Safety and Effectiveness Study of the AngioSafe Peripheral CTO Crossing System
Phase: NA
Conditions: Peripheral Artery Occlusion, Peripheral Arterial Disease
Sponsor: AngioSafe, Inc.

CONFIDENTIAL 
 
 
 
SAFETY AND EFFECTIVENESS STUDY OF THE  
ANGIOSAFE PERIPHERAL CTO CROSSING SYSTEM (RESTOR-1) 
 
 
PROTOCOL AND STATISTICAL ANALYSIS PLAN (SAP) SUMMARY 
 
 
PROTOCOL NUMBER:  0071 
NCT NUMBER:  NCT04663867 
 
 
SPONSOR: 
ANGIOSAFE, INC. 
 
 
PROTOCOL VERSION:  06 
SAP VERSION:  01 
 
 
DATE: DECEMBER 22, 2025  
 
 

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PROTOCOL AND SAP SUMMARY, RESTOR-1 
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STUDY SYNOPSIS 
A synopsis of the study is presented in Table 1. 
Table 1: Study Synopsis 
Sponsor Name: 
AngioSafe, Inc.(“AngioSafe”) 
Title of Study: 
Safety and Effectiveness Study of the AngioSafe Peripheral CTO Crossing 
System (RESTOR-1) 
Objective: 
To demonstrate the safety and effectiveness of the AngioSafe Peripheral CTO 
Crossing System to facilitate crossing chronic total occlusions (CTOs) in the 
peripheral arteries of lower limbs. 
Name of Investigational 
Device: 
AngioSafe Peripheral CTO Crossing System 
Indications for Use: 
The AngioSafe Peripheral CTO Crossing System is intended to facilitate the 
intraluminal placement of guidewires beyond stenotic lesions, including 
chronic total occlusions (CTOs) in the peripheral vasculature. 
Design: 
This is a prospective, single-arm, multi-center pivotal study assessing the 
safety and effectiveness of the AngioSafe Peripheral CTO Crossing System. 
This system facilitates the crossing of chronic total occlusions (CTOs) in the 
common femoral artery (CFA), superficial femoral artery (SFA), and popliteal 
artery, and allows for placement of a guidewire in the distal true lumen. 
Planned Enrollment: 
To evaluate the primary endpoint, a minimum of 70 subjects will be treated at 
up to 20 sites.  
Subject Population: 
Adult men and women ≥ 22 years of age with peripheral vascular disease and 
symptoms of intermittent claudication/critical limb ischemia and a CTO in the 
lower extremity to which the symptoms can be attributed. 
Clinical Sites: 
Up to 20 study centers within the United States will participate. 
Length of Subject 
Follow-Up: 
All subjects will be followed for 30 days (± 7 days) after their procedure. 
Study Duration: 
The duration of the study will be approximately six (6) months from the date 
of the first subject’s consent to the last subject’s 30-day follow-up completion.   

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PROTOCOL AND SAP SUMMARY, RESTOR-1 
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Inclusion Criteria: 
1. Subject is able and willing to comply with protocol requirements, has been 
informed of the nature of the study, and has signed the IRB-approved 
informed consent form. 
2. Subject is ≥ 22 years of age at the time of enrollment/consent. 
3. Subject has peripheral arterial disease as defined by the Rutherford 
Clinical Classification (Category 2 “Moderate claudication” through 
Category 5 “Minor tissue loss – nonhealing ulcer, focal gangrene with 
diffuse pedal ischemia”). 
4. Peripheral artery disease in the affected extremity is confirmed by imaging 
including at least one of the following: catheter-based angiography, 
computed tomographic angiography (CTA), and/or magnetic resonance 
angiography (MRA).  
Note: Duplex ultrasound should not be the sole imaging modality to confirm 
subject eligibility. 
Angiographic Inclusion 
Criteria: 
1. Subject’s target lesion is in native de novo common femoral artery (CFA), 
superficial femoral artery (SFA), and/or popliteal artery.  
2. Reference vessel diameter(s) for subject’s target lesion is ≥ 3.0mm and ≤ 
10mm by visual estimate. 
3. Subject’s target lesion is a severely stenosed segment of ≤ 200mm that 
involves the CTO(s). 
4. Subject’s target lesion involves at least one CTO, i.e., is deemed as total 
occlusion (100% stenosis). 
5. Subject has at least one patent tibial vessel (≤ 70% stenosis) with run-off 
to the foot. 
Note: Only one target lesion per subject may be treated in the study, regardless 
of whether it is a contiguous occlusion or if there is intermittent reconstituted 
flow with multiple CTOs. In the case of bilateral disease with eligible lesions 
on both sides, one target lesion may be enrolled in the study if clinically 
indicated. Although the subject’s target lesion length should be no more than 
200mm, this does not preclude a total treated length of greater than 200mm at 
the discretion of the investigator. 
Exclusion Criteria: 
1. Subject has a systemic infection or an infection in the extremity of the 
target lesion.  
2. Subject’s target lesion is within native vein or synthetic vessel grafts or is 
in-stent occlusion. 
3. Subject’s contralateral limb requires planned intervention concurrently 
with the study procedure.  
4. Subject’s target limb requires intervention of a chronic total occlusion in 
the inflow vessels concurrently with the study procedure. 
5. Subject requires planned intervention of the lower extremities after the 
study procedure within the timeframe for the 30-day follow-up visit. 
6. Subject has a known coagulopathy or bleeding diatheses, 
thrombocytopenia with platelet count less than 50,000/μl, or INR > 1.7 

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(unless corrected prior to procedure, as verified by a lab test no older than 
5 days prior to the investigational procedure). 
7. Subject in whom antiplatelet, anticoagulant, or thrombolytic therapy is 
contraindicated. 
8. Subject has known allergy to contrast agents or medications used to 
perform endovascular intervention that cannot be adequately pre-treated. 
9. Subject has known allergy to nickel, titanium, urethane, nylon, or 
silicone. 
10. Subject has history of myocardial infarction within 30 days prior 
to enrollment/consent. 
11. Subject has history of stroke within 30 days prior to 
enrollment/consent. 
12. Subject has chronic kidney disease (CKD) of stage 4 or greater based on 
an Estimated Glomerular Filtration Rate (eGFR) <30ml/Min. 
13. Subject has baseline hemoglobin levels <10g/dL verified by a lab test no 
older than 14 days prior to enrollment. 
 
14. Subject is pregnant or nursing, for females of child-bearing potential (< 50 
years of age). 
15. Subject is participating in another interventional research study that may 
interfere with study endpoints.    
16. Subject has limited life expectancy or co-morbid conditions, or 
social/psychological problems that, in the opinion of the Investigator, will 
preclude them from participation and completion of study procedures or 
requirements. 
17. Subject has had prior major amputation (above ankle) in the extremity that 
is being treated.  
18. Subject is presenting with acute limb ischemia (ALI). 
19. Subject has had a prior unsuccessful attempt to cross the target lesion. 
Primary Endpoint: 
Clinical Success of the AngioSafe Peripheral CTO Crossing System to 
facilitate placement of a guidewire into the distal true lumen of a 
femoropopliteal artery CTO, in the absence of device-related major adverse 
events through discharge or 24 hours post-procedure, whichever is sooner. 
Secondary Endpoints: 
1. Technical Success of the AngioSafe Peripheral CTO Crossing System. 
Technical Success is defined as the ability of catheter to facilitate placement 
of a guidewire into the distal lumen. 
2. Procedural Success is defined as Technical Success without a procedural 
complication within 30 days after the procedure.  Procedural complication 
is defined as the need for open or repeat endovascular surgical repair in the 
treated limb, or a major bleeding event as defined by Bleeding Academic 
Research Consortium (BARC) criteria 3 – 5. 

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PROTOCOL AND SAP SUMMARY, RESTOR-1 
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3. Evaluation of intraluminal CTO crossing facilitated by the AngioSafe 
Peripheral CTO Crossing System, as assessed by an Intravascular 
Ultrasound (IVUS).  
4. The primary endpoint in the subgroup of the degree of calcification 
(none/focal/mild/moderate, severe). 
Safety Endpoints: 
1. Frequency of device-related MAEs through discharge or 24 hours following 
the procedure, whichever is sooner. 
2. Frequency of MAEs at 30 days. 
Ancillary Endpoints: 
1. Performance of the AngioSafe Peripheral CTO Crossing System defined as 
the following:  
a. Pre-treatment assembly of the catheter over the guidewire and into the 
guide catheter without damage or kinking. 
b. Delivery of the device, guidewire, and guide catheter assembly to the 
desired location, i.e., proximal to the proximal cap of the CTO. 
c. Extension and expansion of the Centering System out of the guide 
catheter. 
d. Ability of the device to penetrate the proximal cap. 
e. Ability to place a guidewire in the true vessel lumen distal to the target 
CTO. 
2. Lesion crossing time defined as: time starting from the placement of the 
Peripheral CTO Crossing System at the proximal cap to the time the 
guidewire is placed in the distal true vessel lumen. 
3. Rutherford Clinical Classification assessment at 30 days versus baseline. 
4. Pain Numeric Rating Scale (NRS) assessment at 30 days versus baseline. 
5. Healthcare services utilization/billing assessment for peripheral CTO 
treatment procedure (e.g., number of accessories used/expense, fluoroscopy 
time/expense, catheter lab time/expense, medications used/expense). 
Statistical Analysis: 
Primary endpoint analysis: The primary analysis will be performed by 
comparing the device result to the performance goal at a one-sided 0.05 level 
of significance using the exact test based on the binomial distribution. 
Sample Size and Power: 
In Banerjee et al., the technical success rate of the CTO crossing device group 
was 0.74 (184/248) (CI: 0.68, 0.80)1. The primary endpoint of clinical success 
(defined as technical success without a device-related MAE through discharge 
or 24 hours post-procedure, whichever is sooner) of the AngioSafe Peripheral 
CTO Crossing System is expected to be 0.85.  
The null hypothesis is that the AngioSafe Peripheral CTO Crossing System 
will perform better than 0.70, which is within the lower bound of the 95% 
confidence interval of the technical success rate of the CTO crossing device 
group reported by Banerjee et al. (CI: 0.68, 0.8). 
The primary endpoint null and alternative hypotheses of interest are:  
H0: π ≤ 0.70 vs. Ha: π > 0.70. Assuming the true performance is 0.85,  

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at α 1-sided =0.05 and a power of 90%, the sample size estimate for the 
binomial exact test is 70. 
Only one target lesion per subject may be treated in the study. If data are 
submitted by a study center on more than one lesion in a subject, the lesion to 
be included in the study will be chosen at random. Where an analysis is 
presented for treated subjects, the indicated sample size numbers (N or n) 
represent the number of treated subjects, which corresponds to the number of 
treated lesions. 
Analysis Sets:  
FULL ANALYSIS SET (FAS): the FAS will consist of all enrolled subjects 
who have the AngioSafe CTO Crossing System inserted into the vasculature. 
The FAS population will be the primary analysis population for the primary 
effectiveness evaluation. 
PER-PROTOCOL ANALYSIS SET (PP): the PP analysis set is a subset of the 
FAS and will consist of all patients for whom no major protocol deviations (no 
deviations which may affect the study effectiveness outcome) is documented. 
In identifying this population, major protocol deviations are identified prior to 
database lock as those impacting the interpretation of the data. 
The PP analysis set may be used to provide supportive data for the 
effectiveness analyses of primary and secondary endpoints if those analyses 
using the FAS set produce unexpected results. 
Statistical Methods: 
All statistical procedures will be completed using SAS® version 9.4 or higher. 
The analyses of all endpoints will include relevant descriptive statistics. 
Continuous variables will be summarized by number of observations (N), 
mean (m), standard deviation (SD), and 95% confidence interval of the mean 
(95% CI). If the data are skewed or otherwise non-normal, the median and 
IQR will also be reported. 
Categorical variables will be summarized by N, the proportion in each 
category (pi), and 95% CI of each pi. 
Count variables will be summarized as continuous or categorical variables, 
depending on the number of unique counts. Generally, 5 or fewer counts will 
be treated as categorical and more than 5 as continuous. 
Time-to-event variables will be summarized as the proportion of subjects 
experiencing an event at a series of relevant time points (pi), the N, and the 
95% CI. These proportions will be estimated by Kaplan- -Meier analysis with 
covariates). 
For summary purposes, if not otherwise specified, the baseline value of a 
parameter is defined as the last non-missing assessment prior to the procedure. 
All patient data, including those derived, will be presented in individual 
patient data listings. All listings will be sorted by patient ID, date/time, and 
visit. Data listings will be based on all available data. 

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SUMMARY OF STUDY DESIGN 
This is a prospective, single-arm, multi-center pivotal study assessing the safety and 
effectiveness of the AngioSafe Peripheral CTO Crossing System. This system facilitates the 
crossing of chronic total occlusions (CTOs) in the common femoral artery (CFA), superficial 
femoral artery (SFA), and popliteal artery, and allows for placement of a guidewire in the distal 
true lumen. 
• Eligibility will be evaluated and subjects will be enrolled (consented) based on medical 
history and prior diagnosis of peripheral arterial disease (PAD) and peripheral CTO in 
accordance with institutional routine clinical care practices (symptoms, laboratory 
findings, diagnostic angiography, and/or other modalities employed per the institutional 
standard of care).  
• Screening imaging will be reviewed by a central Screening Committee to approve each 
subject’s participation in the study. Imaging reviewed by the committee should include at 
least one of the following: catheter-based angiography, computed tomographic 
angiography (CTA), and/or magnetic resonance angiography (MRA). Imaging should 
generally be current within the last 90 days prior to Screening Committee submission. 
Imaging older than 90 days, or duplex ultrasound of high quality may be sufficient to 
receive conditional approval by the Screening Committee, with the requirement that final 
eligibility must be verified by the Investigator based on the pre-procedure angiogram on 
the day of the index procedure. 
• Upon consent, the research staff will perform baseline assessments, document subject 
eligibility and schedule the PTA procedure within an approximately 1-week timeframe, 
and no more than 30 days from the time of the baseline assessment. Subjects who have 
recently had vascular interventions in the target limb or contralateral limb may be 
enrolled in the study, though their investigational procedure must be deferred for 30 days 
or more from the date of the previous intervention. Baseline assessments and the 
investigational procedure must be scheduled accordingly. 
• On the day of the procedure, a pre-procedure angiogram of the target lesion will be 
performed to confirm CTO length, percent of stenosis, reference vessel diameter, and 
target vessel tortuosity, and to verify final subject eligibility based on the angiographic 
inclusion criteria. 
• The investigational device will be prepped per the Instruction for Use (IFU) and 
positioned at the target lesion.  A guidewire will be advanced across the distal cap and 
into the distal true lumen.  
• The device will be removed and an IVUS catheter will be introduced over the guidewire, 
advanced into the track made by the device passage and intraluminal disposition of the 
track will be recorded.  
• The IVUS catheter will be removed and the target lesion will be treated either with a 
balloon and/or stent and/or atherectomy, at the discretion of the investigator.  
• Cine-angiography will capture the entire procedure. 

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• Patients will be monitored and followed through discharge and 30 days post-procedure. 
 
BIBLIOGRAPHY  
 
1 Banerjee S, Jeon-Slaughter H, Tsai S, et al. Comparative Assessment of Procedure Cost and 
Outcomes Between Guidewire and Crossing Device Strategies to Cross Peripheral Artery 
Chronic Total Occlusions. JACC Cardiovasc Interv. 2016;9(21):2243-2252