Directional Versus Orbital Atherectomy Plaque Modification and Luminal Area Assessment of the Femoro-popliteal Artery Via Intravascular Ultrasound
Phase: NA
Conditions: Peripheral Artery Disease
Sponsor: NYU Langone Health

 
 
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Directional versus Orbital Atherectomy plaque modification and luminal area assessment of the 
femoro-popliteal artery Via Intravascular Ultrasound  
(DIRECT TRIAL) 
 
Principal Investigator: 
 
Anvar Babaev, MD, PhD 
Department of Medicine 
530 First Ave HCC14 Cath Lab 
New York, NY 10016 
Anvar.Babaev@nyumc.org 
212-263-5656 
 
Additional Investigators: 
 
TBD 
NYUSOM Study Number: 
 
S18-00005 
Funding Sponsor:  
Medtronic Vascular, INC 
3576 Unocal Place, Santa Rosa, CA 95403  
(707) 566-1238 
Regulatory sponsor: 
NYU 
Study Product: 
CSI’s DIAMONDBACK 360® Peripheral Orbital Atherectomy 
System (St.Paul, MN); Medtronic’s Hawkone Directional 
Atherectomy system (DAS) (Minneapolis, MN).  
Study Product Provider: 
[If applicable] 
N/A 
ClinicalTrials.gov 
Number                 
TBD 
 
Initial version: 09FEB2018 
Amended: 
19APR2018 
Amended: 
23JUL2020
NCT03495453 

 
 
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Statement of Compliance 
 
This study will be conducted in accordance with the Code of Federal Regulations on the 
Protection of Human Subjects (45 CFR Part 46), 21 CFR Parts 50, 56, 312, and 812 as 
applicable, any other applicable US government research regulations, and institutional research 
policies and procedures. The International Conference on Harmonisation (“ICH”) Guideline for 
Good Clinical Practice (“GCP”) (sometimes referred to as “ICH-GCP” or “E6”) will be applied 
only to the extent that it is compatible with FDA and DHHS regulations. The Principal 
Investigator will assure that no deviation from, or changes to the protocol will take place without 
prior agreement from the sponsor and documented approval from the Institutional Review Board 
(IRB), except where necessary to eliminate an immediate hazard(s) to the trial participants. All 
personnel involved in the conduct of this study have completed Human Subjects Protection 
Training. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
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Table of Contents 
STATEMENT OF COMPLIANCE .................................................................................................. 1 
LIST OF ABBREVIATIONS ......................................................................................................... 4 
PROTOCOL SUMMARY ................................................................................................................ 5 
DIRECTIONAL VERSUS ORBITAL ATHERECTOMY PLAQUE MODIFICATION AND 
LUMINAL AREA ASSESSMENT OF THE FEMORO-POPLITEAL ARTERY VIA 
INTRAVASCULAR ULTRASOUND .............................................................................................. 5 
1. 
KEY ROLES ........................................................................................................................... 7 
2. INTRODUCTION ........................................................................................................................ 8 
2.1 REGULATORY CLASSIFICATION ......................................................................................... 8 
2.2 STUDY DESCRIPTION ......................................................................................................... 8 
2.3 STUDY BACKGROUND AND JUSTIFICATION ........................................................................ 9 
2.4 STUDY OBJECTIVES AND ENDPOINTS............................................................................... 10 
2.4.a. Primary Objective ........................................................................................ 10 
3.   INVESTIGATOR SELECTION AND RESPONSIBILITIES ................................................... 11 
3.1 INVESTIGATOR SELECTION .............................................................................................. 11 
3.2 INVESTIGATOR RESPONSIBILITIES .................................................................................... 11 
4. METHODOLOGIES .................................................................................................................. 11 
4.1 STUDY DESIGN ................................................................................................................ 11 
4.2   SUBJECT SELECTION ..................................................................................................... 11 
4.2.1. STRATEGIES FOR RECRUITMENT .................................................................................. 11 
4.3. Inclusion Criteria ............................................................................................ 12 
4.4. Exclusion Criteria ........................................................................................... 12 
5.  STUDY PROCEDURES .......................................................................................................... 13 
5.1   OVERVIEW OF DATA COLLECTION REQUIREMENTS ........................................................ 13 
5.2   INFORMED CONSENT ...................................................................................................... 14 
5.3 BASELINE VISIT (PRE-PROCEDURE ASSESSMENTS - UP TO 30 DAYS)................................ 14 
5.6 UNSCHEDULED VISITS ..................................................................................................... 17 
5.7 TRIAL COMPLETION ......................................................................................................... 17 
5.8 Study Exit ......................................................................................................... 17 
5.8.a. Lost to Follow-up ......................................................................................... 17 
5.8.b. Subject Withdrawal ..................................................................................... 17 
6. ADVERSE EVENTS, DEVIATIONS & COMPLAINTS ............................................................ 18 
6.1.   ADVERSE EVENTS ......................................................................................................... 18 
6.2. Serious Adverse Event Definitions............................................................... 18 
6.3. Serious Adverse Event Classification .......................................................... 18 
6.4. Serious Adverse Event Reporting ................................................................ 18 
6.5. STUDY DEVIATIONS ........................................................................................................ 18 
6.6. PRODUCT RETURN, DEVICE MALFUNCTION, AND COMPLAINTS ....................................... 18 
7. RISK ANALYSIS ...................................................................................................................... 19 
7.1   POTENTIAL RISKS AND MITIGATIONS .............................................................................. 19 

 
 
 
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7.2   POTENTIAL BENEFITS .................................................................................................... 19 
8. STATISTICAL METHODS AND DATA ANALYSIS ................................................................ 20 
8.1 DATA MANAGEMENT........................................................................................................ 20 
8.2   STATISTICAL AND DATA ANALYSIS METHODS ................................................................ 20 
IVUS DICOM Image Analysis .................................................................................. 20 
9. MONITORING ........................................................................................................................... 20 
10. INVESTIGATOR RECORDS AND REPORTS ...................................................................... 20 
10.1 INVESTIGATOR RECORDS............................................................................................... 21 
10.2 INVESTIGATOR REPORTS ............................................................................................... 21 
11. PUBLICATION ....................................................................................................................... 21 
11.1CLINICAL TRIAL REGISTRATION ...................................................................................... 21 
11.2 PUBLICATION REVIEW ................................................................................................... 22 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
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List of Abbreviations 
 
ABI: Ankle Brachial Index 
ACC/AHA: American College of Cardiology/American Heart Association 
AE: Adverse Event 
AEAC: Adverse Event Adjudication Committee 
BA: Baloon angioplasty 
CFR: Code of Federal Regulations 
CLI: Critical Limb Ischemia 
CRF: Case Report Form 
CSI: Cardiovascular Systems, Inc. 
DAS: Directional Atherectomy System 
DCB: Drug coated balloon 
DICOM: Digital Imaging and Communications in Medicine 
DSMB: Data Safety Monitoring Board 
FDA: Food and Drug Administration 
HIPAA: Health Insurance Portability and Accountability Act 
ICF: Informed Consent Form 
ICMJE: International Committee of Medical Journal Editors 
IDE: Investigational Device Exemption 
IRB: Institutional Review Board 
IVUS: Intravascular Ultrasound 
NYU: New York University 
OAD: Orbital Atherectomy Device 
OAS: Orbital Atherectomy System 
PAD: Peripheral Artery Disease 
PI: Principal Investigator 
QCA: Qualitative Comparative Analysis 
QoL: Quality of Life 
RGA: Returned Goods Authorization 
SAE: Serious Adverse Event 
SFA: Superficial Femoral Artery 
US: United States 
VIAS: Video Image Analysis Software 
 
 
 
 
 
 

 
 
 
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Protocol Summary 
Title 
Directional versus Orbital Atherectomy plaque modification 
and luminal area assessment of the femoro-popliteal artery 
Via Intravascular Ultrasound 
Short Title 
DIRECT TRIAL 
Brief Summary 
A single center prospective, randomized study will be 
conducted to investigate plaque removal and luminal gain 
using CSI’s DIAMONDBACK 360® Peripheral Orbital 
Atherectomy System (OAS) (St.Paul, MN) versus 
Medtronic’s Hawkone Directional Atherectomy system (DAS) 
(Minneapolis, MN) assessed by angiography and 
Intravascular Ultrasound (IVUS) in patients diagnosed with 
symptomatic obstructive femoro-popliteal disease will be 
analyzed. 
Subjects will be randomized in a 1:1 fashion to receive 
treatment with either OAS (using CSI device) followed by 
Inpact Admiral drug coated balloon (DCB) or DAS (using the 
Hawkone device) followed by DCB. Subjects in both arms 
will undergo IVUS before and after atherectomy, as well as 
at the conclusion of the procedure.  
Clinical data will be collected at baseline, immediately prior 
to the procedure, during and immediately after the 
procedures, and within 30 days, 6 and 12 months office visits 
after the procedure. Data may also be collected at office or 
hospital visits that are not scheduled but occur up to 12 
months after the procedure, if they pertain to treatment 
related to the obstructive femoro-popliteal disease. Data to 
be collected for this study includes demographics, medical 
history, procedural parameters and follow-up.    
The study will be conducted at one study center, 60 subjects 
will be accrued in the trial with 30 patients enrolled in the 
OAS arm and 30 patients enrolled in the DAS arm.   

 
 
 
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Objectives 
        To investigate the hard and soft plaque removal with 
directional and orbital atherectomy by analyzing changes in 
plaque volume and composition and vessel size using 
intravascular ultrasound (IVUS). Freedom from 
complications, target vessel patency and target lesion 
revascularization (TLR) at 6 months and one year will also 
be evaluated.  
Endpoint 
Primary Endpoint:  
Acute luminal gain (increase in minimal luminal area via 
IVUS measurement immediately following atherectomy)  
Secondary Endpoints: 
-Plaque burden reduction. The plaque composition and 
amount of removed plaque will be analyzed via IVUS.  
-Device success (≤ 30% residual stenosis following 
atherectomy, as measured by angiography, without 
adjunctive endovascular interventions) 
-Rate of procedural angiographic complications such as 
dissection, perforation, emboli, abrupt closure, need for bail 
out stenting. 
-Major Adverse Event Rate at 30 days post procedure 
defined as clinical TLR, major unplanned amputation of the 
treated limb, or all-cause mortality  
-Rate of clinical TLR, unplanned amputation of the treated 
limb, or all-cause mortality at 6 and 12months post index 
treatment. 
-Primary patency at 1 year defined as freedom from target 
lesion restenosis detected with duplex ultrasound Peak 
Systolic Velocity Ratio (PSVR) is ≤ 2.4 
-Rate of Hemodynamic Improvement as assessed by 
changes in ABI at 6 and 12 months as compared to post-
procedural baseline (i.e., within 30 days). 
-Improvement in Rutherford Clinical Category within 30 days, 
at 6 months and at 12 months, defined as an improvement in 
clinical status indicated by a decrease of one or more in 
Rutherford Clinical Category compared to baseline, that is 
attributable to the treated limb (in cases of bilateral disease).   
 

 
 
 
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Study Duration 
The duration of the study is expected to be approximately 2 
years from the date of first enrollment (1 year for enrollment 
of approximately 100 subjects and a year for follow-up of 60 
accrued subjects). 
Participant Duration 
It will take 12 month for each individual participant to 
complete all participant visits. 
Population 
• 
The patients with obstructive superficial femoral or 
popliteal arteries 
disease as the main reason for their symptoms will be 
enrolled in this study. 
Study Sites 
NYU Langone Health 
Number of participants 
Number of participants projected for the entire study 100 
Description of Study 
Procedure 
All subjects will undergo percutaneous revascularization of 
the femoro-popliteal arteries using a DAS or OAS device and 
balloon angioplasty as per the randomization arm. 
All patients will undergo at least 3 runs of IVUS:  
• 
a pre-treatment run to assess the severity and 
morphology of the plaque composition  
• 
a post-atherectomy run to assess changes post 
atherectomy treatment 
• 
a post drug coated balloon angioplasty (followed 
atherectomy) to assess changes in overall volumes. 
 
Statistical Analysis 
The sample size for the study is not based on any statistical 
hypothesis.  
The mean differences between pre-procedure and post-
procedure measures will be analyzed using paired t-tests. A 
p-value of ≤ 0.05 will be considered to indicate statistical 
significance.  Descriptive statistics will be generated to 
describe study findings (i.e. subject demographics, plaque 
volume, lumen volume, vessel size, etc.).   
 
 
1. Key Roles 
 

 
 
 
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Investigator: 
Anvar Babaev, MD, PhD, FACC 
530 First Ave HCC14 Cath Lab 
New York, NY 10016 
212-263-5656 
Anvar.Babaev@nyumc.org 
 
Co-Investigators: 
TBD 
 
Center: 
NYU Langone Health 
530 First Ave  
New York, NY 10016 
 
2. Introduction 
2.1 Regulatory Classification 
The sponsor has determined that this study is a medical device study which involves products 
currently on the market in the USA and these products have received clearance for use by the 
Food and Drug Administration (FDA).  The clinical study requires the medical devices to be 
used in accordance with its FDA-cleared labeling.  Therefore, it is a study which is exempt from 
the investigational device exemption (IDE) regulations of the FDA.  There are no investigational 
products or procedures used in this study. 
2.2 Study Description 
A single center prospective, randomized study will be conducted to investigate plaque removal 
and luminal gain using CSI’s DIAMONDBACK 360® Peripheral Orbital Atherectomy System 
(OAS) (St.Paul, MN) versus Medtronic’s Hawkone Directional Atherectomy system (DAS) 
(Minneapolis, MN) assessed by angiography and Intravascular Ultrasound (IVUS) in patients 
diagnosed with symptomatic obstructive femoro-popliteal disease will be analyzed. 
Subjects will be randomized in a 1:1 fashion to receive treatment with either OAS (using CSI 
device) followed by Inpact Admiral drug coated balloon (DCB) or DAS (using the Hawkone 
device) followed by DCB. Subjects in both arms will undergo IVUS before and after 
atherectomy, as well as at the conclusion of the procedure.  
Clinical data will be collected at baseline, immediately prior to the procedure, during and 
immediately after the procedures, and within 30 days, 6 and 12 months office visits after the 
procedure. Data may also be collected at office or hospital visits which are not scheduled but 
may occur up to 12 months after the procedure, if they pertain to treatment related to the 
obstructive femoro-popliteal disease. Data to be collected for this study includes demographics, 
medical history, procedural parameters and follow-up.    
The study will be conducted at one study center, 100 subjects will be enrolled, with 60 subject 
accrued in the trial: 30 patients randomized to the OAS arm and 30 patients randomized to the 

 
 
 
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DAS arm.  The duration of the study is expected to be approximately 2 years from the date of 
first enrollment (1 year for enrollment of 60 subjects and a year for follow-up). 
2.3 Study Background and Justification 
 
Peripheral arterial disease (PAD) of the lower extremities has an incidence and prevalence equal 
to that of coronary artery disease and is a major cause of morbidity and mortality. Endovascular 
treatment of femoral-popliteal lesion in patients with symptomatic PAD has been shown to 
improve exercise capacity and quality of life1. Heavy plaque burden calcification is one of the most 
important predictors of unsuccessful angioplasty and poor short and long term procedural 
outcomes. Fitzgerald et al.2 demonstrated that 74% of dissections after balloon angioplasty 
occurred in lesions with significant calcification.  
 
Percutaneous removal of atherosclerotic material using atherectomy devices reduces the 
complications of traditional angioplasty such as dissection, elastic recoil and disruption of the 
internal elastic lamina of the artery. Directional and orbital atherectomy are two of the most 
common atherectomy approaches used to treat lower extremity PAD. 
 
Directional atherectomy devices such as the Hawkone, Turbohawk and Silverhawk use a side 
cutting steerable blade that also has a distal nosecone to capture debris. The directional cutting 
design allows for extensive removal of calcific debris from the entire lumen while minimizing the 
direct trauma to the true intima. The Definitive LE study was an 800 patient prospective registry 
that demonstrated the safety and effectiveness of DAS in infrainguinal PAD. Primary patency 
rates were >90% after 6 months in both the claudicant and critical limb ischemia(CLI) groups.3 
Smaller randomized trials of directional atherectomy vs traditional balloon angioplasty have 
demonstrated superior outcomes with directional atherectomy especially when treating long 
calcified lesions4.  
 
Orbital atherectomy devices such as the Diamondback 360 use a diamond coated eccentrically 
mounted burr that spins in an orbit and increases in size at higher revolutions. This technique 
causes preferential sanding of the calcified plaque and a fixed luminal gain and can be used in 
vessel ranging from 2mm-7mm in diameter. IVUS analysis of lesions treated with orbital 
atherectomy significant lesion modification by modifying the calcified component of the plaque 
burden.5 The Compliance 360 trial randomized 65 patients to either balloon angioplasty (BA) or 
OAS and BA. This trial showed that compared to BA alone, OAS+ BA yields better luminal gain 
and decreases incidence of adjunctive stenting.6 Similarly, the Calcium 360 randomized trial of 
orbital atherectomy + BA vs. BA alone showed superiority with use of the orbital atherectomy 
device.7  
 
Most trials comparing atherectomy + BA to BA alone were done without the use drug coated 
balloons. DCB's have shown superiority when compared to plain old balloon angioplasty alone. 
A recently published meta-analysis of 11 trials with 1838 patients confirmed that DCB's are 
superior with regards to endpoints such as primary vessel patency, restenosis rates and target 
lesion revascularization.8 The combination of both atherectomy with DCB may further improve the 
results of lower extremity PAD percutaneous intervention. Several trials are currently in progress 
that are evaluating this hypothesis. The Definitive AR trial is a randomized control trial comparing 
DAS+ DCB vs DCB alone. Long term data has yet to be published but preliminary results show 
that DAS+DCB may be superior especially in long as well as calcified lesions when appropriate 
de-bulking was attained (<30% residual post DAS stenosis). 
 

 
 
 
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While both directional and orbital atherectomy systems have demonstrated improved outcomes 
versus balloon angioplasty alone, no studies have been performed to directly compare whether 
one form of atherectomy is superior to the other. With the increased incidence of significant PAD 
and the increased need for atherectomy in order to achieve successful percutaneous intervention, 
it would be extremely beneficial to know whether one type of atherectomy system is preferred 
over another. There are several theoretical advantages of DAS over OAS: DAS allows for possibly 
larger amount of plaque removal (de-bulking) which leads to a larger luminal gain and vessel 
diameter that in turn may lead to a better long term vessel patency rates and lower rates of target 
vessel revascularization. The purpose of this study will be to evaluate whether directional 
atherectomy is superior to orbital atherectomy in treating long femoro-popliteal lesions.  
2.4 Study Objectives and Endpoints 
2.4.a. Primary Objective 
• 
To investigate the hard and soft plaque removal with directional and orbital atherectomy by 
analyzing changes in plaque volume and composition and vessel size using IVUS). Freedom 
from complications, target vessel patency and target lesion revascularization (TLR) at 6 
months and one year will also be evaluated.  
 
2.4.b. Primary Endpoint 
 
Acute luminal gain (increase in minimal luminal area via IVUS measurement immediately 
following atherectomy) 
 
2.4.c. Secondary Endpoints 
 
• 
Plaque burden reduction. The plaque composition and amount of removed plaque will be 
analyzed via IVUS. 
• 
Device success (≤ 30% residual stenosis following atherectomy, as measured by              
angiography, without adjunctive endovascular interventions) 
• 
Rate of procedural angiographic complications such as dissection, perforation, emboli, abrupt 
closure, need for bail out stenting. 
• 
Major Adverse Event Rate at 30 days post procedure defined as clinical TLR, major unplanned 
amputation of the treated limb, or all-cause mortality 
• 
Rate of clinical TLR, unplanned amputation of the treated limb, or all-cause mortality at 6 and 
12months post index treatment. 
• 
Primary patency at 1 year defined as freedom from target lesion restenosis detected with 
duplex ultrasound Peak Systolic Velocity Ratio (PSVR) is ≤ 2.4 
• 
Rate of Hemodynamic Improvement as assessed by changes in ABI at 6 and 12 months as 
compared to post-procedural baseline (i.e., within 30 days). 
• 
Improvement in Rutherford Clinical Category within 30 days, at 6 months and at 12 months, 
defined as an improvement in clinical status indicated by a decrease of one or more in 
Rutherford Clinical Category compared to baseline, that is attributable to the treated limb (in 
cases of bilateral disease). 

 
 
 
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3.   Investigator Selection and Responsibilities 
3.1 Investigator Selection 
In order for investigators to participate in the study, they must meet the following criteria: 
• 
A qualified physician, such as an interventional radiologist, vascular surgeon or    
cardiologist 
• 
Qualified to practice medicine at NYU 
• 
Able to provide adequate time and staff support for the study 
• 
Able to comply with the protocol and legal contract for the study 
• 
At an institution that has access to a registered IRB. 
3.2 Investigator Responsibilities 
The investigator is responsible for protecting the rights, safety, and welfare of subjects. An 
investigator must conduct the investigation in accordance with the study contract with the 
sponsor of the study, the protocol, the FDA regulations that apply to this study including 21 CFR 
50 [Protection of Human Subjects] and 21 CFR 56 [Institutional Review Boards (IRB)], and any 
conditions of approval imposed by an IRB. 
The Principal Investigator (PI) and other staff conducting the study will be trained prior to 
performing any activities for the study.  Should the PI choose to delegate study related tasks to 
qualified personnel under their supervision, they must be trained on the study relative to the 
tasks that have been assigned to them. 
 
4. Methodologies 
4.1 Study Design 
The study design is a single-center, prospective, randomized control trial to assess the 
performance of OAS and DAS for removal of plaque including calcium in patients who have 
femoro-popliteal disease. Subjects will have a baseline visit to determine eligibility for the study, 
will receive treatment according to this study protocol, and will be followed with office visits at 
within 30 days, 6 and 12 months after the procedure to collect data.  Study participation will be 
complete when the last study subject enrolled has been followed for 12 months after the 
procedure.  
4.2   Subject Selection 
The research coordinator (RC) and IRB-approved study team doctor will have primary 
responsibility for screening and enrolling eligible candidates. The RC will review NYULMC’s 
Epic system to identify patients with peripheral artery disease from the NYU cardiology practices 
and patients scheduled for a revascularization procedure in the Cardiac Catheterization 
Laboratory. The research coordinator will review the medical records to identify the patient and 
confirm with the principal investigator or Sub Investigator if the patient meets the clinical 
inclusion and exclusion criteria. If the physician is amenable, the coordinator will approach the 
patient for a possible consent and enrollment. 

 
 
 
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It is expected that approximately 100 participants will sign IRB approved consent in order to 
accrue 60 subjects to the trial: 30 patients randomized to the OAS arm and 30 patients 
randomized to the DAS arm.   
Once the subject has signed the approved study informed consent form (ICF), and has met all 
inclusion and no exclusion criteria, the subject will be considered eligible to be enrolled to the 
trial. Subjects may be either male or female, and must meet all of the inclusion criteria and none 
of the exclusion criteria in order to be randomized to the either arm of the trial treatment. 
 
 
 
4.3 Inclusion Criteria 
• 
Subject’s age ≥ 18 years; 
• 
Subject (or Legal Guardian if applicable) is willing and able to provide consent before any 
study-specific test or procedure is performed, signs the consent form, and agrees to attend all 
required follow-up visits. 
• 
Chronic, symptomatic lower limb ischemia defined as Rutherford categories 1-4 
• 
Target lesion(s) located in a superficial femoral or popliteal arteries 
• 
Degree of stenosis ≥70% via Qualitative Comparative Analysis (QCA) 
• 
Total Lesion Length ≥ 80 mm and ≤ 250 mm  
• 
Reference Vessel ≥ 3.0 mm and <6.5mm 
• 
Patent infrapopliteal artery, i.e., single vessel runoff or better with at least one of three vessels 
patent (<50% stenosis) to the ankle or foot with no planned intervention. 
• 
Subject is an acceptable candidate for percutaneous intervention using the OAS or DAS in 
accordance with their labeled indications and instructions for use 
 
4.4 Exclusion Criteria 
Subjects who have an: 
• 
Previously stented target lesion/vessel. 
• 
Subjects who have undergone prior surgery of the SFA/PA in the target limb to treat      
atherosclerotic disease.  
• 
Presence of aneurysm in the target vessel.  
• 
Interventional treatment is intended for in-stent restenosis at the peripheral vascular site. 
• 
Target vessel with moderate or severe angulation (e.g., > 30°) or tortuosity at the     
treatment segment that precludes safe advancement of the atherectomy device. 
• 
Pre-planned interventional treatment includes planned laser, brachytherapy or atherectomy 
procedure other than OAS or DAS.  
• 
Known hypersensitivity or contraindication to contrast dye that, in the opinion of the 
investigator, cannot be adequately pre-medicated.  
• 
Known hypersensitivity/allergy to antiplatelet, anticoagulant, thrombolytic medications  
• 
Platelet count <80,000 mm3 or >600,000 mm3 or history of bleeding diathesis.  
• 
Patient has any known coagulation disorder, including hypercoagulability  
• 
Receiving dialysis or immunosuppressant therapy.  
• 
Patient has evidence of intracranial or gastrointestinal bleeding within last 3 months. 
• 
Patient has history of severe trauma, fracture, major surgery or biopsy of a parenchymal   
organ within past 14 days,  

 
 
 
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• 
Female patient who is pregnant or nursing a child,  
• 
Current participation in another investigational drug or device clinical study that has not 
completed the primary endpoint at the time of randomization/enrollment or that clinically 
interferes with the current study endpoints. 
 
4.5 Data Storage 
All subjects who sign the ICF will receive a study ID number. The Subject’s source documents 
and  data, under this ID number, will be placed in a subject research binder and inputted into the 
REDCap database, which is stored on NYULMC’s password protected, strongly firewalled 
server that has been certified by NYULMC’s HIPAA Compliance Officer in adherence to DHHS 
data collection policies. This electronic data storage complies with the FDA Title 21 CFR Part 11 
standards for Electronic Records and Electronic Signatures. The subject’s research binders will 
be kept in the secure place in the research office.  
5.  Study Procedures 
5.1   Overview of Data Collection Requirements 
Clinical data will be collected upon enrollment at the Baseline Visit, at the time of the 
procedure, and at within 30 days, and 6 and 12 months after the procedure.  Data will also be 
collected during unscheduled office visits should adverse events connected to the procedure or 
device occur or should a subject death occur during the 12 months of study follow up after the 
subject’s procedure. Data to be collected includes demographics, medical history, etc.  The 
data requirements are summarized in Table 1. 
Data Criteria 
Baseline 
visit 
 
 
Procedure 
 
Visit 1 
Visit 2  
(6 mon) 
 
Visit 3 
 (12 mon) 
Compliance Window 
30 days 
prior to 
procedure 
n/a 
Within 
30 days 
after 
procedur
e 
 
+/- 30 days 
 
 
+/- 30 days 
Subject Informed 
Consent 
✓ 
 
 
 
 
Inclusion/Exclusion 
Criteria 
✓ 
 
 
 
 
Subject Medical 
History 
✓ 
 
 
 
 
IVUS/DICOM images* 
 
✓ 
 
 
 
ABI 
✓ 
 
✓ 
✓ 
✓ 
Arterial Duplex 
Ultrasound 
 
 
✓ 
 
✓ 
Rutherford 
✓ 
 
✓ 
✓ 
✓ 

 
 
 
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Table 1 Study Data Collection 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
5.2   Informed Consent 
Prior to initiation of any study specific procedures, an IRB approved Informed Consent Form must 
be signed and dated by the subject.  Subjects must be given ample time to review the ICF and 
have questions answered before signing. The signed Informed Consent Form must be filed in the 
hospital/clinic medical chart or with the study subject documentation and be available for review 
by the IRB.  A copy of the signed ICF must also be given to the subject for their records. A subject 
number will be assigned to the subject after the consent has been signed.  
  
5.3 Baseline Visit (Pre-procedure assessments - up to 30 days) 
Follow-up  Visit Form 
 
 
✓ 
✓ 
✓ 
Adverse Event Form 
 
As they occur 
Deviation Form 
*IVUS/DICOM images to be collected immediately prior to and immediately following use of 
the OAS/Hawkone and again following Drug Coated Balloon Angioplasty procedures. 

 
 
 
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The following data must be collected within 30 days prior to the index procedure for all subjects:  
• 
Demographics and medical history obtained  
• 
Physical assessment including:  
• 
Weight and height  
• 
Rutherford Clinical Category Assessment  
• 
Ankle-Brachial Indices (ABI) measurements  
• 
Antiplatelet medication usage (if applicable) 
 
5.4 Procedure Visit 
 
Prior to Index procedure the confirmation of clinical assessments of the inclusion and exclusion 
criteria must have been met. On the day of the procedure, the patient will be prepped for 
percutaneous intervention per institutional standards. 
Patients may be admitted on the day of the procedure for hydration, if deemed medically 
necessary.  Antiplatelet medication should be initiated prior to procedure at a dose deemed 
appropriate by the Investigator.  Investigator will manage the cardiovascular risk factors and 
comorbidities for all patients according to standard care.  Investigator should ensure close 
monitoring of the amount of contrast for subjects with elevated serum creatinine levels.  
Diagnostic angiography of the lower extremities must be performed using standard techniques 
to confirm angiographic eligibility of the target lesion. Femoro-popliteal arterial lesions intended 
for treatment at the time of the index procedure that met the inclusion and didn’t meet exclusion 
criteria will be considered target lesions.  
 
Randomization Protocol  
A statistician generated list of random treatment allocations (i.e., a randomization schedule) will 
be used to assign subjects to treatments in a 1:1 ratio of directional atherectomy to orbital 
atherectomy treatment groups after successfully crossing the target lesion. The randomization 
assignment sheet will be blinded to the PI.  
Index Procedure 
After randomization, all subjects will undergo percutaneous revascularization of the femoro-
popliteal arteries using a DAS or OAS device and drug coated balloon angioplasty as per the 
randomization arm. 
Adjunctive procedures will be performed at the treating physician’s discretion. Use of the same 
balloon for all dilations is strongly recommended, 1:1 balloon to healthy segment ratio to 
nominal pressure for at least 3 minutes of duration of balloon inflation.  
During the index procedure, the angiographic complications such as emboli, dissections, 
perforations or abrupt closures will be assessed, treated and recorded as needed.  
Intravascular Ultrasound (IVUS) 
All patients will undergo at least 3 runs of IVUS:  
• 
a pre-treatment run to assess the severity and morphology of the plaque composition  
• 
a post-atherectomy run to assess changes post atherectomy treatment 
• 
a post drug coated balloon angioplasty (followed atherectomy) to assess changes in overall 
volumes. 

 
 
 
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The ruler must be utilized for each procedure for precise measurement of the diseased, treated, 
and IVUS evaluated segment(s).  
The OpticrossTM 18 peripheral imaging catheter (Boston Scientific Corp) is a 6-French (Fr) 
compatible catheter that performs intravascular analysis of the culprit lesion, measuring grey-
scale images over a 0.014˝ guidewire.  This device is used routinely at the study center. 
1. Automated pullback (1.0 mm/sec) must be implemented by using the disposable pullback 
device.  
2. All pullbacks must be performed at a sufficiently distal point using an external ruler to mark 
the precise start point. 
3. Images should be recorded on DICOM format and archived on DVD for off-line analysis. 
Anonymized IVUS images and selected angiograms (pre-treatment view of stenosis, 
IVUS location and final post-treatment angiogram) will be sent to the Core Laboratory for 
evaluation.  
Adverse Event Collection 
Complete SAE collection and assessment  
 
5.5 Follow up.  
All randomized/enrolled subjects will be evaluated prior to discharge from the index procedure 
and continue follow up evaluation at 30 days, 6 months, and 12 months after the index 
procedure. Requirements of each follow-up evaluation are described below. 
Visit 1. 30 days Follow up (within 30 days)  
 
All enrolled subjects must be evaluated within 30 days after the index procedure. The following 
assessments must be performed during this visit.  
• 
Rutherford Clinical Category Assessment  
• 
ABI Measurements  
• 
Serious Adverse Events collection and assessment  
• 
Arterial Duplex Ultrasound 
• 
Antiplatelet medications assessment 
 
Visit 2.  6 month Follow up (182 days +/-30 days) 
All enrolled subjects must be evaluated 6 months after the index procedure. The following 
assessments must be performed during 6 month office visit.  
• 
Rutherford Clinical Category Assessment 
• 
ABI Measurements  
• 
Serious Adverse Events collection and assessment  
• 
Antiplatelet medications assessment 
 
Visit 3.  12 month Follow up (365 days +/-30 days) 

 
 
 
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All enrolled subjects must be evaluated 12 months after the index procedure. The following 
assessments must be performed during 12 month office visit.  
• 
Rutherford Clinical Category Assessment 
• 
ABI Measurements  
• 
Serious Adverse Events collection and assessment  
• 
Arterial Duplex Ultrasound 
• 
Antiplatelet medications assessment 
 
5.6 Unscheduled Visits 
An unscheduled follow-up is defined as an office or hospital visit or phone call to the clinic by 
the subject that is not required by the study protocol but is usually related to an event and 
occurs between the study baseline visit and 12 months after the procedure.  If the subject has 
an unscheduled follow-up and:  
• 
No serious adverse events noted during unscheduled visit – no forms need to be 
completed 
• 
Serious adverse event noted – The Adverse Event CRF needs to be completed for each 
event.  
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.   
5.7 Trial Completion 
The trial will be considered complete:  
• 
after all subjects have completed the 12-month follow-up visit;  
• 
withdrew from the study prior to the 12-month follow-up visit;  
• 
have died;  
• 
or presented at time when the follow-up visit window is closed. 
 
5.8 Study Exit 
5.8.a. Lost to Follow-up 
Every effort must be made to retain study subjects for the duration of the study. If the subject 
fails to comply with the protocol requirements to attend the follow up visits, the study center 
should make at least two attempts to contact the subject. Each of the attempts to contact the 
subject must be documented in the subject’s medical record.  
5.8.b. Subject Withdrawal 
If the subject chooses to withdraw from the study, the Investigator should attempt to obtain the 
reasons for the subject’s request to withdraw from the study.  Once a subject has voluntarily 
withdrawn, all of the subject’s data will be used in the study up to and including the date of 
withdrawal. 

 
 
 
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6. Adverse Events, Deviations & Complaints 
6.1  Adverse Events 
The only Adverse Events (AE) that will be collected in the study are those events that meet the 
definition of serious injury, also called a serious adverse event (SAE) , which is required for post 
market surveillance of medical devices by the FDA 
6.2. Serious Adverse Event Definitions 
Serious Adverse Event (SAE) that: 
1. Led to a death; 
2. Led to a serious deterioration in the health of the subject that: 
• 
resulted in a life-threatening illness or injury; 
• 
resulted in permanent impairment of a body structure or a body function; 
• 
or a persistent or significant incapacity or substantial disruption of the ability to conduct      
normal life functions; 
• 
resulted in in-patient hospitalization or prolongation of existing hospitalization; 
• 
resulted in medical or surgical intervention to prevent permanent impairment to body structure 
or a body function; 
3. Led to fetal distress, fetal death or a congenital abnormality or defect. 
 
6.3. Serious Adverse Event Classification 
The relationship of the SAE to the atherectomy device will be classified by the investigator.   
The investigator will use the following definitions in classifying the relationship of SAE to the 
study procedures or the medical device: 
Device Related: A SAE that is directly related to the atherectomy device. 
Procedure Related:  A SAE that is directly attributable to the procedure using the atherectomy 
device.  Usually, these events occur within 2 weeks of the procedure. 
6.4. Serious Adverse Event Reporting 
 
All serious adverse events must be collected, assessed and recorded on the appropriate eCRF.  
All relevant source documentation for event will be stored in the subject binder. 
Adverse event information will be collected up until each subject’s study completion of the trial.  
All adverse events will be reported as per IRB requirements.  
6.5. Study Deviations 
A study deviation is defined as an event where the study is not conducted according to the 
protocol, the study contract, FDA regulations or requirements imposed by the reviewing IRB. 
6.6. Product Return, Device Malfunction, and Complaints 
In the case of device malfunction, device-related adverse events, compromised product, or 
complaints, the device is to be returned to the manufacturer.  Contact CSI Customer Service at 

 
 
 
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1-877-274-0901; or Medtronic Customer Service at 1 800-633-8766 to obtain a Returned Goods 
Authorization (RGA) number.  Every effort should be made to return the device to the Sponsor 
in a timely manner.     
 
7. Risk Analysis 
7.1   Potential Risks and Mitigations 
The medical devices used in this study have received clearance by the FDA to be on the market 
in the US.  Therefore, the risk profile is established and there should be no additional risk to the 
subject due to the use of the OAS/DAS during the procedure as a result of this study.  
  
The risks associated with the endovascular procedure may include, but are not limited to the 
following:  
• 
Amputation  
• 
Aneurysm  
• 
Arterial dissection  
• 
Arterial perforation  
• 
Arterial rupture  
• 
Arterial spasm  
• 
Arteriovenous fistula  
• 
Bleeding complications   
• 
Death  
• 
Embolism or arterial thrombosis 
• 
Emergency or non-emergency arterial bypass surgery 
• 
Hematoma 
• 
Hypotension 
• 
Infection 
• 
Ischemia 
• 
Restenosis of the treated segment 
• 
Total occlusion of the peripheral artery 
• 
Vascular complications that could require surgical repair 
 
7.2   Potential Benefits 
Participation in this study is voluntary. There will be no direct benefits of participating in this 
study. Information gathered from this study may help with further DAS/OAS development that 
may benefit future patients who suffers from peripheral artery disease.   
 
 

 
 
 
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8. Statistical Methods and Data Analysis 
8.1 Data Management 
Electronic case report forms (CRF) will be used to collect the data from the study.  Data will be 
stored in a secure, password-protected database which will be backed up at periodic intervals to 
archive data.  At the end of the study, data will be archived and retained by NYU.     
8.2   Statistical and Data Analysis Methods 
The Biostatistician from NYULMC will perform the analysis in collaboration with the Principal 
Investigator.  No interim analyses are planned.  
Descriptive statistics will be generated to describe study findings (i.e. subject demographics, 
plaque volume, lumen volume, vessel size, etc.).The mean differences between pre-procedure 
and post-procedure measures will be analyzed using paired t-tests. The pre- and post-
procedure changes in the primary and secondary outcomes will be compared between the two 
treatment arms by the Intention to treat (ITT) principle. Multivariable linear regressions will be 
used to compare the change between treatments adjusting for subject demographics and other 
covariates. A p-value of ≤ 0.05 will be considered to indicate statistical significance.     
Group sample sizes of 30 and 30 achieve 80% power to detect a difference of 0.7 standard 
deviation difference in the mean of the primary outcome between the two groups with a 
significance level 0.05. 
IVUS DICOM Image Analysis 
Anonymized IVUS Images and selected angiograms should be recorded on DICOM format and 
archived on DVD for off-line analysis.  
 
Quantitative assessment of the treated segments will be performed using planimetry 
echoPlaque software (Inedc, Mountain View, CA). 
 
9. Data Safety Monitoring 
Due to the fact that this is an investigator initiated trial there will be no external monitoring or 
auditing for this study. In this study, a Clinical Event Committee (CEC) or a Data Safety 
Monitoring Board (DSMB) will not be used. The Principal Investigator will conduct interim 
monitoring of any serious adverse event at the time of occurrence and annually to assure the 
continuing safety of participants, relevance of the study question, appropriateness of the study 
protocol compliance and integrity of the accumulating data. The PI in conjunction with NYU IRB 
will be responsible for monitoring the data and conducting safety reviews every12 months when 
annual re-approval is sought. During the review process, the PI and NYU IRB will evaluate 
whether the study should continue unchanged, require modification/amendment, or close to 
enrollment. This study will not have predefined stopping rules due to the fact that both devices 
are proven to be safe in multiple clinical trials and approved by FDA for routine clinical practice.  
 

 
 
 
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10. Investigator Records and Reports 
10.1 Investigator Records 
The investigator is responsible for the preparation (review and signature) and/or retention of the 
records cited below.  
• 
Subject’s case history records, including: signed/dated subject consent form, 
observations of serious adverse events, relevant medical history and results of tests or 
exams performed in this study, and dates of follow-up office visits. 
• 
Protocol and amendments 
• 
IRB approval documents and correspondence 
10.2 Investigator Reports 
The investigator is responsible for the preparation (review and signature) and submission of all 
case report forms (CRFs), serious adverse events (SAEs), and deviations from the protocol.  
The investigator shall prepare and submit in a complete, accurate and timely manner the reports 
listed in Table 2. 
 
 
 
 
 
 
 
 
11. Publication 
11.1 Clinical Trial Registration 
This study will be submitted for inclusion in the clinical trial registry at: 
http://www.ClinicalTrials.gov for publication purposes. 
 
The following statement will be included in the informed consent form for the study to notify the 
prospective subjects for the study: "A description of this clinical trial will be available on 
http://www.ClinicalTrials.gov, as required by U.S. Law. This website will not include information 
that can identify you. At most, the Web site will include a summary of the results. You can 
search this Web site at any time." 
Table 2: Investigator Reports for Study 
Report: 
 
To: 
Description/Constraints: 
 
Serious Adverse 
Events (SAEs) 
 
IRB per 
policy 
Immediate notification, but no later than 5 
business days after discovery of event. 
Death 
IRB per 
policy 
Immediate notification, but no later than 5 
business days after discovery of death. 
Deviations to the 
Protocol 
 
As soon as possible after occurrence of 
deviation. 

 
 
 
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11.2 Publication Review 
Any previously unpublished information provided to the Investigators 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. 
 
An Investigator may publish the study experience from his/her own site. The Sponsor reserves 
the right to review the manuscript prior to submission in order to verify accuracy of the data.  
The Investigator may proceed with the publication when notified by the Sponsor. 
 
 
 
12. Bibliography  
 1)  Fakhry F et al. Endovascular Revascularization and Supervised Exercise for Peripheral 
Artery Diseasand Intermittent Claudication: A Randomized Clinical Trial. JAMA,  2015 
Nov;314(18):1936-44. 
2) Fitzgerald PJ, Ports TA, Yock PG. Contribution of localized calcium deposits to dissection 
after angioplasty. An observational study using ultrasound. Circulation 1992; 86:64-70.  
 
3) Mckinsey JF et al. Lower Extremity Revascularization Using Directional Atherectomy. 12  
Month Prospective results of the DEFNITIVE LE Study. J AM Coll Cardiol Intv 2014;7:923-33 
 
4) Shammas NW et al. Percutaneous Lower-extremity Arterial Interventions with Primary 
Balloon Angioplasty Versus SilverHawk Atherectomy and Adjunctive Balloon Angioplasty: 
Randomized Trial J Vasc Interv Radiol 2011; 22:1223:1228 
 
5) Babaev A et al. Orbital Atherectomy Plaque Modification of the Femoropopliteal Artery Via 
Intravascular Ultrasound ( TRUTH Study) Vascular and Endovascular Surgery 2015; 49: 188-
194 
 
6) Datillo R et al. The COMPLIANCE 360° Trial: a randomized, prospective, multicenter, pilot 
study comparing acute and long-term results of orbital atherectomy to balloon angioplasty for 
calcified femoropopliteal disease. J Invasive Cardiol 2014; 26:8 355-60 
 
7) Shammas NW et al. Comparison of Orbital Atherectomy Plus Balloon Angioplasty vs Balloon 
Angioplasty Alone in Patients with Critical Limb Ischemia. Results of the CALCIUM 360 
Randomized Pilot Trial. J Endovasc Ther 2015;19:480-488 
 
8) Kayssi a et al. Drug-eluting balloon angioplasty versus uncoated balloon angioplasty for 
peripheral arterial disease of the lower limbs. Cochrane database syst rev ; 2016 
4;(8):CD011319.