The PARTNER II Trial: Placement of AoRTic TraNscathetER Valves: Continued Access Program for SAPIEN 3 Intermediate Risk (S3iCAP)
Phase: NA
Conditions: Aortic Stenosis
Sponsor: Edwards Lifesciences

PROPRIETARY DATA: This document and the information contained herein may not be reproduced, used 
or disclosed without written permission from Edwards Lifesciences LLC. 
Edwards Lifesciences, Edwards, the stylized logo, and SAPIEN XT are trademarks of Edwards Lifesciences 
Corporation 
The PARTNER II Trial: 
Placement of AoRTic TraNscathetER Valves: 
Continued Access Program for SAPIEN 3 Intermediate Risk 
(S3iCAP) 
NCT02687035 
September 2015 

The PARTNER II–US-IDE Trial S3i CAP  
   Edwards Lifesciences 
PII Amendment H September 2015  
     CONFIDENTIAL  
 Page   1  
The PARTNER II Trial for SAPIEN 3 Intermediate Continued 
Access  
The Safety and Effectiveness of the SAPIEN 3 Transcatheter Heart Valve 
with Associated Delivery Systems in Intermediate Patients with Severe 
Symptomatic Aortic Stenosis 
Study 2010-12-US Amendment H 
IDE G090216 
Edwards Lifesciences LLC 
One Edwards Way 
Irvine, CA 92614

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   Edwards Lifesciences 
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     CONFIDENTIAL  
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TABLE OF CONTENTS 
1.0 
PURPOSE ....................................................................................................................... 3
2.0 
DEVICE DESCRIPTION ................................................................................................... 3
3.0 
BACKGROUND ............................................................................................................... 3
4.0 
DESIGN ........................................................................................................................... 4
5.0 
CONTINUED ACCESS PROTOCOL ENDPOINTS .......................................................... 4
6.0 
SITES ............................................................................................................................... 4
7.0 
ENROLLMENT ................................................................................................................ 5
8.0 
CONTINUED ACCESS STUDY DURATION .................................................................... 5
9.0
PATIENT POPULATION .................................................................................................. 5
10.0  STUDY VISITS ................................................................................................................ 7
11.0  MONITORING OF STUDY ..............................................................................................11
12.0 PROTOCOL DEVIATIONS .............................................................................................11

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1.0   Purpose 
The purpose of this protocol is to provide continued access of the Edwards SAPIEN 3 
Transcatheter Heart Valve Model 9600TFX (20, 23, 26, 29 mm) and delivery systems 
(transfemoral, transapical and transaortic), which are intended for use in patients with 
symptomatic, calcific, severe aortic stenosis for patients with intermediate risk for standard 
aortic valve replacement. 
2.0  Device Description 
The Edwards SAPIEN 3 transcatheter heart valve (THV) is comprised of a balloon-expandable, 
radiopaque, cobalt-chromium alloy frame, trileaflet bovine pericardial tissue valve, and 
polyethylene terephthalate (PET) internal fabric skirt, and a PET outer skirt. The valve is treated 
according to the Edwards ThermaFix process, and is packaged and terminally sterilized in 
glutaraldehyde. 
Refer to the instructions for use for descriptions of the following SAPIEN 3 Edwards accessory 
devices: 

Edwards Commander Delivery System, models 9610TF23, 9610TFX23, 9610TF29 for
the transfemoral procedure

Edwards Expandable Introducer Sheath Set, models 9610ES14, 916ES23 for the
transfemoral procedure

Edwards Certitude Delivery System, models 9620TA23, 9620TA26, and 9620TA29  for
transapical and transaortic procedure

Edwards Certitude Introducer Sheath Set, models 9620IS18 and 9620IS21 for the
transapical and transaortic procedure

Ascendra Balloon Aortic Valvuloplasty Catheter model 9100BAVC for the transapical
and transaortic procedure

Crimper, model 9600CR
3.0  Background 
A total of 1,078 intermediate risk patients were enrolled in the PARTNER II SAPIEN 3 
intermediate (PIIS3i) cohort. Edwards has received strong feedback from the PARTNER 
Community that further research for both the SAPIEN 3 valve as well as the intermediate risk 
group is warranted to expand the device and procedural related learning as well as to address 
the needs of patients that are in the screening process or could present at the investigating 
centers.   

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4.0 
 Design 
All data from Screening through 1 year; including adverse events (AE) will be entered in The 
Society of Thoracic Surgeons (STS) and the American College of Cardiology (ACC), TVT 
Registry™ (TVTR). Data excerpts of the TVTR data entered by enrolling sites will be transferred 
to the Sponsor on a monthly basis. All patient personal identifiers will be redacted prior to data 
transfer. The annual one year follow-up visit data will be entered in the TVTR, and data from 
years 2-5 will be obtained from the Centers for Medicare and Medicaid Services (CMS) via 
TVTR linkage. 
Edwards or designee will monitor the patient 30-day follow up visit data. 
The TVTR is a benchmarking tool developed to track patient safety and real-world outcomes 
related to transcatheter valve replacement, repair procedures and emerging treatments for valve 
disease patients. It is designed to monitor the safety and efficacy of these new technologies for 
the treatment of valve disease. 
Patients in PIIS3i continued access must be covered by Medicare. This will enable Edwards to 
link to the CMS database for long term follow-up through 5 years.  No other insurance provider 
will be accepted for enrollment.  
Participating sites will maintain patient files in the same manner as they do for the initial 
Investigational Device Exemption (IDE) study patient populations. Refer to the PARTNER II 
protocol version 6.0 or most current protocol version for additional information. 
5.0  Continued Access Protocol Endpoints 
The primary safety and effectiveness endpoint is stroke, aortic valve reintervention and death at 
the 30-day follow-up visit. 
Summary statistic reports for the primary safety and effectiveness endpoint will be provided at 
the 1 year follow-up visit.   
Secondary safety endpoints will include death, annular dissection, aortic dissection, major 
access vascular site complication, unplanned vascular surgery or intervention, and 
retroperitoneal, GI and GU bleeds, and bleeding at access sites collected through the 30 day 
follow-up visit.  
Summary statistic reports for individual rates of death and all other safety endpoints included in 
the TVTR data collection form in sections F, I, and on the adjudicated event rates (section J) for 
stroke and aortic reintervention will be provided. 
6.0  Sites 
Up to a total of 60 actively enrolling sites. 

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7.0 
 Enrollment 
A total of 1,078 intermediate risk patients were implanted in the PIIS3i cohort. Enrollment in this 
continued access protocol will consist of up to a maximum of 2,000 PIIS3i patients. Patients 
enrolled under the PIIS3i continued access will become part of the TVTR database.  Edwards 
will receive data excerpts from the TVTR on a monthly basis through the first year of patient 
registration and then yearly through follow-up year 5. Edwards will provide annual reports to the 
FDA based on this data through year 5 of follow up.  
To ensure enrollment is representative and balanced across study sites, no site will enroll more 
than 15 percent of the total enrollment or implant approach. 
8.0  Continued Access Study Duration 
Enrollment will continue up to a maximum of 2,000 continued access patients. 
Initial Enrollment: January 2015 
Anticipated Enrollment Close: August 2016 
9.0  Patient Population 
Inclusion Criteria  
All candidates for this study must meet the following criteria: 
1. Patients must be covered by Medicare. This will enable Edwards to link to the CMS
database for long term follow-up through 5 years.  No other insurance provider will
be accepted.
2. Assessment of intermediate surgical risk defined as STS 4-8% or heart team
assessment of intermediate risk factors.
3. Patient has senile degenerative aortic valve stenosis with echocardiographically
derived criteria: mean gradient > 40 mmHg or jet velocity greater than 4.0 m/s and
an initial aortic valve area (AVA) of  < 0.8 cm2 or indexed EOA < 0.5
cm2/m2.  Qualifying echo must be within 60 days of the date of the procedure.
4. Aortic valve annulus area range (273mm2-680 mm2) per 3D imaging (echo, CT, or
MRI).
5. Patient is symptomatic from his/her aortic valve stenosis, as demonstrated by NYHA
Functional Class II or greater.
6. The heart team agrees (and verified in the case review process) that valve
implantation will likely benefit the patient.
7. Heart team agrees (a priori) on treatment strategy for concomitant coronary disease
(if present).
8. The study patient or the study patient’s legal representative has been informed of the
nature of the study, agrees to its provisions and has provided written informed

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consent as approved by the Institutional Review Board (IRB) of the respective clinical 
site.  
9. The study patient agrees to comply with all required post-procedure follow-up visits
including annual visits through 5 years and analysis close date visits, which will be
conducted as a phone follow-up.
Exclusion Criteria 
Candidates will be excluded from the study if any of the following conditions are present: 
1. Heart team assessment of inoperability (including examining cardiac surgeon).
2. Evidence of an acute myocardial infarction ≤ 1 month (30 days) before the intended
treatment [(defined as: Q wave MI, or non-Q wave MI with total CK elevation of CK-
MB ≥ twice normal in the presence of MB elevation and/or troponin level elevation
(WHO definition)].
3. Aortic valve is a congenital unicuspid or congenital bicuspid valve, or is non-calcified.
4. Mixed aortic valve disease (aortic stenosis and aortic regurgitation with predominant
aortic regurgitation >3+).
5. Pre-existing mechanical or bioprosthetic valve in any position.
6. Complex coronary artery disease:
a) Unprotected left main coronary artery
b) Syntax score > 32 (in the absence of prior revascularization)
7. Any therapeutic invasive cardiac procedure resulting in a permanent implant that is
performed within 30 days of the index procedure (unless part of planned strategy for
treatment of concomitant coronary artery disease).  Implantation of a permanent
pacemaker or ICD is not considered exclusion criteria.
8. Any patient with a balloon valvuloplasty (BAV) < 30 days of the procedure (unless
BAV is a bridge to procedure after a qualifying ECHO).
9. Patients with planned concomitant surgical or transcatheter ablation for atrial
fibrillation.
10. Leukopenia (WBC < 3000 cell/mL), acute anemia (Hgb < 9 g/dL), thrombocytopenia
(Plt < 50,000 cell/mL).
11. Hypertrophic cardiomyopathy with or without obstruction (HOCM).
12. Hemodynamic or respiratory instability requiring inotropic support, mechanical
ventilation or mechanical heart assistance within 30 days of screening evaluation.
13. Need for emergency surgery for any reason.
14. Severe ventricular dysfunction with LVEF < 20%.
15. Echocardiographic evidence of intracardiac mass, thrombus or vegetation.

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16. Active upper GI bleeding within 3 months (90 days) prior to procedure.
17. A known contraindication or hypersensitivity to all anticoagulation regimens, or
inability to be anticoagulated for the study procedure.
18. Native aortic annulus size < 16 mm or > 28mm as measured by echocardiogram.
19. Clinically (by neurologist) or neuroimaging confirmed stroke or transient ischemic
attack (TIA) within 6 months (180 days) of the procedure.
20. Renal insufficiency (creatinine > 3.0 mg/dL) and/or renal replacement therapy at the
time of screening.
21. Estimated life expectancy < 24 months (730 days) due to carcinomas, chronic liver
disease, chronic renal disease or chronic end stage pulmonary disease.
22. Expectation that patient will not improve despite treatment of aortic stenosis.
23. Significant aortic disease, including marked tortuosity (hyperacute bend), aortic arch
atheroma [especially if thick (> 5 mm), protruding or ulcerated] or narrowing
(especially with calcification and surface irregularities) of the abdominal or thoracic
aorta, severe “unfolding” and tortuosity of the thoracic aorta. (Transfemoral)
24. Iliofemoral vessel characteristics that would preclude safe placement of 14F or 16F
introducer sheath such as severe obstructive calcification, severe tortuosity or
minimum average vessel size less than 5.5 mm. (Transfemoral).
25. Currently participating in an investigational drug or another device study.  Note:
Trials requiring extended follow-up for products that were investigational, but have
since become commercially available, are not considered investigational trials.
26. Active bacterial endocarditis within 6 months (180 days) of procedure.
27. Evidence of intracardiac mass, thrombus, vegetation, active infection or endocarditis.
28. Inability to tolerate anticoagulation/antiplatelet therapy.
29. For transfemoral approach only: Femoro-iliac vessels < 5.5 mm for the 23 mm and
the 26 mm system and < 6.0 mm for the 29 mm system.
10.0   Study Visits 
The data in the following sections will be collected for all patients (see Table 1.0). Assessments 
listed throughout this section are an overview of key assessments; however, please refer to the 
TVTR data collection form for all required assessments.  
10.1   Screening 
The screening phase is designed to meet the following objectives: 
1. Determine patient eligibility, operability risk assessment and access site for THV
procedure.

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2. Patient informed consent.
10.1.0 Screening Assessments
Screening assessments should be completed within 30 days of patient
enrollment unless otherwise specified.

Medical history

STS Risk Score

NYHA classification

Syntax Score (conducted in the absence of prior revascularization)

Hemoglobin, Platelet Count, Creatinine

Transthoracic (TTE) or transesophageal echocardiogram (TEE)

Cardiac Imaging (ECHO, CTA, or cardiac MRI) with 3D reconstruction of the
aortic root to determine aortic valve annulus area must be completed within
180 days of patient enrollment.

Reference S3 Sizing Guide (Protocol 6.0, Appendix U) for sizing
recommendations

Thoracic x-ray, an abdominal angiogram, and CT angiograms or MRI, and
with complete visualization of both iliacs and femorals to the aorta.  In the
situation where patients have compromised renal function that precludes
the use of contrast agents, MR imaging may be used as an alternative. CT
scans are strongly recommended, particularly in patients with femoral
arteries less than 7 mm; (must be within 180 days of patient enrollment).
Patients with previously documented inadequate femoral access
[(Iliofemoral vessel characteristics that would preclude safe placement of
22F or 24F introducer sheath (14F or 16F for S3) such as severe
obstructive calcification, severe tortuosity or minimum average vessel size
less than 6 mm (20, 23 and 26 mm THV minimum vessel size ≥ 5.5 mm /
29 mm THV minimum vessel size ≥ 6.0 mm for S3)] don’t require repeat
testing.

Left and right cardiac catheterization to assess the severity of aortic stenosis
and severity of coronary artery disease if applicable (< 90 days before
procedure)
Data must be entered in the STS/ACC TVT Registry. Data in the TVTR data forms will be 
included in monthly data transfers from the TVTR to the Sponsor. All patient personal identifiers 
will be redacted prior to data transfer. 
10.2  Case Review Process 
Patients must meet the fundamental enrollment criteria of severe, symptomatic, calcific aortic 
stenosis. Upon meeting these eligibility criteria, the site investigators (per site heart team 
assessment) shall then determine the patient’s risk for operative morbidity and mortality.
Patients determined to be operable must have a STS score of 4 - 8% or a defensible 

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intermediate risk profile determined by the heart team and approved by the case review board 
process.   
The PARTNER II trial operations include a case review process prior to enrollment of patients. 
After screening assessments are made, the patient’s qualifying criteria are reviewed by the case 
review board where the members will assess patient eligibility and access approach. Upon 
approval, the patient may be enrolled into the study. The case approval decision will be 
documented by the Sponsor.  
The study procedure should occur within two weeks (14 days) of case approval.
10.3  Pre-Procedure Assessments 
The following data will be collected for all patients prior to the procedure (see Table 1.0). 
Assessments must be completed within 30 days of patient enrollment unless otherwise 
specified.   

Height and weight closest to the time of the procedure

Medication classification (anticoagulants, anti-platelet/anti-thrombins, inotropes)

STS Score

5 Meter Walk Test

KCCQ

Pulmonary Function Test (FEV1, DCLO); optional

Albumin

Bilirubin, total

INR
Data must be entered in the STS/ACC TVT Registry. Data in the TVTR data forms will be 
included in monthly data transfers from the TVTR to the Sponsor. All patient personal identifiers 
will be redacted prior to data transfer.  
10.4  Procedure Assessments 
The following procedural data should be collected: 

Intra-procedure medications (inotropes)

AV gradients (post-implant)

Calculated aortic valve area (post-implant)

Radiation dosage

AE Assessment.  For those events considered UADE, refer to protocol 6.0 or the
most current protocol version (Section 11.0) for reporting requirements.
Device accountability will be retained on the Sponsor Device Accountability Forms. 

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Data must be entered in the STS/ACC TVT Registry. Data in the TVTR data forms will be 
included in monthly data transfers from the TVTR to the Sponsor. All patient personal identifiers 
will be redacted prior to data transfer. 
10.5  Post Procedure Assessments 
The post procedure time period is within 48 hours from the time the patient exits the cath lab or 
operating room unless otherwise noted. The following post procedure data will be collected: 

Hemoglobin (lowest)

Creatinine (highest)

12 Lead ECG

TTE or TEE

AE Assessment.  For those events considered UADE, refer to protocol 6.0 or the
most current protocol version (Section 11.0) for reporting requirements.
Data must be entered in the STS/ACC TVT Registry. Data in the TVTR data forms will be 
included in monthly data transfers from the TVTR to the Sponsor. All patient personal identifiers 
will be redacted prior to data transfer. 
10.6  Discharge Assessments 
The following data will be collected for all patients for the index hospitalization: 

RBC/Whole blood transfusions

Medications (cardiac, anticoagulants, anti-platelet/anti-thrombins)

AE Assessment.  For those events considered UADE, refer to protocol 6.0 or the
most current protocol version (Section 11.0) for reporting requirements.
Data must be entered in the STS/ACC TVT Registry. Data in the TVTR data forms will be 
included in monthly data transfers from the TVTR to the Sponsor. All patient personal identifiers 
will be redacted prior to data transfer. 
10.7 
30 Day Follow-Up Visit Assessments 
The following data will be collected: 

Hemoglobin

Creatinine

NYHA

5 Meter Walk

12 Lead ECG

TTE or TEE

KCCQ

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
Medications (cardiac, anticoagulants, anti-platelet/anti-thrombins)

AE Assessment.  For those events considered UADE, refer to protocol 6.0 or the
most current protocol version (Section 11.0) for reporting requirements.
Data must be entered in the STS/ACC TVT Registry. Data in the TVTR data forms will be 
included in monthly data transfers from the TVTR to the Sponsor. All patient personal identifiers 
will be redacted prior to data transfer. 
10.8  1 Year Follow-Up Visit Assessments 
The following data will be collected: 

Hemoglobin

Creatinine

NYHA

5 Meter Walk

12 Lead ECG

TTE or TEE

KCCQ

Medications (cardiac, anticoagulants, anti-platelet/anti-thrombins)

AE Assessment.  For those events considered UADE, refer to protocol 6.0 or the
most current protocol version (Section 11.0) for reporting requirements.
Data must be entered in the STS/ACC TVT Registry database. Data in the TVTR data forms will 
be included in monthly data transfers from the TVTR to the Sponsor. All patient personal 
identifiers will be redacted prior to data transfer. 
10.9  Annual Follow-Up, Years 1-5 
Annual follow-up 1 through 5 years will be obtained for all patients through TVTR linkage to the 
CMS database. Determination of outcomes for death, stroke and rehospitalization will utilize 
data from this linkage.  
11.0  Monitoring of Study 
Edwards or designee will conduct source data verification through the 30-day follow-up visit. 
12.0 Protocol Deviations 
The sponsor will check inclusion/exclusion for violations during the monthly extract receipt from 
the TVTR as well as during source document verification monitoring. 

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Table 1.0 - Schedule of Events 
Screening 
Pre-
Procedure 
During 
procedure 
Post 
Procedure 
Discharge 
30 D 
Follow-Up 
1 yr  Follow-
Up 
Assessments
Informed Consent 
X 
Medical History 
X 
Height/Weight 
X 
Medications 
X 
X 
X 
X 
X 
Screening Assessments 
Screening 
Pre-
Procedure 
During 
procedure 
Post 
Procedure 
Discharge 
30 D 
Follow-Up 
1 yr  Follow-
Up 
STS 
X 
NYHA 
X 
X 
X 
CCS 
Syntax Score 
X 
5 Meter Walk 
X 
X 
X 
KCCQ 
X 
X 
X 
AE / UADE Assessment 
X 
X 
X 
X 
X 
Lab Measurements
Screening 
Pre-Procedure 
During procedure 
Post Procedure 
Discharge 
30 D 
Follow-Up 
1 yr  Follow-Up 
WBC 
X 
Hgb 
X 
X 
X 
X 
X 
Plt Ct 
X 
Crt 
X 
X 
X 
X 
X 
Alb 
X 
Bili 
X 
INR 
X 

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Screening 
Pre-
Procedure 
During 
procedure 
Post 
Procedure 
Discharge 
30 D 
Follow-Up 
1 yr  Follow-
Up 
Non-Invasive Tests
TTE or TEE 
X 
X 
X 
X 
Fluoroscopic imaging 
implanted valve 
X 
Pulmonary Functions 
(optional) 
X 
Radiation Dosage 
X 
12 Lead ECG 
X 
X 
X 
Invasive Tests
Screening 
Pre-
Procedure 
During 
procedure 
Post 
Procedure 
Discharge 
30 D 
Follow-Up 
1 yr  Follow-
Up 
Cardiac Imaging 
X 
CT Thoracic/Abdomen (or 
MRI) with visualization of iliac 
and femoral arteries 
X 
Cardiac Catheterization 
X 
Supra-aortic angiogram or 
TEE 
X 
Hemodynamics (see section 
9.4 of protocol 6.0 or most 
current protocol version) 
X