KAIZEN: Safety and Effectiveness Evaluation of Peripheral Orbital Atherectomy
Phase: NA
Conditions: Peripheral Artery Disease
Sponsor: Abbott Medical Devices



 
KAIZEN Clinical Study 
Cardiovascular Systems, Inc. 
 Revision G 
 
Page 1 of 67 
Clinical Protocol  
KAIZEN: Safety and Effectiveness Evaluation of Peripheral  
Orbital Atherectomy  
Protocol 
 
 
Rev. G 
 
17Apr2023  
 
Sponsored By: 
Cardiovascular Systems, Inc. 
 
 
In-Country Clinical Caretaker: 
 
 
 
 
 
Notwithstanding the contents of this protocol, this clinical study will be conducted in 
accordance with local regulations in Japan. 
 
CONFIDENTIAL INFORMATION 
 
 
 
 

 
KAIZEN Clinical Study 
Cardiovascular Systems, Inc. 
 Revision G 
 
Page 2 of 67 
TABLE OF CONTENTS 
CONTACT INFORMATION ................................................................................. 5 
1. 
WORKING VERSION HISTORY ................................................................ 6 
2. 
STUDY SUMMARY ......................................................................................10 
3. 
ABBREVIATIONS ........................................................................................14 
4. 
DEFINITIONS ...............................................................................................16 
5. 
INTRODUCTION ..........................................................................................25 
6. 
DEVICE DESCRIPTION .............................................................................26 
6.1 Device Name and Indications for Use .............................................................................. 26 
6.2 Device History and Description ........................................................................................ 26 
6.3 Principles of Operation ..................................................................................................... 29 
6.4 Devices Used in the Study ................................................................................................ 29 
6.5 Manufacturer ..................................................................................................................... 29 
6.6 Device Handling and Traceability .................................................................................... 30 
6.7 Device Storage .................................................................................................................. 30 
6.8 Device Accountability ...................................................................................................... 30 
6.9 Device Return ................................................................................................................... 30 
7. 
OBJECTIVE ...................................................................................................30 
8. 
STUDY ENDPOINTS ....................................................................................31 
8.1 Primary Endpoint .............................................................................................................. 31 
8.2 Secondary Endpoints ........................................................................................................ 31 
9. 
STUDY DESIGN ............................................................................................32 
9.1 Description of Study Design ............................................................................................. 32 
9.1.1 Study Duration ......................................................................................................................................... 32 
9.1.2 Enrollment Criteria .................................................................................................................................. 32 
9.1.3 Justification of Performance Goal ............................................................................................................ 33 
9.1.4 Study Hypothesis ..................................................................................................................................... 35 
9.1.5 Justification of the Sample Size ............................................................................................................... 35 
10. DATA COLLECTION ..................................................................................36 
10.1 Study Data Collection ....................................................................................................... 36 
11. STUDY ENROLLMENT ..............................................................................38 
11.1 Baseline ............................................................................................................................. 38 
11.1.1 Study Medications ................................................................................................................................... 38 
11.2 Verify General Inclusion and Exclusion Criteria.............................................................. 38 
11.2.1 General Inclusion Criteria ........................................................................................................................ 38 
11.2.2 General Exclusion Criteria ....................................................................................................................... 39 
11.3 Informed Consent.............................................................................................................. 40 
11.4 Verify Clinical Trial Treatment Inclusion and Exclusion Criteria ................................... 41 
11.4.1 Clinical Trial Treatment Inclusion Criteria .............................................................................................. 41 
11.4.2 Clinical Trial Treatment Exclusion Criteria ............................................................................................. 41 
11.5 Before Clinical Trial Treatment ........................................................................................ 42 

 
KAIZEN Clinical Study 
Cardiovascular Systems, Inc. 
 Revision G 
 
Page 3 of 67 
12. CLINICAL TRIAL TREATMENT .............................................................43 
12.1 CSI Peripheral OAS Guide Wire Insertion ....................................................................... 43 
12.2 OAD, POBA, DCB Procedure .......................................................................................... 44 
12.3 Role of CSI Representatives During the Procedure .......................................................... 45 
12.4 Non-Target Limb Treatment ............................................................................................. 45 
13. DISCHARGE .................................................................................................45 
13.1 Discharge Medications...................................................................................................... 45 
14. FOLLOW-UP .................................................................................................46 
14.1 30-Day In-hospital Follow-up Visit or Telephone Follow-up Assessment ...................... 46 
14.2 6-Month Follow-up Visit .................................................................................................. 46 
15. OVERVIEW OF IMAGING DATA FLOW ...............................................46 
16. ADVERSE EVENTS......................................................................................47 
16.1 Adverse Event Requirements ............................................................................................ 47 
16.2 Adverse Event Definitions ................................................................................................ 47 
16.3 Adverse Event Relatedness ............................................................................................... 48 
16.4 Reporting Adverse Events and Follow-Up ....................................................................... 48 
16.5 Device Deficiencies .......................................................................................................... 49 
17. PROTOCOL DEVIATIONS ........................................................................49 
18. STUDY EXIT .................................................................................................50 
19. STUDY TERMINATION .............................................................................51 
20. STUDY RESPONSIBILITIES AND MANAGEMENT ............................51 
20.1 Conduct of Study .............................................................................................................. 51 
20.2 Investigator Selection and Responsibilities ...................................................................... 51 
20.2.1 Investigator Training ................................................................................................................................ 51 
20.2.2 Investigator / Investigational Site Delegation .......................................................................................... 52 
20.2.3 Investigator Responsibilities .................................................................................................................... 52 
21. MONITORING ..............................................................................................53 
22. INDEPENDENT PHYSICIAN REVIEWER ..............................................54 
23. CLINICAL EVENTS COMMITTEE (CEC)..............................................54 
24. DATA MONITORING COMMITTEE (DMC)..........................................54 
25. STATISTICAL METHODS .........................................................................55 
25.1 Data Analysis .................................................................................................................... 55 
25.1.1 Full Analysis Set (FAS) ........................................................................................................................... 55 
25.1.2 Intent to Treat (ITT) Analysis Set ............................................................................................................ 55 
25.1.3 Modified Intent to Treat (mITT) Analysis Set ......................................................................................... 55 
25.1.4 Per Protocol (PP) Analysis Set ................................................................................................................. 55 
25.1.5 Roll-in Analysis Set ................................................................................................................................. 56 
25.2 Timing of Analysis ........................................................................................................... 56 
25.3 Identifying Target Lesions ................................................................................................ 56 
25.4 Endpoint Analyses ............................................................................................................ 56 

 
KAIZEN Clinical Study 
Cardiovascular Systems, Inc. 
 Revision G 
 
Page 4 of 67 
25.4.1 Primary Endpoint Analysis ...................................................................................................................... 56 
25.4.2 Primary Endpoint Sensitivity Analysis .................................................................................................... 57 
25.4.3 Secondary Endpoint Analysis .................................................................................................................. 57 
25.4.4 Roll-in Analysis ....................................................................................................................................... 57 
26. RISK ANALYSIS ...........................................................................................57 
26.1 Risks Associated with OAS .............................................................................................. 57 
26.2 Risk Associated with DCB ............................................................................................... 58 
26.3 Risk Minimization ............................................................................................................ 58 
26.4 Minimization Bias ............................................................................................................. 59 
26.5 Benefits ............................................................................................................................. 59 
27. CONFIDENTIALITY ...................................................................................60 
28. RECORD KEEPING .....................................................................................60 
28.1 Medical Institution ............................................................................................................ 60 
28.2 Sponsor ............................................................................................................................. 60 
29. PROTOCOL AMENDMENTS ....................................................................61 
30. PUBLICATION OF STUDY DATA ............................................................61 
31. BIBLIOGRAPHY ..........................................................................................62 
Appendix A: Imaging and Procedure Flow Chart .............................................64 
Appendix B: Enrollment Decision Flow Chart ...................................................65 
Appendix C: Investigator’s Brochure ..................................................................66 
Appendix D: Participating Sites and Investigators ............................................67 
 
LISTING OF TABLES 
Table 1: CSI Peripheral OAD Information ..................................................................... 28 
Table 2: OAD Crown Information .................................................................................. 28 
Table 3: CSI OAS Peripheral Guide Wire Information ................................................... 29 
Table 4: Previous Clinical Trials on OAS ....................................................................... 34 
Table 5: Sample Size Parameters and Justification ...................................................... 35 
Table 6: Sample Size Parameters and Justification ...................................................... 36 
Table 7: Summary of Required Tests and Procedures.................................................. 37 
LISTING OF FIGURES 
Figure 1: Protocol Defined Treatment Area and Crown Sizing Guide ........................... 45 
 

 
KAIZEN Clinical Study 
Cardiovascular Systems, Inc. 
 Revision G 
 
Page 15 of 67 
FAS 
Full Analysis Set 
GCP 
Good Clinical Practices 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
ID 
Identity 
IFU 
Instructions for Use 
IRB 
Institutional Review Board 
ISR 
In-stent Restenosis 
ITT 
Intent to Treat 
IV 
Intravenous 
IVUS 
Intravascular Ultrasound 
MAE 
Major Adverse Event 
MI  
Myocardial Infarction 
mITT 
Modified Intent to Treat 
OAD 
Orbital Atherectomy Device 
OAS 
Orbital Atherectomy System 
OA 
Orbital Atherectomy 
PAD 
Peripheral Artery Disease 
PACSS 
Peripheral Artery Calcification Scoring System 
PARC 
Peripheral Academic Research Consortium 
PI 
Principal Investigator 
POBA 
Plain Old Balloon Angioplasty 
POP 
Popliteal   
PP 
Per Protocol 
PTA 
Percutaneous Transluminal Angioplasty 
QVA 
Quantitative Vascular Analysis 
RBP 
Rated Burst Pressure 
RC 
Rutherford Classification 
RCT 
Randomized Controlled Trial 
RMA 
Returned Materials Authorization 
RVD 
Reference Vessel Diameter  

 
KAIZEN Clinical Study 
Cardiovascular Systems, Inc. 
 Revision G 
 
Page 25 of 67 
 INTRODUCTION 
In 2015, an estimated 8.1 to 10.3 million Japanese had peripheral artery disease (PAD).4 The 
prevalence of this disease, often referred to as arteriosclerosis obliterans (ASO), is expected to 
increase up to 11.9 million by 2030.4 PAD of the lower extremities is caused by atherosclerosis 
and the prevalence of atherosclerotic risk factors, such as advanced age, diabetes, kidney 
disease, and smoking which are on the rise in Japan.4,5  Compared to non-PAD patients, within 
the first year of diagnosis PAD patients have a significantly higher risk of adverse cardiovascular 
events, including ischemic stroke and myocardial infarction, and significantly greater health care 
utilization and total annual healthcare costs.6 Thus, PAD poses a significant clinical and economic 
burden in Japan. 
Revascularization is a crucial component for the treatment of patients with PAD, including those 
with claudication and the more advanced form of the disease, critical limb ischemia (CLI).7 
Endovascular intervention may reduce limb pain, improve quality of life, and prolong walking 
distance for patients with claudication and has been associated with lower amputation rates in 
patients with CLI.8 However, the disease severity and anatomical location strongly influence the 
technical challenges and expected outcomes of the treatment.7 In particular, calcification 
represents a significant challenge to current endovascular device strategies and is associated 
with increased procedure-related adverse events, as well as poor long-term clinical outcomes2,9.  
In the CODE Study, severe calcification in a ≥180° arc prevented successful dilation of superficial 
femoral artery (SFA) lesions with either plain balloon angioplasty or a nitinol stent.10 Balloon 
angioplasty (BA) of calcified lesions is limited by acute vessel recoil, frequent flow-limiting 
dissections, high rate of perforation, and poor primary and secondary patency rates.2,11,12 For 
example, in a small study of 67 patients with 62% of them having severely calcified 
femoropopliteal lesions, the aggressive predilation of the calcified plaque led to a 59% perforation 
rate.12 Furthermore, 40-50% of the BA cases require bailout-stenting; in the Resilient and Zilver 
trials, 48.3% and 57% of the lesions were moderately or severely calcified in the BA arm, 
respectively; of the patients in the BA arm, 40.3% and 50.4% required bail-out stenting.13,14 It is 
known that calcification increases the risk of stent fractures [with consecutive thrombosis and 
vessel occlusion15], which is associated with a higher in-stent restenosis (ISR) and reocclusion 
rate.16 In addition, the presence of rigid calcified plaques may result in incomplete and/or eccentric 
stent expansion and significant residual stenosis, which again increases the risk of in-stent 
restenosis and thrombosis.2,15,17 Drug-coated balloons (DCB) could be the solution to stent-
related adverse events in calcified lesions [leaving nothing behind], as well as in reducing the high 
restenosis rates after BA [the antiproliferative drug reduces neointimal hyperplasia, resulting in a 
lower incidence of restenosis and target lesion revascularization18]. However, Fanelli et al. found 
that calcium represents a barrier to optimal drug absorption.19 Circumferential distribution seems 
to be the most influencing factor with the lowest primary patency rate and higher late lumen loss 
in 360° calcium presence. Based on the above, a new endovascular technique [vessel preparation 
prior to DCB angioplasty], such as CSI’s OAS, is available for the treatment of severely calcified 
lesions. The findings of a recently published study suggest, that vessel preparation with orbital 
atherectomy prior DCB angioplasty may enhance the effect of DCBs in calcified lesions, reducing 
the need for stents and maintaining acceptable patency rates.20  

 
KAIZEN Clinical Study 
Cardiovascular Systems, Inc. 
 Revision G 
 
Page 26 of 67 
Calcific plaque is common in lower extremity arteries; in a recent analysis of 394 Japanese PAD 
patients who underwent endovascular therapy for SFA lesions, calcification was present in 46% 
of the lesions.9  
In the US, CSI currently has approval for its Peripheral OAS (Class II).  The prospective 
multicenter Clinical Study of the OAS for the Treatment of Peripheral Vascular Stenosis (OASIS) 
was conducted to evaluate the safety and effectiveness of the orbital atherectomy (OA) in patients 
with symptomatic PAD.  One hundred twenty-four (124) patients from seventeen (17) contributing 
centers were enrolled, and two hundred and one (201) lesions were treated with OA.  For 
additional information about the OASIS study and other CSI peripheral studies, please refer to 
the study Investigator’s Brochure (IB). 
 DEVICE DESCRIPTION 
 Device Name and Indications for Use 
The CSI Peripheral Orbital Atherectomy System (OAS) is a percutaneous orbital atherectomy 
system indicated for use as therapy in patients with calcified occlusive atherosclerotic disease 
in peripheral arteries and who are acceptable candidates for percutaneous transluminal 
atherectomy.  
 Device History and Description 
The orbital atherectomy device (OAD) consists of a diamond-coated abrasive head (referred to 
as a “crown”) mounted on the driveshaft that is designed to track and spin over the CSI 
Peripheral OAS Guide Wire, which can be independently advanced and steered. The OAD 
ablates occlusive material (i.e., peripheral plaque) and improves luminal patency. The diameter 
of the crown’s orbit is a function of crown mass and rotational speed.  During rotation, centrifugal 
forces press the crown laterally against the peripheral plaque, reducing a thin layer of that 
plaque on the vessel wall. 
The first-generation model of the CSI Peripheral OAS received CE Mark in February 2007 and 
US FDA 510(k) clearance in August 2007 for use as therapy in patients with occlusive 
atherosclerotic disease in peripheral arteries and who are acceptable candidates for 
percutaneous transluminal atherectomy. The Peripheral OAS is commercially available in the 
US, Germany, Austria, France, Malaysia, Singapore, and United Arab Emirates. 
The current generation model of the CSI Peripheral OAS intended to be used in KAIZEN 
received US FDA clearance in July 2019.  The components of the OAS are described below.  
• 
CSI Peripheral Orbital Atherectomy Device (OAD) is a hand-held component of the OAS 
that provides the physician with independent control of the OAS. The OAD is a single use 
over-the-wire device consisting of a handle, and a saline line (Table 1).  
o The OAD handle includes a sheath-covered drive shaft and a diamond-coated 
crown. The OAD crown can pass in tight lesions, smaller than the crown size, due 
to its angular front sanding edge and the OAD’s mechanism of action. The handle 

 
KAIZEN Clinical Study 
Cardiovascular Systems, Inc. 
 Revision G 
 
Page 27 of 67 
includes control buttons for operating the OAD and contains the motor and 
electronics that power the rotation of the drive shaft. The crown is a diamond-
coated, abrasive surface mounted on the driveshaft that is designed to track and 
spin over the guide wire and remove or reduce the occlusive tissue into 
microscopic particles (Table 2).  
• 
CSI OAS Pump (OAS Pump model number SIP-3000) provides the saline/lubricant 
pumping mechanism and power to the device.  The small, reusable, and portable OAS 
Pump attaches to a standard five-wheel rolling intravenous (IV) pole and plugs into a wall 
power outlet. The OAS Pump includes a built-in audible 25 second spin time notification, 
system power and priming buttons, and status indicators.  
• 
Note: OAS Pump was approved for use with CSI’s Coronary OAS in Japan in June 
2018.  
• 
CSI OAS Peripheral Guide Wires are single-use, smooth, stainless steel wires, with a 
silicone coating, and a radiopaque distal spring tip (Table 3). The OAS Peripheral Guide 
Wire allows for proper positioning of the OAD crown within peripheral arteries and provides 
a center of rotation for the OAD drive shaft. The OAS Peripheral Guide Wires are provided 
sterile.  
• 
CSI OAS Lubricant (model number VPR-SLD2) is designed to reduce the friction between 
the flexible drive shaft of the CSI OAD and CSI Peripheral Guide Wire. The CSI OAS 
Lubricant is an emulsion composed of soybean oil, egg yolk phospholipids, glycerin, and 
water for injection. An addition of sodium hydroxide adjusts the pH resulting in a final pH 
of 8.0 with a pH range of 6.0 to 8.9.  CSI OAS Lubricant is single use and provided sterile.  
o Note: CSI OAS Lubricant was approved for use with CSI’s Coronary OAS in 
Japan in March 2017. 
 
 
 
 
 
 
 
 
 
 

 
KAIZEN Clinical Study 
Cardiovascular Systems, Inc. 
 Revision G 
 
Page 30 of 67 
 
 Device Handling and Traceability 
The investigational devices will be tracked from the time it is shipped from CSI until it is either 
used in a procedure on a study subject or returned to the Sponsor. To assist in the traceability 
of the investigational devices, each device is labeled with a Model number and Lot or Serial 
number. 
 Device Storage 
All Investigational Devices must be stored in a locked/secure location with access limited only 
to applicable study staff. Refer to the IB for more information on device handling and storage.   
 Device Accountability 
A Device Accountability Log and shipping records will be maintained at each study site. 
Investigational Devices allocated for site use will be recorded in the Device Accountability Log 
upon delivery to the study site until use. Each site will be responsible for tracking the receipt 
and disposition of all study devices. If there is a device accountability discrepancy, the Sponsor 
and site will work to reconcile the discrepancy. Documentation of reconciliation will be 
maintained.   
The Device Accountability Log will be updated as devices are received, opened, used or 
returned.  
Commercially available accessory products will not be required to be tracked on the Device 
Accountability Log. 
 Device Return 
All unused/expired devices must be returned to CSI. Sites should contact their study 
representative to obtain further instruction on device return procedures. At the end of the 
study enrollment period, all remaining investigational devices and study supplies must be 
returned to CSI.  
 OBJECTIVE 
The objective of the study is to collect safety and effectiveness data to support potential 
commercialization of the peripheral OAS device in Japan. 
 
 
 
 

 
KAIZEN Clinical Study 
Cardiovascular Systems, Inc. 
 Revision G 
 
Page 31 of 67 
 STUDY ENDPOINTS 
 Primary Endpoint 
The primary endpoint will demonstrate OAS safety and efficacy via Acute Device Success.  
Acute device success is defined post-procedure as the percentage of subjects with: 
a) ≤50% residual stenosis post OAD + POBA [Angiographic Core Lab assessed] and, 
b) No OAS-related severe angiographic complications defined as severe dissections (D-F), 
perforation, or distal emboli requiring additional treatment during the procedure [CEC 
adjudicated]  
 Secondary Endpoints 
The following secondary endpoints will be evaluated: 
1. Reduction in lesion stenosis both post-OAD and post-OAD+POBA [Angiographic Core 
Lab assessed] (absolute mean percentage change defined as the difference between the 
pre-procedure percent stenosis and the percent stenosis measured post-OAD and post-
OAD+POBA) 
2. Acute technical success defined per the PARC definition of achievement of a final residual 
stenosis <30% for stented and <50% for non-stented subjects by angiography at the end 
of the procedure [Angiographic Core Lab assessed] without severe angiographic 
complications defined as severe dissections (D-F), perforation, or distal emboli requiring 
additional treatment during the procedure [CEC adjudicated] 
3. DCB Device Success defined as the ability to achieve successful delivery and deployment 
of all DCB to the target lesion as described per the Instructions for Use (IFU) within 3 
minutes of insertion without removal and use of an additional device. 
4. Target vessel patency at 6 months defined as absence of clinically-driven Target Lesion 
Revascularization (TLR) and ≤2.4 peak systolic velocity ratio (PSVR) as assessed by 
Duplex Ultrasound [Duplex Ultrasound Core Lab assessed]. Clinically-driven TLR is 
defined as repeat procedure performed for ≥50% stenosis confirmed by angiography 
within all or part of the target lesion after documentation of recurrent clinical symptoms of 
PAD following clinical trial treatment [CEC adjudicated] 
5. Rate of severe angiographic complications defined as severe dissections (D-F), 
perforation, or distal emboli requiring additional treatment during the procedure [CEC 
adjudicated] 
6. Acute procedure success defined as both acute technical success and absence of death, 
stroke, MI, acute onset of limb ischemia, index bypass graft or treated segment 
thrombosis, and/or need for urgent/emergent vascular surgery within 72 hours of the 
clinical trial treatment [CEC adjudicated] 
7. Major Adverse Event (MAE) rate at 30 days and 6 months [CEC adjudicated] defined as: 

 
KAIZEN Clinical Study 
Cardiovascular Systems, Inc. 
 Revision G 
 
Page 32 of 67 
a) All-cause death through 30 days or 
b) Major amputation of the target limb or 
c) Clinically-driven TLR 
8. Adverse Event rates at 30 days and 6 months [CEC adjudicated]  
9. Distribution of Rutherford Classification compared to baseline at 30 days and 6 months 
10. Change in Ankle Brachial Index (ABI) after clinical trial treatment compared to baseline 
 STUDY DESIGN 
 Description of Study Design 
This prospective, single-arm, multi-center study is designed to evaluate the performance of the 
peripheral Orbital Atherectomy System (OAS) in the treatment of the adult Japanese population 
with a de novo symptomatic calcified occlusive atherosclerotic lesion in the SFA and/or POP 
arteries (Figure 1).   
The KAIZEN study will use objective criteria to identify patients to be enrolled. The initial 
enrollment criteria will be assessed by the treating physician. An independent physician review 
of objective computer-aided imaging will determine final eligibility into the primary analyses.  
The rationale for the single-armed study design is based on the significant amount of testing 
completed before human studies and the multiple human clinical trials that have assessed over 
4000 subjects in the US. The peripheral OAS has a well-established safety and performance 
profile. The hypothesis-based performance goals chosen for this study are based on observed 
rates from previous study subjects and lesions similar to those expected to be enrolled in the 
KAIZEN study.  It is expected that the results from this study will be similar to observed rates 
form other Peripheral OAS studies.  
 Study Duration 
 Subject participation in the study may 
last about 6 months. 
 Enrollment Criteria 
 
 
ixty-two (62) subjects who meet the enrollment criteria after an Independent Physician 
Review using objective computer-aided imaging are required for a proper assessment of the 
Primary Endpoint. The study may enroll at approximately (12) sites in Japan. 
Additionally, KAIZEN includes an Independent Physician Reviewer who will verify the 
treating physician’s assessment of eligibility criteria. The Independent Physician Reviewer 
will assess the angiographic and IVUS core laboratory results using objective computer-
aided imaging to identify patients who will be included in the primary analysis of KAIZEN.  

 
KAIZEN Clinical Study 
Cardiovascular Systems, Inc. 
 Revision G 
 
Page 33 of 67 
 Justification of Performance Goal  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
KAIZEN Clinical Study 
Cardiovascular Systems, Inc. 
 Revision G 
 
Page 38 of 67 
5 Verify Procedure eligibility, estimate treatment results, and determine complications (See Section 11 and 12 for 
further details). Subject must meet all Clinical Trial Treatment Inclusion/Exclusion Criteria prior to inserting the 
CSI Peripheral Guide Wire (enrollment). 
6 IVUS must be attempted once; however, if IVUS cannot cross before clinical trial treatment, further procedural 
IVUS measurements are not required.   
7 Submit appropriate source documents for review of Adverse Events. 
8 30-Day Follow-up assessment can be in-hospital follow-up or telephone assessment. 
9 Required if 30-day Follow-Up Assessment occurs in-hospital.  
10 Subjects in whom a CSI Peripheral Guide Wire complication occurred while entering the body, or the OAD 
was never inserted, will have a 6-Month Follow-up visit or telephone follow-up assessment for adverse events 
only.  
11 Angiographic images are required at all time-points noted in Appendix A: Imaging and Procedure Flow Chart 
even if angiography images are not used to determine Calcium Assessment. 
12 Only required for Enrolled and Treated subjects.  
 
 STUDY ENROLLMENT  
Institutional Review Board (IRB) approval of the KAIZEN protocol and Informed Consent Form 
(ICF) must be obtained prior to enrolling patients in the study. The Sponsor and/or Sponsor 
Representative will provide approval in writing to begin enrollment. 
 Baseline  
Baseline assessments must be completed within 30 days of the Clinical Trial Treatment with 
exception of the Pregnancy Test for women of childbearing potentials which must be 
conducted within 24 hours of the start of the Clinical Trial Treatment. Refer to Table 7 for 
Baseline assessment data collection requirements.  
 Study Medications 
Appropriate antiplatelet and/or anticoagulation therapy should be administered per the 
individual institution’s standard practice for intraoperative procedural management. Additional 
medications administered to the subject prior to the procedure, during the procedure, and after 
the procedure are at the discretion of the Investigator.  
 Verify General Inclusion and Exclusion Criteria 
Screen the patient for General Inclusion and Exclusion Criteria.  
 General Inclusion Criteria 
1. Subject is 18 years of age or older 
2. Subject has signed the approved KAIZEN study Informed Consent Form (ICF) prior 
to any study-related procedures 
3. Subject has chronic, symptomatic lower limb ischemia defined as Rutherford 
classification (RC) 2-4 
4. Subject has a clinical indication for percutaneous transluminal angioplasty (PTA) 
intervention in the native SFA and/or POP (P1 and/or P2) artery via femoral access 

 
KAIZEN Clinical Study 
Cardiovascular Systems, Inc. 
 Revision G 
 
Page 39 of 67 
 General Exclusion Criteria 
5. Subject is female who is pregnant and/or breastfeeding  
6. Subject is currently participating in another investigational clinical study that has not 
completed the primary endpoint at the time of enrollment or that clinically interferes 
with the current study endpoints 
7. Subject is unwilling to follow the Investigator’s instructions or follow-up requirements 
8. Subject has had any non-diagnostic peripheral vascular intervention that was 
unsuccessful or had complications within 30 days before clinical trial treatment, per 
the following definition: 
a) >50% residual stenosis and/or 
b) Presence of angiographically assessed dissection (type D-F), perforation, distal 
embolization, thrombus and/or slow flow/no reflow 
9. Subject has had or requires any non-diagnostic coronary intervention within 30 days 
before clinical trial treatment  
10. Subject requires any planned non-diagnostic vascular (coronary or peripheral) 
intervention(s) within 30 days after clinical trial treatment 
11. Subject has any planned procedures or other medical conditions which, in the 
Investigator’s opinion, may interfere with the study result and/or subject’s optimal 
participation in the study 
12. Subject has had a prior major amputation within one year of the clinical trial treatment 
on either limb 
13. Subject has a planned major amputation on either limb 
14. Subject has life expectancy of ≤6 months 
15. Subject has history of coagulopathy or hypercoagulable bleeding disorder 
16. Subject has history of MI, or stroke/cerebrovascular accident (CVA) within 6-months 
prior to the clinical trial treatment 
17. Subject has unstable angina pectoris at the time of the clinical trial treatment 
18. Subject has untreatable hemorrhagic disease or platelet count <80,000mm3 or 
>600,000mm3 at baseline assessment 
19. Subject has evidence of active infection on the day of clinical trial treatment requiring 
oral or intravenous antibiotics 
20. Subject has known hypersensitivity or contraindication to contrast dye that, in the 
opinion of the investigator, cannot be adequately pre-medicated or cannot be 
exposed to the radiation required per the KAIZEN protocol  

 
KAIZEN Clinical Study 
Cardiovascular Systems, Inc. 
 Revision G 
 
Page 40 of 67 
21. Subject has known hypersensitivity/allergy to the investigational atherectomy system 
or protocol-related therapies (e.g., CSI OAS lubricant, soybean oil, egg yolk 
phospholipids, glycerin, nitinol, stainless steel, other stent materials, paclitaxel, 
anticoagulant, or thrombolytic medications) 
22. Subject has known contraindication to antiplatelet therapy 
23. Subject has serum creatinine > 2.5 mg/dL, unless on dialysis 
 Informed Consent  
Patients will undergo a medical record screening. The investigator will pre-screen the patient 
for General Inclusion Criteria and General Exclusion Criteria. The investigator will perform the 
informed consent process. The patient will sign the study ICF. The investigator will verify the 
patient meets ALL General Inclusion and No General Exclusion Criteria.  
The Sponsor will provide a template ICF to each site for IRB submission prior to the site 
initiation.  This template may be modified to meet the requirements of the individual study site.  
The Sponsor must pre-approve all changes to the ICF prior to initial submission to the IRB 
except for administrative changes (e.g., name of Investigator or institution, version date, etc.).  
If the ICF is amended by the reviewing IRB, a copy of the approved documents must be provided 
to the Sponsor prior to enrollment of subjects in the study.  
The Investigator or assigned designee must administer the approved ICF to each prospective 
study subject and obtain the subject's signature along with the date of consent prior to 
enrollment in the study.  Subjects unwilling to provide consent will not be enrolled in this study.  
The ICF must be obtained in accordance with Ordinance 36, GCP, and any additional applicable 
regulations and/or local regulations and laws, whichever represents the greater protection of 
the individual.  An investigator shall seek such consent only under circumstances that provide 
the prospective subject sufficient opportunity to consider whether or not to participate, and that 
minimize the possibility of coercion or undue influence. Subjects must be informed about their 
right to withdraw from the study at any time and for any reason without sanction, penalty, or loss 
of benefits to which the subject is otherwise entitled. The subject must be informed that 
withdrawal from the study will not jeopardize their future medical care.  The subject must be 
informed about that the Principal Investigator could also withdraw the subject from the trial at 
any time if it was felt to be in the subject’s best interest. The subject must be given the 
opportunity to make inquiries about the content of the written information and other study-related 
matters.  A copy of ICF must be given to each subject enrolled in the study.  The institutional 
standard subject consent form does not replace the KAIZEN study ICF. Subjects are not 
considered enrolled until the CSI Peripheral OAS Guide Wire enters the body. Informed consent 
is required at the Baseline visit (within 30 days of clinical trial treatment); however, does not 
expire unless specified per site requirements. 
If an Investigator uses the OAS and/or performs any study-related procedure(s) without first 
obtaining informed consent from the subject, the Investigator must report this to the study 
Sponsor within twenty-four (24) hours and to the reviewing IRB per IRB reporting 

 
KAIZEN Clinical Study 
Cardiovascular Systems, Inc. 
 Revision G 
 
Page 41 of 67 
guidelines after the use occurs. The ICF will be updated as appropriate based on new 
information and/or amendments to the protocol.  The updated ICF will be approved by the 
Sponsor and IRB prior to administering to subjects. 
 Verify Clinical Trial Treatment Inclusion and Exclusion Criteria 
After the ICF is signed, confirm subject meets the Clinical Trial Treatment Inclusion and 
Exclusion criteria. See Section 12 for Clinical Trial Treatment process.  
 Clinical Trial Treatment Inclusion Criteria 
24. De novo target lesion in the native SFA and/or POP (P1 and/or P2) artery 
25. All guidewires cross the Target Lesion within the true lumen without a sub-intimal 
course 
26. Target lesion with ≥70% stenosis [confirmed by visual estimate via angiography]  
27. Target reference vessel diameter (RVD) ≥3.0 mm and ≤6.0 mm [confirmed by visual 
estimate via angiography] 
28. Target lesion length ≤150 mm [confirmed by visual estimate via angiography] 
29. Subject has at least one patent tibial vessel (anterior tibial artery, posterior tibial 
artery, or peroneal artery) on the target leg, defined as having both:  
c) Blood flow to the foot, and  
d) No stenosis >50%  
30. Target lesion has visual evidence of calcification based on the KAIZEN calcification 
definition: 
IVUS Calcium Assessment 
Angiographic Calcium Assessment 
a) ≥ 270° of calcification 
 
b) ≥180° to 269° of calcification 
i) ≥ ½ of target lesion length calcified OR 
ii) > 50mm of calcium  
c) IVUS cannot cross lesion after 
one attempted pass 
i) Bilateral calcification AND ≥ ½ of target lesion 
length calcified OR 
ii) Bilateral calcification AND >50mm of calcium  
 Clinical Trial Treatment Exclusion Criteria 
31. Subject has had any Inflow treatment (ipsilateral iliac and/or common femoral artery) 
that was unsuccessful or had complications  prior to OAS guidewire insertion per the 
following definition:  
a) >50% residual stenosis and/or 
b) Presence of angiographically assessed dissection (type D-F), perforation, distal 
embolization, thrombus and/or slow flow/no reflow 

 
KAIZEN Clinical Study 
Cardiovascular Systems, Inc. 
 Revision G 
 
Page 42 of 67 
32. Target lesion is a chronic total occlusion (CTO) [confirmed by visual estimate via 
angiography]  
33. Subject has presence of any other hemodynamically significant lesions or 
asymptomatic lesions in the target limb requiring a planned surgical intervention or 
endovascular procedure 30-days after clinical trial treatment 
34. Presence of aneurysm in the target vessel 
35. Acute ischemia and/or acute thrombosis of the SFA and/or POP (P1 and/or P2) 
artery 
36. Angiographic evidence of perforation prior to insertion of the CSI Peripheral OAS 
Guide Wire 
37. Angiographic evidence of severe (type D-F) dissection prior to insertion of the CSI 
Peripheral OAS Guide Wire 
38. Planned use of atherectomy (other than CSI Peripheral OAS), laser, other debulking 
devices, CTO devices, cutting balloons, scoring balloons, specialty balloons or similar 
devices in the target limb 
 Before Clinical Trial Treatment   
• 
NON-TARGET LIMB Non-target limb treatment must occur either greater than 30 days 
prior to the clinical trial treatment or greater than 30 days after the clinical trial treatment 
in the study according to  
Section 12.4.  
• 
INFLOW LESIONS IN THE TARGET LIMB Inflow lesions (ipsilateral iliac and/or 
common femoral artery) in the target limb may be treated on the same day as the clinical 
trial treatment provided. 
o The inflow lesion must be successfully treated defined as residual stenosis ≤ 
50% without complications prior to insertion of the OAS guidewire in the target 
lesion to be revascularized. - Refer to Clinical Trial Treatment Exclusion 
Criteria 31. 
o The inflow lesion may only be treated with POBA or stenting. 
o Atherectomy, laser, other debulking devices, CTO devices, cutting balloons, 
scoring balloons, specialty balloons or similar devices cannot be used for the 
inflow treatment.  - Refer to Clinical Trial Treatment Exclusion Criteria 38.   
• 
NON-INFLOW, NON-TARGET LESIONS IN THE TARGET LIMB 
o Treatment of lesion(s) not considered Inflow or Target Lesion cannot occur on 
the day of the clinical trial treatment. 
o Non-target lesion treatment on the target limb must occur greater than 30 days 
after the clinical trial treatment in the study. - Refer to General Exclusion 
Criteria 8 and 10. 
• 
Access artery by operator’s preferred methodology for target limb treatment. 

 
KAIZEN Clinical Study 
Cardiovascular Systems, Inc. 
 Revision G 
 
Page 43 of 67 
• 
Cross the lesion using the operator’s preferred wire (CSI Peripheral OAS Guide Wire 
cannot be used at this point).  
• 
Assess Clinical Trial Treatment Inclusion/Exclusion criteria including Calcium Assessment 
using IVUS and/or angiography – Refer to Appendix A to determine when IVUS and 
angiography images are taken.  
o  IVUS Catheter – refer to IVUS IFU to determine appropriate IVUS catheter size.  
o One pass of the  IVUS Catheter will be attempted in order to perform Calcium 
Assessment. If IVUS cannot cross the lesion, do not attempt crossing with IVUS 
again. 
o Ensure angiographic images have been collected. 
o To complete the Calcium Assessment, Refer to Appendix B to determine how to 
use data from IVUS and/or angiography to determine Calcium Assessment.  
• 
Based on feedback from physician experts, there are no differences in patient 
characteristics that impact outcomes if calcium is measured by IVUS or angiography.  
• 
Refer to Figure 1 for the defined treatment area.  
o If the subject, target lesion, or vessel does not meet ALL Clinical Trial Treatment 
Inclusion Criteria and/or meets ANY Clinical Trial Treatment Exclusion Criteria, the 
subject will not be included in the study and is considered a screen fail. The subject 
will be treated per physician’s standard of care and will not be followed in the study 
or included in the analysis cohorts.  
o Recommended use of ruler to assess lesion length  
• 
Refer to Table 7 for Before Clinical Trial Treatment data collection requirements.  
 CLINICAL TRIAL TREATMENT 
 CSI Peripheral OAS Guide Wire Insertion 
• 
CSI Peripheral OAS Guide Wire must be delivered via a femoral artery.  
o A subject is Enrolled once the CSI Peripheral OAS Guide Wire enters the body.  
• 
The CSI Peripheral OAS Guide Wire must cross the Target Lesion within the true lumen 
without a sub-intimal course. 
o If the CSI Peripheral OAS Guide Wire crosses the Target Lesion without 
complication, the OAD can be inserted and proceed with Clinical Trial Treatment. 
per Section 12. Do not pre-dilate lesion prior to treatment with the OAD. 
o If the CSI Peripheral OAS Guide Wire is inserted with complications and/or does 
not cross the Target Lesion and/or does not cross the true lumen, the OAD must 
not be used. These subjects are treated per standard of care and will continue to 
be followed through the 6-Month Follow-up Visit. Refer to Section 14 for follow up 
instructions for these subjects. 
 
 

 
KAIZEN Clinical Study 
Cardiovascular Systems, Inc. 
 Revision G 
 
Page 44 of 67 
 OAD, POBA, DCB Procedure  
Attempt to insert the OAD.  
If the OAD cannot be inserted, the treating physician should treat the subject per standard of 
care and follow the subject through the 6-Month Follow-Up Visit. Refer to Section 14 for follow-
up instructions for these subjects.  
If the OAD is inserted, the subject is considered Enrolled and Treated.  
• 
Treat with OAD. Refer to the CSI Peripheral OAS, CSI Peripheral OAS Guide Wire, and 
CSI OAS Lubricant IFUs for treatment instructions.  
• 
Refer to Figure 1 for Solid Crown sizing to vessel size.  
• 
Pre-dilate with uncoated PTA catheter (POBA). Refer to the appropriate device IFU for 
further instruction (e.g., balloon sizing, nominal pressure). The balloon diameter should 
be sized appropriately to the reference vessel diameter. The balloon length should 
correspond to the length of the area treated with OAD. Do not use high pressure 
balloons with nominal pressure 20 atm or greater.   
o Inflate the balloon at controlled low-pressure. 
o Continue to inflate to nominal pressure. Do not exceed nominal pressure.  
 
If waist is seen at nominal pressure, recommend repeating OAD treatment 
(unless a complication occurs). 
o Continue inflation as needed.  
• 
Once POBA pre-dilation treatment is complete, deploy DCB (Medtronic IN.PACT™ 
Admiral™). Refer to the appropriate device IFU for further instruction. (e.g., balloon sizing, 
nominal pressure). 
Refer to Table 7 and Appendix A for Clinical Trial Treatment data collection and imaging 
requirements. Required imaging time points are described for Clinical Trial Treatment, however 
additional imaging per standard of care should be collected. 
 

 
KAIZEN Clinical Study 
Cardiovascular Systems, Inc. 
 Revision G 
 
Page 46 of 67 
 FOLLOW-UP 
The following sections describe follow-up requirements for all enrolled subjects in the KAIZEN 
study. All follow-up assessments and visits must be performed by someone who is study-trained 
and delegated to perform study follow-up. 
• 
If the subject is seen by the Investigator between scheduled follow-up visits (i.e., not a 
study required assessment or visit), the assessment/visit should not be recorded on an 
CRF.  However, if any adverse events are noted, an Adverse Event (AE) CRF needs to 
be completed for each event. 
• 
If a revascularization occurs, images are required to be submitted for CEC review. The 
subject will still be required to return for the next scheduled follow-up visit if the 
unscheduled visit is out of the compliance follow-up window.   
 30-Day In-hospital Follow-up Visit or Telephone Follow-up 
Assessment 
All Enrolled / Enrolled and Treated subjects are required to have a follow-up assessment 
occur at 30 days (+14 days) after enrollment. The 30-Day assessment can be an in-hospital 
follow-up visit or may occur by telephone assessment.  
Refer to Table 7 for 30-Day In-hospital Follow-up Visit or Telephone Follow-up Assessment 
data collection requirements.  
 6-Month Follow-up Visit 
All Enrolled subjects are required to have a 6-Month (+30 days) Follow-up assessment phone 
call or in-hospital visit to monitor for adverse events.  
All Enrolled and Treated subjects are required to have a Follow-up assessment occur at 6-
Months (+30 days) after clinical trial treatment. The 6-Month visit must be an in-hospital visit. 
Refer to Table 7 for 6-Month Follow-up Visit data collection requirements. 
All subjects will be exited from the study following the 6-month Follow-up visit.  
 
 OVERVIEW OF IMAGING DATA FLOW 
Perform, record, and submit angiography, IVUS, and DUS images per the appropriate core lab 
guidelines. Refer to Appendix A and Table 7 for imaging requirements. Diagnostic images taken 
≤30 days prior to Clinical Trial Treatment may be requested in supplement to Clinical Trial 
Treatment images to verify Inclusion/Exclusion Criteria.  

 
KAIZEN Clinical Study 
Cardiovascular Systems, Inc. 
 Revision G 
 
Page 47 of 67 
 ADVERSE EVENTS  
 Adverse Event Requirements 
For the purposes of this study the following events will be collected:  
• 
All Clinical Trial Treatment Adverse Events 
• 
All SAEs  
• 
All ADEs, SADEs, USADEs 
o For both the CSI Peripheral OAS and the Medtronic IN.PACT™ Admiral™ DCB 
 Adverse Event Definitions 
An Adverse Event (AE) is any disease or injury, or its clinical signs occurring in a subject who 
has been treated with an investigational device or post-marketing study device (Per Ordinance 
of the Ministry of Health and Welfare No.36) 
A Serious Adverse Events (SAE) is an adverse event that (per ISO14155:2020): 
a) Led to death, 
b) Led to serious deterioration in the health of the subject, users, 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 
disease, or 
o In-patient or prolonged hospitalization, or 
o Medical or surgical intervention to prevent life-threatening illness or injury or 
permanent impairment to a body structure or a body function, 
c) Led to foetal distress, foetal death or a congenital abnormality or birth defect 
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. 
An Adverse Device Effect (ADE) is an adverse event-related to the use of an investigational 
medical device (per ISO14155:2020). 
Note 1: This definition includes adverse events resulting from insufficient or inadequate 
instructions for use, deployment, implantation, installation, or operation, or any malfunction of 
the investigational medical device. 
Note 2: This definition includes any event resulting from use error or from intentional misuse 
of the investigational medical device. 
Note 3: This includes ‘comparator’ if the comparator is a medical device. 

 
KAIZEN Clinical Study 
Cardiovascular Systems, Inc. 
 Revision G 
 
Page 48 of 67 
A Serious Adverse Device Effect (SADE) is an adverse device effect that has resulted in 
any of the consequences characteristic of a serious adverse event (per ISO14155:2020). 
An Unanticipated Serious Adverse Device Effect (USADE) is a serious adverse device 
effect which by its nature, incidence, severity or outcome has not been identified in the current 
risk assessment (per ISO14155:2020).  
Note 1: Anticipated serious adverse device effect (ASADE) is an effect which by its nature, 
incidence, severity or outcome has been identified in the risk assessment. 
 Adverse Event Relatedness 
The relatedness of the AE will be classified by the Investigator for both the CSI Peripheral OAS 
and the Medtronic IN.PACT™ Admiral™ DCB and adjudicated by the CEC for the CSI Peripheral 
OAS.  The Investigator will use the following definitions in classifying the relationship of the 
AE: 
• 
Peripheral Orbital Atherectomy System-Related:  AE is directly related to the 
investigational device(s) used in treatment of the lesion. 
• 
Clinical Trial Treatment Procedure-Related:  AE is directly attributable to the clinical 
trial treatment. 
• 
Target Limb-Related:  AE is related to the limb in which OA was performed. 
• 
IN.PACT Admiral Balloon-Related: AE is directly related to the IN.PACT Admiral 
device used in treatment of the lesion 
 Reporting Adverse Events and Follow-Up 
Adverse events should be reported throughout the subject’s participation in the trial and not 
only at study mandated visits.   Any subject who has unresolved adverse events at the end of 
their study participation will continue to be followed by the investigator per their standard of 
care. Source documents should be submitted to the Sponsor for review of the Adverse Event. 
Prior to submission to the Sponsor the source documents are to be appropriately redacted to 
remove the subject’s name, and any other identifying information and the subjects unique 
Subject ID should be inserted on every page.   
All adverse events, including subject deaths, must be reported on the AE CRF. In the event an 
adverse event cannot be submitted through the electronic database in a timely fashion, 
submission may be made to the Sponsor via email to 
 This does not 
replace the EDC reporting system; however, all information must still be entered in the EDC 
system as soon as feasible. 
All efforts should be made to notify the Sponsor as soon as possible after first learning of an 
SAE.  Additional information, obtained after the initial SAE, must also be reported as soon as 
possible to the study Sponsor.  Deaths must be reported on the Study Exit CRF.  If available, a 
copy of death records, medical records for the events that led to the subject’s death, death 

 
KAIZEN Clinical Study 
Cardiovascular Systems, Inc. 
 Revision G 
 
Page 49 of 67 
certificate and an autopsy report must be sent to the Sponsor as soon as they become available. 
Adverse event information will be collected up until each subject’s study exit or study 
completion.   
All AEs will be reviewed by the Sponsor and determined whether the AE meets regulatory 
reporting requirements.  These events will be reported to the country’s regulatory authorities 
according to the requirements of the country by the Sponsor or designee. The Investigator is 
responsible for reporting to the IRB, as applicable.  In cases where the CEC does not agree 
with the Investigator’s final assessment/classification of an adverse event, the Sponsor shall 
communicate both opinions to the regulatory authorities, if applicable. 
Adverse events meeting the definition of SAEs, SADEs, or USADEs that result in death 
are to be reported to the Sponsor within 24 hours of becoming aware of the event.  
Documentation of AE on the CRF is sufficient for Sponsor reporting; however, if the 
CRF cannot be completed within the specified timeframe, reporting can be completed 
via email to 
.  If the event is reported outside of the required 
timeframe, a protocol deviation must be reported.  
 Device Deficiencies  
All  device deficiencies of the study device and Medtronic IN.PACT™ Admiral™ DCB must be 
documented on the CRF and reported to Sponsor, preferably within 24 hours of knowledge of 
the event. Reporting of device deficiencies includes reporting malfunctions, use errors, and 
inadequacy in the information supplied by the manufacturer including labeling. Documentation 
of device deficiencies  on the CRF is sufficient for Sponsor reporting.  However, if the CRF 
cannot be completed within the specified timeframe, reporting to the Sponsor can be completed 
via email or phone.   In the event of a device  deficiency relating to the study device, return the 
suspected device to the Sponsor for analysis. All device deficiencies will be reported to 
regulatory authorities as required and included in the clinical results (e.g., final report). 
If the investigator or site staff becomes aware of death or any SAE suspected to be attributable 
to device deficiencies of the  study device or Medtronic IN.PACT Admiral™ DCB, the principal 
investigator shall immediately notify the Sponsor and the IRB. In such cases, the principal 
investigator shall provide additional relevant information upon the request of the Sponsor, the 
head of the medical institution, or the IRB. 
 PROTOCOL DEVIATIONS 
A protocol deviation is defined as an instance(s) of failure to follow, intentionally or unintentionally, 
the requirements of the protocol.  The Investigator is not allowed to deviate from the protocol 
except: 
• 
With prior approval from the study Sponsor, and the local IRB if applicable, or 
• 
Under emergency circumstances to protect the rights, safety and well-being of the 
subjects, or 

 
KAIZEN Clinical Study 
Cardiovascular Systems, Inc. 
 Revision G 
 
Page 50 of 67 
• 
Inadvertent protocol deviations (e.g., missed lab test) or deviation outside the control of 
the Investigator/site (e.g., subject does not show up for a scheduled follow-up visit, etc.), 
are not expected to have prior Sponsor approval;  
All deviations must be documented separately on a CRF. Documentation of the deviation should 
include a description of the deviation, the reasons thereof.  Protocol Deviations should be reported 
to the Sponsor and reviewing IRB according to their requirements. If the investigator has failed to 
comply with the protocol to eliminate immediate hazards to subjects or for other inevitable medical 
reasons the investigator shall document the deviation and immediately report it to the Sponsor 
and head of medical institution. Documentation of the Protocol Deviation on the CRF is sufficient 
for Sponsor reporting, however if the CRF cannot be completed within the specified timeframe, 
reporting to the Sponsor can be completed via email or phone. 
The Sponsor may implement measures to reduce the number of deviations such as, but limited 
to, a site Corrective Action Preventive Action plan (CAPA), protocol amendment or additional site 
training.   Repeated and serious non-compliance by the site that is not adequately addressed by 
the PI or his/her staff may lead to corrective action taken by Sponsor including requesting the 
site’s withdrawal from the study. 
 STUDY EXIT 
Active subject participation is expected to last for a maximum of 6 months. The Study Exit CRF 
must be completed when a subject exits the study early or completes the required follow-up 
visits.  Reasons for exiting the study include, but are not limited to the following:   
• 
Subject Lost to Follow-up: If a subject fails to comply with the Protocol requirements to 
attend the follow-up visit, the study site should make at least three (3) documented 
attempts to contact the subject and/or family or emergency contact and send a letter to 
the last known address of the subject by traceable mail before considering the subject 
lost to follow-up.  
• 
Voluntary Withdrawal: A subject may voluntarily withdraw from the study at any time.  
If the subject had an adverse event, where possible, the subject should be followed until 
the resolution of the adverse event. 
• 
Investigator Withdrawal:  An Investigator may withdraw a subject for reasons, which 
may include failure to keep appointments, termination or cancellation of the study by the 
Sponsor, etc. 
• 
Study Completion:  This will be after the last scheduled follow-up visit has occurred as 
defined by the Protocol or subsequent amendments. 
• 
Death:  The Adverse Event CRF must also be completed. 
• 
Other:  Includes other possible reasons for exiting the study which may not be outlined 
above, as determined by the Sponsor or Investigator.   

 
KAIZEN Clinical Study 
Cardiovascular Systems, Inc. 
 Revision G 
 
Page 51 of 67 
 STUDY TERMINATION 
This study may be suspended or prematurely terminated if there is sufficient reasonable cause. 
Written notification, documenting the reason for study suspension or termination, will be 
provided by the suspending or terminating party to study Principal Investigators and applicable 
reviewing bodies. If the study is prematurely terminated or suspended, the Principal Investigator 
will promptly inform the IRB and will provide the reason(s) for the termination or suspension.  
Circumstances that may warrant termination include, but are not limited to: 
• 
Determination of unexpected, significant, or unacceptable risk to subjects 
• 
Insufficient adherence to protocol requirements 
• 
Data that are not sufficiently complete and/or evaluable  
• 
Sponsor management decision to discontinue the study 
 STUDY RESPONSIBILITIES AND MANAGEMENT 
 Conduct of Study 
The study shall be conducted in accordance or compliance with the: 
• 
Protocol; 
• 
Study agreement; 
• 
Conditions of approval imposed by the IRB 
• 
Ethical principles that have their origin in the Declaration of Helsinki; 
• 
Any local or national regulations, as appropriate, including ICH E6: Good Clinical Practices 
(GCP) and Ordinance 36: Ministerial Ordinance on Good Clinical Practice (GCP) for 
Medical Devices  
The study cannot begin until approval from the Sponsor, applicable IRB, and regulatory 
authorities are obtained.  In addition, appropriate insurance for the study to cover the cost of 
treatment of subjects in the event of a study-related injury, will be obtained prior to the start of 
the study, according  to Japan requirements.   
 Investigator Selection and Responsibilities 
 Investigator Training 
All treating physicians must be experienced in peripheral artery treatment (e.g., balloon 
angiography, stenting, atherectomy, etc.).  The Sponsor will be responsible for ensuring that 
physicians are properly trained in the use of the CSI Peripheral OAS and on the protocol prior 
to enrolling subjects in this study.  Training will be performed by qualified personnel from the 
Sponsor or designee.   

 
KAIZEN Clinical Study 
Cardiovascular Systems, Inc. 
 Revision G 
 
Page 52 of 67 
Each investigator must complete at least one (1) roll-in. This will ensure proper device training, 
and procedural and data collection adherence.  Up to three (3) roll-in subjects per Investigator 
(Principal Investigator and/or Sub-Investigator) are permitted. Roll-in subjects will be 
consented and followed per protocol, and their data will be reported separately. 
 Investigator / Investigational Site Delegation 
Only site personnel delegated in writing by the Investigator will conduct study-related 
functions.  All individuals delegated study-related functions must have documented training, 
at a minimum, on the study protocol.   
 Investigator Responsibilities 
The Principal Investigator (PI) is responsible for protecting the rights, safety, and welfare of 
study subjects.  In addition, the Investigator is responsible for:  
• Providing agreement on the content of the protocol and conduct the study in 
compliance with the protocol and applicable regulations 
• Providing adequate oversight of all study-related activities 
• Maintaining control over the investigational devices, ensuring the devices are used 
solely by authorized users under his or her direct supervision, tracking the receipt and 
disposition of all study devices, and returning all devices upon the completion of 
termination of the study 
• Disclosing financial, or other information, that may constitute a potential conflict of 
interest  
• Maintaining source documents throughout the study and making them available/ 
providing direct access as requested during monitoring visits, audits/inspections, and 
IRB review 
• Providing a current signed and dated curriculum vitae (CV). If any changes affecting 
the PI’s qualification, an updated CV is required to be sent to the Sponsor 
• Avoiding improper influence on, or inducement of the subject, monitor and Sponsor or 
other parties participating in, or contributing to, the study by complying with the 
informed consent process for the subject, study agreements and IRB approval of the 
study 
• Obtaining IRB approval of the protocol, ICF and any other study-related documents 
prior to enrolling subjects.  The Investigator will also be responsible for notifying the 
Sponsor within five (5) working days of becoming aware of the IRB withdrawing their 
approval of the study.  
• Explain the appropriate use of the investigational devices to each subject. 

 
KAIZEN Clinical Study 
Cardiovascular Systems, Inc. 
 Revision G 
 
Page 53 of 67 
• If a subject is receiving treatment by another primary physician, the investigators etc. 
shall inform the primary physician, with prior consent of the subject, that the subject 
will participate in the clinical trial. 
• The head of the medical institution and the investigators etc. shall beforehand take 
necessary measures to ensure that adequate medical care is provided to a subject for 
any adverse event. 
• The investigator shall promptly notify the subjects if the study is prematurely 
terminated or suspended and shall provide appropriate medical care to the subjects 
and take other necessary measures.  
• The investigators etc. shall inform subjects of the fact that medical care is needed for 
adverse event(s) of which the investigator becomes aware, if applicable. 
• Upon completion of a clinical trial, the investigator shall report the completion in 
writing and submit a written summary of the trial’s outcome to the head of the medical 
institution. 
The Investigator for each site may not begin enrollment until Sponsor receives and approves 
(when necessary) required documents, including a signed Study Agreement, IRB protocol and 
ICF approvals.  
It is acceptable for the Investigator to delegate study-related functions to an associate or Sub-
Investigator or trained Study Coordinator; however, the Investigator remains responsible for 
the proper conduct of the clinical investigation, including obtaining and documenting proper 
study informed consent, collecting all required data, submitting accurate and complete CRFs, 
maintaining applicable study records, etc. 
At each site, appropriate procedures must be followed to maintain the security and 
confidentiality of individually identifiable health information, and will comply with all applicable 
health information confidentiality laws and regulations, including as applicable, the U.S. 
HIPAA Standards for Privacy of Individually Identifiable Health Information, Title 45 of the U.S. 
Code of Federal Regulations, Part 160 and 164, and the applicable health information privacy 
laws of any state or foreign jurisdiction (including Japan’s Act on the Protection of Personal 
Information and applicable circulars published by Japan’s Ministry of Health, Labor and 
Welfare. Each site may have its own internal procedures or requirements for use and release 
of subject medical information in research studies. Each Investigator is responsible for 
obtaining appropriate approvals, consents, or releases of medical information as dictated by 
their relevant subject privacy laws. 
 MONITORING  
The study Sponsor, or designate, will monitor the study to ensure proper conduct and progress 
of the study including adequate protection of human subjects and the integrity of the clinical study 
data is of the highest quality.  This will include routine, periodic visits to study sites to confirm 
reported results are consistent with source documentation, appropriate subject enrollment, 

 
KAIZEN Clinical Study 
Cardiovascular Systems, Inc. 
 Revision G 
 
Page 54 of 67 
accurate investigational device accountability, compliance with all applicable laws and 
regulations, and compliance with the protocol, and may also include qualification, initiation and 
close-out visits. Remote monitoring may also occur.  A risk-based monitoring approach will be 
utilized and the data points that are source data verified as well as the frequency of monitoring 
visits will be based upon enrollment, data integrity, and site compliance.   
Each monitoring visit will be documented via a monitoring report and a letter will be sent to the 
site’s PI to document the study status at his/her site.  The PI will be responsible for ensuring that 
all action items identified during the monitoring visit are resolved in a timely manner.   
A Monitoring Plan will be written for the study outlining the strategy, methods, responsibility, and 
requirements for monitoring the study. The Monitoring Plan will be kept separate from the 
protocol. Each investigational site will allow monitoring activities to be conducted at their site, 
including visits by the study Sponsor or their designate.  Therefore, access to the subjects’ files 
must be allowed as per the informed consent at the Investigator's site.  
 INDEPENDENT PHYSICIAN REVIEWER 
Subjects will be enrolled in KAIZEN based on treating physician’s assessment. An Independent 
Physician Reviewer will use Before Clinical Trial Treatment images, quantified core lab 
assessments of the images, including quantitative vascular analysis (QVA), and his expert 
judgement to verify the treating physician’s assessment of eligibility criteria listed in Section 11.4. 
A charter or operating procedures will be written to define the responsibilities of the Independent 
Physician Reviewer including format and documentation to be maintained, etc.  The Independent 
Physician Reviewer will be an independent vascular surgeon, interventional cardiologist, 
interventional radiologist or cardiologist who has experience with review of peripheral arteries 
using IVUS and angiography.  The Independent Physician Reviewer will not be affiliated with the 
Sponsor, study/data management, or a site that is actively participating in the study.  
 CLINICAL EVENTS COMMITTEE (CEC) 
A Clinical Events Committee (CEC) will be established for this clinical study to adjudicate adverse 
events reported during the study using angiographic imaging and site reported source documents. 
IVUS imaging will not be used to adjudicate adverse events. The CEC will consist of a minimum 
of three (3) physicians with vascular experience who are not affiliated with the Sponsor or actively 
participating in the study and are independent to an institution conducting this study. A charter 
will be written to define the responsibilities of the CEC including the events to be adjudicated, 
documentation to be maintained, meeting format, etc. Committee membership rosters will be 
maintained at CSI and will be made available upon request.  
 DATA MONITORING COMMITTEE (DMC) 
A Data Monitoring Committee (DMC) will be established for this clinical study to assess at 
intervals during the study, the safety data and to recommend to the Sponsor whether to 
continue, suspend, modify or terminate the study early for safety reasons. The DMC will consist 
of at least two (2) physicians with vascular experience (one (1) of which may be a non-

 
KAIZEN Clinical Study 
Cardiovascular Systems, Inc. 
 Revision G 
 
Page 56 of 67 
 
 Roll-in Analysis Set 
All roll-in subjects will be analyzed as a roll-in analysis set. The roll-in analysis set will be 
analyzed separately from the enrolled population. 
 Timing of Analysis 
Analyses of all primary and secondary endpoints will be performed after all FAS subjects have 
completed the 6-month follow-up assessment and all data have been entered and verified in 
the database. 
 
 
 Identifying Target Lesions 
The protocol permits treatment of only one (1) target lesion in this study. The protocol specifies 
that the target lesion must be contained entirely within the protocol-defined target area (SFA 
and POP including P1 and P2). For the purposes of analysis, in addition to the target lesion any 
lesion treated with the OAD will be considered a target lesion regardless of the protocol 
definition. 
Endpoint data assessed on a subject-level basis requires that all success/failure criteria be 
assessed on all target lesions (i.e., all lesions will need to meet the specified endpoint criteria 
to be qualified as a success). 
In cases where treatment of multiple target lesions has been performed, or treatment has been 
performed outside of the target area, the subject will be excluded from the PP analysis set on 
the basis of an inclusion or exclusion criteria deviation. 
 Endpoint Analyses 
The following analyses will be performed on the populations indicated.    
 Primary Endpoint Analysis 
Analysis of the primary endpoint of Acute Device Success will be assessed post-procedure 
and performed on the mITT analysis set. Acute Device Success is a composite endpoint 
comprised of: 
a) The number of subjects with an Angiographic Core Lab assessed post OAD+POBA 
(and prior to the DCB) residual stenosis of ≤50% and, 
b) No OAS-related severe angiographic complications defined as severe dissections (D-
F), perforation, or distal emboli requiring additional treatment during the procedure as 
adjudicated by the CEC.  
A subject is considered a success if the OAD crosses the lesion and both criteria are met. The 
rate of Acute Device Success and the corresponding 95% confidence interval will be 

 
KAIZEN Clinical Study 
Cardiovascular Systems, Inc. 
 Revision G 
 
Page 57 of 67 
presented. The lower confidence bound of the acute device success rate will be compared 
against the performance goal of 50%. 
 Primary Endpoint Sensitivity Analysis 
Sensitivity analyses will be performed by assessing the observed rate of Acute Device 
Success in the ITT, FAS, and PP analysis sets. 
 Secondary Endpoint Analysis 
There are no formal hypothesis tests associated with the secondary endpoints.  Secondary 
endpoints will be assessed with the appropriate statistical method appropriate for the type of 
data analyzed (e.g., rates, changes over time, Kaplan-Meier). 
 Roll-in Analysis 
All primary and secondary endpoint analyses will be performed for the roll-in subjects and 
will be reported separately.   
 RISK ANALYSIS 
 Risks Associated with OAS 
Study subjects will be informed of all known potential side effects and complications associated 
with the study treatment and evaluations prior to enrollment in the study.  
Potential adverse events that may occur and/or require intervention as a result of the use of this 
device include, but are not limited to:  
• 
Allergic reaction to medication/media/OAD components 
• 
Amputation 
• 
Anemia  
• 
Aneurysm 
• 
Bleeding complications which may require transfusion 
• 
Cerebrovascular accident (CVA) 
• 
Death  
• 
Distal embolization (air, tissue, thrombus, device) 
• 
Entry site complications 
• 
Hemolysis 
• 
Hypotension/hypertension 
• 
Infection 
• 
Myocardial infarction 
• 
Pain 
• 
Pseudoaneurysm 
• 
Restenosis of treated segment that may require revascularization 

 
KAIZEN Clinical Study 
Cardiovascular Systems, Inc. 
 Revision G 
 
Page 58 of 67 
• 
Renal insufficiency/failure 
• 
Slow flow or no reflow phenomenon 
• 
Thrombus 
• 
Vessel closure, abrupt 
• 
Vessel injury, including dissection and perforation that may require surgical repair 
• 
Vessel spasm 
• 
Vessel occlusion  
Possible complications that may be associated with use of the OAS Peripheral Guide Wire are 
similar to those that may occur during percutaneous transluminal angioplasty and during other 
types of atherectomy procedures including:  
• 
Bleeding at the vascular access site 
• 
Perforation 
• 
Dissection 
• 
Acute vessel closure 
• 
Slow flow 
• 
Contrast media reaction 
• 
There may also be complications associated with kinks, distortion, fracture or other 
damage to the guide wire that could lead to patient injury or death. 
 Risk Associated with DCB  
Medtronic IN.PACT™ Admiral™ DCB will be used in this clinical study.  A systematic review 
and meta-analysis of randomized controlled trials (RCT)investigating paclitaxel-coated devices 
in the femoral and/or popliteal arteries was performed using data from 28 RCTs with 4663 
patients.21 The analysis showed that the mortality rate was greater in patients treated with 
paclitaxel devices compared to control at the 2-year and 5-year follow-up suggesting a 
possibility of an increased mortality risk. However, there was no difference at the 1-year follow-
up. Risk assessment has been continued carefully in Japan and overseas and have not found 
suggestions of higher mortality among patients treated with paclitaxel.  
  Risk Minimization 
The Peripheral OAS undergoes rigorous bench and animal testing to ensure device safety. In 
addition, the device and patient risks are reviewed and mitigated as far as possible following 
CSI Risk Management procedures which are compliant with Application of risk management to 
medical devices - ISO14971.  The first-generation model of the peripheral OAS received CE 
Mark in February 2007 and US FDA 510(k) clearance in August 2007. The current generation 
model of the Peripheral OAS intended to be used in KAIZEN received US FDA clearance in 
July 2019. The Peripheral OAS is commercially available in the US, Germany, Austria, France, 
Malaysia, Singapore, and United Arab Emirates. Peripheral OAS has been studied extensively 
by CSI in over 4,000 subjects and has a well-established safety profile in the US population. In 
addition, KAIZEN study investigators will undergo training, and subjects will be screened and 

 
KAIZEN Clinical Study 
Cardiovascular Systems, Inc. 
 Revision G 
 
Page 59 of 67 
evaluated for medical histories/conditions that may compromise successful performance of the 
device.  
  Minimization Bias 
Potential sources of bias in the KAIZEN study that may compromise the outcome of the 
study may result from the selection of subjects, treatment of subjects, and evaluation of 
study data.  Methods incorporated in the study design to minimize potential bias include 
(but are not limited to):   
1. Subjects will be screened to confirm eligibility for enrollment with defined inclusion 
and exclusion criteria prior to enrollment. 
2. A minimum of 1, but up to 3 roll-in subjects per Investigator will be permitted. This will 
ensure proper device training, and procedural and data collection adherence. Roll-in 
subjects will be consented and followed per protocol, and their data will be reported 
separately. 
3. Critical outcome variables, including endpoints, are objectively measured.  Electronic 
data collected to support the primary endpoint will be verified against source 
documents. 
4. An independent core lab will perform assessment of all IVUS and angiographic 
images  
5. An Independent Physician Reviewer will verify the treating physician's assessment of 
eligibility criteria using objective computer-aided imaging. Only subjects who meet 
the Independent Physician review will be included in the primary analysis population. 
6. All study clinicians and CSI personnel and their delegates will be trained on their 
respective aspects of the KAIZEN study using standardized training materials. 
7. No single site can contribute more than 25% of the study enrollments, not including 
roll-in subjects. 
8. A pre-specified statistical analysis plan will be developed prior to analyzing data 
which will document all analyses and analysis methods. 
9. An independent statistician will complete analysis per statistical analysis plan. 
10. Classification rules are defined for important subjective variables such as device-
related, procedure-related, and target limb-related events   
11. An independent Clinical Events Committee (CEC) will be utilized to regularly review 
and adjudicate reported adverse events and will be considered final adverse event 
disposition.  
12. An external, international CRO, will lead study related activities in Japan. 
  
In summary, potential sources of bias that may be encountered in the KAIZEN study have 
been considered and minimized by careful study design. 
 Benefits 
Subject’s participation in this study is voluntary.  There is no direct additional benefit to the 
subjects enrolled in the study.  Information gathered from this study will help confirm the safety 
and efficacy of the OAS in treating de novo, moderate to severe calcific atherosclerotic lesions 

 
KAIZEN Clinical Study 
Cardiovascular Systems, Inc. 
 Revision G 
 
Page 60 of 67 
in the lower limbs.  Ultimately, this knowledge may provide physicians additional information 
which may help improve the care for future subjects.  
 CONFIDENTIALITY 
All information and data sent to the Sponsor concerning subjects or their participation in this study 
will be considered confidential.  All data used in the analysis and reporting of this evaluation will 
be used in a manner without identifiable reference to the subject.   
The Investigator agrees to visits by Sponsor staff, and/or designee, and applicable regulatory 
authorities to review the study-related documents and subjects’ medical records, including any 
test or laboratory data that might have been recorded on diagnostic test media (e.g., angiographic 
cines). 
 RECORD KEEPING   
 Medical Institution  
Per Article 61 of Ordinance 36, the medical institution shall appoint a record-keeping manager.  
The record keeping manager specified in the preceding paragraph shall retain the following 
records (including documents) until the day on which marketing approval of the test device is 
obtained (or the day 3 years after the date of notification in the case of a notification pursuant 
to Article 32, Paragraph 3 or Article 43, Paragraph 3) or the day 3 years after the date of 
premature termination or completion of the clinical trial, whichever comes later:  
1) Source documents  
2) The contract or Approval Document, informed consent forms, written information and other 
documents prepared by persons engaged in the clinical trial at the medical institution in 
accordance with this Ministerial Ordinance, or their copies  
3) The protocol, documents obtained from the IRB etc. pursuant to Article 51, Paragraphs 1 
through 3 (IRB documentation), and other documents obtained in accordance with this 
Ministerial Ordinance  
4) Records of trial-related duties such as control/accountability of investigational devices 
  Sponsor 
Per Article 34 of Ordinance 36, the Sponsor shall appropriately retain the following records 
(including documents and data) related to the clinical trial until the day on which marketing 
approval of the test device is granted (or the day 3 years after the date of notification in the case 
of a notification pursuant to Article 32, Paragraph 3) or the day 3 years after the date of 
premature termination or completion of the clinical trial, whichever comes later:  
1) Protocol, contracts, clinical trial reports, and other documents prepared by the Sponsor in 
accordance with this Ministerial Ordinance, or copies thereof.  

 
KAIZEN Clinical Study 
Cardiovascular Systems, Inc. 
 Revision G 
 
Page 61 of 67 
2) Case report forms, the written notification pursuant to Article 51, Paragraph 6, and other 
records obtained from the heads of medical institutions or investigators etc. in accordance 
with this Ministerial Ordinance  
3) Records of the duties related to sponsoring and managing the clinical trial, such as 
monitoring and audits (excluding those specified in the preceding two items and Items (5)) 
4) Data generated in conducting the clinical trial  
5) Records specified in Article 24, Paragraph 5  
The Sponsor who resides outside Japan shall have a clinical trial in-country representative 
retain the records specified in Article 24, Paragraph 5, during the period specified in the 
preceding paragraph. 
 PROTOCOL AMENDMENTS 
The protocol, IB, CRFs, ICF and other subject information, or other study documents shall be 
amended as needed throughout the study whenever important new information becomes 
available that may be relevant to the proper conduct of the clinical study, such as information on 
the quality, efficacy and safety of the test device. 
The study Sponsor will submit any significant change to the protocol, including a justification for 
the change, to the appropriate regulatory authorities and to the Investigator to obtain approval 
from the local IRB.  The Investigator will only implement the protocol amendment after approval 
of the IRB, and regulatory authority, if applicable.  Administrative changes to the protocol will be 
submitted to the IRB for notification.  Investigators shall sign any approved protocol amendment 
to indicate agreement with the amendment. 
 PUBLICATION OF STUDY DATA 
Any previously unpublished information provided to the Investigator by the Sponsor, such as 
patent applications, manufacturing processes and basic scientific data, is considered confidential 
and will remain the sole property of the Sponsor.  The Investigator agrees to use this information 
only in accomplishing this study and will not use it for other purposes without the Sponsor’s written 
consent. 
A complete manuscript describing the results of this study is considered the primary publication 
for the study. Study publications and authorship will be determined by the Sponsor based upon 
the submission of ideas, significant contributions to the study design, study enrollment, publication 
development, etc. An Investigator may also want to publish the study experience from his/her own 
site. In either case, these secondary publications can only be published after the complete multi-
center study publication is published. 
The Sponsor reserves the right to review and approve all publications and presentations utilizing 
the study data.  The Investigator may proceed with the publication when notified by the Sponsor. 
 

 
KAIZEN Clinical Study 
Cardiovascular Systems, Inc. 
 Revision G 
 
Page 62 of 67 
 BIBLIOGRAPHY 
1.  
Patel MR, Conte MS, Cutlip DE, Dib N, Geraghty P, Gray W, Hiatt WR, Ho M, Ikeda K, 
Ikeno F, Jaff MR, Jones WS, Kawahara M, Lookstein RA, Mehran R, Misra S, Norgren L, 
Olin JW, Povsic TJ, Rosenfield K, Rundback J, Shamoun F, Tcheng J, Tsai TT, Suzuki Y, 
Vranckx P, Wiechmann BN, White CJ, Yokoi H, Krucoff MW. Evaluation and treatment of 
patients with lower extremity peripheral artery disease: consensus definitions from 
Peripheral Academic Research Consortium (PARC). J Am Coll Cardiol. 2015;65(9):931-
941. doi:10.1016/j.jacc.2014.12.036. 
2.  
Rocha-Singh KJ, Zeller T, Jaff MR. Peripheral arterial calcification: prevalence, 
mechanism, detection, and clinical implications. Catheter Cardiovasc Interv. 
2014;83(6):E212-20. doi:10.1002/ccd.25387. 
3.  
Rutherford RB, Baker JD, Ernst C, Johnston KW, Porter JM, Ahn S, Jones DN. 
Recommended standards for reports dealing with lower extremity ischemia: revised 
version. J Vasc Surg. 1997;26(3):517-538. 
4.  
Yost M, The Sage Group. Japan Peripheral Artery Disease and Critical Limb Ischemia 
Prevalence and Incidence.; 2017. 
5.  
Higashi Y, Miyata T, Shigematsu H, Origasa H, Fujita M, Matsuo H, Naritomi H, Matsuda 
H, Nakajima M, SEASON Investigators. Baseline Characterization of Japanese Peripheral 
Arterial Disease Patients - Analysis of Surveillance of Cardiovascular Events in 
Antiplatelet-Treated Arteriosclerosis Obliterans Patients in Japan (SEASON). Circ J. 
2016;80(3):712-721. doi:10.1253/circj.CJ-15-1048. 
6.  
Hosaka A, Miyata T, Onishi Y, Liao L, Zhang Q. Clinical and economic burden in patients 
with diagnosis of peripheral arterial disease in a claims database in Japan. Clin Ther. 
2014;36(8):1223-1230, 1230.e1-4. doi:10.1016/j.clinthera.2014.06.013. 
7.  
Hiramoto JS, Teraa M, de Borst GJ, Conte MS. Interventions for lower extremity peripheral 
artery disease. Nat Rev Cardiol. 2018;15(6):332-350. doi:10.1038/s41569-018-0005-0. 
8.  
Shishehbor MH, Jaff MR. Percutaneous Therapies for Peripheral Artery Disease. 
Circulation. 2016;134(24):2008-2027. doi:10.1161/CIRCULATIONAHA.116.022546. 
9.  
Okuno S, Iida O, Shiraki T, Fujita M, Masuda M, Okamoto S, Ishihara T, Nanto K, Kanda 
T, Takahara M, Uematsu M. Impact of Calcification on Clinical Outcomes After 
Endovascular Therapy for Superficial Femoral Artery Disease: Assessment Using the 
Peripheral Artery Calcification Scoring System. J Endovasc Ther. 2016;23(5):731-737. 
doi:10.1177/1526602816656612. 
10.  Fujihara M, Kozuki A, Tsubakimoto Y, Takahara M, Shintani Y, Fukunaga M, Iwasaki Y, 
Nakama T, Yokoi Y. Lumen Gain After Endovascular Therapy in Calcified Superficial 
Femoral Artery Occlusive Diseas e Assessed by Intravascular Ultrasound (CODE Study). J 
Endovasc Ther. 2019;26(3):322-330. doi:10.1177/1526602819836095. 

 
KAIZEN Clinical Study 
Cardiovascular Systems, Inc. 
 Revision G 
 
Page 63 of 67 
11.  Fitzgerald PJ, Ports TA, Yock PG. Contribution of localized calcium deposits to dissection 
after angioplasty. An observational study using intravascular ultrasound. Circulation. 
1992;86(1):64-70. 
12.  Dias-Neto M, Matschuck M, Bausback Y, Banning-Eichenseher U, Steiner S, Branzan D, 
Staab H, Varcoe RL, Scheinert D, Schmidt A. Endovascular Treatment of Severely 
Calcified Femoropopliteal Lesions Using the “Pave-and-Crack” Technique: Technical 
Description and 12-Month Results. J Endovasc Ther. 2018;25(3):334-342. 
doi:10.1177/1526602818763352. 
13.  Laird JR, Katzen BT, Scheinert D, Lammer J, Carpenter J, Buchbinder M, Dave R, Ansel 
G, Lansky A, Cristea E, Collins TJ, Goldstein J, Jaff MR. Nitinol stent implantation versus 
balloon angioplasty for lesions in the superficial femoral artery and proximal popliteal 
artery: twelve-month results from the RESILIENT randomized trial. Circ Cardiovasc Interv. 
2010;3(3):267-276. doi:10.1161/circinterventions.109.903468. 
14.  Dake MD, Ansel GM, Jaff MR, Ohki T, Saxon RR, Smouse HB, Zeller T, Roubin GS, 
Burket MW, Khatib Y, Snyder SA, Ragheb AO, White JK, Machan LS. Paclitaxel-eluting 
stents show superiority to balloon angioplasty and bare metal stents in femoropopliteal 
disease: twelve-month Zilver PTX randomized study results. Circ Cardiovasc Interv. 
2011;4(5):495-504. doi:10.1161/circinterventions.111.962324. 
15.  Minko P, Katoh M, Jaeger S, Buecker A. Atherectomy of heavily calcified femoropopliteal 
stenotic lesions. J Vasc Interv Radiol. 2011;22(7):995-1000. 
16.  Scheinert D, Scheinert S, Sax J, Piorkowski C, Braunlich S, Ulrich M, Biamino G, Schmidt 
A. Prevalence and clinical impact of stent fractures after femoropopliteal stenting. J Am 
Coll Cardiol. 2005;45(2):312-315. doi:10.1016/j.jacc.2004.11.026. 
17.  Katsanos K, Tepe G, Tsetis D, Fanelli F. Standards of practice for superficial femoral and 
popliteal artery angioplasty and stenting. Cardiovasc Intervent Radiol. 2014;37(3):592-603. 
doi:10.1007/s00270-014-0876-3. 
18.  Tepe G, Zeller T, Albrecht T, Heller S, Schwarzwalder U, Beregi JP, Claussen CD, 
Oldenburg A, Scheller B, Speck U. Local delivery of paclitaxel to inhibit restenosis during 
angioplasty of the leg. N Engl J Med. 2008;358(7):689-699. doi:10.1056/NEJMoa0706356. 
19.  Fanelli F, Cannavale A, Gazzetti M, Lucatelli P, Wlderk A, Cirelli C, d’Adamo A, Salvatori 
FM. Calcium burden assessment and impact on drug-eluting balloons in peripheral arterial 
disease. Cardiovasc Interv Radiol. 2014;37(4):898-907. doi:10.1007/s00270-014-0904-3. 
20.  Foley TR, Cotter RP, Kokkinidis DG, Nguyen DD, Waldo SW, Armstrong EJ. Mid-term 
outcomes of orbital atherectomy combined with drug-coated balloon angioplasty for 
treatment of femoropopliteal disease. Catheter Cardiovasc Interv. 2017;89(6):1078-1085. 
doi:10.1002/ccd.26984. 
21.  Katsanos K, Spiliopoulos S, Kitrou P, Krokidis M, Karnabatidis D. Risk of Death Following 
Application of Paclitaxel-Coated Balloons and Stents in the Femoropopliteal Artery of the 
Leg: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. J Am Heart 
Assoc. 2018;7(24):e011245. doi:10.1161/JAHA.118.011245. 

 
KAIZEN Clinical Study 
Cardiovascular Systems, Inc. 
 Revision G 
 
Page 66 of 67 
Appendix C: Investigator’s Brochure 
The KAIZEN Investigator’s Brochure is provided under separate cover

 
KAIZEN Clinical Study 
Cardiovascular Systems, Inc. 
 Revision G 
 
Page 67 of 67 
Appendix D: Participating Sites and Investigators 
A complete list of participating sites and investigators will be provided under separate cover 
upon request.