Feasibility Clinical Trial of the Cardio Flow FreedomFlow Orbital Atherectomy System to Treat Peripheral Artery Disease
Phase: NA
Conditions: Peripheral Arterial Disease
Sponsor: Cardio Flow, Inc.

Protocol Version 6.0  
Page 1 of 45 
Feasibility Clinical Trial of the Cardio Flow FreedomFlow™ Orbital 
Atherectomy System to Treat Peripheral Artery Disease (FAST Trial) 
 
Protocol Number: 
010-031 
Version 
6.0 
Date 
November 20, 2017 
Investigational Product 
Cardio Flow FreedomFlowTM Orbital Atherectomy System 
Regulatory Status 
Limited to Investigational Use Only 
Principal Investigator 
 
Jihad Mustapha, MD 
 
Sponsor (mailing address for 
clinical study information) 
Cardio Flow, Inc. 
525 Main Street 
PO Box 120018 
St. Paul, MN 55112 
 
Clinical Trial Management 
and Monitoring 
Libra Medical Inc. 
8401 73rd Ave. 
Brooklyn Park, MN 55428 
Angiography Core Laboratory  
Beth Israel Deaconess Medical Center 
Cardiovascular Imaging Core Laboratory  
940-West Commonwealth Avenue, 2nd Floor 
Boston, MA 02215
Duplex Ultrasound Core 
Laboratory 
Massachusetts General Hospital 
The Vascular Ultrasound Core Laboratory 
One Bowdoin Square, 10th Floor 
Boston, Massachusetts 02114 
 
 
This study will be conducted in compliance with Food and Drug Administration (FDA) 
Regulations, 21 CFR Parts 50, 54, 56, 812, and 11.  
 
CONFIDENTIALITY STATEMENT 
This study is confidential in nature. All information related to this study is considered proprietary and 
should not be made available, to those not directly involved in this study. Authorized recipients of this 
information include investigators and co-investigators, other health care personnel necessary to conduct 
the study, and the presiding Institutional Review Boards and governing regulatory agencies. The 
personnel provided with data from this study   are hereby informed of its confidential and proprietary 
nature. Release of these data to individuals other than those listed above requires the prior written 
permission of Cardio Flow, Inc. 
 
 
 

 
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Protocol Review and Approval Page  
 
 
STUDY TITLE: Feasibility Clinical Trial of the Cardio Flow FreedomFlow™ Orbital 
Atherectomy System to Treat Peripheral Artery Disease (FAST Trial) 
PROTOCOL NUMBER: 010-031 
PROTOCOL VERSION: 6.0 
PROTOCOL DATE: November 20, 2017 
 
 
Investigator’s Statement: I agree to conduct this clinical study in accordance with the design and 
specific provisions of this protocol; modifications to the study or protocol are acceptable only 
with a mutually agreed upon protocol amendment. I agree to await IRB approval for the 
protocol and informed consent before initiating the study, to obtain informed consent from 
subjects prior to their enrollment in the study, to collect and record data as required by this 
protocol and case report forms, to prepare annual, final, and adverse event reports as required by 
this protocol, and to maintain study documentation for the period of time required. 
 
 
 
Investigator Name and Signature 
 
Name: _______________________________ 
 
Signature: _____________________________ 
Date of Signature: 
Site Name and Address: 
 
 
 

 
Protocol Version 6.0  
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Protocol Synopsis 
Protocol Number and 
Version Number 
010-031, Version 6.0 
Protocol Title 
Feasibility Clinical Trial of the Cardio Flow FreedomFlow™ Orbital Atherectomy 
System to Treat Peripheral Artery Disease (FAST Trial) 
Investigational Product 
Cardio Flow FreedomFlow™ Orbital Atherectomy System 
 
CM1001 – Control Module 
 
H4001 –User Handle + Tubing Set 
Study Objective: 
To evaluate first-in-human safety and effectiveness of the Cardio Flow 
FreedomFlow™ Orbital Atherectomy System for atherosclerotic plaque removal in 
de novo native target lesions in the peripheral vasculature of the lower extremities. 
Study Design: 
Prospective, 2-centers, non-randomized single-arm study 
Enrollment Size and 
Number of Sites: 
Up to 10 subjects at up to 2 sites in the United States.   
Primary Safety 
Endpoint: 
 
Freedom from a composite of new on-set major adverse events (MAE) at 30-day 
follow-up as adjudicated by an Independent Clinical Events Adjudicator. 
The components of the MAE are defined as: 
 
Cardiovascular related death: All cardiovascular cause mortality.
 
Myocardial infarction (MI): Any newly diagnosed MI post procedure, defined 
as CK-MB ≥2X upper limit normal (ULN).  
 
Clinically driven target lesion revascularization (TLR): any repeat 
percutaneous or surgical intervention to treat objectively documented symptoms 
of recurrent ischemia attributable to the treated lesion.
 
Clinically significant target vessel dissection: NHLBI grade C or greater as 
confirmed by angiography.
 
Clinically significant target vessel perforation: NHLBI Type III as confirmed 
by angiography.
 
Unplanned major target limb amputation: Amputation of the 
transmetatarsals or higher that was not previously planned as part of the overall 
treatment strategy.
 
Clinically relevant distal embolization: Emboli requiring surgical or medical 
intervention and/or the presence of symptoms.
 
Pseudoaneurysm: disruption of the arterial wall at the treatment site as 
confirmed by angiography. 
 
Secondary Safety 
Endpoints: 
 
Hemoglobin, hematocrit, and free hemoglobin (pre-and post-procedure and pre-
discharge) 
 
Device and procedure related serious adverse events at 30 days and 6 months 
Primary Effectiveness:  
 
Technical Success, defined as the ability of the Cardio Flow FreedomFlow™ 
Orbital Atherectomy System to achieve a residual diameter stenosis <50% post 
treatment without adjunctive therapy, as assessed by an Angiographic Core 
Laboratory. 
Secondary Effectiveness:  
Clinical Success, defined as the ability of the Cardio Flow FreedomFlow™ 

 
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Orbital Atherectomy System to achieve a final residual diameter stenosis <50% 
with adjunctive therapy, determined by independent angiographic core 
laboratory. 
 
Procedure Success, defined as: 
o 
No procedure-related MAE 
o 
< 50% residual stenosis at target lesion 
o 
No device malfunction causing the procedure to be aborted 
 
Percent of device run time less than 3 minutes cumulative total 
 
Maximum balloon inflation pressure of the adjunctive plain balloon angioplasty 
and/or drug coated balloon angioplasty  
 
Improvement of ABIs at 30 days and 6 months  
 
Improvement of Rutherford Classification at 30 days and 6 months  
 
Improvement of patient reported outcomes (PRO, VascuQoL questionnaire) at 30 
days and 6 months 
 
Clinical driven target lesion revascularization (TLR), target vessel 
revascularization (TVR) at 30 days and 6 months (to be evaluated by 
angiographic core laboratory) 
 
Primary patency, primary assisted patency and secondary patency at 30 days and 
6 months. Doppler ultrasound examinations at 30 days and 6 months to confirm 
patency (to be evaluated by duplex ultrasound core laboratory). The restenosis is 
defined as peak systolic velocity ratio (PSVR) of 2.5. 
Inclusion Criteria: 
 
 
 
Subjects must meet all of the following criteria to be eligible for participation in the 
study: 
Inclusion Criteria 
1. Age ≥ 18 years old. 
2. Subject is a candidate for percutaneous endovascular intervention for 
peripheral vascular disease in the lower extremity. 
3. Disease is located in the common femoral, superficial femoral, popliteal, 
anterior tibial, posterior tibial, or peroneal artery in arteries.  
4. Objective hemodynamic criteria that subject has a resting ankle-brachial index 
(ABI) ≤ 0.90, OR subjects with non- compressible arteries (ABI>1.1) must 
have a toe-brachial index (TBI) of ≤ 0.80. 
5. Clinical presentation of lifestyle limiting claudication or rest pain as 
characterized by Rutherford Classification 2, 3, 4, or 5. 
6. Subject has de novo target lesion(s) or lesion(s) treated by percutaneous 
transluminal angioplasty (PTA) only greater than 3 months prior with stenosis 
≥70% by visual estimation in the common femoral, superficial femoral, 
popliteal, anterior tibial, posterior tibial, or peroneal artery. Up to three lesions 
can be treated at the index procedure provided the cumulative total lesion 
length is ≤ 30 cm AND all lesions are in the same leg. 
7. Target reference vessel diameter (proximal to and distal to target lesion) is 2 to 
5mm by angiographic visual estimation. 
8. At least one patent vessel run-off to the ankle or foot at baseline.  
9. The target lesion(s) can be successfully crossed with a commercially available 
0.014” atherectomy guidewire without any complications during wiring 

 
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procedure. 
10. Subject signs a written Informed Consent form to participate in the study, prior 
to any study mandated determinations or procedure. 
Exclusion Criteria: 
Subject must be excluded from participation in this study if any of the following 
criteria are met: 
Exclusion Criteria 
1. Is female with childbearing potential not taking adequate contraceptives or is 
currently breastfeeding.   
2. Target lesion is within a native graft or synthetic graft.  
3. Target lesion is an in-stent restenosis. 
4. Chronic total occlusion (CTO) with wire crossed near the advential junction. 
5. Subject has significant stenosis or occlusion of inflow tract (upstream disease) 
not successfully treated during the index procedure and prior to treatment of 
the target lesion.  
6. History of an endovascular procedure or open vascular surgery on the index 
limb within 30 days prior to the index procedure.  
7. Planned endovascular or surgical procedure within 30 days after the index 
procedure.  
8. Signs and symptoms of systemic infection (temperature of  ≥ 38.0° Celsius 
and/or WBC of ≥ 12,000 cells/µL) at the time of assessment;
     Note: If infection is adequately treated and controlled (temperature    < 
38.0° C and WBC < 12,000 cells/µL) patient may be enrolled.  
9. Unstable coronary artery disease or other comorbid condition(s) that, in the 
judgment of the physician precludes safe percutaneous intervention.  
10. Significant acute or chronic kidney disease with a creatinine level > 2.5mg/dL 
and/or requiring dialysis.  
11. Evidence or history of intracranial or gastrointestinal bleeding, intracranial 
aneurysm, myocardial infarction or stoke within 2 months of index procedure. 
12. Evidence or history of aneurysmal target vessel.  
13. Clinical/angiographic evidence of distal embolization. 
14. Known allergy to contrast agents or medications used to perform 
endovascular intervention that cannot be adequately pre-treated.   
15. Subjects in whom anti-platelet, anticoagulant, or thrombolytic therapy is 
contraindicated.  
16. Heparin-induced thrombocytopenia (HIT) not able to use Bivalirudin.  
17. Uncorrectable bleeding diathesis, platelet dysfunction, thrombocytopenia 
with platelet count less than 125,000/mm2, known coagulopathy, or INR > 
1.5.   
18. Thrombolytic therapy within 2 weeks of the index procedure. 
19. Intra-operative (intra-procedure) clinical or angiographic complication (other 
than non-flow limiting dissections) attributed to the use of a currently 
marketed device prior to introduction of the Cardio Flow atherectomy 
driveshaft.  
20. Has life expectancy < 12 months. 
21. Subject is unwilling or unable to comply with the follow-up study 
requirements.  
22. Is currently participating in an investigational drug or another device study. 

 
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23. Has one or more stents in the treatment vessel.  
24. Lacking capacity to provide consent.  
Study Duration / Follow-
up Period: 
Approximately 2 months enrollment period with observation periods at time of 
procedure, 30 days post procedure and 6 months post procedure. An interim report 
will be prepared after 30-day follow-up of all subjects.  A final report will be 
prepared following completion of 6-month follow-up of all subjects. 
 
Subjects will be followed per protocol and institutional standard of care for 
atherectomy treatment of PAD.   
Analysis Population 
The primary analysis will be based on the intent-to-treat (ITT) population. 
 
 
 
 
 

 
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Table of Content 
1 
BACKGROUND AND RATIONALE .................................................................................................... 11 
2 
DEVICE DESCRIPTION AND USE ...................................................................................................... 12 
2.1 
DEVICE DESCRIPTION ............................................................................................................................... 12 
2.1.1 
Control Module .................................................................................................................................. 13 
2.1.2 
Tubing Set .......................................................................................................................................... 14 
2.1.3 
User Handle ....................................................................................................................................... 15 
2.1.4 
Driveshaft Details .............................................................................................................................. 15 
2.2 
INTENDED USE ........................................................................................................................................ 16 
2.3 
INDICATION FOR USE ............................................................................................................................... 16 
3 
STUDY PURPOSE AND OBJECTIVE ................................................................................................... 16 
4 
STUDY DESIGN............................................................................................................................... 16 
4.1 
OVERVIEW ............................................................................................................................................. 16 
4.2 
SAMPLE SIZE AND NUMBER OF CENTERS ...................................................................................................... 17 
4.3 
STUDY DURATION ................................................................................................................................... 17 
5 
STUDY ENDPOINTS ........................................................................................................................ 17 
5.1 
PRIMARY SAFETY ENDPOINTS .................................................................................................................... 17 
5.2 
PRIMARY EFFECTIVENESS ENDPOINT ........................................................................................................... 17 
5.3 
SECONDARY ENDPOINTS ........................................................................................................................... 18 
5.3.1 
Secondary Safety Endpoints ............................................................................................................... 18 
5.3.2 
Secondary Effectiveness Endpoints .................................................................................................... 18 
6 
STUDY PROCEDURE ....................................................................................................................... 18 
6.1 
PATIENT ELIGIBILITY, PRE‐SCREENING AND EXCLUSIONS .................................................................................. 18 
6.1.1 
Inclusion Criteria ................................................................................................................................ 19 
6.1.2 
Exclusion Criteria ............................................................................................................................... 19 
6.2 
PRE‐SCREENING AND WRITTEN INFORMED CONSENT ..................................................................................... 21 
6.3 
ENROLLMENT ......................................................................................................................................... 21 
6.4 
BASELINE EVALUATION (WITHIN 30 DAYS OF INDEX PROCEDURE) .................................................................... 21 
6.5 
INDEX PROCEDURE .................................................................................................................................. 22 
6.5.1 
Angiography ...................................................................................................................................... 22 
6.5.2 
Non‐Target Vessel/Lesion Intervention ............................................................................................. 22 

 
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6.5.3 
Cardio Flow FreedomFlow™ Orbital Atherectomy Procedure ............................................................ 23 
6.5.4 
Procedure Medications ...................................................................................................................... 25 
6.6 
POST PROCEDURE TO DISCHARGE ............................................................................................................... 25 
6.7 
30 DAYS FOLLOW‐UP (± 7 DAYS) ............................................................................................................... 26 
6.8 
6 MONTHS FOLLOW‐UP (± 14 DAYS) ......................................................................................................... 26 
6.9 
UNPLANNED FOLLOW‐UP ......................................................................................................................... 27 
6.10  SUBJECT EARLY DISCONTINUATION / WITHDRAWAL AND REPLACEMENT OF SUBJECTS .......................................... 27 
6.11  LOST TO FOLLOW‐UP ............................................................................................................................... 27 
7 
BENEFIT / RISK ANALYSIS ............................................................................................................... 28 
7.1 
BENEFITS ............................................................................................................................................... 28 
7.2 
RISKS .................................................................................................................................................... 28 
7.3 
MINIMIZATION OF RISK AND MONITORING PROCEDURE ................................................................................. 29 
8 
STATISTICS .................................................................................................................................... 29 
9 
DATA MANAGEMENT .................................................................................................................... 29 
9.1 
SUBJECT IDENTIFICATION .......................................................................................................................... 29 
9.2 
CENTRAL DATABASE ................................................................................................................................ 29 
9.3 
SOURCE DOCUMENTS .............................................................................................................................. 30 
9.4 
DATA COLLECTION................................................................................................................................... 30 
9.5 
DATA PROCESSING .................................................................................................................................. 30 
9.6 
STUDY REPORT ....................................................................................................................................... 30 
10 
STUDY ADMINISTRATION .............................................................................................................. 30 
10.1  MONITORING ......................................................................................................................................... 30 
10.1.1 
Monitoring Procedures ...................................................................................................................... 30 
10.1.2 
Monitoring Visit ................................................................................................................................. 31 
10.1.3 
Study Closure ..................................................................................................................................... 32 
10.2  DEVICE ACCOUNTABILITY .......................................................................................................................... 32 
11 
DEFINITION OF ADVERSE EVENT(S) ................................................................................................ 33 
11.1  SERIOUS ADVERSE EVENTS ........................................................................................................................ 34 
11.2  DEVICE RELATIONSHIP .............................................................................................................................. 34 
11.3  UNANTICIPATED ADVERSE DEVICE EFFECT .................................................................................................... 34 
11.4  ADVERSE EVENT REPORTING ..................................................................................................................... 34 
11.5  ADVERSE EVENT ASSESSMENT ................................................................................................................... 35 

 
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11.5.1 
Initial Assessment .............................................................................................................................. 35 
11.5.2 
Assessment of Severity ...................................................................................................................... 35 
11.5.3 
Device Relatedness ............................................................................................................................ 36 
11.6  DEVICE DEFICIENCY OR MALFUNCTION ........................................................................................................ 36 
11.7  REPORTING OF DEATH .............................................................................................................................. 37 
12 
STUDY ADMINISTRATIV OVERSIGHT .............................................................................................. 37 
12.1  CORE LABORATORY .................................................................................................................................. 37 
12.2  CLINICAL ADVERSE EVENT ADJUDICATION .................................................................................................... 37 
12.3  IRB APPROVAL ....................................................................................................................................... 38 
12.4  INFORMED CONSENT ............................................................................................................................... 38 
12.5  RECORDS ............................................................................................................................................... 39 
12.6  REPORTS ............................................................................................................................................... 39 
12.7  INVESTIGATOR RESPONSIBILITIES ................................................................................................................ 40 
12.8  SPONSOR RESPONSIBILITIES ....................................................................................................................... 41 
12.9  PROTOCOL DEVIATIONS / VIOLATIONS AND MEDICAL EMERGENCIES ................................................................. 42 
12.10 PRE‐STUDY DOCUMENTATION REQUIREMENTS ............................................................................................. 42 
12.11 CRITERIA FOR TERMINATING STUDY ............................................................................................................ 42 
12.12 PUBLICATION POLICY ............................................................................................................................... 43 
13 
REVISION HISTORY ........................................................................................................................ 43 
14 
BIBLIOGRAPHY .............................................................................................................................. 44 
 
 
 

 
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List of Tables 
Table 6-1: Schedule of Events ................................................................................................................... 26 
Table 12-1: Reports Required from Investigators to Sponsor ................................................................... 40 
 
List of Figures 
Figure 2-1: FreedomFlow™ Orbital Atherectomy System ....................................................................... 13 
Figure 2-2: Control Module....................................................................................................................... 14 
Figure 2-3: Tubing Set .............................................................................................................................. 14 
Figure 2-4: User Handle ............................................................................................................................ 15 
Figure 2-5: Driveshaft Tip ......................................................................................................................... 16 
 
 
 

 
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1 BACKGROUND AND RATIONALE 
Atherosclerosis causes symptomatic disease primarily in the coronary arteries, the peripheral 
arteries of the lower extremities, and the extra-cranial carotid arteries.1 Of the three, peripheral 
artery disease (PAD) is probably the most under-diagnosed and least aggressively managed, 
despite its strong association with cardiovascular disease (CVD) and death.  PAD is chronic 
occlusive artery disease of the lower extremities and a strong surrogate marker for atherosclerosis 
in the heart, kidneys, and brain.1,3,4,5 PAD is associated with a 60% incidence of coronary or 
cerebrovascular disease.6 About 90% of patients with symptomatic PAD have coronary artery 
disease (CAD) as well.7 The disease can have devastating effects on quality of life and survival, 
with mortality around 30% in 5 years, 50% in 10 years and 75% in 15 years.8   Overall, CVD 
causes death in 75% of PAD patients. 
Most common among elderly people, diabetics, and smokers, PAD afflicts an estimated 8-12 
million people in the United States alone. Its prevalence is likely to increase greatly in the next 
several decades as the risk factors of diabetes, smoking, hypertension, dyslipidemia and 
cardiovascular incidence increase. 
Classic symptoms of PAD include intermittent claudication (IC), defined as leg muscle pain or 
weakness that occurs during walking and subsides with rest.2 The exercise-induced symptoms are 
distal to the obstruction in the artery that supplies the leg. Rest pain in the toes or foot indicates 
that arterial blood flow cannot meet the needs of resting metabolism. The resulting critical limb 
ischemia (CLI) can progress to ulceration or gangrene in the toes, ankle, heel, or leg, often 
necessitating amputation.2 
Even asymptomatic PAD patients, those without IC, have poor physical function.9 Detecting 
asymptomatic PAD requires measuring and calculating the ankle/brachial index (ABI), obtained 
by dividing blood pressure measured in the ankle by the blood pressure measured in the upper 
arm.10 In a healthy person, the ABI is 0.9 to 1.2. An ABI under 0.9 is 95% sensitive and 99% 
specific for the diagnosis of PAD. The lower the ABI level, the more serious is the ischemia. An 
ABI of 0.5 is associated with a 63% five-year survival rate, and ABIs between 0.25 and 0.4 are 
often associated with rest pain and tissue loss.11 Patients with normal ABIs and IC are advised to 
undergo an exercise ABI assessment.5 Patients with calcified, relatively incompressible arteries 
from diabetes or renal disease may have false normal ABIs. To diagnose such patients, vascular 
laboratories can measure a toe/brachial index or do other noninvasive testing. Physicians can also 
use an exercise ABI measurement to assess IC patients with normal ABI scores.12, 13 
The overall goals of PAD treatment are to maintain or improve function, reduce or eliminate 
ischemic symptoms and prevent disease progression.2 Current treatments include exercise, 
medical  treatment  to  lower  cholesterol  and  blood  pressure,  and  surgery  or percutaneous 
interventions to restore blood flow in patients with intermittent claudication (IC) or critical limb 
ischemia (CLI).14 Invasive treatments include bypass surgery, percutaneous transluminal 
angioplasty (PTA)15, percutaneous atherectomy (directional or rotational)16, endarterectomy, 
excimer laser combined with PTA17 and stenting (drug-eluting stents) of the occluded or stenosed 
vessel. Therapeutic angiogenesis, which uses angiogenic growth factors or bone marrow 
mononuclear cell therapy to stimulate growth of new blood vessels18, and subintimal 

 
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angioplasty, in which a new lumen is tunneled between the intima and the media, are under 
study.19, 20 
Technical challenges involved in treating PAD surgically or percutaneously arise from anatomy, 
co-existing diseases such as diabetes, restenosis, inflammation and disease progression. 
Surgery21 or percutaneous interventions22 in the aorto-iliac arteries have better results than in the 
femoropopliteal arteries, and in turn, results in the femoropopliteal arteries tend to be better than 
those in the smaller lower-leg arteries. 
Atherectomy is a minimally invasive endovascular technique for removing atherosclerotic 
plaque from blood vessels within the body. There are three main types of atherectomy devices: 
directional, laser, and rotational, which includes a subset known as orbital. The current U.S. 
Food and Drug Administration (FDA) cleared devices for peripheral atherectomy include the 
SilverHawk™, TurboElite™, Rotoblator™, Diamondback™, JetStream™, Phoenix™, and 
Pantheris™. Cardio Flow, Inc. has pioneered advances in orbital atherectomy technology for the 
intravascular treatment of PAD using the Cardio Flow FreedomFlowTM Orbital Atherectomy 
System. 
The Cardio Flow FreedomFlowTM Orbital Atherectomy System is intended to remove fibrous and 
calcified stenotic plaque using diamond-coated eccentric spheres attached to a driveshaft in a 
spiral configuration.  The device intended to operate over a commercially available 0.014’ 
atherectomy guidewire to treat vessels from 2mm to 5mm in diameter. No driveshaft lubricant is 
required for use with the Cardio Flow FreedomFlowTM Orbital Atherectomy System.   
One GLP-like porcine studies (2 pigs) were conducted to assess safety and device performance in 
normal peripheral arteries a range of vessel sizes.  Devices were operated according to the 
Instruction for Use.  Animals were survived for three days post-treatment and the treated vessels 
were harvested and histopathological evaluation performed. 
One human cadaver study (3 limbs) was also conducted according to the Instruction for Use.  The 
limb studies were utilized to obtain particulate from the atherectomy procedure for a size 
distribution analysis and to observe device operation in occluded arteries.  
2 DEVICE DESCRIPTION AND USE 
2.1 
Device Description 
The FreedomFlow™ Orbital Atherectomy System consists of a Control Module, Tubing Set, and 
User Handle. It is designed to remove atherosclerotic plaque from peripheral arteries by rotation 
of diamond-coated spheres mounted eccentrically on a coiled driveshaft. The Control Module is 
reusable capital equipment. The Tubing Set and User Handle are single-use sterile devices. The 
User Handle is used to activate rotation and advance the driveshaft on a commercially available 
0.014-inch bare-metal atherectomy guidewire. The guidewire and introducer sheath are not 
included with the system. The Tubing Set and User Handle are the only parts of the system applied 
to the patient. 
 

 
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Figure 2-1: FreedomFlow™ Orbital Atherectomy System 
 
2.1.1 
Control Module 
The Control Module, Model CM1001, is a portable, reusable component of the system that 
integrates delivery of saline and pneumatic power to the User Handle. The Control Module 
touchscreen is the primary interface for operating the peristaltic pump and regulating orbital speed 
of the User Handle. The pre-programmed Control Module includes a pneumatic pressure hose 
and hospital-grade electrical plug. The Control Module can be placed on a table or mounted to a 
standard 5-wheel IV pole. 
 
Control 
Module 
Tubing Set 
User 

 
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Figure 2-2: Control Module  
2.1.2 
Tubing Set 
The Tubing Set is a single-use component that is packaged with the User Handle. The Tubing Set 
is supplied sterile (via Ethylene Oxide gas). The set delivers saline and pressurized gas from the 
Control Module to the User Handle. A cable and sensor relay orbital speed back to the Control 
Module.  
 
 
Figure 2-3: Tubing Set  
 

 
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2.1.3 
User Handle 
The User Handle is a single-use component that provides control over rotation and translational 
movement of the integrated driveshaft. The User Handle is supplied sterile (via Ethylene Oxide 
gas). A spring-loaded button on the User Handle is depressed to activate the pneumatic driveshaft 
and released to stop rotation. The turbine carriage of the User Handle has 7 cm of travel and is 
used to advance and retract the driveshaft’s diamond-coated distal tip and eccentrically mounted 
diamond-coated spheres independently of the catheter tubing. The User Handle guidewire clamp 
prevents guidewire movement during use.  User Handle H4001 will be evaluated in this clinical 
trial and can be used to treat a range of vessel sizes. Refer to Instructions for Use for guidance on 
appropriate vessel sizes that can be treated with User Handle H4001. 
 
Figure 2-4: User Handle 
2.1.4 
Driveshaft Details 
The driveshaft is a hollow multi-strand cable that drives the spinning of the diamond-coated 
spheres. The off-axis eccentric attachment of the spheres onto the driveshaft force the spheres in 
an outward centrifugal direction during rotation. The diamond-coated distal tip is designed to add 
stability and may ease transition into a tight stenotic lesion. 
 
 
 

 
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Figure 2-5: Driveshaft Tip 
The Cardio Flow Orbital Atherectomy User Handle and Tubing Set are sterile, disposable devices 
that are intended for use during a single patient procedure and are used with the Control Module, 
which is a non-sterile, reusable unit that controls system operation. 
2.2 
Intended Use 
The FreedomFlow™ Orbital Atherectomy System is a minimally invasive, catheter-based system 
designed for improving luminal diameter in patients with PAD. 
2.3 
Indication For Use 
The FreedomFlow™ Orbital Atherectomy System is applied as therapy to remove atherosclerotic 
plaque within peripheral arterial vessels. The therapy is intended for patients who are acceptable 
candidates for percutaneous transluminal atherectomy. 
3 STUDY PURPOSE AND OBJECTIVE 
The primary objective of the study is to evaluate the first-in-human safety and effectiveness of 
the FreedomFlow™ Orbital Atherectomy System for atherosclerotic plaque removal in de novo 
target lesions in the peripheral vasculature of the lower extremities. 
4 STUDY DESIGN 
4.1 
Overview 
This is a first in human (FIH) prospective, two-center, non-randomized single-arm study designed 
to evaluate the safety and effectiveness of the FreedomFlow™ Orbital Atherectomy System in 
subjects diagnosed with peripheral arterial disease of the lower extremities.  

 
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4.2 
Sample Size and Number of Centers 
The study may enroll up to 10 subjects and will be conducted at up to 2 investigational sites in 
the United States.  
4.3 
Study Duration 
Enrollment is expected to take approximately 2 months with observation periods at time of 
procedure, pre-discharge, 30 days, and 6 months post-procedure follow-up. 
5 STUDY ENDPOINTS 
5.1 
Primary Safety Endpoints 
The primary safety endpoint is freedom from a composite of new on-set major adverse events 
(MAE) through 30-day follow-up as adjudicated by an independent clinical adjudicator. 
The components of the MAE are defined as: 
 Cardiovascular related death: All cardiovascular cause mortality.
 Myocardial infarction (MI): Any newly diagnosed MI post procedure, defined as 
CK-MB ≥2X upper limit normal (ULN).     
 Clinically driven target lesion revascularization (TLR): any repeat percutaneous 
or surgical intervention to treat objectively documented symptoms of recurrent 
ischemia attributable to the treated lesion.
 Clinically significant target vessel dissection: NHLBI grade C or greater as 
confirmed by angiography.
 Clinically significant target vessel perforation: NHLBI Type III as confirmed by 
angiography.
 Unplanned major target limb amputation: Amputation of the transmetatarsals or 
higher that was not previously planned as part of the overall treatment strategy.
 Clinically relevant distal embolization: Emboli requiring surgical or medical 
intervention and/or the presence of symptoms.
 Pseudoaneurysm: disruption of the arterial wall at the treatment site as confirmed 
by angiography.  
5.2 
Primary Effectiveness Endpoint 
The primary effectiveness endpoint is technical success. The technical success is defined as the 
ability of the FreedomFlow™ Orbital Atherectomy System to achieve a residual diameter stenosis 
<50% immediately post treatment without adjunctive balloon inflation, as assessed by an 
independent Angiographic Core Laboratory. 
 

 
Protocol Version 6.0  
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5.3 
Secondary Endpoints 
5.3.1 
Secondary Safety Endpoints 
 
Hemoglobin, hematocrit, and free hemoglobin (pre-procedure, immediately post-
procedure, and at discharge) will be measured and reported. 
 
All device and procedure related serious adverse events at 30 days and 6 months 
post procedure. 
5.3.2 
Secondary Effectiveness Endpoints 
 Clinical Success, defined as the ability of the FreedomFlow™ Orbital Atherectomy 
System to achieve a final residual diameter stenosis <50% with or without 
adjunctive low pressure balloon therapy, determined by independent angiographic 
core laboratory. 
 Procedure Success, defined as: 
o 
No procedure-related MAE 
o 
< 50% residual stenosis at target lesion 
o 
No device malfunction causing the procedure to be aborted 
 Percent of device run time less than 3 minutes cumulative total 
 Maximum balloon inflation pressure with adjunctive plain balloon angioplasty 
and/or drug coated balloon angioplasty  
 Improvement of ABIs at 30 days and 6 months 
 Improvement of Rutherford Classification at 30 days and 6 months.  
 Improvement of patient reported outcomes (PRO, VascuQoL questionnaire) at 30 
days and 6 months 
 Clinical driven target lesion revascularization (TLR), target vessel revascularization 
(TVR) at 30 days and 6 months (diagnosis of TLR and TVR to be verified by an 
angiographic core laboratory) 
 Primary patency, primary assisted patency and secondary patency at 30 days and 6 
months. Patency will be evaluated by duplex ultrasound and evaluated by a Duplex 
Ultrasound core laboratory). The restenosis is defined as PSVR of 2.5 
6 STUDY PROCEDURE 
6.1 
Patient Eligibility, Pre-screening and Exclusions 
All patients scheduled for a percutaneous endovascular intervention for PAD in the lower 
extremity will be screened for study eligibility. A Screening/Enrollment Log will be provided to 
the study sites, in order to maintain a cumulative tracking of all screened patients. 
Subjects must meet all inclusion/exclusion criteria for enrollment in the clinical study. Reasons 
for screening failure(s) will be documented. 

 
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6.1.1 
Inclusion Criteria 
Subjects must meet ALL of the following criteria to be eligible for participation in the 
study: 
1. 
Age ≥ 18 years old. 
2. 
Subject is a candidate for percutaneous endovascular intervention for 
peripheral vascular disease in the lower extremity. 
3. 
Disease is located in the common femoral, superficial femoral, 
popliteal, anterior tibial, posterior tibial, or peroneal artery.  
4. 
Objective hemodynamic evaluation that subject has a resting ankle-
brachial index (ABI) ≤ 0.90, OR subjects with non- compressible 
arteries (ABI>1.1) must have a toe-brachial index (TBI) of ≤ 0.80. 
5. 
Clinical presentation of lifestyle limiting claudication or rest pain as 
characterized by Rutherford Classification 2, 3, 4, or 5. 
6. 
Subject has de novo target lesion(s) or lesion(s) treated by percutaneous 
transluminal angioplasty (PTA) only greater than 3 months prior with 
stenosis ≥70% by visual estimation in the common femoral, superficial 
femoral, popliteal, anterior tibial, posterior tibial, or peroneal artery. Up 
to three lesions can be treated at the index procedure provided the 
cumulative total lesion length is ≤ 30 cm AND all lesions are in the 
same leg. 
7. 
Target reference vessel diameter (proximal and distal to target lesion) is 
2 to 5 mm by angiographic visual estimation. 
8. 
At least one patent vessel run-off to the ankle or foot at baseline.  
9. 
The target lesion(s) can be successfully crossed with a commercially 
available 0.014” atherectomy guidewire without any complications 
during wiring procedure. 
10. Subject signs a written Informed Consent form to participate in the 
study, prior to any study mandated determinations or procedure. 
6.1.2 
Exclusion Criteria 
Subjects must be EXCLUDED from participation in this study if ANY of the following 
criteria are met: 
1. 
Is female with childbearing potential not taking adequate 
contraceptives or is currently breastfeeding. 
2. 
Target lesion is within a native graft or synthetic graft. 
3. 
Target lesion is an in-stent restenosis. 
4. 
Chronic total occlusion (CTO) with wire crossed near the advential 
junction. 
5. 
Subject has significant stenosis or occlusion of inflow tract (upstream 

 
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disease) not successfully treated during the index procedure and prior 
to treatment of the target lesion. 
6. 
History of an endovascular procedure or open vascular surgery on the 
index limb within 30 days prior to the index procedure. 
7. 
Planned endovascular or surgical procedure within 30 days after the 
index procedure. 
8. 
Signs and symptoms of systemic infection (temperature of  ≥ 38.0° 
Celsius and/or WBC of ≥ 12,000 cells/µL) at the time of assessment; 
     Note: If infection is adequately treated and controlled (temperature    
< 38.0° C and WBC < 12,000 cells/µL) patient may be enrolled. 
9. 
Unstable coronary artery disease or other comorbid condition(s) that, in 
the judgment of the physician precludes safe percutaneous intervention. 
10. Significant acute or chronic kidney disease with a creatinine level > 
2.5mg/dL and/or requiring dialysis. 
11. Evidence or history of intracranial or gastrointestinal bleeding, 
intracranial aneurysm, myocardial infarction or stoke within 2 months 
of index procedure. 
12. Evidence or history of aneurysmal target vessel. 
13. Clinical/angiographic evidence of distal embolization. 
14. Known allergy to contrast agents or medications used to perform 
endovascular intervention that cannot be adequately pre-treated. 
15. Subjects in whom anti-platelet, anticoagulant, or thrombolytic therapy 
is contraindicated. 
16. Heparin-induced thrombocytopenia (HIT) not able to use Bivalirudin. 
17. Uncorrectable bleeding diathesis, platelet dysfunction, 
thrombocytopenia with platelet count less than 125,000/mm2, known 
coagulopathy, or INR > 1.5. 
18. Thrombolytic therapy within 2 weeks of the index procedure. 
19. Intra-operative (intra-procedure) clinical or angiographic complication 
(other than non-flow limiting dissections) attributed to the use of a 
currently marketed device prior to introduction of the Cardio Flow 
atherectomy driveshaft. 
20. Has life expectancy < 12 months. 
21. Subject is unwilling or unable to comply with the follow-up study 
requirements.  
22. Is currently participating in an investigational drug or device study.  
23. Has one or more stents in the treatment vessel. 
24. Lacking capacity to provide consent. 

 
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6.2 
Pre-screening and Written Informed Consent 
The site may pre-screen potential subjects by reviewing medical records to identify the study 
population.  Once identified these subjects are approached for the study and consented.  The site 
may not initiate any study specific (non-standard of care) procedures without first obtaining 
informed consent 
Subjects who pass the initial pre-screening will be asked to sign the study specific IRB approved 
Informed Consent.  A member of the research team will approach the subject to obtain informed 
consent. The background of the proposed study, the procedure, the follow-up schedule and all 
potential benefits and risks will be carefully explained to the subject prior to obtaining the 
potential subject’s informed consent. A subject is considered “Enrolled” after signing the study 
specific Informed Consent and if he/she meets all inclusion and exclusion criteria.   
Informed consent will be obtained prior to any study specific screening/baseline tests are 
performed. This does not include any procedures or tests that are obtained via the standard of care 
related to the subject’s non-study related care, prior to undergoing the index procedure. 
6.3 
Enrollment 
Only subjects who meet the inclusion/exclusion criteria, and provide consent will be eligible to 
receive the treatment and participate in the study.  A subject will be considered officially enrolled 
only if the subject has signed informed consent, meets all the inclusion and none of the exclusion 
criteria and is treated with the device. 
6.4 
Baseline Evaluation (Within 30 Days of Index Procedure) 
Subjects that meet the pre-screening eligibility criteria and signed informed consent will have the 
following collected.  These evaluations can occur anytime within 30 days of the procedure to the 
day of treatment.  Only one angiogram is required. 
 Demographic Information: race, age, weight, height 
 Medical History / Current Status 
 Physical Exam and Vital Signs 
 Angiogram (recorded and sent to sponsor) 
 Duplex Ultrasound (if available, recorded and sent to sponsor) 
 Rutherford Classification 
 Laboratory Assessments: 
o CBC, creatinine, and potassium (on day of procedure) 
o INR & PT if subject is on chronic warfarin therapy (on day of procedure) 
o Urine pregnancy test if female of child-bearing potential (within 7 days of 
procedure) 
o Hemoglobin, hematocrit, and free hemoglobin (pre-procedure, immediately 
post-procedure, and at discharge). 

 
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 VascuQoL Questionnaire 
 Ankle Brachial Index (ABI) 
 Concomitant Medications 
6.5 
Index Procedure 
Subjects who meet all of the eligibility criteria will have their scheduled index procedure 
performed in accordance with physician/investigational site standard practices. 
6.5.1 
Angiography 
At the time of the index procedure, prior to introduction of the Cardio Flow orbital atherectomy 
device, standard angiography will be performed per the guidelines established by the 
Angiographic Core Laboratory, to confirm final anatomic eligibility. Subjects who do not meet 
the final angiographic eligibility criteria, as determined by the investigator at the time of the 
procedure, will be documented as angiographic screen failures and will not be considered enrolled 
in the study and no further data will be collected. A subject is considered as “enrolled” after the 
subject meets all angiographic criteria and a bare-metal atherectomy 0.014” guidewire 
successfully crosses the target lesion via the true vessel lumen.  
Angiography will be performed throughout the procedure to document the treatment outcomes 
and sent to the sponsor.  At a minimum, angiographic images at the following timepoint should 
be taken.   
 
Baseline angiography to determine subject’s eligibility. 
 
Post any lesions that are pre-dilated by balloon angioplasty if performed.  
 
After the Cardio Flow FreedomFlow™ orbital atherectomy treatment session(s). 
 
Post any adjunctive interventions, e.g. balloon angioplasty and/or stenting, to 
optimize the outcome or bailout the procedure due to vascular complications. 
 
Final angiography prior to the end of the procedure. 
Up to 3 target lesions are allowed based on the angiographic criteria by this protocol. If 2 or 3 
target lesions are selected, the lesion will be numbered based on the anatomic order, i.e. common 
femoral artery, proximal, middle or distal segment of superficial femoral artery, P1, P2 or P3 
segment of popliteal artery, anterior tibial artery, posterior tibial artery, and peroneal artery, 
regardless of the treatment order.  
6.5.2 
Non-Target Vessel/Lesion Intervention 
Non-target vessels/lesions can be staged and treated with any commercially available devices 
greater than 30 days prior to or post the index procedure. If a non-target lesion(s) that locates at 
the iliac artery or at the femoral artery with a vessel size greater than 5 mm in diameter in the 
target limb and requires intervention during the index procedure, the lesion(s) MUST be treated 
with commercially available devices prior to the Cardioflow orbital atherectomy procedure. The 
CardioFlow orbital atherectomy procedure can be performed ONLY if there are no angiographic 
complications at the non-target vessel/lesion site and downstream vasculatures and no clinical 

 
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adverse event. If any angiographic complication at the non-target vessel/lesion site and 
downstream vasculatures or clinical adverse event occurred, the subject MUST not proceed to the 
CardioFlow orbital atherectomy procedure. The subject will be considered as an angiographic 
screening failure.     
6.5.3 
Cardio Flow FreedomFlow™ Orbital Atherectomy Procedure 
Subjects that meet the final angiographic eligibility criteria will have the atherectomy 
procedure performed according to the Cardio Flow FreedomFlowTM Orbital Atherectomy 
System Instructions for Use (IFU). 
Performing the Atherectomy Procedure 
Interventionalist will place commercially available 0.014-inch bare-metal atherectomy 
guidewire through appropriate size introducer sheath based on User Handle model. See 
IFU provided with the device for details.  If this summary differs from the IFU, follow 
the IFU 
Caution: If the physician suspects the guidewire is placed sub-intimally, the 
atherectomy procedure must be aborted and alternative care performed. 
1. 
Once the system is prepped with sterile saline, the distal tip of the User Handle 
driveshaft can be inserted onto the proximal end of the placed guidewire. Ensure that 
the guidewire clamp at the back of the User Handle is rotated to the open position to 
allow the guidewire to exit the User Handle. 
2. 
While utilizing imaging technology (fluoroscopy and/or ultrasound), the 
physician advances the User Handle driveshaft over the guidewire through the 
introducer sheath and into the patient’s vasculature. Continue advancement of the 
driveshaft and spheres until positioned proximal to the target lesion. 
Caution: Verify that the guidewire distal tip is advanced as far distally in 
patient vasculature as feasible to ensure User Handle driveshaft does not 
contact the distal tip of the guidewire. 
3. 
Once the driveshaft is in the desired location, rotate guidewire clamp clockwise 
and verify that the guidewire can no longer freely move. Verify that no saline solution 
is leaking from the guidewire clamp. 
4. 
Select the appropriate speed for the vessel size on the touch screen.  
Caution: A tight lesion stenosis may require a lower speed, prior to 
sequential higher speed treatments. Start rotation proximal to a tight lesion 
stenosis. 
5. 
Fully depress the blue activation button to initiate rotation and maintain selected 
speed. 

 
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6. 
Once rotation is started, slowly advance the turbine carriage forward and 
backward through the target lesion. 
Warning: Performing atherectomy in the presence of severe arterial spasm 
can result in vessel dissection or perforation. If severe spasm is observed 
during treatment with the FreedomFlow™ Atherectomy System, 
immediately stop driveshaft rotation. If no dissections or perforations are 
detected, resume treatment only after the vessel spasm has spontaneously 
resolved or is treated pharmacologically. Prophylactic and episodic anti-
spasm treatment may be administered as described in section 6.5.4 
Procedure Medications in this protocol. 
Caution: Do not leave the spheres of the driveshaft in one location for more 
than 5 seconds during rotation. Smooth, slow, continuous motion of the 
driveshaft forward and backward is recommended. 
Caution: Frequent imaging evaluation, such as contrast fluoroscopy and/or 
ultrasound, should be utilized throughout the treatment procedure to 
evaluate lesion removal progress and identify potential dissections.  The 
investigational treatment should be discontinued if a dissection is detected 
7. 
To stop driveshaft rotation, release blue activation button. 
Caution: If rotation does not cease with release of blue activation button, 
disconnect the Tubing Set from the User Handle.  
8. 
To move the driveshaft to a different target lesion, rotate the guidewire clamp 
counterclockwise to allow the driveshaft to move independently of guidewire. 
9. 
Rotate guidewire clamp clockwise to lock guidewire before activating the 
driveshaft again. 
 
Removal of the User Handle and Driveshaft 
1. 
Release blue activation button to stop rotation and retract driveshaft proximal to 
the lesion using the turbine carriage. 
2. 
Rotate guidewire clamp counterclockwise so that User Handle and driveshaft can 
move independently of guidewire. 
3. 
Carefully remove the driveshaft from the guidewire through introducer sheath. 
4. 
Turn off peristaltic pump by tapping the OFF icon on the Control Module touch 
screen. 
5. 
Dispose of User Handle and Tubing Set according to standard hospital practice. 

 
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Changing a Saline Infusion Bag  
To change a saline infusion bag during a procedure, the operation must be paused. If 
the peristaltic pump door is opened during a procedure, pneumatic power to the User 
Handle will cease immediately. 
1. 
Remove the User Handle and driveshaft from patient (see instructions above). 
2. 
Turn off peristaltic pump by tapping the OFF icon on the Control Module touch 
screen. 
3. 
Disconnect current saline infusion bag from IV spike on the Tubing Set and hold 
the spike upward to prevent the introduction of air. 
4. 
Without touching the sterile IV spike tip, insert a new saline infusion bag onto 
the IV spike and rehang on the IV pole. 
5. 
Repeat a complete flush cycle of the User Handle and driveshaft.  
6.5.4 
Procedure Medications  
Warning: Performing atherectomy in the presence of severe arterial spasm can result in 
vessel dissection or perforation. If severe spasm is observed during treatment with the 
FreedomFlow™ Atherectomy System, immediately stop driveshaft rotation. 
Anti-coagulation medication and loading dose of anti-platelet medications will be given prior to 
the atherectomy procedure per investigational site atherectomy standard procedure. 
Antispasmodic medications such as nitroglycerine (200 µg intra-arterial (IA) bolus; up to 3000 
µg  per subject) or papaverine (300 µg IA bolus) may be administered. To avoid frequent IA 
bolus injections, the following solution (500 ml normal saline with 3000 µg heparin, 3000 µg  
nitroglycerin and 2.5 mg Cardizem) can be infused intra-arterially at a rate of 6 mL/min. All 
medications administered for this study should be recorded in the subject’s medical record.   
During the procedure, any device malfunction and device/procedure related adverse 
events, including anaphylaxis to medications or device components will be monitored 
and recorded.  
6.6 
Post Procedure to Discharge 
The following assessments will be performed within 12-24 hours post procedure or prior to 
hospital discharge, whichever occurs first: 
 Physical Exam and Vital Signs 
 Hemoglobin, hematocrit, and free hemoglobin  
 Adverse Events assessment  

 
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6.7 
30 Days Follow-up (± 7 Days) 
Subjects will return for a follow-up visit at 30 days and the following assessments will be 
performed: 
 Physical Exam and Vital Signs 
 Rutherford Classification 
 ABI 
 Duplex Ultrasound of treated lesion per Ultra Sound Core Lab protocol 
 Angiogram – performed only if clinical symptoms requiring intervention during 
follow-up for TVR or TLR 
 VascuQoL Questionnaire 
 Adverse Events assessment 
6.8 
6 Months Follow-up (± 14 Days) 
Subjects will return for a follow-up visit at 6 months and the following assessments will be 
performed: 
 Physical Exam and Vital Signs 
 Rutherford Classification 
 ABI 
 Duplex Ultrasound of treated lesion per Ultra Sound Core Lab protocol 
 Angiogram – performed only if clinical symptoms requiring intervention during 
follow-up for TVR or TLR 
 VascuQoL Questionnaire 
 Adverse Events assessment 
Table 6-1: Schedule of Events 
 
Assessment 
Screening 
/ 
Baseline/Pre-
procedure 
 
Procedure 
 
Discharge 
30 Days 
(±7 days) 
6 months 
(±14 days) 
Informed Consent 
X 
 
 
 
 
Medical History 
X 
 
 
 
 
Physical Exam 
X 
 
X 
X 
X 
Laboratory Assessments 
X 
X 
 
 
 

 
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Urine Pregnancy Test if 
female 
X 
 
 
 
 
Rutherford Classification 
X 
 
 
X 
X 
ABI 
X 
 
 
X 
X 
VascuQoL Questionnaire 
X 
 
 
X 
X 
Hemoglobin, hematocrit, 
and free hemoglobin  
X 
X 
X 
 
 
Angiogram 
X 
X 
 
Xa 
Xa 
Duplex Ultrasound 
Xb 
 
 
X 
X 
Medications 
X 
 
X 
X 
X 
Adverse Events 
X 
X 
X 
X 
X 
aAngiograms will be performed at the follow-up visits for verification of restenosis of the treated 
lesion/vessel site(s) only if the subject has clinical symptoms requiring intervention. 
b if available 
 
6.9 
Unplanned Follow-up 
Subjects returning for unscheduled visits complaining of new signs and/or symptoms will be 
documented as an unplanned follow-up and, at the investigators’ discretion perform diagnostic 
evaluations.  The reason should be reported as an adverse event if applicable.  
6.10 
Subject Early Discontinuation / Withdrawal and Replacement 
of Subjects 
All subjects are informed of their right to withdraw from the clinical study at any time. 
Additionally, the investigator may prematurely discontinue any subject’s participation in the study 
if the investigator feels that the subject can no longer fully comply with the requirements of the 
study or if any of the study procedures are deemed potentially harmful to the subject. However, 
it is anticipated that such withdrawals will be infrequent to ensure the integrity of the study. The 
reason for early discontinuation will be documented in the source documents and case report 
forms. 
6.11 
Lost to Follow-up 
Every attempt will be made to have all subjects complete the follow-up visit schedule. A subject 
will not be considered lost to follow-up unless efforts to obtain compliance are unsuccessful. At 
a minimum, the effort to obtain follow-up information will include three attempts to make contact 

 
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via telephone and if unsuccessful, then a certified letter from the investigator will be sent to the 
subject’s last known address. 
7 BENEFIT / RISK ANALYSIS 
7.1 
Benefits 
Participation in this study is voluntary. There will be no direct benefits of participating in this 
study. Information gathered from this study will help confirm the safety and efficacy of the device 
in treating de novo, severely calcified peripheral lesions.   
7.2 
Risks 
The risks of the investigational procedure to subjects is similar to that of other Atherectomy 
procedures.   
Possible risks associated with the Cardio Flow FreedomFlow™ Orbital Atherectomy System that 
may occur and/or require intervention include, but are not limited to: 
 Allergic reaction to medication/media/device components 
 Amputation 
 Anemia 
 Aneurysm 
 Bleeding complications which may require transfusion 
 Cerebrovascular accident (CVA) 
 Death 
 Distal embolization 
 Device embolization 
 Entry site complications including hematoma 
 Hemolysis 
 Hypotension/hypertension 
 Infection 
 Myocardial infarction 
 Pain 
 Pseudoaneurysm 
 Restenosis of treated segment that may require revascularization 
 Renal insufficiency/failure 
 Slow flow or no reflow phenomenon 
 Dissection 
 Perforation 
 Thrombus 

 
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 Vessel closure, abrupt 
 Vessel injury, including dissection and perforation that may require surgical repair 
 Vessel spasm 
 Vessel occlusion 
7.3 
Minimization of Risk and Monitoring Procedure 
Cardio Flow, Inc. has attempted to mitigate risks as much as possible through product design, 
testing, and through careful labeling and instructions for use. 
8 STATISTICS 
This study is a one or two center, prospective, non-randomized single-arm Early Feasibility Study. 
All clinical endpoints will be summarized with descriptive statistics without hypothesis testing. 
For continuous variables, the range (minimum, maximum), mean, standard deviation, median, 
first and third quartiles (Q1 and Q3) may be reported, while for discrete variables, count and 
percentage will be provided.  
9 DATA MANAGEMENT 
9.1 
Subject Identification 
Subjects that successfully pass the screening tests and wish to participate in the study will be 
assigned a unique identification code (ID) using the format “XXX-YYY” where: 
 
 
XXX = Institution Number, assigned by the Sponsor to each study site 
YYY = Enrollment Number, assigned by the institution as each subject is enrolled  
 
in the study 
 
In addition to the ID, each subject’s initials will be used as an identifier included on documentation 
submitted to the Sponsor. 
9.2 
Central Database 
All study documentation will be collected and compiled in a central database.  Appropriate quality 
control measures will be established to ensure accurate and complete transfer of information from 
the study documentation to the central database. 

 
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9.3 
Source Documents 
Case Report Forms (CRFs) are not considered acceptable source documents. Source documents 
are original records in which raw data are first recorded. These may include hospital/clinic/general 
practitioner records, charts, for example.  Source documents should be kept in a secure, limited 
access area.  Sponsor may request copies of de-identified source document to adjudicate adverse 
events.   
9.4 
Data Collection 
Data will be collected on electronic CRFs supplied by the Sponsor or designee. The principal 
investigator is responsible for the prompt reporting and accuracy and completeness of all study 
documentation.  The study data are entered into the eCRFs. Corrections made after the 
Investigator’s review and approval must be reapproved by the Investigator. 
A unique study number will be assigned to each subject. All information recorded on the CRF 
about the subject will be recorded with the study number on it. The main database will contain 
only the study number to identify the subject. The code with subject name and study number will 
be maintained in a secured location. 
9.5 
Data Processing 
Data will be entered / loaded in a validated electronic database using a clinical data management 
system.  Visual and computer error checks will be carried out. The investigator will be queried on 
errors concerning completeness and consistency. An electronic audit trail system will be 
maintained with the clinical data management system to track all data changes in the database 
once the date has been entered/loaded. Regular backups of the electronic data will be performed. 
9.6 
Study Report 
An interim 30-day report summarizing all relevant observations will be prepared following receipt 
of all patient data forms.  A final report will be prepared following study completion. 
10 STUDY ADMINISTRATION 
10.1 
Monitoring 
10.1.1 Monitoring Procedures 
It is the responsibility of the study sponsor to ensure that proper monitoring of this investigation 
is conducted.  Appropriately trained monitors, appointed by the study sponsor, will complete any 
monitoring that is done.  The monitors will ensure that the investigation is conducted in 
accordance with:  
 The signed Investigator’s Agreement 

 
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 The Investigational Plan  
 Appropriate laws and regulations  
 Any conditions of approval imposed by the reviewing IRB and/or other regulatory 
agencies 
 
The clinical study will be monitored according to the guidelines summarized below.  The sponsor 
may choose to perform random inspections throughout the study as an element of quality 
assurance.  Investigators shall allow auditing of their clinical investigation procedures. 
A study specific monitoring plan standardizes monitoring activities across centers to ensure 
human subject protection and verify data integrity.  The monitors shall receive study specific and 
protocol training prior to conducting any monitoring visits.  Study monitors are selected based on 
their training, qualifications and experience to monitor the progress of an investigation.  This 
study monitoring will include a site qualification, study initiation, interim, and close out visits.  
All study monitors will be required to follow the study monitoring plan and monitoring standard 
operating procedures.  
The study monitoring will be done by the following Sponsor representative: 
Libra Medical Inc 
8401 73rd Ave North, Suite 63 
Brooklyn Park, MN 55428 
10.1.2 Monitoring Visit 
The following factors will be taken into account when determining the frequency of the 
monitoring visits: subject accrual rate at each center, total number of subjects enrolled at each 
center, and Clinical Investigation Plan compliance at each center.  It is anticipated each site will 
be monitored at least once upon the completion of the 30-day follow-up visits for all enrolled 
subjects at the study site.  Monitors will require direct access to subjects’ medical records pertinent 
to the study (and study inclusion criteria), study management documents, regulatory documents 
and Subject Informed Consent documents, as well as other potential applicable records not listed 
here.   
 
Monitors may ensure the clinical investigators have and continue to have staff and facilities to 
conduct the clinical investigation safely and effectively.  Monitors may conduct the following 
monitoring activities throughout the study: 
 
 
Verification that the current IRB-approved informed consent was signed and dated by 
each subject prior to participating in the study required procedures. 

 
Protocol Version 6.0  
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 
Verification of documentation in the subject’s record that informed consent was 
signed prior to initiation of the study procedures and that a copy of the signed and 
dated consent was provided to the subject. 
 
Source documentation verification by reviewing the CRFs against source 
documentation for accuracy and completeness of information. 
 
Verification that the investigation is conducted according to the Clinical Investigation 
Plan, Instructions for Use and, all malfunctions/ IFU deficiencies are reported as 
required. 
 
Verification that subjects met study enrollment criteria. 
 
Verification that study deviations are documented and reported. 
 
Verification that the procedures for recording and reporting adverse events to the 
sponsor are followed. 
 
Ensuring proper error correction. 
 
Verification of training documentation of all study personnel participating in study 
related activities. 
 
Reviewing all correspondence and regulatory documents, including confirmation of 
IRB-approved Clinical Investigation Plan or amendments. 
 
Resolution of outstanding issues and completion of assigned tasks will be 
documented by the monitors. 
Each monitoring visit will be documented via a monitoring report and follow-up letter.  The 
follow-up letter shall be sent to the Investigator to document issues identified, corrective actions 
and if applicable preventative actions.  At subsequent visits any issues resolved shall be 
documented in this letter to demonstrate resolution. 
10.1.3 Study Closure 
Study closure is defined as a specific date that is determined by study completion and/or 
regulatory requirements have been satisfied per the Clinical Investigation Plan (CIP) and/or by 
decision of the Sponsor or FDA.  Study closure visits will be conducted at all enrolling clinical 
sites in order to review record retention requirements with site personnel.  A telephone contact 
may take the place of a study closure visit if appropriate (e.g., low subject enrollment, recent 
monitoring visit, etc.)  Monitoring visits will be conducted by trained monitors and designees.  
The Monitoring Plan identifies the frequency of monitoring and training requirements of the 
monitors. 
10.2 
Device Accountability 
Access to investigational devices shall be controlled and used only in the clinical investigation 
and according to the Protocol.  Each site will be responsible for tracking the receipt and disposition 
of all investigational devices.  All unused devices must be returned to the Sponsor at the end of 
the study. 

 
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The principal investigator or an authorized designee shall keep records documenting the receipt, 
use, return, and disposal of the investigational device, which shall include: 
 The date of receipt 
 Identification of each investigational device (serial or lot number) 
 The date or dates of use 
 Subject identification 
 Date of return of unused, expired, or malfunctioning investigational device, if 
applicable 
 The Investigator must explain in writing the reasons for any discrepancy noted in 
device accountability. 
11 DEFINITION OF ADVERSE EVENT(S) 
For purposes of this study, an adverse event (AE) is defined as any adverse change (i.e., de novo 
or pre-existing condition) from the subject’s baseline medical condition(s) occurring during the 
course of the study.  Adverse events (AE) are any untoward medical occurrence, unintended 
disease or injury, or untoward clinical signs (including abnormal laboratory findings) in subjects, 
whether or not related to the investigational medical device.  For the purpose of AE 
documentation, the start of the course of the study is defined as any time after the treatment has 
been initiated.  All AE’s will be recorded in the CRF whether considered procedure-related or 
not, and will be classified as described in this section.  
Pre-existing conditions will not be reported as an AE unless there is an adverse change in that 
condition.  Any AE which resolved and then recurred will be reported as a separate AE.   
An AE may be volunteered spontaneously by the subject or discovered as a result of questioning 
or physical examination by an investigator or study staff. 
Elective procedures for a pre-existing condition (that has not worsened) are not considered AEs. 
Non-cardiovascular abnormal laboratory values will not be considered AEs unless: 
1) The PI determines that the value is clinically significant,  
2) The abnormal laboratory value required intervention, or  
3) The abnormal laboratory value required subject termination from the trial. 
All adverse events, regardless of relationship to the device, must be recorded, as applicable, on 
the case report forms provided. Adverse events that occur during this study should be treated by 
established standards of care, to protect the life and safety of the subjects. 
Adverse events shall be assessed and documented at the time of the procedure and at all study 
follow-up visits.  Each investigator shall provide source documentation as requested by the 
Sponsor to facilitate reporting and adjudication of these events. 

 
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11.1 
Serious Adverse Events 
An adverse event is considered a Serious Adverse Event (SAE) that: 
a) led to death 
b) led to a serious deterioration in the health of the subject, that either resulted in 
1) a life-threatening illness or injury, or 
2) a permanent impairment of a body structure or a body function, or 
3) in-patient hospitalization or prolongation of existing hospitalization, or 
4) a medical or surgical intervention to prevent permanent life-threatening 
illness or injury or permanent impairment to body structure or a body function. 
11.2 
Device Relationship 
Determination whether there is a reasonable possibility that a study product or device caused or 
contributed to an AE is to be determined by the Investigator and recorded on the appropriate CRF 
form. Determination should be based on assessment of temporal relationships, biologic 
plausibility, association (or lack of association) with underlying disease and presence (or absence) 
of a more likely cause. 
11.3 
Unanticipated Adverse Device Effect 
An unanticipated adverse device effect (UADE) is any serious adverse effect on the health or 
safety of a subject, any life-threatening problem or death caused by, or associated with a device, 
if such effect, problem, or death was not previously identified in nature, severity, or degree of 
incidence in the investigational plan (e.g., ICF, Study Protocol, Instructions for Use (IFU), 
publications, etc.), or any other unanticipated serious problem associated with a device that relates 
to the rights, safety, or welfare of subjects. 
If an unanticipated adverse effect associated with the investigational device occurs, the 
investigator shall notify the Sponsor and the IRB/EC as soon as possible.   
The Sponsor will investigate the event and notify the FDA and all other participating IRBs and 
investigators.  Should the Sponsor determine that an unanticipated adverse effect presents an 
unreasonable risk to all participating subjects, the Sponsor will suspend the clinical investigation 
and notify all participating investigators, IRBs/EC, country regulatory bodies and FDA.  
11.4 
Adverse Event Reporting 
The signs, symptoms and sequelae of an underlying AE should not be reported as separate AEs.  
All AEs must be recorded on a CRF.  All AEs also must be described by (a) duration (start and 
resolution dates); (b) adjudicated for severity; (c) relationship to the study device; (d) action taken 
to resolve the event; (e) outcome of the event; and (f) whether or not such event is considered to 

 
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be serious.  Additional information, such as procedural notes, treatment notes, or a signed clinical 
summary, may be required as supporting documentation for the reported AE. 
Pre-existing medical conditions or symptoms occurring prior to the start of the atherectomy 
procedure should not be reported as adverse events.  In the situation where there is a worsening 
of a pre-existing medical condition or symptom due to a study related procedure, an adverse event 
should be reported. 
For any adverse event that is ongoing at the time of the initial report, periodic follow-up 
information is required until the adverse event is resolved or is judged to be chronically stable. 
The site should submit relevant follow-up information related to the adverse event as soon as it is 
available. 
Depending upon the nature and seriousness of the adverse event, the sponsor or designee may 
request the Investigator to provide copies of the subject’s medical records (such as the subject’s 
laboratory tests and hospital records, Investigator summaries, etc.) to document the adverse event. 
The Investigator will report all serious adverse events, including unanticipated adverse device 
effects, to the IRB according to the IRB requirements. A copy of this IRB communication should 
be sent to the Sponsor. In case of an unanticipated adverse device effect occurred, the investigator 
must report to the Sponsor within 10 working days of the site first becoming aware of the event.  
Within 10 working days of notification, the Sponsor will report all unanticipated adverse device 
effects to the appropriate authority, all participating investigators, and all reviewing IRBs. The 
Sponsor will ensure that safety reporting for the study is conducted in compliance with all 
pertinent requirements and regulations. 
11.5 
Adverse Event Assessment 
11.5.1 Initial Assessment 
The investigator must provide the following information: 
 Date of onset 
 Nature 
 Severity 
 Duration / date of resolution 
 Outcome 
 Relationship to investigational device 
 Other relevant information 
11.5.2 Assessment of Severity 
The Investigator must determine the severity of the adverse event according to the following 
definitions: 

 
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 
Mild - The adverse event is noticeable to the subject, but does not interfere with 
routine activity; the symptoms are easily tolerated and transient in nature. 
 
Moderate – The adverse event interferes with routine activity but responds to 
symptomatic therapy or rest; the symptoms are poorly tolerated and sustained. 
 
Severe – The adverse event significantly limits the subject’s ability to perform 
routine activities despite symptomatic therapy. The adverse event requires 
medical or surgical treatment or results in hospitalization. 
 
Life-Threatening – The subject is at immediate risk of death. 
11.5.3 Device Relatedness 
An adverse event is considered device-related when the clinical event has a reasonable time 
sequence associated with use of the investigational device and is unlikely to be attributed to 
concurrent disease or other procedures or medications. It is reasonable to believe that the device 
directly caused or contributed to the adverse event. 
The Investigator must provide an assessment of the adverse event according to the following 
definitions: 
 Definite – The adverse event is clearly related to the investigational device: the 
event has a temporal relationship to the investigational device, follows a known 
pattern of response, or is otherwise logically related to the investigational device, 
and no alternative cause is present. 
 Probable (Likely) – The adverse event is likely related to the investigational 
device: the event has a temporal relationship to the investigational device, 
follows a known or suspected pattern of response, or is otherwise logically 
related to the investigational device, but an alternative cause may be present. 
 Possible (Unlikely) – The adverse event is unlikely related to the investigational 
device: the event does not follow a clear temporal relationship to the 
investigational device or does not follow a known pattern of response, or is 
otherwise likely to be due to the subject’s clinical state or other modes of 
therapy. 
 Not Related – The adverse event is clearly not related to the investigational 
device: the event has no temporal or other relationship to the administration of 
the investigational device follows no known or suspected pattern of response, 
and an alternative cause is present. 
 Unknown – Unable to determine the relationship based on all available 
information. 
11.6 
Device Deficiency or Malfunction 
A Device Deficiency is an inadequacy of a medical device with respect to its identity, quality, 
durability, reliability, safety or performance (includes malfunctions, use errors, and inadequate 

 
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labeling).  Sponsor, in cooperation with the CEC, will assess all device deficiencies that could 
have led to a serious adverse device effect for potential regulatory reporting requirements. 
In the event of a suspected malfunction or device deficiency, the investigational device(s) shall 
be returned to the manufacture for analysis. Instructions for returning the investigational device 
will be provided by the Sponsor. 
11.7 
 Reporting of Death 
During the study, all deaths must be reported to the Sponsor within the period outlined in Table 
12-1. All deaths also should also be reported on the AE form and End of Study CRF.  A copy of 
the subject’s death records, medical records for the events that led to the subject’s death, and a 
death certificate (if available) and an autopsy report (if performed) should be sent to the sponsor.  
In addition, subject death must be reported to the IRB in accordance with IRB requirements. 
12 STUDY ADMINISTRATIV OVERSIGHT 
12.1 
Core laboratory 
Independent core laboratories shall be utilized to provide a standardized process and assessment 
of all angiographic and duplex ultrasound studies. The core laboratories will be responsible for 
analyzing the angiograms and ultrasound images according to the study eligibility criteria, the 
study endpoints and this study protocol, for providing feedback to the sites and Sponsor regarding 
the quality of the tracings and images and for providing a written summary report of all 
angiograms and duplex ultrasound results to the study Sponsor. 
Investigators will enroll subjects into the study based on inclusion and exclusion criteria. Lesion 
characteristics and measurements will be assessed by investigators using visual estimates; 
however, the core laboratory will assess by quantitative angiography. Baseline measurements and 
post-procedure results will be reported by investigator and by core laboratory. 
Angiographic and Ultra Sound Core Laboratory Protocols shall be provided to the investigational 
sites. 
12.2 
Clinical Adverse Event Adjudication 
An Independent Adverse Event Adjudicator will be responsible for the adjudication of any events. 
For this small-scale feasibility study, one physician independent of the study or the sponsor will 
be responsible for the adjudication of any events that may be considered serious and/or device 
related by the principal investigator and/or study Sponsor. The physician will be familiar with 
PTA procedures who is not an investigator in the trial. The adjudication process will include 
determination of whether the event or device deficiency constitutes a SAE or an UADE, or 
contributes to the endpoint, and whether the subject should be considered a Procedural Success. 
All available data (including lab reports, films, discharge reports, etc.) will be available to 
adjudicate the events. 

 
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12.3 
IRB Approval 
The study protocol shall be reviewed and approved by the investigator’s IRB prior to subject 
enrollment. The Sponsor must review any proposed changes to the investigational informed 
consent prior to implementation.   
Prior to shipment of investigational devices, a signed copy of the IRB approval letter identifying 
the clinical study and investigational site is required to be submitted to the Sponsor. Investigators 
are responsible for obtaining and maintaining annual renewal of the study by their IRB (or 
according to renewal schedule imposed by the IRB). Evidence of renewal and continued IRB 
approval must be provided to the Sponsor accordingly. 
12.4 
Informed Consent 
Informed consent is mandatory and must be obtained from all subjects per local regulations, prior 
to their participation in the study.  Only IRB approved informed consent may be used. 
It is the responsibility of the Investigator to ensure written informed consent from each subject, 
or the legally authorized representative of the subject, is obtained prior to the initiation of any 
study-related procedures. 
Subjects who agree to participate in this study will do so voluntarily. They will be treated on an 
equal basis with all other patients. Choosing not to participate will not affect their care in any way. 
Study personnel fully knowledgeable in the purposes and procedures of the study will approach 
all prospective study participants. The facilities and settings in which prospective participants will 
be presented with the opportunity to learn about and consent to participation in the study will 
provide them sufficient quiet and unhurried time to be informed of the study, to ask questions, 
and between consent being given and the initiation of study procedures. Study personnel will, 
after presenting the study to prospective participants, assess the subject’s understanding and 
autonomy by asking the subject to explain the study in his/her own words. 
Once that step is completed, consent will be able to be given by the subject’s signing the consent 
form. A copy of the consent form will be given to all consented participants. 
Original signed subject consent forms must be retained in the study files by the Investigator, and 
available for review by the Sponsor and/or regulatory agencies, as applicable. 
The informed consent form and any other written information provided to subjects will be revised 
whenever important new information becomes available, or if there is an amendment to the 
protocol which necessitates a change to the content of subject information and/or to the consent 
form. The Investigator will inform the subject of changes in a timely manner, and will ask the 
subject/patient to confirm his/her continuation in the study by signing a revised consent form. 
Any revised informed consent form and other written information provided to subjects must 
receive IRB, Sponsor, and regulatory agency approval, as applicable. 

 
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12.5 
Records 
Each Investigator must maintain the following accurate, complete, and current records relating to 
the conduct of the study investigation.  The final responsibility for maintaining such records 
remains with the Investigator.  These records include, but not limited to: 
 All signed agreements; 
 IRB/EC approval letter(s); 
 Signed ICF; 
 Records of AEs, including supporting documents; 
 Records of protocol deviations, including supporting documents 
 Records showing receipt, use and disposition of all investigational devices, 
including: 
o Date, quantity, model and serial numbers of devices received, 
o Name of person(s) who received, used or disposed of each device, 
o The number of devices returned to the Sponsor and the reason(s) for 
return; 
 All correspondence related to the study; 
 Records of each subject’s case history, including study-required CRFs, signed 
ICF, all relevant observations of AEs, the condition of each subject upon entering 
and during the course of the investigation, relevant medical history, the results of 
all diagnostic testing, etc.; 
 Study personnel visit log; 
 Signature authorization and delegation log; and, 
 Any other records that applicable regulation requires to be maintained. 
The Investigator will maintain all essential trial documents and source documentation that support 
the data collected on the study subjects in compliance with FDA’s GCP guidelines. Documents 
must be retained until at least 2 years have elapsed since the date the investigation is completed 
or terminated or the records are no longer required to support a regulatory submission, whichever 
date is later. These documents will be retained for a longer period of time by agreement with 
Sponsor or in compliance with other regulatory requirements.  The investigator will take measures 
to ensure that these essential documents are not accidentally damaged or destroyed. If for any 
reason the investigator withdraws responsibility for maintaining these essential documents, 
custody must be transferred to an individual who will assume responsibility. The Sponsor must 
receive written notification of this custodial change. 
12.6 
Reports 
Table 12-1 lists those reports that are the investigator's responsibility to deliver to the Sponsor.  
Each study investigator must follow the EC/IRB reporting requirements for their respective site.  
If applicable regulations or EC/IRB requirements mandate stricter reporting requirements than 
those listed, the stricter requirements must be followed. 

 
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Table 12-1: Reports Required from Investigators to Sponsor 
Type of Report 
Prepared by PI for
Notification Time Frame 
UADE 
Sponsor, EC/IRB 
As soon as possible but within 5 working days 
of knowledge 
Death 
Sponsor, EC/IRB 
Written reports (e.g., via e-mail) within 48 hours 
SAE  
Sponsor 
EC/IRB, if required 
Within 10 working days of knowledge  
Per IRB requirement 
Device malfunction 
with clinical sequelae 
Sponsor 
EC/IRB, if required 
Within 48 hours via written communication.  
Return the device to sponsor within 48 hours. 
Serious protocol 
deviations (e.g., ICF 
not obtained, to 
protect the life or 
physical well-being of 
a subject in an 
emergency) 
Sponsor, 
EC/IRB 
As soon as possible but within 5 working days 
of knowledge 
Per IRB requirement 
Withdrawal of 
EC/IRB approval 
Sponsor 
Within 5 working days of knowledge 
Annual progress 
report 
Sponsor, EC/IRB 
Annually 
Interim report 
Sponsor, EC/IRB 
Within 14 days of 30-day follow up 
Final report 
Sponsor, EC/IRB 
Within 3 months of study completion or 
termination 
Note: Each IRB/EC may require more stringent reporting requirements that those listed in this 
table. 
12.7 
Investigator Responsibilities 
 Agree to sign and adhere to the Investigator Agreement. 
 Obtain approval from the IRB including subsequent protocol amendments and 
changes to the Informed Consent form and obtaining annual IRB approval and 
renewal throughout the duration of the study. 
 Await IRB approval, as well as, any additional hospital requirements prior to 

 
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requesting written informed consent from any potential study subject or prior to 
allowing any subject to participate in the study. 
 Complete and provide signed copies of all required investigator documentation such 
as an Investigator Agreement or Disclosure of Financial Interest. 
 Agree to participate in Investigator meetings as scheduled by the Sponsor. 
 Be willing to perform and be capable of performing treatment procedures as outlined 
in this protocol. 
 Comply with all required elements of this protocol (e.g., perform testing and follow-
up as specified, especially during personnel transitions). 
 Agree to obtain written Informed Consent before any study specific procedures are 
performed in accordance with GCP. 
 Be willing to change hospital routine if required by protocol (as long as subject 
safety and well-being is not compromised). 
 Control any investigational device(s) stored at their site. 
 Be aware of, and comply with, GCP and applicable regulatory requirements. 
 Permit monitoring and auditing by the Sponsor, and inspection by the appropriate 
regulatory authorities. 
 Have available an adequate number of qualified staff and adequate facilities to 
properly conduct the study. 
 Ensure study personnel are adequately informed about the protocol, the 
investigational device and study-related duties and functions. 
12.8 
Sponsor Responsibilities 
The Sponsors responsibilities in the study include: 
 Selecting the Principal Investigator(s), all clinical investigators and study sites, and 
other consultants (e.g., monitors) who participate in the study. 
 Provide study protocol, device, and GCP training to participating study sites, in 
quantities sufficient to support study activities, per agreements executed with the 
study sites. 
 Select all qualified clinical Investigators and study sites and other consultants (e.g., 
the study monitors) who participate in the study. 
 Provide financial support to each study site. 
 Follow/promote all regulatory standards per appropriate regulations for study sites, 
core laboratories, and other participants, and ensure compliance by periodically 
monitoring sites. 
 Ensure completion of site monitoring of clinical data at each clinical study site.  

 
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 Retain ownership of all clinical data generated in this study, and control the use of 
the data for appropriate purposes only.   
 Review and approve publication of study results in the literature 
12.9 
Protocol Deviations / Violations and Medical Emergencies 
A protocol deviation or violation is a failure to comply with the requirements of the clinical study 
as specified in the protocol. Examples of protocol deviations include late visits, missed visits, 
required follow-up testing not completed. An example of a major protocol violation includes 
enrollment of a study subject who fails to meet inclusion/exclusion criteria as specified in the 
protocol. Each investigator shall conduct this clinical study in accordance with the study protocol 
and any conditions required by the reviewing IRB. 
Deviations/violations from clinical protocol requirements will be reviewed and evaluated on an 
ongoing basis and, as necessary, appropriate corrective actions put into place.  See Table 12-1: 
Reports Required from Investigators to Sponsor for reporting timelines for emergency deviation. 
12.10 Pre-Study Documentation Requirements 
Prior to shipment or receipt of investigational product, the following documents must be provided 
to Cardio Flow, Inc.: 
 Signed protocol/protocol amendments 
 Signed and dated Investigator Agreement(s) 
 A copy of the written IRB approval of the protocol 
 A copy of the written IRB approval of the Informed Consent Form 
 Signed and dated Curriculum Vitae of the Investigator(s) 
 Copy of the Investigator(s)’ current medical license(s), or equivalent 
 Signed and dated Non-disclosure Agreement(s), if required 
 Signed and dated Certification/Financial Disclosure Form(s) 
12.11 Criteria for Terminating Study 
The Sponsor reserves the right to terminate the study but intends only to exercise this right for 
valid scientific or administrative reasons and reasons related to protection of subjects. 
Investigators and associated IRB will be notified in writing in the event of termination. 
Possible reasons for study termination include: 
 The discovery of an unexpected, significant, or unacceptable risk to the subjects 
enrolled in the study. 
 A decision on the part of the Sponsor to suspend or discontinue development of the 
device. 

 
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12.12 Publication Policy 
It is anticipated that the investigators involved may publish the results of this study. It is expected 
that the results will initially be written in abstract form and submitted to a meeting such as TCT 
or ACC and then submitted to a peer reviewed medical journal. 
13 REVISION HISTORY 
Date 
Description 
May 1, 2017 
Version 1.0.  Initial Release 
May 31, 2017 
Version 2.0. Clarify that H4001 device will be 
used in this trial. 
June 28, 2017 
Version 3.0. Clarify how target lesions will be 
numbered. 
July 7, 2017 
Version 4.0. Incorporate PI’s comments 
October 4, 2017 
Version 5.0. Incorporate FDA’s comments from 
IDE G170219 disapproval letter dated September 
29, 2017 
November 18, 2017 
Version 6.0 Incorporates FDA’s email request to 
insert warnings about the possibility of 
vasospasm and potential tissue damage and 
preventive measures. Added Exclusion of 
subjects Lacking capacity to provide consent.  
 
 
 

 
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