Tack Optimized Balloon Angioplasty Study for the Below The Knee Arteries Using the Tack Endovascular System®
Phase: NA
Conditions: Peripheral Arterial Disease
Sponsor: Philips Clinical & Medical Affairs Global

 
TOBA II BTK Clinical Study Protocol - 
Tack Endovascular System 
CA 0137 Rev C 
DCO No: 
591 
Effective Date: 
14-Sep-2017 
 
   
 
   
CA 0137 Rev C  
CONFIDENTIAL 
Page 1 of 76 
 
 
    
 
 
Clinical Study Protocol 
 
Tack Optimized Balloon Angioplasty Study for the  
Below The Knee Arteries  
Using the Tack Endovascular System® (TOBA II BTK) 
 
Study Device: 
Tack Endovascular System® 
 
Protocol Number: 
CA 0137 
 
Protocol Version: 
Rev C 
 
Effective Date: 
14-Sep-2017 
Study Sponsor: 
 
Intact Vascular, Inc. 
1285 Drummers Lane, Suite 200 
Wayne, Pennsylvania 19087 
United States of America 
NCT No. 02942966 
 
 
 
 
This investigational protocol contains confidential information for use by the principal 
investigators and their designated representatives participating in this clinical investigation. 
It should be held confidential and maintained in a secure location. It should not be copied or 
made available for review by any unauthorized person or firm.

 
TOBA II BTK Clinical Study Protocol – Tack Endovascular System 
CA 0137 Rev C 
   
CA 0137 Rev C  
CONFIDENTIAL 
Page 2 of 76 
 
TABLE OF CONTENTS 
 
Investigator Signature Page....................................................................................................................................... 7 
 
Study Synopsis ................................................................................................................................................................ 8 
 
Study Management Contact List ............................................................................................................................ 14 
 
Introduction ................................................................................................................................................................... 14 
4.1. 
Background and Rationale ............................................................................................................................. 14 
4.2. 
Report of Prior Investigations ...................................................................................................................... 19 
 
Investigational Device ................................................................................................................................................ 24 
5.1. 
Description ............................................................................................................................................................ 24 
5.2. 
Principles of Operation .................................................................................................................................... 25 
5.3. 
Intended Use ........................................................................................................................................................ 26 
 
Clinical Study Objectives ........................................................................................................................................... 27 
6.1. 
Primary Endpoints ............................................................................................................................................. 27 
6.2. 
Secondary Endpoints ........................................................................................................................................ 27 
6.3. 
Observational Endpoints................................................................................................................................. 27 
 
Clinical Study Design .................................................................................................................................................. 28 
7.1. 
Anticipated Number of Subjects and Investigational Sites ............................................................... 28 
7.2. 
Subject Population ............................................................................................................................................. 28 
7.3. 
Clinical Study Duration & Follow-up .......................................................................................................... 29 
7.4. 
Subject Selection ................................................................................................................................................. 29 
7.4.1. 
Inclusion Criteria ...................................................................................................................................... 29 
7.4.2. 
Angiographic Inclusion Criteria .......................................................................................................... 29 
7.4.3. 
Exclusion Criteria ..................................................................................................................................... 31 
7.4.4. 
Angiographic Exclusion Criteria ......................................................................................................... 32 
 
Treatment Plan ............................................................................................................................................................. 33 
8.1. 
Time and Events Schedule .............................................................................................................................. 33 
 
Required Tests and Assessments .......................................................................................................................... 34 
9.1. 
Laboratory Testing ............................................................................................................................................ 34 
9.2. 
Angiographic Assessment & Imaging......................................................................................................... 34 
9.3. 
Ankle and Toe Brachial Indices (ABI and TBI) ....................................................................................... 34 
9.4. 
Duplex Ultrasound (DUS) Assessment ...................................................................................................... 35 
9.5. 
Questionnaires .................................................................................................................................................... 35 
9.6. 
Rutherford Classification ................................................................................................................................ 35 
9.7. 
WIfI Classification .............................................................................................................................................. 35 
9.8. 
Wound Assessment ........................................................................................................................................... 36 
9.9. 
X-Ray Assessment .............................................................................................................................................. 36 
 Screening Procedures ................................................................................................................................................ 36 
10.1. 
Obtaining Informed Consent .................................................................................................................... 37 
10.2. 
Screening Success and Failure Criteria ................................................................................................ 37 
 Baseline Evaluation ..................................................................................................................................................... 37 
11.1. 
Baseline Assessments .................................................................................................................................. 37 
 Study medications ....................................................................................................................................................... 38 
 Index Procedure ........................................................................................................................................................... 38 
13.1. 
Index Baseline Angiogram ......................................................................................................................... 38 
13.1.1. 
Preparation ................................................................................................................................................. 39 

 
TOBA II BTK Clinical Study Protocol – Tack Endovascular System 
CA 0137 Rev C 
   
CA 0137 Rev C  
CONFIDENTIAL 
Page 3 of 76 
13.1.2. 
Baseline Angiographic Requirements .............................................................................................. 39 
13.2. 
Pre-Enrollment Balloon Angioplasty (Treatment PTA) ................................................................ 39 
13.2.1. 
Post-Angioplasty Angiographic Requirements ............................................................................ 40 
13.3. 
Study Device Treatment ............................................................................................................................. 40 
13.3.1. 
Enrollment (Intent-to-Treat) ............................................................................................................... 40 
13.3.2. 
Treatment Recommendations ............................................................................................................. 41 
13.3.3. 
Post-Study Device Treatment Measurements .............................................................................. 41 
13.4. 
Post- Tack Dilation  ....................................................................................................................................... 41 
13.4.1. 
Recommendations .................................................................................................................................... 42 
13.4.2. 
Final Treatment Results ......................................................................................................................... 42 
13.5. 
Bailout Stenting of Target Lesion (Post-Study Device) ................................................................. 42 
 Post-Procedure/Pre-Discharge .............................................................................................................................. 43 
14.1. 
Required Assessments ................................................................................................................................ 43 
 Required Follow-up Visits and Assessments.................................................................................................... 43 
15.1. 
30-day Follow-up Visit (-2 days / +14 days post-Index Procedure) ....................................... 43 
15.2. 
6-month Follow-up Visit (±30 days post-Index Procedure) ....................................................... 43 
15.3. 
12-month Follow-up Visit (±30 days post-Index Procedure) ..................................................... 44 
15.4. 
24-month Follow-up Visit (±30 days post-Index Procedure) ..................................................... 44 
15.5. 
36-month Follow-up Visit (±30 days post-Index Procedure) ..................................................... 45 
15.6. 
Unscheduled Target Limb Angiography/Revascularization ....................................................... 45 
15.7. 
Follow-up Visit Compliance ...................................................................................................................... 46 
15.8. 
Subject Discontinuation and Replacement ......................................................................................... 46 
 Risk/Benefit Assessment .......................................................................................................................................... 46 
16.1. 
Risks .................................................................................................................................................................... 46 
16.2. 
Potential Benefits .......................................................................................................................................... 47 
16.3. 
Justification for Clinical Study .................................................................................................................. 47 
 Safety Reporting ........................................................................................................................................................... 48 
17.1. 
Protocol Reportable Safety Events ......................................................................................................... 48 
17.2. 
Adverse Events (AE) .................................................................................................................................... 49 
17.3. 
Adverse Device Effects (ADE) .................................................................................................................. 49 
17.3.1. 
ADE Reporting ........................................................................................................................................... 50 
17.4. 
Serious Adverse Events (SAE) .................................................................................................................. 50 
17.4.1. 
SAE Reporting ............................................................................................................................................ 50 
17.5. 
Major Adverse Limb Events (MALE) + Perioperative Death (POD) ......................................... 50 
17.5.1. 
MALE+POD Reporting ............................................................................................................................ 51 
17.6. 
Serious Adverse Device Effects (SADE) ................................................................................................ 51 
17.6.1. 
SADE Reporting ......................................................................................................................................... 51 
17.7. 
Unanticipated Adverse Device Effects (UADE) ................................................................................. 51 
17.7.1. 
UADE Reporting ........................................................................................................................................ 51 
 Study Device Event Reporting ................................................................................................................................ 51 
18.1. 
Device Deficiency ........................................................................................................................................... 52 
18.2. 
Device Malfunction ....................................................................................................................................... 52 
18.3. 
Device Returns ................................................................................................................................................ 52 
 Statistical Methods and Considerations ............................................................................................................. 52 
19.1. 
Study Design .................................................................................................................................................... 52 

 
TOBA II BTK Clinical Study Protocol – Tack Endovascular System 
CA 0137 Rev C 
   
CA 0137 Rev C  
CONFIDENTIAL 
Page 4 of 76 
19.2. 
Analysis Populations .................................................................................................................................... 52 
19.3. 
Primary Endpoints ........................................................................................................................................ 52 
19.3.1. 
Safety ............................................................................................................................................................. 52 
19.3.2. 
Efficacy .......................................................................................................................................................... 53 
19.4. 
Secondary Endpoints ................................................................................................................................... 53 
19.5. 
Observational Endpoints ............................................................................................................................ 53 
19.6. 
Sample Size ...................................................................................................................................................... 54 
19.7. 
Baseline Variables ......................................................................................................................................... 55 
19.8. 
Statistical Analysis ........................................................................................................................................ 55 
19.8.1. 
Primary Safety ........................................................................................................................................... 55 
19.8.2. 
Primary Efficacy ........................................................................................................................................ 55 
19.8.3. 
Secondary Efficacy Endpoints ............................................................................................................. 56 
19.8.4. 
Observational Endpoints ....................................................................................................................... 56 
19.9. 
Subgroup Analysis......................................................................................................................................... 56 
19.10. 
Site Pooling Analysis .................................................................................................................................... 57 
19.11. 
Handling of Missing Data ........................................................................................................................... 57 
19.12. 
Study Success Definition ............................................................................................................................ 58 
19.13. 
Multiplicity ....................................................................................................................................................... 58 
 Regulatory and Ethical Obligations ...................................................................................................................... 58 
20.1. 
Institutional Review Board (IRB) / Ethics Committee (EC) Approval .................................... 58 
20.2. 
Informed Consent .......................................................................................................................................... 59 
20.3. 
Protocol Amendment and Emergency Deviations ........................................................................... 59 
20.4. 
Subject Confidentiality ................................................................................................................................ 59 
 Clinical Study Conduct ............................................................................................................................................... 60 
21.1. 
Principal Investigator and Site Qualification ..................................................................................... 60 
21.2. 
Principal Investigator and Site Training .............................................................................................. 60 
21.3. 
Clinical Monitoring ....................................................................................................................................... 60 
21.4. 
Device Accountability .................................................................................................................................. 61 
21.5. 
Investigator Reports .................................................................................................................................... 61 
21.6. 
Data Management ......................................................................................................................................... 62 
21.7. 
Safety Monitoring .......................................................................................................................................... 62 
21.7.1. 
Data Safety Monitoring Board (DSMB) ............................................................................................ 62 
21.7.2. 
Clinical Events Committee (CEC) ....................................................................................................... 63 
21.8. 
Medical Monitoring....................................................................................................................................... 63 
21.9. 
Central Core Laboratories .......................................................................................................................... 64 
21.10. 
Record Retention ........................................................................................................................................... 64 
21.11. 
Audits/Inspections ....................................................................................................................................... 65 
21.12. 
Study Termination (Stopping Rules)..................................................................................................... 65 
21.13. 
Coverage of Subject Expenses .................................................................................................................. 66 
21.14. 
Clinical Study Reports ................................................................................................................................. 66 
21.15. 
Publication Policies....................................................................................................................................... 66 
21.16. 
Medicare Study Criteria .............................................................................................................................. 66 
 Economic Analysis ....................................................................................................................................................... 67 
 WIfI Classification Tables ......................................................................................................................................... 68 
 Study Definitions .......................................................................................................................................................... 70 

 
TOBA II BTK Clinical Study Protocol – Tack Endovascular System 
CA 0137 Rev C 
   
CA 0137 Rev C  
CONFIDENTIAL 
Page 5 of 76 
 
LIST OF ACRONYMS 
ABI  
Ankle Brachial Index 
ADE  
Adverse Device Effect 
AE  
Adverse Event 
AFS 
Amputation Free Survival 
AT 
Anterior Tibial Artery 
ATM 
Atmospheres 
BTK 
Below The Knee 
CABG 
Coronary Artery Bypass Graft 
CD-TLR 
Clinically-Driven Target Lesion Revascularization 
CD-TVR 
Clinically-Driven Target Vessel Revascularization 
CEC  
Clinical Events Committee 
CLI  
Critical Limb Ischemia 
CRF  
Case Report Form 
CTO  
Chronic Total Occlusion 
DCB 
Drug-Coated Balloon 
DEB  
Drug Eluting Balloon 
DES  
Drug Eluting Stent 
DP 
Dorsalis Pedis Artery 
DSMB 
Data Safety and Monitoring Board 
DUS 
Duplex Ultrasound  
EC 
Ethics Committee 
eCRF 
Electronic CRF 
EDC  
Electronic Data Capture 
EQ-5D-3L  EuroQol Group 5-Dimension Self-Report Questionnaire 
FDA  
Food and Drug Administration 
FU  
Follow Up 
GCP  
Good Clinical Practice 
ICF  
Informed Consent Form 
ICH  
International Conference on Harmonization 
IFU  
Instructions For Use 
IRB  
Institutional Review Board 
IVUS 
Intravascular Ultrasound  
LLL 
Late Lumen Loss 
LTFU 
Lost to Follow-up 
MALE  
Major Adverse Limb Events 
NHLBI  
National Heart, Lung, and Blood Institute 
OPG 
Objective Performance Goal 
P1 
Proximal Popliteal Artery 

 
TOBA II BTK Clinical Study Protocol – Tack Endovascular System 
CA 0137 Rev C 
   
CA 0137 Rev C  
CONFIDENTIAL 
Page 6 of 76 
LIST OF ACRONYMS 
P2 
Mid Popliteal Artery 
P3 
Distal Popliteal Artery 
PA 
Peroneal Artery 
PAD  
Peripheral Arterial Disease 
PCI 
Percutaneous Coronary Intervention 
PI  
Principal Investigator 
PIC  
Patient Implant Card 
POD 
Perioperative Death 
PLT  
Platelets/platelet count 
PT 
Posterior Tibial Artery 
PSVR 
Peak Systolic Velocity Ratio 
PT / INR 
Prothrombin time / International Normalized Ratio 
PTA  
Percutaneous Transluminal Angioplasty 
RMA 
Returned Materials Authorization 
RS  
Residual Stenosis 
RVD 
Reference Vessel Diameter 
SADE  
Serious Adverse Device Effect 
SAE  
Serious Adverse Event 
SFA  
Superficial Femoral Artery 
SVS 
Society of Vascular Surgery 
TBI 
Toe Brachial Index 
TMA 
Transmetatarsal Amputation 
TPT 
Tibioperoneal Trunk 
TASC 
Trans-Atlantic Inter-Society Consensus 
TcPO2 
Transcutaneous Oximetry 
TIA 
Transient Ischemic Attack 
TP  
Toe Pressure 
TL  
Target Lesion 
TLR  
Target Lesion Revascularization 
TV  
Target Vessel 
TVR  
Target Vessel Revascularization 
UADE  
Unanticipated Adverse Device Effect 
WIfI 
Wound, Ischemia, foot Infection Score 
WIQ 
Walking Impairment Questionnaire 
% DS   
Percentage Diameter Stenosis 

 
TOBA II BTK Clinical Study Protocol – Tack Endovascular System 
CA 0137 Rev C 
   
CA 0137 Rev C  
CONFIDENTIAL 
Page 7 of 76 
 
 INVESTIGATOR SIGNATURE PAGE 
 
STUDY TITLE: 
TACK OPTIMIZED BALLOON ANGIOPLASTY STUDY FOR THE 
BELOW THE KNEE ARTERIES USING THE 
TACK ENDOVASCULAR SYSTEM® (TOBA II - BTK) 
STUDY CENTER: 
_____________________________________________ 
 (Print name of study center) 
 
I, the undersigned, have read and understand the protocol specified above. As an Investigator, I 
understand that I am responsible for adhering to the terms of this protocol by ensuring the safety of 
study subjects enrolled under my supervision and by providing the Sponsor with complete and 
timely information. In addition, I understand that all information pertaining to this study shall be 
held strictly confidential and I will ensure that the requirement for confidentiality is understood by 
all study staff involved in this study. I agree to abide by the terms of this protocol and to maintain 
the procedures required to conduct this study in accordance with the Investigator Agreement, Good 
Clinical Practice (GCP), Declaration of Helsinki, 21 CFR Parts 50, 54, 56 and 812, ISO 14155:2011, 
and any applicable local regulations. 
 
 
___________________________________________________________________ 
SITE INVESTIGATOR – Print Name 
 
 
___________________________________________________________________ 
SITE INVESTIGATOR – Signature 
 
_______________________ 
DATE 
 
 
 
 
 
 
 
 

 
TOBA II BTK Clinical Study Protocol – Tack Endovascular System 
CA 0137 Rev C 
   
CA 0137 Rev C  
CONFIDENTIAL 
Page 8 of 76 
 STUDY SYNOPSIS 
Study Title: 
Tack Optimized Balloon Angioplasty Study for the Below The Knee Arteries 
Using the Tack Endovascular System® (TOBA II - BTK) 
Study Design: 
This is a prospective, multi-center, single-arm, non-blinded study designed to 
investigate the safety and efficacy of the Tack Endovascular System. 
Study 
Objective:  
To evaluate the safety and efficacy of the Tack Endovascular System in subjects 
with below the knee (BTK) peripheral artery disease (PAD) as compared to a pre-
defined performance goal (PG) established from published, peer reviewed 
scientific literature related to below-the-knee (BTK) PAD. 
Study Device: 
4F Tack Endovascular System manufactured by Intact Vascular, Inc.  
Intended Use:  
The Tack Endovascular System is intended for use in the Mid/Distal Popliteal, 
Tibial, and Peroneal Arteries ranging in diameter from 1.5mm to 4.5mm for the 
treatment of post percutaneous transluminal balloon angioplasty (PTA) 
dissection(s) requiring repair. 
Subject 
Population: 
Subjects with BTK PAD who receive PTA in the Mid/Distal Popliteal, Tibial, and 
Peroneal Arteries and have a resulting dissection(s) that the Investigator would 
otherwise treat by means such as, but not limited to, additional angioplasty 
with extended inflation time or stenting, are eligible for enrollment. To be 
enrolled, subjects must meet all inclusion criteria and not meet any of the 
exclusion criteria.  
Device 
Regulatory 
Status: 
4F Tack Endovascular System is a Class III Investigational Device within the 
United States and Class IIb within the European Union and has been designed and 
is manufactured by Intact Vascular, Inc. under the control of Intact Vascular’s 
Quality Management System. Intact Vascular is ISO 13485 certified.  
Enrollment: 
Up to 232 subjects will be enrolled at up to 60 U.S. and International clinical sites. 
Each clinical site can enroll a maximum of 46 patients, establishing an 
enrollment cap at 20% of the subject sample size.  The follow-up period for 
enrolled subjects that receive at least one Tack® implant is 36 months. 
Primary 
Endpoints: 
Safety: Freedom from major adverse limb events (MALE) plus perioperative 
death (POD) at 30 days defined as a composite of all-cause death, above-ankle 
target limb amputation, or major re-intervention to the target lesion(s) (defined 
as new bypass graft, jump/interposition graft revision, or thrombectomy / 
thrombolysis) 
Efficacy: Freedom from MALE at 6 months + POD at 30 days  
Secondary 
Efficacy 
Endpoints: 
 
Target lesion(s) tacked segment(s) patency at 6 months defined as the 
presence of blood flow using duplex ultrasound. If angiography is 
available within the 6-month follow-up visit window, it should be used 
in place of the duplex ultrasound. Evidence of no blood flow within the 
Tacked segment indicates restenosis/loss of patency.  
 
Target Limb Salvage defined as freedom from any above-ankle target 
limb amputation at 6 months.  

 
TOBA II BTK Clinical Study Protocol – Tack Endovascular System 
CA 0137 Rev C 
   
CA 0137 Rev C  
CONFIDENTIAL 
Page 9 of 76 
Observational 
Endpoints: 
 
Device Success: Successful deployment of the Tack implant(s) at the 
intended target site(s) and successful withdrawal of the delivery catheter 
from the introducer sheath.  
 
Target Lesion Success: Demonstrated target lesion patency [<30% 
residual diameter stenosis (DS), by visual estimate] without the use of a 
bailout stent within the target lesion upon completion of the index 
procedure. This will be assessed for all lesions treated with a Tack 
implant. In addition, target lesion success will also be analyzed by lack 
of bailout stent to tacked segment only. Multiple target lesions treated 
as one lesion with PTA will be analyzed as one lesion. 
 
Procedural Success: Demonstrated target lesion patency (<30% residual 
DS, by visual estimate) without the use of a bailout stent within the target 
lesion and without the occurrence of MALE+POD upon completion of the 
index procedure 
 
Amputation-free survival (AFS): Freedom from above-ankle target limb 
amputation or all-cause death at 6 and 12 months 
 
Freedom from MALE at 12 months + POD at 30 days 
 
Target lesion(s) tacked segment(s) patency at 12 months defined as the 
presence of blood flow using duplex ultrasound. 
 
Target Limb Salvage defined as freedom from any above-ankle target 
limb amputation at 12 months 
 
Assisted primary target lesion Tacked segment patency (flow vs. no flow) 
at 6 and 12 months 
 
Secondary target lesion Tacked segment patency (flow vs. no flow) at 6 
and 12 months 
 
PSVR patency at 6 and 12 months [Freedom from binary restenosis 
defined as Peak Systolic Velocity Ratio (PSVR) of ≥ 2.5 and/or 
angiographic percent diameter stenosis of ≥50%] assessed for the 
following: 
o Target Lesion(s), defined as the entire contiguous arterial 
segment treated with angioplasty, inclusive of an additional 
proximal and distal margin of 5 mm 
o Tacked Segment(s), defined as the Tack device and 5 mm of 
artery proximal and distal to each Tack. If Tacks are within 10 mm 
of each other, they will be considered as a single tacked segment 
for the purposes of this patency assessment. 
 
Clinically-driven target lesion revascularization (CD-TLR) through 6 and 
12 months 
 
Clinically-driven target vessel revascularization (CD-TVR) through 6 and 
12 months 
 
All-cause death through 6 and 12 months 
 
Any Target vessel revascularization (TVR) through 6 and 12 months 

 
TOBA II BTK Clinical Study Protocol – Tack Endovascular System 
CA 0137 Rev C 
   
CA 0137 Rev C  
CONFIDENTIAL 
Page 10 of 76 
 
Any Target lesion revascularization (TLR) through 6 and 12 months 
In addition, the following observational endpoints will be assessed at various 
time points through 36 months (See Time and Events Schedule Section 8.1): 
 
Changes in Wound, Ischemia, and foot Infection (WIfI)1 Classification 
 
Changes in ankle brachial index (ABI) and toe brachial index (TBI) 
 
Changes in Rutherford Classification 
 
Changes in the EQ-5D-3L quality of life questionnaire 
 
Changes in the Walking Impairment Questionnaire (WIQ) 
 
Tack implant Integrity via X-ray (only performed at 12-month visit) 
 
Progress of wound(s) present at study entry (healed, improved, 
unchanged, worsening, amputated) 
 
Appearance of new wound(s) after study entry 
 
Unplanned below-ankle target limb amputation(s): digit or 
transmetatarsal 
Inclusion 
Criteria: 
1. Males or non-pregnant females ≥ 18 years of age at the time of consent  
2. Female subjects of childbearing potential must have a negative pregnancy 
test prior to treatment and must use some form of contraception (abstinence 
is acceptable) through the duration of the study 
3. Subject has been informed of and understands the nature of the study and 
provides signed informed consent to participate in the study. If the subject 
possesses the ability to understand and provide informed consent but due to 
physical inability, the subject cannot sign the informed consent form (ICF), 
an impartial witness may sign on behalf of the subject 
4. Willing to comply with all required follow-up visits 
5. Rutherford Classification 4 or 5  
6. WIfI Wound grade of 0, 1 or modified 2  
7. WIfI Foot Infection grade of 0 or 1  
8. Estimated life expectancy ≥1 year 
Angiographic 
Inclusion 
Criteria: 
1. Reference vessel diameter is between 1.5 mm and 4.5 mm, inclusive (by 
visual estimate)  
2. Only one limb requires treatment during the Index Procedure 
Note: If the subject has bilateral BTK disease, the Investigator should 
choose the limb that most closely meets eligibility criteria. If the chosen 
limb does not meet final eligibility after PTA treatment, the subject 
should not be enrolled at that time. This subject may be brought back for 
potential study device treatment to the contralateral limb per the 
 
1 Joseph L. Mills, Sr, MD, Michael S. Conte, MD, David G. Armstrong, DPM, MD, PhD, Frank B. Pomposelli, MD, Andres Schanzer, MD, Anton 
N. Sidawy, MD, MPH, and George Andros, MD, on behalf of the Society for Vascular Surgery Lower Extremity Guidelines Committee, The 
Society for Vascular Surgery Lower Extremity Threatened Limb Classification System: Risk stratification based on Wound, Ischemia, and 
foot Infection (WIfI). J Vasc Surg. 2014; Volume 59, Issue 1, Pages 220–234.e2 

 
TOBA II BTK Clinical Study Protocol – Tack Endovascular System 
CA 0137 Rev C 
   
CA 0137 Rev C  
CONFIDENTIAL 
Page 11 of 76 
protocol requirements. Only one limb may receive study device 
treatment. 
3. Ability to cross study device(s) antegrade through target lesion  
4. Has de novo or restenotic target lesion(s) with pre-PTA stenosis of ≥70% or 
is occluded (by visual estimate) and is indicated for PTA treatment with a 
standard balloon catheter 
Note: Diseased segments with >30 mm of healthy vessel between them 
are considered separate target lesions 
Note: If any part of the lesion is restenotic, no part of the lesion should 
have more than 1 prior failure (by plain balloon angioplasty only), 
which must have occurred greater than 1 year (360 days) prior to the 
index procedure 
Note: After PTA treatment, the target lesion is defined as the entire 
contiguous arterial segment length treated with angioplasty 
5. Target lesion(s) located in the mid popliteal (P2), distal popliteal (P3), 
tibioperoneal trunk, peroneal, anterior tibial, or posterior tibial arteries  
Note: The mid popliteal artery (P2) begins at the superior aspect of the 
patella. The most distal location of the tibial and/or peroneal artery(ies) 
ends at the beginning of the dorsalis pedis artery (DP). Tacks may not 
be implanted within 1 cm above radiographic tibiotalar joint.  
6. Target vessel(s) reconstitute(s) at or above the ankle or displays normal 
terminal branching  
 
If the target vessel is the peroneal artery, the artery must display 
normal terminal branching.  
 
If the target vessel is the anterior tibial (AT) artery or the posterior 
tibial (PT) artery, the artery(ies) must display reconstitution at least 
1cm proximal to the radiographic tibiotalar joint line, and continue 
into an intact runoff vessel (AT/ dorsalis pedis or PT/plantar 
artery).  
 
If the target vessel is the P2 and/or P3, any 1 of the 3 distal arteries 
must show respective outflow.  
 
If the target vessel is the TPT, then respective outflow for either the 
peroneal artery or posterior tibial artery must be confirmed. 
Note: Normal terminal branching and/or reconstitution of run-off 
vessels as described above should be confirmed prior to PTA treatment 
of the target lesion(s) as well as after PTA treatment to the target 
lesion(s) (prior to Tack deployment) 

 
TOBA II BTK Clinical Study Protocol – Tack Endovascular System 
CA 0137 Rev C 
   
CA 0137 Rev C  
CONFIDENTIAL 
Page 12 of 76 
7. Patent (<50% DS by visual estimate) arterial inflow from aortic bifurcation 
to the distal edge of the proximal popliteal artery (P1) at the superior end of 
the patella.  
Note: Treatment of inflow artery lesions within the iliac (ipsilateral or 
contralateral), common femoral, superficial femoral, and/or the 
proximal popliteal (P1) artery(ies) is allowed during the index 
procedure but must have documented success (<30% residual DS and 
no major vascular complications) prior to target lesion treatment.  
Note: If an inflow lesion requires treatment with atherectomy or 
requires surgical intervention, the patient should not be enrolled 
8. After PTA treatment, the target lesion has <30% residual DS and presence 
of at least one post-PTA dissection (by visual estimate) that the Investigator 
would otherwise treat by means such as but not limited to additional 
angioplasty, with longer inflation time or stenting 
9. No evidence of aneurysm or acute thrombus in target vessel 
Exclusion 
Criteria: 
1. Is pregnant or refuses to use contraception through the duration of the 
study 
2. Previous bypass graft in the target limb 
3. Acute limb ischemia, defined as symptom onset occurring less than 14 days 
prior to the index procedure 
4. Prior or planned above-ankle amputation or complete transmetatarsal 
amputation to the target limb (this does not apply to ray amputation of ≤2 
digits, simple digital amputations or ulcer debridements) 
5. WIfI Foot Infection grade 2 or 3  
6. Any systemic infection or immunocompromised state. Patients with an 
ascending infection/deep foot infection or abscess/white blood count 
(WBC)≥12,000/or febrile state 
7. Endovascular or surgical procedure (not including diagnostic procedures, 
planned simple digital amputation or wound debridement) to the target 
limb less than 30 days prior to or planned for less than 30 days after the 
index procedure 
8. Existing stent implant in the target vessel  
9. Any other endovascular or surgical procedure (not including diagnostic 
procedures, planned simple digital amputation or wound debridement) less 
than 14 days prior to the index procedure or planned procedure less than 
30 days after the index procedure  
10. Known coagulopathy, hypercoagulable state, bleeding diathesis, other blood 
disorder, or a platelet count less than 80,000/microliter or greater than 
500,000/microliter  
11. WIfI Wound grade of 2 or 3.  

 
TOBA II BTK Clinical Study Protocol – Tack Endovascular System 
CA 0137 Rev C 
   
CA 0137 Rev C  
CONFIDENTIAL 
Page 13 of 76 
12. Any subject in which antiplatelet, anticoagulant, or thrombolytic therapy is 
contraindicated 
13. Myocardial infarction, coronary thrombolysis or angina less than 30 days 
prior to the Index Procedure 
14. History of stroke or transient ischemic attack (TIA) less than 90 days prior 
to the Index Procedure 
15. Currently on dialysis 
16. Known hypersensitivity or contraindication to nickel-titanium alloy (Nitinol) 
17. Participating in another ongoing investigational clinical trial in which the 
subject has not completed the primary endpoint(s) 
18. Has other comorbidities that, in the opinion of the investigator, would 
preclude them from receiving this treatment and/or participating in study-
required follow-up assessments 
19. Known hypersensitivity or allergy to contrast agents that cannot be medically 
managed 
20. Subject already enrolled into this study 
21. Restenotic target lesion previously treated by means other than plain balloon 
angioplasty and/or less than 1 year prior to index procedure. 
Angiographic 
Exclusion 
Criteria: 
1. Acute vessel occlusion or acute or sub-acute thrombosis in target lesion 
2. Subject has significant stenosis (≥50% DS) or occlusion of inflow arteries 
(including the iliac, superficial femoral and proximal popliteal arteries) not 
successfully treated (<30% residual DS and without major complication) 
prior to PTA of target lesion 
3. The target lesion shows no dissections after PTA or dissections of a lesser 
grade for which the operator would normally not pursue additional 
treatment 
4. If parallel non-target vessel (anterior tibial, peroneal, or posterior tibial) is 
treated during index procedure and is not successful (<30% residual DS and 
without major complication) prior to PTA of target lesion/vessel  
5. Below the ankle lesion requiring treatment  
6. Use of atherectomy, cryoplasty, cutting/scoring/contoured balloon 
angioplasty, stenting or any other treatment (with the exception of a 
crossing device) of the target lesion/vessel other than plain balloon 
angioplasty PTA during the index procedure 
Note: Use of atherectomy in a parallel, non-target vessel is allowed 
during the index procedure but must have documented success (<30% 
residual DS and no major vascular complications) prior to target 
lesion/vessel treatment 
 
 

 
TOBA II BTK Clinical Study Protocol – Tack Endovascular System 
CA 0137 Rev C 
   
CA 0137 Rev C  
CONFIDENTIAL 
Page 14 of 76 
 STUDY MANAGEMENT CONTACT LIST 
Please see APPENDIX A – Study Management Contact List located at the end of this document. 
 INTRODUCTION 
4.1. 
BACKGROUND AND RATIONALE 
Peripheral artery disease (PAD) is a chronic occlusive artery disease caused by plaque buildup in 
the arterial lumen which leads to diminished blood flow.  Clinical symptoms include pain while 
walking or in more severe cases rest pain or tissue loss.  In the most extreme cases amputations 
can occur.  Lower extremity PAD remains one of the most unrecognized manifestations of 
systemic arteriosclerosis estimated to affect between 3% and 7% of the population and up to one 
in five patients above the age of 75.2  Approximately 15-30% of patients with lower extremity 
PAD will progress from intermittent claudication to critical limb ischemia (CLI) over the course 
of their disease.3, 4  CLI has a yearly incidence of approximately 220 new cases per million 
population.5   
Critical limb ischemia remains a significant problem associated with morbidity and mortality.  
Per, Conte, et al, one year mortality ranges from 10% to 40% and with no revascularization 
interventions, up to 40% of those affected will suffer limb loss within 6 months.6  According to a 
publication by Iida, et al, CLI is associated with a high mortality rate (19%-54% at one year) and 
a high amputation rate (≥25%) at 6 months after failure of primary revascularization.7   
Infrapopliteal arterial occlusive disease is a leading source of CLI.8  The treatment approach for 
these patients ranges from medical management to surgical management which can consist of 
either revascularization or amputation.9  Critical limb ischemia is attributed to severe 
compromise of the blood flow to the affected extremity which manifests as significant limb pain 
at rest.  It results from a chronic lack of blood supply.  Per Varu, et al. the international consensus 
on the definition of CLI is “any patient with chronic ischemic rest pain, ulcers, or gangrene 
attributable to objectively proven arterial occlusive disease.”  Many of these patients, have 
extended diffuse three-vessel disease and only 20-30% present with a simple focal lesion and 
good runoff.10  The primary goal of the treatment of CLI is relief of ischemic rest pain, healing of 
 
2 Davies MG, El-Sayed HF.  Objective performance goals after endovascular intervention for critical limb ischemia. J Vasc Surg. 
2015;621555-63. 
3 Dormandy J, Mahir M, Ascady G., Balsano F, De Leeuw P, Blomberg P, Bousser MG, Clement D, Coffman J, Deutschinoff A, et 
al.  Fate of the patient with chronic leg ischemia: a review article.  J Cardiovasc (Torino).  1989;30:50-57. 
4 McDaniel MD, Cronenwett JL.  Basic data related to the natural history of intermittent claudication.  Ann Vasc Surg.  
1989;3:273-277. 
5 Van Overhagen, Spiliopoulus S, Tsetis D. Below-the-Knee Interventions. Cardiovasc Intervent Radiol. 2013; 36:302-11. 
6 Conte MS, Geraghty PJ, Bradbury AW, Hevelone ND, Lipsitz SR, Moneta GL, Nehler MR, Powell RJ, Sidawy AN. Suggested 
objective performance goals and clinical trial design for evaluating catheter-based treatment of critical limb ischemia. J Vasc 
Surg. 2009;50:1462-73. 
7 Iida O, Nakamura M, Yamauchi Y, Kawasaki D, Yokoi Y, Yokoi H, Soga Y, Zen K, Hirano K, Suematsu N, Inoue N, Suzuki K, 
Shintani Y, Miyashita Y, Urasawa K, Kitano I, Yamaoka T, Murakami T, Uesugi M, Tsuchiya T, Shinke T, Oba Y, Ohura N, Hakasaki 
T, Nanto S, OLIVE Investigators. Endovascular treatment for infrainguinal vessels in patients with critical limb ischemia: OLIVE 
registry, a prospective, multicenter study in Japan with 12-month follow-up. Circ Cardiovasc Interv. 2013;6:68-76. 
8 Van Overhagen, Spiliopoulus S, Tsetis D. Below-the-Knee Interventions. Cardiovasc Intervent Radiol. 2013; 36:302-11. 
9 Varu VN, Hogg ME, Kibbe MR. Critical Limb Ischemia. J Vasc Surg. 2010; 51:230-41. 
10 Randon C, Jacobs B, De Ryck F, Vermassen F. Angioplasty or primary stenting for infrapopliteal lesions: results of a 
prospective randomized trial. Cardiovasc Intervent Radiol. 2010 Apr;33(2):260-9. 

 
TOBA II BTK Clinical Study Protocol – Tack Endovascular System 
CA 0137 Rev C 
   
CA 0137 Rev C  
CONFIDENTIAL 
Page 15 of 76 
ulcers or gangrene, and prevention of limb loss.11,12  While tibial bypass is often utilized, it is 
associated with a 1.8%-6% perioperative mortality.13  As a result, less invasive endovascular 
treatments have been utilized to achieve revascularization. 
Endovascular therapies for lower extremity treatment are well accepted by both patients and 
physicians due to the less invasive approach.  However, there is uncertainty regarding the best 
endovascular treatment strategy for symptomatic patients with atherosclerotic disease of the 
below the knee (BTK) arteries.  The goal in treating patients with PAD is to provide relief of 
symptoms and to restore at least one straight line of blood flow to the distal foot.14  In the more 
advanced cases, the goal is to preserve tissue or limb salvage.  Percutaneous transluminal 
angioplasty (PTA) alone is the most common method of endovascular therapy for BTK arteries.15  
Percutaneous transluminal angioplasty, however, is limited by recoil, dissection, thrombosis and 
early restenosis.  Recently, Trans-Atlantic Inter-Society Consensus (TASC) guidelines were 
updated with lesion characterization guidelines for the infrapopliteal segment; however no 
treatment guidelines have been presented to date.16 
The Tack Endovascular System has been designed to provide a treatment solution for post-PTA 
dissection in the BTK arteries.  To assist in both developing a comparative baseline and to assist 
in clinical protocol development for the Tack Endovascular System, a project was initiated to 
research the peer-reviewed clinical literature to outline the clinical results of the use of PTA in 
the BTK/infrapopliteal arteries and the associated treatment of dissections.  Elements of that 
review are summarized below. 
As stated previously, the primary clinical goal of infrapopliteal arterial interventions for CLI is to 
restore at least one unobstructed line of blood flow to the distal foot with the intention of 
preventing major amputation.  There are several endovascular treatment options that are utilized 
to accomplish this including PTA with traditional balloons, PTA with drug-eluting balloons (DEB) 
or the placement of bare metal stents (BMS) or drug-eluting stents (DES).  To develop a 
comprehensive overview of these interventions, clinical data was obtained and evaluated from 
the literature for all of these technologies.17 
After analysis of the peer-reviewed literature, it was determined to focus on PTA.  The Intact 
Vascular Tack Endovascular System is a first of its kind device where no such FDA approved 
device for treatment of post-PTA vessel dissections exists.  As a consequence, a direct comparator 
is not available.  Under current treatment protocols, dissections that occur following PTA would 
typically be treated with the off-label placement of a stent. When the intent is to treat a lesion 
 
11 Randon C, Jacobs B, De Ryck F, Vermassen F. Angioplasty or primary stenting for infrapopliteal lesions: results of a 
prospective randomized trial. Cardiovasc Intervent Radiol. 2010 Apr;33(2):260-9. 
12 Van Overhagen, Spiliopoulus S, Tsetis D. Below-the-Knee Interventions. Cardiovasc Intervent Radiol. 2013; 36:302-11. 
13 Randon C, Jacobs B, De Ryck F, Vermassen F. Angioplasty or primary stenting for infrapopliteal lesions: results of a 
prospective randomized trial. Cardiovasc Intervent Radiol. 2010 Apr;33(2):260-9. 
14 Karnabatidis D, Katsanos K, Siablis D. Infrapopliteal stents: Overview and unresolved issues. J Endovasc Ther. 2009;16(Suppl 
I):I153-I162. 
15 Razavi MK, Mustapha JA, Miller LE. Contemporary systematic review and meta-analysis of early outcomes with percutaneous 
treatment for infrapopliteal atherosclerotic disease. J Vasc Interv Radiol. 2014 Oct;25(10):1489-96. 
16 TASC Steering Committee, Jaff MR, White CJ, Hiatt WR, Fowkes GR, Dormandy J, Razavi M, Reekers J, Norgren L. An Update 
on Methods for Revascularization and Expansion of the TASC Lesion Classification to Include Below-the-Knee Arteries: A 
Supplement to the Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II). J Endovasc Ther. 
2015;22(5):663-77. 
17 Intact Vascular Document EXT-17-0069 (Clinical review of scientific literature for the endovascular treatment of CLI and 
treatment of post-PTA dissections in the peripheral vasculature: Below-the-Knee Arteries).    

 
TOBA II BTK Clinical Study Protocol – Tack Endovascular System 
CA 0137 Rev C 
   
CA 0137 Rev C  
CONFIDENTIAL 
Page 16 of 76 
with only balloon angioplasty, the use of a Tack device to treat a vessel wall dissection is more 
consistent with the plan to leave as little metal behind as possible, in contrast to placement of a 
stent.  With this in mind, PTA results were concluded to be the most appropriate treatment to 
provide clinical data on endovascular interventions in the BTK arteries for the TOBA clinical trial 
design.   
One outcome of the review was the conclusion that often the clinical results demonstrate a 
discrepancy between patency and clinical success measures such as limb salvage and patient 
survival.  Based on the literature review, the primary patency rate following PTA treatment for 
below knee lesions varied from 18% to 82%. This wide range in reported patency is due in large 
part to variability in key patient and procedural characteristics across studies, such as treated 
lesions (lesion lengths, number of treated lesions/vessels, stenotic vs occluded), the method of 
lesion treatment (PTA only, PTA with stents, pre-treatment with atherectomy or laser), 
allowance for associated treatment of inflow and outflow lesions, definition and method of 
measuring lesion/vessel patency (clinical, duplex ultrasound, magnetic resonance angiography, 
angiography, computed tomographic angiography), as well as composition of patient types 
(studies that focused CLI vs below knee lesions, or on diabetics, or on patients with chronic renal 
failure).  Due to the fact that the Tack device is a first of its kind device and there exists no known 
comparator, the use of relevant PTA outcome data is a reasonable approach in establishing the 
current state of the art in the peer-reviewed clinical literature.  While data are limited, this 
assessment identified information that was successful in identifying literature results on per 
patient and per lesion patency that could be used for this purpose.  This analysis resulted in an 
overall patency range per limb of 18%-82% and per patient of 38%-66% at one year. Where 
reported at 6 months, patency rates per limb/lesion of 35.1%-91% and per patient of 65%-76% 
were observed. When Kaplan-Meier curves were presented, 6 month rates were estimated unless 
otherwise specifically reported. The corresponding limb salvage range at one-year was 84%-
100% and the patient survival range at one-year was 68.4%-94.8%.  The clinical data summary 
did demonstrate that there are clinical benefits associated with the use of endovascular 
interventions in the BTK arteries.  While there is variability in the data reported, the review 
indicated that the most commonly reported outcomes are limb salvage (and/or amputation free 
survival/amputation rate) and patient survival.  Patency is reported less consistently.  All clinical 
endpoints were associated with large ranges for the reported data. 
Due to the variability in the generally reported clinical data, several outcome measures for below-
the-knee interventions were identified utilizing the guidance provided in publications that have 
been focused on developing objective performance goals for endovascular treatment of CLI.  
These objective performance goals (OPGs) and associated classification systems were developed 
by the Society of Vascular Surgery (SVS)18,19,20 and published by Conte, et al. and serve to provide 
a consistent framework for the evaluation of new catheter-based treatments in CLI based on 
evidence from historical controls.  They consist of both safety (30 days) and efficacy profiles (1 
 
18 Conte MS, Geraghty PJ, Bradbury AW, Hevelone ND, Lipsitz SR, Moneta GL, Nehler MR, Powell RJ, Sidawy AN. Suggested 
objective performance goals and clinical trial design for evaluating catheter-based treatment of critical limb ischemia. J Vasc 
Surg. 2009;50:1462-73. 
19 Goodney PP, Schanzer A, Demartino RR, Nolan BW, Hevelone ND, Conte MS, Powell RJ, Cronenwett JL; Vascular Study Group 
of New England. Validation of the Society for Vascular Surgery's objective performance goals for critical limb ischemia in 
everyday vascular surgery practice. J Vasc Surg. 2011 Jul;54(1):100-108. 
20 Mills JL, Conte MS, Armstrong DG, Pomposelli FB, Schanzer A, Sidawy AN, Andros G, Vascular Surgery Lower Extremity 
Guidelines Committee. The Society for Vascular Surgery Lower Extremity Threatened Limb Classification System: Risk 
stratification based on Wound, Ischemia, and foot Infection (WIfI).  J Vasc Surg. 2014:59:220-34. 

 
TOBA II BTK Clinical Study Protocol – Tack Endovascular System 
CA 0137 Rev C 
   
CA 0137 Rev C  
CONFIDENTIAL 
Page 17 of 76 
year).  The SVS OPG values that were reviewed were those for the “Anatomical High Risk Group” 
as defined by Conte.  Data from recent studies that have reported on the use of OPGs are 
summarized in Table 1 and Table 2.21,22,23  
Table 1. OPG Summary—Safety (30 Days)—Anatomical High Risk Group (Infrapopliteal) 
Measure 
OPG 
PTA (Literature Reported) 
30 Day 
1 Year 
30 Day 
1 Year 
MACE 
10% 
 
0.0%-5.0% 
 
MALE 
9% 
 
2.5%-13.0% 
 
Amputation 
4% 
 
1.7%-5.0% 
 
MACE: Major Adverse Cardiovascular Event—MI, Stroke, All Cause Death 
MALE: Major Adverse Limb Event—Above-Ankle Amputation, Major Intervention 
 
Table 2. OPG Summary—Efficacy (1 Year)—Anatomical High Risk Group (Infrapopliteal) 
Measure 
OPG 
PTA (Literature Reported) 
30 Day 
1 Year 
30 Day 
1 Year 
Freedom 
from 
MALE+POD 
 
67% 
 
76.0%-86.0% 
AFS 
 
68% 
 
67.0%-78.7% 
Limb 
Salvage 
 
81% 
 
83.0%-87.0% 
Survival 
 
80% 
 
83.0%-87.0% 
MALE: Major Adverse Limb Event—Above-Ankle Amputation, Major Intervention 
POD: Perioperative Death 
AFS: Amputation Free Survival 
 
This analysis of the relationship of patency with the clinical outcomes of limb salvage and survival 
correlates with information reported elsewhere in the clinical literature.  From the literature, the 
most suitable clinical outcome measures to assess clinical success in BTK CLI interventions are 
safety as assessed by perioperative death (POD) and major adverse limb events (MALE) coupled 
with the clinical efficacy measure associated with limb salvage and survival.  These align with the 
objective performance goals proposed by Conte, et al.  For the proposed clinical study, OPG 
measurements are proposed with a focus on freedom from all cause of death and MALE at 30 
days, freedom from MALE+POD at 6 months and amputation-free survival at 6 months (Limb 
 
21 Davies MG, El-Sayed HF. Outcomes of Isolated Tibial Endovascular Interventions for Tissue Loss in CLI Patients on 
Hemodialysis. J Endovasc Ther. 2015;22(5):681-9 
22Nakano M, Hirano K, Iida O, Yamauchi Y, Soga Y, Kawasaki D, Tazaki J, Suzuki K, Fujiwara M, Yamaoka T. Clinical efficacy of 
infrapopliteal endovascular procedures for hemodialysis patients with critical limb ischemia. Ann Vasc Surg. 2015;29(6):1225-34 
23 Varela C, Acin F, de Maturana IL, de Haro J, Bleda S, Paz B, Esparza L. Safety and efficacy  outcomes of infrapopliteal 
endovascular procedures performed in patients with critical limb ischemia according to the Society for Vascular Surgery 
Objective Performance Goals. Annals Vasc Surg. 2014; 28:284-294 

 
TOBA II BTK Clinical Study Protocol – Tack Endovascular System 
CA 0137 Rev C 
   
CA 0137 Rev C  
CONFIDENTIAL 
Page 18 of 76 
Salvage).   The OPG for 6 months is extrapolated directly from the data provided in Conte, et. al. 
as noted above using identical methodology.   
A review of post-PTA dissections and their impact was also conducted.  Few articles reported any 
data related to dissections in the BTK arteries; however, summaries from those that did is 
presented below.   
The assessment determined that the occurrence of dissection in the BTK arteries ranges from 
6.4%-30.7%.24,25,26,27  Razavi, et al., states related to dissection, “It is conceivable that the reported 
dissection rates in the BTK vessels may have been underestimated because they are harder to detect 
as a result of their smaller diameters and frequent interference with optimal visualization by 
osseous structures.” 
In a study of DEBs versus PTA (in which 24.6% of the patients were treated in the BTK arteries), 
Fanelli, et al. noted that “Another interesting result is correlated with dissections that occurred after 
angioplasty; in DEB group non-flow limiting dissection occurred in 9 over 57 treated lesions (15%) 
but none of them developed a significant restenosis (flow-limiting dissection) during the follow-up.  
In those lesions treated with non-coated balloons, a dissection not limiting the blood flow occurred 
in 20 cases (20/65, 30.7%) but 16 (16/65, 24%) of them developed a significant restenosis during 
follow-up.”  They further go on to discuss that “as reported in other articles28 in case of dissections 
not limiting the blood flow, provisional stenting can be avoided.”  The authors do highlight that this 
is a fairly recent trend in reporting and that further studies with larger populations are required 
to fully understand the implications. 
One study that did address the rate of dissection in the BTK arteries was the IN.PACT clinical 
study (Zeller, et al.).29  The study was designed to assess the efficacy and safety of a DEB compared 
to PTA.  As an element of reporting on post-procedural complications, the freedom from post-
procedural dissection was presented.  The rate was higher in the DEB arm (87.7%) versus the 
PTA arm (80.8%).  In each arm, most dissections were considered “mild” and non-flow limiting.  
The corresponding bailout stent rates were 2.3% and 2.8% in the DEB and PTA arms, 
respectively.  This was the only study identified that discussed dissections in more detail that 
utilized independent core lab adjudication of the data. 
 
24 Fanelli F, Cannavale A, Boatta E, Corona M, Lucatelli P, Wlderk A, Cirelli C, Salvatori FM. Lower limb multilevel treatment with 
drug-eluting balloons: 6-month results from the DEBELLUM randomized trial. J Endovasc Ther. 2012 Oct;19(5):571-80 
25 Fanelli F, Cannavale A, Corona M, Lucatelli P, Wlderk A, Salvatori FM. The "DEBELLUM"--lower limb multilevel treatment with 
drug eluting balloon—randomized trial: 1-year results. J Cardiovasc Surg (Torino). 2014 Apr;55(2):207-16 
26 Randon C, Jacobs B, De Ryck F, Vermassen F. Angioplasty or primary stenting for infrapopliteal lesions: results of a 
prospective randomized trial. Cardiovasc Intervent Radiol. 2010 Apr;33(2):260-9 
27 Razavi MK, Mustapha JA, Miller LE. Contemporary systematic review and meta-analysis of early outcomes with percutaneous 
treatment for infrapopliteal atherosclerotic disease. J Vasc Interv Radiol. 2014 Oct;25(10):1489-96 
28 Fanelli F, Cannavale A, Gazzetti M, D'Adamo A. How Do We Deal With Dissection After Angioplasty? J Endovasc Ther. 
2013;20:801-4; Tepe G, Zeller T, Schnorr B, Claussen CD, Beschorner U, Brechtel K, Scheller B, Speck U. High-Grade, Non-Flow-
Limiting Dissections Do Not Negatively Impact Long-Term Outcome After Paclitaxel-Coated Balloon Angioplasty: An Additional 
Analysis From the THUNDER Study. J Endovasc Ther. 2013;20:792-800. 
29 Zeller T, Baumgartner I, Scheinert D, Brodmann M, Bosiers M, Micari A, Peeters P, Vermassen F, Landini M, Snead DB, Kent 
KC, Rocha-Singh KJ; IN.PACT DEEP Trial Investigators. Drug-eluting balloon versus standard balloon angioplasty for infrapopliteal 
arterial revascularization in critical limb ischemia: 12-month results from the IN.PACT DEEP randomized trial. J Am Coll Cardiol. 
2014 Oct 14;64(15):1568-76. 

 
TOBA II BTK Clinical Study Protocol – Tack Endovascular System 
CA 0137 Rev C 
   
CA 0137 Rev C  
CONFIDENTIAL 
Page 19 of 76 
An additional report that addressed dissection was a single study that reported dissections by 
grade for PTA.30  In this study, the reported dissection rates by grade were 33% Type A, 33% 
Type B, 16.7% Type D and 16.7% Type F.  Similar to previously compiled data for the superficial 
femoral artery (SFA) and popliteal artery, most dissections were lower grade (A/B). 
There has been recent discussion in the literature about the clinical implications of dissections.  
While the direct impact remains unclear, there is interest in investigating the correlation between 
dissection and restenosis.  The literature does highlight that there is a fairly recent trend in 
reporting dissections and that further studies with larger populations are required to fully 
understand the implications.    It was also noted in the literature that as with other peripheral 
interventions, dissections are often under-reported.  The Tack Endovascular System is designed 
to provide a treatment option for all grade dissections.   
4.2. 
REPORT OF PRIOR INVESTIGATIONS 
Intact Vascular has developed the Tack Endovascular System, a system designed to provide 
apposition of dissected tissue with an implantable, cylindrical nitinol (nickel-titanium) Tack 
implant following percutaneous transluminal balloon angioplasty (PTA).  Intact Vascular is 
currently conducting a clinical study in below-the-knee arteries (TOBA-BTK) and a United States 
pivotal investigation device exemption (IDE) study of the 6Fr device in the femoropopliteal 
arteries.  
The TOBA-BTK Study (Prospective, Multicenter Tack Optimized Balloon Angioplasty Below the 
Knee (TOBA - BTK) Study for Infrapopliteal Arteries Using the Tack Endovascular System® 
(Protocol# TD 0109 Rev D)) is a prospective, single arm, multi-center, first in man study designed 
to collect data in support of safety and performance of the Intact Vascular Tack Endovascular 
System® for tissue apposition in peripheral arteries with reference vessel diameters (RVD) 
ranging from 1.5-4.5mm.  Specifically, the population for this study included subjects with critical 
limb ischemia (Rutherford Class 4-5) that had angiographic evidence of type A-F dissection 
following below the knee (BTK) percutaneous transluminal angioplasty (PTA).  TOBA-BTK was a 
feasibility study designed to assess 30-day safety and ease of use.  Long-term follow-up will be 
conducted through 24 months.  Currently, data through 12 months is available.   
The inclusion criteria for the TOBA-BTK study was: 
• 
Rutherford 4 or 5 
• 
RVD 1.5 – 4.5mm 
• 
Lesion located between knee joint and ankle 
• 
De novo lesion ≥70% stenotic or occluded 
• 
Up to 2 tibial arteries can be treated with cumulative length of ≤15cm 
• 
Presence of post PTA dissection 
The exclusion criteria for the TOBA-BTK study was: 
• 
Stenosis or occlusion of inflow vessels not successfully treated 
• 
Previous inflow vessel treatment failure 
 
30 Shammas NW, Lam R, Mustapha J, Ellichman J, Aggarwala G, Rivera E, Niazi K, Balar N. Comparison of orbital atherectomy 
plus balloon angioplasty vs. balloon angioplasty alone in patients with critical limb ischemia: results of the CALCIUM 360 
randomized pilot trial. J Endovasc Ther. 2012 Aug;19(4):480-8 

 
TOBA II BTK Clinical Study Protocol – Tack Endovascular System 
CA 0137 Rev C 
   
CA 0137 Rev C  
CONFIDENTIAL 
Page 20 of 76 
• 
Previous below the knee bypass 
• 
Lesion on plantar surface of heel or Achilles tendon or exposed calcaneus 
Subjects with an optimal result (i.e. no dissections) following primary balloon angioplasty were 
screen failures.  Subjects with suboptimal angioplasty results (i.e. the presence of post-PTA 
dissections) were enrolled and treatment with the Tack implant was attempted.  If a Tack implant 
was attempted, but the Tack device(s) was not successfully deployed and implanted into the 
subject, the subject was followed for 1 month and then exited from the study.  The protocol 
scheduled follow-up visits were to occur at 1, 3, 6, 12, and 24 months.  The primary safety 
endpoint for this study included a safety composite of MALE and POD, which was assessed at 1-
month post-procedure.  Major adverse limb events included major amputation (amputation 
above the ankle) or re-intervention (surgical or endovascular) in the target limb.  Additional 
primary endpoints included:  
• 
Device success – successful delivery and deployment of the study implant(s) at the 
intended target site(s) and successful withdrawal of the delivery catheter.  
• 
Procedure success – Demonstrated vessel patency as reported by the physician (visual 
estimate) without the occurrence of MALE + POD on the date of procedure.  
Secondary endpoints included: 
• 
All-cause mortality at 3, 6, 12, and 24 months 
• 
Amputation of the limb (above the ankle) at 3, 6, 12, and 24 months 
• 
Amputation free survival at 3, 6, 12, and 24 months 
• 
Clinically driven target vessel revascularization (TVR) at 3, 6, 12, and 24 months 
• 
Clinically driven target lesion revascularization (TLR) at 3, 6, 12, and 24 months 
• 
Changes in Rutherford Clinical Category from baseline at 3, 6, 12, and 24 months 
• 
Maintenance of luminal patency of the target lesion by toe brachial index (TBI) (≤0.15 
decrease) as compared to the baseline TBI obtained prior to discharge at 1, 3, 6, 12, and 
24 months 
• 
Doppler Exam (presence of signal) at 1, 3, 6, 12, and 24 months 
A total of 35 subjects were enrolled, all of which are included in the safety sample.  Of these 35 
subjects, 32 had at least one Tack implant placed.  These 32 subjects are included in the 
performance sample.  In the other three subjects, Tack implant(s) were attempted, but device 
catheters could not reach treatment site(s).  These 3 subjects were followed for 30 days post-
treatment for safety analysis.  Three (3) additional subjects in the performance sample exited the 
study prior to the 12-month follow-up visit, one prior to 30 days and two prior to 12 months. 
Demographics for the TOBA-BTK Trial subjects are summarized below in Table 3.  
 
 

 
TOBA II BTK Clinical Study Protocol – Tack Endovascular System 
CA 0137 Rev C 
   
CA 0137 Rev C  
CONFIDENTIAL 
Page 21 of 76 
Table 3. TOBA-BTK Trial Subject Demographics 
Parameter 
Safety Sample  
N = 35 
Performance Sample    
N = 32 
Age at Procedure (mean ± stdev)  
(minimum, median, maximum)  
76.1 ± 9.3 (35)     
(55, 77.0, 91) 
76.1 ± 9.5 (32)      
(55, 77.0, 91) 
Gender  
 
 
   Female  
48.6% (17 / 35) 
43.8% (14 / 32) 
   Male  
51.4% (18 / 35) 
56.3% (18 / 32) 
Ethnicity  
 
 
   Non-Hispanic or Latino  
100.0% (35 / 35) 
100.0% (32 / 32) 
Race  
 
 
   White  
100.0% (35 / 35) 
100.0% (32 / 32) 
History of Hypertension  
91.4% (32 / 35) 
90.6% (29 / 32) 
History of Smoking  
 
 
No  
61.8% (21 / 34) 
58.1% (18 / 31) 
Yes - Current (within last 3 months)  
5.9% (2 / 34) 
6.5% (2 / 31) 
Yes - Former (stopped > 3 months ago)  
29.4% (10 / 34) 
32.3% (10 / 31) 
Yes - Not Specified  
2.9% (1 / 34) 
3.2% (1 / 31) 
History of Diabetes Mellitus  
77.1% (27 / 35) 
81.3% (26 / 32) 
Diet  
11.4% (4 / 35) 
12.5% (4 / 32) 
Insulin  
42.9% (15 / 35) 
46.9% (15 / 32) 
Oral Medications  
34.3% (12 / 35 
34.4% (11 / 32) 
Previous Peripheral Vascular Revascularization  
45.7% (16 / 35) 
43.8% (14 / 32) 
BMI (mean ± stdev)  
(minimum, median, maximum)  
28.2 ± 4.2 (34)     
(22, 27.6, 39) 
28.3 ± 4.2 (31)      
(22, 27.6, 39) 
 
Baseline clinical assessments of the target limb are summarized below in Table 4. Clinical 
assessments were used to measure the extent of peripheral artery disease in the target limb at 
baseline (pre-treatment) and at the 30-day follow up. The majority of the subjects (88.6% safety 
sample; 87.5% performance sample) were Rutherford category 5 with the remainder being 
category 4.  
The ankle-brachial index (ABI) for the treated leg for the safety and performance samples were 
0.95 ± 0.42 and 0.91 ± 0.41, respectively. In the safety sample, 48.6% of subjects report no leg 
pain, of the remaining subjects 28.6% and 28.6% reported pain at rest and pain on exercise, 
respectively.  
 
 

 
TOBA II BTK Clinical Study Protocol – Tack Endovascular System 
CA 0137 Rev C 
   
CA 0137 Rev C  
CONFIDENTIAL 
Page 22 of 76 
Table 4. TOBA-BTK Trial Baseline Clinical Assessment of Target Limb 
Parameter 
Safety Sample 
N = 35 
Performance 
Sample 
N = 32 
Target Limb  
  
  
   Left  
40.0% (14 / 35) 
34.4% (11 / 32) 
   Right  
60.0% (21 / 35) 
65.6% (21 / 32) 
Number of Patent Tibial / Peroneal Vessels in the Target Limb  
 
 
   1  
42.9% (15 / 35) 
46.9% (15 / 32) 
   2  
42.9% (15 / 35) 
37.5% (12 / 32) 
   3  
14.3% (5 / 35) 
15.6% (5 / 32) 
ABI treated leg (mean ± stdev)  
(minimum, median, maximum)  
0.95 ± 0.42 (35)  
(0.0, 0.94, 1.9) 
0.91 ± 0.41 (32)  
(0.0, 0.93, 1.9) 
TBI treated leg (mean ± stdev)  
(minimum, median, maximum)  
0.49 ± 0.30 (24)  
(0.0, 0.47, 1.1) 
0.47 ± 0.28 (23)  
(0.0, 0.46, 1.1) 
Subject Pain Symptoms for Target Limb (check all that apply)     
 
 
   No Leg Pain 
48.6% (17 / 35) 
46.9% (15 / 32) 
   Rest pain  
28.6% (10 / 35) 
28.1% (9 / 32) 
   Pain on exercise  
28.6% (10 / 35) 
31.3% (10 / 32) 
Rutherford Clinical Category for Target Limb  
 
 
   4  
11.4% (4 / 35) 
12.5% (4 / 32) 
   5  
88.6% (31 / 35) 
87.5% (28 / 32) 
 
The mean pre-PTA percent diameter stenosis per lesion was 72.3%± 17.4 and 73.0%± 17.8, for 
the safety and performance samples, respectively.  Total occlusion comprised eight of the lesions 
(22.2% safety sample, 24.2% performance sample).  Of all dissections reported (Safety Sample), 
the most frequently reported worst dissection grade was B (40.5%) followed by A (35.7%), C 
(19.0%), and D (4.8%). The worst post-PTA dissection grades pre-Tack at Tack sites were A 
(21.2%), B (60.6%), and C (18.2%).  The mean number of Tack implant(s) used in the 
Performance Sample was 2.8±2.0 with a range of 1 to 12 per lesion. Tack implant(s) were 
successfully delivered in 33/36 (91.7%) lesions.  Three individual lesions in three subjects were 
not successfully treated as in each case, the catheter was not able to be advanced to the lesion 
location. Of the successfully placed Tack implant(s), the post-Tack implant dissection grade was 
0 in 32/33 (97.0%) and B in 1/33 (3.0%).  Tack implant locations to treat the dissections included 
anterior tibial artery (32.6%), tibio-peroneal trunk (30.4%), peroneal artery (20.7%), and 
posterior tibial artery (16.3%).  In greater than 89.7% of the Performance Sample vessels, the 
Tack was placed on the proximal edge of the dissection being treated and in 76.9% of the vessels 
the Tack was placed on the distal edge of the dissection.   
Device success, which was defined as the ability to successfully deliver and deploy the Tack 
implant(s) to the intended target sites was successfully achieved in 32/35 (91.4%; 95% CI 77.6, 
97.0) subjects.  In all three subjects where device success was not achieved, the physician was 
unable to advance the device to the desired position due to tortuous vessel anatomy and/or 
torque transmission in the delivery catheter.  Procedure Success was defined as demonstrated 

 
TOBA II BTK Clinical Study Protocol – Tack Endovascular System 
CA 0137 Rev C 
   
CA 0137 Rev C  
CONFIDENTIAL 
Page 23 of 76 
vessel patency as reported by the physician (visual estimate) without occurrence of MALE + POD 
on the date of procedure.  Procedure success was achieved in 34/35 (97.1%; 95% CI 85.5, 99.5) 
subjects in the Safety Sample and 31/32 (96.9%; 95% CI 84.3, 99.5) in the Performance Sample. 
These data support that the Tack device performed as intended in this subject cohort.  
ABI was significantly (p<0.05) improved at all time points.  At all post-procedure time points 
there was a significant (p<0.05) in audible Doppler signal.  Specifically, at 12 months, 10/34 
lesions improved, 23/34 had no change, and 1/34 was worse. 
Table 5 below summarizes amputation-free survival, survival, freedom from amputation, 
freedom from clinically driven TVR, and freedom from clinically driven TLR for all subjects. At 12 
months, the amputation free-survival rate was 84.5% (95% CI; 66.6, 93.2) and freedom from 
clinically driven TVR and TLR was 93.5% (95% CI; 76.6, 98.3).  
Table 5. Summary for Amputation-Free Survival, Survival and Freedom from Amputation, 
Clinically Driven Target Vessel Revascularization and Clinically Driven Target Lesion 
Revascularization in All Enrolled Patients 
Parameter 
30 Days 
3 Month 
6 Month 
12 Month 
Amputation-free survival, composite 
of death/amputation 
100% 
93.8% 
93.8% 
84.5% 
Survival 
100% 
97% 
97% 
97% 
Freedom from amputation of the limb 
(above the ankle) 
100% 
96.8% 
96.8% 
87.1% 
Freedom from clinically driven target 
vessel revascularization (TVR) 
100% 
100% 
93.5% 
93.5% 
Freedom from clinically driven target 
lesion revascularization (TLR) 
100% 
100% 
93.5% 
93.5% 
 
Primary patency was defined post-hoc as presence of a Doppler signal, freedom from clinically 
driven target lesion revascularization (CD-TLR) and major amputation (above the knee).  
Primary patency was determined per patient and per vessel.  Primary patency is lost at the first 
occurrence of CD-TLR, major amputation or lack of an audible signal observed at the 1, 3, 6 or 12 
month follow-up.    
Table 6 below summarizes the estimates for primary patency by vessel and by patient. At the 
close of the 6 and 12 month visit windows, the primary patency per patient was 80.6% and 
66.4%, respectively.  
Table 6. Comparison of Per Vessel and Per Patient Estimates for Primary Patency in TOBA-BTK 
Study at 6 and 12 months 
Time Frame in Months 
Kaplan Meier Day 
Per Vessel 
Per Patient 
6 
180 
86.5% (70.5, 94.1) 
87.1% (69.2, 95) 
210* 
81.1% (64.4, 90.5) 
80.6% (61.9, 90.8) 
12 
360 
78.4% (61.4, 88.5) 
77.4% (58.4, 88.5) 
390* 
67.2% (38.6, 84.7) 
66.4% (37.5, 84.2) 
*Close of 6 or 12 month visit window. 
Twenty-six (26) subjects experienced a total of 111 adverse events (AEs).  Overall, there were 55 
serious adverse events (SAEs).  Of these serious adverse events, one was serious and considered 
to be probably related to the device.  The device-related SAE was a high grade re-obstruction of 

 
TOBA II BTK Clinical Study Protocol – Tack Endovascular System 
CA 0137 Rev C 
   
CA 0137 Rev C  
CONFIDENTIAL 
Page 24 of 76 
the target lesion 107 days post-procedure requiring target lesion revascularization.  Five (5) AEs 
were serious and considered to be possibly related or related to the procedure. The procedure-
related SAEs were:   
• 
Hematoma of the right groin spreading into the abdominal wall on the day of the 
procedure that required prolonged hospitalization.  The subject recovered without 
sequelae.  
• 
Restenosis of Tack-treated segment at 115 days post-procedure that required PTA and 
prolonged hospitalization.  The subject recovered without sequelae. 
• 
Patient presented to the emergency department complaining of a 1 week history of left 
leg swelling.  The symptoms started 4 days post-procedure and the subject was admitted 
to the hospital and worked up to eliminate deep vein thrombosis, which was ruled out by 
ultrasound. The subject recovered without sequelae.  
• 
Access site complication on the day of the procedure requiring intervention. Subject had 
an unresolved right SFA stenosis requiring femoral endarterectomy and patch.  The 
subject recovered with sequelae. 
• 
Residual stenosis of right common iliac artery at 102 days post-procedure.  Residual 
stenosis was revealed on ultrasound and repeat angioplasty with an 8 mm Omnilink stent 
placed.  The subject recovered without sequelae. 
Forty-nine (49) additional events were serious, but did not have a causal relationship to the 
device or the procedure.  The most common SAEs not related to the procedure or the device were 
local infection requiring treatment (11 events; 5 subjects), minor amputation (7 events; 4 
subjects), and systemic infection (4 events; 2 subjects).  There were no reports of Unanticipated 
AEs or Unanticipated Adverse Device Effects (UADEs).  
Overall, the Tack Endovascular System demonstrated encouraging clinical results both for safety 
and efficacy.  When comparing these results to the literature-derived values for PTA alone, the 
use of the Tack device demonstrates a potential clinical benefit for patients who have post-PTA 
BTK dissections. 
 INVESTIGATIONAL DEVICE 
5.1. 
DESCRIPTION 
The Tack Endovascular System is designed to treat vascular dissections with Tack implant(s) 
following angioplasty in the mid/distal popliteal, tibial and peroneal arteries, ranging 1.5 
mm to 4.5 mm in diameter.  The 4F (1.33 mm) catheter contains 4 independent self-
expanding Tack implants made of a nickel-titanium alloy (Nitinol).  When deployed, the 
Tack implants are designed to treat acute dissections of the inner wall or lining of an artery 
by tacking the damaged tissue to the inner luminal surface through a low outward radial 
force.  
 
 
 
 
 

 
TOBA II BTK Clinical Study Protocol – Tack Endovascular System 
CA 0137 Rev C 
   
CA 0137 Rev C  
CONFIDENTIAL 
Page 25 of 76 
5.2. 
PRINCIPLES OF OPERATION 
The Tack Endovascular System consists of 4 self-expanding Nitinol implants and a 4F (1.33 
mm) Delivery Catheter (See Figure 1 below). The numbers in parentheses in the following 
section refer to those in Figure 1. 
 
Figure 1. The Tack Endovascular System (representative image) 
 
 
 

 
TOBA II BTK Clinical Study Protocol – Tack Endovascular System 
CA 0137 Rev C 
   
CA 0137 Rev C  
CONFIDENTIAL 
Page 26 of 76 
The Tack implants are approximately 6mm in length and expand to an unconstrained 
diameter of 5.7 mm (See Table 7 below). The Tack implants are designed with a relatively 
flat chronic outward force curve and may be used across all reference vessel diameters 
(RVDs) ranging from 1.5 to 4.5mm. Four RO Markers (16) as well as four pairs of Anchors 
(17) are located around the centerline of each Tack implant. The anchors assist in 
maintaining proper Tack implant position.  
 
Table 7. Tack Implant Length at Various Diameters 
Diameter 
Length 
1.1 mm (Constrained implant) 
6.50 
1.5 mm (Deployed implant) 
6.48 
4.5 mm (Deployed implant) 
6.24 
5.7 mm (Unconstrained implant) 
5.90 
 
The delivery catheter has an effective length of 90cm and 150cm.  The 4F Outer Braided 
Sheath (7), which constrains the Tack implants, is bonded proximally to the Bifurcation 
Luer (9) within the Strain Relief (8). The Hemostatic Valve (11) is integrated proximally to 
the Bifurcation Luer. The Inner Core Shaft (3) slides within the Hemostatic Valve and has 
five Proximal Inner Core Markers (13). The number of visible reference marks corresponds 
to the number of undeployed Tack implants remaining in the distal end of the delivery 
system.  A soft, tapered Distal Tip (2) is bonded to the distal end of the Inner Core Shaft for 
ease of advancement in the blood vessel. Constrained within the Outer Braided Sheath, each 
self-expanding Tack implant is positioned on the Inner Core Shaft (3) between two 
radiopaque Distal Inner Core Markers (4) spaced approximately 7mm apart. A 1mm 
radiopaque Target Band (6) is located on the distal end of the Outer Braided Sheath.  
The catheter is flushed prior to the procedure through the side port of the Bifurcation Luer 
and the Guidewire Port. Tack implant positioning is achieved prior to deployment by using 
as reference the Middle RO Markers on the Tack implant and the Target Band on the outer 
sheath.  During Tack implant deployment; the Hemostatic Valve is unlocked by rotating the 
valve counter-clockwise.  The Tack implants are individually unsheathed by pinning the 
Proximal Inner Core Shaft and pulling back on the outer sheath the distance between 
proximal inner core markers.  After each deployment, the Hemostatic Valve is locked by 
rotating the valve clockwise, ensuring that the proximal edge of the Target Band is secured 
directly over a Distal Inner Core Marker. Between deployments, both the proximal inner 
core markers and the distal inner core markers serve to visually represent the number of 
remaining Tack implants in the delivery catheter. 
 
5.3. 
INTENDED USE 
The Tack Endovascular System is intended for use in the Mid/Distal Popliteal, Tibial, and 
Peroneal Arteries ranging in diameter from 1.5 mm to 4.5 mm for the treatment of post 
percutaneous transluminal balloon angioplasty (PTA) dissection(s) requiring repair. 
 
 

 
TOBA II BTK Clinical Study Protocol – Tack Endovascular System 
CA 0137 Rev C 
   
CA 0137 Rev C  
CONFIDENTIAL 
Page 27 of 76 
 CLINICAL STUDY OBJECTIVES 
6.1. 
PRIMARY ENDPOINTS 
Safety: Freedom from major adverse limb events (MALE) plus perioperative death (POD) at 
30 days defined as a composite of all-cause death, above-ankle target limb amputation, or 
major re-intervention to the target lesion(s) (defined as new bypass graft, 
jump/interposition graft revision, or thrombectomy / thrombolysis). 
Efficacy: Freedom from MALE at 6 months + POD at 30 days. 
6.2. 
SECONDARY ENDPOINTS 
 
Target lesion(s) tacked segment(s) patency at 6 months defined as the presence of 
blood flow using duplex ultrasound. If angiography is available within the 6-month 
follow-up visit window, it should be used in place of the duplex ultrasound. Evidence of 
no blood flow within the Tacked segment indicates restenosis/loss of patency. 
 
Target Limb Salvage defined as freedom from any above-ankle target limb amputation 
at 6 months. 
6.3. 
OBSERVATIONAL ENDPOINTS  
 
Device Success: Successful deployment of the Tack implant(s) at the intended target site(s) 
and successful withdrawal of the delivery catheter from the introducer sheath. 
 
Target Lesion Success: Demonstrated target lesion patency [<30% residual diameter stenosis 
(DS), by visual estimate] without the use of a bailout stent within the target lesion upon 
completion of the index procedure. This will be assessed for all lesions treated with a Tack 
implant. In addition, target lesion success will also be analyzed by lack of bailout stent to 
tacked segment only. Multiple target lesions treated as one lesion with PTA will be analyzed 
as one lesion. 
 
Procedural Success: Demonstrated target lesion patency (<30% residual DS, by visual 
estimate) without the use of a bailout stent within the target lesion and without the 
occurrence of MALE+POD upon completion of the index procedure 
 
Amputation-free survival (AFS): Freedom from above-ankle target limb amputation or all-
cause death at 6 and 12 months 
 
Freedom from MALE at 12 months + POD at 30 days 
 
Target lesion(s) tacked segment(s) patency at 12 months defined as the presence of blood 
flow using duplex ultrasound. 
 
Target Limb Salvage defined as freedom from any above-ankle target limb amputation at 12 
months 
 
Assisted primary target lesion Tacked segment patency (flow vs. no flow) at 6 and 12 months 
 
Secondary target lesion Tacked segment patency (flow vs. no flow) at 6 and 12 months 
 
PSVR patency at 6 and 12 months [Freedom from binary restenosis defined as Peak Systolic 
Velocity Ratio (PSVR) of ≥ 2.5 and/or angiographic percent diameter stenosis of ≥50%] 
assessed for the following: 
o Target Lesion(s), defined as the entire contiguous arterial segment treated with 
angioplasty, inclusive of an additional proximal and distal margin of 5 mm 

 
TOBA II BTK Clinical Study Protocol – Tack Endovascular System 
CA 0137 Rev C 
   
CA 0137 Rev C  
CONFIDENTIAL 
Page 28 of 76 
o Tacked Segment(s), defined as the Tack device and 5 mm of artery proximal and distal 
to each Tack. If Tacks are within 10 mm of each other, they will be considered as a 
single tacked segment for the purposes of this patency assessment. 
 
Clinically-driven target lesion revascularization (CD-TLR) through 12 months 
 
Clinically-driven target vessel revascularization (CD-TVR) through 12 months 
 
All-cause death through 12 months 
 
Any Target vessel revascularization (TVR) through 12 months 
 
Any Target lesion revascularization (TLR) through 12 months 
In addition, the following observational endpoints will be assessed at various time points through 
36 months (See Time and Events Schedule Section 8.1): 
 
Changes in Wound, Ischemia, and foot Infection (WIfI)31 Classification 
 
Changes in ankle brachial index (ABI) and toe brachial index (TBI) 
 
Changes in Rutherford Classification 
 
Changes in the EQ-5D-3L quality of life questionnaire 
 
Changes in the Walking Impairment Questionnaire (WIQ) 
 
Tack implant Integrity via X-ray (only performed at 12-month visit) 
 
Progress of wound(s) present at study entry (healed, improved, unchanged, worsening, 
amputated) 
 
Appearance of new wound(s) after study entry 
 
Unplanned below-ankle target limb amputation(s): digit or transmetatarsal 
 CLINICAL STUDY DESIGN 
This is a prospective, multi-center, single-arm, non-blinded study designed to investigate the safety 
and efficacy of the Tack Endovascular System as compared to a pre-defined performance goal (PG) 
established from published, peer reviewed scientific literature. 
7.1. 
ANTICIPATED NUMBER OF SUBJECTS AND INVESTIGATIONAL SITES 
It is anticipated that up to 232 subjects will be enrolled at up to 60 US and International clinical 
sites. No single clinical site can enroll more than 46 patients, establishing an enrollment cap at 
20% of the subject sample size.  
7.2. 
SUBJECT POPULATION 
Subjects with PAD who receive PTA in the Mid/Distal Popliteal, Tibial, and Peroneal Arteries 
and have a resulting dissection(s) that an operator would attempt to treat by means such as 
additional angioplasty with extended inflation time or stenting, are eligible for enrollment. To 
be enrolled, subjects must meet all general and angiographic inclusion criteria and not meet 
any of the general or angiographic exclusion criteria. 
 
31 Joseph L. Mills, Sr, MD, Michael S. Conte, MD, David G. Armstrong, DPM, MD, PhD, Frank B. Pomposelli, MD, Andres Schanzer, MD, 
Anton N. Sidawy, MD, MPH, and George Andros, MD, on behalf of the Society for Vascular Surgery Lower Extremity Guidelines Committee, 
The Society for Vascular Surgery Lower Extremity Threatened Limb Classification System: Risk stratification based on Wound, Ischemia, 
and foot Infection (WIfI). J Vasc Surg. 2014; Volume 59, Issue 1, Pages 220–234.e2 

 
TOBA II BTK Clinical Study Protocol – Tack Endovascular System 
CA 0137 Rev C 
   
CA 0137 Rev C  
CONFIDENTIAL 
Page 29 of 76 
7.3. 
CLINICAL STUDY DURATION & FOLLOW-UP 
The follow-up duration for each enrolled subject is 36 months. Any subject who is enrolled but 
does not receive at least one Tack implant will be followed for 30 days and then exited from the 
study (see Section 13.3.1). 
7.4. 
SUBJECT SELECTION 
7.4.1. 
INCLUSION CRITERIA 
Subjects must meet all the following Inclusion Criteria. The response for each criterion 
below must be “Yes”:  
1. Males or non-pregnant females ≥ 18 years of age at the time of consent  
2. Female subjects of childbearing potential must have a negative pregnancy test prior to 
treatment and must use some form of contraception (abstinence is acceptable) through 
the duration of the study 
3. Subject has been informed of and understands the nature of the study and provides 
signed informed consent to participate in the study. If the subject possesses the ability to 
understand and provide informed consent but due to physical inability, the subject 
cannot sign the informed consent form (ICF), an impartial witness may sign on behalf of 
the subject 
4. Willing to comply with all required follow-up visits 
5. Rutherford Classification 4 or 5  
6. WIfI Wound grade of 0, 1 or modified 2 
7. WIfI Foot Infection grade of 0 or 1  
8. Estimated life expectancy ≥1 year 
7.4.2. 
ANGIOGRAPHIC INCLUSION CRITERIA 
Subjects must meet all the following Angiographic Inclusion Criteria. The response for each 
criterion below must be “Yes”:  
1. Reference vessel diameter is between 1.5 mm and 4.5 mm, inclusive (by visual estimate)  
2. Only one limb requires treatment during the Index Procedure 
Note: If the subject has bilateral BTK disease, the Investigator should choose the limb 
that most closely meets eligibility criteria. If the chosen limb does not meet final 
eligibility after PTA treatment, the subject should not be enrolled at that time. This 
subject may be brought back for potential study device treatment to the contralateral 
limb per the protocol requirements. Only one limb may receive study device 
treatment. 
3. Ability to cross study device(s) antegrade through target lesion  
4. Has de novo or restenotic target lesion(s) with pre-PTA stenosis of ≥70% or is occluded 
(by visual estimate) and is indicated for PTA treatment with a standard balloon catheter 
Note: Diseased segments with >30 mm of healthy vessel between them are 
considered separate target lesions  

 
TOBA II BTK Clinical Study Protocol – Tack Endovascular System 
CA 0137 Rev C 
   
CA 0137 Rev C  
CONFIDENTIAL 
Page 30 of 76 
Note: If any part of the lesion is restenotic, no part of the lesion should have more 
than 1 prior failure (by plain balloon angioplasty only), which must have occurred 
greater than 1 year (360 days) prior to the index procedure 
Note: After PTA treatment, the target lesion is defined as the entire contiguous 
arterial segment length treated with angioplasty 
5. Target lesion(s) located in the mid popliteal (P2), distal popliteal (P3), tibioperoneal 
trunk, peroneal, anterior tibial, or posterior tibial arteries  
Note: The mid popliteal artery (P2) begins at the superior aspect of the patella. The 
most distal location of the tibial and/or peroneal artery(ies) ends at the beginning of 
the dorsalis pedis artery (DP). Tacks may not be implanted within 1 cm above the 
radiographic tibiotalar joint.  
6. Target vessel(s) reconstitute(s) at or above the ankle or displays normal terminal 
branching 
 
If the target vessel is the peroneal artery, the artery must display normal 
terminal branching.  
 
If the target vessel is the anterior tibial (AT) artery or the posterior tibial (PT) 
artery, the artery(ies) must display reconstitution at least 1 cm proximal to the 
radiographic tibiotalar joint line, and continue into an intact runoff vessel (AT/ 
dorsalis pedis or PT/plantar artery). 
 
If the target vessel is the P2 and/or P3, any 1 of the 3 distal arteries must show 
respective outflow.  
 
If the target vessel is the TPT, then respective outflow for either the peroneal 
artery or posterior tibial artery must be confirmed. 
Note: Normal terminal branching and/or reconstitution of run-off vessels as 
described above should be confirmed prior to PTA treatment of the target lesion(s) 
as well as after PTA treatment to the target lesion(s) (prior to Tack deployment) 
7. Patent (<50% DS by visual estimate) arterial inflow from aortic bifurcation to the distal 
edge of the proximal popliteal artery (P1) at the superior end of the patella.  
Note: Treatment of inflow artery lesions within the iliac (ipsilateral or 
contralateral), common femoral, superficial femoral, and/or the proximal popliteal 
(P1) artery(ies) is allowed during the index procedure but must have documented 
success (<30% residual DS and no major vascular complications) prior to target 
lesion treatment.  
Note: If an inflow lesion requires treatment with atherectomy or requires surgical 
intervention, the patient should not be enrolled 
8. After PTA treatment, the target lesion has <30% residual DS and presence of at least one 
post-PTA dissection (by visual estimate) that the Investigator would otherwise treat by 
means such as but not limited to additional angioplasty, with longer inflation time or 
stenting 
9. No evidence of aneurysm or acute thrombus in target vessel 

 
TOBA II BTK Clinical Study Protocol – Tack Endovascular System 
CA 0137 Rev C 
   
CA 0137 Rev C  
CONFIDENTIAL 
Page 31 of 76 
7.4.3. 
EXCLUSION CRITERIA 
Subjects must not meet any of the following Exclusion Criteria. The response for each 
criterion below must be “No”:  
1. Is pregnant or refuses to use contraception through the duration of the study 
2. Previous bypass graft in the target limb 
3. Acute limb ischemia, defined as symptom onset occurring less than 14 days prior to the 
index procedure 
4. Prior or planned above-ankle amputation or complete transmetatarsal amputation to 
the target limb (this does not apply to ray amputation of ≤2 digits, simple digital 
amputations or ulcer debridements) 
5. WIfI Foot Infection grade 2 or 3.  
6. Any systemic infection or immunocompromised state. Patients with an ascending 
infection/deep foot infection or abscess/white blood count (WBC)≥12,000/or febrile 
state  
7. Endovascular or surgical procedure (not including diagnostic procedures, planned 
simple digital amputation or wound debridement) to the target limb less than 30 days 
prior to or planned for less than 30 days after the index procedure 
8. Existing stent implant in the target vessel 
9. Any other endovascular or surgical procedure (not including diagnostic procedures, 
planned simple digital amputation or wound debridement) less than 14 days prior to 
the index procedure or planned procedure less than 30 days after the index procedure  
10. Known coagulopathy, hypercoagulable state, bleeding diathesis, other blood disorder, 
or a platelet count less than 80,000/microliter or greater than 500,000/microliter  
11. WIfI Wound grade of 2 or 3.  
12. Any subject in which antiplatelet, anticoagulant, or thrombolytic therapy is 
contraindicated 
13. Myocardial infarction, coronary thrombolysis or angina less than 30 days prior to the 
Index Procedure 
14. History of stroke or transient ischemic attack (TIA) less than 90 days prior to the Index 
Procedure 
15. Currently on dialysis 
16. Known hypersensitivity or contraindication to nickel-titanium alloy (Nitinol) 
17. Participating in another ongoing investigational clinical trial in which the subject has not 
completed the primary endpoint(s), as well as subjects who are already enrolled into this 
study, as only one limb may be treated with the 4F study device. 
18. Has other comorbidities that, in the opinion of the investigator, would preclude them 
from receiving this treatment and/or participating in study-required follow-up 
assessments 
19. Known hypersensitivity or allergy to contrast agents that cannot be medically managed 

 
TOBA II BTK Clinical Study Protocol – Tack Endovascular System 
CA 0137 Rev C 
   
CA 0137 Rev C  
CONFIDENTIAL 
Page 32 of 76 
20. Subject already enrolled into this study 
21. Restenotic target lesion previously treated by means other than plain balloon angioplasty 
and/or less than 1 year prior to index procedure. 
7.4.4. 
ANGIOGRAPHIC EXCLUSION CRITERIA 
Subjects must not meet any of the following Angiographic Exclusion Criteria. The response 
for each criterion below must be “No”:  
1. Acute vessel occlusion or acute or sub-acute thrombosis in target lesion 
2. Subject has significant stenosis (≥50% DS) or occlusion of inflow arteries (including the 
iliac, superficial femoral and proximal popliteal arteries) not successfully treated (<30% 
residual DS and without major complication) prior to PTA of target lesion 
3. The target lesion shows no dissections after PTA or dissections of a lessor grade for 
which the operator would normally not pursue additional treatment 
4. If parallel non-target vessel (anterior tibial, peroneal, or posterior tibial) is treated 
during index procedure and is not successful (<30% residual DS and without major 
complication) prior to PTA of target lesion/vessel  
5. Below the ankle lesion requiring treatment  
6. Use of atherectomy, cryoplasty, cutting/scoring/contoured balloon angioplasty, stenting 
or any other treatment (with the exception of a crossing device) of the target 
lesion/vessel other than plain balloon angioplasty PTA during the index procedure 
Note: Use of atherectomy in a parallel, non-target vessel is allowed during the index 
procedure but must have documented success (<30% residual DS and no major 
vascular complications) prior to target lesion/vessel treatment 
 
 

 
TOBA II BTK Clinical Study Protocol – Tack Endovascular System 
CA 0137 Rev C 
   
CA 0137 Rev C  
CONFIDENTIAL 
Page 33 of 76 
 TREATMENT PLAN 
8.1. 
TIME AND EVENTS SCHEDULE 
All subjects will receive the assessments at specific time points as listed in Table 8 below. 
Table 8. Time and Events Schedule 
Assessment12 
Baseline1 
Index Procedure 
Pre-Discharge 
30-day 
(-2 days/+14 
Days) 
6 
Month 
(±30 Days) 
12 
Month 
(± 30 Days) 
24 
Month 
(± 30 Days) 
36 
Month 
(± 30 Days) 
Unscheduled7 
Informed Consent 
X2 
 
 
 
 
 
 
 
 
Medical History / Brief Physical  
X 
 
 
 
 
 
 
 
 
White Blood Count / Platelet 
Count 
X 
 
 
 
 
 
 
 
 
Prothrombin Time (PT) / 
International Normalized Ratio 
(INR)3 
X 
 
 
 
 
 
 
 
 
Urine pregnancy test if female4 
X 
 
 
 
 
 
 
 
 
Ankle Brachial Index (ABI)/ Toe 
Brachial Index (TBI)10 
X 
 
 
X 
X 
X 
X 
X 
X 
TcPO210 
X 
 
 
X 
X 
X 
X 
X 
X 
Rutherford Classification 
X 
 
 
X 
X 
X 
X 
X 
X 
WIfI Classification 
X 
 
 
X 
X 
X 
X 
X 
X 
Wound Assessment9 
X 
 
 
X 
X 
X 
X 
X 
X 
Pre-procedural Medications 
 
X 
 
 
 
 
 
 
 
Angiogram 
 
X 
 
 
 
 
 
 
X8 
Study Medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Duplex Ultrasound (DUS)5 
 
 
 
X 
X 
X 
 
 
X8 
X-ray of Implanted Tacks6 
 
 
 
 
 
X 
 
 
X8 
Adverse Event (AE) Assessment11 
 
X 
X 
X 
X 
X 
X 
X 
X 
EQ-5D-3L 
X 
 
 
X 
X 
X 
X 
X 
X 
Walking Impairment 
Questionnaire (WIQ) 
X 
 
 
X 
X 
X 
X 
X 
X 
1 Assessments may be done up to 30 days prior to the index procedure, with the exception of a pregnancy test  
2 Consent may be obtained up to 30 days prior to index procedure. 
3 PT/INR to be obtained only if subject is on chronic warfarin therapy. 
4 Negative urine pregnancy test within 7 days of the Index Procedure is required for women of childbearing potential. 
5 All scheduled DUS exams should be performed per the protocol established by the core lab. If a DUS is non-diagnostic 
(per the imaging protocol), the site should make every effort to obtain a repeat exam within the visit window.  
6 X-ray assessment of Tack Integrity is only required for subjects in whom at least one Tack was placed during the index 
procedure. All required and unscheduled X-ray exams should be performed in accordance with the core lab protocol. 
7 Unscheduled data should be captured prior to any intervention to target limb; Rutherford classification and wound 
assessment should be documented prior to re-intervention to the target limb.  
8 If clinically indicated. All imaging of the target limb acquired during scheduled visits or a target limb intervention (such 
as Angiogram, DUS or X-Ray) should be submitted to the respective core lab within 3 days of occurrence. 
9 Wound assessment is required and all efforts should be made to acquire photographs of the wound to support the 
assessment for healed, improved, unchanged, worsening, amputated or new (if applicable).  
10 Both ABI and TBI are required at baseline and throughout follow-up. If during baseline, an ABI or TBI is not attainable, 
due to non-compressible arteries or prior digital amputation, this shall be noted on the electronic case report form 

 
TOBA II BTK Clinical Study Protocol – Tack Endovascular System 
CA 0137 Rev C 
   
CA 0137 Rev C  
CONFIDENTIAL 
Page 34 of 76 
(eCRF). If ABI, ankle pressure or toe pressure cannot be acquired, TcPO2 may be recorded, if possible, to confirm a WIfI 
Ischemia Grade.  
11 Only the following types of adverse events (AEs) shall be recorded in the eCRF: Serious adverse events (SAEs), or any 
AE that is classified as ‘possibly’ or’ definitely’ related to the study device and/or study device procedure by the 
investigator. Assessments of MALE+POD will also be part of the AE assessment. 
12 Follow-up assessments (required at the 30-day visit and beyond) that cannot be performed due to a subject’s medical 
condition (i.e., amputation) will not be considered a deviation if it is fully documented in source records.  
 
 REQUIRED TESTS AND ASSESSMENTS 
The required tests and assessments described in this section are required at baseline and/or at 
various follow-up visits according the Time and Event Schedule in Section 8.1. 
9.1. 
LABORATORY TESTING 
Laboratory blood samples must be drawn pre-procedure but may not exceed 30 days 
prior to the index procedure.  
Laboratory samples include:  
 
WBC 
 
Platelet count 
 
PT/INR (only if subject is on chronic warfarin) 
 
Pregnancy test (if female of childbearing potential) within 7 days of index 
procedure  
9.2. 
ANGIOGRAPHIC ASSESSMENT & IMAGING 
The index baseline angiogram is performed during the index procedure. If the subject is 
enrolled, all imaging and accompanying worksheets shall be submitted to the 
angiographic core laboratory for analysis within 3 days. The imaging for the baseline 
angiogram must follow the most current requirements set forth by the core laboratory. 
Failure to acquire/provide all required index procedural sequences and images will 
result in a protocol deviation. In addition, any subsequent angiographic assessments 
performed on the target limb (due to recurrent or worsening symptoms) shall also be 
provided to the respective core laboratory for analysis per the instructions established 
by the core laboratory. 
9.3. 
ANKLE AND TOE BRACHIAL INDICES (ABI AND TBI) 
Target limb resting ABI and TBI should be performed per hospital standard of care and 
consistently among all enrolled subjects through completion of the study.  Both target 
limb resting ABI and TBI are required at baseline and follow-up.  ABI and TBI values, 
including respective individual systolic pressure values must be documented in source 
and recorded on the appropriate electronic case report forms (eCRFs).  
To confirm the WIfI Ischemia grade, Transcutaneous oxygen (TcPO2) may be assessed 
and recorded only if reliable ABI, ankle pressure, or toe pressure are not attainable.  
However, if TcPO2 cannot be conducted, it will not be considered a protocol deviation. 
 

 
TOBA II BTK Clinical Study Protocol – Tack Endovascular System 
CA 0137 Rev C 
   
CA 0137 Rev C  
CONFIDENTIAL 
Page 35 of 76 
9.4. 
DUPLEX ULTRASOUND (DUS) ASSESSMENT 
Lower extremity arterial duplex ultrasound (DUS) assessments will be used to 
determine arterial stenosis as well as Tacked segment patency (Flow/No Flow). The 
peak systolic blood flow velocity within the Tacks as well as the target lesion will be 
taken to determine the PSVR.  
The DUS exam should be performed per the Time and Events Schedule in Section 8.1. 
DUS exams performed outside of window or not at all will result in a protocol deviation. 
Duplex ultrasonography and/or angiography should be performed prior to any 
endovascular intervention during the follow-up period to assess the treated lesion 
patency. Operators should have experience with DUS and follow the DUS core 
laboratory acquisition guidelines and specific methods for measuring the blood flow 
velocities. All scheduled DUS assessments shall be submitted to the respective DUS core 
laboratory for analysis, in addition to any DUS performed prior to or after any events 
meeting MALE criteria.  
A comprehensive overview for DUS acquisition requirements can be found in the core 
laboratory manual.  
9.5. 
QUESTIONNAIRES 
Both the WIQ and the EQ-5D-3L will be used to assess changes in the patient’s quality of 
life throughout the duration of this clinical study. 
9.6. 
RUTHERFORD CLASSIFICATION 
Rutherford Classification should be assessed for the target limb and consistently among 
all patients throughout the duration of this clinical study. 
See Section 24 for a description of Rutherford Classifications. 
9.7. 
WIFI CLASSIFICATION 
The WIfI Classification is a grading system created by the Society of Vascular Surgery 
(SVS). This system focuses on the three main factors that impact amputation risk and 
clinical management: Wound, Ischemia, and foot Infection (WIfI). Each of the three 
factors are graded on a scale from 0 to 3. The 0 represents none, 1-mild, 2-moderate and 
3-severe.32  
The Wound portion of the WIfI classification is required for all subjects. For inclusion 
into the study, the subject must have a Wound Grade 0, 1, or “modified 2”. For the 
purpose of this study only, an additional Wound grade of modified 2 has been added to 
the SVS Wound table in Section 23. The Wound grade “modified 2” permits a deeper 
ulcer without exposed bone, joint or tendon; or shallow or superficial heel ulcer, 
without deep tissue involvement or exposed calcaneus. It also permits gangrenous 
changes limited to digits. In addition, for the purpose of this study, subjects without 
 
32 Joseph L. Mills, Sr, MD, Michael S. Conte, MD, David G. Armstrong, DPM, MD, PhD, Frank B. Pomposelli, MD, Andres Schanzer, MD, 
Anton N. Sidawy, MD, MPH, and George Andros, MD, on behalf of the Society for Vascular Surgery Lower Extremity Guidelines Committee, 
The Society for Vascular Surgery Lower Extremity Threatened Limb Classification System: Risk stratification based on Wound, Ischemia, 
and foot Infection (WIfI). J Vasc Surg. 2014; Volume 59, Issue 1, Pages 220–234.e2 

 
TOBA II BTK Clinical Study Protocol – Tack Endovascular System 
CA 0137 Rev C 
   
CA 0137 Rev C  
CONFIDENTIAL 
Page 36 of 76 
presence of wound and gangrene should be given a WIfI Wound grade of 0, regardless of 
their WIfI Ischemia grade.  
The Ischemia portion of the WIfI classification is required for all subjects and uses 
hemodynamic/perfusion criteria (ABI, Ankle Pressure, Toe Pressure or TcPO2) to 
determine its grade. Subjects are eligible for inclusion regardless of their WIfI Ischemia 
Grade. The Ischemia Grade should reflect the value obtained using the following 
hierarchy: Toe Pressure (or TcPO2) being the first, then the highest Ankle Pressure (if 
TP or TcPO2 is not attained), then ABI (if ankle pressure is not documented).  Therefore, 
it is crucial to follow requirements for these assessments per Table 8. Time and Events 
Schedule Section 8.1. 
The Infection portion of the WIfI classification is required for all subjects and is 
determined by clinical observations of infection. Subjects must have an Infection Grade 
of 0 or 1 to be eligible for enrollment.  
See Section 23 for WIfI classification tables. 
9.8. 
WOUND ASSESSMENT 
An assessment of existing and/or new wound(s) is to be performed per Table 8. Time 
and Events Schedule Section 8.1. Wounds should be classified as: Healed, Improved, 
Unchanged, Worsening, Amputated or New (If applicable). If, at the time of any follow-
up visit, a patients wound is dressed and per PI discretion the dressing should not be 
removed, this should be documented and will not be considered a deviation. 
All assessments shall be accompanied by a photograph of the wound(s) that includes a 
ruler. These photographs shall be part of the subject’s study file.  
9.9. 
X-RAY ASSESSMENT 
An X-Ray assessment will be performed at the 12-month follow-up visit to assess Tack 
implant integrity for all subjects in whom at least one Tack implant was placed during 
the index procedure. If an X-ray is performed prior to the 12-month visit and is within 
the 12-month visit window and all Tacks are imaged, this may be used in lieu of the X-
ray required at the 12-month visit.   
A comprehensive overview of procedural requirements for X-Ray assessments can be 
found in the core laboratory manual. 
 
SCREENING PROCEDURES 
All subjects presenting to the institution with PAD and/or known popliteal (P2 and P3) and/or 
below-the-knee artery disease requiring balloon angioplasty will be screened for initial 
eligibility. A trained member of the research team shall perform a preliminary evaluation of 
the potential subject’s medical history and screen for initial eligibility.  Only assessments 
consistent with the institutions standard of care may be performed prior to obtaining a signed 
consent form. If during the pre-screening the subject is found to meet one or more exclusion 
criteria, the subject would be considered a “pre-screen failure”. No further action shall be 
taken for pre-screen failure subjects. If determined eligible per initial inclusion criteria, the 
subject will be approached by qualified and trained research staff and informed about this 
study through the informed consent process.   

 
TOBA II BTK Clinical Study Protocol – Tack Endovascular System 
CA 0137 Rev C 
   
CA 0137 Rev C  
CONFIDENTIAL 
Page 37 of 76 
10.1. OBTAINING INFORMED CONSENT 
All sites shall comply with 21 CFR 50, provisions of ICH E6 Good Clinical Practices (GCPs), local 
institutional review board (IRB)/ethics committee (EC) policy and all applicable local 
regulations for obtaining Informed Consent. Written informed consent using the most current 
IRB/EC-approved ICF at the time of consent will be obtained for all subjects prior to any 
study-specific screening/baseline tests or procedures are performed.  This does not include 
those procedures or tests that are obtained in the normal course of the subject’s non-study 
related care and prior to undergoing the study procedure, but shall include previously 
performed tests that may need to be repeated to determine eligibility.   
All subjects shall possess the ability to understand the information contained in the informed 
consent form. Subjects will have the study procedures explained in a manner as non-technical 
as possible, including the risks, benefits and follow-up requirements. If the subject agrees to 
participate in this study, the subject will personally sign and date the ICF. If a subject possesses 
the ability to understand the informed consent process and participation in study, but due to 
physical inability cannot sign the ICF, an impartial witness may sign the ICF on behalf of the 
subject. Non-English speaking subjects may only be enrolled if they sign an IRB/EC approved 
and certified translated informed consent form document reflective of his/her spoken 
language. 
Once all required parties have signed the ICF, subjects will receive copies of their signed 
informed consent documentation. 
10.2. SCREENING SUCCESS AND FAILURE CRITERIA 
Final eligibility of a subject will occur during the Index Procedure. Subjects must provide prior 
informed consent no greater than 30 days prior to the index procedure.  Every effort will be 
made to ensure eligibility of the participants prior to enrollment. If no angiographic exclusion 
criteria are met after pre-enrollment angioplasty, subjects will be considered eligible for 
enrollment. If at any point prior to or just after pre-enrollment angioplasty, an angiographic 
exclusion criterion is met, subjects will not be considered eligible for enrollment and will be 
documented as “angiographic screen failures”. No further follow-up will be required for these 
subjects, however; reason for angiographic failure shall be documented by the site into a 
screening log. Both limbs may be considered for enrollment if all study-required timeframes 
per the inclusion/exclusion criteria are met. If 30 days have passed since the subject signed an 
informed consent form, the subject should be re-consented.  
 
BASELINE EVALUATION 
11.1. BASELINE ASSESSMENTS 
The following assessments will be performed during baseline evaluation.  These examinations 
and tests will be used both to screen for eligible subjects and provide baseline information for 
those subjects who meet study criteria. All assessments must be completed no more than 30 days 
prior to undergoing the index procedure, except for the urine pregnancy test which must be 
completed no more than 7 days prior to the index procedure with a negative result prior to 
receiving treatment. 
 
Demographic information and medical history including risk factors  

 
TOBA II BTK Clinical Study Protocol – Tack Endovascular System 
CA 0137 Rev C 
   
CA 0137 Rev C  
CONFIDENTIAL 
Page 38 of 76 
 
Brief physical examination  
o Including height and weight 
 
Target Limb Resting ABI  
 
Target Limb Resting TBI 
 
Target Limb TcPO2 (to confirm WIfI Ischemia score only if ABI, ankle pressure, or toe 
pressure cannot be attained) 
 
Rutherford Classification  
 
WIfI Classification 
 
Wound Assessment 
 
WBC, Platelet count 
 
PT & INR (if on chronic warfarin therapy) 
 
Urine pregnancy test if female of child-bearing age (within 7 days of procedure) 
 
EQ-5D-3L 
 
Walking Impairment Questionnaire (WIQ) 
 
Study medications (antiplatelet/anticoagulants)  
 
STUDY MEDICATIONS 
See Table 9 below for Study Medications. Pre-procedural, intra-procedural and post-
procedural medications will be recorded in the eCRF.  
Table 9: Recommended Study Medications 
Medication 
Pre-Procedure  
Intra-Procedure 
Post-Procedure 
Aspirin 
Loading dose if required, per 
institutional standard of care if not on 
chronic antiplatelet therapy 
N/A 
81-325 mg/QD indefinitely is 
recommended 
Thienopyridine 
Class Agent1 
Loading dose if required, per 
institutional standard of care if not on 
chronic antiplatelet therapy  
N/A 
75 mg/QD for a 
minimum of one month 
recommended2 
Heparin 
Dosage per institutional standard of 
care. 
Achieve 
anticoagulation per 
hospital / institution 
standard of care3 
N/A 
1  Recommended Thienopyridine class agents include Clopidogrel, Ticlopidine or Prasugrel. 
2  Recommended daily dose for Clopidogrel. Respective regimen should be prescribed for other thienopyridine agents per 
Investigator discretion. 
3 An Activated Clotting Time (ACT) of ≥250s is recommended. 
 
INDEX PROCEDURE 
13.1. INDEX BASELINE ANGIOGRAM 
The Index Baseline Angiogram will be performed before Pre-Enrollment Balloon Angioplasty in 
order to assess baseline angiographic eligibility for inclusion as described in Section 13.1.2 
below. The angiogram is to be performed as per guidelines established by the independent core 
laboratory. Index procedure angiograms performed for all enrolled subjects will be reviewed by 

 
TOBA II BTK Clinical Study Protocol – Tack Endovascular System 
CA 0137 Rev C 
   
CA 0137 Rev C  
CONFIDENTIAL 
Page 39 of 76 
the core lab for identification of post-PTA dissections and associated type, as outlined in the 
angiographic core lab protocol. 
All data that is required to be recorded during the Index Procedure is reflected in the index 
procedure interval eCRFs within the EDC. Required measurements and data listed in following 
sections are not exhaustive of all data that is required. Therefore, the required data should be 
reviewed in advance of the procedure to ensure it is understood and captured appropriately. 
The CRF Completion Guidelines contain instructions for data entry and should be referenced as 
necessary. 
13.1.1. PREPARATION 
Procedural techniques will be in accordance with the institutional standard of care for 
balloon angioplasty of the popliteal (P2 and P3) and below-the-knee arteries. 
All subjects should receive the appropriate antiplatelet and anticoagulant therapy per 
Table 9. Study Medications above (Section 12).  
A radiopaque ruler is placed directly on the subject’s target limb under the sterile drapes 
according to the angiographic core lab imaging protocol. In any later angiographic 
assessments, the same ruler placement should be used to identify the treatment location.  
13.1.2. BASELINE ANGIOGRAPHIC REQUIREMENTS 
Baseline angiographic measurements of the target lesion and target vessels (visual 
estimate) shall be captured to determine eligibility and include, but are not limited to the 
following: 
 
Target Lesion(s) details including Vessel location(s), Ruler location(s), Lesion 
length(s) (normal to normal), and pre-PTA %DS 
 
Lesion type(s) (De novo or restenotic) 
 
Reference Vessel Diameter(s) (proximal and distal)  
 
Inflow artery patency  
 
Normal artery branching and/or target vessel reconstitution 
 
Absence of thrombus 
13.2. PRE-ENROLLMENT BALLOON ANGIOPLASTY (TREATMENT PTA) 
All consented subjects undergoing balloon angioplasty for possible enrollment into this study 
shall receive PTA treatment with a standard balloon. 
The recommendations for balloon inflation are as follows: 
 
The operator should select a balloon diameter that can be inflated to a ratio of 1:1 
relative to the target lesion proximal RVD 
 
The length of the balloon should be appropriate for the lesion length, fully covering the 
lesion. When possible, a single balloon should be selected that extends across the entire 
lesion.  

 
TOBA II BTK Clinical Study Protocol – Tack Endovascular System 
CA 0137 Rev C 
   
CA 0137 Rev C  
CONFIDENTIAL 
Page 40 of 76 
 
Balloon Inflation: Inflate the balloon and maintain inflation at the specified 1:1 diameter 
for a minimum of 60 seconds total  
Please refer to the Instructions for Use (IFU) for detailed instructions regarding Pre-
Enrollment Balloon Angioplasty inflation recommendations.  
13.2.1. POST-ANGIOPLASTY ANGIOGRAPHIC REQUIREMENTS  
Final angiographic eligibility of subjects for study device treatment will be determined post 
pre-enrollment balloon angioplasty and include but are not limited to the following target 
lesion measurements (by visual estimate): 
 
Target lesion residual diameter stenosis <30% 
 
Presence of dissection(s)  
 
Absence of thrombus 
 
Normal artery branching and/or target vessel reconstitution 
In addition, other lesion measurements and balloon details will be recorded during Pre-
Enrollment Balloon Angioplasty and include but are not limited to the following: 
 
Total number of dissection(s) visualized 
 
Dissection characteristics (by visual estimate) for each dissection visualized 
including;  
o Dissection Type (A through F)  
o Dissection Length  
o Vessel Location 
o Ruler Location 
 
For each vessel segment inflation: 
o Balloon name/Manufacturer, Length, Diameter  
o Vessel location 
o Ruler location 
o Max Pressure (atm) (across all inflations) 
o Inflation Duration at Max Pressure (across all inflations) 
o Max Inflation Diameter (across all inflations)  
13.3. STUDY DEVICE TREATMENT 
Subjects who meet all inclusion and angiographic inclusion criteria, and do not meet any 
exclusion or angiographic exclusion criteria will be deemed eligible for Study Device Treatment. 
13.3.1. ENROLLMENT (INTENT-TO-TREAT) 
A subject is defined as an intent-to-treat (ITT) and officially enrolled in the study once the 
Tack Endovascular System is advanced through the introducer sheath.  Subjects in whom at 

 
TOBA II BTK Clinical Study Protocol – Tack Endovascular System 
CA 0137 Rev C 
   
CA 0137 Rev C  
CONFIDENTIAL 
Page 41 of 76 
least one Tack implant is not placed, will be exited after 30 days. Subjects in whom at least 
one Tack implant is placed will be followed for 36 months.  
In addition, the per-protocol (PP) population will be defined as ITT subjects with evaluable 
data that have met the definition for device success, excluding subjects with major 
deviations such as: 
 
A major inclusion/exclusion criterion deviation; or 
 
A major procedural deviation 
The criteria for deviations meeting the classification of “major” will be defined by an 
independent designee before study endpoint data is available for statistical analysis.  
13.3.2. TREATMENT RECOMMENDATIONS 
The lesion considered for Tack implant placement is assessed with a minimum of two 
angiographic views, an anterior-posterior view and a 45-degree oblique view, for optimal 
visualization of the dissections. All dissections identified for treatment with the Tack 
implant will be categorized by type by the operator as described in Section 13.2.1. If there 
are no dissections present, the subject may not be enrolled and Tack implants should not be 
placed.  
Intact Vascular recommends deployment of a Tack implant to the distal edge of the target 
dissection. If additional Tack implants are required, the operator should continue 
proximally to the next planned deployment site. A minimum gap distance of 4.0mm 
between Tack implants (end to end) is recommended. Overlapping Tack implants is not 
permitted.  
Please refer to the Instructions for Use (IFU) for detailed instructions regarding 
recommended criteria for Tack Endovascular System placement.  
13.3.3. POST-STUDY DEVICE TREATMENT MEASUREMENTS  
The following information should be recorded Post-Study Device Treatment: 
 
Number of Device Systems used to treat subject and associated lot numbers 
o Number of Tacks deployed from Device 
o Whether device was successfully withdrawn 
 
Number of Tack implants deployed 
o Ruler and vessel location of each deployed Tack implant  
o Number of Tack implants deployed to treat each dissection and whether it 
was successful in treating respective dissection identified in Section 13.2.1 
13.4. POST- TACK DILATION  
Post-dilation of all deployed Tack implants is required to seat the anchors of the Tack implant. 
Use of a new standard balloon catheter is required to reduce the risk of contact with deployed 
Tack implants while advancing the balloon catheter into place. 
 

 
TOBA II BTK Clinical Study Protocol – Tack Endovascular System 
CA 0137 Rev C 
   
CA 0137 Rev C  
CONFIDENTIAL 
Page 42 of 76 
13.4.1. RECOMMENDATIONS 
After Tack implant placement, it is recommended that post-dilation of all deployed Tack 
implants be performed using the following criteria. 
 
The balloon diameter for post-dilation should use the same balloon diameter and 
pressure used during angioplasty prior to Tack implant placement and should be the 
shortest length possible 
 
Post-Dilation Duration at Max Pressure: A minimum of 120 seconds. 
Please refer to the Instructions for Use (IFU) for detailed instructions regarding post-Tack 
implant placement balloon angioplasty recommendations. 
13.4.2. FINAL TREATMENT RESULTS  
The following information should be recorded after post-dilation and upon completion of 
index procedure and includes but is not limited to: 
 
For each vessel segment receiving post-Tack inflation: 
o Balloon name/Manufacturer, Length, Diameter  
o Vessel location 
o Ruler location 
o Max Pressure (atm) (across all inflations) 
o Inflation Duration at Max Pressure (across all inflations) 
o Max Inflation Diameter (across all inflations)  
o Final residual diameter stenosis of target lesion(s) treated with Tacks 
 
Bailout stent occurrence (post-study device treatment) 
o If applicable, bailout stent device details will be recorded 
 
Study Device Procedure time (defined as the time the first Tack Endovascular 
System is advanced through the introducer sheath to the time of withdrawal of last 
post-Tack dilation PTA balloon catheter) 
 
Adverse event occurrence 
 
Device event occurrence 
13.5. BAILOUT STENTING OF TARGET LESION (POST-STUDY DEVICE) 
The use of a bailout stent may occur in the event of persistent flow-limiting dissection not able 
to be treated with the Tack implant (or as otherwise required for safety of the subject). All 
enrolled subjects in whom at least one Tack implant is placed and receive a bailout stent to any 
deployed Tack within the target lesion will be followed for the duration of the study. Details 
around the use of a bailout stent will be captured in the eCRF including but not limited to; 
name/manufacturer, reason for stenting, length diameter, ruler and vessel location(s). 
 

 
TOBA II BTK Clinical Study Protocol – Tack Endovascular System 
CA 0137 Rev C 
   
CA 0137 Rev C  
CONFIDENTIAL 
Page 43 of 76 
 
POST-PROCEDURE/PRE-DISCHARGE  
All subjects will be assessed prior to discharge (Pre-Discharge) and shall receive a medical 
regimen for the medications required post-procedure per Table 9 “Recommended Study 
Medications” in Section 12. All concomitant medications (antiplatelet/anticoagulant) shall be 
captured in the eCRF. 
14.1. REQUIRED ASSESSMENTS  
Assessments required at pre-discharge include the following: 
 
Adverse event occurrence  
 
Study medication assessment (antiplatelet agents/anticoagulants) 
All subjects receiving treatment with a Tack implant should be provided with the Tack 
Endovascular System Patient Implant Card (PIC). The PIC is designed for the patient to carry 
along with their insurance cards. This PIC is to be completed by the designated research 
personnel to include information pertaining to the Tack device(s) including the model, lot 
number and vessel location of the implanted Tack(s) and the date of the index procedure. The 
card also provides manufacturing information and MRI Compatibility. 
 
REQUIRED FOLLOW-UP VISITS AND ASSESSMENTS 
All subjects will be required to return for clinic follow-up visits as outlined in Table 8 of Section 
8.1 and in the sections below.  
15.1. 30-DAY FOLLOW-UP VISIT (-2 DAYS / +14 DAYS POST-INDEX PROCEDURE) 
The following assessments are required to be performed at the 30-day follow-up visit: 
 
Rutherford Classification 
 
WIfI Classification 
 
Wound Assessment 
 
Target limb resting ABI  
 
Target limb resting TBI 
 
Target Limb TcPO2 (if ABI, ankle pressure or toe pressure cannot be acquired) 
 
Duplex ultrasound (DUS) 
 
EQ-5D-3L 
 
Walking Impairment Questionnaire (WIQ) 
 
Adverse event occurrence  
 
Review of study medications (antiplatelets/anticoagulants) 
15.2. 6-MONTH FOLLOW-UP VISIT (±30 DAYS POST-INDEX PROCEDURE) 
The following assessments are required to be performed at the 6-month follow-up visit: 
 
Rutherford Classification 
 
WIfI Classification 

 
TOBA II BTK Clinical Study Protocol – Tack Endovascular System 
CA 0137 Rev C 
   
CA 0137 Rev C  
CONFIDENTIAL 
Page 44 of 76 
 
Wound Assessment 
 
Target limb resting ABI 
 
Target limb resting TBI  
 
TcPO2 (if ABI, ankle pressure or toe pressure cannot be acquired) 
 
Duplex ultrasound (DUS) 
 
EQ-5D-3L 
 
Walking Impairment Questionnaire (WIQ) 
 
Adverse event occurrence  
 
Review of study medications (antiplatelet agents/anticoagulants) 
15.3. 12-MONTH FOLLOW-UP VISIT (±30 DAYS POST-INDEX PROCEDURE) 
The following assessments are required to be performed at the 12-month follow-up visit: 
 
Rutherford Classification 
 
WIfI Classification 
 
Wound Assessment 
 
Target limb resting ABI  
 
Target limb resting TBI 
 
TcPO2 (if ABI, ankle pressure or toe pressure cannot be acquired) 
 
Duplex ultrasound (DUS) 
 
X-Ray assessment 
Note: If an X-ray of all Tack implant(s) is performed before the 12-month visit and is 
within the 12-month visit window, this may be used in lieu of  the x-ray required at 
the 12-month visit. 
 
EQ-5D-3L 
 
Walking Impairment Questionnaire (WIQ) 
 
Adverse event occurrence  
 
Review of study medications (antiplatelet agents/anticoagulants) 
15.4. 24-MONTH FOLLOW-UP VISIT (±30 DAYS POST-INDEX PROCEDURE) 
The following assessments are required to be performed at the 24-month follow-up visit: 
 
Rutherford Classification 
 
WIfI Classification 
 
Wound Assessment 
 
Target limb resting ABI  
 
Target limb resting TBI 

 
TOBA II BTK Clinical Study Protocol – Tack Endovascular System 
CA 0137 Rev C 
   
CA 0137 Rev C  
CONFIDENTIAL 
Page 45 of 76 
 
TcPO2 (if ABI, ankle pressure or toe pressure cannot be acquired) 
 
EQ-5D-3L 
 
Walking Impairment Questionnaire (WIQ) 
 
Adverse event occurrence  
 
Review of study medications (antiplatelet agents/anticoagulants) 
15.5. 36-MONTH FOLLOW-UP VISIT (±30 DAYS POST-INDEX PROCEDURE) 
The following assessments are required to be performed at the 36-month follow-up visit:  
 
Rutherford Classification 
 
WIfI Classification 
 
Wound Assessment 
 
Target limb resting ABI  
 
Target limb resting TBI 
 
TcPO2 (if ABI, ankle pressure or toe pressure cannot be acquired) 
 
EQ-5D-3L 
 
Walking Impairment Questionnaire (WIQ) 
 
Adverse event occurrence  
 
Review of study medications (antiplatelet agents/anticoagulants) 
15.6. UNSCHEDULED TARGET LIMB ANGIOGRAPHY/REVASCULARIZATION 
If a subject presents between study-required follow-up visits for an intervention to the target 
limb, the assessments below should be performed prior to the interventional procedure. In 
addition, all imaging studies performed should follow the guidelines set forth by the respective 
core laboratory. This imaging should be submitted to the respective core laboratories within 3 
business days for review and analysis.  
 
Rutherford Classification 
 
WIfI Classification 
 
Wound Assessment 
 
Target limb resting ABI  
 
Target limb resting TBI 
 
TcPO2 (if ABI, ankle pressure or toe pressure cannot be acquired) 
 
Duplex ultrasound (DUS) (if clinically indicated) 
 
X-Ray assessment (if clinically indicated) 
Note: If an X-ray of all Tack implant(s) is performed before the 12-month visit and is 
within the 12-month visit window, this may be used in lieu of the x-ray required at 
the 12-month visit. 

 
TOBA II BTK Clinical Study Protocol – Tack Endovascular System 
CA 0137 Rev C 
   
CA 0137 Rev C  
CONFIDENTIAL 
Page 46 of 76 
 
EQ-5D-3L 
 
Walking Impairment Questionnaire (WIQ) 
 
Review of study medications (antiplatelet agents/anticoagulants)   
Note: Any change in study medication, including any loading dose provided during 
the unscheduled procedure, should be recorded in the eCRF. 
15.7. FOLLOW-UP VISIT COMPLIANCE 
As part of the informed consent process, all reasonable efforts will be made to obtain complete 
data for all subjects according to the follow-up visit schedule. Investigators and research staff 
will be expected to maintain continuous and open communication with study subjects 
regarding their participation in this study. 
Three attempts via telephone will be made to contact subjects who do not present for a study 
follow-up visit. If after three telephone attempts the subjects cannot be contacted, a certified 
letter should be sent by the PI or designated study coordinator to the subject’s last known 
address. If possible, public records should be searched to ascertain survival status.  If efforts to 
reach the subject are unsuccessful after three telephone contacts and a certified letter, and 
there is no evidence of subject expiration, or the site has not been notified of a subject’s wish to 
withdraw consent, a Protocol Deviation for a visit not done must be documented in the EDC. A 
detailed record of all contact attempts should be maintained in the subject’s file. This process 
should be repeated for every subsequent follow-up visits and documented accordingly. After 
required contact attempts are unsuccessful for at least 2 consecutive visits and the 12-month 
visit window (or any later subsequent visit window) has passed, only then should a subject be 
considered lost-to-follow-up (LTFU) and exited from the study. 
15.8. SUBJECT DISCONTINUATION AND REPLACEMENT 
A subject may discontinue participation at any time without penalty or loss of benefits to which 
the subject is otherwise entitled. In addition, a subject may be discontinued if in the 
investigator’s opinion it is in the subject’s best interest. If a subject prematurely discontinues 
from the study, the reason will be recorded in the eCRF with supporting documentation.  These 
results will be tabulated by number and percent for each category for discontinuation.   
Subjects who prematurely exit the study after treatment will have their data maintained and 
evaluated up until the time of withdrawal. Subjects who are voluntarily or involuntarily (per PI 
discretion or if LTFU) withdrawn cannot re-enter the study. These subjects will not be replaced. 
 
RISK/BENEFIT ASSESSMENT 
16.1. RISKS 
The use of the Tack Endovascular System in percutaneous transluminal balloon angioplasty 
(PTA) may result in anticipated potential risks or complications similar to other available 
endovascular implant devices (such as stents) used in PTA procedures. Such risks are included 
in the Tack Endovascular System Instructions for Use (IFU) and are listed below: 
 
Access failure or abrupt closure 
 
Allergic / anaphylactoid reaction to anticoagulant and/or antithrombotic therapy or 
contrast medium 

 
TOBA II BTK Clinical Study Protocol – Tack Endovascular System 
CA 0137 Rev C 
   
CA 0137 Rev C  
CONFIDENTIAL 
Page 47 of 76 
 
Allergic reaction to nitinol 
 
Amputation of lower extremity 
 
Anemia 
 
Angina / coronary ischemia / myocardial infarction 
 
Arrhythmia 
 
Arterial occlusion / (re) stenosis / dissection / thrombus 
 
Arterial spasm 
 
Arteriovenous fistula 
 
Blue toe syndrome 
 
Claudication or rest pain, worsened 
 
Death 
 
Disseminated intravascular coagulation 
 
Edema, peripheral 
 
Embolism 
 
Emergent repeat hospital intervention 
 
Fever 
 
Gangrene 
 
Gastrointestinal bleed from anticoagulation / antiplatelet medication 
 
Hematoma / hemorrhage 
 
Hypotension / hypertension 
 
Inadvertent venipuncture 
 
Infection / abscess at insertion site 
 
Inflammation  
 
Multi-organ failure 
 
Pain 
 
Pseudoaneurysm 
 
Renal insufficiency or failure 
 
Respiratory distress or failure 
 
Septicemia / bacteremia (sepsis) 
 
Tack implant embolization 
 
Tack implant migration (device moves over time) 
 
Tack implant occlusion / restenosis  
 
Tissue necrosis 
 
Trauma to adjacent structures 
 
Stroke / TIA (hemorrhagic / embolic) 
 
Vascular complications which may require surgical repair 
These risks are present in any endovascular treatment procedure for which the study subjects 
would be indicated because of their disease and will be reviewed with all subjects during the 
informed consent process. 
16.2. POTENTIAL BENEFITS 
Prior human studies validated that the Tack Endovascular System can appose dissected tissue in 
subjects with post-PTA dissections, thereby resulting in acute dissection repair.    
16.3. JUSTIFICATION FOR CLINICAL STUDY 
The safety of the Tack Endovascular System has been established through extensive design 
verification and validation testing, including prior human use, and through a detailed risk 

 
TOBA II BTK Clinical Study Protocol – Tack Endovascular System 
CA 0137 Rev C 
   
CA 0137 Rev C  
CONFIDENTIAL 
Page 48 of 76 
analysis process per ISO 14971. The results of non-clinical and clinical testing have 
demonstrated safety and therefore, it is anticipated that the assessment of risk and benefit is 
appropriate for the intended use of the study device and the initiation of this study. 
This study is being conducted in order to collect safety and effectiveness data on the Tack 
Endovascular System device to support a Premarket Approval (PMA) application. All efforts will 
be made to minimize the occurrence of risk to study subjects through investigator/institution 
qualification, investigator training on the safe and proper use of the device in accordance with 
the IFU, investigator/site training on the protocol, and clearly defining subject eligibility 
requirements (inclusion/exclusion criteria) and contraindications as described in the IFU. 
 
SAFETY REPORTING 
The Principal Investigator at each participating site is ultimately responsible for the timely review 
and reporting of AEs per respective IRB/EC policy and in accordance with FDA and ISO (European 
sites) requirements.  
The safety reporting period will begin at the time of enrollment into the study (See Section 13.3.1) 
and will continue through study completion.  
All protocol reportable AEs will be monitored from the time of enrollment through the follow-up 
period for this study. A description of the event, including the start date, resolution (or date of final 
outcome assessment) date, action taken, and the outcome should be provided, along with the 
Investigator’s assessment of the relationship between the event and the study device or study 
device procedure. Pain, neurological status and functional impairment should be considered AEs 
when a subject’s complaint for any of these symptoms is outside the normal pattern for the illness 
treated. 
All protocol reportable events reported during the safety observation period should be followed 
until the event is resolved or judged to be chronically stable. Follow-up information will be 
submitted to the Medical Monitor and/or the Sponsor as it becomes available. 
The Sponsor or its designee will report all applicable serious adverse events as vigilance reports 
per MEDDEV 2.12.1, Rev 8 (2013) "Guidelines on a Medical Devices Vigilance System” and as 
clinical study reportable events per MEDDEV 2.7/3 “Clinical Investigations: Serious Adverse Event 
Reporting”.  The Sponsor will determine whether all of the local Investigators need to be informed 
immediately of an SAE or UADE, or whether this can be postponed until the next regularly 
scheduled study update. 
17.1. PROTOCOL REPORTABLE SAFETY EVENTS 
The following types of adverse events must be recorded on the Adverse Event eCRF by the 
Investigator (or designee):   
 
Serious Adverse Events 
 
Any event that is “possibly” or “definitely” related to the study device 
 
Any event that is “possible” or “definitely” related to the study device procedure 
The report will include: the AE term, seriousness, severity, action taken, treatment outcome and 
relationship of the adverse event to the study device and/or study device procedure and status. 

 
TOBA II BTK Clinical Study Protocol – Tack Endovascular System 
CA 0137 Rev C 
   
CA 0137 Rev C  
CONFIDENTIAL 
Page 49 of 76 
All events will be made accessible to the Sponsor and/or designee to review the need for FDA 
regulatory reporting. All reported safety events will be reviewed by the Sponsor or designee for 
any events that meet criteria for regulatory reporting. 
Severity of adverse events will be classified according to the following criteria: 
Mild: A mild adverse event is an AE usually transient in nature and generally not interfering 
with normal activities. 
Moderate: A moderate adverse event is an AE that is sufficiently discomforting to interfere 
with normal activities. 
Severe: A severe adverse event is an AE that is incapacitation and prevents normal 
activities. 
The relationship of the AE to the device or study device procedure will be classified according 
to the following criteria: 
Unrelated: No relationship to the study device or study device procedure. 
Possibly: Signs or symptoms may be related to the study device or study device procedure 
and the natural disease process or other injury/illness. 
Definitely: Clearly related to the study device or study device procedure. Signs and 
symptoms not related to natural disease process or other injury/illness. 
Unknown: Unable to determine relationship between study device, study device procedure, 
natural disease process and/or other injury/illness. 
17.2. ADVERSE EVENTS (AE) 
An AE is any untoward medical occurrence, unintended disease or injury, or untoward clinical 
signs (including abnormal laboratory findings) in subjects, users or other persons, whether or 
not related to the investigational device/procedure. 
For purposes of this study, AE’s that are not considered ‘serious’ or not considered at least 
‘possibly’ related to the study device and/or study device procedure are not required to be 
reported on the AE eCRF. 
All protocol reportable AEs will be evaluated by the Investigator using his/her clinical 
judgement to determine whether the event further meets the criteria for ADE, SAE, serious 
adverse device effect (SADE), or UADE and will be subject to the respective reporting 
requirements as outlined in the sections below. Investigator or designee is also responsible for 
informing their IRB / EC of adverse events as required by their IRB / EC procedures and in 
conformance with FDA and local regulatory requirements. In addition, the investigator shall 
provide documentation of the IRB / EC report to Intact Vascular or its designee. 
17.3. ADVERSE DEVICE EFFECTS (ADE) 
An adverse device effect is defined as any untoward adverse event related to the use of an 
investigational or unintended response to a medical device.  
Note 1: This definition includes adverse events resulting from insufficient or inadequate 
Instructions for Use, deployment, implantation, installation, or operation, or any malfunction of 

 
TOBA II BTK Clinical Study Protocol – Tack Endovascular System 
CA 0137 Rev C 
   
CA 0137 Rev C  
CONFIDENTIAL 
Page 50 of 76 
the investigational medical device. This definition includes any event resulting from 
insufficiencies or inadequacies in the Instructions for Use or the deployment of the device or 
any event that is a result of not observing the IFU (See Section 18). 
Note 2: This definition includes any event resulting from use error or from intentional misuse of 
the investigational medical device (See Section 18). 
A list of events that may be associated with the study device and/or the study device procedure 
is provided in Section 16.1.  
17.3.1. ADE REPORTING 
All ADEs must be evaluated to determine whether the event further meets criteria for an 
SADE (See Section 17.6) and would be subject to respective reporting requirements. Non-
serious, anticipated ADEs must be reported by the Investigator (or designee) to the Sponsor 
in a timely manner and must also be submitted to the IRB/EC per policy. If the event 
occurred as a result of a device event, respective reporting requirements must be followed 
as outlined in Section 18.  
17.4. SERIOUS ADVERSE EVENTS (SAE) 
A serious adverse event (SAE) is defined an adverse event that:   
 
led to death,  
 
led to a serious deterioration in the health of the subject, that either resulted in: 
 
a life-threatening illness or injury, or 
 
resulted in a permanent impairment of a body structure or a body function, or 
 
required in-patient hospitalization or prolongation of existing hospitalization, or 
 
resulted in medical or surgical intervention to prevent life-threatening illness or injury 
or permanent impairment to body structure or a body function, or,  
 
led to fetal distress, fetal death or a congenital abnormality or birth defect.  
Note: Planned hospitalization for a pre-existing condition, or a procedure required by the 
investigational plan without serious deterioration in health, is not considered a serious adverse 
event.   
17.4.1. SAE REPORTING 
All SAEs must be evaluated to determine whether the event further meets criteria for an 
SADE (See Section 17.6) and would be subject to respective reporting requirements. All 
events that meet the criteria above for SAEs must be reported by the Investigator (or 
designee) to the Sponsor within 2 business days from first knowledge of event and must 
also be reported to the IRB/EC per the respective policy. 
17.5. MAJOR ADVERSE LIMB EVENTS (MALE) + PERIOPERATIVE DEATH (POD) 
For the purpose of this study, the definition of major limb adverse event(s)(MALEs)+POD 
include the following outcomes: 

 
TOBA II BTK Clinical Study Protocol – Tack Endovascular System 
CA 0137 Rev C 
   
CA 0137 Rev C  
CONFIDENTIAL 
Page 51 of 76 
 
All-cause death less than 30 days after the Index Procedure 
 
Above-ankle target limb amputation 
 
Major re-intervention to the target lesion (defined as new bypass graft, 
jump/interposition graft revision, or thrombectomy / thrombolysis) 
17.5.1. MALE+POD REPORTING 
All events that lead to any of the outcomes meeting criteria above for an MALE+POD must 
be reported by the Investigator (or designee) to the Sponsor within 2 business days from 
first knowledge of the event, and must also be reported to the IRB/EC per the respective 
policy.  
17.6. SERIOUS ADVERSE DEVICE EFFECTS (SADE) 
A serious adverse device effect (SADE) is defined as an adverse device effect (ADE) that results 
in any of the consequences characteristics of a serious adverse event (SAE). 
17.6.1. SADE REPORTING 
All events that meet the criteria above for an SADE must be reported by the Investigator (or 
designee) to the Sponsor within 2 business days from first knowledge of event and must 
also be reported to the IRB/EC per policy. If the event occurred as a result of a device event, 
respective reporting requirements must be followed as outlined in Section 18. 
17.7. UNANTICIPATED ADVERSE DEVICE EFFECTS (UADE) 
Any serious adverse effect on health or safety or any life-threatening problem or death caused 
by, or associated with, a device, if that effect, problem, or death was not previously identified in 
nature, severity, or degree of incidence in the investigational plan or application (including a 
supplementary plan or application), or any other unanticipated serious problem associated 
with a device that relates to the rights, safety, or welfare of subjects. 
17.7.1. UADE REPORTING 
Any event that is suspected of meeting UADE criteria should be reported in the same 
manner as an SAE or SADE and must be reported by the Investigator (or designee) to the 
Sponsor within 2 business days from first knowledge of event and must also be reported 
to the IRB/EC per the respective policy. All SAEs will be reviewed by the Sponsor (or 
designee) to determine if UADE criteria is met, and if so, will immediately conduct an 
evaluation and report the results of the evaluation to FDA, all reviewing IRBs/ECs, and 
participating investigators within 10 business days after the Sponsor first receives notice of 
the effect. 
 
STUDY DEVICE EVENT REPORTING 
A Study Device Event refers to the performance of the study device and the occurrence of a 
deficiency or malfunction as defined in sub-sections below. Device events are to be reported on the 
Device Event eCRF and submitted to the sponsor as soon as possible and within 2 business days 
of first knowledge of occurrence. Any adverse event suspected of resulting from a device event 
must be reported per the required timelines as outlined in Section 17.  

 
TOBA II BTK Clinical Study Protocol – Tack Endovascular System 
CA 0137 Rev C 
   
CA 0137 Rev C  
CONFIDENTIAL 
Page 52 of 76 
18.1. DEVICE DEFICIENCY 
Inadequacy of a medical device related to its identity, quality, durability, reliability, safety or 
performance, such as malfunction, misuse or not observing the IFU, and inadequate labeling. 
18.2. DEVICE MALFUNCTION 
A malfunction is defined as a failure of a device to meet its performance specifications or 
otherwise to perform as intended 
18.3. DEVICE RETURNS 
In the event that a device is suspected of deficiency or malfunction, the Investigator should 
make every effort to return the device to the manufacturer, Intact Vascular. The Investigator or 
designee shall contact Intact Vascular for a return manufacturer authorization (RMA) number 
and for additional instructions for the return of potentially biohazardous material. 
 
STATISTICAL METHODS AND CONSIDERATIONS 
19.1. STUDY DESIGN 
This is a prospective, multi-center, single-arm, non-blinded study designed to investigate the 
safety and efficacy of the Tack Endovascular System. 
19.2. ANALYSIS POPULATIONS 
Subjects with BTK PAD who receive PTA in the Mid/Distal Popliteal, Tibial, and Peroneal 
Arteries and have a resulting dissection(s) that an Investigator would otherwise treat by means 
such as additional angioplasty with extended inflation time or stenting, are eligible for 
enrollment. To be enrolled, subjects must meet all inclusion criteria and not meet any of the 
exclusion criteria 
The intent to treat (ITT) population will consist of all subjects who had the Tack Endovascular 
System advanced through the introducer sheath. ITT subjects are included in both primary and 
secondary endpoint analyses.  
The PP population will be the subset of the ITT population that have met the definition of device 
success and have not had any major protocol deviations. Major protocol deviations include: 
 
A major inclusion/exclusion criterion violation; or 
 
A major procedural deviation 
 
The criteria for deviations meeting the classification of “major” will be defined by an 
independent designee before study endpoint data is available for statistical analysis.  
19.3. PRIMARY ENDPOINTS 
19.3.1. SAFETY 
Freedom from major adverse limb events (MALE) plus peri-operative death (POD) at 30 
days defined as a composite of all-cause death, above-ankle target limb amputation, or 
major re-intervention to the target lesion(s) (defined as new bypass graft, 
jump/interposition graft revision, or thrombectomy / thrombolysis) 

 
TOBA II BTK Clinical Study Protocol – Tack Endovascular System 
CA 0137 Rev C 
   
CA 0137 Rev C  
CONFIDENTIAL 
Page 53 of 76 
19.3.2. EFFICACY 
The primary efficacy endpoint is freedom from MALE at 6 months + POD at 30 days.  
19.4. SECONDARY ENDPOINTS 
 
Target lesion(s) tacked segment(s) patency at 6 months defined as the presence of blood 
flow using duplex ultrasound. If angiography is available within the 6-month follow-up visit 
window, it should be used in place of the duplex ultrasound. Evidence of no blood flow 
within the Tacked segment indicates restenosis/loss of patency.   
 
Target Limb Salvage defined as freedom from any above-ankle target limb amputation at 6 
months. 
19.5. OBSERVATIONAL ENDPOINTS 
 
Device Success: Successful deployment of the Tack implant(s) at the intended target site(s) 
and successful withdrawal of the delivery catheter from the introducer sheath.  
 
Target Lesion Success: Demonstrated target lesion patency [<30% residual diameter stenosis 
(DS), by visual estimate] without the use of a bailout stent within the target lesion upon 
completion of the index procedure. This will be assessed for all lesions treated with a Tack 
implant. In addition, target lesion success will also be analyzed by lack of bailout stent to 
tacked segment only. Multiple target lesions treated as one lesion with PTA will be analyzed 
as one lesion. 
 
Procedural Success: Demonstrated target lesion patency (<30% residual DS, by visual 
estimate) without the use of a bailout stent within the target lesion and without the 
occurrence of MALE+POD upon completion of the index procedure 
 
Amputation-free survival (AFS): Freedom from above-ankle target limb amputation or all-
cause death at 6 and 12 months 
 
Freedom from MALE at 12 months + POD at 30 days 
 
Target lesion(s) tacked segment(s) patency at 12 months defined as the presence of blood 
flow using duplex ultrasound. 
 
Target Limb Salvage defined as freedom from any above-ankle target limb amputation at 12 
months 
 
Assisted primary target lesion Tacked segment patency (flow vs. no flow) at 6 and 12 months 
 
Secondary target lesion Tacked segment patency (flow vs. no flow) at 6 and 12 months 
 
PSVR patency at 6 and 12 months [Freedom from binary restenosis defined as Peak Systolic 
Velocity Ratio (PSVR) of ≥ 2.5 and/or angiographic percent diameter stenosis of ≥50%] 
assessed for the following: 
o Target Lesion(s), defined as the entire contiguous arterial segment treated with 
angioplasty, inclusive of an additional proximal and distal margin of 5 mm 
o Tacked Segment(s), defined as the Tack device and 5 mm of artery proximal and distal 
to each Tack. If Tacks are within 10 mm of each other, they will be considered as a 
single tacked segment for the purposes of this patency assessment. 
 
Clinically-driven target lesion revascularization (CD-TLR) through 6 and 12 months 
 
Clinically-driven target vessel revascularization (CD-TVR) through 6 and 12 months 

 
TOBA II BTK Clinical Study Protocol – Tack Endovascular System 
CA 0137 Rev C 
   
CA 0137 Rev C  
CONFIDENTIAL 
Page 54 of 76 
 
All-cause death through 6 and 12 months 
 
Any Target vessel revascularization (TVR) through 6 and 12 months 
 
Any Target lesion revascularization (TLR) through 6 and 12 months 
In addition, the following observational endpoints will be assessed at various time points through 
36 months (See Time and Events Schedule Section 8.1): 
 
Changes in Wound, Ischemia, and foot Infection (WIfI)33 Classification 
 
Changes in ankle brachial index (ABI) and toe brachial index (TBI) 
 
Changes in Rutherford Classification 
 
Changes in the EQ-5D-3L quality of life questionnaire 
 
Changes in the Walking Impairment Questionnaire (WIQ) 
 
Tack implant Integrity via X-ray (only performed at 12-month visit) 
 
Progress of wound(s) present at study entry (healed, improved, unchanged, worsening, 
amputated) 
 
Appearance of new wound(s) after study entry 
 
Unplanned below-ankle target limb amputation(s): digit or transmetatarsal 
19.6. SAMPLE SIZE 
The sample size for the primary efficacy endpoint of freedom from MALE at 6 months plus POD 
at 30 days was calculated using a one-sided, single group, normal approximation test of a 
proportion (with continuity correction) against a performance goal.  The performance goal for 
this endpoint is 74% developed based on the information reported in table VIIb and figure 2A of  
Conte (2009).  From figure 2A, the estimated 6-month rate of freedom from MALE + POD in the 
infra-popliteal group is 80.5% with 95% confidence interval calculated to be (77%, 84%). 
Applying the recommended 3% margin to the lower bound of the confidence interval yields the 
74% OPG. Assuming the observed freedom from MALE+POD is 84% and a one-sided Type I 
error rate of 0.025, a sample size of 186 subjects provides 90% power to detect this difference 
between observed freedom from MALE+POD and the performance goal of 74%. 
The sample size for the primary safety endpoint of MALE+POD at 30 days was calculated using 
the exact binomial distribution.  This is also a one-sided, single group test of a proportion 
against a performance goal.  The performance goal for this endpoint was established at 12%.  
This performance goal was derived from the information reported in table VIIa of Conte (2009).  
In that table, MALE+POD was not reported, however MALE and 30-day death were reported 
separately.  The sum of those two estimates (8.9%) was used for sample size calculation.  Conte 
(2009) established performance goals for safety endpoints by constructing a 95% confidence 
interval and using the upper bound of that interval as the performance goal.  With some 
algebraic manipulation, a similar 95% confidence interval was established for the 8.9%point 
estimate of 30day MALE+POD which resulted in an upper bound of 11.9%.  Therefore 12% is 
used as the performance goal for this endpoint.  Assuming an observed MALE+POD rate of 5% 
 
33 Joseph L. Mills, Sr, MD, Michael S. Conte, MD, David G. Armstrong, DPM, MD, PhD, Frank B. Pomposelli, MD, Andres Schanzer, MD, 
Anton N. Sidawy, MD, MPH, and George Andros, MD, on behalf of the Society for Vascular Surgery Lower Extremity Guidelines Committee, 
The Society for Vascular Surgery Lower Extremity Threatened Limb Classification System: Risk stratification based on Wound, Ischemia, 
and foot Infection (WIfI). J Vasc Surg. 2014; Volume 59, Issue 1, Pages 220–234.e2 

 
TOBA II BTK Clinical Study Protocol – Tack Endovascular System 
CA 0137 Rev C 
   
CA 0137 Rev C  
CONFIDENTIAL 
Page 55 of 76 
and a one-sided Type I error rate of 2.5%, a sample size of 171 subjects provides 90% power to 
demonstrate that the observed 30-day MALE+POD rate is below the performance goal of 12%. 
Since the required sample size for the primary efficacy endpoint (186), is larger than the 
required sample size for the primary safety endpoint (171), an effective sample size of 186 
subjects meeting the ITT definition will be assumed.  Assuming approximately 20% loss to 
follow-up, total enrollment will be 186/0.80 or 232 subjects.  
The secondary endpoint of primary patency of the tacked segment of the treated lesion at 6 
months will also be formally tested against a performance goal of 64%.  The performance goal 
of 64% was chosen as a result of a meta-analysis combining 13 papers that reported 6-month 
patency for standard PTA or from which the 6-month patency rate could be derived.  These 
papers covered several patient populations, however all these populations are target 
populations for use of the Tack.  A meta-analysis was performed on the results reported in 
these papers and the random effects estimate of 6-month patency was 63.5%.  Therefore, 64% 
was chosen as the performance goal.  Assuming an observed 6-month patency rate of 81% and 
a one-sided Type I error rate of 2.5%, the effective sample size given above for the primary 
efficacy endpoint of 175 would provide greater than 90% power to detect the difference 
between an observed 6-month patency of 81% and the performance goal of 64%. 
19.7. BASELINE VARIABLES 
Baseline variables will be summarized for those subjects enrolled in this trial.  Continuous 
variables will be presented as means, standard deviations, and sample size (N).  Discrete 
variables will be presented as a percent along with the number of subjects displaying the 
characteristic and the total number of subjects.  The types of baseline variables summarized 
will be demographics, medical history and lesion characteristics. 
19.8. STATISTICAL ANALYSIS 
19.8.1. PRIMARY SAFETY 
The primary safety endpoint of MALE+POD at 30 days will be analyzed by constructing a 
one-sided upper 97.5% confidence interval using the exact binomial distribution.  This 
upper bound will be compared to the performance goal of 12%.  The hypotheses being 
tested are: 
                
%
12
:
%
12
 
:
<
≥
+
+
POD
MALE
POD
MALE
P
Ha
P
Ho
 
where PMALE+POD is the proportion of subjects experiencing a MALE+POD event within 30 
days of the procedure.  All subjects that meet the ITT definition are included in this analysis. 
19.8.2. PRIMARY EFFICACY 
The primary efficacy endpoint of freedom from MALE at 6 months plus POD at 30 days will 
be analyzed using a one-sided, single group, Z-test comparing the observed proportion of 
subjects free of MALE and POD to the performance goal of 74%.  The hypotheses are: 
%
74
:
%
74
:
6
_
6
_
>
≤
+
+
POD
MALE
POD
MALE
P
Ha
P
Ho
 

 
TOBA II BTK Clinical Study Protocol – Tack Endovascular System 
CA 0137 Rev C 
   
CA 0137 Rev C  
CONFIDENTIAL 
Page 56 of 76 
where PMALE_6+POD is the proportion of subjects free of MALE at 6 months + POD at 30 days.  
The p-value associated with the standard Z-test will be provided along with a one-sided 
97.5% lower confidence bound on the point estimate observed. All subjects that meet the 
ITT definition are included in this analysis. 
The Z-test that will be used for analysis is the continuity corrected Z under the estimated 
PMALE_6+POD.  That is:  
𝑍𝑍= 
𝑝𝑝̂ −𝑃𝑃0 + 𝑐𝑐
ඥ𝑝𝑝̂ (1 −𝑝𝑝̂)/ 𝑛𝑛
 , 
where𝑝𝑝̂ is the estimate of PMALE_6+POD, P0 is the performance goal of 74% under the null 
hypothesis, and  
𝑐𝑐=
⎩
⎪
⎨
⎪
⎧−1
2𝑛𝑛
𝑖𝑖𝑖𝑖 𝑝𝑝̂ > 𝑃𝑃0
1
2𝑛𝑛
𝑖𝑖𝑖𝑖 𝑝𝑝̂ < 𝑃𝑃0
0
𝑖𝑖𝑖𝑖 |𝑝𝑝̂ −𝑃𝑃0| < 1
2𝑛𝑛.
 
19.8.3. SECONDARY EFFICACY ENDPOINTS 
The secondary efficacy endpoint of 6-month patency will be estimated as the proportion of 
tacked segments of the lesion(s) that are still patent at 6 months.  A one-sided lower 97.5% 
confidence bound will be calculated for this estimate using the standard normal 
approximation.  This lower bound will be compared to the performance goal of 64%.  The 
hypotheses being tested are: 
%
64
:
%
64
:
6
_
6
_
>
≤
month
Patency
month
Patency
P
Ha
P
Ho
 
where PPatency_6month is the proportion of subjects whose tacked portion of the vessel is still 
patent 6 months post procedure.  Patency will also be displayed using a Kaplan-Meier curve. 
The secondary efficacy endpoint of target limb salvage at 6 months will be summarized 
using the Kaplan-Meier method to estimate freedom from above-ankle target limb 
amputation.  The final 6-month estimate will be presented along with 95% confidence 
intervals. All subjects that meet the ITT definition are included in this analysis. 
19.8.4. OBSERVATIONAL ENDPOINTS 
All observational endpoints will be summarized descriptively.   
19.9. SUBGROUP ANALYSIS 
The primary safety and efficacy endpoints will be re-analyzed stratifying by gender and by US 
versus OUS.  Point estimates and 95% confidence intervals will be displayed for each endpoint.  
No formal testing will be done since the reduced sample sizes would result in underpowered 
tests. 
 
 

 
TOBA II BTK Clinical Study Protocol – Tack Endovascular System 
CA 0137 Rev C 
   
CA 0137 Rev C  
CONFIDENTIAL 
Page 57 of 76 
19.10. SITE POOLING ANALYSIS 
For both the primary safety endpoint and the primary efficacy endpoint, a pooling analysis will 
be completed demonstrating that the information on the primary endpoints can be pooled 
across site.  For each endpoint, the site specific estimate of the endpoint will be calculated.  
These site specific rates will then be compared using a standard Pearson chi-square statistic.  A 
p-value greater than 0.15 will indicate poolability of site information.  Low enrolling sites 
(enrollment ≤ 5) will be pooled into an “other site” category for the purposes of this analysis. If 
differences between sites exist at the alpha=0.15 level, summary statistics will be presented for 
each site and any differences by study site will be discussed in the study report. In this case, a 
meta-analytic modeling approach will be used to combine the estimates across sites using the 
random effects estimate based on the inverse variance to account for the heterogeneity of sites. 
Specifically, each of the binary primary endpoints will be modeled as a function of the random 
effect of site and the estimates and resulting confidence intervals used to compare the estimate 
to the performance goal. The DerSimonian-Liard estimator of the variance with inverse 
variance weights will be used to adjust for the random effect of site in the final analysis. 
Additionally, a sensitivity analysis of the primary outcomes will be performed by excluding 
outlying sites one at a time until a statistically significant difference between sites (at 
alpha=0.15) no longer exists.  Then, the pooled results for the remaining sites will be used for 
the sensitivity analysis. 
19.11. HANDLING OF MISSING DATA 
For the primary analysis, only complete data will be used. Data will be considered “complete” if 
the subject had the event of interest at or prior to the time point for analysis and/or if the 
subject’s status is known at any time beyond the analysis window. Subjects without sufficient 
follow-up based on the lower end of the visit window will be excluded from the analysis (that is, 
subjects must have at least 28 days of follow-up for the 30 day endpoints, 6 months minus 30 
days for the 6 month endpoints and 12 months minus 30 days for endpoints defined at 1 year). 
Thus, subjects without events but whom are known to be event free at a later visit will have 
their data imputed backward but not forward for the primary analysis.  
As a sensitivity analysis, missing values for the primary endpoints will be replaced by 
regression imputations based on a multivariate logistic regression analysis of completed cases 
(those that have follow-up at the required time point or experienced the endpoint in question 
prior to final follow-up visit).  Covariates to consider for inclusion in the logistic regression 
include but are not limited to: age, sex, history of hypertension, diabetes, previous peripheral 
vascular intervention, BMI, dissection location (mid popliteal (P2), distal popliteal (P3), 
tibioperoneal trunk, peroneal, anterior tibial, or posterior tibial), and baseline Rutherford class. 
Backward selection will be used to identify predictors. In the event there are no significant 
predictors in the logistic regression model at alpha=0.1, a “hot deck” method will be employed 
where a random selection of the outcome from a group of completed cases with similar baseline 
characteristics will be used as the imputed value using simple random sampling with 
replacement.  The baseline characteristics to be used for the hot deck method will include but 
are not limited to age (<> median), sex, dissection location (mid popliteal (P2), distal popliteal 
(P3), tibioperoneal trunk, peroneal, anterior tibial, or posterior tibial), use of statin medication, 
current smoker status and baseline Rutherford class.  

 
TOBA II BTK Clinical Study Protocol – Tack Endovascular System 
CA 0137 Rev C 
   
CA 0137 Rev C  
CONFIDENTIAL 
Page 58 of 76 
With either method of imputation, five complete datasets will be constructed.  Each dataset will 
be analyzed separately and then combined in an overall analysis across the five complete 
datasets. 
In addition, a tipping point analysis will be conducted whereby all subjects missing data for the 
endpoint of interest will be imputed as a failure one at a time until the point of tipping the 
analysis has been determined. That is, the tipping point analysis starts with the best case 
analysis (all missing subjects are a success) and continues until the worst case analysis is 
completed (all missing subjects are failures), by increasing the number of missing cases 
imputed as failures by one in each analysis.   The goal of the tipping point analysis is to 
determine at what point the imputation of failures causes the statistical evaluation of the 
endpoint to lose statistical significance.   
19.12. STUDY SUCCESS DEFINITION 
The trial will be considered a success if both the primary safety and primary efficacy endpoints 
are met. 
19.13. MULTIPLICITY 
There is no correction to alpha in controlling type I error for the primary endpoints as both 
endpoints must be met in order to declare study success.  Additionally, the type I error will be 
controlled by testing the secondary endpoint hierarchically.  That is, the secondary endpoint of 
6-month patency will be formally tested if and only if the primary study endpoints are met. If 
the 6-month patency endpoint is met then the two-sided 95% confidence interval for the 
secondary endpoint of target limb salvage at 6 months will be reported.  There is no formal 
hypothesis for this endpoint. There are no additional formal hypothesis tests and thus no 
further adjustments are necessary. 
 
REGULATORY AND ETHICAL OBLIGATIONS 
As the study Sponsor, Intact Vascular is responsible for the overall conduct and quality of the study, 
including the assurance that the study complies with the regulations and guidance that apply to 
medical devices evaluated under an Investigational Device Exemption (IDE) and Good Clinical 
Practice (GCP) guidance (FDA Guidance and ICH E6). Additionally, Intact Vascular will ensure that 
qualified monitors and designated personnel are monitoring the study and that the Informed 
Consent process is followed per each site’s local and national requirements. 
20.1. INSTITUTIONAL REVIEW BOARD (IRB) / ETHICS COMMITTEE (EC) APPROVAL  
21 CFR Parts 50 & 56; ISO 14155: 2011 Section 4 
The Principal Investigator at each participating site is responsible for securing IRB/EC approval 
for this study protocol and the Informed Consent documents. The IRB/EC for each specific 
institution must review and approve this study protocol, the specific Informed Consent form and 
any written materials for subjects to be used at that site prior to enrollment of the first subject.  
The Sponsor must also review and approve the final Informed Consent documents prior to their 
use.  The Sponsor must receive a copy of any IRB/EC correspondence as well as the final approval 
letter and the final approved Informed Consent from each IRB/EC. The IRB/EC approval letter 
must be signed by the IRB/EC chair or designee, identify the IRB/EC name and address, the 
clinical study protocol by name or number, and the date the approval was granted. 

 
TOBA II BTK Clinical Study Protocol – Tack Endovascular System 
CA 0137 Rev C 
   
CA 0137 Rev C  
CONFIDENTIAL 
Page 59 of 76 
The site investigator is also responsible for initiating and obtaining continuing review of the 
clinical study. Continuing IRB/EC review and approval should not exceed intervals over one year, 
but may occur at more frequent intervals as required by site specific IRB/EC policies. The 
investigator must also provide the Sponsor with all correspondence and documentation of 
continued IRB/EC approval of the clinical study. 
20.2. INFORMED CONSENT 
All sites shall comply with 21 CFR 50, provisions of ICH Good Clinical Practices (GCPs), local 
IRB/EC policy and all applicable local regulations (i.e. ISO 14155 for European Sites) for 
obtaining Informed Consent. Written, informed consent is to be obtained for all subjects prior to 
treatment as described in Section 10.1.  
Informed Consent templates will be provided by the Sponsor to all participating clinical sites. 
Changes to this template made by the site based upon IRB/EC requirements must be provided 
to the Sponsor for review and approval prior to being submitted to the IRB/EC for review and 
approval. Any revisions required by a site’s IRB/EC should also be provided to the Sponsor for 
review and approval prior to being submitted to the IRB/EC for final review and approval.  
20.3. PROTOCOL AMENDMENT AND EMERGENCY DEVIATIONS 
Changes to the research conducted under this protocol will be implemented with a formal 
protocol amendment. Amendments to the protocol may be initiated by the Sponsor or at the 
request of the Investigator. In either case, changes to the protocol must be approved by the 
Sponsor and submitted to the applicable regulatory agency as appropriate. A protocol 
amendment cannot be implemented at the site without first being signed and acknowledged by 
the Investigator and approved by the IRB/EC. 
Emergency deviations or modifications may be initiated without prior Sponsor or IRB/EC 
approval only in cases when the deviation is necessary to eliminate an immediate potential 
hazard to a subject. Emergency deviations or modifications implemented to protect the life or 
physical well-being of a subject must be reported to the Sponsor and site specific IRB/EC 
within 5 business days of occurrence.   
20.4. SUBJECT CONFIDENTIALITY 
Confidentiality of subjects will be maintained throughout the study. A unique identification 
code will be assigned to each subject enrolled into the study.  Access to the subject’s medical 
records will be limited to authorized personnel of the Sponsor, their designated monitors, 
clinical site study staff and authorized regulatory authorities as required by the IRB/EC and/or 
local or national agencies. Any data that may be published in abstracts or scientific journals 
and/or presented at medical meetings will reference a unique subject code and will not reveal 
the subject’s identity.  The Sponsor and their representatives will make every reasonable effort 
to protect the confidentiality of the subjects participating in the study. 
All U.S. clinical study sites must comply with the provisions of the Health Insurance Portability 
and Accountability Act (HIPAA) and in accordance with all applicable federal, local and 
institutional requirements.  
 

 
TOBA II BTK Clinical Study Protocol – Tack Endovascular System 
CA 0137 Rev C 
   
CA 0137 Rev C  
CONFIDENTIAL 
Page 60 of 76 
 
CLINICAL STUDY CONDUCT 
21.1. PRINCIPAL INVESTIGATOR AND SITE QUALIFICATION 
21 CFR 812.43; ISO 14155:2011 Section 8.2.1 
All Principal Investigator’s (PI) and investigational sites will be selected by Intact Vascular 
through the PI and site qualification process. All selected PI’s will be responsible for complying 
with all study-related and regulatory requirements and will be ultimately responsible for 
overseeing the conduct of the study at their respective investigational sites, per the Investigator 
Agreement.  
All selected PI’s will have the required training and expertise in performing peripheral vascular 
interventional procedures in a clinical research setting. The investigational sites where the 
study procedures and assessments are to be performed must have the adequate volume of the 
target subject population, experienced staff, as well as the appropriate facilities and equipment 
to meet the requirements of the study protocol and the expected enrollment time frames. 
All PI’s and research staff must be willing to undergo all study and device-related training and 
participate and assist with monitoring, audits and inspections initiated by either the Sponsor 
and/or regulatory authorities.  
21.2. PRINCIPAL INVESTIGATOR AND SITE TRAINING 
Training of the Investigators and clinical study staff is the responsibility of the Sponsor and 
their designee.  Investigators and study staff will undergo site initiation visit training on the use 
of the study device, the study protocol, eligibility criteria, and device accountability prior to 
participating in the study. Training will also include, but is not limited to, instructions on timely 
and accurate eCRF completion, safety reporting timelines, as well as procedures for acquiring 
study related images and associated timelines for submission to appropriate core 
laboratory(ies). All training of the Investigators and research staff must be documented on the 
training log before performing any study-related function. 
21.3. CLINICAL MONITORING 
21 CFR 812.46; ISO 14155:2011 Section 8.2.4.2 
Intact Vascular will designate qualified clinical monitor(s) and oversee the conduct of this 
study.  The clinical monitors will evaluate compliance with the protocol, Good Clinical Practices 
(FDA Guidance and ICH E6), any specific recommendations made by the site’s IRB/EC and the 
signed Investigator and Study Agreements.   
The clinical monitor will conduct periodic monitoring visits to verify that the eCRFs are in 
agreement with the source documentation and other records, that the rights and well-being of 
the subjects, and that the trial is being conducted in accordance with the approved 
protocol/amendments and GCPs. Periodic phone contacts will also be conducted to ensure that 
the protocol is being followed and to assist the site with queries that may arise.  
For record verification purposes during site monitoring visits, the clinical monitor and/or 
authorized Sponsor representative will be provided access to hospital records, original 
laboratory data, and other records and data as they relate to the study and as agreed to with the 
Investigator prior to the initiation of the trial.  The Investigator will also make available to the 

 
TOBA II BTK Clinical Study Protocol – Tack Endovascular System 
CA 0137 Rev C 
   
CA 0137 Rev C  
CONFIDENTIAL 
Page 61 of 76 
clinical monitor all regulatory documents, all completed eCRFs, informed consent documents, 
source documentation and other relevant records for all enrolled subjects at the site.  It is 
important that the Investigator and other relevant site personnel are available for consultation 
with the clinical monitors during the monitoring visits and that sufficient time is devoted at the 
site to the monitoring process.  
If the Sponsor and/or their authorized representative become aware that an Investigator is not 
complying with the study protocol, the Investigator Agreement, the Declaration of Helsinki, 
GCPs, applicable privacy standards, or any condition of the study imposed by the IRB/EC, the 
Sponsor or their authorized representative may immediately secure compliance, discontinue 
further shipments of the study devices and/or seize unused devices on-site.  An inability to 
secure compliance and/or to complete an investigation into the factors that are inhibiting 
compliance may result in the Investigator’s termination from the study by the Sponsor.   
Study close-out visits will be conducted after the final follow-up visit is completed at each site.  
Following the resolution of any outstanding data discrepancies and adverse events, the 
remaining study devices will be the collected and returned to the Sponsor.  A final study report 
will be generated and submitted to the Investigator and the appropriate study oversight 
authorities.  Study document retention requirements will be reviewed with each site during the 
close-out visit. 
21.4. DEVICE ACCOUNTABILITY 
All study devices will be provided to the Investigator by the Sponsor after being tested, released 
and shipped according to appropriate standards. The investigator and/or designee is 
responsible for the secure storage of and controlled access to the study devices and 
accountability. The study device shall not be dispensed to any person who is not a consented 
study subject under this protocol. 
21.5. INVESTIGATOR REPORTS 
21CFR Parts 50 & 56; ISO 14155:2011 Section 4 
All investigators will be responsible for preparing and submitting the following complete, 
accurate, and timely reports.  
To the sponsor and the IRB/EC:  
 
Any unanticipated adverse device effect occurring during an investigation as soon as 
possible but no later than 2 working days after first learning of the effect.  
 
Assist sponsor in generating Progress Reports on the investigation at regular intervals, 
but in no event less often than yearly. If there is a study monitor, a copy of the report 
will also be sent to the monitor.  
 
Any deviation from the investigational plan made to protect the life or physical well-
being of a subject in an emergency, as soon as possible but no later than 5 working days 
after the emergency occurs. Except in emergency situations, a protocol deviation may 
require a prior sponsor approval; and if the deviation may affect the scientific 
soundness of the plan or the rights, safety, or welfare of subjects, prior FDA and IRB/EC 
approval are required. 

 
TOBA II BTK Clinical Study Protocol – Tack Endovascular System 
CA 0137 Rev C 
   
CA 0137 Rev C  
CONFIDENTIAL 
Page 62 of 76 
 
Any use of the device without obtaining informed consent, must be reported within 5 
working days after such use.  
 
Assist sponsor in generating a final report within 3 months following termination or 
completion of the investigation or an individual investigator’s part of the investigation.  
 
Any further information requested by FDA or the IRB/EC about any aspect of the 
investigation.  
To the Sponsor:  
 
Withdrawal of IRB/EC approval of the investigator’s part of an investigation. (Due 
within 5 working days of such action). If the Investigator’s IRB/EC withdraws their 
approval to conduct this study for any reason, the Investigator must notify the Sponsor 
as soon as possible, but in no event later than five working days after the withdrawal of 
the approval. 
In addition, the Investigator is responsible for the reporting of all safety and device events per 
the timelines specified in Section 17 and Section 18.  
21.6. DATA MANAGEMENT 
Standardized electronic Case Report Forms (eCRF) will be used to collect complete and 
accurate records of the clinical data required by the study in accordance with Good Clinical 
Practices (GCP) principles.  The Investigator and/or study staff under his/her direction is 
responsible for accurately recording the clinical data for this study within five (5) days after 
each visit. 
21.7. SAFETY MONITORING 
21.7.1. DATA SAFETY MONITORING BOARD (DSMB) 
To meet the ethical responsibilities and standards for research subjects, an independent 
board of multi-disciplinary physicians and subject matter experts shall serve as the Data 
Safety and Monitoring Board (DSMB) for the study.  In order to enhance objectivity and 
reduce the potential for bias, the DSMB shall be independent of the Sponsor as well as the 
investigational sites/ investigators.  
The DSMB shall serve as an independent body conducting a review and oversight of all key 
safety events to monitor the rate of occurrence (both site reported and CEC adjudicated 
events) as part of their mission to protect the rights and safety of research subjects. The 
DSMB will define the types of events that may require real time reporting and the format 
and frequency of interim data reviews for aggregate event rates. The DSMB will conduct 
systematic interim safety reviews at pre-specified intervals as outlined in the DSMB charter.  
The committee will be responsible for making any recommendations to the Sponsor it 
deems necessary to protect subjects enrolled in the trial. 
At the close of each meeting, deliberation will occur and each DSMB member will vote in 
favor of continuation of the study as designed, or modification of the study to protect the 
welfare of subjects enrolled into the study. The result of this vote will be recorded in the 
meeting minutes.  

 
TOBA II BTK Clinical Study Protocol – Tack Endovascular System 
CA 0137 Rev C 
   
CA 0137 Rev C  
CONFIDENTIAL 
Page 63 of 76 
The methodology for performing these responsibilities shall be developed and outlined in 
the DSMB Charter.  
21.7.2. CLINICAL EVENTS COMMITTEE (CEC) 
An independent Clinical Events Committee consisting of a team of clinical experts with 
experience in the conduct of clinical trials shall be formed to review clinical events reported 
by the investigators, or at the request of the Sponsor to determine if they meet the pre-
specified endpoint definitions. The CEC may also be called upon to review relevant Serious 
Adverse Events to make an assessment of relationship to study device and/or study 
procedure. The CEC’s determination of whether a clinical event meets the study defined 
endpoint will be considered the primary determination for the purpose of reporting study 
results with the exception of endpoints derived from Core Laboratory analysis. 
Operational provisions shall be established to minimize potential bias (i.e., the physicians 
serving on the CEC shall be blinded to the clinical site to the extent possible during adverse 
event review and adjudication). The methodology for performing these responsibilities will 
be outlined in the CEC Charter. The CEC will define the minimum required information 
necessary to facilitate their review of an event. This may include information from original 
source documentation and imaging media. 
21.8. MEDICAL MONITORING 
The sponsor will be responsible for identifying a Medical Monitor who possesses the 
appropriate expertise and medical knowledge to oversee all adverse events reported during the 
study. All adverse event reports will be directed to the Sponsor as well as the Medical Monitor. 
The Medical Monitor will be responsible for the first-line and timely review of all adverse 
events in order to identify seriousness, severity, and causality and expectedness (anticipated vs. 
unanticipated) of the event to the study device and/or study procedure. The Medical Monitor 
will also have responsibilities including but not limited to: 
 
Reviewing all reported AEs for UADE potential and notifying the Sponsor of the need for 
regulatory reporting; 
 
Determining the need for additional information or supporting documentation from the 
site regarding an adverse event to facilitate complete assessment; 
 
May help determine if an adverse event meets the criteria for DSMB/CEC review and 
adjudication, as outlined in the charter;  
 
Providing thorough review and assistance (if needed) for generating documents (i.e., 
subject event narratives) subject to CEC review and adjudication; 
 
Providing answers to the sites, IRBs/ECs, and/or Sponsor to questions requiring 
medical expertise that pertain to the protocol (i.e., subject eligibility) or any other 
medical aspect of the study; 
 
Identifying potential need for an amendment to the protocol; 
 
Provide a review of safety information included in regulatory reporting. 

 
TOBA II BTK Clinical Study Protocol – Tack Endovascular System 
CA 0137 Rev C 
   
CA 0137 Rev C  
CONFIDENTIAL 
Page 64 of 76 
The Medical Monitor will review all adverse events throughout the duration of the study until 
study completion. 
21.9. CENTRAL CORE LABORATORIES 
To ensure that the clinical data and images are analyzed in a controlled, non-biased manner and 
that the results are analyzed using a standardized process, all angiograms, duplex ultrasound 
studies and x-rays obtained during this study will be submitted to a respective central core lab 
for analysis. 
The core labs will be responsible for analyzing the angiograms, duplex ultrasound and x-ray 
images according to the study eligibility criteria, the study endpoints and requirement 
measurements according to this study protocol. Feedback will be provided to the sites and 
Sponsor regarding the quality of the tracings and images and for providing a written summary 
report of all angiogram, duplex ultrasound and X-ray results to the study Sponsor. 
21.10. RECORD RETENTION 
The Principal Investigator is responsible for maintaining the following accurate, complete, and 
current records relating to his/her participation in this investigational study:  
 
Correspondence with another investigator, an IRB/EC, the Sponsor, a monitor, or FDA; 
 
Records of receipt, use or disposition of a device that relate to:  
o The type and quantity of the device, dates of receipt, and batch numbers or code 
marks;  
o Names of all persons who received, used, or disposed of each device;  
o The number of units of the device returned to the sponsor, repaired, or 
otherwise disposed of, and the reason(s) therefore. 
 
Records of each subject’s case history and exposure to the device, including:  
o Documents evidencing informed consent and, for any use of a device without 
informed consent, any written concurrence of a licensed physician and a brief 
description of the circumstances justifying the failure to obtain informed 
consent; 
o All relevant observations, including records concerning adverse device effects 
(whether anticipated or not), information and data on the condition of each 
subject upon entering, and during the course of, the investigation, including 
information about relevant previous medical history and the results of all 
diagnostic tests;  
o A record of the exposure of each subject to the investigational device, including 
the date and time of each use, and any other therapy;  
 
The protocol, with documents showing the dates of and reasons for each deviation from 
the protocol; and  
 
Any other records that FDA requires to be maintained by regulation or by specific 
requirement for a category of investigations or a particular investigation. 

 
TOBA II BTK Clinical Study Protocol – Tack Endovascular System 
CA 0137 Rev C 
   
CA 0137 Rev C  
CONFIDENTIAL 
Page 65 of 76 
In addition, all Principal Investigators and Sub-Investigators (Sub-I) shall disclose to the 
sponsor sufficient and accurate financial information to allow the sponsor to submit 
certification or disclosure of financial interests under 21 CFR 54. All PI(s) and Sub-I(s) shall 
update the information if any relevant changes occur during the course of the investigation and 
for one year following completion of the study. 
The Sponsor, Core Laboratories and clinical sites will maintain the study records until two (2) 
years after the last marketing application and until there are no pending or contemplated 
marketing applications or at least two (2) years have elapsed since formal discontinuation of 
clinical development of investigational product. These records may be retained for a longer 
period of time if required by applicable regulatory agencies.  The Sponsor will notify each site 
regarding the regulatory requirements for record retention during the study close-out visit. 
21.11. AUDITS/INSPECTIONS 
In accordance with GCP requirements, the Sponsor and/or Designee may request access to all 
study records, including source documents, for inspection and duplication.  In the event that an 
Investigator is contacted by an applicable regulatory body in relation to this study, the 
Investigator will notify the Sponsor as soon as possible.   
The Investigator and/or designees must be available to respond to reasonable requests by 
authorized Sponsor, CRO and regulatory agency representatives during the monitoring and 
inspection process.  The Investigator must provide the Sponsor with copies of all 
correspondence that may affect the review of the current study (i.e. Inspection Observations) or 
their qualification as an Investigator in clinical studies conducted by the Sponsor. The Sponsor 
will provide any needed assistance to the clinical site for regulatory audits, if any.   
21.12. STUDY TERMINATION (STOPPING RULES) 
The Sponsor, IRBs/ECs, or regulatory authorities may terminate the study if the safety and well-
being of study subjects is in jeopardy. If the Investigator terminates the study at his/her site 
without prior approval by the Sponsor, all details must be provided promptly to the Sponsor 
and IRB/EC. 
The Sponsor reserves the right to terminate or reevaluate a site for continued participation in the 
study for any of the following reasons: 
 
Unsatisfactory enrollment with respect to eligibility criteria 
 
Failure to obtain Informed Consent 
 
Failure to report Serious Adverse Events within 2 business days of knowledge 
 
Loss of or unaccountable device inventory 
 
Repeated protocol violations or safety concerns 
 
Repeated failure to complete Case Report Forms (or inaccurate/incomplete eCRF 
completion) 
 
Failure to enroll an adequate number of subjects 
 
The potential benefits are unlikely to outweigh the risks (Futility) 

 
TOBA II BTK Clinical Study Protocol – Tack Endovascular System 
CA 0137 Rev C 
   
CA 0137 Rev C  
CONFIDENTIAL 
Page 66 of 76 
If the study is terminated by the Sponsor, the Investigator(s) will be promptly informed, who 
must then promptly inform the IRB/EC. If the IRB/EC terminates the study, the Investigator will 
promptly notify the Sponsor providing an explanation. 
21.13. COVERAGE OF SUBJECT EXPENSES 
The treated subjects will not be compensated for their time during the trial.  The Sponsor may 
provide reimbursement for reasonable out-of-pocket costs to the subject associated with travel, 
parking, or other expenses associated strictly with completing the protocol requirements of this 
study that would not normally be covered under routine medical coverage for the subject’s 
underlying medical condition. This will be provided on a case-by-case basis and will require 
Sponsor (and/or Designee) approval. 
21.14. CLINICAL STUDY REPORTS 
All information and data generated in association with the study will be held in strict confidence 
and remains the sole property of the Sponsor.  The Investigator agrees to use this information 
for the sole purpose of completing the study and for no other purpose without prior approval of 
the Sponsor.   
All progress reports will be generated and submitted to FDA by the Sponsor in compliance with 
periodic reporting requirements. If requested, all participating Investigators and clinical sites 
should provide assistance to the Sponsor regarding the data and any other pertinent 
information to be included in the study reports. All progress reports submitted to FDA will be 
summarized by the Sponsor and distributed to each site for IRB/EC review, which shall include 
all relevant feedback and/or approval provided by FDA. 
Upon receipt of the final study data and the final reports from each center, the Sponsor will 
complete a final study report.  Copies of the final report will be provided to each Investigator. 
21.15. PUBLICATION POLICIES 
At the conclusion of the study, a multi-center manuscript led by the national study Principal 
Investigator will be prepared with the assistance of Intact Vascular for publication in a 
reputable scientific journal. The publication of the principal results from any single center 
experience within the trial is not allowed until the preparation and publication of the multi-
center results as indicated in the Clinical Trial Agreement. Exceptions to this rule require the 
prior approval of National PI and Intact Vascular. For the purposes of timely abstract 
presentation and publication, secondary publications will be delegated to the appropriate 
principal authors, and final analyses and manuscript review for all multi-center data and/or 
single-center experience reports will require review from Intact Vascular. 
This study is registered with clinicaltrials.gov (NCT02942966). 
21.16. MEDICARE STUDY CRITERIA 
Access to clinical study data provides opportunities to conduct further research that can help 
advance medical science or improve patient care. This helps ensure the data provided by 
research participants are used to maximum effect in the creation of knowledge and 
understanding. To this end, the study's results information on all pre-specified outcomes, 
including negative outcomes, will be submitted to ClinicalTrials.gov not later than one year 
after the study completion date, where the completion date is defined as the date that the final 

 
TOBA II BTK Clinical Study Protocol – Tack Endovascular System 
CA 0137 Rev C 
   
CA 0137 Rev C  
CONFIDENTIAL 
Page 67 of 76 
subject was examined or received an intervention for purposes of data collection for the 
primary outcome measure. Results submission could be delayed if an extension is granted to 
the results submission deadline; however, the release of all results on pre-specified outcomes 
will be hastened if the study is terminated early. 
It is not anticipated that the device under investigation will treat a Medicare population 
different than the demographics found in the investigators' general population for this same 
condition, including populations eligible for Medicare due to age (e.g., 65 years or older), 
disability, or other eligibility status. Lower extremity peripheral artery disease remains one of 
the most unrecognized manifestations of systemic arteriosclerosis estimated to affect between 
3% and 7% of the population and up to one in five patients above the age of 75.2 While the 
overall prevalence of PAD ranges from 3% to 10%, PAD affects 12% to 20% of Americans aged 
65 years and older.34,35 Because the prevalence of PAD increases with age, the results of this 
study are expected to be generalizable to the Medicare eligible population primarily due to 
program eligibility due to age (E.g., 65 years or older).  
 
ECONOMIC ANALYSIS 
Intact Vascular will collect procedural and reimbursement data (if available) from multiple sources 
including but not limited to hospital billing forms and Medicare claims data. These data will be used 
to perform an economic analysis for the Tack Endovascular System.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
34Norgren L, Hiatt WR, Dormandy JA, et al. Inter-Society consensus for the management of peripheral arterial disease 
(TASC II). J Vasc Surg. 2007;45:S5-S67. 
35 Becker GJ, McClenny TE, Kovacs ME, et al. The importance of increasing public and physician awareness of peripheral 
arterial disease. J Vasc Interv Radiol. 2002;13:7-11. 

 
TOBA II BTK Clinical Study Protocol – Tack Endovascular System 
CA 0137 Rev C 
   
CA 0137 Rev C  
CONFIDENTIAL 
Page 68 of 76 
 
WIFI CLASSIFICATION TABLES 
Table 10, Table 11, and Table 12 below provide the criteria that is shall be used to determine 
WIfI classification.  
Table 10: Wound Grading 
W: WOUND 
SVS grades for rest pain and wounds/tissue loss (ulcers and gangrene): 
0 (ischemic rest pain, ischemia grade 3; no ulcer) 1 (mild) 2 (moderate) 3 (severe) 
Eligible to Enroll 
Wound 
Grade 
Clinical Description 
Ulcer 
Gangrene 
Yes 
0 
Ischemic rest pain 
(requires typical 
symptoms AND ischemia 
grade 3); no wound* 
No Ulcer 
No Gangrene 
Yes 
1 
Minor tissue loss. 
Salvageable with simple 
digital amputation (1 or 
2 digits) or skin 
coverage. 
Small, shallow ulcer(s) on 
distal leg 
or foot; no exposed bone, 
unless limited 
to distal phalanx 
No Gangrene 
Yes 
Modified 
2 
Tissue loss salvageable 
with simple digital 
amputation (1 or 2 
digits) or skin coverage. 
Deeper ulcer without 
exposed bone, joint or 
tendon; shallow or 
superficial heel ulcer, 
without deep tissue 
involvement or exposed 
calcaneus 
Gangrenous changes limited to 
digits 
No 
2 
Major tissue loss 
salvageable with 
multiple (≥3) digital 
amputations or standard 
TMA ± skin coverage. 
Deeper ulcer with exposed 
bone, joint or tendon; 
generally not involving the 
heel; shallow heel ulcer, 
without calcaneal 
involvement 
Gangrenous changes limited to 
digits 
No 
3 
Extensive tissue loss 
salvageable only with a 
complex foot 
reconstruction or 
nontraditional TMA 
(Chopart or Lisfranc); 
flap coverage or complex 
wound management 
needed for large soft 
tissue defect 
Extensive, deep ulcer 
involving forefoot and/or 
midfoot; deep, full thickness 
heel ulcer ± calcaneal 
involvement 
Extensive gangrene involving 
forefoot and /or midfoot; full 
thickness heel necrosis ± 
calcaneal involvement 
TMA, Transmetatarsal amputation. 
*Sponsor note: For the purpose of this study, subjects without presence of wound and gangrene should be classified as a 
Wound Grade of 0, regardless of their Ischemia grade. 
 
 
 
 
 

 
TOBA II BTK Clinical Study Protocol – Tack Endovascular System 
CA 0137 Rev C 
   
CA 0137 Rev C  
CONFIDENTIAL 
Page 69 of 76 
Table 11. Ischemia Grading 
I: Ischemia 
Hemodynamics/perfusion: Measure TP or TcPO2 if ABI incompressible (>1.3) 
SVS grades 0 (none), 1 (mild), 2 (moderate), and 3 (severe). 
Eligible to Enroll 
Ischemia Grade 
ABI 
Ankle Systolic Pressure 
TP,TcPO2 
Yes 
0 
≥0.80 
>100 mm Hg 
≥60 mm Hg 
Yes 
1 
0.60 - 0.79 
70-100 mm Hg 
40-59 mm Hg 
Yes 
2 
0.40 - 0.59 
50-70 mm Hg 
30-39 mm Hg 
Yes 
3 
≤0.39 
<50 mm Hg 
<30 mm Hg 
ABI, Ankle-brachial index; PVR, pulse volume recording; SPP, skin perfusion pressure; TP, toe pressure; TcPO2, 
transcutaneous oximetry. 
Patients with diabetes should have TP measurements. If arterial calcification precludes reliable ABI or TP measurements, 
ischemia should be documented by TcPO2, SPP, or PVR. If TP and ABI measurements result in different grades, TP will be the 
primary determinant of ischemia grade. 
Flat or minimally pulsatile forefoot PVR = grade 3. 
Table 12: Foot Infection Grading 
fI: Foot 
Infection 
SVS grades 0 (none), 1 (mild), 2 (moderate), and 3 (severe: limb and/or life-threatening) 
SVS adaptation of Infectious Diseases Society of America (IDSA) and International Working Group on the 
Diabetic Foot (IWGDF) perfusion, extent/size, depth/tissue loss, infection, sensation (PEDIS) classifications 
of diabetic foot infection 
Eligible to Enroll 
Foot 
Infection 
Grade 
Clinical Manifestation of infection 
IDSA/PEDIS 
infection 
severity 
Yes 
0 
No symptoms or signs of infection  
Uninfected 
Yes 
1 
Infection present, as defined by the presence of at least 2 of the following 
items:-  
 
Local swelling or induration 
 
Erythema >0.5 to ≤2 cm 
around the ulcer 
 
Local tenderness or pain 
 Local warmth 
 Purulent discharge (thick, 
opaque to white, or sanguineous 
secretion) 
Local infection (as described above) involving only the skin and the 
subcutaneous tissue (without involvement of deeper tissues and without 
systemic signs as described below). 
Exclude other causes of an inflammatory response of the skin (eg, trauma, 
gout, acute Charcot neuro-osteoarthropathy, fracture, thrombosis, venous 
stasis) 
Mild 
No 
2 
Local infection (as described above) with erythema >2 cm, or involving 
structures deeper than skin and subcutaneous tissues (eg, abscess, 
osteomyelitis, septic arthritis, fasciitis), and No systemic inflammatory 
response signs (as described below) 
Moderate 
No 
3 
Local infection (as described above) with the signs of SIRS, as manifested by 
two or more of the following: 
- Temperature >38° or <36° C 
- Heart rate >90 beats/min 
- Respiratory rate >20 breaths/min or PaCO2 <32 mm Hg 
- White blood cell count >12,000 or <4000 cu/mm or 10% immature (band) 
forms 
Severea 
PACO2, Partial pressure of arterial carbon dioxide; SIRS, systemic inflammatory response syndrome. 
aIschemia may complicate and increase the severity of any infection. Systemic infection may sometimes manifest with other 
clinical findings, such as hypotension, confusion, vomiting, or evidence of metabolic disturbances, such as acidosis, severe 
hyperglycemia, new-onset azotemia. 

 
TOBA II BTK Clinical Study Protocol – Tack Endovascular System 
CA 0137 Rev C 
   
CA 0137 Rev C  
CONFIDENTIAL 
Page 70 of 76 
 
STUDY DEFINITIONS 
Term 
Definition 
Activated Clotting Time (ACT)  
Clotting test for high-dose heparin anticoagulation. 
Acute Renal Failure 
Acute post-operative renal insufficiency resulting in one or 
more of the following  (a) an increase of > 1.0 mg/dl in serum 
creatinine from most recent prior measured level, and 
current measured absolute value is > 2.2 mg/dl; (b) a new 
requirement for dialysis. 
Adverse Device Effect (ADE) 
An adverse device effect is defined as any untoward adverse 
event related to the use of an investigational or unintended 
response to a medical device.   
  Note 1: This definition includes adverse events resulting 
from insufficient or inadequate Instructions for Use, 
deployment, implantation, installation, or operation, or any 
malfunction of the investigational medical device. This 
definition includes any event resulting from insufficiencies or 
inadequacies in the Instructions for Use or the deployment of 
the device or any event that is a result of not observing the 
IFU. 
  Note 2: This definition includes any event resulting from 
use error or from intentional misuse of the investigational 
medical device. 
Adverse Event (AE) 
An adverse event (AE) is any untoward medical occurrence, 
unintended disease or injury, or untoward clinical signs 
(including abnormal laboratory findings) in subjects, users or 
other persons, whether or not related to the investigational 
device/procedure. 
Allergic Reaction 
An allergic reaction characterized by rash, nausea, vomiting, 
upper respiratory congestion, urticaria, shortness-of-breath, 
vasovagal reaction, or general collapse (anaphylaxis). 
Amputation-free Survival 
Freedom from above-ankle target limb amputation or all-
cause death  
Ankle / Brachial Index (ABI) 
The ratio of systolic blood pressure measured at the ankle to 
systolic blood pressure measured at the brachial artery. The 
ABI is calculated by dividing the ankle pressure [the higher of 
the dorsalis pedis (DP) or posterior tibial (PT) artery] by the 
brachial systolic pressure (the higher of two arm pressures).  
Assisted Primary Target 
Lesion Tacked Segment 
Patency  
Assisted primary patency (freedom from total occlusion) 
achieved with the use of an additional or secondary surgical 
or endovascular procedures, as long as total occlusion of the 
Tacked segment has not occurred prior to such procedures. 
In all cases, freedom from total occlusion is confirmed by 
angiography or DUS (flow vs. no flow) if angiography was not 
performed.  

 
TOBA II BTK Clinical Study Protocol – Tack Endovascular System 
CA 0137 Rev C 
   
CA 0137 Rev C  
CONFIDENTIAL 
Page 71 of 76 
Term 
Definition 
Bailout Stenting 
Unplanned stenting to the target lesion and/or Tack 
implant(s). The use of a bailout stent may occur in the event 
of persistent flow-limiting dissection not able to be treated 
with the Tack (or as otherwise required for safety of the 
subject).  
Balloon Angioplasty 
A catheter containing an inflatable balloon (standard 
uncoated) is advanced through a narrowed or occluded 
portion of an artery and inflated in order to open the artery 
and restore blood flow. Also referred to as “PTA” 
(percutaneous transluminal angioplasty). 
Binary Restenosis 
Greater than or equal to 50% restenosis determined by 
angiography or by duplex ultrasound derived peak systolic 
velocity ratio (PSVR) of ≥2.5:1. 
De Novo Lesion 
A lesion in the artery that has not been previously treated. 
Device Deficiency 
Inadequacy of a medical device related to its identity, quality, 
durability, reliability, safety or performance, such as 
malfunction, misuse or not observing the IFU and inadequate 
labeling. 
Device Malfunction 
A malfunction of a device to perform in accordance with its 
intended purpose when used in accordance with the 
Instructions for Use. 
Device Success 
Successful deployment of the Tack(s) at the intended target 
site(s) and successful withdrawal of the delivery catheter 
from the introducer sheath.  
Dissection 
Disruption of an arterial wall resulting in separation of the 
intimal layer. May or may not be flow limiting. 
  
Dissection Types (National Heart, Lung and Blood 
Institute – NHLBI) 
Type A 
 Small radiolucent area within the lumen of the vessel 
disappearing with the passage of the contrast material. 
Type B 
 Appearance of contrast medium parallel to the lumen of the 
vessel disappearing within a few cardiac cycles. 
Type C 
 Dissection protruding outside the lumen of the vessel 
persisting after passage of the contrast material. 
Type D 
 Spiral shaped filling defect with our without delayed run-off 
of the contrast material in the antegrade flow. 
Type E 
 Persistent luminal filling defect with delayed run-off of the 
contrast material in the distal lumen. 
Type F 
 Filling defect accompanied by total occlusion. 
Drug-Coated Balloon (DCB)  
Drug-coated balloon catheter used for percutaneous 
transluminal (balloon) angioplasty.  
Duplex Ultrasound (DUS) 
A form of medical ultrasonography that includes the 
following elements on the same screen (“duplex”) to facilitate 
interpretation 1) B-mode, pulsed Doppler display to visualize 
the structure within a vessel and 2) Color-Doppler display to 
visualize the blood flow and hemodynamics within a vessel. 

 
TOBA II BTK Clinical Study Protocol – Tack Endovascular System 
CA 0137 Rev C 
   
CA 0137 Rev C  
CONFIDENTIAL 
Page 72 of 76 
Term 
Definition 
DUS Flow / No Flow 
DUS Flow - Visualization of color Doppler and pulsed Doppler 
detectable flow within an arterial segment  
  
DUS No Flow – Absence of color Doppler and pulsed Doppler 
detectable flow within an arterial segment with evidence of 
flow within the corresponding venous segment 
Index Procedure 
The interventional procedure during which the study device 
is advanced through the introducer sheath and the subject is 
enrolled. 
Intent-to-treat (ITT) subjects 
A subject is defined as an intent-to-treat (ITT) patient and 
officially enrolled in the study once the Tack Endovascular 
System is advanced through the introducer sheath. 
Lesion Success 
Demonstrated target lesion patency (<30% residual DS, by 
visual estimate) without the use of a bailout stent. This will 
be assessed for all lesions treated with a Tack. In addition, 
target lesion success will also be analyzed by lack of bailout 
stent to tacked segment only. Multiple target lesions treated 
as one lesion with PTA will be analyzed as one lesion. 
Limb Salvage 
Freedom from any above-ankle target limb amputation 
Major Adverse Event (MALE) 
Above-ankle target limb amputation or major re-intervention 
to the target lesion(s) (defined as new bypass graft, 
jump/interposition graft revision, or thrombectomy / 
thrombolysis) 
Major Re-intervention 
New bypass graft, jump/interposition graft revision, or 
thrombectomy / thrombolysis occurring after the index 
procedure 
Major Amputation 
Any above the ankle amputation to the target limb. 
Minor Amputation 
Any below the ankle amputation to the target limb (digital or 
transmetatarsal (ray or complete)) 
Minor Re-intervention 
Endovascular procedures (PTA, atherectomy, stenting) 
without thrombectomy/thrombolysis, and minor surgical 
revisions (patch angioplasty) occurring after the index 
procedure 
Myocardial Infarction (MI) 
Q wave MI (QWMI): requires one of the following criteria:   
• Chest pain or other acute symptoms consistent with 
myocardial ischemia and new pathological Q waves in two or 
more contiguous ECG leads  
• New pathologic Q waves in two or more contiguous ECG 
leads and elevation of cardiac enzymes above normal.   
  
Non-Q Wave MI (NQWMI): defined as either: elevated CK = 
2X the laboratory upper limit of normal with the presence of 
an elevated CK-MB (any amount above the laboratory upper 
limit of normal) in the absence of new pathological Q waves 
or elevated CK-MB = 3X the laboratory upper limit of normal 
in the absence of new pathological Q waves.   

 
TOBA II BTK Clinical Study Protocol – Tack Endovascular System 
CA 0137 Rev C 
   
CA 0137 Rev C  
CONFIDENTIAL 
Page 73 of 76 
Term 
Definition 
Peak Systolic Velocity Ratio 
(PSVR) 
A measurement (using Duplex Ultrasonography) of peak 
velocity of blood (cm/sec) within a lesion or stented vessel 
segment that is divided by the peak velocity of blood 
(cm/sec) proximal to the lesion of stented segment.  
Per-protocol (PP) subjects 
The per-protocol (PP) population is defined as ITT subjects 
with evaluable data that have met the definition for device 
success, excluding subjects with major protocol deviations 
such as: 
  A major inclusion/exclusion criterion violation; or 
  A major procedural deviation 
 
The criteria for deviations meeting the classification of 
“major” will be defined by an independent designee before 
study endpoint data is available for statistical analysis. 
Perioperative Death (POD) 
All-cause death occurring at 30 days after the Index 
Procedure 
Primary Efficacy Endpoint 
Freedom from major adverse limb events (MALE) at 6 
months plus peri-operative death (POD) at 30 days defined 
as a composite of all-cause death, above-ankle target limb 
amputation, or major re-intervention to the target lesion(s) 
(defined as new bypass graft, jump/interposition graft 
revision, or thrombectomy / thrombolysis) 
Primary Safety Endpoint 
Freedom from BTK MALE+POD at 30 days. Composite of all-
cause death, above-ankle target limb amputation or major re-
intervention to the target lesion(s) (defined as new bypass 
graft, jump/interposition graft revision, or thrombectomy / 
thrombolysis) 
Procedural Success 
Demonstrated target lesion patency (<30% residual DS, by 
visual estimate) without the use of a bailout stent and 
without the occurrence of MALE+POD upon completion of 
the index procedure. 
Restenosis 
Reoccurrence of narrowing or blockage or target lesion. 
Rutherford Classification  
Clinical scale identifying three grades of claudication and 
three grades of critical limb ischemia ranging from rest pain 
alone to minor and major tissue loss.  
Class 
Clinical Description 
0 
Asymptomatic —no hemodynamically significant occlusive 
disease 
1 
Mild claudication 
2 
Moderate claudication 
3 
Severe claudication 
4 
Ischemic rest pain 
5 
Minor tissue loss—nonhealing ulcer, focal gangrene with 
diffuse pedal ischemia 
6 
Major tissue loss—extending above TM level, functional foot 
no longer salvageable 

 
TOBA II BTK Clinical Study Protocol – Tack Endovascular System 
CA 0137 Rev C 
   
CA 0137 Rev C  
CONFIDENTIAL 
Page 74 of 76 
Term 
Definition 
Secondary Efficacy Endpoints: 
 
Target lesion(s) tacked segment(s) patency at 6 
months defined as the presence of blood flow using 
duplex ultrasound. If angiography is available within 
the 6-month follow-up visit window, it should be 
used in place of the duplex ultrasound. Evidence of no 
blood flow within the Tacked segment indicates 
restenosis/loss of patency.  
 
Target Limb Salvage defined as freedom from any 
above-ankle target limb amputation at 6 months. 
Secondary Target Lesion 
Tacked Segment Patency 
Secondary patency (freedom from total occlusion) achieved 
with the use of an additional or secondary surgical or 
endovascular procedures. In all cases, freedom from total 
occlusion is confirmed by angiography or DUS (flow vs. no 
flow) if angiography was not performed. 
Serious Adverse Device Event 
(SADE) 
A serious adverse device effect (SADE) is defined as an 
adverse device effect (ADE) that results in any of the 
consequences characteristics of a serious adverse event 
(SAE). (See ADE) 
Serious Adverse Event (SAE) 
A serious adverse event (SAE) is defined an adverse event 
that:   
  led to death  
  led to a serious deterioration in the health of the subject, 
that either resulted in: 
  a life-threatening illness or injury, or 
  resulted in a permanent impairment of a body structure or 
a body function, or  
  required in-patient hospitalization or prolongation of 
existing hospitalization, or 
  resulted in medical or surgical intervention to prevent life-
threatening illness or injury or permanent impairment to 
body structure or a body function, or  
  led to fetal distress, fetal death or a congenital abnormality 
or birth defect. 
Note: Planned hospitalization for a pre-existing condition, or 
a procedure required by the investigational plan without 
serious deterioration in health, is not considered a serious 
adverse event.   
Standard Balloon Angioplasty  
A standard balloon catheter (non-drug-coated) used to 
perform percutaneous transluminal (balloon) angioplasty. 
Also referred to as Plain Old Balloon Angioplasty (POBA) 
Stroke 
A neurological deficit lasting more than 24 hours with a brain 
imaging study (if performed) showing infarction or 
hemorrhage. 
Study Device Procedure 
Start/End Time 
Start: The time the first Tack Endovascular System is 
advanced through the introducer sheath                                            
End: The time of withdrawal of last post-Tack PTA balloon 
catheter 

 
TOBA II BTK Clinical Study Protocol – Tack Endovascular System 
CA 0137 Rev C 
   
CA 0137 Rev C  
CONFIDENTIAL 
Page 75 of 76 
Term 
Definition 
Tacked Segment 
Defined as the Tack device and 5 mm of artery proximal and 
distal to each Tack. If Tacks are within 10 mm of each other, 
they will be considered as a single tacked segment for the 
purposes of this patency assessment. 
Target Lesion Tacked Segment 
Patency  
Patency defined as the presence of blood flow using duplex 
ultrasound. If angiography is available within the follow-up 
visit window, it should be used in place of the duplex 
ultrasound. Evidence of no blood flow within the Tacked 
segment indicates restenosis/loss of patency. 
Target Lesion 
The lesion(s) that are assessed and if eligible, treated with 
the study device.  
 
After PTA treatment, the target lesion length is defined as the 
entire contiguous arterial segment treated with angioplasty 
and may also be referred to as the “treated lesion”. 
 
The target lesion(s) may be de novo or non-stented 
restenotic with pre-PTA stenosis of ≥70% or is occluded (by 
visual estimate) and is indicated for PTA treatment with a 
standard balloon catheter 
 
Note: If the lesion is restenotic, no part of the lesion should 
have more than 1 prior failure (by plain balloon angioplasty 
only), which must have occurred greater than 1 year (360 
days) prior to the index procedure 
 
Note: Diseased segments with >30mm between them are 
considered separate lesions  
 
Note: After PTA treatment, the target lesion is defined as the 
entire contiguous arterial segment treated with angioplasty 
Target Lesion 
Revascularization, Clinically-
driven (CD-TLR) 
Any re-intervention (endovascular or surgical) to the target 
lesion(s) in subjects with recurrent clinical symptoms 
indicated by a worsening Rutherford classification (increase 
of one category or more) since earliest post-procedure 
classification or a new or worsening wound. The designation 
of CD-TLR should be corroborated by angiographic evidence 
of ≥50% DS at the time of repeat intervention and will be 
adjudicated by the CEC. This trial will evaluate CD-TLR based 
on a per lesion analysis as well as the Tack treated section of 
the target lesion.  
Target Lesion 
Revascularization (TLR)  
Any re-intervention (endovascular or surgical) to the target 
lesion(s) occurring after the index procedure. 

 
TOBA II BTK Clinical Study Protocol – Tack Endovascular System 
CA 0137 Rev C 
   
CA 0137 Rev C  
CONFIDENTIAL 
Page 76 of 76 
Term 
Definition 
Target Vessel  
The vessel location(s) of the target lesion(s). Lesions may be 
eligible for study device treatment if located within the 
following arteries: mid popliteal (P2), distal popliteal (P3), 
tibioperoneal trunk, peroneal, anterior tibial, or posterior 
tibial 
 
Note: The Mid Popliteal artery (P2) begins at the superior 
aspect of the patella. The most distal location of the tibial 
and/or peroneal artery(ies) ends at the beginning of the 
dorsalis pedis artery (DP). Tacks may not be implanted 
within 1cm of, or below, the radiographic tibiotalar joint 
Target Vessel 
Revascularization, Clinically-
driven (CD-TVR) 
Any re-intervention (endovascular or surgical) to the target 
vessel(s) in subjects with recurrent clinical symptoms 
indicated by a worsening Rutherford classification (increase 
of one category or more) since earliest post-procedure 
classification or a new or worsening wound. The designation 
of CD-TVR should be corroborated by angiographic evidence 
of ≥50% DS at the time of repeat intervention and will be 
adjudicated by the CEC. 
Target Vessel 
Revascularization (TVR)  
Any re-intervention (endovascular or surgical) to the target 
vessel(s) occurring after the index procedure. 
Toe/Brachial Index (TBI) 
The ratio of systolic blood pressure measured at the toe to 
systolic blood pressure measured at the brachial artery. The 
TBI is calculated by dividing the toe pressure by the brachial 
systolic pressure (the higher of two arm pressures).  
Transient Ischemic Attack 
(TIA) 
Clinical signs/symptoms of focal neurological deficit lasting 
up to 24 hours 
Treatment PTA 
Refers to the PTA performed to the target lesion(s) prior to 
introduction of the study device 
Unanticipated Adverse Device 
Event (UADE) 
Any serious adverse effect on health or safety or any life-
threatening problem or death caused by, or associated with, a 
device, if that effect, problem, or death was not previously 
identified in nature, severity, or degree of incidence in the 
investigational plan or application (including a 
supplementary plan or application), or any other 
unanticipated serious problem associated with a device that 
relates to the rights, safety, or welfare of subjects. 
Unplanned Procedure 
A procedure that was not planned at the time of subject 
enrollment.