Multi-CenTer Experience With the Rapid Deployment EDWARDS INTUITY Valve System FOR Aortic Valve ReplaceMent
Phase: NA
Conditions: Aortic Valve Stenosis, Aortic Valve Stenosis With Insufficiency, Regurgitation, Aortic Valve, Aortic Valve Incompetence
Sponsor: Edwards Lifesciences

 
 
  Multi-CenTer Experience with the Rapid 
Deployment EDWARDS INTUITY Valve System FOR 
Aortic Valve ReplaceMent (TRANSFORM™ Post 
Approval Phase) 
 
NCT01700439 
 
Study Document Date: 03 November 2017 
 

CLINICAL INVESTIGATION PLAN 
  
TRANSFORMTM Post Approval Phase  
Number: 2011-02 IDE: G110189 / P150036 
 
 
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Version: 3 November 2017, Rev. P 
 
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Edwards 
  Multi-CenTer Experience with the Rapid Deployment EDWARDS 
INTUITY Valve System FOR Aortic Valve ReplaceMent 
(TRANSFORM™ Post Approval Phase) 
Protocol Number: 2011-02  
Version: 3 November 2017, Rev. P 
 
Edwards Lifesciences 
One Edwards Way 
Irvine, CA 92614-5658 
 
 
 
Prepared By: 
 
 
__________________________________________ 
 
_____________ 
 
 
 
 
 
 
 
 
 
Date 
Director, Clinical Affairs 
 
 
Reviewed and Approved By: 
 
 
__________________________________________ 
 
_____________ 
 
 
 
 
 
 
 
 
 
Date 
Vice President, Clinical and Regulatory Affairs 
 
 
__________________________________________ 
 
_____________ 
 
 
 
 
 
 
 
 
 
Date 
Staff Biostatistician – Biostatistics 
 
 
Edwards, Edwards Lifesciences, the stylized E logo, Carpentier-Edwards, PERIMOUNT, ThermaFix, EWARDS INTUITY, and TRANSFORM are 
trademarks owned by Edwards Lifesciences Corporation. All other trademarks are the property of their respective owners. 
 
 

CLINICAL INVESTIGATION PLAN 
  
TRANSFORMTM Post Approval Phase  
Number: 2011-02 IDE: G110189 / P150036 
 
 
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Edwards 
Multi-CenTer Experience with the Rapid Deployment EDWARDS INTUITY 
Valve System FOR Aortic Valve ReplaceMent  
(TRANSFORMTM Post Approval Phase) 
Protocol Number: 2011-02, Version: 3 November 2017, Rev. P 
 
PERSONNEL AND FACILITIES 
Sponsor: 
 
 
 
Edwards Lifesciences 
One Edwards Way 
Irvine, CA 92614-5658 
 
Principal Investigators: 
 
 
 
 
 
 
Trial Director: 
 
 
 
 
Echocardiography Core Lab: 
 
 
 
 
 
 
 
Data Monitoring Committee:  
Chairman:   
 
Members:   
 
 
 
 
 
 
 
 
Clinical Event Committee:   
 
 
 
 
 
 
 
 
 

CLINICAL INVESTIGATION PLAN 
  
TRANSFORMTM Post Approval Phase  
Number: 2011-02 IDE: G110189 / P150036 
 
 
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Edwards 
SIGNATURE PAGE 
Multi-CenTer Experience with the Rapid Deployment EDWARDS INTUITY 
Valve System FOR Aortic Valve ReplaceMent  
(TRANSFORMTM Post Approval Phase) 
Protocol Number: 2011-02, Version: 3 November 2017, Rev. P 
 
Investigator’s Signature 
I have read this protocol and agree to participate in the clinical trialof the EDWARDS 
INTUITY Valve System sponsored by Edwards Lifesciences, LLC.  I agree to conduct this 
trial according to the requirements of the trial protocol and in accordance with Good Clinical 
Practice, applicable State and U.S. Federal regulations and conditions imposed by the 
reviewing Investigational Review Board.  I agree to supervise all sub-investigators at my 
site.   
 
 
 
 
Investigator’s Signature 
 
Date 
 
 
 
Printed Name 
 
 
 
This protocol contains confidential proprietary information with respect to Edwards 
Lifesciences’ products and clinical trials.  I agree to hold this information in confidence and 
not to disclose it to any third parties for a period of five years from the date of this 
agreement, or until this information becomes a matter of public knowledge or until a formal 
agreement for that purpose is entered into by the parties. 
 
 
 
 
Investigator’s Signature 
 
Date 
 

CLINICAL INVESTIGATION PLAN 
  
TRANSFORMTM Post Approval Phase  
Number: 2011-02 IDE: G110189 / P150036 
 
 
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Edwards 
TABLE OF CONTENTS 
PERSONNEL AND FACILITIES ..................................................................................... 2 
SIGNATURE PAGE ........................................................................................................ 3 
SYNOPSIS ..................................................................................................................... 7 
ABBREVIATIONS ..........................................................................................................13 
1.0 
INTRODUCTION .................................................................................................14 
1.1 
BACKGROUND .............................................................................................. 14 
1.2 
EDWARDS INTUITY VALVE SYSTEM .......................................................... 14 
1.2.1 
MODEL 8300ACA/ACD VALVE DIFFERENCES 
17 
1.2.2 
MODEL 8300DCA/DCD DELIVERY SYSTEM DIFFERENCES 
19 
1.3 
MODEL SECTION .......................................................................................... 20 
1.4 
INDICATION FOR USE .................................................................................. 20 
2.0 
TRIAL OBJECTIVES ...........................................................................................20 
2.1 
PRIMARY SAFETY ENDPOINTS ................................................................... 21 
2.2 
EFFECTIVENESS ENDPOINTS .................................................................... 22 
2.3 
OTHER OUTCOMES ..................................................................................... 22 
2.4 
GOOD CLINICAL PRACTICES STATEMENT ................................................ 23 
3.0 
Risk/benefits analysis ..........................................................................................23 
3.1  
RISK ............................................................................................................... 23 
3.2 
MINIMIZING SUBJECT RISK ......................................................................... 23 
3.3  
BENEFITS ...................................................................................................... 23 
4.0 
Follow up PLAN ...................................................................................................24 
4.1 
TRIAL DESIGN .............................................................................................. 24 
4.2 
TRIAL DESCRIPTION .................................................................................... 24 
5.0 
TRIAL POPULATION ..........................................................................................24 
5.1 
INCLUSION CRITERA ................................................................................... 24 
5.2 
EXCLUSION CRITERIA ................................................................................. 25 
6.0 
TRIAL PROCEDURES ........................................................................................26 
6.1 
INFORMED CONSENT .................................................................................. 26 
6.2 
SUBJECT SCREENING ................................................................................. 27 
6.2.1 
POD 195 Visit (-15/+45 Days) 
27 
6.2.2 
POD 390 Visit (- 25/+45 Days) 
28 
6.2.3 
PO Year 2 through SUBSEQUENT ANNUAL Visits 
29 
6.2.4 
Visit Windows 
30 
6.3 
SUBJECT WITHDRAWAL .............................................................................. 30 

CLINICAL INVESTIGATION PLAN 
  
TRANSFORMTM Post Approval Phase  
Number: 2011-02 IDE: G110189 / P150036 
 
 
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6.4 
SUBJECT REMOVAL FROM CLINICAL TRIAL ............................................. 31 
6.5 
TRIAL TERMINATION .................................................................................... 32 
6.6 
INVESTIGATIONAL DEVICE MANAGEMENT ............................................... 32 
7.0 
SAFETY ASSESSMENTS ...................................................................................32 
7.1 
SAFETY PROCESS ....................................................................................... 33 
7.2 
ADVERSE EVENTS ....................................................................................... 34 
7.3 
SERIOUS ADVERSE EVENTS ...................................................................... 34 
7.4 
ANTICIPATED ADVERSE EVENTS ............................................................... 35 
7.5 
UNANTICIPATED ADVERSE DEVICE EFFECT ............................................ 37 
7.6 
ADVERSE EVENT DEFINITIONS/ REPORTABLE EVENTS ......................... 37 
7.7 
ASSESSMENT OF ADVERSE EVENTS ........................................................ 39 
7.8 
ELECTROCARDIOGRAMS ............................................................................ 41 
7.9 
LABORATORY TESTING ............................................................................... 41 
8.0 
EFFECTIVENESS ASSESSMENTS....................................................................42 
8.1 
PERI-PROCEDURAL PARAMETERS ............................................................ 42 
8.2 
NYHA CLASSIFICATION ............................................................................... 42 
8.3 
HEMODYNAMIC PERFORMANCE ................................................................ 42 
9.0 
STATISTICAL METHODS ...................................................................................43 
9.1 
STATISTICAL ANALYSIS .............................................................................. 43 
9.1.1 
Analysis Population 
43 
9.1.2 
Safety Analysis 
43 
9.1.2.1 Primary Safety Endpoints ....................................................................... 43 
9.1.2.2 Other Safety Data ................................................................................... 44 
9.1.3 
Effectiveness Analysis 
44 
9.1.4 
Other Outcomes Analysis 
44 
9.1.5 
Missing data 
45 
9.2 
ADDITIONAL INFORMATION ........................................................................ 45 
10.0 TRIAL COMMITTEES AND CORE LABORATORY .............................................46 
10.1 
CLINICAL EVENTS COMMITTEE .................................................................. 46 
10.2 
DATA MONITORING COMMITTEE ............................................................... 46 
10.3 
ECHOCARDIOGRAPHY CORE LAB ............................................................. 47 
11.0 DATA INTEGRITY, COLLECTION AND QUALITY ASSURANCE .......................47 
11.1 
DATA COLLECTION ...................................................................................... 47 

CLINICAL INVESTIGATION PLAN 
  
TRANSFORMTM Post Approval Phase  
Number: 2011-02 IDE: G110189 / P150036 
 
 
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11.2 
DATA QUALITY ASSURANCE ...................................................................... 48 
12.0 INVESTIGATOR RESPONSIBILITIES ................................................................49 
12.1 
INVESTIGATOR RECORDS .......................................................................... 50 
13.0 SPONSOR RESPONSIBILITIES .........................................................................53 
13.1 
SELECTION OF INVESTIGATORS ............................................................... 54 
13.2 
TRAINING ...................................................................................................... 54 
13.2.1 
Echocardiographic examinations 
55 
13.2.2 
Documentation 
55 
13.3 
MONITORING METHODS ............................................................................. 56 
13.3.1 
Monitoring Visits 
57 
REFERENCES ..............................................................................................................58 
 
 
 
 

CLINICAL INVESTIGATION PLAN 
  
TRANSFORMTM Post Approval Phase  
Number: 2011-02 IDE: G110189 / P150036 
 
 
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SYNOPSIS 
 
Protocol Number 
 
2011-02 
 
Title 
Multi-CenTer Experience with the Rapid Deployment 
EDWARDS INTUITY Valve System FOR Aortic Valve 
ReplaceMent (TRANSFORMTM Post Approval Phase) 
 
Sponsor 
Edwards Lifesciences 
 
Objectives 
To assess the safety and effectiveness of the EDWARDS 
INTUITY Valve System in subjects with aortic stenosis or 
stenosis-insufficiency requiring primary replacement of the 
native aortic valve in the premarket and post market phases.   
 
Safety was determined by comparing safety endpoints to the 
objective performance criteria (OPC) defined by ANNEX R, 
Section R2, Table R.1 of BS EN ISO 5840:2009 
(Cardiovascular implants – Cardiac valve prostheses) and 
effectiveness was evaluated based on improvement in 
NYHA Class and hemodynamic parameters compared to 
baseline.   
 
Trial Design 
Prospective, non-randomized, multi-center trial. Pre market 
analysis was performed when the total late-patient years 
reached 800 and the number of subjects completing the one 
year (or greater) follow-up reached or exceeded 300. Post-
market, all active subjects will be followed until the last 
enrolled subject completes their 5-year follow up. 
 
 
Trial Population 
The trial population consists of subjects enrolled in the 
TRANSFORMTM Trial. 
 
Number of Subjects 
There were 934 subjects enrolled at 29 clinical sites.  All 
active subjects will continue follow up until the last enrolled 
subject completes their 5-year follow up 
Gender/Age 
Males and females, 18 years of age or older 
 
During the enrollment phase of the trial, the following 
Inclusion, Exclusion and Intra-operative Exclusion Criteria 
was required:  

CLINICAL INVESTIGATION PLAN 
  
TRANSFORMTM Post Approval Phase  
Number: 2011-02 IDE: G110189 / P150036 
 
 
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Inclusion Criteria 
 
 
1. Male or female, age 18 years or older 
2. Has aortic stenosis or stenosis-insufficiency of an aortic 
valve requiring a planned replacement as indicated in 
the preoperative evaluation 
3. Is scheduled to undergo planned aortic valve 
replacement with or without concomitant coronary 
bypass surgery 
4. Provide written informed consent 
5. Geographically stable and agrees to attend follow-up 
assessments until all subjects have completed 5 years of 
follow up 
 
Pre-operative 
Exclusion Criteria 
 
 
 
 
 
 
1. Pure aortic insufficiency 
2. Requires emergency surgery 
3. Previous aortic valve replacement 
4. Had prior mitral, tricuspid or pulmonic valve surgery, 
which included implant of a bioprosthetic valve, 
mechanical valve, or annuloplasty ring that will remain in 
situ 
5. Requires multiple valve replacement/repair 
6. Requires a surgical procedure outside of the cardiac 
area (e.g., vascular endarterectomy, vascular bypass, 
tumor removal) 
7. Aneurysm of the aortic root and/or ascending aorta 
requiring surgical intervention 
8. Active endocarditis/myocarditis or endocarditis/ 
myocarditis within 3 months prior to the scheduled AVR 
surgery 
9. Myocardial infarction (MI) within thirty (30) days prior to 
valve replacement surgery 
10. Renal insufficiency as determined by creatinine ≥ 2.5 
mg/dL at screening or end-stage renal disease requiring 
chronic dialysis 
11. Hyperparathyroidism 
12.  MRI or CT-scan confirmed cerebrovascular accident 
(CVA), or transient ischemic attack (TIA) within 6 
months (180 days) of the procedure 
13. Presence of non-cardiac disease limiting life expectancy 
to less than 12 months 
14. Hypertrophic obstructive cardiomyopathy (HOCM) 
15. Left ventricular ejection fraction ≤ 25% 

CLINICAL INVESTIGATION PLAN 
  
TRANSFORMTM Post Approval Phase  
Number: 2011-02 IDE: G110189 / P150036 
 
 
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16. Documented history of substance (drug or alcohol) 
abuse within the last 5 years 
17. Echocardiographic evidence of an intra-cardiac mass, 
thrombus, or vegetation 
18. Hemodynamic or respiratory instability requiring 
inotropic support, mechanical circulatory support, or 
mechanical ventilation within 30 days prior to the 
procedure 
19. Pregnancy, lactation, or planning to become pregnant; 
20. Currently incarcerated or unable to give voluntary 
informed consent  
21. Leucopenia (WBC < 3.5x 103/µL), or acute anemia (Hgb 
< 10.0 gm/dL or 6 mmol/L), or thrombocytopenia 
(platelet count < 50x 103/µL), or history of bleeding 
diathesis or coagulopathy 
22. History of myxomatous disease/connective tissue 
disorders (e.g., Marfan’s Syndrome)  
23. Current or recent participation (within 6 weeks prior to 
surgery) in an investigational drug or device trial 
 
Intra-operative 
Exclusion Criteria 
24. Anatomic variances which contraindicate implant of the 
trial valve, such as: 
a. anomalous coronary arteries 
b. annular deformation or extensive calcification of the 
annulus or aortic root which cannot be removed 
c. significant calcium on the anterior mitral leaflet 
d. pronounced septal calcification 
e. position of coronary ostia relative to Model 
8300ACA/ACD valve that would result in obstruction 
of blood flow 
25. Available devices are not suitably sized for the subject’s 
annulus 
 
Trial Device 
EDWARDS INTUITY Valve System, Model 8300 which 
includes: EDWARDS INTUITY Aortic Valve, Model 
8300ACA and EDWARDS INTUITY Delivery System, Model 
8300DCA or EDWARDS INTUITY Aortic Valve, Model 
8300ACD and EDWARDS INTUITY Delivery System, Model 
8300DCD 
 
Indication for Use 
During the pre-market phase of the TRANSFORMTM Trial, 
the EDWARDS INTUITY Valve System (EDWARDS 
INTUITY Aortic Valve, Model 8300ACA/8300ACD and 
EDWARDS INTUITY Delivery System, Model 

CLINICAL INVESTIGATION PLAN 
  
TRANSFORMTM Post Approval Phase  
Number: 2011-02 IDE: G110189 / P150036 
 
 
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Edwards 
8300DCA/8300DCD) was indicated for use in subjects with 
aortic stenosis or stenosis plus insufficiency of an aortic 
valve requiring a planned replacement of their native aortic 
valve. Post market, the trial device is indicated for the 
replacement of diseased, damaged, or malfunctioning native 
or prosthetic aortic valves. 
 
Schedule of Visits 
– Screening (Day -90 to Day -1) 
– Operative procedure (Day 0) 
– Discharge (Post-op – Day of Discharge) 
– Postoperative day POD 36 (-5/+10 days; by phone) 
– POD 105 (-15/+30 days);  
– POD 195 (-15/+45 days); only for subjects with 
paravalvular leak >mild or an implant related new or 
worsened cardiac conduction disturbance1 on 3-month 
electrocardiogram;  
– POD 390 (-25/+45 days) 
• PO Year 2 (-60/+60 days) 
• PO Year 3 (-60/+60 days)  
• PO Year 4 (-60/+60 days) 
• PO Year 5 (-60/+60 days) 
• Annually thereafter until the last subject completes 5-year 
follow-up visit 
- At the time of this protocol revision, all patients had 
completed these visits 
Safety Endpoints 
The primary safety endpoints consist of:  
• 
All cause mortality 
o Trial valve-related mortality 
• 
Valve thrombosis (trial valve)  
• 
Thromboembolism 
• 
All hemorrhage 
o Major hemorrhage 
• 
All paravalvular leak (trial valve) 
o Major paravalvular leak (trial valve) 
• 
Endocarditis (trial valve) 
• 
Structural valve deterioration (trial valve) 
• 
Non-Structural valve deterioration (trial valve) 
 
1 Defined as new or worsened first degree atrioventricular (AV) block, second degree AV block (Mobitz I or Mobitz II), third 
degree AV block, incomplete right bundle branch block, right bundle branch block,  intraventricular conduction delay, left 
bundle branch block, left anterior fascicular block, or left posterior fascicular block, including block requiring permanent 
pacemaker implant. 

CLINICAL INVESTIGATION PLAN 
  
TRANSFORMTM Post Approval Phase  
Number: 2011-02 IDE: G110189 / P150036 
 
 
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o Valve Malposition 
o Valve Migration/ embolization 
o Valve Instability 
o Valve Dislodgment 
• 
Hemolysis 
• 
Reoperation 
o Trial valve-related reoperation 
• 
Explant 
o Trial valve explant 
• 
Implant-related new or worsened cardiac conduction 
disturbance  
o requiring permanent pacemaker implant 
o not requiring permanent pacemaker implant 
 
The Data Monitoring Committee (DMC) will conduct a final 
meeting after the last subject has completed their 5-year 
follow up 
 
Effectiveness 
Endpoints 
The following effectiveness endpoints will be assessed: 
 
• 
Device technical success is defined as the 
successful delivery and deployment of the trial valve 
with maximum of two attempts and subject leaving 
the OR with valve in place 
• 
Procedural success is defined as device technical 
success followed by the absence of adverse events 
resulting in device reoperation implant of permanent 
pacemaker (with baseline sinus rhythm and no other 
pre-existing conduction issues), or valve-related 
death within discharge or 10 days post index 
procedure, whichever comes first. 
• 
Cross-clamp time (for labeling claim) 
• 
Cardiopulmonary bypass time (for labeling claim) 
• 
Length of time in the intensive care unit 
• 
NYHA functional class compared to baseline 
• 
Hemodynamic performance (mean gradient, peak 
gradient, effective orifice area [EOA], EOA index, 
performance index, cardiac output [CO], cardiac 
index [CI], valvular regurgitation [including 

CLINICAL INVESTIGATION PLAN 
  
TRANSFORMTM Post Approval Phase  
Number: 2011-02 IDE: G110189 / P150036 
 
 
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Edwards 
paravalvular leak] confirmed by echocardiography 
and Core lab evaluation) 
 
Other Outcomes 
The following data also will be collected: 
• 
Change in Quality of Life questionnaire Short Form 
12 version 2 (SF-12v2) from Screening to 1 year 
• 
Laboratory testing (White Blood Cell Count, Red 
Blood Cell Count, Hemoglobin, Hematocrit,  Plasma-
free Hemoglobin or haptoglobin or serum LDH, 
Platelet Count) at screening, discharge and at 3, 6, 
and 12 months and annually thereafter at each 
follow-up visit 
 
 
 

CLINICAL INVESTIGATION PLAN 
  
TRANSFORMTM Post Approval Phase  
Number: 2011-02 IDE: G110189 / P150036 
 
 
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ABBREVIATIONS 
ACC 
American College of Cardiology 
IRB 
Investigational Review Board 
AE 
Adverse Event 
ISO 
International Standardization Organization  
AHA 
American Heart Association 
LVOT 
Left Ventricular Outflow Tract 
AS 
Aortic Stenosis 
MI 
Myocardial Infarction 
ASD 
Atrial Septal Defect 
MOF 
Multi-system Organ Failure 
AVR 
Aortic Valve Replacement 
MR 
Magnetic Resonance 
CABG Coronary Artery Bypass Graft 
NSVD 
Nonstructural Valve Dysfunction 
CEC 
Clinical Events Committee 
NYHA 
New York Heart Association 
CFR 
Code of Federal Regulations 
OPC 
Objective Performance Criteria 
CO/CI Cardiac Output/Cardiac Index 
PFO 
Patent Foramen Ovale 
CRF 
Case Report Form 
PMA 
Premarket Approval  
CV 
Critical Value 
PO 
Postoperative 
CVA 
Cerebrovascular Accident 
POD 
Postoperative Day 
DIC 
Disseminated Intravascular Coagulation 
PT 
Prothrombin Time 
DMC 
Data Monitoring Committee 
PTFE 
Polytetrafluoroethylene 
eCRF Electronic Case Report Form 
PTT 
Partial Thromboplastin Time 
ECG 
Electrocardiogram 
PVL 
Paravalvular Leak 
EDC 
Electronic Data Capture 
QOL 
Quality of Life 
EOA 
Effective Orifice Area 
RBC 
Red Blood Cell Count 
FDA 
Food and Drug Administration 
RGA 
Returned Good Authorization 
FMEA Failure Modes and Effects Analysis 
SAE 
Serious Adverse Event 
GCP 
Good Clinical Practice 
SAR 
Specific Absorption Rate 
GLP 
Good Laboratory Practices 
SAVR 
Surgical Aortic Valve Replacement 
HIPAA Health Insurance Portability & Accountability Act SF-12 
Short Form 12 Health Survey 
HIT 
Heparin Induced Thrombocytopenia 
SVD 
Structural Valve Deterioration 
HOCM Hypertrophic Obstructive Cardiomyopathy 
TAD 
Tissue Annulus Diameter 
ICF 
Informed Consent Form 
TEE 
Transesophageal echocardiography 
ICU 
Intensive Care Unit 
TIA 
Transient Ischemic Attack 
ID 
Identification 
TTE 
Transthoracic echocardiography 
IDE 
Investigational Device Exemption 
UADE 
Unanticipated Adverse Device Effect 
IE 
Infective Endocarditis 
WBC 
White Blood Cell Count 
IFU 
Instructions for Use 
 
INR 
International Normalized Ratio 
 
 
 
 
 
 

CLINICAL INVESTIGATION PLAN 
  
TRANSFORMTM Post Approval Phase  
Number: 2011-02 IDE: G110189 / P150036 
 
 
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1.0 
INTRODUCTION 
1.1 
BACKGROUND 
Regulatory History 
Edwards Lifesciences began discussions of the EDWARDS INTUITY Elite Valve System 
with FDA in September 2007.  The TRANSFORMTM Study Investigational Device 
Exemptions (IDE) application was submitted in October 2011 and IDE G110189 was 
approved in June 2012.  Enrollment in the study began September 26, 2012 and closed 
August 25, 2016. 
Annual follow up will continue on all subjects enrolled in the TRANSFORMTM Study until the 
last subject completes 5-year follow up visit. 
Premarket Approval P150036 (PMA) was granted August 12, 2016. The conditions of the 
PMA approval include the following: 
The sale and distribution of this device are restricted to prescription use in 
accordance with 21CFR 801.109 and under section 515(d)(1)(B)(ii) of the Federal 
Food, Drug, and Cosmetic Act (the act). The device is further restricted under 
section 515(d)(1)(B)(ii) of the act insofar as the labeling must specify the specific 
training or experience practitioners need in order to use the device. 
Submission of Annual Report 
 1.2 
EDWARDS INTUITY VALVE SYSTEM 
The EDWARDS INTUITY Elite valve system consists of the EDWARDS INTUITY Elite 
valve, model 8300AB and the EDWARDS INTUITY Elite delivery system, model 8300DB. 
The pericardial stented aortic valve is based on the design and the proven performance of 
the PERIMOUNT valve family. A balloon expandable stainless steel cloth-covered frame is 
incorporated into the inflow aspect of the valve. The valve is implanted with the aid of a 
delivery system, which incorporates a balloon catheter to expand the frame within the left 
ventricular outflow tract (LVOT). The expandable frame works in conjunction with the 
sewing ring to position and stabilize the valve at implant. The system reduces the number 

CLINICAL INVESTIGATION PLAN 
  
TRANSFORMTM Post Approval Phase  
Number: 2011-02 IDE: G110189 / P150036 
 
 
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Edwards 
of sutures required to secure the valve, while the frame establishes a seal within the LVOT. 
The system may be used in both traditional and less invasive surgical procedures for heart 
valve replacement. 
Two generations of the EDWARDS INTUITY Valve System were investigated in the 
TRANSFORM Trial: 
 GEN-I:  Valve Model 8300ACA and Delivery System Model 8300DCA 
 GEN-II:  Valve Model 8300ACD and Delivery System Model 8300DCD 
The GEN-I device was used early on in the IDE trial and was replaced by the GEN-II 
device. 
The trial valve system consists of the trial valve, model 8300ACA, (Figure 1-A) and the trial 
delivery system, model 8300DCA (Figure 1-C) or trial valve, model 8300ACD (Figure 1-B) 
and the trial delivery system, model 8300DCD, (Figure 1-D). The trial valve is a modified 
Carpentier-Edwards PERIMOUNT Magna Ease Aortic bioprosthesis (model 3300TFX2). 
The trial valve enables the surgeon to position and secure the valve with three sutures and 
then further secure the valve in the annulus with a balloon expandable frame to control 
paravalvular leak. An expandable stainless steel cloth-covered frame is incorporated into 
the inflow aspect of the valve and is implanted with the aid of a delivery system, which is 
used to expand the frame within the left ventricular outflow tract (LVOT) and works in 
conjunction with the sewing ring to position and stabilize the trial valve at implant. The 
system reduces the number of sutures required to secure the trial valve, while establishing 
the seal between the aortic annulus and the frame. The system may be used in both 
traditional and less invasive surgical procedures (mini sternotomy or right thoracotomy) for 
aortic heart valve replacement in patients with aortic stenosis or aortic 
stenosis/insufficiency.  It is not intended for patients with pure insufficiency and it cannot be 
implanted using a transcatheter or transapical approach.  
 
 
 
2 PMA P860057/S042 approved on May 7, 2009 
 

CLINICAL INVESTIGATION PLAN 
  
TRANSFORMTM Post Approval Phase  
Number: 2011-02 IDE: G110189 / P150036 
 
 
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Edwards 
 
Figure 1-A: Trial Valve System, model 8300ACA 
 
Figure 1-B: Trial Valve System, model 8300ACD 
 
 
The trial valve is a stented trileaflet valve comprised of bovine pericardium that has been 
preserved in a buffered glutaraldehyde solution.  
The leaflets are mounted on a flexible cobalt-chromium alloy wireform. The inflow of the 
bioprosthesis incorporates the cloth-covered balloon expandable stainless steel frame that 
is attached to the inflow side of the valve. The valve leaflets are treated with the Carpentier-
Edwards ThermaFix process, which involves heat treatment of the tissue in glutaraldehyde 
and uses ethanol and polysorbate-80 (a surfactant). The valve is packaged and terminally 
sterilized in glutaraldehyde. Glutaraldehyde is shown to both reduce the antigenicity of 
8300ACA
8300ACD

CLINICAL INVESTIGATION PLAN 
  
TRANSFORMTM Post Approval Phase  
Number: 2011-02 IDE: G110189 / P150036 
 
 
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tissue xenograft bioprostheses and increase tissue stability. The trial valve is available in 
sizes 19, 21, 23, 25, and 27 mm.   
The wireform is made of a corrosion resistant, cobalt-chromium alloy chosen due to its 
spring efficiency and fatigue-resistant characteristics. The wireform is covered with a 
knitted polyester fabric. A thin, cobalt-chromium alloy/polyester film laminate band 
surrounds the base of the wireform. A silicone sewing ring which is covered with a porous, 
seamless polytetrafluoroethylene (PTFE) cloth is attached to the wireform. The scalloped 
sewing ring is designed to conform to the natural aortic annulus. The annulus frame which 
is made from stainless steel (SST) is sewn to the inflow side of the valve in order to control 
paravalvular leak. The annulus frame has a scallop-shaped continuous ring on the outflow 
side which matches the contour of the inflow side of the model 3300TFX valve.  The 
scallop-shaped ring is sewn and not welded to the valve wireform and hence does not 
affect the outward cusp movement of the trial valve wireform during valve operation. The 
annulus frame sits in the intra-annular position. The inner and outer surfaces of the frame 
are covered with a knitted PTFE cloth and the annulus frame is covered with 
polyethyleneterephthalate (PET) cloth.  The annulus frame is crimped as part of the 
manufacturing process and remains in this state until used. Please note that the base valve 
in the trial valve system is never crimped. The compliant nature of the sewing ring 
facilitates coaptation between the bioprosthesis and an often irregular or calcific tissue bed. 
The sewing ring has three suture markers to aid in valve orientation and suture placement. 
A holder is attached to the valve by means of sutures to facilitate handling, deployment, 
and suturing the valve during implantation. The holder is easily detached by the surgeon. 
1.2.1 MODEL 8300ACA/ACD VALVE DIFFERENCES 
Three minor modifications were made to achieve the valve model 8300ACD.  1) In order to 
enhance seating of the valve during implant the cloth on the frame was shifted down closer 
to the inflow edge of the annulus frame.   Since the cloth on the annulus frame was moved 
down, the resulting tissue annulus diameter (TAD) was reduced by one mm, which is 
identical to the model 3300TFX.  2) The single crimped cloth-covered expandable stainless 
steel frame is now double crimped to further reduce the implant profile.   3) The valve 
holder is cusp-mounted instead of commissural-mounted to increase the visibility for the 
nadir suture markers. Also, there was a modification in the method of sewing the holder 

CLINICAL INVESTIGATION PLAN 
  
TRANSFORMTM Post Approval Phase  
Number: 2011-02 IDE: G110189 / P150036 
 
 
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Edwards 
onto the valve. Additionally, the holder material was changed to Delrin 500 which is the 
same material used with all Edwards’ valve holders and can now be molded as opposed to 
machined.  Finally, the new holder has a key-lock fitting which is size-dependent to match 
the modified delivery system, Model 8300DCD.   
There are no changes to the implant procedure, materials, or packaging. The valve is still 
attached to the native annulus with only three sutures and uses a pressure-based delivery 
system to expand the annulus frame.  The product name remains the same.  
The trial delivery system is designed to introduce the trial valve to the surgical site after 
removal of the diseased native leaflets. A delivery system is available for each size of the 
trial valve and consists of the following components:  
Model 8300DCA Delivery System 
• Balloon Introducer 
• Insertion Tool 
• Distal Handle 
• Frame Expansion Balloon Catheter 
 
Figure 1-C:  Model 8300DCA Delivery System 

CLINICAL INVESTIGATION PLAN 
  
TRANSFORMTM Post Approval Phase  
Number: 2011-02 IDE: G110189 / P150036 
 
 
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Model 8300DCD Delivery System 
• Insertion Tool/Balloon Introducer 
• Integrated Balloon Catheter 
 
Figure 1-D:  Model 8300DCD Delivery System 
 
1.2.2 MODEL 8300DCA/DCD DELIVERY SYSTEM DIFFERENCES  
All modifications to Model 8300DCD delivery system were to enhance device safety, 
ease of use and manufacturability.  The delivery system includes an integrated balloon 
catheter and tubular handle shaft through which the catheter extends. The major change 
was the distal handle is now incorporated into the balloon catheter as a one-piece 
design in the modified delivery system and this modification provides one less 
component for the end user to assemble. The distal end of the handle shaft includes an 
adapter, which mates with the holder of the valve, and a locking sleeve for rapidly 
connecting the delivery system to the valve holder. The balloon portion of the delivery 
system resides within the adapter, and advances distally into position for expanding the 
frame. A tubular balloon introducer sleeve, attached when removing the valve from a 
storage jar, facilitates passage of the balloon through the valve.  The malleable handle is 
made of aluminum and has chromate conversion coating applied over the entire surface 
of the part. 
 

CLINICAL INVESTIGATION PLAN 
  
TRANSFORMTM Post Approval Phase  
Number: 2011-02 IDE: G110189 / P150036 
 
 
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1.3 
MODEL SECTION 
Model 8300ACA/DCA and 8300ACD/DCD were included in the trial.  Investigational 
sites utilizing Model 8300ACA/DCA were transitioned to Model 8300ACD/DCD upon 
completion of the following; IRB approval, device training and scheduling of 
investigational product exchange.  Each site only had access to either model 
8300ACA/DCA or 8300ACD/DCD at any given time.  No site had concurrent access to 
both models. 
1.4 
INDICATION FOR USE 
The EDWARDS INTUITY Elite valve is indicated for the replacement of diseased, 
damaged, or malfunctioning native or prosthetic aortic valves. 
 
 
2.0 
TRIAL OBJECTIVES 
The purpose of this clinical investigation is to assess the safety and effectiveness of the 
EDWARDS INTUITY Valve System in subjects with aortic stenosis or  
stenosis-insufficiency requiring replacement of the native aortic valve in premarket and 
post market phases. 
Safety was determined by comparing safety endpoints to the objective performance 
criteria (OPC) defined by ANNEX R, Section R2, Table R.1 of BS EN ISO 5840:2009 
(Cardiovascular implants – Cardiac valve prostheses) and effectiveness was evaluated 
based on improvement in NYHA Class and hemodynamic parameters compared to 
baseline.   
 
 

CLINICAL INVESTIGATION PLAN 
  
TRANSFORMTM Post Approval Phase  
Number: 2011-02 IDE: G110189 / P150036 
 
 
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2.1 
PRIMARY SAFETY ENDPOINTS 
The primary safety endpoints consist of:  
• 
All cause mortality 
o Trial valve-related mortality 
• 
Thromboembolism  
• 
Valve thrombosis (trial valve)  
• 
All hemorrhage  
o Major hemorrhage 
• 
All paravalvular leak (trial valve) 
o  Major paravalvular leak (trial valve) 
• 
Endocarditis (trial valve) 
• 
Structural valve deterioration (trial valve) 
• 
Non-Structural valve deterioration (trial valve) 
• 
Valve Malposition 
• 
Valve Migration/ embolization 
• 
Valve Instability 
• 
Valve Dislodgment 
• 
Hemolysis 
• 
Reoperation  
o Trial valve-related reoperation 
• 
Explant 
o Trial valve explant 
• 
Implant-related new or worsened cardiac conduction disturbance*  
o requiring permanent pacemaker implant 
o not requiring permanent pacemaker implant 
*Defined as new or worsened first degree atrioventricular (AV) block, second degree AV 
block (Mobitz I or Mobitz II), third degree AV block, incomplete right bundle branch block, 
right bundle branch block, intraventricular conduction delay, left bundle branch block, left 
anterior fascicular block, or left posterior fascicular block. 

CLINICAL INVESTIGATION PLAN 
  
TRANSFORMTM Post Approval Phase  
Number: 2011-02 IDE: G110189 / P150036 
 
 
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2.2 
EFFECTIVENESS ENDPOINTS 
The following effectiveness endpoints for assessment are: 
• 
Device technical success is defined as the successful delivery and deployment of 
the trial valve with maximum of two attempts and subject leaving the OR with 
valve in place  
 
Procedural success is defined as device technical success followed by the 
absence of adverse events resulting in device reoperation implant of permanent 
pacemaker (with baseline sinus rhythm and no other pre-existing conduction 
issues), or valve-related death within discharge or 10 days post index procedure, 
whichever comes first. 
• 
Cross-clamp time 
• 
Cardiopulmonary bypass time 
• 
The length of time in the intensive care unit (ICU) 
 
New York Heart Association (NYHA) functional class compared to baseline 
 
Hemodynamic performance (mean gradient, peak gradient, effective orifice area 
[EOA], EOA index, performance index, cardiac output [CO], cardiac index, 
valvular regurgitation (including paravalvular leak) by echocardiography) 
 
A comparison of all effectiveness data for the EDWARDS INTUITY valve were made 
to current state of the art prosthetic heart valve literature published in peer reviewed 
journals at the time of PMA submission. 
 
2.3 
OTHER OUTCOMES 
The following outcomes for additional evaluation are: 
• 
Change in Short Form 12 version 1 (SF-12v2) Quality of Life questionnaire from 
Baseline to 1 year  
• 
Laboratory testing (White Blood Cell Count, Red Blood Cell Count, Hemoglobin, 
Hematocrit, Plasma-free Hemoglobin or haptoglobin or serum LDH, Platelet 
Count) at screening and at 3, 6, 12 months and annually thereafter from post 
implant 

CLINICAL INVESTIGATION PLAN 
  
TRANSFORMTM Post Approval Phase  
Number: 2011-02 IDE: G110189 / P150036 
 
 
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2.4 
GOOD CLINICAL PRACTICES STATEMENT 
This trial was conducted in compliance with all applicable U.S. Federal regulations 
pertaining to trial devices including but not limited to: 21 CFR Part 50, Part 54, Part 56, 
Part 812, Good Clinical Practice (GCP) standards, and Health and Insurance Portability 
and Accountability Act (HIPAA). 
 
3.0 
RISK/BENEFITS ANALYSIS 
3.1  
RISK 
As with all prosthetic heart valves, serious complications, sometimes leading to death, 
may be associated with the use of tissue valves. In addition, complications due to 
individual patient reaction to an implanted device, or to physical or chemical changes in 
the components, particularly those of biological origin, may occur at varying intervals 
(hours or days) necessitating reoperation and replacement of the prosthetic device. 
For a complete listing of anticipated adverse events in this trial, see section 7.4 of this 
document.  All safety events will be reported throughout the entire trial.  Investigators will 
be notified of any additional risks identified that could affect the health, safety or welfare 
of the trial subjects. 
3.2 
MINIMIZING SUBJECT RISK 
All adverse event rates will be collected, reviewed and evaluated.  Clinical outcomes for 
all trial subjects will be routinely monitored by the Sponsor during the course of the trial.  
An independent Clinical Events Committee (CEC) will review and adjudicate safety 
endpoint related events as outlined in the CEC charter.   
3.3  
BENEFITS 
Information gained from the continued follow up of these subjects may be of benefit to 
other patients with the same medical condition in the future.  

CLINICAL INVESTIGATION PLAN 
  
TRANSFORMTM Post Approval Phase  
Number: 2011-02 IDE: G110189 / P150036 
 
 
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4.0 
FOLLOW UP PLAN 
4.1 
TRIAL DESIGN 
This is a multi-center, prospective, non-randomized, single-arm, clinical trial to assess 
the safety and effectiveness of the trial valve system in subjects with aortic stenosis or 
stenosis-insufficiency requiring primary replacement of the native aortic valve. Premarket 
analysis was performed when the total late-patient years reached 800 and the number of 
subjects completing the one year (or greater) follow-up reached and/or exceeds 300.  
Post-market, all active subjects will be followed until the last enrolled subject completes 
their 5-year follow up. 
4.2 
TRIAL DESCRIPTION 
Continued follow-up evaluations will be conducted on all active enrolled TRANSFORMTM 
Trial subject until the last enrolled subject complete the 5-year follow up.  
 
5.0 
TRIAL POPULATION 
 The trial population consists of subjects enrolled in the TRANSFORMTM Trial.  
5.1 
INCLUSION CRITERA 
During the enrollment phase of the trial, the following Inclusion, Exclusion and Intra-
operative Exclusion Criteria was required: 
1. Male or female, age 18 years or older 
2. Subject has aortic stenosis or stenosis-insufficiency of an aortic valve 
requiring a planned replacement as indicated in the preoperative evaluation  
3. Subject is scheduled to undergo planned aortic valve replacement with or 
without concomitant coronary bypass surgery 
4. Provide written informed consent 
5. Geographically stable and agrees to attend follow-up assessments until all 
subjects have completed 5 years of follow up 

CLINICAL INVESTIGATION PLAN 
  
TRANSFORMTM Post Approval Phase  
Number: 2011-02 IDE: G110189 / P150036 
 
 
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5.2 
EXCLUSION CRITERIA 
Pre-operative Exclusion Criteria: 
1. Subjects with pure aortic insufficiency 
2. Subjects requiring emergency surgery 
3. Previous aortic valve replacement 
4. Had prior mitral, tricuspid or pulmonic valve surgery, which included implant of a 
bioprosthetic valve, mechanical valve, or annuloplasty ring that will remain in situ; 
5. Subjects requiring multiple valve replacement/repair 
6. Requires a surgical procedure outside of the cardiac area (e.g., vascular 
endarterectomy, vascular bypass, tumor removal) 
7. Aneurysm of the aortic root and/or ascending aorta requiring surgical intervention 
8. Active endocarditis/myocarditis or endocarditis/myocarditis within 3 months prior to 
the scheduled AVR surgery 
9. Myocardial infarction (MI) within thirty (30) days prior to valve replacement surgery; 
10. Renal insufficiency as determined by creatinine ≥ 2.5 mg/dL at Screening or end-
stage renal disease requiring chronic dialysis 
11. Hyperparathyroidism 
12.  MRI or CT-scan confirmed cerebrovascular accident (CVA),  or transient ischemic 
attack (TIA) within 6 months (180 days) of the procedure 
13. Presence of non-cardiac disease limiting life expectancy to less than 12 months; 
14. Hypertrophic obstructive cardiomyopathy (HOCM) 
15. Left ventricular ejection fraction ≤ 25% 
16. Documented history of substance (drug or alcohol) abuse within the last 5 years 
17. Echocardiographic evidence of an intracardiac mass, thrombus, or vegetation 
18. Hemodynamic or respiratory instability requiring inotropic support, mechanical 
circulatory support, or mechanical ventilation within 30 days prior to the procedure 
19. Pregnancy, lactation, or planning to become pregnant 
20. Currently incarcerated or unable to give voluntary informed consent  
21. Leukopenia (WBC < 3.5x 103/µL), or acute anemia (Hgb < 10.0 gm/dL or 6 mmol/L), 
or thrombocytopenia (platelet count < 50x 103/µL), or history of bleeding diathesis or 
coagulopathy 

CLINICAL INVESTIGATION PLAN 
  
TRANSFORMTM Post Approval Phase  
Number: 2011-02 IDE: G110189 / P150036 
 
 
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22. History of myxomatous disease/connective tissue disorders (e.g., Marfan’s 
Syndrome) 
23. Current or recent participation (within 6 weeks prior to surgery) in an investigational 
drug or device trial 
 
Intra-operative Exclusion Criteria  
24. Subjects with anatomic variances which contraindicate implant of the trial valve, 
such as: 
a. anomalous coronary arteries 
b. annular deformation or extensive calcification of the annulus or aortic root 
which cannot be removed 
c. significant calcium on the anterior mitral leaflet 
d. pronounced septal calcification 
e. position of coronary ostia relative to Model 8300ACA/ACD valve that 
would result in obstruction of blood flow 
25. Available devices are not suitably sized for the subject’s annulus 
6.0 
TRIAL PROCEDURES 
A trial scheme in tabular format is provided in xxxxxx. 
6.1 
INFORMED CONSENT 
All trial subjects were consented appropriately prior to enrollment in the TRANSFORMTM 
Trial. If re-consenting is required, an Institutional Review Board’s (IRB’s) approved 
informed consent will be utilized.  
Each subject shall be given ample time to read the ICF in its entirety and ask questions 
in order to make an informed decision.  The subject must sign and date the trial site’s 
IRB approved ICF.  In addition, the Investigator, or designee, and any witnesses will sign 
and date the ICF, as indicated.  

CLINICAL INVESTIGATION PLAN 
  
TRANSFORMTM Post Approval Phase  
Number: 2011-02 IDE: G110189 / P150036 
 
 
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6.2 
SUBJECT SCREENING 
At the time of this protocol revision, all subjects were enrolled in the trial and followed 
through 1-year follow up. For a complete description of the Subject Screening, Surgical 
Procedure, Subject Enrollment, Implant Procedure, Post Procedure Follow-Up, 
Discharge, POD 36, and POD 105 visits, please refer to a previous version (Revision N) 
of the TRANSFORMTM Protocol. 
 
6.2.1 POD 195 VISIT (-15/+45 DAYS) 
This visit is only required if echocardiography at three months showed a PVL 
>mild as determined by the Echo Core Lab or an implant-related new or worsened 
cardiac conduction disturbance. 
 
These subjects will return for follow-up between POD 180 to 240 and the following 
assessments will be performed: 
Subject status 
 
Date of Follow-Up 
 
 
NYHA Classification 
 
Echocardiography (TTE) 
Peak and mean pressure gradients, EOA, EOA 
index, performance index, cardiac output, cardiac 
index, valvular regurgitation (including 
paravalvular leak)  
Electrocardiogram  
12-Lead ECG (Cardiac Rhythm) 
Anticoagulant therapy/Concomitant 
cardiovascular medications 
Anticoagulants/anti-platelets and other  
Concomitant cardiovascular medications  
Coagulation profile 
May include PTT or PT or INR if subject is on 
anticoagulant therapy only 
Laboratory Testing 
WBC, RBC, hemoglobin, hematocrit, platelets,   
plasma-free hemoglobin ( a 2nd lab draw for 
plasma free hemoglobin is required within 48 
hours if the first draw is >40mg/dl) or haptoglobin 
or serum LDH 
Vital signs 
Blood pressure, heart rate, weight 
Adverse events/Complications 
If applicable 
 
 

CLINICAL INVESTIGATION PLAN 
  
TRANSFORMTM Post Approval Phase  
Number: 2011-02 IDE: G110189 / P150036 
 
 
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6.2.2 POD 390 VISIT (- 25/+45 DAYS) 
Subjects will return for follow-up between POD 365 to 435 and the following 
assessments will be performed: 
 
Subject status 
 
Date of Follow-Up 
 
 
NYHA Classification 
 
Echocardiography (TTE) 
Peak and mean pressure gradients, EOA, EOA 
index, performance index, cardiac output, cardiac 
index, valvular regurgitation (including 
paravalvular leak)  
Electrocardiogram  
12-Lead ECG (Cardiac Rhythm) 
Anticoagulant therapy/Concomitant 
cardiovascular medications 
Anticoagulants/anti-platelets and other  
Concomitant cardiovascular medications  
Coagulation profile 
May include PTT or PT or INR if subject is on 
anticoagulant therapy only 
Laboratory Testing 
WBC, RBC, hemoglobin, hematocrit, platelets,   
plasma-free hemoglobin ( a 2nd lab draw for 
plasma free hemoglobin is required within 48 
hours if the first draw is >40mg/dl) or haptoglobin 
or serum LDH 
QOL Survey 
SF-12v2 
Vital signs 
Blood pressure, heart rate, weight 
Adverse events/Complications 
If applicable 
 
 

CLINICAL INVESTIGATION PLAN 
  
TRANSFORMTM Post Approval Phase  
Number: 2011-02 IDE: G110189 / P150036 
 
 
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6.2.3 PO YEAR 2 THROUGH SUBSEQUENT ANNUAL VISITS 
After the POD 390 visit, the subject will return for follow-up site annually -60/+60 days 
until the trial ends.  The following assessments will be performed: 
 
 
Subject status  
 
Date of Follow-Up 
 
 
NYHA Classification 
 
Echocardiography (TTE) 
Peak and mean pressure gradients, EOA, EOA 
index, performance index, cardiac output, cardiac 
index, valvular regurgitation (including 
paravalvular leak)  
Electrocardiogram  
12-Lead ECG (Cardiac Rhythm) 
Anticoagulant therapy/Concomitant 
cardiovascular medications 
Anticoagulants/anti-platelets and other  
Concomitant cardiovascular medications  
Coagulation profile 
May include PTT or PT or INR if subject is on 
anticoagulant therapy only 
Laboratory Testing 
WBC, RBC, hemoglobin, hematocrit, platelets,   
plasma-free hemoglobin ( a 2nd lab draw for 
plasma free hemoglobin is required within 48 
hours if the first draw is >40mg/dl) or haptoglobin 
or serum LDH 
Vital signs 
Blood pressure, heart rate, weight 
Adverse events/Complications 
If applicable 
At each postoperative assessment, the Investigator will determine the subject's 
availability for future follow-up visits. If any subject is seen at a time in addition to 
regularly scheduled follow-up visits, the visit will be recorded as an interim visit.  The 
procedures performed at an unscheduled visit will be at the Investigator’s discretion.  
Available data obtained at an unscheduled visit will be transcribed onto an Unscheduled 
Visit CRF.   
 
 

CLINICAL INVESTIGATION PLAN 
  
TRANSFORMTM Post Approval Phase  
Number: 2011-02 IDE: G110189 / P150036 
 
 
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6.2.4 VISIT WINDOWS 
Visits must be scheduled for specific times before and after the date of the index 
procedure.  It is important that this schedule is maintained for all subjects.  To facilitate 
compliance, each visit has a visit window as described in Table 1 below.  Visits not 
completed within these windows will be considered “done out of window.”  Additional 
visits completed will be considered unscheduled visits.  Trial visits should be scheduled 
as close to the early part of the visit window as possible so that if it is necessary to 
cancel and reschedule the visit, the visit may still be conducted within the required visit 
window. 
Table 1:  Follow-up Visit Days & Visit Windows 
Visit 
Visit Window (Days) 
Timing from Implant (Day 0) 
POD 195* 
- 15/+45 
Day 180 to Day 240 
POD 390 
- 25/+45 
Day 365 to Day 435 
PO Year 2 
- 60/+60 
Day 670 - 790 
PO Year 3 
- 60/+60 
Day 1035 - 1155 
PO Year 4 
- 60/+60 
Day 1400 - 1520 
PO Year 5 
- 60/+60 
Day 1765 - 1885 
* Required for subjects with PVL >mild  on POD 105  echocardiography as determined by the Echo Core 
Lab or an implant-related new or worsened cardiac conduction disturbance. 
 
 
6.3 
SUBJECT WITHDRAWAL 
Subjects may voluntarily withdraw consent at any time during the clinical trial without 
jeopardizing their medical care.  In addition, the Investigator, the IRB and or Edwards 
Lifesciences has the right to withdraw subjects from the trial for the following reasons: 
when continuation may jeopardize the health of the subject, protocol violations, adverse 
events or concurrent conditions, administrative or other reasons.   
Subjects who withdraw from the trial for any reason will not be replaced 
. 

CLINICAL INVESTIGATION PLAN 
  
TRANSFORMTM Post Approval Phase  
Number: 2011-02 IDE: G110189 / P150036 
 
 
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6.4 
SUBJECT REMOVAL FROM CLINICAL TRIAL 
Although all subjects are informed of their right to withdraw from the clinical trial at any 
time, it is anticipated that such withdrawals will be infrequent.  All measures should be 
taken by the Investigator and his/her staff to encourage subjects to return for required 
follow-up visits.  The clinical trial objectives may be jeopardized if large numbers of 
subjects are lost to follow-up. 
All subjects are expected to continue in the trial until the Sponsor notifies the Investigator 
in writing that further follow-up is no longer required, except in the event of death or upon 
the subject’s written request for early withdrawal from the clinical trial.  A copy of such 
requests will be kept with the source documentation.   
A subject will be considered “lost to follow-up” and terminated from the trial when all of 
the following criteria are met: 
 
Failure to complete two consecutive visits without due cause 
 
Documentation of three unsuccessful attempts on three different dates over a 
period of at least 1 month by the Investigator or designee to contact the subject 
or next of kin. 
All subjects who receive a commercial (a non-trial) heart valve and any subjects who 
have the EDWARDS INTUITY heart valve explanted will be followed through the end of 
the trial.  Subjects previously exited from the trial due to receiving a commercial valve (at 
any time point) will be contacted and a request will be made to have them re-consented 
and reenrolled in the trial and followed through the end of the trial.  
 
 

CLINICAL INVESTIGATION PLAN 
  
TRANSFORMTM Post Approval Phase  
Number: 2011-02 IDE: G110189 / P150036 
 
 
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6.5 
TRIAL TERMINATION 
If the Sponsor and/or the Principal Investigator should discover conditions arising during 
the trial that indicate that the trial should be terminated prematurely, an appropriate 
schedule for termination will be instituted.  All trial subjects enrolled at the time the trial is 
terminated, will be followed by the Clinical Investigator for a period of five (5) years from 
the date of enrollment. 
The trial plan includes continued annual follow-up until 5 years of follow up are 
completed on all subjects enrolled in the clinical trial.   
 
6.6 
INVESTIGATIONAL DEVICE MANAGEMENT 
At the time of this protocol revision, all subjects were enrolled in the trial.  Unused 
devices were returned to the Sponsor and investigational device reconciliation was 
complete.  For a description of investigational device management, please refer to a 
previous version (Revision N) of the TRANSFORMTM Protocol 
 
7.0 
SAFETY ASSESSMENTS 
Safety assessments will include examination and reporting of adverse events, ECGs, 
laboratory parameters, vital signs and any changes from baseline. 
Adverse events, whether observed by the Investigator or reported by the subject, will be 
recorded on the Adverse Event CRF.  At each visit, the Investigator or designee will 
determine whether any adverse events occurred by evaluating the subject.  Adverse 
events may be observed directly, reported spontaneously, or identified by questioning 
the subject at each trial visit.  Questioning subjects should be in a general way, without 
asking about the occurrence of any specific symptoms.  The Investigator must appraise 
all trial related laboratory values. The Investigator should follow subjects with adverse 
events until the event has resolved or the condition has stabilized.  

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Pre-existing medical conditions or symptoms reported prior to device implant will not be 
recorded as an AE. In the event there is worsening of a pre-existing medical condition or 
symptoms following the index procedure, then an AE must be recorded.  The adverse 
event report should note the existence of pre-index procedure history when appropriate. 
7.1 
SAFETY PROCESS 
The Safety Process in the TRANSFORMTM Trial has been established with three (3) 
levels of independent review of reported clinical outcomes (Adverse Events; AE) 
conducted by Data Monitoring Committee (DMC), Sponsor’s Safety Department (HVT 
Safety), and an independent Clinical Endpoints Committee (CEC). 
Data Monitoring Committee (DMC):  The DMC provided a consistent, independent 
review of clinical outcomes reported in TRANSFORMTM trial during the enrollment 
period, The Committee will also review the data at the end of the study follow-up. The 
DMC reviews data reported from the sites, along with CEC-adjudicated data and Echo 
Core Lab data, and identifies any potential safety issues such as higher than expected 
SAE and/or death rates, Unanticipated Adverse Device Effects (UADE), or 
hemodynamic performance that is substantially worse than expected, to determine if the 
trial should be stopped, suspended, or modified at any time, as specified in the DMC 
Charter. 
Sponsor’s Safety Department (HVT Safety):  HVT Safety provides an initial review of 
new adverse events directly following notification that an event has occurred.  The 
review includes  a Serious Adverse Event (SAE) and UADE assessment and reporting to 
the relevant regulatory or trial groups, within the appropriate time frame, in accordance 
with the applicable regulatory requirements which include, 21 CFR Part 812 
(Investigational Device Exemptions), 21 CFR Part 814 (Premarket Approval of Medical 
Devices), MEDDEV 2.7/3 (Clinical Investigations: Serious Adverse Event Reporting, 
2010), and ISO 14155:2011 (Clinical Investigation of Medical Devices for Human 
Subjects), as well as with the Sponsor’s internal standard operating procedures.  
 
 

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Clinical Endpoints Committee (CEC):  The primary role of the CEC is to review 
(adjudicate) and decide on safety endpoints which will be included in the final analysis. 
The adjudication process and the events selection is based on the approved study 
endpoints definitions and the CEC Charter. HVT Safety may also include events 
determined to be possibly related to a safety endpoint during their initial review of the 
event. Events designated as requiring CEC review are forwarded with relevant source 
documentation to the CEC by HVT Safety. The CEC can also identify additional events, 
not previously reported, during their review. These events will also be adjudicated. 
7.2 
ADVERSE EVENTS 
An adverse event (AE) is defined as any untoward medical occurrence, unintended 
disease or injury, or untoward clinical event in a subject, whether or not related to the 
investigational medical device.  Note: A procedure is not an AE, but the reason for the 
procedure may be an AE. 
7.3 
SERIOUS ADVERSE EVENTS 
A serious adverse event (SAE), defined as an event that leads to one of the following: 
• 
death; 
• 
a serious deterioration in the health of the trial subject that:  
o Results in life-threatening illness or injury;  
o Results in a permanent impairment of a body structure or a body function;  
o Requires in-subject hospitalization or prolongation of existing hospitalization;  
o Results in medical or surgical intervention to prevent life-threatening illness or 
injury or permanent impairment;  
• 
Congenital defect or anomaly 
Note:  Elective hospitalizations for pre-treatment conditions (e.g., elective cosmetic 
procedures, cataract removal) are not serious adverse events (SAE). 
Each AE/SAE is considered to be either anticipated or unanticipated as described below. 

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7.4 
ANTICIPATED ADVERSE EVENTS 
As with all prosthetic heart valves, serious complications, sometimes leading to death, 
are associated with the use of tissue valves as well as the replacement procedure.  In 
addition, complications due to individual subject reaction to an implanted device, or to 
physical or chemical components, particularly those of biological origin, may occur at 
varying intervals (hours or days) necessitating reoperation and replacement of the 
prosthetic device. 
Known risks associated with the use of stented bioprosthetic heart valves include: 
• Allergic reaction to valve materials 
• Angina 
• Annulus (damage, dissection, tear) 
• Aortic Insufficiency –Regurgitation/Stenosis 
• Aorta (damage, dissection, tear) 
• Blood - Coagulopathy 
• Blood - Hemolysis 
• Blood - Hemorrhage/anemia 
• Blood Pressure alteration (hypotension, 
hypertension) 
• Cardiac Arrest 
• Cardiac Arrhythmias/conduction 
disturbances 
• Cardiac Failure (heart failure) 
• Chordae Tendineae damage (Mitral valve) 
• Coronary artery Ostia blockage  
• Death 
• Endocarditis 
• Explant 
• Infection – local  
• Neurologic Events 
– Stroke (CVA) 
– Transient Ischemic Attack (TIA) 
• Reduced exercise tolerance  
• Thromboembolism  
• Transvalvular or Valvular Leaking 
• Valve instability/ migration/ embolization 
• Valve dislodgement 
• Valve - Non structural dysfunction 
– Paravalvular Leak 
– Leaflet impingement (Aortic or Mitral 
valve) 
– Leaflet tissue damage (instruments 
/sutures or pannus) 
– Subject Prosthesis Mismatch (PPM) (due 
to inappropriate sizing) 
– Distortion at implant 
• Valve - Structural dysfunction/deterioration 
(e.g., wear, leaflet tear, calcification, leaflet 
detachment from stent posts, component 
deterioration – physical or chemical) 
• Valve - Thrombosis  
• Valve Wireform and or Frame Fracture or 
Distortion (from chest compression or 
trauma)  
• Valve stent fracture 
• Valve stent separation 
• Annulus frame fracture  
• Annulus frame separation 
  

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Potential risks associated with aortic valve replacement surgery include: 
• Allergic reaction 
• Annular dissection 
• Aortic or arterial dissection 
• Asystole and/or cardiac arrest 
• Bleeding 
– 
Peri- or post-procedural 
– 
Anticoagulant related 
– 
Pericardial tamponade 
– 
Hematoma 
– 
Cerebral vascular 
• Cardiogenic shock 
• Disseminated intravascular coagulation 
(DIC) 
• Embolism, pulmonary 
• Esophageal tear/rupture 
• Heart failure 
• Hypo- or hypertension 
• Hypoxemia 
• Infection, local or wound or systemic 
• Infection, Septicemia – bacterial, viral, fungal 
• Myocardial infarction 
• Myocardial perforation, free wall 
• Multi-system organ failure (MOF) 
• Pericardial effusion 
• Pleural effusion 
• Pulmonary edema 
• Pneumonia 
• Renal failure, acute 
• Respiratory failure 
• Thrombocytopenia, (Non-HIT) 
• Thrombocytopenia, heparin induced (HIT) 
• Thromboembolism 
o Venous, peripheral or central 
o Arterial, peripheral or central 
o Pulmonary, thrombus or other 
 
Based on a review of the scientific literature, preliminary animal studies, risk analysis 
and a Failure Modes and Effects Analysis (FMEA), other potential risks associated with 
the use of the trial valve include: 
• 
Loss of frame structural integrity resulting in damage to LVOT 
• 
Delivery system impingement resulting in mitral leaflet chordae trauma or damage 
• 
Annular frame damage or under-flaring resulting in a reduction of EOA 
• 
Annular frame overexpansion resulting in conduction interruptions or disturbances 
(i.e., arrhythmia) 
• 
Separation of the annular frame from the sewing ring 
• 
Mitral valve impingement or abrasion with or without mitral regurgitation 
• 
Insufficient frame expansion/suturing resulting in PVL requiring intervention or 
reoperation 
• 
Device malpositioning resulting in coronary ostial blockage 
• 
Device embolization into the aorta or ventricle 

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7.5 
UNANTICIPATED ADVERSE DEVICE EFFECT 
An unanticipated adverse device effect (UADE) is defined as any serious adverse event 
on health and safety, or any life-threatening problem or death caused by, or associated 
with, this device, if that event, problem, or death was not previously identified in nature, 
severity, or degree of incidence in the investigational plan, or application.  Additionally, 
an unanticipated adverse event includes any other unanticipated serious problem 
associated with a device that relates to the rights, safety, or welfare of subjects. 
The Investigator must submit to the Sponsor or its designee and to the reviewing IRB, a 
report of any UADE occurring during this clinical investigation as soon as possible, but 
under no circumstance, later than 10 working days after the Investigator first learns of 
the event.  Full and complete written documentation must follow this report.  The 
Investigator must document all UADE, including the time and date of onset, complete 
description of the event, severity, duration, actions taken and outcome.  Record all 
UADE on the appropriate CRF. 
The Sponsor will immediately conduct an evaluation of any unanticipated device-related 
event.  In addition, the Sponsor will notify the DMC of an UADE within five (5) business 
days after Edwards or its designee first receives notice of the event.   
7.6 
ADVERSE EVENT DEFINITIONS/ REPORTABLE EVENTS 
Since assessment of safety requires comparison of the occurrence of adverse events to 
the OPC, it is extremely important to provide definitions of adverse events and to adhere 
to these definitions.  The method of reporting shall conform to the most recently 
published “Guidelines for reporting mortality and morbidity after cardiac valve 
interventions” by Akins et al [14]. 
In addition, it is of utmost importance to determine the primary event since secondary 
morbid events will not be included in the calculation of any complication rates. However, 
secondary events will be reported for informational purposes.  For example, if a subject 
has endocarditis and develops a PVL secondary to the infection, the PVL will not be 
counted in the PVL rate.  The endocarditis will be included in the calculation of the 
endocarditis rate.    

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Multiple events of the same complication in the same subject will be counted as a single 
event if the complication does not resolve.  For example, if a subject experiences 
multiple TIAs in a two-week period, only one event will be included in the linearized rate, 
although all events will be reported as a cluster.  Similarly, if a subject exhibits a PVL at 
six months, and that leak remains at the POD 365-415 visit, only one event will be 
included in the linearized rate calculation.  If, however, a subject has a stroke and then 6 
months later experiences another stroke, both events will be included in the calculation 
of the linearized stroke rate. 
MORTALITY REPORTING: 
In the event of subject death, every effort should be made to obtain a copy of the 
autopsy report and/or death summary.  The Investigator will provide information about 
the cause of death and will determine relationship to the clinical investigational device.  
The Clinical Events Committee (CEC) will adjudicate each death for device relatedness 
and procedure relatedness.  The site will send the Sponsor copies of an autopsy report, 
if available, and/or a death summary. 
If explant of a device occurs during autopsy, return the device to the Sponsor for 
analysis.  Return kits for explanted devices will be provided upon request by the clinical 
site manager. 
   
 
 

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EXPLANT REPORTING: 
In the event a trial valve is explanted in the late post-operative period, the Investigator 
will provide information on the explant and determine the relationship to the trial valve.  
Every effort should be made to supply copies of available explant reports, to the 
Sponsor.  As soon as possible, explanted trial valves should be returned to the Sponsor 
for analysis.  Sponsor will provide “return kits” for explanted devices upon request by the 
clinical site manager. 
A complete list of Adverse Event Definitions/ Reportable Events is located in XXX. 
7.7 
ASSESSMENT OF ADVERSE EVENTS 
The Investigator at each participating site is ultimately responsible for reporting AEs and 
complications.  Medical and scientific judgment should be exercised in determination of 
the AE description while adhering to the provided definitions.  The Investigator is 
required to complete the adverse event case report form (Adverse Event CRF see 
xxxxx) at each trial visit.  The Adverse Event CRF for a given visit must report all 
adverse events that occurred since the last documented visit. 
Description of each AE must be as follows: AE description, the date of onset, date of 
resolution, serious (yes/no; see Section 7.2), frequency of the event (single episode, 
intermittent, continuous), action taken (none, medical and/or surgical), relationship to 
device, relationship to the procedure, and seriousness criteria. 
 
CAUSALITY: 
The causal relationship of the AE to the device and the procedure should be rated as 
follows:  
• 
Not Related: Evidence exists that the adverse event definitely has a cause other than 
the trial procedure or device (e.g., pre-existing condition or underlying disease, 
intermittent illness, or concomitant medication) and does not meet any other criteria 
listed.  There is no relationship between the event and the device or procedure. 

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• 
Related: Evidence exists that the trial device or procedure caused the adverse event.  
There is a temporal relationship between the event onset and trial device or 
procedure.  The subject’s clinical state and concomitant therapies are ruled out as a 
cause. 
• 
Unknown: There is no evidence or relevant data available to assess the relationship 
between the event and the device or procedure. 
 
Adverse event outcome defined as follows: 
• 
Recovered/Resolved (the subject fully recovered from the adverse event with no 
residual effect observed). 
• 
Recovered/Resolved with Sequelae (the residual effects of the adverse event are still 
present and observable). 
• 
Ongoing (The adverse event itself is still present and observable). 
• 
Death. 
• 
Explant. 
• 
 Ongoing at the time of trial exit 
• 
Chronic Condition ( e.g., Cancer, Shingles, Herpes)  
Action Taken for Event (identify all that apply): 
• 
None (no treatment was required). 
• 
Medication required (prescription and/or over the counter medication was required to 
treat the adverse event. 
• 
Hospitalization or Prolongation of Hospitalization Required (hospitalization was 
required or prolonged due to the adverse event) 
• 
Surgical intervention (not involving the trial valve) 
• 
Reoperation or explant of the trial valve 
• 
Other (specify). 

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7.8 
ELECTROCARDIOGRAMS 
An ECG will be performed with the subject in supine position at, POD 180-240 (optional), 
and annually thereafter until the trial ends.  An expert cardiologist knowledgeable in 
cardiac conduction disturbances will determine the cardiac rhythm, and assess the ECG 
as normal or abnormal, and will specify any clinically significant abnormal findings.  
Any new or worsened cardiac conduction disturbance defined as new or worsened first 
degree atrioventricular (AV) block, second degree AV block (Mobitz I or Mobitz II), third 
degree AV block, incomplete right bundle branch block, right bundle branch block,  
intraventricular conduction delay, left bundle branch block, left anterior fascicular block, 
or left posterior fascicular block will be reported. 
7.9 
LABORATORY TESTING 
Blood data (red blood count, white blood count, hematocrit, hemoglobin, platelet count, 
and plasma-free hemoglobin or haptoglobin or serum LDH) will be collected POD 180-
240 (optional), POD 365-435, and annually thereafter until the trial ends. 
For all measured blood parameters, individual results will be compared to documented 
normal ranges.  The Investigator will determine for each parameter that is out-of-range 
whether the value is abnormal not clinically significant, or abnormal clinically significant.  
Since summary statistics involving laboratory parameters will be provided, an out-of-
range value does not necessarily constitute an AE; other signs and symptoms must be 
taken into an account in order to report the occurrence of an AE.  
Coagulation profile (which may include prothrombin time [PT], or partial thromboplastin 
time [PTT], or international normalized ratio [INR]) will be collected at the POD 180-240 
(optional visit) and annually thereafter, coagulation profile will only be determined for 
subjects on anticoagulant therapy. 
 

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8.0 
EFFECTIVENESS ASSESSMENTS 
8.1 
PERI-PROCEDURAL PARAMETERS 
Device technical success was defined as the successful delivery and deployment of 
the trial valve with maximum of two attempts and subject leaving the OR with valve in 
place.  In addition, cross-clamp and cardiopulmonary bypass times, and length of 
stay in the ICU will be documented. 
Procedural success was defined as device technical success followed by the 
absence of adverse events resulting in device reoperation implant of permanent 
pacemaker (with baseline sinus rhythm and no other pre-existing conduction issues), 
or valve-related death within discharge or 10 days post index procedure, whichever 
comes first. 
8.2 
NYHA CLASSIFICATION 
The percentage of subjects in each specific NYHA functional class and the change in 
NYHA classifications from screening will be analyzed at each time point where NYHA is 
obtained to evaluate if implanting the trial valve results in an improvement in NYHA 
classification.   
8.3 
HEMODYNAMIC PERFORMANCE 
Echocardiography will be conducted at POD 180-240 (optional), POD 365-435 and 
annually thereafter until the trial ends.  The Echocardiography Core Lab Manual is 
provided in XXX for specific information regarding the conduct of these procedures.     
 
The echo core lab will determine: peak systolic and mean aortic valve gradient, EOA, 
EOA index, performance index, cardiac output, cardiac index, valvular regurgitation 
(including paravalvular leak), left and right atrial size, left and right ventricular size, left 
and right ventricular function, ventricular septal and left ventricular posterior wall 
thickness, cavitary thrombi or other masses, pericardial abnormalities (e.g., effusion) and 
aortic root diameter.  

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9.0 
STATISTICAL METHODS 
The following section describes only those activities that will be conducted after the 
approval of the study product. All detailed analyses conducted for the PMA submission 
are XXXX and a xxxx all post approval analyses. 
 
9.1 
STATISTICAL ANALYSIS 
9.1.1 ANALYSIS POPULATION 
There will be two analysis populations for the trial: the enrolled or intent-to-treat 
population and the valve implant or as-treated population. The valve implant population 
will include all subjects who receive the trial valve and leave the operating room with the 
trial valve in place.   
The valve implant population will be used for all analyses of NYHA and 
echocardiographic data. 
9.1.2 SAFETY ANALYSIS 
The analyses of the safety data will be performed for enrolled (ITT) patientsand all valve 
implant (as-treated) patients.  However, the primary analysis population for all safety 
analyses will be the valve implant (as-treated) population.  
9.1.2.1 Primary Safety Endpoints 
For the safety endpoints listed in Section 2.1, the early adverse events within 30 days of 
implant will be reported as the number of events divided by the number of patients for 
the events.  Linearized rates will be used to summarize adverse events for the late (>30 
days) post-operative period.  The linearized rates will be calculated as the number of late 
events divided by the total late-patient years.  
Actuarial analysis using the Kaplan-Meier method will be used to estimate the probability 
of freedom from each primary safety endpoint. Primary analyses of the primary safety 
endpoints (post 30 days) will be based on linearized rates, which account for multiple 

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events from a single patient. Actuarial (Kaplan-Meier) analysis of the time to first event 
per patient will be provided as an additional analysis. 
9.1.2.2 Other Safety Data 
Percentages for the early events and linearized rates for the late events will be 
calculated for all complications.  If valve malposition, valve instability, valve 
dislodgement or valve migration/embolization occurs, any consequent adverse events or 
procedures (e.g. coronary ostia blockage, mitral valve impingement, or abrasion, 
intraoperative intervention, or reoperation) will be noted and rates presented.  
 
9.1.3 EFFECTIVENESS ANALYSIS 
 
Subjects will be analyzed according to the NYHA classification preoperatively, at POD 
31-46, POD 90-135, and annually post implant for 5 years.  The distribution (numbers of 
subjects and percentages) in the various NYHA classes and the change from baseline 
(improved, same and worse) will be tabulated and stratified by baseline NYHA at each 
follow-up interval. Echocardiography data will be obtained preoperatively, 
intraoperatively, at discharge, POD 90-135, POD 180-240 (optional) and annually post 
implant until the trial ends.  Descriptive statistics for the continuous echo variables (e.g. 
mean, standard deviation, and range) will be categorized by time interval and valve size.  
Regurgitation data will be summarized by counts and percentages at each severity level. 
A comparison of all effectiveness data for the EDWARDS INTUITY valve will be made to 
current state of the art prosthetic heart valve literature published in peer reviewed 
journals at the time of PMA submission. 
9.1.4 OTHER OUTCOMES ANALYSIS 
The change in Short Form 12 version 1 (SF-12v2) Quality of Life questionnaire from 
screening to 1 year will be summarized by N, mean, and standard deviation. 

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Blood data will be analyzed to determine if significant subclinical and unreported 
hemolysis is occurring due to the implant of the trial valve.  A trend analysis of two 
postoperative data points will be conducted to determine if hemolysis is increasing over 
time.  The following parameters will be included in the trend analysis: plasma-free 
hemoglobin, haptoglobin, serum LDH, hemoglobin and hematocrit.   
For all measured blood parameters, individual results will be compared to documented 
normal ranges.  The Investigator will determine for each parameter that is out-of-range 
whether the value is abnormal not clinically significant or abnormal clinically significant 
and summary statistics will be provided.   
9.1.5 MISSING DATA 
All statistical tests on the effectiveness endpoints will be performed using only those 
subjects with available data required for endpoint analysis.  No missing value imputation 
will be performed. 
9.2 
ADDITIONAL INFORMATION 
The following additional information will be provided: 
• 
the follow-up duration information, including the mean follow-up, standard deviation 
and range of follow-up and cumulative follow-up in late-patient years will be 
determined and reported;   
• 
subject compliance data for follow-up visits, NYHA functional classification data, 
echocardiographic data and clinical laboratory results will be determined and 
reported; 
• 
listing of AEs/complications by subject ID number; 
• 
case summaries of each death with a determination whether the death represents an 
early or late death; 
• 
available autopsy reports; 
• 
case summaries of explants and reoperations; 
• 
analyses of valves when a valve was explanted or an autopsy performed; 

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• 
summary of subjects not completing the trial due to lost to follow-up, explant or 
death; and 
• 
confounding factors such as gender, age at implant, preoperative NYHA Class, 
concomitant procedures, co-existing (cardiac) conditions, valve size, etc., will be 
considered in a hazard regression analysis to determine which factors may affect the 
incidence of reoperation, explant and death; 
• 
summary of subject complaints received. 
 
10.0 TRIAL COMMITTEES AND CORE LABORATORY  
10.1 
CLINICAL EVENTS COMMITTEE 
A CEC consisting of independent physicians familiar with the treatment of valvular heart 
disease and cardiac surgery will evaluate the adverse events including adverse events 
resulting in death as outlined in their charter and adjudicate these events for their 
relatedness to the trial device, and the trial device procedure.  
Members of the CEC will not have scientific, financial, or other conflict of interest related 
to the Sponsor or the Investigators.  CEC members must sign a non-conflict-of-interest 
statement in this regard.   
10.2 
DATA MONITORING COMMITTEE 
A DMC composed of two or more independent physicians including a cardiothoracic 
surgeon and cardiologist, and a statistician evaluated the rates of OPC’s, study 
endpoints and serious adverse events including deaths and explants for all subjects in 
the clinical investigation as well as the hemodynamic performance of the EDWARDS 
INTUITY aortic valve during the enrollment phase.  Members of the DMC did not have 
scientific, financial, or other conflict of interest related to the Sponsor or the 
Investigators.  DMC members signed a non-conflict-of-interest statement in this regard.   
The DMC activities and meeting schedule was regulated by the DMC Charter. 
 

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Number: 2011-02 IDE: G110189 / P150036 
 
 
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10.3 
ECHOCARDIOGRAPHY CORE LAB 
The purpose of the Echocardiographic Core Laboratory is to ensure unbiased, timely 
and consistent analysis of these diagnostic data. The Core Lab is responsible for 
evaluating changes in subject status over the course of the trial based on serial 
echocardiographic studies conducted in the same subject. Personnel at the Core Lab 
will have training and experience appropriate for analyzing Doppler Echocardiography 
data. The Sponsor will ensure that Core Lab personnel are familiar with the valve. The 
Sponsor or its designee will periodically perform audits of the Core Lab. The Sponsor will 
review the data provided by the Core Lab as appropriate.  
Doppler echocardiograms must be conducted as described in xxx; original videotapes or 
CDs of Doppler echocardiograms will be sent directly from the trial sites to the Core Lab. 
The Core Lab will review the Doppler echocardiograms upon receipt and notify the site 
promptly if the quality of the echocardiogram is insufficient for analysis.   
 
11.0 DATA INTEGRITY, COLLECTION AND QUALITY ASSURANCE 
To protect subject confidentiality, the subject’s name must not appear anywhere on the 
imaging media sent for evaluation by the Core Lab, or on copies of supporting 
documentation removed from the investigational center.  Each page should be identified 
with the subject’s ID number only.  All other subject identifiers (e.g., subject name, 
address, medical record number etc.) are to be obscured.  Electronic records will be 
compliant with 21 CFR Part 11. 
11.1 
DATA COLLECTION 
All required data for this investigation are to be collected on standardized eCRFs for 
individual enrolled subjects; sample eCRFs are provided in xxxxx.  The eCRF must be 
electronically signed by the Principal Investigator or co-Investigator listed in the Clinical 
Studies Agreement and/or Delegation of Authority Log. If for any reason the eCRFs are 
unavailable and/or inaccessible, paper CRFs will be provided by the Sponsor to be 
completed, signed by the Principal Investigator or designee and submitted to the 
Sponsor. Case Report Form Instructions will be provided to assist the Investigator(s) and 
appropriate investigational staff in the completion of the required eCRFs. 

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Number: 2011-02 IDE: G110189 / P150036 
 
 
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Source documents are original documents, data, and records from which the subject’s 
CRF data are obtained. These include, but are not limited to, hospital records, clinical 
and office charts, laboratory records, and correspondence.     
Electronic CRFs must be kept current to reflect enrolled subject status during the course 
of the investigation. 
11.2 
DATA QUALITY ASSURANCE 
Edwards Lifesciences clinical affairs and data management departments have quality 
assurance procedures to ensure that complete, accurate and timely data are collected, 
that the Investigational Plan requirements are followed and that all complications and 
adverse events are reported in a timely manner. 
Electronic CRFs are used for collecting and recording of data for enrolled subjects at all 
trial sites.  Investigators or their designees are responsible for the timely completion of 
these forms. 
Entered data are reviewed to identify inconsistent or missing data and adverse events.  
Data problems will be addressed by phone or written communication with the trial sites 
and/or during site visits.  All forms and data files will be secured to ensure confidentiality. 
Investigators are to maintain all source documents required by regulation, including 
diagnostic test reports, laboratory results, completed CRFs, supporting medical records 
and informed consents.  The source documents will be referenced during regular 
monitoring visits to verify the information documented on the CRFs.   
 
Follow-up Doppler echocardiograms will be evaluated by the designated Echo Core Lab.  
A standardized written report generated by the Core Lab for each Doppler 
echocardiogram will be entered into an electronic database maintained by the Sponsor.  
The Clinical Site Manager or Sponsor designee shall notify the Investigator should there 
be any indication of a complication or discrepancy that the Investigator may not have 
noted.  This will allow the Investigator an opportunity to further review the test results 
and clarify the findings if necessary.  

CLINICAL INVESTIGATION PLAN 
  
TRANSFORMTM Post Approval Phase  
Number: 2011-02 IDE: G110189 / P150036 
 
 
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The electronic database is subject to predefined electronic data checks to identify 
potential discrepancies and inconsistencies.  Furthermore, trial content data reviews are 
conducted to ensure that data collected are scientifically and medically valid.  Regular 
feedback and reports will be provided to the site manager, so that all queries can be 
resolved in a timely fashion.      
12.0 INVESTIGATOR RESPONSIBILITIES 
The Investigator is responsible for ensuring that this clinical trial is conducted according 
to the Investigator Agreement, Protocol, all conditions of FDA and IRB approval and 
applicable FDA regulations. Written IRB approval of the protocol and ICF must be 
provided to the Sponsor.  
Subjects were informed that their medical records will be subject to review by the 
Sponsor, its authorized designee or representatives of FDA.  Subjects were informed 
that they may withdraw at any time without prejudice to future care.  The informed 
consent provided by each trial site’s IRB was signed prior to trial participation.  The 
original signed informed consent for each subject must be retained by the Investigator 
and is subject to review by the Sponsor and the FDA.  A copy of the informed consent 
will be provided to the subject.  
Other specific responsibilities of the Investigator include: 
Financial Disclosure: 
The Investigator provided sufficient and accurate financial disclosure information prior to 
trial, and will promptly update the Sponsor of relevant changes during the course of the 
trial and for 1 year following completion of the trial. 
. 
Inspection: 
The Investigator shall permit authorized FDA employees at reasonable times and in as 
reasonable manner to enter and inspect any establishment where devices are held, 
inspect and copy all records relating the investigation, to inspect and copy records that 
identify subjects when the FDA has reason to suspect that records are incomplete, 
inaccurate, false or misleading. 

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TRANSFORMTM Post Approval Phase  
Number: 2011-02 IDE: G110189 / P150036 
 
 
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12.1 
INVESTIGATOR RECORDS 
Investigators will maintain complete, accurate and current trial records for whichever of 
the following periods is shortest: 
a. A period of two years after the date on which the FDA approves the marketing of 
the device for the purpose that was the subject of the trial. 
b. A period of five years after the date on which the results of the trial are submitted 
to the FDA in support of the marketing of the device for the purpose that was the 
subject of the trial. 
If the Investigator withdraws from the responsibility to maintain records, the custody of 
records may be transferred.  Notice of transfer shall be given to the FDA no later than 10 
working days after transfer occurs. 
Investigator records shall include the following materials: 
Correspondence: 
Documentation of all verbal and written correspondence with FDA, the Sponsor or its 
designee including the Clinical Monitor, the Medical Monitor, the DMC and other 
Investigators regarding this clinical trial or any subject enrolled therein. 
Device Accountability: 
Accountability records of receipt, use and disposition of all investigational devices and 
other trial materials, including: 
• 
The type and quantity of the devices, dates of receipt and serial or lot numbers 
• 
The names of all persons who received, used or disposed of each device and 
• 
Why and how many units of the device are returned to Edwards Lifesciences, or 
otherwise disposed of. 
Subject records: 
Available subject records will include: signed informed consent, supporting documents 
(admission summary, operative reports, discharge letters, pertinent consultation reports 
diagnostic tests, laboratory tests, medical records, etc.) and records of exposure of each 
subject to the device.   

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Number: 2011-02 IDE: G110189 / P150036 
 
 
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Investigational Plan (Trial Protocol): 
A Trial Site Regulatory binder will be maintained by the Investigator and site coordinator 
and will include a current copy of the Investigational plan including the IFU of the trial 
valve and other specified documents as listed in the binder table of contents. 
Unanticipated Adverse Device Effects: 
The Investigator will maintain records of all reports and information pertaining to 
unanticipated device effects. 
IRB Information: 
All information pertaining to IRB review and approval of this clinical trial including a copy 
of the IRB letter and that the IRB approved the Investigational Plan, a blank ICF 
approved by the IRB, and certification from the IRB Chairman that the IRB complies with 
FDA regulations (21CFR, Part 56). 
Investigator Agreements: 
The Investigator will maintain copies of signed Investigator Agreements and current CVs 
of all participating clinical trial staff members. 
Other: 
The Investigator will maintain any other records that may be required by applicable state 
or U.S. federal laws. 
 
Investigator Reports: 
 
The Investigator will prepare and submit the following reports: 
Withdrawal of IRB Approval: 
If applicable, withdrawal of approval shall be reported to the Sponsor within five working 
days.  The Investigator will provide a written report of the reason(s) approval was 
withdrawn. 
 
 
 
 

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TRANSFORMTM Post Approval Phase  
Number: 2011-02 IDE: G110189 / P150036 
 
 
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Progress Reports: 
The Investigator will submit progress reports to the Sponsor in the form of completed 
CRFs.  The same forms will be used at all trial sites for the recording of data on the 
findings of follow-up evaluations and complications.  In addition, the Investigator may be 
asked to submit progress reports to the Sponsor and the reviewing IRB that include the 
number of trial subjects, a summary of follow-up data and AEs/complications and a 
general description of trial progress. 
Final Report: 
The Investigator shall submit a final report within three months of termination, completion 
of the trial or completion of the Investigator’s participation in the trial, to the Sponsor and 
the IRB. 
Deviations from the Trial Protocol: 
The Investigator will not deviate from the protocol without the prior written approval of 
the Sponsor except in medical emergencies or in unforeseen, isolated instances where 
minor changes are made that will not increase the subject’s risk or affect the validity of 
the trial. Any subsequent revisions to the protocol, including the Informed Consent Form 
and the Case Report Forms, other than very minor revisions, must be approved by the 
Sponsor, the FDA, and the IRB.  In medical emergencies, prior approval for protocol 
deviations will not be required, but the Sponsor or its designee and IRB must be notified 
within 5 working days of the incident.  Periodic monitoring of protocol compliance will be 
performed for each site.  Deviations will be documented on the appropriate case report 
form.  
Other Reports: 
Upon the request of FDA, the reviewing IRB, or the Sponsor, the Investigator will provide 
accurate and timely information about any aspect of the clinical trial. 
 
 

CLINICAL INVESTIGATION PLAN 
  
TRANSFORMTM Post Approval Phase  
Number: 2011-02 IDE: G110189 / P150036 
 
 
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13.0 SPONSOR RESPONSIBILITIES 
 
The Sponsor is responsible for ensuring that this trial will be conducted in compliance 
with all applicable U.S. Federal regulations pertaining to investigational devices including 
but not limited to: 21 CFR Part 50, Part 54, Part 56, Part 812, Good Clinical Practice 
(GCP) standards, and Health and Insurance Portability and Accountability Act (HIPAA). 
 
The Sponsor will prepare and submit the following complete, accurate and timely 
reports: 
Unanticipated Adverse Device Effects (UADE) 
UADEs shall be reported to FDA and to all reviewing IRBs and participating investigators 
within 10 working days after the Sponsor receives notice of the effect. 
Withdrawal of IRB Approval 
Any withdrawal of approval of an investigation or a part of an investigational by a 
reviewing IRB shall be reported to FDA and all reviewing IRBs and participating 
investigators within 5 working days after receipt of the withdrawal of approval.   
Withdrawal of FDA Approval 
Any withdrawal of approval of an investigation or a part of an investigational by FDA 
shall be reported to all reviewing IRBs and participating investigators within 5 working 
days after receipt of the withdrawal of approval.   
Progress Report 
A progress report shall be submitted to FDA and reviewing IRBs annually. 
Final Report 
A final report shall be submitted to FDA and all reviewing IRBs within 6 months of trial 
completion or termination. 
. 
The Sponsor will provide Investigators with the information and training required to 
conduct the clinical trial properly and in accordance with the clinical protocol.  The 
Sponsor must ensure proper monitoring of the Clinical Trial, that IRB approval is 

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TRANSFORMTM Post Approval Phase  
Number: 2011-02 IDE: G110189 / P150036 
 
 
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obtained and remains current, and that FDA and the IRB are informed of significant new 
information about the clinical trial.  The Sponsor of this trial is Edwards Lifesciences, 
LLC. 
 
Trial Director: 
  
 
  
The clinical trial manager is responsible for the conduct and administration of this clinical 
trial. These responsibilities include maintaining regular contact with each trial site and 
ensuring the conduct of all on-site monitoring visits at each trial site to ensure 
compliance with this clinical, to verify that accurate and complete data are being 
submitted in a timely manner and to verify that the investigational site facilities continue 
to be adequate. The Clinical Manager of this trial is: 
 
 
Trial Manager: 
  
 
13.1 
SELECTION OF INVESTIGATORS 
Edwards Lifesciences will select qualified Investigators by education, training and 
experience and verify the adequacy of the trial site. 
13.2 
TRAINING 
The Sponsor or designee will train the Principal Investigator(s) and support staff on the 
use of the trial Valve and the trial delivery system, the Protocol, eCRFs and Electronic 
Data Capture (EDC) system, GCP Guidelines and other investigation documents as 
applicable.  A “Delegation of Authority Form” will be maintained at each investigational 
center designating which individuals are allowed to perform specific clinical investigation 
related tasks.  The delegated tasks will determine what the training requirements are for 
each member of the investigation support staff. Training will be documented for each 
site. 
 

CLINICAL INVESTIGATION PLAN 
  
TRANSFORMTM Post Approval Phase  
Number: 2011-02 IDE: G110189 / P150036 
 
 
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13.2.1 ECHOCARDIOGRAPHIC EXAMINATIONS 
Clinical sites may be trained by the core lab staff or may self–train.  See xxxx for a copy 
of the Echo Core Lab Manual. 
13.2.2 DOCUMENTATION 
Training will be documented on a training record provided by the Sponsor, which the 
trainee must sign and date. The training of investigation support staff must be completed 
and documented before the staff member may perform the specific clinical investigation 
related tasks delegated to them by the Principal Investigator. 
 
 

CLINICAL INVESTIGATION PLAN 
  
TRANSFORMTM Post Approval Phase  
Number: 2011-02 IDE: G110189 / P150036 
 
 
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13.3 
MONITORING METHODS   
The Sponsor has established procedures for monitoring clinical investigations to assure 
the quality of the trial and to assure that each person involved in the monitoring process 
carries out his or her duties. Standardized written procedures, sufficiently detailed to 
cover the general aspects of clinical investigations, will be used as a basic monitoring 
plan and will be supplemented by more specific or additional procedures, as required by 
the clinical investigation. A pre-investigation “Qualification Visit” was conducted to 
ensure that the Investigator clearly understood and accepted the obligations incurred in 
undertaking the clinical investigation as set forth in 21 CFR 56 and 21 CFR 812, and that 
the facilities are acceptable throughout the clinical investigation. Only qualified 
investigational sites participated in the trial. Periodic monitoring visits will be conducted 
with adequate frequency to ensure that the Investigator’s obligations as set forth in 21 
CFR 56 and 21 CFR 812 are being fulfilled and that the facilities continue to be 
acceptable. The Sponsor assigns a monitor to oversee the progress of the clinical 
investigation at each investigational center. The monitor will remain in close contact with 
each investigational center throughout the duration of the investigation to provide any 
needed materials, (i.e., investigation forms) and answer any questions.  The monitor will 
be responsible for verifying that the subject signed the consent, reviewing all data 
recorded on the eCRFs (100% source data verification), and visiting each investigational 
center periodically to observe trial progress and compliance with clinical protocol and 
regulations applicable to this clinical investigation.  
Monitoring visits will be scheduled throughout the duration of the clinical investigation 
between the monitor and the Principal Investigator at a mutually convenient and 
available time. These visits will assure that the facilities are still acceptable, the protocol 
and investigational plan are being followed, the IRB is notified of approved protocol 
changes as required, complete records are being maintained, appropriate timely reports 
(incl. AEs, SAEs and UADEs) are made to the Sponsor and IRB, and device inventory is 
controlled and the Investigator is carrying out all agreed upon  activities. Any personnel 
changes must be reported to the monitor immediately and a training program must be 
scheduled and documented. Additionally, the monitor will perform 100% source data 

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Number: 2011-02 IDE: G110189 / P150036 
 
 
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verification of events contributing to the primary safety endpoints and unanticipated 
device effects (UADEs) to assure CRF data accuracy and completeness.   
13.3.1 MONITORING VISITS 
Periodic monitoring visits will be made at all trial centers in accordance with center 
enrollment rates. Trial centers should be visited a minimum of once each year by the 
monitor. 
Upon termination or conclusion of the clinical investigation, the monitor will perform a 
close-out visit to ensure that all clinical trial materials and patient data are properly 
documented and returned to the Sponsor. 
 
 

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Number: 2011-02 IDE: G110189 / P150036 
 
 
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Baumgartner Predictors of outcome in severe asymptomatic aortic stenosis. N Engl J Med. 
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6. Florath I, Rosendahl UP, Mortasawi A, Bauer SF, Dalladaku F, Ennker IC, Ennker JC. 
Current determinants of operative mortality in 1400 subjects requiring aortic valve 
replacement. Ann Thorac Surg. 2003;76(1):75-83 
7. Tjang YS, van Hees Y, Körfer R, Grobbee DE, van der Heijden GJ. Predictors of mortality 
after aortic valve replacement. Eur J Cardiothorac Surg. 2007;32(3):469-74. 
8. Melby SJ, Zierer A, Kaiser SP, Guthrie TJ, Keune JD, Schuessler RB, Pasque MK, Lawton 
JS, Moazami N, Moon MR, Damiano RJ Jr. Aortic valve replacement in octogenarians: risk 
factors for early and late mortality. Ann Thorac Surg. 2007;83(5):1651-6; discussion 1656-7 
9. Powell, D. E., Tunick, P. A., Rosenzweig, B. P., Freedberg, R. S., Katz, E. S., Applebaum, R. 
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10. Chitwood, WR Minimally Invasive Valve Surgery: Trends for the Future. Euro J Card Thorac 
Surg 1999;16(Suppl 1):S64-5. 
11. Schmitto JD, Mohr FW, Cohn LH. Minimally invasive aortic valve replacement: how does this 
perform in high-risk subjects? Curr Opin Cardiol. 2011;26(2):118-22. 
12. Plass A, Scheffel H, Alkadhi H, Kaufmann P, Genoni M, Falk V, Grünenfelder J. Aortic valve 
replacement through a minimally invasive approach: preoperative planning, surgical 
technique, and outcome. Ann Thorac Surg. 2009;88:1851-6. 
13. Bonow, R. O., Carabello, B. A., Kanu, C., de Leon, et al. ACC/AHA 2006 guidelines for the 
management of subjects with valvular heart disease: a report of the American College of 
Cardiology/American Heart Association Task Force on Practice Guidelines (Writing 
Committee to revise the 1998 Guidelines for the Management of Subjects With Valvular 
Heart Disease): developed in collaboration with the Society of Cardiovascular 

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TRANSFORMTM Post Approval Phase  
Number: 2011-02 IDE: G110189 / P150036 
 
 
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Anesthesiologists: endorsed by the Society for Cardiovascular Angiography and Interventions 
and the Society of Thoracic Surgeons. Circulation 2006;114:84-231. 
14. Akins C.W., Miller, D.G., Turina M.I.et al.  Guidelines for reporting mortality and morbidity 
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15. Kocher, A. A., Laufer, G., et. Al.  One-year outcomes of the Surgical Treatment of Aortic 
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