VIRTUS Safety and Efficacy of the Veniti Vici™ Venous Stent System (Veniti, Inc.) When Used to Treat Clinically Significant Chronic Non-malignant Obstruction of the Iliofemoral Venous Segment
Phase: NA
Conditions: Chronic Venous Disorder, Venous Outflow Obstruction, Symptomatic Venous Outflow Obstruction of Iliofemoral Vein
Sponsor: Boston Scientific Corporation

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VIRTUS 
Safety and Efficacy of the Veniti Vici® 
Venous Stent System (Veniti Inc.) when 
Used to Treat Clinically Significant 
Chronic Non-malignant Obstruction of 
the Iliofemoral Venous Segment  
 
 
 Protocol Number: 
STE-HUM-007P 
 
 
   Revision: 
            C 
 
 
                                                           Date:  
 
  
06Nov2015 
 
 
Product: 
  
Veniti Vici Venous Stent System 
 
 
 
Sponsored By: 
Veniti, Inc. 
1610 Des Peres Road, Suite 385 
St. Louis, MO  63131 
 
This investigational protocol contains confidential information for the sole use of the investigators and 
their designated representatives participating in Veniti protocol STE-HUM-007P.  This protocol 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. 

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Statement of Compliance and Signature Page 
 
 
 
 
I have read this Investigational Protocol and agree to adhere to the requirements.     
I will provide copies of this Investigational Protocol and all pertinent information to the Study 
personnel under my supervision.  
I will discuss this material with them and ensure they are fully informed regarding the Study 
products.  
I will ensure that the study is conducted in compliance with the Investigational Protocol, Good 
Clinical Practice (GCP), the Declaration of Helsinki, ICH (Sixth Revision, 2008), ISO 14155-2011, 
EU Confidentiality Requirements, and all applicable regulatory and Independent Ethics 
Committee (EC) requirements. 
 
 
Clinical Site Name: ______________________________________________________ 
Please print 
 
 
 
The signature below constitutes the approval of this Investigational Protocol and any 
attachments, and provides the necessary assurances that this trial will be conducted according 
to the above conditions. 
 
 
Site Principal Investigator:   
 
____________________________________________________________ 
                                                              Print Name & Title 
 
 
Signature: 
 
 
 
Date: 
 
 
 
 
 
DD/MMM/YYYY 
 
 
 
 
 

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Table of Contents 
1 KEY PROTOCOL DEFINITIONS ...................................................................................................... 9 
2 PROTOCOL SUMMARY ................................................................................................................. 12 
3 KEY ROLES AND STUDY CONTACTS ........................................................................................ 17 
4 INTRODUCTION .............................................................................................................................. 19 
4.1 
ETIOLOGY AND PATHOPHYSIOLOGY OF VENOUS DISEASE ................................................... 19 
4.2 
BENEFITS AND RISKS OF VENOUS STENTING ......................................................................... 19 
4.3 
ASSESSMENT OF CURRENT VENOUS STENTS .......................................................................... 20 
5 INVESTIGATIONAL PRODUCT ................................................................................................... 21 
5.1 
DEVICE DESCRIPTION .............................................................................................................. 21 
5.2 
INTENDED USE ......................................................................................................................... 22 
6 POTENTIAL RISKS AND BENEFITS ........................................................................................... 22 
6.1 
POTENTIAL RISKS .................................................................................................................... 22 
6.2 
POTENTIAL BENEFITS/ADVANTAGES OF TREATMENT/PRODUCT...................................... 22 
7 STUDY OBJECTIVE AND DESIGN ............................................................................................... 23 
7.1 
PRIMARY ENDPOINT – EFFICACY: .......................................................................................... 23 
7.2 
PRIMARY ENDPOINT – SAFETY: .............................................................................................. 23 
7.3 
SECONDARY ENDPOINT – EFFICACY: ...................................................................................... 23 
7.4 
ANCILLARY OUTCOMES: .......................................................................................................... 23 
8 PATIENT POPULATION ................................................................................................................ 24 
8.1 
INITIAL DSMB SAFETY EVALUATION .................................................................................... 24 
8.2 
INCLUSION/EXCLUSION CRITERIA .......................................................................................... 25 
8.2.1 
INCLUSION CRITERIA – PRE-PROCEDURAL CRITERIA ...................................................... 25 
8.2.2 
EXCLUSION CRITERIA - PRE-PROCEDURAL CRITERIA ...................................................... 25 
8.2.3 
EXCLUSION CRITERIA – INTRA-PROCEDURAL CRITERIA .................................................. 26 
9 STUDY PROCEDURES AND DATA COLLECTION ................................................................... 26 
9.1 
PATIENT SCREENING PROCEDURE .......................................................................................... 26 
9.2 
INFORMED CONSENT ................................................................................................................ 27 
9.3 
BASELINE EVALUATION (WITHIN 30 DAYS OF IMPLANT PROCEDURE) ............................... 27 
9.4 
PRE-PROCEDURAL EVALUATION ............................................................................................ 27 
9.5 
VENOUS STENT IMPLANT PROCEDURE .................................................................................. 27 
9.5.1 
PROCEDURE GUIDELINES ....................................................................................................... 27 
9.5.2 
PERIOPERATIVE ANTICOAGULATION REGIMEN ................................................................. 28 
9.5.3 
POST-STENT PLACEMENT ASSESSMENTS ........................................................................... 28 

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9.6 
DISCHARGE OR THREE DAYS POST-PROCEDURE (WHICHEVER COMES FIRST) .................. 30 
9.7 
1 MONTH EVALUATION (30 DAYS -7/+14 DAYS) ............................................................... 30 
9.8 
6 MONTH EVALUATION (180 DAYS ± 30 DAYS) .................................................................. 30 
9.9 
12 MONTH EVALUATION (365 DAYS ± 60 DAYS) ................................................................ 30 
9.10 INTERVAL EVALUATION........................................................................................................... 31 
9.11 24 MONTH EVALUATION (730 DAYS ± 90 DAYS) ................................................................ 31 
9.12 36 MONTH EVALUATION (1,095 DAYS ± 90 DAYS) ............................................................ 31 
9.13 48 MONTH EVALUATION (1,460 DAYS ± 90 DAYS) ............................................................ 32 
9.14 60 MONTH EVALUATION (1,825 DAYS ± 90 DAYS) ............................................................ 32 
10 SUMMARY OF PROCEDURES ...................................................................................................... 33 
11 ADVERSE EVENTS .......................................................................................................................... 34 
11.1 EVENT DEFINITIONS ................................................................................................................ 34 
11.1.1 ADVERSE EVENT ..................................................................................................................... 34 
11.1.2 SERIOUS ADVERSE EVENT ..................................................................................................... 34 
11.1.3 DEVICE DEFICIENCY ............................................................................................................... 35 
11.1.4 MAJOR ADVERSE EVENT (MAE) .......................................................................................... 35 
11.1.5 ADVERSE DEVICE EFFECTS (ADE) ...................................................................................... 35 
11.1.6 SERIOUS ADVERSE DEVICE EFFECTS (SADE) ................................................................... 35 
11.1.7 UNANTICIPATED SERIOUS ADVERSE DEVICE EFFECTS (USADE) ................................. 36 
11.2 REPORTING OF ADVERSE EVENTS .......................................................................................... 36 
11.3 RELATEDNESS TO THE STUDY PROCEDURE, STUDY DEVICE ................................................ 36 
11.4 REPORTING A DEATH .............................................................................................................. 37 
11.5 PROTOCOL DEVIATIONS .......................................................................................................... 37 
11.6 DEVICE MALFUNCTIONS .......................................................................................................... 37 
12 CLINICAL EVENTS COMMITTEE (CEC) .................................................................................... 37 
13 DATA SAFETY MONITORING BOARD (DSMB) ..................................................................... 37 
14 INVESTIGATIONAL DEVICE DISTRIBUTION AND TRACKING ......................................... 38 
15 STATISTICAL METHODS .............................................................................................................. 38 
15.1 OVERVIEW OF STUDY DESIGN ................................................................................................. 38 
15.2 MISSING DATA ......................................................................................................................... 39 
15.3 PRIMARY ANALYSIS:  PER-PROTOCOL .................................................................................... 39 
15.3.1 SENSITIVITY ANALYSES:  WORST-CASE AND TIPPING POINT .......................................... 39 
15.4 POOLABILITY ANALYSIS .......................................................................................................... 39 
15.5 DEVELOPMENT OF THE PERFORMANCE GOAL (PG) – PRIMARY EFFICACY ENDPOINT ..... 40 
15.5.1 RATIONALE .............................................................................................................................. 40 
15.5.2 HISTORICAL PATENCY RATES ............................................................................................... 40 
15.5.3 ENROLLMENT IN THE VIRTUS STUDY ................................................................................ 42 
15.6 HYPOTHESES AND SAMPLE SIZE ESTIMATE ........................................................................... 43 

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15.7 PRIMARY EFFICACY ENDPOINT ............................................................................................... 43 
15.7.1 PRIMARY SAFETY ENDPOINT ................................................................................................ 44 
15.7.2 PRIMARY SECONDARY ENDPOINT ........................................................................................ 45 
15.8 EVALUATION OF ENDPOINTS ................................................................................................... 45 
15.8.1 PRIMARY EFFICACY ENDPOINT ............................................................................................ 45 
15.8.2 PRIMARY SAFETY ENDPOINT ................................................................................................ 46 
15.8.3 SECONDARY EFFICACY ENDPOINT ....................................................................................... 47 
15.9 EVALUATION OF ANCILLARY ENDPOINTS .............................................................................. 47 
15.9.1 PROCEDURAL ENDPOINTS ..................................................................................................... 47 
15.9.2 CLINICAL ENDPOINTS ............................................................................................................. 47 
16 CORE LAB ASSESSMENTS ............................................................................................................ 48 
16.1 VENOGRAM CORE LABORATORY............................................................................................. 48 
16.2 DUPLEX ULTRASOUND CORE LABORATORY .......................................................................... 48 
16.3 IVUS CORE LABORATORY ....................................................................................................... 48 
17 INSTRUCTIONS FOR USE ............................................................................................................. 48 
18 INVESTIGATOR TRAINING ......................................................................................................... 48 
19 MONITORING PROCEDURES ...................................................................................................... 48 
19.1 SITE MONITORING PLAN ......................................................................................................... 48 
19.2 SITE INITIATION VISIT............................................................................................................. 49 
19.3 ROUTINE MONITORING ........................................................................................................... 49 
19.4 CLOSEOUT VISIT ....................................................................................................................... 50 
20 INSTITUTIONAL REVIEW BOARD/ETHICS COMMITTEE (IRB/EC) .............................. 50 
21 SUBJECTS’ CONFIDENTIALITY .................................................................................................. 50 
22 PUBLICATIONS ............................................................................................................................... 51 
23 DATA MANAGEMENT ................................................................................................................... 51 
24 TERMINATION OF STUDY ........................................................................................................... 52 
25 ADDITIONAL RECORDS AND REPORTS ................................................................................. 52 
25.1 INVESTIGATOR RECORDS ........................................................................................................ 52 
25.2 INVESTIGATOR REPORTS......................................................................................................... 52 
25.3 IRB/EC RECORDS ................................................................................................................... 54 
26 APPENDIX 1: VENOUS ANATOMY DESIGNATIONS ............................................................. 55 
27 APPENDIX 2: EXTENDED ANTICOAGULATION PROTOCOL ............................................ 56 

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28 APPENDIX 3: FRACTURES ........................................................................................................... 57 
29 APPENDIX 4: ADDITIONAL STUDY DEFINITIONS............................................................... 58 
30 APPENDIX 5: CHRONIC VENOUS INSUFFICIENCY QUESTIONAIRRE (CIVIQ-2)......... 61 
31 APPENDIX 6: VISUAL ANALOG SCALE (VAS PAIN SCALE) ................................................ 64 
32 APPENDIX 7: VENOUS CLINICAL SEVERITY SCORE (VCSS) ............................................. 65 
32.1 VCSS DEFINITIONS .................................................................................................................. 66 
33 APPENDIX 8: REFERENCES ......................................................................................................... 69 

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Abbreviations  
List of Abbreviations 
ADE 
Adverse Device Effect 
AE 
Adverse Event/Adverse Experience 
ANOVA 
Analysis of Variance 
CEAP 
Clinical-Etiology-Anatomic-Pathophysiologic 
CEC 
Clinical Events Committee 
CFV 
Common Femoral Vein 
CIV 
Common Iliac Vein 
CIVIQ-2 
Chronic Venous Insufficiency Questionnaire 
CFR 
Code of Federal Regulations 
CRF 
Case Report Form 
CRO 
Contract Research Organization 
CT-V 
Computed Tomography Venography 
CVD 
Chronic Venous Disorder(s) 
CVI 
Chronic Venous Insufficiency 
DSMB 
Data Safety Monitoring Board 
DUS 
Duplex Ultrasound 
DVT 
Deep Venous Thrombosis 
EC 
Ethics Committee 
eCRF 
Electronic Case Report Form 
EDC 
Electronic Data Capture 
eGFR 
Estimated Glomerular Filtration Rate 
EIV 
External Iliac Vein 
EKG/ECG 
Electrocardiogram 
GCP 
Good Clinical Practice 
HIPAA 
Health Insurance Portability and Accountability Act 
HO  
Null Hypothesis 
HA 
Alternative Hypothesis 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization 

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List of Abbreviations 
IDE 
Investigational Device Exemption 
IFU 
Instructions for Use 
IRB 
Institutional Review Board 
ITT 
Intention to Treat 
IVC 
Inferior Vena Cava 
IVUS 
IntraVenous UltraSound 
MAE 
Major Adverse Events 
MI 
Myocardial Infarction 
MR-V 
Magnetic Resonance Venography 
OUS 
Outside the United States 
PHI 
Protected Health Information 
PI 
Principal Investigator 
QoL 
Quality of Life 
RIE 
Rate of Intervention of Extremity 
RIL 
Rate of Intervention Lesion 
RVD 
Reference Vein Diameter 
SAE 
Serious Adverse Event 
UADE 
Unanticipated Adverse Device Effect 
VCSS 
Venous Clinical Severity Score 
VKA 
Vitamin K Agonists 
 
 
 

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1 
KEY PROTOCOL DEFINITIONS 
PRE-PROCEDURAL DEFINITIONS 
Term 
Definition 
Extremity thrombosis 
Acute symptomatic thrombosis of the venous system of either 
lower extremity that is not located within the target vessel  
Iliofemoral venous segment 
The venous system comprised of the common femoral vein, 
the external iliac vein, and the common iliac vein (2012 
SVS/AVF Guidelines.  See Appendix 1). 
Nonmalignant venous 
obstruction 
Non-thrombotic or post-thrombotic obstruction of the 
iliofemoral venous segment that is not due to direct incursion 
of the vein by malignancy 
Venous Obstruction 
Reduction of the venous lumen diameter ≥ 50% when 
compared to the diameter of the normal vein/RVD 
immediately peripheral to the obstructed vein as measured by 
venogram.   
Venous Occlusion 
Total obliteration of the venous lumen 
PROCEDURAL DEFINITIONS 
Term 
Definition 
Binary stenosis (or 
obstruction) 
≥50% reduction of the venous lumen diameter when 
compared to the venous lumen diameter of the normal vein 
immediately peripheral to the obstructed vein as measured by 
venogram  
Lesion success 
Achievement of ≤50% residual diameter stenosis of the target 
lesion using any percutaneous method (including the use of 
non-study devices)  
Migration 
Device movement >10mm related to anatomical landmarks or 
any migration leading to symptoms or requiring therapy 
Procedural success 
Technical success without the occurrence of major adverse 
event between the index procedure and discharge 
Residual diameter stenosis 
The greatest degree of stenosis in the target lesion post-
procedure, defined by the percent reduction in vessel lumen 
diameter when compared to the normal vein immediately 
peripheral to the target lesion as measured by venogram. 
Stent Embolization 
Dislodgement of the entire stent, which is carried by the blood 
flow to a different anatomical site of the vascular system, with 
no overlap in comparison to the original stent placement 

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Target lesion 
The treated segment starting 5 mm peripheral and ending 5 
mm centrally to the study device(s) 
Target vessel  
Native vein containing the target lesion such as the common 
iliac vein (CIV), external iliac vein (EIV) or common femoral 
vein (CFV) 
Target vessel stenosis 
Maximum percentage reduction in target lesion diameter 
when compared with the diameter of the normal vein/RVD 
immediately below the lesion as measured by venogram 
Reference Vein Diameter 
(RVD) 
Reference Vein Diameter (RVD) is defined as the normal 
diameter of the target vessel (CIV, EIV, or CFV) 
Procedural technical success 
Achievement of a final residual target vessel diameter 
stenosis of ≤50% as measured on the post procedural 
venogram, without skipped lesion regions, with placement of 
the study device alone with or without post-stenting balloon 
dilation as needed 
POST-PROCEDURAL DEFINITIONS 
Term 
Definition 
Device or procedure related 
death 
• 
Death specifically attributable to the Veniti Vici Venous 
Stent System or the stent placement procedure 
Late technical success 
• 
Absence of device movement >10mm related to 
anatomical landmarks or any migration leading to 
symptoms or requiring therapy 
• 
Absence of stent occlusion by thrombosis or restenosis, 
defined as reduction in treated segment lumen more than 
50% from the post-procedure vessel lumen diameter as 
measured by post-procedural venogram or DUS 
• 
Structural integrity, defined as the absence of pinching 
(focal compression), recoil (poor radial resistive force) or 
kinking (stent bending upon itself) that results in >50% 
diameter reduction of the stent, or fracture 
Patency (Primary Endpoint) 
At 12 months post-intervention, freedom from occlusion by 
thrombosis AND freedom from surgical or endovascular 
intervention on target vessel with re-stenosis or stent 
occlusion to maintain patency AND freedom from in stent 
diameter stenosis more than 50% as measured by venogram. 
For patients refusing the venographic assessment at 12 
months, DUS-determined patency will be used instead 

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Rate of intervention lesion 
(RIL) 
Re-intervention within the target vessel with in-stent stenosis 
or thrombosis to achieve patency  (constitutes failure on the 
primary endpoint) 
Rate of intervention of 
extremity (RIE) 
Re-intervention of a non-target lesion venous segment of the 
ipsilateral (target) extremity required to maintain ipsilateral 
extremity venous outflow (does NOT constitute failure of the 
primary endpoint) 
In-stent stenosis (primary 
endpoint) 
Non-occlusive reduction in the treated segment lumen 
diameter more than 50% from the post-procedural vessel 
lumen diameter per venogram or DUS  
In-stent thrombosis  
(primary endpoint) 
Occlusion of the stented target vessel due to thrombosis; early 
thrombosis is that which occurs ≤30 days; late thrombosis is 
that which occurs >30 days 
Structural integrity 
Absence of the following changes in stent morphology: 
• 
Pinching, defined as focal compression of the stent with 
>50% diameter reduction of the stent 
• 
Kinking, defined as >50% diameter reduction of the stent 
with the stent doubling or bending on itself  
• 
Recoil, defined a poor radial resistance to diffuse collapse, 
which results in >50% diameter reduction of the stent 
(i.e., stent diameters obtained throughout the study 
period as compared to the final stent diameter after 
insertion measured by DUS or venogram)  
• 
Fracture(s) as defined in Appendix 3  
 
 
 

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2 
PROTOCOL SUMMARY 
Study Title 
VIRTUS: Safety and Efficacy of the Veniti Vici® Venous Stent System 
(Veniti, Inc.) when Used to Treat Clinically Significant Chronic Non-
malignant Obstruction of the Iliofemoral Venous Segment 
Study Device 
Veniti Vici Venous Stent System 
Regulatory Status 
The Veniti Vici Venous Stent System has the CE mark.  In the United 
States, the Veniti Vici Venous Stent System will be studied under an 
Investigational Device Exemption (IDE), upon approval/conditional 
approval of an IDE submission. 
Study Objective 
The objective of this study is to assess the safety and efficacy of the 
Veniti Vici Venous Stent System in achieving patency of the target 
venous lesion in patients who present with clinically significant 
chronic non-malignant obstruction of the iliofemoral venous outflow 
tract. 
Study Design 
Prospective, multicenter, single arm, non-randomized study to define 
safety and efficacy of the Veniti Vici Venous Stent System in relation 
to pre-defined Objective Performance goals. 
Patient Population 
A maximum of 200 patients at 45 centers worldwide will be enrolled. 
Thirty (30) feasibility patients will be enrolled at approximately 7-10 
centers and 170 pivotal patients will be enrolled at approximately 45 
centers worldwide. 
Both the feasibility and the pivotal patient populations will include 
symptomatic adults ≥18 years of age with clinically significant chronic 
non-malignant obstruction of the iliofemoral venous outflow tract.    
 
Number of Centers 
There will be up to 45 centers worldwide.  Approximately 7-10 of 
these centers are anticipated to be in the European Union.   
Inclusion Criteria – Pre 
Procedural 
1. Age ≥18 years   
 
2. Willing and capable of complying with all follow-up 
evaluations at the specified times 
 
3. Able and willing to provide written informed consent prior to 
study specific procedures 
 
4. Presence of unilateral, clinically significant, chronic non-
malignant obstruction of the common femoral vein, external 
iliac vein, common iliac vein, or any combination thereof, 
defined as a ≥50% reduction in target vessel lumen diameter 
(to be  measured by venogram during procedure, per 
Exclusion 25). 

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5. Clinically significant venous obstruction defined as meeting 
at least one of the following clinical indicators:  
• 
Clinical severity class of CEAP classification ≥3 (See 
Appendix 4.) 
• 
VCSS Pain Score ≥2 (See Appendix 7.) 
6. Negative pregnancy test in females of child-bearing potential  
 
7. Intention to stent the target lesion only with the Veniti Vici 
Venous Stent 
Exclusion Criteria – Pre-
Procedural 
8. Presence or history of clinically significant pulmonary emboli 
within 6 months prior to enrollment. 
9. Venous obstruction that extends into the inferior vena cava 
 
10. Contralateral disease of the common femoral vein, external 
iliac vein, common iliac vein, or any combination thereof 
with planned treatment within 30 days after subject 
enrollment 
 
11. Life expectancy <12 months 
 
12. Female of childbearing potential who is pregnant or plans to 
become pregnant during the duration of the clinical study 
13. A. Uncontrolled or active coagulopathy OR  
B. Known uncorrectable bleeding diathesis with the 
following definitions: 
• 
Uncorrected INR ≥2.0 or aPTT ≥1.5 X normal local lab 
value 
• 
Platelet count <80,000 
14. Uncorrected hemoglobin of ≤9 g/dL 
 
15. Patients with an estimated glomerular filtration rate (eGFR) 
<30 mL/min. In patients with diabetes mellitus, eGFR <45 
mL/min. 
 
16. Known hypersensitivity to nickel or titanium 
 
17. Contrast agent allergy that cannot be managed adequately 
with pre-medication 
 
18. Intended concurrent thrombolysis or thrombectomy 
procedure OR intended or planned (within 30 days) adjuvant 
procedure such as creation of temporary AV fistula, 

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placement of IVC filter, endovenectomy or saphenous vein 
ablation 
 
19. Current or recent (within 30 days) active participation in 
another drug or device clinical trial (Participation in 
observational studies is acceptable.) 
 
20. Patient judged to be a poor candidate by the primary 
investigator 
21. Patients who have had any prior surgical or endovascular 
intervention of the target vessel 
Note: Patients who have had catheter-directed or mechanical 
thrombolysis in the target vessel for DVT at least 3 month (90 
days) prior to the VIRTUS index procedure may be included in the 
trial. 
Exclusion Criteria – 
Intra-Procedural 
22. Patients in whom the lesions cannot be traversed with a 
guide wire. These patients will not count against the study 
sample size. 
 
23. Patients where the obstruction extends into the inferior vena 
cava or below the level of the lesser trochanter. These 
patients will not count against the study sample size. 
 
24. Patients whose vein diameters are not within limits stated in 
current Instructions for Use as determined by venogram. 
These patients will not count against the study sample size. 
 
25. Patients who do not meet the venogram binary stenosis 
definition above, as determined by the treating physician.  
These patients will not count against the study sample size. 
Follow-Up 
The follow-up period is 60 months. 
The 12-month data from at least 156 patients will be submitted to 
FDA to support a Pre-Market Approval (PMA) application. 
Primary Efficacy 
Endpoint  
The primary efficacy endpoint for this study will be the primary 
patency rate at 12 months post-intervention, defined as freedom 
from occlusion by thrombosis AND freedom from surgical or 
endovascular intervention on target vessel which are found to have 
re-stenosis or stent occlusion to maintain patency AND freedom from 
in-stent stenosis more than 50% by venogram.  For patients refusing 
the venographic assessment at 12 months, DUS-determined patency 
will be used instead. 
Primary Safety 
The primary safety endpoint for this study will be a composite 
endpoint of any major adverse event within 30 days, as adjudicated 

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Endpoint 
by a Clinical Events Committee.  Major Adverse Events are listed in 
Section 11.1.4. 
 
Secondary Efficacy 
Endpoint 
The formal secondary endpoint for this study will be a binary 
response variable based on an improvement in VCSS by at least 50% 
at 12 months post-intervention. 
Ancillary Analyses 
Procedural Endpoints 
 
• 
Procedural technical success, defined as achievement of a final 
residual diameter stenosis of ≤50% as measured by venogram 
without skipped lesion areas with placement of the study device 
alone with or without post-stenting balloon dilation 
• 
Lesion success defined as achievement of ≤50% residual diameter 
stenosis using any percutaneous method (including use of non-
study devices) 
• 
Procedural success defined as procedural technical success 
without the occurrence of major adverse event between the 
index procedure and discharge 

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Ancillary Analyses 
(continued) 
Late technical success (through 12 months) defined as: 
• 
Absence of migration  
• 
Absence of stent embolization 
• 
Achievement of primary patency 
• 
Structural integrity, defined as the absence of: 
• 
Pinching, defined as focal compression of the stent with > 
50% diameter reduction of the stent 
• 
Kinking, defined as >50% diameter reduction of the stent 
with the stent doubling or bending on itself  
 
• 
Recoil, defined a poor radial resistance to diffuse collapse, 
which results in >50% diameter reduction of the stent (i.e., 
stent diameters obtained throughout the study period as 
compared to the final stent diameter after insertion 
measured by DUS or venogram).   
• 
Fracture(s)  
Fractures will be assessed as per Jaff, et al.1 (See Appendix 
3.) Data to be collected for each fracture identified includes: 
o Limb (right or left) 
o Venous segment(s) where fractures are located 
o Overlapping versus non-overlapping  
o Type of fracture (Type I, II, III, IV) 
• 
Subgroup analysis to evaluate device performance across 
genders. 

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3 
KEY ROLES AND STUDY CONTACTS 
Key Roles and Study Contacts 
Sponsor 
Veniti, Inc. 
1610 Des Peres Road, Suite 385 
St. Louis, MO  63131 
+1 (314) 282-3753 
Sponsor Contacts 
Karen Fraser, RN, MS 
Sr. Director of Clinical Affairs 
Tel. +1 (314)-282-3746 
Fax +1 (636) 628-9991 
Email: kfraser@venitimedical.com 
Clinical Monitors 
Clinical Affairs Department 
Veniti, Inc. 
1610 Des Peres Road, Suite 385 
St. Louis, MO  63131 
USA 
European CRO: MedPass 
International 
MedPass International 
95 bis, Boulevard Pereire ; 75017 Paris – France 
www.medpass.org 
Phone: +33 (0)1 42 12 83 30 
United States CRO: Prairie 
Education and Research 
Cooperative (PERC) 
Prairie Education and Research Cooperative (PERC) 
317 N 5th St, Springfield, IL 62701 
http://www.thepercdifference.com  
(217) 492-9100 
Authorized Representative: 
European Union 
Emergo 
Prinsessegracht 20 
2514AP The Hague 
The Netherlands 
http://www.emergogroup.com  

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Key Roles and Study Contacts 
Overall Study Co-PIs 
 Dr. William Marston, MD 
Chief, Division of Vascular Surgery 
Professor, Department of Surgery 
Division of Vascular Surgery, CB #7212 
UNC Department of Surgery 
Chapel Hill, NC 27599-7212 
Phone: +1 (919) 966-3391 
Fax: +1 (919) 966-2898 
Dr. Mahmod Razavi, MD 
Director, Department of Clinical Trials 
Vascular and Interventional Specialists of Orange County 
1140 W La Veta Ave Suite 850 
Orange, CA 92868 
Phone: +1 (714)560-4450 
Intravascular Ultrasound (IVUS) 
Core Laboratory 
St. Luke’s Hospital of Kansas City 
4401 Wornall Road 
Kansas City, MO 64111 
+1 (816) 932-2000 
Syntactx (Venogram Core 
Laboratory) 
7 World Trade Center 
250 Greenwich Street, 46th Floor 
New York, NY  10007 
http://www.syntactx.com/ 
+1 (212) 266-0135   
Vascore (Duplex Ultrasound Core 
Laboratory) 
Vascore, a division of the MGPO 
Massachusetts General Physicians Organization, Inc. (MGPO) 
55 Fruit Street 
Boston, MA 02114 
http://www.vascore.org 
+1 (617) 726-5552 
 

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4 
INTRODUCTION 
4.1 
Etiology and Pathophysiology of Venous Disease 
Chronic venous disorders (CVD) have a significant social and economic cost, 
impacting an estimated 50% of Western populations, and consuming an 
estimated 2-3% of healthcare budgets.2   Although CVD is recognized to have 
several contributing pathophysiological factors, the main emphasis has for 
decades been on valve incompetence with reflux.  Other aspects, such as 
obstruction to the outflow, a poor calf muscle pump, low compliance and 
geometrical changes of the flow channels were largely ignored.  Endovascular 
treatment of iliofemoral venous outflow obstruction, introduced in the 1990s, 
has shown that obstruction of this anatomical site plays an important role in the 
clinical expression of CVD, particularly pain and ulcer development. 3, 4 Chronic 
obstruction of the iliofemoral vein (common iliac, external iliac and common 
femoral veins) often results in severe symptoms (venous claudication 5, 
extensive edema, skin changes, limb ulcer 6 7 8, disability 9 and decreased quality 
of life) 10 11. It has been shown that, following a conservatively treated DVT of 
the iliofemoral vein segment, there is remaining, variable obstruction in 
approximately 80% of patients. 6  Additionally, the recurrence rate of DVT is 
increased 2.4 times 12, and the risk of developing post-thrombotic symptoms is 
increased 3.4 times. 13Over a 5-year period, chronic venous obstruction results 
in venous claudication 5 in 15-44% of patients, with 15% developing venous 
ulcers. 4 5 6 Although the initiating cause can be either simple anatomic 
compression of the iliac vein or chronic post-thrombotic disease, chronic venous 
obstruction frequently leads to thrombotic events regardless of the inciting 
index event. 
4.2 
Benefits and Risks of Venous Stenting 
Percutaneous stenting of the iliofemoral venous outflow system has developed 
over the past decade as the “method of choice” to manage chronic venous 
obstruction.  The procedure can be performed with low morbidity, no mortality, 
long-term high patency rate, and low rate of in-stent restenosis.  It has replaced 
bypass surgery as the primary treatment.  In 2007, the American Venous Forum 
stated that “iliocaval venoplasty and stenting has emerged as the ‘method of 
choice’ in relieving proximal iliofemoral obstruction”.  In 2011, the American 
Heart Association, in its recommendation on the management of iliofemoral 
deep venous thrombosis, stated that, “The placement of iliac vein stents to 
reduce post-thrombotic syndrome (PTS) symptoms and heal venous ulcers in 
patients with advanced PTS and iliac vein obstruction is reasonable” (Class IIa; 
Level of Evidence C) 14.  Moreover, Guidelines of the European Society of 
Vascular Surgery (to be published in 2014) state that “Clinically relevant central 
venous obstruction or stenosis might be eligible for interventional treatment 
with a self‐expandable stent with a sufficient large diameter” (Class I; Level of 
evidence B). 
 

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Prior conservative therapies, such as chronic extended anticoagulation and 
compression, have been shown to be ineffective.  Surgical bypass procedures 
are invasive with significant complication rate and have been exclusively 
performed as an end-stage procedure in the most severely compromised 
patients.  Today open surgery is offered only to surgically fit patients with 
severe symptoms after unsuccessful or failed stenting. 15   There are no, 
randomized or multicenter studies on venous stenting, but multiple single 
center large (over 50 patients) registries cohort studies 9 16 17 18 have reported 
technical success rates superior to 90% and patency rates of 79-98% at 5 years. 
18  It is difficult to determine the exact expected patency rates from these 
studies, as these studies included different etiologies, extent of the disease, 
concomitant reflux and clinical status, typically do not state the degree of 
obstruction prior to procedure, have variability in inflow to the stent system and 
often base the definition of patency on duplex-scan.  (There is no reported 
comparison between duplex ultrasound scanning and venography in the 
assessment of stent patency.  Venography is, therefore, still considered the gold 
standard.)  However, given the very high rate of recurrence of thrombotic 
disease or clinical deterioration after non-stenting approaches, even a patency 
rate of 50-60% would offer significant improvement over current approved 
therapy. 
The data available indicate that stenting for chronic obstructive iliofemoral 
lesions comes with a very low risk.  So far, in the published literature, neither 
death nor pulmonary embolism nor life-threatening complications have 
occurred.  In the largest single-center report on 953 stented limbs with 
ultrasound guided venous access 16, there were only four access-related adverse 
events: three femoral artery pseudoaneurysms treated with thrombin injection 
alone, and one arteriovenous fistula 5.  In addition to the access complications, 
there was one case where the guidewire became trapped in the stent and the 
stent/guidewire was removed via a cutdown of the femoral vein.  In this large 
series, there were 47 thrombotic events that occurred over a 5-year period 
(5%).  
The benefits to patients with a decompression of the lower limb after stenting 
such as alleviation of clinical symptoms, improvement of quality of life and less 
venous disability, far outweigh the potential risks associated with the stenting 
procedure.  The results of clinical reports demonstrate the safety and potential 
benefits of vascular stents as a treatment of adults with symptomatic CVD and 
venous outflow obstruction. 
4.3 
Assessment of Current Venous Stents 
All stents used in the venous system in the United States currently are used off-
label. In Europe, there are available stents developed for placement in the 
venous outflow, however,  none have undergone rigorous assessment of 
efficacy or safety for use in the venous system.  The stent most commonly used 
in the iliofemoral venous outflow system is the Wallstent Stent (Boston 
Scientific, Minneapolis, MN), with well-recognized deficiencies.  This stent, 

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designed for use in the arterial system, has moderate radial force and is subject 
to significant foreshortening during its deployment (40%) with balloon dilation, 
leading to problems with lesion coverage or separation of contiguous stents.  
Stents specifically designed for the unique environment of the venous system 
need to be tested in controlled and scientific prospective studies.  There are no 
randomized multicenter studies on venous stenting.  The difficulty is to find an 
adequate control group.  The natural alternative to stenting would be to 
perform open invasive surgery.  However, multiple studies reporting results of 
open bypass surgery of the outflow of the lower limb total only about 400 
patients in the literature and show variable results often with poor bypass-
related endpoints. 21  Already, thousands of patients have had percutaneous 
stent placement with uniformly better clinical and stent-related outcome than 
bypass surgery and adequate stent related follow-up with minimal morbidity. 22  
It is generally considered that the surgical alternative in a randomized study is 
unethical due to the significant invasiveness and poorly documented outcome.  
Another alternative would be a comparison between stenting of the chronic 
venous outflow versus conservative treatment.  However, the patients 
scheduled for stenting are those that already had optimal conservative 
treatment, which has failed.  Thus, a carefully controlled prospective cohort 
study with well-defined inclusion criteria and critical clinical and stent-related 
follow-up needs to be performed showing no inferiority to results achieved in 
previous reports of less stringent studies. 
5 
INVESTIGATIONAL PRODUCT 
5.1 
Device Description 
One such stent, designed specifically for use in the venous system, is the Veniti 
Vici Venous Stent System (Veniti, St. Louis, MO).  The Vici Venous Stent System, 
manufactured by Veniti, is comprised of two components: the implantable 
prosthesis and the stent delivery system. The stent is a laser cut self-expanding 
stent composed of a nickel titanium alloy (nitinol). The stent has closed-cell 
segments and flexible interconnections designed specifically for use in venous 
anatomy.  It is available in 60-, 90- and 120-mm lengths and 12-, 14- and 16-mm 
diameters.  The delivery system is a coaxial design with an exterior shaft to 
protect and constrain the stent prior to deployment.  The delivery system is an 
Over-The-Wire system compatible with 0.035 in. (0.89 mm) guidewires, and a 
9French sheath introducer which allows delivery via either a jugular, femoral or 
popliteal vein approach.   
The Veniti Vici Venous Stent System has the CE mark.  In the United States, the 
Veniti Vici Venous Stent System will be studied under an Investigational Device 
Exemption (IDE), upon approval/conditional approval of an IDE submission. 
 

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5.2 
Intended Use 
The Veniti Vici Venous Stent System is intended for improving luminal diameter 
in the iliofemoral veins for the treatment of symptomatic venous outflow 
obstruction in symptomatic adult patients (age 18 and older). 
6 
POTENTIAL RISKS AND BENEFITS 
6.1 
Potential Risks 
The potential risks of venous stenting are those associated with any intra-
vascular procedure up to and including death, although at lower rates than those 
typically seen for arterial procedures. 
o Access complications 
o Access bleeding or hematoma 
o Arterial or venous injury 
o Arterial pseudoaneurysm 
o Retroperitoneal hematoma 
o Pain 
o Procedure related 
o Mis-deployment of the stent 
o Stent migration 
o Stent embolization 
o Thrombus formation (femoral vein, iliac vein, inferior vena cava) 
o Distant thrombo-embolism (pulmonary) 
o Pain 
o Anticoagulation: although many of these patients are on long-term 
anticoagulation, those that are not may be required to be anticoagulated 
for a limited period of time; the risks of this study include bleeding related 
to anticoagulation.  (See Appendix 2.) 
6.2 
Potential Benefits/Advantages of Treatment/Product 
Prior therapies, such as chronic anticoagulation or surgical bypass procedures, 
are either ineffective, or significantly invasive.  The potential risks of venous 
stenting are those associated with any intra-vascular procedure up to and 
including death, although at lower rates than those typically seen for arterial 
procedures.  With demonstrated primary patency rates of 60-90% through 12 
months, and demonstrated serious adverse event rates of <1%, the benefits of 
the proposed study outweigh the potential risks. 
Currently marketed venous stents have sufficient clinical data regarding their use 
in veins of the lower extremities and pelvis for the treatment of venous outflow 
obstruction in adults and their risk profiles are not known or considered to be 
different from the Veniti Vici Venous Stent. 
 

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7 
STUDY OBJECTIVE AND DESIGN 
The VIRTUS trial is a prospective, multicenter, single arm, non-randomized study to 
define safety and efficacy of the Veniti Vici Venous Stent System in relation to pre-
defined Objective Performance goals.  The objective of this study is to assess the safety 
and efficacy of the Veniti Vici Venous Stent System in achieving patency of the target 
venous lesion in patients who present with clinically significant chronic non-malignant 
occlusion of the iliofemoral venous outflow tract. 
7.1 
Primary Endpoint – Efficacy:   
The primary efficacy endpoint for this study will be the primary patency rate at 
12 months post-intervention, defined as freedom from occlusion by thrombosis 
AND freedom from surgical or endovascular intervention on target vessel which 
are found to have re-stenosis or stent occlusion to maintain patency AND 
freedom from in-stent stenosis more than 50% by venogram.  For patients 
refusing the venographic assessment at 12 months, DUS-determined patency 
will be used instead.   
7.2 
Primary Endpoint – Safety:  
The primary safety endpoint for this study will be a composite endpoint of any 
Major Adverse Event within 30 days, as adjudicated by a Clinical Events 
Committee.  Major Adverse Events are listed in Section 11.1.4. 
7.3 
Secondary Endpoint – Efficacy: 
The formal secondary endpoint of this study is a binary response variable based 
on whether or not a subject achieves at least 50% improvement on the Venous 
Clinical Severity Scoring (VCSS) scale at 12 months post-intervention. 
7.4 
Ancillary Outcomes: 
Procedural Endpoints 
1. Procedural technical success, defined as achievement of a final residual 
target vessel diameter stenosis of ≤50% as measured on the post-
procedural venogram, without skipped lesion regions, with placement of 
the study device alone with or without post-stenting balloon dilation as 
needed 
2. Lesion success defined as achievement of ≤50% residual diameter stenosis 
using any percutaneous method (including the use of non-study devices) 
3. Procedural success defined as procedural technical success without the 
occurrence of major adverse event between the index procedure and 
discharge 
4. Late technical success (through 12 months) defined as: 
a. Absence of migration  
b. Absence of stent embolization 
c. Achievement of primary patency 
d. Structural integrity, defined as the absence of:   
i. 
Pinching, defined as focal compression of the stent with > 50% 
diameter reduction of the stent 

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ii. 
Kinking, defined as >50% diameter reduction of the stent with the 
stent doubling or bending on itself 
iii. 
Recoil, defined a poor radial resistance to diffuse collapse, which 
results in >50% diameter reduction of the stent (i.e., stent 
diameters obtained throughout the study period as compared to 
the final stent diameter after insertion measured by DUS or 
venogram).   
iv. 
Absence of fractures, which will be assessed as per Jaff, et al.1 (See 
Appendix 3.) Data to be collected for each fracture identified 
includes: 
Limb (right or left) 
Venous segment(s) where fractures are located 
Overlapping versus non-overlapping  
Type of fracture (Type I, II, III, IV) 
5. Subgroup analysis to evaluate device performance across genders. 
Clinical Endpoints 
6. Improvement in Venous Clinical Severity Scoring (VCSS) at 6 and 12 months  
7. Improvements in Quality of Life (CIVIQ-2) at 12 months (See Appendix 5.) 
8. Minor outcomes: complications occurring within 30 days of the procedure 
that do not meet the definition of an MAE, do not require hospitalization 
and do not delay discharge. 
8 
PATIENT POPULATION 
A maximum of 200 patients at 45 centers worldwide will be enrolled.  Thirty feasibility 
patients will be enrolled at approximately 7 – 10 centers and 170 pivotal patients will be 
enrolled at approximately 45 centers worldwide.  A minimum of 114 pivotal patients will 
be enrolled at US centers. 
The 12-month data from at least 156 evaluable pivotal patients, as well as detailed 
summary data on the 30 feasibility patients will be submitted to FDA to support a Pre-
Market Approval (PMA) application. 
Patients will include symptomatic adults ≥18 years of age with clinically significant 
chronic non-malignant obstruction of the iliofemoral venous outflow tract.    
8.1 
Initial DSMB Safety Evaluation 
Thirty (30) patients will be enrolled at approximately 7 centers.  These patients 
will not be included in the pivotal study population, but will be evaluated 
separately for the primary safety and efficacy endpoints as well as for all 
secondary endpoints.  When these 30 patients have completed their 30-day 
follow-up, a Data Safety Monitoring Board (DSMB) will review the safety data 
and will determine if the study can proceed with enrollment of the pivotal 
population.  The DSMB report will be submitted to FDA for reference.   

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8.2 
Inclusion/Exclusion Criteria 
Patients meeting all pre-procedural inclusion and exclusion criteria will have the 
study presented to them.  Patients giving informed consent will complete 
protocol-required testing, undergo baseline evaluation, and undergo the 
protocol-defined determination of binary stenosis, as measured by venogram.  
Patients meeting the venogram binary stenosis definition, as determined by the 
treating physician, will undergo the protocol-defined stenting procedure and all 
protocol-defined follow-up visits.     
8.2.1 Inclusion Criteria – Pre-Procedural Criteria 
1. Age ≥18 years   
2. Willing and capable of complying with all follow-up evaluations at 
the specified times 
3. Able and willing to provide written informed consent prior to study 
specific procedures 
4. Presence of unilateral, clinically significant, chronic non-malignant 
obstruction of the common femoral vein, external iliac vein, 
common iliac vein, or any combination thereof, defined as a ≥50% 
reduction in target vessel lumen diameter ( to be measured by 
venogram during procedure, per Exclusion 25). 
5. Clinically significant venous obstruction defined as meeting at least 
one of the following clinical indicators:  
• 
Clinical severity class of CEAP classification ≥3 (See Appendix 4.) 
• 
VCSS Pain Score ≥2 (See Appendix 7.) 
6. Negative pregnancy test in females of child-bearing potential  
7. Intention to stent the target lesion only with the Veniti Vici Venous 
Stent 
8.2.2 Exclusion Criteria - Pre-Procedural Criteria 
8. Presence or history of clinically significant pulmonary emboli within 
6 months prior to enrollment. 
9. Venous obstruction that extends into the inferior vena cava 
10. Contralateral disease of the common femoral vein, external iliac 
vein, common iliac vein, or any combination thereof with planned 
treatment within 30 days after subject enrollment 
11. Life expectancy <12 months 
12. Female of childbearing potential who is pregnant or plans to 
become pregnant during the duration of the clinical study 
13. A. Uncontrolled or active coagulopathy OR 
B. Known, uncorrectable bleeding diathesis with the following 
definitions: 
• 
Uncorrected INR ≥2.0 or aPTT ≥1.5 X normal local lab value  
• 
Platelet count <80,000 
14. Uncorrected hemoglobin of ≤9 g/dL 

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15. Patients with an estimated glomerular filtration rate (eGFR) <30 
mL/min.  In patients with diabetes mellitus, eGFR <45 mL/min. 
16. Known hypersensitivity to nickel or titanium 
17. Contrast agent allergy that cannot be managed adequately with 
pre-medication 
18. Intended concurrent thrombolysis or thrombectomy procedure OR 
intended or planned (within 30 days) adjuvant procedure such as 
creation of temporary AV fistula, placement of IVC filter, 
endovenectomy or saphenous vein ablation 
19. Current or recent (within 30 days) active participation in another 
drug or device clinical trial  (Participation in observational studies is 
acceptable.)  
20. Patient judged to be a poor candidate by the primary investigator  
21. Patients who have had any prior surgical or endovascular 
intervention of the target vessel 
Note: Patients who have had catheter-directed or mechanical 
thrombolysis in the target vessel for DVT at least 3 month (90 days) 
prior to the VIRTUS index procedure may be included in the trial. 
8.2.3 Exclusion Criteria – Intra-procedural Criteria 
22. Patients in whom the lesions cannot be traversed with a guide wire. 
These patients will not count against the study sample size. 
23. Patients where the obstruction extends into the inferior vena cava 
or below the level of the lesser trochanter. These patients will not 
count against the study sample size. 
24. Patients whose vein diameters are not within limits stated in 
current Instructions for Use as determined by venogram. These 
patients will not count against the study sample size. 
25. Patients who do not meet the venogram binary stenosis definition 
above, as determined by the treating physician.  These patients will 
not count against the study sample size. 
9 
STUDY PROCEDURES AND DATA COLLECTION  
9.1 
Patient Screening Procedure 
Patients who have been diagnosed with chronic nonmalignant obstruction of 
the iliofemoral venous segment of either extremity will undergo screening to 
determine their appropriateness for inclusion in the study. 
• 
Patient medical history and physical examination 
• 
Review of diagnostic investigations to ascertain diagnosis of chronic non-
malignant venous obstruction (See Section 1.) 
• 
The investigator must maintain detailed source documents on all patients 
who are enrolled or who undergo screening in the study.  Investigators will 
maintain a screening log that must include at a minimum: screening date, 
enrollment status (enrolled/excluded) and the reason for exclusion for all 
screen failures. 

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9.2 
Informed Consent 
All patients who meet the pre-procedural inclusion criteria will have the study 
presented to them, as well as their family if possible.  Patients must document 
consent to the study by signing the approved consent form.  One copy of the 
informed consent will be placed in the patient’s medical record, a second will be 
given to the patient or representative, and a third may be placed in the study 
records. 
Patients that sign the informed consent will be considered enrolled in the study.  
These patients should also be entered into the electronic data capture (EDC) 
system and monitored for protocol deviations and adverse events until 
discharge from the hospital.  Subjects that sign consent, but are found to not 
meet Inclusion/Exclusion criteria (i.e. screen failures) will not be included in the 
statistical analysis.  
9.3 
Baseline Evaluation (within 30 days of implant procedure) 
Patients who sign an informed consent will undergo baseline testing: 
• 
History and physical examination 
• 
Laboratory evaluation (CBC and eGFR will be required for all patients; 
Patients on a Vitamin K antagonist or direct thrombin or Factor Xa 
inhibitors, prior to the intervention, require a PT with INR; subjects on 
heparin prior to the intervention require an aPTT.  Patients with history of 
liver disease will require a PT with INR and an aPTT.)   
• 
Medication review  
• 
Pregnancy test in females of child-bearing age (within 48 hours of implant 
procedure) 
• 
CEAP Assessment  (See Appendix 4.) 
• 
CIVIQ-2 Quality of Life questionnaire (See Appendix 5.) 
• 
VAS pain score (See Appendix 6.) 
• 
VCSS (See Appendix 7.) 
9.4 
Pre-Procedural Evaluation 
Patients who consent, and who meet the pre-procedural inclusion and exclusion 
criteria, will undergo baseline venography to verify appropriateness for 
enrollment, as determined by the treating physician.  
• 
Venography only to ascertain obstruction with at least a ≥50% in the target 
vessel lumen diameter compared to the normal vein lumen diameter 
immediately peripheral to the target lesion as measured by venogram.  IVUS 
may not be used to fulfill this requirement. 
• 
Absence of obstruction extending into the inferior vena cava (IVC) as 
determined by any imaging modality. 
9.5 
Venous Stent Implant Procedure  
9.5.1 Procedure Guidelines 

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Patients who meet all of the inclusion and exclusion criteria will undergo 
the venous stenting procedure.  During the venous stenting procedure, 
the current Veniti Vici Venous Stent System Instructions for Use will be 
followed. 
• 
Patients will be monitored, per local institutional guidelines. 
• 
Patients will receive appropriate sedation and anesthesia, per local 
institutional guidelines. 
• 
Venography will be performed to determine sizing for venous 
stenting with the Veniti Vici Venous Stent System and to evaluate 
lesion characteristics.  
• 
IVUS will be performed to confirm sizing for venous stenting with 
the Veniti Vici Venous Stenting System. Assessment of target lesion 
presence/absence, lesion severity (maximal binary stenosis), and 
lesion characteristics, per the case report form (location, length). 
• 
Occluded veins will require guidewire recanalization before 
stenting. 
• 
The lesion(s) must be adequately covered by the stent(s). 
• 
If 2 or more stents are required to cover the target lesion, the stents 
will be overlapped by at least 1 cm to insure adequate stent cover 
without skipped areas. 
• 
The diameter of the stent should be 2 mm greater than (“over”) the 
measured diameter of the surrounding “normal” vessel.  The stent 
should be at least 1 cm longer than the obstructive venous lesion 
(0.5 cm (peripherally) and 0.5 cm centrally. When selecting stent 
length, the expected foreshortening should be taken into account.  
9.5.2 Perioperative Anticoagulation Regimen 
• 
Patients on long-term warfarin therapy should be bridged prior to 
the intervention with LMWH or other anticoagulant per local 
institution guidelines, and will restart warfarin therapy within 24 
hours. 
• 
All patients will receive prophylactic LMWH or other anticoagulant 
prior to the intervention and following the procedure, per local 
institutional guidelines. 
o This applies to all patients, including those bridged, as 
described in Bullet 1 of Section 9.5.2 above.  
• 
All patients should be appropriately anticoagulated during the 
procedure, per hospital protocol. 
• 
SCD compression/early ambulation post-intervention will occur in 
all patients. 
9.5.3 Post-Stent Placement Assessments 
• 
Venography to assess post-procedural target vessel lumen diameter 
and to determine residual target lesion stenosis.  This assessment 
will serve as the baseline for determining the primary efficacy 

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endpoint at the 12 month follow-up (or prior Interval Evaluation, 
when applicable).  When venographic data is available at the 12 
month visit, values from the venogram obtained at the Post-Stent 
Placement will serve as the subject’s baseline.   
• 
Adverse event assessment 
• 
Extended Anticoagulation Protocol (See Appendix 2.)  
Anticoagulation or antiplatelet treatment for concomitant 
conditions should be continued at the discretion of the enrolling 
physician.  Study patients should also receive anticoagulation or 
antiplatelet therapy, per the following guidelines.  These guidelines 
apply through the 12 month visit.   
o Patients on extended Vitamin K antagonists or direct thrombin 
or Factor Xa inhibitors prior to enrollment should continue on 
warfarin post-procedure with a target INR of 2-3, or within the 
documented therapeutic range for INR per local guidelines. 
o Patients with a history of ≥2 thrombo-embolic event(s) and not 
on extended Vitamin K antagonists or direct thrombin or 
Factor Xa inhibitors prior to enrollment will be anticoagulated 
following the procedure and continue through the 12 month 
visit, as per ACCP guidelines7 (Vitamin K antagonists such as 
warfarin to achieve an INR of 2-3 [or an INR within the 
documented therapeutic range for INR per local guidelines] or 
direct thrombin or Factor Xa inhibitors such as rivaroxaban per 
recommended dosing). 
o Patients with a history of <2 prior thrombo-embolic event OR 
patients with no history, but where the obstruction is 
determined to be caused by previous silent thrombotic event, 
will begin anticoagulation post-procedure and continue for 6 
months in the case of non-occlusive obstruction (Vitamin K 
antagonists such as warfarin to achieve an INR of 2-3 [or an INR 
within the documented therapeutic range for INR per local 
guidelines], or direct thrombin or Factor Xa inhibitors such as 
rivaroxaban per recommended dosing).  From 6 months 
through the 12 month visit, these patients should receive low-
dose ASA. 
▪ 
Patients with occlusive obstruction should receive Vitamin K 
antagonists such as warfarin to achieve an INR of 2-3 (or an 
INR within the documented therapeutic range for INR per 
local guidelines),  or direct thrombin or Factor Xa inhibitors 
such as rivaroxaban per recommended dosing through the 
12 month visit. 
o Patients who were on clopidogrel or prasugrel pre-procedure 
will resume their baseline dose within 24 hours of the 
procedure and continue as required for the underlying 
condition UNLESS the enrolling physician believes that the 

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need for anticoagulation outweighs the need for anti-platelet 
drugs. 
o All patients not receiving anticoagulation therapy or anti-
platelet therapy as noted above will receive low-dose ASA (i.e. 
75 mg, 81mg, etc.) daily throughout the 12 month visit. 
• 
IVUS to assess stent characteristics (apposition, webbing, coverage 
of target lesion, etc.)  
• 
Physician evaluation of technical difficulty of implantation 
9.6 
Discharge or Three Days Post-Procedure (whichever comes first) 
• 
Duplex ultrasound to determine post-procedural target vessel lumen 
diameter (For patients refusing the venographic assessment at 12 months 
[or prior Interval Evaluation, as applicable], DUS-determined patency will be 
used instead, with the DUS obtained at the Discharge or Three Days Post-
Procedure visit serving as the baseline).  
• 
Determination of discharge  
• 
 Anticoagulation Review, based on the Extended Anticoagulation Protocol 
(See Appendix 2.) 
• 
Adverse event assessment 
• 
Patients who do not meet intra-procedural inclusion criteria (and who do 
not receive the implanted study device) should be followed only through 
hospital discharge for protocol deviations and adverse events.  This visit will 
conclude participation for these screen failed patients.  These subjects will 
not be included in the statistical analysis. 
9.7 
1 Month Evaluation (30 days -7/+14 days) 
• 
Physical examination (to assess for the presence of Adverse Events) 
• 
Anticoagulation Review, based on the Extended Anticoagulation Protocol 
(See Appendix 2.) 
9.8 
6 Month Evaluation (180 days ± 30 days) 
• 
Physical examination (to assess for the presence of Adverse Events) 
• 
Duplex ultrasound (required only for first 30 patients to assess patency) 
• 
CIVIQ-2 Quality of Life questionnaire (See Appendix 5.) 
• 
VAS pain score 
• 
VCSS (See Appendix 7.) 
• 
Anticoagulation Review, based on the Extended Anticoagulation Protocol 
(See Appendix 2.) 
9.9 
12 Month Evaluation (365 days ± 60 days) 
Patients that refuse the venogram and IVUS at this visit should have all other 
assessments listed here performed:  
• 
Physical examination (to assess for the presence of Adverse Events) 
• 
Assessment of primary patency by venography  

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• 
Determination of residual external venous segment compression, stent 
recoil, and lesion coverage by IVUS  
• 
Duplex ultrasound for all patients (For patients refusing the venographic 
assessment at this visit, DUS-determined patency will be used towards the 
primary efficacy endpoint instead.)  
• 
Assessment of stent integrity by bi-plane X-Ray (See Appendix 3.) 
• 
CIVIQ-2 Quality of Life questionnaire (See Appendix 5.) 
• 
VAS pain score (See Appendix 6.) 
• 
VCSS (See Appendix 7.) 
• 
Anticoagulation Review, based on the Extended Anticoagulation Protocol 
(See Appendix 2.) 
9.10 
Interval Evaluation 
At any point following the venous stenting procedure, the patient may present 
with symptoms of clinically significant obstruction of the target vessel.  Patients 
with possible obstruction should undergo all medical examinations and 
interventions as deemed appropriate for medical care.   All technical 
examinations (DUS, IVUS, or venograms) obtained during the course of the 
evaluation will be submitted as part of the case report form and will be 
submitted to the Core Laboratory for determination of primary endpoint. 
Patients who undergo re-intervention, but who are found on Core Laboratory 
assessment to have vessel patency prior to the re-intervention will not be 
counted as a primary efficacy endpoint failure.  Patients who undergo an 
interval evaluation but do not receive an intervention will have their status 
(patency/non-patency) determined by the Core Laboratory.  Patients who are 
found to be patent by Core Laboratory analysis will continue in the study 
through 12 months. 
Patients who undergo another intervention at any time prior to the 12 month 
evaluation, or who are found to have in-stent stenosis > 50%, by Core 
Laboratory assessment, will be considered to have failed the primary efficacy 
endpoint and will not be required to have further assessment of vessel patency 
or other secondary endpoints. 
All patients will complete the 30-day safety assessment regardless of primary 
patency status. 
9.11 
24 Month Evaluation (730 days ± 90 days) 
• 
Telephone follow-up for SAE assessment. May be performed in-person, at 
the discretion of the investigator. 
• 
Duplex ultrasound to assess vessel patency. (Office or laboratory visit) 
9.12 
36 Month Evaluation (1,095 days ± 90 days) 
• 
Telephone follow-up for SAE assessment. May be performed in-person, at 
the discretion of the investigator.  
• 
Duplex ultrasound to assess vessel patency. (Office or laboratory visit) 

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9.13 
48 Month Evaluation (1,460 days ± 90 days) 
• 
Telephone follow-up for SAE assessment.  May be performed in-person, at 
the discretion of the investigator. 
9.14 
60 Month Evaluation (1,825 days ± 90 days) 
• 
Telephone follow-up for SAE assessment.  May be performed in-person, at 
the discretion of the investigator. 
 
 
 

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10 
SUMMARY OF PROCEDURES  
Visit  
(window) 
Description 
Screening 
Baseline 
Evaluation 
(30 days from 
implant) 
Implant 
Procedure 
(Day 0) 
Post-stent 
placement 
assessment 
Discharge 
or 3 days 
post-
procedurea 
1 Month 
Evaluation 
(30 days  
-7/+14 days) 
6 Month 
Evaluation 
(180 ±30 days) 
12 Month 
Evaluation 
(365 ±60 days) 
24 and 36 
Month 
Evaluation 
(±90 days) 
48 and 60 
Month 
Evaluation 
(±90 days) 
Interval 
Evaluationb 
Assessment of 
Inclusion and 
Exclusion 
Criteria 
Medical 
records 
X 
X 
Xc 
 
 
 
 
 
 
 
 
Informed 
Consent 
IC 
 
Xd 
 
 
 
 
 
 
 
 
 
Assessment of 
baseline 
characteristics 
H&P, labs, 
CEAP 
 
X 
 
 
 
Physical 
Exam Only 
Physical 
Exam Only 
Physical 
Exam Only 
 
 
Physical Exam 
Duplex 
Ultrasound 
DUS 
 
 
 
 
 
X 
 
Xe 
X 
Xi 
 
X 
Venogram 
VG 
 
 
X 
X 
 
 
 
Xh 
 
 
X 
IVUS 
IVUS 
 
 
X 
X 
 
 
 
X 
 
 
X 
AE Assessment 
 
 
 
X 
X 
X 
X 
X 
X 
 
 
X 
SAE Assessment 
 
 
 
 
 
 
 
 
 
Xj 
Xj 
 
Anticoagulation 
Regimen 
 
 
 
X 
 
X 
X 
X 
X 
 
 
X 
Pregnancy Test 
(women of child 
bearing years) 
 
 
Xf 
 
 
 
 
 
 
 
 
 
CIVIQ-2 
 
 
X 
 
 
 
 
X 
X 
 
 
 
VAS 
 
 
X 
 
 
 
 
X 
X 
 
 
 
VCSS 
 
 
X 
 
 
 
 
X 
X 
 
 
 
Biplane X-rayg 
 
 
 
 
 
 
 
 
X 
 
 
 
a: Discharge or 3 days post-procedure, whichever comes first 
b: Performed if patients present with symptoms of clinically significant obstruction of the target vessel.  (See Section 9.10.) 
c: Evaluate intra-procedural exclusion criteria prior to implant (See Section 8.2.3.)  
d: Informed consent may be collected before or at the Baseline Evaluation visit. 
e: Required only for the first 30 study patients to assess patency 
f. Pregnancy test in females of child-bearing age must be collected within 48 hours of implant procedure 
g: To assess stent integrity. 
h: To assess primary patency 
i:  To assess patency 
j:  SAE Assessment may be performed via telephone. 

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11 
ADVERSE EVENTS 
11.1 
Event Definitions 
11.1.1 Adverse Event 
All Adverse Event (AE) data will be collected and recorded on the 
Adverse Event Form.  At each evaluation, the Investigator or 
Investigator’s designee will determine whether an AE has occurred.  
An AE will be defined as any untoward medical occurrence in a subject 
that does not necessarily have a causal relationship with the 
investigational treatment.  This will include any new undesirable 
experience (signs, symptoms, illness or other medical event), or 
worsening of a pre-existing condition.  An AE may or may not be related 
to the medical (investigational) product. 
If a pre-existing condition (any clinically significant abnormality) is 
present at the start of the study, it must be recorded as an adverse 
event if the frequency, intensity, or the character of the condition 
worsens during the Investigational Plan-defined surveillance. 
Alterations in laboratory parameters will not be considered AEs unless 
such alteration is qualified as medical condition. For example, decrease 
in hemoglobin will not be considered an AE unless it meets the 
definition of anemia.   
11.1.2 Serious Adverse Event 
All serious adverse events (SAEs) must be reported immediately to the 
Sponsor or Sponsor Designee. For the purposes of this Investigational 
Plan, when an AE or complication meets the definition for a SAE as 
noted below, it will be considered as such and reported within 24 hours 
of becoming aware of the event to the Sponsor or Sponsor’s 
designee.  These events may also need to be reported per requirements 
of the reviewing EC.   
Serious Adverse Events are defined according ISO 14155 and are 
adverse events that: 
1. Led to death 
2. Led to a serious deterioration in the health of a patient that: 
a. Resulted in a life-threatening illness or injury 
b. Resulted in a permanent impairment of a body structure or a 
body function 
c. Required in-patient hospitalization or prolonged hospitalization 
d. Resulted in medical or surgical intervention to prevent 
permanent impairment to a body structure or a body function 
3. Resulted in fetal distress, fetal death or a congenital abnormality or 
birth defect 

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11.1.3 Device Deficiency 
Device deficiency is inadequacy of a medical device related to its 
identity, quality, durability, reliability, safety or performance, such as 
malfunction, misuse or use error and inadequate labeling.  
In addition to reporting qualifying event(s) (as described above) the 
study Investigator and Sponsor must each determine (in writing) 
whether device deficiency could have led to a serious adverse device 
effect (see definition below) if: 
a. suitable action had not been taken or  
b. intervention had not been made or  
c. if circumstances had been less fortunate. 
11.1.4 Major Adverse Event (MAE) 
All major adverse events (MAEs) must be reported within 24 hours of 
knowledge of the event to the Sponsor or Sponsor Designee.   A 
subcategory of SAEs include any of the following primary safety 
endpoints occurring within 30 days of the study procedure:  
• 
Device or procedure-related death 
• 
Device or procedure-related bleeding at the target vessel and/or the 
target lesion or at the access site requiring surgical or endovascular 
intervention or blood transfusion ≥2 units 
• 
Device or procedure-related arterial or venous injury occurring in 
the target vessel segment and/or target lesion location or at the 
access site requiring surgical or endovascular intervention 
• 
Device or procedure related acute DVT outside of the target vein 
segment 
• 
Clinically significant pulmonary embolism defined as being 
symptomatic with chest pain, hemoptysis, dyspnea, hypoxia etc… 
AND be documented on CT 
• 
Embolization of stent 
These events may also need to be reported per requirements of the 
reviewing EC. 
11.1.5 Adverse Device Effects (ADE) 
Adverse event related to the use of an investigational medical device.  
This includes any event resulting from: insufficiencies or inadequacies in 
the instructions for use, the deployment, the implantation, the 
installation, the operation, or any malfunction of the investigational 
medical device.   
11.1.6 Serious Adverse Device Effects (SADE) 
ADE that has resulted in any of the consequences and characteristic of a 
SAE. 

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11.1.7 Unanticipated Serious Adverse Device Effects (USADE) 
SADE which by its nature, incidence, severity or outcome has not been 
identified in the current version of the risk analysis report. 
11.2 
Reporting of Adverse Events 
The event is considered to be reported to the Sponsor once the site completes 
an AE eCRF in electronic data capture (EDC) system. 
The information provided for each AE on Adverse Event eCRF must include: 
• 
Description of the event 
• 
Date of event onset 
• 
Date of event outcome 
• 
Date of discovery by site 
• 
Seriousness of the event (e.g., SAE vs. non-SAE) 
• 
Severity of the event 
• 
Relationship of the event to the study procedure, study device 
• 
Actions taken as a result of the event 
• 
Outcome of the event   
Every effort should be made to gather as much information as possible 
regarding reporting serious or unanticipated event within 24 hours. As 
additional information regarding reporting event becomes available, it should 
be entered in EDC and source documents should be sent to the Sponsor or 
Sponsor’s designee. 
11.3 
Relatedness to the Study Procedure, Study Device  
Relationship Assignment: Relationship assessment of AEs to the study 
procedure, study device will be made by the Investigator using the following 
definitions: 
Definitely Related  
The clinical event occurs in a plausible time relationship to study 
procedure/study device and cannot be explained by any concurrent disease or 
other devices, drugs or chemicals.  
Probably Related   
The clinical event occurs within a reasonable time sequence to study 
procedure/study device and the possibilities of factors other than the study 
procedure/study such as concurrent disease or other devices, drugs or 
chemicals can be probably excluded.  
Possibly Related 
The clinical event occurs within a reasonable time sequence to study 
procedure/study device and there is some evidence to “possibly” suggest a 
causal relationship. However, the influence of other factors such as underlying 
disease, concomitant medications, or concurrent treatment may have 
contributed to the event.  

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Not related 
The clinical event is completely independent of study procedure/study device 
and/or evidence exists that the event is definitely related to another etiology.  
11.4 
Reporting a Death 
If a site becomes aware of a subject’s death, phone or electronic notification to 
the Sponsor or Sponsor’s designee is expected within 24 hours of site learning 
of the death. Completed appropriate CRF(s) should be submitted to the sponsor 
within 48 hours of learning of the event. 
In addition, the following materials must be submitted to the Sponsor or 
Sponsor’s designee as soon as possible:  
• 
A copy of the subject’s death certificate. 
• 
Any additional requested information if available (e.g., hospital records and 
autopsy reports). 
11.5 
Protocol Deviations 
Each Investigator should conduct the study in compliance with the Study 
Protocol. Any deviation from the Study Protocol will be documented on 
appropriate CRFs by explaining the deviation and corrective actions taken to 
prevent possible re-occurring deviations. Any emergency deviations (deviations 
from the study protocol to protect the life or physical wellbeing of a subject) 
must also be reported to the Sponsor within 48 hours and the site EC per their 
local guidelines.  
11.6 
Device Malfunctions 
A device malfunction is defined as any inadequate performance of the study 
device when used per the most current IFU.  Each device malfunction will be 
reported on the appropriate CRF by the site.  Every effort must be made by the 
site to return the suspected device to the Sponsor for analysis. All device 
performance issues/malfunctions will be reported in the clinical results (e.g., 
final report).  Device malfunction by itself should not be reported as AE unless it 
led to the new medical condition or worsening of pre-existing condition or met 
the definition of an Adverse Device Effect in Section 11.1.5. 
12 
CLINICAL EVENTS COMMITTEE (CEC) 
The purpose of the CEC is to complete unbiased reviews and classification of adverse 
events.  The CEC will consist of physicians who are not Investigators in the Veniti Trial 
and who do not have any significant investment in Sponsor’s or any of their entities.  
Committee membership will be limited to the specialties of interventional cardiology, 
vascular surgery, or interventional radiology. 
13 
DATA SAFETY MONITORING BOARD (DSMB) 
The purpose of the DSMB committee is to complete unbiased review of all safety data in 
comparison to the established criteria in order to determine if the rate of SAEs is 
acceptable, to evaluate interim data analysis results, to provide related advice on study 

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management and progress, and to make any recommendations regarding the study 
protocol. Members of the DSMB will be comprised of a multidisciplinary group of 
physicians and a biostatistician, they will not be employees or shareholders of Veniti, 
Inc., and they will not be participating VIRTUS Investigators. 
The DSMB will be responsible to communicate any safety, scientific concerns, or other 
perceived concerns to Veniti or Veniti’s designee as soon as possible. The DSMB will 
provide, after each scheduled meeting, written recommendation regarding the 
continuation of the trial, early stopping, or any suggested changes for the conduct of the 
trial. Veniti is responsible for informing the IEC if the DSMB has advised them of any 
major safety concerns and has recommended the study be stopped or if they have made 
any recommendations to alter the study. 
DSMB decisions are final and non-negotiable by the sites. 
14 
INVESTIGATIONAL DEVICE DISTRIBUTION AND TRACKING  
Investigators are prohibited from providing an investigational device to any person not 
authorized to receive it (21 CFR 812.110(c)). Investigators must also maintain complete, 
current, and accurate records of the receipt, use, or disposition of investigational 
devices (21 CFR 812.140(a)(2)) that relate to: 
• 
The type and quantity of the devices received at the site, dates of receipt, and lot 
numbers (or other reference numbers) for each received device, 
• 
The type and quantity of the devices received returned to the Sponsor or disposed 
at the site, 
• 
Name of person who received or dispose each device, 
• 
Subject number(s) correlated to each used device. 
Upon completion or termination of the study (or the Investigator's part of the study), or 
at the Sponsor's request, an Investigator is required to return to the Sponsor any 
remaining supply of the device or otherwise to dispose of the device as the Sponsor 
directs (21 CFR 812.110(e)). 
15 
STATISTICAL METHODS 
15.1 
Overview of Study Design 
This study will be a single-arm trial compared to performance goals developed 
from the medical literature (See Section 15.5).  Enrollment will be stratified 
according to etiology of disease.  A total of 125 subjects (approximately 74% of 
enrollees) enrolled in the pivotal arm will have obstruction associated with 
thromboembolic disease (post-thrombotic, PT).  A total of 45 subjects 
(approximately 26% of enrollees) enrolled in the pivotal arm will have 
iliofemoral venous segment obstruction without previous thrombo-embolic 
disease without intraluminal disease (non-thrombotic, NT).  The feasibility stage 
will aim to acrue approximately the same relative proportion of NT:PT subjects. 
 

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15.2 
Missing Data 
Every effort will be made to collect all data points in the study.  The sponsor 
plans to minimize the amount of missing data by appropriate management of 
the prospective clinical trial, proper screening of study subjects, and training of 
participating investigators, monitors and study coordinators.  The sponsor will 
provide a list of patients who do not complete the trial along with the best 
information available on why the each left the trial prematurely. 
15.3 
Primary Analysis:  Per-protocol 
All patient data that is available on subjects who drop out during the course of 
the study will be included.  In the primary analysis of the primary endpoints, we 
will assume that data are missing at random (i.e., it is not the study treatment 
that is causing the data to be missing) and ignore missing values in the analyses. 
15.3.1 Sensitivity Analyses:  Worst-case and Tipping point 
Supportive, sensitivity analyses will be performed to assess the impact 
of missing endpoint data.  In the worst-case analysis, subjects with 
missing primary endpoints will be analyzed as failures with regard to 
that endpoint.  For the primary efficacy endpoint, patients with missing 
data will be treated as clinical failures, i.e., re-stenosed or occluded 
stents.  For the tipping-point analysis, the number of subjects with 
missing data required to be failures in order to reverse the trial 
conclusion will be determined. 
15.4 
Poolability Analysis 
This study will be conducted such that 1) the same protocol will be used at each 
site; 2) site investigators and personnel will receive uniform training; and 3) 
central data management and monitoring will be applied with equal rigor at all 
sites.  The diversity of settings will add to the scientific validity and 
generalizability of the findings.  
Two types of poolability analyses will be performed to assess whether the data 
from the centers can be treated as one population: 1) on the patient 
demographic variables, and 2) on the endpoint data.  Centers with fewer than 
10 implants will be treated as a single center.   
For the assessment of patient demographic variables, centers will be compared 
using a random-effects ANOVA for continuous variables such as age, or a 
random-effects logistic regression for categorical variables such as sex. 
For the assessment of the primary endpoints, both of which are binary (Y/N or 
S/F) variables, a random-effects logistic regression will be used to assess the 
comparability of results across centers. 

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15.5 
Development of the Performance Goal (PG) – Primary Efficacy 
Endpoint 
15.5.1 Rationale 
The FDA has indicated that venous stent trials should establish a 
performance goal to be met in the study, as described in Rocha-Singh et 
al.8  In that article, the authors performed a literature search and 
identified 11 controlled studies of femoropopliteal stenting in arterial 
stenotic lesions where the patency rate of the control arm was 
described.  The studies were all prospective, with clearly defined 
enrollment criteria and with pre-specified patency definitions (all using 
quantitative rather than qualitative criteria).  Independent investigators 
performed the review of the anatomic endpoints in four of the five 
included studies (core laboratories). 
The historical literature for venous stenting is considerably different. A 
total of 6 studies (See Table 15.5.2.a and Table 15.5.2.b) have been 
included in our review, all of which are retrospective, single arm, 
uncontrolled, and with variable populations. The endpoint of “primary 
patency” is qualitative in some studies, i.e., based on absence of 
symptoms in most cases, and quantitative in others, using an 
assessment of in-stent stenosis by an imaging modality such as 
venography or Doppler ultrasound (DUS). None of the studies used an 
outside, objective independent core laboratory assessment of pre-
defined patency. Without independent core laboratory assessment of 
patency, there is an inherent, if subconscious bias to report higher 
patency rates, as authors are biased to report the best results possible.  
Despite these issues, a clinical evaluation based on a performance goal 
is the best available approach in the absence of an already marketed 
comparator.  These issues support a delta of 10% from the literature-
based patency rate in the determination of the performance goal. This 
conclusion is supported by the variability in primary patency rates 
reported, ranging from 61%-80% (19% delta) for PT and 83-98% (15% 
delta) for NT patients (See Table 15.5.2a and Table 15.5.2b). 
15.5.2 Historical Patency Rates 
A literature search was performed to identify peer-reviewed articles 
with original data about patency rates at 12 months in patients with 
chronic venous obstruction who underwent iliofemoral stenting. Two 
separate searches were conducted: the first one had been done 
previously (10/9/2011) for company review; the second one was 
repeated July 31, 2013. Both searches used the terms listed below with 
limits of English, after 2000, and  
• 
“human”,  
• 
"venous stenting"  

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• 
((“May-Thurner syndrome” OR “May Thurner syndrome”) AND 
stent) 
• 
"Iliac vein" AND stent  
• 
((“venous occlusion” OR “venous insufficiency” OR “post-
thrombotic syndrome” OR “venous thrombosis” OR “venous 
obstruction” OR “iliac vein compression syndrome” OR “iliofemoral 
vein” OR “iliocaval vein” OR “femoral vein”) AND stent). 
A total of 36 articles (31 in the original search, and 5 in the update 
search) were identified for further review, and 6 were included in 
development of the Performance Goal. Only papers that reported 
primary patency data at 12 months for adult patients who underwent 
stenting for chronic venous obstruction without adjuvant procedures 
were included.  
The exclusion criteria for the articles we used for the historical control 
were based on our intended study population.  Studies were excluded 
from the control if the study included: 
• 
Patients who had thrombolysis, thrombectomy, or creation of an AV 
fistula during the index procedure, or other adjuvant procedures 
(endovenous laser ablation)  
• 
Patients who did not have stenting of the iliofemoral tract 
• 
Adolescents or pediatric patients 
• 
Patients with acute venous thrombosis 
A weighted average of qualitative patency, i.e., patients free from 
reintervention and free from occlusion (flow present on DUS) and free 
from ≥50% stenosis (per venogram or DUS lumen diameter) was 
created.  
Table 15.5.2.a.  NT Patients  (no prior history of thromboembolic event) 
Author, date 
Limbs 
studied at 
1 yr 
≥50% 
stenosis 
N (%) 
Limbs 
occluded 
Quantitative 
patency rate 
Limbs with 
quantitative 
patency 
Meng, 20116 
143 
1 
2 
(97.9%) 
140 
Neglén, 20075 
132 
(1%) 
(6%) 
(93%) 
123 
Total 
275 
 
 
(95.5%) 
262.8 
 

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Table 15.5.2 b.  PT Patients (history of prior thromboembolic event) 
Author, date 
Limbs 
studied 
at 1 yr 
≥50% 
stenosis 
N (%) 
Limbs 
occluded 
Qualitative 
patency rate 
Limbs with 
qualitative 
patency 
Rosales, 20099 
34a 
Not eval 
 
(75%) 
25.5 
Neglén, 20075 
135 
(3%) 
(17%) 
(80%) 
108 
Kölbel, 200910 
40 
 
 
(78)b 
31.2 
Wahlgren, 201011 
11 
(1 pt, in PP) 
 
(61%)b 
6.7 
Kurklinsky, 201112 
91 
Not eval 
(17%) 
(81%) 
73.7 
Total 
311 
 
 
(78.8%) 
245.1 
a 
Patients were only studied if symptomatic. 
b 
Authors made note of patients in the re-intervention group who had stenosis, so we 
concluded some evaluation of in-stent stenosis was included in assessment of primary 
patency.  Possibly, it could represent only those patients with in-stent stenosis with 
symptoms. 
In addition to these data, we used evidence from Neglén3 and Neglén 
and Raju13 that there are patients with greater than 50% restenosis who 
are asymptomatic, and therefore unlikely to be evaluated for flow under 
usual clinical practice.  These studies estimated that approximately 3% 
of asymptomatic patients had re-stenoses of 50% or greater.  Table 
15.5.2.c shows this adjustment to the rates in Table 15.5.2.b.  (This 
phenomenon was noted only in PT patients, hence no adjustments were 
made to Table 15.5.2.a.) 
Table 15.5.2.c.   Table 15.5.2.b Revised to Include In-stent Restenosis of 3%  
Author, date 
Limbs 
studied at 
1 yr 
≥50% 
stenosis 
N (%) 
Limbs 
occluded 
Quantitative 
patency rate 
Limbs with 
quantitative 
patency 
Rosales 20099 
34 
(3%) 
 
(72%) 
24.5 
Neglén 20075 
135 
(3%) 
(17%) 
(80%) 
108 
Kölbel, 200910 
40 
 
 
(78%) 
31.2 
Wahlgren 201011 11 
No chg 
 
(61%) 
6.7 
Kurklinsky 
201112 
91 
(3%) 
(19%) 
(78%) 
71 
Total 
311 
 
 
(77.9%) 
242.1 
 
15.5.3 Enrollment in the VIRTUS Study 
Historically, about 50% of patient reported in mixed series are patients 
without thrombotic history5.  The mix of thrombotic and non-
thrombotic obstruction in those with chronic venous insufficiency is not 
known (varies from zero to approximately 50%).  At the present time, 

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we expect that approximately 74% (n=148 of our enrolled subjects will 
have a history of thrombo-embolic disease (i.e., be PT patients), and 
26% (n=52) will not (i.e., be NT patients).  
Though the specified hypothesis test and corresponding sample size 
calculation utilizes different performance goals for the PT and NT 
populations, Table 15.5.3 shows the combined patency rate in a control 
group adjusted to 74% PT and 26% NT patients.  The overall or pooled 
patency rate is approximately 85%.   
Table 15.5.3.   Combined Estimates of Tables 15.5.2.a and 15.5.2.c.  
Author, Date 
Weight 
Limbs studied 
at 1 yr 
Quantitative 
patency rate 
Non-thrombotic 
.25 
275 
95.5% 
Thrombotic 
.75 
311 
77.9% 
Total using Weights 
1.00 
302 
(85.3%) 
 
15.6 
Hypotheses and Sample Size Estimate 
The minimum required sample size is calculated based on the hypothesis-driven 
primary efficacy objective.   
15.7 
Primary Efficacy Endpoint 
The minimum required sample size was determined using a  Monte Carlo power 
simulation, conducted in R, testing the following hypothesis:  
HO: 𝑞𝑁𝑇∗(𝑝𝑁𝑇−𝑃𝐺𝑁𝑇) + 𝑞𝑃𝑇∗(𝑝𝑃𝑇−𝑃𝐺𝑃𝑇) ≤0 
HA: 𝑞𝑁𝑇∗(𝑝𝑁𝑇−𝑃𝐺𝑁𝑇) + 𝑞𝑃𝑇∗(𝑝𝑃𝑇−𝑃𝐺𝑃𝑇) > 0, 
where 𝑝𝑁𝑇 and 𝑝𝑃𝑇 are the observed 12-month patency rates for NT and PT 
subjects, respectively; 𝑃𝐺𝑁𝑇 and 𝑃𝐺𝑃𝑇 are pre-specified fixed performance 
goals for NT and PT subjects, respectively; and 𝑞𝑁𝑇 and 𝑞𝑃𝑇, both are fixed 
weights for NT subjects (0.26) and PT subjects (0.74), respectively. The sample 
weights will not be adjusted based on actual enrollment rates. 
The literature-based patency rate for the PT population is assumed to be 0.779, 
with corresponding performance goal (𝑃𝐺𝑃𝑇) of 0.779 – 0.10 = 0.679.  The 
literature-based patency rate for the NT population is assumed to be 0.955, with 
corresponding performance goal (𝑃𝐺𝑁𝑇) of 0.955 – 0.10 = 0.855.  Sample size is 
calculated to achieve at least 85% power at the one-sided 2.5% significance 
level:   

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Characteristic 
Value 
Performance Goal 
𝑃𝐺𝑃𝑇 = 0.679; 𝑃𝐺𝑁𝑇 = 0.855 
Confidence level α 
0.025, one-sided 
Power 1-β 
≥85% 
Estimated Vici patency rates 
𝑝𝑃𝑇T = 0.779; 𝑝𝑁𝑇 = 0.955 
RESULT:  Sample Size 
156 evaluable subjects 
 
The estimated power is 84% for the primary efficacy endpoint (Patients who 
have a non-patent lesion prior to 12 months can be included in the analysis 
whether or not they are still being followed at 12 months because the 12-month 
patency status of their lesion is known). 
In addition to rejecting the above hypothesis, overall success of the trial will also 
be determined based on whether a) the observed patency rate in the PT group 
is greater than 0.679, AND b) the observed patency rate in the NT group is 
greater than 0.855.   
15.7.1 Primary Safety Endpoint 
None of the case series in the literature used pre-specified adverse 
event definitions. The complication rate appears to be low, but there 
are no controlled studies to indicate what a true adverse event rate 
might be under controlled reporting conditions. It is expected that the 
true rate of the pre-specified safety endpoint will be approximately 1%.  
The primary safety evaluation will test the following hypothesis: 
HO:  PVici ≤ 0.94 
HA:  PVici > 0.94, 
where PVici is the freedom from event rate of pre-specified safety events 
associated with use of the Veniti Vici Venous Stent and 0.94 is the pre-
specified performance goal.  The hypothesis will be tested under a one-
sided, one-sample exact binomial test.  The hypothesis will be tested at 
the 2.5% significance level, and approximately 170 subjects provide 
greater than 90% power.  Power was calculated using PASS 2008 
software. 

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15.7.2 Primary Secondary Endpoint 
The primary secondary endpoint is the binary response variable based 
on achieving at least 50% improvement in VCSS.  In a review of 
manuscripts by Hartung14, Rosales9, and Wahlgren11, information on 
VCSS improvements are provided, as follows:   
Hartung14: Median VCSS from 8.5 to 2 (n=44) 
Rosales9: Median VCSS from 9 to 1 (n=27) in group 1; median VCSS from 
21 to 7 (n=7) 
Wahlgren11: Mean VCSS from 9.1 to 6 (n=15) 
However, distributional information (variance, specifically) is not 
provided.  There also exists no generally agreed upon or accepted 
definition of a clinically meaningful improvement in VCSS to establish a 
performance goal.  Therefore, Veniti will test a hypothesis test based on 
50% of subjects improving by at least 50% as a means to demonstrate 
clinical benefit with the Veniti Vici Venous Stent.  The formal hypothesis 
test takes the form:  
HO:  PVici ≤ 0.50 
HA:  PVici > 0.50, 
where PVici is the proportion of subjects achieving at least 50% VCSS 
improvement (success rate), and 0.50 is the pre-specified performance 
goal.   Based on the literature cited above, it is reasonable to assume a 
62% success rate.  Assuming this underlying rate of success, at least 156 
evaluable subjects provides greater than 80% power to evaluate this 
objective at the 2.5% significance level under a one-sided, one-sample 
exact binomial test.  Power was calculated using PASS 2008 software.     
15.8 
Evaluation of Endpoints 
15.8.1 Primary Efficacy Endpoint   
The primary efficacy endpoint for this study will be the primary patency 
rate at 12 months post-intervention.  Stented limbs will be assigned the 
status of patency failure if they are known to have a patency failure 
event:   
• 
Thrombosis including the stented area of the vein 
• 
Re-intervention including the stented area 
• 
Venous imaging study at any time through 12 months showing a 
restenosis of greater than 50%.  
Patients will be assigned the status of patency success if their venous 
imaging study at 12 months showed no greater than 50% restenosis 
(and no prior study showed greater than 50% restenosis).  

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In the per-protocol (PP) analysis, only patients that meet either of these 
two criteria will be included. Patients with no imaging study at 12 
months and no patency failure event will be ignored in the analysis. 
In the worst-case and tipping point analyses, all patients will be 
included.  Patients who were ignored in the PP analysis will be treated 
as patency failures. 
Both the PP and worst-case analyses will test the following hypotheses:   
HO: 𝑞𝑁𝑇∗(𝑝𝑁𝑇−𝑃𝐺𝑁𝑇) + 𝑞𝑃𝑇∗(𝑝𝑃𝑇−𝑃𝐺𝑃𝑇) ≤0 
HA: 𝑞𝑁𝑇∗(𝑝𝑁𝑇−𝑃𝐺𝑁𝑇) + 𝑞𝑃𝑇∗(𝑝𝑃𝑇−𝑃𝐺𝑃𝑇) > 0, 
where 𝑝𝑁𝑇 and 𝑝𝑃𝑇 are the observed 12-month patency rates for NT 
and PT subjects, respectively; 𝑃𝐺𝑁𝑇 and 𝑃𝐺𝑃𝑇 are pre-specified fixed 
performance goals for NT and PT subjects, respectively; and 𝑞𝑁𝑇 and 
𝑞𝑃𝑇, both are fixed weights for NT subjects (0.26) and PT subjects (0.74), 
respectively. The sample weights will not be adjusted based on actual 
enrollment rates. 
The hypothesis test for this endpoint will be tested using a one-sided 
weighted Z-test at the 0.025 significance level. The test statistic for this 
hypothesis test is: 
𝑍=
𝑞𝑁𝑇∗(𝑝𝑁𝑇−𝑃𝐺𝑁𝑇) + 𝑞𝑃𝑇∗(𝑝𝑃𝑇−𝑃𝐺𝑃𝑇)
√𝑞𝑁𝑇2 ∗𝑃𝐺𝑁𝑇(1 −𝑃𝐺𝑁𝑇)
𝑛𝑁𝑇
+ 𝑞𝑃𝑇2 ∗𝑃𝐺𝑃𝑇(1 −𝑃𝐺𝑃𝑇)
𝑛𝑃𝑇
 
where 𝑝𝑁𝑇 is the proportion of successes in the NT population, 𝑃𝐺𝑁𝑇 is 
the performance goal of 85.5% for the NT population, 𝑞𝑁𝑇 is the pre-
defined weight of 0.266 for the NT population, 𝑝𝑃𝑇 is the proportion of 
successes in the PT population, 𝑃𝐺𝑃𝑇 is the performance goal of 67.9% 
for the PT population, 𝑞𝑃𝑇 is the pre-defined weight of 0.74 for the PT 
population. 
The p-value for the one-sided hypothesis test will be calculated as 
Φ(−𝑍), where Φ is the normal cumulative distribution function. 
15.8.2 Primary Safety Endpoint  
The primary safety events are listed in Section 8.2.  Patients who 
experience any of these events will be counted as safety failures in the 
analysis.  Detailed summaries of reported events will be provided, 
including calculated rates of events and corresponding 95% confidence 
intervals.  The following hypothesis test will be evaluated under a one-
sample, one-sided exact binomial test at the 0.025 significance level: 
HO:  PVici ≤ 0.94 
HA:  PVici > 0.94, 

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where PVici is the freedom from event rate of pre-specified safety events 
associated with use of the Veniti Vici Venous Stent System and 0.94 is 
the pre-specified performance goal. 
15.8.3 Secondary Efficacy Endpoint  
In order to control the overall type I error rate, the formal secondary 
efficacy endpoint will only be assessed if the primary endpoint objective 
is met.  The secondary efficacy endpoint is a binary response variable 
based on achieving at least 50% improvement in VCSS.  The following 
hypothesis test will be evaluated under a one-sample, one-sided exact 
binomial test at the 0.025 significance level: 
HO:  PVici ≤ 0.50 
HA:  PVici > 0.50, 
where PVici is the VCSS success rate,  and 0.50 is the pre-specified 
performance goal. 
15.9 
Evaluation of Ancillary Endpoints 
General Considerations 
None of the evaluations of ancillary endpoints will include hypothesis tests.  
Instead, the mean or proportion of each will be estimated along with the 95% 
confidence interval (CI).  Only the PP analysis will be performed on secondary 
endpoints (i.e., patients or limbs who contribute data will be included;  those 
without data on a particular endpoint will be ignored). 
15.9.1 Procedural Endpoints 
Procedural technical success.  The proportion of limbs with procedural 
technical success and the 95% CI will be reported. 
Lesion success. The proportion of limbs with lesion success and the 95% 
CI will be reported. 
Procedural success. The proportion of limbs with procedural success 
and the 95% CI will be reported. 
Late technical success. The proportion of limbs with late technical 
success and the 95% CI will be reported. 
Subgroup analysis. A subgroup analysis will be performed to evaluate 
device performance across genders. 
15.9.2 Clinical Endpoints 
Change in Venous Clinical Severity Scoring System (VCSS). Each limb’s 
change VCSS will be calculated; the mean of the changes and its 95% CI 
will be reported.  
Change in Quality of Life (CIVIQ-2).  Each patient’s area under the curve 
(AUC) will be calculated for the CIVIQ-2; the mean AUC and its 95% CI 
will be reported. 

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Minor outcomes. The proportion of patients with minor outcomes and 
the 95% CI will be reported. 
16 
CORE LAB ASSESSMENTS 
16.1 
Venogram Core Laboratory 
A copy of all venographic studies collected in the study will be sent to the 
angiographic core laboratory for review.  Venographic site assessment 
guidelines and shipping requirements will be provided by angiographic core lab 
(e.g., during the site training).  
16.2 
Duplex Ultrasound Core Laboratory 
All duplex ultrasound examinations collected through the 36 month follow-up of 
the study will be sent to the duplex ultrasound core laboratory for review and 
assessment. Duplex assessment guidelines, technician training (if required), and 
data submitting guidelines will be provided by the duplex ultrasound core 
laboratory (e.g., during the site training).  
Pre-enrollment DUS is considered an investigator-determined inclusion 
criterion, and does not require Core Laboratory confirmation.  
16.3 
IVUS Core Laboratory 
All IVUS evaluations will be analyzed by the independent core laboratory.  
17 
INSTRUCTIONS FOR USE 
See the Instructions for the Veniti Vici Venous Stent System. 
18 
INVESTIGATOR TRAINING 
Investigators responsible for delivering the Veniti Vici Venous Stent will receive 
sufficient training to ensure competence in the execution of all aspects of the 
procedures required to deliver the Veniti Vici Venous Stent.  Training may include hands 
on experience with demonstration devices, didactic presentations, or observing 
placement procedures performed by another physician and will include an extensive 
review of this study protocol and the Veniti Vici Venous Stent System Instructions for 
Use.   
19 
MONITORING PROCEDURES 
19.1 
Site Monitoring Plan 
It is the responsibility of Veniti to ensure that proper monitoring of the 
investigation is conducted and that IRB/EC review and approval of the 
investigation is obtained.  Monitoring visits will occur based on enrollment at 
the site, and at least annually.  Adequately trained Veniti personnel or delegates 
appointed by the study sponsor will monitor in order to ensure that the 
investigation is conducted, recorded and reported in accordance with: 
• 
The signed Investigator Responsibility Agreement 

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• 
The Investigational Plan 
• 
Applicable laws and regulations 
• 
Any requirements imposed by Veniti 
All monitoring activities will be performed and/or supervised by the overall 
study manager, Karen Fraser, RN, MS, Senior Director of Clinical Affairs, Veniti. 
Monitoring will be planned periodically at the study site to assure compliance 
with the study protocol.  The sponsor (or an appropriate designee) must 
therefore be allowed access to the patients’ files as per the informed consent at 
the investigator's site when so requested.   The monitoring visits may include 
but are not limited to the following: 
19.2 
Site Initiation Visit   
Site Initiation visits will be conducted by Veniti personnel or delegates.  The 
Veniti personnel or delegates will be responsible for the training of the 
investigators and other personnel.  The Veniti personnel or delegates will review 
all documentation collected from the site and ensure that each site has met the 
regulatory requirements and has all the necessary documentation and training 
to begin the clinical study and assures that the Investigator/staff: 
• 
Understands the investigational status of the device; 
• 
Understands the Investigational Plan including the protocol, records and 
reports (as specified in section F); 
• 
Understands the requirements for conducting a clinical study on medical 
devices; 
• 
Submits the Investigational Plan and required supporting documentation to 
the study center’s Institutional Review Board (IRB) or Ethics Committee (EC) 
for their review/approval; 
• 
Submits all FDA and annual reports to their IRB/EC; 
• 
Maintains all correspondence, the Investigational Plan, and all required 
records on file, and submits required reports in due time; 
• 
Assumes responsibility for the investigation at his/her institution which may 
include supervision of some tasks. 
19.3 
Routine Monitoring 
Routine monitoring visits are made periodically to assess the investigator’s 
adherence to the Investigational Plan, IRB/EC review of study progress (if 
appropriate), maintenance of records and reports, continued acceptability of 
the facilities, and selected review of source documents to assess accuracy, 
completeness, legibility and omissions to the Case Report Forms. The monitors 
will acquire information to assess the progress of the study (toward meeting 
study objectives) and identify any concerns that stem from observation of 
device performance and/or review of the investigator’s patient records, study 
management documents, device tracking and patient informed consent 
documents.  Resolution of concerns and completion of assigned tasks may be 
documented by the monitors.  Review of any ongoing findings may occur during 
monitoring visits. 

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19.4 
Closeout Visit 
Veniti personnel or delegates will schedule and conduct a Site Closeout Visit 
upon study or site closure.  If the site has not enrolled any subjects in the study, 
the closeout visit can be done via phone.  All investigational product will be 
returned to Veniti at the time of the closeout. 
20 
INSTITUTIONAL REVIEW BOARD/ETHICS COMMITTEE (IRB/EC) 
The protocol, informed consent document, and relevant supporting information must 
be submitted to the IRB for review and must be approved before the study is initiated.  
In addition, any subject recruitment materials must be approved by the IRB/EC prior to 
use. This study will be conducted in accordance with the ethical principles that have 
their origin in the Declaration of Helsinki and that are consistent with Good Clinical 
Practice, ISO 14155-2011, and applicable regulatory requirements. The study must be 
conducted in accordance with the regulations of the United Stated Food and Drug 
Administration (FDA) as described in 21 CFR 50 and 56, applicable laws and the IRB 
requirements. 
The sponsor must submit any change to the protocol to the IRB for review and approval 
before implementation.  A protocol change intended to eliminate an apparent 
immediate hazard to subjects may be implemented immediately, provided the FDA and 
the reviewing IRB are notified within 5 working days. 
It is the responsibility of the investigator to provide each subject with full and adequate 
verbal and written information, before inclusion in the study, using the IRB approved 
informed consent document, including the objective and procedures of the study and 
the possible risks involved.  Informed consent must be obtained prior to performing any 
study-related procedures, including screening and changes in medications including any 
washout of medications.  A copy of the signed informed consent document must be 
given to the study subject. 
The investigators have been selected because of their medical qualifications, interest in 
participation, ability to conduct and document the results of the study, ability to accrue 
patients.   
All investigators will provide their curriculum vitae to Veniti, Inc. and sign a Financial 
Disclosure and Investigator Agreement.   
21 
SUBJECTS’ CONFIDENTIALITY 
Information about study subjects will be kept confidential and managed according to 
the requirements of the Health Insurance Portability and Accountability Act of 1996 
(HIPAA).  The HIPAA regulations require a signed subject authorization informing the 
subject of the following:  
• 
What protected health information (PHI) will be collected from subjects in this study 
• 
Who will have access to that information  
• 
Who will use or disclose that information 
• 
The rights of a research subject to revoke their authorization for use of their PHI.  

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In the event that a subject revokes authorization to collect or use PHI, the Investigator 
retains the ability to use all information collected prior to the revocation of subject 
authorization.  For subjects that have revoked authorization to collect or use PHI, 
attempts should be made to obtain permission to collect at least vital status (i.e., fact 
whether the subject is alive) at the end of their scheduled study period. 
All data used in the analysis and summary of this study will be anonymous. Access to 
subject files will be limited to authorized personnel involved in the study.  
At time of enrollment, subjects will be assigned a trial-specific number identifier. This 
identifier will be used throughout the course of the study (instead of patient name, 
hospital ID, etc.) to ensure subjects confidentiality. 
22 
PUBLICATIONS 
At the conclusion of all follow-up visits, a multi-site abstract reporting the preliminary 
results may be prepared and presented at a major endovascular meeting.  A complete 
multi-center trial manuscript is the primary publication for the study. The publication of 
results from any single-site experience within the study must not be submitted for 
publication or presentation until a multi-center manuscript is published, unless 
otherwise approved by the Sponsor.   
The Sponsor will establish a publication committee and policy. The committee 
membership may include the overall Principal Investigator, other investigators from the 
study, and representatives of Veniti (e.g. statistician, clinical research specialist, etc.). 
The committee will establish a publication strategy.  The committee will be responsible 
for overseeing the development of any multi-site study manuscripts or abstracts. Any 
multi-site publications of study data must be reviewed and approved by at least two 
physician members of the publication committee prior to submission. Any previously 
unpublished information provided to the investigators by Veniti, such as patent 
applications, manufacturing processes and basic scientific data, is considered 
confidential and will remain the sole property of Veniti. The investigator agrees to use 
this information only in accomplishing this study and will not use it for other purposes 
without Veniti’s written consent. 
In addition, all multi-site and single-site abstracts or manuscripts must be reviewed by 
Veniti prior to submission. Veniti will limit its review to a determination of whether or 
not confidential information is disclosed, and will not attempt to censor the data or 
conclusions made in the publication.  
23 
DATA MANAGEMENT  
An electronic database capture (EDC) system (Mednet, Minneapolis, MN) will be used to 
record all subjects’ data in the study. This secure EDC will be backed up regularly to 
ensure collected data storage. The server will be accessible by password for all approved 
users via the internet, and data analytical workstations will be used for data processing 
and management.   
Conventional data verification sub-routines will be extensively programmed to test 
entry and logical errors, while all individual (subject-based) eCRFs will be linked for 

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cross-reference.  Periodic analysis of each data field (across subjects) will be performed 
in order to examine the expected distributions of data, and to identify outliers for 
possible data mistakes.  Corrections to data mistakes will be requested via queries.   
All information and data concerning subjects or their participation in this study will be 
considered confidential.  Only authorized personnel involved in the study will have 
access to these confidential files. As described in Section 21, each subject will be 
assigned unique identifier; therefore, all data used in the analysis and reporting of this 
evaluation will be without identifiable reference to the subject. 
24 
TERMINATION OF STUDY 
Investigators will be notified by Veniti, Inc. of study termination for any reason.  
Investigators are required to submit all patient and study data in a timely manner and 
comply with Veniti, Inc.’s request regarding disposition of the outstanding 
investigational devices.  
25 
ADDITIONAL RECORDS AND REPORTS 
25.1 
Investigator Records 
Records are subject to FDA inspection and must be retained for a period of two 
(2) years after the latter of the two dates: 
• 
the date on which the investigation is terminated or completed; or 
• 
the date that the records are no longer required for purposes of supporting 
an application to the FDA to market the device. 
• 
the investigator is responsible for the preparation (review and signature) 
and retention of the records cited below. 
• 
All correspondence which pertains to the investigation including required 
reports 
• 
Device Disposition Record 
• 
Screening Logs 
• 
Subject's case history records, including:  
• 
Signed Informed Consent document 
• 
All relevant patient complaints 
• 
Observations of adverse events 
• 
Medical history 
• 
All case report forms and supporting data 
• 
Documentation of protocol deviations, including date(s) and reason(s) for 
deviation(s) 
• 
Signed Protocol, Curriculum Vitae and Financial Disclosure (These must be 
submitted to Veniti and kept on file at the investigative center.) 
25.2 
Investigator Reports 
The investigator is responsible for the preparation (review and/or signature) 
and submission of the reports cited in Table 25.2.1 as required by 21 CFR 812 

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Subpart G and sponsor.  These are also subject to FDA inspection and the 
retention requirements described above for Investigator Records. 
Table 25.2.1:  Investigator Reports 
REPORT 
TO 
SUBMIT TO 
DESCRIPTION/CONSTRAINTS 
Unanticipated 
Adverse Device 
Effect 
Monitor & 
IRB/EC 
If an unforeseen complication is determined to be an 
unanticipated adverse device effect, then the investigator's 
report must be submitted within 10 working days after the 
investigator first learns of the effect.   
Withdrawal of 
IRB/MEC Approval 
Sponsor 
The investigator must report a withdrawal of the reviewing 
IRB/MEC approval within 5 working days.  
Progress Report 
IRB/EC 
The investigator must submit this report if the study lasts 
longer than one year. 
Deviation from 
Investigational 
Plan 
Sponsor & 
IRB/EC 
If the deviation may affect the scientific soundness of the 
plan or the rights, safety and welfare of the subjects the 
deviation must be approved by Veniti, reviewing IRB/MEC, 
and the FDA.  If the deviation does not affect these issues 
(study soundness, rights, safety, etc.) then only Veniti must 
approve it. 
Failure to Obtain 
Informed Consent 
Sponsor & 
IRB/EC 
The Investigator must make notification within 5 working 
days after device use.  The report must include a brief 
description of the circumstances justifying the failure to 
obtain informed consent and include written concurrence 
by a licensed physician not involved in the investigation. 
Final Report 
Sponsor & 
IRB/MEC 
This report must be submitted within three months after 
termination or completion of the investigation. 
Veniti Records 
Veniti will maintain the following records and submit reports per Table 25.2.2: 
1 
All vital correspondence that pertains to the investigation including reports 
2 
Device Shipment/Disposition Record 
3 
Signed Protocol Cover Pages, Investigator Agreements Curriculum Vitae 
4 
IRB/EC Approval Letter 
5 
Adverse events and complaints 
6 
Case Report Forms  
7 
Clinical Investigation Plan  
8 
 Monitoring Reports 

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Table 25.2.2:  Veniti Reports 
REPORT 
SUBMIT TO 
DESCRIPTION 
Unanticipated 
Device Related 
Adverse Event 
FDA, all IRBs/MECs 
and all Investigators 
Veniti will report on any and all unanticipated 
device-related adverse event evaluation within 10 
working days. 
Withdrawal of 
IRB/MEC 
Approval 
FDA, all IRBs/MECs 
and all Investigators 
Notification will be made within 5 working days. 
Withdrawal of 
FDA Approval 
All IRBs/MECs and all 
Investigators 
Notification will be made within 5 working days. 
Current 
Investigator List 
FDA 
Veniti will submit a list of names and addresses of 
all participating investigators at 6 month intervals. 
Progress Report 
FDA, all IRBs/MECs 
and all Investigators 
A progress report will be submitted at least yearly. 
Recall and 
Disposition 
FDA, all IRBs/MECs 
and all Investigators 
Notification will be made within 30 working days 
and will include the reasons for any request that an 
investigator return, repair or otherwise dispose of 
any devices. 
Final Report 
FDA, all IRBs/MECs 
and all Investigators  
Veniti will notify FDA within 30 working days of the 
completion or termination of the investigation.  A 
final report will be submitted within 6 months after 
completion or termination. 
Failure to Obtain 
Informed Consent 
FDA/IRB/ 
MEC 
A copy of the investigator's report will be submitted 
within 5 working days of notification. 
 
25.3 
IRB/EC Records 
Each reviewing IRB/MEC must maintain the following records relating to the 
investigation: 
• 
Records of protocols and continuing review 
• 
All pertinent correspondence between IRB and Investigator 
• 
Statement of significant new finding provided to subjects 
• 
All records of membership and affiliation 
• 
Meeting minutes 

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26 
APPENDIX 1: VENOUS ANATOMY DESIGNATIONS 
 
 
 
 
 
• 
Supra-renal inferior vena cava 
• 
Infra-renal inferior vena cava 
• 
Left common iliac vein 
• 
Left external iliac vein 
• 
Left common femoral vein 
• 
Left femoral vein 
• 
Right common iliac vein 
• 
Right external iliac vein 
• 
Right common femoral vein 
• 
Right femoral vein 
 
 
 
 
 
 
Infra-renal inferior vena cava 
   Supra-renal inferior vena cava 

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27 
APPENDIX 2: EXTENDED ANTICOAGULATION PROTOCOL 
 
 
Was the patient on 
anti-platelet prior to 
surgery?  
Does the need for 
anticoagulation outweigh need 
for antiplatelet therapy?  
Yes 
Resume antiplatelet agent 
within 24 hours.  Continue 
through the 12 month visit.  
 
No 
Does the patient have a history of 
thrombo-embolic events? (Prior DVT 
and/or target vessel obstruction 
found to be due to previous silent 
thrombosis)
Yes 
Was the patient on 
extended 
anticoagulation prior 
to procedure?  
No 
No 
Resume anticoagulation (VKA to 
maintain therapeutic INR, or 
rivaroxaban recommended 
dosing), continue through the 12 
month visit 
Yes 
Low dose ASA daily through 
the 12 month visit 
No 
History of ≥2 events? (Prior 
DVT/PE and target vessel 
obstruction found to be due to 
previous thrombosis)  
Yes 
Anticoagulation through the 
12 month visit (VKA to 
maintain therapeutic INR, 
or rivaroxaban 
recommended dosing)  
Yes
Patients with 1 thromboembolic event: 
Prior DVT/PE or target vessel obstruction 
found to be due to previous silent 
thrombosis AND target lesion is occlusive 
No 
Anticoagulation for 6 
months (VKA to maintain 
therapeutic INR, or 
rivaroxaban, as 
recommended dosing)  
No 
Yes
After 6 months 

 
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28 
APPENDIX 3: FRACTURES 
Assessment of the venous stents will be performed at 12 months, and at any interval 
evaluation, for analysis of strut fracture.  High-resolution digital images should be 
obtained in a diagnostic X-Ray unit, or in an angiography suite (if performed as part of 
an interval evaluation).  All images will be submitted to the Core Laboratory for 
assessment of strut fracture. 
Fractures will be assessed as per Jaff, et al.6 Data to be collected for each fracture 
identified includes: 
o Limb (right or left) 
o Venous segment(s) where fractures are located 
o Overlapping versus non-overlapping  
o Type of fracture (Type I, II, III, IV) 
 
 
 
 

 
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29 
APPENDIX 4: ADDITIONAL STUDY DEFINITIONS 
Allergic Reaction: A physical reaction to a substance that can cause wheezing, edema 
(swelling), induced thrombotic events, uticaria (rash), and/or shock.  
Arterio-venous (AV) Fistula:  A communication between an artery and a vein in which 
the arterial blood flows directly into a neighboring vein. 
Bleeding:  Blood loss resulting from the percutaneous interventional procedure or 
adjunctive drug therapy that may require transfusion of blood products. 
Catheter-Directed pharmacologic thrombolysis: An image guided technique involving 
infusion of thrombolytic agents through a multi-side hole infusion catheter or wire 
placed directly into a venous thrombus through a remote puncture site. 
CEAP Classification:  A method for evaluating venous disease of the leg based 
on clinical, etiologic, anatomic, and pathophysiologic data. 
Table 29.1: CEAP Classification of CVI 
Class 0 
No visible or palpable signs of venous disease (only symptoms) 
Class 1  
Telangiectasias or reticular veins 
Class 2  
Varicose veins 
Class 3  
Oedema 
Class 4  
Skin changes ascribed to venous disease (e.g. pigmentation, venous 
eczema, lipo-dermatosclerosis) 
Class 5 
Skin changes as defined above with healed ulceration 
Class 6  
Skin changes as defined above with active ulceration 
Central: closer to the heart; antegrade to the flow 
CIVIQ-2 (Chronic Venous Insufficiency Questionnaire): A self-administered 
questionnaire which explores four dimensions related to chronic lower limb venous 
insufficiency.  The four dimensions are psychological, physical and social functioning and 
pain.15 
Death: The termination of life. 
Diabetes (History of):  Defined as patients who have been diagnosed with either Type I 
or Type II diabetes and are currently taking oral hypoglycemics or insulin or have a 
hemoglobin A1C > 7%. 
Discharge:  The time point when the subject is released from the admitting hospital, 
transferred to another facility, or has expired. 
Femoropopliteal DVT: A DVT involving the femoral or popliteal venous segments, or 
both without extension to the common femoral or iliac veins. 
Fever:  An increase in internal body temperature to levels that are above normal (37°C, 
98.6°F). 

 
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Gastrointestinal (GI) bleeding:  any bleeding that starts in the gastrointestinal tract, 
which may extend from the mouth to the anus. 
Hematoma:  Localized mass of extravasated blood ≥ 5 cm that prolongs hospitalization. 
Hemorrhage:  Bleeding requiring hospitalization, repeat procedure, operation or 
transfusion.  
Hypertension: Increase in systolic blood pressure above 140 mm Hg or a diastolic blood 
pressure above 90 mm Hg. 
Hypotension: Fall in systolic blood pressure that requires intravenous treatment with 
vasopressors or inotropic agents. 
Iliofemoral DVT: DVT involving complete or partial thrombosis of the iliac vein or the 
common femoral vein, or both, with or without femoropopliteal DVT. 
Index Procedure: The procedure in which the subject has the study procedure 
performed or attempted. 
Infection:  Inflammation caused by bacterial or viral sources, such as, urinary tract 
infection, puncture site infection, sepsis, endocarditis, and bacteremia from IV site.   
Inflammation: An immunologic response to infection or trauma that can result in 
localized redness, swelling, heat, pain and dysfunction of the organs involved. 
Invasive Assessment/Procedure:  Any assessment, intervention or therapy that 
penetrates the skin, excluding administration of parenteral fluids or drugs. 
Kidney Failure:  Failure of the kidneys to perform essential functions that requires 
dialysis. 
Myocardial Infarction (Non-Q wave):  Post-treatment elevation of CK-MB more than 3 
times the upper limit of lab normal value without evidence of pathologic Q-waves 
present on EKG.  Elevated serum troponin levels are not sufficiently validated to be 
considered sole evidence of an MI in the absence of CK-MB elevations. 
Myocardial Infarction (Q wave):  Development/appearance of new pathological Q-
waves in more than 2 contiguous leads per 12-lead electrocardiogram (EKG/ECG). 
Peripheral: refers to a location away from the heart; retrograde to the flow 
Physician-Directed Subject Withdrawal:  Withdrawal of a subject from the study at the 
direction of the Principal Investigator.  Reasons for physician-directed subject 
withdrawal include, but are not exclusive to: the subject is not adhering to the Study 
Protocol requirements, the subject has enrolled in another study that conflicts with the 
VIRTUS outcomes of interest, or the physician deems it in the best interest for the safety 
or welfare of the subject to withdraw. 
Principal Investigator:  Physician responsible for overall clinical management of subjects 
enrolled at his/her institution. Assumes overall responsibility and accountability for the 
clinical team and for data obtained from each subject participating in the study. Ensures 
compliance with the Study Protocol, applicable laws, and applicable regulations; ensures 

 
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informed consents are signed, and reviews and signs eCRF indicating documents are 
accurate and complete. 
Protocol Deviation:  Any divergence from the Study Protocol. 
Pseudoaneurysm: Perforation of the vessel with arterial blood flow outside of the 
vessel.  
Sepsis:  Systemic inflammatory response to infection. 
Serious Adverse Device Effects:  Any adverse device effects that result in any 
consequences characteristic of a serious adverse event or might have led to any of these 
consequences if suitable action had not been taken or intervention had not been made 
or if circumstances had been less opportune. 
Serious Adverse Event:  Any adverse events that led to a death or led to a serious 
deterioration in the health of the subject that 1) resulted in a life-threatening illness or 
injury, 2) resulted in a permanent impairment of a body structure or a body function, 3) 
required inpatient hospitalization or prolongation of existing hospitalization, or 4) 
resulted in medical or surgical intervention to prevent permanent impairment to a body 
structure or body function.  This definition also includes any adverse event that led to 
fetal distress, fetal death or a congenital abnormality or birth defect.   
Stroke:  Neurological dysfunction caused by a brain disturbance or ischemia, with clinical 
symptoms lasting >24 hours or imaging of an acute clinically relevant brain lesion in 
patients with rapidly vanishing symptoms. 
Study Coordinator:  Employee at study site who assists Principal Investigator with study 
activities as delegated by the Principal Investigator, including tracking subjects involved 
in the study, scheduling testing and follow-up visits, maintaining study records, 
completing and providing eCRFs to the Sponsor in a timely manner. 
Sub-Investigator(s): Physician(s) responsible for study activities in coordination with 
Principal Investigator and in accordance to the Study Protocol.   
Systemic Infection: the bloodstream infection that affects a number of organs and/or 
tissues, or affects the body as a whole. 
Transient Ischemic Attack (TIA):  Brief episode of neurological dysfunction caused by a 
focal disturbance of brain or retinal ischemia, with clinical symptoms typically lasting 
less than 1 hour, and without evidence of infarction. 
Vascular Complications: Adverse sequelae within the vasculature which can result from 
catheter-based interventions, including arterio-venous fistula, bleeding, hematoma, 
infection and pseudoaneurysm (see Access Site Complications), aneurysm, venous 
perforation, venous rupture, venous spasm, hemorrhage, hypertension, hypotension,  
sub-acute closure, and thrombosis.  
Venous Clinical Severity Score (VCSS): An objective means to clinically assess venous 
disease16.  (See Appendix 7.) 
Visual Analog Scale (VAS): A scale for patients to report their pain level during activity 
or movement.   (See Appendix 6.) 
 

 
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30 
APPENDIX 5: CHRONIC VENOUS INSUFFICIENCY QUESTIONAIRRE  
(CIVIQ-2) 
Many people in the country complain of heavy or aching legs. We are trying to find the 
frequency of these leg problems, and how they can affect the everyday life of the 
people suffering from them. 
You will find hereafter a certain number of symptoms, sensations or discomforts that 
you may feel, and that can make everyday life more or less difficult.  
For each symptom, sensation or discomfort listed, we ask you to answer the 
corresponding question: 
Please indicate whether you have really experienced what is described in the sentence, 
and if so, to what intensity. Five answers are provided, please circle the intensity most 
suited to your situation. 
1 
If you do not feel concerned by the symptom, sensation of discomfort described 
2, 3, 4, or 5 
If you have felt it with more or less intensity. 
1. In the past four weeks, if you have felt pain in the ankles or legs, what was the 
intensity of this pain? (Circle the number corresponding to the right answer) 
No pain 
Light pain 
Moderate pain 
Strong pain 
Intense pain 
1 
2 
3 
4 
5 
 
2. During the past four weeks, to what extent did you feel bothered/limited in your work 
or your other daily activities because of your leg problem? (Circle the number 
corresponding to the right answer) 
Not 
bothered/limited 
A little 
bothered/limited 
Moderately 
bothered/limited 
Very 
bothered/limited 
Extremely 
bothered/limited 
1 
2 
3 
4 
5 
 
3. During the past four weeks, did you sleep badly because of your leg problems, and 
how often? (Circle the number corresponding to the right answer) 
Never 
Seldom 
Fairly often 
Very often 
Every night 
1 
2 
3 
4 
5 
 

 
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During the past four weeks, to what extent did your leg problems bother/limit you while 
doing the movement or activities listed below?  
(For each of the sentences listed in the left hand column of the table below, indicate to 
what extent you are bothered/limited by circling the corresponding number.) 
 
Not bothered 
/ limited at all 
A little 
bothered / 
limited 
Moderately 
bothered / 
limited 
Very 
bothered / 
limited 
Impossible 
to do 
4. To stand for a long time 
1 
2 
3 
4 
5 
5. To climb stairs 
1 
2 
3 
4 
5 
6. To crouch, to kneel 
1 
2 
3 
4 
5 
7. To walk briskly 
1 
2 
3 
4 
5 
8. To travel by car, bus, plane 
1 
2 
3 
4 
5 
9. To do housework such as 
standing about in the kitchen, 
carrying a child in your arms, 
ironing, cleaning floors or 
furniture, doing handy work 
1 
2 
3 
4 
5 
10. To go to discos, weddings, 
parties, cocktails 
1 
2 
3 
4 
5 
11. To do a sport, to make 
physically strenuous efforts 
1 
2 
3 
4 
5 
 
 
 

 
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Leg problems can also have an effect on one’s morale. To what extent do the following 
sentences correspond to the way you have felt during the past four weeks?  
(For each of the sentences listed in the left hand column of the table below, circle the 
number that best corresponds to the right answer.) 
 
 
Not at all  
A little  
Moderately 
A lot  
Absolutely  
12. I feel on edge. 
1 
2 
3 
4 
5 
13. I become tired quickly. 
1 
2 
3 
4 
5 
14. I feel I am a burden to 
 people. 
1 
2 
3 
4 
5 
15. I must always take 
precautions (such as to 
stretch my legs, to avoid 
standing for a long time...). 
1 
2 
3 
4 
5 
16. I am embarrassed to  
  show my legs. 
1 
2 
3 
4 
5 
17. I get irritated easily. 
1 
2 
3 
4 
5 
18. I feel handicapped. 
1 
2 
3 
4 
5 
19. I have difficulty to get going in 
the morning. 
1 
2 
3 
4 
5 
20. I do not feel like going out. 
1 
2 
3 
4 
5 
 
 
 

 
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31 
APPENDIX 6: VISUAL ANALOG SCALE (VAS PAIN SCALE) 
Directions:  Answer the following question by making a mark through the scale at the 
point which best describes your condition. Your mark should cross the line at only one 
point.  
 
                                                              Example: 
 
 
 
 
 
 
How bad is your pain with activity or movement? 
 
 
 
 
 
                               No pain at all                                                                                Worst possible pain 
 
 

 
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32 
APPENDIX 7: VENOUS CLINICAL SEVERITY SCORE (VCSS) 
Right Leg (Please see below for definitions.) 
 N/A 
1. 
Pain 
 
 
 
 
 
 0 (Absent) 
 1 (Mild)  
 2 (Moderate)  
 3 (Severe) 
2. 
Varicose Veins  
 
 
 
 0 (Absent) 
 1 (Mild)  
 2 (Moderate)  
 3 (Severe) 
3. 
Venous Edema  
 
 
 
 0 (Absent) 
 1 (Mild)  
 2 (Moderate)  
 3 (Severe) 
4. 
Skin Pigmentation  
 
 
 0 (Absent) 
 1 (Mild)  
 2 (Moderate)  
 3 (Severe) 
5. 
Inflammation 
 
 
 
 
 0 (Absent) 
 1 (Mild)  
 2 (Moderate)  
 3 (Severe) 
6. 
Induration  
 
 
 
 
 0 (Absent) 
 1 (Mild)  
 2 (Moderate)  
 3 (Severe) 
7. 
Active Ulceration (Number) 
 0 (Absent)  
 1 (Mild)  
 2 (Moderate)  
 3 (Severe) 
8. 
Active Ulceration (Duration) 
 0 (Absent)  
 1 (Mild)  
 2 (Moderate)  
 3 (Severe) 
9. 
Active Ulceration (Size) 
 
 0 (Absent)  
 1 (Mild)  
 2 (Moderate)  
 3 (Severe) 
10. Compression  
 
 
 
 0 (Absent)  
 1 (Mild)  
 2 (Moderate)  
 3 (Severe) 
Left Leg (Please see below for definitions.) 
 
 N/A 
11. Pain 
 
 
 
 
 
 0 (Absent)  
 1 (Mild)  
 2 (Moderate)  
 3 (Severe) 
12. Varicose Veins  
 
 
 
 0 (Absent)  
 1 (Mild)  
 2 (Moderate)  
 3 (Severe) 
13. Venous Edema  
 
 
 
 0 (Absent)  
 1 (Mild)  
 2 (Moderate)  
 3 (Severe) 
14. Skin Pigmentation  
 
 
 0 (Absent)  
 1 (Mild)  
 2 (Moderate)  
 3 (Severe) 
15. Inflammation 
 
 
 
 
 0 (Absent)  
 1 (Mild)  
 2 (Moderate)  
 3 (Severe) 
16. Induration  
 
 
 
 
 0 (Absent)  
 1 (Mild)  
 2 (Moderate)  
 3 (Severe) 
17. Active Ulceration (Number) 
 0 (Absent)  
 1 (Mild)  
 2 (Moderate)  
 3 (Severe) 
18. Active Ulceration (Duration) 
 0 (Absent)  
 1 (Mild)  
 2 (Moderate)  
 3 (Severe) 
19. Active Ulceration (Size) 
 
 0 (Absent)  
 1 (Mild)  
 2 (Moderate)  
 3 (Severe) 
20. Compression  
 
 
 
 0 (Absent)  
 1 (Mild)  
 2 (Moderate)  
 3 (Severe) 
 
 
 

 
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32.1 
VCSS Definitions 
Pain 
The clinician describes the four categories of leg pain or discomfort that are outlined below to 
the patient and asks the patient to choose, separately for each leg, the category that best 
describes the pain or discomfort the patient experiences. 
0 
Absent 
None 
1 
Mild 
Occasional pain or discomfort that does not restrict regular daily activity 
2 
Moderate 
Daily pain or discomfort that interferes with, but does not prevent regular 
daily activities 
3 
Severe 
Daily pain or discomfort that limits most regular daily activities 
 
Varicose Veins 
The clinician examines the patient’s legs and, separately for each leg, chooses the 
category that best describes the patient’s superficial veins.   Veins must be >3 mm 
diameter to qualify as “varicose veins”. 
0 
Absent 
None 
1 
Mild 
Few, scattered, varicosities that are confined to branch veins or clusters. 
Includes “corona phlebectatica” (ankle flare), defined as greater than 5 
blue telangiectases at the inner or sometimes the outer edge of the foot. 
2 
Moderate 
Multiple varicosities that are confined to the calf or the thigh 
3 
Severe 
Multiple varicosities that involve both the calf and the thigh 
 
Venous Edema 
The clinician examines the patient’s legs and, separately for each leg, chooses the category 
that best describes the patient’s pattern of leg edema. The clinician’s examination may be 
supplemented by asking the patient about the extent of leg edema that is experienced. 
0 
Absent 
None 
1 
Mild 
Edema that is limited to the foot and ankle 
2 
Moderate 
Edema that extends above the ankle but below the knee 
3 
Severe 
Edema that extends to the knee or above 
 
Skin Pigmentation 
The clinician examines the patient’s legs and, separately for each leg, chooses the category 
that best describes the patient’s skin pigmentation. Pigmentation refers to color changes of 
venous origin and not secondary to other chronic diseases (i.e. vasculitis purpura). 
0 
Absent 
None, or focal pigmentation that is confined to the skin over varicose 
veins 
1 
Mild 
Pigmentation that is limited to the perimalleolar area 
2 
Moderate 
Diffuse pigmentation that involves the lower third of the calf 
3 
Severe 
Diffuse pigmentation that involves more than the lower third of the calf 
 

 
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Inflammation 
The clinician examines the patient’s legs and, separately for each leg, chooses the category 
that best describes the patient’s skin inflammation. Inflammation refers to erythema, cellulitis, 
venous eczema, or dermatitis, rather than just recent pigmentation. 
0 
Absent 
None 
1 
Mild 
Inflammation that is limited to the perimalleolar area 
2 
Moderate 
Inflammation that involves the lower third of the calf 
3 
Severe 
Inflammation that involves more than the lower third of the calf 
 
Induration 
The clinician examines the patient’s legs and, separately for each leg, chooses the category 
that best describes the patient’s skin induration. Induration refers to skin and subcutaneous 
changes such as chronic edema with fibrosis, hypodermitis, white atrophy and 
lipodermatosclerosis. 
0 
Absent 
None 
1 
Mild 
Induration that is limited to the perimalleolar area 
2 
Moderate 
Induration that involves the lower third of the calf 
3 
Severe 
Induration that involves more than the lower third of the calf 
 
Active Ulceration - Number 
The clinician examines the patient’s legs and, separately for each leg, chooses the category 
that best describes the number of active ulcers. 
0 
Absent 
None 
1 
Mild 
One ulcer 
2 
Moderate 
Two ulcers 
3 
Severe 
Three or more ulcers 
 
Active Ulceration - Duration 
If there is at least one active ulcer, the clinician describes the four categories of ulcer duration 
that are outlined below to the patient and asks the patient to choose, separately for each leg, 
the category that best describes the duration of the longest unhealed ulcer. 
0 
Absent 
No active ulcers 
1 
Mild 
Ulceration present for less than 3 months 
2 
Moderate 
Ulceration present for 3 to 12 months 
3 
Severe 
Ulceration present for more than 12 months 
 

 
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Active Ulceration - Size 
If there is at least one active ulcer, the clinician examines the patient’s legs, and separately for 
each leg, chooses the category that best describes the size of the largest active ulcer. 
0 
Absent 
No active ulcer 
1 
Mild 
Ulcer of less than 2cm diameter 
2 
Moderate 
Ulcer of 2 to 6cm diameter 
3 
Severe 
Ulcer of greater than 6cm diameter 
 
Compression 
Choose the level of compliance with medical compression therapy 
0 
Absent 
Not used 
1 
Mild 
Intermittent use 
2 
Moderate 
Wears stockings most days 
3 
Severe 
Full compliance: stockings 
 
 
 

 
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33 
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