Trifecta™ Durability Study
Conditions: Aortic Valve Disease
Sponsor: Abbott Medical Devices

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TRIFECTA  DURABILITY  STUDY_CIP_vA.0_20101007 
TRIFECTA DURABILITY STUDY 
Clinical Investigational Plan (CIP)  
and Statistical Analysis Plan (SAP) 
Project Name: 
Trifecta Durability Study 
ClinicalTrials.gov Study ID 
NCT01256710
NCT01256710 
CIP/SAP Version: 
A 
Date: 
2010 10 07 
SPONSOR 
SJM International, Inc. 
The Corporate Village 
Da Vincilaan 11- box F1 
B-1935 Zaventem 
Belgium 
Tel: 0032 2 774 69 37 
Fax: 0032 2 774 69 46 

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1 TABLE OF CONTENTS 
1 
Table of Contents ................................................................................................... 2 
2 
Background ............................................................................................................ 3 
3 
Objectives ............................................................................................................... 4 
3.1 
Primary Objective .............................................................................................. 4 
3.2 
Secondary Objectives .................................................................................... 4 
4 
Endpoints ................................................................................................................ 4 
4.1 
Primary Endpoint ............................................................................................ 4 
4.2 
Secondary Endpoints ..................................................................................... 4 
5 
Patient Selection Criteria ........................................................................................ 5 
5.1 
Patient Enrollment .......................................................................................... 5 
5.2 
Inclusion Criteria ............................................................................................... 5 
5.3 
Exclusion Criteria ........................................................................................... 6 
6 
Investigation Design ............................................................................................... 7 
6.1 
Type ................................................................................................................ 7 
6.2 
Duration .......................................................................................................... 7 
6.3 
Enrollment Target ........................................................................................... 7 
6.4 
Design ............................................................................................................ 7 
7 
Product ................................................................................................................... 8 
8 
Statistical Analysis Plan ......................................................................................... 9 
8.1 
Sample Size Justification ............................................................................... 9 
8.2 
Endpoint Analysis ............................................................................................. 9 
8.3 
Additional Data ............................................................................................... 9 
9 
Protocol Description ............................................................................................. 10 
9.1 
Protocol Procedures - Overview .................................................................. 10 
9.2 
Adverse Events ............................................................................................ 10 
9.3 
Patient Death ................................................................................................ 13 
9.4 
Early Conclusion To Patient Participation .................................................... 15 
9.5 
Deviations ..................................................................................................... 16 
9.6 
Enrollment .................................................................................................... 17 
9.7 
Baseline Visit (Intervention) ......................................................................... 18 
9.8 
Pre-Discharge Visit ....................................................................................... 19 
9.9 
Protocol Required Follow-up ........................................................................ 20 
10 
Risk Description and Minimization ..................................................................... 21 
10.1 
Potential Benefits ......................................................................................... 21 
10.2 
Potential Risks .............................................................................................. 21 
11 Ethical Basis ............................................................................................................ 21 
Appendix A: Abbreviations ........................................................................................... 22 
Appendix B: References .............................................................................................. 23 
Appendix C: Declaration of Helisinki ............................................................................24 

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2 BACKGROUND 
Valvular heart disease is responsible for nearly 93,000 valve related 
operations and 20,000 deaths each year in the United States. It is also a 
contributing factor for another 42,000 deaths each year. The majority of these 
cases involve disorders of the aortic valve (63%).1 Specific aortic valvular 
disorders include: aortic stenosis, aortic regurgitation, or a combination of the 
two, with aortic stenosis being the leading indication for aortic valve 
replacement in adults. 
The most common cause of aortic stenosis in adults is an idiopathic 
degenerative calcification process that produces an immobilization of  the 
aortic valve cusps.2 This disease progresses from the base of the cusps to 
the free edge, eventually causing a reduction in the effective valve area. 
Other causes include a congenital malformation (often a bicuspid valve) and 
rheumatic fever. Classic symptoms of aortic stenosis include angina, 
syncope, dyspnea, heart murmur, fatigue, and heart failure. 
Common causes of aortic valve regurgitation include idiopathic aortic 
dilatation, congenital abnormalities (bicuspid valve), degenerative calcification, 
rheumatic fever, infective endocarditis, systemic hypertension, dissection of 
the ascending aorta, Marfan’s syndrome, and many others that occur much 
less frequently.2 Symptoms of aortic regurgitation include: angina, syncope, 
dyspnea, heart murmur, fatigue, and heart failure. 
Patients with either aortic stenosis, regurgitation, or both may remain 
asymptomatic for many years however, after the onset of symptoms (angina, 
syncope, or dyspnea); the average survival is less than two to three years.2
Aortic valve replacement (AVR) appears to be the only effective treatment for 
these patients.2 For certain patients with severe aortic regurgitation who are 
not considered good surgical candidates, therapy with vasodilating agents 
may provide some benefit.2
Presently, there are two broad categories of aortic valve prostheses; 
mechanical and tissue (bioprosthesis). The ball and cage, tilting-disc, and 
bileaflet are the three basic types of mechanical valve prostheses available 
today. There is a wide variety of bioprostheses available including: autografts 
(a valve moved from one anatomical position to another within the same 
individual), homografts/allografts (human valves or tissue taken from 
cadavers), and heterografts/xenografts (valves or tissue taken from animals). 
There are currently several different heterografts available. Heterografts are 
primarily constructed from porcine aortic valves that have been preserved and 
sewn onto a frame (stented) or left intact (stentless). A stented bovine 
pericardial valve is another type of commonly accepted heterograft.3, 4

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Each valve type, mechanical or tissue, has associated risks and benefits. 
Mechanical valves are associated with potential lifetime durability but require 
long-term anticoagulation therapy. Tissue valves are reported to have 
reduced device durability, but typically do not require long-term anticoagulation 
therapy and are therefore associated with lower incidence of thromboembolic 
and hemorrhagic events.5, 6 Implanting physicians must not only consider the 
various valve characteristics when deciding which aortic prosthesis to implant, 
but also various patient factors including, but not limited to age, coexisting 
medical 
conditions, 
anticoagulation 
therapy 
tolerance, 
and 
cardiac 
physiology.2, 3, 4
3 OBJECTIVES 
3.1 
PRIMARY OBJECTIVE 
3.1.1 The  primary  objective  of  this  investigation  is  to  evaluate  the  long-term 
durability of the Trifecta valve. 
3.2 
SECONDARY OBJECTIVES 
3.2.1 The secondary objectives of this investigation are to evaluate valve-related 
complications in the long-term. 
4 ENDPOINTS 
4.1 
PRIMARY ENDPOINT 
4.1.1 Actuarial freedom from reoperation due to Structural Valve Deterioration7 
(SVD) at year 10 post implant for patients who have the Trifecta valve 
implanted. 
4.2 
SECONDARY ENDPOINTS 
4.2.1 The secondary endpoints of this investigation are: 
4.2.1.1 Actuarial survival rate; 
4.2.1.2 Freedom from valve related death; 
4.2.1.3 Freedom from structural valve deterioration. 

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5 PATIENT SELECTION CRITERIA 
5.1 
PATIENT ENROLLMENT 
A patient who meets all the inclusion criteria and does not meet any of the exclusion 
criteria is eligible to participate in the investigation. A patient is enrolled in the 
investigation only when s/he has provided written informed consent. Once enrolled, a 
patient is expected to comply with the scheduled visits and required activities 
according to the protocol. 
5.2 
INCLUSION CRITERIA 
5.2.1 Patients implanted for less than 9 months, or candidate for implantation with 
a St Jude Medical Trifecta valve, as per current guidelines; 
5.2.2 Patient requires aortic valve replacement. (Note: patients undergoing 
concomitant 
procedures, 
e.g. 
coronary 
artery 
bypass 
grafting, 
supracoronary replacement of ascending aorta, mitral valve repair, tricuspid 
valve repair, atrial fibrillation ablation, patients that had previous aortic valve 
replacement or CABGs are eligible for this study). 
5.2.3 Patient is legal age in host country. 
5.2.4 Patients must be able and willing to provide written informed consent to 
participate in this investigation; and 
5.2.5 Patients must be willing and able to comply with all follow-up requirements. 

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5.3 
EXCLUSION CRITERIA 
5.3.1 Patients with contraindication for cardiac surgery; 
5.3.2 Patients who are pregnant. 
5.3.2.1 Pregnancy will be assessed by patients informing the physicians. 
5.3.3 Patient is unwilling to or has an inability that reduces his mobility in order to 
attend the required follow-up visits. 
5.3.4 Patient has active endocarditis (patients with previous endocarditis must 
have two documented negative blood culture results prior to enrollment). 
5.3.5 Patient has had an acute preoperative neurological event defined as patient 
has not returned to baseline 30 days prior to the planned valve implantation 
surgery. 
5.3.6 Patient is undergoing renal dialysis. 
5.3.7 Patient has a documented history of substance abuse within one year of 
enrollment or is currently a prison inmate. 
5.3.8 Patient has a documented thrombus in left atrium or left ventricle. 
5.3.9 Patient had in the past mitral or tricuspid valve replacement. 
5.3.10 Patient needs mitral and/or tricuspid valve replacement. 
5.3.11 Patient has an Ejection Fraction < 25% 
5.3.12 Patient had the Trifecta™ valve implanted as part of this study, but then had 
the device explanted (a patient cannot be enrolled twice in this study). 
5.3.13 Preoperative 
evaluation 
indicates 
other 
significant 
cardiovascular 
abnormalities such as aortic dissection or ventricular aneurysm. 
5.3.14 Patient has a life expectancy less than two years. 

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6 INVESTIGATION DESIGN 
6.1 TYPE
This investigation is a multicenter, prospective, observational study. 
6.2 
DURATION 
6.2.1 The first enrollment is anticipated in 2010. 
6.2.2 The enrollment period will be approximately 15 months. 
6.2.3 The patient will participate in this investigation for approximately 10 years 
from enrollment to the last follow-up. 
6.2.4 The patient may withdraw from the investigation at any time, for any reason. 
In this case, the procedures for reporting should be followed as mentioned 
in the section 0 Early Conclusion to Patient Participation. 
6.3 
ENROLLMENT TARGET 
6.3.1 The enrollment target for this investigation is 801 patients. For more 
information, refer to section 8.1 Sample Size Justification. 
6.4 
DESIGN 
Implant and until 9 months 
post-implant 
1 Year 
2 Years 
3 Years 
4 Years 
5 Years 
9 Years    10 Years 
• Pre-Intervention form 
• Intervention form 
• Discharge form 
• Follow-up form 
• Adverse Event form (if applicable) 
• Death form (if applicable) 
• Echocardiography (if performed) 
FU period (yearly) 
Enrollment 

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7 PRODUCT 
The following market approved St. Jude Medical products are required to be used in 
the investigation: 
7.1.1  The Trifecta valve: 
The Trifecta valve is a tri-leaflet stented pericardial valve designed for supra- 
annular placement in the aortic position. The valve is fabricated using a 
polyester-covered titanium stent. The stent, excluding the sewing cuff, is then 
covered with porcine pericardial tissue. This covering minimizes mechanical 
wear by allowing only tissue-to-tissue contact during valve function. A silicone 
insert within the polyester sewing cuff is contoured to conform to the shape of 
the native annulus. The valve leaflets are fabricated from bovine pericardium. 
The porcine and bovine pericardium are preserved and crosslinked in 
glutaraldehyde. Glutaraldehyde, formaldehyde, and ethanol are used in the 
valve sterilization process. The Trifecta valve is processed using Linx™ anti- 
calcification technology. The Trifecta valve received CE mark in March 2010. 
7.1.2 Trifecta Sizer Set TF2000: 
The Trifecta™ Sizer Set Model TF2000 is a double-ended tool with a 
cylindrical annular sizing end and a valve replica end. The cylindrical annular 
sizing end of the sizer is used to determine the size of the annulus. The 
replica end of the sizer is used to visualize placement of the sewing cuff above 
the annulus and to confirm placement and fit of the valve in the supra annular 
space. Both the cylindrical sizing head and the valve replica head are 
connected to the sizer handle via a bendable section that allows for easier 
access to the aortic anatomy. The UT2000 Holder Handle interfaces with the 
Trifecta valve holder via a click-in mechanism. The holder handle is used to 
transport the valve from the jar and through the valve rinse procedure. In 
addition, the holder handle helps to facilitate valve suturing and delivery of the 
valve into the implant position. 

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8 STATISTICAL ANALYSIS PLAN 
8.1 
SAMPLE SIZE JUSTIFICATION 
8.1.1 The sample size estimation is based on the primary endpoint of this study, 
freedom from reoperation due to SVD at year 10 post implant for patients 
who have the Trifecta valve implanted. 
8.1.2 It is assumed that the expected freedom rate from reoperation due to SVD 
at year 10 post implant will be 96.5%1.52%, in order to establish a one 
side 95% confidence interval for the freedom rate with the lower bound as 
94%, the required number of patients at risk at year 10 post implant is at 
least 142 using non-parametric survival analysis with Peto’s variance. 
Assuming the overall mortality rate will be 39.50% at year 5 and 63.4% at 
year 10, the minimum sample size is 641 patients. 
8.1.3 With 20% drop out rate, in total at least 801 patients need to be recruited. 
8.1.4 Taking into account the effect of learning curve of the surgeons, the first 3 
patients implanted by each surgeon without any experience with the 
Trifecta valve are not counted as part of the sample size. 
8.2 
ENDPOINT ANALYSIS 
8.2.1 
Non-parametric survival analysis will be used to calculate the freedom 
rate(S) from reoperation due to SVD at year 10 post implant and the 
corresponding variance (Vars) will be computed with Peto’s formula for 
survival analysis. i   The lower bound of the 95% confidence interval for S 
will be calculated using the formula S-Z0.5 * (Vars) ½. If the lower bound of
S is bigger than or equal to 94%, then the expected estimate is confirmed. 
The survival time will be calculated as the number of days from implant 
date to reoperation date due to SVD. A Kaplan-Meier curve with the 
cumulative survival rate will also be presented. 
8.2.2 A Cox regression model will be used to further investigate the effects of 
the factors on the primary endpoint. These factors include baseline factors 
such as learning curve (1, 2, 3, >3), age, gender, NYHA Class etc.. 
8.3 
ADDITIONAL DATA 
8.3.1 For the time to event data, survival analysis will be used to estimate the 
survival rate and 95% confidence interval, and a Kaplan Meier curve will 
also be presented. 
8.3.2 Continuous data will be summarized with mean, standard deviation, 
median and range. Frequency and percentage will be reported for all 
categorical data. 
i Reference : Alan B cantor , SAS survival analysis techniques for medical research 

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9 PROTOCOL DESCRIPTION 
9.1 
PROTOCOL PROCEDURES - OVERVIEW 
Table 1 – Protocol Procedure Overview 
These activities are applicable to all patients. 
(*) This is only when available 
(**) This is only to be performed when applicable. 
When 
Window 
Activities 
Pre-Intervention 
Not Applicable • Patient Eligibility
• Patient Informed Consent
• Patient Demographics & Physical Examination
• Patient Cardiovascular History
• Patient Current Cardiac Medications
• Patient Medical History
• Echo (*)
Intervention 
(+baseline) 
Not Applicable • Aortic Valve Replacement Information
• Operative Information
• Adverse Events(**)
• Echo (*)
Pre-discharge 
Not Applicable • Patient Current Cardiac Medications
• Adverse Events(**)
• Echo (*)
Yearly follow-up Yearly 
<30 days 
>61 days 
• Patient Current Cardiac Medications
• Adverse Events (**)
• Echo (*)
9.2 
ADVERSE EVENTS 
9.2.1 Definition of Adverse Event, Adverse Device Effect, Serious Adverse Event 
and Serious Adverse Device effect according to ISO 14155: 
9.2.1.1 Adverse Event (AE) is defined as any untoward medical 
occurrence in a patient or clinical investigation patient. 
9.2.1.1.1 This definition does not necessarily imply that there is a 
causal relationship between the adverse event and the 
device under investigation. 
9.2.1.2 Adverse Device Effect (ADE) is defined as any untoward and 
unintended response to a medical device. This definition includes 
any  event  resulting  from  insufficiencies  or  inadequacies  in  the 

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instructions for use or the deployment of the device. It also 
includes any event that is a result of a user error. 
9.2.1.2.1  Valve-related adverse events 
Valve-related adverse events will be defined according to the 
definitions included in the current available guidelines: Akins CW, 
Miller CD, Marko I. Turina MI, Kouchoukos NT, Blackstone EH, 
Grunkemeier GL, Takkenberg JJM, David TE, Butchart EG,. 
Adams DH, David M. Shahian DM, Hagl S, Mayer JE , Lytle BW. 
Guidelines for reporting mortality and morbidity after cardiac valve 
interventions. EJCTS 33 528 (2008) 523—528. 
9.2.1.3 Serious Adverse Event (SAE) is defined as an adverse event 
that: 
9.2.1.3.1 Led to death; 
9.2.1.3.2 Led to a serious deterioration in the health of a patient 
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; and
•
Resulted in medical or surgical intervention to
prevent permanent impairment to a body structure
or a body function.
9.2.1.3.3 Led  to  foetal  distress,  foetal  death  or  a  congenital 
abnormality or birth defect. 
9.2.1.4 Serious Adverse Device Effect (SADE) is defined as an adverse 
device effect that has resulted in any of the consequences 
characteristic of a serious adverse event or that might have led to 
any of these consequences if suitable action had not been taken or 
intervention had not been made or if circumstances had been less 
opportune. 
9.2.2 List of Anticipated Adverse Events and Adverse Device Effects: 
The following represents a list of anticipated Adverse Events (AE) and 
Adverse Device Effects (ADE) experienced in either animal and/or clinical 
studies to date with aortic valve replacement operations, or reported in 
instructions for use and literature. Anticipated Adverse Events (AE) and 
Adverse Device Effects (ADE) include: Angina (chest pain), Cardiac 
arrhythmias, Bleeding events (including pre-operative bleeds), Death (valve 
and non-valve related), embolism, endocarditis, explant, hearth failure, 
hemolysis, 
haemolytic 
anemia, 
myocardial 
infarction, 
non-structural 
dysfunction, paravalvular leak, valve regurgitation, reoperation, stroke, 
structural deterioration, valve thrombosis, valvular pannus. 

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9.2.3 Procedure for Recording and Reporting Adverse Events 
9.2.3.1 Safety surveillance and reporting will be done for all patients 
enrolled in the investigation. 
9.2.3.2 Safety surveillance and reporting starts at the time when the 
patient is enrolled into the investigation (date of signature of the 
informed consent) until the last investigational visit has been 
performed, or the patient has died, or the patient concludes his 
participation into the study. 
9.2.3.2.1 All Serious Adverse Events and all Adverse Device 
Effects are to be documented and reported to the 
sponsor immediately. 
9.2.3.2.2 Non-Serious Adverse Events documentation and 
reporting 
are 
limited 
to 
cardiovascular 
and 
neurovascular events. 
9.2.3.3 Should an AE occur, record AE information in the hospital records, 
document the information into the Adverse Event case report form 
(CRF) as soon as possible. By completing the CRF the sponsor 
will be notified. 
9.2.3.3.1 Refer to appendices “Data Collection” and “Data 
Collection Method”. 
9.2.3.3.2 Access the eCRF application. 
9.2.3.3.3 
Select the visit the AE is related to or indicate it as 
unscheduled visit. 
9.2.3.3.4 Enter 
adverse 
event 
information 
into 
the 
AE 
Notification section of the CRF. 
•
Date the AE occurred;
•
Date  the  center  investigator  or  delegate  became
aware of the AE;
•
Main complaints/symptoms of the AE;
•
Initial diagnosis of the AE;
•
Potential cause of the AE;
•
Pre-existing medical conditions related to the AE;
•
Seriousness of the AE;
•
Device relationship to AE; and
•
Status of the AE.
9.2.3.3.5 The CRF must be authorized by the principal 
investigator or delegated co-investigator. 
9.2.3.3.6 Submit the CRF. When the CRF is submitted, an alert is 
generated notifying the sponsor. 

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9.2.3.3.7 As soon as the final details are available for the adverse 
event, the information should be reported on the AE 
Follow-Up section of the CRF. 
9.2.3.3.8 Access the eCRF application. 
9.2.3.3.9 Edit AE CRF, document information into the AE Follow- 
Up section of the case report form. 
•
Hospitalization details (if applicable);
•
Diagnostic test information (if applicable);
•
Treatment given (if applicable);
•
Final medical diagnosis & cause;
•
Patient condition;
•
Final AE status;
•
Seriousness of AE based on final medical diagnosis
and cause;
•
Relationship of AE to device based on final medical
diagnosis & cause.
9.2.3.3.10 The CRF must be authorized by the principal 
investigator or delegated co-investigator. 
9.2.3.3.11 Submit the CRF. 
9.2.3.4 Additional information will be requested, if necessary, by the 
Sponsor for reporting of AEs to regulatory authorities. 
9.2.3.5 The investigator must notify the EC or IRB, if appropriate, in 
accordance with national and local laws and regulations. 
NOTE: If an adverse event is documented at the patient’s last follow up visit (10 
years), both the notification and follow-up information on the AE CRF are to 
be provided to the sponsor.  
Pre-existing cardiac conditions that require planned hospitalization are not 
to be considered as AE. 
9.3 Patient Death 
9.3.1 Procedure for Recording and Reporting Patient Death 
9.3.1.1 Safety surveillance and reporting will be done for all patients 
enrolled in the investigation. 
9.3.1.2 Safety surveillance and reporting starts at the time when the 
patient is enrolled into the investigation (date of signature of the 
informed consent) until the last investigational visit has been 
performed. 

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9.3.1.2.1 All Patient Deaths are to be documented and reported 
to the sponsor immediately. 
9.3.1.3 Should death occur, record death information in the hospital 
records, immediately document the information in the Death case 
report form (CRF). By completing the CRF the sponsor will be 
notified. 
9.3.1.3.1 Refer   to   appendices   “Data   Collection”   and   “Data 
Collection Method”. 
9.3.1.3.2 Access the eCRF application. 
9.3.1.3.3 Select the visit the patient death is related to or indicate 
it as visit unscheduled visit. 
9.3.1.3.4 Enter patient death information into the Patient Death 
CRF. 
•
Date the death occurred;
•
Date the center investigator or delegate became
aware of the death;
•
Place where death occurred (e.g. hospital, nursing
home, patient’s home);
•
If death was witnessed;
•
If autopsy was performed;
•
If the Trifecta Valve was returned to SJM? If not,
reason should be specified.
•
Temporal cause of death
•
Primary cause of death including if death was
caused by valve-related complications (hemolysis,
bleeding 
event, 
structural 
valve 
deterioration,
endocarditis, 
non-structural 
dysfunction, 
valve
reoperation, embolism, sudden unexplained, valve
thrombosis)
•
Details regarding death; and
•
If details of serious adverse event associated to the
death 
are 
known 
by 
the
center/investigator/delegate.
9.3.1.3.5 
The 
CRF must be authorized by 
the 
principal 
investigator or delegated co-investigator. 
9.3.1.3.6 Submit the CRF. When the CRF is submitted, an alert is 
generated notifying the sponsor. 

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9.3.1.4 Patient death may be an outcome of a serious adverse event 
(SAE). If the death is related to a SAE, all the efforts to get SAE 
details should be made and the Adverse Event CRF must be 
completed. 
9.3.1.5 Patient death is an early conclusion to the patient’s participation in 
the investigation. Complete Termination CRF. 
9.3.1.6 The investigator must notify the EC or IRB, if appropriate, in 
accordance with national and local laws and regulations. 
9.4 
EARLY CONCLUSION TO PATIENT PARTICIPATION 
9.4.1 All reasonable efforts should be made to retain the patient in the clinical 
investigation until completion of the clinical investigation. 
9.4.2 If a patient concludes their participation in the investigation, the patient’s 
future medical care will not be influenced by this decision, whether it is 
voluntary or otherwise, 
9.4.2.1 A patient/family member may request to withdraw from the 
investigation at any time; She/he would be able to do so without 
having to justify it and without affecting her/his relationship with the 
investigator. 
9.4.2.2 An investigator may withdraw a patient from the investigation at 
any time if she/he thinks it is in the patient’s best interest; or 
9.4.2.3 An investigator may withdraw a patient, if the patient does not 
come for their scheduled visits and/or is not compliant with the 
regimen of the protocol. This patient will be considered “lost to 
follow-up”; A patient will be considered “lost to follow-up” when 3 
attempts to contact the patient were unsuccessful: A minimum of 2 
documented 
phone 
calls 
by 
a 
physician/delegate 
to 
the 
patient/emergency contact and a certified letter sent to the last 
known address. 
9.4.2.4 The Investigation is temporarily stopped or terminated, either at the 
local, national or international level, at the request of Ethics 
Committees, Competent Authorities, Departments of Health or the 
investigational Sponsor. 
9.4.2.5 
A patient dies. Refer to section 9.3, “Patient Death”; 
9.4.3 Should a patient withdraw and conclude participation in the investigation, 
document the information in the Termination case report form (CRF) as 
soon as possible. By completing the CRF the sponsor will be notified. 
9.4.3.1 Refer to appendices “Data Collection” and “Data Collection 
Method”. 
9.4.3.2 Access the eCRF application. 

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9.4.3.3 
Select the visit the patient death is related to or indicate it as visit 
unscheduled visit. 
9.4.3.4 Enter  patient  early  conclusion  information  into  the  Termination 
CRF. 
•
Date the early conclusion occurred; and
•
Reason for the early conclusion;
9.4.4 The CRF must be authorized by the principal investigator or delegated co- 
investigator. 
9.4.5 Submit the CRF. When the CRF is submitted, an alert is generated notifying 
the sponsor. 
9.5 
DEVIATIONS 
9.5.1 Investigators are required to adhere to the Clinical Investigational Plan, the 
signed Investigator’s Agreement, applicable national or local laws and 
regulations, and any conditions required by the appropriate Ethics 
Committees or applicable regulatory authorities. 
9.5.2 A Deviation is defined as a situation in which there is a non-compliance with 
the protocol. 
9.5.3 Anticipated deviations: 
9.5.3.1 Patient Informed Consent is not approved by Ethics Committee; 
9.5.3.2 Patient Informed Consent is not signed and/or dated by the patient 
and/or investigator; 
9.5.3.3 Study  specific  procedure  was  performed  before  the  Patient 
Informed Consent was signed and dated by patient; 
9.5.3.4 Investigational Required Visit not performed; 
9.5.3.5 
Investigational Required Visit performed outside the visit window; 
9.5.4 Should a deviation occur, document the information in the Deviation case 
report form (CRF). By completing the CRF the sponsor will be notified. 
NOTE: When a deviation occurs after enrollment for patient consent, 
record the information in the hospital record, immediately document 
the information in the Deviation and Termination case report  form 
(CRF). By completing the CRF the sponsor will be notified. 
o
Refer to appendices “Data Collection” and “Data Collection
Method”.
o
Access the eCRF application.
o
Select  the  scheduled  or  unscheduled  visit  to  which  the
deviation is related.
o
Enter deviation information into the Termination CRF.
•
Date of deviation

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•
When the deviation occurred
•
Type of deviation
•
Medical justification
o
The CRF must be authorized by the principal investigator or
delegated co-investigator.
o
Submit the CRF. When the CRF is submitted, an alert is
generated notifying the sponsor.
When a deviation occurs after enrollment for patient eligibility, record 
the information in the hospital record, immediately document the 
information in the Deviation case report form (CRF). By completing the 
CRF the sponsor will be notified. All the efforts should be made to 
keep the patient in the study. 
The investigator must notify the EC or IRB, if appropriate, in 
accordance with national and local laws and regulations. 
9.6 
ENROLLMENT 
9.6.1 Enrollment activities are performed after patients are screened and may 
occur prior to or at the same time as the baseline visit. 
9.6.2 The site should maintain a Patient Screening Log, accounting for the 
patients who are and are not eligible for the investigation. All patients that 
are considered for this investigation, should be mentioned on this Patient 
Screening Log. 
9.6.3 A patient who meets the inclusion criteria and does not meet the exclusion 
criteria is eligible to participate in the investigation. 
9.6.3.1 
If a patient does not meet inclusion or meets exclusion criteria 
cannot participate in the investigation. 
9.6.4 Inform the eligible patient about the investigation and provide the informed 
consent form to the patient. 
9.6.4.1 The process of obtaining written consent from an eligible patient 
needs to comply with the Declaration of Helsinki, International 
Standards Organization (ISO) 14155-1 and applicable local laws 
and regulations. 
9.6.5 Obtain the signature and date from the eligible patient on the ethics 
committee (EC) approved informed consent form. 
9.6.5.1 If the eligible patient cannot sign and date the EC approved 
informed consent him/herself then refer to ISO 14155-1 regarding 
alternatives for obtaining signature on the informed consent. 
9.6.5.2 If an eligible patient does not sign and date the informed consent, 
s/he cannot participate in the investigation. No further protocol 
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9.6.6 Obtain the signature and date from the principal investigator or delegate on 
the ethics committee (EC) approved informed consent form. 
9.6.7 The patient is enrolled in the investigation when both the patient and 
investigator signed/dated the informed consent. 
9.6.7.1 If there are deviations with regards to obtaining informed consent, 
notify the EC/IRB appropriately. 
9.6.8 Provide one original signed and dated copy by patient and the principal 
investigator or delegate to the patient. 
9.6.9 File the second original appropriately in the Investigator Study Binder (ISB). 
9.6.10 
Record enrollment information (name of the investigation, consent and 
inclusion/exclusion criteria) in the hospital records, complete the 
Enrollment Case Report Form. Every effort will be made to notify the 
sponsor within 5 working days of enrollment. The CRF must be authorized 
by the principal investigator or delegate. 
9.6.10.1 
Refer to “Appendix Data Collection” for access and information 
regarding patient data collected for this investigation. 
9.7 
BASELINE VISIT (INTERVENTION) 
9.7.1 All Baseline activities are performed after the patient is enrolled in the 
investigation and no more than 30 days prior to undergoing cardiac surgery 
procedure. 
9.7.2 The following information will be collected at the baseline visit either from 
hospital records or through patient interaction documented in the hospital 
records: 
9.7.2.1 Patient Demographics & Physical Examination 
•
Collect the age;
•
Collect the gender;
•
Provide the most recent value (within the last month) of the
patient height;
•
Provide the most recent value (within the last month) of the
patient weight;
9.7.2.2 Patient Cardiovascular History 
•
Provide the most recent value (within the last month) of the
New York Heart Association (NYHA) classification;
9.7.2.3 Patient Anticoagulant/Antiplatelet Medication 
•
Identify the Anticoagulant/Antiplatelet medications the patient is
taking currently;

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9.7.2.4 Patient Medical History 
•
Indicate   the pre-existing cardiac   conditions and cardiac
procedures; and
•
Indicate the relevant non-cardiac medical conditions.
9.7.2.5 Baseline echo data (if available) 
•
Provide the most recent values (within the last month) of the
specified echo variables;
9.7.2.6 Aortic Valve Replacement Information 
•
Indicate the details about valve being replaced (type, etiology,
pathology, ect..)
9.7.2.7 Operative Information 
•
Indicate the details about valve replacement (suture technique,
implanting surgeon and experience, details about Trifecta valve
implanted and concomitant procedures).
9.7.2.8 Refer to “Appendix Data Collection” for access and information 
regarding patient data collected for this investigation. 
9.7.3 Adverse Event (when applicable) 
9.7.3.1 Check if any adverse event or adverse device effect occurred. 
9.7.3.2 Report the adverse event according to specifications in section 
“Adverse Event”. 
9.8 PRE-DISCHARGE VISIT
9.8.1 The following information will be collected at the pre-discharge visit either 
from hospital records or through patient interaction (documented in the 
hospital records): 
9.8.1.1 Patient Cardiac Medication 
•
Provide information on cardiac medication;
9.8.1.2 Echocardiography (if available) 
•
Provide pre-discharge echo data;
9.8.2 Record the pre-discharge information in the hospital records and complete 
the Follow Up Case Report Form (CRF). 
9.8.3 Adverse Event (when applicable) 
9.8.3.1 Check if any adverse events or adverse device effect occurred 
since the last visit and document this in the hospital records. 
9.8.3.2 Report the adverse event according to specifications in section 
“Adverse Event” of the Case Report Form (CRF). 
9.8.4 Patient Death (when applicable) 

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9.8.4.1 If the patient died before hospital discharge, report it immediately 
to the sponsor as indicated in section “Patient Death”. 
9.8.5 Early Withdrawal (when applicable) 
9.8.5.1 If the patient decides to withdraw from the investigation for 
whatever reason, report this immediately to the sponsor as 
indicated in section "Early conclusion to patient participation". 
9.8.6 Refer to “Appendix Data Collection” for access and information regarding 
patient data collected for this investigation. 
9.9 
PROTOCOL REQUIRED FOLLOW-UP 
9.9.1 Scheduled visits will occur yearly over 10 years after the implant date. The 
follow up will occur in the outpatient department of each participating 
institution or, if not possible, by telephone contact with the patient. 
9.9.2 The Follow Up schedule is summarized in Table 1. 
9.9.3 The following information will be collected at the follow up visit either from 
hospital records or through patient interaction (documented in the hospital 
records): 
9.9.3.1 Provide the most recent value (within the last month) of the New 
York Heart Association (NYHA) classification; 
9.9.3.2 Patient Cardiac Current Medication 
•
Provide information on cardiac medication therapy.;
9.9.3.3 Echocardiography (if available) 
•
Provide follow-up echo data (echo date must be in the follow-
up window);
9.9.4 Record the follow up information in the hospital records and complete the 
Follow Up Case Report Form (CRF). 
9.9.5 Adverse Event (when applicable) 
9.9.5.1 Check with the patient if any adverse events or adverse device 
effect occurred since the last visit and document this in the hospital 
records. 
9.9.5.2 Report the adverse event according to specifications in section 
“Adverse Event” of the Case Report Form (CRF). 
9.9.6 Patient Death (when applicable) 
9.9.6.1 If the patient died before the visit took place, report it immediately 
to the sponsor as indicated in section “Patient Death”. 
9.9.7 Early Withdrawal (when applicable) 
9.9.7.1 If the patient decides to withdraw from the investigation for 
whatever reason, report this immediately to the sponsor as 
indicated in section "Early conclusion to patient participation". 
9.9.8 Refer to “Appendix Data Collection” for access and information regarding 
patient data collected for this investigation. 

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10 RISK DESCRIPTION AND MINIMIZATION 
10.1 
POTENTIAL BENEFITS
Potential benefits to the patients may include, but are not limited to, relief of valvular 
stenosis and/or incompetence and related symptoms. A patient may benefit from the 
improved longevity of the valve, due to the Linx™ treatment of the Trifecta valve (if 
the Linx™ treatment is proven effective). The patient will be monitored throughout the 
duration of the clinical study. Patients will be evaluated at pre-determined time points 
to assess their status. In addition, similar benefits may accrue to future subjects 
through experience gained in this clinical study. 
10.2 
POTENTIAL RISKS
It is expected that the study related procedures: clinical assessment and the 
determination of the NYHA classification entail no additional risks to the patient other 
than those commonly associated with the follow-up of patients who have had a 
prosthetic heart valve implanted. 
11 ETHICAL BASIS
This investigation will be performed in accordance with the World Medical Association 
Declaration of Helsinki (appendix C), ISO 14155 and all local legal and regulatory 
requirements. 
Prior to the start of the investigation, the clinical investigational plan will be submitted 
together with its associated documents (patient information sheets, patient informed 
consent forms in the local language) to the relevant Ethics Committee (EC) / 
Institutional Review Board (IRB) for review. 
EC/IRB approval document should clearly identify 
•
the date of the meeting,
•
constitution of the committee and voting members present at the meeting
•
the approved version of the clinical investigational plan CIP
•
the approved version of the patient information and informed consent.
Approval from the EC/ IRB is necessary prior to the start of the investigation. The 
original approval is to be filed in the Investigator Study Binder and a copy of the 
approval is provided to St. Jude Medical prior to the first investigational assessment. 
Any amendments to the protocol should be submitted to the relevant EC/IRB. 
EC/IRB will be informed about SAEs and UADEs in accordance with local  and 
national requirements. 

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APPENDIX A: ABBREVIATIONS 
Abbreviation 
Description 
ACC 
American College of Cardiology 
ADE 
Adverse Device Effect 
AE 
Adverse Event 
AF 
Atrial Fibrillation 
AHA 
American Heart Association 
AVR 
Aortic Valve Replacement 
CA 
Competent Authority 
CABG 
Coronary Artery Bypass Grafting 
CIP 
Clinical Investigation Plan 
CPL 
Clinical Projects Leader 
CRA 
Clinical Research Associate 
CV 
Cardiovascular 
CRF 
Case Report Form 
EC 
Ethics Committee 
eCRF 
Electronic Case Report Form 
FU 
Follow Up 
INR 
International Normalized Ratio 
IFU 
Instruction for Use 
IRB 
Institutional Review Board 
ISB 
Investigator Study Binder 
PIC 
Patient Informed Consent 
SAE 
Serious Adverse Event 
SMF 
Site Master File 
SOP 
Standard Operating Procedures 
SVD 
Structural Valve Deterioration 
SJM 
St. Jude Medical 

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APPENDIX B: REFERENCES 
1.
American Heart Association. Heart Disease and Stroke Statistics – 2005 Update.
Dallas, Texas.: American Heart Association 2005. 
2.
Bonow RO, Carabello B, de Leon AC Jr, et al. ACC/AHA Guidelines for the
Management of Patients with Valvular Heart Disease. J Am Coll Cardiol 
1998;32:1486-588. 
3.
Werner JA,  Crawford MH. 
Choosing  a Prosthetic Heart Valve.  Cardiol Clin.
1998;16:491-504. 
4.
Fann JI, Burdon TA. Are the Indications for tissue valves different in 2001 and
how do we communicate these changes to our cardiology colleagues? Curr 
Opin Cardiol. 2001;16:126-35. 
5.
Cartier PC, Metras J, Dumesnil JG, Pibarot P, Lemieux M. Midterm Follow-up of
Unstented Biological Valves. Seminars in Thoracic and Cardiovascular 
Surgery 1999;11:22-7. 
6.
Fradet G, Bleese N, Busse E, Jamieson E, Raudkivi P, Goldstein J, Metras J.
The Mosaic Valve Clinical Performance at Seven Years: Results from a 
Multicenter Prospective Clinical Trial. J Heart Valve Dis 2004;13:239-47. 
7.
iAkins CW, Miller CD, Marko I. Turina MI, Kouchoukos NT, Blackstone EH,
Grunkemeier GL, Takkenberg JJM, David TE, Butchart EG,.  Adams  DH, 
David M. Shahian DM, Hagl S, Mayer JE , Lytle BW. Guidelines for reporting 
mortality and morbidity after cardiac valve interventions. EJCTS 33 528 (2008) 
523—528 
8.
Alan B Cantor , SAS survival analysis techniques for medical research, page 17-
25. 
9.
NCSS, PASS User ‘s Guide III, 700 single log rank – 705 advanced log rank.

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APPENDIX C: DECLARATION OF HELSINKI 
WORLD MEDICAL ASSOCIATION DECLARATION OF HELSINKI 
Ethical Principles for Medical Research Involving Human Subjects 
Adopted by the 18th WMA General Assembly, Helsinki, Finland, June 1964, and amended by 
the: 
29th WMA General Assembly, Tokyo, Japan, October 1975 
35th WMA General Assembly, Venice, Italy, October 1983 
41st WMA General Assembly, Hong Kong, September 1989 
48th WMA General Assembly, Somerset West, Republic of South Africa, October 1996 
52nd WMA General Assembly, Edinburgh, Scotland, October 2000 
53rd WMA General Assembly, Washington 2002 (Note of Clarification on paragraph 29 
added) 
55th WMA General Assembly, Tokyo 2004 (Note of Clarification on Paragraph 30 added) 
59th WMA General Assembly, Seoul, October 2008 
A. INTRODUCTION 
1.
The World Medical Association (WMA) has developed the Declaration of Helsinki
as a statement of ethical principles for medical research involving human 
subjects, including research on identifiable human material and data. 
The Declaration is intended to be read as a whole and each of its constituent 
paragraphs should not be applied without consideration of all other relevant 
paragraphs. 
2.
Although the Declaration is addressed primarily to physicians, the WMA
encourages other participants in medical research involving human subjects to 
adopt these principles. 
3.
It is the duty of the physician to promote and safeguard the health of patients,
including those who are involved in medical research. The physician's 
knowledge and conscience are dedicated to the fulfilment of this duty. 
4.
The Declaration of Geneva of the WMA binds the physician with the words, “The
health of my patient will be my first consideration,” and the International Code of 
Medical Ethics declares that, “A physician shall act in the patient's best interest 
when providing medical care.” 
5.
Medical progress is based on research that ultimately must include studies
involving human subjects. Populations that are underrepresented in medical 
research should be provided appropriate access to participation in research. 
6.
In medical research involving human subjects, the well-being of the individual
research subject must take precedence over all other interests. 
7.
The primary purpose of medical research involving human subjects is to
understand the causes, development and effects of diseases and improve 
preventive, diagnostic and therapeutic interventions (methods, procedures and 
treatments). Even the best current interventions must be evaluated continually 
through research for their safety, effectiveness, efficiency, accessibility and 
quality. 

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8.
In medical practice and in medical research, most interventions involve risks and
burdens. 
9.
Medical research is subject to ethical standards that promote respect for all
human subjects and protect their health and rights. Some research populations
are particularly vulnerable and need special protection. These include those who
cannot give or refuse consent for themselves and those who may be vulnerable to
coercion or undue influence.
10. Physicians should consider the ethical, legal and regulatory norms and standards
for research involving human subjects in their own countries as well as applicable
international norms and standards. No national or international ethical, legal or
regulatory requirement should reduce or eliminate any of the protections for
research subjects set forth in this Declaration.
B. PRINCIPLES FOR ALL MEDICAL RESEARCH 
11. It is the duty of physicians who participate in medical research to protect the life,
health, dignity, integrity, right to self-determination, privacy, and confidentiality of
personal information of research subjects.
12. Medical research involving human subjects must conform to generally accepted
scientific principles, be based on a thorough knowledge of the scientific literature,
other relevant sources of information, and adequate laboratory and, as
appropriate, animal experimentation. The welfare of animals used for research
must be respected.
13. Appropriate caution must be exercised in the conduct of medical research that
may harm the environment.
14. The design and performance of each research study involving human subjects
must be clearly described in a research protocol. The protocol should contain a
statement of the ethical considerations involved and should indicate how the
principles in this Declaration have been addressed. The protocol should include
information regarding funding, sponsors, institutional affiliations, other potential
conflicts of interest, incentives for subjects and provisions for treating and/or
compensating subjects who are harmed as a consequence of participation in the
research study. The protocol should describe arrangements for post-study access
by study subjects to interventions identified as beneficial in the study or access to
other appropriate care or benefits.
15. The research protocol must be submitted for consideration, comment, guidance
and approval to a research ethics committee before the study begins. This
committee must be independent of the researcher, the sponsor and any other
undue influence. It must take into consideration the laws and regulations of the
country or countries in which the research is to be performed as well as applicable
international norms and standards but these must not be allowed to reduce or
eliminate any of the protections for research subjects set forth in this Declaration.
The committee must have the right to monitor ongoing studies. The researcher
must provide monitoring information to the committee, especially information
about any serious adverse events. No change to the protocol may be made
without consideration and approval by the committee.
16. Medical research involving human subjects must be conducted only by individuals
with the appropriate scientific training and qualifications. Research on patients or

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healthy volunteers requires the supervision of a competent and appropriately 
qualified physician or other health care professional. The responsibility for the 
protection of research subjects must always rest with the physician or other health 
care professional and never the research subjects, even though they have given 
consent. 
17. Medical research involving a disadvantaged or vulnerable population or
community is only justified if the research is responsive to the health needs and
priorities of this population or community and if there is a reasonable likelihood
that this population or community stands to benefit from the results of the
research.
18. Every medical research study involving human subjects must be preceded by
careful assessment of predictable risks and burdens to the individuals and
communities involved in the research in comparison with foreseeable benefits to
them and to other individuals or communities affected by the condition under
investigation.
19. Every clinical trial must be registered in a publicly accessible database before
recruitment of the first subject.
20. Physicians may not participate in a research study involving human subjects
unless they are confident that the risks involved have been adequately assessed
and can be satisfactorily managed. Physicians must immediately stop a study
when the risks are found to outweigh the potential benefits or when there is
conclusive proof of positive and beneficial results.
21. Medical research involving human subjects may only be conducted if the
importance of the objective outweighs the inherent risks and burdens to the
research subjects.
22. Participation by competent individuals as subjects in medical research must be
voluntary. Although it may be appropriate to consult family members or
community leaders, no competent individual may be enrolled in a research study
unless he or she freely agrees.
23. Every precaution must be taken to protect the privacy of research subjects and
the confidentiality of their personal information and to minimize the impact of the
study on their physical, mental and social integrity.
24. In medical research involving competent human subjects, each potential subject
must be adequately informed of the aims, methods, sources of funding, any
possible conflicts of interest, institutional affiliations of the researcher, the
anticipated benefits and potential risks of the study and the discomfort it may
entail, and any other relevant aspects of the study. The potential subject must be
informed of the right to refuse to participate in the study or to withdraw consent to
participate at any time without reprisal. Special attention should be given to the
specific information needs of individual potential subjects as well as to the
methods used to deliver the information. After ensuring that the potential subject
has understood the information, the physician or another appropriately qualified
individual must then seek the potential subject’s freely-given informed consent,
preferably in writing. If the consent cannot be expressed in writing, the non-written
consent must be formally documented and witnessed.

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25. For medical research using identifiable human material or data, physicians must
normally seek consent for the collection, analysis, storage and/or reuse. There
may be situations where consent would be impossible or impractical to obtain for
such research or would pose a threat to the validity of the research. In such
situations the research may be done only after consideration and approval of a
research ethics committee.
26. When seeking informed consent for participation in a research study the physician
should be particularly cautious if the potential subject is in a dependent
relationship with the physician or may consent under duress. In such situations
the informed consent should be sought by an appropriately qualified individual
who is completely independent of this relationship.
27. For a potential research subject who is incompetent, the physician must seek
informed consent from the legally authorized representative. These individuals
must not be included in a research study that has no likelihood of benefit for them
unless it is intended to promote the health of the population represented by the
potential subject, the research cannot instead be performed with competent
persons, and the research entails only minimal risk and minimal burden.
28. When a potential research subject who is deemed incompetent is able to give
assent to decisions about participation in research, the physician must seek that
assent in addition to the consent of the legally authorized representative. The
potential subject’s dissent should be respected.
29. Research involving subjects who are physically or mentally incapable of giving
consent, for example, unconscious patients, may be done only if the physical or
mental condition that prevents giving informed consent is a necessary
characteristic of the research population. In such circumstances the physician
should seek informed consent from the legally authorized representative. If no
such representative is available and if the research cannot be delayed, the study
may proceed without informed consent provided that the specific reasons for
involving subjects with a condition that renders them unable to give informed
consent have been stated in the research protocol and the study has been
approved by a research ethics committee. Consent to remain in the research
should be obtained as soon as possible from the subject or a legally authorized
representative.
30. Authors, editors and publishers all have ethical obligations with regard to the
publication of the results of research. Authors have a duty to make publicly
available the results of their research on human subjects and are accountable for
the completeness and accuracy of their reports. They should adhere to accepted
guidelines for ethical reporting. Negative and inconclusive as well as positive
results should be published or otherwise made publicly available. Sources of
funding, institutional affiliations and conflicts of interest should be declared in the
publication. Reports of research not in accordance with the principles of this
Declaration should not be accepted for publication.

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C. ADDITIONAL PRINCIPLES FOR MEDICAL RESEARCH COMBINED WITH 
MEDICAL CARE 
31. The physician may combine medical research with medical care only to the extent
that the research is justified by its potential preventive, diagnostic or therapeutic
value and if the physician has good reason to believe that participation in the
research study will not adversely affect the health of the patients who serve as
research subjects.
32. The benefits, risks, burdens and effectiveness of a new intervention must be
tested against those of the best current proven intervention, except in the
following circumstances:

The use of placebo, or no treatment, is acceptable in studies where no current
proven intervention exists; or

Where for compelling and scientifically sound methodological reasons the use
of placebo is necessary to determine the efficacy or safety of an intervention
and the patients who receive placebo or no treatment will not be subject to
any risk of serious or irreversible harm. Extreme care must be taken to avoid
abuse of this option.
33. At the conclusion of the study, patients entered into the study are entitled to be
informed about the outcome of the study and to share any benefits that result from
it, for example, access to interventions identified as beneficial in the study or to
other appropriate care or benefits.
34. The physician must fully inform the patient which aspects of the care are related
to the research. The refusal of a patient to participate in a study or the patient’s
decision to withdraw from the study must never interfere with the patient-physician
relationship.
35. In the treatment of a patient, where proven interventions do not exist or have been
ineffective, the physician, after seeking expert advice, with informed consent from
the patient or a legally authorized representative, may use an unproven
intervention if in the physician's judgement it offers hope of saving life, re-
establishing health or alleviating suffering. Where possible, this intervention
should be made the object of research, designed to evaluate its safety and
efficacy. In all cases, new information should be recorded and, where appropriate,
made publicly available.