A Multi-center, Non-randomized Study to Evaluate the Safety and Effectiveness of the Abre Venous Self-expanding Stent System in Patients With Symptomatic Iliofemoral Venous Outflow Obstruction
Phase: NA
Conditions: Iliofemoral Venous Obstruction
Sponsor: Medtronic Endovascular

 
 
 
 
ABRE Study 
A prospective, multi-center, follow-up of the ABRE pivotal 
study to evaluate the long-term safety and effectiveness of 
the Abre venous self-expanding stent system in patients with 
symptomatic iliofemoral venous outflow obstruction. 
 
 
 
Clinical Investigation Plan (CIP) 
 
CIP IDENTIFIER: APV – ABRE 
ClinicalTrials.gov Identifier: NCT03038438 
PMA number: P200026 
VERSION 2.0 
02/MAR/2021 
 
 
 
 
 
 
Confidentiality Statement 
The information contained in this document is confidential and the proprietary property of Medtronic. Any 
distribution, copying, or disclosure without the prior written authorization of Medtronic is strictly prohibited. 
Persons to whom the information is disclosed must know that it is confidential and that it may not be 
further disclosed by them. 
 

056-F275, Clinical Investigation Plan Template, Version 2.0 
CIP: ABRE Study  
 
 
Medtronic Confidential 
 
 
 
Page 2 of 152 
CIP Identifier: APV – ABRE 
Version 2.0: 02/MAR/2021 
1 Version History 
Version 
Summary of changes 
Justification 
of changes 
Potential 
impact of the 
change on 
performance
, 
effectiveness
, or safety or 
other 
endpoints 
Identificati
on of the 
affected 
study 
documents 
Author(s)/
Title 
1.0  
28/JUN
/2016 
Not applicable, new document 
N/A 
N/A 
N/A 
Myriam 
Demas / 
Principal 
Clinical 
Research 
Specialist 
1.1 
21/NOV
/2016 
• Administrative updates 
• Synopsis: Expected First Enrollment 
changed to ‘2017’ 
• Major Bleeding definition updated 
• Inclusion Criteria 6, ii updated: IVUS 
added  
• Inclusion Criteria 7: successful 
treatment of acute DVT patients 
specified 
• Exclusion Criteria 9 updated: upper 
limit for WBC added 
• Medication: Statins information 
added to be collected 
• Section 10: clarifications added to 
procedures 
• 10.12.1: Clarification added to 
Antiplatelet treatment 
• 10.12.5: Pregnancy test specified 
• 10.12.7: Physical assessment of limbs 
specified 
• 14.2 power adapted according to 
results of updated literature search 
• 14.3 Populations specified 
• 14.4 Statistical tests for primary 
endpoints specified 
• 14.3 Evaluable data specified 
• 14.6 Handling missing data specified 
• 14.7 Poolability assessment specified 
• Section 18: clarification added to 
Justification for the Study 
• Appendix A: updated scientific 
literature search 
N/A 
N/A 
N/A 
Myriam 
Demas / 
Clinical 
Research 
Manager 

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CIP: ABRE Study  
 
 
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CIP Identifier: APV – ABRE 
Version 2.0: 02/MAR/2021 
1.2 
06/APR
/2017 
• Administrative updates 
• Front page: ClinicalTrials.gov Identifier 
and IDE number added. 
• Removed reference to Good Clinical 
Practice in “Investigator Statement” 
and “Glossary” as the ABRE study will 
follow the good clinical practice 
principles as outlined in ISO14155. 
• “Synopsis - Lead Principal 
Investigators”: address of Dr. Erin 
Murphy updated. 
• The Abre stent system has obtained 
CE mark. All references to “CE mark 
will be obtained” updated 
accordingly. Applicable sections are: 
“Synopsis”, “7. Study Design”, “8.1.2 
Abre Stent Delivery System”. 
• “Synopsis - Expected first enrollment” 
updated to 2017. 
• PMA will be submitted to FDA when 
all 12-month follow-up data are 
available. All references to “PMA will 
be submitted to FDA when the 
evaluable data are available” updated 
accordingly. Applicable sections are: 
“Synopsis - Statistics” and “14.3 
Analysis Sets”.   
• “Race / ethnicity” data are collected in 
this study. Rationale provided in the 
“Background” section. Race and 
Ethnicity information added/updated 
in the following sections: “10.3.1 
Demographics, Medical History & 
Physical Examination”, “14.6 Handling 
of Dropouts and Missing Data”, “14.7 
Assessment of Data Pooling” and 
“14.8 Minimizing Bias”. 
• “7.2 Rationale”: rationale added for 
single-arm study design. 
• “9.3 Subject Screening” and “10.15 
Table 8”: Enrolled subjects do not 
need to be recorded on the Subject 
Screening Log. They will only be 
recorded on the Subject Identification 
& Enrollment Log. 
• “9.4 Inclusion Criteria”: renal 
compromise specified. 
• Duplex ultrasound image of the 
contralateral limb is required. All 
applicable sections updated. These 
are “10.6 Hospital Discharge”, “10.7 
30 Day (-7/+14 days) Post-Procedure 
N/A 
N/A 
N/A 
Myriam 
Demas / 
Clinical 
Research 
Manager 

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CIP Identifier: APV – ABRE 
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Follow-Up Assessment”, “10.8 6 
Months (± 30 days) Post-Procedure 
Follow-Up Assessment”, “10.9 12 
Months (± 30 days) Post-Procedure 
Follow-Up Assessment”, 10.10 24 and 
36 Months (± 30 days) Post-Procedure 
Follow-Up Assessment”, “10.11 
Unscheduled Visits”, “10.12.6 
Imaging”. 
• “10.12.7 Physical Assessment of 
Limbs”. Changed ‘diameter of the leg” 
to “diameter of the thigh” and 
“presence of lymphedema” added. 
• “11.2 Potential Benefits”. Added 
potential benefit for participation in 
the study. 
• “Appendix C CEAP Classificiation”: 
correction made (LSV changed to 
SSV). 
 
1.3a 
31/JUL/
2018 
• Administrative updates 
• ”Synopsis – Sample Size”. Added 
‘implanted’ to following statement - 
“A maximum of 200 implanted 
subjects will be included in the study”. 
• “Synopsis – Sample Size”. Changed 
from the maximum number of OUS 
subjects will not exceed 50% to “A 
minimum of 40% of included subjects 
will be from the US”. 
• “Synopsis – Estimated Time Course 
and “7.1 Duration”. Updated 
‘Expected First Enrollment’ to ‘First 
Enrollment – 19/DEC/2017’ and 
changed ‘Expected Enrollment 
Duration’ from ’17’ to ‘13’ months. 
• “Synopsis – Inclusion/Exclusion 
Criteria” and “9.4 Inclusion Criteria” 
following language added to Imaging-
based inclusion criterion #5: “Patient 
must have good inflow involving 
either the femoral or deep femoral 
vein being patent and at aleast a 
caudal section of the common 
femoral vein that is free of significant 
disease”. 
• “Synopsis – Inclusion/Exclusion 
Criteria” and “9.4 Inclusion Criteria” 
following language deleted from 
Imaging-based inclusion criterion #7: 
“by catheter-based techniques”. 
N/A 
N/A 
N/A 
Stephanie 
Brucato / 
Principal 
Clinical 
Research 
Specialist 

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CIP: ABRE Study  
 
 
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CIP Identifier: APV – ABRE 
Version 2.0: 02/MAR/2021 
• “Synopsis – Inclusion/Exclusion 
Criteria” and “9.5 Exclusion Criteria” 
following language removed from 
exclusion criterion #3: “negative” in 
relation to pregnancy test and 
parentheses added around 
requirement to complete a pregnancy 
test within 7 days prior to the index 
procedure. 
• “Synopsis – Study Procedures and 
Assessments” and “10.1 Table 6” 
clarification added to 
‘Screening/baseline’ window to 
indicate assessments should be 
completed <30 days “before 
procedure”. 
• “Synopsis – Study Procedures and 
Assessments” and “10.1 Table 7” 
language added to footnote 1 stating 
“If both screening and pre-procedure 
venogram/IVUS are performed, then 
the pre-procedure venogram/IVUS 
should be sent to the core laboratory. 
• “6.3.1 Primary Endpoints – Primary 
safety endpoint” clarification added to 
indicate MAEs will be adjudicated by a 
CEC “except for stent thrombosis and 
stent migration as they are confirmed 
by core laboratory”.  
• “6.3.2 Secondary Endpoints - #7 Major 
Adverse Events through 6-, 12-, 24-, 
and 36 months” clarification added to 
indicate MAEs will be adjudicated by a 
CEC “except for stent thrombosis and 
stent migration as they are confirmed 
by core laboratory”. 
• “6.3.2 Secondary Endpoints - #9, #10, 
#11, and #12” timepoints for analysis 
extended from 12M out to include 24- 
and 36 month timepoints.  
• “6.3.2 Secondary Endpoints - #14”. 
Added ‘through 36 months’. 
• “8.7 Product Receipt and Tracking” 
Device ‘serial’ number deleted and 
‘Device lot number’ added. 
• “9.3 Subject Screening” remove 
requirement for sites to complete a 
Subject Screening Log. All applicable 
sections updated including “Table 5”, 
“Figure 4”, and “Table 8”. 
• “9.3 Subject Screening – Enrolled – 
not included” added statement “No 

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CIP Identifier: APV – ABRE 
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imaging needs to be sent to the core 
laboratory for these subjects.” Same 
reference added to footer 4 of “Table 
8”. 
• “9.3 Subject Screening – Enrolled – 
not implanted” added statement “The 
pre-procedure/pre-stenting imaging 
must be submitted to the core 
laboratory.” 
• “10.1 Schedule of Events” additional 
detail added to indicate that the 
Screening/Baseline Duplex Ultrasound 
is to be performed on both limbs in 
parenthesis. 
• “10.4 Acute DVT Subjects” minor edits 
made to section to clarify the 
requirements. 
• “10.5.4 Inflow Requirements” added 
“significant” in the following 
sentence: “Good inflow involves 
either the femoral or deep femoral 
vein being patent and at aleast a 
caudal section of the common 
femoral vein that is free of significant 
disease.” 
• “10.5.5 Lesions” added ‘iliac’ after 
‘common’ in first sentence for clarity. 
• “10.5.6 Predilation”. Sentence related 
to predilation updated to clarify that a 
balloon of the same size diameter of 
the stent to be implanted must be 
used. 
• “10.5.7 Stent Size Selection – Stent 
Length”. Clarification added to state 
that the ends of the stents lie in a 
“relatively” normal/healthy venous 
segment. 
• “10.5.7 Stent Size Selection – Stent 
diameter”. For number 2, 
specification of AP and 60 LAO for 
venogram planes removed to 
correspond to core lab manual. 
• “10.5.7 Stent Size Selection – Stent 
diameter”. Clarifications made to 
section for reference vessel diameter 
assessment. For all three methods the 
phrase “an appropriate segment of” 
has been added to replaceme the 
previously used phrase “the same 
anatomical segment”. 
• “10.5.8 Stent Placement”. Following 
sentence added “Whenever possible, 

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one stent should be used to cover the 
entire length of the target lesion.” 
And clarification added to section in 
the event that stents of differing 
diameters are needed. In this case the 
following statements were added: “If 
different diameters are needed, the 
smaller diameter stent should be 
placed first.” And clarification added 
to ensure no skip areas. 
• “10.12.1 Antithrombotics”. Added 
“bolus of 5000 units or” to second 
bullet under ‘Peri-procedure’ section. 
• “10.12.3 Scores – Villalta Score” 
corrected reference to indicate 
“Villalta” instead of “VCSS” in third 
sentence. 
• “10.12.7 Physical Assessment of 
Limbs”. Corrected ‘diameter’ of thigh 
and calf to ‘circumference’. 
• “Table 8: Overview data collection for 
different scenarios”. Removed 
requirement to complete ‘Procedure’ 
eCRFs for Enrolled – not included 
subjects who are screening failures 
during implant procedure. 
• “10.15 Recording Data - Source 
Documents”. Exception updated to 
indicate that select data on the 
Product Accountability Log may serve 
as source. Removed example of 
exception related to quality of life and 
clinical scores. 
• “12.1.1 Definitions – Table 10: 
Definitions – Unanticipated Serious 
Adverse Device Effect”. Extra 
language removed to match 
referenced ISO definition. 
• “12.1.2 Classification of Causal 
Relationships – Table 11”. Abre stent 
implant procedure definition updated 
to ‘Any AE that occurs within 30 days 
of the Abre stent implant procedure 
unless specifically shown not to be 
related to that procedure.’. 
• “12.2.1 Evaluation and 
Documentation of Adverse Events and 
Device Deficiencies”. Clarification 
added to last paragraph of section to 
specify that “…specific endpoint-
related adverse events as described in 
the CEC Manual of Operations…”. 

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CIP Identifier: APV – ABRE 
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• “Table 13: Unavoidable events”. Low 
grade fever ’27.8°C’ corrected to 
’37.8°C’. 
• “Table 14” Timeframe for reporting 
Adverse Events changed from ‘no 
later than 10 working days of’ to ‘In a 
timeline manner from’. 
• “15.1 Statement(s) of Compliance”. 
Reference to 45 CFR Part 11 added. 
• “16.5 Site Activation/Supply of Study 
Materials”. Added ‘Other relevant 
documentation for key site staff (i.e. 
DUS Technicians) is allowable’ as sub-
bullet to Curriculum vitae 
requirement. 
• “Appendix B Definitions”. ‘Iliac’ added 
after ‘common’ to specify ‘common 
iliac’ in Target lesion and Target vessel 
definitions.  
1.3b 
20/AUG
/2018 
• “Appendix B Definitions”. ‘Stent 
migration’ definition changed to 
“Position change of a properly sized 
venous stent observed with an 
imaging modality, with displacement 
of the stent outside of the intended 
treatment segment after the 
conclusion of the index procedure, as 
determined with regard to a 
reference anatomic structure. Stent 
migration occurs following the proper 
deployment of a venous stent after 
the index procedure (i.e. stent 
movement or dislodgement during 
the index procedure will not be noted 
as stent migration).” 
N/A 
N/A 
N/A 
Stephanie 
Brucato / 
Principal 
Clinical 
Research 
Specialist 
1.3c 
20/SEP/
2018 
• “Secondary Endpoints”. ‘Delayed 
Stent Migration at 12-, 24-, and 36 
months’ added as secondary endpoint 
#8. All subsequent secondary 
endpoint #s updated. 
• “Appendix B Definitions”. ‘Stent 
migration’ definition updated to state 
that existing stent migration definition 
is part of the primary safety and 
secondary MAE endpoints, and 
‘delayed stent migration’ definition 
added as part of secondary endpoint. 
N/A 
N/A 
N/A 
Sue Kim / 
Sr. Clinical 
Program 
Manager 
1.4 
24/SEP/
2018 
• Update to correct version per internal 
procedures 
N/A 
N/A 
N/A 
Stephanie 
Brucato / 
Principal 
Clinical 

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CIP: ABRE Study  
 
 
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CIP Identifier: APV – ABRE 
Version 2.0: 02/MAR/2021 
Research 
Specialist 
2.0 
02/MA
R/2021 
• Administrative updates including 
tense corrections at this timpoint in 
the study. 
• Updated Section “1 Version History” 
for ISO 14155:2020 compliance. 
Additional columns are marked as 
‘N/A’ in previous CIP versions. 
• Added ‘Post-Approval Study – PAS’ 
and ‘Premarket approval application – 
PMA’ to Section “3. Glossary”. 
• Section “4 Synopsis” updated ‘Title’ 
and ‘Clinical Study Type’ per PMA 
Approval Order. Added PMA approval 
status to ‘Indication under 
investigation’ and ‘Product Status. 
Added the post-approval primary 
objective to evaluate freedom from 
target lesion revascularization at 36 
months to ‘Primary Objectives’. 
Updated ‘Sample Size’ to indicate 200 
subjects were implanted and included 
in the study from 24 investigational 
sites and clarification that no new 
subjects are allowed in the study. 
Updated ‘Number of sites’ to reflect 
24 sites participated. ‘Statistics’ text 
updated to outline the newly added 
primary endpoint to assess freedom 
from target lesion revascularization 
through 36 months will be 
characterized with descriptive 
statistics.  
• Added text to Section “5.2 Purpose” 
to outline current PMA approval 
status and update the post-approval 
study phase primary endpoint. 
• Updated Section “6.1 Primary 
Objectives” with the newly added 
post-approval study phase objective. 
• Added the post-approval study phase 
primary effectiveness endpoint 
(freedom from TLR through 36 
months) to Section “6.3.1 Primary 
Endpoints” 
• Removed sub-categories ‘acute 
success secondary endpoints’ and 
‘late success secondary endpoints 
from “Section 6.3.2 Secondary 
Endpoints”. 
Changes 
made to 
align with 
the Abre 
Venous Self-
expanding 
Stent 
System 
Approval 
Order 
(P200026, 
21/OCT/202
0). 
 
Updates 
made to 
align with 
ISO14155:2
020 
N/A  
As a result 
of these 
changes 
the ABRE 
Study 
Adverse 
Event CRF 
will be 
updated to 
include the 
new 
ISO14155:2
020 AE 
definitions. 
Samantha 
Sparks / 
Senior 
Clinical 
Research 
Specialist 

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• Added Section “6.4 Post-Approval 
Objectives and Endpoints”. 
• Added ’24- and 36-months’ to both 
the ‘Primary Assisted Patency’ and 
‘Secondary Patency’ Secondary 
Endpoints in “Section 6.3.2 Secondary 
Endpoints”. 
• Added to note below Secondary 
Endpoint #7 to indicate that ‘stent 
thrombosis’ and ‘stent migration’ are 
confirmed by the core laboratory (not 
the CEC) in “Section 6.3.2 Secondary 
Endpoints”. 
• Section 10.10 text update, the ‘Phone 
Encounter’ does not replace the 24- 
and / or 36-month visit. An in-clinic 
visit is required.  
• Section 10.13 text update, COVID-19 
related protocol deviations must 
provide details. 
• Updated references to ISO 
14155:2011 to ISO 14155:2020 and 
updated associated language as 
applicable throughout entire 
document. 
• Adverse event and device deficiency 
definitions updated within Section 
12.1 to align with ISO 14155:2020 as 
applicable. 
• Updated Section 12.2 Reporting of 
Adverse Events. Reporting of all 
adverse events is no longer required. 
Only adverse events related to the 
device / procedure as well as any 
adverse event with major adverse 
event potential, (S)ADE, DD, U(S)ADE, 
and SAE is required as outlined in 
Table 14. 
• Updated Section ’12.2.5 Vigilance 
Reporting’ to ‘Complaint Reporting’. 
Updated bullet two from ‘Vigilance 
Reporting’ to ‘Vigilance and Medical 
Device Reporting’.  
• Updated ‘Section 14.4’ to add the 
statistical method for PAS primary 
endpoint.  
• Added sub-sections 14.4.1 and 14.4.2 
outlining the statistical method for 
each study phase. 
• Updated text to indicate the success 
of the study in Section 14.5 

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CIP Identifier: APV – ABRE 
Version 2.0: 02/MAR/2021 
• Removed incorrect reference to 45 
CFR Part 11 and 46 in Section 15.1 
Statement(s) of Compliance.  
• Updated text in Section 15.1 to 
further describe ouside US 
compliance. 
• Outlined a risk-based methology text 
in Section ‘16.6 Monitoring’ 
•  
 
  
 
 
 
 

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2 Investigator Statement 
Study product name 
Abre venous self-expanding stent system 
Global sponsor 
Medtronic Vascular Inc. 
3576 Unocal Place 
Santa Rosa 
California 95403 
United States 
Local sponsor Europe 
Medtronic Bakken Research Center B.V. 
CardioVascular Department, Aortic & Peripheral Vascular 
Endepolsdomein 5 
6229 GW Maastricht 
The Netherlands 
Clinical Investigation Plan identifier 
APV - ABRE 
Version number/date  
2.0 / 02/MAR/2021 
I have read the protocol, including all appendices, and I agree that it contains all necessary details for 
me and my staff to conduct this study as described. I will conduct this study as outlined herein and will 
make a reasonable effort to complete the study within the time designated. 
I agree to comply with all applicable regulatory guidelines under which the study is being conducted, e.g., 
United States Food and Drug Administration regulations and International Standard ISO14155. I agree 
to conduct the study in compliance with country, local and internal institutional requirements. I agree to 
ensure that the confidential information contained in this document will not be used for any purpose other 
than the evaluation and conduct of the clinical investigation without the prior written consent of Medtronic. 
I will provide all study personnel under my supervision copies of the protocol and access to all information 
provided by Medtronic. I will discuss this material with them to ensure that they are fully informed about 
the products and the study. 
Investigator’s signature 
 
Investigator’s name 
 
Institution 
 
Date 
                                                    (DD/MMM/YYYY) 
 
 

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Table of Contents  
 
1 
Version History .............................................................................................................. 2 
2 
Investigator Statement .................................................................................................. 12 
Table of Contents ............................................................................................................... 13 
3 
Glossary ........................................................................................................................ 16 
4 
Synopsis ....................................................................................................................... 20 
5 
Introduction ................................................................................................................. 27 
5.1 
Background ....................................................................................................................... 27 
5.1.1 
Literature Review ................................................................................................................... 29 
5.2 
Purpose ............................................................................................................................. 30 
6 
Objectives and Endpoints ............................................................................................ 30 
6.1 
Primary Objectives ............................................................................................................ 30 
6.2 
Secondary Objectives ......................................................................................................... 30 
6.3 
Endpoints .......................................................................................................................... 31 
6.3.1 
Primary Endpoints ................................................................................................................. 31 
6.3.2 
Secondary Endpoints.............................................................................................................. 32 
7 
Study Design ................................................................................................................ 34 
7.1 
Duration ............................................................................................................................ 34 
7.2 
Rationale ........................................................................................................................... 34 
8 
Product Description ..................................................................................................... 35 
8.1 
General .............................................................................................................................. 35 
8.1.1 
Stent ....................................................................................................................................... 35 
8.1.2 
Abre Stent Delivery System .................................................................................................... 36 
8.2 
Manufacturer ..................................................................................................................... 40 
8.3 
Packaging .......................................................................................................................... 40 
8.4 
Intended Population .......................................................................................................... 40 
8.5 
Equipment......................................................................................................................... 40 
8.6 
Product Training Requirements......................................................................................... 41 
8.7 
Product Receipt and Tracking ........................................................................................... 41 
8.8 
Product Storage ................................................................................................................. 41 
8.9 
Product Return .................................................................................................................. 42 
9 
Selection of Subjects ..................................................................................................... 42 
9.1 
Study Population ............................................................................................................... 42 
9.2 
Subject Enrollment (Point of Enrollment and Inclusion) ................................................... 42 
9.3 
Subject Screening .............................................................................................................. 42 
9.4 
Inclusion Criteria ............................................................................................................... 45 
9.5 
Exclusion Criteria .............................................................................................................. 46 
10 
Study Procedures ....................................................................................................... 47 
10.1 
Schedule of Events ......................................................................................................... 47 
10.2 
Subject Consent .............................................................................................................. 49 

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10.2.1 
Consent Materials ................................................................................................................... 49 
10.2.2 
Informed Consent Process ..................................................................................................... 49 
10.2.3 
Special Circumstances for Informed Consent Process and Signature ...................................... 50 
10.3 
Screening/Baseline Procedures (-30 days) ...................................................................... 50 
10.3.1 
Demographics, Medical History & Physical Examination ....................................................... 51 
10.3.2 
Blood Tests ............................................................................................................................ 51 
10.4 
Acute DVT Subjects ....................................................................................................... 51 
10.5 
Implant Procedure .......................................................................................................... 52 
10.5.1 
Procedure Data ...................................................................................................................... 52 
10.5.2 
Imaging .................................................................................................................................. 52 
10.5.3 
IVC Filter Placement .............................................................................................................. 52 
10.5.4 
Inflow Requirements .............................................................................................................. 52 
10.5.5 
Lesion(s)................................................................................................................................. 52 
10.5.6 
Predilation .............................................................................................................................. 54 
10.5.7 
Stent Size Selection ................................................................................................................. 54 
10.5.8 
Stent Placement ...................................................................................................................... 55 
10.5.9 
Post-dilation ........................................................................................................................... 55 
10.6 
Hospital Discharge......................................................................................................... 55 
10.7 
30 Day (-7/+14 days) Post-Procedure Follow-Up Assessment ......................................... 55 
10.8 
6 Months (± 30 days) Post-Procedure Follow-Up Assessment ........................................ 56 
10.9 
12 Months (± 30 days) Post-Procedure Follow-Up Assessment ....................................... 56 
10.10 
24 and 36 Months (± 30 days) Post-Procedure Follow-Up Assessment ............................ 57 
10.11 
Unscheduled Visits ......................................................................................................... 57 
10.12 
Assessments ................................................................................................................... 58 
10.12.1 
Antithrombotics ................................................................................................................. 58 
10.12.2 
CEAP Classification ........................................................................................................... 59 
10.12.3 
Scores ................................................................................................................................. 59 
10.12.3.1 
Villalta Score ................................................................................................................................. 59 
10.12.3.2 
Venous Clinical Severity Score (VCSS) .......................................................................................... 59 
10.12.4 
Quality of Life questionnaires ............................................................................................. 59 
10.12.5 
Pregnancy Test ................................................................................................................... 60 
10.12.6 
Imaging .............................................................................................................................. 60 
10.12.6.1 
Venogram ..................................................................................................................................... 60 
10.12.6.2 
Duplex Ultrasound (DUS) ............................................................................................................ 60 
10.12.6.3 
Intravascular ultrasound (IVUS) .................................................................................................... 61 
10.12.6.4 
X-ray ............................................................................................................................................. 61 
10.12.7 
Physical Assessment of Limbs ............................................................................................ 61 
10.13 
Deviation Handling ........................................................................................................ 62 
10.14 
Subject Withdrawal or Discontinuation .......................................................................... 63 
10.14.1 
Subject Withdrawal ............................................................................................................. 63 
10.14.2 
Lost-to-Follow-up .............................................................................................................. 63 
10.14.3 
Subject Discontinuation ...................................................................................................... 63 
10.14.4 
Medical Care after Study Exit .............................................................................................. 63 
10.15 
Recording Data .............................................................................................................. 64 
11 
Risks and Benefits ..................................................................................................... 66 
11.1 
Potential Risks ............................................................................................................... 66 
11.2 
Potential Benefits ........................................................................................................... 67 
11.2.1 
Potential Benefits of the Abre System..................................................................................... 67 

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11.2.2 
Potential Benefits of the ABRE Study .................................................................................... 68 
11.3 
Risk-Benefit Rationale .................................................................................................... 68 
12 
Adverse Event Assessments....................................................................................... 69 
12.1 
Definitions/Classifications ............................................................................................. 69 
12.1.1 
Definitions ............................................................................................................................. 69 
12.1.2 
Classification of Causal Relationships ..................................................................................... 70 
12.1.3 
Anticipated Adverse Events ................................................................................................... 71 
12.2 
Reporting of Adverse Events .......................................................................................... 76 
12.2.1 
Evaluation and Documentation of Adverse Events and Device Deficiencies .......................... 76 
12.2.2 
Reporting of Device Deficiencies ........................................................................................... 77 
12.2.3 
Non-Reportable Medical Occurrences .................................................................................... 77 
12.2.4 
Requirements for Adverse Event Reporting ........................................................................... 78 
12.2.5 
Complaint Reporting .............................................................................................................. 79 
12.2.6 
Emergency Contact Details for Reporting Events and Device Deficiencies ............................ 80 
13 
Committees / Core Laboratories ............................................................................... 80 
13.1 
Data Safety Monitoring Board ........................................................................................ 80 
13.2 
Clinical Events Committee ............................................................................................. 80 
13.3 
Duplex Ultrasound Core Laboratory ............................................................................... 81 
13.4 
Venography, X-ray, and IVUS Core Laboratory .............................................................. 81 
14 
Statistical Design and Methods ................................................................................. 82 
14.1 
Performance Goals ......................................................................................................... 82 
14.1.1 
Performance Goal: Primary Effectiveness Endpoint ............................................................... 82 
14.1.2 
Performance Goal: Primary Safety Endpoint .......................................................................... 83 
14.2 
Sample Size Calculation ................................................................................................. 83 
14.3 
Analysis Sets ................................................................................................................... 84 
14.4 
Statistical Method ........................................................................................................... 84 
14.4.1 
ABRE Pivotal Study Phase ..................................................................................................... 84 
14.4.2 
ABRE Post-Approval Study Phase ......................................................................................... 85 
14.5 
Study Success Criteria .................................................................................................... 85 
14.6 
Handling of Dropouts and Missing Data ........................................................................ 85 
14.7 
Assessment of Data Pooling ........................................................................................... 86 
14.8 
Minimizing Bias ............................................................................................................. 87 
15 
Ethics ........................................................................................................................ 88 
15.1 
Statement(s) of Compliance............................................................................................ 88 
16 
Study Administration ................................................................................................. 89 
16.1 
Investigator / Investigational Site Selection ................................................................... 89 
16.2 
Clinical Trial Agreement ................................................................................................ 90 
16.3 
Study Insurance /Subject Indemnification ..................................................................... 90 
16.4 
Subject Compensation .................................................................................................... 90 
16.5 
Site Activation/Supply of Study Materials ....................................................................... 91 
16.6 
Monitoring ..................................................................................................................... 91 
16.6.1 
Site Initiation Visit .................................................................................................................. 92 
16.6.2 
Periodic Monitoring Visit ....................................................................................................... 92 
16.6.3 
Study Closure ......................................................................................................................... 93 
16.7 
Data Management .......................................................................................................... 93 

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16.7.1 
Electronic Data Capture ......................................................................................................... 93 
16.7.2 
Data Collection ...................................................................................................................... 93 
16.7.3 
Data Validation ...................................................................................................................... 94 
16.8 
Direct Access to Source Data/Documents ...................................................................... 94 
16.9 
Confidentiality ................................................................................................................ 94 
16.10 
CIP Amendments ........................................................................................................... 94 
16.11 
Record Retention ........................................................................................................... 95 
16.12 
Publication and Use of Information ................................................................................ 95 
16.13 
Suspension or Early Termination ................................................................................... 95 
16.13.1 
Planned Study Closure ........................................................................................................ 95 
16.13.2 
Early Termination or Suspension ........................................................................................ 96 
16.13.2.1 
Criteria for Study-wide Termination or Suspension ....................................................................... 96 
16.13.2.2 
Criteria for Investigator/center Termination or Suspension........................................................... 96 
16.13.3 
Procedures for Planned Study Closure, Termination, or Suspension ................................... 97 
16.13.3.1 
Medtronic-initiated ........................................................................................................................ 97 
16.13.3.2 
Investigator-initiated ..................................................................................................................... 97 
16.13.3.3 
Ethics Board-initiated ................................................................................................................... 97 
17 
Records and Reports ................................................................................................. 98 
17.1 Responsibilities of the Investigator ........................................................................................ 98 
17.2 
Responsibilities of Medtronic ....................................................................................... 101 
17.3 
Final Report ................................................................................................................. 105 
18 
Report of Prior Investigations of the Device and Justification for the Study ............ 106 
19 
References ............................................................................................................... 107 
20 
Appendices .............................................................................................................. 110 
Appendix A Scientific Literature Search .............................................................................................. 110 
Appendix B Definitions ...................................................................................................................... 136 
Appendix C CEAP Classification ........................................................................................................ 140 
Appendix D Villalta Score ................................................................................................................... 142 
Appendix E Venous Clinical Severity Score (VCSS) ............................................................................ 143 
Appendix F EQ-5D ............................................................................................................................ 145 
Appendix G VEINES-QOL/Sym questionnaire................................................................................. 148 
Appendix H Center for Medicare and Medicaid Services (CMS) IDE Study Criteria ........................... 152 
 
3 Glossary 
Term 
Definition 
AE 
Adverse Event 
ACT 
Activated Clotting Time 
ADE 
Adverse Device Effect 
CA 
Competent Authority 

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Term 
Definition 
CAD 
Coronary Artery Disease 
CBC 
Complete Blood Count 
CEAP 
Clinical Etiologic Anatomic Pathophysiologic 
CEC 
Clinical Events Committee 
CI 
Confidence Interval 
CIP 
Clinical Investigation Plan 
COPD 
Chronic Obstructive Pulmonary Disease 
CPT 
Chronic Postthrombotic 
CRF 
Case Report Form 
CTPA 
Computed Tomography Pulmonary Angiography 
CVA 
Cerebrovascular Accident 
DOAC 
Direct Oral Anticoagulants (e.g. Dabigatran, Rivaroxaban, Apixaban, or 
Edoxaban) 
DSMB 
Data Safety Monitoring Board 
DUS 
Duplex Ultrasound 
DVT 
Deep Vein Thrombosis 
EC 
Ethics Committee 
eCRF 
Electronic Case Report Form 
EDC 
Electronic Data Capture 
EQ5D 
Euro QOL 5 Dimensions 
FDA 
Food and Drug Administration 
GFR 
Glomerular Filtration Rate 
HBP 
High Blood Pressure 
HDPE 
High-Density Polyethylene 
HIPAA 
Health Insurance Portability and Accountability Act 
ICF 
Informed Consent Form 

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Term 
Definition 
IDE 
Investigational Device Exemption 
I/E Criteria 
Inclusion and Exclusion Criteria 
IFU 
Instructions for Use 
INR 
International Normalized Ratio 
IRB 
Institutional Review Board 
IVC 
Inferior Vena Cava 
IVUS 
Intravascular Ultrasound 
MAE 
Major Adverse Events 
MDD 
Medical Devices Directive 
MI 
Myocardial Infarction 
NIVL 
Nonthrombotic Iliac Vein Lesion 
NSAID 
Non-Steroidal Anti-Inflammatory Drug 
OTW 
Over-The-Wire 
OUS 
Outside the US 
PAD 
Peripheral Artery Disease 
PAS 
Post-Approval Study 
PEEK 
Polyether Ether Ketone 
PTFE 
Polytetrafluoroethylene 
PG 
Performance Goal 
PHI 
Protected Health Information 
PI 
Principal Investigator 
PMA 
Premarket approval application 
PVD 
Peripheral Vascular Disease 
PTS 
Postthrombotic syndrome 
QOL 
Quality of Life 

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Term 
Definition 
SADE 
Serious Adverse Device Effect 
SAE 
Serious Adverse Event 
SFA 
Superficial Femoral Artery 
SID 
Subject Identification Number 
SVS 
Society for Vascular Surgery 
TLR 
Target Lesion Revascularization 
UADE 
Unanticipated Adverse Device Effect 
US 
United States 
USADE 
Unanticipated Serious Adverse Device Effect 
VCSS 
Venous Clinical Severity Score 
VEINES 
Venous Insufficiency Epidemiological and Economic Study 
 
 

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4 Synopsis 
Name of Study 
ABRE Study 
Title 
A prospective, multi-center, continued follow-up of the ABRE pivotal 
study to evaluate the long-term safety and effectiveness of the Abre 
venous self-expanding stent system in patients with symptomatic 
iliofemoral venous outflow obstruction 
Clinical Study Type 
Pivotal (through 12-month follow-up, US only) 
Post-Approval (through 36-month follow-up, all geographies)  
Product Name 
AbreTM venous self-expanding stent system  
(hereafter, “Abre stent” in case only the stent is meant, “Abre system” in 
case the Abre stent including the delivery system is meant) 
Global Sponsor  
Medtronic Vascular Inc. 
3576 Unocal Place 
Santa Rosa, California 95403 
United States 
Local Sponsor Europe 
Medtronic Bakken Research Center B.V. 
Cardiac and Vascular Group, Aortic & Peripheral Vascular 
Endepolsdomein 5 
6229 GW Maastricht 
The Netherlands 
Lead Principal 
Investigators 
Erin H. Murphy, MD  
Division of Vascular and Endovascular Surgery 
Sanger Heart and Vascular Institute 
10625 Park Rd.  
Charlotte, North Carolina 28210 
United States 
 
Stephen Black, MD 
Department of Vascular Surgery 
Guy's & St Thomas' NHS Foundation Trust, St Thomas’ Hospital 
1 Westminster Bridge Road 
London, SE1 7EH 
United Kingdom 

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Indication under 
investigation  
 
The Abre venous self-expanding stent system is intended for use in the 
iliofemoral veins for the treatment of symptomatic venous outflow 
obstruction. 
In the United States (US) the device was approved in October 2020 by 
premarket approval application (PMA).  
Outside the US, the device is CE marked. The study will be conducted 
within the approved indication. 
Investigation Purpose 
Evaluate the safety and effectiveness of the Abre venous self-expanding 
stent system for treatment of symptomatic iliofemoral venous outflow 
obstruction in patients with venous occlusive disease. The collected data 
will be used to support regulatory applications to seek market approval in 
the US and potentially other geographies. 
Product Status 
The Abre system was investigational in the US at the time of study 
enrollment. The product was approved by the FDA on 21/OCT/2020. The 
Abre system is CE marked in countries that require CE.  
Geographies where CE mark is accepted might participate in the study. 
Primary Objective(s) 
The primary objectives are to evaluate effectiveness (i.e. achieving a 
performance goal of 75% primary patency at 12 months) and safety (i.e. 
achieving a performance goal of 12.5% incidence of major adverse 
events within 30 days) of the Abre system in subjects with iliofemoral 
venous obstruction. 
The post-approval primary objective is to evaluate freedom from target 
lesion revascularization (TLR) at 36 months.   
Secondary Objective(s) 
Secondary objectives include descriptive analyses of secondary 
endpoints as well as acute procedural observations and clinical utility 
measures.  
Study Design 
This is a prospective, interventional, non-randomized, single arm, multi-
center, worldwide study, with each center following a common protocol. 
Sample Size 
A maximum of 200 implanted subjects were to be included in the United 
States (US) and outside the United States (OUS) to support the ABRE  
study primary endpoint evaluations. A total of 200 subjects were 
implanted and included in the study from 24 investigational sites. No new 
sites will be added and no new subjects will be enrolled under this 
protocol, only those already in the study are eligible to continue. Data 
from 160 subjects was needed to evaluate the primary effectiveness 
endpoint of primary patency at 12 months, and data from 193 subjects 
was needed to evaluate the primary safety endpoint of major adverse 
events at 30 days. 
A minimum of 40% of included subjects were to be from the US. 

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Sites in the ABRE study were limited to including a maximum number of 
40 subjects per site (20% of the total study population). 
Number of sites 
Up to 35 sites worldwide were to be included in the ABRE study. A total 
of 24 sites participated. 
Study Population 
Patients between 18 and 80 years (inclusive) requiring treatment of a 
non-malignant venous obstruction within the common iliac, external iliac 
and/or common femoral vein. 
Follow-up 
Subjects who are implanted with the Abre stent will be followed for 3 
years. They will have scheduled follow-up visits at 30-days, 6-, 12-, 24-, 
and 36-months post index procedure. 
Estimated Time Course 
Activities 
Timeline 
First Enrollment 
19/DEC/2017 
Enrollment Duration 
12 months 
Completion of Follow-Up 
3 years, or until study closure 
   Expected Study Duration  
5 years, or until study closure 
 
Inclusion/Exclusion 
Criteria 
General Inclusion Criteria 
1. 
Patient is ≥ 18 and ≤ 80 years of age; 
2. 
Patient has at least one of the following clinical manifestations 
(i.e. symptoms and/or signs) of venous disease in lower 
extremity: 
a. 
CEAP score ≥ 31 
b. 
Venous Clinical Severity Score pain score (VCSS) ≥2 (1) 
c. 
Suspected deep vein thrombosis (DVT); 
3. 
Patient is willing and capable of complying with specified follow-
up evaluations at the specified times; 
4. 
Patient has been informed of the nature of the study, agrees to 
its provisions and has provided written informed consent, 
approved by the appropriate Ethics Board. 
 
Imaging-based Inclusion Criteria 
 
 
1 Patients subject to the literature review are similar to the subjects that will be included in the study as more than 90% of the 
patients in the literature review were classified as CEAP 3 or higher. 

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5. Patient has diagnosis of non-malignant venous obstruction within 
the common iliac, external iliac, and/or common femoral vein. The 
proximal point of the obstruction may extend to the iliac venous 
confluence of the inferior vena cava and the distal point may be at 
or above the deep femoral vein. Diagnosis must be made based 
on objective imaging by using venography and/or intravascular 
ultrasound (IVUS). Patient must have good inflow involving either 
the femoral or deep femoral vein being patent and at least a 
caudal section of the common femoral vein that is free of 
significant disease; 
6. 
Patient has an obstructive lesion defined as: 
i. Occluded, or 
ii. ≥50% in diameter reduction on venography or 
IVUS, or 
iii. ≥50% area reduction on IVUS 
7. 
Acute DVT patients should be treated with the Abre stent within 
14 days after onset of symptoms. Patients with acute DVT must 
first undergo successful treatment of acute thrombus; successful 
treatment is defined as 30% or less residual thrombus by 
venogram, as determined by physician, no bleeding, no 
symptomatic pulmonary embolism (confirmed by imaging), and 
no renal compromise (renal compromise defined as GFR<30). 
Patients with underlying obstructive lesions can then be included 
in the study within the same procedure; 
8. 
Target vessel can accommodate a 9F Sheath, from insertion site 
to target segment; 
9. 
Exchangeable guidewire must cross target lesion(s) with 
successful predilation. 
 
General Exclusion Criteria 
1. Patient with DVT in the target limb of which the onset of symptoms 
is between 15 days and 6 months prior to planned treatment or 
patient has an acute DVT anywhere else than in the target vessel;  
2. Patient has peripheral arterial disease causing symptoms in target 
limb; 
3. Patient is pregnant (female patients of child-bearing potential must 
have a pregnancy test done within 7 days prior to the index 
procedure); 
4. Patient has a known or suspected systemic infection at the time of 
the index procedure; 
5. Patient has a planned percutaneous or surgical intervention within 
30 days prior or 30 days following index procedure, or a 
contralateral iliofemoral lesion requiring planned treatment within 
12 months; 

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6. Patient requires femoral endovenectomy and patch venoplasty, 
greater saphenous vein ablation, and/or small saphenous vein 
stripping during the index procedure; 
7. Patient has an active vasculitic inflammatory disorder (e.g. Behcet 
disease) predisposing the patient to thrombosis and requiring 
systemic corticosteroid therapy; 
8. Patient has impaired renal function (GFR < 30) or is on dialysis; 
9. Patient has a platelet count < 50,000 cells/mm3 or > 1,000,000 
cells/mm3 and/or a WBC < 3,000 cells/mm3 or > 12,500 cells/mm3; 
10. Patient has a history of bleeding diathesis or either a history or 
presence of heparin-induced thrombocytopenia antibodies; 
11. Patient has a known hypersensitivity or contraindication to 
antiplatelets or anticoagulation, nitinol, or a contrast sensitivity that 
cannot be adequately pre-medicated; 
12. Patient has presence of other severe co-morbid conditions, which 
in the investigator’s opinion may interfere with the patient’s 
compliance with study visits and procedures, or may confound 
interpretation of study data (e.g. congestive heart failure Class III 
and IV, non-ambulatory patients, severe hepatic dysfunction, life 
expectancy < 1 year); 
13. Patient belongs to a vulnerable population per investigator's 
judgment or patient has any kind of disorder that compromises 
his/her ability to give written informed consent and/or to comply 
with study procedures. Patient must be able to consent for 
themselves; 
14. Patient is currently participating in another investigational drug or 
device study or observational competitive study. 
Imaging-based Exclusion Criteria 
15. Patient has a vena cava obstruction or lesion extending into the 
inferior vena cava (IVC), or the presence of bilateral iliofemoral 
venous lesions requiring planned treatment within 12 months; 
16. Patient has significant venous bleeding, arterial dissection or other 
injury requiring additional percutaneous or surgical intervention 
prior to enrollment; 
17. Patient has a previously placed stent in the ipsilateral venous 
vasculature;  
18. Patient has disease that precludes safe advancement of the 
venous stent to the target lesion(s). 

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Statistics 
The study is designed to meet performance goals (PG) established via 
review of the clinical venous stent literature. A 30-day Major Adverse 
Event PG of 12.5% and a 12-month Primary Patency PG of 75% in 
patients with venous occlusive disease are used. 
200 subjects are planned for inclusion. This includes correction for 20% 
lost-to-follow-up on the effectiveness endpoint and 3.5% lost-to-follow-up 
on the composite safety endpoint. The sample size is driven by the 
primary effectiveness and safety endpoints and based on a one-sided 
alpha of 0.025 and at least 80% overall study power. 
Primary analyses will be conducted after a minimum of 160 subjects 
have evaluable primary patency data at 12 months to evaluate the 
primary effectiveness endpoint and 193 subjects have evaluable follow-
up data at 30 days to evaluate the primary safety endpoint.  
A premarket approval application was submitted to FDA once all 
available 12-month follow-up data was collected on April 27, 2020.  
The primary effectiveness endpoint of the post-approval study phase is 
Target Lesion Revascularization (TLR) through 36 months. The newly 
added objective will be characterized with descriptive statistics. Time-to-
event analysis will be performed for the TLR rate through 36 months 
(1080 days), subjects with no TLR will be censored at the last contact 
date.  Kaplan-Meier estimate and the 95% confidence interval for the 
freedom from TLR rate through 36 months will be reported. 
 
 
 
 
 
 Study 
Procedures 
and 
Assessments 
Schedule of Assessments and Visit Windows 
Data Collection  
Requirement 
Screening/Baseline 
(<30 days before 
procedure unless 
otherwise specified) 
Procedure 
Hospital Discharge 
30 Day (-7/+14 days) 
6 Months (± 30 days) 
12 Months (± 30 days) 
24 &  36  Months 
(± 30 days) 
Unscheduled visit for 
intervention in target 
vein 
Informed Consent 
X 
 
 
 
 
 
 
 
Demographics, Medical 
History & Physical Exam 
X 
 
 
 
 
 
 
 
Pregnancy Test1 
X 
 
 
 
 
 
 
 
CEAP Classification 
X 
 
 
 
 
 
 
 
Physical Assessment of 
Limbs 
X 
 
X 
X 
X 
X 
X 
X 

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Villalta Score, VCSS 
X 
 
 
X 
X 
X 
X 
X4 
VEINES-QOL/Sym,  
EQ-5D QOL 
X 
 
 
 
X 
X 
X 
X4 
Procedure Data 
 
X 
 
 
 
 
 
X 
Serum Creatinine, CBC 
X 
 
 
 
 
 
 
 
INR (if on warfarin) 
X 
 
 
X 
X 
X 
X 
X 
Document Adverse 
Events 
X2 
X 
X 
X 
X 
X 
X 
X 
Document Device 
Deficiencies 
 
X 
X 
X 
X 
X 
X 
X 
Medication3 
X 
X 
X 
X 
X 
X 
X 
X 
Discontinuation 
Information5 
 
 
X 
X 
X 
X 
X 
X 
1 Pregnancy test for women of child-bearing potential only. Must be done within 7 days prior to the index 
procedure. 
2 Adverse Event assessment need to be done as of the moment the subject is enrolled in the study (i.e. 
subject signed and dated the informed consent form).   
3 Medication which will be collected: Antithrombotics, Antibiotics, Immunosuppressants, NSAIDs, Steroids, 
Diuretics, Calcium-channel blockers, Statins 
4 Assessments and questionnaires should be taken before any intervention. 
5 The discontinuation data is needed whenever the subject ends involvement in the study. 
 
Schedule of Imaging Assessments and Visit Windows 
Data 
Collection  
Requirement 
Screening/Baseline (<30 days) 
Procedure 
Hospital Discharge 
30 Day (-7 days, +14 days) 
6 Months (± 30 days) 
12 Months (± 30 days) 
24 &  36  Months (± 30 days) 
Unscheduled visit for intervention 
in target vein 
Pre-stenting 
Post-stenting 
Duplex 
Ultrasound 
X 
 
 
X2 
X 
X 
X4 
X 
X 
Venogram 
1 
X1 
X 
 
 
 
4 
 
X 
IVUS 
1 
X1 
X 
 
 
 
 
 
X 
X-ray 
 
 
 
 
3 
 
X 
X 
X5 
1 Diagnosis can be made during the screening/baseline prior to the index procedure based on objective 
imaging using venography or IVUS. Diagnosis can also be made during the index procedure, prior to 
stenting. In case venogram and IVUS are not performed pre-stenting at the time of the index procedure, 
the pre-procedure venogram and IVUS should be sent to the core laboratory. If screening and pre-
procedure venogram/IVUS are performed, then the pre-procedure venogram/IVUS should be sent to the 

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core laboratory.2 The DUS examination immediately after the index procedure needs to be performed 
between 0 and 7 calendar days from the index procedure. When the first examination after the procedure 
is non-diagnostic, a second examination has to be performed as soon as possible. Every effort should be 
made to perform this within 7 calendar days after the index procedure.  
3 X-rays at 30 days will be performed on the first 30 subjects only. They will be assessed for first safety 
analysis (i.e. stent fracture). 
4 An additional venogram must be performed when: 
(1) DUS assessment is suggestive of ≥50% restenosis or occlusion per investigator assessment, or; 
(2) when DUS is non-diagnostic or suboptimal such as when a subject is obese (e.g. with a BMI >40 ), or;  
(3) is clinically required, or in other words when the subject is having symptoms of venous disease in the 
target limb requiring a venogram.  
5 Plain x-ray is required pre and post re-intervention to assess for stent fracture. 
 
 
 
5 Introduction  
5.1 Background  
Iliofemoral venous obstruction has been recognized with increasing frequency as the underlying cause of 
lower extremity symptoms including edema, pain, skin changes and, in advanced cases, ulceration. When 
the presentation is that of acute deep venous thrombosis (DVT), swelling and pain predominate. However, 
in addition to these symptoms, patients with chronic venous obstruction from nonthrombotic or 
postthrombotic etiologies often have skin and subcutaneous changes which can present as 
hyperpigmentation, lipodematosclerosis, or venous ulceration. (2) The latter pattern of symptoms comprises 
the postthrombotic syndrome. The etiologic mechanism of the symptoms is two-fold; venous valvular 
incompetence (reflux) and outflow obstruction. These two mechanisms are interlinked; obstruction can lead 
to dilatation of veins resulting in valvular incompetence. As well, spontaneous recanalization after venous 
thrombosis often results in destruction of the valves in the involved segments. The relative contribution of 
these two mechanisms to the development of symptoms varies from patient to patient, but the best results 
can be achieved when both reflux and obstruction can be treated. (3) (4) 
The prevalence of chronic iliofemoral outflow obstruction, whether postthrombotic or nonthrombotic, is 
difficult to discern from the literature. Many live for years with the disease and only seek treatment when 
the symptoms become incapacitating. For this reason, there is a paucity of strong data on which to base 
estimates of disease prevalence. An estimate of the size of the population appropriate for iliofemoral venous 
stenting relies on two assumptions. First, venous stenting is indicated only in patients with significant 
symptoms (CEAP class C3 or greater). Second, venous stenting is not appropriate for those patients with 
valvular incompetence as the primary etiology for symptoms, or in those with venous obstruction limited to 
the femoral and more caudal veins. 
Estimates vary for the prevalence of significant (CEAP class C3 or greater) venous disease. For C3/C4 
disease, estimates range from 5% to 17%. For C5/C6 disease, estimates range between 1% and 2%. (5) (6) 
(7) (8) Using a midpoint of 12%, the prevalence of C3 – C6 disease is approximately 29 million in the US adult 
population. Among these, Lurie and colleagues estimate that 90% will manifest iliofemoral venous outflow 

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obstruction. Thus, approximately 25 million patients in the US have iliofemoral venous obstruction of a 
severity where iliofemoral venous stenting might be appropriate. 
Despite the basis of this calculation on a consensus document, many will find this estimate far too high. To 
approach the problem from a different angle, we consider again the epidemiology study by Criqui, et. al. 
(2003) (5). These authors found that 1.0% prevalence of deep functional disease and trophic changes (C4 - 
C6 disease). While this excludes C3 patients who might also benefit from stent placement, it also includes 
patients with deep venous reflux without obstruction, or obstruction in the femoral vein that does not extend 
into the iliofemoral segment. Assuming that these exclusions and inclusions are approximately equal, the 
1.0% estimate suggests that about 2.4 million patients have iliofemoral outflow obstruction suitable for 
venous stenting. So we conclude that the true prevalence of iliofemoral venous outflow obstruction lies 
between 2.4 million and 25 million US adults. 
The aforementioned estimates do not include those patients appropriate for stenting after acute iliofemoral 
deep venous thrombosis (DVT). These patients, by and large, have chronic, often asymptomatic iliofemoral 
venous lesions; lesions unmasked after removing the acute thrombus. Based on US hospital discharge 
data, approximately 600,000 DVT are diagnosed in the US annually (ICD-9-CM code 453.xx). There are 
varying estimates of how many of these involve the iliofemoral segment. One recent estimate from (9) 
documented iliofemoral involvement in 38% of patients with DVT.  
Discounting the overall estimate for recurrent DVT in the same patients, estimated to be approximately 30% 
over long-term follow-up, (10) (11) the incidence of acute iliofemoral DVT suitable for stenting is approximately 
160,000 per year (600,000 x 38% x 70%).  
Even today, most patients presenting with acute iliofemoral DVT are treated with anticoagulation alone. (12) 
(13) (14) Patients with postthrombotic symptoms are often followed with non-interventional management 
consisting of compression hose and elevation of the extremity. (11) While effective at preventing pulmonary 
embolism and recurrent DVT, medical management of symptomatic venous obstruction is associated with 
the development of debilitating symptoms over long-term follow-up. (15) A variety of definitive modalities have 
been used to restore venous outflow and alleviate symptoms. For acute DVT, active thrombus removal 
techniques such as pharmacologic thrombolysis and percutaneous mechanical thrombectomy in 
combination with venous angioplasty and stenting has emerged as the first line treatment to rapidly re-
establish venous patency. (16) (17) (18) (19) Venous stenting has been successfully employed as a stand-alone 
primary intervention for symptomatic non-acute postthrombotic and nonthrombotic iliofemoral outflow 
obstruction. (17) (18) (20) (21) 
Despite the increasing use of stents for acute DVT, chronic postthrombotic and nonthrombotic venous 
obstruction, most studies have employed stents originally designed for arteries or for biliary indications. 
Most publications comprise single-center retrospective series. Prospective, protocol-driven, monitored 
studies with core laboratory analyses of imaging studies are rare. (22) This observation must be taken into 
account when assessing the frequency of clinical events; with the possibility of underreporting due to the 
retrospective nature of data collection. 
Currently, there are several societal guideline documents on the standard of care for the treatment of 
iliofemoral venous lesions. Most of these are heavily weighted toward the treatment of acute DVT. A 
guideline document published by the American College of Phlebology in October 2015 (23) supplements a 
2014 clinical practice guidelines document from the Society of Vascular Surgery and the American Venous 
Forum for the management of venous leg ulcers, (24)  and other earlier societal guideline documents. (25) (26) 
(27) While many of the guideline documents are focused on the management of acute thrombotic venous 
obstruction, some caveats regarding venous stenting have been included. As well, several review articles 

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have been published, some recently, providing some insight to current practice in the field. (28) (29) (30) (31) (32) 
(33) (34) 
Today, venous stenting can be considered as a standard of care for symptomatic, anatomically-significant 
iliofemoral venous outflow obstruction. (21) (28) (33) Currently, however, no dedicated venous stent is approved 
for the iliac vein indication in the US, although several are CE marked and marketed outside the US.  
5.1.1 Literature Review 
A scientific literature search has been performed to provide an up-to-date review of published data on the 
safety and effectiveness of stenting for iliac and iliofemoral venous disease. The review included peer-
reviewed publications identified by the web-based search strategy with the National Library of Medicine 
National Center for Biotechnology Information PubMed resource and Cochrane Library through a search 
date of October 1, 2016. The substance of the literature review was formed by 63 selected publications. 
Most publications were single-center, retrospective, non-randomized series. Articles were published 
between 1996 and 2016 with treatment dates between 1987 and 2014. The reviewed publications outline 
the clinical and anatomic characteristics of the population of patients with iliofemoral venous obstruction 
who were medically-managed and/or treated with venous stents and provided the conclusions below. 
The average age at presentation was 52.7 years, although patients presented throughout all age ranges. 
Females presented more often than males; 63.5% versus 36.5%, respectively. Lesions were more often on 
the left than the right; 70.0% vs. 20.4%. Bilateral lesions were treated in 9.6% of patients. At baseline, two-
thirds of patients were within the C3 or C4 CEAP categories; more mild symptomatology was found in only 
8.7% of cases; 26.4% presented with a healed (C5, 7.5%) or active ulcerations (C6, 18.9%). 
The literature has shown that venous stenting is generally safe. Major hemorrhage occurred in 1.1% of 
patients with access site hematomas in 3.6%. Other access site complications such as false aneurysms or 
arteriovenous fistulae were very rare, as was pulmonary embolism or death within 30 days of the procedure; 
each occurring in 0.2% or fewer patients. When major adverse events (MAE) were defined as the composite 
occurrence of death, stent thrombosis, pulmonary embolism or stent migration, 5.6% experienced an MAE 
within 30 days. Stent fracture was reported in only 1.4% of patients, with stent dislodgement (at the index 
procedure) in 0.6% and stent migration (after the index procedure) in 1.6%.  
Effectiveness as measured by patency rate was also satisfactory. At 12 months primary, primary-assisted 
and secondary patency rates were 85.7%, 93.8% and 95.2%, respectively. Target lesion revascularization 
(TLR) at 12 months was 8.3%. There did not appear to be substantial differences in outcome between 
patients treated with off-label or CE marked venous stents, but the relatively small sample for CE marked 
stents precludes a robust analysis. In summary, iliofemoral venous stenting as reported in the literature 
appears to be associated with relatively few perioperative and longer-term complications, with a primary 
patency rate of approximately 85.7% at one year. 
The literature shows that angioplasty and venous stenting are safe and effective in patients presenting with 
acute deep vein thrombosis, chronic postthrombotic syndrome (PTS) and chronic nonthrombotic iliac vein 
lesion (NIVL). The Abre system was developed specifically for this need. This study will evaluate safety and 
effectiveness of the Abre system specifically in order to support regulatory submissions in the US and other 
geographies.  
The 63 selected publications on past trials for the target indication (Appendix A Scientific Literature Search) 
did not report any race and ethnicity-specific prevalence. Although evidence exists that incidence rates of 
venous thromboembolism (including pulmonary embolism and deep vein thrombosis) show significant 

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variation among different ethnic/racial groups, (35) the prevalence of venous thromboembolism (and more 
specific iliofemoral outflow obstruction) in different racial and ethnic groups has not yet been thoroughly 
studied. In the ABRE Study, race and ethnicity data will be collected to improve the completeness and 
quality of demographic subgroup data to better understand whether there are potentially clinically important 
racial/ethnic-based differences in the anticipated effect of the intervention. 
5.2 Purpose 
The purpose of the ABRE study is to evaluate the safety and effectiveness of the Abre venous self-
expanding stent system for the treatment of patients with symptomatic iliofemoral outflow obstruction. The 
clinical performance of the Abre system was evaluated during the pivotal study phase through a 
prospective, single-arm, non-randomized multi-center clinical study that treated and included 200 subjects 
from 24 investigational sites with a hypothesis-based 30-day composite safety endpoint and a hypothesis-
based 12-month effectiveness endpoint to be tested against performance goals. 
With anticipated 20% loss of data on the effectiveness endpoint and 3.5% loss on data on the composite 
safety endpoint, a Premarket Approval application was to be submitted to FDA when all available 12-month 
follow-up data have been collected, including the data needed to demonstrate primary safety (193 subjects 
have evaluable follow-up data at 30 days) and primary effectiveness (160 subjects have evaluable primary 
patency data at 12 months) are obtained.  
The premarket approval application was submitted to FDA and approval was received on October 21, 2020.  
Subjects who were implanted with the Abre stent in the pivotal study phase will continue to be followed 
through 36 months in the post-approval study phase to evaluate long-term safety and effectiveness. The 
primary endpoint to be assessed during the post-approval study phase is freedom from target lesion 
revascularization (TLR) at 36 months.  
6 Objectives and Endpoints 
6.1 Primary Objectives 
The primary objective was to evaluate the effectiveness (i.e. achieving a performance goal of 75% primary 
patency at 12 months) and safety (i.e. achieving a performance goal of 12.5% incidence of major adverse 
events within 30 days) of implanting the Abre stent in subjects with iliofemoral venous obstruction.  
The primary objective of the post-approval study phase is to evaluate the long-term effectiveness by 
assessing the freedom from target lesion revascularization (TLR) at 36 months. 
6.2 Secondary Objectives 
Secondary objectives include descriptive analyses of secondary endpoints as well as acute procedural 
observations and clinical utility measures.  

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6.3 Endpoints 
6.3.1 Primary Endpoints 
The primary effectiveness endpoint for this study has been chosen based on the results of an extensive 
literature review (Appendix A Scientific Literature Search). Individual components of the primary safety 
composite endpoint have been reported in a number of venous stenting studies. 
Primary effectiveness endpoint 
Primary Patency is defined as meeting all of the following criteria at 12 months post-procedure: 
• 
Freedom from occlusion2 of the stented segment of the target lesion; 
• 
Freedom from restenosis2 ≥50% of the stented segment of the target lesion; 
• 
Freedom from clinically-driven3 target lesion revascularization4 
Primary effectiveness endpoint of the ABRE Post-Approval Study Phase 
The primary effectiveness endpoint is Target Lesion Revascularization (TLR) through 36 months, defined 
as any re-intervention of the stented segment of the target lesion. 
 
 
Primary safety endpoint 
The primary safety endpoint of this study will be the incidence of composite Major Adverse Events (MAE) 
at 30 days following stenting of an obstruction in the iliofemoral venous segment. MAEs will be adjudicated 
by a Clinical Events Committee (CEC), except for stent thrombosis and stent migration as they are 
confirmed by core laboratory. 
The components of the 30-day MAE composite include: 
• 
All-cause death occurring post-procedure  
• 
Clinically significant (i.e. symptomatic, confirmed by CT pulmonary angiography) pulmonary 
embolism  
• 
Major bleeding complication (procedural) 
• 
Stent thrombosis confirmed by imaging as assessed by core laboratory 
• 
Stent migration confirmed by imaging as assessed by core laboratory 
Note: Migration excludes stent dislodgement at the index procedure as may occur with under-sizing 
of a stent. 
 
 
2All subjects will undergo DUS assessments for determination of patency. 
 An additional venogram must be performed when:  
(1) DUS assessment is suggestive of ≥50% restenosis or occlusion per investigator assessment, or  
(2) when DUS is non-diagnostic or suboptimal such as when a patient is obese (e.g. with a BMI >40), or  
(3) is clinically required, or in other words when the patient is having symptoms of venous disease in the target limb requiring a venogram.  
All DUS and venographic imaging examinations will be analyzed by respective independent core laboratories.   
3Clinically driven is defined as the recurrence of symptoms present at baseline or the onset of new symptoms including, but not limited to venous pain, 
swelling, dermatitis, or ulceration related to the target limb. 
4Clinically driven target lesion revascularization will be adjudicated by the CEC based on core laboratory adjudicated imaging data and relevant clinical 
information provided by the site.   
 

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6.3.2 Secondary Endpoints 
To assess how the subjects are doing clinically, the following secondary endpoints will be evaluated.  
  
1. Device success: Successful delivery and deployment of the Abre stent in the target lesion with 
successful removal of the delivery system. 
 
2. Lesion success: Venographic evidence of <50% final residual stenosis of the stented segment of 
the target lesion after post-dilation, when applicable, and as assessed by core laboratory. 
 
3. Procedure success: Lesion success without procedure-related MAEs prior to hospital discharge 
within 30 days.  
 
Note: If core laboratory is unable to assess the venographic evidence, site reported data will 
be used. 
 
4. Primary Patency at 24- and 36 months: Freedom from occlusion of the stented segment of the 
target lesion, freedom from restenosis ≥50% of the stented segment, and freedom from clinically 
driven target lesion revascularization (CD-TLR).  
5. Primary Assisted Patency at 12-, 24- and 36 months: Uninterrupted patency of the stented 
segment of the target lesion with a secondary intervention, also known as an adjunctive treatment 
(e.g. balloon venoplasty, subsequent stenting, etc.).5  
6. Secondary Patency at 12-, 24-, and 36 months: Patency of the stented segment of the target 
lesion after subsequent intervention for an occlusion.5  
7. Target Lesion Revascularization (TLR) through 30 days, 6-, 12-, 24- and 36 months: Any re-
intervention of the stented segment of the target lesion. 
 
8. Major Adverse Events (MAE) through 6-, 12-, 24- and 36 months: 
MAEs include: 
• 
All-cause death occurring post-procedure 
• 
Clinically significant (i.e. symptomatic, confirmed by CT pulmonary angiography) pulmonary 
embolism  
• 
Major bleeding complication (post-procedural) 
• 
Stent thrombosis confirmed by imaging as assessed by core laboratory 
• 
Stent migration  confirmed by imaging as assessed by core laboratory 
Note: Migration excludes stent dislodgement at the index procedure as may occur with under-sizing 
of a stent 
All MAEs will be adjudicated by a CEC, except stent thrombosis and stent migration which are 
confirmed by the core laboratory. 
 
 
5 Confirmed by Duplex ultrasound scan evaluated by independent core laboratory. In cases where both DUS and venography were used at the same 
time point, venography would be used for the primary assessment. 
 

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9. Delayed Stent Migration at 12-, 24-, and 36 months: position change of a venous stent observed 
with an imaging modality > 1 cm from its original location at the conclusion of the index procedure, 
as 
determined 
with 
regard 
to 
a 
reference 
anatomic 
structure. 
 
10. Stent Fracture at 30 days, 12-, 24- and 36 months: 
Fracture or breakage of any portion of the stent. 
Determined by X-ray for the first 30 subjects at 30 days and for all subjects (including the first 30 
subjects) at 12-, 24- and 36 months using the following classifications (36) as adjudicated by a venous 
stent fracture core laboratory: 
i. Type 0 – No strut fractures 
ii. Type I – Single tine fracture 
iii. Type II – Multiple tine fractures 
iv. Type III – Stent fracture(s) with preserved alignment of the components 
v. Type IV – Stent fracture(s) with mal-alignment of the components 
vi. Type V – Stent fracture(s) in a trans-axial spiral configuration 
                                
 
 
11. Change in VEINES-QOL/Sym Score at 6-, 12-, 24- and 36 months: Defined as the change in 
VEINES-QOL/Sym score at 6, 12, 24, and 36 months compared to baseline. (37) 
 
12. Change in VILLALTA Score at 6-, 12-, ,24-, and 36 months: Defined as the change in VILLALTA 
score at 6, 12, 24, and 36 months compared to baseline.  
 
13. Change in EQ5D Quality of life Score at 6-, 12-, 24-, and 36 months: Defined as the change in 
Quality of Life Score as assessed by EQ5D questionnaire at 6, 12, 24, and 36 months compared to 
baseline. 
 
14. Change in VCSS Score at 6-, 12-, 24-, and 36 months: Defined as the change in VCSS Score at 
6, 12, 24, and 36 months compared to baseline. 
 
15. Major bleeding complication at 30 days, 6-, 12-, 24- and 36 months: A blood loss leading to 
transfusion of whole blood or red cells provided hemoglobin drop of 3 g/dL (1.86 mmol/L) or more is 
related to bleeding occurring during the index procedure through 36 months post-index procedure. 
 
16. Medical resource utilization through 36 months including length of stay and re-hospitalizations.  
 
 
 

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7 Study Design  
This is a prospective, multi-center continued follow-up of the ABRE pivotal study, to assess the long-term 
safety and effectiveness of the Abre venous self-expanding stent system in subjects with symptomatic 
lliofemoral venous outflow obstruction with each site following a common protocol. A total of 200 subjects 
were included in the ABRE study at 24 sites in the US and selected countries outside of the US. The 
participating sites and principal investigators are listed in a separate overview, which is maintained in the 
Trial Master File and Investigator Site File. To avoid introduction of bias to the study results due to 
disproportionate inclusion, the maximum number of subjects included per site was restricted to no more 
than 40 (or 20% of the total study population). Study-wide, 200 subjects were implanted with one or more 
Abre stent(s). A total of 302 stents were used during the study as subjects could receive more than one 
stent when needed. It was expected that the average subject will require 1 or 2 stents. Refer to the IFU for 
additional device use and sizing details. Subjects who were implanted with the Abre stent were planned to 
be evaluated at baseline, procedure, hospital discharge, 30 days, 6 months, and annually thereafter through 
3 years or until study closure. Protocol-required evaluations are performed at the investigative study sites 
by authorized study staff. The collected data was planned to be used to support regulatory applications in 
seeking market approval for the Abre system in the US, and potentially other geographies.  
In the US, the data collected in the ABRE pivotal study phase through 12-month follow-up was used to 
support  a pre-market application. The Abre Venous System was approved by the FDA on 21/OCT/2020. 
In the US, after receiving PMA approval the ABRE study has transitioned to a post-approval study. Outside 
the US, the study is a post-market study. A common protocol is being followed at all investigational sites. 
7.1 Duration 
Once included, subjects will remain in the study through completion of the required follow-up duration, 
unless the subject withdraws consent, the investigator withdraws the subject for the subject’s best medical 
interest, or Medtronic terminates the study for any reason.  
The enrollment phase was planned to last approximately 13 months. Enrollment of 200 subjects was 
completed in 12 months. The ABRE study had a planned follow-up duration for each subject of 36 months. 
The ABRE post-approval study phase will maintain the same follow-up schedule with follow-up completing 
for each subject at 36 months. The total expected duration of the study is approximately 5 years. 
7.2 Rationale  
The clinical performance of the Abre system was evaluated through a prospective, single-arm, non-
randomized multi-center clinical study in a total of 200 included subjects with a hypothesis-based 30-day 
composite safety endpoint and a hypothesis-based 12-month effectiveness endpoint derived from 
performance goals. The study was designed to meet a primary patency performance goal of 75% and a 
safety performance goal of 12.5% to achieve study success. 
An extensive scientific literature review (Appendix A Scientific Literature Search) was undertaken with the 
objective to provide an up-to-date review of published data on the safety and effectiveness of stenting for 
iliac and iliofemoral venous disease. 

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Critical appraisal of the information collected in the literature review established a 30-day post-procedure 
composite MAE rate and a 12-month post-procedure primary patency rate in order to assess respectively 
the safety and effectiveness of the Abre system. 
The design was single-arm since (1) no gold standard exists to treat iliofemoral vein obstruction and (2) 
“medical treatment alone” cannot assess the effectiveness endpoint of primary patency of the stented 
segment, meaning comparisons are not relevant. 
Significant pre-clinical testing via bench and animal models along with research feasibility activities have 
been performed to ensure product quality and optimize system performance. The study will evaluate the 
safety and effectiveness in subjects.  
8 Product Description 
8.1 General 
The Abre system is intended for use in the iliofemoral veins for the treatment of symptomatic venous outflow 
obstruction. 
The Abre system consists of a stent and stent delivery system designed specifically for implantation in the 
peripheral venous system. The Abre system consists of a flexible self-expanding stent made of a nickel-
titanium alloy (nitinol) provided in multiple lengths and diameters and an over-the-wire stent delivery system. 
Table 1 lists the stent diameters and lengths for the Abre stent.  
 
Table 1: Stent Diameters and Lengths 
 
 
 
Stent Length (mm) 
Nitinol Tube 
Wall 
Thickness 
40 
60 
80 
100 
120 
150 
Stent 
Diameter 
(mm) 
10 
x 
x 
x 
x 
x 
x 
0.018” 
12 
 
x 
x 
x 
x 
x 
14 
 
x 
x 
x 
x 
x 
16 
 
x 
x 
x 
x 
x 
0.028” 
18 
 
x 
x 
x 
x 
x 
20 
 
x 
x 
x 
x 
x 
8.1.1 Stent 
The Abre stent is a flexible self-expanding nitinol (nickel-titanium alloy) stent provided in multiple lengths 
and diameters. The stent is laser machined from a continuous seamless piece of nitinol tubing into an open 
lattice design.  
A drawing of the laser cut Abre stent is seen in Figure 1. There are no welds, joints, or bonds used in the 
construction of the stent. The Abre stent cell geometry includes three wave peaks between connection 
bridges. An alternating off-line pattern used for the connection bridges is intended to increase stent 
flexibility. The Abre stent is designed for durability. Compound radii were applied to specific nodes in order 
for high strain locations to be further reduced resulting in a higher fatigue life. These radii can be seen in 
the figures below. After being laser cut, the stent is electropolished and passivated. The Abre stent uses 
integral nitinol markers for visibility. Figure 2 is a picture of the finished stent. Upon deployment, the stent 
achieves its predetermined diameter and exerts an outward force to maintain patency and placement (i.e. 
no migration) in the target vessel. 

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Cell lengths and strut widths vary linearly with stent diameter across two groups of  stent diameters:  
(1) the 10-14 mm diameter stents, which are cut from a starting tube thickness of 0.018”; and  
(2) the 16-20 mm diameter stents, which are cut from a starting tube thickness of 0.028”.   
 
Figure 1: Abre laser cut pattern 
 
 
 
Figure 2: Abre finished stent 
8.1.2 Abre Stent Delivery System 
The Abre stent delivery system is an over-the-wire (OTW), 9 Fr, 0.035” guide wire compatible, delivery 
system for deploying the Abre self-expanding nitinol stent in the iliofemoral vein. The catheter is a triaxial 
shaft configuration consisting of an inner shaft, a retractable sheath, and an isolation sheath. The inner 
shaft is PEEK (polyether ether ketone) with a radiopaque Pebax tip. The retractable sheath is a braid 
reinforced nylon with a PTFE liner. The isolation sheath is High-Density Polyethylene (HDPE). The 
retractable sheath has one 90% Platinum/10% Iridium radiopaque marker that aids in positioning the 
catheter. The isolation sheath is attached to the deployment handle assembly via the strain relief. A single 
luer port is located on the proximal end of the deployment handle. Saline is injected into this port to flush 
air from the system. The handle assembly contains a thumbwheel actuated deployment mechanism that, 
along with the isolation sheath, provides control and accuracy during stent deployment. A locking pin 
prevents the stent from being deployed prior to intended use and must be removed to actuate the 
thumbwheel.   
As the thumbwheel is rotated, a stainless steel Pull Cable is wound onto the thumbwheel and pulls the 
retractable sheath toward the handle, deploying the stent.  
 
Figure 3 provides a drawing of the Abre stent delivery system. 
 

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Figure 3: Abre stent delivery system 
 
 

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Abre system model numbers are listed in Table 2 for the US and Table 3 for outside the US. No model 
numbers were added to the study during the enrollment period. 
 
Table 2: Abre system model numbers in US 
Model 
Stent Ǿ (mm) 
Stent Length (mm) 
Working Length (cm) 
AB9T10040090 
10 
40 
90 
AB9T10060090 
10 
60 
90 
AB9T10080090 
10 
80 
90 
AB9T10100090 
10 
100 
90 
AB9T10120090 
10 
120 
90 
AB9T10150090 
10 
150 
90 
AB9T12060090 
12 
60 
90 
AB9T12080090 
12 
80 
90 
AB9T12100090 
12 
100 
90 
AB9T12120090 
12 
120 
90 
AB9T12150090 
12 
150 
90 
AB9T14060090 
14 
60 
90 
AB9T14080090 
14 
80 
90 
AB9T14100090 
14 
100 
90 
AB9T14120090 
14 
120 
90 
AB9T14150090 
14 
150 
90 
AB9T16060090 
16 
60 
90 
AB9T16080090 
16 
80 
90 
AB9T16100090 
16 
100 
90 
AB9T16120090 
16 
120 
90 
AB9T16150090 
16 
150 
90 
AB9T18060090 
18 
60 
90 
AB9T18080090 
18 
80 
90 
AB9T18100090 
18 
100 
90 
AB9T18120090 
18 
120 
90 
AB9T18150090 
18 
150 
90 
AB9T20060090 
20 
60 
90 
AB9T20080090 
20 
80 
90 
AB9T20100090 
20 
100 
90 
AB9T20120090 
20 
120 
90 
AB9T20150090 
20 
150 
90 
 
 
 

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Table 3: Abre system model numbers outside the US 
Model 
Stent Ǿ (mm) 
Stent Length (mm) 
Working Length (cm) 
AB9G10040090 
10 
40 
90 
AB9G10060090 
10 
60 
90 
AB9G10080090 
10 
80 
90 
AB9G10100090 
10 
100 
90 
AB9G10120090 
10 
120 
90 
AB9G10150090 
10 
150 
90 
AB9G12060090 
12 
60 
90 
AB9G12080090 
12 
80 
90 
AB9G12100090 
12 
100 
90 
AB9G12120090 
12 
120 
90 
AB9G12150090 
12 
150 
90 
AB9G14060090 
14 
60 
90 
AB9G14080090 
14 
80 
90 
AB9G14100090 
14 
100 
90 
AB9G14120090 
14 
120 
90 
AB9G14150090 
14 
150 
90 
AB9G16060090 
16 
60 
90 
AB9G16080090 
16 
80 
90 
AB9G16100090 
16 
100 
90 
AB9G16120090 
16 
120 
90 
AB9G16150090 
16 
150 
90 
AB9G18060090 
18 
60 
90 
AB9G18080090 
18 
80 
90 
AB9G18100090 
18 
100 
90 
AB9G18120090 
18 
120 
90 
AB9G18150090 
18 
150 
90 
AB9G20060090 
20 
60 
90 
AB9G20080090 
20 
80 
90 
AB9G20100090 
20 
100 
90 
AB9G20120090 
20 
120 
90 
AB9G20150090 
20 
150 
90 
 
 

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The Abre system was investigational in the US during the pivotal study enrollment phase and was labeled 
as such. The label was provided separate from the CIP. The Abre system was approved by FDA on 
21/OCT/2020. Outside the US, the Abre system is CE marked and was labeled as such. Labeling was 
provided in local language for CE marked devices. The CE marked devices were used within intended use 
as described in the approved IFU for which CE mark has been obtained. In countries where no market 
release is obtained, the use of the Abre system was limited to the clinical investigation and according the 
Clinical Investigation Plan. Instructions for Use were available separate from this CIP. The device 
classification of the Abre system is listed in Table 4. 
Table 4: Device Classification 
Device 
Classification by Geography 
USA  
(FDA) 
European Union  
(MDD) 
Abre system 
Class III 
Class IIb 
8.2 Manufacturer 
The Abre self-expanding venous stent system was manufactured in accordance with standard procedures 
and specifications under 21 CFR 820 and ISO13485. The manufacturer is listed below: 
 
Medtronic Inc. 
710 Medtronic Parkway 
Minneapolis, Minnesota 55432  
USA 
8.3 Packaging 
The Abre system was delivered in a sterile package for single use only. The label was provided separate 
from the CIP. 
8.4 Intended Population 
The Abre system is intended for use in the iliofemoral veins for the treatment of symptomatic venous outflow 
obstruction. 
The Abre stent must not be used in patients in whom anticoagulant or antiplatelet therapy is contraindicated 
and with known hypersensitivity to nickel titanium (nitinol). 
8.5 Equipment 
Any test equipment critical to be used for assessing endpoints (e.g., Duplex Ultrasound, X-ray, IVUS, 
venography) will be maintained/calibrated according to the site’s standard protocol. Maintenance and 
calibration reports will be monitored periodically. 

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8.6 Product Training Requirements 
The implanting investigator was evaluated to ensure that he/she was qualified by training, education, and 
experience to implant iliofemoral venous stents. Each implanting investigator was required to meet the 
predefined minimum requirement of having performed at least 10 iliofemoral venous stent cases in the year 
prior to site activation. It was also required that the study site had performed at least 20 venous stenting 
cases in the year preceding site activation. 
The implanting investigator was trained on the Abre system including, but not limited to at least the following: 
• 
Instructions for Use of the Abre system 
• 
Bench top model of the Abre system including deployment of at least one stent 
No roll-in patients were planned for the pivotal study phase. 
Additional training requirements are included in the ABRE Study Training Plan. 
8.7 Product Receipt and Tracking 
All sites were trained on device accountability, including the return of open or unopened devices (for defect, 
damage, malfunction, expired inventory).  
The PI was responsible for maintaining adequate records of the receipt and disposition of all Abre systems 
as per the Device Accountability Instructions provided in the Investigator Site File. 
All sites were required to maintain (investigational) device records that contained the following information 
on all components shipped to the site for the study:  
• 
(Investigational) device name 
• 
Device model number 
• 
Device lot number 
• 
Date of receipt of device 
• 
Name of person receiving the device 
• 
Name of person using/opening the device (if applicable) 
• 
Date of implant or use (if applicable) 
• 
Subject Identification Number (SID) of subject receiving or using the device (if applicable) 
• 
Disposition (implanted, disposed of, or returned to Medtronic) 
For devices that were returned to Medtronic or disposed of, sites were required to document the following 
additional information: 
• 
The reason for the device being returned to Medtronic or disposed of 
• 
Name of the person who returned or disposed of each device 
• 
Date shipped to Medtronic, if returned 
• 
If device is disposed of, the method of disposal 
8.8 Product Storage 
Where investigational, the sites were required to store devices as labeled and within a secured area away 
from sunlight that was accessible and controlled only by the assigned, trained study personnel at the site. 
Where market-released, the sites were required to store devices as labeled. 

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8.9 Product Return 
In the event of a device malfunction of the Abre system prior to, during, or after implant (due to conversion 
to surgery during the index procedure, stent infection, integrity issues triggering explant or identification 
during autopsy), the device was to be returned to Medtronic. Sites were instructed to contact their Medtronic 
clinical study representative to obtain further instruction on device return procedures. All explanted devices 
were to be analyzed by Medtronic. At the end of the study enrollment period, all remaining investigational 
devices (in US) were returned to Medtronic. 
9 Selection of Subjects 
9.1 Study Population 
Patients between 18 and 80 years (inclusive) requiring treatment of a non-malignant venous obstruction 
within the common iliac, external iliac, and/or common femoral vein were considered for the study if they 
met all of the inclusion and exclusion criteria (I/E criteria). 
9.2 Subject Enrollment (Point of Enrollment and Inclusion) 
The point of enrollment was the time at which the subject signed and dated the informed consent form.  
The point of inclusion was the time at which the subject who signed and dated the informed consent form, 
adhered to all I/E criteria and the Abre system entered the vasculature.  
9.3 Subject Screening 
Patients identified with symptomatic venous outflow obstruction in the iliofemoral veins requiring a venous 
stent were screened by the site’s investigative team for possible inclusion in the study.  
During the course of the study, Medtronic had the option to limit enrollments to specific indications (i.e. 
acute DVT, postthrombotic syndrome (PTS), or nonthrombotic iliac vein lesion (NIVL)), if needed in order 
to achieve a distribution that was similar to the literature review used to develop the study performance 
goals. Investigators were notified of specific indications that would no longer be considered for enrollment. 
This determination would be made during the screening process, at which time the subject would become 
a screening failure. 
Enrolled 
Patients who met all general screening criteria were asked to participate in the study. If the patient agreed 
to participate, prior to any study-specific tests or procedures, a personally signed and dated informed 
consent was obtained. Signing and dating the informed consent form was considered the point of 
enrollment. Once informed consent was obtained study-specific tests were performed to assess any 
remaining I/E criteria. 
Enrolled – not included 
Consented subjects who did not meet all I/E criteria were to not be treated with the Abre stent. This might 
have been based on the outcome of imaging during the implant procedure. If subjects left the study before 
the implant date, safety assessments could be stopped at the date of screening failure. If subjects were 

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excluded based on failing the I/E criteria during the implant procedure, they were to be followed for 30 days 
for safety assessment only. No imaging needed to be sent to the core laboratory for these subjects. 
Included 
Consented subjects who met all study-specific I/E criteria were eligible to be treated with the Abre stent. 
During the study procedure, the point at which the Abre system entered the vasculature was considered 
the point of inclusion into the study. Subjects who were implanted with the Abre stent were to be followed 
for the duration of the study.  
Two hundred (200) subjects were included in the ABRE study. 
Included – not implanted 
This is a sub-category of the Included group. Consented subjects who met all study-specific I/E criteria 
were treated with the Abre stent. During the study procedure, the point at which the Abre system entered 
the vasculature was considered the point of inclusion into the study. Those subjects who were not implanted 
with the Abre stent were to be followed for 30 days for safety assessment only. These subjects were to be 
included in the primary analysis. The pre-procedure/pre-stenting imaging was to be submitted to the core 
laboratory. No subjects were included-not implanted in the ABRE study. 
The subject’s medical record must have indicated that the subject was enrolled in the ABRE Study. Sites 
were required to maintain a Subject Identification and Enrollment Log. 
These subject categories are described in Table 5. 
Table 5: Description of subject categories 
Subject category 
Description 
Enrolled 
Subjects who signed and dated the informed consent form. 
These subjects were to be recorded on the Subject Identification & 
Enrollment Log. 
Enrolled - not included 
Subjects who signed and dated the informed consent form and where the 
Abre system did not enter the vasculature. For example due to not fulfilling 
all I/E criteria which could only be assessed after the point of enrollment.  
These subjects were to be recorded on the Subject Identification & 
Enrollment Log. 
Included 
Subjects, who signed and dated the informed consent form, adhered to all 
I/E criteria and where the Abre system entered the vasculature. 
These subjects were to be recorded on the Subject Identification & 
Enrollment Log. 
Included - not implanted 
Subjects, who signed and dated the informed consent form, adhered to all 
I/E criteria and where the Abre system entered the vasculature and the Abre 
stent was not implanted. 

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These subjects were to be recorded on the Subject Identification & 
Enrollment Log. 
 
Failure to obtain a handwritten signed and hand-dated informed consent prior to any study-specific 
procedures constituted a deviation, which is reportable to the Institutional Review Board (IRB)/Ethics 
Committee (EC) (henceforth referred to as ”Ethics Board”), the FDA, and other regulatory authorities as 
applicable. However, if any required baseline exams (e.g. IVUS, venography, Duplex Ultrasound, blood 
labs) had been performed as standard of care prior to consenting the patient, they could be used as the 
baseline/qualifying exams (and will not be considered a deviation), provided they met the following criteria: 
• 
the investigator determined that the exams contained the protocol-required data and were adequate 
for evaluation; 
• 
the exams were completed within 30 days prior to the scheduled implant procedure. 
 
 
Figure 4: Flow-Diagram from Subject Screening to Follow-up 
 

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9.4 Inclusion Criteria 
Candidates for the ABRE study were appropriate subjects for iliofemoral venous stenting and were required 
to fulfill all of the following inclusion criteria to be eligible for recruitment in the study:  
General Inclusion Criteria 
1. Patient is ≥ 18 and ≤ 80 years of age; 
2. Patient has at least one of the following clinical manifestations (i.e. symptoms and/or signs) of 
venous disease in lower extremity: 
a. CEAP score ≥ 3 6 
b. Venous Clinical Severity Score pain score (VCSS) ≥2 (1) 
c. Suspected deep vein thrombosis (DVT); 
3. Patient is willing and capable of complying with specified follow-up evaluations at the specified 
times; 
4. Patient has been informed of the nature of the study, agrees to its provisions and has provided 
written informed consent, approved by the appropriate Ethics Board. 
Imaging-based Inclusion Criteria 
5. Patient has diagnosis of non-malignant venous obstruction within the common iliac, external iliac, 
and/or common femoral vein. The proximal point of the obstruction may extend to the iliac venous 
confluence of the inferior vena cava and the distal point may be at or above the deep femoral vein. 
Diagnosis must be made based on objective imaging by using venography and/or intravascular 
ultrasound (IVUS). Patient must have good inflow involving either the femoral or deep femoral vein 
being patent and at least a caudal section of the common femoral vein that is free of significant 
disease; 
6. Patient has an obstructive lesion defined as: 
i. Occluded, or 
ii. ≥50% in diameter reduction on venography or IVUS, or 
iii. ≥50% area reduction on IVUS 
7. Acute DVT patients should be treated with the Abre stent within 14 days after onset of symptoms. 
Patients with acute DVT must first undergo successful treatment of acute thrombus ; successful 
treatment is defined as 30% or less residual thrombus by venogram, as determined by physician, 
no bleeding, no symptomatic pulmonary embolism (confirmed by imaging), and no renal 
compromise (renal compromise defined as GFR<30). Patients with underlying obstructive lesions 
can then be included in the study within the same procedure; 
8. Target vessel can accommodate a 9F Sheath, from insertion site to target segment; 
9. Exchangeable guidewire must cross target lesion(s) with successful predilation. 
 
 
 
 
 
6 Patients subject to the literature review are similar to the subjects that will be included in the study as more than 90% of the 
patients in the literature review were classified as CEAP 3 or higher. 

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9.5 Exclusion Criteria 
Candidates who met any of the following exclusion criteria were not eligible for recruitment in the ABRE 
study: 
General Exclusion Criteria 
1. Patient with DVT in the target limb of which the onset of symptoms is between 15 days 
and 6 months prior to planned treatment or patient has an acute DVT anywhere else than 
in the target vessel;  
2. Patient has peripheral arterial disease causing symptoms in target limb; 
3. Patient is pregnant (female patients of child-bearing potential must have a pregnancy test 
done within 7 days prior to the index procedure); 
4. Patient has a known or suspected systemic infection at the time of the index procedure; 
5. Patient has a planned percutaneous or surgical intervention within 30 days prior or 30 
days following index procedure, or a contralateral iliofemoral lesion requiring planned 
treatment within 12 months; 
6. Patient requires femoral endovenectomy and patch venoplasty, greater saphenous vein 
ablation, and/or small saphenous vein stripping during the index procedure; 
7. Patient has an active vasculitic inflammatory disorder (e.g. Behcet disease) predisposing 
the patient to thrombosis and requiring systemic corticosteroid therapy; 
8. Patient has impaired renal function (GFR < 30) or is on dialysis; 
9. Patient has a platelet count < 50,000 cells/mm3 or > 1,000,000 cells/mm3 and/or a WBC < 
3,000 cells/mm3 or > 12,500 cells/mm3; 
10. Patient has a history of bleeding diathesis or either a history or presence of heparin-
induced thrombocytopenia antibodies; 
11. Patient has a known hypersensitivity or contraindication to antiplatelets or anticoagulation, 
nitinol, or a contrast sensitivity that cannot be adequately pre-medicated;  
12. Patient has presence of other severe co-morbid conditions, which in the investigator’s 
opinion may interfere with the patient’s compliance with study visits and procedures, or 
may confound interpretation of study data (e.g. congestive heart failure Class III and IV, 
non-ambulatory patients, severe hepatic dysfunction, life expectancy < 1 year); 
13. Patient belongs to a vulnerable population per investigator's judgment or patient has any 
kind of disorder that compromises his/her ability to give written informed consent and/or to 
comply with study procedures. Patient must be able to consent for themselves; 
14. Patient is currently participating in another investigational drug or device study or 
observational competitive study. 
Imaging-based Exclusion Criteria 
15. Patient has a vena cava obstruction or lesion extending into the inferior vena cava (IVC), 
or the presence of bilateral iliofemoral venous lesions requiring planned treatment within 
12 months; 
16. Patient has significant venous bleeding, arterial dissection or other injury requiring 
additional percutaneous or surgical intervention prior to enrollment; 
17. Patient has a previously placed stent in the ipsilateral venous vasculature;  
18. Patient has disease that precludes safe advancement of the venous stent to the target 
lesion(s). 
 
 

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10 Study Procedures  
10.1 Schedule of Events 
The clinical study required follow-up visits at hospital discharge, 30 days, 6-, 12-, 24-, and 36-months post 
index procedure. Table 6 and Table 7 show a detailed overview of the schedule of clinic evaluations and 
follow-up visits. 
Table 6: Schedule of Assessments and Visit Windows 
Data Collection  
Requirement 
Screening/Baseline 
(<30 days before 
procedure unless 
otherwise specified) 
Procedure 
Hospital Discharge 
30 Day (-7/+14 days) 
6 Months (± 30 days) 
12 Months (± 30 days) 
24 &  36  Months 
(± 30 days) 
Unscheduled visit for 
intervention in target 
vein 
Informed Consent 
X 
 
 
 
 
 
 
 
Demographics, Medical History & 
Physical Examination 
X 
 
 
 
 
 
 
 
Pregnancy Test1 
X 
 
 
 
 
 
 
 
CEAP Classification 
X 
 
 
 
 
 
 
 
Physical Assessment of Limbs 
X 
 
X 
X 
X 
X 
X 
X 
Villalta Score, VCSS 
X 
 
 
X 
X 
X 
X 
X4 
VEINES-QOL/Sym, EQ-5D QOL 
X 
 
 
 
X 
X 
X 
X4 
Procedure Data 
 
X 
 
 
 
 
 
X 
Serum Creatinine, CBC 
X 
 
 
 
 
 
 
 
INR (if on warfarin) 
X 
 
 
X 
X 
X 
X 
X 
Document Adverse Events 
X2 
X 
X 
X 
X 
X 
X 
X 
Document Device Deficiencies 
 
X 
X 
X 
X 
X 
X 
X 
Medication3 
X 
X 
X 
X 
X 
X 
X 
X 
Discontinuation Information5 
 
 
X 
X 
X 
X 
X 
X 
 
1  Pregnancy test for women of child-bearing potential only. Must be done within 7 days prior to the index procedure. 
2 Adverse Event assessment need to be done as of the moment the subject is enrolled in the study (i.e. subject signed and dated the 
informed consent form).   
3 Medication which will be collected: Antithrombotics, Antibiotics, Immunosuppressants, NSAIDs, Steroids, Diuretics, Calcium-channel 
blockers, Statins 
4 Assessments and questionnaires should be taken before any intervention. 
5 The discontinuation data is needed whenever the subject ends involvement in the study. 
 
Note: Only approved devices and therapies may be used during the entire study duration. 
 
 

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Table 7: Schedule of Imaging Assessments and Visit Window 
Data Collection  
Requirement 
Screening/Baseline (<30 days) 
Procedure 
Hospital Discharge 
30 Day (-7 days, +14 days) 
6 Months (± 30 days) 
12 Months (± 30 days) 
24 &  36  Months (± 30 days) 
Unscheduled visit for intervention in target vein 
Pre-stenting 
Post-stenting 
Duplex 
Ultrasound 
X 
 
 
X2 
X 
X 
X4 
X 
X 
Venogram 
1 
X1 
X 
 
 
 
4 
 
X 
IVUS 
1 
X1 
X 
 
 
 
 
 
X 
X-ray 
 
 
 
 
3 
 
X 
X 
X5 
 
1 Diagnosis can be made during the screening/baseline prior to the index procedure based on objective imaging using venography or 
IVUS. Diagnosis can also be made during the index procedure, prior to stenting. In case venogram and IVUS are not performed pre-
stenting at the time of the index procedure, the pre-procedure venogram and IVUS should be sent to the core laboratory.   
If both screening and pre-procedure venogram/IVUS are performed, then the pre-procedure venogram/IVUS should be sent to the 
core laboratory. 
 
2 The DUS examination immediately after the index procedure needs to be performed between 0 and 7 calendar days from the index 
procedure. When the first examination after the procedure is non-diagnostic, a second examination has to be performed as soon as 
possible. Every effort should be made to perform this within 7 calendar days after the index procedure.  
 
3 X-rays at 30 days will be performed on the first 30 subjects only. They will be assessed for first safety analysis (i.e. stent fracture). 
 
4 An additional venogram must be performed when: 
(1) DUS assessment is suggestive of ≥50% restenosis or occlusion per investigator assessment, or; 
(2) when DUS is non-diagnostic or suboptimal such as when a subject is obese (e.g. with a BMI >40), or;  
(3) is clinically required, or in other words when the subject is having symptoms of venous disease in the target limb requiring 
a venogram.  
 
5 Plain x-ray is required pre and post re-intervention to assess for stent fracture. 
 
All imaging examinations as defined in Table 7 should be performed according to the core laboratory 
guidelines and will be analyzed by respective independent core laboratories. Exceptionally, the 
Screening/Baseline Duplex Ultrasound (both limbs) was to be performed according to standard of care 
and was not required to be sent to the core laboratory. 
 
 
 

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10.2 Subject Consent 
10.2.1 Consent Materials 
Geography-specific templates of the Patient Information and Informed Consent Form (PI/ICF) are available 
separate from this CIP. These templates may be modified to suit the requirements of the individual site. For 
US sites, this must include Health Insurance Portability and Accountability Act (HIPAA) Authorization 
language. This language may be incorporated into the ICF or (if required by the Ethics Board) included as 
a separate document.   
Medtronic, Ethics Boards, and Competent Authorities (CA), where applicable, shall approve all informed 
consent documents prior to implementation in the study. Medtronic, Ethics Boards, and CAs, where 
applicable must pre-approve all language changes to the PI/ICF throughout the course of the study prior to 
implementation; this includes initial submission, annual reviews (if applicable), and protocol amendment 
reviews. The original Ethics Board-approved PI/ICF must be retained at the investigational site.  
Any revisions required by the Ethics Board must be forwarded to Medtronic for review and approval before 
the revised consent form is returned to the Ethics Board for final review and full approval. 
Medtronic will provide any important new information that impacts the health, safety or welfare of study 
subjects, for inclusion in PI/ICF updates as it becomes available. Sites should follow any Medtronic, CA, or 
Ethics Board requirements for disseminating new information and re-consenting subjects during the course 
of the study. 
10.2.2 Informed Consent Process 
The investigator (or authorized designee) was required to administer the approved PI/ICF to each 
prospective study patient without coercion or undue improper influence on, or inducement of, the patient to 
participate. During the consent discussion the investigator (or authorized designee) was required to fully 
inform the patient of all pertinent aspects of the study, using native non-technical language that was 
understandable to the patient. The patient was required to be informed about their right to withdraw from 
the study at any time and for any reason without sanction, penalty, or loss of benefits to which the patient 
was otherwise entitled, and also be informed that withdrawal from the study would not jeopardize their 
future medical care. The patient was required to also be informed that by participating in the study, they 
were not waiving their legal rights. The patient was required to have ample time and opportunity to inquire 
about details of the study, and to decide whether or not to participate in the clinical study. All questions 
about the study were to be answered to the satisfaction of the patient. All items discussed in the PI/ICF was 
required to be explained. 
Informed consent was to be obtained in writing from the patient. The date of consent and process by which 
the consent was obtained (including documentation of special circumstances, if applicable) was to be 
documented in the patient’s medical record prior to any study-specific procedures. Patient informed consent 
was required to be obtained in accordance with the national and local laws, regulations and guidelines of 
each site. The institutional standard procedure consent form does not replace the study PI/ICF. 
The subject’s signature and date of consent serve to document that they understood the written and verbal 
information that the investigator (or authorized designee) provided, and their agreement to participate and 
collect their medical data. The investigator (or authorized designee) who conducted the informed consent 
process was required to provide their handwritten signature and date the consent was completed on the 
ICF. The ICF was required to be signed and dated prior to any specific protocol assessments or procedures.  

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However, if any required baseline exams (e.g. IVUS, venography, Duplex Ultrasound, blood labs) had been 
performed as standard of care prior to consenting the subject, they could have been used as the 
baseline/qualifying exams (and were not considered a deviation), provided they met the following criteria: 
• 
the investigator determined that the exams contained the protocol-required data and were adequate 
for evaluation; 
• 
the exams were completed within 30 days prior to the scheduled implant procedure. 
 
The original signed and dated ICF is kept at the investigational site. A copy of the signed and dated ICF 
was to be provided to the subject.  
10.2.3 Special Circumstances for Informed Consent Process and Signature 
If a patient could not read or write, an impartial witness was required to be present during the entire informed 
consent discussion. The written PI/ICF (and any other information) could be read aloud and explained to 
the patient and witness. The witness would then sign and personally date the ICF attesting that the 
information was accurately explained and that consent was freely given. The patient would sign and date if 
possible.   
Given the investigational status of the Abre system in the US at the time of enrollment, and the availability 
of approved endovenous stents in some geographies, emergency cases were not allowed under this 
protocol. 
Given the commercial availability of other endovenous stents in some geographies, requests for 
compassionate use of the Abre stent were not anticipated. 
10.3 Screening/Baseline Procedures (-30 days) 
The following baseline evaluations were completed and recorded on the appropriate eCRF. Baseline 
evaluations were to be completed within 30 days of the scheduled implant procedure unless otherwise 
specified. 
• 
Informed consent 
• 
Demographics   
• 
Medical history  
• 
Physical examination 
• 
Pregnancy test for women of child bearing potential only. This must be done within 7 days prior to 
the index procedure. 
• 
CEAP classification (for both limbs) 
• 
Physical assessment of limbs 
• 
Villalta score, VCSS (for both limbs) 
• 
Quality of life questionnaires: EQ-5D and VEINES-QOL/Sym 
• 
Blood tests (See Section 10.3.2 Blood Tests) 
• 
INR required for subjects on warfarin 
• 
Venogram or IVUS for diagnosis if performed as standard of care. This diagnosis can also be made 
during the index procedure, prior to stenting. 
• 
Duplex ultrasound (DUS) (both limbs) 
• 
Medications: Antithrombotics, Antibiotics, Immunosuppressants, NSAIDs, Steroids, Diuretics, 
Calcium-channel blockers 

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• 
Adverse event assessment need to be done as of the moment the subject is enrolled in the study 
(i.e. subject signed and dated the informed consent form). 
10.3.1 Demographics, Medical History & Physical Examination 
A careful medical history and physical examination were to be taken prior to the implant procedure. For any 
interventions, the date of the most recent intervention was to be captured. 
Data collected at baseline: 
• 
Gender 
• 
Age at time of enrollment 
• 
Race/Ethnicity, to be collected per the FDA Guidance for Collection of Race and Ethnicity Data in 
Clinical Trials (2016) (38), in support of regulatory submissions in the US (FDA).   
• 
Risk factors, such as hypertension, diabetes, hyperlipidemia, tobacco use, obesity (BMI), previous 
knee/hip replacement, immobility and any other cardiovascular risk factors, with measure of 
severity and current treatment 
• 
Co-existing cardiovascular conditions (including, but not limited to superficial ablation, congestive 
heart failure,  peripheral vascular disease, previous myocardial infarction (MI)) 
• 
Symptoms 
• 
Physical examination 
• 
Assessment of target lesion and access vessel characteristics 
• 
Medications: Antithrombotics, Antibiotics, Immunosuppressants, NSAIDs, Steroids, Diuretics, 
Calcium-channel blockers, Statins; 
10.3.2 Blood Tests 
The following blood tests were required: 
• 
Serum creatinine for GFR calculation (GFR must be ≥30 to be included in the study). Any method 
to perform the GFR calculation is allowed; 
• 
White Blood Cell (WBC) count (must be ≥3,000 cells/mm3 and ≤ 12,500 cells/mm3 to be included 
in the study) 
• 
Platelet count (must be ≥ 50,000 cells/mm3 and ≤1,000,000 cells/mm3 to be included in the study); 
• 
Hemoglobin; 
• 
Hematocrit; 
• 
INR required for subjects on warfarin. 
 
10.4 Acute DVT Subjects 
Acute DVT subjects were required to be treated with the Abre stent within 14 days after onset of symptoms. 
Subjects with acute deep vein thrombosis (DVT) were required to first undergo successful treatment of 
acute thrombus. This was required to be done within 14 days after the onset of symptoms and only with 
market released devices. Successful treatment was defined as less than 30% residual thrombus by 
venogram, as determined by physician, and no bleeding, no symptomatic pulmonary embolism (confirmed 
by imaging), and no renal compromise. Subjects with underlying obstructive lesions were then permitted to 
be included in the study within the same procedure, or the procedure may have been staged. 

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10.5 Implant Procedure 
Detailed information on intended use of the device, indications, and contraindications, as well as a complete 
list of warnings, precautions, and potential adverse events, were included in the IFU. The IFU was provided 
with each device. 
10.5.1 Procedure Data 
The following data was to be recorded for each subject in the study: 
• 
Date of procedure 
• 
Indication for stenting: acute DVT, NIVL, PTS, and any combination of these 
• 
Identification data for the stent(s)  
• 
Details of procedure, including any adjunctive vascular procedure performed 
• 
Chosen access sites 
• 
Medications: Antithrombotics, Thrombolytics   
• 
Assessment of handling, visualization, deployment, and withdrawal 
• 
Assessment of patency, positioning, and integrity of the stent 
• 
Adverse events  
• 
Comparison of intended and actual stent location 
• 
Date of hospital discharge 
10.5.2 Imaging 
During the index procedure, venography and IVUS were required, prior and post stent placement to aid 
with stent sizing and lesion assessment. 
10.5.3 IVC Filter Placement 
Inferior Vena Cava (IVC) filter placement was at the discretion of the physician. IVC filter placement was 
not encouraged, however may have been considered in the following situations:  
• 
presence of floating thrombus in iliocaval segments;  
• 
planned use of mechanical thrombectomy in the presence of acute thrombus.  
IVC filter was recommended to be removed as soon as deemed safe by the operating physician. 
10.5.4 Inflow Requirements 
Negative outcomes are best avoided by good inflow directed by IVUS in the least diseased portion of the 
vein above the deep femoral vein. Good inflow involves either the femoral or deep femoral vein inflow being 
patent and at least a caudal section of the common femoral vein that is free of significant disease. Good 
inflow was to be determined by the investigator. 
10.5.5 Lesion(s) 
The target lesion was defined as non-malignant venous obstruction within the common iliac, external iliac, 
and/or common femoral vein: the proximal point of the obstruction may have extended to the iliac venous 
confluence of the inferior vena cava and the distal point may have been at or above the deep femoral vein. 

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When stented, the complete stented area was considered ‘lesion’ and was to be treated as such during 
follow-up assessments. 
 
 
 
Figure 5. Venous anatomy 
 
 

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10.5.6 Predilation 
Access site was to be at the discretion of the physician, however it was strongly recommended not to use 
the ipsilateral common femoral vein and access from the ankle. 
Predilation of the lesion with a balloon catheter was required  to be the same diameter of the stent to be 
implanted, i.e. if a 14 mm stent was to be implanted, a 14 mm diameter balloon was required to be used. A 
high pressure balloon was highly recommended.  
At a minimum the balloon should have been inflated up to nominal pressure and should have been inflated 
within the segment that was intended to be stented. The balloon would then have been removed from the 
subject while access with the guidewire was maintained. 
10.5.7 Stent Size Selection 
To optimize visualizing of the true extent of a venous lesion, venogram and IVUS could have been used. 
However, IVUS was the preferred modality.  
 
Stent length 
It is important that the proximal and distal ends of the stents lie in a relatively normal/healthy venous 
segment. Therefore, a stent length must have been chosen that extended cranial and caudal to the target 
lesion, covering at minimum 1 cm cranial and 1 cm caudal, if the disease allowed. Additional coverage can 
reduce the risk of restenosis. The Abre stent should not have occluded the inflow of the contralateral limb 
or touch the contralateral wall.  
 
Stent diameter 
Vein diameters could be measured using one of the following two methods: 
1. Using IVUS: take the average of the minimum and maximum diameters of a normal segment of 
vein in the same anatomical segment; 
2. Using Venogram: take the average diameter of a normal segment of vein in the same anatomical 
segment in two planes.  
Considering the estimated anatomic vessel diameter, the appropriate Abre stent diameter was to be 
selected. A stent with a diameter of at least 2 mm more than the chosen reference vessel diameter was 
recommended to achieve good wall apposition.  
Reference vessel diameter could have been obtained by one of the following methods: 
1. Measure the diameter of a normal segment of an appropriate segment of the target vein 
(which generally should be the most caudal segment); 
2. Measure the diameter of the vein in an appropriate segment of the contralateral limb; 
3. Use the literature reference vessel diameter for the appropriate segment:  
a. Common Iliac Vein:  
16 mm 
b. External Iliac Vein:  
14 mm 
c. Common Femoral Vein:  12 mm 
Proper size selection reduces stent migration and ensures appropriate stent apposition to the vessel wall. 
 
 

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10.5.8 Stent Placement 
The Abre delivery system should have been advanced until the leading edge of the stent is beyond the 
target lesion. Whenever possible, one stent should have been used to cover the entire length of the target 
lesion. 
 
Multiple stents 
If multiple stents were needed to cover the entire length of the target lesion, they should have been 
implanted in an overlapping manner with a minimum overlap of 1.5 cm. The more cranial stent should have 
been placed first. It was recommended to use the same stent diameter. If different diameters were needed, 
the smaller diameter stent should have been placed first. Non-stented areas in between stents, i.e. skip 
areas, were not allowed.  Stents ending in the inguinal ligament were to be avoided.  
10.5.9 Post-dilation 
Post-dilation of the lesion with a balloon catheter was recommended up to the diameter of the implanted 
stent to achieve the expected nominal stent diameter.  
10.6 Hospital Discharge 
The discharge visit occurred at the time of subject’s discharge from the hospital. The following evaluations 
were completed and data was recorded on the Discharge eCRF: 
• 
Duplex ultrasound (target limb). The DUS examination immediately after the index procedure needs 
to be performed between 0 and 7 calendar days from the index procedure. When the first 
examination after the procedure is non-diagnostic, a second exam has to be performed as soon as 
possible. Every effort should be made to perform this within 7 calendar days after the index 
procedure;  
• 
Duplex ultrasound (contralateral limb); image of the CFV waveform only.  
• 
Physical assessment of limbs; 
• 
Adverse events/device deficiency; 
• 
Medications: Antithrombotics, Antibiotics, Immunosuppressants, NSAIDs, Steroids, Diuretics, 
Calcium-channel blockers, Statins; 
• 
Compression stockings. Subjects will be instructed to wear medical grade (≥ 20 mm Hg) 
compression stockings (above or below knee) as instructed by their physician with compliance 
encouraged. The use of compression stockings will be evaluated via the VCSS; 
• 
Discontinuation information (in case the subject ends involvement in the study). 
10.7 30 Day (-7/+14 days) Post-Procedure Follow-Up Assessment 
Subjects were seen in the office at 30 days (23-44 days) post-procedure. The following evaluations were 
completed and data was recorded on the Follow-up eCRF: 
• 
Physical assessment of limbs; 
• 
Villalta Score and VCSS (both limbs); 
• 
INR for subjects on warfarin; 
• 
Duplex Ultrasound (target limb); 
• 
Duplex ultrasound (contralateral limb); image of the CFV waveform only.  

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• 
X-ray (target limb); only on the first 30 subjects in the study for first safety analysis (i.e. stent 
fracture). Sites will be notified if this is no longer needed; 
• 
Adverse events/device deficiency; 
• 
Medications: Antithrombotics, Antibiotics, Immunosuppressants, NSAIDs, Steroids, Diuretics, 
Calcium-channel blockers, Statins; 
• 
Discontinuation information (in case the subject ends involvement in the study). 
10.8 6 Months (± 30 days) Post-Procedure Follow-Up Assessment 
Subjects were seen in the office at 6 months (150-210 days) post-procedure. The following evaluations 
were completed and data was recorded on the Follow-up eCRF: 
• 
Physical assessment of limbs; 
• 
Villalta Score and VCSS (both limbs); 
• 
Quality of Life Questionnaires: EQ-5D and VEINES-QOL/Sym; 
• 
INR for subjects on warfarin; 
• 
Duplex Ultrasound (target limb); 
• 
Duplex ultrasound (contralateral limb); image of the CFV waveform only.  
• 
Adverse events/device deficiency; 
• 
Medications: Antithrombotics, Antibiotics, Immunosuppressants, NSAIDs, Steroids, Diuretics, 
Calcium-channel blockers, Statins; 
• 
Discontinuation information (in case the subject ends involvement in the study). 
10.9 12 Months (± 30 days) Post-Procedure Follow-Up Assessment 
Subjects were seen in the office at 12 months (330-390 days) post-procedure. The following evaluations 
were completed and data was recorded on the Follow-up eCRF: 
• 
Physical assessment of limbs; 
• 
Villalta Score and VCSS (both limbs); 
• 
Quality of Life Questionnaires: EQ-5D and VEINES-QOL/Sym; 
• 
INR for subjects on warfarin; 
• 
Duplex Ultrasound (target limb); 
• 
Duplex ultrasound (contralateral limb); image of the CFV waveform only.  
• 
Venogram (target limb), when required.  
o 
An additional venogram must be performed when: 
(1) DUS assessment is suggestive of ≥50% restenosis or occlusion per investigator 
assessment; 
(2) when DUS is non-diagnostic or suboptimal such as when a subject is obese (e.g. with 
a BMI >40), or;  
(3) is clinically required, or in other words when the subject is having symptoms of venous 
disease in the target limb requiring a venogram. 
• 
X-ray (target limb); 
• 
Adverse events/device deficiency; 
• 
Medications: Antithrombotics, Antibiotics, Immunosuppressants, NSAIDs, Steroids, Diuretics, 
Calcium-channel blockers, Statins; 
• 
Discontinuation information (in case the subject ends involvement in the study). 
 
 

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10.10 24 and 36 Months (± 30 days) Post-Procedure Follow-Up Assessment 
Subjects will be seen in the office at 24 months (690-750 days) and 36 months (1050-1110 days) post-
procedure. The following evaluations will be completed and data recorded on the Follow-up eCRF: 
• 
Physical assessment of limbs; 
• 
Villalta Score and VCSS (both limbs); 
• 
Quality of Life Questionnaires: EQ-5D and VEINES-QOL/Sym; 
• 
INR for subjects on warfarin; 
• 
Duplex Ultrasound (target limb); 
• 
Duplex ultrasound (contralateral limb); image of the CFV waveform only.  
• 
X-ray (target limb); 
• 
Adverse events/device deficiency; 
• 
Medications: Antithrombotics, Antibiotics, Immunosuppressants, NSAIDs, Steroids, Diuretics, 
Calcium-channel blockers, Statins; 
• 
Discontinuation information (in case the subject ends involvement in the study). 
 
In the event that an in-clinic 24 and/or 36 Month visit is unable to be performed (i.e. Missed Visit) a ‘Phone 
Encounter’ may be completed. The purpose of the ‘Phone Encounter’ is to capture subject status including 
the following: 
• 
Date of contact (phone encounter) 
• 
Medications: Antithrombotics, Antibiotics, Immunosuppressants, NSAIDs, Steroids, Diuretics, 
Calcium-channel blockers, Statins; 
• 
Adverse events/device deficiency; 
 
The ‘Phone Encounter’ does not replace the 24- and/or 36-month visit. If a ‘Phone Encounter’ is completed 
for the 36-month visit, the subject should not be immediately exited from the study. The site should continue 
to attempt to schedule an in-clinic visit as specified above when it is appropriate to do so and work with 
Medtronic to understand how long the study will remain open. 
10.11 Unscheduled Visits 
Unscheduled visits are additional non-scheduled visits that occur at times other than the predetermined 
intervals and during which an intervention in the target vein takes place. If the Abre stent(s) is(are) 
explanted, the subject will be followed for safety reporting only for 30 days post-explant. AE data should be 
collected on the AE eCRF, and study exit data should be collected on the Study Exit eCRF. It is not allowed 
to implant a new Abre stent during the reintervention. The following assessments will be completed and the 
data will be recorded on the Follow-up eCRF: 
• 
Physical assessment of limbs 
• 
Villalta Score and VCSS (for both limbs, should be taken before any intervention) 
• 
Quality of Life Questionnaires: EQ-5D and VEINES-QOL/Sym (should be taken before any 
intervention) 
• 
INR for subjects on warfarin 
• 
Duplex ultrasound (target limb) 
• 
Duplex ultrasound (contralateral limb); image of the CFV waveform only.  
• 
Venogram (target limb) 
• 
IVUS (target limb) 
• 
Plain X-ray (target limb) is required pre and post re-intervention to assess for stent fracture 

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• 
Secondary procedure data 
• 
Adverse events/device deficiency 
• 
Medications: Antithrombotics, Antibiotics, Immunosuppressants, NSAIDs, Steroids, Diuretics, 
Calcium-channel blockers, Statins 
• 
Discontinuation information (in case the subject ends involvement in the study) 
10.12 Assessments 
10.12.1 Antithrombotics 
The following anticoagulation and antiplatelet treatment was recommended pre-, peri-, and post-stenting 
procedure.  
Pre-procedure 
If subject is taking an anticoagulant, this needs to be stopped prior to intervention with an appropriate 
transition regime.  
If subject is on warfarin, a slight increase in the pre-procedure prothrombin time (INR ≤ 1.7) is not a 
contraindication to proceed with the procedure.  
Peri-procedure 
In all subjects, full anticoagulation is instituted prior to the index procedure and it is important to maintain 
adequate treatment throughout the procedure. The regimen is to be determined by the investigator.  
A suggested anticoagulation regimen for chronic subjects is:  
• 
a heparin bolus of 5000 units, after placement of the sheath in the access vessel;  
• 
followed by bolus of 5000 units or infusion of 100 U/kg to keep ACT>200 seconds for a full 
systemic anticoagulation.  
Post-procedure 
Full anticoagulation should be commenced within 4 hours of completion of the procedure. Anticoagulation 
should follow local guidance. However, when using warfarin, an INR>2.0 with appropriate bridging cover is 
recommended. DOAC (dabigatran, rivaroxaban, apixaban, or edoxaban) can be used instead of warfarin. 

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Duration 
The following minimum anticoagulation treatment time is recommended: 
• 
6 months in non-thrombotic subjects; 
• 
12 months in thrombotic subjects; 
• 
long-term treatment for subjects with thrombophilia.  
Antiplatelets 
With respect to antiplatelet treatment, the following recommendations were provided: 
• 
A regimen of dual antiplatelet treatment in addition to anticoagulation should be carefully 
considered in light of the high bleeding risk. If used, dual antiplatelet treatment in addition to 
anticoagulation should be limited to only the first 6 weeks following the index procedure.  
• 
After discontinuation of anticoagulation therapy, consider switching subjects to an antiplatelet 
therapy (if not currently ongoing); 
 
10.12.2 CEAP Classification 
At baseline, the American Venous Forum CEAP classification (2004) was used to provide a comprehensive 
objective classification of the severity of the veins. This assessment was required to be performed for both 
limbs. The CEAP Classification needs to be assessed by a medical doctor or qualified delegated person. 
See Appendix C CEAP Classification. 
10.12.3 Scores 
10.12.3.1 Villalta Score 
The Villalta score categorizes the severity of postthrombotic syndrome (PTS). The Villalta score is assessed 
for all subjects for both limbs at baseline, 30-days, 6-, 12-, 24-, 36-Month and Unscheduled follow-up visits. 
At Unscheduled visits, the Villalta should be taken before an intervention in the target vein takes place. The 
Villalta Score needs to be assessed by a medical doctor or qualified delegated person. See Appendix D 
Villalta Score. 
10.12.3.2 Venous Clinical Severity Score (VCSS) 
The VCSS is used to assess changes in disease severity over time. The VCSS is assessed for both limbs 
at baseline, 30-days, 6-, 12-, 24-, 36-Month and Unscheduled follow-up visits. At Unscheduled visits, the 
VCSS should be taken before an intervention in the target vein takes place. The VCSS needs to be 
assessed by a medical doctor or qualified delegated person. See Appendix E Venous Clinical Severity Score 
(VCSS). 
10.12.4 Quality of Life questionnaires 
Health-related quality of life outcomes are assessed at baseline and 6-, 12-, 24-, 36-Month follow-up visits 
using the EQ-5D and VEINES-QOL/Sym questionnaires. See Appendix F EQ-5D and Appendix G VEINES-
QOL/Sym questionnaire. These questionnaires need to be completed either by the subject or by a delegated 
person who asks the questions to the subject and completes the questionnaire on behalf of the subject. In 
case it is needed a proxy EQ-5D questionnaire might be used.  

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10.12.5 Pregnancy Test 
For female subjects of child-bearing potential, a (urine or blood) pregnancy test was required to be done at 
baseline (within 7 days prior to the index procedure) to confirm that the subject was not pregnant. Subjects 
exempt from this requirement were those who had been surgically sterilized, who were infertile, or who had 
been post-menopausal for at least 12 months (no menses). 
 
10.12.6 Imaging 
10.12.6.1 Venogram 
A venogram (target limb) must be performed: 
• 
during the index procedure, prior and post stent placement to aid with stent sizing and lesion 
assessment; 
• 
in case a re-intervention in the target vein takes place; 
• 
to assess the primary effectiveness performance goal endpoint during the 12 month follow-up visit 
only when: 
(1) DUS assessment is suggestive of ≥50% restenosis or occlusion per investigator 
assessment, 
(2) when DUS is non-diagnostic or suboptimal such as when a subject is obese (e.g. with 
a BMI>40), or  
(3) clinically required, or in other words when the subject is having symptoms of venous 
disease in the target limb requiring a venogram. 
Furthermore, a venogram (target limb) may be performed:  
• 
during screening: the diagnosis can be made based on objective imaging using venography or 
IVUS; 
• 
at all other time points, an additional venogram may be performed at the investigator discretion.   
In case that the subject refuses a venogram, it will be documented in the eCRF. This is not considered a 
deviation.  
All venographic imaging examinations should be performed according to the core laboratory guidelines and 
are analyzed by an independent core laboratory (See Section 13.4).  
10.12.6.2 Duplex Ultrasound (DUS) 
The screening DUS was to be performed per standard of care in both limbs. All DUS after the index 
procedure were to be performed in the target limb, including an image of the contralateral CFV waveform.  
The DUS exam immediately after the index procedure was to be performed between 0 and 7 calendar days 
from the index procedure. When the first exam after the procedure was non-diagnostic, a second exam 
was to be performed as soon as possible. Every effort should have been made to perform this within 7 
calendar days after the index procedure. DUS was/will be performed to assess patency during the 6, 12, 
24, 36 months follow-up visits.  
All DUS examinations, except the screening DUS, should be performed according to the core laboratory 
guidelines and are analyzed by an independent core laboratory (See Section 13.3). 

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10.12.6.3 Intravascular ultrasound (IVUS) 
During the following timepoints, IVUS (target limb) is required: 
• 
during the index procedure, IVUS was required, prior and post stent placement to aid with stent sizing 
and lesion assessment; 
• 
during unscheduled follow-up visits, if the subject returns to the hospital at times other than the 
predetermined intervals and during which an intervention in the target vein takes place, prior and post 
intervention. 
Furthermore, an IVUS (or venography) may have been performed during the screening for diagnostic 
purposes.   
All IVUS examinations should be performed according to the core laboratory guidelines and are analyzed 
by an independent core laboratory (See Section 13.4).  
10.12.6.4 X-ray 
During the following timepoints an X-ray (target limb) is required to assess stent fracture: 
• 
at 30-days for first safety analysis for the first 30 subjects; 
• 
at 12, 24, and 36 months for all subjects; 
• 
during reinterventions (unscheduled visits) pre- and post- reintervention. 
All X-ray examinations should be performed according to the core laboratory guidelines and are analyzed 
by an independent core laboratory (See Section 13.4). 
10.12.7 Physical Assessment of Limbs 
Physical assessment of both limbs is performed at baseline, hospital discharge, 30-days, 6-, 12-, 24- and 
36-months follow-up visit and unscheduled visits. The following assessments are done:  
• 
circumference of the thigh (highest value between hip and knee) 
• 
circumference of the calf (highest value between knee and ankle) 
• 
time of the assessment 
• 
presence of lymphedema 
Other physical assessment (e.g. ulcers) are covered by the clinical scores.  
These should be performed by principal investigator or delegated persons.  
 
 

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10.13 Deviation Handling 
A deviation is any event in which the study is not conducted according to the CIP and/or agreement. 
Deviations may include, but are not limited to the following: 
• 
Failure to obtain informed consent prior to participation 
• 
Incorrect version of the informed consent form used 
• 
Failure to obtain Ethics Board approval before the start of enrolling subjects in the study 
• 
Included subject did not meet inclusion/exclusion criteria 
• 
Required testing and/or measurements not done or incorrectly done 
• 
Subject did not complete follow-up visit  
• 
Follow-up visit was completed outside window 
• 
Unauthorized use of Abre system(s) 
• 
Adverse events/UADE or device deficiencies not reported in the required timeframe by country 
regulation or as specified in the CIP 
• 
Control of study devices not maintained 
• 
Source data permanently lost 
• 
Enrollment of subjects during lapse of Ethics Board approval 
• 
Subject inclusion limits exceeded 
The investigator is not allowed to deviate from the CIP, except when necessary to protect the life or physical 
well-being of a subject in an emergency situation. Deviations must be reported to Medtronic on the 
Deviation eCRF. 
In the event the deviation involves a failure to obtain a subject’s consent, or is made to protect the life or 
physical well-being of a subject in an emergency, the deviation must be reported to the Ethics Board as 
well as Medtronic as soon as possible but no later than five (5) working days from the date of the deviation 
occurrence.  
Reporting of all other deviations should comply with Ethics Board policies, local laws, regulatory agency 
requirements and must be reported to Medtronic as soon as possible upon the center becoming aware of 
the deviation.  
Refer to Table 16 and Table 17 for geography-specific deviation reporting requirements and timeframes 
for reporting to Medtronic and/or regulatory bodies. 
The COVID-19 global pandemic started during the 24-month follow-up phase of this study.If a protocol 
deviation is related to COVID-19, details must be reported as to how the deviation is related to the 
pandemic. Examples include: Patient preference – declined / did not feel safe and/or comfortable; Patient 
in quarantine however not tested positive with COVID-19; Research staff – site staffing issue due to COVID-
19; Institutional policy – no research activities permitted on site, etc. 
Medtronic is responsible for analyzing deviations, assessing their significance, and identifying any 
additional corrective and/or preventive actions which may include amending the CIP, conducting additional 
training, terminating the investigation, etc.  Repetitive or serious investigator compliance issues may 
represent a need to initiate a corrective action plan with the investigator and site, and in some cases, 
necessitate suspending enrollment at that site until the problem is resolved or ultimately terminating the 
investigator's participation in the study. Medtronic may provide center-specific reports to investigators 
summarizing information on deviations that occurred at the investigational site on a periodic basis. 
 
 

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10.14 Subject Withdrawal or Discontinuation  
10.14.1 Subject Withdrawal 
It is the subject’s right to withdraw at any time from the study and for any reason without sanction, penalty, 
or loss of benefits to which the subject is otherwise entitled, and without jeopardizing their future medical 
care. The investigator may withdraw the subject at any time to protect the health, safety, or welfare of the 
subject. At the last point of contact (if outside a study-required visit), the subject’s vital status should be 
recorded on a Study Exit eCRF, and every effort should be made to collect the status of any ongoing 
adverse events prior to withdrawal. 
10.14.2 Lost-to-Follow-up 
The subject may only be considered lost to follow-up after all efforts to obtain compliance are exhausted.  
At a minimum, four attempts must be made to contact the subject and documented in the subject’s records: 
• 
3 telephone attempts to the subject’s last known phone number, and if unsuccessful,  
• 
1 certified letter from the PI to the subject’s last known address  
 
If the site is unable to reach the subject after the documented attempts, the site should make every attempt 
to verify the subject’s vital status (alive or deceased). A Study Exit eCRF should be completed. If the subject 
returns to the study site thereafter, the Study Exit eCRF can be deleted and follow-up data can be collected. 
A Deviation eCRF should be completed for the missed visit(s), if appropriate.  
10.14.3 Subject Discontinuation 
All subjects will be encouraged to remain in the study through the last follow-up visit. Included subjects who 
discontinue participation prematurely will be included in the analysis of results, but will not be replaced in 
the inclusion of total study subjects. If the subject discontinues participating in the study prior to completing 
the study requirements, the reason for withdrawal will be recorded in the subject’s study records and on the 
Study Exit eCRF. 
There are many scenarios in which a subject may exit the study. Table 8 details how the data will be 
handled for each scenario. 
10.14.4 Medical Care after Study Exit 
After study exit, the subjects will be followed as per routine standard of care by the investigational site or a 
treating physician. Relevant medical records may be made available by the investigational sites for the 
treating physician per local laws and regulations if needed for further subject treatment. As per local law 
and regulation, the investigator may be contacted by the treating physician in case of questions related to 
the study device and treatment. 
Sites shall request permission from the subject to follow-up outside of the study, if issues arise with the 
Abre stent safety or performance. 
 
 

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10.15 Recording Data 
Source Documents 
Data entered must be traceable to source documents. Source documentation is defined as the first time 
data appear, and may include original documents, data, and records (e.g., hospital records, clinical and 
office charts, procedure reports, laboratory notes, memoranda, subjects’ diaries or evaluation checklists, 
pharmacy dispensing records, recorded data from automated instruments, copies or transcriptions certified 
after verification as being accurate copies, microfiches, photographic negatives, microfilm or magnetic 
media, X-rays, subject files, and records kept at the pharmacy, at the laboratories and at medico-technical 
departments involved in the clinical study). 
In general, eCRFs (or paper copies) may not serve as source documents. An exception is select data on 
the Product Accountablity Log.. Source documentation for data elements not routinely captured in medical 
records may vary from site to site; the site may use source document worksheets if identified as source 
documents. 
The investigator must ensure the availability of source documents from which the information on the eCRFs 
was derived. Where printouts of electronic medical records, are provided as source documents, or where 
copies of source documents are retained as source documents, those should be certified. Certification must 
contain (1) the signature of the individual making the copy, (2) the date the copy was made, and (3) a 
statement attesting to the accuracy and completeness of the copy.  
The source documents must be made available for monitoring or auditing by Medtronic’s representative or 
representatives of the competent authorities and other applicable regulatory agencies.   
 
 

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Data Collection 
Table 8 describes which data will be collected for each scenario and subject category. 
Table 8: Overview data collection for different scenarios 
Category 
Subcategory 
 
PIC signed 
Subject identification & 
enrollment log 
I/E criteria met 
Required 
eCRF’ s 
Screening 
Baseline 
Procedure 
AE 
Device deficiency 
Reintervention 
FU 
Study Exit 
Enrolled1 – 
not included  
Study Exit before intended 
procedure date 
 
X 
X 
 
X 
 
 
X3 
 
 
 
X 
Screening 
failure 
during 
implant procedure 
 
X 
X 
 
X 
X 
 
X3 
 
 
 
X4 
Included2 
Not implanted, Abre system 
entered the vasculature 
 
X 
X 
X 
X 
X 
X 
X3,5 
X3 
 
 
X4 
Implanted – 36m FU 
 
X 
X 
X 
X 
X 
X 
X3 
X3 
X3 
X 
X 
Implanted – Explanted 
 
X 
X 
X 
X 
X 
X 
X3 
X3 
X 
X5 
X5 
Implanted – Early study 
discontinuation 
 
X 
X 
X 
X 
X 
X 
X3 
X3 
X3 
X6 
X6 
 
1 Enrolled: subject who signed and dated the informed consent form. 
2 Included: subject who signed and dated the informed consent form, adhered to all I/E criteria and where the Abre system entered 
the vasculature. 
3 As applicable. 
4 Subject must be followed for 30 days for safety assessment, then complete Study Exit eCRF. No images need to be sent to the core 
laboratories if Abre system did NOT enter the vasculature. 
5 After explant, subject must be followed for 30 days for safety assessment, then complete Study Exit eCRF. 
6 Complete all required/unscheduled FU visit eCRFs through last visit completed, then complete Study Exit eCRF. 
 
 
 

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11 Risks and Benefits 
11.1 Potential Risks 
There are risks associated with any endovascular procedure. The risks associated with the Abre system 
are believed to be similar to those associated with the existing endovascular stent systems in clinical use 
or commercially available for the treatment of symptomatic iliofemoral venous outflow obstruction. Table 9 
lists all potential adverse events associated with the implantation of the Abre stent. 
Table 9: Potential adverse events 
- 
Access failure 
- 
Access site infection 
- 
Allergic reaction to contrast 
medium or procedure 
medications  
- 
Allergic reaction to nitinol or 
other device materials 
- 
Arrhythmia 
- 
AV fistula 
- 
Bleeding 
- 
Bruising 
- 
Death 
- 
Device breakage 
- 
Device maldeployment 
- 
Edema 
- 
Fever 
- 
Hematoma 
- 
Hypotension, nausea, or 
other vasovagal response 
- 
Infection 
- 
Myocardial infarction 
- 
Pain 
- 
Pseudoaneurysm 
- 
Pulmonary embolism 
- 
Renal insufficiency/renal 
failure (new or worsening) 
- 
Sepsis 
- 
Stent fracture 
- 
Stent malapposition 
- 
Stent malposition 
- 
Stent migration 
- 
Stroke/paradoxical 
embolism/transient ischemic 
attack/intracerebral 
hemorrhage 
- 
Tissue necrosis 
- 
Transfusion reaction 
following blood transfusion 
for treatment of major 
bleeding  
- 
Vessel damage, including 
perforation or rupture 
- 
Venous 
occlusion/thrombosis, within 
or outside of stented 
segment 
 
Additional risks for the subject due to participation in the study may include: 
- 
Discomfort during the imaging scans 
- 
Potential significant radiation exposure due to beam intensity and length of time of imaging, resulting in 
acute radiation injury as well as increased risk for physical and genetic defects to subjects. 
The following measures will be implemented to minimize any risks to study subjects:  
• 
Investigator and study personnel will be trained to the design of the Abre system, its application 
and preclinical results. 
• 
Eligibility criteria and screening procedures will be followed to ensure that appropriate subjects are 
enrolled and included. 
• 
Investigator will adhere to the Abre system Instructions For Use packaged with the device. 
• 
The subjects will be carefully monitored throughout the study period. 
• 
The investigator will evaluate the subject adverse events during the course of the study. 
• 
Data submitted from the investigative centers will be monitored during the course of the study. 
• 
Monitoring visits will be conducted to evaluate protocol compliance and data quality. 
 
 

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• 
Safety and effectiveness data obtained during the course of the study will be shared with 
investigators in periodic reports to increase understanding of the device and potential adverse 
events. 
• 
A Data Safety Monitoring Board, Clinical Events Committee, and imaging core laboratory will be 
established to independently evaluate subject health status, device performance, and identify any 
safety concerns regarding subjects’ well-being. 
• 
If a woman is pregnant or becomes pregnant, implantation of the study device may involve risks to 
the embryo or fetus that are unknown at this time. Therefore, pregnant women will be excluded 
from the study. If a female subject becomes pregnant during the conduct of this clinical research 
study they need to inform the investigational site immediately without any unjustified delay. 
Continuation in the study or withdrawal from the study will be up to the investigator’s discretion.  
Potential treatments for the foreseeable risks may include medication, surgery, medical monitoring or other 
applicable treatments, and will be provided at the discretion of the investigator. 
Any unanticipated or unforeseen complications will be reported by the principal investigator (or authorized 
designee) to the Ethics Board and Medtronic. Medtronic is responsible to report any necessary findings to 
the appropriate regulatory agencies/bodies in each of the respective geographies. 
11.2 Potential Benefits 
11.2.1 Potential Benefits of the Abre System 
Potential benefits from use of the Abre system have not been documented; nevertheless, they are expected 
to be similar to those associated with venous stent systems currently in clinical trials or commercially 
available. The primary benefit is the recanalization of iliofemoral stenosis or occlusion with restoration of 
blood flow. The potential benefits are improvement of limb pain, swelling, skin changes and ulcer healing, 
and enhancement of quality of life.  
The Abre system has several design features that positively impact the performance of the device for its 
intended use and is expected to offer additional benefits. 
These design features are reflected in Figure 6. 
 
Figure 6: Design features Abre stent 
 
 
 
 

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The Abre stent: 
• 
is available in a wide range of sizes in order to provide individually tailored treatment; 
• 
is structurally strong, possessing lateral compression resistance and radial outward force which allow 
for maintenance of lumen patency in both compressive and non-compressive lesions; 
• 
is flexible to avoid possible stent fracture caused by the extensive kinking which occurs due to  
placement in the highly mobile groin; 
• 
is durable which may result in reduced likelihood of loss of lumen patency as a result of stent fracture 
over the lifetime of the stent; 
• 
is accurate in deployment and enables repeatable (consistent) product performance due to minimal 
stent foreshortening, reduced jumping and enhanced isolation sheath. 
11.2.2 Potential Benefits of the ABRE Study 
Subjects enrolled in the study may have additional contact with their physicians or other medical care staff 
beyond their normal standard of care visits, which may provide benefit from a patient care perspective. 
Furthermore, the information obtained during this study will be used scientifically. The results of this study 
can help physicians understand the safety and effectiveness of the Abre system. 
11.3 Risk-Benefit Rationale 
It has been demonstrated that stent placement for iliofemoral venous outflow obstruction can be performed 
safely and that these devices are effective in restoring and maintaining iliofemoral vessel patency. 
Any potential risks with this study are minimized by selecting qualified investigators, careful assessment of 
each subject prior to, during, and after implantation. Medtronic has further minimized the possibility of risks 
by completing product testing prior to the use of the Abre system in this clinical study, implementing quality 
control measures into production processes, providing guidelines for subject selection and evaluation, and 
providing adequate instructions and labeling.  
The investigator in addition performs a continuous monitoring, assessment, and documentation of any risks. 
The risks associated with the Abre stent or participation in this study are not anticipated to be worse than 
the risks normally associated with the use of other commercially available devices.  
Risk management for the Abre system is performed in accordance with EN ISO 14971:2012. Furthermore, 
the indications and contraindications are provided in the Instructions for Use. 
 
 

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12 Adverse Event Assessments 
12.1 Definitions/Classifications 
12.1.1 Definitions 
The definitions to be applied for the purposes of safety reporting are provided in Table 10. 
Table 10: Definitions  
Event Type 
Definition 
Adverse Event (AE) 
(EN 
ISO14155:2020 
3.2) 
Untoward medical occurrence, unintended disease or injury, or untoward clinical 
signs (including abnormal laboratory findings) in subjects, users or other persons, 
whether or not related to the investigational medical device and whether 
anticipated or unanticipated. 
NOTE 1: This definition includes events related to the investigational medical 
device or the comparator. 
NOTE 2: This definition includes events related to the procedures involved. 
NOTE 3: For users or other persons, this definition is restricted to events related to 
the use of investigational medical devices or comparators. 
Serious Adverse 
Event (SAE) 
(EN 
ISO14155:2020 
3.45) 
Adverse event that led to any of the following: 
a) 
death, 
b) 
serious deterioration in the health of the subject, users or other persons as 
defined by one or more of the following: 
1) 
a life-threatening illness or injury, or  
2) 
a permanent impairment of a body structure or a body function, 
including chronic disease or 
3) 
in-patient or prolonged hospitalization, or  
4) 
medical or surgical intervention to prevent life-threatening illness or 
injury or permanent impairment to a body structure or a body 
function, 
c) 
foetal distress, foetal death or a congenital abnormality or birth defect 
including physical or mental impairment.  
NOTE 1: Planned hospitalization for a pre-existing condition, or a procedure 
required by the CIP, without serious deterioration in health, is not considered a 
serious adverse event. 
Adverse Device 
Effect (ADE) 
Adverse event related to the use of an investigational medical device. 
NOTE 1: This definition includes adverse events resulting from insufficient or 
inadequate instructions for use, deployment, implantation, installation, or 
operation, or any malfunction of the investigational medical device. NOTE 2: This 

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Event Type 
Definition 
(EN 
ISO14155:2020 
3.1) 
definition includes any event resulting from use error or from intentional misuse of 
the investigational medical device. 
NOTE 3: This includes ‘comparator’ if the comparator is a medical device. 
Serious Adverse 
Device Effect 
(SADE)  
(EN 
ISO14155:2020 
3.44) 
Adverse device effect that has resulted in any of the consequences characteristic 
of a Serious Adverse Event. 
Unanticipated 
Adverse Device 
Effect (UADE) 
(21 CFR 812.3) 
Any serious adverse effect on health or safety or any life-threatening problem or 
death caused by, or associated with, a device, if that effect, problem, or death was 
not previously identified in nature, severity, or degree of incidence in the 
investigational plan or application, or any other unanticipated serious problem 
associated with a device that relates to the rights, safety, or welfare of subjects. 
Unanticipated 
Serious Adverse 
Device Effect 
(USADE) 
(EN 
ISO14155:2020 
3.51) 
Serious adverse device effect which by its nature, incidence, severity or outcome 
has not been identified in the current risk assessment.  
NOTE 1: Anticipated serious adverse device effect (ASADE) is an effect which by 
its nature, incidence, severity or outcome has been identified in the risk 
assessment. 
Serious Health 
Threat 
(EN 
ISO14155:2020 
3.46) 
Signal from any adverse event or device deficiency that indicates an imminent risk 
of death or a serious deterioration in the health in subjects, users or other persons, 
and that requires prompt remedial action for other subjects, users or other persons. 
NOTE 1: This would include events that are of significant and unexpected nature 
such that they become alarming as a potential serious health hazard or possibility 
of multiple deaths occurring at short intervals. 
Device Deficiency 
(EN ISO 
14155:2020 3.19) 
 
Inadequacy of a medical device with respect to its identity, quality, durability, 
reliability, usability, safety or performance.  
NOTE 1: Device deficiencies include malfunctions, use errors, and inadequacy in 
the information supplied by the manufacturer including labeling. 
NOTE 2: This definition includes device deficiencies related to the investigational 
medical device or the comparator. 
 
12.1.2 Classification of Causal Relationships 
For each reported AE, the causal relationship between the AE and the study devices and implant procedure 
will be classified as not related, unlikely, possible, probably, causal relationship.  

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In some particular cases the event may be not adequately assessed because information is insufficient or 
contradictory and/or the data cannot be verified or supplemented. Medtronic and the investigators will make 
the maximum effort to define and categorize the event and avoid these situations. Where Medtronic remains 
uncertain about classifying the adverse event, it should not exclude the relatedness and classify the event 
as ‘possible related’. 
The causal relationships to the Abre system and Abre stent implant procedure are defined in Table 11. 
Table 11: Adverse Event Causal Relationship Definitions 
Related to  
Definition 
Abre system 
Any AE involving the function of the device, or the presence of the device in the body. 
Included in this category are events that are directly attributed to the device. 
Abre stent implant 
procedure 
Any AE that occurs within 30 days of the Abre stent implant procedure unless 
specifically shown not to be related to that procedure. 
12.1.3 Anticipated Adverse Events 
The list of anticipated adverse events and anticipated adverse product effects, including their likely 
incidence, mitigation and recommended treatment are included in Table 12. 
 
Table 12: Foreseeable Adverse Events and anticipated Adverse Device Effects 
Adverse Event / Product 
Effect 
Likely 
Incidence 
Mitigation 
Recommended treatment 
Access failure 
Not available 
Proper screening of the 
planned access point 
with duplex ultrasound 
and ultrasound-guided 
vessel puncture 
Reattempt from alternative access  
Access site infection 
Not available 
Proper surgery 
preparation and 
preventive antibiotic 
treatment 
Targeted antibiotic treatment 
Wound drainage as necessary 
Allergic reaction to 
contrast medium or 
procedure medications 
Not available 
Appropriate patient 
screening 
Appropriate treatment 
per hospital protocol for 
known allergy 
Appropriate treatment per hospital 
protocol 
Allergic reaction to nitinol 
or other device materials 
Not available 
Appropriate patient 
screening 
Appropriate treatment per hospital 
protocol 

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Adverse Event / Product 
Effect 
Likely 
Incidence 
Mitigation 
Recommended treatment 
Steroids and referral to 
immunology/allergy for long-term 
treatment strategy 
Possible excision of stent in rare cases 
(severe allergies) 
 
 
Arrhythmia 
Not available 
Appropriate patient 
screening 
Appropriate arrhythmia treatment per 
standard of care 
AV fistula 
0.1% 
Ultrasound-guided 
vascular access 
User training 
Monitor 
Additional procedure or surgery 
occasionally required 
Bleeding 
1.1%* 
Stop oral 
anticoagulants prior to 
surgery when safe and 
indicated 
Appropriate levels of 
anticoagulant effect 
with proper dosing and 
INR for those on 
warfarin 
Ultrasound-guided 
vessel puncture for 
access-related bleeding 
Local manual pressure 
Transfusion, if needed  
Additional procedure or surgery 
occasionally required (i.e. if from 
pseudoaneurysm for example) 
Bruising 
Not available 
Stop oral 
anticoagulants prior to 
surgery when safe and 
indicated 
Appropriate levels of 
anticoagulant effect 
with proper dosing and 
INR for those on 
warfarin 
Ultrasound-guided 
vessel puncture for 
access-related bleeding 
Monitor 
Death 
0.0% 
Appropriate screening 
Not applicable 
Device breakage 
Not available 
User training 
Additional procedure, surgery 
Device maldeployment 
Not available 
User training 
Additional procedure, surgery 

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Adverse Event / Product 
Effect 
Likely 
Incidence 
Mitigation 
Recommended treatment 
Edema 
Not available 
Limb elevation pre-
procedure 
Physical exercise 
Compression stockings 
Specific treatment of the cause (i.e. 
lymphedema, heart surgery, stent 
problem, worsening venous reflux, 
musculoskeletal injury).   
Limb elevation  
Physical exercise 
Compression stockings 
Edema therapy 
Management of coincident lymphedema 
(lymph pump, lymphedema therapy) 
Referral to cardiology 
Medication changes (i.e. stop calcium 
channel blockers) 
Fever 
Not available 
Antipyretics 
Antipyretics 
Hematoma 
3.6%* 
Stop oral 
anticoagulants prior to 
surgery when safe and 
indicated 
Appropriate levels of 
anticoagulant effect 
with proper dosing and 
INR for those on 
warfarin 
Ultrasound-guided 
vessel puncture for 
access-related bleeding 
Local manual pressure 
Surgical intervention, if needed 
Transfusion, if needed 
Hypotension, nausea, or 
other vasovagal response 
Not available 
Not applicable 
Symptomatic treatment according to 
standard of care 
Infection (other than 
access site) 
Not available 
Preventive antibiotics 
Antibiotics 
Myocardial infarction 
Not available 
Appropriate screening 
Treatment per standard of care 
Pain 
Not available 
Consider preventive 
analgesics 
Local anesthesia for 
periprocedural pain 
Minimize hematoma 
formation as described 
above (Hematoma) 
Analgesics 

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Adverse Event / Product 
Effect 
Likely 
Incidence 
Mitigation 
Recommended treatment 
Pseudoaneurysm 
0.2% 
Stop oral 
anticoagulants prior to 
surgery when safe and 
indicated.  
Appropriate levels of 
anticoagulant effect 
with proper dosing and 
INR for those on 
warfarin 
Ultrasound-guided 
vessel puncture for 
access-related bleeding 
Transfusion, if needed 
Thrombin injection or surgery if 
symptomatic, greater than 2 cm or 
ruptured 
 
Pulmonary embolism 
0.2% 
Appropriate screening 
Early mobilization 
Resumption of 
anticoagulation in those 
with a history of 
DVT/PE 
Treatment per standard of care 
Renal insufficiency/renal 
failure (new or worsening) 
Not available 
Periprocedural 
hydration 
Hold  
ACE/ARBs/Diuretics/ 
Metformin in the 
morning of surgery 
Limitation of NSAID use 
Limitation of contrast 
administration 
Treatment per standard of care 
Sepsis 
Not available 
Perioperative antibiotics 
Standard preparation of 
the access site 
Emergency treatment per standard of care 
Stent fracture 
1.4% 
User training 
Avoid overlap under the 
inguinal ligament 
Monitor 
Additional procedure/surgery, if needed 
Stent malapposition 
Not available 
User training 
Appropriate stent sizing 
Additional post-
dilatation 
Additional procedure/surgery, if needed 
Stent malposition 
Not available 
User training 
Appropriate stent sizing 
Additional procedure/surgery, if needed 

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Adverse Event / Product 
Effect 
Likely 
Incidence 
Mitigation 
Recommended treatment 
Stent migration 
1.6% 
User training 
Appropriate stent sizing 
Additional procedure/surgery, if needed 
Stroke/paradoxical 
embolism/transient 
ischemic 
attack/intracerebral 
hemorrhage 
Not available 
Appropriate screening 
Use of INR to guide 
warfarin anticoagulation 
and avoid supra-
therapeutic effect 
Treatment per standard of care 
Tissue necrosis 
Not available 
Appropriate screening 
Pre- and post-op care 
Avoid hematoma  
Wound care 
Surgery, if needed 
Treatment per standard of care 
Transfusion reaction 
following blood transfusion 
for treatment of major 
bleeding  
Not available 
Appropriate screening   
Avoid bleeding 
Treatment per standard of care 
Vessel damage, including 
perforation or rupture 
Not available 
User training 
Additional procedure, surgery 
Venous 
occlusion/thrombosis, 
within or outside of 
stented segment 
Not available 
Appropriate 
anticoagulation 
Avoidance of skip areas 
between two stents 
Establishment of 
adequate inflow and 
outflow 
Appropriate anticoagulation 
Additional procedure, surgery 
(percutaneous mechanical thrombectomy, 
thrombolysis, balloon maceration, 
additional stenting) 
*The percentages are based on the literature review which represents major bleedings and wound hematoma only. 
 
The list of foreseeable adverse events and anticipated adverse device effects will regularly be updated 
during the study. The updated list will be kept separate from the Clinical Investigation Plan. 
 
 

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12.2 Reporting of Adverse Events 
12.2.1 Evaluation and Documentation of Adverse Events and Device Deficiencies 
Investigators are required to assess and document in the medical record Adverse Events (AEs) and Device 
Deficiencies (DDs) (per the definitions in Table 10) observed in subjects from the time of enrollment. AEs 
will be followed until the event has resolved or until study exit. In case of permanent impairment, the event 
will be followed until the event stabilizes and the overall clinical outcome has been ascertained. Reporting 
of AEs and DDs will end once the subject exits the study. In case AEs are unresolved at the time of study 
exit, this will be documented in the eCRF. 
The following subjects will be followed for 30 days after the procedure: 
• 
subjects in whom the Abre system did not enter the vasculature during the implant procedure (for 
example because of not meeting the I/E criteria);  
• 
subjects in whom the Abre system entered the vasculature, but who did not have an Abre stent 
implanted.  
All AEs during this 30 day follow-up period will be handled as per the described study requirements. 
Adverse events and device deficiencies (see also Section 12.2.4) that occur during this study are 
required to be reported to Medtronic by completing the Adverse Event or Device Deficiency eCRF, which  
will be accessible by Medtronic and designees who have authorized access to the EDC system. All 
reported adverse events will be reviewed by Medtronic or authorized designee to determine whether the 
adverse event meets regulatory reporting requirements. 
The general process for reporting Adverse Events is as follows:  
• 
Report the event to Medtronic as soon as possible, but no later than the timeframes outlined in 
Table 14  
• 
Sites will be provided with the contact information of the appropriate Medtronic authorized 
designee 
• 
Complete all sections of the Adverse Event eCRF 
• 
Each unique event/diagnosis must be documented separately 
• 
The Adverse Event eCRF must be reviewed and approved by the investigator 
 
The following information should be collected on the Adverse Event eCRF: 
• 
Date of onset or first observation (if full date not available the date when diagnosis was established 
can be used) 
• 
Date of first awareness by investigator 
• 
Description of the event (single diagnosis term) 
• 
AE code number (provided by Medtronic) 
• 
Seriousness of the event 
• 
Causal relationship of the event to the Abre system 
• 
Causal relationship of the event to the implant procedure 
• 
Action taken, including any medical or surgical intervention and date of intervention 
• 
Narrative (describe any additional details relevant to the AE) 

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• 
Outcome or status of the event; any reported event should be followed until it has resolved, has a 
stable level of sequelae, or is no longer clinically significant in the investigator’s opinion 
 
In addition, for specific endpoint-related adverse events as described in the CEC Manual of Operations, 
sites should submit relevant, de-identified source documents to Medtronic for the Clinical Events Committee 
(CEC) members to use in their adjudication of the event. The CEC may request source documentation on 
additional events, at their discretion and according to the CEC Manual of Operations. Additional information 
regarding the CEC is detailed in Section 13.2. 
12.2.2 Reporting of Device Deficiencies 
Device deficiencies that led to an AE are reported on the AE eCRF (one for each AE).   
Device deficiencies that did not lead to an AE should be reported on a Device Deficiency eCRF (one for 
each device deficiency). 
Device deficiencies that did not lead to an adverse event, but might have led to an SADE if: a) a suitable 
action had not been taken, or b) an intervention had not been made, or c) circumstances had been less 
fortunate, should be reported to Medtronic immediately (but no later than 72 hours of the investigator’s / 
site’s first knowledge of the event (or sooner if required by local regulation) of the site’s first learning of the 
event on a Device Deficiency eCRF.  
Any device or accessory involved with a device deficiency should be returned to Medtronic (unless 
implanted) for analysis (see Section 8.9).  
12.2.3 Non-Reportable Medical Occurrences  
Documented pre-existing conditions or a procedure required by the CIP, are not considered AEs and should 
not be reported unless there is a change in the nature or severity of the condition. Pre-existing events 
should be reported as Adverse Events in the situation where a new treatment has to be started or an 
existing treatment has to be changed to treat the adverse event and the event is accompanied with signs 
and symptoms. 
Unavoidable events are conditions inherent to an endovenous procedure that can potentially occur in each 
subject for a projected duration according to the investigator’s opinion, including, but not limited to the 
events listed in Table 13. Unavoidable events should not be reported unless the event worsens or is present 
outside the stated timeframe from the endovenous procedure. 
 
 
 

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Table 13: Unavoidable events 
Event Description 
Timeframe (hours/days) from 
the endovenous procedure 
Anesthesia related nausea / vomiting (with or without treatment) 
24/1 
Low-grade fever (<100°F or 37.8°C)  
48/2 
Pain at access site (with or without standard treatment and subject not 
returning to clinic to have additional treatment) 
72/3 
Mild to moderate bruising / ecchymosis at access site(s) 
168/7 
Sleep problems (insomnia) (with or without treatment) 
72/3 
Back pain (with or without treatment) 
168/7 
Bleeding at access site (not requiring treatment) 
24/1 
Longitudinal movement of the stent of less than 1 cm and without 
clinical symptoms 
N/A 
 
12.2.4 Requirements for Adverse Event Reporting 
Adverse events and device deficiencies should be reported by the investigator to Medtronic as soon as 
possible after the event occurs, but no later than the timeframes listed in Table 14 or local requirements, 
whichever is more stringent.  
 
Reporting all adverse events is no longer required effective with this version of the CIP (v 2.0) as 
unrelated adverse events greater than 12-months post-procedure do not have clinical impact on the long-
term analysis of the safey and effectiveness, the post-market clinical follow-up (PMCF), or clinical 
evaluation of the device. This is the rationale for deviating from ISO 14155:2020 (7.4). Adverse events 
related to the device and / or procedure will continue to be reported as well as adverse events with major 
adverse event (MAE) potential such as: any target limb revascularization, any signs or symptoms 
pulmonary embolism, any bleeding complication (procedural & post-procedural), stent migration, and 
stent thrombosis. Serious and unanticipated events are still required to be reported. Adverse events that 
were reported in the ABRE pivotal study phase that are currently ongoing, must be followed to the AE 
resolution. 
 
In addition, investigators are obligated to report adverse events and device deficiencies in accordance 
with the requirements of their reviewing Ethics Board and local regulations. 
 
Medtronic is obligated to report adverse events and device deficiencies that occur during this study to the 
Regulatory Authorities and Ethics Board as per local requirements.  
 
 

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Table 14: Required Timeframes for Adverse Event reporting by investigator to Medtronic 
Timeframe for Reporting 
Event Type 
Immediately, but no later than 72 hours 
of the investigator’s / site’s first 
knowledge of the event (or sooner if 
required by local regulation) 
• 
Adverse Device Effect (ADE) or Device Related 
Adverse Event 
• 
Device Deficiency (DD) 
• 
Device Deficiency that might have led to an SADE 
• 
Serious Adverse Device Effect (SADE) 
• 
Serious Adverse Event (SAE) 
• 
Unanticipated Adverse Device Effect (UADE) 
• 
Unanticipated Serious Adverse Device Effect 
(USADE) 
In a timely manner from  the 
investigator’s / site’s first knowledge of 
the event 
Adverse Event (AE): effective with this version of the CIP 
(v2.0), only procedure and/or device-related AEs (including 
those already called out in the row above as ADEs), or AEs 
that may potentially be adjudicated as an MAE1, are required 
to be reported.2  
1 Any target limb revascularization, any signs or symptoms pulmonary embolism, any bleeding complication 
(procedural & post-procedural), stent migration, and stent thrombosis. 
2Unrelated AEs, in particular those greater than 12-months post-procedure do not have a clinical impact on 
the long-term analysis of the safety and effectiveness, the post-market clinical follow-up (PMCF), or clinical 
evaluation of the device, and is the rationale for deviating from ISO 14155:2020 (7.4).   
12.2.5 Complaint Reporting  
The Abre system is CE marked and obtained FDA approval in October 2020. All product complaints must 
be reported for Post Market Surveillance. The reporting of product complaints is not part of the clinical study 
and should be done in addition to the Adverse Event reporting requirements. 
• 
Product Complaint: Any written, electronic or oral communication that alleges deficiencies related to 
the identity, quality, durability, reliability, safety, effectiveness or performance of a medical device that 
has been placed on the market. 
• 
Vigilance and Medical Device Reporting: A system used to notify the regulatory body about 
incidents with regard to medical devices that carry the CE mark or are FDA approved. This system 
requires a manufacturer to notify the regulatory body of incidents immediately on learning of them. 
• 
Incident: Any malfunction or deterioration in the characteristics and/or performance of a device, as 
well as any inadequacy in the labeling or the instructions for use which, directly or indirectly, might lead 
to or might have led to the death of a subject, or user or of other persons or to a serious deterioration 
in their state of health.  
It is the responsibility of the investigator to report all product complaint(s) associated with a medical device 
distributed by Medtronic regardless whether they are related to intended use, misuse, or abuse of the 
product. Reporting must be done within 48 hours and per the regular channels for market released products. 

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12.2.6 Emergency Contact Details for Reporting Events and Device Deficiencies 
In case of an immediately reportable Adverse Event or in a medical emergency situation, the investigator 
can contact the Medtronic Study Manager or designee. Contact details of Medtronic Study Management 
are subject to change and will be maintained in the Investigational Site File and updated contact details will 
be provided to sites whenever applicable.  
 
13 Committees / Core Laboratories 
13.1 Data Safety Monitoring Board 
A Data Safety Monitoring Board (DSMB) is composed of at least four members with pertinent expertise (3 
physicians and at least 1 biostatistician) who are not participants or directly involved in the conduct of the 
study. A minimum of one interventionalist will serve as a member of the DSMB. 
 
The responsibility of the DSMB is to evaluate safety data during the course of the study and to advise 
Medtronic about the continuing safety of the study, to ensure the well-being of the current participants and 
those yet to be enrolled as well as the continuing validity and scientific merit of the study.  
 
Based on the safety data, the DSMB may recommend that Medtronic modify or stop the study. DSMB 
composition, duties, procedures, deliberation rules are detailed and documented in the DSMB Charter. 
 
The Data Safety Monitoring Board will be established and led by: 
Syntactx 
4 World Trade Center 
150 Greenwich Street 
New York, New York 10006, USA 
Phone: +1-212-228-9000 
Fax: +1-646-375-3183 
 
13.2 Clinical Events Committee 
The Clinical Events Committee (CEC) is made up of clinicians (interventional and non-interventional) with 
pertinent expertise (i.e. vascular surgeons, interventional radiologists) who are not participants in the study 
and who do not have any other real or potential conflicts of interest. The CEC is charged with the 
categorization of selected adverse events and clinical endpoints in the study, using criteria established at 
the outset of the study and specified by the ClP, the CEC Manual of Operations, and relevant societal 
reporting standards. The CEC Manual of Operations will specify explicit rules outlining the minimum amount 
of data required and the algorithm followed in order to classify an event.   
 
Database automated alerts and the independent Medical Monitor at Medtronic’s designated Contract 
Research Organization (CRO) will identify clinical events requiring adjudication as specified in the CEC 
Manual of Operations. The CEC will regularly evaluate and adjudicate these events, as well as other events 
as may be requested by Medtronic.  

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The CEC will be established and led by: 
Syntactx 
4 World Trade Center 
150 Greenwich Street 
New York, New York 10006, USA 
Phone: +1-212-228-9000 
Fax: +1-646-375-3183 
 
13.3 Duplex Ultrasound Core Laboratory 
The Duplex Ultrasonography Core Laboratory (Duplex Core laboratory) is responsible for developing 
protocol requirements, reviewing DUS exams, interpreting subject DUS data, and providing feedback on 
the quality of the DUS exams to participating sites. The Duplex Core laboratory will review, analyze, and 
record data on the Duplex Core laboratory Assessment eCRF. The Duplex Core laboratory’s reviewer’s 
interpretation of all DUS exams will be used for the data analyses. All DUS exams will be evaluated by:   
VASCORE 
The Vascular Ultrasound Core Laboratory 
1 Bowdoin Street 
Boston, MA 02114, USA 
Phone: +1-617-726-5552 
Fax: +1-617-726-1977 
13.4 Venography, X-ray, and IVUS Core Laboratory 
The venography, X-ray, and IVUS Core Laboratory is responsible for developing protocol requirements, 
reviewing and interpreting venograms; X-ray, and IVUS studies, and providing feedback on the quality of 
the imaging studies to participating sites. The core laboratory will review, analyze, and record data on the 
applicable Core laboratory assessment eCRF. The core laboratory’s reviewer’s interpretation of all 
imagings will be used for the data analyses. All venogram, X-ray, and IVUS recordings will be evaluated 
by: 
 
 
 
 
 
 
 
 
 
 
 
Syntactx 
4 World Trade Center 
150 Greenwich Street 
New York, New York 10006, USA 
Phone: +1-212-228-9000 
Fax: +1-646-375-3183 

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14 Statistical Design and Methods 
This section outlines the statistical design and methods set at the start of the study, and statistical methods 
for post-approval study phase. Primary endpoint and study success criteria has been added in the below 
corresponding sections. The clinical performance of the Abre system will be evaluated through a 
prospective, single-arm, non-randomized, multi-center, global clinical study in a total of 200 included 
subjects with a hypothesis-based 30-day composite safety endpoint and a hypothesis-based 12-month 
effectiveness endpoint assessed by performance goals. 
Statistical analysis will be performed by Medtronic statisticians or their designated representatives. A 
separate Statistical Analysis Plan (SAP) has been developed to further describe pre-specified statistical 
methods, data handling rules, and analyses that will be employed. Any deviation from the original statistical 
analysis plan will be reported in the final study report, along with justification for the deviation(s). 
One-sided statistical tests will have p-values less than 0.025 deemed significant while two-sided tests will 
have p-values less than 0.05 deemed significant. Statistical analyses will be conducted in SAS version 9.4 
or above (SAS Institute, Cary, N.C.) or another validated statistical software package. 
For adverse event reporting, the primary analysis will be based on subject counts, not event counts. Both 
subject counts and event counts will be presented in tabular summaries of results, as appropriate. 
14.1 Performance Goals 
14.1.1 Performance Goal: Primary Effectiveness Endpoint 
The primary effectiveness performance goal endpoint in the study is primary patency. The statistical 
hypothesis on this endpoint is that primary patency through 12 months will exceed a performance goal 
established from historical literature references using venous stenting as the treatment of choice. Formally, 
the null and alternative hypotheses to be tested appear below: 
H0: π ≤ PG 
HA: π > PG 
Where π is the primary patency at 12 months in the study population and PG is the performance goal, 
which is calculated as follows. An extensive and independent review of the available literature produced 
references on venous stenting in similar patient populations. These data are derived from published studies 
of venous stenting which measured target vessel patency as an endpoint. In order to estimate the expected 
rate of primary patency in the study population at 12 months, the review of the available literature was used 
(see Appendix A Scientific Literature Search). 
Based on the literature, the weighted mean expected primary patency was 85.7%. By subtracting a margin 
of indifference of 10% from expected performance (85.7% - 10% = 75.7%); consequently, the value of 75% 
is therefore taken as the performance goal for the current study.  
For analysis of the imaging component of primary patency, if a subject has both a valid venogram and DUS 
during the 12-month follow-up period then the venogram will be used. If no venogram is available, then the 
DUS will be used. 

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14.1.2 Performance Goal: Primary Safety Endpoint 
The study’s primary safety endpoint is defined as a composite of all-cause death occurring post-procedure, 
clinically significant (i.e. symptomatic, confirmed by CT pulmonary angiography) pulmonary embolism, 
major bleeding complication (procedural), stent-migration and stent thrombosis confirmed by imaging as 
assessed by core laboratory within 30 days of the index procedure. The review of the literature that provided 
results on these endpoints suggests an expected rate of 5.6% (see Appendix A Scientific Literature 
Search). It should be noted that considerably less data, compared to primary patency, was found for the 
components of this composite endpoint.  
Therefore, due to the greater uncertainty, a relatively larger margin of indifference was used of 6.8% giving 
a performance goal of 12.5%. Formally, the null and alternative hypotheses to be tested appear below: 
H0: P ≥ PG 
HA: P < PG 
where P is the primary safety endpoint at 30 days in the study population and PG is the performance goal. 
14.2 Sample Size Calculation 
Primary Effectiveness: Using the assumptions above on the performance goal and anticipated outcome, 
we assume desired power of at least 92% under difference testing relative to the performance goal at a 
one-sided alpha of 0.025. The resulting evaluable sample size required is then 160 subjects using exact 
binomial test for a single proportion. Accounting for attrition during follow-up, the sample size is augmented 
by 20% to 200 subjects. Every effort will be made, however, to minimize loss to follow-up.  
Primary Safety: Using the assumptions above on the performance goal and anticipated outcome, we 
assume desired power of at least 92% under difference testing relative to the performance goal at a one-
sided alpha of 0.025. The resulting evaluable sample size required is then 193 subjects using exact binomial 
test for a single proportion. Accounting for attrition during follow-up, the sample size is augmented by 3.5% 
to 200 subjects. Every effort will be made, however, to minimize loss to follow-up.  
In summary, the overall power of the study is at least 84% while the effectiveness and safety performance 
goals are as follows: 
Table 15: Effectiveness and safety performance goals 
Endpoints 
PGs 
Primary Patency at 12 months 
75% 
MAE at 30 days 
12.5% 
 
 

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14.3 Analysis Sets 
The primary analysis set will consist of all subjects who were enrolled and had the Abre system introduced 
into the vasculature. In general, all analyses will be performed using all evaluable subjects for primary 
effectiveness and safety analyses (evaluable subject definitions provided below).  
The PMA primary analysis will occur when all 12-month follow-up data have been collected.    
For the primary effectiveness endpoint, subjects will be included in the primary analysis when:  
a) the subject experiences at least one clinically-driven target lesion revascularization within 390 
days; or  
b) the subject has occlusion or restenosis ≥50% of the stented segment of the target lesion confirmed 
by core laboratory at 12 months visit; or  
c) the subject has at least 330 days follow up without an event in the primary effectiveness endpoint. 
 
For the primary safety endpoint, subjects will be included in the primary analysis when:  
a) the subject experiences at least one of the primary safety composite events within 30 days; or  
b) stent-migration and stent thrombosis confirmed by imaging as assessed by core laboratory at 30-
day visit; or 
c) the subject has at least 23 days of clinical follow up without an event in the primary safety 
endpoint.   
Secondary analyses for primary safety endpoint will be conducted on all implanted subjects in whom the 
denominator for the primary safety endpoint will be the number of implanted subjects who had sufficient 
follow up (at least 23 days for 30-day visit) plus any subjects who had an event prior to the 30-Day Follow-
Up visit.  
One interim analysis will be performed on safety for the DSMB. The interim analysis is planned when 30-
day follow-up data have been obtained on 30 subjects. The interim analysis does not permit early stopping 
for effectiveness and therefore no alpha-spending or other adjustment to the study’s statistical hypotheses 
is required. The DSMB Charter may specify additional safety analyses.  
Additional exploratory analyses of the data may be conducted as deemed appropriate. 
14.4 Statistical Method  
14.4.1 ABRE Pivotal Study Phase  
The primary patency rate is calculated as the number of subjects without loss of primary patency divided 
by the number of subjects having evaluable primary endpoint data for primary patency rate at 12 months. 
The 12-month patency rate and lower limit of the 97.5% one-sided confidence interval will be reported. The 
primary effectiveness objective will be considered to be met if the lower limit of the 97.5% one-sided 
confidence interval of the 12-month patency rate is above 75%. For analysis of the imaging component of 
primary patency, if a subject has both a valid venogram and DUS during the 12-month follow-up period 
then the venogram will be used. If no venogram is available, then the DUS will be used. 
The primary safety failure rate is calculated as the number of subjects who had an event prior to the 
milestone visit divided by the number of evaluable subjects who had sufficient follow up (at least 23 days 
for 30-day visit) plus any subjects who had an event prior to the milestone visit.  

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Primary safety failure rate and the exact one-sided 97.5% upper confidence limit (UCL) will be reported. 
The primary safety objective will be considered to be met if the exact one-sided 97.5% UCL is below 12.5%.   
14.4.2 ABRE Post-Approval Study Phase 
The primary effectiveness endpoint of the post-approval study phase is Target Lesion Revascularization 
(TLR) through 36 months, defined as any re-intervention of the stented segment of the target lesion. Target 
limb revascularizations are adjudicated by the CEC to determine TLR status in addition to assessing 
relatedness and clinically driven status.  Time-to-event analysis will be performed for the TLR rate through 
36 months (1080 days), subjects with no TLR will be censored at the last contact date.  Kaplan-Meier 
estimate and the 95% confidence interval for the freedom from TLR rate through 36 months will be reported.  
14.5 Study Success Criteria 
The study success criteria set at the start of the study were as follows: the study will be considered a 
success if both the primary endpoints meet their respective performance goals. For the effectiveness 
endpoint this translates into observing a one-sided 97.5% lower confidence limit (LCL) of the point estimate 
above 75% and for the safety endpoint it means observing a one-sided 97.5% upper confidence limit (UCL) 
below 12.5%.  
The ABRE post-approval study phase has no pre-specified hypothesis testing or study success criteria.  All 
analyses will be presented with descriptive statistics.  
14.6 Handling of Dropouts and Missing Data 
For those subjects not evaluable for primary effectiveness endpoint, multiple imputations will be carried out 
using the logistic regression approach for a dichotomous outcome using PROC MI in SAS for patients not 
experiencing the event and not having endpoint data for at least 330 days of follow-up.   
The following variables will be included in the imputation model as covariates:  
• 
Age 
• 
Gender 
• 
Race 
• 
Ethnicity 
• 
Diabetes 
• 
Total occlusion 
• 
Venous disease category 
• 
Villalta score at baseline 
• 
CEAP score at baseline 
• 
VCSS class at baseline 
• 
Reference vessel diameter 
• 
Lesion length 
If there are relatively few missing data points (e.g., <10%) for a given variable, a simple gender-specific 
imputation using the mean (for continuous variables) or median (for dichotomous or categorical variables) 
of the non-missing values will be done. If there are >10% missing data points, the variable will be excluded 
from the imputation analysis. Five data sets will be imputed from these covariates and will mimic different 
realizations of the missing data. For the endpoint, the numerator (the numerator is the point estimate of the 
treatment for the effectiveness endpoint) and its relevant standard error (the pooled standard error of 

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treatment for the effectiveness endpoint) will be pooled across the 5 data sets using established variance-
adjustment methods (e.g., via PROC MIANALYZE in SAS) to create one overall numerator and 
denominator. The lower bound of the 97.5% pooled CI will be compared to the effectiveness PG. 
The Tipping Point method will be adopted to further evaluate study primary objectives by assessing the 
impact of missing or unknown outcome data on study results. Tipping point analysis results for both primary 
effectiveness endpoint and primary safety endpoint will be reported.  
 
14.7 Assessment of Data Pooling 
Poolability of data across clinical study sites is justified on a clinical basis (i.e. all study sites use the same 
protocol). The sponsor monitors the site for protocol compliance, and the data gathering instruments are 
identical. The Food and Drug Administration also requires a statistical assessment of poolability. Poolability 
is assessed by comparing the baseline characteristics across study sites. For categorical baseline variables 
such as gender, a generalized Fisher’s exact test or equivalent test will be used and for quantitative 
variables, parametric or non-parametric analysis of variance (general linear models or an equivalent 
procedure) will be used.  
The above statistical analyses do not result in an impediment to pooling, but rather assess the balance of 
baseline covariates across study sites. If any baseline covariate is found to be statistically significant by this 
process, multivariate analyses will be done to determine if the imbalance affected study outcome. This is 
done by using both the variable found out of balance and study site as possible covariates.   
It may be necessary to combine two or more low enrolling study sites into pseudo-sites to allow these 
analyses. Sites with fewer than 6 subjects will be ranked by enrollment from low to high. Starting from the 
lowest enrolling site, sites will be combined into a pseudo site until the combined size reaches the median 
enrollment among all sites. This process will be repeated until all resulting sites have enrollment equal to 
or greater than 6 subjects. This will be done in a manner to preserve the structure of the study and prevent 
bias. 
Because the ABRE Study is being conducted in the US and outside the US (OUS), an analysis will be 
undertaken to determine if the study sites within the US and OUS subsets are homogeneous in the 
baseline covariates. Similar analyses will be conducted on gender. The statistical tests used will be the 
same as those discussed for site poolability. 
Baseline characteristics to be considered as possible covariates are as following: 

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• 
Age 
• 
Gender 
• 
Race 
• 
Ethnicity 
• 
Coronary Artery Disease (CAD) 
• 
Chronic Obstructive Pulmonary Disease (COPD) 
• 
Myocardial Infarction (MI)  
• 
Hyperlipidemia 
• 
Cerebrovascular Accident (CVA) 
• 
High Blood Pressure (HBP) 
• 
Diabetes 
• 
History of Tobacco Use   
• 
History of Peripheral Artery Disease (PAD)  
• 
Villalta score 
• 
VCSS 
• 
Venous disease category 
 
If there are relatively few missing data points (e.g., <10%) for a given variable, a simple gender-specific 
imputation using the mean (for continuous variables) or median (for dichotomous or categorical variables) 
of the non-missing values will be done.  If there are >10% missing data points, the variable will be 
excluded from the imputation analysis. 
Poolability analysis will also be performed on the primary endpoints comparing across sites and 
geographical regions after adjusting for covariates difference. Logistic regression model will be utilized to 
include unbalanced covariates and site as an independent variable, and the study outcome as dependent 
variable to assess outcome difference.  If the p-value of site effect is less than 0.10, further analyses will 
be undertaken to investigate the inbalance of the study outcome.    
14.8 Minimizing Bias 
Medtronic shall avoid improper influence on, or inducement of, the subject, monitor, any investigator(s) or 
other parties participating in, or contributing to, the clinical study.  
Selection of subjects, treatment of subjects and evaluation of study data are potential sources of bias.  
Methods incorporated in the study design to minimize potential bias include (but are not limited to): 
• 
For sites that are participating in other endovenous stent studies, which may have similar I/E criteria 
as the ABRE Study, a written process for avoiding selection bias is required. 
• 
Subjects will be screened to confirm study eligibility with defined inclusion/exclusion criteria prior to 
inclusion. Sites are required to maintain a log of all subjects screened and enrolled for the study. 
• 
Demographics (including race and ethnicity data) and medical history will be collected at baseline 
in order to later assess possible characteristics that may influence endpoints. 
• 
Data collection requirements and study procedures will be standardized across all geographies. 
• 
All geographies will follow the same version of the CIP and eCRFs. 
• 
No more than 20% of expected inclusions may come from a single site. 
• 
All study investigators will be required to meet the requirements of 21 CFR Part 54, Financial 
Disclosure by Clinical Investigators. 

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• 
All study site and Medtronic personnel will be trained using standardized training materials. 
• 
Regular monitoring visits will be conducted to verify adherence to the CIP and source data. 
• 
An independent CEC will be utilized to regularly review and adjudicate reported adverse events. 
• 
An independent DSMB will be utilized to review data, help safeguard the interests of study subjects, 
and monitor the overall conduct of the study. 
• 
Independent core laboratories will be utilized to interpret imaging results which will be used for the 
analysis. 
 
15 Ethics 
15.1 Statement(s) of Compliance  
The ABRE Study is designed to reflect the good clinical practice (GCP) principles outlined in ISO 
14155:2020. These include the protection of the rights, safety, and well-being of human subjects, controls 
to ensure the scientific conduct and credibility of the clinical investigation, and the definition of 
responsibilities of Medtronic and investigators. 
The study will be conducted according to federal, national and local laws, regulations, standards, and 
requirements of the countries/geographies where the study is being conducted.  
The study will also be conducted in accordance with the Declaration of Helsinki. The principles of the 
Declaration of Helsinki are implemented in this study by means of the patient informed consent (IC) process, 
Ethics Board approval, study training, clinical study registration, pre-clinical testing, risk benefit assessment, 
and publication policy. 
In the US, the study will be conducted under an FDA Investigational Device Exemption (IDE) in compliance 
with 21 CFR Parts 11, 50, 54, 56, and 812 throughout the entire study (pivotal and post-approval study 
phases).  
In addition, the study will be conducted in compliance with 21 CFR Part 11 and 54 in all participating 
geographies. 
Outside US, the study will be conducted in compliance with ISO 14155:2020, MDD 93/42/EEC, and EU 
MDR 745/2017 as of Date of Application (where applicable) will also be followed. As described in section 
12.2.4, reporting all adverse events is no longer required as of this CIP version which is  a deviation from 
ISO 14155:2020 (7.4). 
Where applicable, regulatory authority notification/approval will be done/obtained. Investigational sites will 
not be activated, nor begin enrolling subjects until the required approval/favorable opinion from the 
respective regulatory agency and Ethics Board has been obtained (as appropriate).  
Additionally, any requirements imposed by a local regulatory agency or Ethics Board shall be followed, as 
appropriate. 
Each site must provide Medtronic with a copy of the investigational site’s Ethics Board approval letter and 
the Ethics Board-approved Informed Consent Form. Ethics Board approval letters must contain the 
following elements: 

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• 
Study Title and the Medtronic Protocol Number; 
• 
Medtronic’s Protocol Version (revision letter and/or date of issue); 
• 
A list of the documents reviewed at the meeting covered by the approval letter; 
• 
If applicable, the required interval for the site’s continuing review by the Ethics Board; and 
• 
Expiration date, if applicable and/or allowed by the site’s system, of the current approval. 
If applicable, approvals for the continuation of the study at each investigational site must be kept current in 
accordance with the Ethics Board’s review schedule, but at a minimum, the study must be re-reviewed by 
the Ethics Board regularly based on local requirements. All site communications to and from the Ethics 
Board must be forwarded to Medtronic as they are sent/received. 
Medtronic will be informed by the Ethics Board and/or the investigator in case any action is taken by an 
Ethics Board with respect to this investigation. 
This study will be publicly registered on www.clinicaltrials.gov prior to first enrollment in accordance with 
the 2007 Food and Drug Administration Amendments Act (FDAAA) and Declaration of Helsinki. 
16 Study Administration 
16.1 Investigator / Investigational Site Selection 
The role of the principal investigator is to implement and manage the day-to-day conduct of the clinical 
study as well as ensure data integrity and the rights, safety, and well-being of the subjects involved in the 
clinical study.  
An investigator may be included in the clinical study if compliant with the following requirements:  
• 
Investigator is qualified, educated, and has experience documented by at least 10 iliofemoral venous 
stent placements in the past year, while in total 20 venous stenting cases should have taken place at 
the site in the past year. For example, has experience with Zilver Vena (Cook Medical), sinus-Venous 
(OptiMed), Vici (Veniti), or Wallstent (Boston Scientific) stents or any off-label arterial stent.  
• 
Investigator is qualified, educated, has experience with and has the resources available to conduct 
endovenous IVUS  
• 
Investigator has interest in the Abre Venous Self-expanding Stent. 
• 
Investigator is not debarred, disqualified, or working under sanctions in applicable regions. Investigator 
is not on the FDA list of investigators who have been disqualified, restricted, or debarred from 
conducting clinical studies. Investigator has not been excluded from participation in all Federal Health 
Care programs (e.g. Medicare, Medical, Medicaid). 
• 
Investigator/site expects to have adequate time and resources to conduct the study throughout the 
duration of the study. Each site must have a designated research coordinator assigned to the study.  
• 
Investigator/site has access to an adequate number of eligible subjects. The number of venous stent 
placements in the center meeting the I/E criteria should allow for an estimated enrollment of 1 subject 
per month. 
• 
Investigator/site has the ability to comply with applicable Ethics Board and regulatory requirements.  
• 
Site has participated in at least one pre-market study in the last 5 years.  
• 
Lack of potential conflict(s) of interest. 
 

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• 
Anticipated study startup timeline, including contracting and Ethics Board and regulatory submission 
and approval (if applicable) is acceptable.  
• 
Anticipated competition for same subject population from competitive ongoing studies is at an 
acceptable rate. 
16.2 Clinical Trial Agreement 
A clinical trial agreement shall be in place, signed by the participating investigational site and/or principal 
investigator of each investigational site, as per the local legal requirements, and returned to Medtronic prior 
to the commencement of any clinical study activities. The investigator is indicating approval of the clinical 
investigation plan and subsequent amendments, with a fully executed agreement. 
16.3 Study Insurance /Subject Indemnification 
Medtronic, plc (including all wholly owned subsidiaries) maintains appropriate clinical trial liability insurance 
coverage as required under applicable laws and regulations and will comply with applicable law and custom 
concerning specific insurance coverage. If required, a Clinical Trial Insurance statement/certificate will be 
provided to the Ethics Board.  
Medtronic will provide subject indemnification according to local laws where this study will be conducted. 
16.4 Subject Compensation 
Subjects will not receive any compensation for their participation in this study (including follow-up); however, 
Medtronic may, at its option, provide reimbursement for participants who will incur extraordinary 
travel costs related to their participation in the study, including airfare, mileage, or hotel expenses. The 
participating Institution will make such request(s) in writing to Medtronic (de-identified of participant 
information), detailing the unusual circumstances and the excessive costs that the participant will 
incur. Medtronic will evaluate requests on a case-by-case basis, and will notify the Participating Institution 
of its decision in writing. 
 
 

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16.5 Site Activation/Supply of Study Materials 
Investigational sites will receive a formal letter of site activation, upon receipt of or completion of the 
following: 
• 
Curriculum vitae of the principal investigator, sub-investigators, and all key site staff 
• 
Other relevant documentation for key site staff (i.e. DUS Technicians) is allowable 
• 
A signed research agreement 
• 
Financial disclosure from the investigators 
• 
FDA/Competent Authority approval (as applicable to the geography) 
• 
A copy of the Ethics Board approval letter, along with the voting roster 
• 
The Ethics Board approved patient information and informed consent form 
• 
Documented training of the investigative team 
• 
Delegated Task List 
• 
Lab certificate and lab normal values/ranges 
• 
Confirmation of adequacy of equipment/facilities 
Medtronic will control the supply of devices and study materials (i.e. Investigator Site File), and will only 
ship investigational devices once the above activation criteria are met, and the site receives a formal 
activation letter from Medtronic. 
16.6 Monitoring  
Monitoring and monitoring oversight will be provided by Medtronic and detailed in a Monitoring Plan 
separate from this CIP. Representatives of Medtronic (i.e. contractors and authorized designees) may also 
act as the study monitors to the site. A list of the study monitors will be kept separate from the Monitoring 
Plan. 
The study data has been 100% source document verified at least up to the timepoint that all data are 
available to assess both primary endpoints for the pivotal study phase.  Thereafter, an adaptive, risk-based 
monitoring methodology will be applied to this study. A risk assessment was conducted to define the 
appropriate monitoring methodology and rigor. Considerations assessed include, but are not limited to: 
study objectives, purpose, design, complexity, size, critical data (including the endpoints), degree of 
deviation from standard of care and regulatory requirements. Key Risk Indicators and associated tolerance 
thresholds were defined and will be reviewed and documented by the clinical team. Additionally, critical 
data and processes were evaluated to establish the Source Data Verification (SDV) requirements.  
 
Findings from each monitoring visit will be provided to the clinical study personnel at the site. Corrective 
action will be taken to resolve any issues of noncompliance. If Medtronic finds that an investigator is not 
complying with the executed Investigator Agreement, the Investigational Plan, the applicable laws and 
regulations, or the requirements of the reviewing Ethics Board, prompt action will be taken to secure 
compliance. Medtronic will reserve the right to stop shipment of Abre systems, or suspend or terminate the 
participation of the investigator or the investigational site. 
When source data verification is performed, the monitor must have direct access to original source 
documentation or certified copies of the original source must be provided.  
If electronic source documentation is used at the site, the site must provide to the monitor: 

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• 
Direct access to the electronic medical record (e.g. the monitor is given a guest password to 
directly access the system or  
• 
Direct access to the electronic medical record by reviewing alongside appropriate study staff (e.g. 
a research coordinator) or 
• 
Certified copies of the electronic medical record.  The monitor shall verify that he/she has 
complete access to all original source required for the study (e.g. the monitor does not have a 
lower level of access to the original source documentation than the research coordinator or 
principal investigator necessary for the study). 
Further details on Monitoring are outlined in the Monitoring Plan. 
16.6.1 Site Initiation Visit 
Medtronic has conducted a site initiation visit prior to first enrollment to prepare the site to conduct the 
study, as outlined in the Monitoring Plan.  Medtronic may conduct investigator meetings in place of, or in 
addition to on-site initiation visits. Monitors (and/or other Medtronic representatives) will ensure that the PI 
and study staff (depending on their role in the study): 
• 
Have received and understand the requirements and contents of 
o 
CIP 
o 
Patient Information/Informed Consent Form (PI/ICF) 
o 
Electronic CRFs 
o 
IFU 
o 
Any written clinical investigation agreements (as appropriate) 
• 
Have access to an adequate number of Abre systems 
• 
Have been trained in the use of the Abre system 
• 
Are familiar with the responsibilities of the principal investigator 
16.6.2 Periodic Monitoring Visit 
Periodic monitoring visits will be made at all active investigational sites to ensure the safety and wellbeing 
of the subjects, verify that the investigator obligations are fulfilled, and all applicable regulations and 
guidelines are being followed per the Monitoring Plan.  
 
 

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Monitors will review at a minimum: 
• 
Data submitted on eCRFs are complete and accurate with respect to the subject source 
documentation (see Monitoring Plan for details of requirements) 
• 
Facilities remain acceptable 
• 
Subject informed consent is being obtained and properly documented 
• 
The CIP is being followed 
• 
Complete records are being maintained 
• 
Appropriate and timely reports have been made to Medtronic and/or its authorized designees and 
the Ethics Board 
• 
Device and Device inventory are controlled 
• 
The investigator is carrying out all agreed activities 
• 
Only authorized individuals are participating in the clinical study 
• 
Any equipment to be used for assessing the clinical investigation variables are maintained/calibrat
ed according to the site’s standard protocol 
16.6.3 Study Closure 
Upon study completion or at the time a site is terminated, Site Closeout Visits will be conducted, as outlined 
in the Monitoring Plan. 
After the study has been completed, medical care will be provided to the subjects upon the discretion of the 
treating physician. 
16.7 Data Management 
Study sites will designate a unique subject ID number (SID) at the point of subject enrollment, which is 
assigned by Medtronic in the EDC system. Records of the subject/SID relationship will be maintained by 
the study site. 
16.7.1 Electronic Data Capture 
Medtronic will use the Oracle Clinical Remote Data Capture database system for data collection. The 
database is located on a secure server at a Medtronic facility located in the US. All users will be trained on 
the use of the database prior to obtaining access. Once access is granted, users will have a unique User 
ID and will create their own password. Data stored electronically shall be maintained in compliance with 21 
CFR Part 11. The database for this study will be maintained according to corporate policy and record 
retention schedule. 
16.7.2 Data Collection 
It is the responsibility of the participating investigator to ensure the quality of the data being collected.  
Required data will be recorded on electronic case report forms (eCRFs) by authorized site personnel as 
indicated on the Delegated Task List. The eCRFs must be completed and/or updated to reflect the latest 
observations on the subjects participating in the study.   
 
The investigator (or authorized sub-investigator) will electronically sign each eCRF. The EDC system 
maintains an audit trail on entries, changes or corrections in eCRFs, once the eCRF is saved as complete. 
If changes are made to an already signed eCRF, the investigator shall re-sign this eCRF. 

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16.7.3 Data Validation 
Medtronic and/or assigned designee will be responsible for the processing and quality control of the data 
(data management) per the Data Management Plan, which describes the procedures for data review, 
database cleaning, and issue/resolution of data queries. Data will be collected and stored in a validated, 
password protected database. Data analysis will be conducted utilizing validated software and analysis 
programs by qualified biostatisticians.  
Study data collected will be monitored and verified against source documents in accordance with 
ISO14155:2020 guidelines and international standards. Any data discrepancies will be addressed through 
queries posted within the EDC system. 
16.8 Direct Access to Source Data/Documents  
Medtronic may conduct audits at participating clinical sites. The purpose of an audit is to verify the 
performance of the monitoring process and the study conduct, independently of the personnel directly 
involved in the study. Regulatory bodies, such as the Food and Drug Administration, may also perform 
inspections at participating sites. The investigator and/or institution shall permit Medtronic and regulatory 
bodies direct access to source data and documents during monitoring, audits and inspections. 
16.9 Confidentiality 
All information and data sent to parties involved in study conduct concerning subjects or their participation 
in this study will be considered confidential. Study sites will assign a unique subject ID number (SID) to 
each subject. Records of the subject/SID relationship will be maintained by the study site. The SID number 
is to be recorded on all study documents to link them to the subject’s medical records at the site.   
Confidentiality of data will be observed by all parties involved at all times throughout the clinical 
investigation. All data shall be secured against unauthorized access. The privacy of each subject and 
confidentiality of his/her information shall be preserved in reports and when publishing any data. 
In the US, “Protected Health Information” (PHI) will be maintained in compliance with the Health Insurance 
Portability and Accountability Act of 1996 (HIPAA). To maintain confidentiality, the subject’s name or any 
other PHI should not be recorded on any study document other than the informed consent form. This 
scenario will be covered in the Patient Information-Informed Consent Form. In the event a subject’s 
name/PHI is included for any reason, it will be blinded as applicable. In the event of inability to blind the 
identification (e.g., digital media), it will be handled in a confidential manner by the authorized personnel. 
Data relating to the study might be made available to third parties (for example in case of an audit performed 
by regulatory authorities), provided the data are treated as confidential and that the subject’s privacy is 
guaranteed. No identifiable subject information will be published. 
16.10 CIP Amendments 
Any revisions or amendments to the CIP or Informed Consent document, along with a statement of 
justification for the changes, will be submitted to all affected Regulatory Authorities (FDA, Competent 
Authority) and governing Ethics Boards, according to applicable regulations. All amendments to the CIP 
shall be agreed between Medtronic and the principal investigator(s). Approval by regulatory agencies and 
Ethics Board (where applicable) must be obtained prior to implementing a CIP revision at the site. 

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16.11 Record Retention 
All study-related documents must be retained for a period of at least two years after market-release in 
his/her region and after study closure (or longer if required by local law). Medtronic will inform the 
investigator/site when these documents are no longer required to be retained. 
No study document or image will be destroyed without prior written agreement between Medtronic and the 
investigator. The investigator should take measures to prevent accidental or premature destruction of 
documents. Should the investigator wish to assign the study records to another party or move them to 
another location, advance written notice must be given to Medtronic. 
Medtronic will retain the study records according to Medtronic corporate policy and record retention 
schedule. 
16.12 Publication and Use of Information 
The study will be registered at http://clinicaltrials.gov (and any other database per local requirement) before 
first enrollment in the study. Study data and results will be made available as required per regulations. 
Medtronic, recognizing the seminal importance of this investigation, is committed to the widespread 
dissemination of all endpoint results. A multisite publication may be prepared for publication in a scientific 
journal. The publication of the principal results from any single site experience within the study is not allowed 
until both the preparation and publication of the multisite results, and then only with written permission from 
Medtronic.  
 
Following analysis and presentation of the endpoint results, participation of investigators may be solicited 
for data analysis and abstract and manuscript preparation.  
A separate Publication Plan will provide detailed information about the Publication Committee, authorship, 
publication proposals, and requests for data. 
16.13 Suspension or Early Termination 
16.13.1 Planned Study Closure 
Study closure is defined as closure of a clinical study that occurs when Medtronic and/or regulatory 
requirements have been satisfied per the Clinical Investigation Plan and/or by a decision by Medtronic or 
regulatory authority, whichever occurs first. Study Closure is a process initiated by distribution of an initial 
study closure letter. In all geographies, the study closure process is complete upon distribution of the Final 
Report or after final payments, whichever occurs last. For each center, Ethics Board approval renewals are 
required per local/country regulation until the study closure process is complete at that center. 
 
 

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16.13.2 Early Termination or Suspension 
Termination of the Study is discontinuance, by Medtronic or by withdrawal of Ethics Board or FDA approval, 
or local regulatory body of an investigation before completion. This is possible for the whole study, for all 
centers in a country, or for a single center. Study suspension is a temporary postponement of study activities 
related to enrollment and distribution of the investigational product(s). This is possible for the whole study, 
for all centers in a country, or for a single center. 
16.13.2.1 Criteria for Study-wide Termination or Suspension 
Possible reasons for considering study suspension or termination of the study for all centers include but 
are not limited to: 
• 
AEs and device deficiencies associated with the system or product under investigation which 
might endanger the safety or welfare of subjects 
• 
Observed/suspected performance different from the product’s design intent 
• 
Decision by Medtronic or regulatory body (medically/ethically justifiable) where the study is 
operating under regulatory body authority 
16.13.2.2 Criteria for Investigator/center Termination or Suspension 
Possible reasons for clinical investigator or center termination or suspension include but are not limited to: 
• 
Failure to obtain initial Ethics Board approval or annual renewal of the study 
• 
Consistent non-compliance to the CIP (e.g. failure to adhere to inclusion/exclusion criteria, failure 
to follow subjects per scheduled follow-ups, etc.) 
• 
Lack of enrollment 
• 
Noncompliance to regulations and the terms of the Clinical Study Agreement (e.g. failure to submit 
data in a timely manner, failure to follow-up on data queries and monitoring findings in a timely 
manner, etc.) 
• 
Ethics Board suspension of the center 
• 
Fraud or fraudulent misconduct (as defined by local law and regulations) 
• 
Investigator request (e.g. no longer able to support the study) 
 
 

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16.13.3 Procedures for Planned Study Closure, Termination, or Suspension 
Medtronic will promptly inform the investigators of the reasons for a study termination or suspension and 
inform the regulatory authorities (where required per regulatory requirements). 
16.13.3.1 Medtronic-initiated 
In the case of study termination or suspension for reasons other than a temporary Ethics Board approval 
lapse, the investigator will promptly inform the Ethics Board. 
In the case of study termination, the investigator must inform the subjects and may inform the personal 
physician of the subjects to ensure appropriate care and follow-up is provided. 
In the case of a study suspension, subject enrollment must stop until the suspension is lifted by Medtronic. 
Subjects already included should continue to be followed out of consideration of their safety, rights, and 
welfare. 
16.13.3.2 Investigator-initiated 
• 
The investigator will promptly inform: 
o Medtronic and provide a detailed written explanation of the termination or suspension 
o The institution (where required per regulatory requirements) 
o The Ethics Board 
o The subjects and may inform the personal physicians of the subjects to ensure appropriate care 
and follow-up is provided 
• 
In the case of a study suspension: 
o Subject enrollment must stop until the suspension is lifted 
o Subjects already enrolled should continue to be followed out of consideration of their safety, 
rights, and welfare 
16.13.3.3 Ethics Board-initiated 
• 
The investigator will promptly inform: 
o Medtronic and provide a detailed written explanation of the termination or suspension within 5 
business days 
o The institution (where required per regulatory requirements) 
o The subjects and may inform the personal physicians of the subjects, with the rationale for the 
study termination or suspension 
• 
In the case of a study suspension: 
o Subject enrollment must stop until the Ethics Board suspension is lifted 
o Subjects already enrolled should continue to be followed in accordance with Ethics Board policy 
or its determination that an overriding safety concern or ethical issue is involved 
 
 

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17 Records and Reports 
17.1 Responsibilities of the Investigator 
The investigator is responsible for the preparation, review, and signature (as applicable), and retention of 
the records listed as follows: 
• 
All essential correspondence that pertains to the investigation 
• 
Device use/disposition records 
• 
Records of each subject’s case history and exposure to the device. Case histories include the 
eCRFs and supporting data (source documentation), including, for example: 
o Signed and dated consent forms 
o Medical records, including, for example, progress notes of the physicians, the subject’s 
hospital chart(s) and the nurses’ notes 
o All adverse event/device deficiency information 
o A record of the exposure of each subject to the Abre system (e.g., date of implant 
procedure and follow-up assessment dates) 
• 
Documentation of any deviation from the CIP, including the date and the rationale for such deviation 
• 
Signed Investigator Agreement, signed and dated curriculum vitae of the PI, sub-investigator(s) 
and key members, signed Delegated Task List 
• 
The approved CIP, PI/ICF and any amendments 
• 
Insurance certificate, where applicable 
• 
Ethics Board approval documentation and voting list 
• 
Sample eCRFs 
• 
Regulatory authority notification and approval documentation 
• 
List of Medtronic/monitor contacts 
• 
List of investigation sites 
• 
Training records 
• 
Disclosure of conflict of interest 
• 
Certification of adequacy of equipment 
• 
Lab certificate/lab normal ranges 
• 
Subject ID and Subject Identification & Enrollment Log 
• 
Medtronic’s statistical analyses and clinical investigation report 
 
The investigator may withdraw from responsibility to maintain records by transferring custody to another 
person, who will accept responsibility for record and report maintenance. The investigator is responsible for 
the preparation, review, signature, and submission of the reports listed in Table 16 and Table 17. These 
are also subject to inspection by government agencies and must be retained. 
Reports will be submitted to regulatory authorities per local reporting requirements/regulations. For Adverse 
Event reporting requirements, see Table 14. 
 
 

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Table 16: Investigator records and reporting responsibilities applicable to the US 
Investigator reports applicable to the US 
Report 
Submit To 
Description/Constraints 
Withdrawal of Ethics 
Board approval 
Medtronic 
An investigator shall report to Medtronic, within 5 
working days, a withdrawal of approval by the 
reviewing IRB of the investigator's part of an 
investigation.  (21 CFR 812.150(a)(2)). 
Progress report  
Medtronic and 
Ethics Board 
An investigator shall submit progress reports on the 
investigation to Medtronic, the monitor, and the 
reviewing IRB at regular intervals, but in no event less 
often than yearly. (21 CFR 812.150(a)(3)).   
Deviations  
Medtronic and 
Ethics Board 
An investigator shall notify Medtronic and the reviewing 
IRB of any deviation from the investigational plan to 
protect the life or physical well-being of a subject in an 
emergency. Such notice shall be given as soon as 
possible, but in no event later than 5 working days 
after the emergency occurred. Except in such an 
emergency, prior approval by Medtronic is required for 
changes in or deviations from a plan, and if these 
changes or deviations may affect the scientific 
soundness of the plan or the rights, safety, or welfare 
of human subjects, FDA and IRB in accordance with 
812.35(a) also is required. (21 CFR 812.150(a)(4)) 
Failure to obtain IC prior 
to investigational device 
use 
Medtronic and 
Ethics Board 
If an investigator uses a device without obtaining 
informed consent, the investigator shall report such 
use to Medtronic and the reviewing IRB within 5 
working days after the use occurs. (21 CFR 
812.150(a)(5)) 
Final report 
Medtronic, Ethics 
Boards 
An investigator shall, within 3 months after termination 
or completion of the investigation or the investigator's 
part of the investigation, submit a final report to 
Medtronic and the reviewing IRB. (21 CFR 
812.150(a)(6)) 
Other 
Ethics Board and 
FDA 
An investigator shall, upon request by a reviewing IRB 
or FDA, provide accurate, complete, and current 
information about any aspect of the investigation. (21 
CFR 812.150(a)(7)) 
 
 
 

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Table 17: Investigator records and reporting responsibilities applicable to Europe 
Investigator reports applicable to Europe 
Report 
Submit To 
Description/Constraints 
Withdrawal of Ethics 
Board approval 
Medtronic 
An investigator shall report to Medtronic, within 5 
working days, a withdrawal of approval by the 
reviewing Ethics Board of the investigator's part of an 
investigation. (Medtronic Requirement) 
Progress Report  
Medtronic and 
Ethics Board 
Provide if required by local law or Ethics Board. (ISO 
14155:2020) 
Deviations  
Medtronic and 
Ethics Board and 
Regulatory 
Authority 
Any deviation from the CIP shall be recorded together 
with an explanation for the deviation. Deviations shall 
be reported to Medtronic who is responsible for 
analyzing them and assessing their significance.   
Note: When relevant, Ethics Boards, CAs, or the 
appropriate regulatory authorities should be informed. 
(ISO 14155:2020) 
An investigator shall notify Medtronic and the 
reviewing Ethics Board of any deviation from the 
investigational plan to protect the life or physical well-
being of a subject in an emergency. Such notice shall 
be given as soon as possible, but in no event later 
than 5 working days after the emergency occurred. 
(Medtronic Requirement) 
Failure to obtain IC  
Medtronic and 
Ethics Board 
If an investigator uses a device without obtaining 
informed consent, the investigator shall report such 
use to Medtronic and the reviewing Ethics Board 
within 5 working days after the use occurs. (Medtronic 
Requirement) 
Final report 
Ethics Boards and 
relevant 
Authorities 
An investigator shall, within 3 months after termination 
or completion of the investigation or the investigator's 
part of the investigation, submit a final report to 
Medtronic and the reviewing Ethics Board. (Medtronic 
Requirement) 
 
 

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17.2 Responsibilities of Medtronic 
In conducting this study, Medtronic will have certain direct responsibilities and may delegate other 
responsibilities to consultants and/or contract research organizations; however, Medtronic remains 
ultimately responsible for the conduct of the study. 
Medtronic will maintain the following records, including but not limited to: 
• 
All essential correspondence related to the clinical study 
• 
Signed Investigator Agreement 
• 
Signed and dated current curriculum vitae for each investigator 
• 
Records of device shipment and disposition (shipping receipts, material destruct records, etc.) 
• 
Adverse event and device deficiency information  
• 
Device complaint documentation 
• 
All data forms, prepared and signed by the investigators, and received source documentation and 
core laboratory reports 
• 
CIP, Report of Prior Investigations and subsequent amendments 
• 
Site monitoring reports 
• 
Financial disclosure information 
• 
Study training records for site participants and internal study staff members 
• 
Contact lists of all participating investigators/investigative sites, Ethics Board information, study 
monitors and Medtronic staff members; Medtronic will maintain these lists and provide updates to 
the necessary parties.  
• 
Sample of device labeling attached to Abre system 
• 
Insurance certificates 
• 
Ethics Board approval documentation and voting list 
• 
Regulatory authority notification and approval documentation 
• 
Lab certificates / Lab normal ranges 
• 
Statistical analyses 
• 
Clinical investigation report 
Medtronic is responsible for the preparation of, the accuracy of the data contained in, the review of and 
the submission of the reports listed in Table 18 and Table 19. 
 
 

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Table 18: Medtronic records and reporting responsibilities applicable to the US 
Medtronic reports for US 
Report 
Submit To 
Description/Constraints 
Premature 
termination or 
suspension of the 
clinical investigation 
Investigators, 
Ethics Board, and 
relevant 
authorities 
Medtronic will provide prompt notification of termination or 
suspension and reason(s) to investigator and where 
required to IRB/EC and RAs. 
Unanticipated 
Adverse Device 
Effect (UADE) 
Investigators, 
Ethics Board, 
FDA, and relevant 
authorities 
Notification within 10 working days after Medtronic first 
receives notice of the effect. (21 CFR 812.150(b)(1)) 
Withdrawal of 
Ethics Board 
approval 
Investigators, 
Ethics Board, 
FDA, and relevant 
authorities 
Notification within 5 working days after receipt of the 
withdrawal of approval.  (21 CFR 812.150(b)(2))   
Withdrawal of FDA 
approval 
Investigators, 
Ethics Board, and 
relevant 
authorities 
Notification within 5 working days after receipt of notice of 
the withdrawal of approval.  (21 CFR 812.150(b)(3)) 
Investigator List 
FDA 
Submit at 6-month intervals, a current list of the names and 
addresses of all investigators participating in the 
investigation.  (21 CFR 812.150(b)(4)) 
Progress Reports 
Ethics Board and 
FDA 
Progress reports will be submitted at least annually. (21 
CFR 812.150(b)(4)(5), 812.36(f)   
Recall and device 
disposition 
Investigators, 
Ethics Board, 
relevant 
authorities, and 
FDA 
Notification within 30 working days after the request is made 
and will include the reasons for any request that an 
investigator return, repair, or otherwise dispose of any 
devices.  (21 CFR 812.150(b)(6)) 
Failure to obtain IC  
FDA 
Investigator’s report will be submitted to FDA within five 
working days of notification.  (21 CFR 812.150(b)(8)) 
Final Report 
Investigators, 
Ethics Board,  
Regulatory 
authorities upon 
request, and FDA 
Medtronic will notify FDA within 30 working days of the 
completion or termination of the investigation.  A final report 
will be submitted to the FDA, investigators, and Ethics 
Boards within six months after completion or termination of 
this study.  (21 CFR 812.150(b)(7)) 

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Report 
Submit To 
Description/Constraints 
Deviation  
Investigators 
Ensure that all deviations from the CIP are reviewed with 
the appropriate investigator(s), are reported on the case 
report forms and the final report of the clinical investigation.   
Study site specific deviations will be submitted to 
investigators periodically.   
 
 
 

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Table 19: Medtronic records and reporting responsibilities applicable to Europe 
Medtronic reports for Europe 
Report 
Submit To 
Description/Constraints 
Unanticipated Serious 
Adverse Device 
Effects (USADE) 
Ethics Board, 
investigators, 
Competent 
Authorities 
Medtronic will notify investigators and Ethics Board in all 
geographies as soon as possible, but not later than 10 
working days after Medtronic first learns of the effect.  
 
Serious Adverse 
Event (SAE) 
Ethics Board, 
Competent 
Authorities 
Submit to Ethics Board per local reporting requirement.  
Submit to Competent Authority per local reporting 
requirement.  
Serious Adverse 
Device Effects 
(SADE) 
Ethics Board, 
Competent 
Authorities 
Submit to Ethics Board per local requirement (ISO 
14155:2020).  Submit to regulatory authority as per local 
competent authority reporting timelines. 
Device Deficiency 
that might have led to 
an SADE 
Ethics Board,  
Competent 
Authorities 
Submit to Ethics Board per local requirement. Submit to 
regulatory authority as per local competent authority 
requirement. 
Premature 
termination or 
suspension of the 
clinical investigation 
Investigators, 
Ethics Board, 
Relevant Authority 
Provide prompt notification of termination or suspension 
and reason(s). (ISO 14155:2020)  
Withdrawal of Ethics 
Board approval 
Investigators, 
Ethics Board, 
Relevant Authority 
All applicable investigators will be notified only if required 
by local laws or by the Ethics Board. 
Withdrawal of 
Competent Authority 
approval 
Investigators, 
Ethics Board, and 
Regulatory 
Authority 
Investigators and Ethics Boards will be notified only if 
required by local laws or by the Ethics Board. 
Progress Reports 
Ethics Board, 
Regulatory 
Authority (if 
required) 
This will be submitted to the Ethics Board and/or 
Regulatory Authority if required.  
Final Report 
Investigators, 
Ethics Board, and 
Regulatory 
Authority (if 
required) 
The investigator shall have the opportunity to review and 
comment on the final report.  If a clinical investigator does 
not agree with the final report, his/her comments shall be 
communicated to the other investigator(s).  The principal 
clinical investigator in each center shall sign the report. 
(ISO 14155:2020) 

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Medtronic reports for Europe 
Report 
Submit To 
Description/Constraints 
Deviation  
Investigators 
Ensure that all deviations from the CIP are reviewed with 
the appropriate clinical investigator(s), are reported on the 
case report forms and the final report of the clinical 
investigation.   
Site specific deviations will be submitted to investigators 
quarterly. (ISO 14155:2020) 
Significant new 
information 
Ethics Board and 
Regulatory 
Authority 
Ensure that the Ethics Boards and Regulatory Authorities 
are informed of significant new information about the 
clinical investigation (ISO 14155:2020) 
17.3 Final Report 
Medtronic will provide a final written report of the study results according to applicable regulations, and will 
include: 
• 
Identification of the device(s) 
• 
Description of the methodology and design of the clinical investigation 
• 
Summary of the deviations from the CIP 
• 
Statistical analysis of the study data 
• 
Critical appraisal of the aims of the study 
 
Medtronic will submit this final report to the PIs for review and comment, and shall document and 
disseminate discrepant comments to all study PIs. The Lead Principal Investigators will provide their 
signatures, indicating their agreement with the content of the final report. 
All required study reports will be submitted to regulatory authorities and Ethics Boards per local reporting 
requirements/regulations. 
 
 

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18 Report of Prior Investigations of the Device and Justification for the 
Study 
A clinical evaluation has been performed to verify the clinical performance and safety of the Abre stent 
system, according to their intended use, and that the benefits of the devices outweigh associated risks.  
Pre-clinical testings met the defined acceptance criteria in-line with applicable International standards, 
thereby demonstrating specifications and all acceptance criteria set for the devices. The Report of Prior 
Investigations requirements will be available in the Investigator’s Brochure separate from this CIP. 
Risk management activities for the Abre stent system assessed the risk associated with the design, 
process, and clinical use of the proposed device. It was concluded that any risks identified as part of this 
activity are considered acceptable by the Medtronic Risk Management Team when weighed against the 
benefits to the patient and are compatible with a high level of protection of health and safety.  
 
Based on the assessment of the performance of Abre stent; including the state of the art for endovenous 
stenting, the benefits of the use of this stent outweigh the associated overall residual risk and confirm the 
conclusion of the risk assessment that the residual risk associated with the Medtronic Abre stent is deemed 
to be acceptable. 
 
The use of human subjects is required as part of an IDE clinical study to evaluate the safety and 
effectiveness of the use of device in humans which includes evaluations that cannot be made using bench 
testing. 
The results from the clinical evaluation and the need for an IDE clinical study evaluating safety and 
effectiveness of the Abre system use in humans, justifies the conduct of the ABRE Study. 
 
 

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19 References 
1. Revision of the venous clinical severity score: Venous outcomes consensus statement: Special 
communication of the American Venous Forum Ad Hoc Outcomes Working Group. Vasques MA, Rabe 
E, McLafferty RB, Marston WA, Gillespie D, Meissner MH, Rutherford RB. s.l. : J Vasc Surg, 
2010. 52:1387-96. 
2. 'Real' epidemiology of varicose veins and chronic venous diseases: the San Valentino Vascular 
Screening Project. Cesarone MR, Belcaro G, Nicolaides AN, et al. s.l. : Angiology, 2002. 53:119-30. 
3. Unexpected major role for venous stenting in deep reflux disease. Raju S, Darcey R, Neglen P. s.l. : 
J Vasc Surg, 2010. 51:401-8; discussion 8. 
4. Iliac-femoral venous stenting for lower extremity venous stasis symptoms. Alhalbouni S, Hingorani 
A, Shiferson A, et al. s.l. : Ann Vasc Surg, 2012. 26:185-9. 
5. Chronic venous disease in an ethnically diverse population: the San Diego Population Study. Criqui, 
MH, et al. 5, s.l. : Am J Epidemiol., 2003, Vol. 158. 448-56. 
6. Chronic venous insufficiency: clinical and duplex correlations. The Edinburgh Vein Study of venous 
disorders in the general population. Ruckley, CV, et al. 3, s.l. : J Vasc Surg, 2002, Vol. 36. 520-5. 
7. The influence of environmental factors in chronic venous insufficiency. Jawien, A. 1, s.l. : Angiology, 
2003, Vol. 54. S19-31. 
8. The epidemiology of chronic venous insufficiency and varicose veins. Beebe-Dimmer, JL, et al. 3, 
s.l. : Ann Epidemiol., 2005, Vol. 15. 175-84. 
9. Analysis of 1,338 Patients with Acute Lower Limb Deep Venous Thrombosis (DVT) Supports the 
Inadequacy of the Term "Proximal DVT". De Maeseneer, MG, et al. 3, s.l. : Eur J Vasc Endovasc Surg., 
2016, Vol. 51. 415-20. 
10. Predictors of recurrence after deep vein thrombosis and pulmonary embolism: a population-based 
cohort study. Het JA, Mohr DN, Silverstein MD, Petterson TM, O'Fallon WM, Melton LJ, 3rd. s.l. : 
Arch Intern Med, 2000. 160:761-8. 
11. The long-term clinical course of acute deep venous thrombosis. Prandoni P, Lensing AW, Cogo A, 
et al. s.l. : Ann Intern Med, 1996. 125:1-7. 
12. Initial and long-term treatment of deep venous thrombosis: recent clinical trials and their impact on 
patient management. Liew A, Douketis J. s.l. : Expert Opin Pharmacother, 2013. 14:385-96. 
13. Home Treatment of Deep Venous Thrombosis According to Comorbid Conditions. Stein PD, Matta F, 
Hughes MJ. s.l. : Am J Med, 2015. 
14. Low molecular weight heparin versus oral anticoagulants in the long-term treatment of deep venous 
thrombosis. Lopez-Beret P, Orgaz A, Fontcuberta J, et al. s.l. : J Vasc Surg, 2001. 33:77-90. 
15. Use of percutaneous aspiration thrombectomy vs. anticoagulation therpay to treat acute iliofemoral 
venous thrombosis. Cakir V, Gulcu A, Akay E, et al. s.l. : Cardiovasc Intervent Radiol, 2014. 37:969-
76. 
16. Catheter-directed thrombolysis for lower extremity deep venous thrombosis: report of a national 
multicenter registry. Mewissen MW, Seabrook GR, Meissner MH, Cynamon J, Labropoulos N, 
Haughton SH. s.l. : Radiology, 1999. 37:969-76. 
17. Combined catheter-directed thrombolysis and iliac vein recanalization for iliac vein compression 
syndrome with secondary acute deep vein thrombosis: effectiveness and long-term outcome. Cui YF, Fu 
YF, Liu HT, Xu H. s.l. : Int Angiol, 2015. 

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18. Outcome of venous stenting following catheter directed thrombolysis for acute proximal lower limb 
venous thrombosis: a prospective study with venous Doppler follow-up at 1-year. Srinivas BC, Patra S, 
Reddy B, Nagesh CM, Agarwal N, Manjunath CN. s.l. : Cardiovasc Interv Ther, 2015. 30:320-6. 
19. Our Short-Term Resulta with Percutaneous Mechanical Thrombectomy for Treatment of Acute Deep 
Vein Thrombosis. Ozpak B, Ilhan G, Ozcem B, Kara H. s.l. : Thorac Cardiovasc Surg, 2015. 
20. Catheter-directed thrombolysis and stenting in the treatment of iliac vein compression syndrome with 
acute iliofemoral deep vein thrombosis: outcome and follow-up. Xue GH, Huang XZ, Ye M, et al. s.l. : 
Ann Vasc Surg, 2014. 28:957-63. 
21. Stenting is the "Method-of-Choice" to treat iliofemoral venous outflow obstruction. P, Neglen. s.l. : J 
Endovasc Ther, 2009. 16:492-3. 
22. Editor's Choice-- A Systematic Review of Endovenous Stenting in Chronic Venous Disease Secondary 
to Iliac Vein Obstruction. Seager MJ, Busuttil A, Dharmarajah B, Davies AH. s.l. : Eur J Vasc 
Endovenous Surg, 2016. 51:100-20. 
23. Management of obstruction of the femoroiliocaval venous system. American College of Phlebology. 
[Online] 2015. [Cited: 11 15, 2015.] 
24. Clinical practice guidelines of the Society for Vascular Surgery (SVS) and the American Venous Forum 
(AVF)--Management of venous leg ulcers. O'Donnell TF, Jr., Passman MA. s.l. : J Vasc Surg, 2014. 
60:1S-2S. 
25. Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and 
chronic thromboembolic pulmonary hypertension: a scientific statement from the American Heart 
Association. Jaff MR, McMurtry MS, Archer SL, et al. s.l. : Circulation, 2011. 123:1788-830. 
26. Early thrombus removal strategies for acute deep venous thrombosis: clinical practice 
guidelines of the Society for Vascular Surgery and the Anmerican Venous Forum. Meissner 
MH, Gloviczki P, Comerota AJ, et al. s.l. : J Vasc Surg, 2012. 55:1449-62. 
27. The postthrombotic syndrome: evidence-based prevention, diagnosis, and treatment strategies: a 
scientific statement from the American Heart Association. Kahn SR, Comerota AJ, Cushman M, et al. 
s.l. : Circulation, 2014. 130-1636-61. 
28. Safety and Effectiveness of Stent Placement for Iliofemoral Venous Outflow Obstruction: Systematic 
Review and Meta-Analysis. Razavi MK, Jaff MR, Miller LE. s.l. : Circ Cardiovasc Interv, 2015. 
8:e002772. 
29. Stenting for chronic venous obstructions a new era. de Graaf R, Arnoldussen C, Wittens CH. s.l. : 
Phlebology, 2013. 28 Suppl 1:117-22. 
30. May-Thurner syndrome: update and review. Mousa AY, AbuRahma AF. s.l. : Ann Vasc Surg, 2013. 
27:984-95. 
31. Multifaceted management of the postthrombotic syndrome. Nayak L, Vedantham S. s.l. : Semin 
Intervent Radiol, 2012. 29:16-22. 
32. Treatment of iliac-caval outflow obstruction. S, Raju. s.l. : Semin Vasc Surg, 2015. 28:47-53. 
33. Stenting for chronic obstructive venous disease: A current comprehensive meta-analysis and 
systematic review. Wen-da W, Yu Z, Yue-Xin C. s.l. : Phlebology, 2015. 
34. Iliocaval reconstruction in chronic deep vein thrombosis. DM, Williams. s.l. : Tech Vasc Interv 
Radiol, 2014. 17:109-13. 
35. Effects of race and ethnicity on the incidence of venous thromboembolism. White RH, Keenan CR. 
s.l. : Thrombosis Research, 2009;123:Suppl.4:S11-17. 

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36. Performance Goals and Endpoint Assessments for Clinical Trials of Femoropopliteal Bare Nitinol Stents 
in Patients with Symptomatic Peripheral Arterial Disease. Rocha-Singh, Jaff, Crabtree, Block, Ansel. 
s.l. : Catheterization and Cardiovascular Interventions, 2007. 69:910-919. 
37. VETO Study investigators. VEINS-QOL/Sym questionnaire was a reliable and valid disease-specific 
quality of life measure for deep venous thrombosis. Kahn SR, Lamping DL, Dcruet T, Arsenault L, 
Miron MJ, Roussin A, Desmarais S, Joyal F, Kasis J, Solymoss S, Desjardins L, Johri M, Shrier 
I. s.l. : J Clin Epidemoil, 2006. 59(10):1049-56. 
38. www.fda.gov. [Online] Oct 26, 2016. 
https://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM126396.pdf. UCM126396. 
39. The Fundamentals of Phlebology: Venous Disease for Clinicians. Fronek HS, Bergan JJ, et al. 2004. 
40. Late hemodynamic sequelae of deep venous thrombosis. Raju S, Fredericks RK. 1986, J Vasc Surg. 
41. High prevalence of nonthrombotic iliac vein lesions in chronic venous disease: a permissive role in 
pathogenicity. Raju S, Neglen P. s.l. : J Vasc Surg, 2015, Safety and Effectiveness of Stent Placement 
for Iliofemoral Venous Outflow Obstruction, p. 1. 2006;44:136-143, discussion 144. 
42. Iliac vein compression as risk factor for left- versus right-sided deep venous thrombosis:case-control 
study. Narayan A, Eng J, Carmi L, McGrane S, Achmed M, Sharret AR, Streiff M, Coresh J, 
Powe N, Hong K. 2015, Safety and Effectiveness of Stent Placement for Iliofemoral Venous Outflow 
Obstruction, p. 1. 2012;265:949-957. doi 10.1148/radiol.12111580. 
43. Iliocaval compression syndrome. Taheri SA, Williams J, Powell S, Cullen J, Peer R, 
Nowakowski P, Boman L, Pisano S. s.l. : Am J Surg, 2015, Safety and Effectiveness of Stent 
Placement for Iliofemoral Venous Outflow Obstruction, p. 1. 1987;154:169-172. 
44. Iliofemoral venous stenting extending into the femoral region: initial clinical experience with the 
purpose-designed Zilver Vena stent. O'Sullivan. s.l. : J Cardiovasc Surg, 2013. 54:255-61. 
 

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20 Appendices  
Appendix A Scientific Literature Search 
Literature Search Objective and Strategy 
Iliofemoral venous obstruction has been recognized with increasing frequency as the underlying cause of lower 
extremity symptoms including edema, pain, skin changes and, in advanced cases, ulceration. When the presentation 
is that of acute deep venous thrombosis (DVT), swelling and pain predominate. By contrast, when the process is 
chronic the symptoms include skin and subcutaneous tissue changes that can progress to ulceration. The latter 
pattern of symptoms comprises the post-thrombotic syndrome. 
Even today, most patients presenting with acute iliofemoral DVT are treated with anticoagulation alone.1-3 Patients 
with post-thrombotic symptoms are often followed with non-interventional management consisting of compression 
hose and elevation of the extremity. Pharmacologic thrombolysis and mechanical thrombectomy have been used to 
restore venous patency in the setting of acute DVT, and venous stenting has emerged as a useful intervention to 
address the underlying venous stenosis in such patients. As well, venous stenting has been employed successfully 
as a primary intervention in patients presenting with symptomatic chronic iliofemoral venous occlusion or non-
thrombotic stenosis. 
Despite the increasing use of stents in the venous circulation, most studies have employed stents originally designed 
for arteries or for biliary indications. For this reason, most publications comprise single-center retrospective series.  
Prospective, protocol-driven, monitored studies with core laboratory analyses of imaging studies are rare. This 
observation must be taken into account when assessing the frequency of clinical events; with the possibility of 
underreporting due to the retrospective nature of data collection. 
The objective of this literature search is to provide an up-to-date review of published data on the safety and 
effectiveness of stenting for iliac and iliofemoral venous disease.g Currently, no device is approved for the iliac vein 
indication in the United States, although several are CE marked and available outside the US. This literature search 
will evaluate the body of existing literature on the use of predicate stents used in the iliofemoral venous segment, and 
will include data on stents irrespective of whether or not they were cleared or approved for marketing at the time of 
the study or thereafter. 
Currently, there are several societal guideline documents on the standard of care for the treatment of iliofemoral 
venous lesions. Most of these are heavily weighted toward the treatment of acute DVT. A guideline document 
published by the American College of Phlebology in October 20154 supplements a 2014 clinical practice guidelines 
document from the Society of Vascular Surgery and the American Venous Forum for the management of venous leg 
ulcers,5 and other earlier societal guideline documents.6-8  While many of the guideline documents are focused on the 
management of acute thrombotic venous obstruction, some caveats regarding venous stenting have been included. 
As well, several review articles have been published, some recently, providing some insight to current practice in the 
field.9-15 For the most part, the guideline documents and review articles are based upon data from original research 
publications. This Scientific Literature Review is limited to a review of these original publications and the data 
incorporated therein. 
 
 
 
 
g For the purposes of this review, the iliac venous segment is defined as the common iliac vein (CIV) and external iliac vein (EIV), and includes 
treatment of the most caudal inferior vena cava with a stent to obtain complete coverage of a central common iliac vein lesion. It does not include 
treatment of isolated IVC lesions or extension of CIV lesions beyond the first few millimeters into the IVC.  The iliofemoral venous segment is 
defined as the iliac venous segment and the common femoral vein, but does not include disease progressing into the profunda femoral vein or the 
femoral vein. 

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The specific objectives of the search include the following: 
a) The primary objective of this search is to evaluate the clinical safety and effectiveness of stents used in the iliac 
and iliofemoral venous segments, including predecessor, equivalent and current devices. 
• 
Collected data will include the frequency of device-related and certain other adverse events that occur at the 
index procedure and over follow-up. The effectiveness of the devices will be characterized by the patency 
rates; primary, primary-assisted and secondary, when available. 
• 
Safety and effectiveness data will be limited to one-year follow-up in most cases, noting the paucity of longer-
term follow-up data in published studies. 
• 
Performance with respect to symptom resolution and Quality of Life (QoL) is covered in this document to the 
extent that the original publications included standard measures of symptomatic improvement and QoL. A 
minority of publications include data on baseline and post-procedure assessment of QoL indices and the 
number of indices accounts for a relatively small number of publications with outcome on any one index. 
b) As a secondary objective of the review, outcome data will be characterized by the presenting clinical scenario; 
acute, post-thrombotic, or non-thrombotic.h Therapeutic outcome may vary considerably in these different 
categories of presentation, so where possible, evaluations will be subcategorized by presentation. 
c) Secondary objectives include the analysis of the natural history of iliac and iliofemoral venous segment disease 
left untreated or managed medically without the use of balloon angioplasty or implanted devices. While the 
outcome after medical management of iliofemoral venous obstruction is included in this literature review, acute 
cases are over-weighted, with a paucity of data on the non-interventional treatment of chronic iliofemoral venous 
disease. 
Review of Literature Search Results 
This literature review included peer reviewed publications identified by the web-based search strategy with the 
National Library of Medicine National Center for Biotechnology Information PubMed resource through a search date 
of October 1, 2016 (Figure1).  
 
Figure 1. Search strategy 
 
 
h For the purposes of this review, the acute subset will be defined when intraluminal thrombus is present and symptoms are of ≤30 days in 
duration. The post-thrombotic subset includes those patients with a history of deep venous thrombosis in the iliofemoral segment or those where 
intraluminal thrombotic obstruction is observed on imaging studies with symptoms beginning >30 days prior to presentation. The non-thrombotic 
subset includes those patients without evidence of intraluminal thrombus. The most common presentation in this group is left central common iliac 
vein stenosis from the May-Thurner syndrome. 

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PubMed was the primary source for the review; supplemented with references from review articles published 
between January 1 and October 1 of 2016.9,13,14 With one exception, only full original article publications were 
included in the search results. The exception comprised a non-indexed abstract presented at a scientific meeting but 
where no manuscript has been published.16 
The search criteria included the following high-level characteristics: 
a) Citations where any field contained the phrase “venous stent” or “vein stent”. 
b) Citations where any field contained the word “iliac” or “femoral”. 
c) Citations with the word “endovascular” in the title were excluded.i 
d) Human clinical studies; animal and in vitro studies were excluded. 
e) Studies with a sample size of less than ten (10) patients with attempted stenting of the iliofemoral venous 
segmentj were excluded. 
f) 
Studies where outcome could not be subcategorized by stented versus non-stented patients were not 
included. 
g) Review articles were not included. 
h) When two or more publications reported outcome from the same patients, only the latest (or in some 
cases the most complete) article was included. 
i) 
Non-English publications were excluded. 
The search was repeated twice; once for citations where any field contained the word “iliac” and once for citations 
containing the word “femoral”. Duplications in these two datasets were removed thereafter, since many citations 
contained the words iliac and femoral. Once a list of references meeting the search criteria was identified, each full-
length article was obtained. The publications were reviewed; excluding those where stented and non-stented patients 
were studied but outcome was not stratified by the stented versus non-stented cohorts. In aggregate, the search and 
selection process was conducted to include all relevant scientific literature, both favorable and unfavorable with 
respect to iliofemoral venous stenting. 
The search strategy results are listed in Table I. The search strategies yielded 635 citations; 323 iliac and 312 
femoral. Among these, however, there were many duplicates that were identified in the iliac and the femoral 
searches (search step 3 in Table I). After exclusion of the 132 duplicates, 503 abstracts remained. 
Next, the text of each of the 503 abstracts were manually reviewed. A total of 218 of 503 abstracts were excluded 
based on the text of the abstract alone, leaving  285 full publications where review was necessary. After review of 
each full article, 223 were excluded, based upon the reasons listed in Table III). This process left a total of 62 
publications appropriate for the iliofemoral venous stenting literature review. 
As an added measure to identify pertinent publications, a review of the Cochrane Library was performed (search step 
14 in Table I). Two searches were performed; one for “venous stent” and one for “vein stent.” A total of 140 and 261 
citations were returned, respectively. The titles and/or abstracts of these citations were manually reviewed and 16 
potential articles were identified. After review of these 16 articles, one article, a study performed in China, was found 
to be relevant. This study was included in the literature review, raising the total number of articles on iliofemoral 
venous stenting to 63.  
An additional search of publications on patients with medically-managed iliofemoral venous obstruction was also 
performed. A total of 9 suitable articles were found; 6 of which comprised publications with stented versus non-
stented treatment arms and were already included in the main literature search outlined above. The publications on 
medical management of iliofemoral obstruction are reviewed separately in this document. Including the 3 additional 
articles on medical management alone. In sum, a total of 66 articles comprised the full literature search. 
 
 
i A preliminary review found approximately 100 citations with the word endovascular in the title and almost all were on the topic of endovascular 
aneurysm repair. The few that were relevant to iliofemoral venous stenting were added back into the search cohort in the manual addition step. 
j The iliofemoral venous segment is defined as the common iliac, external iliac, and common femoral veins. Patients with stent placement limited to 
the femoral vein or other veins peripheral to the common femoral vein were excluded from the review. Publications were excluded when 
iliofemoral and more peripheral stenting was studied but where outcome could not be stratified to estimate results specific to the iliofemoral 
venous segment. 

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Appraisal of literature 
Clinical research on the use of stents in the iliofemoral venous segment has, by and large, comprised single-center, 
retrospective analyses. Few prospective studies have been performed, and randomized clinical trials are non-
existent. The preponderance of retrospective studies accounts for a less robust level of evidence than is 
characteristic of prospective, protocol-based trials. Further complicating the issue, most publications report results 
from a diverse patient population and do not stratify outcome by category of presentation. 
For the purposes of analysis, it has been common to group patients by the presenting clinical category for the 
procedure. In this regard, patients undergoing iliofemoral venous stenting can be grouped into the following three 
categories; acute, post-thrombotic, and non-thrombotic. 
 
a) Acute. This category comprises patients presenting with acute iliofemoral DVT. For the purposes of this 
review, acute has been defined as venous thrombus that has formed within 30 days of treatment. Since it 
is often impossible to determine the exact timing of the process, acute is defined as the onset of 
symptoms ≤30 days before treatment, or, in the absence of data on the onset of symptoms, the 
appearance of acute thrombus on imaging studies has been used as a surrogate.k In general, patients 
presenting with acute DVT were treated with thrombus management technologies such as catheter-
directed, intravenous thrombolysis, percutaneous or mechanical or open surgical thrombectomy, followed 
by deployment of venous stents to address the stenosis unmasked after thrombus removal. 
b) Post-thrombotic. The post-thrombotic category comprises those patients who have experienced a 
thrombotic occlusion of the iliofemoral venous segment but present >30 days after occurrence. In general, 
such patients present months or years after the DVT which, in many cases, may have gone unnoticed by 
the patient. Such patients generally have an abundance of collateralization around the occlusion and 
thrombus, when it remains, is often well-organized and resistant to pharmacologic or mechanical 
thrombectomy. Patients presenting with post-thrombotic iliofemoral venous occlusion are most often 
treated with recanalization and stenting alone, without the use of pre-stenting thrombolysis or 
thrombectomy. Many post-thrombotic patients have an underlying left common iliac vein stenosis (May-
Thurner Syndrome) that has gone on to thrombosis, which then propagates to the hypogastric vein orifice, 
the external iliac vein and/or the common femoral vein. 
c) Non-thrombotic. The non-thrombotic category is defined by imaging findings. These patients have a 
stenosis in the iliofemoral venous segment, usually but not always at the central aspect of the left 
common iliac vein (May-Thurner Syndrome). This category can be difficult to define with precision, since a 
significant percentage of the population has a mild to moderate stenosis at the central left common iliac 
vein. Where inclusion/exclusion criteria of a prospective trial may be able to differentiate symptomatic 
stenosis from asymptomatic stenosis, retrospective case series without well-defined criteria may include 
treated patients who may have had lower extremity symptoms from an alternate etiology. 
 
 
 
 
k The appearance of intraluminal thrombus on duplex ultrasound, venography, CTV and other imaging studies has not been well-defined. While 
findings such as an enlarged, occluded vein and an absence of an abundant collateral network are suggestive of an acute process, the literature 
review could not apply strict criteria to the determination of acute DVT. For this reason, the categorization of the authors was utilized, without 
modification. 

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Table I. Search strategy and initial results 
Step 
Operator 
Field 
Term 
Iliac Search 
Femoral 
Search 
1 
 
All fields 
venous stent 
8,894 
2 
or 
All fields 
vein stent 
10.037 
3 
and 
All fields 
iliac/femoral 
672 
656 
4 
and 
Language 
English 
600 
575 
5 
not 
Title 
fistula 
544 
537 
6 
not 
Title 
aneurysm 
523 
514 
7 
not 
Title 
artery 
501 
453 
8 
not 
Title 
transplant 
494 
450 
9 
not 
Title 
endovascular 
384 
369 
10 
not 
All fields 
animal 
323 
312 
Abstracts Identified from Iliac & Femoral Searches 
635 
11 
Deletions of Duplicates from Iliac & Femoral Searches 
(132) 
Total Abstracts Reviewed 
503 
12 
Deletions after Review of Abstracts (Table II) 
(218) 
Total Full Publications Reviewed 
285 
13 
Deletions after review of Full Publications (Table III) 
(223) 
14 
Addition of Cochrane Publications 
1 
Total Publications Included in Data Analysis 
63 

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A total of six groups were defined, as follows:l,m 
• 
Group 1: Series with ≥90% of acute cases with post-stenting outcome reported (N = 22) 
• 
Group 2: Series with a mix of acute and chronic (post-thrombotic and/or non-thrombotic) cases, 
where outcome was not stratified by category of presentation (N = 14) 
• 
 Group 3: Series with ≥90% chronic cases but where outcome was not subcategorized by post-
thrombotic or non-thrombotic etiology (N = 8) 
• 
Group 4: Series with ≥90% of cases with non-thrombotic etiology (N = 6) 
• 
Group 5: Series with ≥90% of cases with post-thrombotic etiology (N = 18) 
• 
Group 6: Series comprising medically-managed iliofemoral venous obstructions; either as a 
single publication or as a separately-described treatment arm of a study that includes stented 
patients (N = 9) 
The publications identified in this review were grouped by study design; retrospective vs. prospective, single center 
vs. multicenter, single-arm vs. dual or multiple arms, and randomized vs. non-randomized. Publications were also 
categorized by treatment; stented, balloon angioplasty alone, or medical management. Publications that described 
open surgical thrombectomy with stenting of unmasked lesions were not included in this analysis.  
 
 
 
 
l The 6 groups have overlap; some articles report data on more than one indication. Where outcome was stratified by indication, the article is 
included more than once, with data reported separately for each indication. Where results are not segregated, however, data is reported from the 
article as a whole (Groups 2 and 3). 
m The number of stent series is 68, comprising 63 unique stent articles among which four articles reported results from more than a single 
indication. For example, an article that separately reported outcome of stented patients with a) non-thrombotic and b) post-thrombotic chronic 
venous obstruction would appear as one article with two series; reported within Groups 4 and 5, respectively. Among the 63 articles, three articles 
separately reported data from 2 indications (series) and one article separately reported data from 3 indications – for a total of 68 (63 + 5) total stent 
series. 
These numbers do not include series from medically-managed, non-stented patients. In all, there were nine articles that reported data on 
medically-managed patients. Among these, six articles also separately reported data on stented patients and three reported data on medically-
managed patients alone. Therefore, including medically-managed articles/series, the total number of articles in the literature review is 66 (66 + 3) 
and the total number of series is 77 (68 + 9). 

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Table II. Reasons for exclusions among 503 abstracts identified by the search 
strategy 
Category of Publication 
Publications Excluded 
Number 
Percent 
Coronary, heart and valves 
70 
32.1% 
Arterial and aneurysms 
57 
26.1% 
Stents in upper extremity veins 
26 
11.9% 
Hemodialysis access 
14 
6.4% 
Trauma (including iatrogenic) 
10 
4.6% 
Tumor obstruction of veins 
9 
4.1% 
Arteriovenous fistulae/malformation 
6 
2.8% 
No stents in series 
5 
2.3% 
TIPS and hepatic transplantation 
5 
2.3% 
Transplantation (not hepatic) 
4 
1.8% 
Vena caval filters 
3 
1.4% 
Ureteral stents 
3 
1.4% 
Pre-clinical study 
3 
1.4% 
Pulmonary embolism/ hypertension 
3 
1.4% 
Total Excluded 
218 
100.0% 
 
 

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. 
Table III. Exclusion of 163 citations after review of full text 
Reason for exclusion 
Citations (%) 
Fewer than 10 patients 
89 (39.9%) 
Reviews and meta-analyses 
28 (12.6%) 
Overlapping patient series 
20 (9.0%) 
Outcome not stratified by stented and non-stented patients  
11 (4.9%) 
Commentaries and editorials 
7 (3.1%) 
Open surgical revascularization 
6 (2.7%) 
Treatment of stent complications  
6 (2.7%) 
Imaging studies and studies without venous stents 
30 (13.5%) 
Obstruction from tumor or radiation 
5 (2.2%) 
Traumatic obstruction 
3 (1.3%) 
Inferior Vena Cava stenting (primary or principal procedure) 
7 (3.1%) 
Congenital and pediatric series 
3 (1.3%) 
Animal studies 
3 (1.3%) 
Guideline documents 
5 (2.2%) 
Total Excluded 
223 (100.0%) 

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Table IV. Listing of iliofemoral venous stenting publications with key endpoints 
Reference 
Number 
Lead Author 
Publication 
Year 
Indication 
Design 
N 
1-Year 
Patency 
30-Day Safety Endpoints 
Mortality 
Stent  
Thrombosis 
Stent 
Migration 
Pulmonary 
Embolism 
Major 
Bleed 
Composite 
MAE 
12 
Nayak L 
2012 
Chronic, Post-Thrombotic 
Retrospective 
39 
69.6% 
0.0% 
NS 
NS 
0.0% 
0.0% 
0.0% 
16 
Hager ES 
2012 
Acute 
Retrospective 
38 
94.7% 
NS 
NS 
NS 
NS 
NS 
NS 
16 
Hager ES 
2012 
Chronic, Non-Thrombotic 
Retrospective 
15 
100.0% 
NS 
NS 
NS 
NS 
NS 
NS 
17 
AbuRahma AF 
2001 
Acute 
Prospective 
18 
83.3% 
0.0% 
16.7% 
NS 
0.0% 
11.1% 
27.8% 
18 
Alhalbouni S 
2012 
Chronic, Mixed NT & PT 
Retrospective 
53 
48.2% 
NS 
3.8% 
NS 
NS 
1.9% 
5.7% 
19 
Bjarnason H 
1997 
Mixed, Acute and Chronic 
Retrospective 
29 
55.3% 
NS 
NS 
NS 
3.4% 
10.3% 
13.8% 
20 
Blattler W 
1999 
Chronic, Post-Thrombotic 
Retrospective 
14 
78.6% 
NS 
21.4% 
NS 
NS 
NS 
21.4% 
21 
Cakir V 
2014 
Acute 
Prospective 
14 
85.7% 
NS 
7.1% 
NS 
7.1% 
NS 
14.3% 
22 
Cho H 
2015 
Acute 
Retrospective 
48 
25.0% 
NS 
NS 
0.0% 
NS 
NS 
0.0% 
23 
de Wolf MA 
2015 
Chronic, Mixed NT & PT 
Retrospective 
75 
96.3% 
NS 
NS 
NS 
NS 
NS 
NS 
24 
Delis KT 
2007 
Chronic, Post-Thrombotic 
Retrospective 
16 
NS 
0.0% 
6.3% 
NS 
0.0% 
12.5% 
18.8% 
25 
Gao B 
2011 
Acute 
Retrospective 
25 
92.0% 
0.0% 
NS 
NS 
0.0% 
0.0% 
0.0% 
26 
George R 
2014 
Chronic, Mixed NT & PT 
Retrospective 
38 
97.7% 
0.0% 
2.6% 
NS 
0.0% 
0.0% 
2.6% 
27 
Husmann MJ 
2007 
Acute 
Retrospective 
11 
90.9% 
0.0% 
0.0% 
NS 
0.0% 
0.0% 
0.0% 
28 
Jeon UB 
2010 
Acute 
Retrospective 
30 
83.3% 
NS 
3.3% 
NS 
NS 
NS 
3.3% 
29 
Juhan C 
2001 
Mixed, Acute and Chronic 
Retrospective 
15 
86.7% 
NS 
6.7% 
NS 
NS 
NS 
6.7% 
30 
Kim JY 
2006 
Acute 
Retrospective 
18 
88.2% 
NS 
0.0% 
NS 
0.0% 
5.6% 
5.6% 
31 
Knipp BS 
2007 
Chronic, Mixed NT & PT 
Retrospective 
58 
74.1% 
0.0% 
NS 
1.7% 
0.0% 
0.0% 
1.7% 
32 
Kolbel T 
2007 
Acute 
Retrospective 
29 
80.8% 
0.0% 
NS 
5.0% 
0.0% 
6.9% 
11.9% 
33 
Kurklinsky AK 
2012 
Chronic, Post-Thrombotic 
Retrospective 
89 
81.3% 
NS 
1.1% 
NS 
NS 
NS 
1.1% 
34 
Kwak HS 
2005 
Acute 
Retrospective 
22 
95.5% 
NS 
NS 
4.5% 
NS 
4.5% 
9.1% 
35 
Kwon SH 
2009 
Acute 
Retrospective 
22 
95.5% 
0.0% 
0.0% 
NS 
0.0% 
0.0% 
0.0% 
36 
Lamont JP 
2002 
Mixed, Acute and Chronic 
Retrospective 
15 
100.0% 
0.0% 
0.0% 
NS 
0.0% 
0.0% 
0.0% 
37 
Lee KH 
2006 
Acute 
Retrospective 
20 
90.0% 
0.0% 
0.0% 
NS 
0.0% 
0.0% 
0.0% 
38 
Matsuda A 
2014 
Chronic, Post-Thrombotic 
Retrospective 
13 
90.9% 
0.0% 
7.7% 
NS 
0.0% 
0.0% 
7.7% 
39 
Meng QY 
2013 
Acute 
Prospective 
45 
86.7% 
0.0% 
NS 
NS 
0.0% 
NS 
0.0% 
40 
Mewissen MW 
1999 
Mixed, Acute and Chronic 
Prospective 
99 
80.8% 
NS 
NS 
NS 
1.0% 
11.1% 
12.1% 
41 
Nazarian GK 
1996 
Mixed, Acute and Chronic 
Retrospective 
29 
65.5% 
NS 
NS 
NS 
NS 
NS 
NS 
42 
Neglen P 
2007 
Chronic, Non-Thrombotic 
Retrospective 
459 
95.0% 
0.0% 
0.0% 
NS 
NS 
0.2% 
0.2% 

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Reference 
Number 
Lead Author 
Publication 
Year 
Indication 
Design 
N 
1-Year 
Patency 
30-Day Safety Endpoints 
Mortality 
Stent  
Thrombosis 
Stent 
Migration 
Pulmonary 
Embolism 
Major 
Bleed 
Composite 
MAE 
42 
Neglen P 
2007 
Chronic, Post-Thrombotic 
Retrospective 
411 
81.8% 
0.0% 
1.9% 
NS 
NS 
0.2% 
2.2% 
43 
O'Sullivan GJ 
2013 
Mixed, Acute and Chronic 
Retrospective 
20 
85.0% 
0.0% 
15.0% 
NS 
0.0% 
0.0% 
15.0% 
44 
Park C 
2015 
Acute 
Retrospective 
37 
100.0% 
NS 
NS 
NS 
NS 
0.0% 
0.0% 
45 
Park JY 
2014 
Acute 
Retrospective 
51 
92.2% 
0.0% 
5.9% 
0.0% 
0.0% 
0.0% 
5.9% 
46 
Park SI 
2014 
Acute 
Retrospective 
74 
88.5% 
NS 
4.1% 
NS 
NS 
NS 
4.1% 
47 
Raju S 
2014 
Chronic, Mixed NT & PT 
Retrospective 
210 
83.9% 
0.0% 
0.0% 
0.9% 
NS 
NS 
0.9% 
48 
Rosales A 
2010 
Chronic, Post-Thrombotic 
Retrospective 
34 
76.5% 
NS 
NS 
NS 
NS 
NS 
NS 
49 
Sarici IS 
2013 
Chronic, Post-Thrombotic 
Retrospective 
52 
86.4% 
0.0% 
0.0% 
NS 
0.0% 
0.0% 
0.0% 
50 
Semba CP 
1996 
Mixed, Acute and Chronic 
Retrospective 
24 
94.7% 
0.0% 
NS 
NS 
0.0% 
NS 
0.0% 
51 
Titus JM 
2011 
Mixed, Acute and Chronic 
Retrospective 
36 
78.8% 
0.0% 
2.8% 
NS 
0.0% 
0.0% 
2.8% 
52 
Vedantham S 
2004 
Mixed, Acute and Chronic 
Retrospective 
18 
87.0% 
0.0% 
11.1% 
NS 
0.0% 
5.6% 
16.7% 
53 
Vogel D 
2012 
Chronic, Post-Thrombotic 
Retrospective 
10 
80.0% 
10.0% 
10.0% 
NS 
0.0% 
0.0% 
20.0% 
54 
Warner CJ 
2013 
Mixed, Acute and Chronic 
Retrospective 
32 
75.8% 
0.0% 
0.0% 
NS 
0.0% 
0.0% 
0.0% 
55 
Xue GH 
2014 
Chronic, Post-Thrombotic 
Retrospective 
61 
90.2% 
0.0% 
3.3% 
NS 
0.0% 
0.0% 
3.3% 
56 
Ye K 
2014 
Chronic, Post-Thrombotic 
Retrospective 
110 
78.1% 
0.0% 
12.7% 
NS 
0.0% 
0.0% 
12.7% 
57 
Ye K 
2012 
Chronic, Non-Thrombotic 
Retrospective 
205 
98.7% 
0.0% 
0.0% 
1.3% 
0.0% 
0.0% 
1.3% 
58 
Liu Z 
2014 
Chronic, Post-Thrombotic 
Retrospective 
12 
81.8% 
0.0% 
0.0% 
0.0% 
0.0% 
8.3% 
8.3% 
58 
Liu Z 
2014 
Chronic, Non-Thrombotic 
Retrospective 
36 
96.9% 
0.0% 
0.0% 
8.3% 
0.0% 
0.0% 
8.3% 
59 
Hartung O 
2009 
Chronic, Mixed NT & PT 
Retrospective 
89 
89.5% 
0.0% 
2.2% 
NS 
0.0% 
2.2% 
4.5% 
60 
Lou WS 
2009 
Acute 
Retrospective 
44 
81.8% 
0.0% 
11.4% 
0.0% 
0.0% 
0.0% 
11.4% 
60 
Lou WS 
2009 
Chronic, Non-Thrombotic 
Retrospective 
38 
89.5% 
0.0% 
5.3% 
0.0% 
0.0% 
0.0% 
5.3% 
60 
Lou WS 
2009 
Chronic, Post-Thrombotic 
Retrospective 
29 
51.7% 
0.0% 
34.5% 
0.0% 
0.0% 
0.0% 
34.5% 
61 
Oguzkurt L 
2008 
Mixed, Acute and Chronic 
Retrospective 
36 
75.0% 
0.0% 
2.8% 
NS 
0.0% 
0.0% 
2.8% 
62 
Patel NH 
2000 
Acute 
Retrospective 
10 
90.0% 
0.0% 
0.0% 
NS 
0.0% 
0.0% 
0.0% 
63 
Zhu QH 
2014 
Acute 
Prospective 
26 
96.2% 
0.0% 
0.0% 
NS 
0.0% 
0.0% 
0.0% 
64 
Sang H 
2014 
Chronic, Post-Thrombotic 
Retrospective 
67 
83.6% 
0.0% 
4.5% 
0.0% 
0.0% 
0.0% 
4.5% 
65 
Wahlgren CM 
2010 
Chronic, Post-Thrombotic 
Retrospective 
18 
62.5% 
0.0% 
16.7% 
NS 
0.0% 
0.0% 
16.7% 
66 
Gutzeit A 
2011 
Mixed, Acute and Chronic 
Retrospective 
13 
100.0% 
NS 
NS 
NS 
NS 
NS 
NS 
67 
Kolbel T 
2009 
Chronic, Post-Thrombotic 
Retrospective 
62 
79.7% 
0.0% 
0.0% 
NS 
0.0% 
3.2% 
3.2% 
68 
Alernay MB 
2014 
Chronic, Post-Thrombotic 
Retrospective 
36 
78.0% 
0.0% 
8.3% 
NS 
0.0% 
0.0% 
8.3% 

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Reference 
Number 
Lead Author 
Publication 
Year 
Indication 
Design 
N 
1-Year 
Patency 
30-Day Safety Endpoints 
Mortality 
Stent  
Thrombosis 
Stent 
Migration 
Pulmonary 
Embolism 
Major 
Bleed 
Composite 
MAE 
69 
Ahmed 
2015 
Chronic, Non-Thrombotic 
Retrospective 
34 
67.6% 
0.0% 
0.0% 
NS 
0.0% 
0.0% 
0.0% 
70 
Bozkaya 
2015 
Mixed, Acute and Chronic 
Retrospective 
21 
95.2% 
NS 
4.8% 
NS 
NS 
4.8% 
9.5% 
71 
Chung 
2016 
Acute 
Retrospective 
21 
83.3% 
0.0% 
0.0% 
NS 
NS 
4.8% 
4.8% 
72 
Ganelin 
2015 
Chronic, Mixed NT & PT 
Retrospective 
137 
97.6% 
NS 
2.9% 
NS 
NS 
0.7% 
3.6% 
73 
Jia 
2016 
Acute 
Retrospective 
32 
87.5% 
0.0% 
0.0% 
NS 
0.0% 
0.0% 
0.0% 
74 
Jiang 
2016 
Acute 
Retrospective 
27 
74.1% 
NS 
0.0% 
NS 
NS 
NS 
0.0% 
75 
Klitfod 
2015 
Chronic, Post-Thrombotic 
Retrospective 
19 
94.7% 
NS 
5.3% 
NS 
NS 
NS 
5.3% 
76 
Shi 
2016 
Mixed, Acute and Chronic 
Retrospective 
233 
90.1% 
0.0% 
NS 
NS 
NS 
0.0% 
0.0% 
77 
Yin 
2015 
Chronic, Mixed NT & PT 
Retrospective 
122 
82.8% 
0.0% 
NS 
NS 
0.0% 
0.0% 
0.0% 
Weighted Average 
85.7% 
0.0% 
2.9% 
1.4% 
0.2% 
1.1% 
5.6% 

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Analysis and Discussion of Literature 
The reviewed publications outline the clinical and anatomic characteristics of the population of patients 
with iliofemoral venous obstruction who were treated with venous stents. In addition 9 publications 
described the outcome of iliofemoral venous obstruction when treated without intervention; generally with 
anticoagulation alone. The series that comprised patients followed with medical management alone are 
reported separately. 
Study Design 
Most publications were single-center, retrospective, non-randomized series (Table V). Articles were 
published between 1996 and 2016 with treatment dates between 1987 and 2014. 
Table V. Study design of publications in final dataset14 
 
Study Design 
Series 
Patients 
Limbs 
Retrospective 
63 (93%) 
3,741 (94.9%) 
4,045 (95.2%) 
Prospective 
5 (7%) 
202 (5.1%) 
202 (4.8%) 
Non-randomized 
66 (97%) 
3,884 (98.5%) 
4,188 (98.6%) 
Randomized 
2 (3%) 
59 (1.5%) 
59 (1.4%) 
Single-center 
67 (99%) 
3,844 (97.5%) 
4,148 (97.7%) 
Multicenter 
1 (1%) 
99 (2.5%) 
99 (2.3%) 
Total Stent Series 
68 
3,943 
4,247 
Clinical Categories of Treated Patients 
Patients undergoing iliofemoral venous stenting are treated for symptomatic outflow obstruction of the 
lower extremity veins. The symptoms may be acute (<30 days in duration) or chronic. When chronic, the 
process can be one of occlusion occurring after a silent or asymptomatic iliofemoral DVT (post-thrombotic 
group) or stenosis in the absence of prior DVT (non-thrombotic group). 
Many publications did not subgroup outcome by clinical category. Mixed categories were created to 
account for such publications. Where a single publication encompassed more than one category but 
where outcome was grouped, the publication is listed separately in the row for each category. A summary 
of the frequency of each category of clinical presentation is included in Table VI. 
There were many more publications on stenting for acute presentations than for the other categories, 
although these series were characteristically smaller in size. This accounted for a smaller proportion of 
data on the acute category with respect to patients or limbs. The fewest number of publications were in 
the non-thrombotic category, although these series were larger, with the greatest average patients/study 
and limbs/study. 
 
 
14 Stent series alone; medical management is reported separately. A single publication may contain more than one series if different 
cohorts (e.g. acute and post-thrombotic cases) are reported separately. 

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Table VI. Number of publications with patients and limbs by indication 
Clinical Category 
Series 
Patients 
Limbs 
Acute 
22 (32%) 
662 (16.8%) 
674 (15.9%) 
Post-thrombotic 
18 (26%) 
1,092 (27.7%) 
1,185 (27.9%) 
Non-thrombotic 
6 (9%) 
787 (20.0%) 
865 (20.4%) 
Mixed, Acute & Chronic15 
14 (21%) 
620 (15.7%) 
639 (15.0%) 
Mixed; PT and NT 
8 (12%) 
782 (19.8%) 
884 (20.8%) 
All Series 
68 
3,943 
4,247 
PT= post-thrombotic; NT= non-thrombotic.  
Individual percentages may not add to 100% due to rounding 
Demographics and Other Baseline Characteristics 
In general, authors specified the patient population by age (mean years), gender, and laterality (left only, 
right only, bilateral). 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Baseline QoL Indices 
 
 
15 Chronic includes both post-thrombotic and non-thrombotic 
16 Weighted averages; by number of patients in each series 
Table VII. Baseline characteristics by publication category16 
Clinical Categories in Publications 
Females 
Age 
Left 
Right 
Bilateral 
Acute 
65.5% 
56.2 
87.2% 
9.8% 
3.0% 
Post-thrombotic 
61.3% 
50.2 
67.3% 
18.0% 
14.7% 
Non-thrombotic 
64.6% 
53.9 
70.6% 
21.7% 
7.7% 
Mixed, Acute & Chronic 
56.4% 
47.4 
73.7% 
21.3% 
4.9% 
Mixed; PT and NT 
68.9% 
55.3 
60.8% 
28.1% 
11.1% 
All Series 
63.5% 
52.7 
70.0% 
20.4% 
9.6% 
Individual percentages may not add to 100% due to rounding 

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Publications were inconsistent in reporting QoL data at baseline. Most commonly, the Clinical, Etiologic, 
Anatomic, and Pathologic (CEAP) categories were reported.78 The CEAP classification was introduced to 
simplify and standardize the reporting for chronic venous disease. The CEAP definitions were revised in 
2004 by a committee of the American Venous Forum. While CEAP is the most frequently reported venous 
index, both pre- and post-intervention, it does not include subjective complaints and has been criticized 
as a good index for longitudinal follow-up.79  
Mean CEAP were reported in some studies and where it was not, the mean CEAP was calculated by a 
weighted average of the number of limbs in each category. In general, studies were performed for 
symptomatic limbs with CEAP 2 or greater. The mean baseline CEAP was 3.8 in the studies where it was 
reported. 
Table VIII. CEAP categories at pre-intervention baseline 
Clinical Category 
CEAP 
0-2 
CEAP 
3 
CEAP 
4 
CEAP 
5 
CEAP 
6 
Mean 
CEAP 
Acute 
20.3% 
66.7% 
10.1% 
1.4% 
1.4% 
3.0 
Post-thrombotic 
4.6% 
44.1% 
26.2% 
7.3% 
18.7% 
3.9 
Non-thrombotic 
9.7% 
42.7% 
19.9% 
8.1% 
19.7% 
3.9 
Mixed, Acute & Chronic17 
5.6% 
69.4% 
22.2% 
0.0% 
2.8% 
3.3 
Mixed; PT and NT 
11.3% 
37.8% 
22.4% 
8.0% 
20.6% 
3.9 
All Stent Publications 
8.7% 
42.6% 
22.6% 
7.5% 
18.9% 
3.8 
Treatment and Follow-up 
Patients were most commonly treated with the Wallstent, although a wide variety of other stents were 
used in the studies; particularly in the more recent publications (Table IX). Patients were followed for a 
mean of 24 months after the procedure. Duplex ultrasound was the most frequent imaging modality, 
although many studies used venography when the duplex study was abnormal and some more recent 
studies employed computed tomographic venography. Post-procedure anticoagulation varied by the 
clinical category (indication) for the stent placement, but warfarin was most commonly used; for at least 6 
months after stent implantation. 
 
 
 
 
 
 
 
 
 
 
 
17 Chronic includes both post-thrombotic and non-thrombotic. 

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Table IX. Types of stents used in the series 
Stent 
Series 
% of Series18 
Wallstent 
44 
64.7% 
Luminexx 
14 
20.6% 
SMART 
15 
22.1% 
Palmaz 
5 
7.4% 
Zilver 
5 
7.4% 
Protégé 
4 
5.9% 
Gianturco 
4 
5.9% 
Others 
13 
19.1% 
Percentages add to more than 100% since many series use more than one 
type of stent. 
 
Safety Outcomes 
Adverse events were generally tabulated as periprocedural (≤30 days) or later. This review focused on 
those events that occurred within 30 days of the index procedure. The following occurrences were 
tabulated: periprocedural (≤30 day) death, major hemorrhage (using the Bleeding Academic Research 
Consortium, or BARC definition; Types 3a or greater80), clinically-evident pulmonary embolism, and 
access site complications (wound hematoma, false aneurysm and arteriovenous fistula). 
The findings suggested that periprocedural death and pulmonary embolism were exceedingly uncommon 
in the patient populations studied; each occurring in fewer than 1% of patients treated (Table X and Table 
XI). The most common events were wound hematoma, stent thrombosis, and stent 
dislodgement/migration. Major hemorrhagic complications (BARC Type 3a or greater) occurred in 
approximately 1.1% of patients. 
It was often impossible to determine whether major hemorrhagic complications occurred as a result of 
pharmacologic thrombolytic therapy in those series in which it was employed, accounting for a higher 
frequency of hemorrhagic complications in series that included patients with acute venous thromboses. 
Similar findings were evident for wound hematomas. Early (<30 day) stent thrombosis was more common 
in post-thrombotic cases (4.9%) and was rare in non-thrombotic cases (0.2%). In this literature review, 
loss of stent patency within 30 days was synonymous with stent thrombosis; no effort was made to 
differentiate different thrombosis from other causes of occlusion since few publications specified the 
etiology of the process. Stent migration (exclusive of dislodgement19) occurred more often in acute (2.4%) 
and non-thrombotic cases (2.0%) compared with the other groups (0.8%), possibly related to the absence 
of chronic stenotic disease in these cohorts; where chronic stenoses may have protective effects on the 
 
 
18 Percentages refer to the number of series that reported use of a particular stent. Percentages add to more than 100 since many 
series used more than a single type of stent. 
19 Dislodgement is defined as stent displacement from the initial deployment site due to catheter/wire/balloon manipulations at the 
index procedure. 

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stability of a stent. Neither stent migration or stent dislodgement was reported in any of the post-
thrombotic cases. 
Adverse occurrences beyond 30 days were also tabulated and included Target Lesion Revascularization 
(TLR), stent fracture and stent migration. TLR occurred in 8.3% of patients overall through 12 months, 
and appeared most common in post-thrombotic cases (13.1%). Stent fracture was reported in 1.4% of 
patients. Stent dislodgement and stent migration were observed in 0.6% and 1.6% of cases, respectively 
(including migration beyond 30 days).  
Table X. Periprocedural (≤30 day) safety events 
 
Clinical Category 
Major 
Hemorrhage 
False 
Aneurysm 
Arteriovenous 
Fistula 
Wound 
Hematoma 
Acute 
1.8% 
0.0% 
0.7% 
0.4% 
Post-thrombotic 
0.6% 
0.3% 
0.1% 
1.0% 
Non-thrombotic 
0.1% 
0.1% 
0.0% 
1.3% 
Mixed, Acute & Chronic 
3.0%20 
0.0% 
0.0% 
17.2%21 
Mixed; PT and NT 
0.8% 
0.3% 
0.0% 
1.6% 
All Stent Publications 
1.1% 
0.2% 
0.1% 
3.6% 
 
 
 
 
 
20 The high rate of Major Hemorrhage in the Mixed, Acute and Chronic group is skewed the Mewissen series (Radiology,1999) 
where all patients were treated with thrombolytic agents prior to stenting. Excluding the Mewissen data, the rate of major 
hemorrhage falls to 0.9% for the Mixed, Acute and Chronic cohort and to 0.7% overall. 
21 The high frequency of wound hematoma is principally a result of the Mewissen series (Radiology,1999) where all patients were 
treated with thrombolytic agents prior to stenting. Excluding the Mewissen article, the frequency of wound hematoma falls to 2.0% 
for the Mixed, Acute and Chronic cohort and to 1.2% overall.  

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Table XI. Periprocedural (≤30 day) death, pulmonary embolism and stent complications 
Clinical Category 
Death 
Pulmonary 
Embolism 
Stent 
Thrombosis* 
Stent 
Dislodgement* 
Acute 
0.0% 
0.3% 
3.8% 
0.0% 
Post-thrombotic 
0.1% 
0.0% 
4.9% 
0.0% 
Non-thrombotic 
0.0% 
0.0% 
0.2% 
0.0% 
Mixed, Acute & Chronic 
0.0% 
0.6% 
4.8% 
2.6% 
Mixed; PT and NT 
0.0% 
0.0% 
1.9% 
1.3% 
All Stent Publications 
0.0%22 
0.2% 
2.9% 
0.6% 
*Reported by number of events per limb, not per patient for stent-related complications 
PT= Post-thrombotic 
NT= Non-thrombotic 
 
Table XII. Complications through 12 months 
Clinical Category 
Target Lesion 
Revascularization 
Stent Fracture 
Stent 
Migration23 
Acute 
4.8% 
0.0% 
2.4% 
Post-thrombotic 
13.0% 
0.0% 
0.0% 
Non-thrombotic 
Not Specified 
0.0% 
2.0% 
Mixed, Acute & Chronic 
7.0% 
5.3% 
Not Specified 
Mixed; PT and NT 
4.5% 
Not Specified 
1.1% 
All Stent Publications 
8.3% 
1.4% 
1.6% 
 
 
 
 
 
 
 
22 The actual weighted average is 0.03%. 
23 Where specified, stent migration included only those events occurring after the index procedure. Stent movement occurring during 
the index procedure is tabulated as “stent dislodgement” in Table XI. 

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Effectiveness Outcomes 
The effectiveness outcomes of the publications comprised technical success and patency rates; primary, 
primary-assisted and secondary. Technical success at the time of the index procedure was defined 
differently from study to study. In general, technical success implied successful delivery and deployment 
of the stent at the intended location without significant residual stenosis. Primary patency was defined as 
the absence of occlusion or target lesion reintervention. Primary-assisted patency was defined as the 
absence of occlusion irrespective of whether TLR was performed. Secondary patency was defined when 
the target lesion was patent irrespective of reintervention, as long as patency was restored. Duplex 
ultrasound was the most common post-procedure imaging surveillance modality utilized, but many 
studies also employed contrast venography in follow-up. 
Technical success at the index procedure was 95.8% and was highest in non-thrombotic cases (98.8%) 
and lowest in post-thrombotic cases (92.0%). The primary patency rate for venous stenting was 85.7% at 
one year (Table XIII). Reintervention was often successful when stent stenosis or occlusion occurred, 
with primary-assisted and secondary patency rates of 93.8% and 95.2%, respectively. Patency rates were 
highest in patients with non-thrombotic disease (12-month primary patency 94.8%) and lowest in post-
thrombotic patients (12-month primary patency 80.5%). 
Table XIII. Patency rates at 12 months after iliofemoral venous stenting 
Clinical Category (Limbs) 
12-Month Patency Rates 
Primary 
Primary-Assisted 
Secondary 
Acute (N = 662) 
84.0% 
91.1% 
96.7% 
Post-thrombotic (N = 1,175) 
80.5% 
88.1% 
91.9% 
Non-thrombotic (N = 901) 
94.8% 
100.0% 
100.0% 
Mixed, Acute & Chronic (N = 649) 
83.6% 
85.0% 
93.6% 
Mixed; PT and NT (N = 958) 
83.8% 
92.9% 
89.5%24 
All Stent Publications (N = 4,247) 
85.7% 
93.8% 
95.2% 
 
 
 
 
 
24 Secondary patency for this cohort is lower than primary-assisted patency since different series are included in the two measures. 

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Quality of Life Measures after Intervention 
Post-intervention Quality of Life measures were not consistently reported in the studies. The post-
intervention CEAP, Villalta, VCSS and CIVIQ-20 scores were reported in only four, six, nine and one of 
the series, respectively. The VEINES score was not reported in any of the series. 
The QoL results indicated improvement from pre- to post-intervention, evident in all four indices studied; 
as listed in Table XIV. 
Table XIV. Pre- and post-intervention venous Quality of Life indices. 
Scale 
Pre-Intervention 
Post-intervention 
Change 
CEAP 
3.8 
2.2 
1.6 
Villalta 
17.3 
6.6 
10.7 
VCSS 
9.7 
3.7 
6.0 
CIVIQ-2049 
64 
83 
19 
 
Results in Medically-Managed Patients    
There were nine series reporting outcome in patients with iliofemoral venous obstruction after medical 
management alone.17,21,39,40,44,77,81-83 A total of 364 subjects and 367 limbs were studied; 58.6% were 
female with an average age of 48.8 years and mean CEAP 4.2 at presentation. The majority (64.9%) of 
patients in the medically-managed series were patients with acute iliofemoral venous thrombosis, and the 
process was on the left in 67.6%, right in 22.9% and bilateral in 9.5%. The follow-up averaged 23 months 
and, where specified in the publications, the primary treatment modality was heparin follow-up by long-
term warfarin anticoagulation. The weighted primary patency rate was 47.1% at 1 year. 
Data from Publications on CE-Marked Stents for the Iliofemoral Venous Indication 
While there are no stents approved for the iliofemoral venous indication in the US, several are CE marked 
in Europe (Table XV). These include the Cook Zilver Vena, OptiMed sinus-Venous, Veniti Vici, and the 
Boston Scientific Wallstent, The Wallstent, while the most commonly employed stent for two decades, did 
not receive CE mark for the iliofemoral venous indication until 2015.  
It is not possible to parse data on the on-label venous stents from other, off-label venous stents for most 
of the publications evaluated in the scientific literature review. Authors rarely report results by type of 
stent. As well, to date (October 2016) there have been no publications on the Veniti Vici stent and Bard 
Venovo stent. Noting these limitations, the outcome after on-label venous stenting is reported from a 
small subset of the articles reviewed and is limited to those reports that specify outcome separately for 
one of the four CE-marked venous stents. 
CIVIQ-20 scores were reported in only one publication. Higher scores mean better quality of life. 
The findings in the on-label venous stents are dominated by publications that used the Wallstent (Table 
XVI). While this analysis is limited by the relatively small sample size in the on-label group, currently 
available data do not reveal marked differences between data from studies on CE marked stents 
compared to those that used other stents. 
 
 
 
 

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Table XV. Venous stents with CE Mark 
Company 
Stent Brand 
Name 
Material 
Character 
CE Mark 
Cook Medical  
Zilver Vena 
Nitinol 
Self-expanding 
2011 
OptiMed  
sinus-Venous 
Nitinol 
Self-expanding 
2012 
Veniti 
Vici 
Nitinol 
Self-expanding 
2013 
Boston Scientific 
Wallstent 
Elgiloy 
Self-expanding 
201525 
 
Table XVI. Outcome reported from on-label venous stents26 
 
Stent (Series/Limbs) 
Primary 
Patency 
Safety 
Clinical 
30-day 
Thrombosis 
Stent 
Fracture 
Stent 
Migration 
Villalta 
Change 
Cook Zilver Vena (1/20)43 
85.0% 
15.0% 
NS 
NS 
NS 
OptiMed Sinus (1/80)23 
96.3% 
NS 
NS 
NS 
6.5 
Boston Sci Wallstent (22/2,008) 
88.8% 
1.7% 
1.6% 
2.4% 
7.6 
All CE-Marked Stents (24/2,108) 
89.0% 
1.8% 
1.6% 
2.4% 
6.6 
NS- Not Specified 
 
 
 
 
 
25 While an article in Endovascular Today stated that the Wallstent was recently CE marked, there is no confirmation of same on the 
Boston Scientific corporate website.  
26 There were no publications on the Veniti Vici stent. 

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Conclusions 
The results of this Scientific Literature Search suggest that venous stenting was associated with 
acceptable outcomes in patients presenting with acute, chronic post-thrombotic, and chronic non-
thrombotic iliofemoral venous obstruction. 
The average age at presentation was 52.7 years, although patients presented throughout all age ranges. 
Females presented more often than males; 63.5% versus 36.5%, respectively. Treated lesions were more 
often on the left than the right; 70.0% vs. 20.4%. Bilateral lesions were treated in 9.6% of patients. At 
baseline, 65.2% of patients were within CEAP 3 or 4 categories; more mild symptomatology was found in 
8.7% of cases; 26.4% presented with a healed (C5, 7.5%) or active ulcerations (C6, 18.9%). 
The venous stenting procedure was quite safe. Major hemorrhage occurred in 1.1% of patients with 
access site hematomas in 3.6%. Other access site complications such as false aneurysms or 
arteriovenous fistulae were very rare as was pulmonary embolism or death within 30 days of the 
procedure; each occurring in 0.2% or fewer patients. When MAE were defined as the composite 
occurrence of major procedural bleeding (BARC Type 3a or greater80), all-cause mortality, stent 
thrombosis, pulmonary embolism or stent migration, 5.6% experienced an MAE within 30 days. Stent 
fracture was reported in 1.4% of patients, with stent dislodgement (at the index procedure) in 0.6% and 
stent migration (after the index procedure) in 1.6%. 
Effectiveness as measured by patency rate was satisfactory. At 1 year, primary, primary-assisted and 
secondary patency rates were 85.7%, 93.8% and 95.2%, respectively. TLR at 12 months was 8.3%. 
There did not appear to be substantial differences in outcome between patients treated with off-label or 
CE-marked venous stents, but the relatively small sample for CE-marked stents precluded a robust 
analysis. 
In summary, iliofemoral venous stenting as reported in the literature appears to be associated with 
relatively few perioperative and longer-term complications, with a 30-day MAE rate of 5.6% and a primary 
patency rate of 85.7% at one year. 
 
 

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endoluminal recanalization improves symptoms and quality of life in patients with postthrombotic 
iliofemoral obstruction. J Vasc Surg 2012;55:129-35. 
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iliac vein compression syndrome with acute iliofemoral deep vein thrombosis: outcome and follow-up. 
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56. 
Ye K, Lu X, Jiang M, 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;25:925-32. 
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Ye K, Lu X, Li W, et al. Long-term outcomes of stent placement for symptomatic nonthrombotic 
iliac vein compression lesions in chronic venous disease. J Vasc Interv Radiol 2012;23:497-502. 
58. 
Liu Z, Gao N, Shen L, et al. Endovascular treatment for symptomatic iliac vein compression 
syndrome: a prospective consecutive series of 48 patients. Ann Vasc Surg 2014;28:695-704. 

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Hartung O, Barthelemy P, Arnoux D, Boufi M, Alimi YS. Management of pregnancy in women 
with previous left ilio-caval stenting. J Vasc Surg 2009;50:355-9. 
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Lou WS, Gu JP, He X, et al. Endovascular treatment for iliac vein compression syndrome: a 
comparison between the presence and absence of secondary thrombosis. Korean J Radiol 2009;10:135-
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61. 
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;68:487-92. 
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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;11:1297-302. 
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Zhu QH, Zhou CY, Chen Y, et al. Percutaneous manual aspiration 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 Surg 
2014;47:68-74. 
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Sang H, Li X, Qian A, Meng Q. Outcome of endovascular treatment in postthrombotic syndrome. 
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Wahlgren CM, Wahlberg E, Olofsson P. Endovascular treatment in postthrombotic syndrome. 
Vasc Endovascular Surg 2010;44:356-60. 
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Gutzeit A, Zollikofer Ch L, Dettling-Pizzolato M, Graf N, Largiader J, Binkert CA. Endovascular 
stent treatment for symptomatic benign iliofemoral venous occlusive disease: long-term results 1987-
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Kolbel T, Lindh M, Akesson M, Wasselius J, Gottsater A, Ivancev K. Chronic iliac vein occlusion: 
midterm results of endovascular recanalization. J Endovasc Ther 2009;16:483-91. 
68. 
Blanch Alerany M, Izquierdo Lamoca LM, Ramirez Ortega M, Lago Rivas I, Zotta Desboeufs R, 
Stefanov Kiuri S. Endovascular treatment of iliofemoral chronic post-thrombotic venous flow obstruction. J 
Vasc Surg Venous Lymphat Disord 2014;2:2-7. 
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Ahmed O, Ng J, Patel M, et al. Endovascular Stent Placement for May-Thurner Syndrome in the 
Absence of Acute Deep Vein Thrombosis. J Vasc Interv Radiol 2016;27:167-73. 
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Bozkaya H, Cinar C, Ertugay S, et al. Endovascular Treatment of Iliac Vein Compression (May-
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Catheter-Directed Thrombolysis. Ann Vasc Dis 2015;8:21-8. 
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Chung HH, Lee SH, Cho SB, Kim YH, Seo TS. Single-Session Endovascular Treatment of 
Symptomatic Lower Extremity Deep Vein Thrombosis: Is it Possible Even for Aged Thrombosis. Vasc 
Endovascular Surg 2016;50:321-7. 
72. 
Ganelin A, Hingorani A, Ascher E, et al. Complications with office-based venoplasties and 
stenting and their clinical correlation. J Vasc Surg Venous Lymphat Disord 2015;3:376-9. 
73. 
Jia Z, Tu J, Zhao J, et al. Aspiration thrombectomy using a large-size catheter for acute lower 
extremity deep vein thrombosis. J Vasc Surg Venous Lymphat Disord 2016;4:167-71. 
74. 
Jiang K, Li XQ, Sang HF, Qian AM, Rong JJ, Li CL. Mid-term outcome of endovascular treatment 
for acute lower extremity deep venous thrombosis. Phlebology 2016. 
75. 
Klitfod L, Just S, Foegh P, Baekgaard N. Excellent long-term results with iliac stenting in local 
anesthesia for post-thrombotic syndrome. Acta Radiol Open 2015;4:2058460115592164. 
76. 
Shi WY, Gu JP, Liu CJ, He X, Lou WS. Endovascular treatment for iliac vein compression 
syndrome with or without lower extremity deep vein thrombosis: A retrospective study on mid-term in-
stent patency from a single center. Eur J Radiol 2016;85:7-14. 
77. 
Yin M, Shi H, Ye K, et al. Clinical Assessment of Endovascular Stenting Compared with 
Compression Therapy Alone in Post-thrombotic Patients with Iliofemoral Obstruction. Eur J Vasc 
Endovasc Surg 2015;50:101-7. 

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Catarinella FS, Nieman FHM, Wittens CHA. An overview of the most commonly used venous 
quality of life and clincial outcome measurements. J Vasc Surg and Ven Lym Dis 2015;3:333-40. 
79. 
Rabe E, Pannier F. Clinical, aetiological, anatomical and pathological classification (CEAP): gold 
standard and limits. Phlebology 2012;27 Suppl 1:114-8. 
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Mehran R, Rao SV, Bhatt DL, et al. Standardized bleeding definitions for cardiovascular clinical 
trials: a consensus report from the Bleeding Academic Research Consortium. Circulation 2011;123:2736-
47. 
81. 
Plate G, Einarsson E, Ohlin P, Jensen R, Qvarfordt P, Eklof B. Thrombectomy with temporary 
arteriovenous fistula: the treatment of choice in acute iliofemoral venous thrombosis. J Vasc Surg 
1984;1:867-76. 
82. 
Arnesen H, Heilo A, Jakobsen E, Ly B, Skaga E. A prospective study of streptokinase and 
heparin in the treatment of deep vein thrombosis. Acta Med Scand 1978;203:457-63. 
83. 
Elliot MS, Immelman EJ, Jeffery P, et al. A comparative randomized trial of heparin versus 
streptokinase in the treatment of acute proximal venous thrombosis: an interim report of a prospective 
trial. Br J Surg 1979;66:838-43. 
 
 
 

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Appendix B Definitions 
Acute deep vein 
thrombosis 
Formation of a blood clot (thrombus) in one or more of the deep veins less 
than 14 days old. 
Note: this does not include deep venous thrombus contiguous to and 
occurring as a result of stent occlusion. 
Acute success 
• 
Device Success: Successful delivery and deployment of the Abre 
stent in the target lesion with successful removal of the delivery 
system. 
• 
Lesion Success: Venographic evidence of <50% final residual 
stenosis of the stented segment of the target lesion after post-
dilation, when applicable, and as assessed by core laboratory. 
• 
Procedure Success: Lesion success without procedure-related 
MAEs prior to hospital discharge within 30 days. 
 
Note: If core laboratory is unable to assess the venographic evidence, site 
reported data will be used. 
Chronic venous 
obstruction 
Obstruction of the deep veins related to a previous deep vein thrombosis or 
stenosis from external compression > 6 months before study inclusion.  
Clinically driven 
Defined as the recurrence of symptoms present at baseline or the onset of 
new symptoms including, but not limited to venous pain, swelling, dermatitis, 
or ulceration related to the target limb. 
Major adverse events 
(primary endpoint)  
• 
All-cause death occurring post-procedure 
• 
Clinically significant (i.e. symptomatic, confirmed by CT pulmonary 
angiography) pulmonary embolism  
• 
Major bleeding complication (procedural) 
• 
Stent thrombosis confirmed by imaging as assessed by core 
laboratory 
• 
Stent migration confirmed by imaging as assessed by core 
laboratory 
 
Note: Migration excludes stent dislodgement at the index procedure as may 
occur with under-sizing of a stent. 
Major adverse events  
(secondary endpoint) 
• 
All-cause death occurring post-procedure 
• 
Clinically significant (i.e. symptomatic, confirmed by CT pulmonary 
angiography) pulmonary embolism  
• 
Major bleeding complication (post-procedural) 
• 
Stent thrombosis confirmed by imaging as assessed by core 
laboratory 
• 
Stent migration  confirmed by imaging as assessed by core 
laboratory 
Note: Migration excludes stent dislodgement at the index procedure as may 
occur with under-sizing of a stent 

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Major amputation 
Surgical removal of tissue in the target limb above the level of the ankle, 
requiring a prosthetic limb to ambulate:   
• 
Above knee amputation (amputation of limb with resection 
point above the knee) 
• 
Below knee amputation (amputation of limb with resection 
point below the knee and above the ankle)  
Major bleeding 
complication 
A blood loss leading to transfusion of whole blood or red cells provided 
hemoglobin drop of 3 g/dL (1.86 mmol/L) or more is related to bleeding 
occurring during the index procedure through 36 months post-index 
procedure. 
Major bleeding 
complication 
(procedural) 
A blood loss leading to transfusion of whole blood or red cells provided 
hemoglobin drop of 3 g/dL (1.86 mmol/L) or more is related to bleeding 
occurring during the index procedure through 30 days post-index procedure. 
Major bleeding 
complication (post-
procedural) 
A blood loss leading to transfusion of whole blood or red cells provided 
hemoglobin drop of 3 g/dL (1.86 mmol/L) or more is related to bleeding 
occurring at 30 days through 36 months post-index procedure. 
Minor amputation 
Surgical removal of tissue in the target limb: 
• 
Trans-metatarsal amputation (amputation with resection point 
at the level of the metatarsal bones of the foot)  
• 
Toe amputation (amputation of one or more toes) 
Obstructive lesion 
 
Obstructive lesion is defined as: 
i. Occluded, or 
ii. ≥50% in diameter reduction on venography or IVUS, or 
iii. ≥50% area reduction on IVUS 
Point of enrollment 
The point of enrollment is the time at which the subject signs and dates the 
informed consent form.  
Point of inclusion 
The point of inclusion is the time at which the subject who signed and dated 
the informed consent form, adhered to all I/E criteria and where the Abre 
system enters the vasculature. 
Postthrombotic 
syndrome (PTS) 
Complication of deep vein thrombosis (DVT) or stenosis of a deep vein with 
symptoms ≥ 6 months before study inclusion. Symptoms may include 
brownish discoloration of the skin, itching, swelling, slow-healing sores, pain 
in the area, fragile skin on the area, which may bruise easily, dry or peeling 
skin. 
Primary assisted 
patency 
Uninterrupted patency of the stented segment of the target lesion with a 
secondary intervention, also known as an adjunctive treatment (e.g. balloon 
venoplasty, subsequent stenting, etc.). 

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Secondary patency 
Patency of the stented segment of the target lesion after subsequent 
intervention for an occlusion.  
 
Note: Confirmed by DUS, evaluated by independent core laboratory. In 
cases where both DUS and venography were used at the same time point, 
venography would be used to for the primary assessment. 
Serious adverse health 
consequences 
(CFR 21-814) 
Any significant adverse experience, including those which may be either life-
threatening or involve permanent or long term injuries, but excluding injuries 
that are non-life-threatening and that are temporary and reasonably 
reversible.  
Target lesion  
The target lesion is defined as non-malignant venous obstruction within the 
common iliac, external iliac and/or common femoral vein: the proximal point 
of the obstruction may extend to the iliac venous confluence of the inferior 
vena cava and the distal point may be at or above the deep femoral vein. 
Target lesion 
revascularization (TLR) 
Any re-intervention of the stented segment of the target lesion. 
 
Target vessel 
The target vessel is defined as the common iliac, external iliac and/or 
common femoral vein. 
 
 

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Stent fracture 
Fracture or breakage of any portion of the stent. 
 
Stent Fracture Classification: Determined by X-ray (assessed by core 
laboratory): 
• 
Type 0 – No strut fractures 
• 
Type I – Single tine fracture 
• 
Type II – Multiple tine fractures 
• 
Type III – Stent fracture(s) with preserved alignment of the 
• 
components 
• 
Type IV – Stent fracture(s) with mal-alignment of the components 
• 
Type V – Stent fracture(s) in a trans-axial spiral configuration 
 
Stent migration 
Stent migration (as part of primary safety and secondary MAE 
endpoints): position change of a properly sized venous stent observed with 
an imaging modality, with displacement of the stent outside of the intended 
treatment segment after  the conclusion of the index procedure, as determined 
with regard to a reference anatomic structure.  
 
Delayed stent migration (as part of secondary endpoint): position change 
of a venous stent observed with an imaging modality > 1 cm from its original 
location at the conclusion of the index procedure, as determined with regard to 
a reference anatomic structure. 
 
Stent migration occurs following the proper deployment of a venous stent after 
the index procedure (i.e. stent movement or dislodgement during the index 
procedure will not be noted as stent migration). 
Stent thrombosis 
Occlusion of the stented venous segment occurring at any time following stent 
placement.  
Stent thrombosis may be diagnosed by Duplex Ultrasound. It needs to be 
confirmed by venogram or IVUS. 
Thrombosis 
 
 
A total occlusion due to thrombus formation as confirmed by sudden onset of 
symptoms and documented by DUS and venogram and/or IVUS at the target 
vessel. 
Vein compression 
syndrome 
A condition in which compression of the common iliac venous outflow tract of 
the left lower extremity may cause discomfort, swelling, pain, or blood clots 

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(deep vein thrombosis) in the iliofemoral vein (also known as the May-Thurner 
syndrome). 
Venous occlusive 
disease 
Any pathologic process that occurs from underlying stenosis or occlusion of 
the veins. 
Appendix C CEAP Classification 
The CEAP classification (39) is a method for evaluating venous disease of the leg based on clinical, etiologic, 
anatomic, and pathophysiologic data. 
The CEAP system consists of two parts: classification and severity scoring: 
Classification 
C- clinical manifestation 
E- etiologic factors 
A- anatomic distribution 
P- pathophysiologic dysfunction 
Severity Scoring 
1. Number of anatomic segments affected 
2. Grading of signs and symptoms 
3. Disability 
CLINICAL CLASSIFICATION  
C0: no visible or palpable signs of venous disease 
C1: telangiectasies or reticular veins 
C2: varicose veins 
C3: edema 
C4a: pigmentation and eczema 
C4b: lipodermatosclerosis and atrophie blanche 
C5: healed venous ulcer 
C6: active venous ulcer 
 
S: symptoms including ache, pain, tightness, skin irritation, heaviness, muscle cramps, as well as 
other complaints attributable to venous dysfunction.  
A: asymptomatic.  
 
ETIOLOGIC CLASSIFICATION  
Ec: congenital 
Ep: primary 
Es: secondary (postthrombotic) 
 
ANATOMIC CLASSIFICATION 
s: superficial veins 
p: perforator veins 
d: deep veins 
 
 
 

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PATHOPHYSIOLOGIC CLASSIFICATION  
Basic CEAP:  
Pr: reflux 
Po: obstruction 
Pr,o: reflux and obstruction 
Pn: no venous pathophysiology identifiable 
Advanced CEAP:  
Same as Basic with the addition that any of 18 named venous segments can be utilized as locators for 
venous pathology:  
Superficial veins:  
1. 
telangiectasies/reticular veins 
2. 
GSV above knee 
3. 
GSV below knee  
4. 
SSV 
5. 
Nonsaphenous veins 
Deep veins:  
6. 
IVC 
7. 
Common iliac vein 
8. 
Internal iliac vein 
9. 
External iliac vein 
10. Pelvic: gonadal, broad ligament veins, other 
11. Common femoral vein 
12. Deep femoral vein 
13. Femoral vein 
14. Popliteal vein 
15. Crural: anterior tibial, posterior tibial, peroneal veins (all paired) 
16. Muscular: gastrocnemial, soleal veins, other 
Perforating veins:  
17. Thigh  
18. Calf 
 
 

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Appendix D Villalta Score 
The Villalta Score is a reliable and valid measure of Postthrombotic syndrome (PTS) in patients with 
previous, objectively confirmed deep vein thrombosis noting responsiveness to clinical change in PTS. 
The Villalta score will categorize the severity of PTS. 
Symptoms/clinical signs 
None 
Mild 
Moderate Severe 
Symptoms 
 
 
 
 
 Pain 
0 points 1 point 2 points 
3 points 
 Cramps 
0 points 1 point 2 points 
3 points 
 Heaviness 
0 points 1 point 2 points 
3 points 
 Paresthesia 
0 points 1 point 2 points 
3 points 
 Pruritus 
0 points 1 point 2 points 
3 points 
Clinical signs 
 
 
 
 
 Pretibial edema 
0 points 1 point 2 points 
3 points 
 Skin induration 
0 points 1 point 2 points 
3 points 
 Hyperpigmentation 
0 points 1 point 2 points 
3 points 
 Redness 
0 points 1 point 2 points 
3 points 
 Venous ectasia 
0 points 1 point 2 points 
3 points 
 Pain on calf compression 
0 points 1 point 2 points 
3 points 
Venous ulcer 
Absent  
 
Present 
A total score of 0 to 4 indicates no postthrombotic syndrome; score of ≥ 5 indicates PTS. PTS severity: total 
score of 5 to 9, mild PTS; score of 10 to 14, moderate PTS; and score of ≥ 15 or venous ulcer present, 
severe PTS. 
 
 

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Appendix E Venous Clinical Severity Score (VCSS) 
Venous disease severity measurement intended to evaluate the responses to changes in disease severity 
over time and in response to treatment.   
 
 
None: 0 
Mild: 1 
Moderate: 2 
Severe: 3 
Pain 
or other discomfort 
(i.e. aching, 
heaviness, fatigue, 
soreness, burning) 
 
Presumes venous 
origin 
 
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 
 
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 
 
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 (i.e., 
vasculitis purpura) 
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) 
 
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 
 
Limited to 
perimalleolar area 
Diffuse over lower 
third of calf 
Wider distribution 
above lower third 
of calf 
 
 

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Active Ulcer 
Number 
0 
1 
2 
≥3 
Active Ulcer 
Duration (longest 
active) 
N/A 
<3 mo 
>3 mo but <1 y 
Not healed for >1 
y 
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 
 
 
 

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Appendix F EQ-5D 
 
 
 
 
 
 
 
 
 
Health Questionnaire 
 
 
English version for the USA 
 
 
 

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Under each heading, please check the ONE box that best describes your health TODAY. 
MOBILITY 
 
I have no problems walking 
❑ 
I have slight problems walking 
❑ 
I have moderate problems walking 
❑ 
I have severe problems walking 
❑ 
I am unable to walk 
❑ 
SELF-CARE 
 
I have no problems washing or dressing myself 
❑ 
I have slight problems washing or dressing myself 
❑ 
I have moderate problems washing or dressing myself 
❑ 
I have severe problems washing or dressing myself 
❑ 
I am unable to wash or dress myself 
❑ 
USUAL ACTIVITIES (e.g. work, study, housework, family or leisure activities) 
 
I have no problems doing my usual activities 
❑ 
I have slight problems doing my usual activities 
❑ 
I have moderate problems doing my usual activities 
❑ 
I have severe problems doing my usual activities 
❑ 
I am unable to do my usual activities 
❑ 
PAIN / DISCOMFORT 
 
I have no pain or discomfort 
❑ 
I have slight pain or discomfort 
❑ 
I have moderate pain or discomfort 
❑ 
I have severe pain or discomfort 
❑ 
I have extreme pain or discomfort 
❑ 
ANXIETY / DEPRESSION 
 
I am not anxious or depressed 
❑ 
I am slightly anxious or depressed 
❑ 
I am moderately anxious or depressed 
❑ 
I am severely anxious or depressed 
❑ 
I am extremely anxious or depressed 
❑ 
 
 
 
 

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The worst health 
you can imagine 
 
 
• 
We would like to know how good or bad your health is TODAY. 
• 
This scale is numbered from 0 to 100. 
• 
100 means the best health you can imagine. 
0 means the worst health you can imagine. 
• 
Mark an X on the scale to indicate how your health is TODAY. 
• 
Now, please write the number you marked on the scale in the box below. 
 
  
 
 
The best health 
you can imagine 
YOUR HEALTH TODAY = 
10 
0 
20 
30 
40 
50 
60 
80 
70 
90 
100
5 
15 
25 
35 
45 
55 
75 
65 
85 
95 

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Appendix G VEINES-QOL/Sym questionnaire 
 
 
 
 
 

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Appendix H Center for Medicare and Medicaid Services (CMS) IDE Study Criteria 
 
Beneficiaries 
Medicare beneficiaries may be affected by the device because in 2014, 57% of the patients diagnosed with 
venous embolism were Medicare aged. Additionally, 52% of patients treated with a primary diagnosis of 
venous embolism were of Medicare age. Study results are expected to be generalizable within the Medicare 
beneficiary population based on the prevalence of venous embolism in patients 65 and older. 
Reference: Truven Health Analytics, MarketScan Inpatient View; 2014 
 
Health and Human Services (HHS) Human Subjects Protection Regulations 
All IRBs should comply with 45 CFR Part 46.