Orbital Vessel PreparaTIon to MaximIZe Dcb Efficacy in Calcified Below the Knee (BTK) Lesions - A Pilot Study
Phase: NA
Conditions: PAD, Vascular Calcification
Sponsor: Abbott Medical Devices



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Table of Contents 
1. 
ABBREVIATIONS............................................................................................................... 8 
2. 
DEFINITIONS ................................................................................................................... 10 
3. 
INTRODUCTION .............................................................................................................. 13 
4. 
PRIMARY OBJECTIVE ................................................................................................... 13 
5. 
DEVICES USED IN THE STUDY .................................................................................... 14 
6. 
STUDY DESIGN AND STATISTICAL METHODOLOGY ........................................... 14 
6.1. 
Study Design ..................................................................................................................... 14 
6.2. 
Statistical Methodology .................................................................................................... 14 
7. 
SAMPLE SIZE, SUBJECT ENROLLMENT, AND SUBJECT RANDOMIZATION ... 15 
7.1. 
Sample Size ....................................................................................................................... 15 
 
 
7.3. 
Subject Randomization .................................................................................................... 15 
8. 
SUBJECT SELECTION .................................................................................................... 16 
8.1. 
Subject Selection .............................................................................................................. 16 
8.2. 
Inclusion Criteria ............................................................................................................. 16 
8.3. 
Exclusion Criteria ............................................................................................................ 17 
8.4. 
Outcome Measures ........................................................................................................... 18 
 
 
 
 
 
 
 
 
 
 
 
11. 
ADVERSE EVENT DEFINITIONS, COLLECTION, RELATEDNESS AND 
REPORTING ..................................................................................................................... 23 
11.1. 
Adverse Event Definitions................................................................................................ 23 
11.2. 
Adverse Event Collection ................................................................................................. 24 
11.3. 
Adverse Event Relatedness .............................................................................................. 24 
11.4. 
Adverse event Reporting .................................................................................................. 24 
 
13. 
RISKS AND BENEFITS .................................................................................................... 25 
13.1. 
Risks ................................................................................................................................. 25 
13.2. 
Benefits ............................................................................................................................. 25 

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14. 
PROTOCOL DEVIATIONS ............................................................................................. 26 
15. 
SITE NON-COMPLIANCE............................................................................................... 26 
16. 
SUBJECT STUDY EXIT ................................................................................................... 26 
17. 
STUDY MANAGEMENT .................................................................................................. 27 
17.1. 
Monitoring........................................................................................................................ 27 
17.2. 
Early Termination/Withdrawal ....................................................................................... 27 
 
 
 
 
 
19. 
ADMINISTRATIVE RESPONSIBILITIES ..................................................................... 29 
19.1. 
Ethical Basis of Study ...................................................................................................... 29 
19.2. 
Ethics Committee (EC) Approval .................................................................................... 29 
19.3. 
Informed Consent Form (ICF) Approval ........................................................................ 30 
19.4. 
Confidentiality .................................................................................................................. 30 
19.5. 
Sponsor Responsibilities .................................................................................................. 31 
19.6. 
Investigator Responsibilities ............................................................................................ 31 
20. 
INVESTIGATOR RECORDS AND REPORTS ............................................................... 32 
20.1. 
Investigator Records ........................................................................................................ 32 
20.2. 
Investigator Reports ......................................................................................................... 32 
21. 
PUBLICATION OF STUDY DATA ................................................................................. 32 
22. 
REFERENCES ................................................................................................................... 33 
 
Figures 
 
 
 
 
 
 
 
 
 

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1. 
ABBREVIATIONS 
 
 
ACO 
Anticoagulation 
ADE 
Adverse Device Effect 
AE 
Adverse Event 
ASA 
Aspirin 
AT 
Anterior Tibial 
ATK 
Above the Knee 
BA 
Balloon Angioplasty 
BTK 
Below the Knee 
CLI 
Critical Limb Ischemia 
CSI 
Cardiovascular Systems, Inc. 
CTA 
Clinical Trial Agreement 
DAP 
Data Analysis Plan 
DCB 
Drug Coated Balloon 
DS 
Diameter Stenosis 
DUS 
Duplex Ultrasound 
eCRF 
Electronic Case Report Form 
EC 
Ethics Committee 
EDC 
Electronic Data Capture 
 
 
EU 
European Union 
IC 
Intermittent Claudication  
 
 
ICF 
Informed Consent Form 
IFU 
Instructions for Use 
ISR 
In-stent restenosis 
LLL 
Late Lumen Loss 
MAE 
Major Adverse Event 
OAS 
Orbital Atherectomy System 
OA 
Orbital Atherectomy 
PAD 
Peripheral Artery Disease 
PI 
Principal Investigator 

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POBA 
Plain Old Balloon Angioplasty 
POP 
Popliteal 
PR 
Peroneal  
PT 
Posterior Tibial 
PTA 
Percutaneous Transluminal Angioplasty 
 
 
 
 
QVA 
Quantitative Vascular Angiography 
RBP 
Rated Burst Pressure 
 
 
SADE 
Serious Adverse Device Effect 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
 
 
TLR 
Target Lesion Revascularization  
TVR 
Target Vessel Revascularization 
TPT 
Tibial Peroneal Trunk 
USADE 
Unanticipated Serious Adverse Device Effect 
 
 

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• 
Length of calcium ≥ 25 % of total lesion length ≥ 2 cm in total length 
 
• 
Target lesion length up to 20 cm 
8.3. EXCLUSION CRITERIA 
• 
Subject or subject’s legal representative is not willing to sign an Ethics Committee 
approved informed consent form or comply with the study protocol requirements  
 
• 
Contraindicated by either device, per IFU 
 
• 
Presence of inflow lesion (≥ 50 % DS) or inflow not successfully treated (≥ 50 % DS 
and/or unresolved significant angiographic complication) 
 
• 
Compromised outflow distal to the target lesion (≥ 70 % DS) or presence of lesion(s) 
or occlusion(s) located from 5 cm above the ankle to below the ankle joint space 
 
• 
Subject has more than 2 target vessels requiring treatment 
 
• 
The guide wire cannot be passed across the target lesion(s) and/or guide wire position 
distal to target lesion(s) outside vessel lumen  
 
• 
Pre-dilatation of the target lesion prior to randomization and OA treatment 
 
• 
Presence of significant (≥ 70 % DS) lesion(s) or occlusion(s) not meeting the study 
criteria which were not successfully treated during the index procedure (≥ 50 % DS 
and/or significant angiographic complication)  
 
• 
Subject has planned amputation (including minor) of the index limb or previous 
major amputation of the contralateral limb 
 
• 
Creatinine > 2.5 mg/dL, unless on dialysis 
 
• 
Subject has any significant medical condition which, in the Investigator’s opinion, 
may interfere with the subject’s optimal participation in the study 
 
• 
Subject is participating in an investigational drug or device study that has the 
potential to clinically interfere with the study outcome measures 
 
• 
Subject is pregnant or planning to become pregnant within the study period 
 
• 
Subject has an unresolved severe systemic infection 
 
• 
Subject has an anticipated life span of less than one year 
 
• 
Subjects with known hypersensitivity to paclitaxel or paclitaxel related compounds 
 
• 
Subjects who cannot receive recommended anti-platelet and/or anticoagulant therapy 
 
 

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   NOTE:  Planned hospitalization for a pre-existing condition, or a procedure   
   required by the Protocol, 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. 
 
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. 
 
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 version of the risk analysis report.  
11.2. ADVERSE EVENT COLLECTION 
Adverse events must be documented starting from the time of randomization until 
study completion. Angiographic complications, including but not limited to: 
o Bleeding complications 
o Dissections 
o Perforations  
o Distal embolization 
o Abrupt closure 
o Slow flow/no flow  
o Spasm 
o Thrombus 
will be considered AEs and must be recorded accordingly on the AE electronic Case Report 
Form (eCRF). 
 
Following discharge, only events that meet any of the seriousness criteria must be collected 
(SAE, SADE, USADE). 
11.3. ADVERSE EVENT RELATEDNESS 
The relatedness of the AE to the treatment device(s) and procedure(s), index limb, and target 
lesion will be classified by the Investigator and reviewed by the Sponsor.  The Investigator 
will use the following definitions in classifying the relationship of the AE: 
• Device Related:  AE is directly related to the device(s) used in treatment of the lesion. 
• Procedure Related:  AE is directly attributable to the index procedure. 
• Limb Related:  AE is related to the index limb. 
• Lesion Related:  AE is related to the target lesion. 
11.4. ADVERSE EVENT REPORTING 
Adverse events defined above must be reported to the Sponsor via the AE eCRF as well as to 
each reviewing regulatory body [e.g., Competent Authority(CA), EC, etc.] per policy, as 
required.   Note: not all AEs collected in the study may be reportable to the reviewing EC/CA 
per policy (e.g., pre-planned interventions noted at baseline, minor dissections, etc.). 

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    Withdrawal of EC approval is reportable to the Sponsor within five (5) business days. 
19.3. INFORMED CONSENT FORM (ICF) APPROVAL 
The Sponsor will provide a template Informed Consent Form (ICF) to each site for EC 
submission prior to site initiation if a site ICF template is not available.  This template may be 
modified to suit the requirements of the study site; however, the Sponsor must pre-approve all 
changes to the ICF template prior to submission to the reviewing EC.  If changes to a 
submitted ICF are required prior to approval by the reviewing EC, changes must be reviewed 
and approved by the Sponsor and a copy of the final approved document must be provided by 
the Investigator to the Sponsor prior to enrollment of any study subjects.  A copy of the final 
EC-approved ICF must be sent to the Sponsor prior to study start in addition to any 
subsequent revisions which are reviewed and approved by the EC.   
 
Prior to enrolling in the clinical study, subjects shall be fully informed of the details of the 
participation as required by applicable regulations and the center’s EC. Informed consent must 
be obtained from each subject, or a legally authorized representative (as allowed by the study 
Investigator/EC), prior to any participation, using the Informed Consent Form (ICF) approved 
by site’s reviewing EC.  The ICF must be signed and dated by the subject or legal 
representative and by the person obtaining the consent. All information pertinent to the 
clinical study shall be provided in writing and in native, non-technical language that is 
understandable to the subject or subject’s legally authorized representative.  
 
If a subject or legally authorized representative is unable to read or write, the informed 
consent (as allowed by the study Investigator/EC) shall be obtained through a supervised oral 
process. An independent witness shall be present throughout the process. Upon completion of 
the supervised oral process, the ICF must be signed and dated by the subject or legal 
representative and by the person obtaining the consent attesting that the information was 
accurately explained and that informed consent was freely given.  
 
Prior to the subject or legal representative signing the ICF, the Investigator or authorized 
delegate will fully explain to the subject or legal representative the nature of the research, 
clinical study procedures, anticipated benefits, and potential risks of participation in the 
clinical study. The Investigator or delegate will allow adequate time for the subject or legal 
representative to read and review the ICF and ask questions.  
 
The Investigator or authorized delegate must document in the subject’s medical records that 
the subject was consented and the date on which the consent was obtained. The original 
signed consent form will be retained in the subject’s clinical study records. A copy of the 
signed informed consent will be provided to the subject or legal representative and a copy 
placed in the subject’s medical record. 
19.4. 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 data 
will be used in a manner without identifiable reference to the subject.  The Investigator 
consents to visits by the Sponsor or designee and authorized governmental body to review the 

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study subjects’ medical records, including any test or laboratory data that might have been 
recorded on diagnostic test media (e.g., angiogram). 
 
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. 
19.5. SPONSOR RESPONSIBILITIES 
Sponsor responsibilities include but are not limited to: 
• Protection of the rights, safety, and welfare of subjects by conducting the clinical study in 
accordance with the Declaration of Helsinki, the Study Protocol, all applicable laws and 
regulations, and any conditions of approval imposed by the reviewing EC and other  
applicable regulatory authorities (e.g., National Competent Authority, Radiation 
Committee, etc.) where the study is performed. 
• Selection of qualified Investigators, study sites, and Core Labs who participate in the 
study; 
• Training of participating study sites including the Investigator and staff conducting the 
study; 
• Adverse Event/Incident reporting: 
o Relaying adequate information on AEs and SAEs to the regulatory authorities per 
country’s applicable reporting requirements and complying with medical devices 
vigilance reporting per country-specific regulations.  
• Providing financial support to each study site which is fair, reasonable, and equitable to 
fair market value; 
• Following/promoting all applicable regulatory standards per applicable regulations at 
each study site; and, 
• Ownership and control of the use of data, including review and approval of study-related 
publications/presentations, etc. 
19.6. INVESTIGATOR RESPONSIBILITIES 
Investigator responsibilities include, but are not limited to, the following: 
• Protection of the rights, safety, and welfare of subjects by conducting the clinical study in 
accordance with the Declaration of Helsinki, the Study Protocol, all applicable laws and 
regulations, and any conditions of approval imposed by the reviewing EC and other  
applicable regulatory authorities (e.g., National Competent Authority, Radiation 
Committee, etc.) where the study is performed. 
• Conduct of the study in accordance with the Clinical Trial Agreement (CTA) with the 
Sponsor, the Protocol, applicable laws and regulations and any conditions of approval 
imposed by the reviewing EC/CA or other applicable regulatory body. 
• Delegation of study-related tasks to qualified personnel under their supervision as may be 
applicable; however, the Investigator remains responsible for the proper conduct of the 
clinical study.   
• Not commencing enrollment until the Sponsor has received all required documentation, 
including but not limited to the signed CTA and required regulatory approvals. 

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• Following appropriate procedures to maintain subject confidentiality according to the 
applicable laws and regulations.  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 site’s relevant patient privacy laws. 
• Not transferring the study to other sites attended by the Principal Investigator unless prior 
approval is obtained from the reviewing EC and the Sponsor. 
• Keeping records pertaining to this study for a minimum of two (2) years following the 
date on which the study is terminated or completed. 
 
20. INVESTIGATOR RECORDS AND REPORTS 
20.1. INVESTIGATOR RECORDS 
Investigator responsibilities include, but are not limited to, preparation and/or retention of the 
following records: 
• Subject’s records including the signed/dated ICF, adverse event documentation, relevant 
medical history, results of study-related tests/exams, and dates and data collected during 
the study visits 
• Protocol approvals with associated amendments 
• Regulatory correspondence 
 
20.2. INVESTIGATOR REPORTS 
The Investigator is responsible for preparation and submission to the Sponsor of all eCRFs, 
adverse event reports, and deviations from the protocol.  If any action is taken by the EC/CA 
or other applicable regulatory body, the information must be forwarded to the Sponsor in a 
timely manner. 
 
Note: reviewing regulatory bodies may impose additional requirements and/or require a 
different notification timeframe. 
 
21. PUBLICATION OF STUDY DATA 
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 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, with the help of the Steering Committee, reserves the right to review and 
approve all publications and presentations utilizing the study data.  The Investigator may 
proceed with the publication or presentation only when approved by the Sponsor. 
 

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22. REFERENCES 
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Predictors of failure and success of tibial interventions for critical limb ischemia. Journal of 
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2. Schnorr B and Albrecht T. Drug-coated balloons and their place in treating peripheral 
arterial disease. Expert review of medical devices. 2013;10:105-14. 
3. Liistro F, Grotti S, Porto I, Angioli P, Ricci L, Ducci K, Falsini G, Ventoruzzo G, Turini 
F, Bellandi G and Bolognese L. Drug-Eluting Balloon in Peripheral Intervention for the 
Superficial Femoral Artery: The DEBATE-SFA Randomized Trial (Drug Eluting Balloon in 
Peripheral Intervention for the Superficial Femoral Artery). JACC Cardiovascular 
interventions. 2013;6:1295-302. 
4. Schmidt A, Piorkowski M, Werner M, Ulrich M, Bausback Y, Braunlich S, Ick H, 
Schuster J, Botsios S, Kruse HJ, Varcoe RL and Scheinert D. First experience with drug-
eluting balloons in infrapopliteal arteries: restenosis rate and clinical outcome. Journal of the 
American College of Cardiology. 2011;58:1105-9. 
5. Byrne RA, Joner M, Alfonso F and Kastrati A. Drug-coated balloon therapy in coronary 
and peripheral artery disease. Nature reviews Cardiology. 2014;11:13-23. 
6. Mustapha JA, Diaz-Sandoval, L.J., Karenko, B., Saab, F. . Atherectomy and critical limb 
ischemia: a treatment approach for severely calcified vessels. Vascular Disease Management. 
2013;10:E198-E207. 
7. Cioppa A, Stabile E, Popusoi G, Salemme L, Cota L, Pucciarelli A, Ambrosini V, 
Sorropago G, Tesorio T, Agresta A, Biamino G and Rubino P. Combined treatment of heavy 
calcified femoro-popliteal lesions using directional atherectomy and a paclitaxel coated 
balloon: One-year single centre clinical results. Cardiovascular revascularization medicine : 
including molecular interventions. 2012;13:219-23. 
8. Fanelli F, Cannavale A, Gazzetti M, Lucatelli P, Wlderk A, Cirelli C, d'Adamo A and 
Salvatori FM. Calcium burden assessment and impact on drug-eluting balloons in peripheral 
arterial disease. Cardiovascular and interventional radiology. 2014;37:898-907.