Zenith TX2® TAA Endovascular Graft Post-approval Study
Phase: NA
Conditions: Descending Thoracic Aortic Aneurysm
Sponsor: Cook Research Incorporated

 
POST-APPROVAL STUDY PLAN 
 
 
 
Zenith® TX2® TAA Endovascular Graft Post-Approval Study 
 
Global Clinical Number 08-005 
 
Version: 08-005-05 
Version Date: 14 March 2018 
 
 
 
 
Global Sponsor: 
Cook Research Incorporated 

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STUDY PLAN SIGNATURE PAGE 
 
 
Global Sponsor Contact: 
 
I hereby acknowledge that the content presented in this Study Plan has been reviewed and 
agreed upon  
 
 
 
 
  
 
 
 
Jennifer L. Kerr - President, Cook Research Incorporated 
Printed Name 
,;Jt?i 77} ;;Ml/tf 
Date (DD Mon YYYY) 

Zenith® TX2® TAA Endovascular Graft – P070016 
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STUDY PLAN SIGNATURE PAGE 
 
 
Principal Investigator: 
 
I hereby acknowledge that the content presented in this Study Plan has been reviewed and 
agreed upon. 
 
 
X 
 
  
 
Signature 
Date (DD Mon YYYY) 
 
 
 
Printed Name 

Zenith® TX2® TAA Endovascular Graft – P070016 
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Post-Approval Study Investigational Plan 
The following is a proposed investigational plan for a post-approval study to evaluate 
long-term safety and performance of the Zenith® TX2® TAA Endovascular Graft through 
5 years. 
 
 
1. Purpose 
The purpose of the post-approval study is to evaluate the long-term safety and 
performance of the Zenith® TX2 TAA Endovascular Graft in the elective treatment of 
patients with descending thoracic aortic aneurysms or ulcers. 
 
 
2. Name and Intended Use of the Device 
The Zenith® TX2® TAA Endovascular Graft (proximal and distal components) is 
indicated for endovascular treatment of patients with aneurysms/ulcers of the descending 
thoracic aorta having morphology suitable for endovascular repair, including: 
• 
Adequate iliac/femoral access compatible with the required introduction systems 
• 
Non-aneurysmal aortic segments (fixation sites) proximal and distal to the aneurysm: 
 with a length of at least 25 mm, 
 with a diameter measured outer-wall to outer-wall of no less than 24 mm and no 
greater than 38 mm, 
 with a radius of curvature greater than 35 mm for aortic arch landing zones, and 
 with an angle less than 45 degrees (any angle in the arch or distal aorta). 
 
 
Note: A diagram of these parameters is presented in Figure 2-1. 

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Figure 2-1. Anatomical inclusion criteria 
 
3. Specific Aims 
The specific aims of the study include assessment of: 
1) long-term safety of the device, as measured by the freedom from aneurysm- 
related mortality through 5 years [Information redacted due to confidential 
content.] 
25 mm  
25 mm  

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4. Duration of the Investigation 
Patient recruitment should be completed within 72 months of initiating the study. All 
subjects will be evaluated at pre-procedure, pre-discharge (within 7 days), 1, 6, and 12 
months, and yearly thereafter through 5 years. Informed consent will allow for following 
of patients through 5 years post-procedure. 
 
 
5. Study Design 
5.1. Hypothesis to be Tested 
The primary endpoint will be evaluated according to the hypothesis that patients treated 
with the Zenith® TX2® TAA Endovascular Graft will have a rate of aneurysm-related 
mortality at 5 years that meets an objective performance criterion of 7.7% with a margin 
of δ = 7%. With regards to delta, it should be noted that this would require an allowable 
mortality in the endovascular treatment group at 5 years that is lower than the mortality 
reported in some prior surgical studies at 30 days, setting a standard for endovascular 
repair that some surgical studies do not meet. 
The hypothesis is formulated as follows: 
Null Hypothesis: the 5-year TAA-related mortality rate, γ, is greater than or equal 
to 7.7% + 7%. (Interpretation: the TAA-related mortality rate does not meet the 
OPC.) 
Ho: γ ≥ 7.7% + δ 
Alternative Hypothesis: the 5-year TAA-related mortality rate, γ, is less than 
7.7% + 7%. (Interpretation: the TAA-related mortality rate does meet the OPC.) 
Ha: γ < 7.7% + δ 
The hypothesis will be tested by using an exact binomial test (StatXact 8.0) where the test 
statistic is defined as follows: 
γˆ  = nTAA 
N 
where nTAA is the number of patients with TAA-related death within 5 years, and 
N is the total number of patients with 5 year follow-up or death (any cause) within 
5 years. 

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5.2. Design of the Study 
This study will be conducted as a post-approval registry, where the 5-year aneurysm- 
related mortality following endovascular treatment will be compared to an objective 
performance criterion (OPC) of 5-year aneurysm-related mortality following open 
surgical repair. The OPC of 5-year survival from aneurysm-related mortality will be 
established based on results from a meta-analysis of published reports on open thoracic 
aneurysm repair in combination with survival rates from the open surgical control 
patients that were enrolled in the multi-center pivotal clinical study (development of the 
OPC is discussed further in Section 10). 
The study will be conducted at up to 50 multi-national investigative sites, with the 
minimum expected number of participating centers being 15, and the maximum number 
of patients to be enrolled at any one center will be 25. Patients may be enrolled 
prospectively or retrospectively, if they received the Zenith® TX2® TAA Endovascular 
Graft on or after May 21, 2008. All subjects, if found to be eligible for study 
participation, will be invited to participate in the study. The entry criteria for the 
endovascular treatment group are listed in Section 6. 
 
Patient with descending thoracic aneurysm or ulcer 
Pre-procedural CT, Angiography (if necessary), Blood tests, Pulses, Clinical Exam 
Patient meets inclusion/exclusion criteria 
Informed consent is obtained 
Endovascular Repair 
Procedural angiography 
Pre-discharge:, Blood tests, Pulses, Clinical Exam 
1-month: CT,  Clinical Exam 

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6-month:  CT, Clinical Exam 
12-month and yearly thereafter through 5 years: 
CT, CXR, Clinical Exam 
Figure 5-1.  Study flow diagram 
 
 
5.3. Sample Size Determination 
As directed by the Division of Postmarket Surveillance within FDA, the sample size for 
the study can be calculated using EpiInfo (available through the Centers for Disease 
Control and Prevention) by assuming a 9.5% rate of TAA-related mortality in the 
endovascular treatment group at 5 years (2 year estimate is currently 7.1% in the pivotal 
clinical trial). α = 0.05 and power = 0.80. The resultant sample size is 273 endovascular 
treatment patients. A total of 300 patients will be included in the study (273 + 27 for 
possible lost to follow-up), consisting of the 185 endovascular treatment patients from the 
IDE clinical trial (160 pivotal + 25 continued access) plus an additional 115 endovascular 
patients to be enrolled in the post-approval study. 
 
 
5.4. Participation Endpoints of the Study 
A patient’s follow-up in the study will end after any of the following: 
1) Explant of the prosthesis + 30 days 
2) Patient withdrawal 
3) Patient death 
4) Closure of the post-approval study 
5) Completion of all scheduled clinical and imaging visits, through 5 years 
 
 
5.5. Limitations of the Study 
This study is inherently limited by the small number of patients with descending thoracic 
aortic aneurysms. The estimated incidence of thoracic aortic aneurysms is 6 per 100,000 
person years. However, this incidence rate is inclusive of all etiologies and conditions 
[e.g., atherosclerotic aneurysm, degenerative aneurysm, mycotic aneurysm, inflammatory 
aneurysm, symptomatic aneurysm, chronic dissection, acute dissection, traumatic injury, 

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leaking/ruptured aneurysm, impending rupture, aortobronchial fistula, aortoesophogeal 
fistula, diagnosed or suspected congenital degenerative collagen disease (Marfan’s 
syndrome or Ehlers-Danlos syndrome)]. Recognizing that different etiologies may 
respond differently to endovascular repair with the Zenith® TX2 TAA Endovascular 
Graft, etiology and condition must be considered when selecting patients. 
Based on indications for use of the device gained through experience to date, this study 
will include only those patients who have undergone or will undergo elective repair of 
degenerative/atherosclerotic aneurysms, including degenerative/atherosclerotic ulcers ≥ 
10 mm in depth and 20 mm in diameter, inflammatory aneurysms, and symptomatic 
aneurysms; but not including mycotic aneurysm, chronic dissection, acute dissection, 
traumatic injury, leaking/ruptured aneurysm, impending rupture, aortobronchial fistula, 
aortoesophogeal fistula, or diagnosed or suspected congenital degenerative collagen 
disease (no Marfan’s or Ehlers-Danlos syndrome). 
The proportion of eligible patients is further confounded by anatomic considerations. 
Performance and safety of the Zenith® TX2 TAA Endovascular Graft can be 
compromised by use in unsuitable endovascular anatomy. Therefore, inclusion in the 
study requires that a patient’s anatomy be amenable to endovascular repair. Specific 
anatomical characteristics (vessel diameters and lengths) are often different between 
patients, and although the device is designed to treat a wide range of anatomy, a number 
of patients with descending thoracic aortic aneurysms are expected to be ineligible due to 
unsuitable endovascular anatomy. In light of the influence of etiology and anatomy on 
patient selection, the proportion of patients with descending thoracic aortic aneurysms 
eligible for study enrollment is expected to be small. 
The limitations imposed on this study by the target patient population dictate the choice 
of study design. Although a randomized controlled study is a preferred study design due 
to its academic appeal, randomization is not feasible given the small target patient 
population. In addition, eligible patients would need to meet both the endovascular and 
open surgical inclusion/exclusion criteria, further lowering the potential study population. 
Lastly, it is expected that patients would be less likely to participate in the study if 
randomized to the surgical control group. Together, these factors would result in 
untenable enrollment rates with a randomized design. 
A non-randomized study with a concurrent open surgical control has strengths and was 
chosen for the pivotal study, supplemented with retrospective cases. Despite substantial 
efforts to complete enrollment in a reasonable timeframe, patient accrual was slow. It 

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took roughly 2.5 years to enroll 70 open surgical control patients from over 40 eligible 
institutions. Importantly, commercial availability of a thoracic endograft had a profound 
effect on enrollment of surgical controls, with a 50% decrease in enrollment rate 
following approval of the Gore TAG device. The decreased surgical enrollment rate has 
persisted through the continued access phase of the pivotal study; only a single patient 
has been enrolled since July 2006. Reduced availability of surgical control patients is 
expected, given that endografts are often considered a viable treatment alternative for 
surgical candidates who are also reasonable controls (i.e., have similar extent of disease). 
The confounding effect of commercially available endografts will only be exacerbated 
with the impending approval of additional endografts that will expand the range of 
anatomies amenable to endovascular treatment. Cook has evaluated the multiple 
confounding factors and concluded that use of concurrent surgical controls is not a viable 
option for a post-approval study. 
Consequently, in the setting of a post-approval study, a registry design with comparison 
to an OPC is the only good option for comparing the long-term safety and performance of 
endovascular treatment to open surgery. 
This study is also limited by the anticipated comorbidities likely to be found in these 
patients, which may confound data analysis. 
 
 
5.6. Safety Monitoring 
The post-approval study will be monitored by a Data Safety Monitoring Board (DSMB) 
according to a written safety monitoring plan. Safety monitoring will include collecting 
and reviewing data on major and other adverse events. Section 11 (Risk Analysis) lists 
the possible adverse events associated with this study. A DSMB consisting of 
independent physicians, who are not investigators in the study, nor have a perceived 
conflict of interest with the conduct and administration of the study, will be convened as 
applicable to review adverse events according to standardized procedures. 
An independent Clinical Events Committee (CEC) consisting of physicians, who are not 
investigators in the study, nor have a perceived conflict of interest with the conduct and 
administration of the study, will be established to adjudicate death, rupture, and 
conversion reported during the study. This adjudication will be performed according to 
standard operating procedures to assess whether the events were due to a pre-existing or 
unrelated condition, procedure-related, technique-related, and/or device-related. 

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A central core lab will be used for image analysis to provide uniformly defined 
morphological and morphometric analysis of images. 
Bioresearch monitoring including on-site visits will be conducted, in part, for 
identification of adverse events and assurance they are correctly reported to the DSMB 
and CEC. 
 
 
Study Administration 
This study is based on the STARZ TX2 pivotal trial, the design of which had been 
counseled by a National Principal Investigator and Steering Committee consisting of 
physicians with endovascular device and clinical study experience. These consisted of 
Jon Matsumura, MD and Richard Cambria, MD; Michael Dake, MD; Roy Greenberg, 
MD; and Lars Svensson, MD, PhD. 
 
6. Specific Protocol 
6.1. Definitions 
Please see Appendix A. 
 
 
6.2. Inclusion and Exclusion Criteria 
Consecutive patients who are willing to participate and who meet the inclusion/exclusion 
criteria will be selected for the study. All patients eligible for aneurysm repair or who 
have been treated with the Zenith® TX2® TAA Endovascular Graft will be evaluated for 
enrollment in this study according to the inclusion/exclusion criteria. All patients eligible 
for entry into the study will have the potential risks and benefits of the procedures and the 
overall study protocol explained to them. Each patient who wishes to participate in this 
study will provide written informed consent prior to his or her enrollment into the study. 
All patients must meet at least one of the general inclusion criteria to be enrolled in the 
study. No patients may be enrolled in the study if any of the general exclusion or medical 
exclusion criteria is true. Patients may not be enrolled if any of the anatomical exclusion 
criteria are true. 
The general exclusion criteria will be assessed during the initial patient evaluation by 
conducting a history and physical examination. Anatomical criteria will be assessed 
using a variety of imaging techniques that are routinely performed during the evaluation 

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of descending thoracic aortic aneurysms. Sectional imaging will be performed by CT 
scan. Angiography and intravascular ultrasound will be performed selectively. 
Assessment of inclusion and exclusion criteria will be based upon data available prior to 
enrollment. Data obtained peri-operatively and post-operatively may contradict pre- 
enrollment assessment, and such is anticipated in several cases. However, such 
contradiction should not be construed as evidence of inadequate or inaccurate pre- 
enrollment assessment with respect to the enrollment criteria or evidence of inappropriate 
enrollment. Enrollment is to be based upon the best available pre-enrollment data. 
Therefore, some criteria relate to subjective assessment while other criteria are 
considered absolute and able to be determined definitively. Variability in assessment 
between centers, investigators and observers is expected with several criteria. 
 
 
General Inclusion Criteria: 
A patient may be suitable for inclusion if treatment is clinically indicated and the 
patient has at least one the following: 
1) Descending thoracic aneurysm with diameter ≥ 5.0 cm 
2) Descending thoracic aneurysm with a history of growth ≥ 0.5 cm within the 
previous 12 months 
3) Descending thoracic degenerative or atherosclerotic ulcers ≥ 10 mm in depth 
and 20 mm in diameter 
General Exclusion Criteria: 
Patients must be excluded if any of the following are true: 
1) Age < 18 years 
2) Other medical condition (e.g., cancer, congestive heart failure) that may cause 
the patient to be non-compliant with the protocol, confound the results, or is 
associated with limited life expectancy (i.e., less than 2 years) 
3) Pregnant, breast-feeding, or planning on becoming pregnant within 24 months 
4) Unwilling or unable to comply with the follow-up schedule 
5) Inability or refusal to give informed consent 
6) Simultaneously participating in another investigative device or drug study. 

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(The patient must have completed the primary endpoint of any previous 
study at least 30 days prior to enrollment in this study.) 
 
Medical Exclusion Criteria: 
Patients must be excluded if any of the following are true: 
1) 
Receiving home oxygen therapy 
2) 
FEV1 < 1 liter 
3) 
Left ventricular ejection fraction < 20% 
4) 
New York Heart Association Classification 4 
5) 
Myocardial infarction within the last 3 months 
6) 
Stroke within the last 3 months 
7) 
Diagnosed or suspected congenital degenerative collagen disease (no 
Marfan’s or Ehlers-Danlos syndrome) 
8) 
Systemic infection (e.g., sepsis) 
9) 
Bleeding diathesis, uncorrectable coagulopathy or refuses blood transfusion 
10) Allergy to stainless steel, polyester, solder (tin, silver), polypropylene, nitinol, 
or gold 
11) Untreatable reaction to contrast, which in the opinion of the investigator, 
cannot be adequately premedicated 
12) Symptomatic carotid disease warranting intervention, which will not be 
performed prior to TAA repair 
13) Mycotic aneurysm, leaking/ruptured aneurysm, impending rupture, 
aortobronchial fistula, aortoesophogeal fistula, dissection or traumatic injury 
14) Surgical or endovascular AAA repair within 30 days before or after TAA 
repair 
15) Previous placement of a thoracic endovascular graft 
16) Aortic dissection 
17) Prior open repair involving descending thoracic aorta including supra-renal 
aorta and/or arch (except prior elephant trunk procedure is acceptable if > 30 
days post-procedure) 

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18) Interventional and/or open surgical procedures (unrelated to TAA repair) 
within 30 days before or after TAA repair 
Anatomical Endovascular Exclusion Criteria: 
Patients must be excluded if any of the following are true: 
1) 
Treatment length (i.e., aneurysm/ulcer length including fixation sites) along 
greater curvature is: 
a) > 357 mm (for 28 to 32 mm diameter straight graft or 32 mm diameter 
tapered graft) 
b) > 354 mm (for 34 to 36 mm diameter tapered graft) 
c) > 338 mm (for 34 to 38 mm diameter straight graft or 38 mm diameter 
tapered graft) 
d) > 364 mm (for 40 to 42 mm diameter straight graft) 
e) > 356 mm (for 40 to 42 mm diameter tapered graft) 
2) 
Proximal neck length measuring < 25 mm between the left common carotid and 
aneurysm (covering subclavian is acceptable except in patients with anomalous 
vertebral off of the arch in the region of the subclavian or a dominant vertebral 
off of the subclavian) 
3) 
Distal neck length measuring < 25 mm between celiac and aneurysm 
4) 
Aortic arch radius ≤ 35 mm (if device deployed in arch) 
5) 
Proximal neck diameter, measured outer-wall to outer-wall on a sectional image 
or multiplanar reconstruction (CT), < 24 mm or > 38 mm 
6) 
Distal neck diameter, measured outer-wall to outer-wall on a sectional image or 
multiplanar reconstruction (CT), < 24 mm or > 38 mm (estimate from more 
proximal segment if diaphragm makes identification of the outer-wall difficult) 
7) 
Tortuosity, calcification or arterial diameter, measured inner-wall to inner-wall 
on a sectional image, that are not conducive to placement of the introducer 
sheath (20 Fr. for 28 to 34 mm diameter graft or 22 Fr. for 36 to 42 mm 
diameter grafts) 
8) 
Prohibitive calcification, occlusive disease or tortuosity of intended access 
vessels 

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9) 
Prohibitive calcification, occlusive disease, or tortuosity of intended fixation 
sites 
10) Circumferential thrombus in region of intended fixation sites 
11) Inverted funnel-shaped proximal neck with ≥ 3 mm increase in diameter from 
proximal fixation site to the aneurysm (over the 25 mm fixation site) 
12) Funnel-shaped distal neck with ≥ 3 mm increase in diameter from distal fixation 
site to the aneurysm (over the 25 mm intended fixation site) 
13) Inability to preserve the left common carotid artery and celiac artery 
14) Aneurysm or angulation in the distal thoracic aorta that would preclude 
advancement of the introduction system 
 
 
6.3. Registration 
Patient registration will be accomplished by a telephone call to a centralized computer 
system that tracks patient enrollment. The central computer system is located at Cook 
Research Incorporated, in West Lafayette, Indiana. The system can be contacted 24 
hours a day via a toll-free number. A valid password must be entered to access the 
system. The caller is asked to say their name, which is digitally recorded. The caller is 
asked to enter the patient’s initials and date of birth. A check is made to ensure that a 
patient with identical initials and date of birth has not already been enrolled at that 
investigative site. If so, the caller is requested to contact Cook Research Incorporated for 
clarification. Otherwise, the system then provides the caller with an enrollment number 
to be used for identification on all subsequent paperwork (e.g., Case Report Forms, 
Follow-up Forms, Complication Forms) related to this patient. 
Upon completing the registration procedure, the computer automatically faxes a 
confirming document to the investigative site indicating that a patient with the specific 
initials and birth date was enrolled on the specified date and assigned the indicated 
enrollment number. 
 
 
7. Methods 
For information related to endovascular graft planning and sizing, choosing and 
measuring proximal and distal fixation sites, determining anatomical lengths, 

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endovascular graft placement procedure, peri-operative care, and treatment of endoleaks, 
please refer to the device Instructions for Use (IFU). 
 
 
8. Measurements and Data Collection 
A dedicated study coordinating nurse and physician team will complete standardized, 
preprinted, electronically scanable data collection forms, which may serve as source 
documents. The original data forms, pertinent procedural and follow-up imaging data 
will be sent to Cook Research Incorporated, which will coordinate shipment to the core 
lab for independent analysis. Data will be reviewed, processed and entered into 
electronic databases by the data coordinating center (Cook Research Incorporated) 
according to validated standardized procedures. 
The results of the endovascular repair will be assessed by radiological and clinical 
follow-up through five years, as outlined in Table 8-1. 
 
Table 8-1. Study exam schedule 
Month 
Pre-op 
Intra-op 
Pre-discharge 
1 
6 
123 
CT Scan 
X1 
X1,2 
X1,2 
X1,2 
4-view device X-ray 
X 
Angiography 
X4 
X 
Pulses 
X 
X 
Blood tests 
X 
X 
X 
Clinical Exam 
X 
X 
X 
X 
X 
1CT scan must be able to support electronic submission, or have the ability to reproduce 3-D 
reconstruction, multi-planar, or trans-axial images. 
2Physician’s discretion as to additional imaging modalities necessary to evaluate patients 
experiencing renal failure or who are otherwise unable to undergo contrast-enhanced CT scan. 
3Endovascular patients will be followed at yearly intervals through five years 
4Pre-procedure angiography to be performed electively, or as needed depending on adequacy of 
3-D reconstruction and complexity of patient anatomy. 
 
 
8.1. Pre-operative Assessment Data 
Detailed pre-procedural examination data will be collected for patients meeting the 
selection criteria who have provided informed consent. Data will be collected and stored 
in a database. For specific data included, please refer to case report forms attached in 
Appendix B. 

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8.2. Intra-operative Data Collection 
The endovascular aneurysm procedure will be documented in such a way to permit 
analysis of any untoward occurrences in terms of cause and effect. Data will be collected 
and stored in a database. For specific data included, please refer to case report forms 
attached in Appendix B. 
 
 
8.3. Post-operative Data Collection 
The interval between graft deployment and discharge will be documented. For specific 
data included, please refer to case report forms attached in Appendix B. 
 
 
8.4. Follow-up 
The results of the endovascular repair will be assessed by radiological and clinical 
evaluation, as described in Table 8-1. 
For specific data included, please refer to case report forms attached in Appendix B. 
 
 
8.5. Deaths 
Details of any deaths occurring during the study will be stored in a database. Along with 
the death form, copies of the death certificate (if available) and autopsy report (if 
applicable) will be maintained. For specific data included, please refer to case report 
form attached in Appendix B. 
 
 
8.6. Explants 
An autopsy will be requested in all patients who die with a prosthesis in place. At the 
autopsy, the entire thoracic aorta will be excised from the aortic arch, proximal to the 
graft, down to and including the celiac artery. Both the excised aorta and the 
endovascular graft will be fixed in 4% formaldehyde and sent for subsequent 
examination. 
If the prosthesis is excised in the course of conversion to open repair, the position, and 
attachment of the prosthesis within the arterial tree will be recorded. In addition, every 
care should be taken to ensure that the prosthesis is removed intact, as long as patient 

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safety is not compromised. For example, if possible vascular clamps should be applied at 
remote sites from stent attachments. The prosthesis will then be washed with saline to 
remove surface thrombus. The graft components will be fixed in 4% formaldehyde and 
sent for subsequent examination. Do not soak in bleach since bleach affects the 
evaluation of explant corrosion. 
Explanted devices will be examined radiographically while still within the aorta (if 
applicable) before destructive studies are initiated. Explanted devices will undergo gross 
and microscopic examination to assess structural integrity of the graft material and stent 
components. Gross photography and/or scanning electron microscopy will be used to 
examine the structural integrity of the z-stent components and the attachment barbs as 
well as the overlap joint. Any device-related gross pathology will also be documented. 
Histopathologic studies will be conducted on the aortic tissues in the near vicinity of the 
endovascular graft as well as in the regions of the attachment sites, the mid-graft region 
and the main body/leg extension docking sites. 
Sites that are unable to comply with the explant protocol will be instructed to contact 
Cook Research Incorporated for instructions. Data will be collected and stored in a 
database. For specific data included, please refer to case report form attached in 
Appendix B. 
Fixed explanted device will be sent to: 
Cook Research Incorporated 
1 Geddes Way 
West Lafayette, IN 47906 
 
 
8.7. Lost to Follow-up 
For specific data included, please refer to case report form attached in Appendix B. To 
ensure maximum follow-up, sites will be expected to attempt contacting a patient for 
follow-up via telephone, mail, and through the last known contact for the patient. Only 
when each attempt has been unsuccessful should a patient be considered lost to follow- 
up. 
 
 
9. Assessing Outcome 

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The primary assessment of outcome will be based on long-term survival and device 
performance (change in aneurysm size, endoleak, migration, device integrity, and 
secondary interventions). [Information redacted due to confidential content.] 
 
 
The prevalence of morbidity events in a defined index, occurring within 30 days post- 
procedure will be assessed. Adverse events comprising the morbidity index are classified 
into 7 categories. These categories are cardiovascular, pulmonary, renal, gastrointestinal, 
neurologic, vascular, and wound. Events known to be related to pre-existing conditions 
or existing at admission are not considered adverse events in the index (e.g., prior 
medically-treated cardiac arrhythmia with no change in status during the endovascular 
procedure). Additionally, common standard of care practices are excluded as adverse 
events (e.g., centers located at high geographical altitudes that discharge all patients on 
home oxygen therapy regardless of procedure). For specific events to be recorded, please 
refer to case report form attached in Appendix B. 
The events within a category are not of equal severity, but are equally weighted in the 
index.  Because events are equally weighted in the index, an assessment of outcome 
based on events considered to be severe (disabling) will also be performed. Adverse 
events comprising the severe (disabling) morbidities were identified consistent with the 
reporting standards for endovascular repair.2 The severe morbidities were categorized as 
cardiovascular, pulmonary, renal, gastrointestinal, neurologic, vascular, and wound. Also 
included is related death within the same hospitalization or within 30 days of the adverse 

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event. 
 
 
Cardiovascular: 
1) Q-wave myocardial infarction 
2) Cardiac event involving arrest, resuscitation, or balloon pump 
Pulmonary: 
1) Ventilation >72 hours or re-intubation 
2) Pulmonary event requiring tracheostomy or chest tube 
Renal: 
1) Permanent dialysis, hemofiltration or kidney transplant in a patient with a normal 
pre-procedure serum creatinine level 
Gastrointestinal: 
1) Bowel resection 
Neurologic: 
1) Stroke or severe impairment 
Vascular: 
1) Amputation involving more than the toes 
2) Aneurysm or vessel leak requiring re-operation 
3) Deep vein thrombosis requiring surgical or lytic therapy 
4) Pulmonary embolism involving hemodynamic instability or surgery 
5) Coagulopathy requiring surgery 
Wound: 
1) Wound complication requiring return to the operating room 
 
 
Quantitative and qualitative analysis will be performed on the pre-procedural, procedural 
and follow-up films for all patients. Independent analysis of the images, following 
standardized protocols and procedures will be conducted by a centralized imaging core 
laboratory. 

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10. Statistical Methods 
10.1. OPC Development 
The OPC is determined from a standard meta-analysis (mixed model approach) of 
appropriate literature-based control data (in combination with surgical control data from 
the pivotal study). The reported operative/30-day/in-hospital mortality rates from the 
selected literature (range 3.0% - 14.3%) were combined with the 365-day mortality rate 
for open surgery in the pivotal study (11.8%) to generate an OPC for aneurysm-related 
mortality. Development of the OPC utilized a mixed model approach using SAS’s PROC 
GENMOD (binomial distribution with logit link) with the study as the subject factor in 
the REPEATED statement. This resulted in an estimate of the overall probability of an 
aneurysm-related death (7.7%) and corresponding 95% confidence interval (6.6%, 9.0%). 
It should be noted that assuming a 5-year TAA-related mortality based on the early 
mortality rate for the population establishes a rigorous comparison for endovascular 
treatment, as late TAA-related deaths following open repair, which are known to occur to 
a limited extent (such as due to rupture at the surgical anastomosis), are not captured in 
the OPC, but are captured in the endovascular treatment arm. 
 
 
10.2. Analysis Plan [Information redacted due to confidential content.] 
The analysis plan for this study will encompass the analyses necessary to perform 
summary statistics as well as statistical comparisons to an objective performance criterion 
(OPC). Demographic data, co-morbidities and procedural data will be summarized to 
provide an overall picture of the endovascular treatment patients prospectively enrolled in 
the post-approval study. These data will be accompanied by the available literature- 
derived data, in cases where it is possible to interpret the literature data accurately. 
Aneurysm-related mortality is the primary study endpoint, and the primary hypothesis for 
the post-approval study is non-inferior 5-year aneurysm-related mortality in the 

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endovascular treatment group compared to open surgery (as derived from literature and 
the open surgical control patients enrolled in the pivotal study). The hypothesis will be 
tested by using an exact binomial test (StatXact 8.0) where the test statistic is defined as 
follows: 
γˆ = nTAA 
N 
where nTAA is the number of patients with aneurysm-related death within 5 years, 
and N is the total number of patients with 5 year follow-up or death (any cause) 
within 5 years. This statistic excludes patients that are withdrawn or lost to 
follow-up, and is consistent in its construction with the formulation and 
assumptions of the derived OPC. 
Other sensitivity analyses may be performed to assess the influence of missing data and 
cases where the available demographic and co-morbid data suggest imbalances between 
the control and endovascular treatment data. 
 
 
11. Risk Analysis 
This will be a study of an approved device for which the risks and benefits are described 
in the labeling. There are no known additional risks from participation in the study. 
Oversight by the DSMB will allow for detection and assessment of any new information 
that may affect the known risk/benefit profile. 
 
 
12. Description of Device 
 
[Information redacted due to confidential content.  Refer to the IFU for further information.] 
 
13. Monitoring Procedures 
The study will be monitored in accordance with written standard operating procedures 
consistent with 21 CFR 812 and other applicable regulations. 
 
 
Name and Address of the Monitor  
Cook Research Incorporated 
1 Geddes Way 
West Lafayette, IN 47906 
Telephone: 765-463-7537 

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Written Procedures for Monitoring the Investigation 
Written procedures for monitoring the investigation are maintained by the monitor. 

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APPENDIX A 
Contact Information 
 
 
Global Sponsor and Monitor 
Cook Research Incorporated 
1 Geddes Way 
West Lafayette, IN 47906 
USA 
 
 
 
Manufacturer 
William Cook Europe 
Sandet 6 
Bjaeverskov, 4632, DK 

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APPENDIX B 
Definitions 
 

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DEFINITIONS 
 
Aneurysm-related 
Mortality: 
Death from any cause occurring within 30 days of the 
initial procedure or a secondary intervention; or any death 
determined by the independent clinical events committee to 
be causally related to the initial implant procedure, 
secondary intervention, or rupture of the treated aneurysm. 
Barb Separation: 
Radiographic evidence of detachment of barbs from the 
stent strut as confirmed by the independent 
angiographic core laboratory 
Calcification:  
Calcification will be graded based upon the following: 
None: 
Lack of calcification 
Mild: 
Less than 40% circumferential calcification; 
Moderate: 
40-70% circumferential calcification; or 
Severe: 
Greater than 70% circumferential. 
Disabling COPD: 
Forced expiratory volume (FEV1) < 1.0 liter or receiving 
home oxygen therapy. 
Embolization: 
Clinical evidence of ischemic tissue remote from the 
operative field, caused by air, thrombus dislodged from the 
aneurysmal sac and/or aortic neck, including those tissues 
supplied by vessels in the head, renal arteries, superior 
mesenteric artery (SMA), pelvic (IIA) vessels and vessels 
of the lower limbs. This is, of course, distinct from pre- 
operative, operative or post-operative intentional 
embolization procedures. 
Endoleak: 
Contrast-enhanced blood entering the aneurysm sac from 
around the proximal or distal end of the graft system (Type 
I), between joints of the graft and extension (if applicable) 
or through defects in the graft material (Type III), via 
collateral vessels (Type II), or graft fabric porosity (Type 
IV).1 

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Endoleak Type Classification: 
Type I endoleak: 
A peri-prosthetic leak occurring at the proximal and/or 
distal attachment zones. 
Type II endoleak: 
A leak caused by retrograde flow from patent vessels. 
(Requires imaging documentation of Type II source. To 
classify an endoleak as Type II, documentation with a 
selective angiogram clearly showing the source is required. 
Type IIa include significant subclavian, celiac or 
anomalous vertebral arteries. Type IIb include bronchial 
and intercostals artery involvement or minor leaks.) 
Type III endoleak: 
A leak caused by a defect in the graft fabric, inadequate 
seal (between graft components only), or disconnection of 
graft ancillary components. 
Type IV endoleak: 
A leak caused by graft fabric porosity, often resulting in a 
generalized blush of contrast within the aneurysm sac. 
Unknown endoleak: Continuing blood flow into the aneurysmal sac with 
undefined origin. 
Endoleak (early): 
Endoleak within 30 days of device deployment.1 
Endoleak (late): 
Endoleak occurring after 30 days from device deployment, 
which was not documented during the first 30 days post- 
deployment. 
Left Ventricular 
Ejection Fraction: 
The measurement of the left ventricular function in the 
resting state. The normal LVEF lies between 55% and 80% 
(mean = 67%). 
Major Complications: 
Cardiac events requiring surgical management, prolonged 
ventilation requiring tracheostomy, renal failure requiring 
dialysis where not previously needed, aortic fistula, 
mesenteric ischemia (interruption in blood flow to all or 
part of the small or large bowel), paralysis or paraperesis 
unresolved after 30 days of therapy, pulmonary embolism, 
stroke, and multi-system organ failure. 

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MI (Non-Q-Wave): 
Clinical evidence of a myocardial infarction with elevated 
peak CK values greater than or equal to three times the 
upper limit of normal with elevated CK-MB (above the 
institution’s upper limit of normal) in the absence of new 
pathological Q-waves or clinical evidence of a myocardial 
infarction with troponin greater than three times the upper 
limit of normal, as determined by the investigator. 
MI (Q-Wave): Requires one of the following criteria: 
• Post-procedure chest pain or other acute symptoms 
consistent with myocardial ischemia and the presence of 
new pathological Q-waves in two or more contiguous ECG 
leads in the absence of timely cardiac enzyme data. 
• New, post-procedure pathological Q-waves in two or more 
contiguous ECG leads as determined by independent 
review of the CEC and elevation of cardiac enzymes. 
Migration (radiographic): 
Core laboratory determination of antegrade or retrograde 
movement of the proximal or distal components of the 
endoprosthesis > 10 mm relative to anatomical landmarks 
identified on the first post-operative CT scan. 
Migration (clinical): 
Antegrade or retrograde movement of the proximal or distal 
components of the endoprosthesis resulting in the need for 
a secondary intervention. 

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New York Heart Association Classification: 
1. Patient with cardiac disease but without resulting limitations of physical activity. 
Ordinary physical activity does not cause undue fatigue, palpitation or dyspnea. 
2. Patients with cardiac disease resulting in slight limitation of physical activity. They 
are comfortable at rest, ordinary physical activity results in fatigue, palpitation 
or dyspnea. 
3. Patients with cardiac disease resulting in marked limitation of physical activity. 
They are comfortable at rest, less than ordinary physical activity causes fatigue, 
palpitation or dyspnea. 
4. Patients with cardiac disease resulting in inability to carry out any physical activity 
without discomfort. Symptoms of cardiac insufficiency may be present even at 
rest. If any physical activity is undertaken, discomfort is increased. 
Occlusive Disease of Iliacs: Occlusive disease will be graded based upon the following: 
None: 
Lack of occlusive disease 
Mild: 
Some disease, focal with less than 30% narrowing 
Moderate: 
Between 30-50% narrowing not requiring 
interventional techniques to meet inclusion criteria 
Severe: 
Greater than 50% or any patient requiring angioplasty prior 
to endograft delivery. 
Refractory Hypertension: 
Systolic arterial pressure > 160 mmHg despite receiving 
medication. 
Renal Failure: 
Acute or progressive renal insufficiency leading to the need 
for dialysis or hemofiltration. 
Reversible Ischemic 
Neurologic Deficit (RIND): Clinically significant central nervous system deficit lasting 
> 24 hours and < 72 hours. 
Renal Insufficiency: 
A rise in serum creatinine of more than 30% above the pre- 
procedure level, resulting in a serum creatinine level > 2.0 
mg/dl that does not spontaneously resolve (does not include 
those patients with a pre-procedure serum creatinine > 2.0 
mg/dl). 

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Serious Adverse Events: 
Conversion to open repair, aneurysm leak or rupture (blood 
external to the aneurysm sac as evidenced by contrast 
enhancement on CT scan, or open visual observation), or 
death. 
Stent/Attachment System 
Fracture/Break: 
Fracture or breakage of any portion of the stent or 
attachment system including metallic fracture or breakage 
of any suture material used to construct the stent or secure 
the stent or attachment system to the graft material. 
Stroke: 
Permanent clinically significant central nervous system 
deficit lasting > 24 hours. 
Tortuosity of Iliac Arteries: Tortuosity will be graded based upon the following: 
None: 
Lack of tortuosity 
Mild: 
Fairly straight arteries 
Moderate: Angulation manageable with stiff wires, < 70 degrees 
Severe: 
Angulation difficult, may require surgical exposure for 
straightening, not straightened entirely with wires 
Transient Ischemic Attack: 
Clinically significant central nervous system deficit lasting 
≤ 24 hours.