Evaluation of WIRION™ EPS in Lower Extremities Arteries
Phase: NA
Conditions: Peripheral Arterial Disease (PAD)
Sponsor: Gardia Medical

Title: Evaluation of WIRION™ EPS in Lower Extremities Arteries    
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Version 2.2 
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WISE LE Study protocol synopsis dated July 20 2016 
NCT02780349 
 
Title: 
WISE LE: Evaluation of WIRION™ EPS in Lower Extremities Arteries    
Study Objective 
Demonstrate the safety and performance of the WIRION™ EPS in subjects 
undergoing lower extremity atherectomy for the treatment of Peripheral 
Arterial Disease (PAD).  
Study Design 
Prospective, multi-center, non-randomized, open label, single arm study. Up 
to 153 consented subjects who undergo atherectomy due to lower limb PAD 
will be enrolled. All subjects will undergo baseline assessment, intervention 
(atherectomy in conjunction with WIRIONTM EPS) and post procedure follow 
up. All subjects will have a follow up visit at 30±7 days post procedure. 
Results will be compared to a performance goal based on an analysis of 
previous trials that studied atherectomy with an embolic protection filter in 
similar patient cohorts. 
Study Population: 
Both male and female subjects who meet all the eligibility criteria and give 
written informed consent will be enrolled in the study.  
Inclusion Criteria 
1) Subject is at least 18 years of age 
2) Subject or authorized representative, signed a written Informed 
Consent form to participate in the study, prior to any study related 
procedures   
3) Subject is willing to comply with the protocol requirements and 
return to the treatment center for all required clinical evaluations 
4) Rutherford classification 2-4 
5) Has moderate to severe calcification visualized on angiogram in 
the femoropopliteal arteries 
6) Planned atherectomy of the native femoropopliteal arteries  
7) Reference vessel diameter for intended filter location must be 
visually estimated to be ≥3.5mm and ≤6.0mm 
8) An adequate “landing zone” for placement of the WIRION™ device 
distal to the target lesion of at least 30mm 
9) A female subject is eligible if not of child bearing potential or has a 
negative pregnancy test within the previous 7 days and agrees to 
remain on birth control throughout the study 
 
Exclusion Criteria 
1) Any planned surgical or endovascular intervention within 30 days 
before or after the index procedure 
2) A lesion deemed not accessible by the  WIRION™ EPS  
3) Inability to take aspirin or ADP receptor antagonists 
4) History of bleeding diathesis or coagulopathy or will refuse blood 
transfusion if deemed necessary 

Title: Evaluation of WIRION™ EPS in Lower Extremities Arteries    
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5) Has perforation, dissection, or other injury of the access or target 
vessel requiring additional stenting or surgical intervention before 
enrollment 
6) Subject is enrolled in another drug or device study protocol that 
has not reached its primary endpoint (participating in registry 
studies is not excluded) 
7) Life expectancy less than 12 months 
8) Known severe renal insufficiency (eGFR <30 ml/min/1.72m2). 
9) ≤1-vessel tibial run-off status 
Number of 
subjects: 
 Up to 153 with an interim analysis after 100 subjects 
Clinical sites: 
Up to 10 sites; up to 1/3 of the study patients at OUS sites 
Investigational 
Product: 
WIRION™ Embolic Protection System (Gardia Medical Ltd.) 
Primary end 
point 
Freedom from major adverse events (MAE) to 30 days post procedure. 
MAE defined as a serious adverse event that results in death, acute myocardial 
infarction, thrombosis, pseudo-aneurysm, dissection (grade C or greater) or 
clinical perforation at the filter location, distal embolism (clinically relevant), 
unplanned amputation, or clinically-driven target vessel revascularization 
(TVR), through 30 days post-procedure, as adjudicated by the Clinical Events 
Committee (CEC). 
Secondary end 
points 
• 
Device success 
Defined as: 
- 
A successful delivery and deployment of WIRION™ distal to the 
intervention site without complications, AND 
- 
Successful retrieval of WIRION™ following completion of the stenting 
procedure, without complications  
• 
Clinical success 
Defined as: Device success with freedom from procedure related 
serious adverse events ascribed to the WIRION 
• 
Technical success  
Defined as:  Freedom from device malfunctioning causing the 
procedure to be aborted 
• 
Percent of filters with visible debris 
Assessment 
Schedule: 
Baseline Visit: 
a) Eligibility according to inclusion and exclusion criteria 
b) Obtaining signed Informed Consent Form (ICF) 
c) Demographics (sex, year of birth, smoking status) 
d) Risk factors & medical history 
e) Concomitant medications 
f) Disease oriented physical examination including vital signs (weight, 
height, BMI, heart rate, blood pressure) and ABI (except in cases 

Title: Evaluation of WIRION™ EPS in Lower Extremities Arteries    
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where blood pressure cuff occlusion of the extremity is 
contraindicated) 
g) Blood test including: RBC, Hemoglobin, WBC, Platelet count, PT, aPTT, 
INR, serum creatine-kinase isoform MB (CK-MB) and serum creatinine 
h) Pregnancy test, if applicable 
i) 
Safety evaluation (AE/SAE evaluation) 
Intervention (Use of WIRION™): 
a) Investigational procedure & materials (atherectomy device, EPS, guide 
wires and contrast medium) 
b) Intervention details (investigator name, procedure duration and 
fluoroscopy time) 
c) Angiography of target lesion 
d) Dilation after atherectomy 
e) Stent placement after atherectomy 
f) Angiographic assessment of visible distal embolization, as evidenced 
by new angiographic filling defect, slow flow, and/or loss of distal tibial 
runoff 
g) AE/SAE  
h) Usability questionnaire 
i) Visual assessment of debris in the filter 
j) Concomitant medications 
Pre-Discharge Follow-up: 
a) Disease oriented physical exam including vital signs (heart rate and 
blood pressure) and ABI (except in cases where blood pressure cuff 
occlusion of the extremity is contraindicated) 
b) AE/SAE evaluation 
c) Blood test including: RBC, Hemoglobin, WBC, Platelet count, PT, aPTT, 
INR and serum creatine-kinase isoform MB (CK-MB) and serum 
creatinine  
d) Concomitant medications 
End-of-Study Follow-up Visit (30±7 days post procedure): 
a) AE/SAE evaluation 
b) Disease oriented physical exam including vital signs (heart rate and 
blood pressure) and ABI (except in cases where blood pressure cuff 
occlusion of the extremity is contraindicated) 
Statistical 
Considerations: 
A performance goal  group sequential design with a maximum of two stages 
with rejection boundaries according to Lan-DeMets alpha spending function 
with O’Brien- Fleming boundaries. The expected proportion of subjects who 
would meet the primary endpoint if treated according to current clinical 
practice is 10.7%. This performance goal is based on the DEFINITVE LE and 
DEFINITVE Ca++ trials.  
The study is designed to test the primary null hypothesis that the 30-day MAE 
outcome using the WIRIONTM EPS in conjunction with atherectomy is equal to 
or higher than the PG of 19.26%, as opposed to the alternative hypothesis 
that the MAE is less than this PG. An interim analysis will be carried out when 

Title: Evaluation of WIRION™ EPS in Lower Extremities Arteries    
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100 (68.5%) of the originally planned subjects have reached the 30-day 
follow-up. Using an Exact Binomial Test and under the following assumptions:  
Alpha (one-sided) = 
0.025 
β= 
 
 
0.20 
PE= 
 
 
10.7% 
Performance goal= 
19.26% 
An estimated 145 evaluable subjects will be required for 80% power if the 
study reaches the final analysis. With an anticipated combined loss-to-follow-
up of up to 5%, 153 patients will be enrolled in the study. 
An interim analysis will be performed when 100 subjects (approximately 
68.5% of the 145 evaluable subjects) have completed the study; two 
potential options will be pursued: 
The study will be stopped for efficacy if the primary null hypothesis is 
rejected at one sided alpha = 0.0068 based on the Lan-DeMets alpha 
spending function with O’Brien - Fleming boundaries. 
If based on the interim analysis the primary null hypothesis cannot be 
rejected, then the trial will continue to a total sample size of 153 enrolled 
subjects (i.e., 145 evaluable subjects). This test will be conducted at one-
sided alpha = 0.0229, in order to control the overall Type I error at 2.5%.  
Study success is defined as rejecting the null hypothesis. 
Duration of Study   The estimated study duration is ten months, including a recruitment phase 
and follow up period of 30±7  days