusion Criteria #18 (successfully 
treat inflow lesion), and 
administrative clarification of 
Angiographic Exclusion criteria #19 
• 
Section 7.4, Table 1, Schedule of 
Events and Evaluations:  Months 
Clinical