Valiant Evo International Clinical Trial
Phase: NA
Conditions: Aortic Aneurysm, Thoracic
Sponsor: Medtronic Cardiovascular

 
 
 
 
 
 
 
 
 
 
 
Clinical Investigation Plan 
 
 
 
Version  3.0,  
 APV-Valiant EVO OUS 
Page 1 of 72  
22 September 2017 
Valiant Evo International Clinical Trial 
BRC_T432 V5.0 
 
Medtronic Confidential 
 
 
 
Clinical Investigation Plan 
Clinical Investigation Plan/Study Title  Valiant EVO International Clinical Trial 
Study Product Name 
Valiant™ Evo Thoracic Stent Graft System 
Sponsor/Local Sponsor 
Medtronic Bakken Research Center BV 
Endepolsdomein 5 
6229 GW Maastricht 
The Netherlands 
Document Version 
3.0 
Lead Principal Investigator(s) 
Prof. Fabio Verzini 
S.C. Chirurgia Vascolare – VI piano  
Ospedale S. Maria della Misericordia 
Piazzale Menghini, 1  
06129 Perugia 
Italy  
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. 
 
 
 
 
 

 
 
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Approval sheet 
Design Assurance Engineer 
(name) 
(functional role) 
 
 
(signature) 
(date) (dd MMM yyyy) 
Following signatures are collected electronically in the trial master file: 
 
Role 
Name 
Title 
Author 
 
Sr. Clinical Research Specialist 
Clinical Leadership 
 
Sr. Clinical Research Director 
Clinical Leadership 
 
Clinical Research Manager 
Program Lead 
 
Clinical Research Manager 
Clinical Quality 
 
Clinical Quality Manager 
Clinical Quality 
 
Sr. Clinical Quality Specialist 
Regulatory Affairs 
 
Sr. Regulatory Affairs Specialist 
Regulatory Affairs 
 
U.S. Senior Regulatory Affairs 
Specialist 
Medical Writer 
 
Sr. Clinical Research Specialist 
Statistician 
 
Principal Statistician 
Clinical Study Manager 
 
Sr. Clinical Research Specialist 
Safety 
  
Clinical Safety Specialist 
Monitor 
 
Sr. Clinical Research Monitor 
Therapy Subject Matter 
Expert 
 
Clinical Research Manager 
 
 

 
 
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TABLE OF CONTENTS 
 
A 
SYNOPSIS ......................................................................................................... 7 
B 
GENERAL INFORMATION .............................................................................. 12 
B.1 
Introduction ........................................................................................................................ 12 
B.2 
Device information ............................................................................................................. 14 
 Device Description .................................................................................................. 14 
B.2.1
B.2.1.1 
Valiant Evo Thoracic Stent Graft ............................................................. 14 
B.2.1.2 
Valiant Evo Delivery System .................................................................... 16 
B.2.1.3 
Device sizes and configurations .............................................................. 17 
 Indications for Use ................................................................................................... 19 
B.2.2
 Device Approval Status ........................................................................................... 20 
B.2.3
B.3 
Comparator information ..................................................................................................... 20 
C 
STUDY PLAN ................................................................................................... 20 
C.1 
Study objectives................................................................................................................. 20 
 Primary objectives ................................................................................................... 20 
C.1.1
 Secondary objectives .............................................................................................. 20 
C.1.2
C.2 
Clinical endpoints............................................................................................................... 21 
 Primary endpoint ..................................................................................................... 21 
C.2.1
 Secondary endpoints ............................................................................................... 21 
C.2.2
C.2.2.1 
30-day Secondary Endpoint .................................................................... 21 
C.2.2.2 
12-month Secondary Endpoints .............................................................. 21 
 Additional observations ........................................................................................... 22 
C.2.3
C.3 
Study Hypothesis ............................................................................................................... 22 
C.4 
Study population ................................................................................................................ 22 
C.5 
Study design ...................................................................................................................... 22 
C.6 
Randomization and blinding .............................................................................................. 23 
C.7 
Sample size ....................................................................................................................... 23 
C.8 
Number of investigation sites and study duration .............................................................. 24 
D 
SUBJECT SELECTION .................................................................................... 24 
D.1 
Inclusion criteria ................................................................................................................. 24 
D.2 
Exclusion criteria................................................................................................................ 25 
E 
STUDY PREPARATION PROCEDURES ........................................................ 27 
E.1 
Investigator/Investigation site selection ............................................................................. 27 
 Investigator selection criteria ................................................................................... 27 
E.1.1
 Investigation site selection criteria .......................................................................... 27 
E.1.2
 Clinical Investigation Agreement ............................................................................. 27 
E.1.3
 Curriculum Vitae ...................................................................................................... 28 
E.1.4
E.2 
Ethics ................................................................................................................................. 28 
 EC approval ............................................................................................................. 28 
E.2.1
 Informed consent process ....................................................................................... 28 
E.2.2
 Revisions in Patient Information and Informed Consent Form ............................... 29 
E.2.3
 Regulatory submission ............................................................................................ 29 
E.2.4

 
 
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E.3 
Regulatory compliance ...................................................................................................... 29 
E.4 
Training requirements ........................................................................................................ 30 
E.5 
Clinical study materials and clinical study-specific equipment .......................................... 30 
E.6 
Study device/product traceability ....................................................................................... 30 
 Supply of investigational devices/products ............................................................. 30 
E.6.1
 Storage and handling of investigational devices/products ...................................... 30 
E.6.2
 Device explant and return procedures/products ..................................................... 31 
E.6.3
 Medtronic device/product disposition requirements ................................................ 31 
E.6.4
F 
STUDY METHODS ........................................................................................... 31 
F.1 
Point of enrollment and Point of Inclusion ......................................................................... 31 
F.2 
Implant or procedure aspects ............................................................................................ 34 
 Index Procedure ...................................................................................................... 34 
F.2.1
 Treatment failure ..................................................................................................... 34 
F.2.2
 Hospital Discharge .................................................................................................. 34 
F.2.3
 Follow-Up Visits and Procedures ............................................................................ 34 
F.2.4
F.3 
Data collection requirements ............................................................................................. 35 
F.4 
Role of the sponsor’s representatives ............................................................................... 36 
F.5 
Source documents ............................................................................................................. 36 
F.6 
Adverse events .................................................................................................................. 37 
 Definition/classification ............................................................................................ 37 
F.6.1
 Recording and reporting of Adverse Events ........................................................... 39 
F.6.2
 Recording and reporting of Device Deficiencies ..................................................... 40 
F.6.3
 Adverse Event and Device Deficiency review process ........................................... 40 
F.6.4
 Potential Complaint Reporting ................................................................................ 41 
F.6.5
 Clinical Event Committee ........................................................................................ 42 
F.6.6
 Data Monitoring Committee..................................................................................... 42 
F.6.7
 Emergency contact details in case of serious AEs ................................................. 42 
F.6.8
F.7 
Subject accountability ........................................................................................................ 42 
 Criteria and procedures for exit from study ............................................................. 43 
F.7.1
 Study Withdrawal .................................................................................................... 43 
F.7.2
 Missed follow-up ...................................................................................................... 43 
F.7.3
 Lost-to-follow-up ...................................................................................................... 43 
F.7.4
 Medical care after study exit.................................................................................... 43 
F.7.5
F.8 
Study deviations and CIP changes.................................................................................... 43 
 Request for approval of study deviations ................................................................ 44 
F.8.1
 Reporting requirements for study deviations........................................................... 44 
F.8.2
 Amendments to the Clinical Investigation Plan ....................................................... 45 
F.8.3
G 
QUALITY CONTROL PROCEDURES ............................................................. 45 
G.1 
Procedures for database management ............................................................................. 45 
 Data collection ......................................................................................................... 45 
G.1.1
 Source data to be directly recorded on the Case Report Forms............................. 46 
G.1.2
 Time windows for completion and submission of Case Report Forms ................... 46 
G.1.3
 Data review and processing .................................................................................... 46 
G.1.4
G.2 
Monitoring procedures ....................................................................................................... 46 
 Accessibility of investigation site staff and study materials ..................................... 46 
G.2.1

 
 
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 Audits and investigation site inspections ................................................................. 46 
G.2.2
G.3 
Study suspension or early termination .............................................................................. 47 
 Early study suspension or termination .................................................................... 47 
G.3.1
 Early investigation site suspension or termination .................................................. 47 
G.3.2
 Subject follow-up in case of termination .................................................................. 47 
G.3.3
G.4 
Study close out .................................................................................................................. 47 
H 
DATA ANALYSIS AND REPORTING .............................................................. 48 
H.1 
Analysis of clinical data ..................................................................................................... 48 
H.2 
Publication Policy............................................................................................................... 49 
I 
STUDY MANAGEMENT ................................................................................... 50 
I.1 
Study staff .......................................................................................................................... 50 
I.2 
Advisory committees ......................................................................................................... 50 
 Clinical Event Committee (CEC) ............................................................................. 50 
I.2.1
 Data Monitoring Committee..................................................................................... 50 
I.2.2
 Publication Committee ............................................................................................ 50 
I.2.3
 Imaging Core Lab .................................................................................................... 50 
I.2.4
I.3 
Records and reports .......................................................................................................... 50 
 Investigator records ................................................................................................. 50 
I.3.1
 Investigator reporting responsibilities ...................................................................... 51 
I.3.2
 Sponsor records ...................................................................................................... 51 
I.3.3
 Sponsor reporting responsibilities ........................................................................... 52 
I.3.4
 Record retention ...................................................................................................... 52 
I.3.5
I.4 
Miscellaneous .................................................................................................................... 53 
 Insurance ................................................................................................................. 53 
I.4.1
 Subject compensation and indemnification ............................................................. 53 
I.4.2
 Subject confidentiality .............................................................................................. 53 
I.4.3
J 
RISKS AND BENEFITS ................................................................................... 53 
J.1 
Anticipated Clinical Benefits .............................................................................................. 53 
J.2 
Risks .................................................................................................................................. 54 
J.3 
Risk-to-benefit rationale ..................................................................................................... 55 
K 
REFERENCES ................................................................................................. 57 
L 
APPENDICES .................................................................................................. 59 
L.1 
Abbreviations ..................................................................................................................... 59 
L.2 
Definitions .......................................................................................................................... 61 
 Primary and Secondary Endpoints .......................................................................... 61 
L.2.1
 Major Adverse Events (MAEs) ................................................................................ 64 
L.2.2
 Device Deficiencies ................................................................................................. 66 
L.2.3
 Additional Definitions ............................................................................................... 67 
L.2.4
L.3. Investigational Plan Extension of Follow-Up Requirements ................................................. 68 
L.3.1 Background............................................................................................................... 68 
L.3.2 Rationale................................................................................................................... 68 
L.3.3 Study Plan ................................................................................................................ 68 
L.3.3.1 Secondary Endpoints at 24, 36, 48 and 60 months .................................... 68 
L.3.3.2 Subject accountability ................................................................................. 68 

 
 
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L.3.3.3 Study duration ............................................................................................. 68 
L.3.3.4 Number of investigational sites and study duration .................................... 69 
L.3.4 Study preparation procedures .................................................................................. 69 
L.3.4.1 Revisions in Informed Consent form ........................................................... 69 
L.3.5 Study Methods .......................................................................................................... 69 
L.3.5.1 Follow-Up Visits and Procedures ................................................................ 69 
L.3.5.2 Data collection requirements ....................................................................... 69 
M 
VERSION HISTORY ......................................................................................... 72 
 

 
 
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A SYNOPSIS 
 
Title 
Valiant Evo International Clinical Trial 
Investigational 
Device 
Valiant™ Evo Thoracic Stent Graft System 
Study Design 
The Valiant Evo International Clinical Trial is a prospective, multi-center, pre-market, 
non-randomized, single-arm trial. 
Purpose 
The purpose of the Valiant Evo International Clinical Trial is to demonstrate the safety 
and effectiveness of the Valiant Evo Thoracic Stent Graft System in subjects with a 
descending thoracic aortic aneurysm (DTAA) who are candidates for endovascular 
repair. The Valiant Evo International Clinical Trial is a first-in human experience with the 
objective to provide clinical data for supporting CE marking via case series and 
descriptive statistics. 
Data collected during this trial may also be used in conjunction with data collected during 
a concurrently enrolling IDE trial to support commercial approval of the Valiant Evo 
Thoracic Stent Graft System in the United States. 
Primary objective 
The primary objective is to demonstrate the safety and effectiveness of the Valiant Evo 
Thoracic Stent Graft System in subjects with a DTAA who are candidates for 
endovascular repair.  
Secondary 
objective 
Secondary objectives include descriptive analyses of secondary endpoints as well as 
acute procedural observations and clinical utility measures.  
Safety and effectiveness data will be collected over a one year period following 
endograft implantation. 
Primary Endpoint 
Composite safety and effectiveness endpoint that is based on the proportion of subjects 
who experienced:  
(a) Access and/or deployment failures; and/or  
(b) Major device effect (MDE) within 30 days post index procedure 
MDEs include the occurrence of any of the following and are defined in Appendix L.2.1: 
• 
Device-related secondary procedures  
• 
Device-related mortality 
• 
Conversion to open surgery 
• 
Thoracic aortic aneurysm rupture 
An independent Clinical Events Committee (CEC) will be established to adjudicate 
MDEs. 
Secondary 
Endpoints 
30-day Secondary Endpoints: 
The following secondary endpoints will be evaluated within 30 days post treatment: 
• 
Peri-operative mortality 
• 
All adverse events (AE) within 30 days including: 
• 
Major Adverse Event(s) (MAE)  
• 
Serious Adverse Event(s) (SAE) 
• 
Secondary procedures  
• 
Loss of stent graft patency at 30 day visit based on imaging findings 
• 
Endoleaks at 30 day visit based on imaging findings 
Major adverse events include the occurrence of any of the following: 

 
 
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• Respiratory complications: atelectasis, pneumonia, pulmonary 
embolism, pulmonary edema, respiratory failure  
• Renal complications: renal failure, renal insufficiency  
• Cardiac complications: Myocardial infarction (MI), unstable angina, 
new arrhythmia, exacerbation of congestive heart failure (CHF)  
• Neurological complications: new cerebrovascular accident (CVA),  
cerebrovascular embolic events, paraplegia, paraparesis  
• Gastrointestinal complications: bowel ischemia  
• Major bleeding complication (procedural or post-procedural), 
coagulopathy  
• Vascular complications: aortic rupture, aneurysm rupture, hematoma 
at access site, pseudo or false aneurysm, arteriovenous (AV) fistula, 
retroperitoneal bleed, limb ischemia, thrombosis 
12-month Secondary Endpoints: 
The following secondary endpoints will be evaluated: 
• All-cause mortality within 365 days 
• Aneurysm-Related Mortality within 365 days 
• MDEs within 365 days 
• All AEs within 365 days including: 
• 
MAEs 
• 
SAEs 
• Secondary procedures within 365 days 
• Loss of stent graft patency within 12 months based on imaging findings 
• Endoleaks at 12 months based on imaging findings 
• Stent graft migration at 12 months as compared to 1-month imaging 
• Aneurysm expansion > 5mm at 12 months based on imaging findings 
relative to the 1-month visit 
Note: Medtronic will classify each Adverse Event according to ISO 14155:2011. 
For subjects that re-consented to extended study follow up, the above 12-month 
secondary endpoints are to be evaluated at 24, 36, 48, and 60 months 
Supplementary data analysis will be performed on acute procedural observations and 
clinical utility measures such as the amount of blood loss, blood products transfused, 
duration of implant procedure, time in Intensive Care Unit, and overall hospital stay.  
Subject 
Population 
Subject population will include subjects diagnosed with DTAA who are considered 
candidates for endovascular repair, and who meet the Inclusion/Exclusion Criteria for the 
Valiant Evo International Clinical Trial. 
Number of 
subjects 
47 subjects will be included and assessed per the study’s primary endpoint to support 
regulatory approval.   
Number of Sites 
Subjects will be recruited from up to 17 medical centers. Target geographies include, but 
are not limited to, the Netherlands, Italy, Denmark, France, the United Kingdom and 
Canada. 
Clinical 
Procedures and 
Follow Up 
Schedule 
Inclusion: Those subjects who sign and date the informed consent document, meet all of 
the study eligibility criteria, and are approved by the Independent Reviewer, will be 
eligible for inclusion into the Valiant Evo International Clinical Trial. A subject will only be 
considered included when arterial access is established and an attempt to introduce the 
Valiant Evo Thoracic Stent Graft is made. 
At all required follow-up visits subjects will undergo the following assessments and 
procedures: 
 
 

 
 
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Procedures  
Screening / 
Baseline 
 
Index 
Procedure 
Hospital 
Discharge 
1-Mo. F/U 
(±15 days) 
12-Mo. F/U 
(+60 days) 
CLINICAL 
 
Physical 
examination 
 
 
 
 
 
Adverse event 
assessment 
 
 
 
 
 
EQ-5D 
questionnaire 
 
 
 
 
 
IMAGING 
 
CT/MRI with 
contrast  
 
 
 
 
 
Health-related quality of life outcomes will be assessed at all scheduled follow-up visits 
using the EQ-5D questionnaire. 
Any interim imaging of the stent graft region done within one year of implantation should 
be recorded on the interim image eCRF (e.g. 6-month imaging follow-up when 
performed as standard of care and/or when performed further to any issue observed at 
previous imaging follow-up. All subjects will be consented for up to 2 years of follow-up. 
This is to accommodate any global clinical investigational requirements, if required.  
For subjects that re-consented to extended study follow up, the assessments as 
performed during the 12 month visit is to be repeated at 24, 36, 48 and 60 month visits. 
Principal 
Investigator 
 
Prof. Fabio Verzini 
S.C. Chirurgia Vascolare – VI piano  
Ospedale S. Maria della Misericordia 
Piazzale Menghini, 1  
06129 Perugia 
Italy 
Inclusion Criteria 
Candidates for the Valiant Evo International Clinical trial must be appropriate subjects 
for endovascular repair of aneurysms of the descending thoracic aorta (evidenced by 
screening contrast-enhanced computerized tomography (CT) or contrast-enhanced 
Magnetic Resonance Imaging (MRI)) and have to fulfill all of the following inclusion 
criteria to be eligible for recruitment in the study: 
1. Subject is ≥18 years old 
2. Subject understands and voluntarily has signed and dated the Patient Informed 
Consent approved by the Sponsor and by the Ethics Committee for this study. 
 Note: Patients that belong to vulnerable population groups and are at risk of being 
influenced to participate in the trial without making a well-informed and voluntary decision 
will not be considered for participation.   
3. Subject presents a DTAA which is localized below the ostium of left subclavian 
artery (LSA) and above the ostium of celiac trunk 
4. Subject has a DTAA that is one of the following27: 
a. A fusiform aneurysm with a maximum diameter that:  
• 
is ≥ 50 mm and/or: 
• 
is ≥ 2 times the diameter of the non-aneurysmal thoracic aorta 
and/or:  
• 
is <50 mm and has grown ≥ 5 mm within previous 12 months 
b. A saccular aneurysm or a penetrating atherosclerotic ulcer 

 
 
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5. Subject’s anatomy must meet all of the following anatomical criteria as 
demonstrated on contrast-enhanced CT and/or on contrast-enhanced MRI 
obtained within four (4) months prior to implant procedure:  
a. Proximal and distal non-aneurysmal aortic neck diameter measurements 
must be ≥ 16 mm and ≤ 42 mm 
b. Proximal non-aneurysmal aortic neck length must be ≥ 20 mm (for FreeFlo 
configuration) and ≥ 25 mm (for Closed Web configuration) 
c. Distal non-aneurysmal aortic neck length must be ≥ 20 mm 
6. Subject has adequate arterial access site or can tolerate a conduit that allows 
endovascular access to the aneurysmal site with the delivery system of the 
appropriate sized device chosen for the treatment. 
Exclusion Criteria 
Candidates who meet any of the following exclusion criteria will not be eligible for 
recruitment in the study: 
1. Subject has a life expectancy of less than 1 year 
2. Subject is participating in another investigational drug or device study which 
would interfere with the endpoints and follow-ups of this study 
3. Subject is pregnant 
a. 
Note: A positive pregnancy test may be required by local regulations 
4. Subject requires planned placement of the covered proximal end of the stent 
graft to occur in zones 0 or 1 
5. Subject has a thoracic aneurysm with a contained rupture or localized at the 
anastomosis of a previous graft (pseudo-/false aneurysm) 
6. Subject has a mycotic aneurysm 
7. Subject has a dissection (type A or B) or an intramural hematoma or an aortic 
rupture in addition to the thoracic aneurysm 
8. Subject requires emergent aneurysm treatment, e.g., trauma or rupture 
9. Subject has received a previous stent or stent graft or previous surgical repair in 
the ascending and/or descending thoracic aorta, and/or in the aortic arch 
10. Subject requires surgical or endovascular treatment of an infra-renal aneurysm 
at the time of implant 
11. Subject has had previous surgical or endovascular treatment of an infra-renal 
aortic aneurysm 
12. Treatment with the Valiant Evo Thoracic Stent Graft would require intentional 
revascularization of the brachio-cephalic artery, the left common carotid artery 
or the celiac trunk 
13. Subject has had or plans to have a major surgical or interventional procedure 
within 30 days before or 30 days after the planned implantation of the Valiant 
Evo Thoracic Stent Graft. This does not include planned procedures that are 
needed for the safe and effective placement of the stent graft (i.e., 
carotid/subclavian transposition, carotid/subclavian bypass procedure) 
14. Subject has a significant and/or circumferential aortic mural thrombus at either 
the proximal or distal attachment sites that could compromise fixation and seal 
of the implanted stent graft 
15. Subject has a connective tissue disease (e.g., Marfan’s syndrome, aortic medial 
degeneration) 
16. Subject has a bleeding diathesis or coagulopathy, or refuses blood transfusion. 
17. Subject has had a MI within 3 months of the procedure 
18. Subject has had a CVA within 3 months of the procedure 

 
 
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19. Subject has a known allergy or intolerance to the device materials 
20. Subject has a known allergy to anesthetic drugs 
21. Subject has a known hypersensitivity or contraindication to anticoagulants, or 
contrast media, which is not amenable to pretreatment 
22. Subject has active or systemic infection at the time of the index procedure 
Data Oversight 
An Independent Medical Monitor, Data Monitoring Committee, Clinical Events 
Committee, and imaging core lab with and Independent Physician Reviewer will be 
established to independently evaluate subject anatomical eligibility, health status, 
device performance, and identify any safety concerns regarding subjects’ well-being. 
Contact details of the committees and the core lab will be available in the 
investigational site file. 
 

 
 
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B GENERAL INFORMATION 
B.1 
Introduction 
This clinical investigational plan describes study requirements for the Valiant Evo Thoracic stent 
graft system International Clinical Trial (hereafter referred to as the Valiant Evo International 
Clinical Trial). 
For further literature review, pre-clinical testing and previous clinical experience refer to the 
Investigator’s Brochure. The purpose of this study is to investigate the safety and effectiveness 
of the Valiant Evo Thoracic Stent Graft System in subjects with a DTAA who are candidates for 
endovascular repair. The Valiant Evo International Clinical Trial is a first-in human experience 
with the objective to provide clinical data for supporting CE marking via case series and 
descriptive statistics. Additionally, data collected during the international trial described herein 
may be used in conjunction with data collected during a concurrently enrolling US IDE trial to 
support the US PMA-S of the Valiant Evo Thoracic Stent Graft System.   
Background: 
An aortic aneurysm is defined as a dilatation of the aortic vessel greater than 50% of its normal 
diameter for a given segment of the adhering normal vessel.1 An aneurysm of the Descending 
Thoracic Aorta (DTA) is defined as involving any portion of the thoracic aorta distal to the LSA 
and extending to above the diaphragm.2 In adults, the diameter of the aorta is about 30 mm at 
the aortic root and about 25 mm at the level of the diaphragm. Age is the major influential factor 
in the aneurysm diameter size increase and all diameters increase with age.3 It has been 
reported that aortic diameters increase about 1 mm per decade during adulthood.4 Generally, a 
diameter in the thoracic aorta > 4.5 cm is considered aneurysmal. 1, 2,3,4,5  
A thoracic aortic aneurysm (TAA) is a life-threatening condition. Annually, the incidence of TAA 
in a population-based study is 10.4 per 100,000 person-years, and the DTA is involved in about 
40% of those cases.6 The number of people diagnosed with an aneurysm of the DTA is thought 
to be increasing. Factors that contribute to this rise include increased longevity of the 
population and improved diagnostic capability.6, 7, 8  
The natural history of TAAs, including aneurysms of the DTA, is one of progressive 
enlargement and rupture, and rupture is almost invariably fatal. An early study on the natural 
history reported that over 90% of patients sustained aneurysm growth during the period of 
observation.9 Risk of rupture has been found to be correlated to aneurysm size and growth 
rate.5 An average growth rate of 0.19 cm per year has been observed in aneurysms of the DTA 
in the past.10 An aneurysm diameter of 6-cm has been generally considered the urgent point of 
the risk for rupture.  
Degenerative change of the aortic wall is the cause of most aneurysms of the DTA. Medial 
degenerative disease is responsible for most fusiform aneurysms of the DTA. The smooth 
muscle cells and elastic laminae in the media are replaced by cystic spaces filled with mucoid 
material, which produces progressive weakening and dilatation of the aortic wall, with eventual 
aneurysm formation and subsequent complications such as rupture.11 Arteriosclerosis is a 
process that primarily involves the aortic intima, which accounts for 80% of the aneurysms 
found in the thoracic aorta.12 The intima degenerative change is characterized by raised 
atheromatous intimal plaques consisting of a lipid core and fibrous cap, which eventually 
compromises blood flow and weaken the vessel wall. TAAs that are caused by atherosclerosis 
are frequently saccular, and could result from penetrating atherosclerotic ulcers.11, 12 Current 
available treatments include medical treatment, open surgical repair and endovascular stent-
graft repair.  
Standard surgical treatment involves a thoracotomy, aortic clamping to re-section the 
aneurysmal segment and replacement using a Dacron graft. Endovascular stent graft repair 
consists of trans femoral or iliac introduction of the device. When the stent graft device is 
deployed and expanded within the aneurysmal blood vessel, it creates a new aortic lumen for 
the blood flow, excluding the aneurysm sac from blood flow while maintaining perfusion to the 
lower body. Studies comparing open surgical repair versus endovascular repair concluded that 
the latter offers a less invasive, less expensive alternative, a decrease in mortality and 

 
 
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morbidity in high-risk patients, associated with shorter hospital stay and quicker return to 
normal activities after surgery.13, 14 
In Europe, where thoracic aortic endovascular devices have been commercially available for 
more than two decades, endovascular stent graft treatment is becoming the standard of care in 
the management of the whole spectrum of thoracic aortic diseases. Mid-term experiences in 
using thoracic stent grafts in the management of aneurysm of the DTA have been published 
reporting satisfactory outcomes.14, 15, 16 Rapid advances in technology and procedural 
breakthroughs have contributed to the achievement of a near-complete transformation of the 
whole field of thoracic aortic surgery less than 15 years after the first report by Dake et al17 on 
stent graft repair of thoracic aortic aneurysms.  
However, despite the wide spread adoption of TEVAR in modern treatment of TAAs, not all 
patients are candidates for thoracic endovascular aneurysm repair (TEVAR) due to anatomical 
limitations. Since TEVAR devices often require a large-profile delivery system (often outer 
diameter of 22 Fr to 27 Fr), the presence of large, femoral-iliac arteries is necessary. 
Anatomical limitations represent a significant contributor to the risks of access-vessel injury, 
which continues to be a significant cause of serious morbidity and even mortality related to 
thoracic endovascular procedures. Furthermore, female patients make up >30% of TEVAR 
subjects and tend to have small arteries, which compounds the vessel-access problems 
described. Other anatomical characteristics such as limited proximal and distal aortic neck 
lengths and angulated aortic arch have been identified as risks factors that can limit TEVAR 
too. Complications associated with challenging proximal neck anatomy include type I endoleak 
and stent graft migration while limited distal fixation may lead to inadequate distal seal that 
affects long-term treatment success. In addition, patients that have challenging angulated aortic 
arches have the potential for significant problems during TEVAR due to non-conformability of 
stent grafts, especially along the lesser curve. Landing or fixating in the area of the distal arch 
which transitions into the descending aorta can lead to potentially fatal complications.18  
Today’s commercially available stent graft systems have markedly improved upon first-and 
second-generation systems dating back from the early 1990s and tend to resolve these issues 
by addressing such limitations. Manufacturers have designed stent grafts to be more flexible 
and conformable in addition to enhancing delivery systems with respect to tip design, flexibility, 
sheaths and other features to improve deployment controllability and accuracy. Delivery system 
profiles have been reduced with the intent to minimize endothelial trauma that lead to access 
vessel complications and improve accessibility in patients with smaller access vessels. Despite 
these enhancements, challenges remain in terms of TEVAR applicability. Next-generation 
systems are faced with the challenge of minimizing complications and secondary-procedure 
rates while safely treating increasingly complex and challenging anatomies.   
Medtronic has a long history with the design and commercialization of thoracic aortic stent 
grafts, most recently with the Valiant Captivia stent graft system.  
The Valiant stent graft on the Xcelerant Delivery System was CE marked in March, 2005 
followed by CE marking of the Valiant Captivia Stent Graft System in September, 2009. Valiant 
Captivia was commercially released in the European Union in October, 2009. The same stent 
graft system received FDA commercial approval in April 2011 leveraging data from the VALOR 
II Clinical Study, the Talent Thoracic Stent Graft with Captivia Delivery System Clinical Study, 
and the Valiant Captivia Post-Market Registry. To date, over 75,000 patients (ca. 92,500 units 
used) have been implanted worldwide with this commercially available device since its launch 
in October 2009. Medtronic’s next generation thoracic aortic stent graft is the Valiant Evo 
Thoracic Stent Graft. 
Valiant Evo Thoracic Stent Graft System is designed to allow treatment of patients without the 
need for alternative access methods, expand overall patient applicability, and improve 
procedural ease of use of the system. This device will address an important TEVAR need: a 
significant reduction of the delivery system profile (profile of 18Fr for diameters ≤25 mm, profile 
of 20Fr for diameters ≤37 mm and profile of 22Fr for diameters ≥ 40 mm). A lower profile will 
better facilitate the endovascular treatment of patients with smaller vessel diameters as well as 
narrow, tortuous and/or calcified iliac arteries. Lower profile will potentially enable a 

 
 
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percutaneous approach which could reduce complications related to cut down, shorten 
procedure time, blood loss, improve patient comfort and reduce the time to ambulation.  
The Valiant Evo Thoracic Stent Graft System has incorporated design changes from the Valiant 
Captivia stent graft system with the following of notable importance:  
• 
Introduction of the Closed Web configuration with the tip capture mechanism as the 
proximal or distal device 
• 
Reduced length of tapered tip of the delivery system  
• 
Stent graft configurations with longer length (up to 225 mm) and increased taper (5 – 6 
mm) 
• 
An optimized size matrix, including 60 mm extensions for use as cuffs in the 
descending aorta.  
These enhancements were incorporated in the Valiant Evo Thoracic Stent Graft System design 
with an expressed focus on maintaining the high durability and high performance standards 
established with the previous Valiant Captivia stent graft system. When designing the features 
of the Valiant Evo device, it was critical that the durability, clinical safety and performance 
standards established with Valiant were maintained. All design changes and device attributes 
incorporated within the Valiant Evo design will be evaluated via the full suite of planned design 
verification and validation testing, which includes bench and in vivo testing. This ensures that 
the modified device meets the pre-established design and performance specifications and to 
ensure that product performance will not be negatively affected. Residual risks associated with 
the overall performance of the Valiant Evo Thoracic Stent Graft System will be confirmed in a 
clinical investigation designed to evaluate system performance.  
B.2 
Device information 
The study device being evaluated in this clinical study is the Valiant Evo Thoracic Stent Graft 
System which is an investigational device manufactured by Medtronic.  
 
Device Description 
B.2.1
The Valiant Evo Thoracic Stent Graft System is designed for the endovascular repair of lesions 
in the DTA. When placed within the target lesion, the stent graft provides an alternative conduit 
for blood flow within the patient’s vasculature by excluding the lesion from blood flow and 
pressure. 
The Valiant Evo Thoracic Stent Graft System is composed of two main components: the 
implantable Valiant Evo Thoracic Stent Graft and the disposable delivery system. The Valiant 
Evo Thoracic Stent Graft is preloaded into the delivery system, which is inserted endoluminally 
via the femoral or iliac artery and tracked through the patient’s vasculature to deliver the stent 
graft to the target site. Upon deployment, the stent graft self-expands to conform to the shape 
and size of the seal zones above and below the lesion. 
The Valiant Evo Thoracic Stent Graft System does not contain natural rubber latex; however, 
during the manufacturing process, it may have had incidental contact with latex-containing 
products. 
B.2.1.1 
Valiant Evo Thoracic Stent Graft 
A single, primary stent graft may be used by itself if its size is sufficient to provide the desired 
coverage. Alternatively, it may be used in combination with additional stent graft sections that 
increase the graft length distally or proximally to the primary section.  
All stent graft components are composed of a self-expanding spring scaffold made from nitinol 
wire sewn to a polyester fabric graft with non-resorbable sutures. The metal scaffolding is 
composed of a series of serpentine stents stacked in a tubular configuration. Radiopaque (RO) 
markers are sewn onto each component of the stent graft to aid in visualization and to facilitate 
accurate placement. The nitinol stents are also visible under fluoroscopy. The materials used in 
the Valiant Evo Thoracic Stent Graft are listed in Table B-1. 
 

 
 
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Table B-1: Valiant Evo Thoracic Stent Graft materials 
Component  
Material 
Springs 
Nitinol (nickel-titanium) alloy 
RO markers 
Platinum-iridium alloy 
Graft fabric 
Polyester (PET) 
Suture 
Polyester (PET) and Ultra-high-molecular-weight 
polyethylene (UHMWPE) 
 
The Valiant Evo Thoracic Stent Graft System is available in four different configurations (see 
Figure B-2): FreeFlo Straight, FreeFlo Tapered, Closed Web Straight, and Closed Web 
Tapered.  
Each stent graft configuration can be used either as a proximal or distal component. 
 
 
1. FreeFlo Straight 
2. FreeFlo Tapered 
3. Closed Web Straight 
4. Closed Web 
Tapered 
5. Proximal End 
6. Distal End 
7. FreeFlo 
8. Closed Web 
9. Support Spring 
10. RO marker 
11. Covered Length 
12. Total Length 
Figure B-2: Stent Graft Configuration Components 
 
Note: Figure B-2 and all other product graphics appearing in this document are not drawn to 
scale. They are for graphical representation only, and the stent graft and delivery system 
components may appear differently under fluoroscopy. 
FreeFlo Straight configuration 
This configuration includes a FreeFlo proximal end and a Closed Web distal end. At the 
proximal end, a 6-peak (18 Fr or 20 Fr) or 7-peak (22 Fr) bare stent extends past the covered 
stent graft to provide additional fixation while maintaining transvessel flow. The diameters of the 
proximal end and distal end of the FreeFlo Straight configuration are constant throughout the 
covered length of the device. A proximal end of a FreeFlo stent graft should not be placed 
inside the fabric-covered section of another stent graft. 
 
 

 
 
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FreeFlo Tapered configuration 
This configuration includes a FreeFlo proximal end and a Closed Web distal end. At the 
proximal end, a 6-peak (18 Fr or 20 Fr) or 7-peak (22 Fr) bare stent extends past the covered 
stent graft to provide additional fixation while maintaining transvessel flow. The diameter of the 
proximal end of the FreeFlo Tapered configuration is larger than the diameter of the distal end. 
A proximal end of a FreeFlo stent graft should not be placed inside the fabric-covered section of 
another stent graft. 
Closed Web Straight configuration 
This configuration includes Closed Web proximal and distal ends. The diameters of the 
proximal end and distal end of the Closed Web Straight configuration are constant throughout 
the covered length of the device. 
Closed Web Tapered configuration 
This configuration includes Closed Web proximal and distal ends. The diameter of the proximal 
end of the Closed Web Tapered configuration is larger than the diameter of the distal end. 
B.2.1.2 
Valiant Evo Delivery System 
The Valiant Evo delivery system consists of a single-use, disposable catheter with an integrated 
handle to provide controlled deployment. It is available in an outer diameter of 18, 20, or 22 Fr 
and a working length of 93 cm. The catheter assembly is flexible and exclusively compatible 
with a 0.035-in (0.89-mm) guidewire.  
A flexible tapered tip is attached to the end of the inner member and provides a smooth 
transition from the guidewire to the outer graft cover. The external surfaces of the tapered tip 
and graft cover are coated with a lubricious hydrophilic coating. Once activated with a sterile 
gauze saturated in saline, this coating will facilitate vessel access and tracking through the 
anatomy. A distal RO marker indicates the graft cover edge under fluoroscopy. A hemostasis 
valve at the proximal end of the delivery system minimizes blood loss and leakage during the 
procedure. The stent graft is deployed by rotating or retracting the integrated slider handle. The 
tip capture release handle at the rear of the delivery system is unlocked and retracted to 
release the proximal end of the stent graft. The flush port provides access to the graft cover 
lumen and is used for flushing the system prior to use. The flush port includes a one-way valve 
that prevents back-flow of flush fluid or blood during the procedure. 
 
 
 
 
1. Luer Connector 
2. Screw Gear 
3. Retractor Handle 
4. Trigger 
5. Front Grip 
6. Graft Cover/Introducer 
Sheath 
7. Stent Stop 
8. Tip Capture Mechanism 
9. RO Marker Band 
10. Tapered Tip 
11. Back End Lock 
12. Tip Capture Release 
Handle 
13. Screw Gear Retainer 
14. Flush Port 
 

 
 
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Figure B-3: Valiant Evo Thoracic Stent Graft delivery system 
For detailed description of the Valiant Evo Thoracic Stent Graft System components, materials, 
and sizing configurations please see the Instructions for Use (IFU) and the Investigator’s 
Brochure (IB). The IFU will be provided with each investigational device. 
B.2.1.3 
Device sizes and configurations 
Table B-2 presents the proposed sizes and configurations of the Valiant Evo Thoracic Stent 
Graft System.  
Table B-2: Valiant Evo Thoracic Stent Graft System size matrix 
Model Numbers/ 
Customer Facing 
Numbers (CFNs) 
Catheter 
Crossing 
Profile 
(Fr) 
Stent Graft 
Description 
(Diameter*length) 
Stent Graft Type 
VEEF3434C60CE 
20 
34x60mm 
FreeFlo Straight Extension 
VEEF3737C60CE 
20 
37x60mm 
FreeFlo Straight Extension 
VEEF4040C60CE 
22 
40x60mm 
FreeFlo Straight Extension 
VEEF4343C60CE 
22 
43x60mm 
FreeFlo Straight Extension 
VEEF4646C60CE 
22 
46x60mm 
FreeFlo Straight Extension 
VEMF2020C100CE 
18 
20x100mm 
FreeFlo Straight 
VEMF2222C100CE 
18 
22x100mm 
FreeFlo Straight 
VEMF2525C100CE 
18 
25x100mm 
FreeFlo Straight 
VEMF2828C100CE 
20 
28x100mm 
FreeFlo Straight 
VEMF3131C100CE 
20 
31x100mm 
FreeFlo Straight 
VEMF3434C100CE 
20 
34x100mm 
FreeFlo Straight 
VEMF3737C100CE 
20 
37x100mm 
FreeFlo Straight 
VEMF4040C100CE 
22 
40x100mm 
FreeFlo Straight 
VEMF4343C100CE 
22 
43x100mm 
FreeFlo Straight 
VEMF4646C100CE 
22 
46x100mm 
FreeFlo Straight 
VEMF2222C175CE 
18 
22x175mm 
FreeFlo Straight 
VEMF2525C175CE 
18 
25x175mm 
FreeFlo Straight 
VEMF2828C175CE 
20 
28x175mm 
FreeFlo Straight 
VEMF3131C175CE 
20 
31x175mm 
FreeFlo Straight 
VEMF3434C175CE 
20 
34x175mm 
FreeFlo Straight 

 
 
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Model Numbers/ 
Customer Facing 
Numbers (CFNs) 
Catheter 
Crossing 
Profile 
(Fr) 
Stent Graft 
Description 
(Diameter*length) 
Stent Graft Type 
VEMF3737C175CE 
20 
37x175mm 
FreeFlo Straight 
VEMF4040C175CE 
22 
40x175mm 
FreeFlo Straight 
VEMF4343C175CE 
22 
43x175mm 
FreeFlo Straight 
VEMF4646C175CE 
22 
46x175mm 
FreeFlo Straight 
VEMF3131C225CE 
20 
31x225mm 
FreeFlo Straight 
VEMF3434C225CE 
20 
34x225mm 
FreeFlo Straight 
VEMF3737C225CE 
20 
37x225mm 
FreeFlo Straight 
VEMF4040C225CE 
22 
40x225mm 
FreeFlo Straight 
VEMF4343C225CE 
22 
43x225mm 
FreeFlo Straight 
VEMF4646C225CE 
22 
46x225mm 
FreeFlo Straight 
VEEC3434C60CE 
20 
34x60mm 
Closed Web Extension 
VEEC3737C60CE 
20 
37x60mm 
Closed Web Extension 
VEEC4040C60CE 
22 
40x60mm 
Closed Web Extension  
VEEC4343C60CE 
22 
43x60mm 
Closed Web Extension  
VEEC4646C60CE 
22 
46x60mm 
Closed Web Extension 
VEMC2020C100CE 
18 
20x100mm 
Closed Web Straight 
VEMC2222C100CE 
18 
22x100mm 
Closed Web Straight 
VEMC2525C100CE 
18 
25x100mm 
Closed Web Straight 
VEMC2828C100CE 
20 
28x100mm 
Closed Web Straight 
VEMC3131C100CE 
20 
31x100mm 
Closed Web Straight 
VEMC3434C100CE 
20 
34x100mm 
Closed Web Straight 
VEMC3737C100CE 
20 
37x100mm 
Closed Web Straight 
VEMC4040C100CE 
22 
40x100mm 
Closed Web Straight 
VEMC4343C100CE 
22 
43x100mm 
Closed Web Straight 
VEMC4646C100CE 
22 
46x100mm 
Closed Web Straight 
VEMC2222C175CE 
18 
22x175mm 
Closed Web Straight 
VEMC2525C175CE 
18 
25x175mm 
Closed Web Straight 
VEMC2828C175CE 
20 
28x175mm 
Closed Web Straight 
VEMC3131C175CE 
20 
31x175mm 
Closed Web Straight 
VEMC3434C175CE 
20 
34x175mm 
Closed Web Straight 
VEMC3737C175CE 
20 
37x175mm 
Closed Web Straight 
VEMC4040C175CE 
22 
40x175mm 
Closed Web Straight 
VEMC4343C175CE 
22 
43x175mm 
Closed Web Straight 

 
 
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Model Numbers/ 
Customer Facing 
Numbers (CFNs) 
Catheter 
Crossing 
Profile 
(Fr) 
Stent Graft 
Description 
(Diameter*length) 
Stent Graft Type 
VEMC4646C175CE 
22 
46x175mm 
Closed Web Straight 
VEMC3131C225CE 
20 
31x225mm 
Closed Web Straight 
VEMC3434C225CE 
20 
34x225mm 
Closed Web Straight 
VEMC3737C225CE 
20 
37x225mm 
Closed Web Straight 
VEMC4040C225CE 
22 
40x225mm 
Closed Web Straight 
VEMC4343C225CE 
22 
43x225mm 
Closed Web Straight 
VEMC4646C225CE 
22 
46x225mm 
Closed Web Straight 
VEMF2520C175CE 
18 
25x20x175mm 
FreeFlo Tapered 
VEMF2822C175CE 
20 
28x22x175mm 
FreeFlo Tapered 
VEMF3125C175CE 
20 
31x25x175mm 
FreeFlo Tapered 
VEMF3428C175CE 
20 
34x28x175mm 
FreeFlo Tapered 
VEMF3731C175CE 
20 
37x31x175mm 
FreeFlo Tapered 
VEMF4034C175CE 
22 
40x34x175mm 
FreeFlo Tapered 
VEMF4337C175CE 
22 
43x37x175mm 
FreeFlo Tapered 
VEMF4640C175CE 
22 
46x40x175mm 
FreeFlo Tapered 
VEMC2520C175CE 
18 
25x20x175mm 
Closed Web Tapered 
VEMC2822C200CE 
20 
28x22x200mm 
Closed Web Tapered 
VEMC3125C200CE 
20 
31x25x200mm 
Closed Web Tapered 
VEMC3428C200CE 
20 
34x28x200mm 
Closed Web Tapered 
VEMC3731C200CE 
20 
37x31x200mm 
Closed Web Tapered 
VEMC4034C200CE 
22 
40x34x200mm 
Closed Web Tapered 
VEMC4337C200CE 
22 
43x37x200mm 
Closed Web Tapered 
VEMC4640C200CE 
22 
46x40x200mm 
Closed Web Tapered 
 
Indications for Use  
B.2.2
The Valiant Evo Thoracic Stent Graft System is indicated for the endovascular repair of fusiform 
aneurysms and saccular aneurysms/penetrating ulcers of the DTA in patients having the 
appropriate anatomy, including the following: 
• 
Iliac or femoral access vessel morphology that is compatible with vascular access 
techniques, devices, or accessories 
• 
Non-aneurysmal aortic diameter from 16 to 42 mm 
• 
Non-aneurysmal aortic proximal neck length ≥ 20mm (for FreeFlo configuration) and ≥ 
25mm (for Closed Web configuration) 
• 
Distal neck length ≥ 20 mm 
Detailed information on intended use of the device, indications and contraindications, as well as 
a complete list of warnings, precautions and potential adverse events, will be included in the 
IFU and the IB. The IFU will be provided with each investigational device. 

 
 
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Device Approval Status 
B.2.3
The Valiant Evo Thoracic Stent Graft System is an investigational Class III device in all geographies 
except for Canada where it is an investigational Class IV device. The Valiant Evo Thoracic Stent Graft 
System has not received any regulatory approval yet. For the purpose of this study  each 
investigational device will be labelled with “Exclusively for clinical investigations” or similar wording in 
corresponding local language. In Canada, the labelling will be as follows: “Investigational Device: To 
be used by qualified investigators only / Instrument de recherche: Réservé uniquement à l’usage de 
chercheurs compétents”.  ‘ 
The use of the Valiant Evo Thoracic Stent Graft System is limited to this clinical investigation 
and has to be done according to the Clinical Investigational Plan and the Instructions for Use 
(IFU). Required Investigator training for the use of the Valiant Evo Thoracic Stent Graft System 
is described in Section E. 4. 
B.3 
Comparator information 
No comparator will be used for this clinical trial. All analysis will be descriptive in nature and no 
statistical comparisons are planned. 
C STUDY PLAN 
C.1 
Study objectives 
The purpose of the Valiant Evo International Clinical Trial is to demonstrate the safety and 
effectiveness of the Valiant Evo Thoracic Stent Graft System in subjects with a DTAA who are 
candidates for endovascular repair.  
The Valiant Evo International Clinical Trial is a first-in human experience with the objective to 
provide clinical data for supporting CE marking via case series and descriptive statistics. Data 
collected during this trial may also be used in conjunction with data collected during a 
concurrently enrolling IDE trial to support commercial approval of the Valiant Evo Thoracic 
Stent Graft System in the United States. 
 
Primary objectives 
C.1.1
The primary objective is to demonstrate the safety and effectiveness of the Valiant Evo 
Thoracic Stent Graft System in subjects with a DTAA who are candidates for endovascular 
repair.  
The Valiant Evo Thoracic Stent Graft System is Medtronic’s next generation thoracic stent graft 
system and this study is designed to assess the design changes from the commercially 
available Valiant Captivia stent graft system that have been incorporated into the design of the 
Valiant Evo Thoracic Stent Graft System, as the safety and effectiveness of the Valiant Captivia 
stent graft system has been established through its clinical trials. 
(See section C.2 Clinical Endpoints for a detailed description of the evaluation criteria used to 
assess Primary Objectives.) 
 
Secondary objectives 
C.1.2
Secondary objectives include descriptive analyses of secondary endpoints as well as acute 
procedural observations and clinical utility measures.  
Safety and effectiveness data will be collected over a one year period following endograft 
implantation. 
(See section C.2 Clinical Endpoints for a detailed description of the evaluation criteria used to 
assess Secondary Objectives.) 

 
 
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C.2 
Clinical endpoints 
 
Primary endpoint 
C.2.1
The primary objective will be assessed by the composite safety and effectiveness endpoint that 
is based on the proportion of subjects who experienced:  
(a) Access and/or deployment failures; and/or  
(b) MDE within 30 days post index procedure 
MDEs include the occurrence of any of the following: 
• 
Device-related secondary procedures  
• 
Device-related mortality 
• 
Conversion to open surgery 
• 
Thoracic aortic aneurysm rupture 
Detailed definitions of MDEs are defined in Appendix L. 2.1. 
An independent CEC will be established to adjudicate MDEs. 
 
Secondary endpoints 
C.2.2
C.2.2.1 
30-day Secondary Endpoint 
The following secondary endpoints will be evaluated within 30 days post treatment: 
• 
Peri-operative mortality 
• 
All adverse events (AE) within 30 days including: 
• 
Major Adverse Event(s) (MAE)  
• 
Serious Adverse Event(s) (SAE) 
• 
Secondary procedures  
• 
Loss of stent graft patency at 30 day visit based on imaging findings 
• 
Endoleaks at 30 day visit based on imaging findings 
Major adverse events include the occurrence of any of the following: 
• 
Respiratory complications: atelectasis/pneumonia, pulmonary embolism, pulmonary 
edema, respiratory failure 
• 
Renal complications: renal failure, renal insufficiency 
• 
Cardiac complications: MI, unstable angina, new arrhythmia, exacerbation of CHF 
• 
Neurological complications: new cerebrovascular accident (CVA) cerebrovascular 
embolic events, paraplegia, paraparesis 
• 
Gastrointestinal complications: bowel ischemia 
• 
Major bleeding complication (procedural or post-procedural), coagulopathy 
• 
Vascular complications: aortic rupture, aneurysm rupture, hematoma at access site, 
pseudo or false aneurysm, arteriovenous (AV) fistula, retroperitoneal bleed, limb 
ischemia, thrombosis 
Detailed definition of MAEs is defined in Appendix L.2.2. 
C.2.2.2 
12-month Secondary Endpoints 
The following secondary endpoints will be evaluated: 
• 
All-cause mortality within 365 days 
• 
Aneurysm-Related Mortality within 365 days 
• 
MDEs within 365 days 
• 
All AEs within 365 days including: 

 
 
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• 
MAEs 
• 
SAEs 
• 
Secondary procedures within 365 days 
• 
Loss of stent graft patency within 12 months based on imaging findings 
• 
Endoleaks at 12 months based on imaging findings 
• 
Stent graft migration at 12 months as compared to 1-month imaging 
• 
Aneurysm expansion > 5mm at 12 months based on imaging findings relative to the 1-
month visit 
 
Additional observations 
C.2.3
The following acute procedural observations and clinical utility measures will be analyzed:  
• 
Mean duration (min) of procedure  
• 
Proportion of subjects who underwent general anesthesia  
• 
Proportion of subjects who underwent percutaneous access  
• 
Proportion of subjects requiring blood transfusions  
• 
Mean number of units of blood transfused, if required  
• 
Mean volume (cc) of estimated blood loss  
• 
Mean length of time (hours) in intensive care unit  
• 
Mean length of time (days) of hospital stay (from the index procedure to hospital 
discharge) 
Health-related quality of life outcomes will be assessed at all scheduled follow-up visits using 
the EQ-5D questionnaire.  
C.3 
Study Hypothesis 
The Valiant Evo International Clinical Trial is not hypothesis driven; all endpoints will be 
analyzed descriptively. There is no intention to make any clinical claim based on a statistical 
hypothesis. The limitation of the descriptive design is that there is no statistical comparison or 
hypothesis to test and thus no pass/fail criteria. 
Given the established safety and performance profile of the commercially available Valiant 
Captivia stent graft system, and the relatively low risk associated with the new features 
incorporated in the Valiant Evo device design, the goal of this trial is to provide clinical data via 
descriptive statics demonstrating that the Valiant Evo system performs as expected clinically. 
C.4 
Study population 
The study population will include those subjects who are appropriate candidates for 
endovascular repair of DTAA, and who meet the Inclusion/Exclusion criteria (defined in Section 
D). 
C.5 
Study design 
The Valiant Evo International Clinical Trial is a non-randomized, multicenter, open-label, 
prospective, single-arm trial. The trial is designed to assess the clinical safety and effectiveness 
of the Valiant Evo Thoracic Stent Graft System. A sample of 47 subjects will be included and 
evaluated for the 30-day primary endpoint. Data from these 47 subjects will be analyzed and 
used to support CE Mark approval. All subjects included will continue to be followed under this 
investigational protocol beyond the 30-day primary endpoint out to 12 months post-
implantation. Subjects will have required follow-up evaluations at the following time points: 
• 
1-month following the index procedure 
 
• 
12-months following the index procedure 

 
 
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All subjects will be consented for up to 2 years of follow-up. This is to accommodate any global 
clinical investigational requirements, if required.   
Number of devices being used within this trial: 
For subjects that are treated with the Valiant Evo Thoracic Stent Graft a single, primary stent 
graft may be used by itself if its size is sufficient to provide the desired coverage. Alternatively, 
it may be used in combination with additional stent graft sections that increases the graft length 
distally or proximally to the primary section in order to cover the complete target lesion length. 
C.6 
Randomization and blinding 
Randomization and blinding will not be utilized as the proposed trial is descriptive in nature, 
with a single-arm, open-label design, without a control. 
C.7 
Sample size 
A sample of 47 subjects will be included and analyzed to support CE marking. The sample size 
of 47 subjects is considered adequate to assess the primary endpoint, which is defined as the 
proportion of subjects who experienced access/deployment failure or MDE within 30-days post 
index procedure.  
Based upon the reported events from the VALOR II study19 on the Valiant Xcelerant stent graft 
system, the primary endpoint defined by this protocol would have a failure rate of 5.6% (9/160) 
within 30 days post index procedure. Considering the failure rate of Valor II, it is expected that 
Valiant Evo would perform similarly, meaning that 3 out of 47 subjects (6.4%) would likely fail 
within 30 days of implantation. The precision of this assumed 6.4% point estimate can be 
assessed by calculating the distance from the calculated 1-sided 95% upper confidence limit. 
This distance, or margin of error, is calculated to be <10% for this trial; therefore, considered 
adequate20, 21 to assess the primary endpoint.  
Due to sampling variation, different number of MDEs, anywhere from 0 to 47, might be 
observed, which would result in different confidence intervals depending on the outcomes as 
shown in Table C-1. 
 
 
 
Table C-1: Sampling Variation and Its Impact to Study Results 
Observed 
number 
of events 
(k) 
Observed 
event 
rate 
Probability 
to observe 
k events 
Probability 
to observe 
k or less 
events 
One-sided 
95% Upper 
Confidence 
Limit 
Two-sided 95% 
Confidence 
Interval 
0 
0% 
0.0666 
0.0666 
6.2% 
[0%, 7.5%] 
1 
2.1% 
0.1858 
0.2524 
9.7% 
[0.1%, 11.3%] 
2 
4.3% 
0.2535 
0.5059 
12.8% 
[0.5%, 14.5%] 
3 
6.4% 
0.2256 
0.7314 
15.7% 
[1.3%, 17.5%] 
4 
8.5% 
0.1472 
0.8786 
18.4% 
[2.4%, 20.4%] 
5 
10.6% 
0.0751 
0.9537 
21.1% 
[3.5%, 23.1%] 
6 
12.8% 
0.0312 
0.9849 
23.6% 
[4.8%, 25.7%] 
7 
14.9% 
0.0108 
0.9957 
26.2% 
[6.2%, 28.3%] 

 
 
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8 
17.0% 
0.0032 
0.9989 
28.6% 
[7.6%, 30.8%] 
9 
19.1% 
0.0008 
0.9998 
31.0% 
[9.1%, 33.3%] 
10 
21.3% 
0.0002 
1.0000 
33.4% 
[10.7%, 35.7%] 
Note: Only 0 to 10 events are tabulated as probability of observing larger number of events is decreasing quickly. 
Probabilities were calculated based on the 5.6% MDE rate in the target population. An exact method (Clopper-Pearson) 
was used in calculating confidence interval, the same method to be used for data analysis. 
Table C-1 also shows that the probability of observing 3 or less events in a 47-subject sample is 0.7314. The probability 
of observing 6 or more events is 0.0463 (=1 – probability of 5 or less). Based on this, the expectation is to see less than 
6 events in this trial provided that the Valiant Evo performs similarly to its predicate. 
Given the sample size of 47 subjects, the confidence interval estimate provides limited but 
desired precision of a statistical estimation or control of sampling variation (C.I. width) as 
shown. 
C.8 
Number of investigation sites and study duration 
Forty-seven (47) subjects will be included in approximately 17 investigation sites. Target 
countries include, but are not limited to the Netherlands, France, Italy, Denmark, Canada and 
the United Kingdom. No more than 20% of the total study population (i.e. 9 subjects of a total of 
47 subjects) will be included from a single investigational site. Inclusion will be halted at sites 
that reach the 20% inclusion cap. There will be no minimum number of subjects for a single 
investigational site.  
The total inclusion period is not expected to exceed 12 months. All included subjects will be 
followed up at 1 and 12 months post-implantation.  
All subjects will be consented for up to 2 years of follow-up. This is to accommodate any global 
clinical investigational requirements, if required.   
A list of names and addresses of the investigational sites and principal investigators in which 
the clinical study will be conducted will be kept separate from the clinical investigation plan and 
is stored in the Trial Master File. This list is provided to the investigators. The sponsor will 
maintain an updated list. 
D SUBJECT SELECTION 
D.1 
Inclusion criteria 
Candidates for the Valiant Evo International Clinical trial must be appropriate subjects for 
endovascular repair of aneurysms of the descending thoracic aorta (evidenced by screening 
contrast-enhanced computerized tomography (CT) or contrast-enhanced Magnetic Resonance 
Imaging (MRI)) and have to fulfill all of the following inclusion criteria to be eligible for 
recruitment in the study: 
1. Subject is ≥18 years old 
Subject understands and voluntarily has signed and dated the Patient Informed Consent 
approved by the Sponsor and by the Ethics Committee for this study. 
 Note: Patients that belong to vulnerable population groups and are at risk of being influenced to 
participate in the trial without making a well-informed and voluntary decision will not be 
considered for participation 
2. Subject presents a DTAA which is localized below the ostium of LSA and above the 
ostium of celiac trunk 
3. Subject has a DTAA that is one of the following27: 
a. A fusiform aneurysm with a maximum diameter that: 

 
 
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• 
is ≥ 50 mm and/or: 
• 
is > 2 times the diameter of the non-aneurysmal thoracic aorta and/or: 
• 
is < 50 mm and has grown ≥ 5 mm within previous 12 months 
b. A saccular aneurysm or a penetrating atherosclerotic ulcer 
4. Subject’s anatomy must meet all of the following anatomical criteria as demonstrated 
on contrast-enhanced CT and/or on contrast-enhanced MRI obtained within four (4) 
months prior to implant procedure:  
a. Proximal and distal non-aneurysmal aortic neck diameter measurements must 
be ≥ 16 mm and ≤ 42 mm 
b. Proximal non-aneurysmal aortic neck length must be ≥ 20 mm (for FreeFlo 
configuration) and ≥ 25 mm (for Closed Web configuration) 
c. Distal non-aneurysmal aortic neck length must be ≥ 20 mm 
5. Subject has adequate arterial access site or can tolerate a conduit that allows 
endovascular access to the aneurysmal site with the delivery system of the appropriate 
sized device chosen for the treatment 
D.2 
Exclusion criteria 
Candidates who meet any of the following exclusion criteria will not be eligible for recruitment in 
the study: 
1. Subject has a life expectancy of less than 1 year 
2. Subject is participating in another investigational drug or device study which would 
interfere with the endpoints and follow-ups of this study 
Subject is pregnant  
 Note: A positive pregnancy test may be required by local regulations 
3. Subject requires planned placement of the covered proximal end of the stent graft to 
occur in zones 0 or 1 

 
 
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Figure D-1: Landing zones of the thoracic aorta 
(See appendix L.2.4 for definitions of zones) 
4. Subject has a thoracic aneurysm with a contained rupture or localized at the 
anastomosis of a previous graft (pseudo-/false aneurysm) 
5. Subject has a mycotic aneurysm 
6. Subject has a dissection (type A or B) or an intramural hematoma or an aortic rupture 
in addition to the thoracic aneurysm 
7. Subject requires emergent aneurysm treatment, e.g., trauma or rupture 
8. Subject has received a previous stent or stent graft or previous surgical repair in the 
ascending and/or descending thoracic aorta, and/or in the aortic arch 
9. Subject requires surgical or endovascular treatment of an infra-renal aneurysm at the 
time of implant  
10. Subject has had previous surgical or endovascular treatment of an infra-renal aortic 
aneurysm 
11. Treatment with the Valiant Evo Thoracic Stent Graft would require intentional 
revascularization of the brachio-cephalic artery or the left common carotid artery or the 
celiac trunk 
12. Subject has had or plans to have a major surgical or interventional procedure within 30 
days before or 30 days after the planned implantation of the Valiant Evo Thoracic Stent 
Graft. This does not include planned procedures that are needed for the safe and 
effective placement of the stent graft (i.e., carotid/subclavian transposition, 
carotid/subclavian bypass procedure) 
13. Subject has a significant and/or circumferential aortic mural thrombus at either the 
proximal or distal attachment sites that could compromise fixation and seal of the 
implanted stent graft 

 
 
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14. Subject has a connective tissue disease (e.g., Marfan’s syndrome, aortic medial 
degeneration) 
15. Subject has a bleeding diathesis or coagulopathy, or refuses blood transfusion 
16. Subject has had a MI within 3 months of the procedure 
17. Subject has had a CVA within 3 months of the procedure 
18. Subject has a known allergy or intolerance to the device materials 
19. Subject has a known allergy to anesthetic drugs 
20. Subject has a known hypersensitivity or contraindication to anticoagulants, or contrast 
media, which is not amenable to pretreatment 
21. Subject has active or systemic infection at the time of the index procedure 
E STUDY PREPARATION PROCEDURES 
E.1 
Investigator/Investigation site selection 
 
Investigator selection criteria 
E.1.1
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:   
• 
Investigators are appropriately qualified practitioners and experienced in the diagnosis 
and treatment of subjects requiring an endovascular procedure with a thoracic stent 
graft 
• 
Investigators have adequate time to follow up on the clinical study 
• 
Investigators are willing to comply with the clinical investigation plan 
• 
Investigators are willing to sign the appropriate clinical trial agreement 
• 
Investigators have past experience with conducting clinical studies or appropriate 
training 
• 
Investigators are familiar with ISO 14155:2011 requirements. If not, Investigators are 
willing to undergo an ISO 14155:2011 training 
• 
Investigators are willing to undergo auditing by sponsor or regulatory bodies 
• 
Investigators are willing to undergo study specific training 
 
Investigation site selection criteria 
E.1.2
An investigation site may be selected for participation in the clinical study if compliant with the 
following requirements:  
• 
Adequate staff (sub-investigator and/or research coordinator) that is accessible and 
has time to manage the trial and data reporting requirements 
• 
Site personnel has demonstrated experience with conducting clinical (specifically 
device) trials that comply with applicable regulatory standards. If not, site personnel is 
willing to undergo an ISO 14155:2011 training 
• 
Site has sufficient annual case volume of TAA stent graft procedures 
• 
Ability to securely store devices according to the Instructions for Use  
• 
Ability to perform required imaging assessments at site 
 
Clinical Investigation Agreement 
E.1.3
A Clinical Investigation Agreement shall be in place, signed by the participating investigation 
site and/or principal investigator of each investigation site, as per the local legal requirements, 

 
 
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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, by a fully executed agreement. Amendments to this Clinical Investigation Plan 
shall be agreed upon between Medtronic and investigator(s) and be recorded with a justification 
for the amendments.  
 
Curriculum Vitae  
E.1.4
An up to date signed and dated Curriculum Vitae from all key members of the investigation site 
team participating in this clinical study as listed on the Delegated task List shall be obtained, 
evidencing the required qualifications, including the year and where obtained, and including 
their current position at the investigation site. The signature on the CV must be dated within 3 
years prior to the date of activation of the investigation site.  
E.2 
Ethics 
 
EC approval 
E.2.1
Prior to enrolling subjects in this clinical study, each investigation site’s EC will be required to 
approve the current Clinical Investigation Plan, the Patient Information and Informed Consent 
form, including any other written information to be provided to the subjects and, if applicable, 
the Investigator’s Brochure and materials used to recruit subjects. EC approval of the clinical 
study must be received in the form of a letter and provided to Medtronic before commencement 
of the clinical study at an investigation site. The approval letter must contain enough information 
to identify the version or date of the documents approved. If this information is not contained in 
the approval letter, it must be retrievable from the corresponding submission letter. In addition, 
the approval letter needs to be accompanied by an EC roster or letter of compliance, to allow 
verification that the investigator, other investigation site personnel, and/or Medtronic personnel 
are not members of the EC. If they are members of the EC, written documentation is required 
stating that he/she did not participate in the approval process. If the EC imposes any additional 
requirements (e.g. safety reports, progress reports etc.), Medtronic will prepare the required 
documents and send them to the investigator for reporting to the EC. Investigators must inform 
Medtronic of any change in status of EC approval once the investigation site has started 
enrolment. If any action is taken by an EC with respect to the investigation, that information will 
be forwarded to Medtronic by the respective investigator. 
 
Informed consent process 
E.2.2
The investigator or authorized designee must obtain written informed consent before any 
clinical study related activity takes place.   
Well in advance of the consent discussion, the subject should receive the EC approved Patient 
Information and Informed Consent Form. The informed consent template is kept separate from 
the clinical investigation plan and is stored in the Trial Master File. During the consent 
discussion the investigator or his/her authorized designee must fully inform the subject of all 
aspects of the clinical study that are relevant to the subject’s decision to participate in the 
clinical study. If a subject is unable to read or write, an impartial witness must be present during 
the entire informed consent discussion. All items addressed in the Patient Information and the 
Informed Consent Form must be explained. The language used shall be as non-technical as 
possible and must be understandable to the subject and the impartial witness, where 
applicable. Subjects who are unable to make a decision to participate in a clinical investigation 
and who would need a legal authorized representative will not be enrolled in the study. 
The subject must have ample time and opportunity to read and understand the Patient 
Information and the Informed Consent Form, to inquire about details of the clinical study, and to 
decide whether or not to participate in the clinical study. All questions about the clinical study 
should be answered to the satisfaction of the subject. 

 
 
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Neither the investigator, nor the investigation site staff shall coerce or unduly influence a 
subject to participate or to continue to participate in the clinical study. The informed consent 
process shall not waive or appear to waive the subject’s rights. 
When the subject decides to participate in the clinical study, the Informed Consent Form must 
be signed and personally dated by the subject and investigator or authorized designee. If 
applicable, the witness shall also sign and personally date the consent form to attest that the 
information in the Patient Information and Informed Consent Form was accurately explained 
and clearly understood by the subject, and that informed consent was freely given. The 
informed consent process must be documented in the medical records of each consented 
subject. 
After all persons have signed and dated the Informed Consent Form, the investigator must 
provide the subject with a copy of the Patient Information and the signed and dated Informed 
Consent Form.  
An implant card will be provided to the sites and can be distributed to all included subjects 
based on routine practice. This card will be distributed by the investigational team after the 
implant procedure. 
 
Revisions in Patient Information and Informed Consent Form 
E.2.3
Medtronic will inform the investigators whenever information becomes available that may be 
relevant to the subject’s confirmed participation in the clinical study. The investigator or his/her 
authorized designee should inform the subject in a timely manner.  
Medtronic will revise the written Patient Information and Informed Consent Form whenever new 
information becomes available that may be relevant to the subject’s confirmed participation in 
the clinical study. The revised information will be sent to the investigator for approval by the EC 
and sent to the Competent Authority (CA)/ Regulatory Agencies (RA)  if required by local law 
and regulations. After approval by the EC and CA/RA as applicable, a copy of this information 
must be provided to the participating subjects, and the informed consent process as described 
above needs to be repeated.  
 
Regulatory submission 
E.2.4
No subjects will be enrolled in the clinical study until all applicable Regulatory Authorities have 
approved the current Clinical Investigation Plan and other documents as required according to 
local requirements. 
If a Regulatory Authority imposes any additional requirements (e.g. safety reports, progress 
reports etc.), Medtronic will prepare the required documents and send them to the respective 
authority. 
Other documents that are referred to in this Clinical Investigation Plan are listed below and will 
be made available upon request: 
• 
Monitoring Plan 
• 
Data Management Plan 
• 
Patient Information and Informed Consent Form 
• 
Case Report Forms 
E.3 
Regulatory compliance 
This clinical study will be conducted in compliance with the latest version of the Declaration of 
Helsinki (October 2013), the international standard ISO 14155:2011 ('Clinical Investigation of 
medical devices for human subjects'), Medical Device Directive 93/42/EEC, for Canada, 
SOR/98-282, Sections 79-88, and Canadian Regulatory Guidelines for Mandatory Problem 
Reporting for Medical Devices, 2011 (H164-145/2011E) and all laws.  
In addition, the study will be conducted in compliance with 21 CFR Part 11 and 54 in all 
participating geographies. 

 
 
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All principles of the Declaration of Helsinki have been implemented in this clinical study by 
means of the informed consent process, EC approval, study training, clinical trial registration, 
preclinical testing, risk benefit assessment, publication policy, etc.  
The sponsor will avoid improper influence on, or inducement of the subject, monitor, and 
investigator(s) or other parties participating in, or contributing to, the clinical study by 
implementing the informed consent process, Clinical Investigation Agreements, EC approval. 
This study will be publicly registered in accordance with the Declaration of Helsinki on 
www.clinicaltrials.gov. 
In case of conflicting requirements, the regulation affording the greatest protection to the 
subject will be followed. 
E.4 
Training requirements 
Prior to investigational site activation or subsequent involvement in clinical study activities, 
Medtronic will provide clinical study training relevant and pertinent to the involvement of 
personnel conducting clinical study activities. At a minimum, investigator responsibilities, ISO 
14155:2011, the CIP, PIC, use of data collection tools, applicable local regulations, as well as 
device/product training are required. Study-specific training and any training required by local 
regulations, when applicable, will be documented prior to investigation site activation. 
Performed training will be documented prior to investigation site activation.  
Medtronic and/or its designees are responsible for the training of appropriate clinical site 
personnel, including the investigator, co-investigator(s), study coordinator(s), and as necessary 
other site personnel. Initial training will be conducted by Medtronic or its designees at a site 
initiation visit and/or Investigator meeting to ensure proper reporting of adverse events, uniform 
data collection and compliance with the protocol, consent processes and applicable regulations.   
Also after initial training, Medtronic will provide training to other clinical site study team 
members. Once the primary endpoint has been reached for all subjects, qualified investigators 
may also provide training to other clinical site study team members. All study specific training 
must be documented on a formal training record that will be provided by Medtronic. 
E.5 
Clinical study materials and clinical study-specific equipment 
Medtronic will provide study materials to the site after approval of the site for participation. 
Before a study site can enroll a subject or have access to the electronic data capture (EDC) 
system, the investigator must be in receipt of an “Activation Letter” (this may be an email, fax or 
other written communication means) from Medtronic.  
E.6 
Study device/product traceability 
 
Supply of investigational devices/products 
E.6.1
Medtronic will only allow shipment of investigational devices/products to the investigation site or 
investigator, after the Clinical Study Manager has declared the investigation site ready to start 
the clinical study. 
Once the site has been activated and an eligible subject has been identified and consented 
through the protocol required screening process investigational devices/products will be 
ordered and shipped to the site. 
 
Storage and handling of investigational devices/products 
E.6.2
Investigational devices/products must be stored in a secured area. The method of storage shall 
prevent the use of investigational devices/products for other applications than mentioned in this 
Clinical Investigation Plan. In addition, all information for the use, storage and handling of the 
investigational device/product as indicated in the Investigator’s Brochure and Instructions for 
use must be taken into account. 

 
 
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Device explant and return procedures/products 
E.6.3
Non-functioning or explanted investigational devices/products must be returned to Medtronic as 
soon as possible for investigation. Information pertaining to the explant procedure should be 
recorded. If a product is explanted and not returned to Medtronic, an explanation should be 
provided. The final disposition of the device must be recorded on the device disposition log. 
Relevant information should also be recorded on associated case report forms, e.g. Adverse 
Event and Study Exit Form. Detailed instructions for the return of non-functioning devices and 
explant of the device will be provided in the investigational site file. 
 
Medtronic device/product disposition requirements 
E.6.4
Investigational devices/products will be traced during the clinical study by assigning specific 
unique identifiers to each device/product. The investigator is responsible for maintenance of a 
Device Accountability Log in the Investigator Site File. On this log, the receipt, use, return and 
disposal of the investigational devices/products shall be documented. At the end of the clinical 
study the principal investigator must sign and date the final Device Accountability Log.  
F STUDY METHODS 
F.1 
Point of enrollment and Point of Inclusion 
Pre Screening: 
Investigators will assess potential subjects with a DTAA that are candidates for endovascular 
repair for their suitability for recruitment in the trial. Initial subject eligibility will be determined by 
the investigator based upon review of their medical history, disease process and anatomic 
suitability for inclusion in the trial as evidenced on screening contrast-enhanced CT/MRI. If the 
subject appears to meet the eligibility criteria, then the investigator will discuss the study with 
the subject and provide information relating to the potential risks and benefits, and required 
follow-up procedures per the informed consent process.  
Test results that are within the timeframes specified below may be used even though the actual 
test was done prior to a patient’s informed consent. This may be done only for standard of care 
tests with the intent to minimize stress and discomfort to the subject and reduce costs. 
Required evaluations include the following. 
• 
CT or MRI with contrast of the chest, abdomen and pelvis completed within four 
months prior to the index procedure. This will be used to visualize and assess the 
characteristics, length, and diameters of the DTAA and the surrounding anatomy. 
Screening/ Baseline Assessments: 
After the subject has voluntarily signed and dated the informed consent document, the subject 
will be considered enrolled in the trial. If a subject does not sign the informed consent 
document, then no further screening procedures for the Valiant Evo International Clinical Trial 
will occur. 
Collection of screening and baseline information will take place only after the subject has given 
voluntary, documented informed consent and will include the following: 
 
• 
Subject demographics 
• 
Medical history 
• 
Current health status 
• 
Risk factors 
• 
ASA Physical Status Classification 
• 
EQ-5D Questionnaire 
 

 
 
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Baseline CT/MRI images will be reviewed by the investigator to confirm eligibility. The imaging 
will also be sent to a core lab for analysis. An Independent Physician Reviewer (IPR) will review 
the screening CT/MRI images to assess the anatomical inclusion/exclusion requirements and 
confirm subject eligibility. Approval by the IPR must be obtained prior to a subject’s actual 
inclusion in the study. The decision of the IPR will be communicated to the investigational site 
by the Sponsor. Those subjects who sign and date the Informed Consent, meet all study 
eligibility criteria, and are approved by the IPR will be eligible for inclusion in the study. Subjects 
that are not approved by the IPR are considered screen failures and will not be followed per 
study protocol. However, investigators will be requested to enter safety information in the eCRF 
from date of point of enrolment until date of screen failure. Full IPR review process will be 
documented in a separate document. 
Screen failures will be documented on the Screening, Enrollment and Inclusion log and the 
reason for screen failure will be documented on the screening eCRF. 
Inclusion:  
Those subjects who sign and date the informed consent document, meet all of the study 
eligibility criteria, and are approved by the Independent Reviewer will be eligible for inclusion 
into the Valiant Evo International Clinical Trial. The subject will only be considered included 
when arterial access is established and an attempt to introduce the Valiant Evo Thoracic Stent 
Graft is made. 
Included subjects will be documented on the Screening, Enrollment and Inclusion log and will 
be followed per the study protocol. Subjects who are enrolled and attempted to be implanted 
with the device but the Valiant Evo Thoracic Stent Graft could not be implanted during the 
procedure (treatment failure) will be followed through the 1 month follow-up per the study 
protocol and thereafter as per hospital standard of care. Serious Adverse Events will be 
collected for these subjects over the whole duration of the study. The reason for not including 
the subjects into the trial will be documented on the Screening, Enrollment and Inclusion log 
and will be documented on the screening eCRF.  
The investigator will maintain a log of all subjects screened, enrolled, and included in the 
clinical study, assigning an identification code linked to their names, alternative subject 
identification or contact information. 
As the point of enrollment is considered the point in time the subject signs and dates the 
Informed Consent Form, which is different from the point that the subject is actually included in 
the trial, more subjects will be enrolled in the trial than included. A 10 to 20% screen failure rate 
is expected. Therefore, approximately 57 subjects are expected to be enrolled in order to 
include 47 subjects.  

 
 
 
 
 
 
 
 
 
 
 
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F.2 
Implant or procedure aspects 
 
Index Procedure 
F.2.1
All investigators will read, understand and be trained to the Valiant Evo Thoracic Stent Graft 
System IFU prior to initiation of the procedure. The IFU is packaged with the device and must 
be followed for implantation of the stent graft system. The index procedure will include the 
following: 
• 
Arterial access and implantation of the Valiant Evo Thoracic Stent Graft(s) per the IFU 
• 
Fluoroscopic guidance will be used for placement of the stent graft throughout the 
procedure 
• 
Additional procedures performed during the treatment will be documented on the 
appropriate eCRFs 
• 
Upon completion of the index procedure, a final run-off angiography should be 
performed to document the status of the Valiant Evo device(s), the aneurysmal sac, 
and the surrounding vasculature 
Identification and/or serial numbers for all investigational components of the Valiant Evo 
Thoracic Stent Graft System used or opened during the index procedure will be recorded. 
Adverse event assessment should be done for all subjects as of the moment the subject is 
considered to be enrolled in the study. For subjects enrolled in the trial but not included in the 
trial, adverse event assessments will be done until the point of screen failure and the reason for 
not including will be documented on the Screening, Enrollment and Inclusion log and on the 
screening eCRF. 
 
Treatment failure 
F.2.2
Inability to implant the Valiant Evo Thoracic Stent Graft System following arterial access due to 
deployment issues or entrapment of the delivery system will be considered a treatment failure. 
These subjects will be followed for 30 days and thereafter per institutional standard of care. 
Serious adverse events will be recorded in the eCRF until the total duration of the trial. At the 
end of the study the exit form should be completed. 
If a primary conversion to open repair is required during the index procedure, then the subject 
will be followed for 30 days and thereafter per institutional standard of care. Serious adverse 
events will be recorded in the eCRF until the total duration of the trial. At the end of the study 
the exit form should be completed. 
 
Hospital Discharge 
F.2.3
The following assessments will be performed at hospital discharge and respective data will be 
collected on eCRFs: 
• 
Adverse event assessment 
• 
Duration of intensive care unit stay after index procedure (in hours) 
 
Follow-Up Visits and Procedures 
F.2.4
Each subject will have required post-implantation follow-up visits at 30 days and 12 months 
Follow-up visits and associated timeframe windows are summarized in Table F-1.      
Table F-1:  Post-Implantation Follow-Up Visit Schedule and Windows 
Follow-Up Visit 
Window Start Day 
Target Day 
Window Close Day 
1 Month (± 15 days) 
15 
30 
45 
12 Months (365 ±60 days) 
305 
365 
425 

 
 
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At all required follow-up visits subjects will undergo the following assessments and procedures: 
• 
Physical Examination 
• 
Chest CT/MRI with contrast 
• 
EQ-5D questionnaire   
• 
Adverse event assessment 
A CT/MRI with contrast acquired at discharge (or before day 15) due to medical necessity may 
be used to meet the 1-month follow-up visit CT/MRI requirement if a CT/MRI with contrast 
cannot be obtained within the 1-month follow-up window due to the subject’s health status 
based upon physician discretion. If conversion to open repair is required during the follow-up 
period, then the subject will return for the 30-day follow-up visit, if applicable. Thereafter the 
subject will be followed per institutional standard of care and. serious adverse events will be 
recorded in the eCRF until the total duration of the trial. At the end of the study the exit form 
should be completed. 
F.3 
Data collection requirements 
Clinical data will be collected preoperatively to establish eligibility, at baseline, during the index 
procedure, throughout the hospital stay, and postoperatively at the required follow-up visits 
described in Section F.2. The data collection schedule is summarized in Table F-2. Imaging for 
baseline and follow-up assessments, as specified in Table F.2, will be sent to a Core Lab for 
analysis. In addition, any interim imaging of the stent graft region done within one year of 
implantation should be recorded on the interim image eCRF (e.g. 6-month imaging follow-up 
when performed as standard of care and/or when performed further to any issue observed at 
previous imaging follow-up). In case further analysis is needed, procedural and interim imaging 
exams are to be submitted to Core Lab.   
Study data will be collected using electronic case report forms (eCRFs) as will be described in 
Section G.1. eCRFs should be electronically reviewed and approved by the clinical 
investigators. Medtronic monitors will perform source document verification of the eCRFs. The 
monitoring strategy will be defined in the monitoring plan. 
For test equipment critical for assessing endpoints (e.g., CT scan, MRI, Transesophageal 
echography (TEE)) maintenance and calibrations will be monitored periodically. 
It is expected that the Investigator enrolling the subject at the participating site where the 
implantation occurred will follow the subject during the course of the study. It is the 
responsibility of the Investigator to make sure that the subject is followed and that integrity and 
accuracy of the data is maintained.   
Table F-2:  Data Collection Schedule 
DATA  
Screening / 
Baseline 
 
Index 
Procedure 
Hospital 
Discharge 
1-Mo. F/U 
(±15 days) 
12-Mo. F/U 
(+60 days) 
GENERAL 
 
Informed Consent 
 
 
 
 
 
Inclusion Criteria/ 
Exclusion Criteria 
 
 
 
 
 
Physical Examination  
 
 
 
 
 
Medical History 
 
 
 
 
 
Current Health Status and 
Risk Factors 
 
 
 
 
 
Device and Procedure 
Information  
 
 
 
 
 
Pre-implant Adjunctive 
 
 
 
 
 

 
 
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DATA  
Screening / 
Baseline 
 
Index 
Procedure 
Hospital 
Discharge 
1-Mo. F/U 
(±15 days) 
12-Mo. F/U 
(+60 days) 
Procedures 
Hospital Discharge 
Information 
 
 
 
 
 
Adverse event  
assessment 
a 
 
 
 
 
EQ-5D questionnaire 
 
 
 
 
 
IMAGING 
 
CT/MRI with contrast b 
 
 
 
c, d 
d 
Angiography 
 
e 
 
 
 
a In case of screen failures, investigators will be requested to enter safety information in the 
eCRF from time point of enrolment until time point of screen failure 
b CT evaluation may include “3-phase technique”, volume studies, 3-D reconstruction, or 
computer-aided measurements 
c A CT/MRI with contrast acquired at discharge (or before Day 15) due to medical necessity 
may be used to meet the 1-month follow-up visit CT/MRI requirement if a CT/MRI with 
contrast cannot be obtained within the 1-month follow-up window due to the subject’s health 
status based upon physician discretion. 
d MRI with contrast may be used for those patients experiencing renal failure or who are 
otherwise unable to undergo contrast-enhanced CT scan, with TEE being an additional option 
in the event of suboptimal MR imaging. 
e Required to complete Procedure eCRF but not expected to be submitted to Medtronic or 
Core Lab unless further analysis is needed.  
 
F.4 
Role of the sponsor’s representatives 
Sponsor’s representatives may provide support as required for the clinical study, including 
technical support during implant. The sponsor’s representative is an experienced expert of 
device sizing, placement and the technical features of the device and will advise the implanting 
physician during the implant procedure if needed. The sponsor’s representative will not be 
involved actively during the placement and deployment of the Valiant Evo Thoracic Stent Graft 
System. 
F.5 
Source documents 
Investigators are required to maintain records of each subject’s case history, exposure to the 
device and clinical follow-ups. Source documents include subject’s hospital files (electronic or 
paper), images, programmer printouts, and device labels. For data that is not recorded as 
standard in the subject file, separate worksheets that will be marked as source data can be 
used. The investigator will clearly mark clinical records to indicate that the subject is enrolled in 
this clinical investigation. Note: there may be some country-specific requirements in this regard.  
Investigators should maintain source documents to support the data recorded on the study 
case report forms. Complete medical (clinical and hospital) records include, but are not limited 
to, the following documentation: 
• 
Medical history/physical condition of the subject before involvement in the study 
sufficient to verify clinical protocol entry criteria 
• 
Description of device implantation procedure (material used, drugs administered 
during the procedure, device identification information and disposition, date, time, 
angiographic and clinical findings, etc.) 

 
 
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• 
Signed notes in the subject’s medical record on the enrollment day that identify and 
include: the subject’s date of enrollment/procedure date, the study sponsor, clinical 
site name, the subject number, and documentation and confirmation that the 
appropriate informed consent was obtained 
• 
Dated and signed notes for each subject’s study visit 
• 
Lab results 
• 
All CT/MRI reports, etc. 
• 
Dated printouts or reports of special assessments (ECG report, imaging report, etc.) 
• 
Adverse event reporting and follow-up of the adverse events. Information in the 
medical chart should include at a minimum the following: event description, severity, 
seriousness, onset date, date site became aware of event, duration, relation to study 
device, treatment, and outcome of the adverse event 
• 
Study subject’s condition upon completion of or withdrawal from the study 
Where copies of the original source document as well as print outs of original electronic source 
documents are retained, these shall be signed and dated by a member of the investigation site 
team with a statement that it is a true reproduction of the original source document. In case 
subject contact has been performed by phone, the investigator needs to record as a minimum 
the date of contact in the subject’s hospital file. Furthermore, the reason for withdrawal and 
actions to trace lost to follow-up subjects should be documented in the medical records of the 
subjects.  
The investigator(s) and study personnel must be accessible to the Medtronic field clinical 
support and the clinical study team. This accessibility is of particular importance for the 
completion and clarification of the data on the case report forms and regulatory responsibilities. 
Access to the subject records and other source data must be provided to study monitors, 
auditors and/or inspectors. 
F.6 
Adverse events 
 Definition/classification  
F.6.1
For the purposes of the clinical report, Medtronic will classify each Adverse Event according to 
ISO 14155:2011.* In case country specific definitions and safety reporting regulations are 
stricter than mandated per ISO 14155:2011, reporting will be done in compliance with the 
country specific safety regulations.  
All adverse events that meet the study definitions will be reported to the sponsor and 
documented on the Adverse Event eCRF and in the subject’s medical records.   
 
Clinical events that are inherent to a surgical procedure and expected to occur in the majority of 
subjects for a projected duration may be considered unavoidable. Such events are listed in 
Table F-3. These events should not be to be reported as adverse events during this study. 
 
*: For example, the definition of Serious Adverse Event (SAE) in Germany per the MPSV, § 2 nr 5 is the 
following: 
Serious adverse event is any adverse event, which occurs in an approved clinical investigation or 
performance evaluation and which has led, might have led or could lead directly or indirectly to the death 
or any serious deterioration in the state of health condition of a subject, a user or any other person without 
considering if the event has been caused by the medical device. 
 
 
Table F-3: Expected and unavoidable adverse events related to the surgical procedure. 
Description of the Event 
Time Frame from the Index Procedure 
Endoleaks observed and resolved during 
Resolved by the time the subject leaves 

 
 
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the index procedure 
the OR 
Anesthesia-related nausea and/or vomiting 
Within 24 hours 
Low-grade fever (< 100° F or < 37.8° C) 
Within 48 hours 
Back pain related to laying on OR table 
Within 72 hours 
Incisional pain (pain at access site) 
Within 72 hours 
Sleep problems or insomnia or post 
procedural delirium 
Within 72 hours 
Mild to moderate bruising or ecchymosis 
Within 168 hours 
Where the definition indicates “device”, it refers to any device used in the study. This might be 
the device under investigation, or any market released component of the system. 
Adverse Event (AE): (ISO 14155:2011 3.2) 
Any untoward medical occurrence, unintended disease or injury, or untoward clinical signs 
(including abnormal laboratory findings) in subjects, users or other persons, whether or not 
related to the investigational medical device 
 
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 investigational 
medical devices. 
Adverse Device Effect (ADE): (ISO 14155:2011 3.1) 
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 definition includes any event resulting from use error or from intentional misuse of the 
investigational medical device 
Serious Adverse Event (SAE): (ISO 14155:2011 3.37) 
Adverse event that  
a) 
led to death, 
b) 
led to serious deterioration in the health of the subject, that either resulted in  
1) 
a life-threatening illness or injury, or  
2) 
a permanent impairment of a body structure or a body function, 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) 
led to fetal distress, fetal death or a congenital abnormality or birth defect.   
 
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. 
 
Serious Adverse Device Effect (SADE): (ISO 14155:2011 3.36) 
Adverse device effect that has resulted in any of the consequences characteristic of a Serious 
Adverse Event  
Unanticipated Serious Adverse Device Effect (USADE): (ISO 14155:2011 3.42) 

 
 
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Serious adverse device effect which by its nature, incidence, severity or outcome has not been 
identified in the current version of the risk analysis report 
 
NOTE:  Anticipated serious adverse device effect (ASADE) is an effect which by its nature, incidence, 
severity or outcome has been identified in the risk analysis report. 
 
Unanticipated Adverse Device Effect (UADE): (21CFR812.3) 
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. 
NOTE: Although the collection of UADEs is a US 21CRF812.3 requirement, any event from the Valiant Evo 
International Clinical Trial that meets the UADE criteria will be reported as such and will be adjudicated by 
the Clinical Event Committee (CEC) in order to be pooled with data collected during the concurrently 
enrolling IDE trial.  
Device deficiency: (ISO 14155:2011 3.15) 
Inadequacy of a medical device with respect to its identity, quality, durability, reliability, safety or 
performance 
 
NOTE: Device deficiencies include malfunctions, use errors, and inadequate labelling. 
For the Valiant Evo International Clinical trial Medtronic has defined Major Device Effects 
(MDEs) which will be used to assess the primary endpoint.   
MDEs include the occurrence of any of the following and are defined in Appendix L.2.1: 
• 
Device-related secondary procedures  
• 
Device-related mortality 
• 
Conversion to open surgery 
• 
Thoracic aortic aneurysm rupture 
For the Valiant Evo International Clinical trial Medtronic has defined Major Adverse 
Events which will be used to assess the secondary endpoints.   
MAEs include the occurrence of any of the following and are defined in Appendix L.2.2: 
• 
Respiratory complications: atelectasis, pneumonia, pulmonary embolism, pulmonary 
edema, respiratory failure.  
• 
Renal complications: renal failure, renal insufficiency.  
• 
Cardiac complications: MI, unstable angina, new arrhythmia, exacerbation of CHF.  
• 
Neurological complications: new cerebrovascular accident (CVA), cerebrovascular 
embolic events, paraplegia, paraparesis.  
• 
Gastrointestinal complications: bowel ischemia.  
• 
Major bleeding complication (procedural or post-procedural), coagulopathy. 
• 
Vascular complications: aortic rupture, aneurysm rupture, hematoma at access site, 
pseudo or false aneurysm, arteriovenous (AV) fistula, retroperitoneal bleed, limb 
ischemia, thrombosis 
 Recording and reporting of Adverse Events 
F.6.2
Adverse Event (AE) information will be collected throughout the study and reported to 
Medtronic on the Adverse Event eCRF. All Adverse Events (except the ones listed in table F-3), 
regardless of relatedness or outcome, must be reported. The investigator is responsible for 
reporting all AE to Medtronic. 
See the Adverse Event eCRF for the information to be reported for each Adverse Event. 

 
 
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For Adverse Events that require immediate reporting (see Table F-4), initial reporting may be 
done by phone, e-mail (contact details will be provided in the investigational site file), or on the 
eCRF with as much information as is available. In case the investigator requires information 
from the Sponsor in an emergency situation, the contact details for emergency situations are 
given in section F.6.7. 
 Recording and reporting of Device Deficiencies 
F.6.3
Device Deficiency information will be collected throughout the study and reported to Medtronic. 
Device Deficiencies should be reported on a Device Deficiency Form in the eCRF. In case the 
eCRF is not available the Device Deficiency form needs to be completed manually and must be 
sent to Medtronic. Contact details are given in the investigational site file. The investigator is 
responsible for reporting all Device Deficiencies to Medtronic. 
See the Device Deficiency eCRF for the information to be reported for each Device Deficiency.   
Device deficiencies that did not lead to an Adverse Event but could have led to an SAE 
a) if either suitable action had not been taken, 
b) if intervention had not been made, or 
c) if circumstances had been less fortunate, 
require immediate reporting (see Table F-4). Initial reporting may be done by eCRF, phone, e-
mail, with as much information as available.  
 Adverse Event and Device Deficiency review process 
F.6.4
All Adverse Events and Device Deficiencies will be reviewed by Medtronic Study Management 
and/ or designee. This review will include the determination whether the Adverse Event/Device 
Deficiency meets regulatory reporting requirements (see table F-4). The sponsor will ensure 
timely Adverse Event/Device Deficiency reporting to meet global and country specific regulatory 
requirements. 
A list of anticipated adverse events that are expected in nature is included in section J.2. 
Table F-4: Adverse Event Reporting Requirements 
Serious Adverse Device Effects (SADE), including Unanticipated Serious Adverse Device Effect 
(USADE): 
Investigator submit to: 
 
Medtronic 
As soon as possible, but in no case later than 3 calendar days after the 
clinical site study team first learns of the event or of new information in 
relation with an already reported event. 
Regulatory Authority 
As per local reporting requirement 
EC 
Reporting timeframe as per local EC requirement. 
Sponsor submit to: 
 
Regulatory Authorities 
Reporting timeframe as per local requirement. 
EC 
Submit to EC per local reporting requirement. 
Serious Adverse Events (SAE) 
Investigator submit to: 
 
Medtronic 
As soon as possible, but in no case later than 3 calendar days after the 
clinical site study team first learns of the event or of new information in 
relation with an already reported event. 
Regulatory Authority 
As per local reporting requirement 
EC 
Submit to EC per local reporting requirement. 
Sponsor submit to: 
 

 
 
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Regulatory Authorities 
Reporting timeframe as per local requirement. 
EC 
Submit to EC per local reporting requirement. 
Adverse Device Effects (ADE) 
Investigator submit to: 
 
Medtronic 
As soon as possible, but in no case later than 3 calendar days after the 
clinical site study team first learns of the event. 
Regulatory Authority 
As per local reporting requirement 
EC 
Submit to EC per local reporting requirement. 
Sponsor submit to: 
 
Regulatory Authorities 
Reporting timeframe as per local requirement 
EC 
Submit to EC per local reporting requirement. 
All other AEs 
Investigator submit to: 
 
Medtronic 
Submit in a timely manner after the clinical site study team first learns of 
the event. 
Regulatory Authority 
As per local reporting requirement 
EC 
Submit to EC per local reporting requirement. 
Device Deficiency with SADE potential 
Investigator submit to: 
 
Medtronic 
As soon as possible, but in no case later than 3 calendar days after the 
clinical site study team first learns of the deficiency or of new information in 
relation with an already reported deficiency. 
Regulatory Authority 
As per local reporting requirement 
EC 
Submit to EC per local reporting requirement. 
Sponsor submit to: 
 
Regulatory Authorities 
Reporting timeframe as per local requirement 
EC 
Submit to EC per local reporting requirement. 
All other Device Deficiencies 
Investigator submit to: 
 
Medtronic 
Submit in a timely manner after the clinical site study team first learns of 
the deficiency. 
Regulatory Authority 
As per local reporting requirement 
EC 
Submit to EC per local reporting requirement. 
In addition, Investigators are obligated to report adverse events in accordance with the 
requirements of their EC and local regulations. The Sponsor is obligated to report adverse 
events and device deficiencies that occur during this trial to the Regulatory Authorities and EC 
as per local requirements.  
 
Potential Complaint Reporting 
F.6.5
Potential complaints sourced from the study are reported to the Global Complaint Handling Unit 
(GCH)  

 
 
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Potential complaints may be found throughout clinical study data as reported on CRFs and 
reviewed, or potential complaints may be learned about in alternative fashions within source 
documents or in discussions with investigational site staff. Potential complaints are considered 
for the following: 
• 
All adverse events collected deemed related to the procedure/product/therapy 
• 
All product deficiencies or technical observations, if applicable 
• 
All deaths deemed related to the procedure/product/therapy 
Relationship is to be determined by the investigator and the sponsor. The CEC will assess 
relationship for adjudicable events only.  
 
 
Clinical Event Committee 
F.6.6
A clinical event committee (CEC) will be established. The CEC is an independent committee 
made up of clinicians (interventional) with pertinent expertise who are not participants in the 
study and who do not have any other real or potential conflicts of interest. The CEC will meet 
periodically to review and adjudicate all MDEs, deaths and all DTAA ruptures that occur 
throughout the conduct of the clinical trial. A charter will be developed that will detail the criteria 
for selected complications and clinical events that need to be adjudicated as well as the CEC 
composition, duties, procedures and adjudication rules and meeting frequency. 
 
 
Data Monitoring Committee 
F.6.7
A Data Monitoring Committee (DMC) will be established. The DMC is composed of several 
members with pertinent expertise who are not participants or directly involved in the conduct of 
the trial. 
The responsibility of the DMC is to evaluate safety data during the course of the trial and to 
advise Medtronic about the continuing safety of the trial to ensure the wellbeing of the current 
participants and those yet to be enrolled as well as the continuing validity and scientific merit of 
the trial.  
Based on the safety data, the DMC may recommend that Medtronic modifies or stops the trial. 
DMC composition, duties, procedures, deliberation rules are detailed and documented in the 
DMC Charter. 
In addition to DMC members an Independent Medical Monitor will be appointed. Medtronic will 
provide listings of all Adverse Events and Device Deficiencies to this Independent Medical 
Monitor on a monthly basis to evaluate safety of the study device. All events, including any 
device related events will be reviewed on a case by case base by the Independent Medical 
Monitor. In case of a safety concern the Independent Medical Monitor can trigger a DMC 
meeting. 
Trial data will be reviewed on a periodic basis as defined in the DMC Charter. 
 
Emergency contact details in case of serious AEs 
F.6.8
In case of an immediately reportable Adverse Event the investigators can contact Medtronic. 
Contact details of Medtronic Study Management are given in the Investigational Site File. In 
case the investigator requires information in a medical emergency situation the investigator can 
contact the Medical Expert. Contact details of Medical Expert are given in the Investigational 
Site File. 
F.7 
Subject accountability 
Every subject should be encouraged to remain in the study until they have completed the 
required follow up per the study protocol. 
If a subject is withdrawn from the clinical study, the reason for withdrawal shall be recorded on 
the appropriate eCRF and in the subject’s hospital record. If discontinuation is because of 
safety or lack of effectiveness, the subject shall be asked to be followed for collecting safety 

 
 
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data outside the clinical study. Subjects will not be replaced in case of premature study 
discontinuation. 
 
Criteria and procedures for exit from study  
F.7.1
The Study Exit Form should be completed at the time a subject is exited from the study. A 
subject will be considered to have exited from the study for any of the following reasons: 
• 
Subject completes follow-ups required by the investigational plan 
• 
Subject dies 
• 
Subject requests to be withdrawn 
• 
Investigator requests that subject be withdrawn to protect the welfare of the subject 
• 
Subject is lost to follow-up 
• 
Other (specify) 
 
Study Withdrawal  
F.7.2
Subjects may withdraw from the study at any time and for any reason. If a subject decides to 
withdraw from the study, the investigator will document the reason for withdrawal and indicate 
any relationship of the withdrawal to the study or products being investigated in the subject’s 
hospital record in the subjects file. If discontinuation is because of safety or lack of 
effectiveness, the subject shall be asked to be followed for collecting safety data outside the 
clinical study. In addition, subject withdrawal will be documented on Study Exit eCRF.  
If the subject is unable to be followed, the investigator has to notify the sponsor in a timely 
manner. 
 
Missed follow-up 
F.7.3
A missed follow-up visit should be documented by the investigator and reported in the eCRF, 
including the reason. If the date the subject is last known to be alive is obtained, this should be 
recorded on the Follow-up visit eCRF and the method of obtaining this date should be 
documented in the medical record. 
 
Lost-to-follow-up  
F.7.4
A subject may be considered lost to follow-up once there are 3 documented attempts by the 
investigator and/or research staff to contact the subject. The third attempt should be made by 
mail to the subject and phone call or mail to the subject’s emergency contact.  
 
Medical care after study exit 
F.7.5
After study exit the subjects will be followed as per routine standard of care by the 
investigational site or a treating physician which might be in line with the guidelines described in 
the ESC (European Society of Cardiology) Guidelines on the diagnosis and treatment of aortic 
diseases27. 
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 trial investigator may be contacted by the treating physician in case of 
questions related to the study device and treatment. 
F.8 
Study deviations and CIP changes 
A study deviation is an event where the investigator or investigation site personnel did not 
conduct the clinical study according to the Clinical Investigation Plan or Clinical Investigation 
Agreement. The investigator is not allowed to deviate from the above mentioned documents 
except with prior approval and under emergency circumstances. All deviations shall be 
documented and explained, regardless the reason for the deviation. 
Deviations will be recorded at the site and reported to Medtronic on the Study Deviation eCRF.  

 
 
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Medtronic shall review reports of deviations upon receipt and determine appropriate action, 
including any associated Ethics Committee (EC), and/or regulatory reporting requirements. The 
clinical study team shall follow up with the center on the implementation and closure of any 
preventive or corrective actions. Deviations will be entered into a database to allow a 
comprehensive review on a quarterly basis for identifying trends that warrant additional 
preventive or corrective actions to mitigate further occurrence. This review shall be conducted 
by clinical study management. 
Specific examples of deviations include but are not limited to: 
• 
Failure to obtain informed consent prior to participation 
• 
Incorrect version of the informed consent form used 
• 
No EC approval before the start of the study 
• 
Enrolled subject did not meet inclusion/exclusion criteria 
• 
CIP required testing and/or measurements not done or incorrectly done 
• 
Subject did not attend follow up visit or follow up visit outside window 
• 
Unauthorized use of investigational devices 
• 
Adverse event not reported by investigators in the required time frame as 
specified in the CIP 
• 
Control of study devices not maintained 
• 
Source data lost or unavailable 
• 
Enrollment of subjects during elapse of EC approval 
• 
Exceeding inclusion limits specified by Medtronic 
• 
Subject not implanted according to the Instructions for Use.  
Medtronic will assess the significance of all deviations and evaluate the need to amend the 
Clinical Investigation Plan or to early terminate the investigation, in accordance with Medtronic 
SOPs. 
In case a deviation may occur multiple times over the course of the clinical study in the same 
subject because of a permanent change (e.g. CT scan/MRI with contrast not performed at 
Follow Up visits due to renal insufficiency developed post-operatively) deviation should be 
reported only once per subject at the time of first occurrence. 
 
Request for approval of study deviations 
F.8.1
The investigator shall obtain documented approval from Medtronic, before implementation, for 
any change in- or deviation from the Clinical Investigation Plan. In case of study deviations that 
can affect the subject’s rights, safety and well-being or the scientific integrity of the clinical 
study, approval from the EC and Regulatory Authority must also be obtained before 
implementation. The investigator shall timely contact the Clinical Study Manager for review of 
the proposed change/deviation. 
Prior approval is not always realistic in situations where unforeseen circumstances are beyond 
the investigator’s control. However, also in these cases, the event is considered a deviation, 
and shall be reported.  
In any emergency situation the investigator shall exercise his/her judgment to safeguard the 
subject’s interest. Such deviations from the Clinical Investigation Plan do not require the prior 
approval of Medtronic. The investigator shall report the deviation as soon as possible to 
Medtronic and the reviewing EC, if applicable. Medtronic will inform the Regulatory Authorities, 
if required. 
 
Reporting requirements for study deviations 
F.8.2
The investigator shall adhere to EC requirements and procedures for reporting study 
deviations. 

 
 
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Medtronic is responsible for analyzing deviations, assessing their significance, and identifying 
any additional corrective and/or preventive actions (e.g. amend the CIP, additional training, 
terminate the study, etc.). Repetitive or serious investigator compliance issues may result in the 
need to initiate a corrective action plan, and in some cases freeze enrolment or ultimately 
terminate the investigator’s participation in the clinical study: 
• 
Non-compliance to obtain patient informed consent 
• 
Non-compliance to the inclusion/exclusion criteria 
• 
Failure to follow subjects per scheduled follow-ups 
• 
Failure to submit data in a timely manner 
• 
Failure to follow-up with findings on monitoring reports 
• 
EC approval expiration 
• 
EC suspension of the center 
If a center is terminated or suspended, no additional enrollments will be allowed at the center. 
Unused investigational product allocated to the center will be returned to Medtronic. 
Medtronic will provide investigation site-specific reports to the investigators on a periodic basis 
summarizing information on deviations that occurred at the investigation site.  
 
Amendments to the Clinical Investigation Plan 
F.8.3
The investigator may propose any appropriate modification(s) of the Clinical Investigation Plan 
or investigational device/product or investigational device/product use. Medtronic will review 
this proposal and decide whether the modification(s) will be implemented. Medtronic will submit 
any significant amendment to the Clinical Investigation Plan, including a justification for this 
amendment, to the appropriate Regulatory Authorities and to the investigators to obtain 
approval from their EC and Regulatory Authorities, if required. The investigator will only 
implement the amendment after approval of the EC, Regulatory Authority (if required) and 
sponsor. Administrative amendments to the Clinical Investigation Plan will be submitted to the 
EC and Regulatory Authority (if required) for notification. Furthermore investigators shall sign 
any approved amendment for agreement.  
G QUALITY CONTROL PROCEDURES 
G.1 
Procedures for database management 
 Data collection 
G.1.1
The investigator must ensure accuracy, completeness and timeliness of the data reported in the 
CRFs and in all other required reports. Data reported on the CRFs which are derived from 
source documents must be consistent with the source documents and discrepancies need to be 
justified in a documented rationale, signed and dated by the (principal) investigator, and filed in 
the subject medical file. 
Only authorized persons can complete CRFs. CRFs shall be signed by investigators 
(physicians only) as specified on the Delegated Tasks List included in the Investigator Site File. 
The Electronic Data Capture (EDC) system maintains an audit trail on entries, changes or 
corrections in CRFs. If a person is only authorized to complete CRFs or to make changes to an 
already signed CRF, the investigator shall re-sign this CRF. 
Any source documentation as well as any imaging (e.g., procedure reports, imaging material, 
lab reports, death certificates, autopsy reports) that is sent to the sponsor should have all 
subject identifiers removed and replaced with the subject’s study ID. 
A paper copy of the eCRFs as well as access to the EDC system will be provided to the 
investigation site prior to subject enrollment. 

 
 
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 Source data to be directly recorded on the Case Report Forms 
G.1.2
All data reported on the eCRFs shall be derived from source documents and be consistent with 
these source, and any discrepancies shall be explained in writing. There are no data that will be 
recorded directly on the eCRF without corroborating source documentation. 
 Time windows for completion and submission of Case Report Forms 
G.1.3
All data entry should be completed as soon as possible after the visit takes place. Adverse 
event and device deficiencies should be reported as described in the section F.6. 
 Data review and processing 
G.1.4
Data management will be done according to Medtronic SOPs and the Data Management Plan 
for this clinical study. These documents will be made available on request. 
All collected data will be reviewed for completeness, correctness and consistency. In case of 
issues, queries will be sent to the investigator to complete, correct or comment the data.  
G.2 
Monitoring procedures 
A site qualification visit may be conducted by Medtronic personnel (or designees) to review the 
clinical investigational plan and regulatory and study requirements with the investigator and 
study personnel. A site initiation visit will be performed after it has been verified that the site is 
prepared for the study and that the site requirements for study participation are met. 
Monitoring visits will be conducted at the start, during and at the closure of the clinical study in 
accordance with Medtronic SOPs and the Monitoring Plan. Frequency and timing of monitoring 
visits shall be determined by the Sponsor for each site based on enrollment rate and volume, 
study compliance and findings from previous visits.  
It will be verified whether signed and dated Informed Consent Forms have been obtained from 
each subject before any clinical study related procedures are undertaken. Medtronic or 
designee will conduct site monitoring visits to monitor compliance with the protocol and 
adherence to the data collection procedures, to assess the accuracy and completeness of 
submitted clinical data, and to verify that records and documents are being properly maintained 
for the duration of the study. 
 Accessibility of investigation site staff and study materials 
G.2.1
The principal investigator(s), his/her delegate(s) and the study coordinator(s) shall be 
accessible to Medtronic field personnel and the Clinical Study Manager. This accessibility is of 
particular importance for reviewing data in the Case Report Form (CRF). Direct access to 
subject medical files for source data verification will need to be granted and prepared prior to 
any monitoring visits. If direct access cannot be provided per local laws and regulations, 
certified copies need to be made available or monitor needs to obtain access by reviewing 
alongside with study staff.  
 Audits and investigation site inspections  
G.2.2
In addition to regular monitoring visits, Medtronic may conduct audits at participating 
investigation sites. The purpose of an audit is to verify the adequate performance of the clinical 
study related activities. Independent of the employees involved in the clinical study. Regulatory 
bodies may also perform inspections at participating investigation sites. Any Regulatory 
Authority inspection announcements shall be forwarded immediately to the Clinical Study 
Manager.  
The investigator and/or institution shall permit Medtronic and regulatory bodies direct access to 
source data and documents, taking into account any restrictions due to local law, to perform 
clinical study-related monitoring, audits, EC review, and regulatory inspections. 

 
 
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G.3 
Study suspension or early termination 
 Early study suspension or termination 
G.3.1
Medtronic or Regulatory Authority may decide to suspend or prematurely terminate the clinical 
study (e.g. if information becomes available that the risk to study subject is higher than initially 
indicated, if interim analysis indicates that the results significantly differ from the clinical study 
objectives or statistical endpoints). If the clinical study is terminated prematurely or suspended, 
Medtronic shall promptly inform the investigators of the termination or suspension and the 
reason(s) for this. The investigator shall then promptly inform the reviewing EC and the study 
subjects. Medtronic will inform the Regulatory Authority(ies) where required by applicable 
regulatory requirements. 
 Early investigation site suspension or termination 
G.3.2
Medtronic, EC or Regulatory Authority may decide to suspend or prematurely terminate an 
investigation site (e.g. in case of expiring approval of the reviewing EC, non-compliance to the 
Clinical Investigation Plan or lack of enrollment). If an investigation site is suspended or 
prematurely terminated, Medtronic shall promptly inform the investigator(s) of the termination or 
suspension and the reason(s) for this. The investigator shall then promptly inform the reviewing 
EC and the study subjects or their legal representative.  
If an investigation site is suspended or prematurely terminated: 
• 
Medtronic shall promptly inform the clinical investigator(s) of the termination or 
suspension and the reason(s) for this 
• 
The investigator shall then promptly inform the reviewing EC  
• 
The investigator shall then promptly inform study subjects 
• 
The investigator agreement will be terminated 
• 
The investigator will inform the institution (where required by applicable regulatory 
requirements) 
• 
Medtronic will inform the Regulatory Authority(ies) (where required by applicable 
regulatory requirements) 
When the risks are found to outweigh the potential benefits or when there is conclusive proof of 
definite outcomes, investigators must assess whether to continue, modify or immediately stop 
the clinical study in the respective investigation site and immediately inform the sponsor and 
EC, if applicable. 
 Subject follow-up in case of termination 
G.3.3
If the study is terminated early, subjects will be followed as per routine standard of care by the 
investigational site or a treating physician which might be in line with the guidelines described in 
the ESC (European Society of Cardiology) Guidelines on the diagnosis and treatment of aortic 
diseases.27 
After study termination 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 trial investigator may be contacted by the treating 
physician in case of questions related to the study device and treatment. 
G.4 
Study close out 
Prior to completion of study close out, all data must be entered and monitored in the EDC 
system.    
Medtronic and/or its designees will notify the site of the intention to close the study. Study close 
out visits may be performed. During these visits, the monitors will ensure that the investigator’s 
regulatory files are up to date and complete and that any outstanding issues from previous 
visits have been resolved. Medtronic will notify and inform the site(s) that all requirements have 
been met with a study closure letter.  

 
 
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If required, EC and/or Regulatory Authority will be informed by Medtronic about the study close 
out. 
H DATA ANALYSIS AND REPORTING 
Any deviations from this section and/or the Statistical Analysis Plan will be described and 
justified in the Final Clinical Study Report, as appropriate. 
H.1 
Analysis of clinical data 
The Valiant Evo International Trial is not hypothesis driven. All endpoints will be analyzed 
descriptively. The limitation of the design for this study is that there are no pass/fail criteria from 
a statistical hypothesis testing.  
All endpoints will be analyzed descriptively. Event rates corresponding to the primary endpoint 
of the study will be analyzed by calculating the distribution frequencies and the associated 1-
sided 95% confidence limits using an exact method.  
In general, qualitative parameters will be described by their distribution frequencies; quantitative 
parameters will be described by their mean, standard deviation, minimum, maximum, median, 
and number of subjects with assessable data.  
The survival from all-cause mortality over one year time or longer will be described by the 
Kaplan-Meier survival curve and the associated Kaplan-Meier estimate will be calculated along 
with its standard error using the Greenwood method.  
For events, such as AEs, deaths and secondary procedures, that can occur or are observed at 
any time during the study, no time window will be applied. For such events, an event that 
occurs “within 30 days” is an event that takes place between Days 0 to 30, inclusive. Similarly, 
an event that occurs “within 365 days” is an event occurring between Day 0 to Day 365, 
inclusive. Date of event onset will be used to determine when the event occurred. Day 0 is 
referring to the day of index procedure. 
For image-based assessments, such as stent-graft endoleak, patency and device deficiencies, 
the following time windows will be applied for by-visit data summaries: 
Table H-1:  Time Windows for Statistical Analyses 
Study Visit 
Target Day 
Time Window 
Implant 
0 days 
Day 0  
1 Month 
30 days 
1 – 90 days 
12 Months 
365 
305 – 548 Days 
If there are two or more assessments in the same time window, then the assessment closest to 
the target day will be used in the analysis of event rate at a given time point. In addition to 
endpoints, summaries of subject disposition, demographics, baseline characteristics, and 
subject accountability will be provided. 
Subset analysis will be performed by-sex separately for the primary endpoint descriptively and 
reviewed for clinical significant difference.  
All analysis will be performed on the modified intent-to-treat analysis set, which includes all 
included subjects. Subjects will be considered as included in the study as described in section 
F.1.  
During statistical analysis, imputation of missing data will not be performed except for data 
related to the onset date of an adverse event or a death. In cases where the onset date of an 
event or a death is incomplete and unresolvable via data query, the 15th day of the known 
month or July 1st of the known year will be used.  

 
 
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Statistical analyses for this study will be performed using the Statistical Analysis System (SAS) 
for Windows (Version 9.1 or higher) or other widely-accepted statistical or graphical software.  
Analysis for the Regulatory Submission:  
For the primary endpoint, which is defined as the proportion of subjects experiencing an MDE 
within 30 days post-implantation, a 1-sided 95% confidence interval using the exact method 
(Clopper-Pearson) will be constructed in addition to event count frequency.   
Additionally, a two-sided 95% confidence interval will also be provided. The SAS procedure 
PROC FREQ will be used for calculation of the confidence interval. 
The analysis for the regulatory submission will take place when the first 47 subjects have been 
implanted with the study device for at least 30 days except that a subject expires early.  
Endpoints will be analyzed for these 47 included subjects as defined in Section C.2.  
Interim Analysis:  
No interim analysis is planned prior to the CE Mark Submission.  
Annual Report:  
An annual report will be provided for all enrolled subjects at the time of reporting according to 
requirements from notified bodies in the European Union and regulatory agencies in various 
countries. 
H.2 
Publication Policy 
Publications and presentations referring to this clinical study will be coordinated by Medtronic to 
allow the use of all available data. The following publication policy will have to be adhered to by 
all participating investigation sites: 
Medtronic may use the study data for Regulatory Authority submission results, may publish the 
results in peer reviewed scientific journal(s) and present the data at major congresses. 
Authorship on any publication(s) resulting from this clinical study will be assigned according to 
substantial contributions to conception and design, acquisition of data, or analysis and 
interpretation of data, drafting the article or revising it critically for important intellectual content 
and final approval of the version to be published. This is in accordance with the Vancouver 
principles (The Uniform Requirements for Manuscripts Submitted to Biomedical Journals: 
Writing and Editing for Biomedical Publication, ICMJE, October 2008), as agreed upon by the 
editors of all major medical journals.  
The number of authors will be dependent on the regulations of the concerning journal with a 
maximum of 10 authors. Names of all participating investigators will appear in the 
Acknowledgment of the paper. 
Based on the principle that Medtronic owns the data of this clinical study, a single investigation 
site may access and use the data provided by itself for scientific publications following prior 
approval by Medtronic. 
Pooling data from several investigation sites for publication purposes, national projects and 
international projects all require prior approval from Medtronic. 
Medtronic as the owner of the data can use the data and/or any results derived from the data or 
publications based on that data for marketing purposes, further research and development of 
devices or educational use. 
The study sponsor will collect data in such way that no subject can be identified, and monitor 
study records. 
Participating subjects will not be identified by name in any published reports about the clinical 
study.  

 
 
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I 
STUDY MANAGEMENT 
I.1 
Study staff 
The study is sponsored by the Medtronic Bakken Research Center B.V. based in the 
Netherlands. Study staff contact details will be provided in the investigational site file. 
I.2 
Advisory committees 
 
Clinical Event Committee (CEC) 
I.2.1
A clinical event committee (CEC) will be established. The CEC is an independent committee 
made up of clinicians (interventional) with pertinent expertise who are not participants in the 
study and who do not have any other real or potential conflicts of interest.  Please refer to 
section F.6.5 for further details regarding the CEC. 
 
Data Monitoring Committee 
I.2.2
A Data Monitoring Committee (DMC) will be established. The DMC is composed of several 
members with pertinent expertise who are not participants or directly involved in the conduct of 
the study. Please refer to section F.6.6 for further details regarding the DMC. 
 
Publication Committee 
I.2.3
A publication committee is not expected to be established for the Valiant Evo International 
Clinical trial. The publication policy for this trial is described in section H.2. 
 
Imaging Core Lab 
I.2.4
An imaging core lab will be established to independently analyze images based on the imaging 
protocol/core lab guidelines. Imaging guidelines will be provided in the investigational site file. 
I.3 
Records and reports 
 
Investigator records 
I.3.1
At a minimum, the following records must be kept by the investigator:  
• 
Clinical Investigation Plan and, if applicable, any amendments 
• 
Investigator’s Brochure and/or Instructions for Use 
• 
Medtronic and EC approved Patient Informed Consent form 
• 
Regulatory Authority approval or notification 
• 
Fully signed Clinical Investigation Agreement and confidentiality agreement (if not 
included in the Clinical Investigation Agreement) 
• 
Financial disclosures 
• 
Insurance certificates 
• 
Completed Delegated Task List and Curriculum Vitae of all investigation site personnel 
• 
Training documentation of all investigation site personnel 
• 
Relevant communications 
• 
Subject screening log and/or subject identification log  
• 
Signed, dated and fully executed Patient Informed Consent forms 
• 
Fully executed CRFs and corrections 
• 
Reports of Adverse Events and Device Deficiencies 
• 
Device accountability records 
• 
EC approval(s) or notification(s) and correspondence 

 
 
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• 
Monitoring follow-up letter 
• 
Monitor contact list 
• 
Source documents 
 
Investigator reporting responsibilities 
I.3.2
Report 
Submitted to 
Description 
Adverse Events 
Sponsor, EC, and 
local Regulatory 
Authority, where 
applicable 
Refer to section F.6 for reporting requirements. 
Progress Report 
Sponsor and EC 
Provide if required by local law or EC.  
(ISO 14155:2011) 
Withdrawal of EC 
approval 
Sponsor 
Investigator will inform Medtronic in case EC 
approval is withdrawn. 
Final Clinical Study 
Report 
EC 
A copy of the Final Clinical Study Report will be 
provided to the EC. 
Deviations from Investigational Plan 
Emergency Use 
Sponsor, EC, 
Regulatory Authority 
Investigator will report deviation as soon as 
possible to the sponsor and EC. 
Planned deviation 
Sponsor, EC, 
Regulatory Authority 
Prior approval from Medtronic must always be 
obtained from Medtronic. If the deviation affects 
scientific soundness of the clinical study or the 
rights, safety, or welfare of the subject and is not 
an emergency, prior approval must be obtained 
from the EC and Regulatory Authority. 
Other Deviations 
Sponsor 
Deviations that are beyond the control of the 
investigator (such as subject who fails to return to 
follow-up visit) or deviations that do not affect the 
scientific soundness of the clinical study or the 
rights, safety, or welfare of the subject and are not 
an emergency, should be submitted as they are 
identified by the investigation site or Medtronic 
staff. 
 
Sponsor records 
I.3.3
At a minimum, the sponsor will keep the following records: 
• 
All essential study documents and correspondence that pertains to the clinical study 
• 
CIP and, if applicable, any amendments 
• 
Investigator Brochure and/or Instructions for Use 
• 
Sample of labeling attached to the investigational device 
• 
Curriculum Vitae of investigators and investigation site personnel 
• 
Delegated Task Lists and training records of investigators and investigation site 
personnel 
• 
EC approvals/notifications and regulatory approvals/notifications 
• 
Signed Clinical Investigation Agreements and signed agreements with third parties 
• 
Insurance certificates, 

 
 
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• 
Shipping records for investigational devices and clinical-investigation related 
documents and materials 
• 
Medtronic and EC/IRC approved Patient Informed Consents 
• 
Site selection reports, site initiation reports and monitoring visit reports  
• 
Adverse event and Device Deficiency reports 
• 
Financial disclosure information 
• 
Fully executed CRFs and corrections 
 
Sponsor reporting responsibilities 
I.3.4
Report 
Submit to 
Description 
Adverse Events 
EC, Investigators, 
and Regulatory 
Authorities, where 
applicable 
Medtronic will report adverse events as 
required and in compliance with local 
regulatory requirements, as applicable. 
Withdrawal of EC 
approval 
EC, Investigators, 
and Regulatory 
Authorities, where 
applicable 
In case of withdrawal of EC approval 
Medtronic will suspend the clinical study as 
described below. 
Premature termination or 
suspension of study 
EC, Investigators, 
and Regulatory 
Authorities, where 
applicable 
Medtronic will provide prompt notification of 
termination or suspension and reason(s) to 
investigator and where required to EC and 
Regulatory Authorities. 
Progress Reports  
EC, Regulatory 
Authority (upon 
request)  
Progress reports will be submitted to the EC 
and/or Regulatory Authority only if required. 
Final Report 
Investigators, and 
Regulatory 
Authorities, where 
applicable 
Medtronic will provide all investigators with a 
copy of the Final Clinical Study Report of the 
clinical study.  
ECs and Regulatory Authorities will be 
informed when required. 
Study 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.  
Emergency Deviations 
from Investigational Plan 
Regulatory 
Authorities, where 
applicable 
If required, Medtronic will inform Regulatory 
Authorities as soon as possible about any 
emergency deviations that affect scientific 
soundness of the clinical study or the rights, 
safety, or welfare of the subject. 
Significant new 
information  
EC and Regulatory 
Authority  
Ensure that the EC and Regulatory 
Authorities are informed of significant new 
information about the clinical investigation 
(ISO 14155:2011). 
 
Record retention  
I.3.5
The investigator must retain the Investigator Site File, subject medical files and CRFs in 
accordance with local law and regulations for a minimum period of 2 year (or longer if local laws 

 
 
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require) after market-release in his/her region. The investigator should take measures to 
prevent accidental or early destruction of the clinical study related materials. 
I.4 
Miscellaneous 
 
Insurance 
I.4.1
The Medtronic Bakken Research Center B.V is a wholly owned subsidiary of Medtronic Inc., 
which as the parent company of such entity maintains appropriate clinical study 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 EC and the Regulatory Authorities. 
 
Subject compensation and indemnification 
I.4.2
Medtronic shall reimburse the institution/hospital in which the subjects are treated for 
reasonable and necessary travel expenses incurred by the subjects enrolled and/or included in 
the study including, but not limited to travel to/from the hospital, provided that such expenses 
are properly documented in the subject files and that the study evaluation is not performed 
under a regularly scheduled follow-up. These expenses will be payable to the 
institution/hospital upon receipt by Medtronic of a detailed invoice, which, however, shall not 
contain any identifying characteristics concerning the subjects. Finally the site in which the 
subject is treated shall be solely responsible for the reimbursement of expenses directly to the 
subject. 
 
Subject confidentiality 
I.4.3
Subject confidentiality will be maintained throughout the clinical study to the extent permitted by 
law. That is, every attempt will be made to remove subject identifiers from clinical study 
documents. For this purpose, a unique subject identification code (site number and subject 
number) will be assigned and used to allow identification of all data reported for each subject. 
This will also ensure that the information can be tracked back to the source data. 
Study data may be made available to third parties, e.g., in the case of an audit performed by 
Regulatory Authorities, provided the data are treated confidentially and that the subject’s 
privacy is guaranteed. The identity of a subject will never be disclosed in the event that study 
data are published. 
J 
RISKS AND BENEFITS 
J.1 
Anticipated Clinical Benefits 
The potential benefits of the Valiant Evo Thoracic Stent Graft System have not been 
documented; nevertheless, they are expected to be similar to those associated with 
endovascular stent graft systems currently in clinical trials or commercially available.  
The minimally invasive endoluminal intervention offers an alternative method of treatment that 
is potentially less invasive, less expensive, and less risky than standard operative repair 22. 
Thoracic aortic endoluminal procedures are likely to have an even greater impact than those of 
the abdominal aorta, where conventional open surgery offers a low mortality rate for many 
patients. This minimally invasive endovascular intervention offers an innovative treatment 
strategy for a significant number of patients with serious thoracic aortic lesions, such as 
aneurysms, dissections, traumatic disruptions, and penetrating ulcers. 
The potential benefits of using stent graft repair in the treatment of DTAA are based on 
comparing the results of endovascular repair against surgical repair.  
The most superior potential benefit is that stent graft repair provides a treatment modality for 
many patients who otherwise would not be candidates for surgical repair because of their co-
morbidities.17, 23, 24 

 
 
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Other potential benefits include a reduction in short-term and mid-term mortality and morbidity; 
a reduction of risk of cardiovascular, pulmonary, neurologic and renal complications as a 
consequence of shorter exposure to general anesthesia, a less invasive procedure, a 
preservation of the distal aortic pressure due to maintenance of aortic blood flow; reduced 
estimated blood loss; lower post-operation complications such as paraplegia; decreased length 
of Intensive Care Unit and hospital stay, shorter recovery time and better quality of 
life.17,23,24,25,26 
J.2 
Risks 
Following is a list of potential (expected) risks that may be associated with use of the Valiant 
Evo Thoracic Stent Graft System. The occurrence of the listed complications may lead to a 
repeat endovascular intervention and/or open surgical repair. Since the Valiant Evo Thoracic 
Stent Graft System is an investigational device, all risks may not be known. However, they are 
believed to be similar to those associated with the existing endovascular devices in clinical use 
or commercially available, as well as the risks associated with standard open surgical repair of 
DTAAs.  
Table J-1: Potential Adverse Events or complications associated with the use of the 
Valiant Evo Thoracic stent graft system 
- 
Access failure 
- 
Access site complications 
(e.g., spasm, trauma, 
bleeding, rupture, dissection) 
- 
Adynamic Ileus 
- 
Allergic reaction (to contrast, 
antiplatelet therapy, stent 
graft material)  
- 
Amputation 
- 
Anaphylaxis 
- 
Anesthetic complications 
- 
Aneurysm expansion 
Aneurysm rupture 
- 
Angina 
- 
Aortic valve damage 
- 
Aortic vessel rupture 
- 
Arrhythmia 
- 
Arterial stenosis 
- 
Atelectasis 
- 
Blindness 
- 
Bowel ischemia 
- 
Bowel necrosis 
- 
Bowel obstruction  
- 
Branch vessel occlusion  
- 
Breakage of the metal 
portion of the device 
- 
Buttock claudication 
- 
Cardiac tamponade 
- 
Catheter breakage 
- 
Cerebrovascular accident 
(CVA)/Stroke 
- 
Change in mental status 
- 
Coagulopathy 
- 
Congestive heart failure 
- 
Contrast toxicity 
- 
Conversion to surgical repair 
- 
Death  
- 
Deployment 
difficulties/failures 
 
- 
Dissection, perforation, or rupture 
of the aortic vessel & surrounding 
vasculature 
- 
Embolism  
- 
Endoleaks 
- 
Excessive or inappropriate 
radiation exposure 
- 
Extrusion/erosion 
- 
Failure to deliver the stent graft 
- 
Femoral neuropathy 
- 
Fistula (including aortoenteric, 
arteriovenous, and lymph) 
- 
Gastrointestinal 
bleeding/complications 
- 
Genitourinary complications 
- 
Hematoma 
- 
Hemorrhage/bleeding 
- 
Hypotension/hypertension 
- 
Infection or fever 
- 
Insertion or removal difficulty 
- 
Intercostal pain 
- 
Intramural hematoma 
- 
Leg edema/foot edema 
- 
Lymphocele 
- 
Myocardial infarction  
- 
Neuropathy 
- 
Occlusion - Venous or Arterial 
- 
Pain/Reaction at catheter 
insertion site 
- 
Paralysis 
- 
Paraparesis 
- 
Paraplegia 
- 
Paresthesia 
- 
Peripheral ischemia 
- 
Peripheral nerve injury 
- 
Pneumonia 
- 
Postimplant syndrome 
 
- 
Post-procedural bleeding 
- 
Procedural bleeding 
- 
Prosthesis dilatation 
- 
Prosthesis infection 
- 
Prosthesis rupture 
- 
Prosthesis thrombosis 
- 
Pseudoaneurysm 
- 
Pulmonary edema 
- 
Pulmonary embolism  
- 
Reaction to  anesthesia 
- 
Renal failure  
- 
Renal insufficiency 
- 
Reoperation 
- 
Respiratory depression or 
failure 
- 
Retrograde type A dissection 
- 
Sepsis 
- 
Seroma 
- 
Shock 
- 
Spinal neurological deficit 
- 
Stent graft migration 
- 
Stent graft misplacement 
- 
Stent graft occlusion 
- 
Stent graft twisting or kinking 
- 
Transient ischemic attack (TIA) 
- 
Thrombosis 
- 
Tissue necrosis 
- 
Vascular ischemia 
- 
Vascular trauma 
- 
Wound dehiscence 
- 
Wound healing complications 
- 
Wound infection 
All efforts will be made to minimize these risks by selecting investigators who are experienced 
and skilled in using endoluminal aortic devices and who have been adequately trained. Also, 

 
 
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risk minimization activities were performed during development and design verification tests of 
the device. Activities intended to minimize risks include the following. 
• 
Investigator and study personnel training will be conducted to share information 
regarding the design of the Valiant Evo Thoracic Stent Graft System, its application and 
pre-clinical results. 
• 
Adherence to eligibility criteria and screening procedures will ensure that appropriate 
subjects are enrolled. 
• 
Adherence to the Valiant Evo Thoracic Stent Graft System Instructions for Use 
packaged with the device will ensure the use of validated procedural steps. 
• 
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. 
• 
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 monitoring committee, clinical events committee, and core lab will 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 trial 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. The risks will be 
continuously monitored, assessed and documented by the investigator. Any unanticipated or 
unforeseen complications will be reported by the investigator (or authorized designee) to the 
EC and to Medtronic. Medtronic will in turn report any necessary findings to the appropriate 
regulatory agencies in each of the respective geographies. 
Summary of the risk analysis, including identification of residual risks, result of the risk 
assessment and anticipated risks, contra-indications, warnings, etc. for the investigational 
device will be described in the Investigator’s Brochure.  
J.3 
Risk-to-benefit rationale 
The results of risk analysis, balancing benefits against risks associated with both the device 
system itself and procedures involved in its use, is included in the Investigator’s Brochure. 
The benefits and risks associated with Medtronic’s thoracic stent grafts are well-characterized 
through robust history of testing and successful clinical results. The Valiant Evo thoracic stent 
graft system is Medtronic’s third generation thoracic stent graft which is not only designed using 
established design characteristics and long term experience from previous generation 
Medtronic stent grafts but also uses the same principles of operation and technological 
characteristics. Furthermore, it has been demonstrated that implantation of thoracic 
endovascular stent grafts can be performed safely, and that these devices provide benefits over 
surgical repair.  
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 device in 
this clinical study, implementing quality control measures into production processes, providing 
guidelines for subject selection and evaluation, and providing adequate instructions and 
labeling. 

 
 
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Although there are risks associated with this trial, they are not anticipated to be worse than the 
risks normally associated with the use of the predicate device or other commercially available 
devices. 
Risk management for the Valiant Evo thoracic stent graft system is performed in accordance 
with ISO 14971:2012 and the results are detailed in the Investigator Brochure. 

 
 
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K REFERENCES 
1. 
Johnston KW, Rutherford RB, Tilson MD, et al. Suggested standards for reporting on 
arterial aneurysms. Subcommittee on Reporting Standards for Arterial Aneurysms, Ad Hoc 
Committee on Reporting Standards, Society for Vascular Surgery and North American 
Chapter, International Society for Cardiovascular Surgery. J Vasc Surg. Mar 
1991;13(3):452-458. 
2. 
Fann JI. Descending thoracic and thoracoabdominal aortic aneurysms. Coron Artery Dis. 
Apr 2002;13(2):93-102. 
3. 
Hager A, Kaemmerer H, Rapp-Bernhardt U, et al. Diameters of the thoracic aorta 
throughout life as measured with helical computed tomography. J Thorac Cardiovasc 
Surg. Jun 2002;123(6):1060-1066. 
4. 
Aronberg DJ, Glazer HS, Madsen K, et al. Normal thoracic aortic diameters by computed 
tomography. J Comput Assist Tomogr. Apr 1984;8(2):247-250. 
5. 
Griepp RB, Ergin MA, Galla JD, et al. Natural history of descending thoracic and 
thoracoabdominal aneurysms. Ann Thorac Surg. Jun 1999;67(6):1927-1930; discussion 
1953-1928. 
6. 
Clouse WD, Hallett JW, Jr., Schaff HV, et al. Improved prognosis of thoracic aortic 
aneurysms: a population-based study. Jama. Dec 9 1998;280(22):1926-1929. 
7. 
Bickerstaff LK, Pairolero PC, Hollier LH, et al. Thoracic aortic aneurysms: a population-
based study. Surgery. Dec 1982;92(6):1103-1108. 
8. 
Temudom T, D'Ayala M, Marin ML, et al. Endovascular grafts in the treatment of thoracic 
aortic aneurysms and pseudoaneurysms. Ann Vasc Surg. May 2000;14(3):230-238. 
9. 
Pressler V, McNamara JJ. Thoracic aortic aneurysm: natural history and treatment. J 
Thorac Cardiovasc Surg. Apr 1980;79(4):489-498. 
10. Elefteriades JA. Natural history of thoracic aortic aneurysms: indications for surgery, and 
surgical versus nonsurgical risks. Ann Thorac Surg. Nov 2002;74(5):S1877-1880; 
discussion S1892-1878. 
11. Dean RH YJ, Brewster DC(eds). Current Diagnosis and Treatment in Vascular Surgery. 
Norwalk, CT: Appleton & Lange; 1995. 
12. Fann JI MD. Descending thoracic aortic aneurysm. Stanford: Appleton & Lange; 1995. 
13. Chuter TAM, Donayre CE, White RA. Endoluminal vascular prostheses. 1st ed. Boston: 
Little, Brown; 1995. 
14. Glade GJ, Vahl AC, Wisselink W, et al. Mid-term survival and costs of treatment of patients 
with descending thoracic aortic aneurysms; endovascular vs. open repair: a case-control 
study. Eur J Vasc Endovasc Surg. Jan 2005;29(1):28-34. 
15. Bortone AS, De Cillis E, D'Agostino D, et al. Endovascular treatment of thoracic aortic 
disease: four years of experience. Circulation. Sep 14 2004;110(11 Suppl 1):II262-267. 
16. Leurs LJ, Bell R, Degrieck Y, et al. Endovascular treatment of thoracic aortic diseases: 
combined experience from the EUROSTAR and United Kingdom Thoracic Endograft 
registries. J Vasc Surg. Oct 2004;40(4):670-679; discussion 679-680. 
17. Dake M, Miller C, Semba CP, et al. Transluminal placement of endovascular stent grafts 
for the treatment of descending thoracic aortic aneurysms. N Engl J Med. 1994; 331:1729-
1734. 
18. Criado F. TEVAR Access, Delivery, and Fixation. Endovascular Today. Nov. 2007: 45-52. 
19. PMA (P100040) Valiant Captivia Stent Graft System (Medtronic internal data using the 
Valiant Evo proposed definition). 
20. United States Government Accountability Office (2010) Report to Congressional 
Requesters: FDA’s Consideration of Evidence from Certain Clinical Trials. GAO-10-798, p 
17.  

 
 
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21. Wangge G, Klungel OH, Roes KCB, de Boer A, Hoes AW, et al. (2010) Room for 
Improvement in Conducting and Reporting Non-Inferiority Randomized Controlled Trials 
on 
Drugs: 
A 
Systematic 
Review. 
PLoS 
ONE 
5(10): 
e13550. 
doi:10.1371/journal.pone.0013550 
22. White RA, Fogarty TJ. Peripheral endovascular interventions. 2nd ed. New York: Springer; 
1999 
23. Bortone AS, Schena S, Mannatrizio G, et al. Endovascular stent-graft treatment for 
diseases of the descending thoracic aorta. Eur J Cardiothorac Surg. Sep 2001;20(3):514-
519. 
24. Dake MD, Miller DC, Mitchell RS, et al. The "first generation" of endovascular stent-grafts 
for patients with aneurysms of the descending thoracic aorta. J Thorac Cardiovasc Surg. 
Nov 1998;116(5):689-703; discussion 703-684.   
25. Lambrechts D, Casselman F, Schroeyers P, et al. Endovascular treatment of the 
descending thoracic aorta. Eur J Vasc Endovasc Surg. Oct 2003;26(4):437-444.   
26. Orend KH, Scharrer-Pamler R, Kapfer X, et al. Endovascular treatment in diseases of the 
descending thoracic aorta: 6-year results of a single center. J Vasc Surg. Jan 
2003;37(1):91-99.     
27. Erbel R, Aboyans V, Boileau C, et al. 2014 ESC Guidelines on the diagnosis and 
treatment of aortic diseases: Document covering acute and chronic aortic diseases of the 
thoracic and abdominal aorta of the adult. The Task Force for the Diagnosis and 
Treatment of Aortic Diseases of the European Society of Cardiology (ESC). Eur Heart J 
2014;35:2873-926. 

 
 
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L APPENDICES 
L.1 
Abbreviations 
ADE 
Adverse Device Effect 
AE 
Adverse event 
ASA 
American Society of Anesthesiologists  
ASADE  Anticipated serious adverse device effect 
AV 
Arteriovenous 
CA 
Competent Authority 
CEC 
Clinical Event Committee  
CFR 
Code of Federal Regulations 
CHF 
Congestive Heart Failure 
CIP 
Clinical Investigation Plan 
CRF 
Case Report Form 
CT 
Computed Tomography 
CVA 
Cerebral Vascular Incident 
CRO 
Clinical Research Organization  
DD 
Device Deficiency 
DMC 
Data Monitoring Committee 
DTAA 
 Descending Thoracic Aortic Aneurysm 
DTA 
Descending Thoracic Aorta 
EC 
Ethical Committee  
eCRF 
Electronic Case Report Form 
EDC 
Electronic Data Capture 
FDA 
Food and Drug Administration 
IB 
Investigator Brochure 
ICU 
Intensive Care Unit 
ICH-GCP International Conference on Harmonization – Good Clinical Practice 
IDE 
Investigational Device Exemption 
IFU 
Instructions for Use 
INR 
International Normalized Ratio 
IPR 
Independent physician reviewer 
ISO 
International Organization for Standardization 
LSA 
Left Subclavian Artery 
MAE 
Major Adverse Event 
MDE 
Major Device Effect 
MI 
Myocardial Infarction 
MRA 
Magnetic Resonance Angiography 
MRI 
Magnetic Resonance Imaging 
PET 
Polyethylene terephthalate  
PIC 
Patient Informed Consent 
PMA-S 
Premarket Approval Supplement 
OD 
Outer Diameter 
RA 
Regulatory Affairs 

 
 
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RAE 
Regulatory Affairs Europe 
SADE 
Serious Adverse Device Effect 
SAE 
Serious Adverse Event 
SOP 
Standard operating procedure 
TAA 
Thoracic Aortic Aneurysm 
TEE  
Transesophageal Echography 
TEVAR Thoracic Endovascular Aortic Repair 
UADE 
Unanticipated Adverse Device Effect 
USADE  Unanticipated Serious Adverse Device Effect 

 
 
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L.2 
Definitions 
 
Primary and Secondary Endpoints 
L.2.1
Term 
Definition 
Access failure 
 
Inability to insert device due to mechanical failure or 
anatomic exclusions of the femoral or iliac arteries 
Deployment Failure  
 
Deployment failure due to subject anatomy or mechanical 
failure. This specifically refers to deployment of the stent graft 
from the delivery system. 
Adverse Event (AE) 
See section F.6.1 
Serious Adverse Event 
(SAE) 
See section F.6.1 
Major Adverse Events 
(MAEs) 
Major Adverse events include the occurrence of any of the 
following : 
• Respiratory 
complications: 
atelectasis/pneumonia, 
pulmonary embolism, pulmonary edema, respiratory 
failure.  
• Renal complications: renal failure, renal insufficiency.  
• Cardiac complications: myocardial infarction (MI), 
unstable angina, new arrhythmia, exacerbation of 
congestive heart failure (CHF).  
• Neurological 
complications: 
new 
cerebrovascular 
accident (CVA), cerebrovascular embolic events, 
paraplegia, paraparesis.  
• Gastrointestinal complications: bowel ischemia.  
• Major bleeding complication (procedural or post-
procedural), coagulopathy.  
• 
Vascular Complications: aortic rupture, aneurysm 
rupture, hematoma at access site, pseudo or false 
aneurysm, arteriovenous (AV) fistula, retroperitoneal 
bleed, limb ischemia, thrombosis. 
See definition of terms in section L.2.2 
Major Device  
 Effects (MDEs) 
Major Device Effects include the occurrence of any of the 
following: 
• Device-related secondary procedures  
• Device-related mortality 
• Conversion to open surgery 
• Thoracic Aortic Aneurysm rupture 
Device-related mortality 
Any death related directly to the implantation, the presence, 
or operation of the investigational device in the medical 
opinion of the Clinical Events Committee (CEC).   
Deaths following complications that are associated with the 

 
 
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Term 
Definition 
device design as it relates to placement, efficacy or durability 
(these may involve the implanted device or the delivery 
system), with endoleak, device migration, and failure to cover 
the aortic injury are included in this definition. 
Peri-operative mortality 
All deaths occurring intra-operatively and within 30 days from 
the primary procedure  
All-cause mortality 
Death from any cause 
Aneurysm-related 
mortality (ARM) 
Any death occurring within 30 days from either the initial 
procedure or any secondary procedure intended to treat the 
aneurysm will be considered ARM unless there is evidence to 
the 
contrary. 
Additionally, 
deaths 
occurring 
as 
a 
consequence of any procedure intended to treat the targeted 
aneurysm, aneurysm rupture, or a conversion to open repair 
will also be considered as ARM.  
Ultimate adjudication of relatedness of death will be made by 
the Clinical Events Committee (CEC). Excluded are 
aneurysms in anatomic areas other than the targeted 
segment treated by the Valiant Evo Thoracic Stent Graft 
System. 
Device-related 
secondary procedure 
Any secondary procedure that is determined by the 
investigator to be clearly related to any of the implanted stent 
graft components.  
Ultimate adjudication of relatedness of secondary procedure 
will be made by the Clinical Events Committee (CEC). 
Secondary procedure 
Any endovascular or surgical procedure performed following 
the completion of the operative initial implantation procedure 
(thus on subsequent occasion after final closure of the last 
artery access site) which involves the targeted vascular 
segment treated by the Valiant Evo Thoracic Stent Graft 
System in which there is either manipulation of the existing 
Valiant Evo Thoracic Stent Graft, implantation of any 
additional stent graft devices or manipulation of covered 
branch(es) by implanted stent grafts. 
Conversion to open 
surgery 
Primary Conversion: Conversion from endovascular to open 
repair required at the time of the original procedure, to treat 
the lesion intended to be treated with the Valiant Evo 
Thoracic Stent Graft System. 
Secondary Conversion: Conversion from endovascular to 
open repair required at a time beyond the initial endovascular 
procedure, to treat the lesion originally treated with the 
Valiant Evo Thoracic Stent Graft System. 
Thoracic Aortic 
Aneurysm rupture 
Rupture or perforation of the targeted thoracic aneurysmal 
sac as detected by angiography, CT scan, or direct 
observation at surgery or autopsy.   
Aneurysm rupture should be reported as either procedure-

 
 
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Term 
Definition 
related aneurysm rupture (i.e., perforation of the aneurysm 
during the course of the implantation procedure) or as a late 
aneurysm rupture that follows device deployment.  
Excluded are aneurysms in anatomic areas other than the 
targeted segment treated by the Valiant Evo Thoracic Stent 
Graft System. 
Aneurysm expansion 
Aneurysm maximum diameter increase > 5 mm as compared 
to the 1- month contrast enhanced imaging measurements 
Stent graft migration 
Evidence of proximal or distal movement of the stent graft 
(>10 mm) relative to fixed anatomic landmarks (e.g. supra 
aortic trunks, coeliac trunk), which is not due to remodeling of 
the subject’s vasculature.   
The 1-month imaging will be used as the baseline for this 
determination. 
Loss of stent graft 
patency 
Defined as a 100% complete blockage (occlusion) of the 
lumen diameter of any implanted stent graft component(s) as 
evidenced by CT, angiography, ultrasound, or other 
appropriate imaging modality, and/or operative pathological 
analysis.  
Endoleak 
Defined by the presence of contrast-enhanced blood outside 
the lumen of the endoluminal graft but within the aneurysm 
sac. Endoleaks are classified as follows:  
Type I a – Leak at the proximal graft attachment site 
Type I b - Leak at the distal graft attachment site. 
Type I c - Leak around a fenestration, branch end point, 
or branch occluding plug (e.g., plug occluding a 
subclavian artery or iliac artery to prevent flow into an 
aneurysm sac). 
Type II – Retrograde flow from branch arteries arising 
from the excluded segment.  
Type III a – Endoleak between the segments of the 
modular graft (junctional endoleak).  
Type III b – Endoleak in the mid-graft region due to the 
defect of fabric. 
Type IV – Transgraft leak due to fabric porosity.  
Type V – Aneurysm enlargement in the absence of any 
demonstrable perfusion of the aneurysmal sac  
Type undetermined - Endoleak of undefined origin 
 

 
 
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Major Adverse Events (MAEs) 
L.2.2
Respiratory complications 
Atelectasis 
Collapse of part or (much less commonly) all of a lung caused by a blockage 
of the air passages (bronchus or bronchioles) or by pressure on the outside 
of the lung. 
Clinical evidence of atelectasis is determined by physical, radiographic, and 
laboratory findings requiring treatment with antibiotics, inhalation therapy, 
intubation, or suctioning. 
Pneumonia 
Inflammation of the lung, usually caused by an infection. 
Clinical evidence of pneumonia is determined by physical, radiographic, and 
laboratory findings requiring treatment with antibiotics, inhalation therapy, 
intubation, or suctioning. 
Pulmonary embolism 
Sudden onset of pleuritic chest pain, cough, hemoptysis, hypoxia, 
tachycardia and a positive ventilation/perfusion (V/Q) scan. 
Pulmonary edema 
Abnormal accumulation of fluid in the lungs. 
Respiratory failure 
The need for ventilatory support for >72 hours associated with an inability to 
wean from the respirator for any reason. 
Renal complications 
Renal failure 
Sudden reversible failure of renal function caused by shock, interruption of 
blood flow to the kidneys, direct damage to the kidney's and/or sudden 
obstruction of urine flow. 
Renal insufficiency 
Slowly progressive failure of renal function resulting from some disease (e.g., 
diabetes, cancer, hypertension, glomerulonephritis) that causes gradual 
destruction of the kidneys or if creatinine levels are available, an increase of 
>25% above the pre-procedure creatinine level. 
Cardiac complications 
Myocardial Infarction 
(MI) 
• 
Non-Q-wave MI is defined as elevated CK > 2X the upper lab normal 
with the presence of elevated CK-MB (any amount above the institutions 
upper limit of normal) in the absence of new pathological Q waves. 
• 
Q wave myocardial infarction is defined as development of new, 
pathological Q waves in 2 or more contiguous leads (as assessed by the 
ECG core laboratory) with post-procedure CK elevation >2x ULN and 
CKMB levels elevated above normal. 
Unstable angina 
Chest pain unrelieved by anti-anginal medications in a subject with known 
coronary artery disease without significant elevations in cardiac enzymes. 
New arrhythmia 
The development of new atrial arrhythmia, new ventricular arrhythmia, 
exacerbation of a prior arrhythmia, a significant increase in severity of a 
current arrhythmia or any episode of cardiac arrest. 
Congestive Heart 
Failure (CHF) 
Failure of the heart to pump blood with normal efficiency. Development of an 
acute episode of or exacerbation of existing low cardiac output or fluid 
overload accompanied by peripheral and/or pulmonary edema. 
 
 
 

 
 
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Central and peripheral neurological complications 
Cerebrovascular 
accident (CVA) / 
Stroke 
Defined as sudden onset of vertigo, numbness, aphasia, or dysarthria due 
to vascular lesions of the brain such as hemorrhage, embolism, thrombosis, 
or rupturing aneurysm, that persisted >24 hours. 
Cerebrovascular 
Embolic event 
The obstruction of a blood vessel from the brain by a blood clot or foreign 
substance (e.g. air, fat, bacteria). 
Paraplegia 
Complete loss of motor function in the lower extremities and lower portions 
of the trunk. A thoracic or lumbar injury can affect leg, bowel and bladder 
control and sexual function. 
Paraparesis 
Mild loss of bilateral lower extremity motor function; bilateral lower extremity 
weakness. 
Gastrointestinal complications 
Bowel ischemia 
A decrease in blood supply to either the large or small intestine that is 
associated with pain, bleeding, abdominal distension, diarrhea or x-ray or 
angiographic evidence of reduced organ flow. 
Major Bleeding complications 
Bleeding, procedural 
A blood loss greater than 750 cc occurring before the subject leaves the OR. 
Bleeding, post-
procedural 
Post-procedural bleeding greater than 750cc occurring after the subject 
leaves the OR. 
Coagulopathy 
The development of an abnormal bleeding disorder (e.g., Disseminated 
Intravascular Coagulopathy or Thrombocytopenia with platelet counts of < 
80,000) documented by appropriate laboratory studies requiring therapy with 
medication or transfusion. 
Vascular complications 
Aortic rupture 
The tearing apart of the aortic tissue. Signs of aortic rupture include 
hemothorax, unrelenting chest or back pain, or hypotension refractory to 
medical management for a period exceeding two (2) days. 
Aneurysm rupture 
See definition of Thoracic Aortic Aneurysm rupture in section L.2.1 
Hematoma at 
access site 
An abnormal localized collection of blood (clotted or partially clotted) and 
situated at level of access site(s) used for endovascular procedure. 
Pseudo or false 
aneurysm 
Enlargements of the aorta, iliac or femoral arteries, which contain some or all 
of the medial layer, the adventitia, and periaortic tissue; most commonly 
associated with previous aortic operative procedures, trauma, and/or 
infection. Pseudo-aneurysms typically present as a well-defined collection of 
blood outside the vessel wall from contained rupture. 
Arteriovenous (AV) 
fistula 
Formation of an abnormal connection between the lumens of an artery and a 
vein as documented by CT, ultrasound, angiography or direct observation. 
Retroperitoneal 
bleed 
Bleeding into the retroperitoneal space due to trauma, surgery or 
percutaneous puncture of an artery or vein. 
Limb ischemia 
A decrease in blood supply to either the inferior or superior limb(s). 
Thrombosis 
Clotting within a blood vessel which may cause infraction of tissues supplied 
by the vessel; it may be occlusive or attached to the vessel or heart wall 
without obstructing the lumen. 

 
 
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Device Deficiencies 
L.2.3
As defined in section F.6.1, every Device Deficiency will be reported by the Investigator on a 
Device Deficiency Form regardless it resulted in an Adverse Event. 
Listing of Device Deficiencies (DD) available in CRF drop down list 
Implant procedure-specific 
DD 
Inadequate labeling 
Inadequate packaging 
Use Error (specify : Not following IFU deployment steps, Not 
following IFU bailout technique instructions, Use of a device 
with an identified malfunction) 
Access Failure 
Insertion Failure 
Delivery Difficulty 
Delivery Failure 
Deployment Difficulty 
Deployment Failure 
Difficulty to release tip capture 
Failure to release tip capture 
Difficulty to remove delivery system 
Failure to remove delivery system 
Delivery system component breakage (e.g., handle, sheath, 
tip, etc.) 
Stent graft Incomplete Deployment (device does not fully 
deploy in target area) 
Misaligned Deployment 
Stent graft Infolding 
Incomplete apposition/mal-apposition of proximal stent with 
aortic wall (bird beak) 
Stent graft Improper placement (Misplacement) related to 
marker interpretation, improper manufacturing, physician 
error 
Any other failure/malfunction of Delivery System during 
procedure, specify:___________ 
Other DD: 
Use Error – Inappropriate device over sizing 
Use Error – Inappropriate device overlap 
Use Error – Other, specify: _______ 
Incomplete sealing, not due to anatomy or disease 
progression 
Stent graft Fabric porosity, not due to subject’s heparinization 
or other anticoagulant medication 
Stent graft Fabric defect (specify: stent graft rupture, stent 
graft extrusion/ erosion) 

 
 
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Stent graft Fracture (Specify: proximal bare stent, support 
spring, body stents, wireform) 
Stent graft Kinking* 
Stent graft Twisting* 
Stent graft Dilatation 
Stent graft Migration 
Stent graft Component Separation 
Stent graft Wire Detachment from Fabric (specify location) 
Any other failure/malfunction of Stent graft, specify: ______ 
* Not intentional and not due to anatomy or disease progression 
 
Additional Definitions 
L.2.4
Term 
Definition 
Landing zones of the 
thoracic aorta 
 
The landing zones in the aorta for endovascular stenting 
are defined as follows: 
Zone 0 – the proximal edge of the covered endograft lies 
proximal to the distal end of the innominate artery  
Zone 1 – from distal end of the innominate artery to the 
distal end of the left common carotid artery  
Zone 2 – from the distal end of the left common carotid 
artery to the distal end of the left subclavian artery  
Zone 3 – from the distal end of the left subclavian artery to 
the end of the aortic arch curvature (≤2 cm of the left 
subclavian artery without covering it)  
Zone 4 – proximal extent of the endograft is >2 cm distal to 
the left subclavian artery and ends within the proximal half 
of the descending thoracic aorta (T6 approximating the 
midpoint of the descending thoracic aorta) 
 
 

 
 
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L.3. Investigational Plan Extension of Follow-Up 
Requirements  
L.3.1 Background  
The purpose of this appendix is to describe the update to the Valiant Evo International Clinical 
Trial requirements increasing subject follow-up requirements to 60 months (5 years).  
L.3.2 Rationale  
The reason for the proposed change is to better understand the long-term safety and 
effectiveness of the Valiant Evo Thoracic Stent Graft System in subjects with a DTAA. The 
extension of clinical follow up requirements provides longer-term evidence on the device’s 
performance beyond the original 12-month term planned in the study, permitting accumulation 
of additional device use experience and clinical outcomes to support the marketing application 
and post-marketing surveillance. 
The clinical evidence collected as part of this expanded follow-up period will be used in 
conjunction with the data collected from the concurrently enrolling Valiant Evo US Clinical Trial 
to support commercial approvals in geographies worldwide. 
L.3.3 Study Plan  
L.3.3.1 Secondary Endpoints at 24, 36, 48 and 60 months 
Secondary endpoints are to be assessed beyond 12 months. The following secondary 
endpoints are to be evaluated at 24, 36, 48, and 60 months: 
• All-cause mortality  
• Aneurysm-Related Mortality  
• MDEs  
• All AEs and SAEs 
• Secondary procedures  
• Loss of stent graft patency based on site reported imaging findings 
• Endoleaks based on site reported imaging findings 
• Stent graft migration as compared to 1-month imaging 
• Aneurysm expansion > 5mm based on site reported imaging findings relative to the 1-
month visit 
Health-related quality of life outcomes are to be assessed at all scheduled follow-up visits using 
the EQ-5D questionnaire. 
L.3.3.2 Subject accountability 
Subjects already enrolled and willing to extend their follow-up from 12 to 60 months are to be 
re-consented. Re-consenting is to occur at or prior to the 12-month follow-up visit. Enrolled 
subjects who decline to continue to participate in follow-up beyond 12-months shall exit the 
study upon the completion of their 12-month visit. 
L.3.3.3 Study duration 
Subjects are followed under this investigational plan up to 60-months post-implantation. 
Subjects have additional follow-up evaluations at the following time points: 
• 24-months following the index procedure 
• 36-months following the index procedure 
• 48-months following the index procedure 
• 60-months following the index procedure 
 

 
 
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A Data Monitoring Committee and Clinical Events Committee continue to evaluate the subject 
health status and device performance and identify any safety concerns regarding subjects’ well-
being. An imaging core lab is not used to perform independent imaging assessments regarding 
device performance beyond 12 months of follow-up. 
L.3.3.4 Number of investigational sites and study duration 
The total enrolment for this study will not exceed 47 patients in up to 17 sites, as originally 
mentioned in section C.7  
The total enrollment period is expected to be approximately 30 months. Enrolled subjects are 
followed up at 1, 12, 24, 36, 48 and 60-months post-implantation. 
L.3.4 Study preparation procedures  
L.3.4.1 Revisions in Informed Consent form 
Medtronic revised the written informed consent template based on the changes contained 
within this appendix. Subjects who are currently participating in the study shall be asked to sign 
the updated informed consent to confirm their continuing informed consent in writing for up to 5 
years of follow-up. Those subjects who have exited the study, or are lost for follow-up, are not 
contacted for study reasons again and are not re-consented to participate in follow-up beyond 
12 months. 
The revised informed consent documents are provided to the investigational sites for approval 
by the EC/IRB and or CA, as applicable by local regulations.  
L.3.5 Study Methods  
L.3.5.1 Follow-Up Visits and Procedures 
Subjects require post-implantation follow-up visits at 30-days, 12, 24, 36, 48 and 60 months. 
Follow-up visits and associated timeframe windows are summarized in Table L-1: 
Table L-1:  Post-Implantation Follow-Up Visit Schedule and Windows 
Follow-Up Visit 
Window Start 
Day 
Target Day 
Window Close 
Day 
1 Month (± 15 days) 
15 
30 
45 
12 Months (365 ±60 days) 
305 
365 
425 
24 Months (730 ±60 days) 
670 
730 
790 
36 Months (1095 ±60 days) 
1035 
1095 
1155 
48 Months (1460 ±60 days) 
1400 
1460 
1520 
60 Months (1825 ±60 days) 
1765 
1825 
1885 
 
At all required follow-up visits subjects will undergo the following assessments and procedures:  
• 
Physical Examination  
• 
Chest CT/MRI with contrast  
• 
EQ-5D questionnaire  
• 
Adverse event assessment  
L.3.5.2 Data collection requirements 
The data collection schedule is summarized in Table L-2. Imaging source data is to be sent to a 
core lab for analysis up to the 12-month follow-up visit. Imaging source data beyond 12-months 
post-index procedure is not to be sent to the core lab for analysis. Instead, study sites are to 
report the results of the imaging performed as standard of care and in line with local and site 

 
 
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requirements directly on the e-CRF. Routinely acquired images may be required for 
adjudication purposes in case of CEC adjudication or any other safety event.  
 
                       Table L-2:  Data Collection Schedule 
DATA  
Screening 
/ Baseline 
 
Index 
Procedure 
Hospital 
Discharge 
1-Mo. F/U 
(±15 days) 
12-Mo. F/U 
(+60 days) 
24, 36, 48 & 
60-Mo. F/U 
(+60 days) 
GENERAL 
 
Informed Consent 
 
 
 
 
 
 
Inclusion Criteria/ 
Exclusion Criteria 
 
 
 
 
 
 
Physical 
Examination  
 
 
 
 
 
 
Medical History 
 
 
 
 
 
 
Current Health 
Status and Risk 
Factors 
 
 
 
 
 
 
Device and 
Procedure 
Information  
 
 
 
 
 
 
Pre-implant 
Adjunctive 
Procedures 
 
 
 
 
 
 
Hospital Discharge 
Information 
 
 
 
 
 
 
Adverse event  
assessment 
a 
 
 
 
 
 
EQ-5D 
questionnaire 
 
 
 
 
 
 
IMAGING 
 
 
CT/MRI with 
contrast b 
f 
 
 
c,d,f 
 d,f 
d,g 
Angiography 
 
e 
 
 
 
 
a In case of screen failures, investigators are requested to enter safety information in the 
eCRF from time point of enrolment until time point of screen failure 
b CT evaluation may include “3-phase technique”, volume studies, 3-D reconstruction, or 
computer-aided measurements 
c A CT/MRI with contrast acquired at discharge (or before Day 15) due to medical necessity 
may be used to meet the 1-month follow-up visit CT/MRI requirement if a CT/MRI with 
contrast cannot be obtained within the 1-month follow-up window due to the subject’s health 
status based upon physician discretion. 
d MRI with contrast may be used for those patients experiencing renal failure or who are 
otherwise unable to undergo contrast-enhanced CT scan, with TEE being an additional option 
in the event of suboptimal MR imaging. 
e Required to complete Procedure eCRF but not expected to be submitted to Medtronic or 
core lab unless further analysis is needed.  
f Imaging assessed by core lab 

 
 
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g Upon sponsor request, core lab analysis of imaging may be required  
 
 

 
 
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M VERSION HISTORY 
 
Version 
Summary of Changes 
Author(s)/Title 
1 
• 
Not Applicable, New Document 
 
 
2 
• 
Minor typo changes 
• 
Changes made in 
o Geographies 
o Principal Investigator 
• 
Exclusion of vulnerable populations 
• 
Protocol made compliant to ISO14155 
• 
Updated to clarify imaging requirements 
• 
Correction of the process of source data 
collection 
• 
Insertion of missing safety and 
compliance definitions and/or references 
to study plans 
 
3 
• 
Added Appendix L to reflect Protocol 
amendment to extend the follow of 
subjects from 12 months to 60 months. 
• 
Administrative changes like correction of 
typo’s, font types and alignments, 
integration of new template,  
• 
Synopsis update with schedule of events 
and secondary endpoints for extended 
follow-up