Clinical Study Plan for the Zenith® Low Profile AAA Endovascular Graft
Phase: NA
Conditions: Abdominal Aortic Aneurysms, Iliac Aneurysms, Aortoiliac Aneurysms
Sponsor: Cook Research Incorporated

Cook Incorporated 
Zenith® Low Profile AAA Endovascular Graft Clinical Study 
Page 1 of 32 
 
 
COMPANY CONFIDENTIAL 
Clinical Investigation Plan 08-013-06 
 
 
 
 
CLINICAL INVESTIGATION PLAN FOR THE ZENITH® LOW 
PROFILE AAA ENDOVASCULAR GRAFT 
 
 
 
 
Zenith® Low Profile AAA Endovascular Graft Clinical Study 
 
 
 
 
Version: 08-013-06 
Version Date: 06 November 2013 
 
 
 
 
Sponsor and Manufacturer: 
Cook Incorporated 
750 Daniels Way 
Bloomington, IN 47404  
USA 
 
 
 

Cook Incorporated 
Zenith® Low Profile AAA Endovascular Graft Clinical Study 
Page 2 of 32 
 
 
COMPANY CONFIDENTIAL 
Clinical Investigation Plan 08-013-06 
 
CLINICAL INVESTIGATION PLAN SIGNATURE PAGE 
 
This clinical trial will be conducted in compliance with the clinical investigation 
plan, ISO 14155, ICH GCP, 21 CFR 812, and other applicable requirements as 
appropriate. 
 
 
 
Sponsor Contact 
 
 
 
 
 
 
Signature 
 
DD/Mon/YYYY 
 
 
 
 
 
 
Printed Name 
Title 
 
 
 
 
 
 
 
CLINICAL INVESTIGATION PLAN SIGNATURE PAGE, CON’T. 
 
 
Coordinating Clinical Investigator  
 
I hereby confirm that I approve of this Clinical Investigation Plan and agree to 
comply with its terms as laid out in this document. 
 
 
 
 
 
 
Signature 
 
DD/Mon/YYYY 
 
 
 
 
 
 
Printed Name 
 
Title 
 
 
 
 
 

Cook Incorporated 
Zenith® Low Profile AAA Endovascular Graft Clinical Study 
Page 3 of 32 
 
 
COMPANY CONFIDENTIAL 
Clinical Investigation Plan 08-013-06 
 
 
CLINICAL INVESTIGATION PLAN SIGNATURE PAGE, CON’T 
 
Principal Clinical Investigator 
 
I hereby confirm that I approve of this Clinical Investigation Plan and agree to 
comply with its terms as laid out in this document. 
 
 
 
 
 
 
Signature 
 
DD/Mon/YYYY 
 
 
 
 
 
 
Printed Name 
 
Title 
 
 
 
 

Cook Incorporated 
Zenith® Low Profile AAA Endovascular Graft Clinical Study 
Page 4 of 32 
 
 
COMPANY CONFIDENTIAL 
Clinical Investigation Plan 08-013-06 
 
CONFIDENTIALITY STATEMENT 
 
 
 
 
 
 
 
 
 
This document shall be treated as a confidential 
document for the sole information and use of the clinical 
investigation team and the Ethics Committee/IRB. 
 
 

Cook Incorporated 
Zenith® Low Profile AAA Endovascular Graft Clinical Study 
Page 5 of 32 
 
 
COMPANY CONFIDENTIAL 
Clinical Investigation Plan 08-013-06 
TABLE OF CONTENTS 
1.0 
General Information ....................................................................................... 7 
1.1 
Sponsor and Manufacturer .................................................................... 7 
1.2 
Data Coordinating Center/Monitor ......................................................... 7 
1.3 
Study Administration .............................................................................. 7 
1.4 
Investigators .......................................................................................... 7 
1.5 
Insurance ............................................................................................... 7 
1.6 
Monitoring Arrangements ...................................................................... 8 
1.7 
Data Management and Quality Assurance ............................................ 8 
2.0 
Approvals and Agreements .......................................................................... 9 
3.0 
Clinical Investigation Plan Overview............................................................ 9 
4.0 
Objectives of the Clinical Investigation ..................................................... 10 
4.1 
Objective .............................................................................................. 10 
4.2 
Claims and Intended Performance that are to be Verified ................... 11 
4.3 
Specific Hypothesis to be Accepted or Rejected by Statistical Data .... 11 
5.0 
Device Description and Intended Purpose ................................................ 13 
5.1 
Device Identification ............................................................................. 13 
5.2 
Intended Purpose ................................................................................ 14 
5.3 
General Device Description ................................................................. 14 
5.4 
Photographs of Device ........................................................................ 15 
5.5 
Instructions for Use and Implantation .................................................. 16 
5.6 
Summary of Necessary Training and Experience ................................ 16 
5.7 
Description of the Necessary Medical or Surgical Procedures ............ 16 
6.0 
Preliminary Investigations and Justification ............................................. 16 
6.1 
Literature Review ................................................................................. 16 
6.2 
Non-clinical Testing ............................................................................. 17 
6.3 
Previous Clinical Experience ............................................................... 17 
7.0 
Risk Analysis and Risk Assessment ......................................................... 17 
7.1 
Risks and Foreseeable Adverse Device Effects .................................. 17 
7.2 
Methods to Minimize Risks .................................................................. 18 
8.0 
Design of the Clinical Investigation ........................................................... 19 
8.1 
Type of Investigation ............................................................................ 19 
8.2 
Rationale ............................................................................................. 19 
8.3 
Measures to be Taken to Avoid or Minimize Bias ................................ 19 
8.4 
Variables to be Measured  to Demonstrate Achievement of 
Endpoints ............................................................................................. 19 
8.5 
Inclusion/Exclusion Criteria .................................................................. 20 
8.6 
Patient Consent ................................................................................... 22 
8.7 
Point of Enrollment .............................................................................. 23 
8.8 
Methods ............................................................................................... 23 
8.9 
Criteria and Procedures for Study Termination .................................... 25 
8.10  Sample Size ........................................................................................ 25 
8.11  Period of Use for the Device or its Control ........................................... 25 

Cook Incorporated 
Zenith® Low Profile AAA Endovascular Graft Clinical Study 
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COMPANY CONFIDENTIAL 
Clinical Investigation Plan 08-013-06 
8.12  Limitations of the Investigation ............................................................ 25 
8.13  Safety Monitoring ................................................................................. 26 
9.0 
Statistical Considerations ........................................................................... 26 
9.1  
Sample Size Calculations .................................................................... 26 
9.2 
Performance Goals .............................................................................. 27 
9.3  
Site-level Poolability ............................................................................. 27 
9.4 
Missing Data ........................................................................................ 28 
9.5 
Future Use of Study Data .................................................................... 29 
10.0 
Emergency Situations ................................................................................. 29 
11.0 
Deviations from Clinical Investigation Plan .............................................. 29 
12.0 
Procedure for Reporting Adverse Events and Adverse Device Effects .. 30 
13.0 
Ethical Considerations ................................................................................ 30 
13.1  Declaration of Helsinki II ...................................................................... 30 
13.2  Ethical Approval ................................................................................... 31 
14.0 
Early Termination or Suspension of the Investigation ............................. 31 
15.0 
Publication Policy ........................................................................................ 31 
16.0 
Data Collection ............................................................................................. 31 
17.0 
Data Reporting ............................................................................................. 32 
 
 
 
 
Attachments  
Written Procedures for Monitoring Studies .............................................. Attachment 1 
Definitions ................................................................................................ Attachment 2 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Cook Incorporated 
Zenith® Low Profile AAA Endovascular Graft Clinical Study 
Page 7 of 32 
 
 
COMPANY CONFIDENTIAL 
Clinical Investigation Plan 08-013-06 
1.0 
General Information 
 
1.1 
Sponsor and Manufacturer 
 
 
Cook Incorporated 
750 Daniels Way 
 
Bloomington, IN 47404 
Contact:  
 
Telephone:   
 
 
Fax:    
 
E-mail:  
 
 
1.2 
Data Coordinating Center/Monitor 
 
MED Institute, Inc. 
 
1 Geddes Way 
 
West Lafayette, IN  47906 
 
Contact: 
 
 
Telephone:
 
 
Fax:  
 
 
E-mail: 
 
  
1.3     Study Administration 
This study will be conducted in compliance with global regulations (e.g., ICH 
GCP, ISO 14155, 21 CFR 812, and other regulations as applicable). 
 
1.4 
Investigators 
Contact information for the Global Principal Investigator and principal 
investigators will be provided in the investigator file.  The contact information and 
qualifications for the Global Principal Investigator, principal investigators and 
coordinating investigators, and core laboratory will be updated and maintained by 
the Data Coordinating Center.   
 
1.5 
Insurance 
The devices are covered by the sponsor’s product liability insurance. A clinical 
study insurance policy will be taken out according to local requirements. 
 
 
 

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Zenith® Low Profile AAA Endovascular Graft Clinical Study 
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COMPANY CONFIDENTIAL 
Clinical Investigation Plan 08-013-06 
1.6 
Monitoring Arrangements 
The conduct of the clinical study will be supervised through a process of 
centralized and on-site monitoring. The data coordinating center will remotely 
monitor the study for data completeness and for adverse events. On-site 
monitoring will be implemented as necessary throughout the course of the study. 
The investigator/institution will provide direct access to source data/documents 
for study-related monitoring, audits, Ethics Committee/IRB review and regulatory 
inspection. Written procedures for monitoring the investigation are maintained by 
the monitor and are provided in Attachment 1. 
 
Name and Address of the Monitor: 
 
MED Institute, Inc. or designee 
 
1 Geddes Way 
 
West Lafayette, IN  47906 
 
 
Contact: 
 
 
Telephone:
 
 
Fax:  
 
 
E-mail: 
 
 
1.7 
Data Management and Quality Assurance 
The principal investigator or appropriately trained designee at each investigative 
site will complete standardized, data collection forms in an electronic data 
capturing (EDC) system (see section 16).  The completed data forms and other 
patient documents pertaining to the study will be reviewed, processed, and 
stored by the sponsor. Data will be reviewed for missing data, data consistency, 
and reasonableness of responses. Discrepancies will be resolved through a 
formal query process involving direct contact with investigators or research 
coordinators.  The data coordinating center is responsible for database 
management, data verification, data archiving, and data retention 
 
Pertinent imaging (pre-procedure, procedural, and follow-up) will be sent to MED 
Institute, who will coordinate shipment of imaging for independent analysis. 
 
As needed to assist the sponsor in its research (e.g., during evaluation of an 
adverse event), data will be accessible to the sponsor, the participating 
investigators, the manufacturer, and companies or individuals the sponsor 
authorizes. 

Cook Incorporated 
Zenith® Low Profile AAA Endovascular Graft Clinical Study 
Page 9 of 32 
 
 
COMPANY CONFIDENTIAL 
Clinical Investigation Plan 08-013-06 
MED Institute, Inc., the data coordinating center, maintains a Safe Harbor 
Privacy Policy that describes the privacy principles followed with respect to the 
transfer of personal information from member states in Europe to the United 
States. 
 
2.0 
Approvals and Agreements 
The sponsor, Global Principal Investigator, and the principal clinical investigators 
for each site shall agree to this document and any modifications.  A justification 
for any modifications will be documented.  Approval and agreement will be 
indicated by signing and dating the appropriate document. 
 
3.0  
Clinical Investigation Plan Overview 
This clinical investigation is designed as a prospective non-randomized study 
enrolling up to 120 patients to receive the Zenith® Low Profile AAA Endovascular 
Graft main body in conjunction with the Zenith® Spiral-Z® AAA Iliac Leg Graft at 
up to 40 global clinical sites with a maximum enrollment of up to 24 patients per 
individual site.  The objective of the study is to evaluate the safety and 
effectiveness of the Zenith Low Profile AAA Endovascular Graft used in 
conjunction with the Zenith Spiral-Z AAA Iliac Leg Graft.  Freedom from major 
adverse events (MAEs) at 30 days and device success at 12 months for this 
treatment cohort will be compared to their respective performance goals derived 
from the results of the Zenith® AAA Endovascular Graft clinical study.   
 
Any patient with an abdominal aortic, aortoiliac, or iliac aneurysm and suitable for 
treatment with the Zenith Low Profile AAA Endovascular Graft with the 16 Fr or 
17 Fr H&L-B One-Shot™ Introduction System in conjunction with the Zenith 
Spiral-Z AAA Iliac Leg Graft with the Z-Trak® Introduction System is eligible for 
enrollment in the study.  The study flow diagram is presented in Figure 1. 
 
 
 
 
 
 
 
 

Cook Incorporated 
Zenith® Low Profile AAA Endovascular Graft Clinical Study 
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COMPANY CONFIDENTIAL 
Clinical Investigation Plan 08-013-06 
 
Patient with abdominal aortic, aortoiliac, or iliac aneurysm and suitable for treatment with the 
Zenith Low Profile AAA Endovascular Graft with the 16 Fr or 17 Fr H&L-B One-Shot Introduction 
System in conjunction with the Zenith Spiral-Z AAA Iliac Leg Graft with the Z-Trak Introduction 
System 
 
 
 
 
 
 
Pre-procedural CTA, Angiography (if necessary), Blood Test, Pulses, Clinical Exam 
 (if standard of care) 
 
 
 
 
 
 
Patient meets inclusion/exclusion criteria  
 
 
 
 
 
 
Informed consent is obtained  
(and additional tests that had not previously been considered standard of care)  
 
 
 
 
Endovascular repair with procedural angiography 
 
 
 
Post-procedural (within 7 days) Blood Test, Pulses, Clinical Exam 
 
 
 
30-day: CTA, Abdominal Device X-ray, Blood Test, Clinical Exam 
 
 
 
6-month: CTA, Abdominal Device X-ray, Blood Test, Clinical Exam 
 
 
 
12-month and annually thereafter up to 5 years:  
CTA, Abdominal Device X-ray, Blood Test, Clinical Exam 
Figure 1.  Study flow diagram 
 
4.0 
Objectives of the Clinical Investigation 
 
4.1 
Objective 
The objective of the study is to evaluate the safety and effectiveness of the 
Zenith Low Profile AAA Endovascular Graft used in conjunction with the Zenith 
Spiral-Z AAA Iliac Leg Graft.  The safety endpoint will be freedom from MAEs at 
30 days and the effectiveness endpoint will be device success at 12 months.   
 
 

Cook Incorporated 
Zenith® Low Profile AAA Endovascular Graft Clinical Study 
Page 11 of 32 
 
 
COMPANY CONFIDENTIAL 
Clinical Investigation Plan 08-013-06 
4.2 
Claims and Intended Performance that are to be Verified 
The following data points will be evaluated to verify device performance: 
- Device success (including technical success)  
- Procedural times 
- Access method (percutaneous, cutdown, or conduit usage) employed during 
the procedure 
- Clinical utility measures 
- Morbidity, including Major Adverse Events (MAEs) as well as events distal to 
the graft limb (e.g., arterial thrombosis) 
- Reinterventions-  
- Endoleak, change in aneurysm size, migration, device patency, device integrity 
 
4.3 
Specific Hypotheses to be Accepted or Rejected by Statistical Data 
The safety endpoint of 30-day freedom from MAEs will be analyzed on a per 
patient basis.  The analysis requires that the agreed upon performance goal of 
88%, which was derived from the 30-day freedom from MAE rate for patients 
treated with the currently approved Zenith AAA Endovascular Graft, be met.  The 
performance goal will be said to have been met provided that the null hypothesis 
is rejected in favor of the alternate with a one-tailed exact binomial test at the 
0.025-level.  Given that πMAE(30) is the probability that a randomly selected patient 
experienced freedom from MAEs at 30 days, the null and alternate hypotheses 
are as follows. 
 
Null Hypothesis:  The 30-day freedom from MAEs for patients treated with 
the Zenith Low Profile AAA Endovascular Graft in conjunction with 
the Zenith Spiral-Z AAA Iliac Leg Graft does not meet the 
performance goal (88%). 
  
H0: πMAE(30) < 88% 
 
Alternate Hypothesis:  The 30-day freedom from MAEs for patients treated 
with the Zenith Low Profile AAA Endovascular Graft in conjunction 
with the Zenith Spiral-Z AAA Iliac Leg Graft meets the performance 
goal (88%). 
 
 
HA: πMAE(30) ≥ 88% 
 
 

Cook Incorporated 
Zenith® Low Profile AAA Endovascular Graft Clinical Study 
Page 12 of 32 
 
 
COMPANY CONFIDENTIAL 
Clinical Investigation Plan 08-013-06 
 
 
 
 
 
 
 
Similarly, the effectiveness endpoint of 12-month device success will be analyzed 
on a per patient basis.  The analysis requires that the agreed upon performance 
goal of 83%, which was derived from the 12-month device success rate for 
patients treated with the currently approved Zenith AAA Endovascular Graft, be 
met.  The performance goal will be said to have been met provided that the null 
hypothesis is rejected in favor of the alternate with a one-tailed exact binomial 
test at the 0.025-level.  Given that πDS(12) is the probability that a randomly 
selected patient experienced device success at 12 months, the null and alternate 
hypotheses are as follows. 
 
Null Hypothesis:  The 12-month device success for patients treated with 
the Zenith Low Profile AAA Endovascular Graft in conjunction with 
the Zenith Spiral-Z AAA Iliac Leg Graft does not meet the 
performance goal (83%). 
  
H0: πDS(12) < 83% 
 
Alternate Hypothesis:  The 12-month device success for patients treated 
with the Zenith Low Profile AAA Endovascular Graft in conjunction 
with the Zenith Spiral-Z AAA Iliac Leg Graft meets the performance 
goal (83%). 
 
 
HA: πDS(12) ≥ 83% 
 
 
 
 
 
 
 
 

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Zenith® Low Profile AAA Endovascular Graft Clinical Study 
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COMPANY CONFIDENTIAL 
Clinical Investigation Plan 08-013-06 
5.0 
Device Description and Intended Purpose 
 
5.1 
Device Identification 
The name of the device is the Zenith Low Profile AAA Endovascular Graft which 
is used in conjunction with the commercially available Zenith Spiral-Z AAA Iliac 
Leg Graft. 
 
The following main body (Table 5.1-1), iliac leg (Table 5.1-2), and ancillary 
device sizes (Tables 5.1-3 and 5.1-4) will be available for the study: 
 
Table 5.1-1. Zenith Low Profile AAA Endovascular Graft Main Body Graft Size Availability* 
ZALB-22-70 
ZALB-24-70 
ZALB-26-70 
ZALB-28-70 
ZALB-30-70 
ZALB-32-70 
ZALB-36-70 
ZALB-22-84 
ZALB-24-84 
ZALB-26-84 
ZALB-28-84 
ZALB-30-84 
ZALB-32-84 
ZALB-36-84 
ZALB-22-98 
ZALB-24-98 
ZALB-26-98 
ZALB-28-98 
ZALB-30-98 
ZALB-32-98 
ZALB-36-98 
ZALB-22-108 
ZALB-24-108 
ZALB-26-108 
ZALB-28-108 
ZALB-30-108 
ZALB-32-108 
ZALB-36-108 
ZALB-22-118 
ZALB-24-118 
ZALB-26-118 
ZALB-28-118 
ZALB-30-118 
ZALB-32-118 
ZALB-36-118 
ZALB-22-128 
ZALB-24-128 
ZALB-26-128 
ZALB-28-128 
ZALB-30-128 
ZALB-32-128 
ZALB-36-128 
* Graft sizes are ZALB-XX-YY where XX mm is the proximal graft diameter and YY mm is the 
length from the proximal graft edge to the distal end of the contralateral leg. 
 
Table 5.1-2. Zenith Spiral-Z AAA Iliac Leg Graft Size Availability*  
ZSLE-9-39 
ZSLE-11-39 
ZSLE-13-39 
ZSLE-16-39 
ZSLE-20-39 
ZSLE-24-39 
ZSLE-9-56 
ZSLE-11-56 
ZSLE-13-56 
ZSLE-16-56 
ZSLE-20-56 
ZSLE-24-56 
ZSLE-9-74 
ZSLE-11-74 
ZSLE-13-74 
ZSLE-16-74 
ZSLE-20-74 
ZSLE-24-74 
ZSLE-9-90 
ZSLE-11-90 
ZSLE-13-90 
ZSLE-16-90 
ZSLE-20-90 
ZSLE-24-90 
ZSLE-9-107 
ZSLE-11-107 
ZSLE-13-107 
 
 
 
ZSLE-9-122 
ZSLE-11-122 
ZSLE-13-122 
 
 
 
* Graft sizes are ZSLE-XX-YY where XX mm is the distal graft diameter and YY mm is the 
working length (from the distal edge of the overlap zone to the distal edge of the graft material). 
 
Table 5.1-3. Zenith Low Profile AAA Endovascular Graft Main Body Extension Graft Size 
Availability* 
ZLBE-22-45 
ZLBE-24-45 
ZLBE-26-45 
ZLBE-28-45 
ZLBE-30-45 
ZLBE-32-45 
ZLBE-36-45 
ZLBE-22-58 
ZLBE-24-58 
ZLBE-26-58 
ZLBE-28-58 
ZLBE-30-58 
ZLBE-32-58 
ZLBE-36-58 
* Graft sizes are ZLBE-XX-YY where XX mm is the proximal graft diameter and YY mm is the 
graft length. 
 
 

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Zenith® Low Profile AAA Endovascular Graft Clinical Study 
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COMPANY CONFIDENTIAL 
Clinical Investigation Plan 08-013-06 
Table 5.1-4. Zenith Low Profile AAA Endovascular Graft Converter Graft Size Availability* 
ZLC-24-66 
ZLC-28-66 
ZLC-32-66 
ZLC-36-66 
* Graft sizes are ZLC-XX-YY where XX mm is the proximal graft diameter and YY mm is the graft 
length. 
 
Devices under investigation will be tracked by the clinical site throughout the 
course of the clinical study.  This includes information such as lot numbers, 
quantity, and disposition of devices.  Additionally, information such as the 
quantity, size(s), and lot number(s) of devices used in patients will be recorded 
on Case Report Forms (CRFs). 
 
5.2 
Intended Purpose 
The Zenith Low Profile AAA Endovascular Graft with the Zenith Spiral-Z AAA 
Iliac Leg Graft and ancillary components are indicated for the endovascular 
treatment of patients with abdominal aortic, aorto-iliac, or iliac aneurysms having 
morphology suitable for endovascular repair, including: 
 Iliac/femoral anatomy that is suitable for access with a 16 Fr (6.0 mm 
nominal sheath O.D.) or 17 Fr (6.5 mm nominal sheath O.D.) introduction 
system; 
 Non-aneurysmal infrarenal aortic segment (neck) proximal to the 
aneurysm: 
o with a length of at least 15 mm, 
o with a diameter measured outer wall to outer wall of no greater than 
32 mm and no less than 18 mm, 
o with an angle less than 60 degrees relative to the long axis of the 
aneurysm, and 
o with an angle less than 45 degrees relative to the axis of the 
suprarenal aorta; and 
 Iliac artery distal fixation site greater than 10 mm in length and 7.5-20 mm 
in diameter (measured outer wall to outer wall). 
 
5.3 
General Device Description 
A general device description, including any materials that will be in contact with 
tissues or body fluids can be located in the Clinical Investigator Brochure.  The 
device does not contain medicinal products, human and/or animal tissues or their 
derivatives, or other biologically active substances. 
 

Cook Incorporated 
Zenith® Low Profile AAA Endovascular Graft Clinical Study 
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COMPANY CONFIDENTIAL 
Clinical Investigation Plan 08-013-06 
5.4 
Photographs of Device  
 
 
Figure 2. Zenith Low Profile AAA Endovascular Graft Main Body 
 
 
Figure 3. Zenith Spiral-Z AAA Iliac Leg Graft 
 
 
Figure 4. Zenith Low Profile AAA Endovascular Graft Introduction System 
 
 
Figure 5. Zenith Low Profile AAA Endovascular Graft Main Body Extension  
 

Cook Incorporated 
Zenith® Low Profile AAA Endovascular Graft Clinical Study 
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COMPANY CONFIDENTIAL 
Clinical Investigation Plan 08-013-06 
 
 
Figure 6. Zenith Low Profile AAA Endovascular Graft Converter 
 
The Zenith Iliac Plug, which is commercially available, may be used in 
conjunction with the Zenith Low Profile AAA Endovascular Graft Converter to 
convert the patient to an aortouni-iliac configuration, if necessary. 
 
5.5 
Instructions for Use and Implantation 
Please reference the manufacturer’s Instructions for Use for complete 
instructions including implantation, storage and handling requirements, 
preparation for use, pre-use checks for safety and performance, and precautions 
to be taken after use. 
 
5.6 
Summary of Necessary Training and Experience 
The Zenith Low Profile AAA Endovascular Graft and Zenith Spiral-Z AAA Iliac 
Leg Graft should be deployed by investigators trained and experienced in 
endovascular procedures.  Please refer to the manufacturer’s Instructions for 
Use for a complete summary of the necessary training and experience required 
for use of these devices. 
 
5.7 
Description of the Necessary Medical or Surgical Procedures 
Please refer to the manufacturer’s Instructions for Use for a complete description 
of the procedures involved in the use of these devices. 
 
6.0 
Preliminary Investigations and Justification 
 
6.1 
Literature Review 
Please refer to the Clinical Investigator Brochure for a complete literature review 
and evaluation. 

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Zenith® Low Profile AAA Endovascular Graft Clinical Study 
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COMPANY CONFIDENTIAL 
Clinical Investigation Plan 08-013-06 
6.2 
Non-clinical Testing 
Non-clinical tests were conducted in accordance with Good Laboratory Practice 
requirements, or performed in compliance with verified methods and Standard 
Operating Procedures to maintain the integrity of the results.  In vitro testing has 
established reasonable safety of the device for the duration of the study and in 
the trial population to be studied.  Please refer to the Clinical Investigator 
Brochure for a summary of non-clinical testing. 
 
6.3 
Previous Clinical Experience 
Please refer to the Clinical Investigator Brochure for a complete description of the 
previous clinical experiences with these devices and other similar devices.  
 
7.0 
Risk Analysis and Risk Assessment 
 
Please refer to the Clinical Investigator Brochure for a complete risk analysis. 
 
7.1      Risks and Foreseeable Adverse Device Effects 
Risks of adverse events are likely to be similar to those reported in recent studies 
of other endovascular AAA grafts.  Adverse events associated either with the 
Zenith Low Profile AAA Endovascular Graft, the Zenith Spiral-Z AAA Iliac Leg 
Graft, or the implantation procedure that may occur and require intervention 
include, but are not limited to: 
 
 
Amputation 
 
Anesthetic complications and subsequent attendant problems (e.g., 
aspiration) 
 
Aneurysm enlargement 
 
Aneurysm rupture and death 
 
Aortic damage, including perforation, dissection, bleeding, rupture and death 
 
Arterial or venous thrombosis and/or pseudoaneurysm 
 
Arteriovenous fistula 
 
Bleeding, hematoma, or coagulopathy 
 
Bowel complications (e.g., ileus, transient ischemia, infarction, necrosis) 
 
Cardiac complications and subsequent attendant problems (e.g., arrhythmia, 
myocardial infarction, congestive heart failure, hypotension, hypertension) 
 
Claudication (e.g., buttock, lower limb) 
 
Death 
 
Edema 

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COMPANY CONFIDENTIAL 
Clinical Investigation Plan 08-013-06 
 
Embolization (micro and macro) with transient or permanent ischemia or 
infarction 
 
Endoleak 
 
Endoprosthesis: improper component placement; incomplete component 
deployment; component migration; suture break; occlusion; infection; stent 
fracture; graft material wear; dilatation; erosion; puncture; perigraft flow; 
barb separation and corrosion 
 
Fever and localized inflammation 
 
Genitourinary complications and subsequent attendant problems (e.g., 
ischemia, erosion, fistula, incontinence, hematuria, infection) 
 
Graft or native vessel occlusion 
 
Hepatic failure 
 
Impotence 
 
Infection of the aneurysm, device or access site, including abscess 
formation, transient fever and pain 
 
Lymphatic complications and subsequent attendant problems (e.g., lymph 
fistula) 
 
Neurologic local or systemic complications and subsequent attendant 
problems (e.g., stroke, transient ischemic attack, paraparesis, paralysis) 
 
Pulmonary/respiratory complications and subsequent attendant problems 
(e.g., pneumonia, respiratory failure, prolonged intubation) 
 
Renal complications and subsequent attendant problems (e.g., artery 
occlusion, contrast toxicity, insufficiency, failure) 
 
Surgical conversion to open repair 
 
Vascular access site complications, including infection, pain, hematoma, 
pseudoaneurysm, or arteriovenous fistula 
 
Vascular spasm or vascular trauma (e.g., iliofemoral vessel dissection, 
bleeding, rupture, death) 
 
Vessel damage 
 
Wound complications and subsequent attendant problems (e.g., dehiscence, 
infection) 
 
7.2 
Methods to Minimize Risks 
The device design, non-clinical testing, clinical study design, and the Instructions 
for Use are intended to minimize the risks associated with the endovascular 
procedures. 

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COMPANY CONFIDENTIAL 
Clinical Investigation Plan 08-013-06 
8.0 
Design of the Clinical Investigation 
 
8.1 
Type of Investigation 
The current investigation is a prospective, non-randomized, non-blinded study. 
 
8.2 
Rationale 
The assessment of safety will be based on freedom from MAEs at 30 days and 
the assessment of effectiveness will be based on device success at 12 months. 
 
8.3 
Measures to be Taken to Avoid or Minimize Bias 
This study is not randomized or blinded, as it is intended to prospectively collect 
information regarding the safety and effectiveness of the Zenith Low Profile AAA 
Endovascular Graft in conjunction with the Zenith Spiral-Z AAA Iliac Leg Graft.  
Similar inclusion/exclusion criteria will be used during patient selection for the 
current patient cohort compared to that for the Zenith AAA Endovascular Graft 
clinical study, which was the basis for the chosen performance goals.   
 
8.4 
Variables to be Measured  to Demonstrate Achievement of Endpoints 
To evaluate deployment characteristics and procedural outcome, the following 
data points will be collected intra-operatively: 
1) 
Assessment of system performance including:  deployment issues, ease 
of insertion, visualization, and ease of removal 
2) 
Complications (if any) 
3) 
Ancillary equipment needed 
4) 
Adjunctive maneuvers including: balloon dilation of iliac arteries, additional 
stents required, and additional surgical procedures 
5) 
Findings of completion assessment: minimum iliac leg graft lumen 
diameter, device patency, endoleak, and kinks 
 
In addition, the results of the endovascular repair will be assessed by clinical 
and/or imaging evaluation at the time of graft insertion, within 7 days post-
procedure, at 30 days 
,   6 months 
, 12 months 
 
, 2 years 
, 3 years 
, 4 years 
 
, and 5 years 
 according to the post-operative study 
schedule below.  
 
  

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Study Schedule 
 
Pre-op 
Intra-op 
Post-
procedure 
30-Day 
6-Month 12-Month5
 Clinical Exam 
X 
 
X 
X 
X 
X 
 Pulses 
X 
 
X 
 
 
 
 Blood Test1 
X 
 
X 
X 
X 
X 
 CTA 
X2 
 
 
X4 
X4 
X4 
 Abdominal 
Device X-ray 
 
 
 
X 
X 
X 
 Angiography 
X3 
X 
 
 
 
 
    1       Blood test for serum creatinine. 
    2 
Imaging should be performed within 6 months prior to implant procedure. 
    3 
Required only to resolve any uncertainties in anatomical measurements    
necessary for graft sizing. 
    4 
A non-contrast CT in conjunction with a duplex ultrasound may be used for 
those patients experiencing renal failure or who are otherwise unable to 
undergo contrast enhanced CT scan.   
    5 
Yearly thereafter through 5 years. 
 
8.5 
Inclusion/Exclusion Criteria 
Patients must meet at least one of the inclusion criteria below to be enrolled in 
the study.  General and medical exclusion criteria will be assessed during the 
initial patient evaluation by conducting a history and physical examination.  
Anatomical exclusion criteria will be assessed using a variety of imaging 
techniques that are routinely performed during the evaluation of abdominal aortic 
aneurysms.  Sectional imaging will be performed by CT scan.   
 
Angiography and intravascular ultrasound will be performed as needed to further 
assess inclusion/exclusion criteria.  
 
Assessment of entry criteria will be based upon data available pre-operatively.  
Data obtained peri-operatively and post-operatively (including the results from 
core lab analysis of pre-procedure imaging) may contradict pre-operative 
assessment.  However, such contradiction is not considered a protocol violation 
and should not be construed as evidence of inadequate or inaccurate pre-
operative assessment with respect to the enrollment criteria or evidence of 
inappropriate enrollment.  Enrollment is to be based upon best available pre-
operative 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.  

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8.5.1 Inclusion Criteria 
A patient is deemed suitable for inclusion in the study if the patient has at least 
one of the following AND is suitable for treatment with the Zenith Low Profile AAA 
Endovascular Graft with the 16 Fr (for 22 – 32 mm diameter grafts) or 17 Fr (for 
36 mm diameter graft) H&L-B One-Shot Introduction System in conjunction with 
the Zenith Spiral-Z AAA Iliac Leg Graft with the Z-Trak Introduction System: 
1) 
Aortic or aortoiliac aneurysm with a diameter ≥ 5.0 cm for males or 
≥ 4.5 cm for females  
2)  
Iliac aneurysm with a diameter ≥ 3.0 cm 
3) 
Aneurysm with a history of growth ≥ 0.5 cm per year. 
 
8.5.2 Exclusion Criteria 
Patients must be excluded from the study if any of the following conditions are 
true: 
 
General Exclusion Criteria 
 1) 
Less than 18 years of age 
 2) 
Other current conditions (e.g., cancer, systemic infection) that may 
cause the patient to be noncompliant with the clinical investigation 
plan, that may confound the results, or that is associated with a life 
expectancy less than 2 years 
 3) 
Pregnant or breastfeeding or planning on becoming pregnant within 
60 months 
 4) 
Unwilling to comply with the follow-up schedule 
 5) 
Inability or refusal to give informed consent 
 6) 
Less than 30 days beyond primary endpoint for other investigative 
drug or device study 
Medical Exclusion Criteria 
 1) 
Known sensitivities or allergies to nitinol (nickel, titanium), 
polyester, polypropylene, gold, stainless steel, or solder (tin, silver) 
 2) 
History of anaphylactic reaction to contrast material that cannot be 
adequately premedicated 
 3) 
Leaking/ruptured or symptomatic aneurysm 
 4) 
Uncorrectable coagulopathy 
 5) 
Planned interventional or surgical procedure that is unrelated to 
AAA repair within 30 days before or after AAA repair 

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Anatomical Exclusion Criteria 
 1) 
Significant occlusive disease, tortuosity, or calcification 
 2) 
Proximal neck <15 mm in length  
 3) 
Proximal neck, measured outer wall to outer wall on a sectional 
image (CT)     > 32 mm in diameter or <18 mm in diameter 
 4) 
Proximal neck angulated more than 60 degrees relative to the long 
axis of the aneurysm 
 5) 
Immediate suprarenal neck angulated more than 45 degrees 
relative to the immediate infrarenal neck 
 6) 
Proximal seal site with inverted funnel shape (change in neck 
diameter > 10% over the first 15 mm of proximal neck length) 
 7) 
Proximal seal site with circumferential thrombus/atheroma 
 8) 
Aortic diameter, measured inner wall to inner wall on a sectional 
image (CT), < 20 mm just proximal to the aortoiliac bifurcation  
 9) 
Iliac/femoral anatomy that is unsuitable for access with the 16 Fr 
(6.0 mm nominal sheath O.D.) or 17 Fr (6.5 mm nominal sheath 
O.D.) introduction system 
10) 
Iliac artery diameter, measured outer wall to outer wall on a 
sectional image (CT), > 20 mm or < 7.5 mm at distal fixation site 
11) 
Iliac artery distal fixation site < 10 mm in length 
12) 
Indispensable inferior mesenteric artery (IMA) 
13) 
Inability to maintain at least one patent hypogastric artery 
14) 
Renal artery stenosis > 80% (and serum creatinine > 2.0 mg/dl) 
15)  
Unsuitable arterial anatomy 
 
8.6 
Patient Consent 
Patients who meet all of the inclusion criteria and none of the exclusion criteria 
will be invited to participate in this study.  All patients eligible for entry will have 
the clinical study explained to them, as well as potential risks and benefits of their 
participation in the study.  Each patient who agrees to participate will be required 
to sign and date an informed consent document prior to the procedure or any 
study-specific testing.  If approved by the local Ethics Committee/IRB, a legally 
authorized representative may provide consent on behalf of the patient.   
 
If new information is obtained after a patient receives treatment with the device, 
patients who have not exited the study will be informed about the new 

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information, and will be reconsented at the discretion of the investigator and/or 
the site’s Ethics Committee/IRB. 
 
8.7 
Point of Enrollment 
Point of enrollment will be based on the intent-to-treat population, and is defined 
to include any patient for which the treatment procedure is initiated.  More 
specifically, once a procedure has begun (i.e., cutdown or percutaneous access 
initiated), this patient would be included in the intent-to-treat population.  The 
patient’s informed consent will be obtained and assessment of the patient’s 
conformance to the inclusion/exclusion criteria will occur prior to the procedure.   
 
8.8 
Methods 
 
8.8.1.  Medication 
The hospital’s standard protocol should be followed with respect to medication.  
  
8.8.2.  Pre-procedure 
Grafts are sized based on the findings from preoperative radiologic studies, 
including computerized tomography (CT) or conventional angiography.  Refer to 
the Instructions for Use for details regarding the suggested imaging studies to be 
obtained and sizing guidelines. 
 
8.8.3.  Procedure 
Standard techniques for placement of arterial access sheaths, guiding catheters, 
angiographic catheters and wire guides should be employed during use of the 
Zenith Low Profile AAA Endovascular Graft and the Zenith Spiral-Z AAA Iliac Leg 
Graft.  The Zenith Low Profile AAA Endovascular Graft and the Zenith Spiral-Z 
AAA Iliac Leg Graft are compatible with 0.035 inch diameter wire guides. 
 
Refer to institutional protocols relating to anesthesia, anticoagulation and 
monitoring of vital signs.  Refer to the Instructions for Use for complete details 
regarding use of the Zenith Low Profile AAA Endovascular Graft and the Zenith 
Spiral-Z AAA Iliac Leg Graft.  Fluoroscopic guidance and angiography should be 
used throughout the procedure to verify positioning of the devices with respect to 
the patient’s anatomy. 
 

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The iliac leg graft should overlap with the main body limb by at least one stent, as 
inadequate overlap (< 1 stent) may increase the risk for migration and/or 
endoleak.  Excessive overlap of the iliac leg graft with the main body (leg 
component more than 10 mm above the main body bifurcation) may restrict flow 
and thereby increase the risk of limb thrombosis.  Additionally, the proximal edge 
of the ipsilateral leg graft should align closely with that of the contralateral leg 
graft (i.e., the ends of both graft legs should be at the same height relative to the 
graft bifurcation).   
 
If the distal seal of the iliac leg graft lands in a location different from that used to 
select the graft size, undersizing or excessive oversizing could result.  Excessive 
oversizing may result in flow restriction with higher risk of limb thrombosis and 
should be treated appropriately at the time of procedure (e.g., with adjunctive 
balloon dilatation and/or stent placement). 
 
Pre-existing regions of stenosis/narrowing less than approximately 20 mm ID in 
the aorta or 7-8 mm ID in the iliac arteries may increase the risk for limb 
thrombosis if left untreated.  Dilatation of these regions with a noncompliant 
balloon and/or stent placement may be necessary to help assure continued graft 
patency.  The completion angiogram (with stiff wire guides removed) should be 
reviewed carefully to determine whether further treatment in these regions is 
necessary (e.g., adjunctive balloon dilatation/stent placement).  Failure to remove 
the stiff wire guide prior to the angiogram could mask any limb kinking or 
narrowing that might occur when the wire guide is removed.   
 
Both graft leg lumens should be evaluated carefully in multiple views at the 
completion of the procedure to assess for any narrowing and to document the 
minimum graft lumen ID.  Patients with a graft leg lumen less than approximately 
5 mm ID may be at increased risk for limb thrombosis.  Intervention (e.g., 
noncompliant balloon dilatation and/or stent placement) should be considered to 
help assure continued graft patency.   
  
8.8.4. Peri-operative Care 
The endovascular method does not require any departure from the usual peri-
operative management of patients undergoing aneurysm repair.   
 

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8.8.5. Post-operative Treatment of Endoleaks 
Type I and type III endoleaks warrant immediate treatment.  Type II endoleaks 
should be treated at the physician’s discretion, depending on aneurysm behavior 
and size, endoleak source, and time from implantation.  If the aneurysm is 
enlarging, treatment by embolization or ligation should be considered.  Type III 
endoleaks should be treated with additional ballooning or prostheses. 
 
8.9 
Criteria and Procedures for Study Termination  
A patient’s follow-up in the study will end after: 
1) 
Failure to deploy the device + 30 days; 
2) 
Conversion to open surgical technique + 30 days; 
3) 
Patient withdrawal or lost to follow-up; 
4) 
Patient death; 
5) 
Closure of the investigation; or 
6) 
Completion of all scheduled clinical and imaging visits through 5 years. 
No medical care related to the clinical study will be provided for the subjects after 
study completion. 
 
8.10 Sample Size 
This investigation will enroll a maximum of 120 subjects at a maximum of 40 
investigative sites.  Patient recruitment is expected to be completed within 12 
months of initiating the study. Follow-up data will continue to be collected for 5 
years after graft deployment for each patient in the study, making the study 
duration at least 72 months. 
  
8.11 Period of Use for the Device or its Control 
The 5-year follow-up period of the clinical investigation should permit the 
demonstration of performance over a period of time sufficient to represent a 
realistic test of the performance of the device and allow identification and risk 
assessment of any associated adverse device effects over that period.  
 
8.12 Limitations of the Investigation 
This study is inherently limited by the number of patients who will be excluded 
due to general, medical, and anatomical exclusion criteria.  Additional challenges 
of the study include the anticipated comorbidities likely to be found in patients 
with aortic, aortoiliac, or iliac aneurysms, which may confound data analysis.  

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Additional confounding elements of the study might include the lower incidence 
of AAA in women, with the anticipation of fewer women than men being enrolled 
in the study. 
 
8.13 Safety Monitoring 
Safety monitoring will include collecting data regarding adverse events.  Section 
7, Risk Analysis, lists the potential adverse events associated with this study. 
 
A Data Safety Monitoring Board (DSMB) consisting of independent physicians 
and at least one independent statistician, who are not investigators in the study, 
nor have a perceived conflict of interest with the conduct and administration of 
the study, will be convened on a regular basis to evaluate the study progress and 
review adverse events. 
 
An independent Clinical Events Committee (CEC) will be established to 
adjudicate clinical events 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 condition, procedure-related, technique-
related, and/or device-related.  In addition, a core lab will be established to 
independently review available imaging. 
 
Regular scheduled monitoring, including on-site visits, will be conducted, in part, 
for identification of adverse events and assurance that they are correctly reported 
to the DSMB, CEC, and Ethics Committees/IRBs. 
 
In addition, incidences of intra-operative conversion to open surgical aneurysm 
repair, access failure, and intra-operative type I or type III endoleak will be 
evaluated by the sponsor on a case-by-case basis.  If a potential safety issue is 
identified, the sponsor may delay additional enrollment until further investigation 
into the incident is performed.   
 
9.0  
Statistical Considerations 
 
9.1  
Sample Size Calculations 
Evaluation of the safety hypothesis, 30-day freedom from MAEs, requires 46 
patients to determine whether the performance goal of 88% has been met.  

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Evaluation of the effectiveness hypothesis, 12-month device success, requires 
59 patients to determine whether the performance goal of 83% has been met.  
Cook intends to enroll 120 patients to account for patients who withdraw or are 
lost to follow-up, and also to provide added enhanced statistical certainty as well 
as the same number of patients as agreed to for a previous similar study.   
 
Sample size calculations for the safety and effectiveness hypotheses can be 
performed with the following assumptions.  Using performance goals of 88% for 
freedom from MAEs and 83% for device success, with an expected rate of 99.2% 
for freedom from MAEs and 93.5% for device success, an exact binomial 
calculation, α=0.025, power=0.80 and a one-sided test, 46 patients for freedom 
from MAEs and 59 patients for device success are required to demonstrate that 
the Zenith Low Profile AAA Endovascular Graft in conjunction with the Zenith 
Spiral-Z AAA Iliac Leg Graft meets the stated performance goals.  
 
9.2 
Performance Goals  
The performance goals used for the hypotheses in section 4.3 and the sample 
size calculations in section 9.1 were derived from the pivotal study of the Zenith 
AAA Endovascular Graft.  The 30-day freedom from MAEs was 98.3% and the 
12-month device success was 93.0% in the pivotal study of the Zenith AAA 
Endovascular Graft.  Therefore, the performance goals of 88% for freedom from 
MAEs and 83% for device success, respectively, have been determined. 
 
9.3  
Site-level Poolability 
Poolability of data from multiple sites will be verified by examining the safety and 
efficacy measures as well as important patient baseline characteristics among 
sites. Site-level poolability will be considered appropriate provided that these 
measures are similar among sites. 
 
 
 
 
 
 
 
 

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9.4 
Missing Data 
Missing data will be addressed using three primary strategies: 1) estimating 
missing data with the best available data, 2) case deletion, and 3) multiple 
imputation. 
 
The first strategy may be used for missing imaging data.  Previous clinical trial 
experience suggests that some portion of the imaging data may not meet the 
criteria for accurate measurements by the core laboratory.  However, it is 
recognized that the treating physician uses this information to provide the best 
possible care for the patient.  Therefore, it is reasonable to substitute any missing 
core laboratory measurements with the corresponding measurements made by 
the treating physician (or his/her staff).  In addition, the absence or presence of 
clinical sequelae may provide the required missing core laboratory assessment 
of device performance. This strategy is a best approximation of the missing data 
value. 
 
The second strategy is case deletion. If the amount of missing data does not 
result in a reduction of analyzable patients to a number that is below that 
required for sufficient statistical power of the endpoints, then case deletion will be 
the method of choice for that analysis. 
 
The third method is multiple imputation.  This method will be used to predict 
missing endpoint or covariate data.  It may be that the study endpoints may 

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depend upon certain covariates. Therefore, it may be possible to model study 
endpoints, given a series of related covariates. This model-based imputation 
exercise may provide estimates of the missing data that can be utilized in 
estimating event rates and confidence bounds.   
 
9.5 
Future Use of Study Data 
The data collected in this study may be used to justify additional studies of 
variations on the Zenith Low Profile AAA Endovascular Graft including, but not 
limited to, design variations. It is anticipated that the safety and effectiveness 
data obtained may serve as prior information in the analysis of the safety and 
effectiveness of future variations of the Zenith Low Profile AAA Endovascular 
Graft. 
 
10.0  Emergency Situations 
Patients will not be treated with the Zenith Low Profile AAA Endovascular Graft in 
conjunction with the Zenith Spiral-Z AAA Iliac Leg Graft in emergency situations 
where prior consent of the patient is not possible. 
 
11.0 Deviations from Clinical Investigation Plan 
Investigators are not allowed to deviate from this Clinical Investigation Plan 
without prior authorization by the sponsor except under emergency situations 
when necessary to preserve the rights, safety, or well-being of study patients. 
 
Deviations or noncompliances will be recorded together with an explanation.  
Deviations or noncompliances that impact the rights, welfare, or safety of patients 
shall be reported to the sponsor and Ethics Committee/IRB as required and as 
soon as possible. If appropriate, corrective and preventive actions will be 
discussed by the sponsor, investigator, and/or the Ethics Committee/IRB to 
determine a suitable course of action.   
 
When available, the reasons for withdrawal and discontinuation of any patient 
from the investigation shall be recorded.  If such discontinuation is because of 
problems with safety or lack of effectiveness of the device, that patient shall still 
be followed-up in the investigation, if possible. 
 
 

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12.0 Procedure for Reporting Adverse Events and Adverse Device Effects 
Events known to be related to pre-existing conditions or existing at admission are 
not considered adverse events (e.g., prior medically-treated cardiac arrhythmia 
with no change in status during the endovascular procedure).  Additionally, 
common standard of care practices are not considered adverse events (e.g., 
centers located at high geographical altitudes that discharge all patients on home 
oxygen therapy regardless of procedure).   
 
All adverse events (i.e., device-related and non-device-related) are to be 
reported using the appropriate case report form (Adverse Event/Complication 
form). In cases of adverse device effects (adverse event with relation to the study 
device) or serious adverse events, completed forms should be submitted to the 
Data Coordinating Center as soon as possible upon knowledge of the event.   
MED Institute, Inc. 
 
1 Geddes Way 
 
West Lafayette, IN  47906 
Telephone:  
 
 
Fax:  
 
 
The Data Coordinating Center will notify the sponsor/manufacturer accordingly.  
In accordance with applicable requirements, the investigator will notify the local 
Ethics Committee/IRB, while the sponsor/manufacturer will notify the regulatory 
authority.  Furthermore, if the sponsor determines that the device presents a 
potential risk to the study patients, all investigators in the study will be notified. 
Clinical sites will be responsible for following their normal reporting process (e.g., 
to manufacturer, to regulatory authority) for any problems with the commercially 
available devices.  Refer to section 7.1 for a list of potential adverse events 
related to this study. 
 
13.0 Ethical Considerations  
 
13.1 
Declaration of Helsinki  
The investigation shall be performed according to the ethical principles that have 
their origin in the Declaration of Helsinki and in accordance with ISO 14155, ICH 
GCP, and 21 CFR 812.  
 

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13.2 
Ethical Approval  
The investigator is responsible for obtaining approval of this clinical investigation 
by the relevant Ethics Committee/IRB, and the clinical study will not begin until a 
favorable opinion of the Ethics Committee/IRB has been obtained. The sponsor 
must be provided with a copy of this approval before delivery of any study device. 
The investigator is responsible for complying with the requirements imposed by 
his/her Ethics Committee/IRB and/or regulatory authority.  Furthermore, the 
investigator will ensure that local regulations concerning data protection are 
followed. 
 
14.0 Early Termination or Suspension of the Investigation 
The sponsor reserves the right to terminate/suspend the study at any point 
should they believe that important harmful events might result from its 
continuation.  If a decision is made to terminate the study, all patients already 
treated will be followed according to the study follow-up schedule.  Subjects may 
withdraw from the study at any time without penalty or loss of benefits.  The 
subject should notify the investigator of his/her desire to withdraw.  The 
investigator may also decide to withdraw a subject from the study at any time on 
the basis of medical judgement.  In any case, the reasons for withdrawal will be 
documented, when available. 
 
15.0 Publication Policy 
Publication and presentation policies are outlined in the study contractual 
documents. 
 
16.0 Data Collection 
Patient data will be collected and entered by trained personnel at the clinical site 
onto electronic Case Report Forms (eCRFs) through an electronic data capturing 
(EDC) system. This is a secure, web-based system, allowing those with 
permission to access data from any location at any time. Source data are to be 
retained for data entered into the EDC system. Data obtained and simultaneously 
entered into the EDC system may also serve as source documentation.  
 
Site personnel are required to undergo data entry training and will have unique 
login names and passwords in order to enter patient data. In accordance with 21 
CFR Part 11, the EDC system creates a secure, computer-generated, time 

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stamped audit trail to record the date and time of operator entries and actions 
that create, modify, or delete electronic records.     
 
17.0 Data Reporting 
Progress reports and a final report at the conclusion of the clinical investigation 
will be submitted by the investigators and sponsor to the regulatory bodies and 
Ethics Committees/IRBs as required by local regulations. 

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Attachment 1 
Written Procedures for Monitoring Studies 
 
 
 
 
 

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Attachment 2 
Definitions 
 
 
 

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Proximal Neck: 
Infrarenal aortic segment from the lowest level of the 
distal-most renal artery intended to remain patent, to the 
proximal end of the aneurysmal aorta. 
 
Calcification:  
Calcification will be graded based upon the following:  
 
None: 
Absence of calcification;  
 
Mild: 
Less than 40% circumferential calcification;  
 
Moderate: 40-70% circumferential calcification; or 
 
Severe: 
Greater than 70% circumferential  
 
 
calcification.  
 
Tortuosity of Iliac Arteries: Tortuosity will be graded based upon the following: 
None:  
No tortuosity; 
Mild:  
Minimal tortuosity (less than one turn  
involving either external or common iliac 
artery); 
Moderate:  Single turn involving either external or  
 
common iliac artery; or 
Severe:  
Compound turns involving external and  
 
common iliac arteries. 
 
Occlusive Disease of Iliacs:  Occlusive disease will be graded based upon the 
following: 
 
None: 
Absence of occlusive disease;  
 
Mild: 
Some disease, focal with less than 30%        
 
 
narrowing; 
 
Moderate:  Between 30-50% narrowing not requiring; 
interventional techniques to meet entry 
criteria; or 
 
Severe: 
Greater than 50% narrowing or any patient  
 
requiring angioplasty prior to endograft 
delivery.  
 
New York Heart Association Classification:  
1 Patient with cardiac disease but without resulting 
limitations of physical activity.  Ordinary physical activity 

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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.  
 
Disabling Chronic Obstructive Pulmonary 
Disease (COPD): 
Having a forced expiratory volume (FEV1) <1.0 liter or 
receiving home oxygen therapy. 
 
Intractable 
Hypertension: 
Having a systolic arterial pressure >160 mmHg despite 
receiving medication. 
 
MI (Non-Q-Wave): 
Investigator identified patients having 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): 
Post-procedure presence of new Q-waves greater than 
0.04 seconds in at least two EKG leads. 
 
 

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Renal Failure:   
Acute or progressive renal insufficiency leading to the 
need for dialysis or hemofiltration.   
 
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).  
 
Embolization: 
Clinical evidence of ischemic tissue remote from the 
operative field, presumably caused by thrombus 
dislodged from the aneurysmal sac, aortic neck, or 
adjacent vessels, including ischemia of the kidneys, 
pelvis (IIA) or lower limbs.  This is, of course, distinct 
from intentional pre-operative, operative, or post-
operative embolization procedures.   
 
Graft Limb Occlusion:  The presence of thrombus within one, or both, of the graft 
limbs (including any legs and extensions) creating 
complete occlusion with no blood flow through the graft 
limb. 
 
Graft Lumen Diameter: The diameter measured inner wall to inner wall within the 
endograft. 
 
Type I Endoleak: 
A peri-prosthetic leak occurring at the proximal and/or 
distal fixation zones. 
 
Type II Endoleak: 
A leak caused by retrograde flow from patent lumbar or 
inferior mesenteric arteries or other collateral vessels. 
 
Type III Endoleak: 
A leak caused by a defect in the graft fabric, or 
inadequate seal of modular graft components. 
 
Type IV Endoleak: 
A leak caused by graft fabric porosity, often resulting in a 
generalized blush of contrast within the aneurysm sac. 

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Zenith® Low Profile AAA Endovascular Graft Clinical Study 
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COMPANY CONFIDENTIAL 
Clinical Investigation Plan 08-013-06 
Endoleak (early): 
Any endoleak observed within 30 days of device 
deployment. 
 
Endoleak (late): 
Any endoleak observed later than 30 days after device 
deployment that was not documented during the first 30 
days post-deployment. 
 
Radiographic Migration 
(stent-graft):  
Antegrade or retrograde movement of the stent-graft ≥10 
mm at the level of the renal arteries as compared to the 
position on the first post-operative CT scan. 
 
Clinical Utility  
Measures: 
Duration of procedural intubation; days to resumption of 
oral fluids; days to resumption of normal diet; days to 
resumption of normal bowel function; days to ambulation; 
duration of ICU stay; days to discharge. 
 
Clinically Significant Migration 
(stent-graft): 
Antegrade or retrograde movement of the stent-graft 
requiring surgical or endovascular intervention.   
 
Barb Separation:  
Radiographic evidence of detachment of barbs from the 
stent strut as confirmed by the CEC.  
 
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 as confirmed by the CEC.  
 
Technical Success: 
Successful access of the aneurysm site and deployment 
of the Zenith Low Profile AAA Endovascular Graft and 
the Zenith Spiral-Z AAA Iliac Leg Graft in the intended 
location.  The endovascular graft must be patent at the 

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COMPANY CONFIDENTIAL 
Clinical Investigation Plan 08-013-06 
time of deployment completion as evidenced by 
intraoperative angiography.  
 
Device Success 
(12-month): 
Technical Success, with none of the following at 12 
months: 
 Type I or type III endoleaks requiring re-intervention; 
 Graft limb occlusion; 
 Aneurysm rupture or conversion to open surgical 
repair; or  
 Aneurysm enlargement greater than 0.5 cm. 
 
Major Adverse Events: All-cause death, Q-wave MI, renal failure requiring 
dialysis, paralysis, stroke, bowel ischemia, re-intubation.  
 
Serious Adverse  
Event: 
An adverse event that led to death, led to a serious 
deterioration in the health of the subject that resulted in a 
life-threatening illness or injury, resulted in a permanent 
impairment of a body structure or a body function, 
required in-patient hospitalization or prolongation of 
existing hospitalization, resulted in medical or surgical 
intervention to prevent permanent impairment to body 
structure or a body function, led to fetal distress, fetal 
death, a congenital abnormality or birth defect.