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

 
 
Clinical Investigation Plan 
 
Version 1B 
 10219498DOC 
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 Valiant Evo US Clinical Trial 
056-F275, v3.0 Clinical 
Investigation Plan Template 
 
Medtronic Confidential 
 
 
 
Clinical Investigation Plan 
Clinical Investigation Plan/Study Title  Valiant EVO US Clinical Trial 
Study Product Name Valiant™ Evo Thoracic Stent Graft System 
Sponsor/Local Sponsor Medtronic Vascular 
3576 Unocal Place 
Santa Rosa, CA 95403 
United States 
Document Version 1B 
Lead Principal Investigator Ali Azizzadeh, MD 
Director, Vascular Surgery 
Cedars-Sinai Medical Center 
127 S. San Vicente Blvd 
Los Angeles, CA 90048 
 
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 
 
  
 
Author 
(name) 
 
(functional role) 
 
 
 
 
 
(signature) 
 
(date) (dd MMM yyyy) 
 
 
 
 
 
 
 
Clinical Leadership & Program Lead 
(name) 
 
(functional role) 
 
 
 
 
(signature) 
 
(date) (dd MMM yyyy) 
 
 
  
 
 
 
Safety 
(name) 
 
(functional role) 
 
 
 
 
 
(signature) 
 
(date) (dd MMM yyyy) 
 
 
  
 
 
 
Monitor 
(name) 
 
(functional role) 
 
 
 
 
 
(signature) 
 
(date) (dd MMM yyyy) 
 
 

 
 
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The following signatures are collected electronically through Agile: 
 
Role 
Name 
Title 
Clinical Quality 
 
Clinical Quality Manager 
Regulatory Affairs 
 
Principal Regulatory Affairs Specialist 
Statistician 
 
Principal Statistician 
Medical Writer &  
Clinical Study Manager 
 
Principal Clinical Research Specialist 
Design Assurance Engineer 
 
Quality Assurance Program Manager 
 
 

 
 
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TABLE OF CONTENTS 
 
A SYNOPSIS ........................................................................................................ 8 
B GENERAL INFORMATION 
............................................................................. 14 
B.1 Introduction 
....................................................................................................................... 
14 
B.2 Device information 
............................................................................................................ 
16 
 Device Description ................................................................................................. 
16 
B.2.1.1 Valiant Evo Thoracic Stent Graft ............................................................ 
16 
B.2.1.2 Valiant Evo Delivery System 
................................................................... 
18 
B.2.1.3 Device sizes and configurations 
............................................................. 
20 
 Indications for Use 
.................................................................................................. 
21 
C STUDY PLAN 
.................................................................................................. 22 
C.1 Study objectives................................................................................................................ 
22 
 Primary objectives 
.................................................................................................. 
22 
 Secondary objectives 
............................................................................................. 
22 
C.2 Clinical endpoints.............................................................................................................. 
22 
 Primary endpoints .................................................................................................. 
22 
 Secondary endpoints 
.............................................................................................. 
23 
C.2.2.1 30-day Secondary Endpoint ................................................................... 
23 
C.2.2.2 6-month Secondary Endpoints: .............................................................. 
23 
C.2.2.3 12-month Secondary Endpoints ............................................................. 
23 
C.2.2.4 24, 36, 48 and 60-month Secondary Endpoints 
..................................... 
24 
 Additional observations 
.......................................................................................... 
24 
C.3 Study Hypothesis 
.............................................................................................................. 
25 
C.4 Study population 
............................................................................................................... 
25 
C.5 Study design 
..................................................................................................................... 
25 
C.6 Randomization and blinding 
............................................................................................. 
26 
C.7 Sample size 
...................................................................................................................... 
26 
C.8 Number of Investigational sites and study duration.......................................................... 
26 
D SUBJECT SELECTION 
................................................................................... 27 
D.1 Inclusion criteria 
................................................................................................................ 
27 
D.2 Exclusion criteria............................................................................................................... 
27 
E STUDY PREPARATION PROCEDURES ....................................................... 29 
E.1 Investigator/Investigation site selection 
............................................................................ 
29 
 Investigator selection criteria 
.................................................................................. 
29 
 Investigation site selection criteria ......................................................................... 
29 

 
 
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 Clinical Trial Agreement 
......................................................................................... 
30 
E.2 Ethics 
................................................................................................................................ 
30 
 EC/IRB approval 
..................................................................................................... 
30 
 Informed consent process 
...................................................................................... 
30 
 Revisions in Informed Consent Form 
..................................................................... 
31 
 Regulatory submission 
........................................................................................... 
31 
E.3 Regulatory compliance 
..................................................................................................... 
31 
E.4 Training requirements 
....................................................................................................... 
32 
E.5 Clinical study materials 
..................................................................................................... 
32 
E.6 Study device/product traceability 
...................................................................................... 
32 
 Supply of investigational devices/products ............................................................ 
32 
 Storage and handling of investigational devices/products 
..................................... 
32 
 Device explant and return procedures/products .................................................... 
32 
F 
STUDY METHODS 
.......................................................................................... 32 
F.1 Point of Enrollment ........................................................................................................... 
32 
F.2 Implant or procedure aspects 
........................................................................................... 
34 
 Index Procedure 
..................................................................................................... 
34 
 Treatment failure 
.................................................................................................... 
34 
 Hospital Discharge 
................................................................................................. 
34 
 Follow-Up Visits and Procedures 
........................................................................... 
34 
F.3 Data collection requirements 
............................................................................................ 
35 
F.4 Role of the sponsor’s representatives 
.............................................................................. 
37 
F.5 Source documents 
............................................................................................................ 
37 
F.6 Adverse events 
................................................................................................................. 
37 
 Definition/classification 
........................................................................................... 
37 
 Recording and reporting of Adverse Events .......................................................... 
39 
 Recording and reporting of Device Deficiencies 
.................................................... 
40 
 Adverse Event and Device Deficiency review process 
.......................................... 
40 
 Clinical Event Committee 
....................................................................................... 
42 
 Data Monitoring Committee.................................................................................... 
42 
 Emergency contact details in case of serious AEs ................................................ 
42 
F.7 Subject accountability 
....................................................................................................... 
42 
 Criteria and procedures for exit from study 
............................................................ 
43 
 Study Withdrawal ................................................................................................... 
43 
 Missed follow-up 
..................................................................................................... 
43 
 Lost-to-follow-up 
..................................................................................................... 
43 
 Medical care after study exit................................................................................... 
43 

 
 
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F.8 Study deviations and CIP changes................................................................................... 
43 
 Request for approval of study deviations 
............................................................... 
44 
 Reporting requirements for study deviations.......................................................... 
44 
 Amendments to the Clinical Investigation Plan 
...................................................... 
44 
G QUALITY CONTROL PROCEDURES 
............................................................ 45 
G.1 Procedures for database management 
............................................................................ 
45 
 Data collection 
........................................................................................................ 
45 
 Source data to be directly recorded on the Case Report Forms............................ 
45 
 Time windows for completion and submission of Case Report Forms 
.................. 
45 
 Data review and processing 
................................................................................... 
45 
G.2 Monitoring procedures 
...................................................................................................... 
45 
 Accessibility of investigation site staff and study materials 
.................................... 
46 
 Audits and investigation site inspections 
................................................................ 
46 
G.3 Study suspension or early termination ............................................................................. 
46 
 Early study suspension or termination 
................................................................... 
46 
 Early investigation site suspension or termination 
................................................. 
46 
 Subject follow-up in case of termination 
................................................................. 
47 
G.4 Study close out 
................................................................................................................. 
47 
H DATA ANALYSIS AND REPORTING 
............................................................. 47 
H.1 Analysis of clinical data .................................................................................................... 
47 
H.2 Publication Policy.............................................................................................................. 
49 
I 
STUDY MANAGEMENT 
.................................................................................. 49 
I.1 Study staff 
......................................................................................................................... 
49 
I.2 Advisory committees ........................................................................................................ 
49 
 I.2.1 Clinical Event Committee (CEC) 
.................................................................... 
49 
 Data Monitoring Committee.................................................................................... 
50 
 Publication Committee ........................................................................................... 
50 
 Imaging Core Lab 
................................................................................................... 
50 
I.3 Records and reports 
......................................................................................................... 
50 
 Investigator records 
................................................................................................ 
50 
 Investigator reporting responsibilities 
..................................................................... 
50 
 Sponsor records 
..................................................................................................... 
51 
 Sponsor reporting responsibilities 
.......................................................................... 
52 
 Record retention 
..................................................................................................... 
52 
I.4 Miscellaneous 
................................................................................................................... 
53 
 Insurance 
................................................................................................................ 
53 
 Subject compensation and indemnification 
............................................................ 
53 

 
 
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 Subject confidentiality 
............................................................................................. 
53 
J 
RISKS AND BENEFITS .................................................................................. 53 
J.1 Anticipated Clinical Benefits 
............................................................................................. 
53 
J.2 Risks 
................................................................................................................................. 
54 
J.3 Risk-to-benefit rationale 
.................................................................................................... 
55 
K REFERENCES ................................................................................................ 56 
L 
APPENDICES ................................................................................................. 57 
L.1 Abbreviations 
.................................................................................................................... 
57 
L.2 Definitions 
......................................................................................................................... 
59 
 Primary and Secondary Endpoints 
......................................................................... 
59 
 Major Adverse Events (MAEs) 
............................................................................... 
62 
 Device Deficiencies 
................................................................................................ 
64 
 Additional Definitions 
.............................................................................................. 
66 
L.3 Imaging Matrix 
.................................................................................................................. 
67 
L.4 Device Explant and Returned Product Instructions 
.......................................................... 
67 
L.5 Informed Consent Template 
............................................................................................. 
72 
L.6 Post PMA-S approval Analysis 
......................................................................................... 
72 
L.7 CMS Study Criteria 
........................................................................................................... 
72 
M VERSION HISTORY 
........................................................................................ 73 
 
 
 

 
 
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A  SYNOPSIS 
Title 
Valiant Evo US Clinical Trial 
Investigational 
Device 
Valiant™ Evo Thoracic Stent Graft System 
Study Design 
The Valiant  Evo  US  Clinical  Trial is  a  prospective,  multi-center,  pre-market,  non-
randomized, single-arm trial. 
Purpose 
The  purpose  of  the  Valiant  Evo US 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 clinical 
evidence collected as part of this trial will be used in conjunction with data collected during 
the concurrently enrolling Valiant Evo International Clinical Trial to support PMA-S Approval 
of the Valiant Evo Thoracic Stent Graft System. The clinical evidence collected as part of 
this clinical  trial  may  also  be  used  to  support  obtaining  commercial  approval  in  other 
international geographies.   
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 
objectives 
Secondary objectives 
include descriptive analyses of secondary endpoints as well as acute 
procedural observations and clinical utility measures.  
Primary Endpoints 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.5: 
• Device-related secondary procedures  
• Device-related mortality 
•  Conversion to open surgery 
• Thoracic aortic aneurysm rupture 
An 
independent Clinical Events Committee (CEC) will be established and 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)/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 
6-month Secondary Endpoints: 
 
The following secondary endpoints will be evaluated: 
• All-cause mortality within 183 days 
• Aneurysm-Related Mortality within 183 days 
• MDEs within 183 days 
• All AEs within 183 days including: 
• MAEs 
• SAEs 
• Secondary procedures within 183 days 
• Loss of stent graft patency within 6 months based on imaging findings 
• Endoleaks at 6 months based on imaging findings 
• Stent graft migration at 6 months as compared to 1-month imaging 
• Aneurysm  expansion  >  5mm  at  6  months  based  on  imaging  findings 
relative to the 1-month visit 
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 
For subjects that re-consent to extended study follow up, the above 12-month secondary 
endpoints will be evaluated at 24, 36, 48, and 60 months. 
Additional 
Observations 
The following acute procedural observations and clinical utility measures will be analyzed:  
• Mean duration (min) of procedure (time between initial skin access to 
• final skin closure) 
• Proportion of subjects who underwent general/local/epidural/spinal 
• anesthesia 
• Proportion of subjects who underwent percutaneous access 
• Proportion of subjects requiring blood transfusions, excluding cell saver 
mean volume (cc) of estimated blood loss 

 
 
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• Mean duration (min) of radiation exposure 
• Radiation exposure (mGy) 
• 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.  
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 US Clinical Trial. 
Number of subjects Globally,  a total  of  100 subjects  will  be  concurrently  enrolled  
in  the  United  States  and 
outside the United States to support the primary endpoints. Up to 50% of subject data used 
to support PMA approval may come from subjects enrolled at sites outside of the US under 
a  separate  CE  Mark  study  protocol;  called  the Valiant Evo  International  Clinical  Trial 
protocol. The  primary  endpoint  analysis  will  be  completed  upon  87  evaluable  subjects 
reaching the 30 day endpoint. 
The data obtained from these 87 evaluable subjects will be used to 
support PMA-S Approval 
of the Valiant Evo Thoracic Stent Graft System. 
The Valiant Evo  US  Clinical  Trial protocol  and Valiant Evo  International  Clinical  Trial 
protocol will be identical with respect to the inclusion/exclusion criteria.  
Number of Sites 
The Valiant Evo Global Clinical program will be conducted at up to 37 sites worldwide, with 
at least 50% of the clinical sites coming from the United States.  
Clinical Procedures 
and Follow Up 
Schedule 
Subjects require follow-up evaluations at the following time points: 
• 1 month following the index procedure (30 ± 15 days) 
• 6 months following the index procedure (183 ± 30 days) 
• 12 months following the index procedure (365 ±60 days) 
• 24 months following the index procedure (730 ± 60 days) 
• 36 months following the index procedure (1095 ± 60 days) 
• 48 months following the index procedure (1460 ± 60 days) 
• 60 months following the index procedure (1825 ± 60 days) 
 
For subjects that re-consent to extended study follow up, the assessments as performed 
during the 12-month visit are to be repeated at 24, 36, 48 and 60 month visits. 
Principal 
Investigator 
Dr. Ali Azizzadeh 
Director, Vascular Surgery 
Cedars-Sinai Medical Center 
127 S. San Vicente Blvd 
Los Angeles, CA 90048 
Indications for Use The Valiant Evo Thoracic Stent Graft System is indicated for the endovascular repair of 
fusiform aneurysms and saccular aneurysms/penetrating ulcers of the 
descending thoracic aorta (DTA) in patients having the appropriate anatomy 
including the following: 
• Iliac  or  femoral  artery  access  vessel  morphology  that  is  compatible with 
vascular access techniques, devices, or accessories 
• Nonaneurysmal aortic diameter from 16 mm to 42 mm 
• Nonaneurysmal aortic proximal neck 
length ≥20 mm (for FreeFlo configuration) 
and ≥25 mm (for Closed Web configuration) 

 
 
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• Distal neck length ≥20 mm 
Inclusion Criteria 
Candidates  for  the  Valiant  Evo  US Clinical  trial  must  be  appropriate  subjects  for 
endovascular  repair  of  aneurysms  of  the  descending  thoracic  aorta  (evidenced  by 
screening contrast-enhanced CT or MRA) 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 Informed  Consent 
Form approved by the Sponsor and by the Ethics Committee for this study.   
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 following: 
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 
5. Subject’s anatomy must meet all of the following anatomical criteria as demonstrated 
on contrast-enhanced computerized tomography (CT) and/or on contrast-enhanced 
Magnetic  Resonance  Angiogram  (MRA)  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) distal  
to  
the  
left 
common carotid artery (LCCA). Note: Proximal aortic neck length may include 
covering  the LSA (with  or  without  discretionary revascularization)  when 
necessary  to  optimize  device  fixation  and  maximize  aortic  neck  length.  If 
occlusion  of  the  LSA  ostium  
is  required to  obtain  adequate  neck  
length  for 
fixation and sealing, transposition or bypass to the LSA may be warranted. 
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. 
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. 

 
 
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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. 
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. 
Study Success 
Criteria 
A 30-day premarket safety and effectiveness endpoint (a minimum of 87 evaluable subjects 
for hypothesis test). The primary endpoint will be tested against a performance goal of 16% 
MDE rate at 30 days. 
Analysis Sets 
The primary analysis set will consist of all subjects who were enrolled. The subject will be 
considered to be enrolled after arterial access is established and the Valiant Evo Thoracic 
Stent Graft System is introduced. 
 
A secondary analysis set will be the Per-Protocol population. This analysis set 
is comprised 
of all enrolled subjects who met inclusion and exclusion criteria, received the test device 
and completed 30-day follow-up (including death but excluding withdrawal or lost to follow-
up subjects within the 30-day follow-up period). 
Data Oversight 
A  Data  Monitoring  Committee,  Clinical  Events  Committee, and  
imaging  core  
lab  will  be 
established  to  independently  evaluate  subject  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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Safety Monitoring  Medtronic Clinical Operations 
710 Medtronic Parkway NE 
Minneapolis, MN 55432 
Monitoring 
Medtronic Clinical Operations 
710 Medtronic Parkway NE 
Minneapolis, MN 55432 
 
 
 
 

 
 
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B  GENERAL INFORMATION 
B.1  Introduction 
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  treatment  includes 
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 
transfemoral  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 morbidity in high-
risk patients, associated with shorter hospital stay and quicker return to normal activities after 
surgery.13,14 
However, despite the wide spread adoption of thoracic endovascular aneurysm repair (TEVAR) 
in  modern  treatment  of  TAAs,  not  all  patients  are  candidates  for  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.  This 
represents 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 arches 

 
 
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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 that 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. 
The Valiant  Evo Thoracic Stent  Graft  System incorporates design  changes  from  the  Valiant 
Captivia Stent Graft System that are targeted to broaden patient applicability, enhance ease of 
use, and 
improve vascular access by way of a reduced profile of the delivery system. This device 
will  address  an  
important TEVAR need:  a  significant  reduction  of  
the  delivery  system  profile 
(profile of 18Fr for stent graft diameters ≤25 mm, profile of 20Fr for stent graft diameters ≤37 mm 
and  profile  of  22Fr  
for  stent  graft 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 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 other 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 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 

 
 
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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, to ensure the device with the design 
modifications meets the pre-established design and performance specifications  and to ensure 
that product performance will be clinically acceptable. 
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 
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 subject’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 subject’s vasculature to deliver the stent 
graft to the target site. 
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 
increases the graft length distally or proximally to the primary section.  
All Valiant Evo Thoracic 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 (see 
Figure B-1 and Figure B-2 below). The metal scaffolding is composed of a series of serpentine 
stents stacked in a tubular configuration. Platinum-Iridium radiopaque (RO) markers are sewn to 
the fabric for radiographic visualization of the edge of the graft material and the minimum overlap 
required  when  multiple  stent  grafts  are  used.  The  
three  proximal  markers,  and  
the  
two  distal 
markers, 
indicate the extremities of the covered stent graft. The single “mid-marker” 
indicates the 
minimum amount of overlap required for multiple components. The materials used in the Valiant 
Evo Thoracic Stent Graft are listed in Table B-1. 
Table B-1: Valiant Evo Thoracic Stent Graft Materials 
Component  
Material 
Springs 
Nitinol wire (55% Nickel, 45% Titanium with 
trace elements) 
Graft Fabric 
High-density woven multifilament polyester 
Sutures 
Ultra-high-molecular-weight polyethylene 
(UHMWPE) and polyester 
RO Markers 
Platinum-Iridium 
 

 
 
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Figure B-1: Valiant Evo FreeFlo Configuration 
 
 
  
Figure B-2: Valiant Evo Closed Web Configuration 
 
During manufacturing, the  Valiant Evo Thoracic Stent Graft will be pre-loaded  
into the  Valiant 
Evo Delivery System. The nitinol stents are also visible under fluoroscopy.  
The Valiant  Evo Thoracic Stent  Graft  System is  available  
in four different  configurations  
(see 
Figure B-3): FreeFlo Straight, FreeFlo Tapered, Closed Web Straight, and Closed Web Tapered. 
All configurations can be used either as a proximal or distal component when multiple stent grafts 
are implanted. Each stent graft consists of a fabric tube on which a series of 6-peak (18 Fr or 20 
Fr) or 7-peak (22 Fr) stents and a support spring are sewn. The support spring contributes to 
diameter  recovery  of  the  stent  graft  following  deployment  and  prevents  the  stent  graft  from 
infolding during and after deployment. Stent graft diameters range from 20 
– 46 mm with covered 
length from 60 – 225 mm (refer to Section B.2.1.3 for full size matrix). 
 

 
 
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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-3: Stent Graft Configuration Components 
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 proximal-end and distal-end 
diameters of the FreeFlo Straight configuration are constant throughout the covered length of the 
device. A FreeFlo end should not be placed inside the fabric-covered section of another stent 
graft. 
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 proximal end of the FreeFlo 
Tapered configuration 
is 
larger 
in diameter than 
its distal end. A FreeFlo end 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 proximal and distal end 
diameters 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 proximal end of the Closed 
Web Tapered configuration is larger in diameter than its 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.  
The Valiant  Evo Delivery System features a tip capture mechanism in which the  stent graft is 
deployed in two stages – (1) retraction of the graft cover, gradually exposing the stent graft while 

 
 
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allowing re-positioning of the implant prior to full deployment (2) release of the first (captured) 
stent which allows the graft to fully open into position. 
The Valiant  Evo Delivery  System is a multi-lumen device,  with each  
lumen serving a different 
function: 
• The PEEK guidewire tube (inner member) provides a lumen to allow the system to track 
over a Ø0.035" guide wire.  
• The capture tube provides a lumen to actuate the tip capture release mechanism.   
• The middle member with flexible stent stop  and stent transition tube helps the device 
track through tortuous anatomy, maintains stent graft position during deployment, and 
improves kink resistance of the catheter. 
• The  graft  cover  
(with  stainless  steel  braid)  provides  a  
lumen  
that  constrains  
the  stent 
graft and flexible stent stop during tracking and final positioning of the system. The stent 
graft is released from the graft cover tube during deployment.  
 
 
 
 
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-4: Valiant Evo Stent Graft Delivery System 
 
The Valiant  Evo  Thoracic  Stent Graft  System  is  an  investigational  class  III  device  in  all 
geographies and is labeled with all the required statements per geography: 
 
• United  States:  “CAUTION:  Investigational Device.  Limited  by  Federal  Law  (USA)  to 
Investigational Use” 
 
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.2.1.3 Device sizes and configurations 
Table B-2 presents the proposed sizes and configurations of the Valiant Evo Thoracic Stent Graft 
System, and the sizing guidelines provided in Table B-3.  
Detailed information on device sizes and configurations will be included in the IFU. The IFU will 
be provided with each investigational device. 
Table B-2: Valiant Evo Thoracic Stent Graft System Size Matrix 
FreeFlo and Closed Web Straight configurations 
 
OD 
(Fr) 
Diameter (mm) Covered Length 
(mm) 
 
18 
20 
100 
22 
 
100, 175 
25 
 
 
20 
28 
31 
100, 175, 225 
34 
 
 
 
60, 100, 175, 225 
37 
 
22 
40 
43 
46 
FreeFlo Tapered configurations 
 

 
 
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OD 
(Fr) 
Proximal × Distal 
Diameter (mm) Covered Length 
(mm) 
18 
25x20
 
 
 
 
 
 
175 
 
 
20 
28×22 
31×25 
34×28 
37×31 
 
22 
40×34 
43×37 
46×40 
Closed Web Tapered configurations 
 
OD 
(Fr) 
Proximal × Distal 
Diameter (mm) 
Covered Length 
(mm) 
18 
25×20 
175 
 
 
20 
28×22 
 
 
 
 
200 
31×25 
34×28 
37×31 
 
22 
40×34 
43×37 
46×40 
 
 
Table B-3: Sizing guidelines for the treatment of aneurysms 
 
Graft Diameter (mm) 
Vessel Diameter Indication (mm) 
20 
16–17 
22 
18–19 
25 
20–22 
28 
23–25 
31 
26–28 
34 
28–31 
37 
30–33 
40 
33–36 
43 
36–39 
46 
39–42 
 
 Indications for Use  
The Valiant Evo Thoracic Stent Graft System is indicated for the endovascular repair of fusiform 
aneurysms and saccular aneurysms/penetrating ulcers of the descending thoracic aorta (DTA) 
in patients having the appropriate anatomy including the following: 
• Iliac or femoral artery access vessel morphology that is compatible with vascular access 
techniques, devices, or accessories 
• Nonaneurysmal aortic diameter from 16 mm to 42 mm 
• Nonaneurysmal aortic proximal neck length ≥20 mm (for FreeFlo configuration) and ≥25 
mm (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. 
The IFU will be provided with each investigational device. 

 
 
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C  STUDY PLAN 
C.1  Study objectives 
The purpose of the Valiant Evo US 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 clinical evidence collected as part of this trial will be used in conjunction with data collected 
during the concurrently enrolling Valiant Evo International Clinical Trial to support PMA Approval 
of the Valiant Evo Thoracic Stent Graft System.    
Clinical follow up requirements will continue to 60 months to provide longer-term evidence on 
the device’s performance, permitting accumulation of additional device use experience and 
clinical outcomes to support post-marketing surveillance. 
The clinical evidence collected through 60 months may be used in conjunction with the data 
collected from the concurrently enrolling Valiant Evo International Clinical Trial to support 
commercial approvals in geographies worldwide. 
 Primary objectives 
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 objectives 
Secondary  objectives  include  descriptive  analyses  of  secondary  endpoints  as  well  as  acute 
procedural observations and clinical utility measures. A hypothesis driven endpoint 
is planned for 
12 months as described in Appendix L6. 
C.2 Clinical endpoints 
 Primary endpoints 
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.5. 
An independent CEC will be established and adjudicate MDEs. 

 
 
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 Secondary endpoints 
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 CVA, 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 definitions of MAEs are defined in Appendix L.2.2 
C.2.2.2  6-month Secondary Endpoints:   
The following secondary endpoints will be evaluated: 
• All-cause mortality within 183 days 
• Aneurysm-Related Mortality within 183 days 
• MDEs within 183 days 
• All AEs within 183 days including: 
• MAEs 
• SAEs 
• Secondary procedures within 183 days 
• Loss of stent graft patency within 6 months based on imaging findings 
• Endoleaks at 6 months based on imaging findings 
• Stent graft migration at 6 months as compared to 1-month imaging 
• Aneurysm expansion > 5mm at 6 months based on imaging findings relative to the 1-
month visit 
C.2.2.3 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 
C.2.2.4 24, 36, 48 and 60-month Secondary Endpoints 
The following secondary endpoints will be evaluated: 
• All-cause mortality up to each timepoint 
• Aneurysm-Related Mortality up to each timepoint 
• MDEs up to each timepoint 
• All AEs up to each timepoint: 
• MAEs 
• SAEs 
• Secondary procedures up to each timepoint  
• Loss of stent graft patency (site-reported) up to each timepoint based on 
imaging findings 
• Endoleaks (site-reported) at each timepoint based on imaging findings 
• Stent graft migration (site-reported) at each timepoint as compared to 1-month imaging 
• Aneurysm expansion > 5mm (site-reported) at each timepoint based on 
imaging findings 
relative to the 1-month visit 
 Additional observations 
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.  

 
 
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C.3 Study Hypothesis 
The Valiant Evo US Clinical Trial  will focus on balancing pre- and post-market clinical data to 
establish safety and effectiveness. 
The primary study endpoint will be tested against a performance goal of 16% at 30 days: 
H0: p ≥ 16% vs. Ha: p <16%, 
where p denotes the true event rate of primary study endpoint in the target population.  
If  
the  null  hypothesis  
(H
0)  
is  
rejected  at  
the  one-sided  0.025  statistical  significance  
level,  
it  
is 
considered that the performance goal for the primary endpoint has been reached. 
IDE cohort will be followed up to 1-year and the primary endpoint will be tested against a 20% 
performance goal at 1 year for the post-approval analysis. Refer to Appendix L-6- PMA-S Post 
Approval analysis. 
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  US  Clinical  Trial  
is  a  prospective,  multi-center,  pre-market,  non-randomized, 
single-arm trial. The trial is designed to assess 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 clinical performance of the Valiant Evo Thoracic Stent Graft will be evaluated in a total of 
100  subjects  with  a  hypothesis-based  30-day  premarket  composite  safety  and  effectiveness 
endpoint.  
 
The proposed primary composite safety and effectiveness endpoint 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: 
 
• Device-related secondary procedures 
• Device-related mortality 
• Conversion to open surgery 
• Thoracic aortic aneurysm rupture 
This primary composite endpoint will be compared to a PG of 16% MDE rate at 30 days. 
All subjects included will continue to be followed under this investigational protocol beyond the 
30-day primary endpoint out to 60 months post-implantation. Subjects will have required follow-
up evaluations at the following time points: 
•  1-month following the index procedure 
•  6-months following the index procedure  
 
• 12, 24, 36, 48 and 60-months following the index procedure 
All subjects were consented for up to 2 years of follow-up. This was to accommodate any global 
clinical investigational requirements, if required. Subjects already enrolled and willing to extend 

 
 
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their follow-up from 12 to 60 months are to be re-consented. 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. 
A  Data  Monitoring  Committee,  Clinical  Events  Committee,  and  imaging  core  lab  will  be 
established  
to  
independently  evaluate  subject  health  status,  device  performance,  and  
identify 
any  safety  concerns  regarding  subjects’  well-being. An  
imaging  core  
lab  will  not  be  used  to 
perform independent imaging assessments regarding device performance beyond 12 months of 
follow-up. 
C.6 Randomization and blinding 
The study is a single arm study, therefore neither randomization nor blinding are applicable to 
this clinical trial. 
 
C.7 Sample size 
Globally, a total of 100 subjects will be concurrently enrolled 
in the United States and outside the 
United States to support the primary endpoints. Up to 50% of subject data used to support PMA 
approval may come from subjects enrolled at sites outside of the US under a separate CE Mark 
study protocol; called the Valiant Evo International Clinical Trial protocol.  
The Valiant Evo International Clinical Trial protocol and Valiant Evo US Clinical Trial protocol will 
be identical with respect to the inclusion/exclusion criteria. 
One hundred (100) enrolled subjects will ensure 87 evaluable subjects at 30 days. The primary 
endpoint analysis will be completed upon 87 evaluable subjects reaching the 30 day endpoint. 
The data from these 87 evaluable subjects at 30-days will be used to file the PMA submission. 
Based  on Valor  
II study  
results,  Valiant  Evo  
is  expected  
to  perform  similarly  and  have  6%  of 
MDEs  combined  with  access  and/or  deployment  
failures  at  30  days.  The  sample  size  of 87 
evaluable subjects will provide 85% statistical power for the study hypothesis.  The type I error is 
controlled at the one-sided 0.025 level.  
Table C-1: Power Analysis  
True rate of MDEs combined with access 
and/or deployment failures at 30 day with 
Valiant Evo 
6% 
Performance Goal  
16% 
Significance level 
0.025 
Statistical test 
One-sided binomial test 
Evaluable sample size 
n=87 
Enrollment 
Minimum of 100 subjects 
enrolled to ensure 87 
evaluable subjects 
Statistical power from the 87 evaluable 
subjects 
85% 
C.8 Number of Investigational sites and study duration 
The Valiant Evo Global Clinical program will be conducted at up to 37 sites worldwide, with at 
least 50% of the clinical sites coming from the United States. Inclusion will be halted at sites 

 
 
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that reach the 20% inclusion cap. There will be no minimum number of subjects for a single 
investigational site. 
The total enrollment period is expected to be approximately 12 months. Enrolled subjects will 
be followed up at 1, 6 and 12 months and annually to 5 years post-implantation. 
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 
provided to the investigators. The sponsor will maintain an updated list. 
D  SUBJECT SELECTION 
D.1 Inclusion criteria 
Candidates for the Valiant Evo US Clinical trial must be appropriate subjects for endovascular 
repair of aneurysms of the descending thoracic aorta (evidenced by screening contrast-enhanced 
CT or MRA) 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 Informed Consent Form 
approved by the Sponsor and by the Ethics Committee for this study.   
3. Subject  presents a  DTAA which  
is  
localized  below  
the  ostium  of LSA and  above  
the 
ostium of celiac trunk 
4. Subject has a DTAA that is one of the following: 
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 
5. Subject’s anatomy must meet all of the following anatomical criteria as demonstrated on 
contrast-enhanced  CT  and/or  on  contrast-enhanced  MRA  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) distal  to  the  left 
common  carotid  artery  (LCCA).  Note:  Proximal  aortic  neck  
length  may  
include 
covering the LSA (with or without discretionary revascularization) when necessary 
to optimize device fixation and maximize aortic neck 
length. If occlusion of the LSA 
ostium  is  required  to  obtain  adequate  neck  length  for  fixation  and  sealing, 
transposition or bypass to the LSA may be warranted. 
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. 
D.2  Exclusion criteria 
Candidates who meet any of the following exclusion criteria will not be eligible for recruitment in 
the study: 

 
 
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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. 
4. Subject  
requires  planned  placement  of  
the  covered  proximal  end of  
the  stent  graft  
to 
occur in zones 0 or 1.  
 
Figure D-1: Landing zones of the thoracic aorta 
(See appendix L.2.4 for definitions of zones) 
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 or the left common carotid artery or the 
celiac trunk. 

 
 
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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. 
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. 
E  STUDY PREPARATION PROCEDURES 
E.1 Investigator/Investigation site selection 
 Investigator selection criteria 
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 FDA/ICH-GCP requirements 
• Investigators are willing to undergo auditing by sponsor or regulatory bodies 
• Investigators are willing to undergo study specific training 
 Investigation site selection criteria 
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 

 
 
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• Site has sufficient annual case volume of DTAA stent graft procedures 
• Ability to securely store devices according to the Instructions for Use  
• Ability to perform required imaging assessments at site 
 Clinical Trial Agreement 
A clinical trial agreement shall be in place, signed by the participating investigational site and/or 
principal 
investigator of each 
investigational site, as per the 
local 
legal requirements, and returned 
to  Medtronic  prior  to  the  commencement  of  any clinical study  activities.  The  investigator  is 
indicating  approval  of  
the  clinical  
investigation  plan  and  subsequent  amendments,  with  a  
fully 
executed agreement. 
E.2 Ethics 
 EC/IRB approval 
Prior to enrolling subjects 
in this clinical study, each 
investigational site’s EC/IRB will be required 
to approve the current Clinical Investigation Plan, the Informed Consent Form, 
including any other 
written  
information  
to  be  provided  
to  
the  subjects  and, if  applicable, materials  used  
to  
recruit 
subjects. EC/IRB approval of the clinical study must be received 
in the form of a 
letter and a copy 
provided to Medtronic before commencement of the clinical study at an investigational 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/IRB 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/IRB. If they are members 
of  
the  EC/IRB,  written  documentation  
is  
required  stating  
that  he/she  did  not  participate  
in  
the 
approval  process.  If  the  EC/IRB  imposes  any  additional  requirements  (e.g.  safety  reports, 
progress  reports),  the  site  must  request  these  additional  requirements  in  writing,  and  then 
Medtronic will prepare the required documents and send them to the investigator for reporting to 
the  EC/IRB.  
Investigators  must  
inform  Medtronic  of  any  change  
in  status  of  EC/IRB  approval 
once  
the  
investigational  site  has  started  enrollment.  
If  any  action  
is  
taken  by  an  EC/IRB  with 
respect  
to  
the  
investigation,  
that  
information  will  be  
forwarded  
to  Medtronic  by  
the  
respective 
investigator. 
 Informed consent process 
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/IRB  approved 
Patient Information and Informed Consent Form. 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 and/ or write, an impartial witness must be present during the entire 
informed  consent  discussion.  All  items  addressed  in  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.  
 
The subject must have ample time and opportunity to read and understand 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. 
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. 

 
 
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When the subject decides to participate 
in the clinical study, the Informed Consent Form must be 
signed  and  personally  dated  by  the  subject  and  the  investigator  or  authorized  designee.  If 
applicable, the  witness shall also sign  and personally  date the consent form to attest that the 
information in the Informed Consent Form was accurately explained and clearly understood by 
the subject, and that informed consent was freely given. 
After all persons have signed and dated the Informed Consent Form the 
investigator must provide 
the subject with a copy of the signed and dated Informed Consent Form. 
 Revisions in Informed Consent Form 
Medtronic  
revised  
the  written  
informed  consent  
template  
to  
include  
the  extension  of  
follow-up 
through 5 years post implant procedure. Subjects who are currently participating in the clinical 
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. The revised informed consent documents will be 
provided to the investigational sites for approval by the local EC/IRB. 
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.  
If new information becomes available that can significantly affect the subject’s future health and 
medical care, Medtronic will revise the written Informed Consent Form. The revised information 
will  be  sent  
to  
the  
investigator  
for  approval  by  
the  EC/IRB.  
  After  approval  by  
the  EC/IRB,  
if 
relevant,  all  affected  subjects  shall  be  asked  
to  confirm  
their  continuing  
informed  consent  
in 
writing.   
 Regulatory submission 
In countries where submission to the Regulatory Authority is required per local law, no subjects 
will  be  enrolled  
in  
the clinical study  until  
the  particular  Regulatory  Authority  has  approved  
the 
current Clinical 
Investigation Plan 
of the clinical study and other documents as required according 
to the local requirements. 
If  
the  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 
• 
Informed Consent Form 
• 
Case Report Forms 
E.3 Regulatory compliance 
The Valiant Evo US Clinical Trial will be conducted under an FDA Investigational Device 
Exemption (IDE) in compliance with ICH-GCP, ISO 14155:2011 3.1, 3.15, 3.2, 3.36, 3.37, 3.42  
and 21 CFR Parts 11, 50, 54, 56 and 812. 21CFR 803 Medical Device Reporting, 21CFR 814 
Premarket Approval of Medical Devices 
 
This study will be publicly registered before recruitment of the first enrollment  in accordance 
with the 2007 Food and Drug Administration Amendments Act (FDAAA) and Declaration of 
Helsinki (October 2013) on www.clinicaltrials.gov (PL 110-85, Section 810(a)). 
In case of conflicting requirements, the regulation affording the greatest protection to the 
subject will be followed. 

 
 
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E.4  Training requirements 
Prior  
to  
investigation  site  activation  or  subsequent  
involvement  
in  clinical  study  activities,  
the 
sponsor will provide clinical study training relevant and pertinent to the involvement of personnel 
conducting clinical study activities. At a minimum, investigator responsibilities, Title 21 CFR, the 
clinical  investigation  plan,  Informed  Consent  Form,  use  of  data  collection  tool,  as  well  as 
applicable  
local regulations are required. Furthermore investigators that  will perform the index 
procedure and implantation of the device will be trained on the Valiant Evo Thoracic Stent Graft 
System. Study-specific training will be documented prior to investigational 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. 
All study specific training must be documented on a formal training record that will be provided 
by Medtronic. 
E.5 Clinical study materials  
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  a  “Go  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 
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 
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 Instructions 
for Use must be taken 
into account. 
 Device explant and return procedures/products 
All non-functioning or explanted 
investigational devices/products should be returned to Medtronic 
for analysis. 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 and in appendix L.4. 
F  STUDY METHODS 
F.1 Point of Enrollment  
Pre Screening: 

 
 
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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/MRA. 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 subject’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 screening evaluations include the following. 
• Pregnancy test (for female subjects of childbearing potential). Test must be completed 
per institutional standard of care at the time of screening (prior to) the index procedure. 
Results must be negative. 
• Screening CT or MRA 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 Form, the subject will 
be considered a study candidate. If a subject does not sign the Informed Consent Form, then no 
further study specific screening procedures can 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 
 
Screening CT/MRA 
images will be reviewed by the investigator to confirm eligibility. The 
imaging 
will  also  be sent  
to  a  core  
lab  
to  assess  
the  anatomical  
inclusion/exclusion  
requirements.  An 
Independent  Physician Reviewer  (IPR) will  review screening  CT/MRA images to  confirm 
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.  
 
Subjects who do not qualify for enrollment will be documented as 
ineligible on the Screening and 
Enrollment log. 
Enrollment:  
Those subjects who sign and date the 
informed consent document, meet all of the study eligibility 
criteria, and are approved by the IPR  will be eligible for inclusion into the Valiant Evo US Clinical 
Trial. The subject  will only  be considered enrolled when  arterial  access is established and  an 
attempt to introduce the Valiant Evo Thoracic Stent Graft is made. 
Enrolled subjects will be documented on the electronic Screening and Enrollment Log. Subjects 
who are enrolled, but not implanted with the device, will be followed through the 1 month follow-
up only. 

 
 
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The  
investigator  will  maintain  a  
log  of  all  subjects  screened  and enrolled  
in  
the  clinical study, 
assigning an identification code linked to their names, alternative subject identification or contact 
information. 
 
F.2 Implant or procedure aspects 
 Index Procedure 
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.  
 Treatment failure 
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  1-month and  
thereafter  per  
institutional  standard  of  care. 
Serious adverse events will be recorded in the eCRF through the total duration of the trial. 
If a primary conversion to open repair is required during the index procedure, then the subject 
will be followed for 1 month and thereafter per institutional standard of care.   
 Hospital Discharge 
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 
Each subject will have required post-implantation follow-up visits at 30-days, 6, 12, 24, 36, 48 
and 60 months. Follow-up visits and associated timeframe windows are summarized in Table 
F-1.        

 
 
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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 
6 Month (183 ±30 days) 
153 
183 
213 
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 
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  be 
followed for 30 days after the conversion, at which time the subject will be exited from the study. 
  
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  
(and  any  
interim 
imaging) follow-up visits described in Section F.2.  The data collection schedule is summarized 
in Table F-2.  Imaging source data will be sent to a Core Lab for analysis up to the 12-month 
follow-up visit. Any interim imaging of the stent graft region but not linked to a study visit should 
be recorded on the Interim Image eCRF (e.g. 
imaging performed as standard of care beyond the 
protocol required time points and/or when performed further to any issue observed at previous 
imaging Follow-up). 
Imaging source data beyond 12-months post-index procedure will not 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 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.  
Study data will be collected using electronic case report forms (eCRFs) as described in Section 
G.1.  Clinical investigators must electronically review and approve all eCRFs. Medtronic 
monitors will perform source document verification of the eCRFs. The monitoring strategy will 
be defined in the monitoring plan.  

 
 
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Table F-2:  Data Collection Schedule 
DATA  
Screening / 
Baseline 
 
Index 
Procedure 
Hospital 
Discharge 
1-Mo. F/U 
(±15 days) 
6-Mo. F/Ud 
(+30 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 
g 
 
 
c,e,g 
e,g 
e,g 
e,h 
Angiography 
 
f 
 
 
 
 
 
a In case of screen failures, investigators will be requested to enter safety information in the eCRF from 
time point of enrollment 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 For subjects enrolled in the Valiant Evo International Clinical Trial in European countries, a six month 
follow up visit is not required per protocol.  
e MRI  with  contrast  may  be  used  
for  
those  patients  experiencing  
renal  
failure  or  who  are  otherwise 
unable to undergo contrast-enhanced CT scan, with Transesophageal echocardiography (TEE) being 
an additional option in the event of suboptimal MR imaging. 
f Required to complete Procedure eCRF but not expected to be submitted to Medtronic or Core Lab 
unless further analysis is needed. 
g Imaging assessed by core lab.
            
h Upon sponsor request, core lab analysis of imaging may be required.  
 
 

 
 
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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 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 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 source data of each subject’s case history, exposure to the 
device and clinical follow-ups. Source data is all information in original records, certified copies 
of original records of clinical findings, observations, or other activities in a clinical investigation, 
necessary for the reconstruction and evaluation of the clinical investigation.  
Examples of these original documents and data records include, but are not limited to:  
• hospital record (paper and electronic, as applicable),  
• subject’s screening documentation,  
• recording media such as CD, DVD, CT or other imaging reports,  
• laboratory reports,  
• device accountability records,  
• worksheets and subject files at other departments.  
Where paper notes and worksheets are retained, these shall be signed and dated by the member 
of the investigational site team. 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  
investigational  site  
team  with  a  statement  
that  
it  
is  a  
true  
reproduction  of  
the 
original source document.  
Source documents will be used for verification of the data documented in subject’s eCRF during 
monitoring visits, audits and inspections, and for the adjudication of AEs and must be accessible 
to the Medtronic field clinical support and the clinical study team 
The investigator will allow inspections of the study site and documentation by Clinical Research 
and audit personnel from Medtronic or designee, EC/IRB, external auditors, or representatives 
of regulatory authorities. The purpose of these inspections is to verify and corroborate the data 
collected  on  the  eCRFs.  In  order  to  do  this,  direct  access  to  medical  or  clinical  records  is 
necessary. 
F.6 Adverse events 
 Definition/classification  
For the purpose of this clinical 
investigation Medtronic will define and classify the following events 
per ISO14155:2011 and Title 21 CFR part 812.3 
 
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 include, but are 
not limited to, those listed in Table F-3. These events should not be to be reported as adverse 
events during this study. 
Table F-3: Expected and unavoidable adverse events related to the surgical procedure. 

 
 
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Description of the Event 
Time Frame from the Index Procedure 
Endoleaks observed and resolved during 
the index procedure 
Resolved by the time the subject leaves 
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 
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): 
(ISO14155:2011 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): 
(ISO14155:2011 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:  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) 

 
 
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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) 
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): (21 CFR 812.3) 
Any serious adverse effect on health or safety or any life-threatening problem or death caused 
by, or associated with, a device, if that effect, problem, or death was not previously identified in 
nature, severity, or degree of incidence in the investigational plan or application, or any other 
unanticipated serious problem associated with a device that relates to the rights, safety, or 
welfare of subjects. 
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 US 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 US 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 
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 
the investigational site file. 
 
 Recording and reporting of Device Deficiencies 
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 
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. 
In case the Adverse Event/Device Deficiency is related to a Medtronic market released device 
used during the study, Medtronic Study Management and/ or designee will immediately report 
this device related Adverse Event/Device Deficiency to the Product Experience Management 
(PXM) group. The PXM group will ensure prompt review, and appropriate reporting. 
 
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/IRB 
Reporting timeframe as per local EC/IRB requirement. 
Sponsor submit to: 
 
Regulatory Authorities 
Reporting timeframe as per local requirement. 
EC/IRB 
Submit to EC/IRB per local reporting requirement. 
Serious Adverse Events (SAE) and Unanticipated Adverse Device Effects (UADE) 
Investigator submit to:  

 
 
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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/IRB 
Submit to EC/IRB per local reporting requirement. 
Sponsor submit to: 
 
Regulatory Authorities 
Reporting timeframe as per local requirement. 
EC/IRB 
Submit to EC/IRB 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/IRB 
Submit to EC/IRB per local reporting requirement. 
Sponsor submit to: 
 
Regulatory Authorities 
Reporting timeframe as per local requirement 
EC/IRB 
Submit to EC/IRB 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/IRB 
Submit to EC/IRB 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/IRB 
Submit to EC/IRB per local reporting requirement. 
Sponsor submit to: 
 
Regulatory Authorities 
Reporting timeframe as per local requirement 
EC/IRB 
Submit to EC/IRB 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 

 
 
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EC/IRB 
Submit to EC/IRB per local reporting requirement. 
 
In  addition,  Investigators  are  obligated  to  report  adverse  events  in  accordance  with  the 
requirements of their IRB/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 
IRB/EC as per local requirements. The applicable timeframes are described in the Valiant Evo 
Clinical Trial safety plan.  
 Clinical Event Committee 
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,  UADEs, 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 
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.  
Medtronic will provide 
listings of all Adverse Events and Device Deficiencies to the Independent 
Medical Monitor 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. 
 
Based on the safety data, the DMC may recommend that Medtronic modify or stop the trial. 
DMC composition, duties, procedures, deliberation rules are detailed and documented in the 
DMC Charter. 
 Emergency contact details in case of serious AEs 
In case of an 
immediately reportable Adverse Event the 
investigators can contact the Medtronic 
Study  Manager. 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 data outside 
the clinical study. Subjects will not be replaced in case of premature study discontinuation. 

 
 
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 Criteria and procedures for exit from study  
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  
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 subject’s  
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 as further 
described 
in section F.7.6. 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 
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  
A subject may be considered  
lost  
to follow-up  once the  
investigator and/or research staff has 
made three documented attempts to contact the subject. The third attempt should be made by 
certified mail to the subject. 
 Medical care after study exit 
After study exit the subjects will be followed as per routine standard of care by the 
investigational 
site or a treating physician. 
F.8 Study deviations and CIP changes 
A protocol deviation is defined as an event where the clinical investigator or site personnel did 
not conduct the study according to the clinical 
investigational plan, applicable 
laws or regulations, 
or the Investigator Agreement. Every attempt must be made to avoid deviations. All deviations 
are recorded  on  a  Protocol  Deviation  Case Report  Form. United States  
regulations  
(21  CFR 
812.140) require that investigators maintain accurate, complete, and current records relating to 
the clinical study. This includes documents showing the dates and reasons for each deviation 
from the clinical 
investigational plan. Depending on the nature of the protocol deviation, expedited 
reporting  and  prior  approval  
from  Medtronic  may  be  
required.  All  protocol  deviations  must  be 
reported to the Institutional Review Board (IRB) 
in accordance with IRB policies and/or 
local 
laws. 
All deviations will be summarized and reported in regular progress reports to the FDA. 
 
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. 

 
 
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 Request for approval of study deviations 
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/IRB  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/IRB,  if  applicable.  Medtronic  will  inform  the  Regulatory 
Authorities, if required. 
 Reporting requirements for study deviations 
The  investigator  shall  adhere  to  EC/IRB  requirements  and  procedures  for  reporting  study 
deviations. 
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 subject’s 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 
The investigator will 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/IRB. The investigator will only implement the amendment after 
approval of the EC/IRB, Regulatory Authority  and sponsor. Administrative amendments to the 
Clinical Investigation Plan will be submitted to the EC/IRB and Regulatory Authority (if required) 
for notification. Furthermore investigators shall sign any approved amendment for agreement.  

 
 
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G  QUALITY CONTROL PROCEDURES 
G.1 Procedures for database management 
 Data collection 
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’s 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. 
 Source data to be directly recorded on the Case Report Forms 
All data reported on the eCRFs shall be derived from source documents and be consistent with 
these  source; 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 
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 
Data management will be done according to Medtronic SOPs and the Data Management Plan 
for this clinical study. These documents will be made available upon 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 

 
 
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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 
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  
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/IRB review, and regulatory inspections. 
G.3 Study suspension or early termination 
 Early study suspension or termination 
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/IRB and the study 
subjects.  
 Early investigation site suspension or termination 
Medtronic, EC/IRB or Regulatory Authority may decide to suspend or prematurely terminate an 
investigation site (e.g. in case of expiring approval of the reviewing EC/IRB, 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/IRB 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/IRB  
• 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) 

 
 
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• 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/IRB, if applicable. 
 Subject follow-up in case of termination 
If the study is terminated early, subjects will be followed as per routine standard of care by the 
investigational site or a treating physician. 
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.  
If required, EC/IRB 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 
All endpoints will be analyzed descriptively. 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.  
The primary study endpoint is a dichotomous study outcome; hence, an exact method based on 
the binomial distribution will be used for the hypothesis testing. 
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  1  month  or  30  days”  is  an  event  that  takes  place  between  Days  0  to  30,  inclusive.  
Similarly, an event that occurs “within 12 months or 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 other observations, 
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 
Day 0  
Day 0  

 
 
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Study Visit 
Target Day 
Time Window 
1 Month 
Day 30  
1 – 90 days 
6 Months 
Day 183  
91 – 304 days 
12 Months 
Day 365 
305 – 548 days 
24 Months 
Day 730 
549 – 913 days  
36 Months 
Day 1095 
914 – 1278 days 
48 Months 
Day 1460 
1279 –1643 days 
60 Months 
Day 1825 
1644 – 2009 days 
 
If there are two or more assessments in the same time window, unless otherwise specified, 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.   
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.  
Sensitivity  analysis  using  
tipping  point  method  may  be  performed,  as  needed,  
to  assess  
the 
impact of missing data for the primary endpoint. 
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. 
Subset analyses by-sex, by-race (based on subjects enrolled in the US only, since collection of 
race  and  ethnicity  data  may  not  be  allowed  outside  
the  US  as  per  
local  
law  and  
regulation), 
FreeFlo versus Closed Web configuration as proximal component, percutaneous access versus 
non-percutaneous,  and  by-region/study  site  will  be  performed  on  
the  primary  study  endpoint 
using descriptive statistics and reviewed for clinical significant difference. 
No  inferential  statistical  analysis  is  planned  for  secondary  or  additional  study  endpoints. 
Descriptive statistics will be provided for all endpoints as well as baseline variables. 
Analysis Sets: 
The primary analysis set will consist of all subjects who were enrolled. Subjects will be considered 
as enrolled in the study as described in section F.1. 
Poolability of the data 
The poolability of subjects enrolled in the Valiant Evo US Clinical trial and subjects enrolled in 
the  Valiant  Evo  
International  Clinical  Trial  
is  assumed  given  
that  both  study  protocols  will  be 
similar with respect to, 
inclusion/exclusion criteria, clinical treatment, definitions of clinical events, 
one data monitoring plan, Data Monitoring Committee (DMC), Clinical Event Committee (CEC), 
Independent Physician Reviewer (IPR) and core imaging laboratory.  
At the data analysis stage, the data poolability will be reviewed for the primary endpoint. Results 
from  Valiant  Evo  US  Clinical  Trial  and  Valiant  Evo  
International  Clinical  Trial  subjects  will  be 
presented separately for clinical review as well as tested using a Chi-square test.  

 
 
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A poolability analysis among geographies/investigational sites will be assessed descriptively for 
the primary endpoints by geographic regions. Small investigational sites (less than 5 subjects) 
will be grouped with other nearby sites for the by-region analysis.  
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.  
I  STUDY MANAGEMENT 
I.1 Study staff 
The study is sponsored by Medtronic Vascular.  Study staff contact details will be provided in the 
investigational site file. 
I.2 Advisory committees 
 I.2.1 Clinical Event Committee (CEC) 
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. 

 
 
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 Data Monitoring Committee 
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 
A publication committee will not be established for the Valiant Evo US and International Clinical 
trials. The publication policy for this trial is described in section H.2. 
 Imaging Core Lab 
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 
At a minimum, the following records must be kept by the investigator:  
• Clinical Investigation Plan and, if applicable, any amendments 
• Instructions for Use 
• Medtronic and EC/IRB approved 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 
• Completed Delegation of Authority Form 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 Informed Consent forms 
• Fully executed CRFs and corrections 
• Reports of Adverse Events and Device Deficiencies 
• Device accountability records 
• IRB/EC correspondence 
 Investigator reporting responsibilities 
 
Report 
Submitted to 
Description 
Adverse Events 
Sponsor, EC/IRB, 
and local Regulatory 
Authority, where 
applicable 
Refer to section F.6 for reporting requirements. 

 
 
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Report 
Submitted to 
Description 
Withdrawal of EC/IRB 
approval 
Sponsor 
An investigator shall report to the sponsor, within 
5 working days, a withdrawal of approval by the 
reviewing IRB of the investigator
's part of an 
investigation. (21 CFR 812.150(a)(2)). 
Final investigator report  
 
Sponsor, IRB s and 
Relevant Authorities  
This report must be submitted within 3 months of 
study completion or termination of the 
investigation or the investigator’s part of the 
investigation. (21 CFR 812.150(a)(6)). 
Study deviations 
Sponsor and IRB 
Notice of deviations from the CIP to protect the life 
or physical well-being of a subject in an 
emergency shall be given as soon as possible, 
but no later than 5 working days after the 
emergency occurred. (21 CFR 812.150(a)(4)). 
Failure to obtain IC 
prior to investigational 
device use  
 
Sponsor and IRBs  
If an investigator uses a device without obtaining 
informed consent, the investigator shall report 
such use within 5 working days after device use. 
(21 CFR 812.150(a)(5)). 
Other  
IRB and FDA  
An investigator shall, upon request by a reviewing 
IRB, FDA or any other regulatory agency, provide 
accurate, complete, and current information about 
any aspect of the investigation. (21 CFR 
12.150(a)(7)). 
 
 Sponsor records 
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 
• Instructions for Use 
• Sample of labeling attached to the investigational device 
• Curriculum Vitae of investigators and investigation site personnel 
• Delegation of Authority Form and training records of investigators and investigation site 
personnel 
• EC/IRB approvals/notifications and regulatory approvals/notifications 
• Signed Clinical Investigation Agreements and signed agreements with third parties 
• Shipping records for investigational devices and clinical-investigation related 
documents and materials 
• Medtronic and EC/IRB approved Informed Consent Forms 
• Site selection reports, site initiation reports and monitoring visit reports  
• Adverse event and Device Deficiency reports 
• Financial disclosure information 
• Fully executed CRFs and corrections 

 
 
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 Sponsor reporting responsibilities 
Report 
Submit to 
Description 
Adverse Events  
EC/IRB, 
Investigators, FDA 
and relevant 
authorities, where 
applicable 
Medtronic will report adverse events as 
required and in compliance with local 
regulatory requirements, as applicable and 
described in the Valiant Evo Safety Plan. 
Unanticipated Adverse 
Device Effect  
Investigators, IRB, 
FDA, and relevant 
authorities  
Notification within ten working days after the 
sponsor first receives notice of the effect. (21 
CFR 812.150(b)(1)). 
Withdrawal of EC/IRB 
approval 
Investigators, IRB, 
FDA, and relevant 
authorities  
Notification within five working days after 
receipt of the withdrawal of approval. (21 
CFR 812.150(b)(2)).  
Withdrawal of FDA 
approval  
Investigators, 
EC/IRB, and relevant 
authorities  
Notification within five working days after 
receipt of notice of the withdrawal of 
approval. (21 CFR 812.150(b)(3)).  
Investigator List  
FDA  
Submit at 6-month intervals, a current list of 
the names and addresses of all investigators 
participating in the investigation. (21 CFR 
812.150(b)(4)).  
Progress Reports  
EC/IRB and FDA  
Progress reports will be submitted at least 
annually. (21 CFR 812.150(b)(4)(5), 812.36(f)  
Recall and device 
disposition  
Investigators, 
EC/IRB, relevant 
authorities, and FDA  
Notification within 30 working days after the 
request is made and will include the reasons 
for any request that an investigator return, 
repair, or otherwise dispose of any devices. 
(21 CFR 812.150(b)(6)).  
Failure to obtain Informed 
Consent  
FDA  
Investigator’s report will be submitted to FDA 
within five working days of notification. (21 
CFR 812.150(b)(8)).  
Premature termination or 
suspension of study 
Investigators, IRB, 
and Relevant 
authorities  
Provide prompt notification of termination or 
suspension and reason(s). (ISO 
14155:2011), (MHLW Ordinance 36, Article 
32).  
Final Report 
Investigators, IRB, 
and regulatory 
authorities, where 
applicable and FDA 
Medtronic will notify FDA within 30 working 
days of the completion or termination of the 
investigation. A final report will be submitted 
to the FDA, investigators, and IRBs within six 
months after completion or termination of this 
study. (21 CFR 812.150(b)(7)). 
Study Deviations 
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.  
 Record retention  
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 
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. 

 
 
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I.4 Miscellaneous 
 Insurance 
Medtronic Vascular 
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/IRB. 
 Subject compensation and indemnification 
 
Subjects will not receive any compensation for their participation in this study (including follow 
up); however, Medtronic may, at its option, provide reimbursement for participants who will incur 
extraordinary travel costs related to their participation in the study, including airfare, mileage or 
hotel expenses.  Participating Institution will make such request(s) in writing to Medtronic (de-
identified of participant 
information), detailing the unusual circumstances and the excessive costs 
that the participant will incur. Medtronic will evaluate requests on a case-by-case basis, and will 
notify the Participating Institution of its decision in writing. 
 Subject confidentiality 
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/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 
- Anaphylax
is 
- 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 tox
icity 
- 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 anaesthesia 
- 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 
 

 
 
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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, 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 IRB/ EC and to 
Medtronic.  Medtronic  will  
in  turn  report  any  necessary  findings  to  the  appropriate  regulatory 
agencies in each of the respective geographies. 
J.3 Risk-to-benefit rationale 
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. 
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. 

 
 
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Risk management for the Valiant Evo Thoracic Stent Graft System is performed in accordance 
with EN 14971:2012 and the results are detailed in the Report of Prior Investigations. 
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. 

 
 
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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.  
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. 
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 
CEC 
Clinical Event Committee  
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 
DTA 
Descending Thoracic Aorta 
DTAA Descending Thoracic Aortic Aneurysm 

 
 
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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 
IRB  
Institutional Review Board  
ISO 
International Organization for Standardization 
MAE 
Major Adverse Event 
MDE 
Major Device Effect 
MI 
Myocardial Infarction 
MRA 
Magnetic Resonance Angiography 
MRI 
Magnetic Resonance Imaging 
PET 
Polyethylene terephthalate  
PMA 
Premarket Approval  
RA 
Regulatory Affairs 
RAE 
Regulatory Affairs Europe 
ROPI 
Report of Prior Investigations 
SADE Serious Adverse Device Effect 
SAE 
Serious Adverse Event 
SOP 
Standard operating procedure 
TAA 
Thoracic Aortic Aneurysm 
TEE 
Transesophageal echocardiography 
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 
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).   

 
 
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Term 
Definition 
Deaths following  complications that  are associated  with  the 
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.   

 
 
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Term 
Definition 
Aneurysm  rupture  should  be  reported  as  either  procedure-
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) 
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. 
 
 

 
 
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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. 
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. 

 
 
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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. 
 Device Deficiencies 
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.) 

 
 
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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) 
Stent graft Fracture (Specify: proximal bare stent, 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 
 
 

 
 
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 Additional Definitions 
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 Imaging Matrix 
Anatomy/Stent Graft 
Issue Detected 
CT with 
contrast 
CT without 
contrast 
MRI with 
contrast 
MRI without 
contrast 
Angiogram/, 
Aortogram, and 
Arteriogram 
Diameter and 
Length 
1 
2 
1 
2 
3 
Stent graft migration 
1 
2 
1 
2 
2-3 
Stent graft fracture 
2 
3 
2 
3 
2-3 
Stent graft kinking 
2 
3 
2 
3 
2-3 
Collapse of stent 
graft 
2 
3 
2 
3 
2-3 
Stent graft twisting 
2 
3 
2 
3 
2-3 
Stent graft patency 
1 
4 
1 
4 
2-3 
Endoleaks 
1 
4 
1 
4 
2-3 
False lumen 
perfusion 
1 
4 
1 
4 
2-3 
Occlusion  
1 
4 
1 
4 
2-3 
Stenosis 
1 
4 
1 
4 
2-3 
Stent Graft Fabric 
Defect 
1 
4 
1 
4 
2-3 
1= Highly visible          2 = visible            3 = Not very visible (potential artifacts)    4 = Invisible 
 
L.4   Device Explant and Returned Product Instructions 
EXPLANT AND AUTOPSY PROCEDURE FOR ENDOVASCULAR PATIENTS 
SURGEON AND SITE RESPONSIBILITY 
 
NOTE: Priority should be given to patient health and safety at all times during the explant 
procedure. 
A. If the explant is part of a late conversion to an open-surgical procedure, consideration of 
the patient is foremost. The surgeon should remove ONLY the endovascular prosthesis, 
damaging or altering the device as little as possible yet providing optimal surgical care to 
the patient. 
B. If the explant is performed on a cadaver, the surgeon should carefully view the adjacent 
body organs and excise the intact aorta containing the endovascular prosthesis, including 
1cm of tissue adjacent to the proximal and distal fixation sites to facilitate histological 
assessment. 
C. It is important that care be given during the collection, handling and examination of the 
implant to ensure that it is not damaged or altered. 
• Particular care should be taken to avoid applying force, traction, or torsion to the stent 
graft during the explant. 

 
 
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• Care should be exercised to avoid excessive manipulation with metallic instruments at 
the proximal and distal fixation sites whenever possible. 
• Stent graft or post mortem specimen should be placed in formalin as is.  Do not 
attempt to clean or remove organic debris. 
D. Using the Explant Procedure Observation Form (UC200103088EN), the physician should 
accurately and fully document the explant procedure and the stent graft ex situ. Any 
possible trauma applied to the device, e.g., clamping, twisting, torsion, or traction should 
also be documented. 
• Physician operation notes may also be used to document the procedure and the 
characteristics of the stent graft prior to and after explant from the body. 
• Mark components that separate during explant.  Attach suture or hemoclip to anterior 
side and on the proximal end for proximal cuffs and distally for distal components. 
E. Follow procedures from Explant Return Instructions (UC200103091) included in the 
explant kit for packaging and return of device to Medtronic. 
EXPLANT RETURN INSTRUCTIONS 
1.0 
Complete the following forms: 
Explant Procedure Observation Form (UC200103088EN)  This form is to be completed at 
the time of the explant procedure. 
Explant Identification Peel-off Labels (UC200103089EN)  Using permanent ink, complete 
the two labels provided in the kit.  Place one completed label on the inner plastic container, 
place the second completed label on the outer metal container.  
Air bill (pre-printed)   Fill in shipper information. 
2.0 
Secure the explant in the explant kit for shipping.  Note:  Medtronic Monitors/Field 
Representatives are not authorized to handle formalin/formaldehyde. 
• Place the explanted device and any associated organic tissue into the labeled inner 
plastic container in a 10% neutral buffered formalin (3.7-4% Formaldehyde) solution to 
maintain tissue integrity. (To be completed by hospital staff only) 
Note:  Any specimen too large for the provided inner container may be sent in any 
securely closed container and placed with provided packing in the metal container and 
box. 
• Seal the plastic container with red tape (provided in kit).  The tape should be stretched 
clockwise around the cap and the container.  Place plastic container into the absorbent 
bag. 
• Place the absorbent bag (with plastic container) inside the labeled metal container.  Fold 
the top flaps of the absorbent lining over the top of the plastic container and secure the 
bag with a twist tie or cable tie (provided in kit).  Place lid on metal can and seal with the 
locking ring provided.  Place the can into the inner partition of the cardboard box, and 
push in the corner tabs on the top of the partition to retain the can. 
• Place the completed Explant Procedure Observation Form, implant and explant 
operative reports, and any radiology follow-up reports (if available), inside the moisture-
resistant plastic bag provided, and place into the box. 
Note:  A Record of Disclosure of Health Information for Public Purposes is included for 
your convenience and can be placed in the patients file. 
Securely seal the box with clear tape (provided in kit).  Affix the shipping airbill to the 
outside of the box.   
• Arrange for pickup from Shipping Company.   
If you have questions about shipping the device, need additional information, or desire additional 
Explant Kits, please contact the Explant Department, at (707) 591-7672 or 1-800-465-5533, Option 3. 
Thank you for completing the Explant Forms and returning the device.  Medtronic uses this 
information to meet FDA requirements and track product performance. 

 
 
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EXPLANT PROCEDURE OBSERVATION FORM 
 
PATIENT INFORMATION 
Patient IDE/ Study ID_____________________________________ 
Name:_________________________________________________ 
DOB (Month/Day/Year):  _____/_____/_____ 
  
IMPLANT INFORMATION  
Date of Implant: _____/_____/_____ 
Implanting Physician: ____________________________________ 
Implanting Hospital Name: ________________________________ 
City and State: 
__________________________________________ 
Country: _______________________________________________ 
 
EXPLANT INFORMATION 
Date of Explant/Autopsy: _____/_____/_____ 
Explanting Physician: _____________________________________ 
Name of Hospital: ________________________________________  
Address: ________________________________________________ 
City and State: ___________________________________________                               
Country: ________________________________________________   
Telephone: (        )_________________________________________ 
 
REASON FOR EXPLANT 
 
__________________________________________________________________________________ 
 
__________________________________________________________________________________ 
 
__________________________________________________________________________________ 
 
  Planned Surgical Conversion 
  Emergent Conversion 
 
  Autopsy Date of Death: ____/____/____  
 
Remarks about procedure:  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
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Evidence of inflammation  
 
  Yes   No
 
Comments:_____________________________________ 
Thrombosis present in the sealzones  
  Yes   No
 
Comments:_____________________________________ 
Calcification present in the sealzones 
 
  Yes   No
 
Comments:_____________________________________ 
 
 
How well was the device attached to the patient’s tissue? 
Proximally:   Comes out easily from aortic vessel 
 
  Appears firmly attached to aortic vessel 
  
Mid body:   Comes out easily from aneurysm contents   
 
  Appears firmly attached to aneurysm contents 
Distally (L):   Comes out easily from iliac/aortic vessel 
 
  Appears firmly attached to iliac/aortic vessel 
  
Distally (R):   Comes out easily from iliac/aortic vessel 
 
  Appears firmly attached to iliac/aortic vessel 
 
 
Comments ____________________________________________________________________ 
 
_____________________________________________________________________________ 
 
Successful Surgical Conversion:    Yes    No 
 
Patient Outcome:    Alive   Expired 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
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EXPLANTED DEVICE INFORMATION 
 
DEVICE 
CATALOG NUMBER 
LOT NUMBER 
Bifurcated Body 
       Distal Left 
       Distal Right 
 
 
Contralateral Limb 
 
 
 
Iliac Extension 
       Left 
       Right 
 
 
Iliac Extension 
       Left 
       Right 
 
 
Iliac Extension 
       Left 
       Right 
 
 
Aortic Cuff 
 
 
 
AUI 
       Distal Left 
       Distal Right 
 
 
 
Thoracic, Proximal Main 
 
 
 
Thoracic, Distal Main 
 
 
 
Thoracic, Distal Main 
 
 
 
Thoracic, Proximal Extension 
 
 
 
Thoracic, Distal Extension 
 
 
 
Other (Specify) 
 
 
 
Additional Comments 
 
 
 
 
 
Form completed by:  ________________________ 
 
Title: _____________________________________ 
 
Date: _________________ 
 

 
 
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L.5 Informed Consent Template 
 
L.6 Post PMA-S approval Analysis 
Following PMA-S approval, the postmarket evaluation will be conducted and results provided to 
the FDA once the last subject in the study completes the 12-month follow-up visit.  
 
A synopsis of this post-approval proposal along with statistical assumptions 
is presented 
in Table 
L-1 below.  Medtronic  has  used  
its  experience  with  Valiant  Captivia  
in  patients  with  DTAA  
to 
establish the assumptions used in the statistical design of this study. The VALOR II study with 
the Valiant stent graft system  enrolled 160 patients  with DTAA and  was assessed through 12 
months  
for  purposes  of  PMA  
(P100040)  approval. Through 1-year post-treatment,  
the rate  of 
MDEs combined with access and/or deployment failures was 7.1% (11/153) (Medtronic internal 
data  using  
the  Valiant  Evo  proposed  definition).  Therefore,  
for the  purpose of  post  approval 
analysis, the rate of MDEs combined with access and deployment failures at 1-year with Valiant 
Evo is estimated to be 7.1% (refer to Table L-1 below for power analysis assumptions). 
Table L-1: Power Analysis Assumptions for Evaluation of Valiant Evo in Patients with 
DTAA at 1-year 
Estimated rate of MDEs combined with 
access and/or deployment failures at 1 
year  with Valiant Evo 
7.1% 
Performance Goal (PG) at 1-year 
20% 
Significance level 
0.05 
Statistical test 
One-sided binomial test 
Evaluable sample size 
N = 63 at 1 year  
Enrollment 
IDE cohort will enroll a minimum of 100 subjects 
and is expected to have a minimum of 63 
evaluable subjects at 1-year follow up. 
Statistical power from 63 or more evaluable 
subjects 
92% (overall study power for passing both 
hypotheses is 81%) 
 
L.7 CMS Study Criteria 
Medicare beneficiaries may be affected by the device because 
in 2013 more than 63% of TEVAR 
cases were performed 
in Medicare beneficiaries, and 59% of claims with principal TAA diagnoses 
involve  patients  age  65  or  older.  Study  results  are  expected  to  be  generalizable  within  the 
Medicare beneficiary population based on the prevalence of TAA in patients age 65 and older. 
 
All IRBs should comply with 45 CFR part 46. 
 
 
 
 
 
 
 

 
 
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M  VERSION HISTORY 
Version 
Summary of Changes 
Author(s)/Title 
1A 
• Not Applicable, New Document 
 
 
1B 
• Synopsis update with schedule of events 
for extended follow-up  
•  Extended the follow of subjects from 12 
months to 60 months 
• Administrative changes like correction of 
typo’s, font types and alignments, 
integration of updated corporate template