Evaluation of the Zilver® Vena™ Venous Stent in the Treatment of Symptomatic Iliofemoral Venous Outflow Obstruction
Phase: NA
Conditions: Symptomatic Venous Outflow Obstruction in the Iliofemoral Vein
Sponsor: Cook Research Incorporated

Cook Research Incorporated 
Evaluation of the Zilver® Vena™ Venous Stent 
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COMPANY CONFIDENTIAL 
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CLINICAL INVESTIGATION PLAN 
 
Evaluation of the Zilver® Vena™ Venous Stent in the Treatment of Symptomatic 
Iliofemoral Venous Outflow Obstruction (VIVO Clinical Study) 
 
 
 
Global Clinical Number 11-010 
 
 
 
Sponsor: 
Cook Research Incorporated 
1 Geddes Way 
West Lafayette, IN 47906 
USA 
 
Manufacturer: 
Cook Ireland Ltd. 
O’Halloran Road 
National Technology Park 
Limerick 
Ireland 
 
 
Summary of Revisions 
 
Version # 
Description 
Date 
11-010-01 
Original version 
06 Nov 2012 
11-010-02 
Clarified exclusion criteria; revised analysis plan 
24 Jan 2013 
11-010-03 
Added exclusion criterion; modified additional measures; 
05 Apr 2013 
revised analysis plan for primary safety hypothesis 
11-010-04 
Added exclusion criterion; clarified exclusion criteria; clarified 
23 Oct 2014 
medication requirements, study procedure, and follow-up schedule 
11-010-05 
Refined study design; modified exclusion criterion; 
24 Jun 2015 
administrative changes 
11-010-06 
Omitted interim analysis 
23 Jan 2017 
11-010-07 
Updated Sponsor information; administrative changes 
22 Mar 2018 

Cook Research Incorporated 
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Clinical Investigation Plan Signature Page 
 
This clinical investigation will be conducted in accordance with the Clinical Investigation Plan, 
ICH GCP, ISO 14155, 21 CFR 812, and other applicable requirements as appropriate. The 
Clinical Investigation Plan will be revised, as appropriate, based on new information. 
 
 
 
 
Sponsor: 
 
dd/mmm/yyyy 
 
Jennifer L. Kerr 
 
President, Cook Research Incorporated 
Printed Name 
Title 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Cook Research Incorporated 
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Evaluation of the Zilver® Vena™ Venous Stent 
 
 
Clinical Investigation Plan Signature Page, Continued 
 
Co-Global Principal Investigator 
 
I hereby confirm that I approve of this Clinical Investigation Plan and agree to comply with its 
terms as laid out in this document. 
 
Signature 
 
Printed Name 
Title 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Cook Research Incorporated 
COMPANY CONFIDENTIAL 
CJP 11-010-07 • 22 Mar 2018 
 
 
 
 
 
 
 
Evaluation of the Zilver®VenaTM Venous Stent 
 
 
Clinical Investigation Plan Signature Page, Continued 
 
Co-Global Principal Investigator 
 
I hereby confirm that I approve of this Clinical Investigation Plan and agree to comply with its 
terms as laid out in this document. 
 
Signature 
 
Printed Name 
/ 
Title 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Clinical Investigation Plan Signature Page, Continued 
 
Principal Clinical Investigator 
 
I hereby confirm that I approve of this Clinical Investigation Plan and agree to comply with its 
terms as laid out in this document. 
 
 
 
Signature 
dd/mmm/yyyy 
 
 
 
Printed Name 
Title 

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Evaluation of the Zilver® Vena™ Venous Stent 
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CONFIDENTIALITY STATEMENT 
 
 
 
 
This document will be treated as a confidential document for the sole 
information and use of the clinical investigation team and the IRB/EC. 

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TABLE OF CONTENTS 
1.0 General Information .............................................................................................................. 9 
1.1 Global Sponsor, Monitor, and Data Coordinating Center ................................................... 9 
1.2 Manufacturer ........................................................................................................................ 9 
1.3 Investigation Administration ............................................................................................... 9 
1.4 Investigator .......................................................................................................................... 9 
1.5 Monitoring Arrangements .................................................................................................. 10 
2.0  Approval and Agreement of the Clinical Investigation Plan ......................................... 100 
3.0  Clinical Investigation Plan Overview ............................................................................... 100 
4.0 Objectives of the Clinical Investigation ............................................................................. 12 
4.1 Objectives .......................................................................................................................... 12 
4.1.1 Primary Safety Endpoint ............................................................................................. 13 
4.1.2 Primary Effectiveness Endpoint .................................................................................. 13 
4.1.3 Secondary Endpoints ................................................................................................... 13 
4.1.4 Additional Measures ................................................................................................... 13 
4.2 Specific Hypotheses to be Accepted or Rejected by Statistical Data ................................ 14 
4.2.1 Primary Safety Hypothesis .......................................................................................... 14 
4.2.2 Primary Effectiveness Hypothesis .............................................................................. 14 
4.2.3 Secondary Endpoint Hypothesis ................................................................................. 15 
5.0 Device Description and Intended Use ................................................................................ 16 
5.1 General Device Description ............................................................................................... 16 
5.2 Indication for Use .............................................................................................................. 17 
5.3 Instructions for Use ............................................................................................................ 17 
6.0 Preliminary Investigations and Justification..................................................................... 17 
6.1 Literature Review .............................................................................................................. 17 
6.2 Non-Clinical Testing .......................................................................................................... 17 
6.3 Previous Clinical Experience ............................................................................................. 17 
7.0 Risk Analysis and Risk Assessment .................................................................................... 17 
7.1 Risks and Foreseeable Adverse Device Effects ................................................................. 18 
7.2 Methods to Minimize Risks ............................................................................................... 18 
8.0 Design of the Clinical Investigation .................................................................................... 18 
8.1 Type of Investigation ......................................................................................................... 18 
8.2 Rationale ............................................................................................................................ 18 
8.3 Measures to be Taken to Avoid or Minimize Bias ............................................................ 19 
8.4 Variables to be Measured to Demonstrate Achievement of Endpoints ............................. 19 
8.5 Inclusion and Exclusion Criteria ........................................................................................ 20 
8.6 Point of Enrollment ............................................................................................................ 22 

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8.7 Methods ............................................................................................................................. 22 
8.7.1 Duration of the Study .................................................................................................. 22 
8.7.2 Medications ................................................................................................................. 23 
8.7.3 Pre-Procedure .............................................................................................................. 23 
8.7.4 Procedure .................................................................................................................... 23 
8.7.5 Post-procedure/Pre-discharge ..................................................................................... 25 
8.7.6 Follow-up Schedule .................................................................................................... 25 
8.7.7 Imaging ....................................................................................................................... 26 
8.7.8 Reintervention within Treated Iliofemoral Venous Segment ..................................... 26 
8.8 Criteria and Procedures for Withdrawal/Lost to Follow-Up ............................................. 27 
8.9 Participation Endpoints of the Study ................................................................................. 28 
8.10 Sample Size ...................................................................................................................... 28 
8.11 Period of Use for the Device or its Control ..................................................................... 28 
8.12 Limitations of the Investigation ....................................................................................... 29 
8.13 Safety Monitoring ............................................................................................................ 29 
9.0 Statistical Considerations .................................................................................................... 30 
9.1 Endpoint Analyses ............................................................................................................. 30 
9.2 Sample Size Calculations ................................................................................................... 30 
9.3 Site-level Poolability .......................................................................................................... 31 
9.4 Planned Subgroups, Interactions, and Covariates .............................................................. 31 
9.5 Missing Data ...................................................................................................................... 32 
9.6 Future Use of Study Data ................................................................................................... 32 
10.0 Emergency Situations ........................................................................................................ 33 
11.0  Deviations from Clinical Investigation Plan .................................................................... 33 
12.0  Procedure for Reporting Adverse Events ........................................................................ 33 
13.0  Early Termination or Suspension of the Investigation ................................................... 34 
14.0 Ethical Considerations....................................................................................................... 34 
15.0 Publication Policy............................................................................................................... 34 
16.0 Data Collection ................................................................................................................... 34 
17.0 Data Reporting ................................................................................................................... 35 
18.0  Data Management and Quality Assurance ...................................................................... 35 
19.0 Insurance ............................................................................................................................ 35 
20.0 References ........................................................................................................................... 35 
 
APPENDICES 
 
Written Procedures for Monitoring Investigations ........................................................ Appendix A 
Definitions...................................................................................................................... Appendix B 

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1.0 
General Information 
1.1 
Global Sponsor, Monitor, and Data Coordinating Center 
Cook Research Incorporated 
1 Geddes Way 
West Lafayette, IN 47906 
USA 
 
1.2 
Manufacturer 
Cook Ireland Ltd. 
O’Halloran Road 
National Technology Park 
Limerick 
Ireland 
 
 
 
1.3 
Investigation Administration 
 
This investigation will be conducted in accordance with global regulations including ICH GCP, 
ISO 14155, and 21 CFR 812. 
 
1.4 
Investigator 
 
Contact information and qualifications of the co-global principal investigators, principal clinical 
investigators, clinical investigators, and core laboratories will be maintained by the data 
coordinating center. 

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1.5 
Monitoring Arrangements 
 
The conduct of the clinical study will be supervised through a process of centralized and on-site 
monitoring. The data coordinating center will remotely monitor the study for data completeness 
and for adverse events. On-site monitoring will be implemented as necessary throughout the 
course of the study. The investigator/institution will provide direct access to source 
data/documents for study-related monitoring, audits, IRB/EC review and regulatory inspection. 
Written procedures for monitoring the study are maintained by the data coordinating center and 
are summarized in Appendix A. 
 
2.0 
Approval and Agreement of the Clinical Investigation Plan 
 
The sponsor, co-global principal investigators, and principal clinical investigators for each 
investigative site will agree to this document and any modifications. Justification for any 
modifications will be documented. Approval and agreement will be indicated by signing and 
dating the signature page included in this document. 
 
3.0 
Clinical Investigation Plan Overview 
 
The following is a Clinical Investigation Plan to evaluate the safety and effectiveness of the 
Zilver® Vena™ Venous Stent in the treatment of symptomatic iliofemoral venous outflow 
obstruction. Patients with symptomatic venous outflow obstruction in one iliofemoral venous 
segment will be eligible to receive the Zilver® Vena™ Venous Stent. The treated venous 
segment (i.e., study lesion) will not extend into the inferior vena cava or below the level of the 
lesser trochanter. 
 
Primary study endpoints will include freedom from major adverse events at 30 days and primary 
quantitative patency at 12 months. The secondary endpoint will be the change from baseline in 
the Venous Clinical Severity Score (VCSS) at 1 and at 12 months. [Information redacted due to 
confidential content.]  

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This study is designed as a prospective, non-randomized, multi-center study involving up to 
40 investigative sites globally. The results of this study will be compared to performance goals 
derived from the literature. The clinical study intends to enroll 243 patients, and will involve 
follow-up through 3 years post stent placement. The study flow diagram is presented in Figure 
3.1. 

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Baseline assessments and screening in accordance with institutional standard of care 
Informed consent obtained 
Study specific baseline assessments and screening to ensure that the patient meets inclusion/exclusion 
criteria based on history, clinical assessment (VDSa, CEAP “C” Classificationb, CIVIQc, VCSSd, and 
assessment of medications), and venographye prior to stent placement 
Zilver® Vena™ Venous Stent placement under fluoroscopy, and completion venographye following 
stent placement 
Post-procedure clinical assessment (assessment of medications) and duplex ultrasound of the treated 
venous segment, and 2 view stent x-raye within 48 hours after the stenting procedure 
1 month: Clinical assessment (VDSa, CEAP “C” Classificationb, CIVIQc, VCSSd, assessment of 
medications, hospitalizations and medical conditions) 
3 months: Telephone contact and assessment of hospitalizations and medical conditions 
6 months: Clinical assessment (VDSa, CEAP “C” Classificationb, CIVIQc, VCSSd, assessment of 
medications, hospitalizations and medical conditions), duplex ultrasound of the treated venous 
segmentf, and 2 view stent x-raye 
12 months: Clinical assessment (VDSa, CEAP “C” Classificationb, CIVIQc, VCSSd, assessment of 
medications, hospitalizations and medical conditions), venographye, duplex ultrasound of the treated 
venous segment, and 2 view stent x-raye 
24 months: Clinical assessment (VDSa, CEAP “C” Classificationb, CIVIQc, VCSSd, assessment of 
medications, hospitalizations and medical conditions), duplex ultrasound of the treated venous 
segmentf, and 2 view stent x-raye 
36 months: Clinical assessment (VDSa, CEAP “C” Classificationb, CIVIQc, VCSSd, assessment of 
medications, hospitalizations and medical conditions), duplex ultrasound of the treated venous 
segmentf, and 2 view stent x-raye 
Figure 3.1. Study flow diagram 
aVDS: Venous Disability Score, bCEAP: score of Clinical, Etiological, Anatomic, and Pathophysiologic features, 
cCIVIQ: Chronic Venous Insufficiency Quality of Life Questionnaire, dVCSS: Venous Clinical Severity Score 
eBoth obliques of the pelvis recommended. 
fIf patient is symptomatic and ultrasound is inadequate to assess clinical patency, venography will be performed. 
 
4.0 
Objectives of the Clinical Investigation 
 
4.1 
Objectives 
 
The objectives of this investigation are to evaluate the safety and effectiveness of the Zilver® 
Vena™ Venous Stent in the treatment of symptomatic iliofemoral venous outflow obstruction. 

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4.1.1 
Primary Safety Endpoint 
 
The primary safety endpoint will be 30-day freedom from major adverse events (MAE), where 
MAE is defined as procedural bleeding requiring transfusion, procedure- or device-related death, 
clinically driven target lesion reintervention, clinical migration, new symptomatic pulmonary 
embolism, or procedure-related perforation requiring open surgical repair or flow-limiting 
dissection of the target vessel. 
 
4.1.2 
Primary Effectiveness Endpoint 
 
The primary effectiveness endpoint will be primary quantitative patency (see Definitions) of the 
Zilver® Vena™ Venous Stent as assessed by venography at 12-month follow-up. 
 
4.1.3 
Secondary Endpoints 
 
The secondary endpoint will be the change from baseline in the VCSS at 1 and at 12 months. 
 
4.1.4 
Additional Measures 
 
[Information redacted due to confidential content.]  

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4.2 
Specific Hypotheses to be Accepted or Rejected by Statistical Data 
 
4.2.1 
Primary Safety Hypothesis 
 
The primary safety endpoint is 30-day freedom from major adverse events (MAE), and will be 
analyzed based on the intent-to-treat population. The analysis requires that the performance goal 
(πPGS) of 87% be met for 30-day freedom from MAE, where πPGS is a weighted average of 85% 
(computed based on safety data for patients with acute disease, defined as initial symptom onset 
within 30 days of the procedure) and 88% (computed based on safety data for patients with 
chronic disease, defined as initial symptom onset greater than 30 days before the procedure), 
with the weight being prespecified as 30% acute patients and 70% chronic patients. Both 85% 
and 88% were computed based on 30-day safety data available in the published literature 
describing patients treated with commercially available stents for acute and chronic iliofemoral 
venous outflow obstruction, respectively.1-39 The safety of the Zilver® Vena™ Venous Stent will 
be established provided the null hypothesis is rejected in favor of the alternative hypothesis with 
the Binomial test for one proportion at the Type I error level of 0.025. 
 
Let πS (where S stands for safety) be the probability that a randomly selected patient is free from 
a MAE at 30 days, then the hypothesis is formulated as follows: 
 
Null Hypothesis: The 30-day freedom from MAE for patients treated with the Zilver® 
Vena™ Venous Stent does not meet the performance goal (87%). 
 
H0: πS ≤ πPGS; or H0: πS ≤ 87% 
 
Alternate Hypothesis: The 30-day freedom from MAE for patients treated with the 
Zilver® Vena™ Venous Stent meets the performance goal (87%). 
 
Ha: πS > πPGS; or Ha: πS > 87% 
 
4.2.2 
Primary Effectiveness Hypothesis 
 
The primary effectiveness endpoint is 12-month primary quantitative patency, and will be 
analyzed based on the intent-to-treat population. The analysis requires that the performance goal 

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(πPGE) of 76% be met for primary quantitative patency at 12 months. The performance goal was 
derived based on 12-month patency data available in published literature describing patients 
treated with commercially available stents for acute and chronic iliofemoral venous outflow 
obstruction.1-39 Patency outcomes were similar among patients with acute and chronic disease. 
The effectiveness of the Zilver® Vena™ Venous Stent will be established provided the null 
hypothesis is rejected in favor of the alternative hypothesis with the Binomial test for one 
proportion at the Type I error level of 0.025. 
 
Let πE (where E stands for effectiveness) be the probability that a randomly selected patient’s 
treated segment is primary patent (quantitative) at 12 months, then the hypothesis is formulated 
as follows: 
 
Null Hypothesis: The 12-month primary quantitative patency for patients treated with the 
Zilver® Vena™ Venous Stent does not meet the performance goal (76%). 
 
H0: πE ≤ πPGE; or H0: πE ≤ 76% 
 
Alternate Hypothesis: The 12-month primary quantitative patency for patients treated 
with the Zilver® Vena™ Venous Stent meets the performance goal (76%). 
 
Ha: πE > πPGE; or Ha: πE > 76% 
 
Study success requires that both primary hypotheses (i.e., safety and effectiveness) be met. 
 
4.2.3 
Secondary Endpoint Hypothesis 
 
The secondary endpoint is the change from baseline in the VCSS at 1 month and at 12 months. 
The change from baseline in VCSS at 1 month and at 12 months will be tested against 0 for 
statistical significance at the Type I error level of 0.05. 
 
Let Sdiff be the change from baseline on VCSS at a specific time point, then the hypothesis is 
formulated as follows: 

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Null Hypothesis: The change from baseline on VCSS at a time point for patients treated 
with the Zilver® Vena™ Venous Stent is not significantly different from 0. 
 
H0: Sdiff = 0 
 
Alternate Hypothesis: The change from baseline on VCSS at a time point for patients 
treated with the Zilver® Vena™ Venous Stent is significantly different from 0. 
 
Ha: Sdiff ≠ 0 
 
Paired t-test will be used to evaluate the secondary hypotheses. In the analyses of VCSS, 
multiplicity will be adjusted using the Holm procedure due to the presence of multiple time 
points. 
 
5.0 
Device Description and Intended Use 
 
5.1 
General Device Description 
 
The Zilver® Vena™ Venous Stent (Figure 5.1) is a self-expanding, slotted tube nitinol stent. It is 
designed to provide support while maintaining flexibility in the vessel upon deployment. Post- 
deployment, the stent is designed to impart an outward radial force upon the inner lumen of the 
vessel, establishing patency in the stented region. The device is intended for insertion into the 
iliofemoral venous system using percutaneous access. The stent is pre-loaded in a 7.0 French 
over-the-wire delivery catheter. The delivery catheter is available in 80 cm and 120 cm lengths. 
 
 
 
 
 
 
Figure 5.1. Zilver® 
Vena™ Venous Stent 
 
Please reference the manufacturer’s Instructions for Use for the device sizes available for the 
clinical investigation. 
 
Devices under investigation will be tracked by the investigative site throughout the course of the 
study through the use of a product log, which includes information such as lot numbers, quantity 
and device disposition. Additionally, information such as the quantity, size(s) and lot number(s) 

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of devices used in patients will be recorded on Case Report Forms (CRFs). 
 
5.2 
Indication for Use 
 
The Zilver® Vena™ Venous Stent is indicated for improving luminal diameter in the iliofemoral 
veins for the treatment of symptomatic venous outflow obstruction. 
 
5.3 
Instructions for Use 
 
Please reference the manufacturer’s Instructions for Use for the following: 
 
• Complete instructions including storage and handling requirements, preparation for use, 
precautions to be taken. 
• Summary of the necessary training and experience required for use of these devices. 
• Complete description of the procedures involved in the use of these devices. 
 
6.0 
Preliminary Investigations and Justification 
 
6.1 
Literature Review 
 
Please reference the Investigator’s Brochure for a complete literature review and evaluation. 
 
6.2 
Non-Clinical Testing 
 
Non-clinical tests were conducted in accordance with Good Laboratory Practice requirements, or 
performed in compliance with verified methods and Standard Operating Procedures to maintain 
the integrity of the results. In vitro and in vivo testing has established the safety of the device for 
its intended purpose. Please reference the Investigator’s Brochure for a summary of non-clinical 
testing. 
 
6.3 
Previous Clinical Experience 
 
Please reference the Investigator’s Brochure for a complete description of the previous clinical 
experiences with the device or other similar devices. 
 
7.0 
Risk Analysis and Risk Assessment 
 
Please reference the Investigator’s Brochure for a complete risk analysis. 

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7.1 
Risks and Foreseeable Adverse Device Effects 
 
Please reference the Investigator’s Brochure for a list of adverse events that may be 
considered as potential risks associated with the use of the Zilver® Vena™ Venous 
Stent 
 
7.2 
Methods to Minimize Risks 
 
The device design, non-clinical testing, clinical study design, and the manufacturer’s Instructions 
for Use are intended to minimize the risks associated with the use of this device. 
 
This device will be used only by trained healthcare professionals who are experienced in the 
study procedure. Patients will be selected according to the labeled indication and in accordance 
with inclusion/exclusion criteria outlined in this document. 
 
The risks of the study have been minimized and the potential benefits outweigh the risks in light 
of the importance of the knowledge to be gained about the safety and effectiveness of the Zilver® 
Vena™ Venous Stent. 
 
8.0 
Design of the Clinical Investigation 
 
8.1 
Type of Investigation 
 
This is a prospective, non-randomized, multi-center study that is intended to enroll 243 patients 
at up to 40 investigative sites globally. At least half of the study patients will be enrolled at US 
sites. The results of this single-arm study will be compared to performance goals derived from 
the literature. 
 
8.2 
Rationale 
 
The purpose of this study is to evaluate the safety and effectiveness of the Zilver® Vena™ 
Venous Stent in patients with symptomatic iliofemoral venous outflow obstruction. 
 
The endpoints were chosen as applicable measures of device effectiveness and safety because of 
their similarity to those of interest in the literature. 

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8.3 
Measures to be Taken to Avoid or Minimize Bias 
 
Patients with symptomatic iliofemoral venous outflow obstruction will be screened consecutively 
to mitigate selection bias. Investigational sites should maintain a screening log of patients. For 
patients who are excluded from the study, the log indicates the primary inclusion/exclusion 
criterion that is violated. 
 
The study will utilize uniform definitions for study endpoints, event adjudication by an 
independent clinical events committee, and imaging data analysis by a centralized core 
laboratory. Study results will be analyzed in accordance with a prospectively defined analysis 
plan. 
 
8.4 
Variables to be Measured to Demonstrate Achievement of Endpoints 
Imaging analysis will be performed by independent core laboratories. 
The clinical data and imaging measurements will be collected on standardized CRFs, which may 
serve as source documents. The schedule for assessments is summarized in Table 8.1. 

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Table 8.1. Data Collection Schedule 
 
Pre-Procedure 
Procedure 
Post-Procedurea 
1 month 
3 months 
6 months 
12 months 
24 months 
36 months 
Prior to reintervention 
Post reintervention 
Clinical assessment 
including CEAP “C” 
classification, CIVIQ, 
VCSS, VDS 
X 
X 
X 
X 
X 
X 
X 
Venographyb 
Xe 
X 
X 
X 
2 view Stent X-rayc 
X 
X 
X 
X 
X 
X 
X 
Duplex Ultrasoundd 
X 
Xf 
X 
Xf 
Xf 
X 
X 
Telephone contact 
X 
aPerformed prior to hospital discharge or within 48 hours. 
bVenography must be in approximately two orthogonal views. 
cBoth obliques of the pelvis recommended. 
dDuplex ultrasound must include the treated venous segment, including cranial and caudal vessel segments. 
eVenography, ultrasound, IVUS, or CTV performed within 1 month prior to the study procedure are acceptable for 
the purposes of documenting in-flow tract patency. Venography, IVUS, or CTV performed within 1 month prior to 
the study procedure are acceptable for the purposes of documenting out-flow tract patency. Venography is required 
pre and post stent placement for all procedural assessments to the study vessel and treated venous segment. 
fIf patient is symptomatic and ultrasound is inadequate to assess clinical patency, venography will be performed. 
 
8.5 
Inclusion and Exclusion Criteria 
 
Patient eligibility for enrollment will be based on known information at the time of the 
procedure. Information obtained at a later date may contradict these criteria, but this will not be 
considered a violation of the Clinical Investigation Plan. [Information has been redacted due to 
confidential content.] 
 
Inclusion Criteria: 
 
1) symptomatic venous outflow obstruction in one iliofemoral venous segment (i.e., one 
limb) per patient, demonstrated by: 
• CEAP “C” ≥ 3, or 
• VCSS pain score ≥ 2 

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General Exclusion Criteria: 
 
1) < 18 years of age; 
2) pregnant or planning to become pregnant in the next 12 months; 
3) surgical or interventional procedures of the target limb (except thrombolysis and/or 
thrombectomy in preparation for the procedure or vena cava filter placement prior to 
stent implantation in patients at high risk for pulmonary embolism) within 30 days prior 
to the study procedure; 
4) surgical or interventional procedures for other medical conditions (i.e., not associated 
with the target limb) within 30 days prior to the study procedure; 
5) lesions with intended treatment lengths extending into the inferior vena cava or below the 
level of the lesser trochanter; 
6) lesion with malignant obstruction; 

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7) previous stenting of the target vessel; and 
 
Venographic Exclusion Criterion: 
 
1) iliofemoral venous segment unsuitable for treatment with available sizes of study devices. 
 
 
8.6 
Point of Enrollment 
 
Patients may be enrolled in the study if all inclusion and no exclusion criteria are met. 
 
Patients who meet the inclusion/exclusion criteria (i.e., meet the inclusion criteria and none of 
the exclusion criteria) will be invited to participate in this investigation. All patients eligible for 
entry into the study will have the Clinical Investigation Plan explained to them, as well as 
potential risks and benefits of their participation in the study. Each patient who agrees to 
participate will be required to sign an informed consent document prior to the procedure or any 
study-specific testing. If new information is obtained after a patient receives treatment with the 
device, patients who have not exited the study will be informed about the new information, and 
will be re-consented at the discretion of the investigator and/or the site’s IRB/EC. 
 
Point of enrollment (and inclusion in the intent-to-treat population) occurs when the Zilver® 
Vena™ Venous Stent delivery system is introduced into the patient’s body. 
 
8.7 
Methods 
 
8.7.1 Duration of the Study 
 
Enrollment is expected to be completed within 60 months of enrolling the first patient. Twelve- 
month post-procedure clinical and imaging data are expected to be available approximately 
14 months after the last patient is enrolled in the study with follow-up to continue for 36 months 
following initial stent placement. 

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8.7.2 Medications 
 
Patients should receive aspirin prior to stent implantation. Following stent implantation, patients 
will receive one anticoagulant for a minimum of 6 months and aspirin for the duration of the 
study. Multiple anticoagulants should only be used for bridging purposes. Clopidogrel may be 
substituted for aspirin at the discretion of the physician. Doses will be in accordance with 
physician discretion and institutional standard of care. Anticoagulant and antiplatelet 
medications will be recorded on the appropriate Case Report Form throughout the study. 
 
8.7.3 Pre-Procedure 
 
A pre-procedure clinical assessment will be completed including medical history and 
documentation of the symptom(s) indicative of venous outflow obstruction, using VDS, CEAP 
“C” Classification, CIVIQ, and VCSS scores, and assessment of medications. 
 
8.7.4 Procedure 
 
• INR will be assessed within 24 hours prior to stent placement and will not be > 3 before 
proceeding with stent placement. 
• I.V. heparin bolus should be administered per institutional standard of care based upon 
clinical indication and underlying disease process. 
• Thrombolysis and/or thrombectomy are permitted prior to stent implantation in patients with 
thrombus present in the intended treatment segment (including the inflow and outflow 
segments). Vena cava filter placement is permitted prior to stent implantation in patients at 
high risk for pulmonary embolism (e.g., patients undergoing pre-procedure thrombolysis, 
those in whom tracking through the diseased vessel may cause material to dislodge from the 
vessel wall, and those at continued risk for pulmonary embolism for some other reason). 
• Venography in approximately two orthogonal views will be performed prior to study 
enrollment to determine the status of the inflow tract (from the level of the popliteal vein to 
just caudal to the study lesion), outflow tract (from the vein just cranial to the study lesion up 
to the level of L1 in the inferior vena cava), and study lesion, as well as the vein size at the 
intended stent location. Ultrasound, IVUS, or CTV performed within 1 month prior to the 
study procedure are acceptable alternatives for the purposes of documenting in-flow tract 
patency. IVUS and CTV performed within 1 month prior to the study procedure are 
acceptable alternatives for the purposes of documenting out-flow tract patency. Any 
thrombus that requires treatment (thrombolysis and/or thrombectomy) must be treated prior 
to enrollment and treatment of the study lesion; there will be no residual obstruction/stenosis 

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>20% in the inferior vena cava or below the level of the lesser trochanter (e.g., in the femoral 
and/or popliteal veins). 
• A calibration source (e.g., LeMaitre Ruler) will be in the field of view, but not overlapping 
the vessel. Vessel diameters immediately proximal and distal to the study lesion will be 
measured. The chosen stent diameter should be oversized 2-4 mm with respect to the 
estimated vessel diameter as determined by the best-available assessment (in preferential 
order): 
1. Diameter of the most normal looking segment of the common iliac, external iliac, 
or common femoral vein; 
2. Expanded balloon diameter used for predilatation; or 
3. Standard diameter of the vein to be stented. 
• The study lesion length will be measured to determine the length of the stent required. To 
cover the entire study lesion, the cranial and caudal aspects of the stent should extend into the 
healthy tissue by 5-10 mm. 
• Pre-dilation is recommended. 
• The Zilver® Vena™ Venous Stent will be deployed in the intended location under 
fluoroscopy according to the manufacturer’s Instructions for Use. 
• Placement of additional stents to cover the full extent of the study lesion (including 
geographical miss or vascular injury) is allowed. Zilver® Vena™ Venous Stent(s) should be 
used. If more than one stent is placed, stents will be deployed and overlapped as 
recommended in the manufacturer’s Instructions for Use. In addition, the diameters of 
additional stents may be increased or decreased depending on the extent of taper along the 
intended treatment length. Proximally, stents may protrude into the IVC, but will not appose 
the walls of the IVC (i.e., a stent protruding into the IVC is intended to protect the iliac 
ostium and prevent the development of stenosis at the IVC-common iliac vein confluence, 
not to treat lesions in the IVC). Distally, stents will not extend beyond the level of the lesser 
trochanter. 
• If incomplete expansion exists within the stent at any point along the lesion, post-deployment 
balloon dilatation with a PTA balloon can be performed at the discretion of the physician. 
An appropriate size balloon catheter should be selected and the inflation diameter of the 
balloon used for post dilatation should approximate the diameter of the target vein. 
• Final completion venography in approximately two orthogonal views will be performed of 
the treated segment and at least 1 cm cranial and caudal to the treated segment to assess stent 
position and patency. 

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8.7.5 Post-procedure/Pre-discharge 
 
Post-procedure, patients will undergo observation and discharge according to institutional 
standard of care. Within 48 hours of the stenting procedure, patients must undergo a duplex 
ultrasound of the treated venous segment, including the cranial and caudal vessel segments, and a 
2 view stent x-ray (both obliques of the pelvis recommended). Patients should resume normal 
activities with ambulation as soon as is feasible. Use of compression therapy is recommended in 
accordance with institutional standard of care. 
 
8.7.6 Follow-up Schedule 
 
Follow-up windows are intended as guidelines only. They are not absolute and are not intended 
to limit data collection due to scheduling conflicts. 
• 1-month clinic visit (30 days ± 5 days): An office visit will be completed including 
documentation of VDS, CEAP “C” Classification, CIVIQ, and VCSS scores, and 
assessment of medications, hospitalizations and medical conditions. 
• 3-month telephone contact (90 days ± 10 days): Patients will be contacted by telephone 
by the investigative site for clinical evaluation and assessment of hospitalizations and 
medical conditions. Up to three attempts should be made to contact the patient. 
• 6-month clinic visit (180 days ± 30 days): An office visit will be completed including 
documentation of VDS, CEAP “C” Classification, CIVIQ, and VCSS scores, and 
assessment of medications, hospitalizations and medical conditions. Duplex ultrasound 
of the treated venous segment (including the cranial and caudal vessel segments) to 
assess clinical patency and 2 view stent x-ray (both obliques of the pelvis recommended) 
to assess device integrity will be performed. Confirmatory venography in approximately 
two orthogonal views will be performed if the patient is symptomatic and the ultrasound 
is inadequate to assess clinical patency. 
• 12-month clinic visit (365 days ± 45 days): An office visit will be completed including 
documentation of VDS, CEAP “C” Classification, CIVIQ, and VCSS scores, and 
assessment of medications, hospitalizations and medical conditions. Venography in 
approximately two orthogonal views will be performed of the treated segment and at least 
1 cm cranial and caudal to the treated segment to assess quantitative patency. A 
calibration source (e.g., LeMaitre Ruler) will be in the field of view, but not overlapping 
the vessel. Duplex ultrasound of the treated venous segment (including the cranial and 

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caudal vessel segments) to assess clinical patency, and 2 view stent x-ray (both obliques 
of the pelvis recommended) to assess device integrity will be performed. 
• 24-month clinic visit (730 ± 60 days): An office visit will be completed including 
documentation of VDS, CEAP “C” Classification, CIVIQ, and VCSS scores, and 
assessment of medications, hospitalizations and medical conditions. Duplex ultrasound 
of the treated venous segment (including the cranial and caudal vessel segments) to 
assess clinical patency and 2 view stent x-ray (both obliques of the pelvis recommended) 
to assess device integrity will be performed. Confirmatory venography in approximately 
two orthogonal views will be performed if the patient is symptomatic and the ultrasound 
is inadequate to assess clinical patency. 
• 36-month clinic visit (1095 ± 75 days): An office visit will be completed including 
documentation of VDS, CEAP “C” Classification, CIVIQ, and VCSS scores, and 
assessment of medications, hospitalizations and medical conditions. Duplex ultrasound 
of the treated venous segment (including the cranial and caudal vessel segments) to 
assess clinical patency and stent 2 view x-ray (both obliques of the pelvis recommended) 
to assess device integrity will be performed. Confirmatory venography in approximately 
two orthogonal views will be performed if the patient is symptomatic and the ultrasound 
is inadequate to assess clinical patency. 
 
8.7.7 Imaging 
 
An Imaging Manual (including venography, duplex ultrasound, and 2 view stent x-ray) will be 
provided by Cook for the investigator’s and site’s reference. Guidelines provided by the core lab 
and Cook should be followed for the imaging exams. 
 
8.7.8 Reintervention within Treated Iliofemoral Venous Segment 
 
If a patient requires reintervention within the treated venous segment (i.e., bypass, 
thrombectomy, PTA, etc.), the patient should be treated with the standard of care for the 
institution. The following must be performed prior to a reintervention: 
• Clinical assessment (medications and adverse events), 
• Documentation of VDS, CEAP “C” Classification, CIVIQ, and VCSS scores, and the 
symptom(s) indicative of the need for revascularization, 
• Duplex ultrasound of the treated venous segment and the cranial and caudal vessel 
segments, 

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• 2 view stent x-ray (both obliques of the pelvis recommended), 
• INR assessed within 24 hours of the reintervention, and 
• The treated segment and at least 1 cm cranial and caudal to the treated segment will be 
assessed by venography in approximately two orthogonal views at the time of 
reintervention (i.e., prior to and immediately after the intervention); a calibration source 
(e.g., LeMaitre Ruler) will be in the field of view, but not overlapping the vessel. The 
venogram will be submitted to the data coordinating center along with a procedural 
report. 
 
The following must be performed following a reintervention: 
 
• Duplex ultrasound of the study lesion and the cranial and caudal vessel segments, and 
• 2 view stent x-ray (both obliques of the pelvis recommended). 
 
All subsequent follow-up visits will remain time-indexed to the original study procedure. 
Patients with amputation or surgical bypass of the study lesion will be followed for thirty days 
after their reintervention. Patients with other reinterventions will return for office visits and will 
undergo all imaging follow-up and be monitored for adverse events and complications out to 36 
months following the original study procedure. However, clinical assessments (i.e., VDS, CEAP 
“C” Classification, CIVIQ, and VCSS scores) will not be collected for the remainder of follow- 
up. 
 
8.8 
Criteria and Procedures for Withdrawal/Lost to Follow-Up 
 
A patient may decide to withdraw from the study at any time either before or after undergoing 
the procedure without prejudice or loss of care. The patient should notify the investigator of 
his/her desire to withdraw. The investigator will notify the sponsor. The investigator may also 
decide to withdraw the patient from the study at any time based on medical judgment. In all 
instances of withdrawal, the appropriate study visit and study termination data will be submitted 
to the data coordinating center, and will include the reason why the patient has been withdrawn 
from the study. Any data collected on the patient up to the point of withdrawal may be used in 
the study. 
 
In the event a patient is lost to follow-up or cannot be contacted for post-treatment assessments, 
at least three attempts may be made to locate the patient, and these efforts will be documented. 
If the patient cannot be located, a lost to follow-up entry will be submitted. 

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8.9 
Participation Endpoints of the Study 
 
A patient’s participation in the study will end after any of the following: 
 
• Completion of all scheduled clinical and imaging evaluations to 36 months; 
• Patient withdrawal or lost to follow-up; 
• Failure to gain target vessel access or deploy device, plus 30 days; 
• Surgical bypass of the study lesion, plus 30 days; 
• Amputation of the study limb, plus 30 days; 
• Closure of the study; or 
• Patient death. 
 
8.10 
Sample Size 
 
Sample size calculations are presented in section 9.1. Based on this analysis, it is estimated that 
a minimum of 218 patients is required to fulfill enrollment. Cook intends to enroll 243 patients 
at up to 40 investigative sites to account for those who withdraw or are lost to follow-up. 
Consistent with the derivation of the primary safety hypothesis, approximately 30% of the 
enrolled patient population will have acute disease (defined as initial symptom onset within 30 
days of the procedure) and approximately 70% of the enrolled patient population will have 
chronic disease (defined as initial symptom onset greater than 30 days of the procedure). At 
least half of the study patients will be enrolled at US sites. It is estimated that enrollment of 243 
patients will take approximately 60 months. 
 
8.11 
Period of Use for the Device or its Control 
 
The follow-up period extends to 36 months after implantation and utilizes both clinical and 
telephone assessments in order to permit a realistic evaluation of the performance of the device 
and to identify associated adverse device effects over that period. 

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8.12 
Limitations of the Investigation 
 
To achieve valid data upon which to base evaluation of the safety and effectiveness of the 
Zilver® Vena™ Venous Stent, all patients will be required to meet clinical investigation plan- 
specified inclusion/exclusion criteria. While controlling the homogeneity of the patient 
population allows inferences to be made about the effect of treatment, it may limit the overall 
range of patients to which the inferences may be applied. 
 
Based on the indications for use of this device learned from non-clinical experience and the 
guidance of clinicians currently treating venous outflow obstruction, certain anatomical 
considerations for device size selection will result in restricting the sample of patients selected 
for the study to a subset of the population of patients experiencing symptomatic iliofemoral 
venous outflow obstruction. Additionally, this study is not designed to provide data beyond 
3 years of follow-up. 
 
8.13 
Safety Monitoring 
 
A Data Safety Monitoring Board (DSMB) consisting of independent physicians and at least one 
independent statistician, who are not investigators in the study, nor have a conflict of interest 
with the conduct and administration of the study, will be convened on a regular basis to evaluate 
study progress and review adverse events. 
 
An independent Clinical Events Committee (CEC) consisting of physicians, who are not 
investigators in the investigation, nor have a perceived conflict of interest with the conduct and 
administration of the investigation, will be established to adjudicate applicable clinical events 
reported during the investigation. This adjudication will be performed to assess whether the 
events were due to a pre-existing or unrelated condition, procedure-related, technique-related, 
and/or device-related. 
 
A central core laboratory will be used for image analysis to provide uniformly defined 
morphological and morphometric analysis of images. 
 
Regularly scheduled review/monitoring of all patient data will be conducted at the data 
coordinating center, in part, for identification of adverse events and assurance that they are 
correctly reported to the DSMB and CEC. 

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9.0 
Statistical Considerations 
 
9.1 
Endpoint Analyses 
 
For the primary effectiveness and safety endpoints, the hypotheses will be tested at the 
significance level of 0.025. If both the safety and effectiveness hypotheses are met, the study 
will be considered successful. 
 
The test statistic for hypotheses testing of the secondary endpoint is the absolute change from 
baseline in the VCSS at 1 month and at 12 months. Paired t-test will be used to evaluate the 
secondary hypotheses. In the analyses of VCSS, multiplicity will be adjusted using the Holm 
procedure due to the presence of multiple time points. 
 
Full statistical details (including endpoint analyses) are in the Statistical Analysis Plan for the 
study. 
 
9.2 
Sample Size Calculations 
 
Evaluation of the primary safety hypothesis of 30-day freedom from MAE and the primary 
effectiveness hypothesis of 12-month primary quantitative patency requires 218 patients to 
determine if the performance goals have been met. Allowing for an additional 10% of patients 
who withdraw or are lost to follow-up, Cook intends to enroll 243 patients. 
 
A Bayesian adaptive study was simulated to determine the sample size required to test the study 
hypotheses with sufficient statistical power (in the frequentist context). For the power 
calculations, the true quantitative patency rate following treatment with the Zilver® Vena™ 
Venous Stent was assumed to be 86% and the true rate of freedom from MAE at 30 days was 
assumed to be 97%. The results of the simulations indicate that a sample size of 218 will 
provide a minimum power of 0.90 with a Type I error of 0.025 for each endpoint. 
 
It has been prespecified that patients enrolled in this study will include approximately 30% acute 
patients and 70% chronic patients. This patient population was defined based on the 
published literature describing patients treated for iliofemoral venous obstruction1-39 and the 
pattern of enrollment for the first 109 patients enrolled. Specific definitions for acute and 
chronic iliofemoral venous outflow obstruction are provided in Appendix B. 
Full statistical details on sample size calculation are in the Statistical Analysis Plan for the study. 

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9.3 
Site-level Poolability 
 
Poolability of data from multiple sites will be verified by examining the primary safety and 
effectiveness measures among sites. Site-level poolability will be considered appropriate 
provided that these measures are similar among sites. It is expected that important patient 
baseline characteristics, such as age, sex/gender, BMI, lesion length, known thrombophilia, 
anticoagulation/antiplatelet medication usage, stent extension below the inguinal ligament, stent 
extension into the common femoral vein, stent expansion into the IVC, presence of occlusive 
obstruction, presence of reflux, adjunctive procedures performed in addition to stent placement 
(thrombolysis, thrombectomy, IVC filter), and previous DVT may differ among sites. The 
influence of these patient characteristics on site poolability will also be examined. 
 
It is expected that some sites will have too few patients to provide reasonable site-level estimates 
of primary and secondary measures. Each investigative site will be allowed to enroll no more 
than 49 patients (20% of the total enrollment) to ensure the overall result is not biased by the 
results from a single site. Pooling of this information will be explored based on hospital size 
(large versus small), site enrollment (large versus small), type of hospital (community versus 
teaching), and other group-wise strategies. 
 
US versus OUS poolability analysis will be accomplished by incorporating a covariate indicating 
whether a patient belongs to US or OUS. 
 
9.4 
Planned Subgroups, Interactions, and Covariates 
 
In addition to the site level poolability, the primary and secondary endpoints will be analyzed 
against relevant demographic and comorbidity variables in the context of sub-group analyses or 
included in the analysis models as covariates. 
 
The analysis may include the covariates of age, BMI, lesion length, known thrombophilia, 
anticoagulation/antiplatelet medication usage, sex/gender, stent extension below the inguinal 
ligament, stent extension into the common femoral vein, stent extension into the inferior vena 
cava, presence of occlusive obstruction, presence of reflux, adjunctive procedures performed in 
addition to stent placement (thrombolysis, thrombectomy, IVC filter), previous DVT, etc. 
 
Planned subset analyses include: non-thrombotic versus post-thrombotic obstruction on chronic 
venous disease, occlusive versus non-occlusive obstruction, presence versus absence of 

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thrombophilia, stent extension into the IVC/common femoral vein, and presence versus absence 
of reflux. 
 
9.5 
Missing Data 
 
Missing data will be addressed using two primary strategies: 1) multiple imputation with best 
available data, if appropriate, and 2) case deletion. The first strategy is multiple imputation with 
best available data, if appropriate. This method will be used to predict missing endpoint and 
imaging data. Previous clinical trial experience suggests that some portion of the imaging data 
may not meet the criteria for accurate review by the core laboratory; however, it is recognized 
that the investigator uses this information to provide the best possible care for the patient. 
Therefore, it is reasonable to substitute any missing core laboratory measurements with the 
corresponding measurements made by the investigator or institutional staff. In addition, the 
absence or presence of clinical sequelae may supplement the required missing core laboratory 
assessment of device performance. This strategy is a best approximation of the missing data 
value. 
 
Statistical imputation strategies originating from Schafer40 may also be used, supplemented with 
notes provided by Schafer.41 The computations (with no covariates) will be performed using 
PROC MI and PROC MIANALYZE in SAS version 9.3 or later, or WinBUGS 1.4 or later. 
Unless evidence suggests otherwise, missing at random data will be assumed. 
 
The second strategy is case deletion. If the amount of missing data does not result in a reduction 
of analyzable patients to a number that is below that which is required for sufficient statistical 
power of the primary endpoints, then case deletion will be the method of choice for that analysis. 
 
Additional analyses may also be performed to address missing data, including tipping point 
analysis. 
 
9.6 
Future Use of Study Data 
 
[Information redacted due to confidential content.] 

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10.0 
Emergency Situations 
 
Patients will not be treated with the Zilver® Vena™ Venous Stent in emergency situations where 
prior consent of the patient is not possible. 
 
11.0 
Deviations from Clinical Investigation Plan 
 
Investigators are not allowed to deviate from this Clinical Investigation Plan without prior 
authorization by the sponsor except under emergency situations when necessary to preserve the 
rights, safety and well-being of study patients. 
 
Deviations (failures to follow requirements of the Clinical Investigation Plan) and non- 
compliances (failures to follow applicable regulations) will be recorded together with an 
explanation. Deviations or non-compliances that impact the rights, welfare, or safety of patients 
will be reported to the sponsor and IRB/EC as required and as soon as possible. 
 
If appropriate, corrective and preventive actions will be discussed by the sponsor, investigator, 
and/or the IRB/EC to determine a suitable course of action. 
 
12.0 
Procedure for Reporting Adverse Events 
 
Events known to be related to pre-existing conditions or existing at admission are not considered 
adverse events. Additionally, common standard of care practices are not considered adverse 
events (e.g., centers located at high geographical altitudes that discharge all patients on home 
oxygen therapy regardless of procedure). 
 
All adverse events are to be reported to the data coordinating center using the appropriate Case 
Report Form. In cases of adverse device effects (adverse event with relation to the study device) 
or major or serious adverse events, completed forms should be submitted to the data coordinating 
center immediately upon knowledge of the event. The data coordinating center will review the 
information submitted for possible reporting to the sponsor. In accordance with applicable 
requirements, the principal investigator will notify the local IRB/EC, while the sponsor will 
notify the regulatory authority. If indicated, all principal investigators and investigative sites in 
the study will be notified of applicable events by the sponsor. Refer to the Investigator’s 
Brochure for a list of potential adverse events related to this study. 

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13.0 
Early Termination or Suspension of the Investigation 
 
Any decision to suspend enrollment or terminate the study, either completely or at one or more 
sites, will be made by the sponsor and, if appropriate, the local IRB/EC. If a decision is made to 
terminate the study, all patients already treated will be followed per institutional standard of care. 
 
14.0 
Ethical Considerations 
 
This clinical investigation will be conducted according to the Declaration of Helsinki and in 
accordance with global regulations including but not limited to: ICH GCP, ISO 14155, and 
21 CFR 812. 
 
The investigator is responsible for obtaining approval of this clinical investigation by the 
relevant IRB/EC at their associated institution. The study will not begin until a favorable 
opinion of the IRB/EC has been obtained. The investigator is responsible for complying with 
requirements imposed by their IRB/EC and/or regulatory authority. Furthermore, the 
investigator will ensure that local regulations concerning data protection are followed. 
 
15.0 
Publication Policy 
 
Publication policy, rights and obligations for this Investigation have been negotiated, detailed 
and defined in the Investigation Contractual Documents and Agreements with the investigation 
site and investigators. 
 
16.0 
Data Collection 
 
Patient data will be collected and entered by trained personnel at the clinical site onto electronic 
Case Report Forms (eCRFs) through an Electronic Data Capturing (EDC) system. This is a 
secure, web-based system, allowing those with permission to access data from any location at 
any time. Source data is to be retained for data entered into the eCRF system. Data obtained and 
simultaneously entered into the EDC system may also serve as source documentation (e.g., 
telephone assessments, CIVIQ). Site personnel are required to undergo data entry training and 
will have unique login names and passwords in order to enter patient data.  In accordance with 
21 CFR Part 11, the eCRF system creates a secure, computer-generated, time stamped audit trail 
to record the date and time of operator entries and actions that create, modify, or delete electronic 
records.. 

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17.0 
Data Reporting 
 
Progress reports and a final report at the conclusion of the clinical investigation will be submitted 
by the investigators and sponsor to the regulatory bodies and IRBs/ECs as required by local 
regulations. 
 
18.0 
Data Management and Quality Assurance 
 
Each principal investigator or appropriately trained designee will enter the clinical data into the 
EDC system on standardized Case Report Forms. Investigators will provide all applicable 
clinical data and documentation to the sponsor. Patient data and documents pertaining to the 
study will be kept and archived by the sponsor. Data will be reviewed for missing data, data 
consistency, and reasonableness of responses. Discrepancies will be resolved through a formal 
query process involving direct contact with investigators or research coordinators. The data 
coordinating center is responsible for database management, data verification, data archiving and 
data retention. 
 
As needed to assist the sponsor in its research (e.g., during evaluation of an adverse event), data 
will be accessible to the sponsor, the participating investigators, the manufacturer, and 
companies or individuals the sponsor authorizes. 
 
19.0 
Insurance 
 
The devices are covered by the sponsor’s product liability insurance. A clinical study insurance 
policy will be taken out according to local requirements. 
 
20.0 
References 
 
1. Gutzeit A, Zollikofer CL, Dettling-Pizzolato M, Graf N, Largiadèr J, Binkert CA. 
Endovascular stent treatment for symptomatic benign iliofemoral venous occlusive 
disease: long-term results 1987-2009. Cardiovasc Intervent Radiol. 2011;34:542-549. 
 
2. Jeon UB, Chung JW, Jae HJ, Kim HC, Kim SJ, Ha J, et al. May-Thurner syndrome 
complicated by acute iliofemoral vein thrombosis: helical CT venography for evaluation 
of long-term stent patency and changes in the iliac vein. Am J Roentgenol. 
2010;195:751-757. 

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3. Wahlgren CM, Wahlberg E, Olofsson P. Endovascular treatment in postthrombotic 
syndrome. Vasc Endovasc Surg. 2010;44:356-360. 
 
4. Rosales A, Sandbæk G, Jørgensen JJ. Stenting for chronic post-thrombotic vena cava 
and iliofemoral venous occlusions: mid-term patency and clinical outcome. Eur J Vasc 
Endovasc Surg. 2010;40:234-240. 
 
5. Hölper P, Kotelis D, Attigah N, Hyhlik-Dürr A, Böckler D. Longterm results after 
surgical thrombectomy and simultaneous stenting for symptomatic iliofemoral venous 
thrombosis. Eur J Vasc Endovasc Surg. 2010;39:349-355. 
 
6. Hartung O, Benmiloud F, Barthelemy P, Dubuc M, Boufi M, Alimi YS. Late results of 
surgical venous thrombectomy with iliocaval stenting. J Vasc Surg. 2008;47:381-387. 
 
7. Oguzkurt L, Tercan F, Ozkan U, Gulcan O. Iliac vein compression syndrome: outcome 
of endovascular treatment with long-term follow-up. Eur J Radiol. 2008;68:487-492. 
 
8. Hartung O, Otero A, Boufi M, Decaridi G, Barthelemy P, Juhan C, et al. Mid-term 
results of endovascular treatment for symptomatic chronic nonmalignant iliocaval venous 
occlusive disease. J Vasc Surg. 2005;42:1138-1144. 
 
9. Neglén P, Hollis KC, Olivier J, Raju S. Stenting of the venous outflow in chronic venous 
disease: long-term stent-related outcome, clinical, and hemodynamic result. J Vasc Surg. 
2007;46:979-990. 
 
10. AbuRahma AF, Perkins SE, Wulu JT, Ng HK. Iliofemoral deep vein thrombosis: 
conventional therapy versus lysis and percutaneous transluminal angioplasty and stenting. 
Ann Surg. 2001;233:752-760. 
 
11. Knipp BS, Ferguson E, Williams DM, Dasika NJ, Cwikiel W, Henke PK, et al. Factors 
associated with outcome after interventional treatment of symptomatic iliac vein 
compression syndrome. J Vasc Surg. 2007;46:743-749. 
 
12. Titus JM, Moise MA, Bena J, Lyden SP, Clair DG. Iliofemoral stenting for venous 
occlusive disease. J Vasc Surg. 2011;53:706-712. 
 
13. Kölbel T, Lindh M, Ǻkesson M, Wassèlius J, Gottsäter A, Ivancev K. Chronic iliac vein 
occlusion: midterm results of endovascular recanalization. J Endovasc Ther. 
2009;16:483-491. 

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14. Husmann MJ, Heller G, Kalka C, Savolainen H, Do DD, Schmidli J, et al. Stenting of 
common iliac vein obstructions combined with regional thrombolysis and thrombectomy 
in acute deep vein thrombosis. Eur J Vasc Endovasc Surg. 2007;34:87-91. 
 
15. Kurklinsky AK, Bjarnason H, Friese JL, Wysokinski WE, McBane RD, Misselt A, et al. 
Outcomes of venoplasty with stent placement for chronic thrombosis of the iliac and 
femoral veins: single center experience. J Vasc Interv Radiol. 2012;23:1009-1015. 
 
16. Meng QY, Li XQ, Qian AM, Sang HF, Rong JJ, Zhu LW. Endovascular treatment of 
iliac vein compression syndrome. Chin Med J (Engl). 2011;124:3281-3284. 
 
17. Park YJ, Choi JY, Min SK, Lee T, Jung IM, Chung JK, et al. Restoration of patency in 
iliofemoral deep vein thrombosis with catheter-directed thrombolysis does not always 
prevent post-thrombotic damage. Eur J Vasc Endovasc Surg. 2008;36:725-730. 
 
18. Kwak HS, Han YM, Lee YS, Jin GY, and Chung GH. Stents in Common Iliac Vein 
Obstruction with Acute Ipsilateral Deep Venous Thrombosis: Early and Late Results. J 
Vasc Interv Radiol. 2005; 16:815-822. 
 
19. Lamont JP, Pearl GJ, Patetsios P, Warner, M, et al. Prospective Evaluation of 
Endoluminal Venous Stents in the Treatment of May-Thurner Syndrome. Ann Vasc 
Surg. 2002 Jan;16(1):61-64. 
 
20. Hartung O, Loundou AD, Barthelemy P, Arnoux D, Boufi M, Alimi YS. Endovascular 
Management of Chronic Disabling Ilio-caval Obstructive Lesions: Long-Term Results. 
Eur J Vasc Endovasc Surg. 2009 Jul;38(1):118-124. 
 
21. Hurst DR, Forauer AR, Bloom JR, Greenfield LJ, Wakefield TW, Williams 
DM. Diagnosis and endovascular treatment of iliocaval compression syndrome. J Vasc 
Surg. 2001;34:106-113. 
 
22. O’Sullivan G, Semba CP, Bittner CA, Kee ST, Razavi MK, Sze DY, et al. Endovascular 
Management of iliac vein compression (May-Thurner) syndrome. J Vasc Interv Radiol. 
2000;11:828-836. 

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23. Park JY, Ahn JH, Jeon YS, Cho SG, Kim JY, Hong KC. Iliac vein stenting as a durable 
option for residual stenosis after catheter-directed thrombolysis and angioplasty of 
iliofemoral deep vein thrombosis secondary to May-Thurner syndrome. Phlebology. 
2013;29:461-470. 
 
24. Warner CJ, Goodney PP, Wallaert JB, Nolan BW, Rzucidio EM, Powell RJ, et al. Vasc 
Endovascular Surg. 2013; 47: 331-334. 
 
25. Xue GH, Huang XZ, Ye M, Liang W, Zhang H, Zhang JW, et al. Catheter-directed 
thrombolysis and stenting in the treatment of iliac vein compression syndrome with acute 
iliofemoral deep vein thrombosis: outcome and follow-up. Ann Vasc Surg. 
2014;28:957:963. 
 
26. DeRubertis BG, Alktaifi A, Jimenez JC, Rigberg D, Gelabert H, Lawrence PF. 
Endovascular management of nonmalignant iliocaval venous lesions. Ann Vasc Surg. 
2013; 27:577-586. 
 
27. Sang H, Li X, Qian A, Meng Q. Outcome of endovascular treatment in postthrombotic 
syndrome. Ann Vasc Surg. 2014;28:1493-1500. 
 
28. Zhu QH, Zhou CY, Chen Y, Wang J, Mo HY, Luo MH, et al. Percutaneous manual 
thrombectomy followed by stenting for iliac vein compression syndrome with secondary 
acute isolated iliofemoral deep vein thrombosis: a prospective study of single-session 
endovascular protocol. Eur J Vasc Endovasc Sur. 2014; 47:68-74. 
 
29. Matsuda A, Yamada N, Ogihara Y, Tsuji A, Ota S, Ishikura K, et al. Early and long-term 
outcomes of venous stent implantation for iliac venous stenosis after catheter-directed 
thrombolysis for acute deep vein thrombosis. Circ J. 2014; 78:1234-1239. 
 
30. George R, Verma H, Ram B, Tripathi R. The effect of deep venous stenting on healing of 
lower limb venous ulcers. Eur J Vasc Endovasc Surg. 2014;48:330-336. 
 
31. Ye K, Lu X, Jiang Mi’er, Yang X, Li Weimin, Huang Y, et al. Technical details and 
clinical outcomes of transpopliteal venous stent placement for postthrombotic chronic 
total occlusion of the iliofemoral vein. J Vasc Interv Radiol. 2014;25:925-932. 

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32. Liu Z, Gao N, Shen L, Yang J, Zhu Y, Li Z, et al. Endovascular treatment for 
symptomatic iliac vein compression syndrome: a prospective consecutive series of 48 
patients. Ann Vasc Surg. 2014;28:695-704. 
 
33. Patel NH, Stookey KR, Ketcham DB, Cragg AH. Endovascular management of acute 
extensive iliofemoral deep venous thrombosis caused by May-Thurner Syndrome. J Vasc 
Interv Radiol. 2000;11:1297-1302. 
 
34. Vedantham S, Vesely TM, Sicard GA, Brown D, Rubin B, Sanchez LA, et al. 
Pharmacomechanical thrombolysis and early stent placement for iliofemoral deep vein 
thrombosis. J Vasc Interv Radiol. 2004;15:565-574. 
 
35. Lee KH, Han H, Lee KJ, Yoon CS, Kim SH, Won JY, et al. Mechanical thrombectomy 
of acute iliofemoral deep vein thrombosis with use of an Arrow-Trerotola percutaneous 
thrombectomy device. J Vasc Interv Radiol. 2006;17:487-495. 
 
36. O’Sullivan GJ, Lohan DG, Gough N, Cronin CG, Kee ST. Pharmacomechanical 
thrombectomy of acute deep vein thrombosis with the Trellis-8 isolated thrombolysis 
catheter. J Vasc Interv Radiol. 2007;18:715-724. 
 
37. Kwon SH, Oh JH, Seo TS, Ahn HJ, Park HC. Percutaneous aspiration thrombectomy for 
the treatment of acute lower extremity deep vein thrombosis: is thrombolysis needed? 
Clinical Radiology. 2009;64:484-490. 
 
38. Demirtürk OS, Oğuzkurt L, Coşkun I, Gülcan O. Endovascular treatment and the long- 
term results of postpartum deep vein thrombosis in 18 patients. Diagn Interv Radiol. 
2012;18:587-593. 
 
39. Engelberger RP, Fahrni J, Willenberg T, Baumann F, Spirk D, Diehm N, et al. Fixed low- 
dose ultrasound-assisted catheter-directed thrombolysis followed by routine stenting of 
residual stenosis for acute ilio-femoral deep-vein thrombosis. Thromb Haemost. 
2014;1153-1160. 
 
40. Schafer JL. Analysis of Incomplete Multivariate Data. London: Chapman & Hall; 1997. 
 
41.  Schafer J.L. Missing Data: a Review. Seminar sponsored by the Cleveland Chapter of 
the American Statistical Association; October 14, 2002; Cleveland, Ohio. 

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APPENDIX A 
 
 
Written Procedures for Monitoring Investigations 
 
A. 
Selection of the monitor. 
Designated by the sponsor to oversee the investigation, the monitor may be an employee 
of Cook, an employee of a monitoring organization (CRO) or an independent contractor 
or consultant. The monitor will be qualified by training and experience to monitor the 
investigation in accordance with all applicable regulations and standards for conducting 
clinical investigations. 
 
B. 
General duties of the monitor. 
The monitor must ensure that the investigation is conducted in accordance with: 
1. The signed investigator agreement. 
2. The Clinical Investigation Plan (CIP). 
3. Any conditions imposed by the IRB/EC or regulatory authority. 
4. The requirements of the applicable regulations and standards. 
 
C. 
Reports by the monitor to the sponsor. 
1. Any non-compliance with the items listed above. In the event that the investigator is 
not complying with the requirements outlined above, it is the sponsor's responsibility 
to secure compliance. 
2. Any adverse events/effects that are potentially reportable to a regulatory authority. 
 
D. 
Initiating the investigation. 
Prior to initiating any clinical use of the device, the monitor will participate in a pre- 
investigation or initiation visit with each investigative site. 
At a minimum, the following items will be addressed during the site initiation visit: 
• 
Provide training to investigator on his/her responsibilities per the investigator 
agreement, applicable laws, regulations and standards; and 
• 
Provide training to investigator that the IRB/EC approval letter and informed 
consent/patient information is on file before initiation of the clinical investigation. 

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Additionally, training may be provided to the investigator on: 
• 
The regulatory status of the device/product(s) and the requirements for the 
accountability of same; 
• 
The nature of the CIP; 
• 
The requirements for an adequate and well-controlled clinical investigation; 
• 
His or her obligation to obtain informed consent in accordance with applicable 
regulations; 
• 
His or her obligation to ensure continuing review of the clinical investigation by the 
IRB/EC in accordance with conditions of approval and applicable regulations and to 
keep the sponsor informed of such IRB/EC approval and subsequent IRB/EC actions 
concerning the investigation; 
• 
The importance of access to an adequate number of suitable subjects to conduct the 
investigation; 
• 
The importance of adequate facilities for conducting the clinical investigation; and 
• 
The importance of sufficient time from other obligations to carry out the 
responsibilities to which the investigator is committed by applicable regulations. 
 
E. 
During the course of the investigation, at the direction of the Project Manager, the 
monitor should visit the site frequently enough to ensure that: 
• 
The facilities and research staff used by the investigator continue to be acceptable for 
purposes of the clinical investigation; 
• 
The applicable version of the CIP and agreements are being followed; 
• 
Changes to the CIP, informed consent/patient information have been approved by 
the IRB/EC and/or reported to the sponsor and the IRB/EC; 
• 
Accurate, complete, and current records are being maintained; 
• 
Accurate, complete, and timely reports are being made to the sponsor and IRB/EC; 
and 
• 
The investigator is carrying out the agreed-upon activities and has not delegated 
them to other previously unspecified staff. 
 
As appropriate, the following tasks could be performed during periodic visits: 
• 
Adverse event review to ensure that events are appropriately reported within the time 
periods required by the sponsor, CIP, IRB/EC, and applicable regulatory 
requirements; and 

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• 
Source data verification per the monitoring plan to determine that: 
o 
Informed consent/patient information has been documented in accordance with 
applicable regulations and expectations of local IRB/EC; 
o 
The information recorded in the Case Report Forms (paper or electronic) is 
complete, accurate, and legible; 
o 
There are no omissions in the CRFs of specific data elements, such as the 
administration to any patient of concomitant test articles or the development of 
an intercurrent illness; 
o 
Missing visits or examinations are noted; and 
o 
Subjects failing to complete the clinical investigation and the reason for each 
failure are noted. 
 
F. 
Records of the monitor. 
The monitor will prepare and maintain records of each initiation visit and each periodic 
visit, general site contact, or discussion. These will include: 
1. 
Date, name and address of the investigator, and names of other staff members 
present at each meeting. 
2. 
A summary of the findings of the visit. 
3. 
A statement of any action taken by the monitor or investigator to correct any 
deficiencies noted. 
4. 
The monitor will immediately notify the sponsor of any conditions of non- 
compliance with the CIP, conditions of IRB/EC or regulatory authority approval, or 
the applicable regulations. 

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APPENDIX B 
 
 
Definitions 
 
Adverse Event, Early – Undesirable clinical event that occurs ≤ 30 days following initial stent 
placement. 
 
Adverse Event, Late – Undesirable clinical event that occurs > 30 days following initial stent 
placement. 
 
Adverse Event, Major (MAE) – Procedural bleeding requiring transfusion, procedure- or 
device-related death, clinically driven target lesion reintervention, clinical migration, new 
symptomatic pulmonary embolism, or procedure-related perforation requiring open surgical 
repair or flow-limiting dissection of the target vessel (note: bleeding events occurring prior to 
study enrollment, and related to procedures such as thrombolysis or thrombectomy, are not 
considered procedural bleeding events). 
 
CEAPa – A system of scoring venous disease according to Clinical, Etiological, Anatomic, and 
Pathophysiologic features. For the purpose of this investigation, the clinical classification (‘C’) 
will be used. The scoring system for the clinical classification is as follows: 
 
 
CEAP Clinical Classification 
Class 
Presenting feature 
C0 
No visible or palpable signs of venous disease 
C1 
Telangiectasias or reticular veins 
C2 
Varicose veins 
C3 
Edema 
C4a 
Pigmentation and/or eczema 
C4b 
Lipodermatosclerosis and/or atrophie blanche 
C5 
Healed venous ulcer 
C6 
Active venous ulcer 
 
 
 
 
 
 
 
 
a Eklöf B, Rutherford RB, Bergan JJ, et al. Revision of the CEAP classification for chronic venous disorders: 
consensus statement. J Vasc Surg 2004;40:1248-1252. 

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Clinically driven Reintervention – A reintervention performed in a patient with recurrent 
symptoms of venous outflow obstruction of the target lesion and with venography showing a 
treated venous segment (including the region within ± 1 cm proximal and/or distal to the treated 
venous segment) minimum lumen diameter ≤ 50% of the immediate post-procedure stented 
minimum lumen diameter. 
 
CIVIQb – The Chronic Venous Insufficiency Quality of Life Questionnaire (CIVIQ) is a 
validated, independent measure of perceived quality of life specific for patients with chronic 
lower limb venous insufficiency. The questionnaire evaluates pain and the psychological, 
physical, and social effect of the disease on overall quality of life. 
 
Hematoma/hemorrhage – A localized collection of blood, usually clotted, in an organ, intra- or 
extravascular space or tissue, due to a break in the wall of a blood vessel. Extravascular 
hemorrhage includes bleeding outside the body. 
 
Iliofemoral Venous Outflow Obstruction, Acute – Initial onset of symptoms is ≤30 days prior 
to the study procedure. 
 
Iliofemoral Venous Outflow Obstruction, Chronic – Initial onset of symptoms is >30 days 
prior to the study procedure. 
 
INR – The International Normalized Ratio is a measure of coagulation expressed as the ratio of 
prothrombin time to a normal, control sample, raised to the power of the International Sensitivity 
Index (ISI) sample used as control. 
 
Migration, Clinical – Proximal or distal movement of a stent requiring surgical or endovascular 
intervention. 
 
Migration, Radiographic – Greater than 1 cm proximal or distal movement of a stent 
confirmed with imaging with no clinical sequelae. 
 
 
 
 
 
 
 
 
 
b Launois R, Reboul-Marty J, Henry B. Construction and validation of a quality of life questionnaire in chronic 
lower limb venous insufficiency (CIVIQ). Qual Life Res 1996;5:539-554. 

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New York Heart Association Classification 
Class I: Cardiac disease resulting in no limitation of ordinary physical activity. Ordinary 
physical activity (i.e., walking several blocks or climbing stairs) does not cause undue fatigue, 
palpitation, dyspnea, or anginal pain. Symptoms may occur with marked exertion. 
 
Class II: Cardiac disease resulting in slight limitation of ordinary physical activity. Patient is 
comfortable at rest. Ordinary physical activity such as walking more than two blocks or 
climbing more than one flight of stairs results in fatigue, palpitation, dyspnea, anginal pain, or 
similar symptoms. 
 
Class III: Cardiac disease resulting in marked limitation of physical activity. The patient is 
comfortable at rest, but activities such as walking one to two blocks or climbing one flight of 
stairs cause fatigue, palpitation, dyspnea, anginal pain or similar symptoms. 
 
Class IV: Cardiac disease resulting in dyspnea at rest which increases with any physical activity 
and inability to perform any physical activity without discomfort. Symptoms of cardiac 
insufficiency or anginal syndrome may be present even at rest. If any physical activity is 
undertaken, discomfort is increased. 
 
Occlusion, Early – No flow within the treated venous segment (including the region within 
± 1 cm proximal and/or distal to the treated venous segment) occurring < 24 hours of the 
procedure as demonstrated by duplex ultrasound or venography. An occlusion occurring within 
24 hours of the procedure will be considered thrombotic in nature, regardless of whether it is 
successfully treated with thrombolysis/thrombectomy. 
 
Occlusion, Intermediate – No flow within the treated venous segment (including the region 
within ± 1 cm proximal and/or distal to the treated venous segment) occurring > 24 hours after 
the procedure, but < 30 days after the procedure as demonstrated by duplex ultrasound or 
venography. An occlusion occurring within 30 days of the procedure will be considered 
thrombotic in nature, regardless of whether it is successfully treated with 
thrombolysis/thrombectomy. 
 
Occlusion, Late – No flow within the treated venous segment (including the region within 
± 1 cm proximal and/or distal to the treated venous segment) occurring > 30 days after the 
procedure as demonstrated by duplex ultrasound or venography. 

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Outflow Obstruction – Documented iliofemoral venous obstruction (e.g., recanalization of the 
vein with multiple channels, documented collaterals as determined by imaging). 
 
Patency, Clinical – Lack of occlusion of the treated venous segment determined by evidence of 
blood flow both proximal and distal to the study lesion assessed via ultrasound and/or 
venography and no worsening of pain or edema symptoms from baseline (according to Venous 
Clinical Severity Score; VCSS) as related to the target lesion. 
 
Patency, Quantitative – A treated venous segment (including the region within ± 1 cm proximal 
and/or distal to the treated venous segment) minimum lumen diameter > 50% of the immediate 
post-procedure stented minimum lumen diameter as demonstrated by venography. 
 
Patency, Primary Quantitative – A treated venous segment retains primary quantitative 
patency provided that uninterrupted (intervention-free) quantitative patency remains since the 
initial procedure as determined by the core laboratory. Failure of primary quantitative patency 
occurs at the time of one of the following: loss of quantitative patency, occlusion of the treated 
segment, surgical bypass of the treated segment, or amputation of the extremity determined to 
result from venous outflow occlusion. 
 
Patency, Assisted Primary Quantitative – A treated venous segment retains assisted primary 
quantitative patency if, following successful treatment at the initial procedure, the segment 
subsequently requires an intervention to assist quantitative patency without an episode of 
occlusion. Failure of primary assisted quantitative patency occurs at the time of one of the 
following: total occlusion of the treated segment, surgical bypass of the treated segment, or 
amputation of the extremity determined to result from venous outflow occlusion. 
 
Patency, Secondary Quantitative – A treated venous segment retains secondary quantitative 
patency if, following successful treatment at the initial procedure, the segment subsequently 
becomes totally occluded and then successfully reopened in a secondary procedure. Failure of 
secondary quantitative patency occurs at the time of surgical bypass of the treated segment or 
amputation of the extremity determined to result from venous outflow occlusion. 

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Pulmonary Embolism (PE) – Emboli to lungs via the pulmonary artery, which can arise from 
deep venous thrombosis in the lower extremities or pelvis. Pulmonary emboli should be 
objectively documented using pulmonary arteriography, cross-sectional imaging, or significant 
change in ventilation/perfusion lung scan indicative of PE, or at autopsy. PE will be categorized 
by type.c 
Pulmonary Embolism (PE), Massive – Acute PE with sustained hypotension (systolic 
blood pressure < 90 mmHg for at least 15 minutes or requiring inotropic support, not due to a 
cause other than PE, such as arrhythmia, hypovolemia, sepsis, or left ventricular [LV] 
dysfunction), pulselessness, or persistent profound bradycardia (heart rate < 40 bpm with 
signs or symptoms of shock). 
 
Pulmonary Embolism (PE), Submassive – Acute PE without systemic hypotension 
(systolic blood pressure ≥ 90 mmHg) but with either right ventricular (RV) dysfunction or 
myocardial necrosis, where: 
RV dysfunction is defined as the presence of at least 1 of the following: 
- 
RV dilation (apical 4-chamber RV diameter divided by LV diameter > 0.9) or RV 
systolic dysfunction on echocardiography; 
- 
RV dilation (4-chamber RV diameter divided by LV diameter > 0.9) on CT; 
- 
Elevation of BNP (> 90 pg/mL); 
- 
Elevation of N-terminal pro-BNP (> 500 pg/mL); or 
- 
Electrocardiographic changes (new complete or incomplete right bundle-branch 
block, anteroseptal ST elevation or depression, or anteroseptal T-wave inversion). 
Myocardial necrosis is defined as either of the following: 
- 
Elevation of troponin I (> 0.4 ng/mL) or 
- 
Elevation of troponin T (> 0.1 ng/mL). 
 
Pulmonary Embolism (PE), Low-risk – Acute PE and the absence of the clinical markers 
of adverse prognosis that define massive or submassive PE. 
 
 
 
 
 
 
c Jaff MR, McMurtry MS, Archer SL, et al. Management of massive and submassive pulmonary embolism, 
iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension: A scientific statement from 
the American Heart Association. Circulation. 2011;123:1788-1830. 

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Pulmonary Embolism (PE), Symptomatic – Thrombotic embolism to the lungs via the 
pulmonary artery that causes symptoms (hypoxia and chest pain) and/or is associated with a 
clinical sign, biomarker elevation, or abnormal test (e.g., bradycardia or tachycardia, sustained 
hypotension, elevated troponins or natriuretic peptides, right ventricular 
dysfunction). Symptomatic PE will be objectively documented showing occlusive filling defects 
in the lobar or main pulmonary arteries on pulmonary arteriography or cross-sectional imaging. 
Similarly, changes in ventilation/perfusion lung scan or at autopsy may be indicative of lobar or 
main pulmonary artery PE. 
 
Reintervention – Any endovascular or surgical intervention performed in a treated venous 
segment. 
 
Renal Failure – Acute or progressive renal insufficiency leading to the need for dialysis. 
 
Renal Insufficiency – A rise in creatinine of more than 30% above the pre-procedure level 
resulting in a creatinine level > 2.0 mg/dl that does not spontaneously resolve. 
 
Restenosis (binary) – Recurrent narrowing of the treated venous segment (including the region 
within ± 1 cm proximal and/or distal to the treated venous segment) resulting in a minimum 
lumen diameter ≤ 50% of the immediate post-procedure stented minimum lumen diameter as 
demonstrated by venography. 
Stent Strut Fractured,e 
Type I: 
Single strut fracture only 
Type II: 
Multiple single strut fractures that can occur at different sites 
Type III: 
Multiple strut fractures resulting in complete transection of the stent, 
without displacement of the stent segments 
Type IV: 
Multiple stent fractures resulting in displacement of segments of the stent. 
Type V: 
Spiral fractures, without complete transection, which could result in stent 
displacement. 
 
 
 
 
 
d Rocha-Singh KJ, Jaff MR, Crabtree TR, et al. Performance goals and endpoint assessments for clinical trials of 
femoropopliteal bare nitinol stents in patients with symptomatic peripheral arterial disease. Catheter Cardiovasc 
Interv 2007;69:910-919. 
e Jaff M, Dake M, Pompa J, et al. Standardized evaluation and reporting of stent fractures in clinical trials of 
noncoronary devices. Catheter Cardiovasc Interv 2007;70:460-462. 

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Success, Procedural – Improved flow through the target vessel demonstrated by diminished 
flow through collateral veins and/or reduced filling defect in the target vessel and no major 
adverse events before discharge. 
Success, Technical – Successful delivery and deployment of the Zilver® Vena™ Venous Stent. 
 
Thrombosis – Platelet or fibrin deposition within the treated venous segment successfully 
treated with thrombolysis or thrombectomy. 

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Venous Clinical Severity Scoref – a method of classifying the disease severity in chronic 
venous insufficiency, validated for use post-intervention. 
 
Attribute 
Absent (0) 
Mild (1) 
Moderate (2) 
Severe (3) 
Pain or other discomfort 
(i.e., aching, heaviness, 
fatigue, soreness, 
burning) 
-Presumes venous origin 
None 
Occasional pain or 
other discomfort 
(i.e., not restricting 
regular daily 
activities) 
Daily pain or other 
discomfort (i.e., 
interfering with but 
not preventing 
regular daily 
activities) 
Daily pain or 
discomfort (i.e., 
limits most regular 
daily activities) 
Varicose Veins 
-“Varicose” veins must be 
> 3 mm in diameter to 
qualify in the standing 
position. 
None 
Few: scattered (i.e., 
isolated branch 
varicosities or 
clusters) 
Also includes 
corona phlebectatica 
(ankle flare) 
Confined to calf or 
thigh 
Involves calf and 
thigh 
Venous Edema 
-Presumes venous origin 
None 
Limited to foot and 
ankle area 
Extends above ankle 
but below knee 
Extends to knee and 
above 
Skin Pigmentation 
-Presumes venous origin 
-Does not include focal 
pigmentation over 
varicose veins or 
pigmentation due to other 
chronic diseases 
None or focal 
Limited to 
perimalleolar area 
Diffuse over lower 
third of calf 
Wider distribution 
above lower third of 
calf 
Inflammation 
-More than just recent 
pigmentation (i.e., 
erythema, cellulitis, 
venous eczema, 
dermatitis) 
None 
Limited to 
perimalleolar area 
Diffuse over lower 
third of calf 
Wider distribution 
above lower third of 
calf 
Induration 
-Presumes venous origin 
of secondary skin and 
subcutaneous changes 
(i.e., chronic edema with 
fibrosis, hypodermitis). 
Includes white atrophy 
and lipodermatosclerosis 
None 
Limited to 
perimalleolar area 
Diffuse over lower 
third of calf 
Wider distribution 
above lower third of 
calf 
Active ulcer number 
0 
1 
2 
> 3 
Active ulceration 
duration (longest active) 
N/A 
< 3 mo 
> 3 mo but < 1 yr 
Not healed > 1 yr 
Active ulcer size (largest 
active) 
N/A 
Diameter < 2 cm 
Diameter 2-6 cm 
Diameter > 6 cm 
Use of compression 
therapy 
0 
Not used 
1 
Intermittent use of 
stockings 
2 
Wears stockings 
most days 
3 
Full compliance: 
stockings 
Venous Disability Scoringg – A method of classifying the extent of disability based on venous 
symptoms and the ability to perform normal activities with or without lower extremity 
compression: 

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Venous Disability Scoring 
Score 
Presenting feature 
0 
Asymptomatic 
1 
Symptomatic, usual activity*, without use of lower 
extremity compression 
2 
Usual activities only with compression and/or limb 
elevation 
3 
Unable to complete usual activity, even with 
compression and/or limb elevation 
*usual activities are patients activities before onset of disability 
from venous disease 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
f Vasquez M, Rabe E, McLafferty R, Shortell C, Marston W, Gillespie D, Meissner M, and Rutherford R. Revision 
of the venous clinical severity score: Venous outcomes consensus statement: Special communication of the 
American Venous Forum Ad Hoc Outcomes Working Group. J Vasc Surg 2010 Nov; 52(5):1387-1396. 
g Rutherford RB, Padberg FT, Comerota AJ, Kistner RL, Meissner MH, and Moneta GL. Venous severity scoring: 
An adjunct to venous outcome assessment. J Vasc Surg 2000; 31:1307-1312.